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IntroductionGastric cancer is a major global health concern, being the final stage of a long-term process, primarily associated with Helicobacter pylori (H. pylori) infection. Early childhood acquisition of H. pylori with low spontaneous eradication rates underscores the need for preventive measures. Our previous pilot treatment study revealed high eradication rates, favourable tolerance profile and a decline in serum biomarkers indicative of gastric damage in asymptomatic school-aged children. The purpose of this study is to determine the potential benefit of a ‘screen-and-treat’ strategy targeting persistently infected, asymptomatic adolescents. Specific aims are to assess eradication efficacy, its clinical and molecular outcomes and potential clinical and microbiological side effects.Methods and analysisThe screening phase will involve testing 500–1000 asymptomatic adolescents aged 14–18 from three cities in Chile using the urea breath test (UBT) to identify 210 participants with persistent infection. They will proceed to a randomised, non-blinded, controlled trial, receiving either a sequential eradication scheme for H. pylori or no treatment. Follow-up will span up to 24 months post-treatment, involving UBT, gastroenterological assessments and blood and stool sample collections. Concurrently, a subset of 60 uninfected adolescents will undergo matched follow-up. Enzyme-linked immunosorbent assay (ELISA) commercial kits will evaluate gastric damage biomarkers in serum (pepsinogen I and II, gastrin-17, VCAM-1, CXCL13). Stool samples will be employed for Escherichia coli and Enterococcus spp—culture, assessing AMR via the disk diffusion method. H. pylori clarithromycin resistance will be determined by molecular method from stool samples. The gut microbiome will be characterised by amplifying and sequencing the 16S rRNA gene from stool samples, followed by bioinformatics analysis.Ethics and disseminationApproved by the Human Research Ethics Committee at the Faculty of Medicine, University of Chile (073–2022). Findings will be disseminated in peer-reviewed journals and scientific meetings to guide future practices.Trial registration numberNCT05926804.

Antecedentes: Moringa oleifera es una especie vegetal; sus hojas, flores y frutos son apreciados por la riqueza de nutrientes y potencial antioxidante. Objetivo: evaluar el efecto de una infusión de hojas secas de Moringa oleifera en los valores sanguíneos de hemoglobina y ferritina de un grupo de adolescentes. Materiales y métodos: estudio longitudinal de tipo antes y después durante seis meses en 31 adolescentes de la comunidad Cerro Guayabal, Ecuador. Para la suplementación nutricional, se utilizaron 4 gramos de polvo de hojas de Moringa oleifera en dos bolsas para infusión. Se cuantificaron macronutrientes y minerales en el polvo de hojas secas de Moringa oleifera y en su infusión. Los análisis de minerales se llevaron a cabo por triplicado, en un equipo de absorción atómica. Se midió la hemoglobina y la ferritina de los adolescentes al inicio y después de seis meses de la suplementación. Resultados: incremento significativo de 1,29 g en la cifra media de hemoglobina y disminución del número de adolescentes en riesgo de anemia, según los valores de ferritina y hemoglobina. Conclusiones: estos resultados sitúan a la especie vegetal Moringa oleifera como un alimento potencial y útil para combatir carencias nutricionales, en especial la anemia por deficiencia de hierro.

Y, sin embargo, todas son especulaciones. Los académicos han sorprendido y shockeado al público más de una vez. Cuando se esperaba una mujer, han premiado año tras año a un hombre; cuando se esperaba a un representante de algún grupo idiomático \"menor\", la elección ha caído en un representante políticamente \"incorrecto\", como fue el galardonado del año pasado: Harold Pinter: hombre, blanco, anglosajón. Pero los académicos se sacuden las críticas y reafirman el sentido de su \"misión\" y el espíritu del testamento de [Alfred Nobel]: premiar la calidad literaria. Mucho más no suele saberse, los miembros de la Academia Sueca parecen ser insobornables: callan de manera consecuente ante la prensa. Casi no dan entrevistas y, en las pocas que dan, nunca revelan más del proceso que lo que ya se sabe. Jamás hacen comentarios sobre nombres concretos y reafirman, obstinadamente, el criterio de calidad literaria como punto central de la decisión, tomando distancia de la opinión de los \"expertos\" de distinta índole, que ya exigen una mujer, un autor del Tercer Mundo, un representante de una minoría idiomática, etcétera. Normalmente suelen llegar a la Academia unas 350 propuestas por año. Muchas mencionan al mismo candidato, por lo cual la cantidad de nombres suele reducirse a unos 200. Cuando la lista está aprobada, a fines de febrero, pasa a ser revisada por el Comité Nobel, de enorme influencia en el proceso de selección. El Comité del Nobel es un grupo pequeño, selecto y poderoso: cuatro o cinco miembros de la Academia, elegidos por un periodo de tres años, con rotación. Tienen la tarea de componer la nómina de candidatos, realizar investigaciones, familiarizarse con los autores que tengan reales posibilidades de obtener el premio y, finalmente, son los que presentan las recomendaciones a la totalidad de los miembros de la Academia. Es el comité del Nobel el que realiza la eliminación más severa de nombres: por no alcanzar la calidad exigida para recibir el premio o por responder las nominaciones a motivos no literarios (políticos, étnicos, religiosos, de género, etcétera). Cuando esta primera eliminación está lista, se inicia el proceso de selección más profundo. Para su ayuda cuentan los miembros del Comité Nobel con grupos de asesores: expertos que redactan recensiones, comentarios e inclusive pueden realizar traducciones de prueba en el caso de que el idioma original no sea accesible para los académicos y no existan traducciones ya publicadas. El resultado del trabajo del comité suele presentarse en la Academia en la sesión de abril y para entonces la lista está compuesta de unos 15 ó 20 nombres. Esta lista es sometida a discusión y finalmente se adopta como oficial, con eventuales modificaciones, en el mes de mayo. Nuevamente es el comité quien tiene la tarea de seguir profundizando la obra de los \"elegidos\" (muchos de ellos reaparecen año tras año, lo cual simplifica la tarea, puesto que sólo se revisa la aparición eventual de nuevas obras) y decidir finalmente cuáles cinco autores o autoras integrarán la lista definitiva de candidatos a presentarse en la sesión de junio, la llamada \"lista corta\" de donde saldrá el flamante Premio Nobel.

Collective Kitchens are groups of women that prepare food together, distribute it to be frozen and used later. Collective Kitchens have the potential to be the starting point for building communities. Despite the strength of the Collective Kitchens phenomena, little opportunity has been provided for participants in Collective Kitchens to share their experiences. The knowledge and experiences of participants needs to be integrated with the literature to increase our understanding about Collective Kitchens. This study provided a group of Latin American women with the opportunity to share their experiences. The data, collected from interviews with collaborators and analysis of documents, was enriched by the application of an ecological framework. Data analysis included: level one analysis of collaborators' emergent thematic areas, themes and sub themes and level two analysis of emergent formats of Collective Kitchens. Formats were integrated with knowledge paradigms from education literature. Emergent issues were discussed and recommendations made.

The use of protease inhibitors in human immunodeficiency virus type 1 (HIV-1) treatment is limited by adverse effects, including metabolic complications. To address these challenges, efforts are underway in the pursuit of more potent and less toxic HIV-1 protease inhibitors. Repurposing existing drugs offers a promising avenue to expedite the drug discovery process, saving both time and costs compared to conventional de novo drug development. This study screened FDA-approved and investigational drugs in the DrugBank database for their potential as HIV-1 protease inhibitors. Molecular docking studies and cell-based assays, including anti-HIV-1 in vitro assays and XTT cell viability tests, were conducted to evaluate their efficacy. The study findings revealed that CBR003PS, an antibiotic currently in clinical use, and CBR013PS, an investigational drug for treating endometriosis and uterine fibroids, exhibited significant binding affinity to the HIV-1 protease with high stability. Their EC50 values, measured at 100% cell viability, were 9.4 nM and 36.6 nM, respectively. Furthermore, cell-based assays demonstrated that these two compounds showed promising results, with therapeutic indexes higher than 32. In summary, based on their favorable therapeutic indexes, CBR003PS and CBR013PS show potential for repurposing as HIV-1 protease inhibitors.

The medial habenula (mHb) is an understudied small brain nucleus linking forebrain and midbrain structures controlling anxiety and fear behaviors. The mechanisms that maintain the structural and functional integrity of mHb neurons and their synapses remain unknown. Using spatiotemporally controlled Cre-mediated recombination in adult mice, we found that the glial cell–derived neurotrophic factor receptor alpha 1 (GFRα1) is required in adult mHb neurons for synaptic stability and function. mHb neurons express some of the highest levels of GFRα1 in the mouse brain, and acute ablation of GFRα1 results in loss of septohabenular and habenulointerpeduncular glutamatergic synapses, with the remaining synapses displaying reduced numbers of presynaptic vesicles. Chemo- and optogenetic studies in mice lacking GFRα1 revealed impaired circuit connectivity, reduced AMPA receptor postsynaptic currents, and abnormally low rectification index (R.I.) of AMPARs, suggesting reduced Ca 2+ permeability. Further biochemical and proximity ligation assay (PLA) studies defined the presence of GluA1/GluA2 (Ca 2+ impermeable) as well as GluA1/GluA4 (Ca 2+ permeable) AMPAR complexes in mHb neurons, as well as clear differences in the levels and association of AMPAR subunits with mHb neurons lacking GFRα1. Finally, acute loss of GFRα1 in adult mHb neurons reduced anxiety-like behavior and potentiated context-based fear responses, phenocopying the effects of lesions to septal projections to the mHb. These results uncover an unexpected function for GFRα1 in the maintenance and function of adult glutamatergic synapses and reveal a potential new mechanism for regulating synaptic plasticity in the septohabenulointerpeduncular pathway and attuning of anxiety and fear behaviors.

Translational science has been introduced as the nexus among the scientific and the clinical field, which allows researchers to provide and demonstrate that the evidence-based research can connect the gaps present between basic and clinical levels. This type of research has played a major role in the field of cardiovascular diseases, where the main objective has been to identify and transfer potential treatments identified at preclinical stages into clinical practice. This transfer has been enhanced by the intromission of digital health solutions into both basic research and clinical scenarios. This review aimed to identify and summarize the most important translational advances in the last years in the cardiovascular field together with the potential challenges that still remain in basic research, clinical scenarios, and regulatory agencies.

By-products of Capsicum chinense Jacq., var Jaguar could be a source of bioactive compounds. Therefore, we evaluated the anti-inflammatory effect, antioxidant activity, and their relationship with the polyphenol content of extracts of habanero pepper by-products obtained from plants grown on black or red soils of Yucatán, Mexico. Moreover, the impact of the type of extraction on their activities was evaluated. The dry by-product extracts were obtained by maceration (ME), Soxhlet (SOX), and supercritical fluid extraction (SFE). Afterward, the in vivo anti-inflammatory effect (TPA-induced ear inflammation) and the in vitro antioxidant activity (ABTS) were evaluated. Finally, the polyphenolic content was quantified by Ultra-Performance Liquid Chromatography (UPLC), and its correlation with both bioactivities was analyzed. The results showed that the SFE extract of stems of plants grown on red soil yielded the highest anti-inflammatory effect (66.1 ± 3.1%), while the extracts obtained by ME and SOX had the highest antioxidant activity (2.80 ± 0.0052 mM Trolox equivalent) and polyphenol content (3280 ± 15.59 mg·100 g−1 dry basis), respectively. A negative correlation between the anti-inflammatory effect, the antioxidant activity, and the polyphenolic content was found. Overall, the present study proposed C. chinense by-products as a valuable source of compounds with anti-inflammatory effect and antioxidant activity.

Background The androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown. Aim This study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma. Methods Forty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis. Results Most of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p  = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p  = 0.004). Conclusion Circulating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD.