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Medicina, Volume 59, Issue 7 (July 2023) – 176 articles

Cover Story (view full-size image): Our work seeks to dispel the myth that Failed Back Surgery Syndrome (FBSS) is solely a reflection of surgical inefficacy. Rather, we argue that FBSS represents an intricate interplay of biological, psychological, and technical factors. This review consolidates the latest research to not only better understand FBSS, but also to offer multidisciplinary treatment approaches that offer new hope for patients. It is not the end of the road, but the beginning of a more nuanced path to healing. View this paper
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9 pages, 611 KiB  
Article
Role of Capillaroscopy in Early Diagnosis of Ionizing Radiation Damage in Healthcare Professionals
by Luca Di Bartolomeo, Federica Li Pomi, Francesco Borgia, Federico Vaccaro, Fabrizio Guarneri and Mario Vaccaro
Medicina 2023, 59(7), 1356; https://doi.org/10.3390/medicina59071356 - 24 Jul 2023
Viewed by 1481
Abstract
Background and Objectives: Chronic ionizing radiation has biological effects on exposed healthcare workers, particularly on the skin. Capillaroscopy of the nail bed represents an easy, low cost, and non-invasive test to obtain information on the effects of chronic radiation exposure in healthcare [...] Read more.
Background and Objectives: Chronic ionizing radiation has biological effects on exposed healthcare workers, particularly on the skin. Capillaroscopy of the nail bed represents an easy, low cost, and non-invasive test to obtain information on the effects of chronic radiation exposure in healthcare workers. The aim of this study was to evaluate which capillaroscopic parameters are most associated with biological damage by chronic radiation exposure. Materials and Methods: We conducted a case-control study, in which cases were represented by healthcare workers exposed to ionizing radiations and controls by healthy subjects. We recorded anamnestic and personal data, including age and gender, before capillaroscopic examination of proximal nail folds of the fingers of both hands. Ten morphological qualitative/quantitative parameters were taken into consideration, assigning each of them a score on a scale from 0 to 3 (0 = no changes, 1 = <33% abnormal capillaries, 2 = 33–66% of abnormal capillaries, 3 = >66% of abnormal capillaries, for single magnification field at 200×). The parameters evaluated were: changes in the length, distribution and density of capillary loops, reduced visibility, decreased flow, visibility of the sub-papillary plexus, and presence of morphological atypia, such as ectasia, tortuosity, hemorrhage, and signs of neoangiogenesis. Results: We enrolled 20 cases and 20 controls. The two groups did not differ significantly for gender and age. Cases differed from controls in a statistically significant way for the following parameters: decreased capillary length (number of shortened capillaries) (p < 0.05), increased visibility of the subpapillary venous plexus (p < 0.05), tortuosity (p < 0.01), neoangiogenesis (p < 0.01), and ectasias (p < 0.001). Conclusions: We found that some capillaroscopic parameters, such as variability in length of capillaries, visibility of subpapillary venous plexus, presence of ectasias, tortuosity, and neoangiogenesis signs, are particularly associated with exposure to ionizing radiation in healthcare professionals. Alterations of these parameters may represent capillaroscopic clues of biological damage by chronic radiation exposure in healthcare professionals. Based on these observations, capillaroscopy may provide clinical data useful to the prevention and follow-up of radiation-exposed healthcare professionals. Full article
(This article belongs to the Section Dermatology)
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<p>(<b>A</b>–<b>C</b>): Capillaroscopic images in healthcare professionals exposed to ionizing radiation; (<b>D</b>–<b>F</b>): capillaroscopic images in healthy controls. Capillaroscopy showed that tortuosities of capillaries were more prominent in subjects exposed to ionizing radiation than in healthy controls (<b>A</b>,<b>D</b>), as well as the subpapillary venous plexus was more visible in the former than in the latter. Subjects exposed to ionizing radiation presented more frequently loop ectasias (<b>B</b>,<b>E</b>), while there were no significant differences between the two groups as regards the presence of hemorrhages (<b>C</b>,<b>F</b>).</p>
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21 pages, 777 KiB  
Article
The Effects of Cardiac Rehabilitation including Nordic Walking in Patients with Chronic Coronary Syndromes after Percutaneous Coronary Interventions in Elective Mode
by Rafał Januszek, Bożena Kocik, Wojciech Siłka, Iwona Gregorczyk-Maga and Piotr Mika
Medicina 2023, 59(7), 1355; https://doi.org/10.3390/medicina59071355 - 24 Jul 2023
Cited by 2 | Viewed by 2660
Abstract
Background: Percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) is a worldwide method of coronary revascularisation. The aim of this study was to assess the immediate and long-term effects of Nordic Walking (NW) training added to a standard cardiac [...] Read more.
Background: Percutaneous coronary intervention (PCI) in patients with chronic coronary syndrome (CCS) is a worldwide method of coronary revascularisation. The aim of this study was to assess the immediate and long-term effects of Nordic Walking (NW) training added to a standard cardiac rehabilitation programme on physical activity (PA) and capacity and life quality, as well as selected proatherogenic risk factors. Methods: The studied group comprised 50 patients (considering exclusion criteria, 40 patients), aged 56–70, with CCS after elective PCI qualified them for a 6-weeks-long cardiac rehabilitation. The follow-up period lasted 4 months, and control visits occurred at 2 and 4 months. The studied patients were randomly divided into two groups: control group—standard cardiac rehabilitation programme and experimental group—standard cardiac rehabilitation programme additionally combined with NW training. Results: The cardiac rehabilitation programme in the experimental, compared to the control group, increased intense PA (from 731.43 ± 909.9 to 2740 ± 2875.96 vs. from 211.43 ± 259.43 to 582.86 ± 1289.74 MET min/week) and aerobic efficiency—VO2peak (from 8.67 ± 0.88 to 9.96 ± 1.35 vs. from 7.39 ± 2 to 7.41 ± 2.46 METs), as well as quality of life according to the WHOQOL-BREF questionnaire (from 3.57 ± 0.51 to 4.14 ± 0.36 vs. from 3.29 ± 0.47 to 3.57 ± 0.51 points). The walking distance assessed with the 6-min walk test did not differ between the groups before the beginning of the rehabilitation programme. Both at the I follow-up and II follow-up time points, a significant increase in the walking distance was noted in the control and experimental groups compared to baseline, and the difference between both groups was significant at the end of follow-up (378.57 ± 71.35 vs. 469.29 ± 58.07, p = 0.003). Moreover, NW had a positive effect on the modulation within selected biochemical risk factors of atherosclerosis, as well as subjective quality of life and well-being. Conclusions: Introducing NW training into the cardiac rehabilitation process proved to be a more effective form of therapy in patients with CCS treated via PCI, as compared to the standard cardiac rehabilitation programme alone. Full article
(This article belongs to the Section Cardiology)
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<p>Patient flow chart—6MWT: 6-Minute Walk Test; ABI: ankle-brachial index; CPET: cardiopulmonary exercise testing; FMD: flow mediated dilatation; HRV: heart rate variability; IPAQ: international physical activity questionnaire; PCI: percutaneous coronary intervention; PWV: pulse-waive velocity.</p>
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14 pages, 665 KiB  
Review
Quality Standard for Rehabilitation of Young Deaf Children Receiving Cochlear Implants
by Leo De Raeve, Marinela-Carmen Cumpăt, Aimée van Loo, Isabel Monteiro Costa, Maria Assunção Matos, João Canossa Dias, Cristian Mârțu, Bogdan Cavaleriu, Alois Gherguț, Alexandra Maftei, Ovidiu-Cristian Tudorean, Corina Butnaru, Roxana Șerban, Tatiana Meriacre and Luminița Rădulescu
Medicina 2023, 59(7), 1354; https://doi.org/10.3390/medicina59071354 - 24 Jul 2023
Cited by 3 | Viewed by 3774
Abstract
Background and objectives: More and more children with severe-to-profound hearing loss are receiving cochlear implants (CIs) at an early age to improve their hearing and listening abilities, speech recognition, speech intelligibility, and other aspects of spoken language development. Despite this, the rehabilitation outcomes [...] Read more.
Background and objectives: More and more children with severe-to-profound hearing loss are receiving cochlear implants (CIs) at an early age to improve their hearing and listening abilities, speech recognition, speech intelligibility, and other aspects of spoken language development. Despite this, the rehabilitation outcomes can be very heterogeneous in this population, not only because of issues related to surgery and fitting or the specific characteristics of the child with his/her additional disabilities but also because of huge differences in the quality of the support and rehabilitation offered by the therapist and the family. These quality standards for the rehabilitation of young deaf children receiving CIs are developed within the European KA202 Erasmus+ project “VOICE”—vocational education and training for speech and language therapists and parents for the rehabilitation of children with CIs, Ref. No.: 2020-1-RO01-KA202-080059. Material and methods: To develop these quality standards, we used the input from the face-to-face interviews of 11 local rehabilitation experts in CIs from the four partner countries of the project and the outcomes of the bibliographic analysis of 848 publications retrieved from six databases: Pub Med, Psych Info, CINAHL, Scopus, Eric, and Cochrane. Based on all this information, we created a first set of 32 quality standards over four domains: general, fitting, rehabilitation, and for professionals. Further on, the Delphi method was used by 18 international rehabilitation experts to discuss and agree on these standards. Results: The results from the literature analysis and the interviews show us that more than 90% of the consulted international experts agreed on 29 quality standards. They focus on different aspects of rehabilitation: the multidisciplinary team, their expertise and knowledge, important rehabilitation topics to focus on, and programming issues related to rehabilitation. Conclusions: These quality standards aim to optimize the activity of speech rehabilitation specialists so that they reach the optimal level of expertise. Also presented is the necessary equipment for the IC team to carry out the rehabilitation sessions in good conditions. This set of quality standards can be useful to ensure the appropriate postoperative care of these children. As a result, the rehabilitation process will be more relaxed, and therapists will have the opportunity to focus more on the specific needs of each child, with the provision of quality services, which will result in better results. This theme is particularly complex and dependent on multifactorial aspects of medicine, education, speech therapy, social work, and psychology that are very intricate and interdependent. Full article
(This article belongs to the Special Issue Current Trends in Otorhinolaryngology and Head and Neck Pathology)
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<p>Flowchart of reviewed papers with exclusion and inclusion criteria.</p>
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11 pages, 2991 KiB  
Article
The Anti-Inflammatory and Skin Barrier Function Recovery Effects of Schisandra chinensis in Mice with Atopic Dermatitis
by Yoorae Son, Wonjin Yang, Sangjun Park, Jinkyu Yang, Soyeon Kim, Ji-Hyo Lyu and Hyungwoo Kim
Medicina 2023, 59(7), 1353; https://doi.org/10.3390/medicina59071353 - 24 Jul 2023
Cited by 5 | Viewed by 2935
Abstract
Background and Objectives: The fruit of Schisandra chinensis (Turcz.) Baill. is widely used medicinally to treat coughs, asthma, exhaustion, eczema, and pruritus in Northeast Asian countries, including Korea, China, and Japan. This study was designed to investigate the effects of S. chinensis [...] Read more.
Background and Objectives: The fruit of Schisandra chinensis (Turcz.) Baill. is widely used medicinally to treat coughs, asthma, exhaustion, eczema, and pruritus in Northeast Asian countries, including Korea, China, and Japan. This study was designed to investigate the effects of S. chinensis on dermatitis in mice with calcipotriol (MC-903)-induced atopic dermatitis (AD), and its effects on skin barrier dysfunction was also investigated. Materials and Methods: The inhibitory effects of an ethanolic extract of S. chinensis (EESC) on skin lesions, water content, water-holding capacity (WHC), histopathological abnormalities, and inflammatory cytokine and chemokine levels were evaluated in mice with AD induced by MC903. Results: Topical EESC ameliorated skin lesions, reduced skin water content, and increased MC903-induced WHC. EESC also prevented MC-903-induced histopathological abnormalities such as epidermal disruption, hyperkeratosis, spongiotic changes, and immune cell infiltration in inflamed tissue. Moreover, topical EESC reduced MC-903-induced levels of pro-inflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL-8, monocyte chemotactic protein (MCP)-1, and thymic stromal lymphopoietin (TSLP). Furthermore, unlike dexamethasone, EESC did not reduce the spleen/body weight ratio. Conclusions: These results suggest that S. chinensis can be used as an alternative to external corticosteroids and that its anti-inflammatory and skin barrier dysfunction-restoring effects are related to the downregulation of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-4, IL-6, IL-8, and TSLP. Full article
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<p>Effects of EESC on skin lesions and color in AD mice. (<b>A</b>) (<b>a</b>) Non-treated naïve (NOR); (<b>b</b>) AD control (CTL); (<b>c</b>) 60 μg/day of EESC; (<b>d</b>) 180 μg/day of EESC; (<b>e</b>) 600 μg/day of EESC; (<b>f</b>) 150 μg/day of DEX. (<b>B</b>) Skin lesion scores. (<b>C</b>) Skin thicknesses. (<b>D</b>) Erythema indices. (<b>E</b>) Melanin indices. A.U., arbitrary unit; N.D., undetectable; EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SDs. # <span class="html-italic">p</span> &lt; 0.05 and ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 vs. the CTL group.</p>
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<p>Effects of EESC on skin water content and WHC in AD mice. (<b>A</b>) Water content; (<b>B</b>) WHC. EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SD. # <span class="html-italic">p</span> &lt; 0.05 and ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 vs. the CTL group.</p>
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<p>Effects of EESC on histopathological abnormalities in inflamed tissue. (<b>A</b>) The abbreviations used are the same as those used in <a href="#medicina-59-01353-f001" class="html-fig">Figure 1</a>A. The solid arrow indicates a blood vessel near the epidermis. White arrows show epidermis disruption. The solid wedge indicates an indistinct boundary between the epidermis and dermis. (<b>B</b>) Severity scores; (<b>C</b>) infiltrated immune cells. N.D., undetectable.; EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SDs. ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 vs. the CTL group.</p>
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<p>Effects of EESC on MC-903-induced increases in cytokine and chemokine mRNA levels in skin tissue. (<b>A</b>) IL-1β; (<b>B</b>) IL-4; (<b>C</b>) IL-6; (<b>D</b>) IL-8; (<b>E</b>) MCP-1; (<b>F</b>) TSLP. N.D., undetectable. EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SDs. ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 vs. the CTL group.</p>
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<p>Effects of EESC on MC-903-induced increases in cytokine and chemokine mRNA levels in skin tissue. (<b>A</b>) IL-1β; (<b>B</b>) IL-4; (<b>C</b>) IL-6; (<b>D</b>) IL-8; (<b>E</b>) MCP-1; (<b>F</b>) TSLP. N.D., undetectable. EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SDs. ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001 vs. the CTL group.</p>
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<p>Effects of EESC on the MC-903-induced production of TNF-α, IL-4, IL-6, and IL-2 in skin tissue. (<b>A</b>) TNF-α; (<b>B</b>) IL-4; (<b>C</b>) IL-6; (<b>D</b>) IL-2. N.D., undetectable. EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SDs. # <span class="html-italic">p</span> &lt; 0.05 and ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 vs. the CTL group.</p>
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<p>Effects of EESC on MC903-induced changes in body weight and spleen/body ratio. (<b>A</b>) Body weight; (<b>B</b>), spleen/body weight ratios. EESC, ethanol extract of <span class="html-italic">S. chinensis</span>; DEX, dexamethasone. Results are presented as means ± SDs. ### <span class="html-italic">p</span> &lt; 0.001 vs. the NOR group; *** <span class="html-italic">p</span> &lt; 0.001 vs. the CTL group.</p>
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20 pages, 1897 KiB  
Article
The Relationship between Burnout and Wellbeing Using Social Support, Organizational Justice, and Lifelong Learning in Healthcare Specialists from Romania
by Roxana Mihaela Claponea and Magdalena Iorga
Medicina 2023, 59(7), 1352; https://doi.org/10.3390/medicina59071352 - 24 Jul 2023
Cited by 4 | Viewed by 3384
Abstract
Background and objectives: The goal of this study was to evaluate the levels of organizational justice, social support, wellbeing, and lifelong learning associated with the level of burnout experienced by medical and non-medical staff from public and private medical units. Materials and [...] Read more.
Background and objectives: The goal of this study was to evaluate the levels of organizational justice, social support, wellbeing, and lifelong learning associated with the level of burnout experienced by medical and non-medical staff from public and private medical units. Materials and Methods: A cross-sectional study was conducted on a sample of 497 healthcare professionals: 367 medical personnel (Mage = 43.75 ± 0.50), including 216 nurses, 97 physicians, and 54 respondents with other medical specialities such as biologists, psychologists, physical therapists, pharmacists, etc., and 130 non-medical staff respondents (Mage = 45.63 ± 0.80), including administrative personnel. The Maslach Burnout Inventory, the ECO System, the Multidimensional Scale of Perceived Social Support, the WHO Wellbeing Index, and the revised Jefferson Scale of Physician’s Lifelong Learning were used. Results: Burnout was measured in terms of emotional exhaustion, depersonalization, and personal accomplishment. Medical personnel registered higher values of personal accomplishment (38.66 ± 0.39 vs. 35.87 ± 0.69), while non-medical personnel registered higher values of depersonalization (6.59 ± 0.52 vs. 4.43 ± 0.26) and emotional exhaustion (27.33 ± 1.24 vs. 19.67 ± 0.71). In terms of organizational justice, higher scores were observed for medical staff, while non-medical staff recorded lower values (24.28 ± 0.24 vs. 22.14 ± 0.38). For wellbeing, higher scores were also registered for medical staff (11.95 ± 0.21 vs. 10.33 ± 0.37). Conclusions: For lifelong learning and social support, no statistically significant differences were found. In the case of the proposed parallel moderated mediation model, the moderated mediation effects of organizational justice, lifelong learning, and burnout on the relationship between social support and wellbeing were valid for every dimension of burnout (emotional exhaustion, depersonalization, and personal accomplishment), but lifelong learning was not found to be a viable mediating variable, even if high levels of social support correspond to high levels of lifelong learning and wellbeing. Full article
(This article belongs to the Special Issue Work Culture in Medicine: Ethical, Legal and Social Challenges)
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<p>Model 1. The designed parallel moderated mediation model.</p>
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<p>Chart of the moderated effect of organizational justice through emotional exhaustion on wellbeing.</p>
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<p>Model 2. The designed parallel moderated mediation model.</p>
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<p>Chart of the moderated effect of organizational justice through personal accomplishment on wellbeing.</p>
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<p>Model 3. The designed parallel moderated mediation model.</p>
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<p>Chart of the moderated effect of organizational justice through depersonalization on wellbeing.</p>
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19 pages, 4992 KiB  
Article
SIRT1/Nrf2/NF-κB Signaling Mediates Anti-Inflammatory and Anti-Apoptotic Activities of Oleanolic Acid in a Mouse Model of Acute Hepatorenal Damage
by Manea A. I. Alqrad, Dina S. El-Agamy, Sabrin R. M. Ibrahim, Alaa Sirwi, Hossam M. Abdallah, Essam Abdel-Sattar, Ali M. El-Halawany, Wael M. Elsaed and Gamal A. Mohamed
Medicina 2023, 59(7), 1351; https://doi.org/10.3390/medicina59071351 - 24 Jul 2023
Cited by 10 | Viewed by 2425
Abstract
Background and objectives: Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from Viscum schimperi (Loranthaceae), against TAA [...] Read more.
Background and objectives: Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from Viscum schimperi (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. Materials and Methods: Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. Results: The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2–related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. Conclusions: OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage. Full article
(This article belongs to the Section Pharmacology)
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<p>(<b>A</b>) Scheme for isolation of oleanolic acid (OA); (<b>B</b>) Chemical structure of OA.</p>
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<p>Oleanolic acid (OA) mitigated thioacetamide-induced acute hepatorenal damage. (<b>A</b>) Liver sections show the normal liver structure of the control and OA groups, while the TAA group showed disruption of the normal liver architecture with obliteration of the interhepatic sinusoids (arrows) and diffuse inflammatory cell infiltration (arrow heads) in the vicinity of the central veins. The OA + TAA groups exhibited less marked pathological changes in variable degrees (hematoxylin and eosin × 200). (<b>B</b>) Kidney sections showing normal the structure of the control and OA groups. The TAA group exhibited cytoplasm vacculation (arrow heads) and congestion (arrows). The OA + TAA groups showed remarkable improvement in TAA-induced changes (hematoxylin and eosin × 200). Data are the mean ± SE (n = 6). * <span class="html-italic">p</span> &lt; 0.05 vs. control group; <sup>#</sup><span class="html-italic">p</span> &lt; 0.05 vs. TAA group (one-way ANOVA).</p>
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<p>Oleanolic acid (OA) lessened thioacetamide (TAA)-induced upregulation and release of interleukins (IL-1β&amp;6). (<b>A</b>,<b>B</b>) Relative mRNA expression and level of IL-1β; (<b>C</b>,<b>D</b>) Relative mRNA expression and level of IL-6. Data are the mean ± SE (n = 6). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group; <sup>#</sup><span class="html-italic">p</span> &lt; 0.05, <sup>##</sup><span class="html-italic">p</span> &lt; 0.01, <sup>###</sup><span class="html-italic">p</span> &lt; 0.001 vs. TAA group (one-way ANOVA).</p>
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<p>Oleanolic acid (OA) attenuated thioacetamide (TAA)-induced activation of NF-κB/TNF-α signalling. (<b>A</b>) Immunostaining of NF-κB and TNF-α of the liver and kidney tissue; (<b>B</b>,<b>C</b>) % of immuno-positive cells of NF-κB and TNF-α respectively; (<b>D</b>,<b>E</b>) Activation and level of NF-κB respectively; (<b>F</b>,<b>G</b>) Level and mRNA of TNF-α. Data are the mean ± SE (n = 6). <sup>##</sup><span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span>&lt; 0.001 vs. TAA group * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group (one-way ANOVA).</p>
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<p>Oleanolic acid (OA) attenuated thioacetamide (TAA)-induced activation of NF-κB/TNF-α signalling. (<b>A</b>) Immunostaining of NF-κB and TNF-α of the liver and kidney tissue; (<b>B</b>,<b>C</b>) % of immuno-positive cells of NF-κB and TNF-α respectively; (<b>D</b>,<b>E</b>) Activation and level of NF-κB respectively; (<b>F</b>,<b>G</b>) Level and mRNA of TNF-α. Data are the mean ± SE (n = 6). <sup>##</sup><span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span>&lt; 0.001 vs. TAA group * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group (one-way ANOVA).</p>
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<p>Oleanolic acid (OA) offset thioacetamide (TAA)-induced apoptosis in liver and kidney. (<b>A</b>) mRNA and level of Bax, Bcl2 and caspase-3; (<b>B</b>) Immunostaining of Bcl2 and caspase-3 of the hepatic and kidney tissue. Data are the mean ± SE (n = 6). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. TAA group (one-way ANOVA).</p>
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<p>Oleanolic acid (OA) augmented SIRT1/Nrf2/HO-1 signaling in the liver and kidney. (<b>A</b>) mRNA expression of Nrf2/SIRT1/HO-1; Nrf2 binding activity, and HO-1 level. (<b>B</b>) Nrf2 immuno-expression in the kidney and liver tissue. The TAA specimen possessed minimal immuno-stain compared to the control group while the OA-pre-treated groups showed much higher Nrf2 immuno-stain. Data are the mean ± SE (n = 6). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group; <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. TAA group (one-way ANOVA).</p>
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<p>Summary of the molecular pathways modulated by oleanolic acid (OA) against thioacetamide (TAA)-induced acute hepatic and kidney injury.</p>
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11 pages, 325 KiB  
Article
Associations between Smoking Status and Health-Related Physical Fitness and Balance Ability among Older Males in Taiwan
by Yi-Chuan Hung, Po-Fu Lee, Chi-Fang Lin, Yan-Jhu Su, Jenn-Woei Hsieh, Yu-Ju Lin, Chien-Chang Ho and Yun-Tsung Chen
Medicina 2023, 59(7), 1350; https://doi.org/10.3390/medicina59071350 - 23 Jul 2023
Cited by 1 | Viewed by 2275
Abstract
The primary aim of this study was to examine the relationships between smoking status and health-related physical fitness and balance ability in older males residing in Taiwan. This investigation adopted a cross-sectional design, utilizing data from 7688 older males who took part in [...] Read more.
The primary aim of this study was to examine the relationships between smoking status and health-related physical fitness and balance ability in older males residing in Taiwan. This investigation adopted a cross-sectional design, utilizing data from 7688 older males who took part in the 2014–2015 wave of the National Physical Fitness Survey of Taiwan. Various data sources, including a standardized structured questionnaire, anthropometric measurements, health-related physical fitness assessments, and balance ability tests, were analyzed. The participants were divided into three categories based on their smoking habits: never smokers, former smokers, and current smokers. Multiple regression analyses were performed to evaluate the linear association between cigarette smoking status and health-related physical fitness and balance ability performance. Health-related physical fitness and balance performance were significantly greater (p < 0.05) in the never smoker group than in the current smoker group. Current smoking status was significantly negatively (p < 0.05) associated with cardiopulmonary function, muscular endurance, flexibility, and balance performance. A history of smoking (former smoker) was significantly negatively (p < 0.05) associated with the 2-min step test, 30-s arm curl and chair stand, as well as the 8-foot up-and-go test; however, the association was not significant for the back scratch, chair sit-and-reach, and one-leg stance with eyes open performance. These results suggest that current cigarette smoking is detrimental to health-related physical fitness and balance performance in older males. Quitting smoking may reverse the effects of smoking on overall body flexibility and static balance performance in Taiwanese older adults, thereby reducing the risk of falls and incapacity. Full article
(This article belongs to the Special Issue Towards Exercise and Physical Activity for Elderlies Quality of Life)
8 pages, 1088 KiB  
Case Report
Persistent Pancytopenia as a Long-COVID Manifestation in a Patient with Adult-Onset Still’s Disease: A Case Report
by Mattia Massimino, Francesco Salvatore Iaquinta, Saverio Naty, Francesco Andreozzi and Rosa Daniela Grembiale
Medicina 2023, 59(7), 1349; https://doi.org/10.3390/medicina59071349 - 23 Jul 2023
Viewed by 2683
Abstract
Background: Adult-onset Still’s disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the [...] Read more.
Background: Adult-onset Still’s disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the case of a patient affected by refractory AOSD presenting with severe pancytopenia as a long-COVID manifestation. The purpose of this case report is to illustrate the clinical presentation, diagnostic and therapeutic management of this unusual manifestation. Moreover, we examine the mechanisms that are potentially responsible for the onset of the pancytopenia observed in our patient. Case presentation: We describe the case of a 40-year-old male who presented with a history of fever for 2 years, arthralgia, maculopapular salmon-pink rash and a previous SARS-CoV-2 infection which required admission to intensive care. The patient’s laboratory results revealed elevated inflammatory markers levels (erythrocyte sedimentation rate and C-reactive protein), hyperferritinemia and severe pancytopenia that needed multiple transfusions. A diagnosis of AOSD was made based on clinical and laboratory presentation after excluding neoplastic, infectious and other rheumatic diseases. The previous empirical treatment was not adequate to control the condition; therefore, treatment with high-dose steroids, canakinumab and epoetin alfa was started and led to the resolution of the man’s symptoms and a reduction in inflammatory marker levels, whereas blood cell count remained stable without a need for further blood transfusions. The patient is currently under rheumatologic and hematologic follow-up every month. Conclusions: Neither AOSD nor SARS-CoV-2 infection usually manifests with pancytopenia, except in hemophagocytic syndrome or immunodeficient patients, respectively. Identifying the underlying etiology of pancytopenia is mandatory to establish a prompt treatment that generally resolves the disorder. However, in our case, all common causes of pancytopenia were excluded, suggesting a potential manifestation of the long-COVID syndrome. Despite the resolution of the acute infection and the remarkable treatment of AOSD, pancytopenia persists. Herein, we propose for refractory AOSD patients with previous SARS-CoV-2 infection a novel approach to the diagnosis and treatment of pancytopenia. Full article
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<p>Evanescent “salmon-pink” skin rash on the trunk observed at the patient’s admission in April 2021.</p>
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<p>Axial CT image showing ground-glass opacities, peripheral septal thickening and minimal pericardial effusion; P: posterior.</p>
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13 pages, 1364 KiB  
Article
Using Hormone Data and Age to Pinpoint Cycle Day within the Menstrual Cycle
by Elinor Hills, Mark B. Woodland and Aparna Divaraniya
Medicina 2023, 59(7), 1348; https://doi.org/10.3390/medicina59071348 - 23 Jul 2023
Cited by 3 | Viewed by 5476
Abstract
Background and Objectives: Menstrual cycle tracking is essential for reproductive health and overall well-being. However, there is still an over-reliance on estimations that standard cycles are 28 days long, divided evenly between the follicular and luteal phases. Due to the variability of [...] Read more.
Background and Objectives: Menstrual cycle tracking is essential for reproductive health and overall well-being. However, there is still an over-reliance on estimations that standard cycles are 28 days long, divided evenly between the follicular and luteal phases. Due to the variability of cycle length and cycle phase lengths, common methods of identifying where an individual is in their cycle are often inaccurate. This study used daily hormone monitoring obtained through a remote hormone-monitoring platform to evaluate hormone levels across a menstrual cycle to identify nuances in the follicular and luteal phases in individuals of different age groups. Materials and Methods: This study used a remote fertility testing system that quantitatively tracks luteinizing hormone (LH) and pregnanediol-3-glucuronide (PdG) through urine tests read by an AI-powered smartphone app. The study analyzed cycle data from 1233 users with a total of 4123 evaluated cycles. Daily levels for LH and PdG were monitored across multiple cycles. Results: This study determined that calculated cycle lengths tended to be shorter than user-reported cycle lengths. Significant differences were observed in cycle phase lengths between age groups, indicating that follicular phase length declines with age while luteal phase length increases. Finally, the study found that if an individual’s age, first cycle day, and current hormone levels are known, population-level hormone data can be used to pinpoint which cycle phase and cycle day they are in with 95% confidence. Conclusions: At-home hormone monitoring technologies can allow patients and clinicians to track their cycles with greater precision than when relying on textbook estimations. The study’s findings have implications for fertility planning, clinical management, and general health monitoring. Prior to this study, no standard existed for pinpointing where a person was in their cycle through only one measure of LH and PdG. These findings have the potential to fill significant gaps within reproductive healthcare and beyond. Full article
(This article belongs to the Special Issue Quantitative Hormone Monitoring of the Menstrual Cycle)
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<p>Self-reported and calculated cycle lengths across age groups. Across all age groups, calculated cycle lengths tended to be shorter than self-reported cycle lengths, with a significance level of *** <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>The distribution of the follicular and luteal phases across all age groups, with a significance level of *** <span class="html-italic">p</span> &lt; 0. 001. Significance was found in follicular phase lengths between 25–29 and 30–34, and 35–39 and 40–44, but not displayed in this graph. Significance was also found in luteal phase lengths between 25–29 and 30–34, 25–29 and 40–44, and 30–34 and 35–39, but are not displayed in this graph. For a full list of associated <span class="html-italic">p</span>-values, see <a href="#app1-medicina-59-01348" class="html-app">Supplemental Materials, Tables S1 and S2</a>.</p>
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<p>Panels (<b>A</b>,<b>B</b>) depict LH levels across age groups in follicular and luteal phases. Panels (<b>C</b>,<b>D</b>) depict PdG levels across age groups in follicular and luteal phases. Each panel shows the LH or PdG data for the specific phase for the designated age group. The data points indicate the mean hormone level on a specific cycle day. The error bars indicate the standard error. The shaded region designates the confidence interval. LH levels are shown in mIU/L while PdG is in ng/mL.</p>
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<p>Panels (<b>A</b>,<b>B</b>) depict LH levels across age groups in follicular and luteal phases. Panels (<b>C</b>,<b>D</b>) depict PdG levels across age groups in follicular and luteal phases. Each panel shows the LH or PdG data for the specific phase for the designated age group. The data points indicate the mean hormone level on a specific cycle day. The error bars indicate the standard error. The shaded region designates the confidence interval. LH levels are shown in mIU/L while PdG is in ng/mL.</p>
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10 pages, 319 KiB  
Article
Prevalence, Recognition, and Risk Factors of Constipation among Medically Hospitalized Patients: A Cohort Prospective Study
by Jawahar Al Nou’mani, Abdullah M. Al Alawi, Juhaina Salim Al-Maqbali, Nahid Al Abri and Maryam Al Sabbri
Medicina 2023, 59(7), 1347; https://doi.org/10.3390/medicina59071347 - 23 Jul 2023
Cited by 9 | Viewed by 5287
Abstract
Background and Objective: Constipation is a prevalent gastrointestinal condition that has a substantial impact on individuals and healthcare systems. This condition adversely affects health-related quality of life and leads to escalated healthcare expenses due to an increase in office visits, referrals to [...] Read more.
Background and Objective: Constipation is a prevalent gastrointestinal condition that has a substantial impact on individuals and healthcare systems. This condition adversely affects health-related quality of life and leads to escalated healthcare expenses due to an increase in office visits, referrals to specialists, and hospital admission. This study aimed to evaluate the prevalence, recognition, risk factors, and course of constipation among hospitalized patients in medical wards. Materials and Methods: A prospective study was conducted, including all adult patients admitted to the General Medicine Unit between 1 February 2022 and 31 August 2022. Constipation was identified using the Constipation Assessment Scale (CAS), and relevant factors were extracted from the patients’ medical records. Results: Among the patients who met the inclusion criteria (n = 556), the prevalence of constipation was determined to be 55.6% (95% CI 52.8–58.4). Patients with constipation were found to be older (p < 0.01) and had higher frailty scores (p < 0.01). Logistic regression analysis revealed that heart failure (Odds ratio (OR) 2.1; 95% CI 1.2–3.7; p = 0.01), frailty score (OR 1.4; 95% CI 1.2–1.5; p < 0.01), and dihydropyridines calcium channel blockers (OR 1.8; 95% CI 1.2–2.8; p < 0.01) were independent risk factors for constipation. Furthermore, the medical team did not identify constipation in 217 patients (64.01%). Conclusions: Constipation is highly prevalent among medically hospitalized patients. To ensure timely recognition and treatment, it is essential to incorporate a daily constipation assessment scale into each patient’s medical records. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
9 pages, 13846 KiB  
Case Report
Leiomyoma with Uncommon Localization—Incisive Papilla and Palatal Fibromucosa: A Case Report
by Marina Rakitovan, Adrian Nicoara, Raluca Maria Closca, Nicolae Constantin Balica, Eugen Horatiu Stefanescu and Flavia Baderca
Medicina 2023, 59(7), 1346; https://doi.org/10.3390/medicina59071346 - 23 Jul 2023
Cited by 3 | Viewed by 3375
Abstract
The current paper presents a case of a 33-year-old female with an uncommon localization of a leiomyoma in the oral cavity—the anterior palatal fibromucosa and the incisive papilla. The patient referred to the Oro-Maxillo-Facial Surgery Clinic of Emergency City Hospital Timisoara, Romania, complaining [...] Read more.
The current paper presents a case of a 33-year-old female with an uncommon localization of a leiomyoma in the oral cavity—the anterior palatal fibromucosa and the incisive papilla. The patient referred to the Oro-Maxillo-Facial Surgery Clinic of Emergency City Hospital Timisoara, Romania, complaining of a slight discomfort in the act of mastication and the occurrence and persistence of a diastema between the upper central incisors, due to the presence of a nodule located in the anterior palatal mucosa, between the upper central incisors, without any changes of the subjacent bone structure in the anterior hard palate visible on a cone beam computed tomography image (CBCT). The lesion was removed using a surgical excisional biopsy and a histopathological examination was performed using morphological Hematoxylin–Eosin (HE) staining and additional immunohistochemical (IHC) reactions, in order to confirm the diagnosis. On microscopic examination, bundles of spindle cells were found with eosinophilic cytoplasm and vesicular nuclei, with finely granular chromatin. The immunohistochemical reactions were positive for smooth muscle actin (SMA) and desmin and negative for vimentin. The treatment of choice for leiomyoma of the oral cavity is surgical excision with clear margins, followed by periodical clinical monitoring. Full article
(This article belongs to the Section Dentistry and Oral Health)
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<p>Intraoral aspect: (<b>a</b>) aspect of the lesion at the level of the incisive papilla and anterior palatal fibromucosa; (<b>b</b>) aspect of the lesion (buccal view), interincisal diastema and gingivo-mucosal scar.</p>
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<p>Cone beam computed tomography showed no underlying bone structure alteration.</p>
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<p>Microscopic aspects of HE-stained slides: (<b>a</b>) tumor proliferation in the oral mucosa with spindle-shaped cells arranged in different-sized fascicles, ob. 5x; (<b>b</b>) different-sized spindle cell fascicles disposed in the lamina propria of the oral mucosa, ob. 5x; (<b>c</b>) fascicles of tumor cells arranged among acinar structures in the lamina propria of the mucosa, ob. 5x; (<b>d</b>) fusiform tumor cells in a fasciculate pattern, with large, eosinophilic cytoplasm and elongated monotonous blunt-ended nuclei, ob. 20x.</p>
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<p>Microscopic images of IHC reactions for desmin, ob. 40x: (<b>a</b>) tumor cells with diffuse and intense positive reaction for desmin; (<b>b</b>) intense and diffuse cytoplasmic positive reaction in all the tumor cells.</p>
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<p>Microscopic images of IHC reactions for smooth muscle actin, ob. 40x: (<b>a</b>) intense and diffuse positive reaction in all tumor cells; (<b>b</b>) positive reaction with cytoplasmic distribution.</p>
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<p>Microscopic images of IHC reactions for vimentin: (<b>a</b>) negative reaction of tumor cells, with positive control, ob. 5x; (<b>b</b>) positive reaction at the level of the vascular component, ob. 20x.</p>
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<p>Microscopic images of IHC reactions for Ki67: (<b>a</b>) positive reaction in the nuclei of basal layer cells of the covering epithelium, ob. 5x; (<b>b</b>) only a few positive nuclei of the tumor cells, ob. 40x.</p>
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8 pages, 921 KiB  
Case Report
A Case of Milk-Alkali Syndrome Caused by Diuretic-Induced Alkalosis and Polypharmacy
by Naoya Mizutani, Ken Goda and Tsuneaki Kenzaka
Medicina 2023, 59(7), 1345; https://doi.org/10.3390/medicina59071345 - 22 Jul 2023
Cited by 2 | Viewed by 2549
Abstract
Milk-alkali syndrome, which is characterized by hypercalcemia, metabolic alkalosis, and renal dysfunction, typically results from the ingestion of large amounts of calcium and absorbable alkaline products. However, these symptoms can also manifest when alkalosis and calcium loading occur simultaneously, owing to other factors. [...] Read more.
Milk-alkali syndrome, which is characterized by hypercalcemia, metabolic alkalosis, and renal dysfunction, typically results from the ingestion of large amounts of calcium and absorbable alkaline products. However, these symptoms can also manifest when alkalosis and calcium loading occur simultaneously, owing to other factors. We report a case of milk-alkali syndrome caused by loop-diuretic-induced alkaline load and polypharmacy in an 85-year-old Japanese woman with multiple comorbidities, including osteoporosis, hypertension, type 2 diabetes, dyslipidemia, and Parkinson’s disease. The patient regularly took 14 drugs, including calcium L-aspartate, eldecalcitol, celecoxib, and a fixed-dose combination of losartan and hydrochlorothiazide. Immediately before admission, furosemide was administered for the treatment of edema. The patient presented with chest discomfort, general malaise, and clinical signs of dehydration, hypercalcemia, hypophosphatemia, hypokalemia, and hypomagnesemia, accompanied by electrocardiogram abnormalities, renal dysfunction, and chloride-resistant metabolic alkalosis. The hypercalcemia was specifically induced by calcium L-aspartate and eldecalcitol. The hypomagnesaemia and hypophosphatemia were caused by diuretics and hypercalcemia. Thus, all the oral medications were discontinued, and rehydration and electrolyte correction therapy were administered. The final diagnosis was milk-alkali syndrome caused by the concomitant use of loop diuretics and other medications, without absorbable alkaline preparation use. This case underscores the importance of considering drug-related factors, checking concomitant medications, and being aware of the benefits, harmful effects, and side effects of polypharmacy in older adults with multimorbidity. Full article
(This article belongs to the Section Pharmacology)
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<p>An abdominal computed tomography scan without enhancement. The images are in the order (<b>a</b>–<b>c</b>). Bilateral kidney and ureteral stones (yellow arrows). Left-sided hydronephrosis and left-sided hydroureter (red circle).</p>
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<p>The course of treatment for the first six days after hospitalization.</p>
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6 pages, 524 KiB  
Case Report
A New Neurological Screening Approach for Diagnosing Brainstem Infarction Using the Calling Method and Familiar Voices
by Yuzuru Ohshiro
Medicina 2023, 59(7), 1344; https://doi.org/10.3390/medicina59071344 - 21 Jul 2023
Viewed by 1749
Abstract
This report proposes a new approach to assess dysarthria in patients with brainstem infarction by involving familiar individuals. Collaboration provides valuable insights compared to subjective traditional methods. A man in his 70s presented with resolved positional vertigo. Standard neurological tests showed no abnormalities, [...] Read more.
This report proposes a new approach to assess dysarthria in patients with brainstem infarction by involving familiar individuals. Collaboration provides valuable insights compared to subjective traditional methods. A man in his 70s presented with resolved positional vertigo. Standard neurological tests showed no abnormalities, and inquiries with the patient’s friend did not reveal voice changes. While inquiring about voice changes with family, friends, and acquaintances is a common practice in clinical settings, our approach involved the patient calling out to his friend from a distance. Despite the physician detecting no abnormalities, the friend noticed a lower voice. Subsequent magnetic resonance imaging (MRI) confirmed brainstem infarction. Early and subtle symptoms of brainstem infarction pose a detection challenge and can lead to serious outcomes if overlooked. This report provides the first evidence that distance calling can detect subtle voice changes associated with brainstem infarction potentially overlooked by conventional neurological examinations, including inquiries with individuals familiar with the patient’s voice. Detecting brainstem infarction in emergency department cases is often missed, but conducting MRIs on every patient is not feasible. This simple method may identify patients overlooked by conventional screening who should undergo neuroimaging such as MRI. Further research is needed, and involving non-professionals in assessments could significantly advance the diagnostic process. Full article
(This article belongs to the Special Issue Advances and Challenges in Stroke Therapy: A Regenerative Prospective)
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<p>Diffusion-weighted magnetic resonance imaging showed evidence of acute brainstem infarction in the right lateral medulla.</p>
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7 pages, 323 KiB  
Brief Report
Comparison of Central Aortic Pressure between Women with Preeclampsia and Normotensive Postpartum Women from an Urban Region of Western Mexico
by Francisco J. Hernández-Mora, Claudia K. Cerda-Guerrero, Leonel García-Benavides, Enrique Cervantes-Pérez, Sol Ramírez-Ochoa, Janet Cristina Vázquez-Beltrán, Gabino Cervantes-Guevara, Ernesto Ledezma-Hurtado, Adriana Nápoles-Echauri, Alejandro González-Ojeda, Clotilde Fuentes-Orozco, María Isabel Hernández-Rivas, Mariana Chávez-Tostado and Guillermo A. Cervantes-Cardona
Medicina 2023, 59(7), 1343; https://doi.org/10.3390/medicina59071343 - 21 Jul 2023
Cited by 1 | Viewed by 1829
Abstract
Background and Objectives: Central aortic pressure (CAP) can be measured through noninvasive methods, and CAP wave analysis can provide information about arterial stiffness. The objective of this study was to compare CAP in women with preeclampsia and normotensive postpartum women from an [...] Read more.
Background and Objectives: Central aortic pressure (CAP) can be measured through noninvasive methods, and CAP wave analysis can provide information about arterial stiffness. The objective of this study was to compare CAP in women with preeclampsia and normotensive postpartum women from an urban region in western Mexico. Materials and Methods: We recruited 78 women in immediate puerperium, including 39 with preeclampsia and 39 with normotension, who received delivery care in our hospital between September 2017 and January 2018. Pulse wave analysis was used to assess central hemodynamics as well as arterial stiffness with an oscillometric device. For this purpose, the measurement of the wave of the left radial artery was obtained with a wrist applanation tonometer and the ascending aortic pressure wave was generated using the accompanying software (V 1.1, Omron, Japan). Additionally, the systolic CAP, diastolic pressure, pulse pressure, heart rate, and rise rate adjusted for a heart rate of 75 bpm were determined. The radial pulse wave was calibrated using the diastolic and mean arterial pressures obtained from the left brachial artery. For all the statistical analyses, we considered p < 0.05 to be significant. Results: The results were as follows: a systolic CAP of 125.40 (SD 15.46) vs. 112.10 (SD 10.12) with p < 0.0001 for women with and without preeclampsia, respectively. Systolic CAP was significantly elevated in women with preeclampsia and could indicate an elevated risk of cardiovascular disease. Conclusion: CAP is an important parameter that can be measured in this group of patients and is significantly elevated in women with postpartum preeclampsia, even when the brachial blood pressure is normal. Full article
(This article belongs to the Section Obstetrics and Gynecology)
10 pages, 1291 KiB  
Article
Negative Pressure Wound Therapy (NPWT) after Hybrid Reconstruction of Occipital Pressure Sore Using Local Flap and Skin Graft
by Seungchul Baek and Jun Ho Park
Medicina 2023, 59(7), 1342; https://doi.org/10.3390/medicina59071342 - 21 Jul 2023
Cited by 3 | Viewed by 2392
Abstract
Background and objectives: Pressure sores are a common medical burden among patients, particularly those who are bedridden or frail. Surgical management of occipital pressure sores poses unique challenges due to limited elasticity and the spherical shape of the scalp. This study aims to [...] Read more.
Background and objectives: Pressure sores are a common medical burden among patients, particularly those who are bedridden or frail. Surgical management of occipital pressure sores poses unique challenges due to limited elasticity and the spherical shape of the scalp. This study aims to evaluate the efficacy and safety of a novel reconstruction method utilizing a local transpositional flap and split-thickness skin graft with negative pressure wound therapy (NPWT) for occipital pressure sore treatment. Material and methods: A retrospective analysis was performed on patients with occipital pressure sores who underwent hybrid reconstructions using a local flap and split-thickness skin graft in conjunction with NPWT. Surgical outcomes, including flap survival rate, graft take percentage, and complications, were assessed. A comparative analysis was performed between the NPWT group and the conventional dressing group. Results: The NPWT group (n = 24) demonstrated a significantly higher mean graft take percentage at postoperative day 14 compared with the conventional dressing group (n = 22) (98.2% vs. 81.2%, p < 0.05). No significant difference in flap survival rate was observed between the two groups. Conclusions: As the aging population continues to grow, occipital pressure sores have gained significant attention as a crucial medical condition. The innovative surgical method incorporating NPWT offers an efficient and safe treatment option for patients with occipital pressure sores, potentially establishing itself as the future gold standard for managing this condition. Full article
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<p>(<b>A</b>) A 52-year-old female presented with two separate occipital scalp pressure sores. (<b>B</b>) Local flap elevation, leaving deep tissue containing periosteum. (<b>C</b>) Postoperative photographic finding immediate after operation. (<b>D</b>) Postoperative photographic findings in 3-month after operation.</p>
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<p>(<b>A</b>) A 75-year-old female presented with an occipital scalp pressure sore. (<b>B</b>) Bone exposure after debridement. (<b>C</b>) Local flap elevation, through subgaleal dissection. (<b>D</b>) Postoperative photographic finding with NPWT dressing. (<b>E</b>) Postoperative photographic findings 3 months after operation.</p>
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Case Report
Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma Presenting as a Colonic Polyp: Report of a Case with a Literature Review
by Jiahui Hu, Dongdong Huang, Chengfu Xu, Yi Chen, Han Ma and Zhe Shen
Medicina 2023, 59(7), 1341; https://doi.org/10.3390/medicina59071341 - 21 Jul 2023
Cited by 3 | Viewed by 2198
Abstract
Background: Follicular dendritic cell (FDC) sarcoma is an uncommon mesenchymal origin neoplasm derived from the abnormal proliferation and differentiation of FDCs. Epstein‒Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ iFDCS), which used to be known as the inflammatory pseudotumour (IPT)-like variant, occurs [...] Read more.
Background: Follicular dendritic cell (FDC) sarcoma is an uncommon mesenchymal origin neoplasm derived from the abnormal proliferation and differentiation of FDCs. Epstein‒Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ iFDCS), which used to be known as the inflammatory pseudotumour (IPT)-like variant, occurs exclusively in the liver and spleen and has rarely been reported in the gastrointestinal tract. Case study: Here, we report a case of a 52-year-old woman with a special family history undergoing a routine physical examination. The colonoscope revealed an approximately 18 mm transverse colonic polyp, and the endoscopic polypectomy was performed. Microscopically, the excised polypoid mass was composed predominantly of inflammatory cells scattered with atypical ovoid to spindle tumor cells. Interestingly, there was a remarkable infiltration of IgG4+ cells. Immunohistochemistry showed that the tumor cells were positive for CD21, CD23 and CD35. EBV-encoded mRNA (EBER) in situ hybridization also gave positive signals. These histopathology features supported the diagnosis of EBV+ iFDCS. The patient was free of disease over 1-year follow-up. Conclusion: Identification of the potential pathogenesis sites of EBV+ iFDCS in extra-hepatosplenic regions is necessary for correct and timely diagnosis, and we consider it very meaningful to share our experience of diagnosing this tumor type. Furthermore, we summarize the clinicopathological features of EBV+ iFDCS presenting as a colon polyp after a thorough review of the literature. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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<p>Endoscopy revealed an 18 mm polyp in the transverse colonic lumen. (<b>A</b>) The endoscopic morphology of the polyp. (<b>B</b>) The lifting sign of the polyp was positive.</p>
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<p>Microscopic examination of the lesion. (<b>A</b>–<b>C</b>) Hematoxylin and eosin (<b>H</b>,<b>E</b>): atypical ovoid to spindle tumor cells with vesicular chromatin, clear nuclei but indistinct cell borders scattered in the background of predominantly lymphoplasmacytic infiltration. (<b>D</b>–<b>F</b>) Immunohistochemistry showed that the tumor cells expressed CD21 (<b>D</b>), CD23 (<b>E</b>) and CD35 (<b>F</b>). (<b>G</b>) EBV-encoded mRNA (EBER) ISH showed positive signals on ovoid to spindle tumor cells (the brown color showed the EBV-positive tumor cells). (<b>H</b>,<b>I</b>) Markedly increased quantities of lgG+ (<b>H</b>) and IgG4+ (<b>I</b>), plasma cells (&gt;100/HPF) in the scope of the lesion, accompanied by an elevated IgG4: IgG ratio (40~50%).</p>
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<p>Positron emission tomography/computed tomography (PET/CT): (<b>A</b>) a titanium clip is seen in the operative area, and there is no obvious thickening or abnormal radiation uptake in the intestinal wall. (<b>B</b>) An approximately 8 × 7 mm slightly low-density nodule in the left thyroid with increased FDG metabolism; the maximum value of the SUV is approximately 14.2.</p>
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11 pages, 315 KiB  
Article
Headache in the Emergency Department: A Multicenter Observational Study from Singapore
by Win Sen Kuan, Ranjeev Kumar, Ying Wei Yau, Wei Ming Ng, Dennis Wen Jie Chia, Ee Yang Ng, Kanwar Sudhir Lather and Mui Teng Chua
Medicina 2023, 59(7), 1340; https://doi.org/10.3390/medicina59071340 - 21 Jul 2023
Cited by 2 | Viewed by 2595
Abstract
Background and Objectives: There is scarce data about the epidemiology, clinical features, investigations, diagnosis, treatment, and outcome in patients attending Singapore emergency departments (EDs) with nontraumatic headache. We sought to describe these characteristics of adult patients presenting to the ED with a [...] Read more.
Background and Objectives: There is scarce data about the epidemiology, clinical features, investigations, diagnosis, treatment, and outcome in patients attending Singapore emergency departments (EDs) with nontraumatic headache. We sought to describe these characteristics of adult patients presenting to the ED with a primary complaint of headache. Materials and Methods: We performed a cross-sectional study on adult patients with nontraumatic headache over 4 consecutive weeks from 18 March 2019 to 14 April 2019 across four EDs in Singapore. Exclusion criteria were history of head trauma within 48 h of presentation, missing records, interhospital transfers, representation with the same headache as a recent previous visit and headache as an associated symptom. Results: During the study period, 579 patients (representing 1.8% of the total ED census) comprising 55.3% males and with a median age of 36 years presented to the four Singapore EDs with a primary complaint of nontraumatic headache. Paracetamol (41.5%), non-steroidal anti-inflammatory drugs (34.4%) and tramadol (31.5%) were the three commonest analgesics used either singly or in combination. Prochlorperazine (22.9%) and metoclopramide (17.4%) were frequent anti-emetic adjuncts. One-third of patients had computed tomography of the brain performed, which found abnormalities among 20.9% of them. ED diagnoses of primary headache conditions were made in 73.6% of patients. Conclusions: Primary headaches constituted most ED headache diagnoses. ED imaging of selected patients yielded a relatively high pick-up rate for significant intracranial abnormalities. Opioid use for symptomatic relief of headaches in the ED was found to be high, underscoring the need for improvement in headache analgesia relief practices in the ED. Full article
(This article belongs to the Section Emergency Medicine)
11 pages, 2188 KiB  
Article
Stability of Direct Oral Anticoagulants Concentrations in Blood Samples for Accessibility Expansion of Chromogenic Assays
by Anna Gavrilova, Jānis Meisters, Gustavs Latkovskis and Inga Urtāne
Medicina 2023, 59(7), 1339; https://doi.org/10.3390/medicina59071339 - 21 Jul 2023
Viewed by 2235
Abstract
Background and Objectives: Direct oral anticoagulants (DOACs) are used for minimising the risk of thromboembolic events. In clinical practice, there is no need to measure DOAC concentration in the routine. Nevertheless, there are cases where such measurements are necessary, as the European [...] Read more.
Background and Objectives: Direct oral anticoagulants (DOACs) are used for minimising the risk of thromboembolic events. In clinical practice, there is no need to measure DOAC concentration in the routine. Nevertheless, there are cases where such measurements are necessary, as the European Society of Cardiology’s guideline recommends. However, determining DOAC levels is not available for everyone due to chromogenic assay availability limitations from sample storage problems, as tests are performed only in a few healthcare settings. This study aimed to assess whether more applicable storage conditions could be used for transportation to provide chromogenic assays for outpatient healthcare and other hospitals’ practices. Materials and Methods: Chromogenic assays measuring anti-FXa (for rivaroxaban and edoxaban) and anti-FIIa (for dabigatran) were used. Concentrations were determined immediately after blood collection as baseline value: (1) after the storage of citrated whole blood in refrigerator (+2–8 °C); (2) of citrated plasma in refrigerator (+2–8 °C); and (3) of citrated frozen plasma (−20 °C) on the third and seventh days of storage. Acceptable change limits were considered stable if the deviation did not exceed ±20% of the baseline value. Results: The median (Cl 95%) baseline value of rivaroxaban was 168 (147–236) ng/mL; of dabigatran 139 (99–178) ng/mL; and of edoxaban—174 (135–259) ng/mL. The median deviation from a baseline value stored as citrate whole blood samples (+2–8 °C) was 5.4% and 3.4%; as citrated plasma (+2–8 °C) was 0.4% and −0.6%; and as citrated frozen plasma (−20 °C) was −0.2% and 0.2% on the third and seventh days of storage, respectively. Conclusions: Our data suggest that whole blood samples stored in a refrigerator, as well as citrated plasma samples stored in both the refrigerator and freezer, preserve DOAC concentration stable at +2–8 °C or −20 °C for up to 7 days, and are suitable for transportation, except for low-concentration samples. Full article
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<p>Collected samples’ processing, storage duration, and conditions for the determination of in vitro stability.</p>
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<p>DOAC concentrations deviations from baseline value expressed as a percentage and confidence level 95% in the whole blood samples stored at +2–8 °C. Range of acceptance is indicated by dotted lines. The median concentration, expressed as a percentage of the baseline concentration, and the 95% confidence interval are shown.</p>
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<p>DOAC concentrations deviations from baseline value expressed as a percentage and confidence level 95% in the citrated plasma stored at +2–8 °C. Range of acceptance is indicated by dotted lines. The median concentration, expressed as a percentage of the baseline concentration, and the 95% confidence interval are shown.</p>
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<p>DOAC concentrations deviations from baseline value expressed as a percentage and confidence level 95% in the citrated plasma stored at −20 °C. Range of acceptance is indicated by dotted lines. The median concentration, expressed as a percentage of the baseline concentration, and the 95% confidence interval are shown.</p>
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20 pages, 1536 KiB  
Review
The Molecular and Genetic Interactions between Obesity and Breast Cancer Risk
by Ghada M. A. Ajabnoor
Medicina 2023, 59(7), 1338; https://doi.org/10.3390/medicina59071338 - 21 Jul 2023
Cited by 8 | Viewed by 4670
Abstract
Breast cancer (BC) is considered the leading cause of death among females worldwide. Various risk factors contribute to BC development, such as age, genetics, reproductive factors, obesity, alcohol intake, and lifestyle. Obesity is considered to be a pandemic health problem globally, affecting millions [...] Read more.
Breast cancer (BC) is considered the leading cause of death among females worldwide. Various risk factors contribute to BC development, such as age, genetics, reproductive factors, obesity, alcohol intake, and lifestyle. Obesity is considered to be a pandemic health problem globally, affecting millions of people worldwide. Obesity has been associated with a high risk of BC development. Determining the impact of obesity on BC development risk in women by demonstrating the molecular and genetic association in pre- and post-menopause females and risk to BC initiation is crucial in order to improve the diagnosis and prognosis of BC disease. In epidemiological studies, BC in premenopausal women was shown to be protective in a certain pattern. These altered effects between the two phases could be due to various physiological changes, such as estrogen/progesterone fluctuating levels. In addition, the relationship between BC risk and obesity is indicated by different molecular alterations as metabolic pathways and genetic mutation or epigenetic DNA changes supporting a strong connection between obesity and BC risk. However, these molecular and genetic alteration remain incompletely understood. The aim of this review is to highlight and elucidate the different molecular mechanisms and genetic changes occurring in obese women and their association with BC risk and development. Full article
(This article belongs to the Collection Frontiers in Breast Cancer Diagnosis and Treatment)
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<p>The main molecular changes induced by obesity and related to BC risk. Created with BioRender.com, Toronto, Canda.</p>
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<p>Molecular and genetic modifications in obesity risk to BC development. Molecular pathway changes in obesity, including increased insulin levels and development of insulin resistance, inducing the synthesis of insulin growth factors I and II (IGF-I, IGF-II), inflammation reactions, and their imbalanced levels of adipokines and cytokines and expression of leptin receptor LEPR and adiponectin receptor ADIPOR1-2. The high aromatization reactions in the fat tissues lead to the high production of estrogen hormone. High levels of cholesterol synthesis are regulated by transcription faction sterol regulated element binding protein-2 (SERP-2, SERP-1). Downstream activation of molecular changes such as Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase/v-Akt murine thymoma viral oncogene homolog/mammalian target of rapamycin (PI3K/Akt/mTOR occur. The molecular changes induce epigenetic alterations and single nucleotide polymorphism (SNP) risk. All these biological modifications induce BC development. The illustration was created with BioRender.com, Toronto, Canda.</p>
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23 pages, 9418 KiB  
Review
Brain Injury: Response to Injury Wound-Healing Mechanisms and Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus
by Melvin R. Hayden
Medicina 2023, 59(7), 1337; https://doi.org/10.3390/medicina59071337 - 20 Jul 2023
Cited by 10 | Viewed by 3103
Abstract
Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury, termed the response to injury wound-healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral [...] Read more.
Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury, termed the response to injury wound-healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes, innate microglia, and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic, as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus, this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell, along with peripheral inflammatory cells and its astroglia, instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVSs), which is the focus of this brief review. EPVSs are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid, and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVSs that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition. Full article
(This article belongs to the Section Neurology)
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<p>Multiple injurious stimuli to brain endothelial cells (BECs) in obesity, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM). This representative illustration does not depict the thin luminal endothelial glycocalyx layer covering the BECs. Ang II = angiotensin 2; AGE/RAGE = advanced glycation end-products and its receptor RAGE; BEC = brain endothelial cell; BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span> = brain endothelial cell activation and dysfunction; LDL = low-density lipoprotein cholesterol; LPa = lipoprotein little a; LPS = lipopolysaccharide; <b><span class="html-italic">p</span></b>CC = peripheral cytokine/chemokine; ROS = reactive oxygen species and the reactive species interactome; T = transcytosis; <span class="html-fig-inline" id="medicina-59-01337-i001"><img alt="Medicina 59 01337 i001" src="/medicina/medicina-59-01337/article_deploy/html/images/medicina-59-01337-i001.png"/></span> = radiation symbol.</p>
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<p>Comparison of peripheral response to injury wound healing (RTIWH) to the unique brain injury RTIWH mechanisms. This image depicts the RTIWH mechanisms as a result of the dual signaling by peripheral cytokines/chemokines (<b><span class="html-italic">p</span></b>CC), soluble lipopolysaccharide (sLPS), and LPS-enriched extracellular exosomes (lpsEVexos). This dual signaling of the brain endothelial cell(s) (BECs) results in BEC activation and dysfunction (BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span>), which in turn results in central nervous system (CNS) neuroinflammation with increased <span class="html-italic">cns</span>CC, reactive polarized microglia, and reactive astroglia—reactive astrogliosis, which results in astrogliosis scarring instead of fibrosis scarring, since the brain does not have fibrocytes/fibroblasts in its parenchyma. Importantly, this RTIWH mechanism contributes to maladaptive remodeling and also contributes to the development of enlarged perivascular spaces (EPVSs). Figure adapted with permission by CC 4.0 [<a href="#B4-medicina-59-01337" class="html-bibr">4</a>].</p>
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<p>Illustration of the origins of the perivascular spaces (PVSs) and representative transmission electron micrograph (TEM) cross-sections of the precapillary arteriole, true capillary, and postcapillary venule. <b>Panel</b> (<b>A</b>) illustrates the whole brain with its surface pia arteries that dive deeply into the grey matter and deeply into the white matter, terminating in capillaries within the interstitial spaces (ISS). <b>Panel</b> (<b>B</b>) reveals the interaction of the PVSs to precapillary arterioles, which allow the vascular lumen influx of oxygen, nutrients, and solutes (red arrow), in addition to the influx of CSF via the PVSs (red arrow true capillaries with delivery of oxygen, nutrients, solutes, and the postcapillary venules that allow the removal of metabolic waste dioxide plus others), and PVSs that are responsible for the removal of the admixture of ISF and CSF, and metabolic waste (MW) that includes misfolded proteins (amyloid beta and tau neurofibrillary fibrils) (blue arrow) in the subarachnoid space (SAS). <b>Panel</b> (<b>C</b>) depicts how the CSF and its admixed metabolic waste from the PVS glymphatic system is transported to the dural venous sinus (DVS) and the systemic circulation. <b>Panels</b> (<b>D</b>–<b>F</b>) demonstrate representative and corresponding cross-sectional TEMs of corresponding labeled capillary images in <b>Panel</b> (<b>B</b>). <b>Panel</b> (<b>D</b>) demonstrates a precapillary arteriole with a PVS (pseudo-colored green). <b>Panel</b> (<b>E</b>) represents a true capillary without a PVS. Importantly, note that the pia membrane of the glia limitans abruptly ends at the true capillary and that the astrocyte endfeet end directly at the brain endothelial cell basement membrane (blue arrows) (numbers 1–7 indicate astrocyte numbers). <b>Panel</b> (<b>F</b>) depicts a postcapillary venule that appears to have a dilated PVS and is thus considered to be an enlarged PVS (EPVS). Note the presence of a resident perivascular macrophage cell within the EPVS. It is important to note that the PVS provides the conduit structure for the glymphatic draining system to deliver metabolic waste products to the CSF and the systemic circulation for disposal. This adapted and modified image is provided with permission by CC 4.0 [<a href="#B7-medicina-59-01337" class="html-bibr">7</a>]. <span class="html-italic">AC = astrocyte; ACef = astrocyte endfeet; ACfp = astrocyte foot process end-feet; AQP4 = aquaporin four; Cl = capillary lumen; CSF = cerebrospinal fluid; EC = brain endothelial cell; ISF = interstitial fluid; N = nucleus; Pc = pericyte; PVS = perivascular space; Mt = mitochondria; RBC = red blood cell; rMΦ = resident reactive macrophage</span>.</p>
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<p>Comparison of normal true capillary and precapillary arterioles to postcapillary venules with enlarged perivascular spaces (EPVSs). <b>Panel</b> (<b>A</b>) demonstrates a true capillary with the astrocyte endfeet (ACef) abutting the shared basement membrane of the brain endothelial cell and pericyte (asterisk and closed arrows) without a pia mater membrane. <b>Panel</b> (<b>B</b>) demonstrates a precapillary arteriole with only a thinned perivascular space (PVS) (pseudo-colored green). Note that the abluminal perivascular space is still ensheathed by the pia matter and basal lamina of the adjacent ACef. <b>Panels</b> (<b>C</b>,<b>D</b>) each depict two different postcapillary venules with enlarged perivascular spaces (EPVS) between 2 and 6.5 μm. Modified image provided with permission by CC 4.0 [<a href="#B7-medicina-59-01337" class="html-bibr">7</a>]. Magnification ×1000; ×2000; scale bars = 2 and 1 μm in <b>Panels</b> (<b>C</b>,<b>D</b>) respectively. <span class="html-italic">AC astrocyte; ACef = astrocyte endfeet; AQP 4 = aquaporin 4; Cl = capillary lumen; EC = brain endothelial cell; Pc = pericyte; Pc N = pericyte nucleus; Pcfp = pericyte foot process—endfeet; RBC = red blood cell</span>.</p>
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<p>Metabolic syndrome (MetS), enlarged perivascular spaces (EPVSs), and cerebral small vessel disease (cSVD). The visceral adipose tissue (VAT), obesity, and hyperlipidemia (atherogenic dyslipidemia) located in the lower left-hand side of the letter X appears to drive the MetS and the other three arms of the letter X, which includes insulin resistance (IR) and the associated hyperinsulinemia, hypertension, vascular stiffening, and hyperglycemia, with or without manifest type 2 diabetes mellitus (T2DM). The global increase in obesity and the accumulation of visceral obesity is thought to be a major driver of the MetS that is related to the excessive metainflammation arising from VAT depots. Follow the prominent closed red arrows emanating from VAT to cerebrocardiovascular disease (CCVD), SVD, TIA, stroke, cerebral microbleeds, and hemorrhages. BEC activation and dysfunction (BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span>), with its proinflammatory and prooxidative properties, result in endothelial nitric oxide synthesis (eNOS) uncoupling with increased superoxide (<span class="html-italic">O</span><sub>2</sub><span class="html-italic"><sup>•−</sup></span>) and decreased nitric oxide (NO) bioavailability. Importantly, note that obesity, MetS, T2DM, and decreased bioavailable NO interact to result in capillary rarefaction that may allow EPVS development, which are biomarkers for cerebral SVD. Figure adapted with permission by CC 4.0 [<a href="#B7-medicina-59-01337" class="html-bibr">7</a>,<a href="#B25-medicina-59-01337" class="html-bibr">25</a>]. <span class="html-italic">AGE = advanced glycation end-products; RAGE = receptor for AGE; AGE/RAGE = advanced glycation end-products and its receptor interaction; βcell = pancreatic islet insulin-producing beta cell; FFA = free fatty acids—unsaturated long chain fatty acids; IGT = impaired glucose tolerance; LOAD = late-onset Alzheimer’s disease; ROS = reactive oxygen species; RSI = reactive species interactome; Sk = skeletal: TG Index = triglyceride/glucose index; TIA = transient ischemia attack</span>.</p>
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<p>Cross- and longitudinal sections representative of pre- and postcapillary arterioles and venules with an encompassing surrounding perivascular space (PVS). <b>Panel</b> (<b>A</b>) depicts a cross-section of a capillary surrounded by a PVS (solid double red arrows) and its increase in total volume to become an enlarged perivascular space (EPVS) (dashed double red arrows), which represents capillary rarefaction. <b>Panel</b> (<b>B</b>) demonstrates a control longitudinal precapillary arteriole, postcapillary venule, and neurovascular unit (NVU) that runs through an encompassing PVS (light blue). <b>Panel</b> (<b>C</b>) depicts capillary rarefaction (CR) in a longitudinal view, and note how the volume of the PVS increases its total percentage volume once the capillary has undergone rarefaction as in obesity, metabolic syndrome, and type 2 diabetes mellitus. <b>Panel</b> (<b>D</b>) depicts the progression of a normal precapillary arteriole and postcapillary venule PVS to an EPVS once the capillary has undergone rarefaction, allowing for an increase in its total percentage volume of the PVS (1.–3.). <b>Panels</b> (<b>B</b>,<b>C</b>) provided with permission by CC 4.0 [<a href="#B7-medicina-59-01337" class="html-bibr">7</a>]. <span class="html-italic">ACef = astrocyte endfeet; AQP4 = aquaporin 4; BEC = brain endothelial cells; BECact/dys = brain endothelial cell activation and dysfunction; CL =capillary lumen; EC = endothelial cell; lpsEVexos = lipopolysaccharide extracellular vesicle exosomes; NVU = neurovascular unit; Pcef = pericyte endfeet</span>.</p>
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<p>The triangulation of Metabolic function, gut dysbiosis, and the metabolic syndrome (MetS) allows the innate immune system, peripheral, proinflammatory cytokines and chemokines (<b><span class="html-italic">p</span></b>CC) to signal the neurovascular unit (NVU) brain endothelial cell(s) (BECs) resulting in BEC activation and dysfunction (BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span>) with subsequent neuroinflammation. This schematic demonstrates that gut microbiota dysbiosis, metabolic dysfunction, and an activated proinflammatory innate immune system are associated with obesity and metabolic syndrome (lower-left red box). Importantly, this triangulation also associates with the metainflammation that is produced in the obese visceral adipose tissue depots (upper-right red box). These two distinct sites of metainflammation (red boxes) and dual signaling of BECs will each signal the central nervous system brain endothelial cells to result in neuroinflammation to result in BEC<span class="html-italic">act/dys</span> and contribute to enlarged perivascular spaces (EPVSs). Importantly, this dual signaling by the gut and visceral adipose tissue (VAT) of BECs may be synergistic in obesity and the MetS. Image provided with permission by CC 4.0 [<a href="#B34-medicina-59-01337" class="html-bibr">34</a>]. <span class="html-italic">Db/db = obese, insulin resistance diabetic genetic mouse model; DIO = diet-induced obesity; BTBRob/ob = black and tan brachyuric ob/ob mouse model of obesity and diabetes; IR = insulin resistance; LR = leptin resistance; sLPS = soluble lipopolysaccharide; lpsEVexos = lipopolysaccharide extracellular vesicle exosomes; MΦ = macrophage; MetS = metabolic syndrome; <b>p</b>CC = peripheral cytokines/chemokines; T2DM = type 2 diabetes mellitus</span>.</p>
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<p>Dual Signaling of BECs by peripheral cytokines/chemokines (<b><span class="html-italic">p</span></b>CC) and soluble lipopolysaccharide (sLPS) and LPS-enriched small extracellular vesicle exosome (lpsEVexos), to result in brain endothelial activation and dysfunction (BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span>). Note the insert lower-left, which depicts a small EVexo liberating multiple LPS-enriched vesicles and the metabolic signaling of BECs to result in central nervous system cytokines chemokines (<span class="html-italic">cns</span>CC) and attracted microglia cells (atMGCs) via CCL5 (RANTES). BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span> results in neuroinflammation, blood–brain barrier (BBB) disruption, and enlarged perivascular spaces (EPVSs) in obesity, insulin resistance (IR), and the metabolic syndrome (MetS). This modified image is provided with permission by CC4.0 [<a href="#B34-medicina-59-01337" class="html-bibr">34</a>]. <span class="html-italic">atMGC = attracted microglia cell; CCL5 = chemokine (C-C motif) ligand 5 (chemoattractant for microglia cells); CD14 = cluster of differentiation 14; CCR5 = C-C chemokine receptor type 5, also known as CD195; CL = capillary lumen; EC = endothelial cell, brain endothelial cells; ecGCx = endothelial glycocalyx; EV = extracellular vesicles; EVMp =EVmicroparticles or microvesicles; EVexo = EVexosomes; IL1-β = interleukin-1 beta; IL-6 = interleukin-6; LPS = lipopolysaccharide; LBP = lipopolysaccharide-binding protein; MAPK = mitogen-activated protein kinase; Mp = microparticles; N = nucleus; PI3K/AKT = phosphatidylinositol 3-kinase/protein kinase B; PM = plasma membrane; RANTES = regulated on activation, normal T cell expressed and secreted; TNFα = tumor necrosis alpha</span>.</p>
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<p>Representative transmission electron microscopic (TEM) images of endothelial cell activation (EC<span class="html-italic">act</span>). <b>Panel</b> (<b>A</b>) demonstrates a control BEC. <b>Panel</b> (<b>B</b>) depicts the thickened electron-lucent areas (red arrows) of EC<span class="html-italic">act</span> as compared to control models in <b>Panel</b> (<b>A</b>). <b>Panel</b> (<b>C</b>) depicts basement membrane (BM) thickening (red arrow) with increased vacuoles and vesicles (V). <b>Panels</b> (<b>D</b>,<b>E</b>) depict monocyte (<b>D</b>) and lymphocyte (<b>E</b>), platelet (<b>F</b>), and red blood cell (RBC) adhesion (<b>G</b>) to activated ECs (adhesions sites denoted by closed white arrows <b>Panels</b> (<b>E</b>,<b>G</b>); yellow arrows in <b>Panel</b> (<b>F</b>). Magnifications and scale bars vary. <b>Panels</b> (<b>C</b>–<b>G</b>) images are reproduced and modified with permission by CC 4.0 [<a href="#B25-medicina-59-01337" class="html-bibr">25</a>]. <span class="html-italic">ACfp = astrocyte foot processes</span>; <span class="html-italic">Cl, capillary lumen</span>; <span class="html-italic">EC = endothelial cells, brain endothelial cells</span>; <span class="html-italic">MP = microparticle of the platelet</span>.</p>
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<p>Response to injury wound-healing (RTIWH) remodeling, neuroinflammation, and enlarged perivascular spaces (EPVSs). <b>Panel</b> (<b>A</b>) illustrates the progression of the perivascular space (PVS) as it undergoes transformation—RTIWH remodeling to EPVSs in a linear fashion from left to right. <b>Panel</b> (<b>B</b>) demonstrates a transmission electron microscopic (TEM) image of a true capillary in a control 20-week-old female model. <b>Panel</b> (<b>C</b>) depicts a TEM image of an EPVS with a resident, reactive, migratory perivascular macrophage (rPVMΦ) in a 20-week-old female lipopolysaccharide-treated model. <b>Panels</b> (<b>D</b>–<b>F</b>) depicts leukocytes that undergo diapedesis across the neurovascular unit (NVU) brain endothelial cell(s) (BECs) disrupted blood–brain barrier (BBB), which enters the perivascular space(s) (PVS(s)). Along with the rPVMΦ, these leukocytes are capable of creating excessive phagocytic cellular debris. This increase in leukocytes and rPVMΦs along with their excessive cellular debris result in obstruction of the PVS and results in the dilation of the PVS proximal to the obstruction, creating the EPVS observed on magnetic resonance imaging (MRI) in the basal ganglia and centrum semiovale structures that appear early on in the development of cerebral small vessel disease and neurodegenerative diseases. While <b>Panels</b> (<b>A</b>–<b>F</b>) depict step one of a two-step process, step two incorporates the reactive oxygen species and the matrix metalloproteinases (MMP2, MMP9) that are capable of digesting the abluminal glia limitans of the EPVS, which allow for the transmigration of leukocytes to enter the interstitial spaces of the parenchymal neurons to complete the neuroinflammation remodeling mechanism in obesity, metabolic syndrome, and type 2 diabetes mellitus. Modified <b>Panels</b> (<b>A</b>,<b>B</b>) provided with permission by CC 4.0 [<a href="#B7-medicina-59-01337" class="html-bibr">7</a>,<a href="#B34-medicina-59-01337" class="html-bibr">34</a>] and <b>Panel</b> (<b>D</b>) by CC 4.0 [<a href="#B7-medicina-59-01337" class="html-bibr">7</a>].</p>
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<p>Enlarged Perivascular Spaces (EPVSs), reactive perivascular macrophages (rPVMΦs), and crosstalk with pericytes and foot processes (Pcfps) and PVS astrocyte endfeet (ACef). <b>Panel</b> (<b>A</b>) demonstrates a normal true capillary in a 20-week-old female C57B6/J control model and note how the ACef are arranged tightly about the shared basement membrane of the brain endothelial cell (BEC) and pericyte (black and white arrows). <b>Panel</b> (<b>B</b>) depicts an EPVS with an aberrant polarized rPVMΦ in a 20-week-old lipopolysaccharide (LPS)-treated male model and note how the ACef are markedly separated from the capillary (red double arrows). Also, note the white dashed-box bounds the area in <b>Panel</b> (<b>C</b>). <b>Panel</b> (<b>C</b>) depicts the communication crosstalk via rPVMΦs contacting the Pcfps and the EPVS abluminal lining ACfps (blue dashed-circles and white dashed-lines). Modified images provided by CC 4.0 [<a href="#B34-medicina-59-01337" class="html-bibr">34</a>]. <span class="html-italic">AQP4 = aquaporin 4; Lys = lysosomes; Mt = mitochondria; N = nucleus; NVU = neurovascular unit; V = vacuoles; ves = vesicles</span>. black/white arrows in subfigure (<b>A</b>) note how the ACef are arranged tightly about the shared basement membrane of the brain endothelial cell (BEC) and pericyte (black and white arrows). In Subfigure (<b>B</b>) white dashed boxed bounds the area in <b>Panel</b> (<b>C</b>) and the EPVS abluminal lining ACfps (blue dashed-circles and white dashed-lines.</p>
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<p>Response to injury wound healing (RTIWH) at regions of injury in the brain and formation of the glial scar. This illustration depicts the RTIWH at regions of brain injury that become surrounded with palysading astroglia that progress to hypertrophic, proliferative, and reactive astrocytes following brain injury, from left to right. Further, this gliosis scar serves to protect the surrounding uninjured brain structures from ongoing injury. This modified image is provided with permission by CC 4.0 [<a href="#B61-medicina-59-01337" class="html-bibr">61</a>].</p>
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<p>Representative illustrations of water channel aquaporin 4 (AQP4), and representative immunohistochemistry (IHC) staining of thalamus AQP4 in models. <b>Panel</b> (<b>A</b>) demonstrates an illustration of the AQP4 water channel localized to the astrocyte endfeet (ACef) at the plasma membrane that extends to the enlarged perivascular spaces (EPVS). <b>Panel</b> (<b>B</b>) illustrates an elongated capillary in the region of the thalamus in a control model and note the mild staining of the AQP4 via IHC staining with the AQP4 antibody (surrounded by dashed-yellow line). <b>Panel</b> (<b>C</b>) depicts marked heavily stained AQP4 water channels with IHC AQP4 antibody staining in a model with acetaminophen-induced liver failure and hepatic encephalopathy (surrounded by yellow-dashed line). AQP4 is known to be upregulated in aging and in ammonia-induced brain injury; however, it becomes maldistributed and there is a loss of plasma membrane (pm) polarity associated with its maldistribution and dysfunction. <b>Panel</b> (<b>D</b>) is a representative illustration of the AQP4 water channel that is polarized to the ACef pm (pseudo-colored green outlined by yellow line) that undergoes a loss of ACef polarization to become maldistributed in the cytosol of ACef in <b>Panel</b> (<b>E</b>). <b>Panel</b> (<b>E</b>) depicts the maldistribution of AQP4 IHC staining (pseudo-colored red outlined by yellow line) and note the increased condensation as compared to the more flocculent IHC staining <b>Panel</b> (<b>D</b>). Representative illustrations in <b>Panels</b> (<b>A</b>,<b>D</b>,<b>E</b>) were created in Microsoft 3-D paint program. Modified in <b>Panel</b> (<b>A</b>) image reproduced with permission by CC 4.0 [<a href="#B34-medicina-59-01337" class="html-bibr">34</a>]. Note the insertion at end of <b>Panels</b> (<b>B</b>,<b>C</b>) (surrounded by dashed-yellow line). Also note in <b>Panel</b> (<b>D</b>) (pseudo-colored green outlined by yellow line) <b>Panel</b> (<b>E</b>) (pseudo-colored red outlined by yellow line) <span class="html-italic">BM = basement membrane; CL = capillary lumen; DAPI = 4′,6-diamidino-2-phenylindole fluorescent stain; EC/Pc = endothelial cell/pericyte; H<sub>2</sub>O = water; pm = plasma membrane</span>.</p>
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<p>Magnetic resonance imaging (MRI) comparisons of basal ganglia (BG) enlarged perivascular spaces (EPVSs) to centrum semiovale (CSO) EPVSs. <b>Panel</b> (<b>A</b>) depicts the paired EPVSs within the BG that are traced in open on the left and masked yellow on the right BG. Note the white spaces within the paired dashed lines just above the paired BG structures. MRI image from a 75 y/o male status post-stroke, recovered with small vessel disease. <b>Panel</b> (<b>B</b>) depicts the paired elongated oval structures outlined by yellow dashed lines to enclose multiple white enlarged perivascular spaces. Note the open white arrows outlined in red pointing to prominent EPVSs. MRI image from a 79 y/o female with history of transient ischemic attacks. Importantly, note that BG EPVSs are strongly associated with cerebral small vessel disease (SVD) in <b>Panel</b> (<b>A</b>) and that CSO EPVSs are strongly associated with late-onset Alzheimer’s disease and cerebral amyloid angiopathy (CAA) in <b>Panel</b> (<b>B</b>).</p>
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<p>Brain injury and the response to injury wound healing (RTIWH) facilitates brain endothelial cell (BEC) activation, neuroinflammation, and enlarged perivascular spaces (EPVSs). <b>Panel</b> (<b>A</b>) illustrates the bidirectional relationship between perivascular spaces (PVSs) and neuroinflammation in relation to EPVSs. <b>Panel</b> (<b>B</b>) demonstrates the contribution and mechanisms to the development of EPVSs. The brain is exposed to many injurious stimuli over time and in multiple diseases and syndromes such as obesity, metabolic syndrome, and type 2 diabetes mellitus. These injurious stimuli result in BEC activation and dysfunction (BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span>), which acts as a pivotal point in the RTIWH and these mechanisms also contribute to multiple wound-healing phases (hemostasis, inflammation–neuroinflammation, proliferation, remodeling, and resolution, only if the injurious stimuli are damped down or removed). Since these injurious stimuli are chronic, the brain remains under the constant influence of the wound-healing phases and chronic remodeling of essential brain structures and the development of EPVSs. Herein we propose a sequence of events in the development of EPVSs as follows: Brain injury, BEC<span class="html-italic">act</span>/<span class="html-italic">dys</span>, neuroinflammation with RTIWH, obstruction of PVSs due to accumulation of inflammatory cell leukocytes within and around the neurovascular unit and postcapillary venular PVS and inflammatory-derived cellular debris, vascular stiffening with deceased pulsatility, and neuronal degeneration with neuronal loss and brain atrophy.</p>
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<p>Transmission electron microscopic image of interstitial spaces (ISS) and illustration of interstitial fluid flow to the glymphatic system. Interstitial spaces (ISS) are nanometer structures; however, they combine to create a total of 20 percent of total brain volume and empty their interstitial fluid contents and metabolic wastes into the perivascular conduit spaces of the glymphatic space, or system (GS) to be delivered to the cerebrospinal fluid (CSF). <b>Panel</b> (<b>A</b>) demonstrates the nanosized diameter of ISS containing the ISS in a control 20-week-old mouse model from the frontal cortical grey matter. <b>Panel</b> (<b>B</b>) depicts how the ISS containing the ISF, solutes (black dots), and metabolic waste empties into the post-capillary venule perivascular space (PVS) or the conduit of the GS, which is responsible for toxic waste clearance. <span class="html-italic">AC = astrocyte; ACef = astrocyte endfeet; EC = endothelial cell; CL = capillary lumen</span>.</p>
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21 pages, 757 KiB  
Review
Coinfections and Superinfections Associated with COVID-19 in Colombia: A Narrative Review
by Diana Dueñas, Jorge Daza and Yamil Liscano
Medicina 2023, 59(7), 1336; https://doi.org/10.3390/medicina59071336 - 20 Jul 2023
Cited by 6 | Viewed by 3622
Abstract
The COVID-19 pandemic has had significant impacts on healthcare systems around the world, including in Latin America. In Colombia, there have been over 23,000 confirmed cases and 100 deaths since 2022, with the highest number of cases occurring in females and the highest [...] Read more.
The COVID-19 pandemic has had significant impacts on healthcare systems around the world, including in Latin America. In Colombia, there have been over 23,000 confirmed cases and 100 deaths since 2022, with the highest number of cases occurring in females and the highest number of deaths in males. The elderly and those with comorbidities, such as arterial hypertension, diabetes mellitus, and respiratory diseases, have been particularly affected. Coinfections with other microorganisms, including dengue virus, Klebsiella pneumoniae, and Mycobacterium tuberculosis, have also been a significant factor in increasing morbidity and mortality rates in COVID-19 patients. It is important for surveillance systems to be improved and protocols to be established for the early detection and management of coinfections in COVID-19. In addition to traditional treatments, alternatives such as zinc supplementation and nanomedicine may have potential in the fight against COVID-19. It is also crucial to consider the social, labor, educational, psychological, and emotional costs of the pandemic and to address issues such as poverty and limited access to potable water in order to better prepare for future pandemics. Full article
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<p>(<b>A</b>) Primary mode of transmission of SARS-CoV-2, which is through respiratory droplets. (<b>B</b>) SARS-CoV-2 enters via the angiotensin-converting enzyme receptor 2 (ACE-2). It also shows toll-like receptors whose function is to recognize viral RNA in endosomes. (<b>C</b>) Activation of the antiviral innate immune response associated with IFN production and activation of proinflammatory cytokines mediated by T lymphocytes causing a cytokine storm. (<b>D</b>) Humoral response to SARS-CoV-2 with the use of neutralizing antibodies (nAb). The figure was created with <a href="https://app.biorender.com" target="_blank">https://app.biorender.com</a> (accessed on 1 June 2023).</p>
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9 pages, 542 KiB  
Article
Immersion Ultrasound Therapy in Combination with Manual Therapy in the Treatment of Ischemic Digital Ulcers in Systemic Sclerosis
by Dalila Scaturro, Antimo Moretti, Fabio Vitagliani, Giuliana Guggino, Sofia Tomasello, Davide Lo Nardo, Lorenza Lauricella, Giovanni Iolascon and Giulia Letizia Mauro
Medicina 2023, 59(7), 1335; https://doi.org/10.3390/medicina59071335 - 20 Jul 2023
Cited by 2 | Viewed by 2140
Abstract
Background and Objectives: Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined [...] Read more.
Background and Objectives: Digital ulcers (DUs) are the most common complication in patients with Systemic Sclerosis (SSc). They cause pain with hand dysfunction and negatively impact activities of daily and working life. Our study aims to evaluate the efficacy of a combined treatment of manual therapy and ultrasound therapy in SSc patients with ischemic DU (IDU) compared to manual therapy alone. Materials and Methods: We conducted a before-and-after study (non-randomized study). We enrolled a consecutive series of IDU patients undergoing rehabilitation treatment and divided them into two groups: a treatment group consisting of patients undergoing a combination of manual therapy and US water immersion and a standard care group consisting of patients subjected to manual therapy alone. At the time of the first visit (T0) and at the end of the 4-week rehabilitation period (T1), we evaluated functional capacity, pain intensity, ulcer evolution, and quality of life. Results: In the treatment group, we observed a statistically significant improvement in the functional capacity of the hand (DHI: 28.15 ± 11.0 vs. 19.05 ± 8.83; p < 0.05), pain (NRS: 5.55 ± 1.2 vs. 2.9 ± 1.09; p < 0.05), and PSST score (24.4 ± 4.0 vs. 16.2 ± 2.36; p < 0.05). In the standard care group, we observed a statistically significant improvement only for the functional capacity of the hand (DHI: 28.85 ± 9.72 vs. 22.7 ± 7.68; p < 0.05). Finally, from the comparison between the treatment group and the standard care group, we observed statistically significant improvements in pain (2.9 ± 1.09 vs. 4.5 ± 1.07; p < 0.05) and in the PSST scale (16.2 ± 2.36 vs. 20.4 ± 4.02; p < 0.05). Furthermore, at the end of treatment in the treatment group, 15 ulcers (62.5%) were completely healed, while in the standard care group, only 3 ulcers were completely healed (14.3%). Conclusions: Combined treatment with manual therapy and ultrasound therapy appears to be useful in the management of IDU in patients with scleroderma. Full article
(This article belongs to the Special Issue Age-Related Musculoskeletal Disorders)
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<p>Patient recruitment.</p>
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35 pages, 1913 KiB  
Review
Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases
by Dario Rusciano and Paola Bagnoli
Medicina 2023, 59(7), 1334; https://doi.org/10.3390/medicina59071334 - 20 Jul 2023
Cited by 5 | Viewed by 3189
Abstract
In this review, we aim to provide an overview of the recent findings about the treatment of neovascular retinal diseases. The use of conventional drugs and nutraceuticals endowed with antioxidant and anti-inflammatory properties that may support conventional therapies will be considered, with the [...] Read more.
In this review, we aim to provide an overview of the recent findings about the treatment of neovascular retinal diseases. The use of conventional drugs and nutraceuticals endowed with antioxidant and anti-inflammatory properties that may support conventional therapies will be considered, with the final aim of achieving risk reduction (prevention) and outcome improvement (cooperation between treatments) of such sight-threatening proliferative retinopathies. For this purpose, we consider a medicinal product one that contains well-defined compound(s) with proven pharmacological and therapeutic effects, usually given for the treatment of full-blown diseases. Rarely are prescription drugs given for preventive purposes. A dietary supplement refers to a compound (often an extract or a mixture) used in the prevention or co-adjuvant treatment of a given pathology. However, it must be kept in mind that drug–supplement interactions may exist and might affect the efficacy of certain drug treatments. Moreover, the distinction between medicinal products and dietary supplements is not always straightforward. For instance, melatonin is formulated as a medicinal product for the treatment of sleep and behavioral problems; at low doses (usually below 1 mg), it is considered a nutraceutical, while at higher doses, it is sold as a psychotropic drug. Despite their lower status with respect to drugs, increasing evidence supports the notion of the beneficial effects of dietary supplements on proliferative retinopathies, a major cause of vision loss in the elderly. Therefore, we believe that, on a patient-by-patient basis, the administration of nutraceuticals, either alone or in association, could benefit many patients, delaying the progression of their disease and likely improving the efficacy of pharmaceutical drugs. Full article
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<p>A schematic drawing illustrating the common elements (center, red) of the three main retinal neovascular diseases dealt with in this review. Oxidative stress, inflammation, and angiogenesis also represent the main targets of pharmacological therapies or nutraceutical treatments. AMD (Age-Related Macular Degeneration); DR (Diabetic Retinopathy); ROP (Retinopathy of Premature).</p>
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<p>A schematic drawing illustrating some pharmacological therapies for neovascular retinal diseases. (<b>A</b>) Anti-VEGF strategies. (<b>B</b>) Alternative strategies.</p>
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<p>A schematic drawing illustrating some pharmacological therapies for neovascular retinal diseases. (<b>A</b>) Anti-VEGF strategies. (<b>B</b>) Alternative strategies.</p>
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<p>A schematic drawing illustrating the complementary and partially overlapping effects of nutraceuticals and pharmacological drugs on the pathways leading to neovascular retinal diseases.</p>
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<p>A schematic representation of the preventive and therapeutic approaches presented in this review.</p>
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18 pages, 7710 KiB  
Article
A Multicenter Retrospective Cohort Study Evaluating the Clinical Outcomes of Patients with Coagulopathy Undergoing Transcatheter Arterial Embolization (TAE) for Acute Non-Neurovascular Bleeding
by Roberto Minici, Federico Fontana, Massimo Venturini, Giuseppe Guzzardi, Filippo Piacentino, Marco Spinetta, Bernardo Bertucci, Raffaele Serra, Davide Costa, Nicola Ielapi, Andrea Coppola, Pasquale Guerriero, Biagio Apollonio, Rita Santoro, MGJR Research Team, Luca Brunese and Domenico Laganà
Medicina 2023, 59(7), 1333; https://doi.org/10.3390/medicina59071333 - 19 Jul 2023
Cited by 5 | Viewed by 1712
Abstract
Background and Objectives: Transcatheter arterial embolization (TAE) is the mainstay of treatment for acute major hemorrhage, even in patients with coagulopathy and spontaneous bleeding. Coagulopathy is associated with worsening bleeding severity and higher mortality and clinical failure rates. Furthermore, some unanswered questions [...] Read more.
Background and Objectives: Transcatheter arterial embolization (TAE) is the mainstay of treatment for acute major hemorrhage, even in patients with coagulopathy and spontaneous bleeding. Coagulopathy is associated with worsening bleeding severity and higher mortality and clinical failure rates. Furthermore, some unanswered questions remain, such as the definition of coagulopathy, the indication for TAE or conservative treatment, and the choice of embolic agent. This study aims to assess the efficacy and safety of TAE for spontaneous non-neurovascular acute bleeding in patients with coagulopathy. Materials and Methods: This study is a multicenter analysis of retrospectively collected data of consecutive patients with coagulopathy who had undergone, from January 2018 to May 2023, transcatheter arterial embolization for the management of spontaneous hemorrhages. Results: During the study interval (January 2018–May 2023), 120 patients with coagulopathy underwent TAE for spontaneous non-neurovascular acute bleeding. The abdominal wall was the most common bleeding site (72.5%). The most commonly used embolic agent was polyvinyl alcohol (PVA) particles or microspheres (25.0%), whereas coils and gelatin sponge together accounted for 32.5% of the embolic agents used. Technical success was achieved in all cases, with a 92.5% clinical success rate related to 9 cases of rebleeding. Complications were recorded in 12 (10%) patients. Clinical success was significantly better in the group of patients who underwent correction of the coagulopathy within 24 h of TAE. Conclusions: Transcatheter arterial embolization (TAE) is effective and safe for the management of acute non-neurovascular bleeding in patients with coagulopathy. Correction of coagulopathy should not delay TAE and vice versa, as better clinical outcomes were noted in the subgroup of patients undergoing correction of coagulopathy within 24 h of TAE. Full article
(This article belongs to the Section Surgery)
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<p>CT angiography reformatted image in the oblique sagittal plane depicting recurrent massive gastric bleeding after endoscopic treatment (<b>A</b>). Selective catheterization of the left gastric artery (arrow) with active bleeding confirmed at fluoroscopy (arrowhead) (<b>B</b>). Digital subtraction angiography showing effective embolization and Onyx 18 cast (arrow) distributed along the left gastric artery (<b>C</b>).</p>
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<p>Reformatted CT angiography images in the oblique axial and coronal planes showing a massive rectal hemorrhage (arrows) (<b>A</b>,<b>B</b>). Digital subtraction angiography identifying the superior rectal artery as the feeding vessel (arrowhead); active bleeding is also noted (arrow) (<b>C</b>). Embolization of the superior rectal artery with PVA particles mixed with iodinated contrast media under fluoroscopy control (<b>D</b>). Digital subtraction angiography confirming successful embolization of the feeding vessel (patency of the middle and inferior rectal arteries, fed by the internal iliac arteries, prevented significant ischemic injury of the rectal wall) (<b>E</b>).</p>
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<p>CT angiography depicting a spontaneous rectus sheath hematoma (arrow) (<b>A</b>). Selective catheterization of the right inferior epigastric artery (arrow) with a pseudoaneurysm confirmed at digital subtraction angiography (arrowhead) (<b>B</b>). Digital subtraction angiography showing effective embolization with coil (arrows) embolization starting distal to a small pseudoaneurysm-feeding vessel, thus preventing “backdoor” bleeding (<b>C</b>).</p>
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<p>CT angiography depicting a spontaneous pectineus muscle hematoma with active bleeding (arrow) (<b>A</b>). Selective catheterization of the right profunda femoris artery and superselective catheterization of the medial circumflex femoral artery (arrow); at digital subtraction angiography active bleeding is noted (arrowhead) (<b>B</b>). Digital subtraction angiography demonstrating successful embolization with a gelatin sponge (arrow); preserved patency of the profunda femoris artery and its other branches is also noted (<b>C</b>).</p>
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14 pages, 14453 KiB  
Review
Gastrointestinal Imaging Findings in the Era of COVID-19: A Pictorial Review
by Xanthippi Mavropoulou, Elisavet Psoma, Angeliki Papachristodoulou, Nikoletta Pyrrou, Ekaterini Spanou, Maria Alexandratou, Maria Sidiropoulou, Anastasia Theocharidou, Vasileios Rafailidis, Theofilos Chrysanthidis and Panos Prassopoulos
Medicina 2023, 59(7), 1332; https://doi.org/10.3390/medicina59071332 - 19 Jul 2023
Cited by 4 | Viewed by 2920
Abstract
The potentially fatal COVID-19 pandemic has been associated with a largespectrum of clinical presentations. Beyond the classical pulmonary manifestations, gastrointestinal tract-related symptoms suchas nausea, diarrhea, abdominal distention and pain have been observed in patients, as a consequence of the binding of SARS-CoV-19 to [...] Read more.
The potentially fatal COVID-19 pandemic has been associated with a largespectrum of clinical presentations. Beyond the classical pulmonary manifestations, gastrointestinal tract-related symptoms suchas nausea, diarrhea, abdominal distention and pain have been observed in patients, as a consequence of the binding of SARS-CoV-19 to Angiotensin-converting Enzyme 2 (ACE2) receptors in the gastrointestinal (GI) tract. The early recognition ofspecific imaging features, including hepatobiliary involvement, pancreatic involvement, development of solid organ infarcts, ischemic bowel changes and vascular occlusion, plays a key role through the course of the disease. Also, suspicious symptoms, especially in critically ill patients with clinical and biochemical markers of hypovolemia, necessitate timely imaging for bleeding complications. The aim of this pictorial review is to illustrate the spectrum of the GIimaging findings in patients with COVID-19. Awareness of diagnostic imaging hallmarks is crucial to optimize the management of these patients. Full article
(This article belongs to the Special Issue The Digestive System in the Era of COVID-19)
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<p>COVID-19 (+) hospitalized 75-year-old male patient with abdominal pain and diarrhea. Abdominal Contrast Enhanced CT (CECT) depicted bowel wall thickening ((<b>a</b>), thick arrow) and mesenteric fat stranding ((<b>b</b>), thin arrow). The imaging findings are indicative of inflammatory colitis.</p>
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<p>COVID-19 (+) 68-year-old patient with a long hospital stay was subjected to an abdominal CECT for acute abdominal pain, which showed colonic wall thickening ((<b>a</b>), thick arrow) and adjacent fat stranding ((<b>b</b>), thin arrow).</p>
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<p>55-year-old male patient with COVID-19 pneumonia with right lower quadrant pain. CT on admission demonstrating a thickened appendix and proximal fat stranding (yellow arrow), indicating acute appendicitis.</p>
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<p>A 48-year-old female patient with COVID-19 pneumonia and no other comorbidities. CT scan depicted a thickened cecum with proximal fat stranding (yellow arrow).</p>
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<p>59-year-old female patient with severe COVID-19 pneumonia hospitalized in the ICU. CT demonstrating distended large bowel with hyperenhanced walls and free abdominal fluid (shock bowel)—yellow arrow. Note the concomitant subcutaneous edema.</p>
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<p>85-year old-patient with small bowel ileus (fluid filled loops—yellow arrow) at the 4th day of hospitalization.</p>
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<p>A 69-year-old man with COVID-19 presented a positive Murphy sign. Ultrasound images showed gallbladder wall striation and increased thickness ((<b>b</b>)-arrowheads). The Color Doppler technique revealed hyperemia (<b>a</b>). No gallbladder stones were present indicating acalculous cholecystitis.</p>
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<p>A 90-year-old COVID-19 patient presented acute right quadrant abdominal pain and cholestasis. Computed tomography on the axial (<b>a</b>) and coronal (<b>b</b>) plane showed acute cholecystitis with diffuse thickening of the gallbladder wall and pericholecystic fluid (arrowheads). Disruption of the gallbladder wall (arrow) is also present with fluid collection around the liver indicating perforation.</p>
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<p>81-year-old patient with COVID-19 pneumonia developed epigastric pain at the second day of hospitalization. CT demonstrating acute pancreatitis (yellow arrow).</p>
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<p>56-year-old hospitalized male patient with COVID-19 pneumonia with raised level of d-dimers. CT depicting the thrombosed portal vein (yellow arrow). Note that in the same scan, there is extended small bowel thickening with mesenteric free fluid.</p>
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<p>A 75-year-old intubated patient with COVID-19 presented with hematemesis, hypotension and acute drop of hemoglobin level. Computed Tomography revealed active intraluminal extravasation of contrast into the 2nd part of duodenum (arrow) on arterial phase (<b>a</b>). Further pooling of the contrast (arrowhead) is shown on portal phase (<b>b</b>).</p>
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7 pages, 21000 KiB  
Case Report
Stercoral Ulcer Presenting in a Patient with Cauda Equina Syndrome Secondary to Postoperative Epidural Hematoma
by Min-Seok Kang, In-Seok Son, Suk-Ha Lee and Tae-Hoon Kim
Medicina 2023, 59(7), 1331; https://doi.org/10.3390/medicina59071331 - 19 Jul 2023
Viewed by 2014
Abstract
Chronic constipation can lead to fecal impaction in the large bowel, which can cause pressure necrosis followed by perforation, known as a stercoral ulcer. In extensive posterior thoracolumbar surgery, a long operation time, large blood loss, and perioperative narcotic use may aggravate constipation. [...] Read more.
Chronic constipation can lead to fecal impaction in the large bowel, which can cause pressure necrosis followed by perforation, known as a stercoral ulcer. In extensive posterior thoracolumbar surgery, a long operation time, large blood loss, and perioperative narcotic use may aggravate constipation. Moreover, sacral root palsy due to cauda equina syndrome (CES) can lead to the deterioration of fecal impaction. This report describes the case of a 77-year-old woman with CES who presented with saddle anesthesia, neurogenic bladder, bowel incontinence, and paraplegia. Five days prior, she had undergone extended posterior lumbar interbody fusion from L1 to L5. Lumbar magnetic resonance imaging (MRI) showed an extended epidural hematoma. After urgent neural decompression, she gradually recovered from the saddle anesthesia, leg pain, and paraplegia over 3 weeks. Thereafter, the patient suddenly developed massive hematochezia and hemorrhagic shock. Urgent colonoscopy was performed, and a stercoral ulcer in the sigmoid colon was diagnosed. After 4 weeks of intensive care for hemorrhagic shock, pneumonia, and systemic sepsis, the patient was transferred to a general ward for intensive rehabilitation. One year after the operation, she was able to walk with assistance, and her urinary and bowel incontinence completely recovered. Chronic constipation, a common clinical problem, can sometimes cause relatively obscure but potentially life-threatening complications such as stercoral ulceration. Possible factors including advanced age, extensive spinal surgeries, prolonged operation time, significant blood loss, perioperative narcotic use, and the presence of spinal cord injury might contribute to the development of this condition. It highlights the importance of recognizing the potential development of stercoral ulcers in patients with CES and emphasizes the need for prompt diagnosis and management to avert catastrophic complications. Full article
(This article belongs to the Special Issue Advances in Spine and Spinal Cord Surgery)
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<p>Radiographic image of X-ray at first surgery. (<b>a</b>) Preoperative lumbar AP, (<b>b</b>) preoperative lumbar lateral, (<b>c</b>) postoperative lumbar AP, and (<b>d</b>) postoperative lumbar lateral.</p>
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<p>Radiographic image of X-ray at second surgery. (<b>a</b>) Preoperative lumbar lateral, (<b>b</b>) preoperative whole spine lateral, (<b>c</b>) postoperative lumbar AP, and (<b>d</b>) postoperative lumbar lateral.</p>
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<p>Postoperative lumbar MRI showed compressive myelopathy by extensive epidural hematoma from L1 to L3. (<b>a</b>) Sagittal; (<b>b</b>) axial cut on T2WI, MRI = magnetic resonance imaging. White arrows point to epidural hematoma.</p>
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<p>Abdominal CT angiography showed a severe small-bowel paralytic ileus. (<b>a</b>) Coronal; (<b>b</b>) axial cut.</p>
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<p>(<b>a</b>–<b>d</b>) Colonoscopy showed a circular ulcer lesion with a diameter of 1 cm at the rectosigmoid junction.</p>
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10 pages, 345 KiB  
Article
Breastfeeding Practices and Postpartum Depression in Mexican Women during the COVID-19 Pandemic: A Cross-Sectional Study
by Mariana Chávez-Tostado, Karla Verónica Chávez-Tostado, Gabino Cervantes-Guevara, Guillermo Cervantes-Cardona, Diana Mercedes Hernandez-Corona, Tonatiuh González-Heredia, Miriam Méndez-del Villar, Fernanda Isadora Corona-Meraz, Milton Omar Guzmán-Ornelas, Francisco José Barbosa-Camacho, Andrea Socorro Álvarez-Villaseñor, Enrique Cervantes-Pérez, Clotilde Fuentes-Orozco, Natalia Guadalupe Barrera-López, Noelia Esthela López-Bernal and Alejandro González-Ojeda
Medicina 2023, 59(7), 1330; https://doi.org/10.3390/medicina59071330 - 19 Jul 2023
Cited by 1 | Viewed by 2705
Abstract
Background: Breastfeeding is a characteristic process of mammals that ensures delivery of an adequate nutritional supply to infants. It is the gold standard food source during an infant’s first months of life. Since the onset of the COVID-19 pandemic in 2020, people [...] Read more.
Background: Breastfeeding is a characteristic process of mammals that ensures delivery of an adequate nutritional supply to infants. It is the gold standard food source during an infant’s first months of life. Since the onset of the COVID-19 pandemic in 2020, people in quarantine have experienced a wide range of feelings, which may make isolation challenging in terms of maternal health. This study focused on the prevalence of breastfeeding practices and postpartum depression (PPD) among Mexican women during the COVID-19 pandemic. Materials and Methods: This cross-sectional study included 586 postpartum women who completed an online survey 4−8 weeks after delivery from April to December 2020 in Guadalajara, Mexico. The aim was to identify potentially depressed mothers according to the Edinburgh Postnatal Depression Scale (EPDS) and describe their breastfeeding practices. Results: The mean maternal age was 30.4 ± 4.6 years, the mean EPDS score was 9.6 ± 5.0, and the PPD prevalence according EPDS scores was 27.1%. Exclusive breastfeeding (EBF) was reported by 32.3% of mothers in the first 48 h and by 70.3% of mothers 48 h after delivery. EBF was associated with a lower prevalence of PPD during the first 48 h (p = 0.015) and after the first 48 h (p = 0.001) after delivery. Skin-to-skin contact (SSC) was reported by 385 (65.7%) mothers. PPD was less frequent in mothers practicing SSC (20.3%) than it was in those not practicing SSC (40.3%) (p = 0.001). A higher percentage of mothers practiced SSC breastfed (66.9%) and used EBF (150, 79.4%) (p = 0.012 and 0.001, respectively). Conclusions: Results suggest that the pandemic emergency and restrictions imposed on the population significantly affected the well-being of mothers after birth, and that these effects may have posed risks to the mental health and emotional stability of postpartum mothers. Therefore, encouraging BF or EBF and SSC may improve or limit depressive symptoms in postpartum mothers. Full article
(This article belongs to the Special Issue Public Mental Health Crisis during SARS-CoV-2 Pandemic)
15 pages, 869 KiB  
Review
MicroRNAs as a Potential Biomarker in the Diagnosis of Cardiovascular Diseases
by Dagmar Kramna, Petra Riedlova and Vitezslav Jirik
Medicina 2023, 59(7), 1329; https://doi.org/10.3390/medicina59071329 - 19 Jul 2023
Cited by 8 | Viewed by 2949
Abstract
Cardiovascular diseases (CVD) are the leading cause of death in most developed countries. MicroRNAs (miRNAs) are highly investigated molecules not only in CVD but also in other diseases. Several studies on miRNAs continue to reveal novel miRNAs that may play a role in [...] Read more.
Cardiovascular diseases (CVD) are the leading cause of death in most developed countries. MicroRNAs (miRNAs) are highly investigated molecules not only in CVD but also in other diseases. Several studies on miRNAs continue to reveal novel miRNAs that may play a role in CVD, in their pathogenesis in diagnosis or prognosis, but evidence for clinical implementation is still lacking. The aim of this study is to clarify the diagnostic potential of miRNAs in some CVDs. Full article
(This article belongs to the Topic Biomarkers in Cardiovascular Disease—Chances and Risks)
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<p>Functions of miRNAs-MiRNAs regulate gene expression by binding to mRNAs leading to mRNA degradation or repression of translation.</p>
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<p>Biogenesis of miRNAs.</p>
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7 pages, 1951 KiB  
Case Report
Successful Hybrid Approach Treatment of a Large Persistent Sciatic Artery Aneurysm—A Case Report
by Vladimir Cvetic, Marko Miletic, Borivoje Lukic, Dragoslav Nestorovic, Ognjen Kostic, Milos Sladojevic, Petar Zlatanovic and Nenad Jakovljevic
Medicina 2023, 59(7), 1328; https://doi.org/10.3390/medicina59071328 - 19 Jul 2023
Cited by 1 | Viewed by 1676
Abstract
Background and Objectives: Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that is often asymptomatic, but can be associated with aneurysm formation and potential complications, such as thromboembolism or aneurysm rupture in some cases. We present a case of a [...] Read more.
Background and Objectives: Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that is often asymptomatic, but can be associated with aneurysm formation and potential complications, such as thromboembolism or aneurysm rupture in some cases. We present a case of a 75-year-old woman with a symptomatic thrombus-containing aneurysm of the left PSA. Materials and Methods: The treatment of the PSA aneurysm involved a successful hybrid approach, which included open surgical bypass and endovascular embolization. The open surgical bypass was performed from the left common femoral artery to the left above-the-knee popliteal artery using a synthetic graft, while the aneurysm exclusion was achieved through endovascular plug embolization. Results: Control angiography revealed complete exclusion of the PSA aneurysm. At the 1-month follow-up, there were no palpable pulsatile masses in the left gluteal region, and the patient reported no symptoms. Conclusions: Given the high incidence of limb- and life-threatening complications associated with a PSA aneurysm, accurate diagnosis and appropriate treatment are crucial. In this case, a combination of open surgical and endovascular techniques resulted in a favorable outcome for the patient, highlighting the effectiveness of the hybrid approach in managing PSA aneurysms. Further studies are warranted to explore and refine treatment strategies for these complex vascular anomalies. Full article
(This article belongs to the Special Issue New Perspectives in Vascular and Endovascular Surgery)
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<p>Computed tomographic arteriogram. (<b>a</b>) Axial cross section showed a pseudoaneurysm that measured 85 mm in diameter, with the parietal thrombus on posterior wall. (<b>b</b>) VR reconstruction revealed a large pseudoaneurysm of the left persistent sciatic artery, as well as the usual anatomical presentation of the right iliac and femoral arteries.</p>
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<p>(<b>a</b>) Selective digital subtraction angiography (DSA) of the left persistent sciatic artery, confirming a large pseudoaneurysm (H—head); (<b>b</b>) DSA after the utilization of sandwich embolization technique. Both inflow and outflow of the pseudoaneurysm were embolized using vascular plugs. Flow through the pseudoaneurysm is not observed after embolization.</p>
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<p>Persistent sciatic artery (PSA) classification by Pillet (1980), modified by Gauffre (1994) [<a href="#B12-medicina-59-01328" class="html-bibr">12</a>].</p>
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11 pages, 749 KiB  
Article
Pre-Trauma Pain Is the Strongest Predictor of Persistent Enhanced Pain Patterns after Severe Trauma: Results of a Single-Centre Retrospective Study
by Katharina Fetz, Rolf Lefering and Sigune Kaske
Medicina 2023, 59(7), 1327; https://doi.org/10.3390/medicina59071327 - 19 Jul 2023
Cited by 1 | Viewed by 1787
Abstract
Background and Objectives: Traumatic injuries are a significant public health issue worldwide, with persistent enhanced pain being a common complication following severe trauma. Persistent and chronic pain can have a profound impact on patients’ quality of life, affecting physical, emotional, and social functioning. [...] Read more.
Background and Objectives: Traumatic injuries are a significant public health issue worldwide, with persistent enhanced pain being a common complication following severe trauma. Persistent and chronic pain can have a profound impact on patients’ quality of life, affecting physical, emotional, and social functioning. This study aimed to investigate the pain patterns of trauma patients before and after severe trauma, and identify the predictors of persisting pain after injury. Materials and Methods: A total of 596 patients of a level-one trauma centre with severe trauma were included in this study. The Trauma Outcome Profile Scale was used to assess pain severity before and after trauma, and a logistic regression analysis was performed to determine the most significant predictors of relevant pain after severe trauma. Results: The mean age of the included patients was 48.2 years, and 72% were males. The most frequent cause of injury was traffic accidents, and the mean Injury Severity Score was 17.6. Nearly half of the patients experienced reduced pain-related quality of life after trauma, with persisting pain predominantly occurring in the neck, spine, shoulder, pelvis, hip, knee, and feet. Even minor injuries led to increased pain scores. Preexisting pain before injury (OR: 5.43; CI: 2.60–11.34), older age (OR: 2.09, CI: 1.22–3.27), female gender (OR: 1.08, CI: 0.73–1.59), and high injury severity (OR: 1.80, CI: 1.20–2.69) were identified as significant predictors of enhanced pain. Conclusions: These findings highlight the importance of considering pre-existing pain, body area, and injury severity in assessing the risk of persistent pain in trauma patients. Full article
(This article belongs to the Special Issue Perioperative Pain Management)
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<p>Median pain score as the measured Trauma Outcome Profile before trauma and two years after trauma (o = outliers and * = extreme values).</p>
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<p>Percentages of patients reporting relevant pain before trauma and two years after trauma for different body regions (dots = percentages; lines = trend pattern).</p>
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