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ABSTRACT Immunocompromised individuals were considered high-risk for severe disease due to SARS COV-2 infection. This study aimed to describe the safety of two doses of COVID-19 adsorbed inactivated vaccine (CoronaVac; Sinovac/Butantan), followed by additional doses of mRNA BNT162b2 (Pfizer/BioNTech) in immunocompromised (IC) adults, compared to immunocompetent/healthy (H) individuals. This phase 4, multicenter, open label study included solid organ transplant and hematopoietic stem cell transplant recipients, cancer patients and people with inborn errors of immunity with defects in antibody production, rheumatic, end-stage chronic kidney or liver disease, who were enrolled in the IC group. Participants received two doses of CoronaVac and additional doses of mRNA BNT162b2. Adverse reactions (AR) data were collected within seven days after each vaccination. Serious adverse events and of special interest (AESI) were monitored throughout the study. We included 241 immunocompromised and 100 immunocompetent subjects. Arthralgia, fatigue, myalgia, and nausea were more frequent in the IC group after CoronaVac. Following the first additional dose of mRNA BNT162, pain, induration, and tenderness at injection site, fatigue and myalgia were more frequent in the H group. A heart transplant recipient had a graft rejection temporally associated with the second CoronaVac dose, but there was no literature evidence of causal association. Four cases of AESI were considered related to the vaccine: three erythema multiforme after CoronaVac, all in IC participants, and one paresthesia after mRNA, in a H participant. Our findings were comparable to other studies that evaluated the safety of COVID-19 vaccines in different immunocompromised populations. Both vaccines were safe for immunocompromised participants.

Background Transplant recipients are chronically ill patients, who require lifelong follow-up to manage co-morbidities and prevent graft loss. This necessitates a system of care that is congruent with the Chronic Care Model. The eleven-item self-report Patient Assessment of Chronic Illness Care (PACIC) scale assesses whether chronic care is congruent with the Chronic Care Model, yet its validity for heart transplant patients has not been tested. Methods We tested the validity of the English version of the PACIC, and compared the similarity of the internal structure of the PACIC across English-speaking countries (USA, Canada, Australia and United Kingdom) and across six languages (French, German, Dutch, Spanish, Italian and Portuguese). This was done using data from the cross-sectional international BRIGHT study that included 1378 heart transplant patients from eleven countries across 4 continents. To test the validity of the instrument, confirmatory factor analyses to check the expected unidimensional internal structure, and relations to other variables, were performed. Results Main analyses confirmed the validity of the English PACIC version for heart transplant patients. Exploratory analyses across English-speaking countries and languages also confirmed the single factorial dimension, except in Italian and Spanish. Conclusion This scale could help healthcare providers monitor level of chronic illness management and improve transplantation care. Trial registration Clinicaltrials.gov ID: NCT01608477 , first patient enrolled in March 2012, registered retrospectively: May 30, 2012.

To assess and compare the prevalence of medication nonadherence (MNA) (implementation and persistence) to immunosuppressants and co-medications in heart transplant recipients. MNA prevalence was assessed using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (self-report) and compared using logistic regression in a 4-continent sample of 1397 heart transplant recipients from 36 heart transplant centers in 11 countries. MNA was significantly (α = 0.05) higher to co-medications than to immunosuppressants (taking nonadherence: 23.9% vs 17.3%; odds ratio [OR] = 1.5; 95% CI, 1.30–1.73; drug holiday: 5.7% vs 1.9%; OR = 3.17; 95% CI, 2.13–4.73; dose alteration: 3.8% vs 1.6%; OR = 2.46; 95% CI, 1.49–4.06; and discontinuation: 2.6% vs 0.5%; OR = 5.15; 95% CI, 2.36–11.20). The observed MNA necessitates adherence-enhancing interventions encompassing the entire post–heart transplant medication regimen. ClinicalTrials.gov identifier: NCT01608477.

Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host–microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host’s metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota–host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.

The deubiquitylase USP30 is an actionable target considered for treatment of conditions associated with defects in the PINK1-PRKN pathway leading to mitophagy. We provide a detailed cell biological characterization of a benzosulphonamide molecule, compound 39, that has previously been reported to inhibit USP30 in an in vitro enzymatic assay. The current compound offers increased selectivity over previously described inhibitors. It enhances mitophagy and generates a signature response for USP30 inhibition after mitochondrial depolarization. This includes enhancement of TOMM20 and SYNJ2BP ubiquitylation and phosphoubiquitin accumulation, alongside increased mitophagy. In dopaminergic neurons, generated from Parkinson disease patients carrying loss of function PRKN mutations, compound 39 could significantly restore mitophagy to a level approaching control values. USP30 is located on both mitochondria and peroxisomes and has also been linked to the PINK1-independent pexophagy pathway. Using a fluorescence reporter of pexophagy expressed in U2OS cells, we observe increased pexophagy upon application of compound 39 that recapitulates the previously described effect for USP30 depletion. This provides the first pharmacological intervention with a synthetic molecule to enhance peroxisome turnover.

After right colectomy, ileocolic anastomoses can be configured as isoperistaltic (ISO) or antiperistaltic (ANTI), with the choice largely based on the surgeon's experience. This study aimed to evaluate these configurations regarding postoperative complications and operative outcomes. We searched PubMed, Scopus, and the Cochrane Central Register of Clinical Trials for studies published up to January 2025. Odds ratios (ORs) and mean differences (MDs), with 95% confidence intervals (CIs), were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic, and analyses were conducted with R Software version 4.4.1. Twelve studies involving patients undergoing colorectal surgery were included, comparing ISO and ANTI ileocolic anastomoses. ISO was associated with a significantly earlier return of flatus (MD: -0.3 days; 95% CI: -0.6 to -0.1; p<0.01). No statistically significant differences were found in anastomotic leak (OR: 0.61; 95% CI: 0.29-1.28; p=0.189), postoperative ileus (OR: 1.47; 95% CI: 0.87-2.50; p=0.149), anastomotic bleeding (OR: 0.70; 95% CI: 0.20-2.49; p=0.582), surgical site infection (SSI) (OR: 0.91; 95% CI: 0.38-2.17; p=0.829), reoperation (OR: 0.92; 95% CI: 0.47-1.82; p=0.813), time to first stool (MD: -0.3 days; 95% CI: -0.7 to 0.1; p=0.19), anastomotic time (MD: -0.2 minutes; 95% CI: -1.9 to 1.4; p=0.79), blood loss (MD: -4.0 mL; 95% CI: -17.8 to 9.8; p=0.57), operative time (MD: 4.2 minutes; 95% CI: -3.0 to 11.3; p=0.25), hospital stay (MD: -0.7 days; 95% CI: -1.7 to 0.4; p=0.19), or 30-day mortality (OR: 0.85; 95% CI: 0.25-2.86; p=0.787). Based on our findings, ISO and ANTI ileocolic anastomoses demonstrated comparable postoperative complication rates and operative outcomes. However, ISO was associated with a faster return of bowel function, evidenced by earlier passage of flatus.

Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal–oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.

Background. To date, there is no reliable marker for the diagnosis of non-celiac gluten sensitivity (NCGS), which benefits from a gluten-free diet (GFD). This condition is characterized by functional gastrointestinal symptoms similar to those occurring in the course of irritable bowel syndrome (IBS). However, IBS has a higher prevalence, and often benefits from the administration of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. The overlap of symptoms between these two pathologies has led to an overestimation of self-made diagnosis NCGS. Aims. To better identify NCGS in subjects with a previous diagnosis of IBS. Methods. All subjects received a low FODMAP diet that was also gluten-free (low FODMAP-GFD), and those presenting an improvement of symptoms were exposed to gluten or placebo (double-blind challenge with wash-out and crossover). The response to dietary treatments was evaluated by visual analogue scale (VAS). Results. Of 30 patients (23 women, seven men, aged 42.2 ± 12.5 years, body mass index (BMI) 24.7 ± 4.1 kg/m2), 26 benefited from the administration of low FODMAP-GFD and were exposed to the gluten/placebo challenge. After the challenge, using an increase of visual analogue scale VAS (Δ-VAS) ≥30%, 46.1% of the patients were NCGS+. However, this percentage became only 19.2% using a different method (mean ∆-VAS score plus two standard deviations). Conclusions. FODMAP intolerance could hide the response to a challenge test with gluten for the identification of NCGS in IBS patients. A low FODMAP-GFD followed by gluten/placebo challenge is able to identify patients with NCGS better. ClinicalTrials.gov registration number NCT04017585.

The negative impacts of community or domestic violence on individuals self-rated health are known, but there is little evidence of the combined effect of these two types of interpersonal violence.To analyze the association between exposure to community and domestic violence and negative self-rated health status, distinguishing the type of violence suffered and also considering its cumulative exposure.Cross-sectional epidemiological study developed with the data from Brazilian ‘National Health Survey – 2013’. We used crude and adjusted multinominal logistic regression models to test the association of variables. All types of violence analyzed were associated with negative self-rated health. Exposure to community violence only was associated with regular (OR=1.39, 95% CI 1.14 to 1.70) and poor (OR=1.81, 95% CI, 1.30 to 2, 52) self-rated health. Exposure to domestic violence was associated with regular (OR=1.59, 95% CI 1.31 to 1.92) and poor (OR=2.93, 95% CI 2.23 to 3.84) self-rated health. Cumulative exposure to the two types of violence was associated with a regular (OR=3.97, 95% CI 2.32 to 6.78) and poor (OR=7.90, 95% CI 3.04 to 20, 56) self-rated health, being this association of greater magnitude.The effect of domestic violence was stronger than that of community violence, and the combined exposure was greater than isolated type violence. When considering violence a psychosocial stressor it is possible to understand such findings, since the characteristics between the types of violence differ, being possible to consider each type of violence a new stressor. In Brazil, community violence is evaluated as endemic, there is an increase in state violence and a structural collapse of public policies, which reinforces the possibility of polivitimization. Therefore, health professionals should be aware of polivitimization and its impact on the health and, above all, public policies should be strengthen aimed at promoting a safer environment and prevention of exposure to violence.

Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (N  = 79, N  = 30, N  = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (N  = 61, N  = 100, N  = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BAC  = 58.5%; BAC  = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. CLINICAL TRIAL REGISTRY NAME: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042.