Polymer-based antibody mimetics (iBodies) target human PD-L1 and function as a potent immune checkpoint blocker.

Immune checkpoint blockade (ICB) using monoclonal antibodies against programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) is the treatment of choice for cancer immunotherapy. However, low tissue permeability, immunogenicity, immune-related adverse effects, and high cost could be possibly improved using alternative approaches. On the other hand, synthetic low-molecular-weight (LMW) PD-1/PD-L1 blockers have failed to progress beyond in vitro studies, mostly due to low binding affinity or poor pharmacological characteristics resulting from their limited solubility and/or stability. Here, we report the development of polymer-based anti-human PD-L1 antibody mimetics (α-hPD-L1 iBodies) by attaching the macrocyclic peptide WL12 to a N-(2-hydroxypropyl)methacrylamide copolymer. We characterized the binding properties of iBodies using surface plasmon resonance, enzyme-linked immunosorbent assay, flow cytometry, confocal microscopy, and a cellular ICB model. We found that the α-hPD-L1 iBodies specifically target human PD-L1 (hPD-L1) and block the PD-1/PD-L1 interaction in vitro, comparable to the atezolizumab, durvalumab, and avelumab licensed monoclonal antibodies targeting PD-L1. Our findings suggest that iBodies can be used as experimental tools to target hPD-L1 and could serve as a platform to potentiate the therapeutic effect of hPD-L1-targeting small molecules by improving their affinity and pharmacokinetic properties.

The effects of green tea extract supplementation on body composition, obesity-related hormones and oxidative stress markers: a grade-assessed systematic review and dose-response meta-analysis of randomised controlled trials.

Research indicates that green tea extract (GTE) supplementation is beneficial for a range of conditions, including several forms of cancer, CVD and liver diseases; nevertheless, the existing evidence addressing its effects on body composition, oxidative stress and obesity-related hormones is inconclusive. This systematic review and meta-analysis aimed to investigate the effects of GTE supplementation on body composition (body mass (BM), body fat percentage (BFP), fat mass (FM), BMI, waist circumference (WC)), obesity-related hormones (leptin, adiponectin and ghrelin) and oxidative stress (malondialdehyde (MDA) and total antioxidant capacity (TAC)) markers. We searched proper databases, including PubMed/Medline, Scopus and Web of Science, up to July 2022 to recognise published randomised controlled trials (RCT) that investigated the effects of GTE supplementation on the markers mentioned above. A random effects model was used to carry out a meta-analysis. The heterogeneity among the studies was assessed using the I2 index. Among the initial 11 286 studies identified from an electronic database search, fifty-nine studies involving 3802 participants were eligible to be included in this meta-analysis. Pooled effect sizes indicated that BM, BFP, BMI and MDA significantly reduced following GTE supplementation. In addition, GTE supplementation increased adiponectin and TAC, with no effects on FM, leptin and ghrelin. Certainty of evidence across outcomes ranged from low to high. Our results suggest that GTE supplementation can attenuate oxidative stress, BM, BMI and BFP, which are thought to negatively affect human health. Moreover, GTE as a nutraceutical dietary supplement can increase TAC and adiponectin.

The effects of conjugated linoleic acid supplementation on anthropometrics and body composition indices in adults: a systematic review and dose-response meta-analysis.

Prior meta-analytic investigations over a decade ago rather inconclusively indicated that conjugated linoleic acid (CLA) supplementation could improve anthropometric and body composition indices in the general adult population. More recent investigations have emerged, and an up-to-date systematic review and meta-analysis on this topic must be improved. Therefore, this investigation provides a comprehensive systematic review and meta-analysis of randomised controlled trials (RCT) on the impact of CLA supplementation on anthropometric and body composition (body mass (BM), BMI, waist circumference (WC), fat mass (FM), body fat percentage (BFP) and fat-free mass (FFM)) markers in adults. Online databases search, including PubMed, Scopus, the Cochrane Library and Web of Science up to March 2022, were utilised to retrieve RCT examining the effect of CLA supplementation on anthropometric and body composition markers in adults. Meta-analysis was carried out using a random-effects model. The I2 index was used as an index of statistical heterogeneity of RCT. Among the initial 8351 studies identified from electronic databases search, seventy RCT with ninety-six effect sizes involving 4159 participants were included for data analyses. The results of random-effects modelling demonstrated that CLA supplementation significantly reduced BM (weighted mean difference (WMD): -0·35, 95 % CI (-0·54, -0·15), P < 0·001), BMI (WMD: -0·15, 95 % CI (-0·24, -0·06), P = 0·001), WC (WMD: -0·62, 95% CI (-1·04, -0·20), P = 0·004), FM (WMD: -0·44, 95 % CI (-0·66, -0·23), P < 0·001), BFP (WMD: -0·77 %, 95 % CI (-1·09, -0·45), P < 0·001) and increased FFM (WMD: 0·27, 95 % CI (0·09, 0·45), P = 0·003). The high-quality subgroup showed that CLA supplementation fails to change FM and BFP. However, according to high-quality studies, CLA intake resulted in small but significant increases in FFM and decreases in BM and BMI. This meta-analysis study suggests that CLA supplementation may result in a small but significant improvement in anthropometric and body composition markers in an adult population. However, data from high-quality studies failed to show CLA's body fat-lowering properties. Moreover, it should be noted that the weight-loss properties of CLA were small and may not reach clinical importance.

Hybrid WT-CNN-GRU-based model for the estimation of reservoir water quality variables considering spatio-temporal features.

Water quality indicators (WQIs), such as chlorophyll-a (Chl-a) and dissolved oxygen (DO), are crucial for understanding and assessing the health of aquatic ecosystems. Precise prediction of these indicators is fundamental for the efficient administration of rivers, lakes, and reservoirs. This research utilized two unique DL algorithms-namely, convolutional neural network (CNNs) and gated recurrent units (GRUs)-alongside their amalgamation, CNN-GRU, to precisely gauge the concentration of these indicators within a reservoir. Moreover, to optimize the outcomes of the developed hybrid model, we considered the impact of a decomposition technique, specifically the wavelet transform (WT). In addition to these efforts, we created two distinct machine learning (ML) algorithms-namely, random forest (RF) and support vector regression (SVR)-to demonstrate the superior performance of deep learning algorithms over individual ML ones. We initially gathered WQIs from diverse locations and varying depths within the reservoir using an AAQ-RINKO device in the study area to achieve this. It is important to highlight that, despite utilizing diverse data-driven models in water quality estimation, a significant gap persists in the existing literature regarding implementing a comprehensive hybrid algorithm. This algorithm integrates the wavelet transform, convolutional neural network (CNN), and gated recurrent unit (GRU) methodologies to estimate WQIs accurately within a spatiotemporal framework. Subsequently, the effectiveness of the models that were developed was assessed utilizing various statistical metrics, encompassing the correlation coefficient (r), root mean square error (RMSE), mean absolute error (MAE), and Nash-Sutcliffe efficiency (NSE) throughout both the training and testing phases. The findings demonstrated that the WT-CNN-GRU model exhibited better performance in comparison with the other algorithms by 13% (SVR), 13% (RF), 9% (CNN), and 8% (GRU) when R-squared and DO were considered as evaluation indices and WQIs, respectively.

Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Previous studies have shown a potential association between nonalcoholic fatty liver disease (NAFLD) and some immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), but this association has not been analyzed systematically. Therefore, we aimed to perform a systematic review and meta-analysis to ascertain a pooled prevalence estimate of NAFLD among patients with RA to fill this gap in knowledge. METHODS: We conducted a literature search in PubMed, Embase, Web of Science, Scopus, and ProQuest, for observational studies published from inception to August 31, 2022, which reported prevalence of NAFLD in 100 or more adult (age, ≥18 y) patients with RA. To be included, NAFLD diagnosis was based on either imaging or histologic assessment. The results were presented as pooled prevalence, odds ratio, and 95% CI. The I2 statistic was used to measure the heterogeneity between studies. RESULTS: This systematic review included 9 eligible studies derived from 4 continents comprising 2178 patients (78.8% women) with RA. The pooled prevalence of NAFLD was 35.3% (95% CI, 19.9-50.6; I2 = 98.6%; P < .001) in patients with RA. All studies used ultrasound for the diagnosis of NAFLD, except for 1 study that used transient elastography. The pooled prevalence of NAFLD in men with RA was significantly higher than in women with RA (35.2%; 95% CI, 24.0-46.5 compared with 22.2%; 95% CI, 17.9-26.58; P for interaction = .048). Each 1-unit increase in body mass index was associated directly with a 24% increased risk of NAFLD in RA patients (adjusted odds ratio, 1.24; 95% CI, 1.17-1.31; I2 = 0.0%; P = .518). CONCLUSIONS: Based on this meta-analysis, 1 in 3 patients with RA had NAFLD, which appears comparable with its overall prevalence among the general population. Clinicians should actively screen for NAFLD in patients with RA.

Risk of Major Adverse Cardiovascular Events in Immune-Mediated Inflammatory Disorders on Biologics and Small Molecules: Network Meta-Analysis.

BACKGROUND AND AIMS: Recent studies raise concern for increased risk of major adverse cardiovascular events (MACE) with Janus kinase (JAK) inhibitors used to treat immune-mediated inflammatory disorders (IMIDs). We aimed to examine MACE risk with licensed biologics and small molecules used commonly between IMIDs: inflammatory bowel disease, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis. METHODS: Data were obtained from systematic searches (from inception to May 31, 2022) in PubMed, Embase, Ovid Medline, Scopus, Cochrane Central, and ClinicalTrials.gov. Studies that assessed a predefined MACE (myocardial infarction, cerebrovascular accident, unstable angina, cardiovascular death, or heart failure) risk in those ≥18 years of age with IMIDs treated with anti-interleukin (IL)-23 antibodies, anti-IL-12/23, anti-tumor necrosis factor α antibodies (anti-TNF-α), or JAK inhibitors were included in a network meta-analysis using a random-effects model with pooled odds ratios (ORs) reported with 95% credible intervals (CrIs) by drug class and disease state. RESULTS: Among 3528 studies identified, 40 (36 randomized controlled trials and 4 cohort studies) were included in the systematic review, comprising 126,961 patients with IMIDs. Based on network meta-analysis of randomized controlled trials, regardless of disease state, anti-TNF-α (OR, 2.49; 95% CrI, 1.14-5.62), JAK inhibitors (OR, 2.64; 95% CrI, 1.26-5.99), and anti-IL-12/23 (OR, 3.15; 95% CrI, 1.01-13.35) were associated with increased MACE risk compared with placebo. There was no significant difference in the magnitude of the MACE risk between classes or based on IMID type. CONCLUSIONS: Anti-IL-12/23, JAK inhibitors, and anti-TNF-α were associated with higher risk of MACE compared with placebo. The magnitude of the increased MACE risk was not different by IMID type. These results require confirmation in larger prospective studies.

Association Between Anxiety/Depression and Gastroesophageal Reflux: A Systematic Review and Meta-Analysis.

INTRODUCTION: An association between gastroesophageal reflux disease (GERD) and common psychiatric conditions, most notably anxiety and depression, has been reported. However, the magnitude of this association is poorly understood. Therefore, we aimed to systematically assess this issue. METHODS: We comprehensively searched multiple bibliographic databases (Embase, PubMed, Scopus, and Web of Science) from inception to May 15, 2023. We retrieved observational studies that reported the prevalence of anxiety and/or depressive symptoms diagnosed by validated questionnaires in ≥100 adults (aged 18 years or older) with GERD. We also included cohort studies that explored the risk of incident GERD in subjects with anxiety/depression vice versa scenario. Finally, we included Mendelian randomization studies that assessed the cause-and-effect relationship between anxiety/depression and GERD. The extracted data were combined using a random-effects model. RESULTS: In total, 36 eligible studies were included. The pooled prevalences of anxiety and depressive symptoms were 34.4% (95% confidence interval [CI] 24.7-44.2; I2 = 99.4%) and 24.2% (95% CI 19.9-28.5; I2 = 98.8%) in subjects with GERD based on 30 studies, respectively. Both anxiety and depressive symptoms were more common in subjects with GERD compared with those in healthy controls (odds ratio = 4.46 [95% CI 1.94-10.25] and odds ratio = 2.56 [95% CI 1.11-5.87], respectively). According to 3 cohort studies, subjects with GERD were at an increased risk of developing anxiety/depression and vice versa. Finally, 3 Mendelian randomization studies showed that genetic liability to these mood disorders is linked to an increased risk of developing GERD and vice versa. DISCUSSION: Up to 1 in 3 subjects with GERD experience anxiety and depression. There is likely a bidirectional causal relationship between anxiety/depression and GERD.

Increased risk of COVID-19 mortality rate in IFITM3 rs6598045 G allele carriers infected by SARS-CoV-2 delta variant.

BACKGROUND: The interferon-induced transmembrane-protein 3 (IFITM3) is a vital component of the immune system's defense against viral infection. Variants in the IFITM3 gene have been linked to changes in expression and the risk of severe Coronavirus disease 2019 (COVID-19). This study aimed to investigate whether IFITM3 rs6598045, quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) values, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are associated with an increased mortality rate of COVID-19. METHODS: The genotyping of IFITM3 rs6598045 polymorphism was analyzed using the amplification refractory mutation system-polymerase chain reaction in 1342 recovered and 1149 deceased patients positive for SARS-CoV-2. RESULTS: In this study, IFITM3 rs6598045 G allele as minor allele frequency was significantly more common in the deceased patients than in the recovered ones. Furthermore, the highest mortality rates were observed in Delta variant and lowest qPCR Ct values. COVID-19 mortality was associated with IFITM3 rs6598045 GG and AG in Delta variant and IFITM3 rs6598045 AG in Alpha variant. A statistically significant difference was observed in the qPCR Ct values between individuals with GG and AG genotypes and those with an AA genotype. CONCLUSION: A possible correlation was observed between the mortality rate of COVID-19, the G allele of IFITM3 rs6598045, and SARS-CoV-2 variants. However, large-scale research is still required to validate our results.

The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Endothelial dysfunction serves as an early marker for the risk of cardiovascular disease (CVD); therefore, it is an attractive site of therapeutic interventions to reduce the risk of CVD. This study was conducted to investigate the effect of folic acid supplementation on endothelial function markers in randomized controlled trials (RCTs). METHODS: PubMed, ISI web of science, and Scopus databases were searched up to July 2022 for detecting eligible studies. A random-effects model was used for meta-analysis, and linear Meta-regression and non-linear dose-response analysis were performed to assess whether the effect of folic acid supplementation was affected by the dose and duration of intervention. Cochrane tools were also used to assess the risk of bias in the included studies. RESULTS: Twenty-one studies, including 2025 participants (1010 cases and 1015 controls), were included in the present meta-analysis. Folic acid supplementation significantly affected the percentage of flow-mediated dilation (FMD%) (WMD: 2.59%; 95% CI: 1.51, 3.67; P < 0.001) and flow-mediated dilation (FMD) (WMD: 24.38 µm; 95% CI: 3.08, 45.68; P = 0.025), but not end-diastolic diameter (EDD) (WMD: 0.21 mm; 95% CI: - 0.09, 0.52; P = 0.176), and intercellular adhesion molecule (ICAM) (WMD: 0.18 ng/ml; 95% CI: - 10.02, 13.81; P = 0.755). CONCLUSIONS: These findings suggest that folic acid supplementation may improve endothelial function by increasing FMD and FMD% levels. TRIAL REGISTRATION: PROSPERO registration cod: CRD42021289744.

The effects of Gymnema Sylvestre supplementation on lipid profile, glycemic control, blood pressure, and anthropometric indices in adults: A systematic review and meta-analysis.

There is a growing interest in the considerable health benefits of Gymnema Sylvestre (GS) supplementation, as some studies have reported that it may improve cardiometabolic risk factors. However, the widespread impact of GS supplementation on the parameters mentioned above is not fully resolved. Consequently, this study aimed to examine the effects of GS supplementation on lipid profile, glycemic control, blood pressure, and anthropometric indices in adults. Eligible randomized controlled trials (RCT), published up to November 2021, were identified through PubMed, Scopus, and ISI Web of Science databases. Six studies were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI). All studies were conducted in adults that used a GC supplement (>1 week) and assessed our selected cardiovascular risk factors. Outcomes revealed that GS supplementation significantly decreased triglyceride (p < .001), total cholesterol (p < .001), low-density lipoprotein (p < .001), fasting blood sugar (p < .001), and diastolic blood pressure (p = .003). Some limitations, including notable heterogeneity, low quality of studies, and lack of diversity among research participants, should be considered when interpreting our results. Our outcomes suggest that GS supplementation may improve cardiovascular risk factors. Future large-high-quality RCTs with longer duration and various populations are needed to firmly establish the clinical efficacy of the plant.

A comparative study of data-driven models for runoff, sediment, and nitrate forecasting.

Effective prediction of qualitative and quantitative indicators for runoff is quite essential in water resources planning and management. However, although several data-driven and model-driven forecasting approaches have been employed in the literature for streamflow forecasting, to our knowledge, the literature lacks a comprehensive comparison of well-known data-driven and model-driven forecasting techniques for runoff evaluation in terms of quality and quantity. This study filled this knowledge gap by comparing the accuracy of runoff, sediment, and nitrate forecasting using four robust data-driven techniques: artificial neural network (ANN), long short-term memory (LSTM), wavelet artificial neural network (WANN), and wavelet long short-term memory (WLSTM) models. These comparisons were performed in two main tiers: (1) Comparing the machine learning algorithms' results with the model-driven approach; In order to simulate the runoff, sediment, and nitrate loads, the Soil and Water Assessment Tool (SWAT) model was employed, and (2) Comparing the machine learning algorithms with each other; The wavelet function was utilized in the ANN and LSTM algorithms. These comparisons were assessed based on the substantial statistical indices of coefficient of determination (R-Squared), Nash-Sutcliff efficiency coefficient (NSE), mean absolute error (MAE), and root mean square error (RMSE). Finally, to prove the applicability and efficiency of the proposed novel framework, it was successfully applied to Eagle Creek Watershed (ECW), Indiana, U.S. Results demonstrated that the data-driven algorithms significantly outperformed the model-driven models for both the calibration/training and validation/testing phases. Furthermore, it was found that the coupled ANN and LSTM models with wavelet function led to more accurate results than those without this function.

Photocatalytic activity of visible-light-driven L-Proline-TiO2/BiOBr nanostructured materials for dyes degradation: The role of generated reactive species.

L-Proline (2%)-TiO2/BiOBr (30%) nanocomposite was synthesized to obtain high photocatalytic performance in the visible light region and infrared radiation(IR) for methylene blue (MB) and congo red (CR) removal from the contaminated wastewater. L-Proline (2%)-TiO2/BiOBr (30%) photocatalyst with strong absorption near IR wavelength and high charge separation ability was fabricated for the first time. X-ray diffraction (XRD), Fourier transform infrared (FTIR), field-emission scanning electron microscope (FESEM)/Energy Dispersive X-ray (EDX), UV-Vis diffuse reflectance spectrum (DRS), photoluminescence (PL) and Brunauer-Emmett-Teller (BET) characterization techniques show that the visible driven nanocomposite was successfully synthesized. According to the UV-DRS analysis, the estimated band gaps for the L-proline (2%)-TiO2 and L-Proline (2%)-TiO2/BiOBr (30%) nanostructures were respectively 2.3 eV and 2.1 eV.The nanoparticles exhibited enhanced photocatalytic activity (93-100%) and high mineralization efficiency (71-89% TOC removal) for both the dyes. The best photocatalytic activity was achieved by adding 2 wt% of L-Proline and 30 wt% of BiOBr into TiO2 sol. Response surface methodology (RSM) was employed to find significant parameters and their optimum values for maximum degradation, which show pH, dye concentration, irradiation time, and catalyst dosage for both the dyes are significant. The best photocatalytic degradation efficiency was achieved at the optimum conditions of pH = 7.7, catalyst dosage = 0.71 g/L, irradiation time = 142 and dye concentration = 11 mg/L for MB. Scavenger study showed that •OH radicals are responsible for the degradation process.

The effects of L-carnitine supplementation on inflammatory and anti-inflammatory markers in adults: a systematic review and dose-response meta-analysis.

L-carnitine supplementation may be beneficial in improving inflammatory conditions and reducing the level of inflammatory cytokines. Therefore, according to the finding of randomized controlled trials (RCTs), the systematic review and meta-analysis aimed to investigate the effect of L-carnitine supplementation on inflammation in adults. To obtain acceptable articles up to October 2022, a thorough search was conducted in databases including PubMed, ISI Web of Science, the Cochrane Library, and Scopus. A random-effects model was used to estimate the weighted mean difference (WMD). We included the 48 RCTs (n = 3255) with 51 effect sizes in this study. L-carnitine supplementation had a significant effect on C-reactive protein (CRP) (p < 0.001), interleukin-6 (IL-6) (p = 0.001), tumor necrosis factor-α (TNF-α) (p = 0.002), malondialdehyde (MDA) (p = 0.001), total antioxidant capacity (TAC) (p = 0.029), alanine transaminase (ALT) (p < 0.001), and aspartate transaminase (AST) (p < 0.001) in intervention, compared to the placebo group. Subgroup analyses showed that L-carnitine supplementation had a lowering effect on CRP and TNF-α in trial duration ≥ 12 weeks in type 2 diabetes and BMI ≥ 25 kg/m2. L-carnitine supplementation reduced ALT levels in overweight and normal BMI subjects at any trial dose and trial duration ≥ 12 weeks and reduced AST levels in overweight subjects and trial dose ≥ 2 g/day. This meta-analysis revealed that L-carnitine supplementation effectively reduces the inflammatory state by increasing the level of TAC and decreasing the levels of CRP, IL-6, TNF-α and MDA in the serum.

Accuracy of artificial intelligence in the detection and segmentation of oral and maxillofacial structures using cone-beam computed tomography images: a systematic review and meta-analysis.

Purpose: The aim of the present systematic review and meta-analysis was to resolve the conflicts on the diagnostic accuracy of artificial intelligence systems in detecting and segmenting oral and maxillofacial structures using cone-beam computed tomography (CBCT) images. Material and methods: We performed a literature search of the Embase, PubMed, and Scopus databases for reports published from their inception to 31 October 2022. We included studies that explored the accuracy of artificial intelligence in the automatic detection or segmentation of oral and maxillofacial anatomical landmarks or lesions using CBCT images. The extracted data were pooled, and the estimates were presented with 95% confidence intervals (CIs). Results: In total, 19 eligible studies were identified. As per the analysis, the overall pooled diagnostic accuracy of artificial intelligence was 0.93 (95% CI: 0.91-0.94). This rate was 0.93 (95% CI: 0.89-0.96) for anatomical landmarks based on 7 studies and 0.92 (95% CI: 0.90-0.94) for lesions according to 12 reports. Moreover, the pooled accuracy of detection and segmentation tasks for artificial intelligence was 0.93 (95% CI: 0.91-0.94) and 0.92 (95% CI: 0.85-0.95) based on 14 and 5 surveys, respectively. Conclusions: Excellent accuracy was observed for the detection and segmentation objectives of artificial intelligence using oral and maxillofacial CBCT images. These systems have the potential to streamline oral and dental healthcare services.

Impact of interferon-induced transmembrane protein 3 gene rs12252 polymorphism on COVID-19 mortality.

BACKGROUND AND AIMS: Interferon-induced transmembrane protein 3 (IFITM3) plays a critical role in the adaptive and innate immune response by preventing membrane hemifusion between the host and viral cell cytoplasm. This study aimed to evaluate whether IFITM3 rs12252 polymorphism is related to an increased mortality rate of coronavirus disease 2019 (COVID-19). METHODS: The IFITM3 rs12252 polymorphism was genotyped using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 548 dead and 630 improved patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: In the present study, the minor allele frequency of IFITM3 rs12252 (C) was significantly more frequent in dead patients than in improved cases. The results of the multivariate logistic regression analysis indicated that the lower lipid profiles, PCR Ct value, 25-hydroxyvitamin D, and uric acid and higher levels of erythrocyte sedimentation rate (ESR), liver enzymes, and creatinine, and IFITM3 rs12252 CC genotypes were related to the COVID-19 infection mortality. CONCLUSIONS: In summary, our findings suggested a possible link between the mortality of COVID-19 infection, the CC genotypes of IFITM3 rs12252, and clinical parameters. Further investigations are required worldwide to prove the link relationship of COVID-19 mortality with host genetic factors.

The effects of conjugated linoleic acid supplementation on liver function enzymes and malondialdehyde in adults: A GRADE-assessed systematic review and dose-response meta-analysis.

BACKGROUND: Previous research reported inconsistent findings regarding the effects of conjugated linoleic acid (CLA) supplementation on liver enzymes. This systematic review and meta-analysis was conducted to summarize data from available randomized clinical trials (RCTs) on the effect of CLA supplementation on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) in adults. METHODS: Google Scholar, PubMed, Web of Science, Scopus, and the Cochrane databases were investigated to identify relevant articles up to July 2022. The weighted mean differences (WMD) and 95 % confidence intervals (CI) were calculated via a random-effects model to evaluate the effect size. Between studies, heterogeneity was evaluated by the Cochran's Q test and I2. RESULTS: 22 RCTs with 26 effect sizes were included. The effect size for ALT (IU/L), AST (IU/L), and MDA (µmol/L) were 19, 19 and 6 respectively. The pooled analysis demonstrated CLA decreases MDA (p = 0.003). However, ALT and AST levels did not change after CLA supplementation compared with control group. CONCLUSION: CLA supplementation may significantly reduce MDA levels as a marker of oxidative stress. However, supplementing with CLA failed to alter ALT and AST.

Worldwide and Regional Efficacy Estimates of First-line Helicobacter pylori Treatments: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Eradication of Helicobacter pylori infection is challenging. We aimed to determine the optimal first-line H. pylori treatments at global and regional levels. METHODS: We searched Embase, PubMed, Cochrane CENTRAL, Web of Science, Scopus, WHO ICTRP, ClinicalTrials.gov, and ISRCTN registry, for randomized controlled trials published during 2011-2020. Utilizing a network meta-analysis in a Bayesian framework, success rates of 23 regimens were compared. The effect size was standardized risk ratio (RR) with 95% credible interval (CrI). Pooled eradication rate (ER) with 95% CrI was also reported for top combinations. The reference regimen was 7-day clarithromycin-based triple therapy. RESULTS: This review identified 121 trials comprising 34,759 participants. Globally, 14-day levofloxacin-based sequential therapy was the most efficient (RR: 1.43; 95% CrI, 1.26-1.59) with low certainty of evidence, followed by modified bismuth-containing quadruple therapy (proton pump inhibitor+bismuth compounds+clarithromycin+amoxicillin) for 10 days (RR: 1.35; 95% CrI, 1.22-1.48) and 14 days (RR: 1.27; 95% CrI, 1.12-1.42), and 14-day hybrid therapy (RR: 1.27; 95% CrI, 1.19-1.36). The corresponding ERs were 98.7% (95% CrI, 86.9-100.0), 93.2% (95% CrI, 84.2-100.0), 87.6% (95% CrI, 82.1-93.8), and 87.6% (95% CrI, 77.3-98.0), respectively. Continentally, the most effective combinations were: 10-day clarithromycin-based sequential therapy [(RR: 1.21; 95% CrI, 1.02-1.42), (ER: 89.5%, 95% CrI, 75.5-100.0)] for Africa, 14-day levofloxacin-based sequential therapy [(RR: 1.41; 95%CrI, 1.27-1.58), (ER: 98.7%, 95% CrI, 88.9-100.0)] for Asia, and 14-day clarithromycin-based triple therapy [(RR: 1.58; 95% CrI, 1.25-2.04), (ER: 94.8%; 95% CrI, 75.0-100.0)] for Europe. For Northern America, no sufficient data were found for network meta-analysis. In South America, none of the combinations were superior to the reference regimen. CONCLUSION: Although results of this network meta-analysis revealed optimal combinations for empiric therapy, the treatment preference would be based on the local pattern of antibacterial resistance, when the necessary information exists.

Angiotensin-converting enzyme 2 rs2285666 polymorphism and clinical parameters as the determinants of COVID-19 severity in Iranian population.

Host genetic factors may be correlated with the severity of coronavirus disease 2019 (COVID-19). Angiotensin-converting enzyme 2 (ACE2) plays a vital role in viral cell entrance. The current study aimed to evaluate the association of ACE2 rs2285666 polymorphism and clinical parameters with COVID-19 mortality. The ACE2 rs2285666 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism in 556 recovered and 522 dead patients. In this study, the frequency of ACE2 rs2285666 CC was significantly higher than TT genotype in dead patients. The multivariate logistic regression analysis results showed that the higher levels of alanine aminotransferase, alkaline phosphatase, creatinine, erythrocyte sedimentation rate, and C-reactive protein and the low levels of uric acid, cholesterol, low density lipoprotein, 25-hydroxyvitamin D, real-time PCR Ct values, and ACE2 rs2285666 CC genotype were associated with increased mortality rates after COVID-19. In conclusion, our findings demonstrated a possible link between COVID-19 mortality, clinical parameters, and ACE2 rs2285666 CC. Further research is required to confirm these results.

Anemia prevalence, severity, types, and correlates among adult women and men in a multiethnic Iranian population: the Khuzestan Comprehensive Health Study (KCHS).

BACKGROUND: Despite all recent health-related improvements, anemia remains an extensive global public health issue affecting the lives of about one-fourth of the world population in a geographically heterogeneous pattern. We, therefore, aimed to illustrate the prevalence, severity, most common types, and major determinants of anemia among adults in Khuzestan, Iran, from 2016 to 2019. METHODS: In a large population-based cross-sectional study comprising of a diverse population, each participant underwent a questionnaire-based interview and laboratory testing for hematological analysis. A hemoglobin (HGB) concentration of < 12 g/dL in non-pregnant women and < 13 g/dL in men were defined anemic. The multivariate logistic regression analysis was performed to explore the association between anemia and its potential determinants. RESULTS: Data on 29,550 (96.87%) males and non-pregnant females between 20-65 years of age (mean age: 41.90 ± 11.88 years; female sex: 63.58%; Arab ethnicity: 48.65%), whose HGB level was available, were included in the study. The mean ± SD HGB concentration was 13.75 ± 1.65 g/dL. The age- and sex-standardized prevalence rate of anemia was 10.86% (95% CI: 10.51-11.23%). The most prevalent degree was mild anemia (7.71%, 95% CI: 7.40-8.03%) and only 0.17% were severely anemic. Of those considered anemic, the highest proportion was related to normochromic/microcytic (50.65%), followed by hypochromic/microcytic (30.29%). In the multiple logistic regression, the parameters of female gender (OR: 3.17, 95% CI: 2.68-3.76), age group of 35-49 years (OR: 1.66, 95% CI: 1.52-1.82), being underweight (OR: 1.58, 95% CI: 1.29-1.93), being unemployed or retired (OR: 1.55, 95% CI: 1.33-1.81), and living in urban areas (OR: 1.18, 95% CI: 1.09-1.29) were major determinants of anemia. Additionally, we observed a minor but significant positive association between anemia status and CKD, older ages, increased night sleep duration, being a housewife and married, as well as a negative association between anemia and factors including hookah smoking, presence of metabolic syndrome, and overweight and obesity. CONCLUSIONS: Taken together, the anemia prevalence in this study population was of mild public health significance. The major suspected causes might be iron deficiency and chronic disease anemias. Comparably higher rates of anemia were observed amongst women, individuals aged 35-49 years, underweights, unemployed or retired subjects, and urban residents.

Seroprevalence of SARS-CoV-2 antibody among urban Iranian population: findings from the second large population-based cross-sectional study.

BACKGROUND: The first large serosurvey in Iran found a SARS-CoV-2 antibody seroprevalence of 17.1% among the general population in the first wave of the epidemic by April, 2020. The purpose of the current study was to assess the seroprevalence of COVID-19 infection among Iranian general population after the third wave of the disease. METHODS: This population-based cross-sectional study was conducted on 7411 individuals aged ≥10 years old in 16 cities across 15 provinces in Iran between January and March, 2021. We randomly sampled individuals registered in the Iranian electronic health record system based on their national identification numbers and invited them by telephone to a healthcare center for data collection. Presence of SARS-CoV-2-specific IgG and IgM antibodies was assessed using the SARS-CoV-2 ELISA kits. The participants were also asked about their recent COVID-19-related symptoms, including cough, fever, chills, sore throat, headache, dyspnea, diarrhea, anosmia, conjunctivitis, weakness, myalgia, arthralgia, altered level of consciousness, and chest pain. The seroprevalence was estimated after adjustment for population weighting and test performance. RESULTS: The overall population-weighted seroprevalence adjusted for test performance was 34.2% (95% CI 31.0-37.3), with an estimated 7,667,874 (95% CI 6,950,412-8,362,915) infected individuals from the 16 cities. The seroprevalence varied between the cities, from the highest estimate in Tabriz (39.2% [95% CI 33.0-45.5]) to the lowest estimate in Kerman (16.0% [95% CI 10.7-21.4]). In the 16 cities studied, 50.9% of the seropositive individuals did not report a history of symptoms suggestive of COVID-19, implying an estimation of 3,902,948 (95% CI 3,537,760-4,256,724) asymptomatic infected individuals. CONCLUSIONS: Nearly one in three individuals were exposed to SARS-CoV-2 in the studied cities by March 2021. The seroprevalence increased about two-fold between April, 2020, and March, 2021.