Benign inheritable disorders of bilirubin metabolism manifested by conjugated hyperbilirubinemia: a narrative review

© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Bilirubin, a breakdown product of heme, is normally glucuronidated and excreted by the liver into bile. Failure of this system can lead to a buildup of conjugated bilirubin in the blood, resulting in jaundice. Hyperbilirubinemia is an important clinical sign that needs to be investigated under a stepwise evaluation. Inherited non-hemolytic conjugated hyperbilirubinemic conditions include Dubin-Johnson syndrome (caused by mutations affecting ABCC2 gene) and Rotor syndrome (caused by the simultaneous presence of mutations in SLCO1B1 and SLCO1B3 genes). Although classically viewed as benign conditions requiring no treatment, they lately gained an increased interest since recent studies suggested that mutations in the responsible genes leading to hyperbilirubinemia, as well as minor genetic variants, may result in an increased susceptibility to drug toxicity. This article provides a comprehensive review on the pathophysiology of Dubin-Johnson and Rotor syndromes, presenting the current knowledge concerning the molecular details and basis of these conditions.info:eu-repo/semantics/publishedVersio

Sensitive bi-enzymatic biosensor based on polyphenoloxidases–gold nanoparticles–chitosan hybrid film–graphene doped carbon paste electrode for carbamates detection

A bi-enzymatic biosensor (LACC–TYR–AuNPs–CS/GPE) for carbamates was prepared in a single step by electrodeposition of a hybrid film onto a graphene doped carbon paste electrode (GPE). Graphene and the gold nanoparticles (AuNPs) were morphologically characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering and laser Doppler velocimetry. The electrodeposited hybrid film was composed of laccase (LACC), tyrosinase (TYR) and AuNPs entrapped in a chitosan (CS) polymeric matrix. Experimental parameters, namely graphene redox state, AuNPs:CS ratio, enzymes concentration, pH and inhibition time were evaluated. LACC–TYR–AuNPs–CS/GPE exhibited an improved Michaelis–Menten kinetic constant (26.9 ± 0.5 M) when compared with LACC–AuNPs–CS/GPE (37.8 ± 0.2 M) and TYR–AuNPs–CS/GPE (52.3 ± 0.4 M). Using 4-aminophenol as substrate at pH 5.5, the device presented wide linear ranges, low detection limits (1.68×10− 9 ± 1.18×10− 10 – 2.15×10− 7 ± 3.41×10− 9 M), high accuracy, sensitivity (1.13×106 ± 8.11×104 – 2.19×108 ± 2.51×107 %inhibition M− 1), repeatability (1.2–5.8% RSD), reproducibility (3.2–6.5% RSD) and stability (ca. twenty days) to determine carbaryl, formetanate hydrochloride, propoxur and ziram in citrus fruits based on their inhibitory capacity on the polyphenoloxidases activity. Recoveries at two fortified levels ranged from 93.8 ± 0.3% (lemon) to 97.8 ± 0.3% (orange). Glucose, citric acid and ascorbic acid do not interfere significantly in the electroanalysis. The proposed electroanalytical procedure can be a promising tool for food safety control

Parainfluenza fusion peptide promotes membrane fusion by assembling into oligomeric porelike structures

© 2022 The Authors. Published by American Chemical SocietyParamyxoviruses are enveloped viruses harboring a negative-sense RNA genome that must enter the host’s cells to replicate. In the case of the parainfluenza virus, the cell entry process starts with the recognition and attachment to target receptors, followed by proteolytic cleavage of the fusion glycoprotein (F) protein, exposing the fusion peptide (FP) region. The FP is responsible for binding to the target membrane, and it is believed to play a crucial role in the fusion process, but the mechanism by which the parainfluenza FP (PIFP) promotes membrane fusion is still unclear. To elucidate this matter, we performed biophysical experimentation of the PIFP in membranes, together with coarse grain (CG) and atomistic (AA) molecular dynamics (MD) simulations. The simulation results led to the pinpointing of the most important PIFP amino acid residues for membrane fusion and show that, at high concentrations, the peptide induces the formation of a water-permeable porelike structure. This structure promotes lipid head intrusion and lipid tail protrusion, which facilitates membrane fusion. Biophysical experimental results validate these findings, showing that, depending on the peptide/lipid ratio, the PIFP can promote fusion and/or membrane leakage. Our work furthers the understanding of the PIFP-induced membrane fusion process, which might help foster development in the field of viral entry inhibition.This work was financially supported by FCT-Fundação para a Ciência e a Tecnologia, Portugal, through project PTDC/CCI-BIO/28200/2017 and by the European Union (H2020-FETOPEN-2018-2019-2020-01, grant no. 828774). This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020_Programa Operacional Competitividade e Internacionalização (POCI). M.V. and D.A.M. thank FCT for their PhD fellowships (SFRH/BD/148542/2019 and PD/BD/136752/2018, respectively). M.N.M. thanks FCT for the Post-Doc fellowship CEECIND/04124/2017. M.N.M. and D.L. thank the MACC for the computing hours in their HPC center (CPCA/A0/7329/2020 and CPCA/A0/7305/2020).info:eu-repo/semantics/publishedVersio

The Effects of a “Health at Every Size®”-Based Approach in Obese Women: A Pilot-Trial of the “Health and Wellness in Obesity” Study

This study explored the effects of Health at Every Size®-based intervention on obese women by qualitatively evaluating participants’ perception towards the program and quantitatively evaluating changes related to psychological, behavioral and body composition assessments. A prospective one-year quasi-experimental mixed-method trial was conducted. The mixed method design was characterized by a spiral method, and quantitative and qualitative findings were combined during the interpretation phase. The qualitative data involved three focus groups; and quantitative data comprised physiological, psychological and behavioral assessments. Initially, 30 participants were recruited; 14 concluded the intervention. From the focus groups, the following interpretative axes were constructed: the intervention as a period of discoveries; shifting parameters: psychological, physical and behavioral changes; eating changes, and; redefining success. Body weight, body mass index, total body fat mass and body fat percentage were significantly decreased after the intervention (-3.6, -3.2, -13.0, and -11.1%, respectively; p≤0.05, within-time effect). Participants reported being more physically active, and perceiving better their bodies. Eating-wise, participants reported that the hunger and satiety cues and the consumption of more frequent meals facilitated their eating changes. Finally, participants reported that they could identify feelings with eating choices and refrain from the restrained behavior. These qualitative improvements were accompanied by modest but significant improvements in quantitative assessments. Clinicaltrials.gov registration: NCT02102061

“É lá, perto da moça gorda”: estudo qualitativo sobre as percepções de mulheres gordas acerca de seus corpos e discriminações relacionadas ao peso corporal

We investigated fat women’s perceptions of their own bodies and their experiences with weightrelated discriminations, and how these situations affected their well-being. Thirty-nine obese women were interviewed, and three axes of analysis were identified: (1) repercussions of being fat, (2) living with a fat body, and (3) am I a person or just a fat body? These axes were composed of eight themes which had similar meaning or complemented each other. The results showed our participants had mechanisms to diminish the magnitude of their stigmatized bodies (e.g., attempting to lose weight and changing their current food choices). Participants also reported being fat had physical and psychological consequences for them. Most notably, their larger bodies influenced their self-evaluation, making them feel devalued, unlovable, incapable, and incomplete. They reported stigmatizing experiences in familiar situations, at the workplace and in public spaces, and reported being stigmatized by both close and unknown individuals, including healthcare professionals. These professionals were reported to treat patients disrespectfully, which urges attention to health care inequalities for obese people. Our results stress stigmatizing attitudes towards fat people and their own considerations about themselves have negative consequences in their physical and mental well-being.Investigamos a percepção de mulheres gordas sobre seu próprio corpo e suas experiências com discriminações relacionadas ao peso e como essas situações afetavam seu bem-estar. Trinta e nove mulheres obesas foram entrevistadas, sendo identificados três eixos de análise: (1) repercussões de ser gorda, (2) vivendo com um corpo gordo, e (3) eu sou uma pessoa ou apenas um corpo gordo? Esses eixos eram compostos por oito temas que se complementavam ou tinham significado semelhante. Os resultados mostraram que nossas participantes utilizavam mecanismos para diminuir a magnitude de seus corpos estigmatizados (por exemplo, tentando perder peso e modificando suas escolhas alimentares atuais). As participantes também relataram que ser gorda teve consequências físicas e psicológicas para elas. É importante ressaltar que seus corpos maiores influenciaram sua autoavaliação, fazendo com que se sentissem desvalorizadas, incapazes, incompletas e sem possibilidade de se sentirem amadas. Elas relataram experiências estigmatizadoras em situações familiares, no local de trabalho e em espaços públicos, e relataram serem estigmatizadas por pessoas próximas e desconhecidas, bem como por profissionais de saúde. Foi relatado que esses profissionais tratam os pacientes com desrespeito, o que exige atenção quanto às desigualdades na assistência à saúde de pessoas obesas. Nossos resultados enfatizam que atitudes estigmatizadoras em relação às pessoas gordas e suas próprias considerações sobre si mesmas têm consequências negativas para seu bem-estar físico e mental

Pathogen-Specific Epitopes as Epidemiological Tools for Defining the Magnitude of Mycobacterium leprae Transmission in Areas Endemic for Leprosy

During recent years, comparative genomic analysis has allowed the identification of Mycobacterium leprae-specific genes with potential application for the diagnosis of leprosy. In a previous study, 58 synthetic peptides derived from these sequences were tested for their ability to induce production of IFN-γ in PBMC from endemic controls (EC) with unknown exposure to M. leprae, household contacts of leprosy patients and patients, indicating the potential of these synthetic peptides for the diagnosis of sub- or preclinical forms of leprosy. In the present study, the patterns of IFN-γ release of the individuals exposed or non-exposed to M. leprae were compared using an Artificial Neural Network algorithm, and the most promising M. leprae peptides for the identification of exposed people were selected. This subset of M. leprae-specific peptides allowed the differentiation of groups of individuals from sites hyperendemic for leprosy versus those from areas with lower level detection rates. A progressive reduction in the IFN-γ levels in response to the peptides was seen when contacts of multibacillary (MB) patients were compared to other less exposed groups, suggesting a down modulation of IFN-γ production with an increase in bacillary load or exposure to M. leprae. The data generated indicate that an IFN-γ assay based on these peptides applied individually or as a pool can be used as a new tool for predicting the magnitude of M. leprae transmission in a given population

Inhibition of Bacterial and Fungal Biofilm Formation by 675 Extracts from Microalgae and Cyanobacteria

Bacterial biofilms are complex biological systems that are difficult to eradicate at a medical, industrial, or environmental level. Biofilms confer bacteria protection against external factors and antimicrobial treatments. Taking into account that about 80% of human infections are caused by bacterial biofilms, the eradication of these structures is a great priority. Biofilms are resistant to old-generation antibiotics, which has led to the search for new antimicrobials from different sources, including deep oceans/seas. In this study, 675 extracts obtained from 225 cyanobacteria and microalgae species (11 phyla and 6 samples belonging to unknown group) were obtained from different culture collections: The Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC), the Coimbra Collection of Algae (ACOI) from Portugal, and the Roscoff Culture Collection (RCC) from France. The largest number of samples was made up of the microalgae phylum Chlorophyta (270) followed by Cyanobacteria (261). To obtain a large range of new bioactive compounds, a method involving three consecutive extractions (hexane, ethyl acetate, and methanol) was used. The antibiofilm activity of extracts was determined against seven different bacterial species and two Candida strains in terms of minimal biofilm inhibitory concentration (MBIC). The highest biofilm inhibition rates (%) were achieved against Candida albicans and Enterobacter cloacae. Charophyta, Chlorophyta, and Cyanobacteria were the most effective against all microorganisms. In particular, extracts of Cercozoa phylum presented the lowest MBIC50 and MBIC90 values for all the strains except C. albicans

Overweight and constipation in adolescents

Background: the association between overweight and gastrointestinal symptoms has been recently studied in the literature; however, few studies have evaluated the association between overweight and constipation in adolescents in a community-based sample. the aim of this study was to analyze the prevalence of constipation and its association with being overweight in a community-based survey with adolescents.Methods: This cross-sectional study included 1,077 adolescents who were enrolled in five schools in the city of Sao Jose dos Campos, Brazil. Constipation was defined according to modified and combined Rome III criteria for adolescents and adults. Being overweight was defined as a body mass index (BMI) that was equal to or greater than that of the 85(th) percentile for age and gender.Results: Constipation was diagnosed in 18.2% (196/1077) of the included adolescents. There was no significant difference in the prevalence of constipation in males and females who were both younger and older than 14 years. Fecal incontinence was observed in 25 adolescents, 22 (88.0%) of whom were diagnosed as being constipated. the prevalence of being overweight was found in 13.5% (145/1077) of the study population. the prevalence of constipation was observed to be similar in adolescents who were (19.4%; 28/144) and were not (18.0%; 168/933) overweight (p = 0.764; OR = 1.10). Fecal incontinence that was associated with constipation was more frequent in adolescents who were overweight (37.0%; 8/28) than in adolescents who were not overweight (8.5%; 14/168; p = 0.005; OR = 4.40).Conclusions: the prevalence of constipation was high among the investigated adolescents. There was no association between being overweight and constipation; however, an association between being overweight and fecal incontinence in constipated adolescents was confirmed.Universidade Federal de São Paulo, Div Pediat Gastroenterol, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Pediat Gastroenterol, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin similar to 100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants