Gut microbiota, a potential cause of higher insulin sensitivity in children with Prader-Willi syndrome.

PURPOSE: Obesity is the main driving factor for comorbidities in Prader-Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls. METHODS: We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples. RESULTS: The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased Akkermansia Eubacterium, Eubacterium rectale, and Roseburia intestinalis and decreased Parabacteroides and Phascolarctobacterium. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that Achromobacter, Acidiphilium, Xylophilus, and Frisingicoccus were significantly negatively correlated with HOMA-IR. CONCLUSION: The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients.

The impact of diabetes mellitus on mortality and infection outcomes in burn patients: a meta-analysis.

OBJECTIVE: Burns are one of the most commonly occurring soft tissue injuries worldwide. It has been reported that burns are associated with a higher prevalence of complications, mortality, and hospitalization-related outcomes in patients with coexisting diabetes mellitus. Moreover, the morbidity and mortality related outcomes associated with diabetes in patients with burns. However, since then, several studies reporting the prognostic role of diabetes in patients with burns have been published. Therefore, in this present study, we attempt to develop a current state of evidence evaluating the prognostic influence of diabetes mellitus on infectious complications, duration of hospital stay and mortality-related outcomes in patients with burns. The aim of the study is to determine the overall effect of diabetes mellitus on infectious complications, duration of hospital stay and mortality-related outcomes in patients with burns. MATERIALS AND METHODS: We performed a systematic search of the academic literature in four academic databases including EMBASE, CENTRAL, Scopus, and MEDLINE according to PRISMA guidelines. A random effect meta-analysis was carried out to evaluate the pooled effect size associated with diabetes mellitus on the outcome of infectious complications, duration of hospital stay and mortality in patients with burns. RESULTS: From a total of 1,397 studies, 13 eligible studies with 16,538 patients (3415F, 8361M) with burns were included in the analysis. Among these patients, 1702 patients had diabetes, and 14,836 patients were reported to be non-diabetic. A random effect meta-analysis revealed small-to-large size positive effect of diabetes on the infectious outcome (Hedge's g: 0.2, 95% CI: -0.03 to 0.44), overall mortality (0.16, -0.06 to 0.39), and duration of hospital stay (0.98, 0.50 to 1.45) in patients with burns. CONCLUSIONS: The present systematic review and meta-analysis provides evidence regarding the high morbidity and mortality related outcomes for diabetic patients with burns. The present study confirms the findings of a previously published systematic review suggesting diabetes to be an important and independent risk factor delineating the prognostic outcome of burns.

Signaling mechanisms mediating muscarinic enhancement of GABAergic synaptic transmission in the spinal cord.

Activation of muscarinic acetylcholine receptors (mAChRs) inhibits spinal nociceptive transmission by potentiation of GABAergic tone through M(2), M(3), and M(4) subtypes. To study the signaling mechanisms involved in this unique mAChR action, GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons were recorded using whole-cell patch clamp techniques in rat spinal cord slices. The mAChR agonist oxotremorine-M caused a profound increase in the frequency of GABAergic sIPSCs, which was abolished in the Ca(2+)-free solution. Inhibition of voltage-gated Ca(2+) channels with Cd(2+) and Ni(2+) largely reduced the effect of oxotremorine-M on sIPSCs. Blocking nonselective cation channels (NSCCs) with SKF96365 or 2-APB also largely attenuated the effect of oxotremorine-M. However, the KCNQ channel blocker XE991 and the adenylyl cyclase inhibitor MDL12330A had no significant effect on oxotremorine-M-induced increases in sIPSCs. Furthermore, the phosphoinositide-3-kinase (PI3K) inhibitor wortmannin or LY294002 significantly reduced the potentiating effect of oxotremorine-M on sIPSCs. In the spinal cord in which the M(3) subtype was specifically knocked down by intrathecal small interfering RNA (siRNA) treatment, SKF96365 and wortmannin still significantly attenuated the effect of oxotremorine-M. In contrast, SKF96365 and wortmannin both failed to alter the effect of oxotremorine-M on sIPSCs when the M(2)/M(4) mAChRs were blocked. Therefore, our study provides new evidence that activation of mAChRs increases synaptic GABA release through Ca(2+) influx and voltage-gated Ca(2+) channels. The PI3K-NSCC signaling cascade is primarily involved in the excitation of GABAergic interneurons by the M(2)/M(4) mAChRs in the spinal dorsal horn.

Relative bioavailability study of a new medium/long-chain triglyceride emulsion of propofol in beagle dogs.

The aim of this study was to evaluate the bioequivalence of a new generic formulation of propofol medium/long-chain triglyceride emulsion (test) and the available branded formulation (reference) to comply with regulatory criteria for marketing of the test product in China. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in 6 beagle dogs. Blood samples were collected before dosing and at different time after dosing. Plasma samples were separated and assayed for propofol using a selective and sensitive HPLC method with fluorescence detection. The pharmacokinetic parameters AUC0-T, AUC0-∞, MRT, t1/2 and CL were determined from plasma concentration-time profile of both formulations. The formulations were considered bioequivalent when the 90% CIs of the geometric mean ratios (test:reference) for AUC0-T and AUC0-∞ were within the regulatory range of 80% to 125%.

Susceptibility-weighted imaging in the diagnosis of early basal ganglia germinoma.

BACKGROUND AND PURPOSE: Germinomas originating from the basal ganglia (BG) are rare. Early diagnosis is important for favorable prognosis, but it is difficult due to the slow clinical course and subtle changes on neuroimaging. The purpose of this study was to evaluate the usefulness of susceptibility-weighted imaging (SWI) in the diagnosis of early BG germinoma. MATERIALS AND METHODS: From 2006 to 2008, 6 BG germinomas were diagnosed in children at our institution by pathology. Conventional MR imaging and SWI were available in all cases. Clinical, neuroradiologic, and follow-up features were retrospectively studied. RESULTS: Three cases were classified as early BG germinomas. Conventional MR imaging demonstrated that the tumor size was <10 mm in the largest diameter. The tumors were invisible or showed slight hyperintensity on T1-weighted images (T1WI) and patchy slight hyperintensity on T2-weighted images (T2WI) without mass effect or enhancement. On SWI, the tumors appeared as obvious hypointensity in the globus pallidus and putamen, and the size was larger than that on conventional T1WI and T2WI. The other 3 cases with tumor size >10 mm in largest diameter were classified as late BG germinomas, with tumor necrosis, fluid-fluid levels, and perifocal edema, including 1 case with subependymal spread. On SWI, only the solid portion of the tumors showed hypointensity. No recurrence was noted on follow-up. CONCLUSIONS: SWI appears to be more sensitive in detecting early BG germinomas than conventional MR imaging. This capability may prove to be useful in future attempts to characterize early BG germinomas.