Downeylohmann7622

Pituitary adenomas (PAs) are intracranial tumors associated with significant morbidity due to hormonal dysregulation, mass effects and have a heavy treatment burden. Growth hormone (GH)-secreting PAs (somatotropinomas) cause acromegaly-gigantism. Genetic forms of somatotropinomas due to germline AIP mutations (AIPmut+) have an early onset and are aggressive and resistant to treatment with somatostatin analogs (SSAs), including octreotide. The molecular underpinnings of these clinical features remain unclear. We investigated the role of miRNA dysregulation in AIPmut+ vs AIPmut- PA samples by array analysis. miR-34a and miR-145 were highly expressed in AIPmut+ vs AIPmut- somatotropinomas. Ectopic expression of AIPmut (p.R271W) in Aip-/- mouse embryonic fibroblasts (MEFs) upregulated miR-34a and miR-145, establishing a causal link between AIPmut and miRNA expression. In PA cells (GH3), miR-34a overexpression promoted proliferation, clonogenicity, migration and suppressed apoptosis, whereas miR-145 moderately affected proliferation and apoptosis. Moreover, high miR-34a expression increased intracellular cAMP, a critical mitogenic factor in PAs. Crucially, high miR-34a expression significantly blunted octreotide-mediated GH inhibition and antiproliferative effects. miR-34a directly targets Gnai2 encoding Gαi2, a G protein subunit inhibiting cAMP production. Accordingly, Gαi2 levels were significantly lower in AIPmut+ vs AIPmut- PA. Taken together, somatotropinomas with AIP mutations overexpress miR-34a, which in turn downregulates Gαi2 expression, increases cAMP concentration and ultimately promotes cell growth. Upregulation of miR-34a also impairs the hormonal and antiproliferative response of PA cells to octreotide. Thus, miR-34a is a novel downstream target of mutant AIP that promotes a cellular phenotype mirroring the aggressive clinical features of AIPmut+ acromegaly.

Delayed syncopal-type complications are infrequent among blood donors, but sometimes have critical consequences, such as severe injury. We retrospectively investigated the characteristics of donors with delayed syncopal-type complications or falls.

We defined a delayed reaction (DR) as syncopal-type complications occurring >20min after needle removal. Subjects were stratified by sex, age, estimated blood volume (EBV), body mass index (BMI) and frequency of donation. Multiple logistic regression analysis and propensity score weighted M estimation were performed to evaluate the covariate-adjusted risk of syncopal DRs among donors giving 400ml of whole blood (WB). The DR rate was calculated as the number of DRs divided by the number of all syncopal-type reactions after needle removal. The risk of falls was assessed similarly. Donors who discontinued before completing phlebotomy (donation of 400ml) were excluded.

Among 3818 syncopal-type reactions after needle removal, there were 359 DRs and 93 falls. Elderly donors and female donors with syncopal-type reactions had a significantly higher risk of DRs (P for trend<0·001). Elderly donors with syncopal-type reactions also had a higher risk of falls (P for trend<0·001). Among all donors with syncopal-type reactions, the risk of DRs or falls was not correlated with EBV, BMI or donation frequency.

In female donors and elderly donors (donating 400ml of WB), syncopal-type reactions tended to be delayed. Elderly donors with syncopal-type reactions had a significantly higher risk of falls.

In female donors and elderly donors (donating 400 ml of WB), syncopal-type reactions tended to be delayed. Elderly donors with syncopal-type reactions had a significantly higher risk of falls.

An increased risk of complications, including death, has been associated with stored red blood cell (RBC) units in observational studies but not in randomized trials. We aimed to evaluate for volume-dependent effects attributable to length of RBC storage in a secondary analysis of the Age of Blood Evaluation (ABLE) trial.

In the 2510 critically ill adults from the ABLE trial randomized to receive RBC units stored not more than 7 days or the oldest compatible RBC units, we estimated the hazard ratio (HR) for death by intensive care unit (ICU) and hospital discharge and by days 28, 90, and 180, within subgroups defined by the number of RBC units received. Extended Cox proportional hazards regression was used to model the HR.

A volume-dependent effect of storage age on survival was present for death by 90 and 180 days, but not earlier endpoints. The HR for death by 90 days was 0.55 (95% confidence interval [CI], 0.11-0.98, fresh vs standard) after transfusion of 6 RBC units but 1.45 (95% CI, 1.06-1.98) after transfusion of 1 RBC unit.

In this exploratory analysis, volume-dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored.

In this exploratory analysis, volume-dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored.The merging of psychiatry and dermatology has resulted in a relatively newer emerging field known as psychodermatology (PD). The aim of this cross sectional study was to assess knowledge, attitudes, and practice patterns of Egyptian dermatologists towards psychodermatology. A cross sectional study was designed and data were collected using structured self-administered online questionnaires. A total of 212 dermatologists completed the full questionnaire. Those with incomplete or partially answered responses were excluded. 171 (81.1%) were females and 40 (18.9%) were males. The majority (n = 109;51.4%) of dermatologists completing the survey were between 30 and 40 years age group while those between 40 and 50 years of age accounted for 48 (22.6%). The vast majority of respondent dermatologists never referred (n = 87; 41%) or very rarely referred (n = 58; 27.5%) any psychocutaneous patients to a psychiatrist. Almost 75% of responding dermatologists were not aware of available community or educational resources for PD and 157 (74.1%) expressed interest in receiving continuing medical education (CME) programs. In conclusion, psychodermatology training among dermatologists shall enhance and improve their approach to psychocutaneous conditions.Schema modes (or modes) are a key concept in the theory underlying schema therapy. Modes have rarely been related to established models of personality traits. The present study thus investigates the associations between trait emotional intelligence (TEI) and 14 modes, and tests a global TEI-mode factors-general psychological distress mediation model. The study draws on self-report data from 173 inpatients from a German clinic for psychosomatic medicine. Global TEI correlated positively with both healthy modes (happy child and healthy adult) and negatively with 10 maladaptive modes. When modes were regressed on the four TEI factors, six (emotionality), five (well-being), four (sociability), and four (self-control) significant partial effects on 10 modes emerged. In the parallel mediation model, the mode factors internalization and compulsivity fully mediated the global TEI-general psychological distress link. Implications of the results for the integration of modes with traits in general and with TEI in particular as well as implications of low TEI as a transdiagnostic feature of personality malfunctioning are discussed.Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio may carry additional information and has been suggested as a better predictor for atherosclerosis progression and cardiovascular disease (CVD) than LDL-C and HDL-C alone. Therefore, we aim to explore the association between LDL-C/HDL-C ratio and high carotid intima-media thickness (CIMT) risk in a large Cohort in Beijing, China. This cohort study included 13,612 adults without high CIMT at first entry and who attended the baseline examination and at least one follow-up annual examination between 2009 and 2016. We used multivariable Cox regression to estimate hazard ratios (HR) with their 95% confidence intervals (CI) for the association between LDL-C/HDL-C ratio and risk of high CIMT. During 37,912 person-years of follow-up, 1996 (1268 men and 728 women) developed high CIMT. Compared with the first quartile of LDL-C/HDL-C ratio, the risk of high CIMT was significantly increased for the fourth quartile of LDL-C/HDL-C ratio (HR = 1.51, 95% CI 1.29-1.78). We observed a significant association between LDL-C/HDL-C ratio and high CIMT risk comparing LDL-C/HDL-C ratio >2.78 with LDL-C/HDL-C ratio ≤2.78 and significant dose-response relationship between LDL-C/HDL-C ratio and risk of high CIMT. The restricted cubic spline showed a significant nonlinear association between LDL-C/HDL-C ratio and the risk of high CIMT (pnon-linearity = 0.009). We identify a significant association between LDL-C/HDL-C ratio and the risk of high CIMT in the Chinese Cohort study. Future studies are needed to evaluate the effectiveness of reducing LDL-C/HDL-C ratio treatment on the development of high CIMT.Ganoderma neo-japonicum is a well-known medicinal mushroom in Asian countries. Caerulein However, scientific validations on its curative activities are confined to cirrhosis and diabetes. In this study, the anticancer properties of G. neo-japonicum were evaluated using cellular and computational models. The ethanolic extract (EtOH) with a promising inhibitory effect was fractionated into four different fractions hexane (Hex), chloroform (Chl), butanol (Btn), and aqueous (Aq). The active fractions were then subjected to cell apoptosis assessment and phytochemical profiling. Molecular docking was conducted to elucidate the affinity of selected constituents towards antiapoptotic Bcl-2 protein. The butanol fraction showed the highest antioxidant activities as well as total phenolic content. Both hexane and chloroform fractions exerted a potent cytotoxic effect on colonic carcinoma cells through the induction of apoptosis. Phytochemical analysis revealed that the chloroform fraction is terpenoid enriched whereas the hexane fraction comprises predominantly sterol constituents. Stellasterol and 1,25-dihydroxyvitamin D3 3-glycoside were demonstrated to have a high affinity towards Bcl-2 protein. Overall, G. neo-japonicum can be considered as a compelling therapeutic candidate for cancer treatment.

To explore the inter- and intra-observer reliability of Sonography-based Volume Computer Aided Diagnosis (SonoVCAD) in the display of 8 diagnostic planes of fetal echocardiography and to evaluate its efficiency.

Three-dimensional volume data sets of the 56 normal singleton fetuses were acquired from a 4-chamber view by using a volume probe. After processing the data sets by using SonoVCAD, 8 cardiac diagnostic planes were displayed automatically. Three doctors with different experiences of performing fetal echocardiography evaluated each diagnostic plane and the success rates of 8 diagnostic planes were calculated. Inter-observer and intra-observer reliabilities were estimated by Cohen's kappa statistics.

A total of 276 volume data sets acquired from the 56 normal fetuses were used for SonoVCAD analysis and display. The success rate of each diagnostic section was more than 90%, ranging from 90.6% to 99.6%. Among 276 volumes, 81.5% (225/276) of volumes were able to generate all 8 diagnostic views successfully.