How to break free: HIV-1 escapes from innovative therapeutic approaches

With nearly 38 million of people worldwide living with HIV-1 and no definitive cure available after almost 40 years of research, AIDS is still a major global public health issue. Modern antiretroviral therapies can achieve viral replication suppression to undetectable levels, thus allowing an almost normal life to HIV-1–infected individuals. However, the virus cannot be fully eradicated. This may lead over time to the accumulation of mutations in the viral genome and, eventually, to the emergence of drug-resistant viruses, which may affect the efficacy of the therapy and the patient’s quality of life. To overcome some of the limitations of the standard antiretroviral therapy, innovative therapeutic approaches such as “shock and kill” and immunotherapies, as well as technologies based on RNA interference and CRISPR-Cas9 genome editing are under investigation. Nevertheless, the virus may find a way to break free even from these novel strategies. In this review, we focus on the mechanisms that enable HIV-1 escape from the most advanced therapies and discuss some of the challenges to prevent this issue

The cascade of care of HIV after one year of follow-up in a cohort of HIV-positive adult patients in three health settings of Morrumbene in rural Mozambique

Objective: To assess the state of the retention in care of HIV patients in three health settings in Morrumbene, a rural district of Inhambane Province, Mozambique. We evaluated potential factors associated with early loss to follow-up (LTFU), retention in care and ART adherence during the first year of follow-up. Material and methods: Retrospective, cross-sectional, observational study. We collected data on patients diagnosed with HIV infection in 2017 in two permanent clinics and one mobile clinic. Demographic, clinical, immunological and therapeutic data were retrieved up to December 31st, 2018. Data on follow-up were collected at 6 and 12 months for medical visits and for ART adherence and analysed for factors associated with LTFU, retention in care and adherence to ART by Stata Version 14 and univariate and stepwise multiple unconditional logistic regression models. Results: In 2017, 960 patients were diagnosed with HIV infection. At 6-month follow-up, 49% attended the medical visit and 157 (25%) adhered to ART. After one year, 34% of patients were available for follow-up, and only 72 patients adhered to ART. In multivariate analysis, factors associated with early LTFU were male sex (p = 0.036) and immediate prescription of ART (p = 0.064). Older age (p < 0.001) and being followed in the mobile clinic (p = 0.001) favoured retention in care. Advanced WHO status (p = 0.005) and being pregnant or breastfeeding showed a negative correlation with adherence to treatment (p = 0.068). Conclusions: Only one-third of patients were available for follow-up after one year, and only 13% adhered to ART. Young individuals, men and pregnant/breastfeeding women seem to be particularly at risk for LTFU and non-adherence to treatment

A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Additional Benefit of a Multistrain Synbiotic (Prodefen®) in the Clinical Management of Acute Viral Diarrhea in Children

This randomized, open-label study evaluated the additional benefits of the synbiotic Prodefen® in the clinical management of acute diarrhea of suspected viral origin in children between 6 months and 12 years of age. Study outcomes included the duration of diarrhea, the recovery from diarrhea, and the tolerability and acceptance of the treatment. The proportion of patients without diarrhea over the study period was greater in the synbiotic group than in the control group at all study time points, showing a statistically significant difference on the fifth day (95% vs 79%, p < 0.001). The duration of diarrhea (median and interquartile range) was reduced by 1 day in the synbiotic-treated patients (3 [2-5] vs 4 [3-5], p = 0.377). The tolerability of the treatment regimen, as evaluated by the parents, was significantly better in those receiving the synbiotic than in the control group. Overall, 96% of the parents of children receiving the synbiotic reported being satisfied to very satisfied with the treatment regimen. The results of this study indicate that the addition of the synbiotic Prodefen® is a well-tolerated and well-accepted approach that provides an additional benefit to the standard supportive therapy in the management of acute viral diarrhea in children

Low-Level Expression of MicroRNAs let-7d and miR-205 Are Prognostic Markers of Head and Neck Squamous Cell Carcinoma

Small noncoding microRNAs (miRNAs) have been shown to be abnormally expressed in every tumor type examined. The importance of miRNAs as potential cancer prognostic indicators is underscored by their involvement in the regulation of basic cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, miRNA expression profiles of head and neck squamous cell carcinoma (HNSCC) tumor and adjacent normal tissue were examined by microarray analysis and validated by quantitative TaqMan real-time polymerase chain reaction. Using TaqMan real-time polymerase chain reaction we measured the quantitative associations between a subset of miRNAs identified on microarrays in primary tumors at diagnosis and cancer survival in a cohort of 104 HNSCC patients undergoing treatment with curative intent. The majority of miRNAs exhibiting altered expression in primary human HNSCC tumors (including miR-1, miR-133a, miR-205, and let-7d) show lower expression levels relative to normal adjacent tissue. In contrast, hsa-miR-21 is frequently overexpressed in human HNSCC tumors. Using univariate and multivariable statistical models we show that low levels of hsa-miR205 are significantly associated with loco-regional recurrence independent of disease severity at diagnosis and treatment. In addition, combined low levels of hsa-miR-205 and hsa-let-7d expression in HNSCC tumors are significantly associated with poor head and neck cancer survival Our results show that miRNA expression levels can be used as prognostic markers of head and neck cancer

Revolution: Museo de las estrellas un paseo por la fama : Hollywood

Convocatoria proyectos de innovación de Extremadura 2020/2021Se describe un proyecto llevado a cabo entre 13 centros educativos extremeños que consistió en desarrollar cinco unidades de trabajo gamificadas, cinco historias detectivescas con misterios por resolver, donde se ponían a prueba las habilidades de lógica, la capacidad de observación, de concentración y de atención de los alumnos. Los objetivos principales de la propuesta fueron: promover la puesta en práctica de proyectos intercentros; impulsar pedagogías activas; desarrollar la competencia digital a través del uso de las pedagogías emergentes lo que ha permitido llevar a cabo una enseñanza presencial, híbrida y virtual y atender a la diversidadExtremaduraES