Alcohol consumption and risks of more than 200 diseases in Chinese men.

Alcohol consumption accounts for ~3 million annual deaths worldwide, but uncertainty persists about its relationships with many diseases. We investigated the associations of alcohol consumption with 207 diseases in the 12-year China Kadoorie Biobank of >512,000 adults (41% men), including 168,050 genotyped for ALDH2- rs671 and ADH1B- rs1229984 , with >1.1 million ICD-10 coded hospitalized events. At baseline, 33% of men drank alcohol regularly. Among men, alcohol intake was positively associated with 61 diseases, including 33 not defined by the World Health Organization as alcohol-related, such as cataract (n = 2,028; hazard ratio 1.21; 95% confidence interval 1.09-1.33, per 280 g per week) and gout (n = 402; 1.57, 1.33-1.86). Genotype-predicted mean alcohol intake was positively associated with established (n = 28,564; 1.14, 1.09-1.20) and new alcohol-associated (n = 16,138; 1.06, 1.01-1.12) diseases, and with specific diseases such as liver cirrhosis (n = 499; 2.30, 1.58-3.35), stroke (n = 12,176; 1.38, 1.27-1.49) and gout (n = 338; 2.33, 1.49-3.62), but not ischemic heart disease (n = 8,408; 1.04, 0.94-1.14). Among women, 2% drank alcohol resulting in low power to assess associations of self-reported alcohol intake with disease risks, but genetic findings in women suggested the excess male risks were not due to pleiotropic genotypic effects. Among Chinese men, alcohol consumption increased multiple disease risks, highlighting the need to strengthen preventive measures to reduce alcohol intake.

Autophagy-related proteins: Potential diagnostic and prognostic biomarkers of aging-related diseases.

Autophagy plays a key role in cellular, tissue and organismal homeostasis and in the production of the energy load needed at critical times during development and in response to nutrient shortage. Autophagy is generally considered as a pro-survival mechanism, although its deregulation has been linked to non-apoptotic cell death. Autophagy efficiency declines with age, thus contributing to many different pathophysiological conditions, such as cancer, cardiomyopathy, diabetes, liver disease, autoimmune diseases, infections, and neurodegeneration. Accordingly, it has been proposed that the maintenance of a proper autophagic activity contributes to the extension of the lifespan in different organisms. A better understanding of the interplay between autophagy and risk of age-related pathologies is important to propose nutritional and life-style habits favouring disease prevention as well as possible clinical applications aimed at promoting long-term health.

Physiology and diseases of tissue-resident macrophages.

Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate from early yolk sac progenitors and are specified into tissue-specific subsets during organogenesis-establishing stable spatial and functional relationships with specialized tissue cells-and persist in adults. Resident macrophages are an integral part of tissues together with specialized cells: for instance, microglia reside with neurons in brain, osteoclasts reside with osteoblasts in bone, and fat-associated macrophages reside with white adipocytes in adipose tissue. This ancillary cell type, which is developmentally and functionally distinct from haematopoietic stem cell and monocyte-derived macrophages, senses and integrates local and systemic information to provide specialized tissue cells with the growth factors, nutrient recycling and waste removal that are critical for tissue growth, homeostasis and repair. Resident macrophages contribute to organogenesis, promote tissue regeneration following damage and contribute to tissue metabolism and defence against infectious disease. A correlate is that genetic or environment-driven resident macrophage dysfunction is a cause of degenerative, metabolic and possibly inflammatory and tumoural diseases. In this Review, we aim to provide a conceptual outline of our current understanding of macrophage physiology and its importance in human diseases, which may inform and serve the design of future studies.

[The placebo effect in functional disorders]. / Effet placebo dans les troubles fonctionnels.

Functional disorders are clinical entities corresponding to complaints mimicking diseases without a clearly identified organic substrate despite a rigorous history and clinical examination. Sometimes, complementary examinations are necessary to rule out an organic lesion that could explain the symptomatology. The notion of a diagnosis of exclusion is therefore very present. The physician must constantly re-evaluate the diagnosis of functional disorder in order not to «miss¼ a diagnosis with an organic cause.The treatment of these functional disorders is sometimes based on psychological treatment when a psychogenic dimension seems to be involved. This is not always the case. In such cases it is necessary to be able to consider a placebo approach with the hope that the placebo effect may improve the patient's condition. This article discusses the placebo effect in functional disorders without omitting to address ethical and philosophical considerations.

Les troubles fonctionnels sont des entités cliniques correspondant à des plaintes mimant des maladies sans substrat organique clairement identifié, malgré une anamnèse et un examen clinique rigoureux. Parfois, certains examens complémentaires sont nécessaires pour infirmer une lésion organique pouvant expliquer la symptomatologie. La notion de diagnostic d'exclusion est donc bien présente. Le praticien se doit de réévaluer sans cesse le diagnostic de trouble fonctionnel afin de ne pas «passer à côté¼ d'un diagnostic avec une cause organique. Le traitement de ces troubles fonctionnels repose parfois sur une prise en charge psychologique lorsqu'une dimension psychogène semble incriminée. Ce n'est pas toujours le cas. Il faut alors pouvoir être capable d'envisager une approche via des placebo en espérant que l'effet placebo puisse améliorer la condition du (de la) patient(e). Cet article décrit l'effet placebo dans les troubles fonctionnels, sans omettre d'aborder des notions éthiques et philosophiques.

Mitochondria in Ageing and Diseases: Partie Deux.

The past several decades has seen a huge expansion of the knowledge and research of mitochondrial dysfunction and the role it plays in ageing and age-related diseases [...].

Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens.

Most variants associated with complex traits and diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome with unknown effects. Using ancestrally diverse, biobank-scale GWAS data, massively parallel CRISPR screens, and single-cell transcriptomic and proteomic sequencing, we discovered 124 cis-target genes of 91 noncoding blood trait GWAS loci. Using precise variant insertion through base editing, we connected specific variants with gene expression changes. We also identified trans-effect networks of noncoding loci when cis target genes encoded transcription factors or microRNAs. Networks were themselves enriched for GWAS variants and demonstrated polygenic contributions to complex traits. This platform enables massively parallel characterization of the target genes and mechanisms of human noncoding variants in both cis and trans.

The AnnotSV webserver in 2023: updated visualization and ranking.

Much of the human genetics variant repertoire is composed of single nucleotide variants (SNV) and small insertion/deletions (indel) but structural variants (SV) remain a major part of our modified DNA. SV detection has often been a complex question to answer either because of the necessity to use different technologies (array CGH, SNP array, Karyotype, Optical Genome Mapping…) to detect each category of SV or to get an appropriate resolution (Whole Genome Sequencing). Thanks to the deluge of pangenomic analysis, Human geneticists are accumulating SV and their interpretation remains time consuming and challenging. The AnnotSV webserver (https://www.lbgi.fr/AnnotSV/) aims at being an efficient tool to (i) annotate and interpret SV potential pathogenicity in the context of human diseases, (ii) recognize potential false positive variants from all the SV identified and (iii) visualize the patient variants repertoire. The most recent developments in the AnnotSV webserver are: (i) updated annotations sources and ranking, (ii) three novel output formats to allow diverse utilization (analysis, pipelines), as well as (iii) two novel user interfaces including an interactive circos view.

Carga de enfermedad en el Perú. Estimación de los años de vida saludables perdidos 2019 / Burden of disease in Peru. Estimated healthy years of life lost 2019

En ese sentido, el estudio de carga de enfermedad en el Perú del 2019 nos presenta las principales enfermedades y lesiones que han aportado mayor número de años de vida saludables perdidos en el país, reconociendo no solo aquellas que producen muerte prematura, sino también discapacidad. De esta manera, podemos disponer de información valiosa para la toma de decisiones en salud pública y dirigir las acciones hacia un mayor beneficio para la población de nuestro país. Los años de vida ajustados por discapacidad -AVISA- estiman la carga de la enfermedad, de acuerdo a las distintas causas o problemas de salud consideradas. Un AVISA corresponde a un año de vida sana perdido y la medición de la carga de enfermedad por este indicador significaría la brecha existente entre la situación actual de salud de una población y la ideal en la que cada miembro de esa población podría alcanzar la vejez libre de enfermedad y discapacidad.

The Saturated Phenomenon of Flesh and Mineness and Otherness of the Body in Illness.

A key topic within the field of the phenomenology of medicine has been the relationship between body and self in illness, including discussions about the otherness and mineness of the body. The aim of this article is to distinguish between different meanings of bodily otherness and mineness in illness with reference to the interpretation of the body as "saturated phenomenon," inspired by the phenomenology of Jean-Luc Marion. With the help of Marion's ideas it is possible to distinguish between two meanings of bodily otherness and of mineness (objective and non-objective forms). These distinctions support and elaborate on ideas already found in the phenomenology of medicine and offer further insights into the nature of the experience of illness.

Leveraging base-pair mammalian constraint to understand genetic variation and human disease.

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

Seminars in immunology special issue: Nutrition, microbiota and immunity The unexplored microbes in health and disease.

Functional characterization of the microbiome's influence on host physiology has been dominated by a few characteristic example strains that have been studied in detail. However, the extensive development of methods for high-throughput bacterial isolation and culture over the past decade is enabling functional characterization of the broader microbiota that may impact human health. Characterizing the understudied majority of human microbes and expanding our functional understanding of the diversity of the gut microbiota could enable new insights into diseases with unknown etiology, provide disease-predictive microbiome signatures, and advance microbial therapeutics. We summarize high-throughput culture-dependent platforms for characterizing bacterial strain function and host-interactions. We elaborate on the importance of these technologies in facilitating mechanistic studies of previously unexplored microbes, highlight new opportunities for large-scale in vitro screens of host-relevant microbial functions, and discuss the potential translational applications for microbiome science.

Structural analysis of the P132L disease mutation in caveolin-1 reveals its role in the assembly of oligomeric complexes.

Caveolin-1 (CAV1) is a membrane-sculpting protein that oligomerizes to generate flask-shaped invaginations of the plasma membrane known as caveolae. Mutations in CAV1 have been linked to multiple diseases in humans. Such mutations often interfere with oligomerization and the intracellular trafficking processes required for successful caveolae assembly, but the molecular mechanisms underlying these defects have not been structurally explained. Here, we investigate how a disease-associated mutation in one of the most highly conserved residues in CAV1, P132L, affects CAV1 structure and oligomerization. We show that P132 is positioned at a major site of protomer-protomer interactions within the CAV1 complex, providing a structural explanation for why the mutant protein fails to homo-oligomerize correctly. Using a combination of computational, structural, biochemical, and cell biological approaches, we find that despite its homo-oligomerization defects P132L is capable of forming mixed hetero-oligomeric complexes with WT CAV1 and that these complexes can be incorporated into caveolae. These findings provide insights into the fundamental mechanisms that control the formation of homo- and hetero-oligomers of caveolins that are essential for caveolae biogenesis, as well as how these processes are disrupted in human disease.

[Is nutritional care during disease a human right?] / ¿Es la atención nutricional durante la enfermedad un derecho humano?

Introduction: Is nutritional care during disease a human right?

Introducción: ¿Es la atención nutricional durante la enfermedad un derecho humano?

A competência emocional dos enfermeiros na prestação de cuidados à pessoa com doença mental / The emotional competence of nurses in providing care to people with mental illness

Introdução: As emoções ocupam um papel fundamental e determinante no desenvolvimento pessoal e profissional dos enfermeiros, assim como na prestação de cuidados que realizam. Objetivos: Conhecer as variáveis sociodemográficas que caraterizam a população em estudo e quais as correlações existentes entre a competência emocional e as suas dimensões. Métodos: Estudo descritivo, exploratório, abordagem quantitativa, desenvolvido num hospital psiquiátrico da Região Norte de Portugal. Para recolha de informação foi utilizada: Escala Veiga da Competência Emocional. A colheita de dados foi realizada durante o mês de dezembro 2021. Foram cumpridos os pressupostos da Comissão de Ética de acordo com Declaração Helsínquia. A população em estudo foi constituída por 40 enfermeiros, sendo os critérios de inclusão: enfermeiros em situação laboral ativa no cuidado à pessoa com doença mental internada. Resultados: Verificou-se que na sua maioria os participantes eram do sexo feminino (58,76%), com idades compreendidas entre 26-55 anos. Quanto às habilitações académicas, a maioria dos participantes (53,4%) apresentava licenciatura, sendo que 38,9% apresentava a especialidade. Relativamente ao grau de importância, atribuído às questões situação profissional, foi considerado numa escala de Likert: 1 “sem importância”, 5 “muito importante”, como sendo, muito importante “relação interpessoal com os outros”, “estabilidade emocional na relação com os outros” e “estabilidade emocional na prestação de cuidados”, 79% (n=31). Conclusão: Verificou-se correlações entre as variáveis sexo/habilitações académicas. No sexo feminino, foi possível verificar que este perceciona-se, “frequentemente”, empático na prestação de cuidados. Enfermeiros com título especialista também se percecionam como profissionais empáticos, quando comparados com enfermeiros de cuidados gerais. (AU)

Introduction: Emotions play a fundamental and decisive role in the personal and professional development of nurses and the provision of care. Objectives: To explore the sociodemographic variables that characterize the sample under study and the correlations between emotional competence and its dimensions. Methods: Descriptive, exploratory study, quantitative approach, developed in a psychiatric hospital in the Northern Region of Portugal. The collection of information was performed using the Veiga Scale of Emotional Competence. Data collection was carried out in December 2021. The Ethics Committee followed the Helsinki Declaration guidelines. The sample consisted of 40 nurses, and the inclusion criteria were: nurses working with hospitalized people with mental illness. Results: Most participants were female (58.76%), aged between 26 and 55. Regarding academic qualifications, most participants (53.4%) had a degree, and 38.9% had a speciality. Concerning the degree of importance attributed to the professional situation issues, a Likert scale was used: 1 «unimportant», 5 «very important», as being very important, «interpersonal relationship with others», «emotional stability in the relationship with others» and «emotional stability in care delivery», 79% (n=31). Conclusion: Correlations were found between gender and academic qualifications. It was possible to verify that women nurses “often” perceive themselves as empathetic in the provision of care. Nurses with a specialist title also perceive themselves as empathetic professionals compared to general care nurses. (AU)

Consideraciones sobre integrantes del acto médico tomadas de la literatura / Considerations on Members of the Medical Act Taken from the Literature

Se acepta que la literatura puede ser útil para la enseñanza de la medicina porque ambas disciplinas trabajan con sentimientos de personas y consideran la relación interpersonal como el marco de referencia de su actividad profesional. En este trabajo se aportan una serie de ejemplos integrados por fragmentos de textos narrativos tomados de diferentes obras literarias que inciden en el valor de las descripciones y percepciones de diversos autores sobre aspectos de la interacción entre diferentes actores del acto médico. En síntesis, se refleja la imagen cambiante de la medicina y los médicos, del médico como persona, del efecto curativo de la interacción médico-enfermo, y de la interacción con el sistema sanitario. Si bien se aprecia el carácter altruista y abnegado de la práctica médica, los testimonios vertidos en algunos textos literarios dejan constancia de la necesidad de prestar más atención a la formación en empatía no sólo de los profesionales sanitarios, sino también de cuantas personas realizan su trabajo en el ámbito sanitario. (AU)

It is well accepted that literature can be useful for the teaching of medicine because both disciplines study people's feelings and consider the interpersonal relationship as the frame of reference for their professional activity. In the present work, a set of examples are provided, made up of fragments of narrative texts taken from different literary works that have impact on the value of the descriptions and perceptions of several authors on aspects of the interaction between different participants in the medical act. Briefly, it reflects the changing picture of medicine and doctors, the doctor as a person, the healing effect of the doctor-patient interaction, and of the interaction with the healthcare system. Whilst the altruistic and selfless nature of medical practice is appreciated, the proofs expressed in some literary texts show the need to pay more attention to training on the empathy not only for health professionals, but also for all the people who work in the healthcare system. (AU)

Quality control ensures fidelity in ribosome assembly and cellular health.

The coordinated integration of ribosomal RNA and protein into two functional ribosomal subunits is safeguarded by quality control checkpoints that ensure ribosomes are correctly assembled and functional before they engage in translation. Quality control is critical in maintaining the integrity of ribosomes and necessary to support healthy cell growth and prevent diseases associated with mistakes in ribosome assembly. Its importance is demonstrated by the finding that bypassing quality control leads to misassembled, malfunctioning ribosomes with altered translation fidelity, which change gene expression and disrupt protein homeostasis. In this review, we outline our understanding of quality control within ribosome synthesis and how failure to enforce quality control contributes to human disease. We first provide a definition of quality control to guide our investigation, briefly present the main assembly steps, and then examine stages of assembly that test ribosome function, establish a pass-fail system to evaluate these functions, and contribute to altered ribosome performance when bypassed, and are thus considered "quality control."