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Adverse drug events (ADEs) during hospitalization are common. Insulin-related events, specifically, are frequent and preventable. At a tertiary children's hospital, we sought to reduce insulin-related ADEs by decreasing the median event rate of hyper- and hypoglycemia over a 12-month period.

Using Lean 6 σ methodology, we instituted a house-wide process change from a single-order ordering process to a pro re nata (PRN) standing order process. The standardized process included parameters for administration and intervention, enabling physician and nursing providers to practice at top of licensure. Automated technology during dose calculation promoted patient safety during dual verification processes. Control charts tracked rates of insulin-related ADEs, defined as hyperglycemia (glucose level >250 mg/dL) or hypoglycemia (glucose level <65 mg/dL). Events were standardized according to use rates of insulin on each nursing unit. The rates of appropriately timed insulin doses (within 30 minutes of a bloodStrategies that decrease the time from patient assessment to drug administration should be studied for other high-risk drugs.This longitudinal study examined the prospective association between toddler-mother attachment to adolescents' (n = 52; 34 boys; Mage = 13.22 years; 90% White) behavioral and neural responses during the evaluation of trustworthiness from unfamiliar, emotionally neutral faces. At 33 months, toddler-mother attachment status (secure vs insecure classification) was assessed using a modified Strange Situation procedure. Results revealed that attachment moderated the processing of trustworthiness facial cues. As faces became less trustworthy, adolescents with a secure (vs insecure) attachment history rated the faces as correspondingly less trustworthy and showed increasing (vs overall blunted) activation in brain regions involved in trustworthiness perception (i.e. bilateral amygdala, bilateral fusiform, right anterior insula and right posterior superior temporal sulcus). Findings suggest that a secure compared with insecure child-mother attachment in toddlerhood may be associated with greater capacity for, or openness to, processing potentially negative social information at both the behavioral and neural levels during adolescence.
Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population.

Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded.

Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID_Pos) and 39 were not. Compared with uninfected patients, COVID_Pos patients more frequently had additional causes of immunosuppression (50%versus 21%; P=.046) and were more often scheduled on the Monday-Wednesday-Friday (MWF) shift (86%versus 39%; P=.002). Moreover, COVID_Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients median 24 BAU/mL [interquartile range (IQR) 3-1163] versus 435 [99-2555]; P=.001 and lower neutralization titres [median 108 (IQR 17-224) versus 2483 (481-43908); P=.007]. Anti-S and neutralization antibody titres are correlated (r=0.92, P<.001). In multivariable analysis, an MWF schedule odds ratio [OR] 10.74 [95% confidence interval (CI) 1.9-93.5], P=.014 and anti-S IgG titres 1 month before the outbreak [<205 BAU/mL OR 0.046 (95% CI 0.002-0.29), P=.006] were independently associated with COVID-19 infection. selleck inhibitor None of the patients with anti-S IgG >284 BAU/mL got infected. Ten of 14 COVID_Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease.

Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.
Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19.Why do people often exhaust unregulated common (shared) natural resources but manage to preserve similar private resources? To answer this question, in this study we combine a neurobiological, economic and cognitive modeling approach. Using functional magnetic resonance imaging on 50 participants, we show that a sharp decrease of common and private resources is associated with deactivation of the ventral striatum, a brain region involved in the valuation of outcomes. Across individuals, when facing a common resource, ventral striatal activity is anticorrelated with resource preservation (less harvesting), whereas with private resources the opposite pattern is observed. This indicates that neural value signals distinctly modulate behavior in response to the depletion of common vs private resources. Computational modeling suggested that overharvesting of common resources was facilitated by the modulatory effect of social comparison on value signals. These results provide an explanation of people's tendency to over-exploit unregulated common natural resources.Brominated flame retardants (BFR) are molecules added to consumer products to reduce fire hazards. They were banned in North America and Europe because of their persistence and biomagnification. However, BFR are still released in the environment due to continued use of products manufactured before restriction, and from waste and recycling processes of those products. As a result, they remain sources of chronic environmental and human exposure worldwide. BFR are well-characterized endocrine disruptors. They have been associated with a wide range of alterations in endocrine and reproductive systems both in humans and experimental models in vivo and in vitro. Paradoxically, the effects of BFR on mammary glands, whose development and carcinogenesis are mainly under hormonal dependency are poorly known. There is increasing weight of evidence that exposure to endocrine disruptors promotes breast cancer, especially if the exposure occurs during sensitivity windows. For the mammary gland, these windows include the perinatal life, puberty, and pregnancy, as important remodeling of the organ happens during those periods. The peak of exposure to BFRs happened during late 1990s and beginning of 2000s in most countries. Women who were pregnant at that time are reaching menopause while their daughters are 20-30 years old. It is thus important to better understand the effects of BFRs on mammary gland development and breast cancer to determine whether these women are more at risk. Thus, this review aims to propose a comprehensive review of data reporting the effects of exposure to BFR on female endocrine and reproductive systems, with a particular focus on mammary gland development and of a potential increased risk of breast cancer.
To evaluate the effectiveness of Δ9-tetrahydrocannabinol (dronabinol [DRO]) as an add-on treatment in patients with refractory chronic pain (CP).

An exploratory retrospective analysis of 12-week data provided by the German Pain e-Registry on adult patients with treatment refractory CP who received DRO.

Between March 10, 2017, and June 30, 2019, the German Pain e-Registry collected information on 89,095 patients with pain, of whom 1,145 patients (1.3%) received DRO (53.8% female, mean ± standard deviation age 56.9 ± 10.6 years), and 70.0% documented use for the entire 12-week evaluation period. The average DRO daily dose was 15.8 ± 7.5 mg, typically in three divided doses (average DRO dose of 5.3 ± 2.1 mg). Average 24-hour pain intensity decreased from 46.3 ± 16.1 to 26.8 ± 18.7 mm on a visual analog scale (absolute visual analog scale difference -19.5 ± 17.3; P < 0.001). Among patients who completed follow-up, an improvement from baseline of at least 50% was documented for pain (46.5%), activities of daily living (39%), quality of life (31.4%), and sleep (35.3%). A total of 536 patients (46.8%) reported at least one of 1,617 drug-related adverse events, none of which were serious, and 248 patients (21.7%) stopped treatment. Over the 12-week period, 59.0% of patients reported a reduction of other pain treatments, and 7.8% reported a complete cessation of any other pharmacological pain treatments.

Add-on treatment with DRO in patients with refractory CP was well tolerated and associated with a significant improvement.
Add-on treatment with DRO in patients with refractory CP was well tolerated and associated with a significant improvement.Proteins isolated from natural sources can be composed of a mixture of isoforms with similar physicochemical properties that coexist in the final steps of purification. Yet, even where unverified, the assumed sequence is enforced throughout the structural studies. Herein, we propose a novel perspective to address the usually neglected sequence heterogeneity of natural products by integrating biophysical, genetic and structural data in our program SEQUENCE SLIDER. The aim is to assess the evidence supporting chemical composition in structure determination. Locally, we interrogate the experimental map to establish which side chains are supported by the structural data, and the genetic information relating sequence conservation is integrated into this statistic. Hence, we build a constrained peptide database, containing most probable sequences to interpret mass spectrometry data (MS). In parallel, we perform MS de novo sequencing with genomic-based algorithms to detect point mutations. We calibrated SLIDER with Gallus gallus lysozyme, whose sequence is unequivocally established and numerous natural isoforms are reported. We used SLIDER to characterize a metalloproteinase and a phospholipase A2-like protein from the venom of Bothrops moojeni and a crotoxin from Crotalus durissus collilineatus. This integrated approach offers a more realistic structural descriptor to characterize macromolecules isolated from natural sources.The DNA damage response (DDR) preserves the genetic integrity of the cell by sensing and repairing damages after a genotoxic stress. Translesion Synthesis (TLS), an error-prone DNA damage tolerance pathway, is controlled by PCNA ubiquitination. In this work, we raise the question whether TLS is controlled locally or globally. Using a recently developed method that allows to follow the bypass of a single lesion inserted into the yeast genome, we show that (i) TLS is controlled locally at each individual lesion by PCNA ubiquitination, (ii) a single lesion is enough to induce PCNA ubiquitination and (iii) PCNA ubiquitination is imperative for TLS to occur. More importantly, we show that the activation of the DDR that follows a genotoxic stress does not increase TLS at individual lesions. We conclude that unlike the SOS response in bacteria, the eukaryotic DDR does not promote TLS and mutagenesis.The life of RNA polymerase II (RNAPII) transcripts is shaped by the dynamic formation of mutually exclusive ribonucleoprotein complexes (RNPs) that direct transcript biogenesis and turnover. A key regulator of RNA metabolism in the nucleus is the scaffold protein ARS2 (arsenic resistance protein 2), bound to the cap binding complex (CBC). We report here that alternative splicing of ARS2's intron 5, generates cytoplasmic isoforms that lack 270 amino acids from the N-terminal of the protein and are functionally distinct from nuclear ARS2. Switching of ARS2 isoforms within the CBC in the cytoplasm has dramatic functional consequences, changing ARS2 from a NMD inhibitor to a NMD promoter that enhances the binding of UPF1 to NCBP1 and ERF1, favouring SURF complex formation, SMG7 recruitment and transcript degradation. ARS2 isoform exchange is also relevant during arsenic stress, where cytoplasmic ARS2 promotes a global response to arsenic in a CBC-independent manner. We propose that ARS2 isoform switching promotes the proper recruitment of RNP complexes during NMD and the cellular response to arsenic stress.
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