A systematic review of relative risks for the relationship between chronic alcohol use and the occurrence of disease

Alcohol use is causally linked to the development of and mortality from numerous diseases. The aim of this study is to provide an update to a previous systematic review of meta-analyses that quantify the sex-specific dose–response risk relationships between chronic alcohol use and disease occurrence and/or mortality. An updated systematic search of multiple databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to identify meta-analyses published from January 1, 2017, to March 8, 2021, which quantified the risk relationships between chronic alcohol use and the risk of disease occurrence and/or mortality. This systematic review was not preregistered. The comparator was people who have never consumed at least one standard drink of alcohol. Measurements included relative risks, odds ratios, and hazard ratios of disease occurrence and/or mortality based on long-term alcohol intake measured in grams per day. The systematic search yielded 5953 articles, of which 14 were included in the narrative review. All diseases showed an increased risk of occurrence as alcohol use increased. At all doses examined, alcohol had a significant detrimental effect on tuberculosis, lower respiratory infections, oral cavity and pharyngeal cancers, esophageal cancer, colorectal cancer, liver cancer, laryngeal cancer, epilepsy, hypertension, liver cirrhosis, and pancreatitis (among men). For ischemic heart disease, ischemic stroke, and intracerebral hemorrhage, protective effects from low-dose chronic alcohol use among both men and women were observed. Low-dose alcohol consumption also had a protective effect for diabetes mellitus and pancreatitis among women (approximately to 50 g/day and 30 g/day, respectively). Alcohol use increases the risk of numerous infectious and noncommunicable diseases in a dose–response manner. Higher levels of alcohol use have a clear detrimental impact on health; however, at lower levels of use, alcohol can have both disease-specific protective and detrimental effects.     

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu–Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre‐ or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease‐causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.     

Effects of surface irrigation on the thermal response of tissue during laser irradiation

Effects of surface irrigation on the thermal response of tissue during laser irradiation are investigated. In particular, influence of temperature and flow rate of the irrigation fluid on the resulting temperature distributions and coagulation depths are studied. Intraluminal Nd:YAG laser irradiation of bovine muscle is performed in vitro for a fixed value of the irrigation flow rate while the irrigation temperature is varied, and for a fixed irrigation temperature while the irrigation flow rate is kept constant. Thermocouples are used to measure the temperatures within the tissue for various irradiation and irrigation conditions. Higher temperatures and deeper coagulation depths are achieved as the temperature of the irrigation fluid is increased. For sufficiently low values of irradiance and exposure time, the use of cold irrigation is shown to prevent or delay tissue carbonization. Beyond a critical irradiance and an exposure time, use of cold irrigation does not prevent tissue carbonization. Coagulation depths and temperature distributions are not affected by a change in the flow rate of laminar irrigation. Application of stagnant irrigation, however, results in an increase in coagulation depth. Results of this study suggest that the dominating mechanism of heat transfer during application of laminar irrigation is thermal diffusion as compared to the bulk motion of the fluid. © 1994 wiley-Liss, Inc.     

Transfusion associated GVHD

Transfusion-associated graft-versus-host disease (TA-GVHD) is an under-diagnosed condition in clinical practice. It can occur in immunocompromised as well as immunocompetent hosts and may follow allogeneic bone marrow transplant or transfusion from a related donor. The clinical course is stormy with a high mortality rate. Avoiding the use of blood transfusions from related donors and irradiation of blood products can prevent graft versus host disease. A case of graft versus host disease following related donor transfusion is presented here     

Parathyroid hormone stimulates extracellular signal-regulated kinase (ERK) activity through two independent signal transduction pathways: role of ERK in sodium-phosphate cotransport

Parathyroid hormone (PTH), a major physiologic regulator of proximal renal tubule cell sodium-phosphate cotransport, stimulates several signal transduction pathways including extracellular signal-regulated kinases (ERK). The physiologic role of PTH-stimulated ERK is unknown. The purpose of the present study was to identify signaling components involved in PTH-stimulated ERK activity and to determine the role of PTH-stimulated ERK activity in regulation of phosphate transport. PTH-stimulated ERK activity was measured in opossum kidney (OK) cell lysates as phosphorylation of myelin basic protein by an in vitro kinase assay. PTH stimulated a dose-dependent increase in ERK activity with a peak at 10(-7) M. The time course was biphasic with an early peak at 10 min and a later peak at 20 min. Pretreatment of OK cells with the nonreceptor tyrosine kinase inhibitors genistein and herbimycin A or with the phosphatidylinositol 3-kinase (PI-3K) inhibitors wortmannin and LY294002 blocked the early and late peaks of PTH-stimulated ERK activity. Pretreatment with the protein kinase C inhibitor calphostin C blocked only the later phase of PTH-stimulated ERK. To determine the role of ERK in regulation of phosphate transport, PTH inhibition of phosphate uptake and PTH regulation of sodium-phosphate cotransporter (NaPi-4) expression were measured in OK cells pretreated with the MEK inhibitor PD098059. PD098059 significantly attenuated PTH inhibition of phosphate uptake but did not prevent PTH downregulation of NaPi-4. It is concluded that PTH stimulates ERK through two signal transduction pathways: an early pathway dependent on tyrosine kinase and PI-3K and a late pathway dependent on protein kinase C. PTH-stimulated ERK regulates phosphate transport by a mechanism other than downregulation of NaPi-4 expression.     

Fully automated hybrid approach to predict the IDH mutation status of gliomas via deep learning and radiomics

BackgroundGlioma prognosis depends on isocitrate dehydrogenase (IDH) mutation status. We aimed to predict the IDH status of gliomas from preoperative MR images using a fully automated hybrid approach with convolutional neural networks (CNNs) and radiomics.MethodsWe reviewed 1166 preoperative MR images of gliomas (grades II–IV) from Severance Hospital (n = 856), Seoul National University Hospital (SNUH; n = 107), and The Cancer Imaging Archive (TCIA; n = 203). The Severance set was subdivided into the development (n = 727) and internal test (n = 129) sets. Based on T1 postcontrast, T2, and fluid-attenuated inversion recovery images, a fully automated model was developed that comprised a CNN for tumor segmentation (Model 1) and CNN-based classifier for IDH status prediction (Model 2) that uses a hybrid approach based on 2D tumor images and radiomic features from 3D tumor shape and loci guided by Model 1. The trained model was tested on internal (a subset of the Severance set) and external (SNUH and TCIA) test sets.ResultsThe CNN for tumor segmentation (Model 1) achieved a dice coefficient of 0.86–0.92 across datasets. Our hybrid model achieved accuracies of 93.8%, 87.9%, and 78.8%, with areas under the receiver operating characteristic curves of 0.96, 0.94, and 0.86 and areas under the precision-recall curves of 0.88, 0.82, and 0.81 in the internal test, SNUH, and TCIA sets, respectively.ConclusionsOur fully automated hybrid model demonstrated the potential to be a highly reproducible and generalizable tool across different datasets for the noninvasive prediction of the IDH status of gliomas.