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13 pages, 1350 KiB  
Article
Prognostic Role of Neutrophil Percentage-to-Albumin Ratio in Patients with Non-ST-Elevation Myocardial Infarction
by Mehmet Karaca and Ayca Gumusdag
Medicina 2024, 60(12), 2101; https://doi.org/10.3390/medicina60122101 (registering DOI) - 22 Dec 2024
Viewed by 159
Abstract
Background and Objectives: This study aimed to investigate whether neutrophil percentage-to-albumin ratio (NPAR) levels on admission have prognostic significance regarding one-year major adverse cardiovascular and cerebrovascular events (MACCEs) in non-ST-elevation myocardial infarction (NSTEMI) patients. Materials and Methods: A total of 464 [...] Read more.
Background and Objectives: This study aimed to investigate whether neutrophil percentage-to-albumin ratio (NPAR) levels on admission have prognostic significance regarding one-year major adverse cardiovascular and cerebrovascular events (MACCEs) in non-ST-elevation myocardial infarction (NSTEMI) patients. Materials and Methods: A total of 464 patients aged 59.2 ± 11.6 years constituted the cohort of this retrospectively designed study. Considering a 1-year follow-up period, the patients were divided into two groups: those with MACCEs and those without. The complete blood count, serum C-reactive protein and serum albumin levels were measured at admission. The NPAR, C-reactive protein/albumin ratio (CAR) and systemic immune-inflammation (SII) index were calculated for all patients, and the associations of these inflammatory-based biomarkers with 1-year MACCEs were evaluated. Results: During the 12-month follow-up period, MACCEs were observed in 75 (16.2%) patients, of which 35 (7.5%) patients died. The patients with MACCEs had higher CRP (p < 0.001), a higher percentage of neutrophils (p < 0.001), lower albumin levels (p < 0.001), a higher CAR (p < 0.001), a higher SII index (p = 0.008) and a higher NPAR (p < 0.001). A high anatomical SxSI score, a high low-density lipoprotein cholesterol level, hypoalbuminemia, high neutrophil counts, a high NPAR level and a high CAR level were independent predictors for one-year MACCEs (all p < 0.05). The NPAR (area under the curve [AUC] = 0.775, p < 0.001) and albumin level (AUC = 0.708, p < 0.001) had better and sufficient discriminatory power and predictive accuracy in determining one-year MACCEs, when compared to the neutrophil (AUC = 0.693, p < 0.001), CAR (AUC = 0.639, p < 0.001) and SII index (AUC = 0.660, p < 0.001), in terms of the receiver operating characteristic curve. The DeLong test revealed that the predictive performance of the NPAR was superior to that of the other inflammatory parameters. In particular, individuals with an NPAR value greater than 17.6 were at greater risk of developing MACCEs (p < 0.001). Conclusions: The NPAR can be used as a newly identified promising inflammatory biomarker to predict one-year MACCEs in NSTEMI patients undergoing revascularization therapy. Full article
(This article belongs to the Section Cardiology)
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<p>The study flow chart for the systematic selection method.</p>
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<p>Comparison of predictive performances of NPAR, ALI, CAR, SII index, albumin and neutrophil determined by ROC curves in predicting long-term MACCEs. Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve; CI, confidence interval; NPAR, neutrophil percentage-to-albumin ratio; ALI, advanced lung cancer inflammation index; CAR, C-reactive protein-to-albumin ratio; SII, systemic immune-inflammation; DBA, difference between areas.</p>
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<p>The Kaplan–Meier plots of the survival curves of patients with low (blue line) and high (green line) NPAR value categories. Abbreviations: NPAR, neutrophil percentage-to-albumin ratio; MACCEs, major adverse cardiovascular and cerebrovascular events.</p>
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23 pages, 2425 KiB  
Article
Oxygen Effect on 0–30 eV Electron Damage to DNA Under Different Hydration Levels: Base and Clustered Lesions, Strand Breaks and Crosslinks
by Yingxia Gao, Xuran Wang, Pierre Cloutier, Yi Zheng and Léon Sanche
Molecules 2024, 29(24), 6033; https://doi.org/10.3390/molecules29246033 (registering DOI) - 21 Dec 2024
Viewed by 263
Abstract
Studies on radiosensitization of biological damage by O2 began about a century ago and it remains one of the most significant subjects in radiobiology. It has been related to increased production of oxygen radicals and other reactive metabolites, but only recently to [...] Read more.
Studies on radiosensitization of biological damage by O2 began about a century ago and it remains one of the most significant subjects in radiobiology. It has been related to increased production of oxygen radicals and other reactive metabolites, but only recently to the action of the numerous low-energy electrons (LEEs: 0–30 eV) produced by ionizing radiation. We provide the first complete set of G-values (yields of specific products per energy deposited) for all conformational damages induced to plasmid DNA by LEEs (GLEE (O2)) and 1.5 keV X-rays (GX(O2)) under oxygen at atmospheric pressure. The experiments are performed in a chamber, under humidity levels ranging from 2.5 to 33 water molecules/base. Photoelectrons from 0 to 30 eV are produced by X-rays incident on a tantalum substrate covered with DNA. Damage yields are measured by electrophoresis as a function of X-ray fluence. The oxygen enhancement ratio GLEE(O2)/GLEE(N2), which lies around 2 for potentially lethal cluster lesions, is similar to that found with cells. The average ratio, GLEE(O2)/GX(O2), of 12 for cluster lesions and crosslinks strongly suggest that DNA damages that harm cells are much more likely to be created by LEEs than any other initial species generated by X-rays in the presence of O2. Full article
(This article belongs to the Special Issue Exclusive Feature Papers in Physical Chemistry, 2nd Edition)
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<p>Exposure–response curves for crosslinks, SSBs, DSBs and loss of supercoiled in 5-monolayer DNA films (■) induced by X-rays on glass (<b>A</b>) and Ta (<b>B</b>) under 100% humidity (Γ = 33), together with the enzymatic treatments with Fpg (●) and Nth (▲). Exposure–response curves were fitted with a linear function. Each data point is the result of three identical bombardment procedures, and the error bars are the standard deviation.</p>
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<p>The yields (per 10<sup>15</sup> photons·molecule·cm<sup>−2</sup>) of (<b>A</b>) CLs, BD−related crosslinks (BD−CLs), DSBs, and non-DSB cluster damages (NDCDs) and (<b>B</b>) isolated BDs, total BDs, SSBs, and total DNA damages induced by LEPEs for different hydration levels Γ under an O<sub>2</sub> atmosphere at SATP. Γ is the number of water molecules per nucleotide. The error bars are the standard deviations from six identical measurements.</p>
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<p>G-values (number of a specific damage D per 100 eV of energy deposited) recorded under O<sub>2</sub> at SATP, as a function of hydration level Γ, for LEPEs (G<sub>LEE</sub>, full symbols) and 1.5 keV X-rays (G<sub>X</sub>, open symbols). The G<sub>HER-1</sub> and G<sub>HER-2</sub> values were obtained at Γ = 2.5 for electron distributions created by the initial and all secondary electrons produced by HER, respectively (half-filled symbols). The G-values are provided for crosslinks (CLs), SSBs, DSBs, BD-related CLs, isolated BDs, non-DSB cluster damages (NDCDs), total BDs, and total DNA damages. The dashed lines are splined curves fitted to the data points. The error bars are the standard deviations resulting from six identical experiments.</p>
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<p>Dependence of the ratio G<sub>LEE</sub> to G<sub>X</sub> on the level of hydration for all measured damages in dry and humid DNA films under O<sub>2</sub> at SATP. The red arrow indicates the right scale for DSBs and the sum of all measured damages. The error bars are the standard deviations obtained from the division of the two G-values.</p>
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<p>Percentage (%) of the direct and indirect effects contributing to G<sub>LEE</sub> (D/100 eV) for CLs, SSBs, DSBs, BD-related CLs, isolated BDs, NDCDs, total BDs, and total (T) DNA damages induced by LEEs as a function of hydration level under an O<sub>2</sub> atmosphere at SATP. The left scale corresponds to the direct effect, whereas the right one (blue arrow), which is inverted, denotes the indirect contribution.</p>
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<p>The oxygen enhancement ratio (OER) of G-values for LEEs (<b>A</b>) and X-rays (<b>B</b>). G<sub>LEE</sub> and G<sub>X</sub> are expressed as a ratio of the values obtained under an oxygen atmosphere to that in nitrogen. The error bars are the standard deviations obtained from the division. OERs of G<sub>LEE</sub> and G<sub>X</sub> for all damages are represented, except X-ray-induced DSBs and BD-CLs whose yields under an N<sub>2</sub> atmosphere were too close to background levels to obtain meaningful results.</p>
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14 pages, 722 KiB  
Article
Circulating Brain-Reactive Autoantibody Profiles in Military Breachers Exposed to Repetitive Occupational Blast
by Shawn G. Rhind, Maria Y. Shiu, Oshin Vartanian, Catherine Tenn, Ann Nakashima, Rakesh Jetly, Zhihui Yang and Kevin K. Wang
Int. J. Mol. Sci. 2024, 25(24), 13683; https://doi.org/10.3390/ijms252413683 (registering DOI) - 21 Dec 2024
Viewed by 206
Abstract
Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. [...] Read more.
Military breachers are routinely exposed to repetitive low-level blast overpressure, placing them at elevated risk for long-term neurological sequelae. Mounting evidence suggests that circulating brain-reactive autoantibodies, generated following CNS injury, may serve as both biomarkers of cumulative damage and drivers of secondary neuroinflammation. In this study, we compared circulating autoantibody profiles in military breachers (n = 18) with extensive blast exposure against unexposed military controls (n = 19). Using high-sensitivity immunoassays, we quantified IgG and IgM autoantibodies targeting glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), and pituitary (PIT) antigens. Breachers exhibited significantly elevated levels of anti-GFAP IgG (p < 0.001) and anti-PIT IgG (p < 0.001) compared to controls, while anti-MBP autoantibody levels remained unchanged. No significant differences were observed for any IgM autoantibody measurements. These patterns suggest that repetitive blast exposure induces a chronic, adaptive immune response rather than a short-lived acute phase. The elevated IgG autoantibodies highlight the vulnerability of astrocytes, myelin, and the hypothalamic–pituitary axis to ongoing immune-mediated injury following repeated blast insults, likely reflecting sustained blood–brain barrier disruption and neuroinflammatory processes. Our findings underscore the potential of CNS-targeted IgG autoantibodies as biomarkers of cumulative brain injury and immune dysregulation in blast-exposed populations. Further research is warranted to validate these markers in larger, more diverse cohorts, and to explore their utility in guiding interventions aimed at mitigating neuroinflammation, neuroendocrine dysfunction, and long-term neurodegenerative risks in military personnel and similarly exposed groups. Full article
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<p>Circulating Autoantibodies in Breachers vs. Controls. Data are displayed as individual scatter plots showing the median and interquartile range (IQR; bars) for plasma concentrations (μg/mL) for each biomarker among blast-exposed Breachers (closed blue symbols) and unexposed Controls (closed red symbols) as indicated for IgG and IgM antibody isotypes; anti-glial fibrillary acidic protein (GFAP; (<b>A</b>)), anti-pituitary (PIT; (<b>B</b>)), anti-myelin basic protein (MBP; (<b>C</b>)). Mann–Whitney <span class="html-italic">U</span>-test significance vs. Controls: ns (not significant), * <span class="html-italic">p</span> &lt; 0.001.</p>
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13 pages, 3940 KiB  
Article
Reaction of Lactone-Containing Poly(benzofuran-co-arylacetic acid) with Diamines to Cross-Linked Products of Improved Thermal Conductivity
by Alexandrina Nan, Xenia Filip and Jürgen Liebscher
Molecules 2024, 29(24), 6020; https://doi.org/10.3390/molecules29246020 - 20 Dec 2024
Viewed by 218
Abstract
The recently developed phenoplast-related polymer, poly(benzofuran-co-arylacetic acid), presents a versatile molecular structure containing lactone and carboxylic acid functionalities that offer significant flexibility in creating cured materials with tailored properties for diverse applications, wherein also the thermal conductivity is an important factor. [...] Read more.
The recently developed phenoplast-related polymer, poly(benzofuran-co-arylacetic acid), presents a versatile molecular structure containing lactone and carboxylic acid functionalities that offer significant flexibility in creating cured materials with tailored properties for diverse applications, wherein also the thermal conductivity is an important factor. This study analyses the possibility of forming amide moieties of poly(benzofuran-co-arylacetic acid) with diamines resulting in cross-linked products in order to control its thermal properties. The cross-linking process is achieved by utilizing three distinct diamines, 1,6-diaminohexane, p-xylylenediamine, and 4,7,10-trioxa-1,13-tridecanediamine, each possessing different degrees of polarity, flexibility, and reactivity. The resulting cross-linked zwitterionic poly(benzofuran-co-arylacetic acids) were structurally and morphologically characterized. By means of measuring the thermal conductivity and diffusivity of the materials, the possibility of adjusting the thermal properties of the cross-linked products by choosing appropriate linkers was determined. A case was developed where the thermal conductivity and diffusivity increased with temperature, a hardly found property in the cross-linking of polymers being important for many practical applications. Full article
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<p>The <sup>13</sup>C ss-NMR spectra of <b>PBAAA</b> (red), <b>PBAA-DAH</b> (blue), and <b>DAH</b> (green) recorded by the CP-MAS sequence as described in <a href="#sec3-molecules-29-06020" class="html-sec">Section 3</a>; asterisks * indicate sidebands.</p>
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<p>The <sup>15</sup>N ss-NMR spectra of <b>PBAA-DAH</b> (blue) and <b>DAH</b> (red) recorded by the CP-MAS sequence as described in <a href="#sec3-molecules-29-06020" class="html-sec">Section 3</a>.</p>
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<p>The <sup>13</sup>C ss-NMR spectra of <b>PBAAA</b> (red) and <b>PBAA-TTD</b> (dark blue) recorded by the CP-MAS sequence as described in <a href="#sec3-molecules-29-06020" class="html-sec">Section 3</a>, * indicating the sidebands.</p>
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<p>The <sup>13</sup>C <span class="html-italic">ss</span>-NMR spectra of <b>PBAAA</b> (red) and <b>PBAA-XLD</b> (dark blue) recorded by the CP-MAS sequence as described in <a href="#sec3-molecules-29-06020" class="html-sec">Section 3</a>, * indicating the sidebands.</p>
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<p>FTIR spectra of <b>PBAAA</b> and the cross-linked polymers <b>PBAA-DAH</b>, <b>PBAA-TTD</b> and <b>PBAA-XLD</b>.</p>
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<p>Scanning electron micrographic (SEM) images of (<b>a</b>) <b>PBAAA</b>; (<b>b</b>) <b>PBAA-DAH</b>; (<b>c</b>) <b>PBAA-TTD</b>; and (<b>d</b>) <b>PBAA-XLD</b>.</p>
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<p>TGA thermograms obtained on the <b>PBAAA</b> and the cross-linked polymers <b>PBAA-DAH</b>, <b>PBAA-TTD</b> and <b>PBAA-XLD</b> from room temperature to 800 °C.</p>
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<p>Thermal conductivity results for <b>PBAAA</b> and cross-linked samples of <b>PBAAA</b> with diamines at RT (blue column), 50 °C (green column), and 100 °C (red column).</p>
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<p>Thermal conductivity of <b>PBAAA</b> and cross-linked samples <b>PBAAA-DAH</b>, <b>PBAA-TTD</b>, and <b>PBAA-XLD</b> at RT (green), 50 °C (blue), and 100 °C (orange).</p>
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<p>Preparation of cross-linked PBAAA with different diamines.</p>
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<p>Carbon atoms with altered <sup>13</sup>C NMR shifts after the cross-linking reaction.</p>
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26 pages, 1000 KiB  
Article
A Long-Term CO2 Emission Forecasting Under Sustainability Policy Using an Advanced Model Complementing the PAARIMAX Framework
by Pruethsan Sutthichaimethee, Worawat Sa-Ngiamvibool, Prapita Thanarak, Jianhui Luo and Supannika Wattana
Agriculture 2024, 14(12), 2342; https://doi.org/10.3390/agriculture14122342 - 20 Dec 2024
Viewed by 176
Abstract
The purpose of this research is to develop an advanced model to serve as a strategic tool for the Thailand government in managing the country and to propose ways for the government to exercise state power through proactive measures to address governance gaps [...] Read more.
The purpose of this research is to develop an advanced model to serve as a strategic tool for the Thailand government in managing the country and to propose ways for the government to exercise state power through proactive measures to address governance gaps and ensure long-term sustainability. This research employs a mixed-methods approach. The research methodology involved the following stages: (1) Quantitative research was conducted by creating the best model, which involved conducting path analysis based on an autoregressive integrated moving average with an exogenous variable model (PAARIMAX (1,1,1)). (2) The results of the quantitative research were optimized to facilitate additional qualitative research in order to identify appropriate ways of using state power for long-term sustainability in country management. The study’s findings suggest that the government will need to exercise its state power in the governance of the country through the development of a long-term national management plan (2024–2043). This plan involves the establishment of a new scenario policy wherein a minimum of 35% clean technology and green materials must be utilized within the economic sector. This is primarily due to their significant impact on environmental change. Furthermore, the government should exercise its state power to mandate an immediate reduction in energy consumption of 50%, achieved through the immediate adoption of renewable energy sources. This research utilized the results derived from the PAARIMAX model to conduct further qualitative analysis to fill the gaps, enhance the value of the quantitative research, and align it more effectively with the context of practical application. The study found that the proactive measures suggested by stakeholders must be implemented alongside the urgent establishment of new scenario policies, including for charges and taxes, subsidies and concession taxes, deposit refund systems, and property rights and market creation. Full article
14 pages, 1764 KiB  
Article
Comparing the Effects of Collagen Hydrolysate and Dairy Protein on Recovery from Eccentric Exercise: A Double Blind, Placebo-Controlled Study
by Rachel Barclay, Jane Coad, Katie Schraders and Matthew J. Barnes
Nutrients 2024, 16(24), 4389; https://doi.org/10.3390/nu16244389 - 20 Dec 2024
Viewed by 497
Abstract
Background: Consuming collagen hydrolysate (CH) may improve symptoms of exercise-induced muscle damage (EIMD); however, its acute effects have not been compared to dairy protein (DP), the most commonly consumed form of protein supplement. Therefore, this study compared the effects of CH and DP [...] Read more.
Background: Consuming collagen hydrolysate (CH) may improve symptoms of exercise-induced muscle damage (EIMD); however, its acute effects have not been compared to dairy protein (DP), the most commonly consumed form of protein supplement. Therefore, this study compared the effects of CH and DP on recovery from EIMD. Methods: Thirty-three males consumed either CH (n = 11) or DP (n = 11), containing 25 g of protein, or an isoenergetic placebo (n = 11) immediately post-exercise and once daily for three days. Indices of EIMD were measured before and 30 min and 24, 48, and 72 h after 30 min of downhill running on a −15% slope at 80% of VO2max speed. Results: Downhill running induced significant EIMD, with time effects (all p < 0.001) for the delayed onset of muscle soreness (visual analogue scale), countermovement jump height, isometric midthigh pull force, maximal voluntary isometric contraction force, running economy, and biomarkers of muscle damage (creatine kinase) and inflammation (interleukin-6, high-sensitivity C-reactive protein). However, no group or interaction effects (all p > 0.05) were observed for any of the outcome measures. Conclusions: These findings suggest that the post-exercise consumption of CH or DP does not improve indices of EIMD during the acute recovery period in recreationally active males. Full article
(This article belongs to the Special Issue Effects of Nutrient Intake on Exercise Recovery and Adaptation)
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<p>CONSORT flow diagram for recruitment and data collection.</p>
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<p>Muscle soreness, measured on a 100 mm visual analogue scale (VAS), during a squat (<b>A</b>) and after three MVICs (<b>B</b>) before (PRE) and after 30 min of downhill running. Participants were allocated into dairy protein (<span class="html-italic">n</span> = 11, DP), placebo (<span class="html-italic">n</span> = 11, PLA), or collagen hydrolysate (<span class="html-italic">n</span> = 11, CH) groups. * Different to PRE (<span class="html-italic">p &lt;</span> 0.05); # different to 30 min (<span class="html-italic">p &lt;</span> 0.05); + different to 24h (<span class="html-italic">p &lt;</span> 0.05); ^ different to 48 h (<span class="html-italic">p &lt;</span> 0.05).</p>
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<p>MVIC (<b>A</b>), IMTP (<b>B</b>), CMJ (<b>C</b>), and running economy (<b>D</b>) before (PRE) and after 30 min of downhill running. Participants were allocated into dairy protein (<span class="html-italic">n</span> = 11, DP), placebo (<span class="html-italic">n</span> = 11, PLA), or collagen hydrolysate (<span class="html-italic">n</span> = 11, CH) groups. * Different to PRE (<span class="html-italic">p &lt;</span> 0.05); # different to 30 min (<span class="html-italic">p &lt;</span> 0.05).</p>
Full article ">Figure 4
<p>nLog of high-sensitivity C-reactive protein (hsCRP; (<b>A</b>)), interleukin 6 (IL-6; (<b>B</b>)), and creatine kinase (CK; (<b>C</b>)) before (PRE) and after 30 min of downhill running. Participants were allocated into dairy protein (<span class="html-italic">n</span> = 11, DP), placebo (<span class="html-italic">n</span> = 11, PLA), or collagen hydrolysate (<span class="html-italic">n</span> = 11, CH) groups. * Different to PRE (<span class="html-italic">p &lt;</span> 0.05); # different to 30 min (<span class="html-italic">p &lt;</span> 0.05); + different to 24 h (<span class="html-italic">p &lt;</span> 0.05); ^ different to 48 h (<span class="html-italic">p &lt;</span> 0.05).</p>
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23 pages, 1739 KiB  
Article
The Interplay Between Vitamin D Deficiency, Iron Status, and Anemia Risk in Moroccan Women of Reproductive Age: A Cross-Sectional Analysis
by Noura Zouine, Ilham Lhilali, Lode Godderis, Adil El Midaoui, Samir El Jaafari and Younes Filali-Zegzouti
Epidemiologia 2024, 5(4), 805-827; https://doi.org/10.3390/epidemiologia5040055 - 19 Dec 2024
Viewed by 566
Abstract
Background: Vitamin D and iron deficiencies are prevalent among Moroccan women of reproductive age (WRA). Research suggests that Vitamin D deficiency (VDD) may impair iron bioavailability, potentially leading to iron deficiency (ID) and anemia. Objectives: This study investigates associations between vitamin D status, [...] Read more.
Background: Vitamin D and iron deficiencies are prevalent among Moroccan women of reproductive age (WRA). Research suggests that Vitamin D deficiency (VDD) may impair iron bioavailability, potentially leading to iron deficiency (ID) and anemia. Objectives: This study investigates associations between vitamin D status, iron levels, and anemia risk in WRA, aged 18–49, from Meknes, Morocco. Methods: A cross-sectional study was conducted among 463 participants, measuring serum 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were assessed through validated questionnaires, and anthropometric data were collected. Linear and logistic regression models analyzed associations, while ROC analysis evaluated VDD’s predictive accuracy for ID and anemia. Results: VDD (25(OH)D < 20 ng/mL) was significantly associated with reduced hemoglobin, hematocrit, red blood cells, and ferritin (all p < 0.01), indicating vitamin D’s role in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19–19.28, p < 0.001), ID (OR: 2.20, 95% CI: 1.32–3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73–12.08, p = 0.004). Dietary iron intake was inadequate, showing minimal protective effects against anemia and ID (β(SE): −0.08(0.03), p = 0.030 and β(SE): −0.05(0.02), p = 0.037). Conclusions: VDD is a significant risk factor for impaired iron status and anemia in Moroccan WRA, highlighting the need for targeted nutritional interventions and further research. Full article
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<p>Participant flow chart.</p>
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<p>Scatter and regression plots of anemia indices against log 25(OH)D3 levels. Abbreviations: 25(OH)D3: 25-hydroxyvitamin D, MCV: Mean corpuscular volume, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, r: Pearson correlation coefficient, Magnitude of the correlation: Negligible (r: 0.00–0.10), weak (r: 0.10–0.39), moderate (r: 0.40–0.69), strong (r: 0.70- 0.89), very strong (r: 0.90–1.00) [<a href="#B83-epidemiologia-05-00055" class="html-bibr">83</a>]. <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>ROC curves of VDD ability in predicting anemia and iron status. Abbreviations: VDD: Vitamin D deficiency, ID: iron deficiency, IDA: Iron deficiency anemia, AUC: Area under the curve, Sens: sensitivity, Spec: specificity. Statistical significance, <span class="html-italic">p</span> &lt; 0.05.</p>
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27 pages, 14209 KiB  
Article
Statistical and Block Copolymers of n-Dodecyl and Allyl Isocyanate via Titanium-Mediated Coordination Polymerization: A Route to Polyisocyanates with Improved Thermal Stability
by Maria Iatrou, Aikaterini Katara, Panagiotis A. Klonos, Apostolos Kyritsis and Marinos Pitsikalis
Polymers 2024, 16(24), 3537; https://doi.org/10.3390/polym16243537 - 19 Dec 2024
Viewed by 326
Abstract
Well-defined amorphous/semi-crystalline statistical copolymers of n-dodecyl isocyanate, DDIC, and allyl isocyanate, ALIC, were synthesized via coordination polymerization using the chiral half-titanocene complex CpTiCl2(O-(S)-2-Bu) as an initiator. In the frame of the terminal model, the monomer reactivity ratios of the statistical copolymers [...] Read more.
Well-defined amorphous/semi-crystalline statistical copolymers of n-dodecyl isocyanate, DDIC, and allyl isocyanate, ALIC, were synthesized via coordination polymerization using the chiral half-titanocene complex CpTiCl2(O-(S)-2-Bu) as an initiator. In the frame of the terminal model, the monomer reactivity ratios of the statistical copolymers were calculated using both well-known linear graphical methods and the computer program COPOINT. The molecular and structural characteristics of the copolymers were also calculated. The thermal properties of these samples were studied by differential scanning calorimetry, DSC, measurements. The kinetics of the thermal decomposition of the statistical copolymers was studied by thermogravimetric analysis, TGA, and differential thermogravimetry, DTG, and the activation energy of this process was calculated by employing several theoretical models. Moreover, block copolymers with the structure P[DDIC-b-(DDIC-co-ALIC)] were synthesized by sequential addition of monomers and coordination polymerization methodologies. The samples were characterized by nuclear magnetic resonance, NMR, spectroscopy; size exclusion chromatography, SEC; and DSC. The thermal stability of the blocks was also studied by TGA and DTG and compared to the corresponding statistical copolymers, showing that the macromolecular architecture greatly affects the properties of the copolymers. A thiol-ene click post-polymerization reaction was performed to introduce aromatic groups along the polyisocyanate chain in order to improve the thermal stability of the parent polymers. Evidently, these statistical and block copolymers can be employed as precursors for the synthesis of novel polyisocyanate-based materials. Full article
(This article belongs to the Special Issue Emerging Trends in Polymer Engineering: Polymer Connect-2024)
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<p>(<b>a</b>) Yield vs. time for the homopolymerization of ALIC. (<b>b</b>) M<sub>w</sub> vs. time and M<sub>w</sub>/M<sub>n</sub> vs. time for the homopolymerization of ALIC.</p>
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<p><sup>1</sup>H NMR spectrum of the sample P(ALIC–co–DDIC) 80/20 in CDCl<sub>3</sub>.</p>
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<p>SEC chromatograms of all the P(ALIC–co–DDIC) samples.</p>
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<p>Dyad sequence distribution of the P(ALIC–co–DDIC) copolymers.</p>
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<p>SEC traces of the P[DDIC-b-(DDIC-co-ALIC)] block copolymers.</p>
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<p><sup>1</sup>H NMR spectrum of the sample P(ALIC–co–DDIC) 60/40 click product in CDCl<sub>3</sub>.</p>
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<p>SEC traces of the thiol-ene click reaction products.</p>
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<p>DSC thermograms for PALIC (<b>left</b>) and PDDIC (<b>right</b>) homopolymers.</p>
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<p>DSC thermograms for the P(ALIC-co-DDIC) statistical copolymer.</p>
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<p>DSC thermograms for the P[DDIC-b-(DDIC-co-ALIC)] block copolymer.</p>
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<p>TGA (<b>left</b>) and DTG (<b>right</b>) plots for the PALIC at all heating rates.</p>
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<p>TGA (<b>left</b>) and DTG (<b>right</b>) plots for the PDDIC at all heating rates.</p>
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<p>TGA (<b>left</b>) and DTG (<b>right</b>) plots for the P(ALIC–co–DDIC) 80/20 at all heating rates.</p>
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<p>Chemical reaction degradation mechanism plot for the PALIC.</p>
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<p>Nucleation (Parabolic Law) (<b>left</b>) and one-dimensional diffusion (<b>right</b>) degradation mechanism plots for the PDDIC.</p>
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<p>TGA (<b>left</b>) and DTG (<b>right</b>) plots for all the P[(DDIC–b–(DDIC-co-ALIC)] at 10 °C/min.</p>
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<p>TGA and DTG plots for the ALIC/DDIC 50/50 Statistical and Block Copolymer at 10 °C/min.</p>
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<p>TGA (<b>left</b>) and DTG (<b>right</b>) plots for the PALIC and the click Product at 10 °C/min.</p>
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<p>TGA and DTG plots for the P(ALIC–co–DDIC) 60/40 and click product at 10 °C/min.</p>
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<p>Synthesis of PALIC.</p>
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<p>Synthesis of PDDIC.</p>
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<p>Synthesis of the statistical copolymers P(ALIC-co-PDDIC).</p>
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<p>Synthesis of the block copolymers P[DDIC-b-(DDIC-co-ALIC)].</p>
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<p>Thiol-ene click reactions.</p>
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17 pages, 1828 KiB  
Article
Dynamic Neuro-Glial-Vascular Responses in a Mouse Model of Vascular Cognitive Impairment
by Ki Jung Kim, Rachel E. Patterson, Juan Ramiro Diaz, Philip O’Herron, Weston Bush, Ferdinand Althammer, Javier E. Stern, Michael W. Brands, Zsolt Bagi and Jessica A. Filosa
Neuroglia 2024, 5(4), 505-521; https://doi.org/10.3390/neuroglia5040032 - 19 Dec 2024
Viewed by 529
Abstract
Background: Chronic hypoperfusion is a risk factor for neurodegenerative diseases. However, the sequence of events driving ischemia-induced functional changes in a cell-specific manner is unclear. Methods: To address this gap in knowledge, we used the bilateral common carotid artery stenosis (BCAS) mouse model, [...] Read more.
Background: Chronic hypoperfusion is a risk factor for neurodegenerative diseases. However, the sequence of events driving ischemia-induced functional changes in a cell-specific manner is unclear. Methods: To address this gap in knowledge, we used the bilateral common carotid artery stenosis (BCAS) mouse model, and evaluated progressive functional changes to neurons, arterioles, astrocytes, and microglial cells at 14 and 28 days post-BCAS surgery. To assess the neuro-glio-vascular response to an acute ischemic insult, brain slices were superfused with low O2 conditions. Using whole-cell patch-clamp electrophysiology, we measured basic membrane properties (e.g., resting membrane potential, capacitance, input resistance) in cortical pyramidal neurons. The activity of astrocytes was evaluated by monitoring Ca2+ from Aldh1l1-CreERT2; R26-lsl-GCaMP6f mice. Vascular reactivity to low O2 from the BCAS mice was also assessed ex vivo. Results: Our data showed no changes to the basic membrane properties of cortical pyramidal neurons. On the other hand, astrocyte activity was characterized by a progressive increase in the resting Ca2+. Notably, at 14 and 28 days post-BCAS, there was an increased expression of anti-inflammatory-related markers (IL-10, S100A10, TRPA1, and Nrf2). These data suggest that, in young mice, BCAS-induced increases in resting Ca2+ were associated with the expression of neuroprotective signals. Contrary to observations in glial cells, vascular function was impaired post-BCAS surgery, as shown by a blunted vasodilatory response to low O2 and the vasodilatory signal, adenosine. Conclusions: Together, these data suggest that, in young mice, BCAS leads to vascular dysfunction (e.g., impaired vasodilation in parenchymal arterioles), and in the absence of neuronal dysfunction, mild ischemia is associated with the activation of glial-derived neuroprotective signals. Full article
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<p>Basic membrane properties from cortical pyramidal neurons post-BCAS surgery. Whole-cell patch-clamp recordings from sham, BCAS 14d, and BCAS 28d neurons. (<b>A</b>) Summary data corresponding to resting membrane potential. (<b>B</b>) Summary data corresponding to cell capacitance. (<b>C</b>) Summary data corresponding to input resistance. (<b>D</b>) Input–output function. One-way ANOVA followed by Dunnett’s multiple comparison test (MCT) (<span class="html-italic">n</span> = 27 neurons for sham, <span class="html-italic">n</span> = 38 neurons for BCAS 14d, and <span class="html-italic">n</span> = 30 neurons for BCAS 28d). Data expressed as mean SEM, * <span class="html-italic">p</span> &lt; 0.05 vs. sham.</p>
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<p>Low O<sub>2</sub>-induced changes in membrane properties of cortical pyramidal neurons from sham, 14, and 28 days post-BCAS surgery mice. (<b>A</b>) Low O<sub>2</sub>-induced changes in resting membrane potential. (<b>B</b>) Proportion of neurons showing depolarization vs. hyperpolarization in response to low O<sub>2</sub>. (<b>C</b>–<b>E</b>) Delta membrane potential resulting from low O<sub>2</sub> exposure to sham, BCAS 14d, and BCAS 28d brain slices. (<b>F</b>,<b>G</b>) Number of action potentials (AP) at various step currents from depolarizing (K) and hyperpolarizing (L) cortical neurons. (<b>A</b>,<b>B</b>) Two-way ANOVA followed by Sidak’s MCT (n-27 sham, <span class="html-italic">n</span> = 38 BCAS 14d, <span class="html-italic">n</span> = 30 BCAS 28d). (<b>C</b>–<b>E</b>) One-way ANOVA, followed by Dunnett’s MCT (C, <span class="html-italic">n</span> = 27 sham, <span class="html-italic">n</span> = 38 BCAS 14, <span class="html-italic">n</span> = 30 BCAS 28d; D/E, <span class="html-italic">n</span> = 18/9 sham, <span class="html-italic">n</span> = 30/8 BCAS 14, <span class="html-italic">n</span> = 24/6 BCAS 28d) (<b>F</b>,<b>G</b>) The mixed-effects model was followed by Dunnett’s MCT (<span class="html-italic">n</span> = 16/11 sham, <span class="html-italic">n</span> = 30/8 BCAS 14d, <span class="html-italic">n</span> = 30/6 BCAS 28d). Data expressed as mean SEM. * <span class="html-italic">p</span> &lt; 0.05, ** or <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, *** or <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001, ns = not significant. Symbols for groups showing significances are * BCAS 14d, and <sup>#</sup> BCAS 28d.</p>
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<p>Low O<sub>2</sub>-induced changes in parenchymal arteriole vasoreactivity. (<b>A</b>) Differential interference contrast image of a cannulated and perfused parenchymal arteriole in a brain slice preparation. (<b>B</b>) Vascular reactivity to bath applied low O<sub>2</sub> treatment in sham, BCAS 14d, and BCAS 28d mice. Two-way ANOVA followed by Sidak’s MCT (<span class="html-italic">n</span> = 6 sham, <span class="html-italic">n</span> = 7 BCAS 14d, <span class="html-italic">n</span> = 7 BCAS 28d). Data expressed as mean SEM. *** <span class="html-italic">p</span> &lt; 0.001 and **** <span class="html-italic">p</span> &lt; 0.0001. Scale bar = 20 µm.</p>
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<p>Parenchymal arteriole responses to adenosine and 10 mM K<sup>+</sup>. (<b>A</b>) Summary data showing percent (%) relaxation of pressurized parenchymal arterioles responses to increasing concentrations of adenosine in sham (<span class="html-italic">n</span> = 6), BCAS 14d (<span class="html-italic">n</span> = 8), and BCAS 28d (<span class="html-italic">n</span> = 7) mice. Two-way ANOVA followed by Dunnett’s MCT (between group comparisons * sham vs BCAS 14d, τ sham vs. BCAS 28d). (<b>B</b>) Summary data showing percent (%) relaxation of pressurized parenchymal arterioles to K<sup>+</sup> in sham (<span class="html-italic">n</span> = 6), BCAS 14d (<span class="html-italic">n</span> = 8), and BCAS 28d (<span class="html-italic">n</span> = 6) mice. One-way ANOVA followed by Dunnett’s MCT vs. sham. Data expressed as means ± SEM. * <span class="html-italic">p</span> &lt; 0.05, **<sup>/ττ</sup> <span class="html-italic">p</span> &lt; 0.01 and <sup>ττττ</sup> <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Spontaneous and low O<sub>2</sub>-induced cortical astrocytic Ca<sup>2+</sup> dynamics post-BCAS ex vivo. (<b>A</b>) Summary data showing astrocyte Ca<sup>2+</sup> events in response to low O<sub>2</sub> in sham, BCAS 14d, and BCAS 28d mice. (<b>B</b>) Proportion of astrocytes responding with an activation or inhibition of Ca<sup>2+</sup> events to low O<sub>2</sub>. (<b>C</b>,<b>D</b>) Summary data showing low O2-induced changes in Ca<sup>2+</sup> events for activated (<b>C</b>) and inhibited (<b>D</b>) astrocytes. (<b>E</b>,<b>F</b>) Summary data showing maximum delta F/F<sub>0</sub> (<b>E</b>) and average delta F/F<sub>0</sub> (<b>F</b>). (<b>A</b>,<b>B</b>,<b>E</b>,<b>F</b>) Two-way ANOVA followed by Sidak’s MCT (sham (<span class="html-italic">n</span> = 32), BCAS 14d (<span class="html-italic">n</span> = 30) and BCAS 28d (<span class="html-italic">n</span> = 18)). (<b>C</b>,<b>D</b>) Two-way ANOVA followed by Sidak’s MCT (sham (<span class="html-italic">n</span> = 9/23), BCAS 14d (<span class="html-italic">n</span> = 10/19) and BCAS 28d (<span class="html-italic">n</span> = 6/12)). Data expressed as mean SEM. * or <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, ** or <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 and **** <span class="html-italic">p</span> &lt; 0.0001. (*) Within-group comparisons, (#) between-group comparisons.</p>
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<p>Astrocyte network Ca<sup>2+</sup> activity changes in response to low O<sub>2</sub> post-BCAS surgery. (<b>A</b>) Representative confocal image of multiple GCaMP6f labeled astrocytes in a brain slice. (<b>B</b>) Summary data showing spatial density changes before and after low O<sub>2</sub> treatment. (<b>C</b>,<b>D</b>) Summary data showing temporal density (<b>C</b>) and temporal density with similar size events (<b>D</b>) before and after low O<sub>2</sub> treatment in sham (<span class="html-italic">n</span> = 32), BCAS 14d (<span class="html-italic">n</span> = 29), and BCAS 28d (n-18) mice. Two-way ANOVA followed by Sidak’s MCT. Data expressed as means ± SEM. <sup>#</sup> <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. (*) Within-group comparisons, (#) between-group comparisons.</p>
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<p>Microglia morphological changes post-BCAS surgery. (<b>A</b>) Representative immunofluorescence confocal images of cortical microglia labeled with Iba1 before and after skeleton analysis used for structural quantification. (<b>B</b>) Summary data showing the quantification of microglia arborization properties in sham (<span class="html-italic">n</span> = 12), BCAS 14d (<span class="html-italic">n</span> = 12), and BCAS 28d (<span class="html-italic">n</span> = 12) mice brain slices. One-way ANOVA followed by Holm–Sidak’s MCT. Data expressed as means ± SEM. * <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Quantitative mRNA expression of inflammatory markers in BCAS brains. (<b>A</b>) Summary data showing fold changes in various inflammatory markers for astrocytes and microglia. (<b>B</b>) Summary data showing fold changes in TRPA1 expression level. (<b>C</b>) Summary data showing fold changes in Nrf2 expression level. One sample t and Wilcoxon test (<span class="html-italic">n</span> = 5 per group). Data expressed as means ± SEM. ** <span class="html-italic">p</span> &lt; 0.014. ns = not significant.</p>
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12 pages, 278 KiB  
Article
Explosive Strength and Speed as Potential Determinants of Success in Youth Figure Skating Competitions
by Jiri Helesic and Michal Lehnert
Appl. Sci. 2024, 14(24), 11861; https://doi.org/10.3390/app142411861 - 19 Dec 2024
Viewed by 358
Abstract
This study aimed to determine the extent to which explosive and reactive strength of the lower limbs, as well as acceleration in running and skating speed, predict figure skating competition results in youth skaters. Talented figure skaters aged 8 to 16 years (n [...] Read more.
This study aimed to determine the extent to which explosive and reactive strength of the lower limbs, as well as acceleration in running and skating speed, predict figure skating competition results in youth skaters. Talented figure skaters aged 8 to 16 years (n = 211) were divided into two groups: Group 1 (basic novice; age: 10.38 ± 1.10 yrs., height: 1.3889 ± 0.07.26 m, weight: 32.75 ± 4.63 kg) and Group 2 (advanced novice and junior; age: 13.02 ± 1.06 yrs., height: 1.527 ± 0.0818 m, weight: 42.73 ± 7.62 kg). Fifteen variables of physical fitness were measured using tests such as repeated vertical jump, standing long jump, triple jump (right/left leg), 15 m running sprint, and 15 m skating sprint. The competition results were recorded according to the International Skating Union Code of Points. The principal component analysis reduced the fifteen variables to four principal components, explaining 84–87% of the variance. Linear regression models showed that these components significantly explained the variability in the competition scores for both groups. For Group 1, R2 ranged from 0.298 to 0.425, while for Group 2, it ranged from 0.086 to 0.237. Pearson’s R was higher for the mean best score of the season than for the National Championship score. The relative importance of these factors varied across age groups. These findings highlight the need for tailored on- and off-ice training that focuses on locomotion and acceleration for younger skaters and dynamic jump training for older skaters. Full article
(This article belongs to the Special Issue Advances in the Biomechanics of Sports)
13 pages, 286 KiB  
Article
Discordance Between Triglycerides, Remnant Cholesterol and Systemic Inflammation in Patients with Schizophrenia
by Jeffrey Wang, Maaike Kockx, Gabrielle J. Pennings, Tim Lambert, Vincent Chow and Leonard Kritharides
Biomedicines 2024, 12(12), 2884; https://doi.org/10.3390/biomedicines12122884 - 18 Dec 2024
Viewed by 313
Abstract
Background/Objectives: Hypertriglyceridaemia and systemic inflammation are prevalent in patients with schizophrenia and contribute to an increased risk of cardiovascular disease. Although elevated triglycerides (TGs) and remnant cholesterol are linked to inflammation in the general population and individuals with metabolic syndrome, whether they are [...] Read more.
Background/Objectives: Hypertriglyceridaemia and systemic inflammation are prevalent in patients with schizophrenia and contribute to an increased risk of cardiovascular disease. Although elevated triglycerides (TGs) and remnant cholesterol are linked to inflammation in the general population and individuals with metabolic syndrome, whether they are associated in patients with schizophrenia remains unclear. Methods: Fasting levels of TG, cholesterol (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and remnant cholesterol)), and markers of systemic inflammation including high-sensitivity C-reactive protein (hsCRP), leukocyte counts and their differentials (neutrophils, monocytes and lymphocytes) were determined in 147 patients diagnosed with schizophrenia on long-term antipsychotic regimens and compared with 56 age- and sex-matched healthy controls. Apolipoprotein B and glycosylation of acute phase reactant (GlycA) signatures were assessed by NMR. Circulating cytokine levels were measured by a cytokine/chemokine multiplex assay. Results: Patients with schizophrenia had markedly elevated TG and remnant cholesterol relative to controls and had evidence of systemic inflammation with increased circulating hsCRP, GlycA, leukocyte, neutrophil counts and neutrophil-to-lymphocyte ratio (NLR). Unexpectedly TG and remnant cholesterol did not correlate with systemic inflammatory markers in patients with schizophrenia, and differences in inflammatory markers between controls and patients persisted after adjusting for the lipid profile. Interleukin (IL)-10 levels were increased in patients with schizophrenia, suggesting an anti-inflammatory signature. Conclusions: The discordance between TG, remnant cholesterol and systemic inflammation in patients with schizophrenia suggests these are likely independent contributors to cardiovascular risk in this population. Full article
(This article belongs to the Special Issue Advanced in Schizophrenia Research and Treatment)
18 pages, 7502 KiB  
Article
The Influence of Stability in New Power Systems with the Addition of Phase Modulation Functions in Thermal Power Units
by Mingyang Liu, Chunsun Tian, Xiaoling Yuan, Chenghao Li, Ze Gao and Di Zhang
Processes 2024, 12(12), 2897; https://doi.org/10.3390/pr12122897 - 18 Dec 2024
Viewed by 251
Abstract
The addition of phase modulation function technology to thermal power units is one of the most effective measures to solve dynamic reactive power shortages in the construction process of new power systems. In this paper, the influence of the phase modulation function transformation [...] Read more.
The addition of phase modulation function technology to thermal power units is one of the most effective measures to solve dynamic reactive power shortages in the construction process of new power systems. In this paper, the influence of the phase modulation function transformation of thermal power units on the stability of a new power system is studied. Firstly, the new power system stability index is deeply analyzed, and an evaluation system for power system transient stability is constructed from five key dimensions: transient voltage, static voltage, power angle stability, power flow characteristics, and grid support. Secondly, a fuzzy comprehensive evaluation method considering the subjective and objective comprehensive weights is proposed, and the influence of the phase modulation transformation of the thermal power unit on the stability of the receiving-end power grid is quantitatively analyzed. Finally, a CEPRI36 node example model was built based on the PSASP v.7.91.04.9258 (China Electric Power Research Institute, Beijing, China) platform to verify the accuracy and effectiveness of the proposed method. The results show that the proposed method can quantitatively analyze the impact of adding a phase modulation function to thermal power units on the stability of the power system. At the point of renewable energy connection, the static voltage stability index improved by 42.9%, the transient power angle stability index improved by 32.1%, the multi-feed effective short-circuit ratio index improved by 33.9%, and the comprehensive evaluation score improved by 14.7%. These results further indicate that adding a phase modulation function to thermal power units can provide a large amount of dynamic reactive power support and improve the voltage stability and operational flexibility of the system. Full article
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<p>Weighted quantization analysis based on multi-binary tables.</p>
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<p>Weighted quantitative analysis based on multiple binary criteria.</p>
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<p>A typical PV curve of load bus.</p>
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<p>The flowchart of stability evaluation index system construction for receiving-end power grid.</p>
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<p>The flowchart of the evaluation methodology for the stability of the receiving-end power grid.</p>
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<p>Construction of membership function model.</p>
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<p>CEPRI36-node topology geographical wiring diagram including renewable energy AC/DC system. The red line represents the 500 kV bus voltage and the green line represents the 220 kV bus voltage in <a href="#processes-12-02897-f007" class="html-fig">Figure 7</a>.</p>
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<p>Comparison of stability evaluation indices and scores of the system before unit retrofitting.</p>
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<p>Comparison of stability evaluation indices and scores of the system after unit retrofitting.</p>
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<p>Comprehensive evaluation scores of system stability before and after unit retrofitting.</p>
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26 pages, 10330 KiB  
Article
Anti-Inflammatory Properties of Novel 1,2-Benzothiazine Derivatives and Their Interaction with Phospholipid Model Membranes
by Berenika M. Szczęśniak-Sięga, Jadwiga Maniewska, Benita Wiatrak, Tomasz Janek, Paulina Nowotarska and Żaneta Czyżnikowska
Membranes 2024, 14(12), 274; https://doi.org/10.3390/membranes14120274 - 18 Dec 2024
Viewed by 381
Abstract
The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the [...] Read more.
The design of novel anti-inflammatory drugs remains a critical area of research in the development of effective treatments for inflammatory diseases. In this study, a series of 1,2-benzothiazine was evaluated through a multifaceted approach. In particular, we investigated the potential interactions of the potential drugs with lipid bilayers, an important consideration for membrane permeability and overall pharmacokinetics. In addition, we evaluated their ability to inhibit cyclooxygenase 1 and cyclooxygenase 2 activity and selectivity using both a cyclooxygenase inhibition assay and molecular docking simulations. To evaluate their therapeutic potential, we performed in vitro assays to measure cytokine mRNA expression in inflamed cells. The antioxidant activity was evaluated using both in vitro assays, such as 2,2-diphenyl-1-picrylhydrazyl and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid scavenging, to determine the compounds’ capacity to neutralize free radicals and reduce oxidative stress. Theoretical calculations, including density functional theory, were used to predict the reactivity profiles of the compounds. Full article
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<p>Structure of the model drug—meloxicam.</p>
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<p>Structures of a non-ulcerogenic 1,2-benzothiazine (<b>a</b>) and new designed arylpiperazine derivatives of 1,2-benzothiazine (<b>b</b>–<b>d</b>).</p>
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<p>The exemplary thermograms obtained for DPPC mixed with compounds: (<b>A</b>) <b>BS23</b> and (<b>B</b>) <b>BS24</b> as well as for pure lipid (the first curve from the top—black color): DPPC molar ratios from the top to the bottom: 0 (pure lipid), 0.06, 0.08, 0.10, and 0.12; the direction of the endothermic reaction is upwards.</p>
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<p>Influence of all studied compounds on the DPPC main transition temperature (<b>A</b>); influence of two studied compounds (<b>BS24</b> and <b>BS27</b>) and meloxicam on the DPPC main transition temperature (<b>B</b>).</p>
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<p>Influence of studied compounds on the DPPC peak half-width.</p>
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<p>Relative main transition temperature (T<sub>m</sub>/T<sub>m</sub><sup>0</sup>) for DPPC and DMPC in the presence of studied compounds at compound: phospholipid molar ratio 1:10; T<sub>m</sub><sup>0</sup>—the main transition temperature for pure lipid; T<sub>m</sub>—the main transition temperature in the presence of studied compounds at compound: phospholipid molar ratio 1:10; full symbols—DPPC, open symbols—DMPC.</p>
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<p>Anti-inflammatory effect after incubation of NHDF cells with lipopolysaccharide (LPS) and then the tested compounds. The black column presents the <b>BS23</b> compound and the white column the <b>BS28</b> compound. (<b>A</b>) MTT assay; (<b>B</b>) DCF-DA assay. Data presented as a mean and SD; * <span class="html-italic">p</span> &lt; 0.05—significant difference compared to the control (cells with only medium); # <span class="html-italic">p</span> &lt; 0.05 significant difference compared to the positive control (cells treated with only LPS).</p>
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<p>Relative expression of TNF-α (<b>left panel</b>) and IL-6 (<b>right panel</b>) in NHDF cells. (A) Control—only NHDF cells, (B) NHDF cells incubated with lipopolysaccharide (LPS), (C) NHDF cells incubated with lipopolysaccharide (LPS) treated with 10 µM of <b>BS23,</b> and (D) NHDF cells incubated with lipopolysaccharide (LPS) treated with 10 µM of <b>BS28</b>. The values represent mean ± SD from three experiments. * <span class="html-italic">p</span> &lt; 0.05—significant difference compared to the control (cells with only medium); # <span class="html-italic">p</span> &lt; 0.05 significant difference compared to the positive control (cells treated with only LPS).</p>
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<p>The binding mode of meloxicam (blue and top) and compound <b>BS23</b> (pink and bottom) in the active center of COX-2.</p>
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<p>Synthesis of new 1,2-benzothiazine derivatives <b>BS23</b>–<b>BS30</b>.</p>
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12 pages, 1705 KiB  
Article
Preeclampsia Treatment Aspirin/Clampsilin: Oxidative Stress, sFlt-1/PIGF Soluble Tyrosine Kinase 1, and Placental Growth Factor Monitoring
by Denitsa Kostadinova-Slavova, Kamelia Petkova-Parlapanska, Irina Koleva, Mariya Angelova, Rafaah Sadi J. Al-Dahwi, Ekaterina Georgieva, Yanka Karamalakova and Galina Nikolova
Int. J. Mol. Sci. 2024, 25(24), 13497; https://doi.org/10.3390/ijms252413497 - 17 Dec 2024
Viewed by 220
Abstract
The present study aimed to investigate and compare oxidative stress biomarkers and antioxidant enzyme activity in the serum of women at risk of developing preeclampsia (PE) to prevent adverse pregnancy outcomes through early intervention. Changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and placental [...] Read more.
The present study aimed to investigate and compare oxidative stress biomarkers and antioxidant enzyme activity in the serum of women at risk of developing preeclampsia (PE) to prevent adverse pregnancy outcomes through early intervention. Changes in soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) levels were measured between 11 and 13 gestational weeks (gw.) before the onset of preeclampsia and its associated complications. This study evaluated the feasibility of the sFlt-1/PlGF biomarker ratio in predicting preeclampsia and adverse pregnancy outcomes, with the goal of preventive therapy with acetylsalicylic acid (150 mg daily), with acetylsalicylic acid (75 mg daily) and Clampsilin. For this purpose, the following were evaluated: (1) the levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as parameters of oxidative stress; (2) lipid oxidation; (3) antioxidant enzyme activity; and (4) cytokine production. Analysis of the results showed that pregnant women at risk of preeclampsia had significantly higher levels of ROS, lipid oxidation, and superoxide anion radical (•O2) levels compared to normal pregnancies. In PE, depleted levels of nitric oxide (NO), impaired NO synthase system (NOS), and reduced antioxidant enzyme activity (p < 0.03) suggest that PE patients cannot compensate for oxidative stress (OS). In conclusion, oxidative stress in PE plays a key role, which arises from placental problems and affects both mother and baby. The groups with acetylsalicylic acid therapy (150 mg and 75 mg) were better affected compared to those on Clampsillin. Full article
(This article belongs to the Special Issue Oxidation in Human Health and Disease)
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<p>Present the NO levels, eNOS, and iNOS in serum samples. (<b>A</b>) NO: Normotensive pregnancy (NP); PE patients; PE + 150 mg/day Aspirin; PE + Clampsilin; PE + Aspirin 75 mg/day. (<b>B</b>) eNOS: NP; PE patients; PE + 150 mg/day Aspirin; PE + Clampsilin; PE + Aspirin 75 mg/day. (<b>C</b>) iNOS: NP; PE patients; PE + 150 mg/day Aspirin; PE + Clampsilin; PE + Aspirin 75 mg/day. LSD post hoc test; * <span class="html-italic">p</span> &lt; 0.05 vs. NP group; ** <span class="html-italic">p</span> &lt; 0.05 vs. PE group.</p>
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<p>The levels of oxidative stress markers are presented as MDA, ROS production, and •O<sub>2</sub><sup>−</sup>. (<b>A</b>) MDA levels -NP; PE; PE + Aspirin 150mg/day; PE + Clampsilin; PE + Aspirin 75 mg/day. (<b>B</b>) ROS production— NP; PE; PE + Aspirin 150mg/day; PE + Clampsilin; PE + Aspirin 75 mg/day. (<b>C</b>) NP; PE; PE + Aspirin 150 mg/day; PE + Clampsilin; PE + Aspirin 75 mg/day. LSD post hoc test; * <span class="html-italic">p</span> &lt; 0.05 vs. NP group; ** <span class="html-italic">p</span> &lt; 0.05 vs. PE group.</p>
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<p>Pro-inflammatory cytokine levels: (<b>A</b>) IL-6; (<b>B</b>) TNF-α; (<b>C</b>) IFN-γ; (<b>D</b>) TGF-β; (<b>E</b>) IL-1α; (<b>F</b>) IL-1β; (<b>G</b>) IL-17; (<b>H</b>) IL-22; LSD post hoc test, * <span class="html-italic">p</span> &lt; 0.05 vs. NP; ** <span class="html-italic">p</span> &lt; 0.05 vs. PE.</p>
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<p>Pro-inflammatory cytokine levels: (<b>A</b>) IL-6; (<b>B</b>) TNF-α; (<b>C</b>) IFN-γ; (<b>D</b>) TGF-β; (<b>E</b>) IL-1α; (<b>F</b>) IL-1β; (<b>G</b>) IL-17; (<b>H</b>) IL-22; LSD post hoc test, * <span class="html-italic">p</span> &lt; 0.05 vs. NP; ** <span class="html-italic">p</span> &lt; 0.05 vs. PE.</p>
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13 pages, 5044 KiB  
Article
Development and Application of a Fully Automated Chemiluminescence Enzyme Immunoassay for the Detection of Antibodies Against Porcine Circovirus 3 Cap
by Lei Wang, Duan Li, Daoping Zeng, Xiaomin Wang, Yanlin Liu, Guoliang Peng, Zheng Xu and Changxu Song
Viruses 2024, 16(12), 1925; https://doi.org/10.3390/v16121925 - 17 Dec 2024
Viewed by 355
Abstract
Porcine circovirus 3 (PCV3) is a small non-enveloped circovirus associated with porcine dermatitis and nephropathy syndrome (PDNS). It has occurred worldwide and poses a serious threat to the pig industry. However, there is no commercially available vaccine. PCV3 capsid protein (Cap) is an [...] Read more.
Porcine circovirus 3 (PCV3) is a small non-enveloped circovirus associated with porcine dermatitis and nephropathy syndrome (PDNS). It has occurred worldwide and poses a serious threat to the pig industry. However, there is no commercially available vaccine. PCV3 capsid protein (Cap) is an ideal antigen candidate for serodiagnosis. Here, a novel fully automated chemiluminescence enzyme immunoassay (CLEIA) was developed to detect antibodies (Abs) to Cap in porcine serum. Recombinant PCV3 Cap, self-assembled into virus-like particles (VLPs), was produced using baculovirus and coupled to magnetic particles (Cap-MPs) as carriers. Combined with an alkaline phosphatase (AP)–adamantane (AMPPD) system, Cap-Abs can be rapidly measured on a fully automated chemiluminescence analyzer. Under optimal conditions, a cut-off value of 31,508 was determined, with a diagnostic sensitivity of 96.8% and specificity of 97.3%. No cross-reactivity was observed with PCV1 and PCV2 and other common porcine pathogens, and both intra-assay and inter-assay coefficients were less than 5% and 10%, respectively. Prepared Cap-MPs can be stored at 4 °C for more than 6 months. Importantly, this CLEIA had a good agreement of 95.19% with the commercially available kit, demonstrating excellent analytical sensitivity and significantly reduced operating time and labor. A serological survey was then conducted, and showed that PCV3 continues to spread widely in South China. In conclusion, our CLEIA provides time and labor-saving, and a reliable tool for PCV3 epidemiological surveillance. Full article
(This article belongs to the Special Issue Porcine Viruses 2024)
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<p>Expression and purification of recombinant PCV3 Cap. (<b>A</b>) SDS-PAGE analysis of expression of recombinant Cap. 1,2 cell lysis forms cells infected with recombinant baculovirus, 3 cell lysis forms control, M protein marker. The blue arrow indicates expressed Cap, and the blue pentagram indicates bovine serum albumin (BSA). (<b>B</b>) SDS-PAGE analysis of Cap expression in <span class="html-italic">E. coli</span>, 1 cell lysis forms <span class="html-italic">E. coli</span> uninduced, 2 cell lysis forms <span class="html-italic">E. coli</span> induced by IPTG, 3 lysed supernatant, 4 precipitation, M protein marker. The blue arrow indicates expressed Cap. (<b>C</b>) Purification of recombinant Cap, 1. Cap from Sf9 cells, 2. Cap from <span class="html-italic">E. coli</span>., M protein marker. (<b>D</b>) IB analysis of recombinant Cap using anti-PCV3 Cap monoclonal antibody, 1. Cap from Sf9 cells, 2. Cap from <span class="html-italic">E. coli</span>., M protein marker. (<b>E</b>) TEM images of purified Cap.</p>
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<p>SEM images of MPs and prepared Cap-MPs. Scale bar: 5.0 μm.</p>
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<p>Optimization results for CLEIA. (<b>A</b>) Determination of optimal coating dosage of purified Cap. (<b>B</b>) Determination of optimal dilution of Cap-MPs. (<b>C</b>) Determination of optimal dilution of AP-conjugated goat anti-pig IgG. (<b>D</b>) Optimal reaction time (1, 3, 5, 8 min) for substrate. (<b>E</b>) Optimal antigen–antibody reaction model, one-step and two-step were assessed, respectively.</p>
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<p>Determination of the cut-off value. The analysis was performed on PCV3-positive serum samples (n = 29) and PCV3-negative serum samples (n = 89) using MedCalc software (Version 19.0.1). (<b>A</b>) Dot plot diagram. (<b>B</b>) ROC analysis.</p>
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<p>Cross-reactivity and stability test. (<b>A</b>) Specificity assay. PCV3-negatitive serum, PCV3-positive serum and PCV1, PCV2, PRV, ASFV, CSFV, PRRSV, PEDV, and FMDV positive serum were measured. Data represent the mean ±SD (standard deviation) from three independent experiments. (<b>B</b>) Prepared Cap-MPs were stored with other components at 4 °C for 0, 1, 2, 3, and 6 months. One positive sample and one negative sample were detected.</p>
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<p>Results of positive rates analysis. (<b>A</b>) PCV3 positive rates on farms in different stages of pigs. (<b>B</b>) PCV3 positive rates on farms in different provinces.</p>
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