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Chelcy E Brumlow,1 Ruth A Luna,2,3 Emily B Hollister,2,3 Javier A Gomez,1 Lindsey A Burcham,1 Madison B Cowdrey,1 Todd P Primm1 1Department of Biological Sciences, Sam Houston State University, Huntsville, TX, USA; 2Department of Pathology, Texas Children’s Microbiome Center, Texas Children’s Hospital, Houston, TX, USA; 3Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA Background: The microbiomes of animals are complex communities that strongly affect the health of the hosts. Microbiomes on mucosal surfaces have the highest densities and most extensive biochemical exchanges with the hosts. Although antibiotics are potent tools to manage infections, they can disrupt the normal microbiota, causing numerous side effects. Materials and methods: Taking a community ecology approach, mucosal microbiome community responses to five disruptive conditions (two broad-spectrum antibiotics, a biocide, elevated temperature, and rinsing) were analyzed. Skin of the fish Gambusia affinis was the mucosal model. Microbiome recovery was measured by culturable counts, community biochemical profiles, genetic fingerprinting, and community 16S gene sequencing (rinsing condition only). Results: Following all disruptions, the total counts rose and then returned to the pre-treatment (PT) level. This overgrowth was confirmed via direct staining and community metabolic activity measurements. After rinsing, diversity decreased and one taxon dominated (family Aeromonadaceae) temporarily, the findings similar to numerous other studies with antibiotics. While the community did not return to the PT taxonomic composition, the biochemical profile did. Conclusion: This suggests that the biochemical pathways in a community are important during recovery, and a return to the original composition is not required to restore original function. Keywords: Gambusia affinis, rifampicin, tetracycline, chlorhexidine

Abstract Unlike the cognitions associated with depressive symptoms, little is known about those associated with antisocial personality and with its related traits (“dark traits”). Using the scrambled sentences task, an instrument from depression research, we investigated cognitions such as justifications (external blaming for one’s behavior) and harm to others (based on the notion that some of these individuals enjoy harming or humiliating others) that we hypothesized may be prevalent in those high in antisocial personality traits. Confirming our hypothesis, these cognitions were associated with ratings on different antisocial personality scales and with antisocial and detachment scores in the alternative model of personality disorders of the DSM-5 (AMPD) in three non-clinical samples, but not with depressive symptoms or neuroticism. Cognitions including harm to others were differentially associated with high sadism. These findings empirically characterize classes of cognitions that are shared by individuals with antisocial tendencies, and that differ from those associated with depressive symptoms.

Recent evidence indicates that the human womb is contaminated with a variety of particulate contaminants. Microplastics (MPs, tiny plastic particles, 0.1 – 5000 µm) generated by the breakdown of larger plastic products in the environment) accumulation in human placenta has recently been described. In addition, recent evidence has correlated the number of air pollution particulates in term placentas to the loading of these particles in dust from the gestational parent home. The current study sought to characterize the accumulation of plastic and non-plastic particles (NPP) within the term human placenta. Placenta tissues were collected from healthy, singleton pregnancies following vaginal (n = 5) and caesarean section (n = 5) deliveries at a tertiary care centre located in an urban Canadian city (Ottawa, ON), with particles detected and characterized by Raman micro-spectroscopy. Both plastic and non-plastic particles were identified in all placentas examined, with an average of 1 ± 1.2 MPs /g and 4 ± 2.9 NPP /g of tissue. Similar tissue concentrations of MPs and NNP were identified in all regions of the placenta (basal plate, chorionic villous, chorionic plate), and did not differ according to mode of delivery. MPs ranged in size (2 – 60 μm), with the most abundant MPs being polyethylene (PE), polypropylene (PP), polystyrene (PS) and polyvinyl chloride (PVC). The most abundantly identified NPP were carbon, graphite, and lead oxide. Collectively, these results demonstrate the accumulation of foreign particles, including MPs, throughout the human placenta. Given the vital functions of the placenta in supporting fetal growth and development, and a potential for MPs to induce toxicity, further investigations into the potential harmful effects of these environmental toxicants on maternal and fetal health is warranted.

The nature of the global signal, i.e. the average signal from sequential functional imaging scans of the brain or the cortex, is not well understood, but is thought to include vascular and neural components. Using resting state data, we report on the strong association between the global signal and the average signal from the part of the volume that includes the cranial bone and subdural vessels and venous collectors, separated from each other and the subdural space by multispectral segmentation procedures. While subdural vessels carried a signal with a phase delay relative to the cortex, the association with the cortical signal was strongest in the parts of the scan corresponding to the laminae of the cranial bone, reaching 80% shared variance in some individuals. These findings suggest that in resting state data vascular components may play a prominent role in the genesis of fluctuations of the global signal. Evidence from other studies on the existence of neural sources of the global signal suggests that it may reflect the action of multiple mechanisms (including cerebrovascular reactivity and autonomic control) concurrently acting to regulate global cerebral perfusion.

IntroductionWith the introduction of the new psychiatric diagnostic manuals, personality functioning has gained new prominence. Several studies have reported consistent findings that individual showing high levels of antisocial features are associated with alterations in interpersonal functioning domains such as empathy and mentalisation. The focus of the current study (N = 198) is to examine antisocial cognitions, as measured by the Scrambled Sentences Task (SST), and to what extent this approach can help to better understand the relationship between antisocial traits and personality functioning/empathy.MethodWe implemented a hypothesis-driven approach using logistic regression and a data-driven approach using machine learning to examine distinct but related measures of personality functioning as predictors of antisocial cognitions.ResultsAntisocial cognitions were associated with low interpersonal functioning as expected, but only when not adjusting for antisocial traits, which accounted for almost all the association. The data-driven analysis revealed that individual items assessing empathic concern in personality functioning scales (as opposed to the whole scores) explained low antisocial cognitions even when adjusting for antisocial traits.DiscussionAntisocial cognitions appear to be associated to two distinct traits, the antisocial and a specific type of personality functioning. This finding is discussed in terms of the possible distinction between two motivational forces: to harm others/prioritize one’s advantage, and to help suffering others.

Microplastics (MPs) are present in ambient air in a respirable size fraction; however, their potential impact on human health via inhalation routes is not well documented. In the present study, methods for a lab-scale generation of MPs from regularly used and littered plastic articles were optimized. The toxicity of 11 different types of MPs, both commercially purchased and in-lab prepared MPs, was investigated in lung epithelial cells using cell viability, immune and inflammatory response, and genotoxicity endpoints. The underlying mechanisms were identified by microarray analysis. Although laborious, the laboratory-scale methods generated a sufficient quantity of well characterized MPs for toxicity testing. Of the 11 MPs tested, the small sized polyethylene terephthalate (PETE) MPs prepared from disposable water bottles induced the maximum toxicity. Specifically, the smaller size PETE MPs induced a robust activation of the interferon signaling pathway, implying that PETE MPs are perceived by cells by similar mechanisms as those employed to recognize pathogens. The PETE MPs of heterogenous size and shapes induced cell injury, triggering cell death, inflammatory cascade, and DNA damage, hallmark in vitro events indicative of potential in vivo tissue injury. The study establishes toxicity of specific types of plastic materials in micron and nano size.

Previous studies confirmed the psychological, psychosomatic, and economic consequences of the COVID-19 outbreak, which lead to the introduction of a new concept of coronaphobia as a persistent and excessive fear of the novel coronavirus. With the beginning of the pandemic, the interest in coronaphobia-related measurement began and until 2021, 12 instruments were created, with a total of 28 (sub)scales. The first aim of this study was to explore the joined factor structure of these measurements. The second aim was to explore a wide range of correlates of coronaphobia (sociodemographic characteristics, general anxiety disorder, Big Five traits, knowledge about coronavirus, and political orientation). The sample included 347 participants (42.1% male) from the general population of Serbia and data were collected in April 2021. Results showed that only one component could be extracted based on 28 (sub)scales of coronaphobia, meaning that physiological, cognitive, emotional, and behavioral aspects of coronaphobia are rather intercorrelated. Furthermore, among explored correlates, general anxiety disorder had the highest contribution to the explanation of coronaphobia. Additionally, Openness showed a negative, and age showed a positive contribution to the explanation of coronaphobia. Our results suggest that coronaphobia should be understood as a syndrome that captures physiological, cognitive, behavioral, and emotional aspects, and that individuals who are already prone to anxiety disorders are more prone to coronaphobia as well.

PDS 70 hosts two massive, still-accreting planets and the inclined orientation of its protoplanetary disk presents a unique opportunity to directly probe the vertical gas structure of a planet-hosting disk. Here, we use high-spatial-resolution (≈0.″1; 10 au) observations in a set of CO isotopologue lines and HCO ^+ J = 4−3 to map the full 2D ( r , z ) disk structure from the disk atmosphere, as traced by ^12 CO, to closer to the midplane, as probed by less abundant isotopologues and HCO ^+ . In the PDS 70 disk, ^12 CO traces a height of z / r ≈ 0.3, ^13 CO is found at z / r ≈ 0.1, and C ^18 O originates at, or near, the midplane. The HCO ^+ surface arises from z / r ≈ 0.2 and is one of the few non-CO emission surfaces constrained with high-fidelity in disks to date. In the ^12 CO J = 3−2 line, we resolve a vertical dip and steep rise in height at the cavity wall, making PDS 70 the first transition disk where this effect is directly seen in line-emitting heights. In the outer disk, the CO emission heights of PDS 70 appear typical for its stellar mass and disk size and are not substantially altered by the two inner embedded planets. By combining CO isotopologue and HCO ^+ lines, we derive the 2D gas temperature structure and estimate a midplane CO snowline of ≈ 56–85 au. This implies that both PDS 70b and 70c are located interior to the CO snowline and are likely accreting gas with a high C/O ratio of ≈ 1.0, which provides context for future planetary atmospheric measurements from, e.g., JWST, and for properly modeling their formation histories.

Medical students report high demands, stressors, pressure to perform, and a lack of resources, and are therefore at a higher risk for mental strain and burnout. Due to the COVID-19 pandemic, study conditions have changed, and new challenges have emerged. Thus, this study aimed to examine medical students’ well-being, mental health, and study characteristics before and during the pandemic. Data from 988 Austrian medical students were included into the cross-sectional comparisons, and 63 students were included into the longitudinal analyses (variance analyses/t-tests or appropriate non-parametric tests). Well-being before and during the pandemic did not differ significantly but the peri-pandemic cohort reported higher study satisfaction, more social support from lecturers, and less emotional exhaustion, cognitive demands, and stressors (information problems, organizational stressors, work overload). Longitudinally, work overload was also perceived to be higher before the pandemic; however, study satisfaction was lower. During the pandemic, approximately every seventh student exceeded the cut-off value for generalized anxiety disorder, and approximately every tenth student exceeded the cut-off value for major depression. These unexpected peri-pandemic results concerning constant high well-being, study satisfaction, and the perception of conditions may be based on response shift effects that require further exploration. The scores exceeding the reasonable cut-point for identifying probable cases of generalized anxiety disorder and depression may reflect medical students’ needs, calling for an in-depth analysis if further health promotion is necessary.

Background and aimsThe COVID-19 pandemic has been accompanied by a worsening of mental health levels in some, while others manage to adapt or recover relatively quickly. Transdiagnostic factors such as personality functioning are thought to be involved in determining mental health outcomes. The present study focused on two constructs of personality functioning, Criterion A of the Alternative Model for Personality Disorders (AMPD, DSM-5) and mentalization, as predictors of depressive symptoms and life satisfaction during the COVID-19 pandemic. A second focus of the study was to examine whether this relationship was mediated by resilience.MethodsLinear regression analyses were used to examine the relationship between personality functioning measured by Criterion A (AMPD, DSM-5) and mentalizing abilities as predictors, and depression and life satisfaction as mental health outcomes. To assess the hypothesis that this relationship is mediated by resilience a structural equation modeling approach was conducted. Data from N = 316 individuals from the general population were collected.ResultsLinear regression models revealed highly significant associations between Criterion A/mentalization and both outcome measures. Structural equation models showed a significant partial mediation by resilience of these relationships.ConclusionOur results support the hypothesis that mentalizing serves as a protective function by promoting resilience to the impact of stress and threats. Criterion A and mentalization performed similarly as predictors of mental health outcomes, providing empirically overlapping operationalizations of personality functioning. This finding emphasizes the importance of personality functioning in positive and negative mental health outcomes. Furthermore, our results are consistent with a mediating role of resilience.

The Nantu Forest in Gorontalo Province, Sulawesi, Indonesia holds one of the few remaining pristine habitats in the island. The reserve is surrounded by human habituation which provide opportunity to study the impact of forest lost on biodversity. In addition, data on Nantu mostly focused on big mammals, as there is no previous herpetofauna survey at the area. Sampling of amphibian and reptile was conducted in June 2013 and in May–June 2014 using Visual Encounter Survey method, glue traps and transect sampling in seven different sites at the eastern part of Nantu. We categorized four habitat types based on human disturbances: high disturbed habitat (HDH), moderate disturbed habitat (MDH), low disturbed habitat (LDH) and pristine habitat (PH). A total of 680 individual amphibians (4 families; 17 species) and 119 individual reptiles (9 families; 29 species) were recorded. Species richness and species composition for amphibians and reptiles differs according to the level of human disturbances. Low level disturbances habitat demonstrated the highest diversity of amphibians and reptiles, whereas as expected, high distubed habitat showed the lowest diversity. Anthropogenic pressures in forest will decrease species richness of amphibian and reptiles. Although most amphibian and reptiles will be able to persist in low disturbances habitat, forest-dependent species will be lost when pristine forests are disturbed.

Introduction Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs—to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.Methods and analysis In this paper, we describe our approach to developing the GEAR Network infrastructure, the scoping reviews to identify research and clinical gaps and its use of consensus-driven research priorities with a transdisciplinary taskforce of stakeholders that includes patients and care partners. We describe how priority topic areas are ascertained, the process of conducting scoping reviews with integrated academic librarians performing standardised searches and providing quality control on reviews, input and support from the taskforce and conducting a large-scale consensus workshop to prioritise future research topics. The GEAR Network approach provides a framework and systematic approach to develop a research agenda and support research in geriatric emergency care.Ethics and dissemination This is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. These reviews will be prepared as manuscripts and submitted for publication to peer-reviewed journals, and the results will be presented at conferences.Open Science Framework registered DOI: 10.17605/OSF.IO/6QRYX, 10.17605/OSF.IO/AKVZ8, 10.17605/OSF.IO/EPVR5, 10.17605/OSF.IO/VXPRS.

We report on an interview with Julian Quijano, founder of Beautiful Glitch. This is an independent developer which produced Monster Prom, an English-language visual novel released in April 2018 and available on Steam. The interview, kindly provided by email in June 2019, addresses the company, the game development, and Julian Quijano’s opinion of game localization. The goal was to learn a little more about the videogame market, moving away from the traditional approach to big companies. The interview was conducted in English and translated into Portuguese to be reported in a bilingual English-Portuguese version as a means to reach a wider audience.

In this work, a structured design method, the Stylistic Design Engineering (SDE), is applied for the construction of a new minivan car, in particular a new city car, which we will call FIAT 600 Omega. The SDE, or Stylistic Design Engineering, is a structured engineering method for carrying out automotive design projects. The SDE method consists of six different phases: (1) Analysis of stylistic trends; (2) Sketches; (3) 2D Computer Aided Design (CAD) drawings; (4) 3D CAD models; (5) Rendering; (6) Solid stylistic model (also called style maquette). This project deals with the external redesign of the Fiat 600 multiple, a small minivan which was very successful in the 1950s and 1960s. SDE is a methodology consisting of various technologies and design methodologies that will be further explained in detail, such as the Pininfarina method, the Quality Function Deployment (QFD) method, Benchmarking (BM), and Top Flop Analysis (TPA). The work was organized according to the different phases. Initially, the Fiat style was studied, in particular the style of the FIAT 600 MULTI PURPOUSE VEHICLE (MPV). This step is essential to better understand the characteristics of the brand and also the main characteristics carried out over the decades. Then we moved on to the freehand sketching phase, based on what we learned in the previous phase of the study. When a satisfactory shape was found for the new car, by analyzing and discarding the different proposals of the various types of style, we proceeded to the evaluation of the proportions and dimensions through two-dimensional drawings and finally we obtained the three-dimensional shape of the new car thanks to 3D CAD software and rendering software. Many advantages in the industrial world SDE takes together with its development. In fact, until the early 2000s, car design and styling was considered quite a craft activity, not a technical or scientific one, mostly based on the great capability of famous car designers and masters, just like Giugiaro, Zagato, Bertone, Pininfarina, Stephenson, Bangle, etc. Then, thanks to the industrial activity of Eng. Lorenzo Ramacciotti, former CEO of Pininfarina Spa and Mechanical Engineer, and also thanks to the academic studies developed at ALMA MATER STUDIORUM University of Bologna, SDE became the object of attention, because it is able to systematize the car design process and reduce costs. With SDE, a good design research or an industrial product development team can complete a car design project, also without the presence of a mentor. Car Design Process finally becomes with SDE a scientific method; Car Design becomes with SDE an industrial method. Industrial needs are nice products made in a short time; SDE is structured to attend these issues. Industrial challenges follow innovation, in shape and functionality; SDE is able to recognize innovation. Industrial benefits can be reached with SDE, ensuring beautiful aesthetic projects are realized systematically and with low costs.

Background: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults., Methods: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age strata compared to adolescents (12-17 years), and for adult age strata compared to young adults (22-49 years)., Results: Of 9101 patients in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence cohort, 1560 were hospitalized for COVID-19 as the primary reason. Compared to adults (22-105 years, n = 675), children (0-21 years, n = 885) were less commonly vaccinated (14.3% vs 34.5%), more commonly infected with the Omicron variant (49.5% vs 26.1%) and had fewer comorbidities ( P < .001 for most comparisons), except for lung disease ( P = .24). After adjusting for confounding variables, children had significantly lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval, .35-.92) and death (aOR, 0.011; 95% confidence interval, <.01-.58) compa--red to adults. Among pediatric age strata, adolescents 12-17 years had the highest odds of receiving supplemental oxygen, high-flow oxygen, and ICU admission. Among adults, those 50-64 years had the highest odds of mechanical ventilation and ICU admission., Conclusions: Clinical outcomes of COVID-19 differed across pediatric and adult age strata. Adolescents experienced the most severe disease among children, whereas adults 50-64 years experienced the most severe disease among adults., Competing Interests: Potential conflicts of interest. C. A. R.'s institution has received funds to conduct clinical research unrelated to this manuscript from the Centers for Disease Control and Prevention, BioFire Inc, GSK, MedImmune, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. C. Y. C. receives research funding from Abbott Laboratories and Delve Bio on unrelated pathogen detection and discovery projects using metagenomic next-generation sequencing and is a cofounder of and owns equity in Delve Bio. C. Y. C. is also on the scientific advisory board for Biomeme, Biomesense, Flightpath Biosciences, Mammoth Biosciences, and Poppy Health. C. K. is a consultant for Ferring/Rebiotix and a scientific advisor for Seres Therapeutics. A. V. A. is a stockholder of Alzeca Inc. and Sensulin LLC and is on the scientific advisory board of Alezeca Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Borolatonin is a potential therapeutic agent for some neuronal diseases such as Alzheimer's disease (AD). Its administration exerts ameliorative effects such as those induced by the equimolar administration of melatonin in behavioral tests on male rats and in neuronal immunohistochemistry assays., Objective: In this study, motivated by sex differences in neurobiology and the incidence of AD, the ability of borolatonin to induce changes in female rats was assessed., Methods: Effects of borolatonin were measured by the evaluation of both behavioral and immunohistopathologic approaches; additionally, its ability to limit amyloid toxicity was determined in vitro., Results: Surprisingly, behavioral changes were similar to those reported in male rats, but not those evaluated by immunoassays regarding neuronal survival; while pro-brain-derived neurotrophic factor (BDNF) immunoreactivity and the limitation of toxicity by amyloid in vitro were observed for the first time., Conclusion: Borolatonin administration induced changes in female rats. Differences induced by the administration of borolatonin or melatonin could be related to the differences in the production of steroid hormones in sex dependence. Further studies are required to clarify the possible mechanism and origin of differences in disturbed memory caused by the gonadectomy procedure between male and female rats., (© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)

Large hiatal hernias, besides being more prevalent in the elderly, have a different clinical presentation: less reflux, more mechanical symptoms, and a greater possibility of acute, life-threatening complications such as gastric volvulus, ischemia, and visceral mediastinal perforation. Thus, surgical indications are distinct from gastroesophageal reflux disease-related sliding hiatal hernias. Heartburn tends to be less intense, while symptoms of chest pain, cough, discomfort, and tiredness are reported more frequently. Complaints of vomiting and dysphagia may suggest the presence of associated gastric volvulus. Signs of iron deficiency and anemia are found. Surgical indication is still controversial and was previously based on high mortality reported in emergency surgeries for gastric volvulus. Postoperative mortality is especially related to three factors: body mass index above 35, age over 70 years, and the presence of comorbidities. Minimally invasive elective surgery should be offered to symptomatic individuals with good or reasonable performance status, regardless of age group. In asymptomatic and oligosymptomatic patients, besides obviously identifying the patient's desire, a case-by-case analysis of surgical risk factors such as age, obesity, and comorbidities should be taken into consideration. Attention should also be paid to situations with greater technical difficulty and risks of acute migration due to increased abdominal pressure (abdominoplasty, manual labor, spastic diseases). Technical alternatives such as partial fundoplication and anterior gastropexy can be considered. We emphasize the importance of performing surgical procedures in cases of large hiatal hernias in high-volume centers, with experienced surgeons.

Valproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as N -(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antiproliferative activity than the VPA in different cancer cell lines. The purpose of this study was to evaluate the liver injury of HO-AAVPA by acute treatment (once administration) and repeated doses for 7 days under intraperitoneal administration. The median lethal dose value (LD 50 ) was determined in rats and mice (females and males) using OECD Guideline 425. In the study, male rats were randomly divided into 4 groups (n = 7), G1: control (without treatment), G2: vehicle, G3: VPA (500 mg/kg), and G4: HO-AAVPA (708 mg/kg, in equimolar ratio to VPA). Some biomarkers related to hepatotoxicity were evaluated. In addition, macroscopic and histological studies were performed. The LD 50 value of HO-AAVPA was greater than 2000 mg/kg. Regarding macroscopy and biochemistry, the HO-AAVPA does not induce liver injury according to the measures of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutathione peroxidase, glutathione reductase, and catalase activities. Comparing the treatment with HO-AAVPA and VPA did not show a significant difference with the control group, while malondialdehyde and glutathione-reduced levels in the group treated with HO-AAVPA were close to those of the control ( p ≤ 0.05). The histological study shows that liver lesions caused by HO-AAVPA were less severe compared with VPA. Therefore, it is suggested that HO-AAVPA does not induce hepatotoxicity at therapeutic doses, considering that in the future it could be proposed as an antineoplastic drug.

Amebiasis is an intestinal infection caused by Entamoeba histolytica . Amebic liver abscess (ALA) is the most common extraintestinal complication of amebiasis. In animal models of ALA, neutrophils have been shown to be the first cells to come into contact with Entamoeba histolytica during the initial phase of ALA. One of the multiple mechanisms by which neutrophils exhibit amebicidal activity is through reactive oxygen species (ROS) and the enzyme NADPH oxidase (NOX2), which generates and transports electrons to subsequently reduce molecular oxygen into superoxide anion. Previous reports have shown that ROS release in the susceptible animal species (hamster) is mainly stimulated by the pathogen, in turn provoking such an exacerbated inflammatory reaction that it is unable to be controlled and results in the death of the animal model. Apocynin is a natural inhibitor of NADPH oxidase. No information is available on the role of NOX in the evolution of ALA in the hamster, a susceptible model. Our study showed that administration of a selective NADPH oxidase 2 (NOX2) enzyme inhibitor significantly decreases the percentage of ALA, the size of inflammatory foci, the number of neutrophils, and NOX activity indicated by the reduction in superoxide anion (O 2 - ) production. Moreover, in vitro, the apocynin damages amoebae. Our results showed that apocynin administration induces a decrease in the activity of NOX that could favor a decrease in ALA progression.

Background: Hispanic people with cystic fibrosis (CF) have decreased life expectancy and earlier acquisition of Pseudomonas aeruginosa compared to non-Hispanic white individuals with CF. Racial and ethnic differences in the airway microbiome of CF may contribute to known health disparity, but have not been studied. The objective was to describe differences in the upper airway microbial community in Hispanic and non-Hispanic white children with CF., Methods: This prospective, observational cohort study of 59 Hispanic and non-Hispanic white children with CF, ages 2-10 years old, was performed at Texas Children's Hospital (TCH) from February 2019 to January 2020. Oropharyngeal swabs were collected from the cohort during clinic visit. Swab samples underwent sequencing (16S V4 rRNA), diversity analysis, and taxonomic profiling. Key demographic and clinical data were collected from the electronic medical record and the CF Foundation Patient Registry (CFFPR). Statistical analysis compared sequencing, demographic, and clinical data., Results: We found no significant difference in Shannon diversity or relative abundance of bacterial phyla between Hispanic and non-Hispanic children with CF. However, a low abundant taxa- "uncultured bacterium" belonging to the order Saccharimonadales was significantly higher in Hispanic children (mean relative abundance = 0.13%) compared to the non-Hispanic children (0.03%). Hispanic children had increased incidence of P. aeruginosa (p = 0.045) compared to non-Hispanic children., Conclusion: We did not find a significant difference in the airway microbial diversity between Hispanic and non-Hispanic white children with CF. However, we found a greater relative abundance of Saccharimonadales and higher incidence of P. aeruginosa in Hispanic children with CF., (© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Amoebiasis is produced by the parasite Entamoeba histolytica ; this disease affects millions of people throughout the world who may suffer from amoebic colitis or amoebic liver abscess. Metronidazole is used to treat this protozoan, but it causes important adverse effects that limit its use. Studies have shown that riluzole has demonstrated activity against some parasites. Thus, the present study aimed, for the first time, to demonstrate the in vitro and in silico anti-amoebic activity of riluzole. In vitro, the results of Entamoeba histolytica trophozoites treated with IC 50 (319.5 μM) of riluzole for 5 h showed (i) a decrease of 48.1% in amoeba viability, (ii) ultrastructural changes such as a loss of plasma membrane continuity and alterations in the nuclei followed by lysis, (iii) apoptosis-like cell death, (iv) the triggering of the production of reactive oxygen species and nitric oxide, and (v) the downregulation of amoebic antioxidant enzyme gene expression. Interestingly, docking studies have indicated that riluzole presented a higher affinity than metronidazole for the antioxidant enzymes thioredoxin, thioredoxin reductase, rubrerythrin, and peroxiredoxin of Entamoeba histolytica , which are considered as possible candidates of molecular targets. Our results suggest that riluzole could be an alternative treatment against Entamoeba histolytica . Future studies should be conducted to analyze the in vivo riluzole anti-amoebic effect on the resolution of amebic liver abscess in a susceptible model, as this will contribute to developing new therapeutic agents with anti-amoebic activity.

Purpose: To determine whether intereye asymmetry of a three-dimensional neuroretinal rim parameter, the minimum distance band, is useful in differentiating normal eyes from those with open-angle glaucoma., Materials and Methods: This is a cross-sectional study of 28 normal subjects and 33 glaucoma subjects. Subjects underwent spectral domain optical coherence tomography imaging of both eyes. From high-density raster scans of the optic nerve head, a custom-designed segmentation algorithm calculated mean minimum distance band neuroretinal rim thickness globally, for four quadrants, and for four sectors. Intereye minimum distance band thickness asymmetry was calculated as the absolute difference in minimum distance band thickness values between the right and left eyes., Results: Increasing global minimum distance band thickness asymmetry was not associated with increasing age or increasing refractive error asymmetry. Glaucoma patients had thinner mean neuroretinal rim thickness values compared to normal patients (209.0 μm vs 306.0 μm [ P < 0.001]). Glaucoma subjects had greater intereye thickness asymmetry compared to normal subjects for the global region (51.9 μm vs 17.6 μm [ P < 0.001]) as well as for all quadrants and all sectors. For detecting glaucoma, a thickness asymmetry value >28.3 μm in the inferior quadrant yielded the greatest sum of sensitivity (87.9%) and specificity (75.0%). Globally, thickness asymmetry >30.7 μm yielded the greatest sum of sensitivity (66.7%) and specificity (89.3%)., Conclusions: This study indicates that intereye neuroretinal rim minimum distance band asymmetry measurements, using high-density spectral domain optical coherence tomography volume scans, may be an objective and quantitative tool for assessing patients suspected of open-angle glaucoma., (Copyright ©2022. All rights reserved. Reproduction in whole or in part in any form or medium without expressed written permission of the Digital Journal of Ophthalmology is prohibited.)

Objectives: Spiders of the Loxosceles genus, known as violin spiders, produce venom with dermonecrotic and systemic effects, as it is a species widely distributed in the world, its study represents a high medical relevance. Systemic loxoscelism, which occurs in 1 in 5 cases and is the most frequent in children, can be fatal, so the study of effective therapy is of great relevance. In the present study, we compared different therapeutic options to mitigate the systemic effects of Loxosceles boneti venom in a model in which prepubertal rats were used., Materials and Methods: A model of systemic intoxication by L. boneti venom was provoked in male Wistar rats. Study groups were formed: healthy control, with venom and untreated control, treatment with N-acetylcysteine, and/or hyperbaric oxygenation therapy. Subsequently, pathological analysis of the kidney and lung was performed. The oxidant-antioxidant response was evaluated, and molecular analysis of the COX-1 and COX-2 enzymes was performed., Results: Regenerative changes were observed at the cellular level in both treatments, being more noticeable in the hyperbaric oxygen therapy (HBO) group. The anti-oxidant response was outstanding in the same group., Conclusion: Both treatments offer considerable benefits, however; further studies are needed to provide adequate therapeutics., Competing Interests: The authors have no conflicts of interest and declare that this article has not been published nor is being considered for publication elsewhere.

Infants and young children receive the highest exposures to antibiotics globally. Although there is building evidence that early life exposure to antibiotics increases susceptibility to various diseases including gut disorders later in life, the lasting impact of early life antibiotics on the physiology of the gut and its enteric nervous system (ENS) remains unclear. We treated neonatal mice with the antibiotic vancomycin during their first 10 postnatal days, then examined potential lasting effects of the antibiotic treatment on their colons during young adulthood (6 weeks old). We found that neonatal vancomycin treatment disrupted the gut functions of young adult female and male mice differently. Antibiotic-exposed females had significantly longer whole gut transit while antibiotic-treated males had significantly lower faecal weights compared to controls. Both male and female antibiotic-treated mice had greater percentages of faecal water content. Neonatal vancomycin treatment also had sexually dimorphic impacts on the neurochemistry and Ca 2+ activity of young adult myenteric and submucosal neurons. Myenteric neurons of male mice were more disrupted than those of females, while opposing changes in submucosal neurons were seen in each sex. Neonatal vancomycin also induced sustained changes in colonic microbiota and lasting depletion of mucosal serotonin (5-HT) levels. Antibiotic impacts on microbiota and mucosal 5-HT were not sex-dependent, but we propose that the responses of the host to these changes are sex-specific. This first demonstration of long-term impacts of neonatal antibiotics on the ENS, gut microbiota and mucosal 5-HT has important implications for gut function and other physiological systems of the host. KEY POINTS: Early life exposure to antibiotics can increase susceptibility to diseases including functional gastrointestinal (GI) disorders later in life. Yet, the lasting impact of this common therapy on the gut and its enteric nervous system (ENS) remains unclear. We investigated the long-term impact of neonatal antibiotic treatment by treating mice with the antibiotic vancomycin during their neonatal period, then examining their colons during young adulthood. Adolescent female mice given neonatal vancomycin treatment had significantly longer whole gut transit times, while adolescent male and female mice treated with neonatal antibiotics had significantly wetter stools. Effects of neonatal vancomycin treatment on the neurochemistry and Ca 2+ activity of myenteric and submucosal neurons were sexually dimorphic. Neonatal vancomycin also had lasting effects on the colonic microbiome and mucosal serotonin biosynthesis that were not sex-dependent. Different male and female responses to antibiotic-induced disruptions of the ENS, microbiota and mucosal serotonin biosynthesis can lead to sex-specific impacts on gut function., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: The influence of body mass index on perioperative complications of hiatal hernia surgery is controversial in the surgical literature., Aims: The aim of this study was to evaluate the influence of body mass index on perioperative complications and associated risk factors for its occurrence., Methods: Two groups were compared on the basis of body mass index: group A with body mass index <32 kg/m2 and group B with body mass index ³32 kg/m2. A multivariate analysis was carried out to identify independent predictors for complications. Complications were classified based on the Clavien-Dindo score., Results: A total of 49 patients were included in this study, with 30 in group A and 19 in group B. The groups were compared based on factors, such as age, Charlson Comorbidity Index, surgical techniques used, type and location of hiatal hernia, and length of stay. Findings showed that 70% of patients had complex hiatal hernia. In addition, 14 complications also occurred: 7 pleuropulmonary and 7 requiring reoperation. From the seven reoperated, there were three recurrences, two gastrointestinal fistulas, one diaphragmatic hernia, and one incisional hernia. Complications were similar in both the groups, with type IV hiatal hernia being the only independent predictor., Conclusions: Body mass index does not affect perioperative complications in anti-reflux surgery and type IV hiatal hernia is an independent predictor of its occurrence.

Hyperserotonemia, or elevated levels of whole blood serotonin (WB5-HT), was the first biomarker linked to autism spectrum disorder (ASD). Despite numerous studies investigating the etiology of hyperserotonemia, results have been inconsistent. Recent findings suggest a relationship between the immune system and hyperserotonemia. The current study investigated whether intestinal 5-HT levels, 5-HT gene expression, or intestinal cell types predict WB5-HT. Participants included thirty-one males aged 3-18 who were classified into one of three groups: ASD and functional GI issues, typically developing with GI issues, and typically developing without GI issues. Samples from a lower endoscopy were analyzed to examine the pathways in predicting WB-5HT. Results demonstrated an association between T-Lymphocytes and WB5-HT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Peanut oral immunotherapy has emerged as a novel, active management approach for peanut-allergic sufferers, but limited data exist currently on the role of the microbiome in successful desensitization., Objective: We examined the oral and gut microbiome in a cohort of 17 children undergoing peanut oral immunotherapy with the aim to identify the microbiome signatures associated with successful desensitization. We also set out to characterize their fecal metabolic profiles after successful therapy., Methods: Participants gradually built up their daily dose from 2 mg (starting dose) to 300 mg (maintenance dose) within approximately 40 weeks. We collected a buccal and stool specimen from each subject at two different time points: at baseline and post-therapy (1 month after reaching maintenance). The oral (buccal) and gut (fecal) microbiome was characterized based on sequencing of 16S rRNA gene amplicons with Illumina MiSeq. Fecal short chain fatty acid levels were measured using liquid chromatography-tandem mass spectrometry., Results: We report increased alpha diversity of the oral microbiome post-therapy and have also identified a significant increase in the relative abundance of oral Actinobacteria, associated with the desensitized state. However, the baseline gut microbiome did not differ from the post-therapy. Additionally, fecal short chain fatty acids increased after therapy, but not significantly., Conclusion: Our research adds to the limited current knowledge on microbiome and metabolic signatures in pediatric patients completing oral immunotherapy. Post-therapy increased trends of fecal fatty acid levels support a role in modulating the allergic response and potentially exerting protective and anti-inflammatory effects alongside successful desensitization. A better understanding of the microbiome-related mechanisms underlying desensitization may allow development of smarter therapeutic approaches in the near future., Clinical Implication: The oral microbiome composition is altered following successful peanut oral immunotherapy, with a significant increase in alpha diversity and the relative abundance of phylum Actinobacteria., Capsule Summary: Significant microbiome changes in children completing peanut immunotherapy include increase in alpha-diversity and overrepresentation of Actinobacteria in the oral microbiome, and increased trends for fecal short chain fatty acids, suggesting a protective effect against the allergic response.

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally injected once during 7 days with CCK8, devazapide (CCKR1 antagonist), L365,260 (CCKR2 antagonist) or vehicle (sham group). In intestinal lavages, total and secretory IgA (SIgA) were determined by ELISA; in lamina propria, IgA + B lymphocytes and IgA + plasma cells were analyzed by flow cytometry; mRNA levels of polymeric immunoglobulin receptor (pIgR) in epithelial cells and α chain, interleukins (ILs) in lamina propria cells were assessed by qRTPCR. Regarding the sham conditions, IgA + plasma-cell percentage and IL-2, IL-5, IL-10 and transforming growth factor-β (TGF-β) mRNA levels were either increased by CCK8 or decreased by both CCKR antagonists. For IgA/SIgA responses, IL-4/IL-6 mRNA levels were decreased by all drugs and pIgR mRNA was increased by CCK8 and reduced by L365,260. IgA + B cell percentage and α chain mRNA levels were elicited by CCK8 and L365,260. Data suggested a presumable differential role of CCK/CCKR on the IgA-response; outcome of L365,260 on the elicitation of IgA + B cells and α chain mRNA needs further examination.

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition. Thirty children (7-12 years of age) with functional abdominal pain provided a baseline stool sample prior to randomization to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). They took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for 1 week, after which the stool collection was repeated. Baseline and post-PMO stools were analyzed for microbiome composition. There was no difference in alpha diversity of the gut microbiome between the baseline and post-PMO treatment. Principal coordinate analysis revealed no significant difference in overall bacterial composition between baseline and post-PMO samples, as well as between the PMO dose groups. However, the very low abundant Collinsella genus and three operational taxonomic units (one belonging to Collinsella) were significantly different in samples before and after PMO treatment. The Firmicutes/Bacteroidetes ratio was lower in children who received 540 mg of PMO compared to the 180 mg and 360 mg dose groups (p = 0.04). Network analysis revealed separation between pre- and post-PMO fecal samples with the genus Collinsella driving the post-PMO clusters. PMO administration appeared to impact only low abundance bacteria. The 540 mg PMO dose differentially impacted the Firmicutes/Bacteroidetes ratio. A higher dose and/or longer duration of treatment might yield different results., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Gut microbes can synthesize multiple neuro-active metabolites. We profiled neuro-active compounds produced by the gut commensal Bacteroides ovatus in vitro and in vivo by LC-MS/MS. We found that B. ovatus generates acetic acid, propionic acid, isobutyric acid, and isovaleric acid. In vitro , B. ovatus consumed tryptophan and glutamate and synthesized the neuro-active compounds glutamine and GABA. Consistent with our LC-MS/MS-based in vitro data, we observed elevated levels of acetic acid, propionic acid, isobutyric acid, and isovaleric acid in the intestines of B. ovatus mono-associated mice compared with germ-free controls. B. ovatus mono-association also increased the concentrations of intestinal GABA and decreased the concentrations of tryptophan and glutamine compared with germ-free controls. Computational network analysis revealed unique links between SCFAs, neuro-active compounds, and colonization status. These results highlight connections between microbial colonization and intestinal neurotransmitter concentrations, suggesting that B. ovatus selectively influences the presence of intestinal neurotransmitters., Competing Interests: J.V. serves on the scientific advisory board of Seed, a USA-based probiotics/prebiotics company, Biomica, an Israeli informatics enterprise. and Plexus World-wide, a USA-based nutrition company. J.S.K. and J.V. receive unrestricted research support from BioGaia AB, a Swedish probiotics company. The remaining authors have no commercial or financial relationships to declare., (© 2022 The Authors.)

Entamoeba histolytica is a protozoan-pathogen-causing amoebic liver abscess (ALA). After amoeba establishment in the liver, it causes abundant infiltrate of neutrophils. Liver tissue damage by neutrophils results in part from anti-amoebic oxidative intermediates, including reactive oxygen species (ROS), reactive nitrogen species (RNS), and hypochlorous acid (HOCl), derived from the myeloperoxidase (MPO) enzyme. Ascorbic acid (ASC) is an antioxidant that acts as a scavenger for ROS and NOS-derived free radicals. No previous information regarding the effect of ASC concerning the participation of MPO in an experimental model of ALA in hamsters has been reported. Thus, the aim of the present work was to analyze the effect of ASC on acute ALA development and to measure the activity and gene expression of the MPO enzyme. Hamsters were treated with ASC (800 mg/kg) and then intrahepatically inoculated with E. histolytica trophozoites. Animals were sacrificed at 3, 6, and 12 h post-inoculation (p.i.), and liver samples were collected. The percentage of lesions, amoeba in situ count, MPO activity, and mpo gene expression were ascertained. Compared to ALA hamsters without ASC treatment as the control group (CT), the ALA group treated with ASC had a significant decrease in liver lesions (all p.i. hours) and viable amoeba count (12 h p.i.) and an increase in MPO activity (12 h p.i.) and mpo gene expression (6 h/12 h p.i.). These data suggest that ASC ameliorated liver damage caused by oxidizing products via modulation of mpo expression and activity., 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 Cruz-Baquero, Jarillo-Luna, Cárdenas-Jaramillo, Drago-Serrano, Serrano-Luna and Pacheco-Yépez.)

Hospital-acquired infections pose significant costly global challenges to patient care. Rapid and sensitive methods to identify potential outbreaks are integral to infection control measures. Whole-genome sequencing (WGS)-based bacterial strain typing provides higher discriminatory power over standard nucleotide banding pattern-based methods such as repetitive sequence-based PCR (rep-PCR). However, integration of WGS into clinical epidemiology is limited by the lack of consensus in methodology and data analysis/interpretation. In this study, WGS was performed on genomic DNA extracted from 22 multidrug-resistant Pseudomonas aeruginosa (MDR-PA) isolates using next-generation sequencing. Resulting high-quality reads were analyzed for phylogenetic relatedness using a whole-genome multilocus sequence typing (wgMLST)-based software program and single-nucleotide variant phylogenomics (SNVPhyl). WGS-based results were compared with conventional MLST and archived rep-PCR results. Rep-PCR identified three independent clonal clusters of MDR-PA. Only one clonal cluster identified by rep-PCR, an endemic strain within the pediatric cystic fibrosis population at Texas Children's Hospital, was concordantly identified using wgMLST and SNVPhyl. Results were highly consistent between the three sequence-based analyses (conventional MLST, wgMLST, and SNVPhyl), and these results remained consistent with the addition of 74 MDR-PA genomes. These WGS-based methods provided greater resolution for strain discrimination than rep-PCR or standard MLST classification, and the ease of use of wgMLST software renders it clinically viable for analysis, interpretation, and reporting of WGS-based strain typing., (Copyright © 2022 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objectives: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources., Methods: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens., Results: FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity., Conclusion: Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities., Competing Interests: Conflicts of Interest: These authors disclose the following: T.C.S. received research funding from Merck, Nivalis, Cubist, Mead Johnson, Rebiotix, BioFire, Assembly BioSciences, and has served on the advisory board for Rebiotix and BioFire. R.J.S. provided consultancy for Nutrinia, IMHealth, and Biogaia AB, and received restricted research support from Mead-Johnson; J.V. received unrestricted research support from Biogaia AB (Stockholm, Sweden) and serves on the Scientific Advisory Boards of Biomica, Plexus Worldwide, and Seed Health; no study sponsors were involved in the design of the study, collection, analysis, or interpretation of the data, or the writing of the manuscript. The remaining authors disclose no conflicts., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Muscarinic-acetylcholine-receptors (mAChRs) modulate intestinal homeostasis, but their role in inflammation is unclear; thus, this issue was the focus of this study. BALB/c mice were treated for 7 days with muscarine (mAChR/agonist), atropine (mAChR/antagonist) or saline. Small-intestine samples were collected for histology and cytofluorometric assays in Peyer's patches (PP) and lamina propria (LP) cell-suspensions. In LP, goblet-cells/leukocytes/neutrophils/MPO + cells and MPO/activity were increased in the muscarine group. In PP, IFN-γ + /CD4 + T or IL-6 + /CD4 + T cell numbers were higher in the muscarine or atropine groups, respectively. In LP, TNF-α + /CD4 + T cell number was higher in the muscarine group and lower in the atropine., (Copyright © 2021. Published by Elsevier B.V.)

Acute appendicitis (AA) is a frequent cause of abdominal pain requiring surgical treatment. During the COVID-19 pandemic, surgical societies considered other therapeutic options due to uncertainties in the evolution of the disease. The purpose of this study is to assess the treatment of AA by members of two Brazilian surgical societies in this period. A common questionnaire was sent in 2020. There were 382 responses. Most surgeons had more than 15 years of profession (68.3%) and treated more than five cases per month (44.8%). About 72.5% would indicate chest CT to investigate COVID-19 in patients with AA. For those patients sustaining uncomplicated AA, without COVID-19, 60.2% would indicate laparoscopic appendectomy (VLA), followed by open appendectomy (OA) (31.7%) and non-operative management (NOM) (1.3%). For those with mild COVID-19, OA was suggested by 51.0%, followed by VLA (29.6%) and NOM (6.0%). For those with severe COVID-19, OA was proposed by 35.3%, followed by NOM (19.9%) and VLA (18.6%). For patients with periappendiceal abscesses, without COVID-19, VLA was suggested by 54.2%, followed by OA (33.2%) and NOM (4.4%). For those with mild COVID-19, OA was proposed in 49.5%, followed by VLA (29.3%) and NOM (8.9%). In those with severe COVID-19, OA was proposed in 36.6%, followed by NOM (25.1%) and VLA (17.3%). This information, based on two recognized Brazilian surgical societies, can help the surgeon to select the best approach individually.

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function. Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment. Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups ( P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum , and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment. Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial. Clinical Trial Registration: www.clinicaltrials.gov, Identifier: NCT00971711., 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 © 2021 Boonma, Shapiro, Hollister, Badu, Wu, Weidler, Abraham, Devaraj, Luna, Versalovic, Heitkemper, Savidge and Shulman.)

Objectives: To examine the association of major depressive disorder (MDD) and selective serotonin reuptake inhibitor (SSRI) use with gut microbiome in older adolescents and younger adults., Methods: Fifteen to 20-year-old participants within a month of starting an SSRI and unmedicated controls were enrolled in a longitudinal study. They underwent a diagnostic evaluation comprising self-completed and rater-administered questionnaires and clinical interview. They also provided a stool sample, which was stored at -80°C until DNA extraction. Microbial DNA was extracted with the MoBio PowerSoil kit, and the V4 region of the 16S rRNA was amplified and sequenced. Raw sequence data was processed with the LotuS pipeline. Only samples with no antibiotic exposure in the last 6 months and with >1000 quality filtered reads were included in the analysis., Results: 160 participants (57.5% female, mean age 20.0±1.9 years, 29% taking SSRIs) were enrolled, comprising 110 MDD patients (60% in acute episode), 27 healthy controls, and 23 psychiatric controls. No significant group differences were observed in bacterial richness or alpha and beta diversity. Differential abundance analysis of bacterial taxa found no significant group differences at the phylum and genus levels. Neither being in a major depressive episode vs. remission nor using SSRIs was associated with differential bacterial composition., Conclusions: In this sizeable sample of older adolescents, neither MDD nor SSRI use was associated with differences in gut bacterial microbiome. In this age group, the bi-directional interaction between the gut bacteria and brain may be more nuanced than in adults, requiring further investigation., (Copyright © 2021. Published by Elsevier B.V.)

Early detection of Alzheimer's disease (AD) is crucial to preserve cognitive functions and provide the opportunity for patients to enter clinical trials. In recent years, some studies have reported that features related to the signal and texture of MRI images can be an effective biomarker of AD. To test these claims, a study was conducted using T2 maps, a sequence not previously studied, of 40 patients with mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative database, who either progressed to AD (18) or remained stable (22). From these maps, the mean value and absolute difference of 37 signal and texture imaging features for 40 contralateral pairs of regions were measured. We used seven machine learning methods to analyze whether, by adding these imaging features to the neuropsychological studies currently used for diagnosis, we could more accurately identify patients who will progress to AD. The predictive models improved with the addition of signal and texture features. Additionally, features related to the signal and texture of the images were much more relevant than volumetric ones. Our results suggest that contralateral signal and texture features should be further investigated as potential biomarkers for the prediction of AD.

Background and Purpose: Changes in diet and lifestyle factors are frequently recommended for persons with irritable bowel syndrome (IBS). It is unknown whether these recommendations alter the gut microbiome and/or whether baseline microbiome predicts improvement in symptoms and quality of life following treatment. Therefore, the purpose of this study was to explore if baseline gut microbiome composition predicted response to a Comprehensive Self-Management (CSM) intervention and if the intervention resulted in a different gut microbiome composition compared to usual care., Methods: Individuals aged 18-70 years with IBS symptoms ≥6 months were recruited using convenience sampling. Individuals were excluded if medication use or comorbidities would influence symptoms or microbiome. Participants completed a baseline assessment and were randomized into the eight-session CSM intervention which included dietary education and cognitive behavioral therapy versus usual care. Questionnaires included demographics, quality of life, and symptom diaries. Fecal samples were collected at baseline and 3-month post-randomization for 16S rRNA-based microbiome analysis., Results: Within the CSM intervention group (n = 30), Shannon diversity, richness, and beta diversity measures at baseline did not predict benefit from the CSM intervention at 3 months, as measured by change in abdominal pain and quality of life. Based on both alpha and beta diversity, the change from baseline to follow-up microbiome bacterial taxa did not differ between CSM (n = 25) and usual care (n = 25)., Conclusions and Inferences: Baseline microbiome does not predict symptom improvement with CSM intervention. We do not find evidence that the CSM intervention influences gut microbiome diversity or composition over the course of 3 months.

It is widely accepted that the pathogen Clostridioides difficile exploits an intestinal environment with an altered microbiota, but the details of these microbe-microbe interactions are unclear. Adherence and colonization of mucus has been demonstrated for several enteric pathogens and it is possible that mucin-associated microbes may be working in concert with C. difficile . We showed that C. difficile ribotype-027 adheres to MUC2 glycans and using fecal bioreactors, we identified that C. difficile associates with several mucin-degrading microbes. C. difficile was found to chemotax toward intestinal mucus and its glycan components, demonstrating that C. difficile senses the mucus layer. Although C. difficile lacks the glycosyl hydrolases required to degrade mucin glycans, coculturing C. difficile with the mucin-degrading Akkermansia muciniphila , Bacteroides thetaiotaomicron , and Ruminococcus torques allowed C. difficile to grow in media that lacked glucose but contained purified MUC2. Collectively, these studies expand our knowledge on how intestinal microbes support C. difficile .

Background: Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction., Objectives: We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype., Methods: Demographics and clinical information, including growth and anthropometric measurements, pubertal status, symptoms, clinical severity score, bowel movement, medication use, and dietary intakes were collected from the participants. Fecal samples were collected for analysis of the gut microbiome using Illumina MiSeq-based next-generation sequencing of the 16S rRNA gene followed by bioinformatics analysis of microbial composition, diversity, and community structure. Selected end-products of microbial protein metabolism were characterized by liquid chromatography-mass spectrometry., Results: The gut bacterial microbiome differed within the RTT cohort based on pubertal status (p<0.02) and clinical severity scores (p<0.02) of the individuals and the type of diet (p<0.01) consumed. Although the composition of the gut microbiome did not differ between RTT and unaffected individuals, concentrations of protein end-products of the gut bacterial metabolome, including γ-aminobutyric acid (GABA) (p<0.001), tyrosine (p<0.02), and glutamate (p<0.06), were lower in the RTT cohort. Differences in the microbiome within RTT groups, based on symptomatic anxiety, hyperventilation, abdominal distention, or changes in stool frequency and consistency, were not detected., Conclusions: Although variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome, we presently cannot infer causality between gut bacterial dysbiosis and gastrointestinal dysfunction. Nevertheless, alterations in the gut metabolome may provide clues to the pathophysiology of gastrointestinal problems in RTT., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: Although Clostridioides difficile infection (CDI) is known to involve the disruption of the gut microbiota, little is understood regarding how mucus-associated microbes interact with C difficile. We hypothesized that select mucus-associated bacteria would promote C difficile colonization and biofilm formation., Methods: To create a model of the human intestinal mucus layer and gut microbiota, we used bioreactors inoculated with healthy human feces, treated with clindamycin and infected with C difficile with the addition of human MUC2-coated coverslips., Results: C difficile was found to colonize and form biofilms on MUC2-coated coverslips, and 16S rRNA sequencing showed a unique biofilm profile with substantial cocolonization with Fusobacterium species. Consistent with our bioreactor data, publicly available data sets and patient stool samples showed that a subset of patients with C difficile infection harbored high levels of Fusobacterium species. We observed colocalization of C difficile and F nucleatum in an aggregation assay using adult patients and stool of pediatric patients with inflammatory bowel disease and in tissue sections of patients with CDI. C difficile strains were found to coaggregate with F nucleatum subspecies in vitro; an effect that was inhibited by blocking or mutating the adhesin RadD on Fusobacterium and removal of flagella on C difficile. Aggregation was shown to be unique between F nucleatum and C difficile, because other gut commensals did not aggregate with C difficile. Addition of F nucleatum also enhanced C difficile biofilm formation and extracellular polysaccharide production., Conclusions: Collectively, these data show a unique interaction of between pathogenic C difficile and F nucleatum in the intestinal mucus layer., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. High bile acid (BA) profiles have been associated with abdominal pain symptoms, mucosal inflammation, and diarrhea in a subgroup of those with IBS. The purpose of this study was to compare: 1) fecal primary and secondary BAs in women with and without IBS; and 2) symptoms, gut microbiome, and diet between women with high and normal BAs (i.e., similar to healthy [HC] women). Women (ages 18-45) with IBS and HCs were recruited from healthcare providers or the community. Participants kept a 28-day symptom diary, completed a 3-day food journal, and collected a stool sample for microbiome analysis (16 S rRNA gene sequencing). Primary and secondary BA levels were determined by mass spectrometry. Primary BAs did not differ between IBS (n = 45) and HC (n = 28) groups; women with IBS had significantly increased conjugated secondary BAs (glycodeoxycholic acid [ p = 0.006], taurodeoxycholic acid [ p = 0.006], and glycolithocholic acid [ p = 0.01]). Sixty percent of women with IBS had normal BAs whereas 40% had high BAs. Women with high fecal BAs were predominantly IBS-Diarrhea or IBS-Mixed and consumed less fiber and vegetable protein and more animal protein compared to women with IBS whose fecal BAs levels were comparable to HCs. Those with high conjugated secondary fecal BAs also had a greater Firmicutes/Bacteroidetes ratio, less abundance of phylum Bacteroidete s and genus Gemmiger , and more abundance of family Erysipelotrichaceae compared to IBS women with normal BAs. Determination of fecal BA levels provides additional insights into pathophysiological links between diet and microbiome in IBS.

Chronic restraint stress (CRS) magnifies restraint-induced corticosterone secretion through a mechanism involving increased adrenocortical 5-HT content and turnover. We analysed the impact of CRS on serotonin transporter (SERT) expression and distribution in rat adrenal glands. Male Wistar rats were submitted to CRS (20 min/day) or undisturbed control conditions for 14 days. Exposure to CRS induced a remarkable increase in SERT-like immunoreactivity in the adrenal cortex, which closely matched that of chromogranin A immunostaining, along with a significant increase in SERT protein and mRNA levels in whole adrenals as determined by immunohistochemistry, Western blot and RT-PCR assays, respectively; all these CRS-induced changes occurred almost exclusively in left adrenals. Closely similar results were obtained in animals that received a 14-day chronic corticosterone treatment. These results unravel an interesting association between chronic stress exposure and SERT expression in adrenocortical chromogranin A-positive cells, which seems to be a glucocorticoid-dependent phenomenon., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The human microbiome evolves rapidly in early life with contributions from various factors such as diet, delivery mode, medical history, antibiotics exposure, genetics, immunomodulators and the environment. A high use of antibiotics in pediatric outpatient settings has been well documented, and improvement in antibiotic selection is required to reduce the risks of antibiotic resistance and disruption of the microbiome., Methods: We performed an exploratory study using 16S rRNA gene-based sequencing to characterize the gut and nasopharyngeal microbiome of children (n = 50) age 1-6 years of age in a pediatric otolaryngology practice., Results: Relative abundance of Haemophilus and Moraxella were higher in nasopharyngeal swabs, while Prevotella, Bacteroides, Porphyromonas and Faecalibacterium were highly abundant in rectal swabs. The gut microbiome composition in children <2 years old was different compared with children ≥2 years age. Gut bacterial diversity increased with an increase in age of the children. Children taking probiotics had a notable increase in abundance of potentially beneficial gut bacteria such as Bacteroides and Akkermansia. The nasopharyngeal microbiome differed between children who received antibiotics in the 3 months before sample collection compared with those that did not. Haemophilus spp. was highly abundant in children who received antibiotics 3 months before sampling., Conclusions: The pediatric nasopharyngeal and rectal microbiomes differ in bacterial composition and diversity. The increased abundance of Haemophilus spp. in the nasopharyngeal microbiome of children who received antibiotics during the 3 months before sampling suggests a potential impact of antibiotics in colonization with the otopathogen and may be relevant to clinical practice.

Objective: In the pathogenesis of pterygium, the protective role of glutathione and nitric oxide production is unclear. These are important factors for homeostasis in the redox state of cells. The aim of this study was to determine the levels of these and related parameters in pterygium tissue. Patients and Methods . The study sample consisted of 120 patients diagnosed with primary or recurrent pterygium. Five groups of tissue samples were examined: control, primary pterygium, recurrent pterygium, and two groups of primary pterygium given a one-month NAC presurgery treatment (topical or systemic). The levels of endothelial nitric oxide synthase (eNOS), nitric oxide (NO), 3-nitrotyrosine (3NT), reduced and oxidized glutathione (GSH and GSSG), and catalase (CAT) were evaluated in tissue homogenates., Results: Compared with the control, decreased levels of eNOS, NO, and 3-nitrotyrosine as well as the degree of oxidation of GSH (GSSG%) were observed in primary and recurrent pterygium. 3-Nitrotyrosine and GSSG% were reduced in the other pterygium groups. GSH and CAT were enhanced in recurrent pterygium and systemic-treated primary pterygium but were unchanged for topical-treated primary pterygium. There was a strong positive correlation of eNOS with NO and 3NT, GSSG% with NO and 3NT, and GSH with GSSG and CAT. Women showed a higher level of GSH and catalase in primary pterygium, whereas a lower level of GSH and a higher level of NO in recurrent pterygium., Conclusion: The results are congruent with the following proposed sequence of events leading to a protective response of the organism during the pathogenesis of primary pterygium: a decreased level of eNOS provokes a decline in the level of NO in pterygium tissue, which then leads to reduced S-nitrosylation of GSH or other thiols and possibly to the modulation of the intracellular level of GSH through synthesis and/or mobilization from other tissues., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Fidelina Parra et al.)