Background Prior studies suggest individuals with body mass index (BMI) above vs. below 60 kg/m2 show lower percentage of excess body weight loss (%EBWL) following bariatric surgery. Objectives 1. Test whether conclusions drawn about the effect of preoperative BMI on postoperative weight loss depend on the outcome measure; 2. Test for evidence of a threshold effect at BMI=60 kg/m2 and; 3. Test the effect from surgery to 12-month, relative to 12- to 36-month, follow-up. Setting Large University-affiliated hospital in New York. Methods Retrospective analyses of participants grouped according to preoperative BMI: 35–39.9 (n=232); 40–49.9 (n=1166); 50–59.9 (n=429); ≥60 (n=166). Results As anticipated, individuals with higher vs. lower preoperative BMI showed greater total body weight loss but lower %EBWL at all postoperative time points (all p’s<0.0005). However, these individuals also showed lower percentage of initial body weight loss (%IBWL) at all time points beyond 1 mo post-surgery (all p’s<0.0005). From 12- to 36-months, individuals with BMI: 35–39.9 showed 3.2±14.3 %IBWL (p<0.0001); 40–49.9 showed 1.0±8.9 %IBWL (p<0.0005); 50–59.9 showed −2.4±10.0 %IBWL (p<0.0005) and; ≥60 showed −3.6±11.5 %IBWL (p<0.0005). Overall F3,1989=20.2, p<0.0005. Conclusions Conclusions drawn about the effect of preoperative BMI may depend on the outcome measure. A dosage effect of preoperative BMI was apparent, with heavier individuals showing lower percentages of initial and excess weight loss, regardless of BMI above or below 60kg/m2. Finally, this effect was particularly apparent following the initial 12-month rapid weight loss phase, when less obese (BMI<50) individuals continued losing weight, while heavier individuals (BMI≥50) regained significant weight.
Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by persistent deficits in social communication/interaction, together with restricted/repetitive patterns of behavior. ASD is among the most heritable neuropsychiatric conditions, and while available evidence points to a complex set of genetic factors, the SHANK gene family has emerged as one of the most promising candidates. Here, we assessed ASD-related phenotypes with particular emphasis on social behavior and cognition in Shank1 mouse mutants in comparison to heterozygous and wildtype littermate controls across development in both sexes. While social approach behavior was evident in all experimental conditions and social recognition was only mildly affected by genotype, Shank1 null mutant mice were severely impaired in object recognition memory. This effect was particularly prominent in juveniles, not due to impairments in object discrimination, and replicated in independent mouse cohorts. At the neurobiological level, object recognition deficits were paralleled by increased brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of Shank1 mice; yet BDNF levels did not differ under baseline conditions. We therefore investigated changes in the epigenetic regulation of hippocampal BDNF expression and detected an enrichment of histone H3 acetylation at the Bdnf promoter1 in Shank1 mice, consistent with increased learning-associated BDNF. Together, our findings indicate that Shank1 deletions lead to an aberrant cognitive phenotype characterized by severe impairments in object recognition memory and increased hippocampal BDNF levels, possibly due to epigenetic modifications. This result supports the link between ASD and intellectual disability, and suggests epigenetic regulation as a potential therapeutic target.
The understanding of locomotion in neurological disorders requires technologies for quantitative gait analysis. Numerous modalities are available today to objectively capture spatiotemporal gait and postural control features. Nevertheless, many obstacles prevent the application of these technologies to their full potential in neurological research and especially clinical practice. These include the required expert knowledge, time for data collection, and missing standards for data analysis and reporting. Here, we provide a technological review of wearable and vision-based portable motion analysis tools that emerged in the last decade with recent applications in neurological disorders such as Parkinson's disease and Multiple Sclerosis. The goal is to enable the reader to understand the available technologies with their individual strengths and limitations in order to make an informed decision for own investigations and clinical applications. We foresee that ongoing developments toward user-friendly automated devices will allow for closed-loop applications, long-term monitoring, and telemedical consulting in real-life environments.
Phosphatase and tensin homolog (PTEN) signalling might influence neuronal survival after brain ischemia. However, the influence of the less studied longer variant termed PTEN-L (or PTENα) has not been studied to date. Therefore, we examined the translational variant PTEN-L in the context of neuronal survival. We identified PTEN-L by proteomics in murine neuronal cultures and brain lysates and established a novel model to analyse PTEN or PTEN-L variants independently in vitro while avoiding overexpression. We found that PTEN-L, unlike PTEN, localises predominantly in the cytosol and translocates to the nucleus 10–20 minutes after glutamate stress. Genomic ablation of PTEN and PTEN-L increased neuronal susceptibility to oxygen-glucose deprivation. This effect was rescued by expression of either PTEN-L indicating that both PTEN isoforms might contribute to a neuroprotective response. However, in direct comparison, PTEN-L replaced neurons were protected against ischemic-like stress compared to neurons expressing PTEN. Neurons expressing strictly nuclear PTEN-L NLS showed increased vulnerability, indicating that nuclear PTEN-L alone is not sufficient in protecting against stress. We identified mutually exclusive binding partners of PTEN-L or PTEN in cytosolic or nuclear fractions, which were regulated after ischemic-like stress. GRB2-associated-binding protein 2, which is known to interact with phosphoinositol-3-kinase, was enriched specifically with PTEN-L in the cytosol in proximity to the plasma membrane and their interaction was lost after glutamate exposure. The present study revealed that PTEN and PTEN-L have distinct functions in response to stress and might be involved in different mechanisms of neuroprotection.
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