Abstract Differentiation of mesenchymal stem cells (MSCs) derived from two different sources of fetal tissues such as umbilical cord blood (UCB) and tissue (UCT) into skeletal muscle have remained underexplored. Here, we present a comparative analysis of UCB and UCT MSCs, in terms of surface markers, proliferation and senescence marker expression. We find that CD45 − CD34 − MSCs obtained from UCT and UCB of term births display differences in the combinatorial expression of key MSC markers CD105 and CD90. Importantly, UCT MSCs display greater yield, higher purity, shorter culture time, and lower rates of senescence in culture compared to UCB MSCs. Using a robust myogenic differentiation protocol, we show that UCT MSCs differentiate more robustly into muscle than UCB MSCs by transcriptomic sequencing and specific myogenic markers. Functional assays reveal that CD90, and not CD105 expression promotes myogenic differentiation in MSCs and could explain the enhanced myogenic potential of UCT MSCs. These results suggest that in comparison to large volumes of UCB that are routinely used to obtain MSCs and with limited success, UCT is a more reliable, robust, and convenient source of MSCs to derive cells of the myogenic lineage for both therapeutic purposes and increasing our understanding of developmental processes.
Summary Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24–72, 72–120, and 120–168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post-treatment in the antibiotic (1.0± 5.1) and placebo (1.4± 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.
All multidrug-resistant tuberculosis (MDR-TB) patients who had completed 6 months of treatment under the Revised National Tuberculosis Control Programme (RNTCP) in Uttar Pradesh, the largest state in northern India.To determine the proportion of MDR-TB patients with regular follow-up examinations, and underlying provider and patient perspectives of follow-up services.A retrospective cohort study was undertaken involving record reviews of 64 eligible MDR-TB patients registered during April-June 2013 in 11 districts of the state. Patients and programme personnel from the selected districts were interviewed using a semi-structured questionnaire.A total of 34 (53.1%) patients underwent follow-up sputum culture at month 3, 43 (67.2%) at month 4, 36 (56.3%) at month 5 and 37 (57.8%) at month 6. Themes associated with irregular follow-up that emerged from the interviews were multiple visits, long travel distances, shortages of equipment at the facility and lack of knowledge among patients regarding the follow-up schedule.The majority of the MDR-TB patients had irregular follow-up visits. Provider-related factors outweigh patient-related factors on the poor follow-up examinations. The programme should focus on the decentralisation of follow-up services and ensure logistics and patient-centred counselling to improve the regularisation of follow up.Contexte : Tous les patients atteints de tuberculose multirésistante (TB-MDR) qui avaient achevé 6 mois de traitement dans le cadre du Programme National Révisé de Lutte contre la Tuberculose (RNTCP) dans l’Uttar Pradesh, le plus grand état dans le nord de l’Inde.Objectif : Déterminer la proportion de patients TB-MDR bénéficiant d’examens de suivi régulier et la vision des prestataires et des patients sur ces services de suivi.Méthodes : Une étude rétrospective de cohorte a été réalisée grâce à la revue des dossiers de 64 patients TB-MDR éligibles enregistrés entre avril et juin 2013 dans 11 districts de l’état. Les patients et le personnel du RNTCP des districts sélectionnés ont également été interviewés grâce à un questionnaire semi-structuré.Résultats : Au total, 34 (53,1%) patients ont bénéficié d’examens de culture de crachats au 3e mois, 43 (67,2%) au 4e mois, 36 (56,3%) au 5e mois et 37 (57,8%) au 6e mois. Les principaux facteurs associés à un suivi irrégulier émanant des entretiens étaient le nombre élevé de consultations, la distance à parcourir, les ruptures de stock dans les structures et le manque de connaissances des patients vis-à-vis du programme de suivi.Conclusion : La majorité des patients TB-MDR ont eu un suivi irrégulier. Les facteurs liés aux prestataires dépassent ceux liés aux patients en matière d’examens de suivi médiocres. Le RNTCP devrait se concentrer sur la décentralisation des services de suivi, assurer la logistique et le conseil centré sur le patient afin d’accroitre la régularité du suivi.Marco de referencia: Todos los pacientes con diagnóstico de tuberculosis multidrogorresistente (TB-MDR) después de haber completado los 6 meses de tratamiento en el contexto del Programa Nacional de Control de la Tuberculosis (RNTCP) en Uttar Pradesh, la provincia más grande del norte de la India.Objetivo: Determinar la proporción de pacientes con TB-MDR en quienes se practicaron exámenes periódicos de seguimiento y conocer las opiniones de los profesionales y de los pacientes sobre los servicios de seguimiento.Métodos: Se llevó a cabo un estudio de cohortes retrospectivo a partir del examen de las historias clínicas de 64 pacientes con diagnóstico de TB-MDR, que cumplían con los requisitos de inclusión, registrados entre abril y junio del 2013 en 11 distritos del estado. Se realizaron además entrevistas a los pacientes y al personal del RNTCP de algunos distritos mediante un cuestionario semi-estructurado.Resultados: En 34 pacientes se practicó el seguimiento del cultivo de esputo al tercer mes (53,1%), en 43 casos al cuarto mes (67,2%), en 36 al quinto mes (56,3%) y en 37 pacientes al sexto mes de tratamiento (57,8%). Los principales factores asociados con la irregularidad del seguimiento que revelaron las entrevistas fueron la multiplicidad de las citas, la larga distancia de los desplazamientos, la carencia de insumos en los centros y el desconocimiento del calendario del seguimiento por parte de los pacientes.Conclusión: El seguimiento de la mayoría de los pacientes con diagnóstico de TB-MDR fue irregular. En las causas de la deficiencia del seguimiento predominaron los factores dependientes de los profesionales en comparación con los factores propios a los pacientes. El RNTCP debe considerar seriamente la descentralización de los servicios de seguimiento, suministrarlos materiales necesarios y proveer una orientación centrada en los pacientes con el objeto de mejorar la regularidad de los seguimientos.
A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.
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