Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity

Insulin receptors (IRs) are expressed in discrete neuronal populations in the central nervous system, including the hippocampus. To elucidate the functional role of hippocampal IRs independent of metabolic function, we generated a model of hippocampal-specific insulin resistance using a lentiviral vector expressing an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR expression in the rat hippocampus without affecting body weight, adiposity, or peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was impaired in LV-IRAS–treated rats. High-frequency stimulation, which evoked robust long-term potentiation (LTP) in brain slices from LV control rats, failed to evoke LTP in LV-IRAS–treated rats. GluN2B subunit levels, as well as the basal level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS rats. Moreover, these deficits in synaptic transmission were associated with impairments in spatial learning. We suggest that alterations in the expression and phosphorylation of glutamate receptor subunits underlie the alterations in LTP and that these changes are responsible for the impairment in hippocampal-dependent learning. Importantly, these learning deficits are strikingly similar to the impairments in complex task performance observed in patients with diabetes, which strengthens the hypothesis that hippocampal insulin resistance is a key mediator of cognitive deficits independent of glycemic control.     

Energy expenditure,body composition and dietary habits in progressive supranuclear palsy

Journal of Neurology - Little is known about metabolic changes in progressive supranuclear palsy. Goals of the present study are to: (1) investigate whether early progressive supranuclear palsy is...     

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients

Neurological Sciences - Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for...     

Vaginal stretching therapy and class IIIB vaginal laser treatment for pelvic floor myofascial pain: a randomized clinical trial

Lasers in Medical Science - Several treatment options are proposed for the management of pelvic floor myofascial pain (PFMP). Manual therapy, such as vaginal stretching (VS), is one of these...     

Photobiomodulation via a cluster device associated with a physical exercise program in the level of pain and muscle strength in middle-aged and older women with knee osteoarthritis: a randomized placebo-controlled trial

Osteoarthritis (OA) is a chronic joint disease that leads to pain and functional incapacity. The aim of the study is to investigate the effects of the incorporation of photobiomodulation (PBM) (via cluster) into a physical exercise program on the level of pain, lower limb muscle strength, and physical capacity, in patients with knee OA. Sixty-two female volunteers with a diagnosis of knee OA were distributed in 4 groups: exercise associated with placebo PBM group, exercise associated with active PBM group, active PBM group, and placebo PBM group. Sixteen sessions of lower limb strength exercises and PBM via cluster (808 nm, 100 mW, 7 points each side, 56 J total) were performed. The level of pain, physical capacity, and lower limb muscle strength were evaluated with the use of the numeric pain rating scale (NPRS), 6-min walking test (6-MWT) and timed up and go (TUG), and maximal voluntary isometric torque (MVIT) before and after the interventions. Both groups presented a significant decrease in the level of pain when compared with the placebo-treated women. Furthermore, the 6-MWT showed that the trained groups (with or without PBM) demonstrated higher values in the distance walked comparing pre and post-treatment values. The same behavior was found for the MVIT load before and after intervention. TUG was higher for all the treated with exercise groups comparing the pre and post-treatment values. Physical exercise and PBM showed analgesic effects. However, PBM did not have any extra effect along with the effects of exercise in improving the distance walked, the TUG, and the muscle strength.

Trial registration: RBR-7t6nzr

     

Comparison of Fracture Prediction Tools in Individuals Without and With Early Chronic Kidney Disease: A Population-Based Analysis of CARTaGENE

Whether fracture prediction tools developed for the management of osteoporosis can be used in chronic kidney disease (CKD) is poorly known. We aimed to compare the performance of fracture prediction tools in non-CKD and CKD. We analyzed CARTaGENE, a population-based survey of 40-year-old to 69-year-old individuals recruited between 2009 and 2010. Renal function was assessed using baseline creatinine and categorized according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines (non-CKD, stage 2, stage 3). Individuals without creatinine measurements or with advanced CKD (stage 4 or 5; prevalence <0.25%) were excluded. Predicted 5-year fracture probabilities (using Fracture Risk Assessment Tool [FRAX], QFracture, and Garvan) were computed at baseline. Fracture incidence (major fracture [MOF] or any fracture) was evaluated in administrative databases from recruitment to March 2016. Discrimination (hazard ratios [HRs] per standard deviation [SD] increase in Cox models; c-statistics) and calibration (standardized incidence ratios [SIRs] before and after recalibration) were assessed in each CKD strata. We included 19,393 individuals (9522 non-CKD; 9114 stage 2; 757 stage 3). A total of 830 patients had any fracture during follow-up, including 352 MOF. FRAX (HR = 1.89 [1.63–2.20] non-CKD; 1.64 [1.41–1.91] stage 2; 1.76 [1.10–2.82] stage 3) and QFracture (HR = 1.90 [1.62–2.22] non-CKD; 1.57 [1.35–1.82] stage 2; 1.86 [1.19–2.91] stage 3) discriminated MOF similarly in non-CKD and CKD. In contrast, the discrimination of Garvan for any fracture tended to be lower in CKD stage 3 compared to non-CKD and CKD stage 2 (HR = 1.36 [1.22–1.52] non-CKD; 1.34 [1.20–1.50] stage 2; 1.11 [0.79–1.55] stage 3). Before recalibration, FRAX globally overestimated fracture risk while QFracture and Garvan globally underestimated fracture risk. After recalibration, FRAX and QFracture were adequately calibrated for MOF in all CKD strata whereas Garvan tended to underestimate any fracture risk in CKD stage 3 (SIR = 1.31 [0.95–1.81]). In conclusion, the discrimination and calibration of FRAX and QFracture is similar in non-CKD and CKD. Garvan may have a lower discrimination in CKD stage 3 and underestimate fracture risk in these patients. © 2020 American Society for Bone and Mineral Research.     

Chest Trauma Outcomes: Public Versus Private Level I Trauma Centers

World Journal of Surgery - The goal of our study was to evaluate the differences in care and clinical outcomes of patients with chest trauma between two hospitals, including one public trauma...