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Abstract Background The exact mechanisms linking the gut microbiota and social behavior are still under investigation. We aimed to explore the role of the gut microbiota in shaping social behavior deficits using selectively bred mice possessing dominant (Dom) or submissive (Sub) behavior features. Sub mice exhibit asocial, depressive- and anxiety-like behaviors, as well as systemic inflammation, all of which are shaped by their impaired gut microbiota composition. Methods An age-dependent comparative analysis of the gut microbiota composition of Dom and Sub mice was performed using 16S rRNA sequencing, from early infancy to adulthood. Dom and Sub gastrointestinal (GI) tract anatomy, function, and immune profiling analyses were performed using histology, RT-PCR, flow cytometry, cytokine array, and dextran-FITC permeability assays. Short chain fatty acids (SCFA) levels in the colons of Dom and Sub mice were quantified using targeted metabolomics. To support our findings, adult Sub mice were orally treated with hyaluronic acid (HA) (30 mg/kg) or with the non-steroidal anti-inflammatory agent celecoxib (16 mg/kg). Results We demonstrate that from early infancy the Sub mouse gut microbiota lacks essential bacteria for immune maturation, including Lactobacillus and Bifidobacterium genera. Furthermore, from birth, Sub mice possess a thicker colon mucin layer, and from early adulthood, they exhibit shorter colonic length, altered colon integrity with increased gut permeability, reduced SCFA levels and decreased regulatory T-cells, compared to Dom mice. Therapeutic intervention in adult Sub mice treated with HA, celecoxib, or both agents, rescued Sub mice phenotypes. HA treatment reduced Sub mouse gut permeability, increased colon length, and improved mouse social behavior deficits. Treatment with celecoxib increased sociability, reduced depressive- and anxiety-like behaviors, and increased colon length, and a combined treatment resulted in similar effects as celecoxib administered as a single agent. Conclusions Overall, our data suggest that treating colon inflammation and decreasing gut permeability can restore gut physiology and prevent social deficits later in life. These findings provide critical insights into the importance of early life gut microbiota in shaping gut immunity, functionality, and social behavior, and may be beneficial for the development of future therapeutic strategies.

Abstract The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

Abstract Background Exercise training (ET) has beneficial effects on multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the intensity‐dependent effects of ET on the systemic immune system in EAE remain undefined. Objective (1) To compare the systemic immune modulatory effects of moderate versus high‐intensity ET protocols in protecting against development of EAE; (2) To investigate whether ET affects autoimmunity selectively, or causes general immunosuppression. Methods Healthy mice performed moderate or high‐intensity treadmill running programs. Proteolipid protein (PLP)‐induced transfer EAE was utilized to examine ET effects specifically on the systemic immune system. Lymph node (LN)‐T cells from trained versus sedentary donor mice were transferred to naïve recipients and EAE severity was assessed, by clinical assessment and histopathological analysis. LN‐T cells derived from donor trained versus sedentary PLP‐immunized mice were analyzed in vitro for proliferation assays by flow cytometry analysis and cytokine and chemokine receptor gene expression using real‐time PCR. T cell‐dependent immune responses of trained versus sedentary mice to the nonautoantigen ovalbumin and susceptibility to Escherichia coli‐induced acute peritonitis were examined. Results High‐intensity training in healthy donor mice induced significantly greater inhibition than moderate‐intensity training on proliferation and generation of encephalitogenic T cells in response to PLP‐immunization, and on EAE severity upon their transfer into recipient mice. High‐intensity training also inhibited LN‐T cell proliferation in response to ovalbumin immunization. E. coli bacterial counts and dissemination were not affected by training. Interpretation High‐intensity training induces superior effects in preventing autoimmunity in EAE, but does not alter immune responses to E. coli infection.

We examined the effects of ALOS4, a cyclic peptide discovered previously by phage library selection against integrin αvβ3, on a human melanoma (A375) xenograft model to determine its abilities as a potential anti-cancer agent. We found that ALOS4 promoted healthy weight gain in A375-engrafted nude mice and reduced melanoma tumor mass and volume. Despite these positive changes, examination of the tumor tissue did not indicate any significant effects on proliferation, mitotic index, tissue vascularization, or reduction of αSMA or Ki-67 tumor markers. Modulation in overall expression of critical downstream αvβ3 integrin factors, such as FAK and Src, as well as reductions in gene expression of c-Fos and c-Jun transcription factors, indirectly confirmed our suspicions that ALOS4 is likely acting through an integrin-mediated pathway. Further, we found no overt formulation issues with ALOS4 regarding interaction with standard inert laboratory materials (polypropylene, borosilicate glass) or with pH and temperature stability under prolonged storage. Collectively, ALOS4 appears to be safe, chemically stable, and produces anti-cancer effects in a human xenograft model of melanoma. We believe these results suggest a role for ALOS4 in an integrin-mediated pathway in exerting its anti-cancer effects possibly through immune response modulation.

Parks and greenspaces can enhance personal health in various ways, including among others, through psychological restoration and improved well-being. However, under certain circumstances, parks may also have adverse effects by providing isolated and hidden spaces for non-normative and crime-related activities. This study uses a survey conducted by the Development Bank of Latin America in a cross-sectional representative sample of 7,110 respondents in eleven Latin-American cities. We examine associations between self-reported park proximity with perceived social disorder (drug use/sales, gangs, prostitution and assault and/or crime), and whether these associations are modified by neighborhood characteristics (informal neighborhoods, poor street-lighting, abandoned buildings, illegal dumping). High self-reported park proximity was associated with lower perceptions of social disorder, but these associations were no longer significant following adjustment for neighborhood characteristics. Significant interactions were observed between park proximity and neighborhood characteristics suggesting that the likelihood of perceiving social disorder increases with high park proximity in informal neighborhoods and in the presence of certain neighborhood characteristics, such as poor street-lighting, abandoned buildings, and illegal dumping in residential streets. The differential associations between reported park proximity and perceived social disorder in different living environments highlight the importance of supportive social and physical infrastructure to maximize the restorative benefits of parks in all urban areas.

Candida auris is a drug-resistant fungal pathogen that has emerged over the past decade as a cause of nosocomial outbreaks with substantial mortality rates (1-3). Widespread resistance to triazole antifungals, [...]

Abstract Background The incidences of tendon injuries in certain sections of human or animal populations such as athletes are high, but every human or animal, regardless of age or level of activity experiences some degree of tendon injury. In spite of the various investigations of injuries and treatment, comprehensive studies dealing with the histological, ultrastructural and biomechanical aspects of healing of load-bearing tendons are rare. This study was designed to compare the outcome of healing of the transverse sectioned superficial digital flexor tendon (SDFT) after 28 and 84 days post injury (DPI) in rabbits. Methods Forty white New Zealand mature female rabbits were randomly divided into two equal groups of 28 and 84 DPI After tenotomy and surgical repair of the left SDFT, the injured legs were casted for 14 days. The weight of the animals, tendon diameter, and clinical, radiographic and ultrasonographic evaluations were conducted at weekly intervals. The animals were euthanized on 28 and 84 DPI and the tendons were evaluated for histopathological, ultrastructural, biomechanical and percentage dry weight parameters. Results Although the clinical, ultrastructural, morphological and biomechanical properties of the injured tendons on day 84 showed a significant improvement compared to those of the 28 DPI, these parameters were still significantly inferior to their normal contra-lateral tendons. Conclusions This study showed that tendon healing is very slow and at 84 days post-injury the morphological and biomechanical parameters were still inferior to the normal tendons and many collagen fibrils still had the same diameter as those seen at 28 DPI.

The purpose of the present study was to identify the protective and risk factors related to psychological distress during COVID-19 in an Israeli sample. An online survey was administered from April 19 to May 2, 2020, while a strict lockdown was in place. Participants were recruited by snowball sampling. Psychological distress was evaluated using the Generalized Anxiety Disorder questionnaire (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Risk and protective factors for psychological distress were assessed on the Multi-dimensional Perceived Social Support (MSPSS), the coping strategies (COPE), the Life Orientation Test (LOT), and the Gratitude questionnaire. Out of the 655 valid questionnaires collected (from participants ranging in age from 18 to 86, 246 males, 409 females), 138 (21.3%) were positive for moderate to very severe depression and 87 (13.2%) for moderate to extremely severe anxiety. Participants who were screened for depression and anxiety were more likely to be women and young adults (18-24). After adjusting statistically for gender, age, and socioeconomic status, depression and anxiety remained significantly associated with both emotion-focused (PHQ-[beta] =.437, p < .001, GAD-[beta]=.441, p < .001) and problem-focused (PHQ-[beta] =-.219, p < .001, GAD-[beta]=-.143, p < .001) coping strategies, as well as on the social support (PHQ-[beta] =-.167, p < .001, GAD-[beta]=-.155, p < .001), life orientation (GAD-[beta]=-.09, p < .001), and gratitude scales (PHQ-[beta] =-.07, p < .001). Levels of anxiety and depression were generally associated with gender (women), age (younger population), socioeconomic status (low), and an emotion-focused strategy as risk factors. A problem-focused strategy, social support, life orientation, and gratitude served as protective factors above and beyond personal background., Author(s): Zohar Oryan [sup.1] , Asia Avinir [sup.1] , Sigal Levy [sup.1] , Einat Kodesh [sup.2] , Odelia Elkana [sup.1] Author Affiliations: (1) grid.430432.2, 0000 0004 0604 7651, Behavioral Sciences, [...]

Background Environmental disinfection is essential for reducing spread of healthcare-associated infections (HAIs). Previous studies report conflicting results regarding the effects of ultraviolet (UV) light in reducing infections. This trial evaluated the impact of adding pulsed-xenon UV (PX-UV) to standard terminal cleaning in reducing environmentally implicated HAIs (eiHAIs). Methods The Lowering the Acquisition of MDROs with Pulsed-xenon (LAMP) trial was conducted in 2 hospitals (15 inpatient wards) utilizing a cluster-randomized, controlled, double-blinded, interventional crossover trial comparing standard terminal cleaning followed by either PX-UV (intervention arm) or sham (control arm) disinfection. The primary outcome was incidence of eiHAIs from clinical microbiology tests on the fourth day of stay or later or within 3 days after discharge from the study unit. EiHAIs included clinical cultures positive for vancomycin-resistant enterococci, extended-spectrum beta-lactamase–producing Escherichia coli or Klebsiella pneumonia , methicillin-resistant Staphylococcus aureus , and Acinetobacter baumannii , and stool polymerase chain reaction (PCR) positive for Clostridiodes difficile. Results Between 18 May 2017 and 7 January 2020, 25 732 patients were included, with an incidence of 601 eiHAIs and 180 954 patient-days. There was no difference in the rate of eiHAIs in the intervention and sham arms (3.49 vs 3.17 infections/1000 patient-days, respectively; RR, 1.10; 95% CI,.94–1.29; P =.23). Study results were similar when stratified by eiHAI type, hospital, and unit type. Conclusions The LAMP study failed to demonstrate an effect of the addition of UV light disinfection following terminal cleaning on reductions in rates of eiHAIs. Further investigations targeting hospital environmental surfaces and the role of no-touch technology to reduce HAIs are needed. Clinical Trials Registration. ClinicalTrials.gov identifier: NCT03349268; R01HS024709. [ABSTRACT FROM AUTHOR]

Sigal Davidi Building a New Land: Women Architects and Women's Organizations in Mandatory Palestine Ra'anana: Open University Press, 2020. 441 pp. (Hebrew) In the summer of 2019, at a conference [...]