Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection.

Introduction: Herpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection. Moreover, neonatal MRV infection results in development of autoimmunity in adult mice, long after resolution of acute infection. This suggests that MRV induces durable immune dysregulation. Methods: In the current studies, we utilized single-cell RNA sequencing (scRNAseq) to study the tropism of MRV in the thymus and determine cellular processes in the thymus that were disrupted by neonatal MRV infection. We then utilized tropism data to establish a cell culture system. Results: Herein, we describe how MRV alters the thymic transcriptome during acute neonatal infection. We found that MRV infection resulted in major shifts in inflammatory, differentiation and cell cycle pathways in the infected thymus. We also observed shifts in the relative number of specific cell populations. Moreover, utilizing expression of late viral transcripts as a proxy of viral replication, we identified the cellular tropism of MRV in the thymus. This approach demonstrated that double negative, double positive, and CD4 single positive thymocytes, as well as medullary thymic epithelial cells were infected by MRV in vivo. Finally, by applying pseudotime analysis to viral transcripts, which we refer to as "pseudokinetics," we identified viral gene transcription patterns associated with specific cell types and infection status. We utilized this information to establish the first cell culture systems susceptible to MRV infection in vitro. Conclusion: Our research provides the first complete picture of roseolovirus tropism in the thymus after neonatal infection. Additionally, we identified major transcriptomic alterations in cell populations in the thymus during acute neonatal MRV infection. These studies offer important insight into the early events that occur after neonatal MRV infection that disrupt central tolerance and promote autoimmune disease.

Side Effects of COVID-19 Vaccines in Pregnant and Lactating Mexican Women and Breastfed Infants: A Survey-Based Study.

COVID-19 vaccines' safety has been extensively studied; however, further analysis is required in pregnant women, nursing mothers, and breastfed infants. Our aim was to compare the extension and severity of self-reported COVID-19 vaccine side effects in pregnant and breastfeeding women, and breastfed infants. In this cross-sectional study, COVID-19-vaccinated subjects were enrolled using an online survey in Mexico. Women were classified by pregnancy and breastfeeding status at the time of vaccination (n = 3167). After the first or only dose, there was a trend toward fewer systemic effects in pregnant women (p = 0.06). BNT162b2 (Pfizer-BioNTech) had a higher frequency of local symptoms in pregnancy. Lactating women experienced fewer local symptoms after the first or single dose (p = 0.04) and the opposite occurred after the second dose (p = 0.001). ChAdOx1 (AstraZeneca) increased the chances of developing both local and systemic symptoms after the first dose but decreased them after the second dose. The severity was similar across groups, although the result of lack of association in pregnancy requires studies with a larger sample size. Irritability was the most reported symptom in breastfed infants. This study contributes to the knowledge about the side effects in pregnant and lactating women, and breastfed babies.

Extension and Severity of Self-Reported Side Effects of Seven COVID-19 Vaccines in Mexican Population.

A few studies examined the comparative side effects of Coronavirus Disease-19 (COVID-19) vaccines. We compared the extension and severity of self-reported side effects of seven COVID-19 vaccines [BNT162b2 (Pfizer-BioNTech), ChAdOx1 (AstraZeneca), mRNA-1273 (Moderna), CoronaVac (Sinovac Life Sciences), Gam-COVID-Vac (Gamaleya's Sputnik V), Ad5-nCoV (CanSinoBIO), and Ad26.CoV2.S (Johnson & Johnson/Janssen)] in the Mexican population. We also evaluated the association of type of vaccine, sex, age, comorbidity, and history of allergies to the extent and severity of side effects. This was a cross-sectional study carried out online between August 12 and September 3, 2021 in Mexico. The first inclusion criterion was to receive a COVID-19 vaccine and the second, being at least 18 years old. The survey link was distributed via multiple social media platforms. We questioned about the type of vaccine and symptoms based on short-term side effects reported in the literature. Side effect extension was classified as local, systemic, or both. We asked about the need to take medicine, stop activities/miss work, or seek medical attention. Then, a severity index was constructed based on responses. Descriptive and stepwise multivariate logistic ordinal regression analyses were used to calculate odds ratio (OR) and 95% CI for each outcome adjusted by potential confounders. The mean age was 38.9 ± 11.0 years (n = 4,024). Prevalence of at least one side effect varied between vaccines and by a number of doses. At dose 1, ChAdOx1 was the vaccine with the highest rate of at least one side effect (85%) followed by Gam-COVID-Vac (80%). Both were associated to greater extension (adjusted OR 2.53, 95% CI 2.16, 2.96 and adjusted OR 2.41, 95% CI 1.76, 3.29, respectively) and severity of side effects (adjusted OR 4.32, 95% CI 3.73, 5.00 and adjusted OR 3.00, 95% CI 2.28, 3.94, respectively). Young age (<50 years), female sex, comorbidity, and history of allergies were associated with greater extension and severity, independent of the type of vaccine and potential confounders. At dose 2, mRNA-1273 was the vaccine with the highest rate of side effects (88%) and the only vaccine associated to greater extension (adjusted OR 2.88, 95% CI 1.59, 5.21) and severity of symptoms (adjusted OR 3.14, 95% CI 1.82, 5.43). Continuous studies are necessary to acknowledge more post-vaccine symptoms in different populations.

Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases.

Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.

Adult-plant resistance to Septoria tritici blotch in hexaploid spring wheat.

KEY MESSAGE: New QTL for Septoria tritici blotch detected in hexapoid spring wheat under field conditions across diverse environments. Septoria tritici blotch caused by the ascomycete fungus Zymoseptoria tritici presents a serious and consistent challenge to global wheat production. In particular the augmented use of soil management practices that leave large amounts of wheat stubble on the soil surface and global warming increases the chance of Septoria tritici blotch epidemics to emerge more frequently including in developing countries. Two recombinant inbred line populations developed from a cross between the susceptible Moroccan spring bread wheat variety 'NASMA' and the CIMMYT resistant lines, 'IAS20*5/H567.71' and 'RPB709.71/COC' were used to study the genetics and map adult-plant resistance to Septoria tritici blotch under field conditions in different environments. Resistance to Septoria tritici blotch in both populations was quantitative and overall, five across environment consistent resistance loci on chromosomes 1BS, 3AL, 5AL and 7AS were detected in the two populations. The QTL on chromosome 1BS and 7AS are likely to be allelic with the known Septoria tritici blotch genes Stb3 and Stb11. All identified QTL were additive and explained between 4 and 27 % of the phenotypic variation. Epistatic interaction was not observed. Low cost KASP assays were developed as flanking markers for all five QTL that will facilitate molecular breeding. Our study represents the first mapping effort under field conditions utilizing two spring bread wheat resistant sources evaluated over multiple environments.

Las enfermedades pulmonares intersticiales difusas en el ámbito laboral / Diffuse interstitial lung diseasesin the workplace

La enfermedad pulmonar intersticial difusa (EPID) se refiere a un grupo heterogéneo de condiciones pulmonares caracterizadas clínicamente por disnea y empeoramiento de la función pulmonar y radiológicamente por una infiltración intersticial evidente que afecta predominantemente las bases pulmonares. No existe una clasificación estándar o internacional sobre la misma, pero muchos autores tienden a clasificarla en uno de los dos siguientes grupos: los de causa conocida, secundarios a enfermedades de causa desconocida y los idiopáticos (que son 7 identidades clínicas claramente descritas). Como se ha visto, una de las causas dilucidadas de esta condición se asocia directamente con materiales irritantes como agentes y sustancias químicas tales como: el asbesto, silicón, y carbón utilizadas comúnmente en distintos ámbitos laborales, por lo que aquellas personas que se vieran continuamente expuestas a estos tienen un riesgo aumentado de desarrollar dicha patología. Las EPID son alteraciones que, a pesar de medidas, precauciones y regulaciones impuestas en distintas organizaciones de la promoción de la salud continúan siendo una de las principales enfermedades adquiridas en ámbitos laborales y además es de suma importancia clínica dado que estos pacientes pueden tener un rápido deterioro de función pulmonar. Este factor, sumado al hecho que su fisiopatología, incidencia e historia natural no han logrado ser suficientemente esclarecidos, constituyen la base que soporta la revisión que se ha propuesto realizar. Finalmente, es importante destacar que puede existir un largo tiempo entre la exposición a los agentes causales de la enfermedad y el inicio de las manifestaciones clínicas, por lo que se han documentado pacientes con estos diagnósticos aún años o hasta décadas después de que ocurrió la exposición, por lo que una adecuada regulación (por ejemplo, vacaciones profilácticas) y prevención a la misma podría evitar las consecuencias...

Diffuse interstitial lung disease (ILD) refers to a heterogeneous group of lung conditions characterized clinically by dyspnea, worsening of lung function and radiologically by an evident interstitial infiltration predominantly affecting the lung bases. There is no standard classification on it, but many authors tend to separate it into one of two groups: those with known cause, secondary to diseases of unknown cause and those idiopathic (with 7 clinical identities described). It is known that the condition is also directly associated with irritating materials, agents and chemicals such as asbestos, silicon, and carbon commonly used in industrial fields, so that people continouslly working with these have an increased risk of developing this disease. Despite measures, precautions and regulations imposed by various organizations of health promotion, ILD remains one of the major diseases acquired in work environments and it is of great clinical importance since these patients may have a rapid impaired lung function. This factor, besides the fact that its pathophysiology , incidence and natural history have failed to be sufficiently understood , constitute the base supporting the following review. Finally, we must know that there may be a long time between exposure to the causative agents of disease and the onset of clinical manifestations so that patients could present the diagnoses years or even decades after exposure. Hence derives the importance of proper regulations (eg, prophylactic holidays) and prevention to avoid the possible consequences...