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The detection of evolutionary transitions in influenza A (H3N2) viruses' antigenicity is a major obstacle to effective vaccine design and development. In this study, we describe Novel Influenza Virus A Detector (NIAViD), an unsupervised machine learning tool, adept at identifying these transitions, using the HA1 sequence and associated physico-chemical properties. NIAViD performed with 88.9% (95% CI, 56.5–98.0%) and 72.7% (95% CI, 43.4–90.3%) sensitivity in training and validation, respectively, outperforming the uncalibrated null model—33.3% (95% CI, 12.1–64.6%) and does not require potentially biased, time-consuming and costly laboratory assays. The pivotal role of the Boman's index, indicative of the virus's cell surface binding potential, is underscored, enhancing the precision of detecting antigenic transitions. NIAViD's efficacy is not only in identifying influenza isolates that belong to novel antigenic clusters, but also in pinpointing potential sites driving significant antigenic changes, without the reliance on explicit modelling of haemagglutinin inhibition titres. We believe this approach holds promise to augment existing surveillance networks, offering timely insights for the development of updated, effective influenza vaccines. Consequently, NIAViD, in conjunction with other resources, could be used to support surveillance efforts and inform the development of updated influenza vaccines. [ABSTRACT FROM AUTHOR]

Background: Recent evidence shows the role of sirtuin 1(SIRT1), a family of evolutionarily conserved proteins, as a potential therapeutic target in the prevention and treatment of obesity and metabolic diseases. Some evidence shows the moderating effects of weight loss interventions on this factor. However, the findings are contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of weight loss interventions on SIRT 1 modulation. Methods: For this study, we searched four electronic databases using predefined keywords from inception until March 2024. We includedrandomized controlled trials that evaluated the effect of weight reduction strategies on SIRT1 levels. The random-effects model analysis was used to obtain the pooled weighted mean difference (WMD) and 95% confidence intervals (95% CI). The meta-analysis was conducted using RevMan version 5.3 software and Stata version 12.0. Results: Twelve studies with 627 volunteers were included. The pooled findings showed that weight loss interventions have no significant effect on the modulation of SIRT1 compared to the control group (pooled WMD of 0.58 ng/mL; 95% confidence interval [CI] -0.17 to 1.33; p = 0.130). However, subgroup analysis showed that weight loss interventions significantly modulate SIRT1 at metabolic disease (WMD: 1.2 ng/mL, 95% CI: 0.11 to 2.62, I2 = 82.9%). In addition, subgroup findings indicated health status and body mass index (BMI) as sources of high and potential heterogeneity. Conclusions: Based on the findings, weight loss therapies in individuals having a metabolic disorder appear to generate a considerable increase in SIRT1 levels. [ABSTRACT FROM AUTHOR]

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multicenter study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in 1 patient, respectively. In 3 patients (18.7%), no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD. Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. The high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD. Graphical Abstract [ABSTRACT FROM AUTHOR]

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression. [ABSTRACT FROM AUTHOR]

Background: Overall, there is conflicting evidence regarding the beneficial effects of optimal lifestyle modification, particularly weight loss interventions, with nonalcoholic fatty liver disease (non‐alcoholic fatty liver disease (NAFLD)). Therefore, this study investigated the effects of weight loss interventions on laboratory and clinical parameters in children and adolescents with NAFLD. Methods: Original databases (PubMed/MEDLINE, Web of Science, SCOPUS, and Embase) were searched using standard keywords to identify all controlled trials investigating the effects of weight loss interventions among NAFLD children and adolescents. Pooled weighted mean difference and 95% confidence intervals were achieved by random‐effects model analysis. Results: Eighteen eligible clinical trials were included in this systematic review and meta‐analysis. The pooled findings showed that especially more intense weight loss interventions significantly reduced the glucose (p = 0.007), insulin (p = 0.002), homeostatic model assessment‐insulin resistance (HOMA‐IR) (p = 0.003), weight (p = 0.025), body mass index (BMI) (p = 0.003), BMI z‐score (p < 0.001), waist circumference (WC) (p = 0.013), triglyceride (TG) (p = 0.001), and aspartate transaminase (AST) (p = 0.027). However, no significant changes were found in total cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), alanine transaminase (ALT), and hepatic steatosis grades (all p > 0.05) following weight loss interventions. Conclusions: Weight loss interventions had significant effects on NAFLD‐related parameters including glucose, insulin, HOMA‐IR, weight, BMI, BMI z‐score, WC, TG, and AST. [ABSTRACT FROM AUTHOR]

Recent evidence shows the beneficial effects of Baltic Sea diet score (BSDS) and healthy Nordic diet index (HNDI) on chronic diseases, however, there is no evidence to investigate them on the risk of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to investigate the associations between BSDS and HNDI with the risk of NAFLD. In this case–control study, 552 people in good health and 340 people with NAFLD over the age of 18 took part. The evaluation of BSDS and HNDI employed a validated 168-item semi-quantitative food frequency questionnaire (FFQ). Binary logistic regression was used to determine how OBS and NAFLD are related. The mean BSDS and HNDI were 16.00 ± 2.49 and 11.99 ± 2.61, respectively. The final model's confounder adjustment revealed that greater HNDI adherence scores gave protection against the occurrence of NAFLD (odds ratio [OR]: 0.42; 95% confidence interval [CI] 0.18–0.98; P for trend = 0.043). In addition, those with the highest BSDS scores had significantly lower risks of developing NAFLD compared to subjects with the lowest scores (OR = 0.48, 95% CI 0.32–0.89; p for trend = 0.003). Our findings showed that following a healthy Nordic diet can significantly prevent the risk of developing NAFLD, and suggest that the highly nutritious components of the Nordic diet are beneficial for the prevention of NAFLD. [ABSTRACT FROM AUTHOR]

Background: Considering the conflicting effects of bupropion on parameters related to metabolic syndrome including glucose metabolism and lipid profile, in this meta‐analysis study, we investigated the effects of this drug alone or in combination with naltrexone on glucose metabolism and lipid profile. Methods: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the glucose and lipid profile. Pooled weighted mean difference and 95% confidence intervals were achieved by random‐effects model. Results: Twelve studies with 5152 participants' were included in this article. The pooled findings showed that bupropion alone or in combination with naltrexone would significantly reduce glucose (weighted mean difference (WMD): −2.25 mg/dL, 95% confidence interval (CI): −4.10, −0.40), insulin (WMD: −4.06 μU/mL, 95% CI: −6.09, −2.03), homeostatic model assessment for insulin resistance (HOMA‐IR) (WMD: −0.58, 95% CI: −0.98, −0.19), triglyceride (TG) (WMD: −11.78 mg/dL, 95% CI: −14.48 to −9.08) and increase high‐density lipoprotein (HDL) (WMD: 2.68 mg/dL, 95% CI: 2.13 to 3.24). A Greater reduction in glucose levels was observed with duration >26 weeks. Dose of bupropion intake ≤360 mg and intervention for more than 26 weeks decreased insulin level significantly. With regard to lipid profile, reduction of triglycerides is more significant with dose of bupropion greater than 360 mg and a shorter intervention length equal to 26 weeks. Conclusions: The addition of combination therapies such as bupropion and naltrexone to lifestyle modification can significantly improve glucose metabolism and some lipid parameters. [ABSTRACT FROM AUTHOR]

Fisheries and aquaculture provide food and economic security, especially in the developing world, but both face challenges from infectious disease. Here, we consider management of disease issues from a structured decision‐making perspective to examine how infectious disease can threaten seafood production and influence management decisions. For both wild fisheries and aquaculture, disease‐management objectives generally aim to mitigate the severity and economic burden of outbreaks. General management strategies include manipulating host densities, reducing system connectivity, conserving or improving habitat, and implementing direct treatments or some other biological interventions. To inform decisions, mathematical models can be used to explore disease dynamics and to forecast the potential effectiveness of alternative management actions. Developing and implementing disease‐management strategies also involve considering uncertainties and balancing competing stakeholder interests and risk tolerances. We conclude by outlining several steps for applying structured decision making that are broadly useful to decision makers facing issues related to disease. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P = < 0.001), steatosis score (P = 0.001), NAFLD activity score (P = < 0.001), weight (P = < 0.001), body mass index (BMI) (P = < 0.001), waist circumferences (WC) (P = < 0.001), BMI-Z score (P = < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P = < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders. Conclusion: The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. Trial Registration: (Clinical trial registry number: IRCT20220409054467N2, with a registration date of 2022–05-13). What is Known: • Among the interventions of interest for the management of pediatric NAFLD, we can mention lifestyle and pharmaceutical measures. What is New: • This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. • The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks. [ABSTRACT FROM AUTHOR]

Prediction and control of emerging pathogens is a fundamental challenge for public health. To meet this challenge, new analytic tools are needed to characterize the underlying dynamics of the geographical spread of pathogens, identify predictable changes in their dynamics, and support strategic planning for disease elimination and control. Nonparametric and model-independent tools are particularly needed. Here, we propose a multivariate method that uses similarity in cross-spectral density between measured spatial time series of disease prevalence as a feature measuring the proximity of a tipping point, i.e., emergence or elimination. In particular, we show that the increase in the average value of spectral similarity in measured epidemiological time series contains crucial information about the underlying dynamics and proximity to critical points in infectious disease systems. Theoretical analysis of a standard metapopulation SIR model and empirical analysis of case reports of pertussis in the continental USA demonstrate that this increase is observed when the disease approaches elimination. Therefore, this nonparametric indicator provides insight into the fundamental underlying state of the epidemiological system, which is key in developing appropriate strategies to more quickly achieve elimination goals. [ABSTRACT FROM AUTHOR]

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric inflammatory bowel disease (IBD). We analyzed 73 pediatric patients with IBD with a retrospective study design who underwent measurement of fecal calprotectin (FC) and endoscopy and 67 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. We also plotted the ROC diagrams separately for markers to obtain the optimal point and a suitable cutoff point. We enrolled 73 pediatric patients less than 18 years of age with IBD, 40 subjects with UC and 33 with CD and 67 healthy subjects as control group with median age of 9.00 ± 4.61 in all subjects. Furthermore, the mean score of PCDAI or PUCAI in the all subjects was 19.26 ± 16.31. In the ROC curve, the optimal cutoff value for NLR and PLR for detecting IBD was 2.04 (sensitivity 82.1%; specificity 82.9%) and 103 (sensitivity 67.9%; specificity 71.4%). Also, the optimal cutoff values for NLR and PLR for differentiating IBD severity (remission vs. active disease) were 2.94 (sensitivity 77.8%; specificity 50.0%) and 157 (sensitivity 88.9%; specificity 54.5%), respectively. Conclusion: Our findings indicate the role of easy and non-invasive markers such as NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease. What is Known: • NLR and PLR are simple and inexpensive inflammatory biomarkers that reflect systemic inflammation based on complete blood count values. What is New: • In this study, we investigate the role of these biomarkers in the diagnosis and severity of pediatric IBD. • Our findings indicate the role of NLR and PLR in order to diagnose the disease in the initial examinations as well as the severity of the disease. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of Tirzepatide. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of subcutaneous Tirzepatide on obesity and overweight. Methods: Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss effects of Tirzepatide. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes. The statistical heterogeneity and publication bias were determined using the Cochran's Q test and I2 statistics and using the funnel plot and Egger's test, respectively. Results: Twenty three treatments arm with 7062 participants' were included in this systematic review and meta-regression analysis. The pooled findings showed that Tirzepatide vs placebo significantly reduced body weight (weighted mean difference (WMD): -11.34 kg, 95% confidence interval (CI): -12.79 to -9.88, P< 0.001), body mass index (BMI) (WMD: -3.11 kg/m2, 95% CI: -4.36 to -1.86, P< 0.001), and waist circumference (WC) (WMD: -7.24 cm, 95% CI -10.12 to -4.36, P< 0.001). These reductions were even greater, especially with higher doses and duration of Tirzepatide. Conclusions: Tirzepatide medication had significant effects on weight management with the reduction of body weight, BMI, and WC. Administration of Tirzepatide can be considered a therapeutic strategy for overweight or obese people. [ABSTRACT FROM AUTHOR]

The spread of SARS-CoV-2 has been geographically uneven. To understand the drivers of this spatial variation in SARS-CoV-2 transmission, in particular the role of stochasticity, we used the early stages of the SARS-CoV-2 invasion in Washington state as a case study. We analysed spatially-resolved COVID-19 epidemiological data using two distinct statistical analyses. The first analysis involved using hierarchical clustering on the matrix of correlations between county-level case report time series to identify geographical patterns in the spread of SARS-CoV-2 across the state. In the second analysis, we used a stochastic transmission model to perform likelihood-based inference on hospitalised cases from five counties in the Puget Sound region. Our clustering analysis identifies five distinct clusters and clear spatial patterning. Four of the clusters correspond to different geographical regions, with the final cluster spanning the state. Our inferential analysis suggests that a high degree of connectivity across the region is necessary for the model to explain the rapid inter-county spread observed early in the pandemic. In addition, our approach allows us to quantify the impact of stochastic events in determining the subsequent epidemic. We find that atypically rapid transmission during January and February 2020 is necessary to explain the observed epidemic trajectories in King and Snohomish counties, demonstrating a persisting impact of stochastic events. Our results highlight the limited utility of epidemiological measures calculated over broad spatial scales. Furthermore, our results make clear the challenges with predicting epidemic spread within spatially extensive metropolitan areas, and indicate the need for high-resolution mobility and epidemiological data. Author summary: Geographic structure in human populations has been widely recognised as a key determinant in the spread of infectious diseases, however the mechanisms underlying it are hard to disentangle. Using two distinct statistical analyses, we sought to address questions surrounding the impact of movement patterns and stochastic events on the spatial spread of SARS-CoV-2 in Washington state. Through our first analysis, which made use of a clustering algorithm, we uncovered a relationship between spatial proximity and the similarity of epidemic trajectories. Clusters of similar trajectories formed a clear geographical pattern. In our second analysis, we performed statistical inference on time series data from the Puget Sound region of Washington state. From our inference, we found that both a high degree of connectivity and atypically fast transmission within the first few weeks of the outbreak were necessary to explain the rapid inter-county spread. Furthermore, this stochastic early spread had a lasting effect on the subsequent epidemic course as non-pharmaceutical interventions were insufficient to temporarily eradicate the virus from the region. [ABSTRACT FROM AUTHOR]

Little is known about the efficacy and safety of esophageal stents for the management of esophageal strictures in children and adolescents. A systematic review was performed to assess the efficacy and safety of esophageal stents for the management of benign esophageal strictures in children and adolescents. Observational studies related to the examination of esophageal stents in pediatrics were extracted using the original databases by December 2021. We found 18 retrospective and prospective studies with a total of 340 children and adolescents. Overall, our findings show that different therapeutic modalities based on esophageal stents were offered to children and adolescents for various indications, in which most studies reported successful cases, although ineffective claims cannot be ignored. Fully covered self-expandable metal stent, self-expandable metal stent, and silastic esophageal stent were the stent types most used, although different materials and prototypes were reported as well. The number of stents used per patient and the duration of the stenting therapy varied widely (ranging from 1 to 584 days). Such treatments were not standardized because of different factors, such as different tolerance to complications in subjects aged 1 month and 16 years, frequent stent migration requiring removal followed or not by its replacement, different guides provided by each stent manufacturer, and successful healing of esophageal lesions. Different esophageal stents may be a reasonable therapeutic approach for the management of benign esophageal strictures in children and adolescents. We believe that esophagus-sparing methods like stents represent a promising alternative or adjunctive treatment to be considered in pediatrics. [ABSTRACT FROM AUTHOR]

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care to 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia during 2015. Our Southern Africa Mother Infant Pertussis Study (SAMIPS) prospectively monitored a cohort of mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for respiratory syncytial virus (RSV) and Bordetella pertussis. Our retrospective analysis of the SAMIPS cohort found that symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off target use of penicillins. [ABSTRACT FROM AUTHOR]

Evidence has also shown that oxidative stress and systemic inflammation, or in other words, disruption of the oxidant and antioxidant balance, can play an important role in the initiation or progression of NAFLD. The purpose of this study was to investigate the associations between the oxidative balance scores (OBS) and the risk of NAFLD. 552 healthy and 340 patients adult over the age of 18 with NAFLD participated in this case–control research. A validated 168-item quantitative food frequency questionnaire (FFQ) and indicators of physical activity, obesity, and smoking status were used to assess OBS score. The connection between OBS and NAFLD was discovered using binary logistic regression. The mean (± SD) age and (body mass index) BMI of the study population was 40.22 ± 9.79 years and 29.06 ± 3.92 kg/m2, respectively. The mean ± SD of OBS was 41.48 ± 5.23. After adjustment for potential confounders, higher scores of adherence to the OBS conferred a protection for the presence of NAFLD (odds ratio [OR]: 0.29; 95% confidence interval [CI]: 0.15–0.49; P for trend < 0.001). The findings of the present study indicate an approximately 80% reduction in the odds of developing NAFLD with higher OBS adherence in the overall population. However, prospective studies are needed to further investigate this association. [ABSTRACT FROM AUTHOR]

Background: Evidence shows the increase of anti-tissue transglutaminase (tTG) levels in various conditions, including infectious agents, independently of celiac disease (CD). The aim of this study was to investigate the effect of helicobacter pylori (H.pylori) infection eradication on serum level of tTG in children with CD. Methods: This study was conducted on children aged 2 to 18 who referred to reference hospitals for diagnosis of CD. After upper endoscopy and biopsy to confirm CD and H.pylori infection, the children were divided into three groups (including group one: 16 CD patients with positive H. pylori; group two: 16 non-CD patients with positive H. pylori; and group three: 56 CD patients with negative H. pylori), respectively. The tTG level in study groups were compared after the eradication of H.pylori. Results: The mean age of the subjects in the group one, two, and three was 9.7 ± 3.33, 11.8 ± 3.14, and 7.6 ± 3.32 years, respectively. Our results showed that in group one, mean tTG increased after eradication of H.pylori infection, however, these changes were not significant (182.43 vs. 157.18, P = 0.121). In the second group, although unlike the first group, mean tTG decreased after eradication of the infection, but still these changes were not significant (9.56 vs. 22.18, P = 0.449). Furthermore, at the baseline level, the mean tTG in the group three was closer to the mean tTG in the first group. Conclusion: Our findings showed that the eradication of H.pylori infection does not have a significant effect on tTG levels in children with and without CD. [ABSTRACT FROM AUTHOR]

Background: There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease (IBD) in the pediatric population. However, the results are contradictory. Therefore, we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD. Methods: We carried out a systematic search in databases from inception until 20 January 2022. We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity, inflammatory factors, and vitamin D and calcium levels in pediatric patients with IBD. Random effects models were used to combine the data. The main outcomes were then analyzed using weight mean difference (WMD) and respective 95% confidence interval (CI). Results: Fifteen treatment arms met the eligibility criteria and were included. Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxyvitamin D3 [25(OH) D3] (pooled WMD of 17.662 ng/mL; CI 9.77–25.46; P < 0.001), calcium (pooled WMD of 0.17 mg/dL; CI 0.04–0.30; P = 0.009), and inflammatory factors including C-reactive protein (CRP) (pooled WMD of −6.57 mg/L; CI −11.47 to −1.67; P = 0.009) and erythrocyte sedimentation rate (ESR) (pooled WMD of −7.94 mm/h; CI −12.65 to −3.22; P = 0.001) levels. In addition, this effect was greater for vitamin D levels at doses greater than 2000 IU, and when follow-up duration was more than 12 weeks. Conclusion: This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH) D3, calcium, and inflammatory factors in children and adolescents with IBD. [ABSTRACT FROM AUTHOR]

Dyslipidemia/hyperlipidemia are among the risk factors for chronic diseases, especially cardiovascular diseases. Red Yeast Rice (RYR) herbal supplement may be helpful in improving serum fat levels due to some mechanisms. Therefore, the aim of this study was to evaluate the effects of RYR consumption on total serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels in adults. Four comprehensive databases (SCOPUS, PubMed/MEDLINE, EMBASE, and Web of Science) were employed until 23 December 2021 RCTs, with 24 treatment arms included after screening 3623 articles. Pooled data showed significant effectiveness in lowering TC (WMD: −33.16 mg/dl, 95% CI: −37.69, −28.63, P < 0.001), LDL-C (WMD: −28.94 mg/dl, 95% CI: −32.90, −24.99, P < 0.001), and TG (WMD: −23.36 mg/dl, 95% CI: −31.30, −15.43, P < 0.001) concentration and increasing HDL-C concentration (WMD: 2.49 mg/dl, 95% CI: 1.48, 3.49, P < 0.001) following RYR supplementation. Furthermore, the effect of this herbal drug in doses less than 1200 mg and with an intervention duration of less than 12 weeks was more in individuals with dyslipidemia. In conclusion, this comprehensive article and meta-analysis showed that RYR significantly decreases TC, TG, and LDL-C as well as increases HDL-C. [ABSTRACT FROM AUTHOR]

Introduction: Fecal calprotectin (FC) is a noninvasive biomarker for assessing the inflammatory status of the gastrointestinal tract. The aim of this study was to determine the association between FC levels and Eosinophilic colitis (EC) before and after treatment in pediatrics. Method: In this cross-sectional study, 330 patients with rectorrhagia and FC levels > 200 μg/g were included in the study. Patients were then subjected to colonoscopy, and if 30 or more eosinophils were observed in the pathology of at least two parts of the colon, EC was diagnosed. Of the 330 patients included in the study, 14 patients were diagnosed as EC. Treatment included seven food elimination diet (food allergens) for 3 months. After 3 months, FC levels were repeated and colonoscopy was performed. Results: The mean age of the children was 5.9 years. After the elimination diet, the number of eosinophils in all segments of colon significantly decreased (P < 0.001) and according to the pathology report, the number of eosinophils improved in 42.9% of patients. Also, the mean number of segments involved in the colon of patients was significantly decreased (P < 0.001). Mean FC levels were significantly decreased after 3 months (P < 0.001). The cut-off point of 114 μg/g of FC had sensitivity (75%), specificity (67%), positive predictive value (75%), negative predictive value (67%), accuracy (71.4%), and area under the ROC curve (0.708) acceptable in predicting EC. Conclusion: This study showed that FC levels can be elevated in patients with EC, which is easily corrected with a targeted elimination of food allergens. [ABSTRACT FROM AUTHOR]

Background: The incidence of acute pancreatitis in children is increasing, but causes and diagnostic and therapeutic methods are various in different centers. The aim of this study was to investigate the common causes and routine diagnostic and therapeutic methods of acute pancreatitis in children in a pediatric gastrointestinal referral center and its accordance with existing guidelines. Methods: In this retrospective, cross-sectional study, a total of 60 children with a diagnosis of acute pancreatitis, were studied. Results: The most common causes of acute pancreatitis were systemic and metabolic diseases and medications. CT scan was performed for 36% of patients, but 31% of patients, for whom a CT scan was performed had no clear indication of CT scan. Only half of the patients received fluid 1.5 times their maintenance in the first 24 h. Antibiotic therapy was performed for 48% of patients but medical indications for antibiotic treatment were found in only 34% of cases. During the COVID-19 pandemic, the relative incidence of acute pancreatitis was increased. Conclusions: In children with systemic and metabolic disease and using anticonvulsant drugs, it is important to consider the incidence of this disease. In clinical education, the risks of radiation due to unnecessary CT scans and inappropriate prescription of antibiotics need to be emphasized. More research should be done to study the association between COVID-19 and acute pancreatitis. [ABSTRACT FROM AUTHOR]

Summary: Background: There is evidence of inconsistency in sequelae of exclusive enteral nutrition (EEN) as induction therapy in paediatric patients with Crohn's disease (CD). Aim: To investigate the potential effects of EEN on paediatric Crohn's disease activity index (PCDAI), inflammation and biochemical parameters in paediatric patients with CD. Methods: We performed a comprehensive systematic search of PubMed/MEDLINE, Web of Science, SCOPUS and Embase until 8 January 2022 regardless of the time of publication or language. Random‐effects model was applied to combine the datasets. The main outcomes were analysed through mean difference (MD) and its 95% confidence interval (CI). Results: Forty six studies met eligibility criteria and were included in the meta‐analysis. Pooled findings indicated that PCDAI score (MD of −27.24; 95% CI −31.84 to −22.64), calprotectin (MD of −842.83 mg/kg; CI −1018.24 to −667.42), CRP (pooled MD of −2.36 mg/dl; CI −2.68 to −2.03), and ESR (MD of −21.09 mm/h; CI −23.79 to −18.38), albumin (MD of 0.65 g/dl; CI 0.58 to 0.72), haemoglobin (MD of 1.12 g/dl; CI 0.87 to 1.37), weight (MD of 4.30 kg; CI 3.39 to 5.22), and height (MD of 0.98 cm; CI 0.35 to 1.62) improved significantly with EEN. Conclusions: Adherence to EEN can have significant, beneficial effects as induction therapy in paediatric patients with CD. [ABSTRACT FROM AUTHOR]

Measurement of traffic flow stability and resilience is a critical step toward evaluating the performance of transportation systems and implementing appropriate management strategies. Quantifying changes in the stability and resilience of transportation systems, however, is hampered by the complexity of real traffic dynamics and the diversity of infrastructures. Here, we demonstrate that changes in traffic flow stability and resilience are signaled by generic features, known as early warning signals in the theory of critical slowing down, observed before traffic instabilities occur. This finding is incorporated in an operational data-driven algorithm to evaluate the risk of traffic jams on highways. Theoretical findings and tests on simulated and empirical case studies support the premise of this approach and identify candidate statistical measures that are sensitive to changes in the stability and resilience of transportation systems. Our use of universal measures advances the monitoring capability, prediction and control of complex transportation systems. [ABSTRACT FROM AUTHOR]

Background: The incidence of acute pancreatitis in children is increasing, but causes and diagnostic and therapeutic methods are various in different centers. The aim of this study was to investigate the common causes and routine diagnostic and therapeutic methods of acute pancreatitis in children in a pediatric gastrointestinal referral center and its accordance with existing guidelines.Methods: In this retrospective, cross-sectional study, a total of 60 children with a diagnosis of acute pancreatitis, were studied.Results: The most common causes of acute pancreatitis were systemic and metabolic diseases and medications. CT scan was performed for 36% of patients, but 31% of patients, for whom a CT scan was performed had no clear indication of CT scan. Only half of the patients received fluid 1.5 times their maintenance in the first 24 h. Antibiotic therapy was performed for 48% of patients but medical indications for antibiotic treatment were found in only 34% of cases. During the COVID-19 pandemic, the relative incidence of acute pancreatitis was increased.Conclusions: In children with systemic and metabolic disease and using anticonvulsant drugs, it is important to consider the incidence of this disease. In clinical education, the risks of radiation due to unnecessary CT scans and inappropriate prescription of antibiotics need to be emphasized. More research should be done to study the association between COVID-19 and acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the serum level of matrix metalloproteinase 7 (MMP7) in infants with cholestasis and the diagnostic values of this biomarker to differentiate biliary atresia (BA) from other causes of cholestasis.Methods: This multi-center study is conducted during 2 years in Mofid children's hospital and Children's Medical Center, Pediatrics Center of Excellence Tehran, Iran. 54 infants with cholestasis were enrolled in this study with a control group consists of 41 healthy infants with the same age. Serum samples were taken from all these patients to assess serum levels of MMP7, Gamma-glutamyl Transferase (GGT). For each biomarker, we calculated the sensitivity and specificity and other statistical characteristics.Results: There were 89 subjects, 22 patients with BA, 32 patients with non-BA cholestasis and 41 subjects as control group. The mean serum MMP7 levels in BA, non-BA cholestasis and control group was 15.91 ng/ml ± 6.64, 4.73 ng/ml ± 2.59 and 0.49 ng/ml ± 0.33, respectively. The best cut-off point is calculated 7.8 ng/ml for MMP7 and 434.5 U/L for GGT. The area under curve (AUC) for these two markers are 0.988 ± 0.008 and 0.854 ± 0.052, respectively. The sensitivity and specificity of MMP7 to differentiate biliary atresia from nonbiliary atresia cholestasis in our study was 95.5% and 94.5%, respectively. The sensitivity and specificity of GGT was 77.3% and 77.8%, respectively. These results show that the MMP7 has more sensitivity and specificity in differentiation.Conclusion: MMP7 demonstrated good accuracy to differentiate biliary atresia from other causes of cholestasis. [ABSTRACT FROM AUTHOR]

Context: Children admitted to the intensive care unit are at risk of malnutrition, mainly due to chronic diseases they are suffering from. These patients require a different nutritional diet regimen from those in a normal or stable disease state due to change in metabolism under the stress of diseases. Methods: According to the SIGN guideline based on evidence, first, articles matching our criteria were extracted from the literature, and then the strength of evidence was evaluated. Finally, a summary of statements consisting of details regarding the strength of evidence and recommendation level was reviewed by 12 experts, and two-round surveys were accomplished according to the Delphi method to reach a consensus. Results: Twenty-seven statements in 5 categories with strength of evidence, grade of recommendations, and expert opinions are summarized. Conclusions: Rapid nutritional assessment, judging patients with malnutrition or at risk of malnutrition, fast intervention with early enteral nutrition, reaching the protein and energy goals under the supervision of an expert registered dietitian, and persistent monitoring with minimizing the time of fasting are some of the key components of proper nutrition management based on evidence found in the literature. [ABSTRACT FROM AUTHOR]

Pediatric inflammatory bowel disease (PIBD) is a multisystem disorder characterized by intestinal and extraintestinal manifestations and complications. Cerebrovascular events (CVE) are rare extraintestinal complications in patients with PIBD. Statistics show that 3.3% patients with PIBD and 1.3-6.4% adult patients with inflammatory bowel disease (IBD) experience CVE during the course of the disease. Therefore, this study aimed to review the records of children with IBD who developed CVE during the course of the disease. We retrospectively reviewed 62 cases of PIBD complicated by CVE. The mean patient age at the time of thrombotic events was 12.48±4.13 years. The incidence of ulcerative colitis was significantly higher than that of Crohn's disease (43 [70.5%] vs. 13 [21.3%] patients). Most patients (87.93%) were in the active phase of IBD at the time of CVE. The mean time interval between the onset of IBD and CVE was 20.84 weeks. Overall, 11 (26.83%) patients showed neurological symptoms of CVE at disease onset. The most frequent symptom on admission was persistent and severe headaches (67.85%). The most common site of cerebral venous thrombosis was the transverse sinuses (n=23, 53.48%). The right middle cerebral artery (n=3, 33.34%) was the predominant site of cerebral arterial infarction. Overall, 41 (69.49%) patients who were mostly administered unfractionated heparin or low-molecular-weight heparin (56.09%) recovered completely. Patients with IBD are at a risk of thromboembolism. CVE may be the most common type of thromboembolism. Based on these findings, the most common risk factor for CVE is IBD flares. In patients with CVE, anticoagulant therapy with heparin, followed by warfarin, is necessary. [ABSTRACT FROM AUTHOR]

Background. Ocular extraintestinal manifestations (O-EIMs) are one of the most well-known EIMs in patients with inflammatory bowel disease (IBD). This study aimed to identify the frequency of O-EIMs in children with IBD, referred to Mofid Children's Hospital, Tehran, Iran, during 2014 to 2019. Methods. Children with IBD, younger than the age of 18 years, who were referred to an ophthalmologist, were included in this study. Results. Ninety-six patients with IBD were examined. Four patients had ocular manifestation of IBD. Two patients had complications due to treatment of IBD. The mean age of the patients was 11.25 ± 4.17 years (range: 5.5-17 years). The O-EIMs included 3 (50.0%) cases of anterior uveitis, 1 (16.7%) case of episcleritis, and 2 (33.3%) cases of posterior subcapsular cataract. Conclusion. O-EIMs are important in children with IBD. Therefore, it is recommended that annual screening for ocular complications be performed in all children with IBD. [ABSTRACT FROM AUTHOR]

The ongoing explosion of fine‐resolution movement data in animal systems provides a unique opportunity to empirically quantify spatial, temporal and individual variation in transmission risk and improve our ability to forecast disease outbreaks. However, we lack a generalizable model that can leverage movement data to quantify transmission risk and how it affects pathogen invasion and persistence on heterogeneous landscapes. We developed a flexible model 'Movement‐driven modelling of spatio‐temporal infection risk' (MoveSTIR) that leverages diverse data on animal movement to derive metrics of direct and indirect contact by decomposing transmission into constituent processes of contact formation and duration and pathogen deposition and acquisition. We use MoveSTIR to demonstrate that ignoring fine‐scale animal movements on actual landscapes can mis‐characterize transmission risk and epidemiological dynamics. MoveSTIR unifies previous work on epidemiological contact networks and can address applied and theoretical questions at the nexus of movement and disease ecology. [ABSTRACT FROM AUTHOR]

Pertussis has resurfaced in the UK, with incidence levels not seen since the 1980s. While the fundamental causes of this resurgence remain the subject of much conjecture, the study of historical patterns of pathogen diffusion can be illuminating. Here, we examined time series of pertussis incidence in the boroughs of Greater London from 1982 to 2013 to document the spatial epidemiology of this bacterial infection and to identify the potential drivers of its percolation. The incidence of pertussis over this period is characterized by 3 distinct stages: a period exhibiting declining trends with 4-year inter-epidemic cycles from 1982 to 1994, followed by a deep trough until 2006 and the subsequent resurgence. We observed systematic temporal trends in the age distribution of cases and the fade-out profile of pertussis coincident with increasing national vaccine coverage from 1982 to 1990. To quantify the hierarchy of epidemic phases across the boroughs of London, we used the Hilbert transform. We report a consistent pattern of spatial organization from 1982 to the early 1990s, with some boroughs consistently leading epidemic waves and others routinely lagging. To determine the potential drivers of these geographic patterns, a comprehensive parallel database of borough-specific features was compiled, comprising of demographic, movement and socio-economic factors that were used in statistical analyses to predict epidemic phase relationships among boroughs. Specifically, we used a combination of a feed-forward neural network (FFNN), and SHapley Additive exPlanations (SHAP) values to quantify the contribution of each covariate to model predictions. Our analyses identified a number of predictors of a borough's historical epidemic phase, specifically the age composition of households, the number of agricultural and skilled manual workers, latitude, the population of public transport commuters and high-occupancy households. Univariate regression analysis of the 2012 epidemic identified the ratio of cumulative unvaccinated children to the total population and population of Pakistan-born population to have moderate positive and negative association, respectively, with the timing of epidemic. In addition to providing a comprehensive overview of contemporary pertussis transmission in a large metropolitan population, this study has identified the characteristics that determine the spatial spread of this bacterium across the boroughs of London. Author summary: Recent years have witnessed a resurgence of pertussis, a vaccine preventable bacterial disease, in countries with high estimated immunization rates. Here, to understand the timing of pertussis epidemics in different populations, we employed signal processing techniques to analyze a rich dataset of weekly incidence across the boroughs of London from 1982 to 2013. We observed 4-year epidemic cycles with a distinctly consistent spatial organization across the boroughs from 1982 to 1990, with some boroughs typically ahead of the wave and others consistently lagging. We identified putative demographic and socio-economic mechanisms that determined this spatial organization of these outbreaks using an interpretable machine learning approach. The reemergence of pertussis from 2006 onward, on the contrary, did not exhibit regular epidemic waves, instead there was a transition from spatially organized waves in the 1980s to a largely unstructured mosaic in the resurgence era. [ABSTRACT FROM AUTHOR]

Background: Octreotide has been used to control bleeding episodes with variceal origin in the pediatric population. To date, there is no clear evidence of octreotide use for non-variceal bleeding in clinical trials. Objectives: We aimed to assess the octreotide efficacy as an add-on therapy to the conventional regimen of proton pump inhibitors for controlling upper non-variceal gastrointestinal (GI) bleeding in the pediatric population. Methods: This prospective randomized controlled clinical trial was performed on pediatric patients aged 1 -15 years and diagnosed with acute non-variceal upper GI bleeding. The participants were allocated to receive octreotide or placebo and pantoprazole con-comitantly. The study was conducted in Mofid Children's Hospital, Tehran, Iran, during February 2019- December 2019. Patients with hepatic failure, liver stigma, and coagulopathy due to thrombocytopenia were excluded. Demographic, clinical, and preclinical data were recorded in prepared sheets. All the patients were followed until therapy discontinuation. P-value < 0.05 was considered significant. Results: Forty-three patients with a mean age of 4.98 ± 3.79 years and confirmed non-variceal upper GI bleeding were included in the present study. Most patients had no specific etiology for their bleeding episodes. Patients in the intervention and control groups received pantoprazole in comparable doses. No differences were observed between the two groups in terms of baseline hemoglobin values (P = 0.08), while final hemoglobin values were significantly higher in the intervention group (P = 0.014). The bleeding duration was not significantly different between the two groups (P = 0.99). Moreover, none of the cases showed adverse drug reactions due to octreotide infusion. Conclusions: Our study demonstrated that octreotide did not alter bleeding duration or need for blood transfusion. However, positive results were observed for hemoglobin, affecting blood loss volume. [ABSTRACT FROM AUTHOR]

Pathogen transport by biotic or abiotic processes (e.g. mechanical vectors, wind, rain) can increase disease transmission by creating more opportunities for host exposure. But transport without replication has an inherent trade‐off, that creating new venues for exposure decreases the average pathogen abundance at each venue. The host dose‐response relationship is therefore required to correctly assess infection risk. We model and analyse two examples—biotic mechanical vectors in plant–pollinator networks, and abiotic‐facilitated long‐distance pathogen dispersal—to illustrate how oversimplifying the dose‐response relationship can lead to incorrect epidemiological predictions. When the minimum infective dose is high, mechanical vectors amplify disease transmission less than suggested by simple compartment models, and may even dilute transmission. When long‐distance dispersal leads to infrequent large exposures, models that assume a linear force of infection can substantially under‐predict the speed of epidemic spread. Our work highlights an important general interplay between dose‐response relationships and pathogen transport. [ABSTRACT FROM AUTHOR]

Background National responses to the Covid-19 pandemic varied markedly across countries, from business-as-usual to complete shutdowns. Policies aimed at disrupting the viral transmission cycle and preventing the overwhelming of healthcare systems inevitably exact an economic toll. Methodology We developed an intervention policy model that comprised the relative human, implementation and healthcare costs of non-pharmaceutical epidemic interventions and identified the optimal strategy using a neuroevolution algorithm. The proposed model finds the minimum required reduction in transmission rates to maintain the burden on the healthcare system below the maximum capacity. Results We find that such a policy renders a sharp increase in the control strength during the early stages of the epidemic, followed by a steady increase in the subsequent ten weeks as the epidemic approaches its peak, and finally the control strength is gradually decreased as the population moves towards herd immunity. We have also shown how such a model can provide an efficient adaptive intervention policy at different stages of the epidemic without having access to the entire history of its progression in the population. Conclusions and implications This work emphasizes the importance of imposing intervention measures early and provides insights into adaptive intervention policies to minimize the economic impacts of the epidemic without putting an extra burden on the healthcare system. Lay Summary We developed an intervention policy model that comprised the relative human, implementation and healthcare costs of non-pharmaceutical epidemic interventions and identified the optimal strategy using a neuroevolution algorithm. Our work emphasizes the importance of imposing intervention measures early and provides insights into adaptive intervention policies to minimize the economic impacts of the epidemic without putting an extra burden on the healthcare system. [ABSTRACT FROM AUTHOR]

Background: Lead exposure is one of the most menacing of environmental exposures, particularly in children. Children are more susceptible to the effects of lead which manifest in many organ systems, including interference with mental and motor development. Lead poisoning can cause colicky abdominal pain. In this study, the authors sought to evaluate the prevalence of elevated blood lead level (BLL) and its contributing factors among pediatric patients presenting with abdominal pain. An epidemic of lead poisoning in adults was previously uncovered, and thus a concern for pediatric lead poisoning was raised.Methods: Pediatric patients presenting to two pediatric clinics in Tehran with abdominal pain were eligible for enrollment in a descriptive prospective cross-sectional study. A predesigned questionnaire was filled for each patient by their consenting parents. The questionnaire queried demographic information, environmental, social, and other relevant parameters for lead exposure. After completion of the questionnaire, biometrics were obtained, and a blood sample was taken from each patient for measurement of BLL and complete blood count.Results: A total of 187 patients were enrolled in the study. Of them, almost 20% had BLL ≥ 5 µg/dL. Univariate analysis showed that age (p = 0.002, OR 3.194, CI 95% 1.504-6.783), weight (p = 0.009, OR 2.817, CI 95% 1.266-6.269), height (p = 0.003, OR 3.155, CI 95% 1.443-6.899), and playing with both plastic and cotton toys (p = 0.03, OR 2.796, CI 95% 1.072-7.295) were significant predictors of high BLLs. Maternal level of education correlated with blood lead concentrations (p = 0.048, OR 2.524, CI 95% 1.006-6.331).Conclusions: A clinically significant number of cases of abdominal pain may have high BLLs. Specific attention should be paid to children presenting with abdominal pain, especially due to the detrimental effects of lead on their mental and motor development. [ABSTRACT FROM AUTHOR]

Early warning tools are crucial for the timely application of intervention strategies and the mitigation of the adverse health, social and economic effects associated with outbreaks of epidemic potential such as COVID-19. This paper introduces, the Epidemic Volatility Index (EVI), a new, conceptually simple, early warning tool for oncoming epidemic waves. EVI is based on the volatility of newly reported cases per unit of time, ideally per day, and issues an early warning when the volatility change rate exceeds a threshold. Data on the daily confirmed cases of COVID-19 are used to demonstrate the use of EVI. Results from the COVID-19 epidemic in Italy and New York State are presented here, based on the number of confirmed cases of COVID-19, from January 22, 2020, until April 13, 2021. Live daily updated predictions for all world countries and each of the United States of America are publicly available online. For Italy, the overall sensitivity for EVI was 0.82 (95% Confidence Intervals: 0.75; 0.89) and the specificity was 0.91 (0.88; 0.94). For New York, the corresponding values were 0.55 (0.47; 0.64) and 0.88 (0.84; 0.91). Consecutive issuance of early warnings is a strong indicator of main epidemic waves in any country or state. EVI's application to data from the current COVID-19 pandemic revealed a consistent and stable performance in terms of detecting new waves. The application of EVI to other epidemics and syndromic surveillance tasks in combination with existing early warning systems will enhance our ability to act swiftly and thereby enhance containment of outbreaks. [ABSTRACT FROM AUTHOR]

When modeling infectious diseases, it is common to assume that infection-derived immunity is either (1) non-existent or (2) perfect and lifelong. However there are many diseases in which infection-derived immunity is known to be present but imperfect. There are various ways in which infection-derived immunity can fail, which can ultimately impact the probability that an individual be reinfected by the same pathogen, as well as the long-run population-level prevalence of the pathogen. Here we discuss seven different models of imperfect infection-derived immunity, including waning, leaky and all-or-nothing immunity. For each model we derive the probability that an infected individual becomes reinfected during their lifetime, given that the system is at endemic equilibrium. This can be thought of as the impact that each of these infection-derived immunity failures have on reinfection. This measure is useful because it provides us with a way to compare different modes of failure of infection-derived immunity. [ABSTRACT FROM AUTHOR]

Aim: This multicenter study is the first one on Iranian children with very early onset ulcerative colitis (UC) and one of the few studies about the effect of biological therapy in children with UC under 7 years of age. Background: Children with very early onset inflammatory bowel disease (IBD) are diagnosed before 6 years of age Methods: The current study was performed on 14 children under 7 years of age with severe UC. Children with severe UC whose therapy with corticosteroid and azathioprine as conventional treatment had failed were treated with infliximab (IFX) and later with adalimumab (ADA). Results: Among the total 14 participants, 6 (43%) patients were female. Mean patient age was 4.9 years (range = 3-7 years), mean age at diagnosis was 3.4 years (range = 1.5-6 years), and mean duration of illness was 1.5 years. At the end of 54 weeks of therapy with IFX, 2 (14%) patients were in remission, 2 (14%) patients were mild, and 4 (29%) patients were moderate, with no secondary treatment failure (during the maintenance phase). A total of 6 (43%) patients had primary treatment failure (no response after 14 weeks of therapy). These patients were treated with ADA. At the end of 52 weeks of therapy, 3 (50%) of those 6 (100%) patients were referred for colectomy, 1 (17%) was in remission, and 2 (33%) patients had mild severity. Conclusion: The current study has shown that IFX is a safe and effective therapy for children with very early onset UC. ADA may be effective in the treatment of children with UC who are refractory to IFX. [ABSTRACT FROM AUTHOR]

Aim: Description of the inflammatory bowel disease natural history in Tehran province. Background: Inflammatory bowel disease (IBD) is a non-homogeneous disorder with an unpredictable natural history that impairs a patient's quality of life over the course of their life. As a result, providing evidence for efficient patient management is critical. Methods: In this case series study, 198 IBD patients who were visited in our clinic at least three times routinely from Oct 2015 to May 2020 were included. Then, two panel-based approaches, the Multi-State Model (MSM) and random-effect ordered logistic, were used to deduce the clinical course of IBD, which included remission, mild, moderate to severe, and surgical states. Results For ulcerative colitis (UC), women had a slightly poorer condition for remission but better for moderate to severe and a faster transition from moderate to severe to mild (HR=1.490, 95% CI: 1.02-2.16) compared to men. For Crohn's disease (CD), they had a better condition for remission but a slightly poorer condition for the severe state and higher transition from mild to moderate to severe (HR=1.221, 95% CI: 0.4713.22) than men. Oral 5-ASA had better efficacy in people with remission and/or mild states but not for those with moderate to severe states, especially in CD (mild to moderate to serve, HR=1.526, 95% CI: 0.59-3.89). Immunosuppressive drugs were better for patients with lower disease severity, especially with UC (mild to remission, HR=1.258, 95% CI: 0.75-2.09). Conclusion: Panel approaches have the potential efficacy to tackle the unpredictable clinical course of IBD (UC/CD). Hence, we highly recommend that our findings be included into the Iranian routine clinical environment of IBD and/or that related studies be conducted in Iran and other regions to gain a better understanding of the natural history of IBD. [ABSTRACT FROM AUTHOR]

Novel pathogen introduction can have drastic consequences for naive host populations, and outcomes can be difficult to predict. Evolutionary rescue (ER) provides a foundation for understanding whether hosts are driven to extinction or survive via adaptation. Currently, patterns of host population dynamics alongside evidence of adaptation are used to infer ER. However, the gap between established ER theory and complexity inherent in natural systems makes interpreting empirical patterns difficult because they can be confounded with ecological drivers of survival under current theory. To bridge this gap, we expand ER theory to include biological selective agents, such as pathogens. We find birth processes to be more important than previously theorised in determining ER potential. We employ a novel framework evaluating ER potential within natural systems and gain ability to identify system characteristics that make ER possible. Identifying these characteristics allows a shift from retrospective observation to a predictive mindset, and our findings suggest that ER occurrence may be more limited than previously thought. We use the plague system of Yersinia pestis infecting Cynomys ludovicianus (black‐tailed prairie dogs) and Spermophilus beecheyi (California ground squirrels) as a case study. [ABSTRACT FROM AUTHOR]

Introduction: According to the World Health Organization, the incidence of severe acute hepatitis of unknown origin in children is increasing worldwide. However, there are no known causes and treatments to deal with this disease. This study presents three children with severe acute hepatitis of unknown origin in a hospital medical center in Iran. Case Presentation: Two 12-year-old children and a six-year-old child were admitted to the hospital with jaundice. Laboratory tests showed markedly elevated liver enzymes and total and direct bilirubin in these patients. However, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Ab), hepatitis A virus (HAV) IgM, HEV IgM, Epstein-Barr virus (EBV) IgM, anti-microsomal Ab, anti-liver kidney (LKM Ab), anti-smooth muscle antibodies (ASMA), anti-nuclear antibodies (ANA), and total IgG were all negative. After excluding the probable infectious causes of acute hepatitis and per the progressive course of fulminant hepatic failure, intravenous methylprednisolone was started for two of three cases during hospitalization. These children were discharged from the hospital in good general condition, and the liver function tests gradually decreased and approximated to near normal during the follow-up visits. Conclusions: General practitioners and pediatricians are advised to examine the underlying causes and consider severe acute hepatitis of unknown origin when visiting children under 16 years with severe jaundice and very high transaminases. [ABSTRACT FROM AUTHOR]

The pandemic of COVID-19 has become one of the greatest threats to human health, causing severe disruptions in the global supply chain, and compromising health care delivery worldwide. Although government authorities sought to contain the spread of SARS-CoV-2, by restricting travel and in-person activities, failure to deploy time-sensitive strategies in ramping-up of critical resource production exacerbated the outbreak. Here, we developed a mathematical model to analyze the effects of the interaction between supply chain disruption and infectious disease dynamics using coupled production and disease networks built on global data. Analysis of the supply chain model suggests that time-sensitive containment strategies could be created to balance objectives in pandemic control and economic losses, leading to a spatiotemporal separation of infection peaks that alleviates the societal impact of the disease. A lean resource allocation strategy can reduce the impact of supply chain shortages from 11.91 to 1.11% in North America. Our model highlights the importance of cross-sectoral coordination and region-wise collaboration to optimally contain a pandemic and provides a framework that could advance the containment and model-based decision making for future pandemics. [ABSTRACT FROM AUTHOR]

The occurrence of functional gastrointestinal disorders (FGIDs) is a formidable challenge for infants, parents, and healthcare professionals. Although data from the Middle East are scarce, experts consider FGIDs a prevalent condition in everyday clinical practice. The new Rome IV criteria revisited the definitions from a clinical perspective to provide a practical and consistent diagnostic protocol for FGIDs. However, the treatment practices for functional disorders vary considerably among Middle Eastern countries, often resulting in mismanagement with unnecessary investigations and treatments. In addition, the role of various treatment modalities, including probiotics such as Lactobacillus reuteri DSM 17938, in FGIDs requires further discussion and evaluation. During a consensus meeting, a locally relevant approach for treating common FGIDs such as infant regurgitation, infant colic, and functional constipation was discussed and approved by regional experts. The participants suggested a simplified treatment plan and protocol for general pediatricians and other primary care physicians managing FGIDs. This easy-to-follow standardized protocol will help streamline the initial management of this complex disorder in the Middle East region and even globally. [ABSTRACT FROM AUTHOR]

Background: The projection studies are imperative to satisfy demands for health care systems and proper response to the public health problems such as inflammatory bowel disease (IBD).Methods: To accomplish this, we established an illness-death model based on available data to project the future prevalence of IBD in Asia, Iran in particular, separately from 2017 to 2035. We applied two deterministic and stochastic approaches.Results: In 2035, as compared to 2020, we expected a 2.5-fold rise in prevalence for Iran with 69 thousand cases, a 2.3-fold increment for North Africa and the Middle East with 220 thousand cases, quadrupling of the prevalence for India with 2.2 million cases, a 1.5-fold increase for East Asia region with 4.5 million cases, and a 1.6-fold elevation in prevalence for high-income Asia-Pacific and Southeast Asia regions with 183 and 199 thousand cases respectively.Conclusions: Our results showed an emerging epidemic for the prevalence of IBD in Asia regions and/or countries. Hence, we suggest the need for immediate action to control this increasing trend in Asia and Iran. However, we were virtually unable to use information about age groups, gender, and other factors influencing the evolution of IBD in our model due to lack of access to reliable data. [ABSTRACT FROM AUTHOR]

We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the IL10 RA, and one had a large deletion in the IL10 RB. Four patients had mutations in genes implicated in host:microbiome homeostasis, including TTC7A deficiency, and two patients with novel mutations in the TTC37 and NOX1. We found a novel homozygous mutation in the SRP54 in a deceased patient and the heterozygous variant in his sibling with a milder phenotype. Three patients had combined immunodeficiency: one with ZAP-70 deficiency (T+B+NK−), and two with atypical SCID due to mutations in RAG1 and LIG4. One patient had a G6PC3 mutation without neutropenia. Eleven of the 14 patients with monogenic defects were results of consanguinity and only 4 of them were alive to this date. [ABSTRACT FROM AUTHOR]

LPS-responsive beige-like anchor protein (LRBA) deficiency is a monogenic primary immunodeficiency characterized by a heterogeneous spectrum of clinical manifestations associated with immune dysregulation. In this study, we reported clinical, immunologic, and genetic evaluation of two Iranian patients from unrelated families, both suffering from recurrent respiratory tract infections, failure to thrive, interstitial lung disease, autoimmune cytopenia, and hypogammaglobulinemia. Pulmonary abscess in one patient and persistent enteropathy in another were also observed. Further investigations revealed causative mutations in the exon (c.2166_2766del) and intron (c.4730–3 T > G) of the LRBA gene. These results may provide further elucidation of the clinical phenotypes and responsible genetic factors of LRBA deficiency. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of a new viral respiratory infection. It has been demonstrated that the microbiota has a crucial role in establishing immune responses against respiratory infections, which are controlled by a bidirectional cross-talk, known as the "gut-lung axis." The effects of microbiota on antiviral immune responses, including dendritic cell (DC) function and lymphocyte homing in the gut-lung axis, have been reported in the recent literature. Additionally, the gut microbiota composition affects (and is affected by) the expression of angiotensin-converting enzyme-2 (ACE2), which is the main receptor for SARS-CoV-2 and contributes to regulate inflammation. Several studies demonstrated an altered microbiota composition in patients infected with SARS-CoV-2, compared to healthy individuals. Furthermore, it has been shown that vaccine efficacy against viral respiratory infection is influenced by probiotics pretreatment. Therefore, the importance of the gut microbiota composition in the lung immune system and ACE2 expression could be valuable to provide optimal therapeutic approaches for SARS-CoV-2 and to preserve the symbiotic relationship of the microbiota with the host. [ABSTRACT FROM AUTHOR]

Exploitative parasites are predicted to evolve in highly connected populations or in expanding epidemics. However, many parasites rely on host dispersal to reach new populations, potentially causing conflict between local transmission and global spread. We performed experimental range expansions in interconnected microcosms of the protozoan Paramecium caudatum, allowing natural dispersal of hosts infected with the bacterial parasite Holospora undulata. Parasites from range front treatments facilitated host dispersal and were less virulent, but also invested less in horizontal transmission than parasites from range cores. These differences were consistent with parameter estimates derived from an epidemiological model fitted on population‐level time‐series data. Our results illustrate how dispersal selection can have profound consequences for the evolution of parasite life history and virulence. Decrypting the eco‐evolutionary processes that shape parasite 'dispersal syndromes' may be important for the management of spreading epidemics in changing environments, biological invasions or in other spatial non‐equilibrium settings. [ABSTRACT FROM AUTHOR]

The rapid growth rate of COVID-19 continues to threaten to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to impose a range of public health strategies achieved via nonpharmaceutical interventions. Broadly, these strategies have fallen into two categories: 1) "mitigation," which aims to achieve herd immunity by allowing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to spread through the population while mitigating disease burden, and 2) "suppression," aiming to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population. Using an age-structured transmission model, parameterized to simulate SARS-CoV-2 transmission in the United Kingdom, we assessed the long-term prospects of success using both of these approaches. We simulated a range of different nonpharmaceutical intervention scenarios incorporating social distancing applied to differing age groups. Our modeling confirmed that suppression of SARS-CoV-2 transmission is possible with plausible levels of social distancing over a period of months, consistent with observed trends. Notably, our modeling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly defined forces. Specifically, we found that 1) social distancing must initially reduce the transmission rate to within a narrow range, 2) to compensate for susceptible depletion, the extent of social distancing must be adaptive over time in a precise yet unfeasible way, and 3) social distancing must be maintained for an extended period to ensure the healthcare system is not overwhelmed. [ABSTRACT FROM AUTHOR]