Handbergharrell3616

Trial Registration This project is registered at clinicaltrials.gov under the name "Antibiotic 'Dysbiosis' in Preterm Infants" with trial number NCT02784821.Clozapine (CLZ), the sole antipsychotic with superior efficacy for ultra-treatment resistant schizophrenia (TRS), is limited by adverse effects, including metabolic dysregulation. Clozapine's main metabolite, N-desmethylclozapine (NDMC), has potent 5-HT2C antagonist properties which may explain this metabolic dysfunction, thus the CLZNDMC ratio is of particular interest. High insulin resistance states could be associated with CYP1A2 induction and lower CLZNDMC ratios. Additionally, lower CLZNDMC ratios have been associated with better cognitive, but worse metabolic functioning. This study investigated associations between metabolic and cognitive parameters with the CLZ/NDMC ratio. Primary outcomes included relationships between the CLZNDMC ratio to the homeostatic model assessment for insulin resistance (HOMA-IR) and Brief Assessment of Cognition in Schizophrenia (BACS) composite z-scores. Secondary outcomes assessed relationships between CLZNDMC ratios to fasting insulin, BMI, weight, fasting glucose, and BACS digit sequencing z-scores. 38 patients who were overweight or obese with schizophrenia or schizoaffective disorder completed fasting bloodwork, anthropometric, psychopathological, and cognitive assessments. Multivariate regressions found a statistically significant inverse association between the CLZ/NDMC ratio and HOMA-IR (B = - 1.028, SE B = .473, β = - 0.348 p = 0.037), which may have been driven by fasting insulin levels (B = - 27.124, SE B = 12.081, β = - 0.351 p = 0.031). The CLZ/NDMC ratio may predict insulin resistance/metabolic comorbidity among patients with TRS receiving clozapine.Extreme sea surface temperatures (SSTs) attract much attention in recent years. However, the detailed spatial and temporal pattern of the extreme SSTs in China Seas has not been well understood. Using the daily SST data set of OISST v2 from January 1, 1982 to December 31, 2013, and based on four extreme SST indices, the frequency and intensity of SST extremes in the China Seas were examined. The analysis showed that the annual mean SST exhibited cooling trend, on pace with a trend of - 0.34 °C/decade during 1998-2013, confirming the previous studies that China Seas also experienced the recent global warming hiatus. But during this recent global warming hiatus, there was a notable asymmetric pattern of greater cooling trends in cold SSTs as compared to the hot SSTs in this region. During 1998-2013, the cold days (CDs) frequency increased significantly by 13 days per decade and cold SST extremes which were below the 10th percentile of each year (SST10p) notably decreased by 0.4 °C per decade. GDC-6036 Hot days (HD) and hot SST extremes which were above the 90th percentile of each year (SST90p) slowed down, but without any distinct tendency. Meanwhile, the rates of SST10p and CDs were highly heterogeneous in space. Cold extremes in the near-shore areas are much more sensitive to the global warming hiatus than these in the eastern of the Kuroshio Current. Importantly, hot extremes do not reveal any distinct cooling tendency during 1998-2013, there were more frequent hot days and more intense hot SSTs in this region comparing with 1982-1997. These hot extremes could push some marine organisms, fisheries and ecosystems beyond the limits of their resilience, with cascading impacts on economies and societies.Sea-level reconstructions are important for understanding past ice sheet variability and its response to past and future warming. Here we present Neogene and Quaternary sea-level snapshots using phreatic overgrowths on speleothems (POS) from caves on Mallorca, Spain. POS are excellent sea level index points because of their clear relationship to sea level and precise U-Pb chronology. We find that local sea-level before and at the onset of the Messinian Salinity Crisis was at 33.3 ± 0.25 m (6.54 ± 0.37 Ma) and 31.8 ± 0.25 m (5.86 ± 0.60 Ma) above present levels, respectively. We further present global mean sea level (GMSL) estimates, i.e. local sea level corrected for glacial isostatic adjustment and long-term uplift, for three other POS. The results show that GMSL during the Pliocene-Pleistocene Transition was 6.4 m (- 2.0-8.8 m) at 2.63 ± 0.11 Ma and during the beginning and the end of the Mid-Pleistocene Transition was - 1.1 m (- 5.6-2.4 m) and 5 m (1.5-8.1 m), respectively. These estimates provide important constraints for the past evolution of sea level and show that local sea level prior to the MSC was similar to the highest stand during the Pliocene, with markedly lower position afterwards.Duchenne muscular dystrophy (DMD) is a common and severe X-linked myopathy, characterized by muscle degeneration due to altered or absent dystrophin. DMD has no effective cure, and the underlying molecular mechanisms remain incompletely understood. The aim of this study is to investigate the metabolic changes in DMD using mass spectrometry-based imaging. Nine human muscle biopsies from DMD patients and nine muscle biopsies from control individuals were subjected to untargeted MSI using matrix-assisted laser desorption/ionization Fourier-transform ion cyclotron resonance mass spectrometry. Both univariate and pattern recognition techniques have been used for data analysis. This study revealed significant changes in 34 keys metabolites. Seven metabolites were decreased in the Duchenne biopsies compared to control biopsies including adenosine triphosphate, and glycerophosphocholine. The other 27 metabolites were increased in the Duchenne biopsies, including sphingomyelin, phosphatidylcholines, phosphatidic acids and phosphatidylserines. Most of these dysregulated metabolites are tightly related to energy and phospholipid metabolism. This study revealed a deep metabolic remodelling in phospholipids and energy metabolism in DMD. This systems-based approach enabled exploring the metabolism in DMD in an unprecedented holistic and unbiased manner with hypothesis-free strategies.