Perseverative responding and neuroanatomical alterations in adult heterozygous reeler mice are mitigated by neonatal estrogen administration

According to the "extreme-male brain" theory, elevated fetal testosterone levels may partly explain the skewed sex ratio found in Autism Spectrum Disorders (ASD). Correcting this testosterone imbalance by increasing estrogen levels may mitigate the abnormal phenotype. Accordingly, while control heterozygous reeler (rl/+) male mice - a putative model of neuroanatomical and behavioral endophenotypes in ASD - show a decreased number of Purkinje cells (PC) compared to control wild-type (+/+) littermates, neonatal estradiol administration has been shown to correct this deficit in the short-term (i.e. on postnatal day 15). Here, we further investigated the neuroanatomical and behavioral abnormalities of rl/+ male mice and the potential compensatory effects of neonatal treatment with estradiol. In a longitudinal study, we observed that: i) infant rl/+ mice showed reduced motivation for social stimuli; ii) adult rl/+ male mice showed reduced cognitive flexibility; iii) the number of amygdalar parvalbumin-positive GABAergic interneurons were remarkably reduced in rl/+ mice; iv) neonatal estradiol administration into the cisterna magna reverted the abnormal profile both at the behavioral and at the neuroanatomical level in the amygdala but did not compensate for the cerebellar abnormalities in adulthood. This study supports the view that an increased excitation-to-inhibition ratio in the cerebellum and in the amygdala during a critical window of development could be crucial to the social and cognitive phenotype of male rl/+ mice, and that acute estradiol treatment during this critical window may mitigate symptoms' severity

Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis

GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control

Commentary: Glucose control: Not just a bystander in GLP-1RA-mediated cardiovascular protection

Cardiovascular (CV) disease prevention in type 2 diabetes (T2D)demands multifactorial interventions including treatment of dyslipidemia, hypertension, hypercoagulability, and certainly hyperglycemia[1]. However, randomized controlled trials specifically addressing the impact of intensive glucose control (IGC) on CV outcomes yielded ambiguous results [2], while real-life evidence from a Swedish nationwide registry showed hyperglycemia as the strongest predictor of myocardial infarction (MI) and stroke [3]. Although CV outcome trials (CVOT) with GLP-1 receptor agonists (GLP-1RA) were designed to achieve glycemic equipoise, all showed a greater HbA1c reduction in the intervention arm [4–10], allowing to consider the potential effect of different degrees of glucose-lowering on their resul

Biometric analysis of seeds of genotypes of physic nut (Jatropha curcas L.).

Procurou-se investigar aspectos da morfologia das sementes de diferentes genótipos de pinhão-manso, em razão da pouca literatura existente em relação aos aspectos biométrico das sementes desta espécie. O delineamento experimental utilizado foi o inteiramente casualizado, em esquema simples, sendo 15 níveis de genótipos (Diamantina, Tominaga, Paraíso, Jales, CNPAE ? C2, CNPAE ? 171, G ? 2, AGE, 167, 200, 210, 315, 316, 1501 e 8001), com quatro repetições. As avaliações foram realizadas com parcelas de 100 sementes para cada repetição, mensurando as variáveis: medida de largura em mm (LAS), comprimento em mm (COS) e massa de 100 sementes e g (MCS), de sementes de pinhão-manso. No geral, para os 15 genótipos de pinhão-manso estudados houve a formação de 3 grupos de médias distintas em relação as variáveis biométricas, destacando-se os genótipos Paraiso e Jales e os acessos CNPAE ? C2 e AGE

Pesquisa, desenvolvimento e inovação em pinhão-manso para produção de biocombustíveis.

Características e potencial da cultura para o mercado de biodiesel; Lacunas de conhecimento e desafios para pesquisa; Situação atual e perspectivas de pesquisa; Banco de germoplasma (BAG-Jatropha) e caracterização de pinhão-manso; Descritores botânicos para pinhão-manso (Jatropha curcas L.); Registro de cultivares e melhoramento de pinhão manso; Possibilidades de parceria, cooperação técnica e financeira; Apropriação de resultados.bitstream/item/17976/1/DOC01.pd

Life cycle inventory of physic nut biodiesel: comparison between the manual and mechanized agricultural production systems practiced in Brazil.

The physic nut (Jatropha curcas L.) is an oleaginous species recently introduced into Brazil for energy purposes. The technological framework for the development of the physic nut biodiesel productive chain in Brazil is still being set up. Two production systems are in practice at the agricultural level, the small scale manual system and the medium scale mechanized system. The objective of the present research was to assess the environmental performance of these two production systems by elaborating life-cycle inventories (LCIs) using a cradle-to-gate approach. The main environmental aspects of these LCIs are the synthetic fertilizers, pesticides, land-use changes and its emissions and the occupation of the land. Making use of the residues from the agroindustrial physic nut chain and the use of biological pest control methods could improve the environmental performance of these systems

Nonhuman gamblers: lessons from rodents, primates, and robots

The search for neuronal and psychological underpinnings of pathological gambling in humans would benefit from investigating related phenomena also outside of our species. In this paper, we present a survey of studies in three widely different populations of agents, namely rodents, non-human primates, and robots. Each of these populations offers valuable and complementary insights on the topic, as the literature demonstrates. In addition, we highlight the deep and complex connections between relevant results across these different areas of research (i.e., cognitive and computational neuroscience, neuroethology, cognitive primatology, neuropsychiatry, evolutionary robotics), to make the case for a greater degree of methodological integration in future studies on pathological gambling

Cardiovascular and Renal Effectiveness of GLP-1 Receptor Agonists vs. Other Glucose-Lowering Drugs in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Real-World Studies

Cardiovascular outcome trials (CVOT) showed that treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) is associated with significant cardiovascular benefits. However, CVOT are scarcely representative of everyday clinical practice, and real-world studies could provide clini-cians with more relatable evidence. Here, literature was thoroughly searched to retrieve real-world studies investigating the cardiovascular and renal outcomes of GLP-1RA vs. other glucose-lowering drugs and carry out relevant meta-analyses thereof. Most real-world studies were conducted in populations at low cardiovascular and renal risk. Of note, real-world studies investigating cardio-renal outcomes of GLP-1RA suggested that initiation of GLP-1RA was associated with a greater benefit on composite cardiovascular outcomes, MACE (major adverse cardiovascular events), all-cause mortality, myocardial infarction, stroke, cardiovascular death, peripheral artery disease, and heart failure compared to other glucose-lowering drugs with the exception of sodium-glucose transporter-2 inhibitors (SGLT-2i). Initiation of SGLT-2i and GLP-1RA yielded similar effects on composite cardiovascular outcomes, MACE, stroke, and myocardial infarction. Conversely, GLP-1RA were less effective on heart failure prevention compared to SGLT-2i. Finally, the few real-world studies addressing renal outcomes suggested a significant benefit of GLP-1RA on estimated glomerular filtration rate (eGFR) reduction and hard renal outcomes vs. active comparators except SGLT-2i. Further real-world evidence is needed to clarify the role of GLP-1RA in cardio-renal protection among available glucose-lowering drugs