Implementación de un método alternativo de cría en la región del caldenal

The beef cattle production system in the east area of Caldenal tends to concentrate the parturition in a short period of time, adjusting the availability of forage production with the maximum nutrient herd demando Nevertheless the current system has the main disadvantage to offer weaning calf in a tiny period of time affecting negatively both the sale price and the provision of animal to feed lot that demand animal year round. The objective of the project was to develop a new methodology to distribute the calving around the year in arder 10 increase the economic and reproductive efficiencies . It was chosen six beef herd on native pasture in the Caldenal area with strategic energy supplementation. The breeding season was planned to be of 90 days of duration, where the last 30 days of breeding of the initial herd mach with the first 30 days of the fol1owing. The percentage of calving detected by the alternative method were the same or higher to those observed by the traditional systemLos modelos de cría utilizados en la región este del caldenal pampeano tienden a concentrar la oferta de terneros en un corto período del año. Este manejo facilita el ajuste entre la producción forrajera y demanda del mismo, pero tiene como restricción que la oferta de terneros al destete es estacional y afecta tanto el precio que se paga por ellos como la provisión de animales para sistemas de engorde intensivo, que pueden requerirlos en otros momentos del año. El objetivo del presente trabajo fue desarrollar una metodología de distribución de pariciones a 10 largo del año con la finalidad de mantener y/o aumentar la eficiencia reproductiva del modelo tradicional, utilizando los mismos recursos disponibles. Se seleccionaron 6 rodeos de vacas en pastizales naturales con suplementación estratégica y cada rodeo pastoreó durante todo el año un mismo circuito de 2 a 5 lotes. Se planificaron servicios de 90 días de duración, donde los últimos 30 días de servicio de cada rodeo coincidían con los primeros 30 días del siguiente. Los porcentajes de pariciones detectados por el método alternativo fueron iguales o superiores a los obtenidos mediante el sistema tradiciona

Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease

Fabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis

Clinical and genetic characteristics of late-onset Huntington's disease

Background: The frequency of late-onset Huntington's disease (&gt;59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P &lt;.001). Overall motor and cognitive performance (P &lt;.001) were worse, however only disease motor progression was slower (coefficient, −0.58; SE 0.16; P &lt;.001) compared to the common-onset group. Repeat size was significantly lower in the late-onset (n = 40.8; SD 1.6) compared to common-onset (n = 44.4; SD 2.8) (P &lt;.001). Fewer late-onset patients (n = 451) had a positive family history compared to common-onset (n = 2940) (P &lt;.001). Conclusions: Late-onset patients present more frequently with gait and balance problems as first symptom, and disease progression is not milder compared to common-onset HD patients apart from motor progression. The family history is likely to be negative, which might make diagnosing HD more difficult in this population. However, the balance and gait problems might be helpful in diagnosing HD in elderly patients