Search Results (742)

Kaposi sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV-8), is the primary etiologic cause of Kaposi sarcoma (KS) and KSHV Inflammatory Cytokine Syndrome (KICS). Patients with KICS demonstrate symptoms of systemic inflammation, high KSHV viral load, elevation of inflammatory markers, and increased mortality. Management requires rapid diagnosis, treatment of underlying HIV, direct treatment of KS, and addressing the hyperimmune response. While a case definition based on clinical presentation, imaging findings, laboratory values, KSHV viral load, and lymph-node biopsy has been proposed, some of the required investigations are frequently unavailable in resource-constrained settings. Due to these challenges, KICS likely remains underdiagnosed and undertreated in these settings. We report a case of a 19-year-old woman living with HIV, and intermittent adherence to her ART, who presented with hypotension and acute hypoxemic respiratory failure. She was found to have high KSHV and HIV viral loads, low CD4 count, anemia, thrombocytopenia, hypoalbuminemia, and elevated inflammatory markers. On bedside ultrasound, she was found to have bilateral pleural effusions, ascites, an enlarged spleen, and hyperechoic splenic lesions. The diagnosis of KICS was made based on this constellation of findings. Weighing the risk and benefits of steroid administration in KS patients, the patient was successfully treated by the continuation of ART and the initiation of paclitaxel chemotherapy and steroids. We propose an adapted case definition relevant to the resource-constrained context. Due to the dual burden of KSHV and HIV in sub-Saharan Africa, additional cases of KICS are likely, and this syndrome will contribute to the burden of early mortality in newly diagnosed HIV patients. Addressing the diagnostic and therapeutic challenges of KICS must be a part of the overall management of the HIV pandemic. Full article

Methotrexate (MTX) is an antifolic agent used in the first line of anti-inflammatory disease treatment and some oncologic issues. The metabolism of MTX is rapid, and the MTX concentration in the blood is not significant 24 h after administration. Unlike this, methotrexate polyglutamates (MTXPGs) can be informative biomarkers of drug exposure. It is widely concluded that MTXPG retention in red blood cells (RBCs) is related to appropriate efficacy, drug exposure, and toxicity during treatment. Therefore, the mentioned biomarker may be appropriately used for the PK/PD monitoring of low-dose MTX (LDMTX) treatment. The presented review study aimed to review published studies about MTX determination in clinical practice, including pre-analytical variability, bioanalytical considerations, and clinical applications of the methods for pharmacotherapy supporting target populations. In total, 14 papers from the field of bioanalytics have been included in the main review. For each phase of an analytical process, the best practises and main findings were defined as guidelines for proper analytical method optimisation, validation, and standard operation procedure implementation in clinical practice. The presented study is the first comprehensive review of MTX and its methods of metabolite determination to account for pre-analytical, analytical, and post-analytical phases concerning the TDM process. Full article

Objectives: This study explores stroke rehabilitation facility design in Australia, identifying the key design typologies at multiple scales and assessing them against the critical design criteria for stroke rehabilitation. Background: The physical environment plays a crucial role in stroke rehabilitation, affecting patient recovery and well-being. However, limited research examines how design can support therapeutic outcomes in these facilities. Method: From a systematic review of 257 Australian stroke rehabilitation facilities, 30 were selected for detailed design review, with an in-depth room-level analysis conducted for 10. Using the modified PRISMA framework and a typology analysis approach, this study integrates architectural precedent with clinical research methods. Results: Typologies were identified at the site, building, ward, and room levels. Acute hospital wards (53%) and ‘blocks’ (73%) were the most common site and building arrangements, respectively. At the ward level, ‘racetrack with courtyard’ layouts enhanced natural light, views, and access to landscaped areas. A room-level analysis revealed limited innovation, with most rooms adhering to standard designs, though some adaptations improved visual connectivity and personal control. Hybrid nurse stations and courtyards supported efficiency, social interaction, and therapeutic stimulation. Conclusions: This study highlights the user-centred design strategies tailored to stroke patients’ needs and the importance of evidence-based approaches prioritising well-being. Future research should incorporate 3D spatial analysis for actionable design recommendations. Full article

Background: Mood disorders are among the most prevalent and debilitating mental conditions in worldwide populations. The aim of this study was to identify the factors influencing life satisfaction, disease acceptance, and therapeutic adherence among people with mood disorders. Methods: This survey-based study included 103 people with mood disorders. It was performed using the author questionnaire, and standardized research tools, namely the Adherence to Refills and Medication Scale (ARMS), the Acceptance of Illness Scale (AIS), the Beck Depression Inventory (BDI), and the Satisfaction with Life Scale (SWLS). Results: The level of life satisfaction decreased with the increase in the severity of the depressive symptoms (SE = −0.665, p < 0.001). Mood disorder patients with more severe depressive symptoms had significantly higher scores on the adherence scale (SE = 0.290, p = 0.003). The patients with higher levels of depressive symptoms showed a lower level of acceptance of the disease. Conclusions: 1. The dosage of medications taken, and the severity of the depressive symptoms determine life satisfaction of people with mood disorders. 2. The respondents with a greater severity of depressive symptoms scored higher on the adherence scale, which means that they were more likely to be non-adherent to the treatment recommendations. The type of mood disorder may affect patient adherence. The subjects with bipolar disorder showed higher adherence and those with anxiety–depressive disorder showed a lower adherence than the patients with depression. 3. The subjects with more severe depressive symptoms showed a lower degree of acceptance of the disease. Full article

Background/Objectives: Structured therapeutic patient education is the key to improving biopsychosocial outcomes in people with type 1 diabetes mellitus. This study aimed to determine the effects of structured therapeutic education on glycemic control and emotional well-being in people with type 1 diabetes mellitus. Methods: This is a systematic review with a meta-analysis (PROSPERO ID: CRD42023390079). Searches were performed in Scopus, MEDLINE, Web of Science, CINAHL, APA PsycInfo, APA PsycArticles, and the Psychology Database (June–August 2024). The eligibility criteria included randomized controlled trials published in English or Spanish within the past 10 years. Data extraction and risk of bias evaluations were independently conducted by two reviewers. The outcomes analyzed included glycated hemoglobin, time in range, emotional well-being, self-management behaviors, and adherence to treatment. Meta-analyses were performed using RevMan with random and fixed effects models. Results: Seventeen studies met the eligibility criteria. There was a significant improvement in glycemic control, stress, anxiety, and treatment satisfaction, although the results for the other emotional outcomes were mixed. Conclusions: Structured therapeutic patient education improves glycemic control and selected emotional outcomes in individuals with type 1 diabetes mellitus. Further trials are needed to refine the characteristics of the intervention and broaden the applicability of the findings to diverse populations. Full article

Objective: Can mobile app intervention via push notifications increase adherence to exercise and reduce disability and pain after a whiplash injury? Methods: A randomized controlled trial was conducted with concealed allocation, blinding of some assessors, and an intention-to-treat analysis. Participants who sustained whiplash injury at most 3 months prior were divided into active and control groups. Both groups completed a two-part physiotherapist-supervised physical therapy program (3-week break in between, ten sessions each, 5x/week). The program included TENS, therapeutic ultrasound, and exercises (breathing, ROM, deep neck flexor activation, and stretching). Both groups were encouraged to exercise at home. The active group additionally received push notifications through the mobile app once a day as a reminder to exercise. Outcomes were adherence to exercise (four-point Likert scale), physical functioning (NDI), pain intensity (VAS), perceived recovery (three-point Likert scale), work information, psychological functioning (PCS), and HRQoL (SF-12) at baseline and 6-month follow-up. Results: At month 6, when comparing the groups, the intervention group showed higher adherence to home exercise (3 [2–4] vs. 2 [2–4]; p = 0.005, median [IQR]) and improved HRQoL (∆SF-12) (20 [6–36] vs. 15 [9–23]; p = 0.038). Unlike the control group, the intervention group showed a significant decrease in pain catastrophizing (31%; p = 0.01). A multivariant analysis showed that mobile app intervention influenced adherence most (≈1 Likert point). The groups did not differ in NDI, pain VAS, perceived recovery, or work limitation. Conclusions: Mobile app intervention increased adherence to home exercise, reduced pain catastrophizing, and increased HRQoL six months after a whiplash injury. Trial registration: ClinicalTrials.gov NCT05704023. Full article

Background: Individuals with celiac disease (CD) often report the persistence of gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). A diet rich in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) could cause symptoms in CD on a GFD, and conversely a low-FODMAP diet could positively influence the therapeutic management of CD and non-celiac gluten sensitivity (NCGS). The aim of this review was to explore the hypothetical impact of the FODMAD diet and the low-FODMAP diet (LFD) in CD and gluten-related disorders. Methods: A complete online search for FODMAP related to CD, NCGS, and the GFD was carried out using the Pubmed, Medline, and Cochrane databases. Results: Indeed, an LFD could successfully provide symptom relief in GFD-treated CD patients. Fructans, typical components of FODMAPs, have been associated with digestive symptoms in NCGS, and an LFD could improve the clinical picture. According to some evidence, an LFD could also improve the psychological status both in celiac patients on a GFD and in NCGS. However, an LFD should not have a significant impact on gut microbiota. Conclusions: Recent evidence supports the role of FODMAP restriction in CD patients with persistent symptoms on a GFD and in decreasing gastrointestinal disturbances in NCGS, although the GFD still represents the first-line therapy. Full article

Essential oils (EOs) are known for their diverse bioactivities, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, skin-barrier repairing and anticancer, and therefore, hold profound potential to be used in cosmetic and skincare products. Owing to these properties, EOs have long been utilized to address a range of dermatological issues, from acne and inflammation to aging and dryness. However, problems associated with EOs beset their practical applications, which include high volatility, oxidation, hydrophobic nature, low bioavailability, skin irritation, chemical transformation and poor stability in air and light. A prospective of nanolipidic formulations, including the nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) system for improved skin delivery of these EOs highlights the possibility of their use in topical applications, which offer several advantages such as improved bioavailability and stability, lower toxicity and higher drug content. These nanoformulations protect the EOs from environmental degradation and improve their penetration into deeper skin layers, leading to prolonged therapeutic benefits. The delivery of bioactive agents using a conventional topical preparation exhibits low penetration, frequent applications, poor adherence and prolonged therapy duration, whereas the novel delivery system exhibits improved stability of the drug, enhanced skin penetration, enhanced retention and better therapeutic efficacy. This review provides a comprehensive compendium of information on EOs, which are widely used in skincare, along with their nanolipidic formulations for maximized skincare uses. The mechanism of action of EOs as skin bioactive agents, challenges associated with their use, advances in nanolipidic formulations and their market value as cosmetic skincare products are also explored. Full article

Background/Objectives: Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic disease of the liver that symptomatically can present with pruritus and fatigue. Its established first- and second-line therapies are ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) although they provide limited symptom management. Liver transplantation offers a potentially curative therapeutic option in refractory cases progressing to cirrhosis. Novel research published after the current guidelines highlights the importance of providing an up-to-date analysis of treatment options available. Methods: In this study, we conducted a literature search using Pubmed, Ovid Medline, and SCOPUS to provide a narrative review of first-line, second-line, and emerging therapies in PBC. Results: UDCA has been well established as a long-term, safe therapy within the literature although it is possible that treatment dosage can be further optimised in refractory patients. It has a favourable side effect profile. Despite improving biochemical markers, histopathological profile, and overall outcomes, up to 30–40% of patients are refractory to it. Age and sex are highlighted as independent indicators of non-responsiveness. This necessitates effective second-line therapies. Future trials could aim to investigate UDCA as a co-first-line therapy. Further supporting results for OCA were found in the interim extension trial of the seminal POISE study. The long-term phase 4 COBOLT trial is still awaiting results to further assess the complications, adherence, and potential adverse effects. It is a viable option in UDCA-refractory patients. The high incidence rate of dose-related pruritis indicates that alternative second-line options are needed. Bezafibrate is an off-label antilipemic agent that shows promise as a prospective second-line therapy option. The landmark BEZURSO trial alleviated some efficacy and safety concerns, but it remains associated with elevated serum creatinine; thus, it should be considered with caution. Other prospective second-line therapies are budesonide, triple therapy, and novel agents such as seladelpar and elafibranor. Conclusions: UDCA should remain the treatment of choice for PBC, though perhaps not as monotherapy. With further investigation, BF shows promise as a new second-line therapy alongside OCA, which it may outperform. Full article

Background/objectives: Overweight and obesity are global public health problems associated with chronic disease and mental health. Physical activity (PA) is essential throughout a person’s life; an active lifestyle helps people to live healthier lives and improve their functional and mental abilities, such as executive function (EF). This systematic review aimed to analyze the evidence on the effects of PA on EF in overweight and/or obese adults (≥18 years old). Methods: Records from the PubMed, ScienceDirect, and JSTOR databases were searched and, following the PRISMA guidelines, seven studies were included in the present systematic review. Risk of bias was assessed using the National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results from the studies included indicate that acute, short-term, and long-term PA interventions are an effective strategy to improve inhibitory control, working memory, and processing speed in overweight and obese adults. Furthermore, evidence indicates that EF can be effective as a measure to predict adherence to PA programs and weight loss. Conclusions: Exercise and physical activity interventions are a promising therapeutic strategy to promote weight loss and improve EF in adults with overweight and obesity. Additionally, EF may be further explored as a predictor of healthy aging due to the choices made throughout life and the long-term benefits that result. Full article

Pharmacogenomics (PGx) has revolutionized personalized medicine by empowering the tailoring of drug treatments based on individual genetic profiles. However, the complexity of drug response mechanisms necessitates the integration of additional biological and environmental factors. This article explores integrating epigenetics, nutrigenomics, microbiomes, protein interactions, exosomes, and metabolomics with PGx to enhance personalized medicine. In addition to discussing these scientific advancements, we examine the regulatory and ethical challenges of translating multi-omics into clinical practice, including considerations of data privacy, regulatory oversight, and equitable access. By framing these factors within the context of Medication Adherence, Medication Appropriateness, and Medication Adverse Events (MA³), we aim to refine therapeutic strategies, improve drug efficacy, and minimize adverse effects, with the goal of improving personalized medicine. This approach has the potential to benefit patients, healthcare providers, payers, and the healthcare system as a whole by enabling more precise and effective treatments. Full article

Background: Lung cancer is an aggressive disease with rapid progression and a high rate of metastasis, leading to a significantly poor prognosis for many patients. While chemotherapy continues to serve as a cornerstone treatment for a large proportion of lung cancer patients, expanding preclinical and clinical evidence indicates that chemotherapy may promote tumor metastasis and cause side effects. Methods: We develop an injectable bait-and-hook hydrogel (BH-gel) for targeted tumor cell eradication, which embedded doxorubicin liposomes as cytotoxic agents and CXCL12 as a chemoattractant to capture and kill tumor cells. The hydrogel backbone was formed through covalent cross-linking between PVA and borax. In vitro, we investigated tumor recruitment and the antitumor effects in A549 cells. In vivo, we explored the anti-metastatic and antitumor activities against lung cancer. Results: BH-gel retained CXCL12 within its three-dimensional porous architecture for gradual release, effectively recruiting tumor cells. In contrast, blank hydrogel failed to achieve this. After encapsulation in BH-gel, the therapeutic efficacy of doxorubicin liposomes for tumor eradication was markedly improved, significantly reducing metastatic tumor presence to near-undetectable levels, while also resulting in notable reductions in cardiotoxicity and hepatotoxicity. Notably, BH-gel adhered well to tissues and exhibited exceptional electrical conductivity, which may be further developed into a real-time tumor monitoring system, facilitating timely therapeutic adjustments. Conclusions: BH-gel utilizes CXCL12 as a bait to recruit and entrap tumor cells in a three-dimensional porous matrix and subsequently kill them with embedded doxorubicin liposomes, thereby tackling the issue of metastatic spread. This bait-and-hook strategy has significant implications for the field of anti-metastasis medicine and shows considerable potential for clinical application. Full article

Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article

Background/Objectives: This case study involved a 24-year-old male with an arteriovenous malformation localized in the long head of the right biceps femoris muscle, with an anterior cruciate ligament injury. The aim was to assess the effects of a five-week kinesiological protocol, which included global postural re-education and strengthening exercises focused on knee stabilization. Methods: The effectiveness of the therapeutic intervention was evaluated using Gait Analysis, clinical examination, and the SF-36 questionnaire to assess the patient’s quality of life. Results: The study revealed significant postural improvements, including the restoration of the spine’s physiological curves, with kyphosis angles measuring 44.7° in indifferent orthostasis and 41.7° in self-corrected standing; and lumbar lordosis measuring 32.8° in indifferent orthostasis and 41.9° in self-corrected standing. Additionally, there was a restoration of the correct knee, hip, and ankle angles, along with a shift in the principal axis of the center of pressure from 7.6° pre-intervention to 12.9° post-intervention. The patient’s perception of physical efficiency also improved, increasing from 60% to 75% over the treatment period. Conclusions: The effectiveness of the kinesiological treatment was confirmed by the improvement in gait stability and overall strengthening. The patient’s active involvement in the treatment process enhanced his confidence in its success, ensuring adherence to the protocols. Full article

Microneedle (MN) technology has emerged as a promising approach for delivering therapeutic agents to the skin, offering significant potential in treating various dermal conditions. Among these technologies, hydrogel-forming microneedles (HFMNs) represent a transformative advancement in the management of dermal diseases through non-invasive drug delivery. These innovative devices consist of micrometer-sized needles made of native or crosslinked hydrophilic polymers, capable of penetrating the stratum corneum without damaging underlying tissues. Upon insertion, HFMNs rapidly absorb interstitial fluid, swelling to form a hydrogel conduit that enables the efficient transport of therapeutic agents directly into the dermal microcirculation. The non-invasive nature of HFMNs enhances patient compliance by eliminating the pain and discomfort associated with traditional hypodermic needles. This technology allows for the delivery of a wide range of drugs, including macromolecules and biomacromolecules, which are often difficult to administer dermally due to their size and polarity. Moreover, HFMNs provide controlled and regulated release profiles, enabling sustained therapeutic effects while minimizing systemic side effects. Additionally, HFMNs can be used for both drug delivery and real-time interstitial fluid monitoring, offering valuable insights into disease states and treatment responses. This dual functionality positions HFMNs as a versatile dermatology tool capable of effectively addressing various dermal complications. This review explores the potential use of polymeric biomaterials in HFMN fabrication and their application in treating major dermal disorders, such as acne, psoriasis, and other skin conditions. Furthermore, the review highlights the non-invasive nature of MN-based treatments, underscoring their potential to reduce patient discomfort and improve treatment adherence, as supported by the recent literature. Full article