Notes

Incomplete eliminating extracellular glutamate regulates synaptic indication as well as intergrated , in a cerebellar synapse.
Sphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans.

Thus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery.

Surprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitirole of ceramides in obesity-associated low-grade inflammation.
The use of non-invasive vascular and perfusion diagnostics are an important part of assessing lower extremity ulceration and amputation risk in patients with diabetes mellitus. Methods for detecting impaired microvascular vasodilatory function in patients with diabetes may have the potential to identify sites at risk of ulceration prior to clinically identifiable signs. Spatial frequency domain imaging (SFDI) uses patterned near-infrared and visible light spectroscopy to determine tissue oxygen saturation and hemoglobin distribution within the superficial and deep dermis, showing distinct microcirculatory and oxygenation changes that occur prior to neuropathic and neuroischemic ulceration.

35 patients with diabetes mellitus and a history of diabetic foot ulceration were recruited for monthly imaging with SFDI. Two patients who ulcerated during the year-long longitudinal study were selected for presentation of their clinical course alongside the dermal microcirculation biomarkers from SFDI.

Patient 1 developed a neuropathic ulcer portended by a focal increase in tissue oxygen saturation and decrease in superficial papillary hemoglobin concentration 3 months prior. Patient 2 developed bilateral neuroischemic ulcers showing decreased tissue oxygen saturation and increased superficial papillary and deep dermal reticular hemoglobin concentrations.

Wounds of different etiology show unique dermal microcirculatory changes prior to gross ulceration. Before predictive models can be developed from SFDI, biomarker data must be correlated with the clinical course of patients who ulcerate while being followed longitudinally.

NCT03341559.
NCT03341559.
To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health.

For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years.

The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p≤0.011). The observed differences were attenuated at 6 years; however, participants in the both intervention groups significantly improved their blood pressure, high-density lipoprotein-cholesterol, and insulin sensitivity compared with the population controls (p≤0.003). FH modified LDL-C and waist circumference responses to exercise at 1 year and 5 years.

Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health.

ClinicalTrials.gov identifier NCT02131701.
ClinicalTrials.gov identifier NCT02131701.
To compare the effectiveness of progressive tendon-loading exercises (PTLE) with eccentric exercise therapy (EET) in patients with patellar tendinopathy (PT).

In a stratified, investigator-blinded, block-randomised trial, 76 patients with clinically diagnosed and ultrasound-confirmed PT were randomly assigned in a 11 ratio to receive either PTLE or EET. find more The primary end point was clinical outcome after 24 weeks following an intention-to-treat analysis, as assessed with the validated Victorian Institute of Sports Assessment for patellar tendons (VISA-P) questionnaire measuring pain, function and ability to play sports. Secondary outcomes included the return to sports rate, subjective patient satisfaction and exercise adherence.

Patients were randomised between January 2017 and July 2019. The intention-to-treat population (mean age, 24 years, SD 4); 58 (76%) male) consisted of patients with mostly chronic PT (median symptom duration 2 years). Most patients (82%) underwent prior treatment for PT but failed to recover fully. 38 patients were randomised to the PTLE group and 38 patients to the EET group. The improvement in VISA-P score was significantly better for PTLE than for EET after 24 weeks (28 vs 18 points, adjusted mean between-group difference, 9 (95% CI 1 to 16); p=0.023). There was a trend towards a higher return to sports rate in the PTLE group (43% vs 27%, p=0.13). No significant between-group difference was found for subjective patient satisfaction (81% vs 83%, p=0.54) and exercise adherence between the PTLE group and EET group after 24 weeks (40% vs 49%, p=0.33).

In patients with PT, PTLE resulted in a significantly better clinical outcome after 24 weeks than EET. PTLE are superior to EET and are therefore recommended as initial conservative treatment for PT.
In patients with PT, PTLE resulted in a significantly better clinical outcome after 24 weeks than EET. PTLE are superior to EET and are therefore recommended as initial conservative treatment for PT.
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