Daily Step Counts Before and After the COVID-19 Pandemic Among All of Us Research Participants.

This cohort study of US adults examines changes in physical activity following the onset of the COVID-19 pandemic.

Breast cancer molecular diagnostics in Rwanda: a cost-minimization study of immunohistochemistry versus a novel GeneXpert® mRNA expression assay

Objective To compare the financial and time cost of breast cancer biomarker analysis by immunohistochemistry with that by the Xpert® STRAT4 assay. Methods We estimated costs (personnel, location, consumables and indirect) and time involved in breast cancer diagnosis at the Butaro Cancer Centre of Excellence, Rwanda, using time-driven activity-based costing. We performed a cost-minimization analysis to compare the cost of biomarker analysis for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status with immunohistochemistry versus STRAT4. We performed sensitivity analyses by altering laboratory-specific parameters for the two methods. Findings We estimated that breast cancer diagnosis in Rwanda costs 138.29 United States dollars (US$) per patient when conducting biomarker analysis by immunohistochemistry. At a realistic immunohistochemistry antibody utilization efficiency of 70%, biomarker analysis comprises 48.7% (US$ 67.33) of diagnostic costs and takes 33 min. We determined that biomarker analysis with STRAT4 yields a reduction in diagnosis cost of US$ 7.33 (10.9%; 7.33/67.33), and in pathologist and technician time of 20 min (60.6%; 20/33), per patient. Our sensitivity analysis revealed that no cost savings would be made in laboratories with antibody utilization efficiencies over 90%, or where only estrogen and/or progesterone receptor status are assessed; however, such operational efficiencies are unlikely, and more laboratories are pursuing human epidermal growth factor receptor-2 analysis as targeted therapies become increasingly available. Conclusion Breast cancer biomarker analysis with STRAT4 has the potential to reduce the required human and capital resources in subSaharan African laboratories, leading to improved treatment selection and better clinical outcomes.

Componente genético de las enfermedades reumatológicas autoinmunes / Genetic Component of Autoimmune Rheumatological Diseases

El propósito de esta revisión es presentar los principales aspectos del componente genético de las enfermedades reumatológicas autoinmunes, incluyendo las características del modelo de herencia multifactorial o poligénico y sus formas monogénicas, así como los principales genes asociados en ambos casos. De igual manera, los cambios epigenéticos implicados, además de la influencia del ambiente y el sexo para conferir mayor riesgo a las mujeres de padecer alguna de estas enfermedades. Finalmente, se comenta acerca de los avances logrados por el estudio de las ciencias ómicas, abriendo camino a una nueva clasificación molecular de estas enfermedades, y así dirigirlo a una medicina personalizada. Se revisó la literatura de los últimos 5 años de publicaciones en lengua inglesa mediante la base de datos PubMed, se incluyeron 28 artículos de revisión y 19 artículos originales. Se discutió el papel de los factores genéticos que participan en la etiología de las enfermedades reumatológicas autoinmunes, gracias a la disponibilidad de estudios moleculares, lo que permite mayor comprensión de la fisiopatología y la posibilidad de realizar en un futuro cercano un diagnóstico y tratamiento basado en marcadores moleculares.(AU)

The purpose of this review is to present the main aspects of the genetic component of autoimmune rheumatic diseases, including the characteristics of the multifactorial or polygenic inheritance model, and its monogenic forms, as well as the main associated genes in both cases. The epigenetic changes involved, and the influence of the environment and sex that confer greater risk to women suffering from any of these diseases. Finally, to make known the advances that the study of omic sciences has allowed, opening the way to a new molecular classification of these diseases, aimed at personalized medicine. A review of the literature of the last 5 years, of English-language publications, in the PubMed database was performed and 28 review articles, and 19 original articles were included. Knowledge of the genetic factors involved in the aetiology of autoimmune rheumatic diseases, thanks to the availability of molecular studies, allows a better understanding of their pathophysiology and the possibility of diagnosis and treatment based on molecular markers in the future.(AU)

Apresentação clínica de osteogênese XV em um menino brasileiro de 4 anos / Clinical presentation of osteogenesis imperfecta XV in a four-year-old brazilian boy

Introdução: Osteogênese Imperfeita (OI) é uma doença genética rara com fragilidade óssea. A classificação inclui muitos tipos. Além do risco de recorrência, o manejo pode variar com o tipo de OI. Relato do caso: Apresentamos um paciente do sexo masculino nascido com 39 semanas, de pais não consanguíneos e saudáveis. A hidrocefalia foi diagnosticada no pré-natal. Com 50 dias de vida, detectamos muitas fraturas e calos ósseos. O teste molecular identificou uma deleção em homozigose do éxon 4 do gene WNT1. Considerações finais: Concluímos que o caso apresentado tinha características clínicas de OI XV, e o teste molecular foi fundamental para o diagnóstico preciso e aconselhamento genético.

Introduction: Osteogenesis Imperfecta (OI) is a rare genetic disease with bone fragility. The classification includes many types. In addition, the risk of a recurrence, the management can vary with the kind of OI. Case report: We report a male patient born at 39 weeks from non-consanguineous healthy parents. The patient was diagnosed with Hydrocephalus at prenatal. At 50 days of life, we detected many fractures and bone calluses. The molecular test identified a homozygous deletion of exon 4 of the WNT1 gene. Final considerations: We conclude this case had clinical features of OI XV, and the molecular test was fundamental for the precise diagnosis and the genetic counseling.

Taquicardia ventricular catecolaminérgica com mutação do GENE RYR2 - troca do nucleotídeo C. 7433T>C em família com histórico de síncope e morte súbita / Catecholaminergic ventricular tachycardia with GENE RYR2 mutation - C.7433T>C nucleotide exchange in a family with a history of syncope and sudden death

INTRODUÇÃO: Eventos súbitos na adolescência são sempre dramáticos e causam impacto na família e na sociedade. Histórias recorrentes são subdiagnosticadas e tragédias familiares ficam sem explicação devido à falta de compreensão do generalista sobre as causas de morte súbita sem cardiopatia estrutural. O diagnóstico de canalopatias muitas vezes depende da análise do ECG em suas diversas modalidades e na maioria dos casos medidas clínicas podem ser o suficiente para salvar vidas. OBJETIVO: Descrever 2 casos de taquicardia ventricular catecolaminérgica (TVPC) em adolescentes primos em primeiro grau com vasto histórico de morte súbita familiar. DESCRIÇÃO DOS CASOS: Caso 1 - Paciente, 14 anos, sexo feminino, coração estruturalmente normal com síncope durante dança. Histórico familiar de morte súbita antes dos 40 anos (irmã, avô e 3 primos de primeiro grau). Todos os eventos relacionados a estresse físico/emocional. Apresentava Holter e ECG de repouso normais. Teste ergométrico com episódios de taquicardia ventricular não sustentada polimórfica, no pico do esforço. Submetida a estudo genético, com mutação no gene RYR2. Introduzido nadolol, mantendo-se sem novos episódios de síncope e com TE sem taquicardia ventricular. Segue assintomática em acompanhamento regular (hoje com 22 anos) e suspensa das atividades esportivas. Caso 2 - Paciente 18 anos, sexo feminino com síncope após estresse emocional. Possui história familiar de morte súbita (avó aos 30 anos, primo aos 14 anos e outro primo aos 17 anos). Possui prima com diagnóstico de TVPC com teste genético positivo para mutação no gene RYR2 com troca do nucleotídeo c.7433T>C. Teste ergométrico com EV frequentes polimórficas ao esforço. Recebe nadolol e evolui estável sem novos episódios de síncope. Teste ergométrico de controle não evidencia taquicardia ventricular. CONCLUSÃO: 1) O diagnóstico de TVPC depende da anamnese, histórico familiar e da avaliação do ECG de esforço; 2) O uso de Nadolol ou Propranolol permite uma redução significativa do número de eventos quando associado à suspensão da atividade física; 3) Apesar da síncope ser um evento de prenúncio de morte sua não repetição após o tratamento promove maior segurança para terapia farmacológica isolada.

"Batesonian Mendelism" and "Pearsonian biometry": shedding new light on the controversy between William Bateson and Karl Pearson.

This paper contributes to the ongoing reassessment of the controversy between William Bateson and Karl Pearson by characterising what we call "Batesonian Mendelism" and "Pearsonian biometry" as coherent and competing scientific outlooks. Contrary to the thesis that such a controversy stemmed from diverging theoretical commitments on the nature of heredity and evolution, we argue that Pearson's and Bateson's alternative views on those processes ultimately relied on different appraisals of the methodological value of the statistical apparatus developed by Francis Galton. Accordingly, we contend that Bateson's belief in the primacy of cross-breeding experiments over statistical analysis constituted a minimal methodological unifying condition ensuring the internal coherence of Batesonian Mendelism. Moreover, this same belief implied a view of the study of heredity and evolution as an experimental endeavour and a conception of heredity and evolution as fundamentally discontinuous processes. Similarly, we identify a minimal methodological unifying condition for Pearsonian biometry, which we characterise as the view that experimental methods had to be subordinate to statistical analysis, according to methodological standards set by biometrical research. This other methodological commitment entailed conceiving the study of heredity and evolution as subsumable under biometry and primed Pearson to regard discontinuous hereditary and evolutionary processes as exceptions to a statistical norm. Finally, we conclude that Batesonian Mendelism and Pearsonian biometry represented two potential versions of a single genetics-based evolutionary synthesis since the methodological principles and the phenomena that played a central role in the former were also acknowledged by the latter-albeit as fringe cases-and conversely.

Speedy light focusing through scattering media by a cooperatively FPGA-parameterized genetic algorithm.

We developed an accelerated Genetic Algorithm (GA) system based on the cooperation of a field-programmable gate array (FPGA) and the optimized parameters that enables fast light focusing through scattering media. Starting at the searching space, which influences the convergence of the optimization algorithms, we manipulated the mutation rate that defines the number of mutated pixels on the spatial light modulator to accelerate the GA process. We found that the enhanced decay ratio of the mutation rate leads to a much faster convergence of the GA. A convergence-efficiency function was defined to gauge the tradeoff between the processing time and the enhancement of the focal spot. This function allowed us to adopt the shorter iteration number of the GA that still achieves applicable light focusing. Furthermore, the accelerated GA configuration was programmed in FPGA to boost processing speed at the hardware level. It shows the ability to focus light through scattering media within a few seconds, 150 times faster than the PC-based GA. The processing cycle could be further promoted to a millisecond-level with the advanced FPGA processor chips. This study makes the evolution-based optimization approach adaptable in dynamic scattering media, showing the capability to tackle wavefront shaping in biological material.

Avances en genética clínica y sus retos actuales / Advances in clinical genetics and its current challenges

Los grandes avances en el desarrollo de las tecnologías genómicas y su incorporación a la práctica clínica habitual está suponiendo un cambio en el que la información genética de un individuo tiene cada vez mayor relevancia en su atención médica. Esto es lo que se conoce como medicina genómica. Su implementación no está exenta de barreras, entre la cuales se encuentran las dificultades en el asesoramiento e interpretación de los datos genómicos, una formación deficiente de los profesionales y los pacientes en este campo, un acceso desigual a unidades con experiencia y una falta de perfiles profesionales e infraestructuras necesarias para la incorporación de las tecnologías genómicas en la práctica clínica habitual. En este artículo se revisan los avances y retos de la medicina genómica. (AU)

The great advances in the development of genomic technologies and their incorporation into routine clinical practice is bringing about a change in which an individual's genetic information is becoming increasingly relevant to their medical care. This is known as genomic medicine. Its implementation is not without barriers, including difficulties in the assessment and interpretation of genomic data, deficient training of professionals and patients in this field, unequal access to units with expertise, and a lack of professional profiles and infrastructures necessary for the incorporation of genomic technologies into routine clinical practice. This article reviews the advances and challenges of genomic medicine. (AU)

Genetic solutions to cultural problems?

In theory, observed correlations between genetic information and behaviour might be useful to members of the WEIRD (western, educated, industrialized, rich, and democratic) populations. Guiding young people to choose educational opportunities that best match their abilities would benefit both the individual and society. In practice, however, such choices are far more profoundly limited by the culture people have inherited than their genes.

Christine Guthrie (1945-2022).

RNA trailblazer who illuminated splicing mechanics.

Guía práctica para la solicitud de marcadores humorales de autoinmunidad y estudios genéticos en diabetes mellitus / A practical guide to request humoral autoimmunity markers and genetic tests in diabetes mellitus

La diabetes mellitus (DM) es una enfermedad heterogénea que presenta fenotipos clínicos diversos, todos con hiperglucemia. Históricamente se han utilizado cuatro factores para identificar esta diversidad: la edad de inicio, la gravedad de la enfermedad o grado de pérdida de la función de la célula beta, el grado de resistencia a la insulina y la presencia de autoanticuerpos asociados a la enfermedad. Actualmente, los parámetros empleados para clasificar los diferentes tipos de DM dificultan el diagnóstico y tratamiento de los pacientes. Las distintas presentaciones clínicas requieren una clasificación diagnóstica más eficaz para un abordaje terapéutico más preciso, valiéndose del avance de la inmunogenética y la bioquímica clínica. Esta guía está orientada a clasificar con precisión las presentaciones clínicas que a menudo generan incertidumbre dentro de los dos tipos principales de DM.

Diabetes mellitus (DM) is a heterogeneous disease, with diverse clinical phenotypes, all with hyperglycemia. Historically, four factors have been used to identify this diversity: the age at onset, the severity of the disease, that is, the degree of loss of beta cell function and insulin resistance, and the presence of circulating autoantibodies. Currently, the parameters used to classify the different types of DM make it difficult to diagnose and treat patients. The different clinical manifestations require an accurate diagnosis to achieve an effective therapeutic approach through the use of immunogenetics and clinical biochemistry. This practical guide aims to accurately classify the often uncertain clinical presentations within the two main types of diabetes.

Mendel's legacy in modern genetics.

A new collection of articles celebrating the bicentennial of Gregor Mendel's birth discuss his life, work and legacy in modern-day genetic research.

The genotype-phenotype distinction: from Mendelian genetics to 21st century biology.

The Genotype-Phenotype (G-P) distinction was proposed in the context of Mendelian genetics, in the wake of late nineteenth century studies about heredity. In this paper, we provide a conceptual analysis that highlights that the G-P distinction was grounded on three pillars: observability, transmissibility, and causality. Originally, the genotype is the non-observable and transmissible cause of its observable and non-transmissible effect, the phenotype. We argue that the current developments of biology have called the validity of such pillars into question. First, molecular biology has unveiled the putative material substrate of the genotype (qua DNA), making it an observable object. Second, numerous findings on non-genetic heredity suggest that some phenotypic traits can be directly transmitted. Third, recent organicist approaches to biological phenomena have emphasized the reciprocal causality between parts of a biological system, which notably applies to the relation between genotypes and phenotypes. As a consequence, we submit that the G-P distinction has lost its general validity, although it can still apply to specific situations. This calls for forging new frameworks and concepts to better describe heredity and development.

The deceptive simplicity of mendelian genetics.

Mendel, a genius experimentalist, meticulously uncovered the genetic basis of heredity in work that transformed the science of biology. But does the alluring simplicity of Mendel's laws sometimes obscure the true complexity of genetics?

Gregor Mendel's legacy in quantitative genetics.

Gregor Mendel's discovery of the laws of segregation and independent assortment and his inference of the existence of non-mendelian interactions between loci remain at the heart of today's explorations of the genetic architecture of quantitative traits.