PLIN1 encodes perilipin-1, which coats lipid droplets in adipocytes and is involved in droplet formation, triglyceride storage, and lipolysis. Rare PLIN1 frameshift variants that extend the translated protein have been described to cause lipodystrophy.

This work aimed to test whether PLIN1 protein-truncating variants (PTVs) cause lipodystrophy in a large population-based cohort.

We identified individuals with PLIN1 PTVs in individuals with exome data in the UK Biobank. We performed gene-burden testing for individuals with PLIN1 PTVs. We replicated the associations using data from the T2D Knowledge portal. We performed a phenome-wide association study using publicly available association statistics. A total of 362 791 individuals in the UK Biobank, a population-based cohort, and 43 125 individuals in the T2D Knowledge portal, a type 2 diabetes (T2D) case-control study, were included in the analyses. Main outcome measures included 22 diseases and traits relevant to lipodystrophy.

The 735 individuals with PLIN1 PTVs had a favorable metabolic profile. These individuals had increased high-density lipoprotein cholesterol (0.12 mmol/L; 95% CI, 0.09 to 0.14, P = 2 × 10-18), reduced triglycerides (-0.22 mmol/L; 95% CI, -0.29 to -0.14, P = 3 × 10-11), reduced waist-to-hip ratio (-0.02; 95% CI, -0.02 to -0.01, P = 9 × 10-12), and reduced systolic blood pressure (-1.67 mm Hg; 95% CI, -3.25 to -0.09, P = .05). These associations were consistent in the smaller T2D Knowledge portal cohort. In the UK Biobank, PLIN1 PTVs were associated with reduced risk of myocardial infarction (odds ratio [OR] = 0.59; 95% CI, 0.35 to 0.93, P = .02) and hypertension (OR = 0.85; 95% CI, 0.73 to 0.98, P = .03), but not T2D (OR = 0.99; 95% CI, 0.63-1.51, P = .99).

Our study suggests that PLIN1 haploinsufficiency causes a favorable metabolic profile and may protect against cardiovascular disease.

Our study suggests that PLIN1 haploinsufficiency causes a favorable metabolic profile and may protect against cardiovascular disease.

as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed.

to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands.

this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality.

a total of 1,376 patients in the first wave (median age 78years, 60% male) and 946 patients in the second wave (median age 79years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval 28-51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty.

compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.

compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder linked to cognitive decline. To understand how specific neuronal circuits are impaired in AD, we have used optogenetic and electrophysiological approaches to reveal the functional changes between prefrontal cortex (PFC) and basal forebrain (BF), 2 key regions controlling cognitive processes, in a tauopathy mouse model. We found that the glutamatergic synaptic responses in BF cholinergic neurons from P301S Tau mice (6-8 months old) were markedly diminished. The attenuated long-range PFC to BF pathway in the AD model significantly increased the failure rate of action potential firing of BF cholinergic neurons triggered by optogenetic stimulations of glutamatergic terminals from PFC. In contrast, the projection from PFC to other regions, such as amygdala and striatum, was largely unaltered. On the other hand, optogenetic stimulation of cholinergic terminals from BF induced a persistent reduction of the excitability of PFC pyramidal neurons from Tau mice, instead of the transient reduction exhibited in wild-type mice. Taken together, these data have revealed a selective aberration of the pathway between PFC pyramidal neurons and BF cholinergic neurons in a tauopathy mouse model. This circuit deficit may underlie the loss of attention and executive function in AD.Since the basic biochemical mechanisms of photosynthesis are remarkably conserved among plant species, genetic modification approaches have so far been the main route to improve the photosynthetic performance of crops. Yet, phenotypic variation observed in wild species and between varieties of crop species implies there is standing natural genetic variation for photosynthesis, offering a largely unexplored resource to use for breeding crops with improved photosynthesis and higher yields. The reason this has not yet been explored is that the variation probably involves thousands of genes, each contributing only a little to photosynthesis, making them hard to identify without proper phenotyping and genetic tools. This is changing, though, and increasingly studies report on quantitative trait loci for photosynthetic phenotypes. So far, hardly any of these quantitative trait loci have been used in marker assisted breeding or genomic selection approaches to improve crop photosynthesis and yield, and hardly ever have the underlying causal genes been identified. We propose to take the genetics of photosynthesis to a higher level, and identify the genes and alleles nature has used for millions of years to tune photosynthesis to be in line with local environmental conditions. We will need to determine the physiological function of the genes and alleles, and design novel strategies to use this knowledge to improve crop photosynthesis through conventional plant breeding, based on readily available crop plant germplasm. In this work, we present and discuss the genetic methods needed to reveal natural genetic variation, and elaborate on how to apply this to improve crop photosynthesis.

The purpose of this study is to develop a standard operational and distributional weighted workload model that is applicable across an integrated, diverse healthcare system. This model aims to not only demonstrate the operational intensity of pharmacy practice but also to inform opportunities to decrease waste, increase efficiency, facilitate growth, and demonstrate value across operational and distributional pharmacy services.

Time studies were conducted at 8 hospitals within the UNC Health system to objectively measure time spent within each operational process in order to create a system-wide weighted workload model. Time study results informed the development of a system-wide weighted workload model. Data from December 29, 2019, through December 26, 2020, was then applied to this weighted workload model. With this model, acute care hospital and infusion center operational areas were compared in thousands of combinations within single operational areas and across any and all operational areas by dispense code, weighted work, and ratio of weighted work to total sum of dispenses at each site.

The model successfully achieved the objective to develop a standard operational weighted workload model that is applicable across the integrated, diverse care system. This model provides a foundation for UNC Health to further productivity measurement and fills a gap in the literature by offering a novel method of developing a system-level operational workload model that can be used to evaluate and compare operational workloads across health-system sites.

The model successfully achieved the objective to develop a standard operational weighted workload model that is applicable across the integrated, diverse care system. This model provides a foundation for UNC Health to further productivity measurement and fills a gap in the literature by offering a novel method of developing a system-level operational workload model that can be used to evaluate and compare operational workloads across health-system sites.

The association of cognitive function with symptoms of psychological distress during the coronavirus 2019 (COVID-19) pandemic or adherence to COVID-19 protective health behaviors is not well understood.

We examined 2,890 older women from the Women’s Health Initiative cohort. Pre-pandemic (i.e., within 12 months prior to pandemic onset) and peri-pandemic global cognitive function scores were assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Anxiety, stress, and depressive symptom severity during the pandemic were assessed using validated questionnaires. We examined adherence to protective behaviors that included safe hygiene, social distancing, mask wearing, and staying home. Multivariable models were adjusted for age, race, ethnicity, education, region of residence, alcohol intake, and comorbidities.

Every five-point lower pre-pandemic TICS-m score was associated with 0.33-point mean higher (95% CI, 0.20,0.45) perceived stress, and 0.20-point mean higher (95% CI, 0.07,0.32) dtive decline; and 3) lower global cognitive function during the pandemic was associated with lower odds of practicing safe hygiene.Genetic variations affecting dopaminergic neuromodulation such as the DRD2/ANKK1 and the COMT Val158Met polymorphisms contribute to goal-directed behavior that requires a balance between stabilization and updating of current states and behaviors. Dopamine is also thought to be relevant for encoding of surprise signals to sensory input and adaptive learning. A link between goal-directed behavior and learning from surprise is therefore plausible. In the present fMRI study, we investigated whether DRD2 and COMT polymorphisms are related to behavioral responses and neural signals in the caudate nucleus and dlPFC during updating or stabilizing internal models of predictable digit sequences. To-be-detected switches between sequences and to-be-ignored digit omissions within a sequence varied by information-theoretic quantities of surprise and entropy. We found that A1 noncarriers and Val-carriers showed a lower response threshold along with increased caudate and dlPFC activation to surprising switches compared with A1-carriers and Met-homozygotes, whose dlPFC activity increased with decreasing switch surprise.