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In unadjusted analyses, RBC transfusion was associated with an increased thrombosis risk [HR = 1.3 (95% CI 1.23-1.36)]. After adjustment for surgical procedures, age, sex, hospital, and comorbidities, no association between RBC transfusion on risk of venous and arterial thrombosis was found [HR 1.0 (95% CI 0.96-1.05)]. Thus, RBC transfusion does not appear to be an important risk factor for thrombosis in most hospitalized patients.

The preference for immediate rewards and high sensation seeking are both potent risk factors for alcohol use disorder (AUD), but how they interact during intoxication is poorly understood. To model decision making linked to AUD risk, we tested heavy drinkers for impulsive choice (delay discounting with alcoholmoney or moneymoney) and behavioral sensation seeking using a novel odor choice task. Laboratory tasks measured actual behavior with real contingencies. Our goals were to determine, in heavy drinkers, (i) alcohol's effects on delay discounting, and (ii) how AUD risk factors relate to delay discounting, and (iii) how delay discounting with alcohol choices compares with strictly monetary choices.

Thirty-five heavy drinkers (≥2 binges per month; age=22.8±2.2; 20 male; 5.8±2.3 drinks/drinking day) performed cross-commodity discounting (CCD) of immediate alcohol vs. delayed money, a monetary delay discounting (DD), and behavioral sensation-seeking tasks. CCD and DD were performed while sober and during cokers-consistent with models highlighting high novelty/sensation-seeking AUD subtypes. Discounting behavior overall appears to be a generalized process, and relatively stable across methods, repeated testing, and intoxication. These findings further support the utility of behavioral tasks in uncovering key behavioral phenotypes in AUD.

Alcohol increased impulsive alcohol choice in high sensation seekers, suggesting an interaction that may underlie impaired control of drinking, at least in a subset of heavy drinkers-consistent with models highlighting high novelty/sensation-seeking AUD subtypes. Discounting behavior overall appears to be a generalized process, and relatively stable across methods, repeated testing, and intoxication. CC-92480 ic50 These findings further support the utility of behavioral tasks in uncovering key behavioral phenotypes in AUD.

To describe the prevalence of malnutrition risk and pain in older hospital patients and characterise the association between these two problems.

The study includes a secondary data analysis of data collected in two cross-sectional studies. Data collection was performed in 2017 and 2018 using a standardised and tested questionnaire. The study protocol was approved by an ethical committee.

Data from 3406 patients were analysed. Among the participants, 24.6% of the patients were at risk of malnutrition, and 59.6% of the patients reported feeling pain. A significantly higher number of patients with pain (26.4%) were at risk of malnutrition than patients without pain (22.1%). The multivariate logistic regression analysis showed that patients with severe/very severe or unbearable pain were 1.439 times more likely to develop a risk of malnutrition than patients without pain. Patients with cancer or diseases of the digestive system were twice as likely to develop malnutrition than those without these diseases.

The results of this study show that older patients with severe pain are at higher risk of developing a risk of malnutrition than those without pain, although the study design (cross-sectional) does not imply causality. Therefore, special efforts should be made to assess pain in these patients to reduce the negative consequences of this pain, such as malnutrition.

The results of this study show that older patients with severe pain are at higher risk of developing a risk of malnutrition than those without pain, although the study design (cross-sectional) does not imply causality. Therefore, special efforts should be made to assess pain in these patients to reduce the negative consequences of this pain, such as malnutrition.Tolerance to prolonged water deficit occurs along a continuum in plants, with dehydration tolerance (DhT) and desiccation tolerance (DT) representing some of the most extreme adaptations to water scarcity. Although DhT and DT presumably vary among individuals of a single species, this variability remains largely unstudied. Here, we characterized expression dynamics throughout a dehydration-rehydration time-course in six diverse genotypes of the dioecious liverwort Marchantia inflexa. We identified classical signatures of stress response in M. inflexa, including major changes in transcripts related to metabolism, expression of LEA and ELIP genes, and evidence of cell wall remodeling. However, we detected very little temporal synchronization of these responses across different genotypes of M. inflexa, which may be related to genotypic variation among samples, constitutive expression of dehydration-associated transcripts, the sequestration of mRNAs in ribonucleoprotein partials prior to drying, or the lower tolerance of M. inflexa relative to most bryophytes studied to date. Our characterization of intraspecific variation in expression dynamics suggests that differences in the timing of transcriptional adjustments contribute to variation among genotypes, and that developmental differences impact the relative tolerance of meristematic and differentiated tissues. This work highlights the complexity and variability of water stress tolerance, and underscores the need for comparative studies that seek to characterize variation in DT and DhT.

Checkpoint inhibitors enhance T-lymphocyte-mediated antitumor responses, resulting in increased survival for patients with neoplastic disease. However, a subset of patients receiving checkpoint inhibitor therapy may experience adverse complications that include the development of autoimmune conditions, such as thrombotic thrombocytopenic purpura (TTP). Given the potential etiologic differences of checkpoint inhibitor-related autoimmunity, TTP that develops in the presence of checkpoint inhibitors may be refractory to current treatment methods and therefore may require additional treatment and prognostic consideration.

Herein, we describe the unique clinical course of a patient who was treated with the combined checkpoint inhibitors nivolumab and ipilimumab for Stage IV malignant melanoma, who subsequently developed TTP. Unlike many patients with TTP, this patient failed to develop a sustained response to therapeutic plasma exchange. Additional use of steroids, anti-CD20, and plasma cell-targeting therapy (bortezomib) also failed to substantially reverse thrombocytopenia in a sustainable fashion. During this time, her melanoma progressed, and she ultimately succumbed.

This case illustrates not only that TTP may be a potential complication of checkpoint inhibitor therapy, but also that TTP developing in this setting may result in an unpredictable response to commonly employed TTP treatment modalities. Ultimately, checkpoint inhibitor-related TTP may require distinct management approaches and prognostic considerations.

This case illustrates not only that TTP may be a potential complication of checkpoint inhibitor therapy, but also that TTP developing in this setting may result in an unpredictable response to commonly employed TTP treatment modalities. Ultimately, checkpoint inhibitor-related TTP may require distinct management approaches and prognostic considerations.

The number of case reports of insulin autoimmune syndrome (IAS) induced by methimazole (MMI) is increasing. The purpose of this study is to explore the clinical characteristics and provide a scientific reference for clinical diagnosis, treatment and prevention.

The literature on IAS cases and case series induced by MMI in Chinese and English was collected for retrospective analysis.

A total of 106 patients (males 33, females 73) were described in the Chinese and English literature. The median age of patients with IAS induced by MMI was 37years (range 15-76) occurring during both regular and irregular MMI therapy or after resumption of medication. The onset of symptoms occurred at night or early morning, within days in some and up to 6months in others; the symptoms were neuropathic in 65.31% and related to the autonomic nervous system in 33.67%. Blood glucose concentration in samples presumably taken during the hypoglycaemic phase was 1.7mmol/L (median; range 0.03-4.7); insulin concentrations were elevated ≥100mU/L (ref range) and associated with low C-peptide levels (<10μg/L; ref range). Tests for IgG insulin autoantibodies (IAA) were positive in 104 patients (98.02%) and negative in two patients (1.98%). The 75-g oral glucose tolerance test (OGTT) showed impaired glucose tolerance and diabetic curves. Pancreatic imaging was unremarkable on computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Withdrawal of MMI alone or with corticosteroid treatment reduced hypoglycaemic episodes within days to 3months. IAA decreased and became negative in 3months (median; range 1-12). Follow-up showed no recurrent hypoglycaemic episodes at 5months (median; range 1-60).

Methimazole-induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment that should be treated promptly.

Methimazole-induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment that should be treated promptly.

Genome-wide association studies (GWAS) of alcohol dependence (AD) and related phenotypes have identified multiple loci, but the functional variants underlying the loci have in most cases not been identified. Noncoding variants can influence phenotype by affecting gene expression; for example, variants in the 3' untranslated regions (3'UTR) can affect gene expression posttranscriptionally.

We adapted a high-throughput assay known as PASSPORT-seq (parallel assessment of polymorphisms in miRNA target sites by sequencing) to identify among variants associated with AD and related phenotypes those that cause differential expression in neuronal cell lines. Based upon meta-analyses of alcohol-related traits in African American and European Americans in the Collaborative Study on the Genetics of Alcoholism, we tested 296 single nucleotide polymorphisms (SNPs with meta-analysis p values≤0.001) that were located in 3'UTRs.

We identified 60 SNPs that affected gene expression (false discovery rate [FDR]<0.05) in SH-SY5Y cells and 92 that affected expression in SK-N-BE(2) cells. Among these, 30 SNPs altered RNA levels in the same direction in both cell lines. Many of these SNPs reside in the binding sites of miRNAs and RNA-binding proteins and are expression quantitative trait loci of genes including KIF6,FRMD4A,CADM2,ADD2,PLK2, and GAS7.

The SNPs identified in the PASSPORT-seq assay are functional variants that might affect the risk for AD and related phenotypes. Our study provides insights into gene regulation in AD and demonstrates the value of PASSPORT-seq as a tool to screen genetic variants in GWAS loci for one potential mechanism of action.

The SNPs identified in the PASSPORT-seq assay are functional variants that might affect the risk for AD and related phenotypes. Our study provides insights into gene regulation in AD and demonstrates the value of PASSPORT-seq as a tool to screen genetic variants in GWAS loci for one potential mechanism of action.