Experience With Four-Month Rifapentine and Moxifloxacin-Based Tuberculosis Treatment in San Francisco.

Background: A multicountry randomized controlled trial has demonstrated that pan-susceptible pulmonary tuberculosis (TB) can be successfully treated with a 4-month regimen of daily isoniazid, rifapentine, moxifloxacin, and pyrazinamide (HPMZ). We piloted HPMZ in San Francisco (SF) using a modified version of the US Centers for Disease Control and Prevention HPMZ treatment guidelines. Methods: In this retrospective cohort, patients consecutively referred to SF TB clinic were evaluated for HPMZ eligibility based on preestablished inclusion/exclusion criteria. All underwent evaluation and management according to national recommendations. We reviewed the medical records of those initiated on HPMZ. Results: From August 2021 to December 2023, 30 (18.8%) of 160 patients diagnosed with active TB met HPMZ inclusion criteria; of these, 22 (13.8%) started HPMZ. The median age (range) was 32.5 (14-86) years, 17 (77.3%) were otherwise healthy, and 19 (86.4%) had pulmonary TB, including 7 (36.8%) with cavitary disease. Eighteen (81.8%) patients had an adverse event, with 11 (50%) prematurely discontinuing HPMZ; the most common adverse events were vomiting, elevated transaminases, and rash. To date, 9 (40.9%) have completed treatment, with most achieving criteria for cure. One patient was diagnosed with possible TB recurrence and restarted standard TB treatment. Conclusions: Our experience, with half of patients to date prematurely discontinuing HPMZ, illustrates the challenge of extrapolating findings from TB clinical trials commonly conducted in high-incidence, non-US settings to US clinical practice. Further experience may help identify best practices for implementing HPMZ, including identifying predictors of which patients may be most likely to benefit from and tolerate this regimen.

Case report: Novel compound heterozygous IL1RN mutations as the likely cause of a lethal form of deficiency of interleukin-1 receptor antagonist.

Undiagnosed monogenic diseases represent a challenging group of human conditions highly suspicious to have a genetic origin, but without conclusive evidences about it. We identified two brothers born prematurely from a non-consanguineous healthy couple, with a neonatal-onset, chronic disease characterized by severe skin and bone inflammatory manifestations and a fatal outcome in infancy. We conducted DNA and mRNA analyses in the patients' healthy relatives to identify the genetic cause of the patients' disease. DNA analyses were performed by both Sanger and next-generation sequencing, which identified two novel heterozygous IL1RN variants: the intronic c.318 + 2T>G variant in the father and a ≈2,600-bp intragenic deletion in the mother. IL1RN mRNA production was markedly decreased in both progenitors when compared with healthy subjects. The mRNA sequencing performed in each parent identified two novel, truncated IL1RN transcripts. Additional experiments revealed a perfect intrafamilial phenotype-genotype segregation following an autosomal recessive inheritance pattern. The evidences shown here supported for the presence of two novel loss-of-function (LoF) IL1RN pathogenic variants in the analyzed family. Biallelic LoF variants at the IL1RN gene cause the deficiency of interleukin-1 receptor antagonist (DIRA), a monogenic autoinflammatory disease with marked similarities with the patients described here. Despite the non-availability of the patients' samples representing the main limitation of this study, the collected evidences strongly suggest that the patients described here suffered from a lethal form of DIRA likely due to a compound heterozygous genotype at IL1RN, thus providing a reliable genetic diagnosis based on the integration of old medical information with currently obtained genetic data.

Phylogenetic and Molecular Analysis of the Porcine Epidemic Diarrhea Virus in Mexico during the First Reported Outbreaks (2013-2017).

The characteristics of the whole PEDV genome that has circulated in Mexico from the first outbreak to the present are unknown. We chose samples obtained from 2013 to 2017 and sequenced them, which enabled us to identify the genetic variation and phylogeny in the virus during the first four years that it circulated in Mexico. A 99% identity was found among the analyzed pandemic strains; however, the 1% difference affected the structure of the S glycoprotein, which is essential for the binding of the virus to the cellular receptor. The S protein induces the most efficacious antibodies; hence, these changes in structure could be implicated in the clinical antecedents of the outbreaks. Antigenic changes could also help PEDV avoid neutralization, even in the presence of previous immunity. The characterization of the complete genome enabled the identification of three circulating strains that have a deletion in ORF1a, which is present in attenuated Asian vaccine strains. The phylogenetic analysis of the complete genome indicates that the first PEDV outbreaks in Mexico were caused by INDEL strains and pandemic strains related to USA strains; however, the possibility of the entry of European strains exists, which may have caused the 2015 and 2016 outbreaks.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Uniting for Ukraine Tuberculosis Screening Experience, San Francisco, California, USA.

Ukraine surveillance data suggest high tuberculosis (TB) incidence, including multidrug resistance. Of 299 newcomers from Ukraine screened in San Francisco, California, USA, by using an interferon-γ-release-assay (IGRA) and chest radiograph, 7.4% were IGRA positive and 1 had laboratory-confirmed pansusceptible TB. Screening with IGRA and chest radiograph can help characterize TB risk.

Adverse Events Associated With Treatment for Pan-Susceptible Tuberculosis in San Francisco.

Of 373 patients treated for drug-susceptible tuberculosis, 35.4% (46.2% aged ≥65 years) developed moderate/severe adverse events that required treatment interruption (34.8%), first-line drug discontinuation (26.2%, primarily pyrazinamide), second-line drug initiation (30.0%), and treatment duration up to 3.8 months longer. More safe and effective options are needed, including for the elderly.

Tuberculosis-Associated Hospitalizations and Deaths after COVID-19 Shelter-In-Place, San Francisco, California, USA.

A mandated shelter-in-place and other restrictions associated with the coronavirus disease pandemic precipitated a decline in tuberculosis diagnoses in San Francisco, California, USA. Several months into the pandemic, severe illness resulting in hospitalization or death increased compared with prepandemic levels, warranting heightened vigilance for tuberculosis in at-risk populations.

El análisis de situación de salud poblacional en América Latina y el Caribe, entre 2000 y 2017. Reflexiones y desafíos / Health Situation Analysis of the Population in Latin America and the Caribbean, from 2000 to 2017. Reflections and challenges / Análises da situação da saúde populacional na América Latina e o Caribe, entre 2000 e 2017. Reflexões e desafios

Resumen Objetivo: Identificar la evolución teórico-metodológica del análisis de situación de salud (asis) en América Latina y el Caribe, y analizar los desafíos en su implementación. Metodología: Revisión narrativa a partir del estudio de trabajos de investigación, artículos de reflexión y manuales publicados en las bases de datos ebsco, PubMed, Redalyc, Scielo y Lilacs, entre los años 2000 y 2017, relacionados con el análisis de la situación de salud a nivel poblacional. Se analizaron los 67 documentos seleccionados y se hizo comparación de contenidos de los asis realizados en la región. Resultados: Se encontró que las guías para orientar la implementación de los asis reproducen un modelo de diagnóstico de salud epidemiológico/administrativo, aunque algunas suscriben, como ejes del análisis, la perspectiva de género, de determinantes sociales, la intersectorialidad y la participación social; esto se refleja en el 90 % de los 19 informes gubernamentales recuperados. El 80 % de las 10 investigaciones originales recuperadas se identifican como estudios descriptivos, observacionales y transversales, con escasa actuación de los equipos de salud del primer nivel y mínima participación de las poblaciones y los representantes de otros sectores vinculados con la salud. Las principales fuentes utilizadas son estadísticas demográficas y epidemiológicas oficiales, y una mínima proporción de los asis concluye en la generación de propuestas de actuación. Conclusiones: La implementación de los asis enfrenta, como desafíos, trascender la noción patológica y sectorial de la salud; incorporar indicadores de salud positiva, así como otros de inequidad en salud, que permitan una valoración amplia de la situación de salud poblacional, sus determinantes sociales y los gradientes de desigualdad en la expresión de la enfermedad y del acceso a servicios para su atención; articular, en su práctica, el método epidemiológico, con técnicas etnográficas y de participación social, para apoyar el análisis integral e interseccional de la salud; y capacitar a los equipos de salud, especialmente de primer nivel, para el desarrollo efectivo de estos estudios, con fines de monitoreo y comprensión de las tendencias y los diferenciales en la salud/enfermedad de los grupos poblacionales.

Abstract Objective: To identify the methodological-theoretical evolution of the Health Situation Analysis (HAS) in Latin America and the Caribbean, and analyze the challenges to implement it. Methodology: A narrative review based on research studies, reflective articles and manuals pu blished in databases as EBSCO, PubMed, Redalyc, Scielo and Lilacs, from 2000 to 2017, related to the analysis of the population's health situation. 67 documents were cho sen and analyzed and contents were compared with HAS conducted in the region. Results: The study found that the guidelines to direct the implementation of HAS reproduced an epidemiological/administrative health diagnosis model, many of which subscribe gender perspective, social deter minants, intersectionality and social participation as their axis of analysis, which is demonstrated in 90 % of the 19 government reports recovered. 80 % of the 10 original re search studies recovered were identified as descriptive, observational and cross-sectional studies, with little par ticipation from first level Healthcare teams and minimum participation from populations and representatives of other sectors linked to health. The main sources used were offi cial demographic and epidemiological statistics, and a very small part of the HSA result in producing action proposals. Conclusions: Implementing HSA represents challenges like transcending the pathological and sectorial notion of health, incorporating positive health indicators, as well as other health inequality indicators that allow a broader as sessment of the population's health situation, their social determinants and the gradients of inequality expressed in diseases and access to health care services. Epidemiological methods with ethnographic and social participation techni ques should be used in practice to support a comprehen sive intersectional health analysis; and healthcare teams, particularly first level teams, should be trained to conduct effective studies to monitor and understand the trends and differentials in the health/diseases of population groups.

Resumo Objetivo: Identificar a evolução teórico-metodológica da análise de situação da saúde (asis) na América Latina e o Ca ribe, e analisar os desafios na sua implementação. Metodo logia: Revisão narrativa partindo do estudo de trabalhos de investigação, artigos de reflexão e manuais publicados nas bases de dados ebsco, PubMed, Redalyc, Scielo e Lilacs, entre os anos 2000 e 2017, enlaçados com a análise da rea lidade da saúde no nível populacional. Se analisaram os 67 documentos escolhidos fazendo um versus de conteúdos dos ASIS compendiados na região. Resultados: Se encontrou que as instruções para indicar a implementação dos asis re produz um modelo de diagnóstico de saúde epidemiológico/ administrativo, ainda que algumas assinalam, como eixos da análise, a visão de género, de determinantes sociais, a pluris setorialidade e o envolvimento social; isto se reflete num 90 % dos 19 informes governamentais recuperados. Um 80 % das 10 investigações originais recuperadas se identificam como estudos descritivos, observacionais e na forma do viés, com escassa atuação dos corpos de saúde do primeiro nível e o mínimo envolvimento das populações e os líderes das outras áreas vinculadas com a saúde. As principais fontes uti lizadas são estatísticas demográficas e epidemiológicas ofi ciais, e uma mínima proporção dos asis concluem na geração de propostas de atuação. Conclusões: A implementação dos asis enfrenta, como desafios, transcender a noção patológica e setorial da saúde; incorporar indicadores de saúde positiva, assim como outros de inequidade em saúde, que permitam uma valoração amplia da situação de saúde populacional, os seus determinantes sociais e os ingredientes de desigualdade na expressão da doença e do acesso aos serviços para a sua atenção; articular, na sua prática, o método epidemiológico, com técnicas etnográficas e de participação social, para su portar a análise integral e interseccional da saúde; e capacitar aos times da saúde, especialmente aqueles de primeiro nível, para o desenvolvimento efetivo destes estudos, com fins de tamisado e compreensão dessas tendências e os diferenciais na saúde/doença dos grupos populacionais.

Chemical-physical characterization of isolated plant cuticles subjected to low-dose γ-irradiation.

Isolated tomato fruit cuticles were subjected to low dose (80Gy) γ-irradiation, as a potential methodology to prevent harvested fruit and vegetables spoilage. Both irradiated and non-irradiated samples have been morphologically and chemically characterized by scanning electron (SEM), atomic force (AFM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopies. Additionally, electrochemical measurements comprising membrane potential and diffusive permeability were carried out to detect modifications in transport properties of the cuticle as the fruit primary protective membrane. It has been found that low dose γ-irradiation causes some textural changes on the surface but no significant chemical modification. Texture modification is found to be due to a partial removal of outermost (epicuticular) waxes which is accompanied by mild changes of electrochemical parameters such as the membrane fixed charge, cation transport number and salt permeability. The modification of such parameters indicates a slight reduction of the barrier properties of the cuticle upon low dose γ-irradiation.

Agregación plaquetaria en mujeres normomenstruales / plaquetaria Agregacio'n in normomenstruales women

Cada mes durante toda la fase fértil de su vida, la mujer produce un óvulo maduro. Cuando ella nace, dichos óvulos ya están presentes en sus ovarios, pero aùn en estado inmaduro. Bajo influencia de la hipófisis un óvulo maduro es liberado en el período medio de 28 días; en el primer dìa del ciclo menstrual los òvulos van madurando lentamente y los ovarios producen cantidades mínimas de estrógenos. Con el bajo nivel de estrógenos la hipófisis produce FSH, hormona que estimula los folículos, el resultado directo es el aumento de la producción de estrógeno, los cuales van a influir sobre la mucosa del útero y sobre el endometrio, preparándole para recibir al óvulo fecundado. Entonces la hipófisis empieza a liberar otra hormona...