AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product for HD

Maternal mortality among refugees and in zones of conflict

Every day, more than 500 women and girls in countries with emergency settings die during pregnancy and childbirth, due to the absence of skilled birth attendants or emergency obstetric procedures and unsafe abortion. Three chronologically ordered delays contribute to the increased maternal morbidity and mortality in conflict zones: (1) delay in recognizing the need to seek obstetrical care, (2) delay in reaching the medical facility, and (3) delay in diagnosing and receiving the proper care. When it comes to the causes of maternal mortality in states of conflict, the trends seem to be concordant with those seen in global estimations. Most common causes are preventable complications that could be avoided if proper care is given in the right time, including obstetrical hemorrhage, hypertensive disorders of pregnancy, and sepsis. Despite the apparent effects of war on interruption of access to reproductive healthcare, its direct consequences on pregnancy outcomes are less clear. Low birth weight, stillbirth, and prematurity were found to be consequences of conflict exposure. According to the World Health Organization, there are multiple evidence-based interventions that have been shown to reduce maternal morbidity and mortality, for which there is moderate-to high-quality evidence. © The Author(s)

The Use of Bovine Pericardial Buttress on Linear Stapler Fails to Reduce Pancreatic Fistula Incidence in a Porcine Pancreatic Transection Model

We investigate the effectiveness of buttressing the surgical stapler to reduce postoperative pancreatic fistulae in a porcine model. As a pilot study, pigs (n = 6) underwent laparoscopic distal pancreatectomy using a standard stapler. Daily drain output and lipase were measured postoperative day 5 and 14. In a second study, pancreatic transection was performed to occlude the proximal and distal duct at the pancreatic neck using a standard stapler (n = 6), or stapler with bovine pericardial strip buttress (n = 6). Results. In pilot study, 3/6 animals had drain lipase greater than 3x serum on day 14. In the second series, drain volumes were not significantly different between buttressed and control groups on day 5 (55.3 ± 31.6 and 29.3 ± 14.2 cc, resp.), nor on day 14 (9.5 ± 4.2 cc and 2.5 ± 0.8 cc, resp., P = 0.13). Drain lipase was not statistically significant on day 5 (3,166 ± 1,433 and 6,063 ± 1,872 U/L, resp., P = 0.25) or day 14 (924 ± 541 and 360 ± 250 U/L). By definition, 3/6 developed pancreatic fistula; only one (control) demonstrating a contained collection arising from the staple line. Conclusion. Buttressed stapler failed to protect against pancreatic fistula in this rigorous surgical model

Evaluación de dietas basadas en grano de maíz entero, sin fibra larga, en engorde a corral

La provisión de fibra es frecuentemente una limitante operativa y económica en dietas de feedlot. El presente trabajo evalúa el potencial de dietas sin fibra larga, basadas en grano entero de maíz. Se utilizaron 48 novillitos y 48 novillos Aberdeen Angus, (155 ± 9,7 y 269 ± 10,8 Kg de peso vivo) bloqueados por categoría, estratificados por peso en 4 estratos homogéneos, asignados de a 4 por corral. Sobre los corrales se impusieron durante 89 días 3 tratamientos, consistentes en tres dietas que incluyeron: T1 = grano de maíz entero + expeller de girasol + heno de alfalfa, T2 = Grano de maíz entero + expeller de girasol y TI = grano de maíz entero + grano de avena entero + expeller de girasol. La primera sirvió de dieta control. Se determinó el aumento diario de peso vivo (ADPV), el consumo de materia seca (CMS) y la eficiencia de conversión (ECMS) en cuatro períodos consecutivos. Se estimó la producción de heces, la calidad de la dieta y de las heces (PB, FDA, FDN, lignina, y almidón) y la fracción de grano visible recuperado de las heces (GrHe), en tres períodos. Los datos se sometieron a análisis de varianza con un modelo totalmente aleatorio, con un arreglo factorial de tratamientos (categoría x dietas) y medidas repetidas en el tiempo. No se detectaron interacciones (P > 0,12) entre tratamientos, categoría y períodos, ni diferencia (P > 0,05) entre tratamientos para ADPV (1,339 ± 0,023 kg), CMS (8,58 ± 0,107 kg día -1), y ECMS (P > 0,12; 5,46 ± 0,03). Los novillos aumentaron de peso a un ritmo superior (P < 0,01), pero la ECMS de los novillitos resultó un 29% mayor (P < 0,01) (4,67:1 vs 6,58:1). La digestibilidad de la MS total consumida resultó similar (P > O) entre categorías y tratamientos. Por su parte, la fracción de GrHe fue mayor en novillos (P < 0,01) Y mayor para T2. En novillitos entre el 7 y el 9% del grano consumido escapó 'en heces en fracciones visibles y en novillos, el 9 y 9,5 %. La utilización del almidón siguió un patrón similar. Los resultados indican que la posible deficiencia de fibra efectiva en dietas de feedlot sin henos, podría ser suplida con la utilización de granos enteros de maíz o maíz y avena complementados con expeller de girasol.Director: Ing. Agr. Anibal Pordomingo. Cátedra Zootécni

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years

Tinuktuk, a Traditional Simalungun Food that Transcends Its Therapeutic Function

This study examines tinuktuk, a traditional Simalungun herbal preparation, not only for its therapeutic uses but also for the social and cultural meanings embedded in its everyday practice. Fieldwork was conducted in two contrasting settings: the rural area where tinuktuk is historically produced and consumed, and an urban context where its presence has spread beyond the Simalungun ethnic group. More than a culinary specialty, tinuktuk represents a distinctive form of local wisdom. The knowledge of its ingredients and preparation is passed orally—predominantly from mothers to daughters—sustaining both its characteristic taste and the values of care and mutual responsibility across generations. This intergenerational transmission strengthens family ties while fostering an awareness of bodily care, from postpartum recovery to maintaining overall physical resilience. Beyond its role in women’s health, tinuktuk operates as a cultural symbol: an expression of maternal affection, a marker of communal solidarity, and a living heritage that interweaves traditional health practices with the Simalungun people’s collective identity

Gender-sensitive Risks and Options Assessment for Decision making (ROAD) to support WiF2

The Gender-Sensitive Risks and Options Assessment for Decision Making (ROAD) to Support WiF-2 (ROAD migration project), a partnership coordinated by the International Food Policy Research Institute (IFPRI), Australian National University, American University Beirut, Lincoln University, and University of Dhaka, evaluated the ILO-DFID Partnership Programme on Fair Recruitment and Decent Work for Women Migrant Workers in South Asia and the Middle East (Work in Freedom, Phase 2 project [WiF-2]), which operated from 2018 to 2023. The WiF-2 project specifically aimed “to reduce vulnerability to trafficking and forced labour of women and girls across migration pathways leading to the care sector and textiles, clothing, leather and footwear industries (TCLFI) of South Asia and Arab States” (ToC WiF-2)

GIS-based assessment for the development of a groundwater quality index towards sustainable aquifer management

This study aims at developing Groundwater Quality Indices (GQIs) that constitute a reliable tool in defining aquifer vulnerability. For this purpose, water quality sampling campaigns were conducted on 60 groundwater wells during most vulnerable periods of early and late summer to ensure the representativeness of the targeted GQI under worst case conditions. The samples were tested for various water quality indicators, which were then used to develop the GQIs through GIS-based mapping with spatial geostatistical analysis. The results contribute in filling a gap in GQI definition and form a basis for planning effective water quality management towards sustainable exploitation of groundwater resources particularly during summer periods when recharge is limited. © Springer Science+Business Media Dordrecht 2014