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Crohn's disease is an inflammatory condition of the intestine characterized by largely unknown etiology and a relapse remission cycle of disease control. While possible triggers have been identified, research is inconsistent on the precise cause of these relapses, especially in the under-researched pediatric population. We hypothesized that patients in remission would have persistent microbial and inflammatory changes in small intestinal tissue that might trigger relapse. To this end, we analyzed intestinal biopsy samples from six patients with pediatric Crohn's disease in remission and a control group of 16 pediatric patients with no evident pathogenic abnormality. We identified compositional microbiota differences, including decreases in the genera Streptococcus and Actinobacillus as well as increases in Oribacterium and Prevotella in patients with controlled Crohn's disease compared to controls. Further, a histologic analysis found that patients with controlled Crohn's disease had increased epithelial integrity, and decreased intraepithelial lymphocytes compared with controls. Additionally, we observed increased peripheral CD4 + T cells in patients with pediatric Crohn's disease. These results indicate that markers of intestinal inflammation are responsive to Crohn's disease treatment, however the interventions may not resolve the underlying dysbiosis. These findings suggest that persistent dysbiosis may increase vulnerability to relapse of pediatric Crohn's disease. This study used a nested cohort of patients from the Bangladesh Environmental Enteric Dysfunction (BEED) study (ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016)., (© 2024. The Author(s).)

Small intestine bacterial overgrowth (SIBO) has been associated with enteric inflammation, linear growth stunting, and neurodevelopmental delays in children from low-income countries. Little is known about the histologic changes or epithelial adherent microbiota associated with SIBO. We sought to describe these relationships in a cohort of impoverished Bangladeshi children. Undernourished 12-18-month-old children underwent both glucose hydrogen breath testing for SIBO and duodenoscopy with biopsy. Biopsy samples were subject to both histological scoring and 16s rRNA sequencing. 118 children were enrolled with 16s sequencing data available on 53. Of 11 histological features, we found that SIBO was associated with one, enterocyte injury in the second part of the duodenum (R = 0.21, p = 0.02). SIBO was also associated with a significant increase in Campylobacter by 16s rRNA analysis (Log 2-fold change of 4.43; adjusted p = 1.9 x 10-6). These findings support the growing body of literature showing an association between SIBO and enteric inflammation and enterocyte injury and further delineate the subgroup of children with environmental enteric dysfunction who have SIBO. Further, they show a novel association between SIBO and Campylobacter. Mechanistic work is needed to understand the relationship between SIBO, enterocyte injury, and Campylobacter., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

WHO works, on a daily basis, with countries globally to detect, prepare for and respond to acute public health events. A vital component of a health response is the dissemination of accurate, reliable and authoritative information. The Disease Outbreak News (DON) reports are a key mechanism through which WHO communicates on acute public health events to the public. The decision to produce a DON report is taken on a case-by-case basis after evaluating key criteria, and the subsequent process of producing a DON report is highly standardised to ensure the robustness of information. DON reports have been published since 1996, and up to 2022 over 3000 reports have been published. Between 2018 and 2022, the most frequently published DON reports relate to Ebola virus disease, Middle East respiratory syndrome, yellow fever, polio and cholera. The DON web page is highly visited with a readership of over 2.6 million visits per year, on average. The DON report structure has evolved over time, from a single paragraph in 1996 to a detailed report with seven sections currently. WHO regularly reviews the DON report process and structure for improvements. In the last 25 years, DON reports have played a unique role in rapidly disseminating information on acute public health events to health actors and the public globally. They have become a key information source for the global public health response to the benefit of individuals and communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Purpose: Rotational malalignment (≥ 10°) is a frequent pitfall of intramedullary-nailing of tibial shaft fractures. This study aimed to develop an intraoperative fluoroscopy protocol, coined 'C-Arm Rotational View (CARV)', to significantly reduce the risk for rotational malalignment and to test its clinical feasibility., Methods: A cadaver and clinical feasibility study was conducted to develop the CARV-technique, that included a standardized intraoperative fluoroscopy sequence of predefined landmarks on the uninjured and injured leg in which the rotation of the C-arm was used to verify for rotational alignment. A mid-shaft tibia fracture was simulated in a cadaver and an unlocked intramedullary-nail was inserted. Random degrees of rotational malalignment were applied using a hand-held goniometer via reference wires at the fracture site. Ten surgeons, blinded for the applied rotation, performed rotational corrections according to (1) current clinical practice after single-leg and dual-leg draping, and (2) according to the CARV-protocol. The primary outcome measure was the accuracy of the corrections relative to neutral tibial alignment. The CARV-protocol was tested in a small clinical cohort., Results: In total, 180 rotational corrections were performed by 10 surgeons. Correction according to clinical practice using single-leg and dual-leg draping resulted in a median difference of, respectively, 10.0° (IQR 5.0°) and 10.0° (IQR 5.0°) relative to neutral alignment. Single-leg and dual-leg draping resulted in malalignment (≥10°) in, respectively, 67% and 58% of the corrections. Standardized correction using the CARV resulted in a median difference of 5.0° (IQR 5.0°) relative to neutral alignment, with only 12% categorized as malalignment (≥10°). The incidence of rotational malalignment after application of the CARV decreased from 67% and 58% to 12% (p =  <0.001). Both consultants and residents successfully applied the CARV-protocol. Finally, three clinical patients with a tibial shaft fracture were treated according to the CARV-protocol, resulting all in acceptable alignment (<10°) based on postoperative CT-measurements., Conclusion: This study introduces an easy-to-use and clinically feasible standardized intraoperative fluoroscopy protocol coined 'C-arm rotational view (CARV)' to minimize the risk for rotational malalignment following intramedullary-nailing of tibial shaft fractures., (© 2022. The Author(s).)

Introduction: Rotational malalignment occurs in up to 30% of cases after intramedullary nailing of tibial shaft fractures. The aim of this study is to assess the clinical feasibility of a newly introduced standardised intraoperative fluoroscopy protocol coined 'C-arm rotational view (CARV)' in order to reduce the risk of rotational malalignment during intramedullary nailing of tibial shaft fractures. The CARV includes predefined fluoroscopy landmark views of the uninjured side to obtain correct alignment of the injured side with use of the rotation of the C-arm., Methods and Analysis: This randomised controlled trial will be conducted in a level 1 trauma centre. Adult patients with an open or closed tibial fracture, eligible for intramedullary nailing, will be enrolled in the study. The interventional group will undergo intramedullary nailing guided by the CARV protocol to obtain accurate alignment. The control group is treated according to current clinical practice, in which alignment control of the tibia is based on clinical estimation of the treating surgeon. The primary endpoint is defined as the degree of rotation measured on low-dose postoperative CT scans., Ethics and Dissemination: The study protocol will be performed in line with local ethical guidelines and the Declaration of Helsinki. The results of this trial will be disseminated in a peer-reviewed manuscript. Future patients are likely to benefit from this trial as it aims to provide a clinically feasible and easy-to-use standardised fluoroscopy protocol to reduce the risk for rotational malalignment during intramedullary nailing of tibial shaft fractures., Trial Registration Number: NCT05459038., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Stretch-induced collagen uncrimping underlies the nonlinear mechanical behavior of the sclera according to what is often called the process of recruitment. We recently reported experimental measurements of sclera collagen crimp and pressure-induced uncrimping. Our studies, however, were cross-sectional, providing statistical descriptions of crimp with no information on the effects of stretch on specific collagen bundles. Data on bundle-specific uncrimping is necessary to better understand the effects of macroscale input on the collagen microscale and tissue failure. Our goal in this project was to measure bundle-specific stretch-induced collagen uncrimping of sclera. Three goat eyes were cryosectioned sagittally (30 μm). Samples of equatorial sclera were isolated, mounted to a custom uni-axial stretcher and imaged with polarized light microscopy at various levels of clamp-to-clamp stretch until failure. At each stretch level, local strain was measured using image tracking techniques. The level of collagen crimping was determined from the bundle waviness, defined as the circular standard deviation of fiber orientation along a bundle. Eye-specific recruitment curves were then computed using eye-specific waviness at maximum stretch before sample failure to define fibers as recruited. Nonlinear mixed effect models were used to determine the associations of waviness to local strain and recruitment to clamp-to-clamp stretch. Waviness decreased exponentially with local strain (p < 0.001), whereas bundle recruitment followed a sigmoidal curve with clamp-to-clamp stretch (p < 0.001). Individual bundle responses to stretch varied substantially, but recruitment curves were similar across sections and eyes. In conclusion, uni-axial stretch caused measurable bundle-specific uncrimping, with the sigmoidal recruitment pattern characteristic of fiber-reinforced soft tissues., (Copyright © 2023 by ASME.)

Introduction: Definitive treatment of distal extra-articular fractures of the tibia is challenging and both minimal invasive plate osteosynthesis (MIPO) and intramedullary nailing (IMN) are considered to be feasible surgical modalities with their own implant-specific merits and demerits. This retrospective study was designed to compare MIPO versus IMN in terms of fracture healing, complications, functional and radiological outcomes and to assess the efficacy of intra-operative alignment control to reduce the rate of malalignment after definitive fixation of distal extra-articular fractures of the tibia., Materials and Methods: All consecutive adult patients with extra-articular distal meta- or diaphyseal tibia fractures that were treated between January 2012 and September 2019 either with MIPO or IMN were included. Outcome measures included fracture healing, complications (infection, malalignment, subsequent surgeries), functional and radiological outcomes. Intra-operative alignment control encompassed bilateral draping of the lower extremities., Results: A total of 135 patients were included out of which 72 patients (53%) were treated with MIPO and 63 patients (47%) underwent IMN. There was a significantly higher incidence of non-union for fractures treated with IMN (13 (22%) vs. 4 (6%), p = 0.04). There was no significant difference between both groups in terms of rotational malalignment (3% vs. 10%) and angular malalignment (4% vs. 5%). A significantly higher rate of infection was found after MIPO after correction of significant differences in baseline characteristics. No differences were found in subsequent surgeries or functional outcomes., Conclusion: Both MIPO and IMN are reliable surgical techniques. IMN is associated with higher rates of non-union, whereas MIPO results in a higher risk for infection. The incidence of malalignment was surprisingly low endorsing the utility of the intra-operative alignment control., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Solvents such as butanol are important platform chemicals and are often produced from petrochemical sources. Production of butanol and other compounds from renewable and sustainable resources can be achieved by solventogenic bacteria, such as the hyper-butanol producer Clostridium saccharoperbutylacetonicum . Its sol operon consists of the genes encoding butyraldehyde dehydrogenase, CoA transferase, and acetoacetate decarboxylase ( bld , ctfA , ctfB , adc ) and the gene products are involved in butanol and acetone formation. It is important to understand its regulation to further optimize the solvent production. In this study, a new long non-coding antisense transcript complementary to the complete sol operon, now called Assolrna, was identified by transcriptomic analysis and the regulatory mechanism of Assolrna was investigated. For this purpose, the promoter-exchange strain C. saccharoperbutylacetonicum ΔP asr :: P asr ** was constructed. Additionally, Assolrna was expressed plasmid-based under control of the native P asr promoter and the lactose-inducible P bgaL promoter in both the wild type and the promoter-exchange strain. Solvent formation was strongly decreased for all strains based on C. saccharoperbutylacetonicum ΔP asr :: P asr ** and growth could not be restored by plasmid-based complementation of the exchanged promoter. Interestingly, very little sol mRNA expression was detected in the strain C. saccharoperbutylacetonicum ΔP asr :: P asr ** lacking Assolrna expression. Butanol titers were further increased for the overexpression strain C. saccharoperbutylacetonicum [pMTL83151&#95; asr &#95;P bgaL ] compared to the wild type. These results suggest that Assolrna has a positive effect on sol operon expression. Therefore, a possible stabilization mechanism of the sol mRNA by Assolrna under physiological concentrations is proposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baur, Poehlein, Renz, Hollitzer, Montoya Solano, Schiel-Bengelsdorf, Daniel and Dürre.)

Purpose: There is currently no consensus regarding the need for fixation of concomitant fibula fractures in patients with surgically treated distal tibia fracture. Although studies have shown it to be beneficial for fractures involving the syndesmosis, it remains unclear for suprasyndesmotic fractures. This study evaluates what effect the fixation of such suprasyndesmotic fibula fractures had on patients who underwent fixation of distal tibia fractures., Methods: This retrospective cohort study included all consecutive adult patients who received surgical treatment for an extra-articular or simple intraarticular distal tibia fracture between 2012 and 2020 and had a concomitant fibula fracture proximal to the syndesmosis. Two groups were formed depending on whether the fibula was stabilized. The need for revision surgery, the occurrence of complications, fracture healing, rotational and angular malalignment were evaluated for both groups., Results: This study included 120 patients, of which 40 (33.3%) had operative treatment of the fibula fracture. Of those with stabilized fibula fractures, 28 (70%) were treated with a plate and 12 (30%) with a titanium elastic nail. The group of patients with surgically treated fibula fractures had significantly more angular malalignments (10% vs 1.2%, p = 0.042), while there was no difference regarding rotational malalignment or fracture healing. Further, infections of the fibular surgical site occurred in 15% of surgically treated patients leading to significantly more revision surgeries in this group (40% vs 20%, p = 0.03). All infections occurred when a plate was used., Conclusion: This study was unable to show any benefit from stabilizing concomitant, suprasyndesmotic fibula fractures in surgically treated distal tibia fractures. On the contrary, infection, revision surgery and angular malalignment were more frequent when the fibula was fixed. Therefore, such concomitant fibula fractures should not routinely be fixed and if stabilization is deemed necessary, the implant should be chosen carefully., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Diarrhea is responsible for the deaths of more than 500,000 children each year, many of whom reside in low-to-middle-income countries (LMICs). Additionally, children with multiple diarrheal infections early in life have increased growth stunting and malnutrition and decreased vaccine efficacy. Two bacteria that contribute to the burden of diarrhea are Campylobacter jejuni and Campylobacter coli, both are endemic in Bangladesh. However, not all children that are exposed to these pathogens, including Campylobacter, will experience diarrhea. We hypothesized that host genetics may influence susceptibility to Campylobacter infections and performed a genome-wide association study in 534 children from two independent birth cohorts in Dhaka, Bangladesh. Infants were monitored for diarrhea for the first 2 years of life and only defined as controls if all diarrheal samples in the first year were negative for Campylobacter jejuni / C. coli. Each cohort was analyzed separately under an additive model and adjusted for length-for-age z-scores at birth and 12 months, sex, water treatment, and ancestry. In a fixed effect inverse-variance weighted meta-analysis of these two cohorts, we identified a genome-wide significant region on chromosome 8 in intron 4 of the rho guanine nucleotide exchange factor 10 gene ( ARHGEF10 ). Individuals with the G allele (rs13281104) had a 2-fold lower risk of having a Campylobacter-associated diarrheal episode than individuals with the A allele (OR 0.41, 95% CI 0.29 to 0.58, P = 3.6 × 10 -7 ). This SNP is associated with decreased expression of the neighboring gene, CLN8 , which may be involved in the transport of the cytolethal distending toxin produced by Campylobacter. IMPORTANCE Children in low-to-middle-income countries often suffer from multiple enteric infections in their first few years of life, many of which have the potential for long-lasting effects. These children are already likely to be malnourished and underweight, and chronic intestinal disturbances exacerbate these conditions. Despite public health interventions aimed at improving water, sanitation, and hygiene, enteric infections are still a leading cause of death for children under five. Previous work has included transmission dynamics, pathogen characteristics, and evaluation of interventions. Here, we examined the role of host genetic variation in susceptibility to diarrhea-associated Campylobacter infection. In our meta-analysis of two independent birth cohorts from Dhaka, Bangladesh, we found that children carrying a specific genetic variant (rs13281104, in an intron of ARHGEF10 ) were half as likely to have a diarrhea-associated Campylobacter infection in their first year of life. This protective effect may be achieved by decreasing gene expression and thereby impacting host-pathogen interactions and host immune response.

Purpose: This study aimed to investigate the association between serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and incident metabolic disease in a cohort of community-based older Chinese people., Patients and Methods: Five thousand healthy Gaohang residents who attended community health checks at the Shanghai East Hospital in 2013 were recruited. Biological, biochemical, and lifestyle variables were collected. The cohort was followed for new-onset metabolic disease in 2014 and 2017, with a final study population of 3,123 (63%) after follow-up. The study outcome included type-2 diabetes mellitus and metabolic syndrome., Results: Baseline AST and ALT were associated with incident type-2 diabetes mellitus (HR 1.019, 95% CI 1.006-1.032, p = 0.003 and HR 1.016, 95% CI 1.008-1.025, p < 0.001 respectively). These associations persisted after adjusting for traditional risk factors including age, sex, income, waist circumference, systolic blood pressure, diastolic blood pressure, HbA1c, triglyceride, cholesterol, HDL and eGFR. Baseline AST and ALT were associated with incident metabolic syndrome in the crude analysis (HR 0.980, 95% CI 0.965-0.996, p = 0.012 and HR 0.992, 95% CI 0.988-0.997, p = 0.001, respectively). However, the association between AST and ALT with metabolic syndrome was non-significant after adjusting for biochemical parameters such as the lipid profile., Conclusion: This study demonstrated that serum AST and ALT are associated with new-onset type-2 diabetes mellitus, independent of traditional risk factors, in a cohort of older Chinese people. These findings may contribute to disease risk stratification and management in type-2 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lan, Zhang, Lin, Meng, Buys, Fan and Sun.)

To mitigate the unprecedented health, social, and economic damage of COVID-19, the Philippines is undertaking a nationwide vaccination program to mitigate the effects of the global pandemic. In this study, we interrogated COVID-19 vaccine intent in the country by deploying a nationwide open-access online survey, two months before the rollout of the national vaccination program. The Health Belief Model (HBM) posits that people are likely to adopt disease prevention behaviors and to accept medical interventions like vaccines if there is sufficient motivation and cues to action. A majority of our 7,193 respondents (62.5%) indicated that they were willing to be vaccinated against COVID-19. Moreover, multivariable analysis revealed that HBM constructs were associated with vaccination intention in the Philippines. Perceptions of high susceptibility, high severity, and significant benefits were all good predictors for vaccination intent. We also found that external cues to action were important. Large majorities of our respondents would only receive the COVID-19 vaccines after many others had received it (72.8%) or after politicians had received it (68.2%). Finally, our study revealed that most (21%) were willing to pay an amount of PHP 1,000 (USD20) for the COVID-19 vaccines with an average willing-to-pay amount of PHP1,892 (USD38)., Competing Interests: The authors declare there are no competing interests., (©2022 Caple et al.)

Geographic information science (GIS) has emerged as a unique tool that is extremely valuable in various research which involves spatial-temporal aspects. The geographical distribution of the epidemic is considered a significant characteristic that can be analyzed using GIS and spatial statistics. Proper knowledge can assist in controlling, mitigating, and mapping factors for detecting the transmission as well as the disease dynamics, and it provides geographical information of the outbreak and it can also give a glimpse of the disease trend and hotspots as well as provide ways to further evaluate the associated risk. This study analyzed the countries' total confirmed cases, total death cases, and the total recovered cases using an (IDW) geospatial technique which is an inherent tool used in ArcMap for spatial analysis. In order to identify the hotspots for COVID-19 cases, the Getis-Ord Gi* statistic method was applied with a confidence level of 95% in Herat and 90% for Kabul, Kapisa, and Logar provinces. The data considered in this research ranged from the period of 23rd July 2020 to 24th February 2021. All the COVID-19 confirmed, recovered, and death cases were correlated with provincial population density using the Pearson Correlation coefficient. Among the total cases 54,487, 32% cases were reported in the capital of the country (Kabul), and the mortality rate was 31% followed by Herat (18% deaths), Balkh (7% deaths), and Nangarhar (6% deaths). Most of the recoveries were observed in Kabul with (30%) followed by Herat (16%), Bamyan (10%), Balkh (5%), and Kandahar (5%). The results for Global Moran's I showed that the incidence rate of the total COVID-19 cases was in the random pattern, with the Moran Index of - 0.14. Given the z-score of - 1.62, the pattern does not appear to be significantly different than random. There was a strong correlation between the COVID-19 variables and population density [with r (33) = 0.827], [ r (33) = 0.819] and [ r (33) = 0.817] for the total cases, death cases, and recovered cases, respectively. Even though GIS has limited applicability in detecting the type and its spatial pattern of the epidemic, there is a high potential to use these tools in managing and controlling the pandemic. Moreover, GIS helps us better in comprehending the epidemic and assists us in addressing those fractions of the population and communities which are underserved during the disease outbreak., Competing Interests: Conflict of interestAuthors declare no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

Disagreement is essential to scientific progress but the extent of disagreement in science, its evolution over time, and the fields in which it happens remain poorly understood. Here we report the development of an approach based on cue phrases that can identify instances of disagreement in scientific articles. These instances are sentences in an article that cite other articles. Applying this approach to a collection of more than four million English-language articles published between 2000 and 2015 period, we determine the level of disagreement in five broad fields within the scientific literature (biomedical and health sciences; life and earth sciences; mathematics and computer science; physical sciences and engineering; and social sciences and humanities) and 817 meso-level fields. Overall, the level of disagreement is highest in the social sciences and humanities, and lowest in mathematics and computer science. However, there is considerable heterogeneity across the meso-level fields, revealing the importance of local disciplinary cultures and the epistemic characteristics of disagreement. Analysis at the level of individual articles reveals notable episodes of disagreement in science, and illustrates how methodological artifacts can confound analyses of scientific texts., Competing Interests: WL, KB, VL, CS, Nv, LW, DM No competing interests declared, (© 2021, Lamers et al.)