A person-centered approach to understanding negative reinforcement drinking among first year college students [post-print]

The current study used a person-centered approach (i.e. latent profile analysis) to identify distinct types of college student drinkers based on the predictions of motivational, social learning, and stress and coping theories of maladaptive drinking. A large sample (N = 844; 53% female) of first-year undergraduates from two institutions, public and private, who reported consuming one or more drinks in the last three months completed measures of depressive and anxiety symptoms, positive alcohol-outcome expectancies, negative life events, social support, drinking motives, drinking level and drinking-related problems. Latent profile analysis revealed a small subgroup of individuals (n = 81, 9%) who conformed to the anticipated high-risk profile; specifically, this group demonstrated high levels of negative affect, coping motives, drinks per week, and drinking-related problems. However, additional groups emerged that showed patterns inconsistent with the proposed vulnerability profile (e.g., high negative affect, positive expectancies, and negative life events, but relatively low drinking levels). Findings from our person-centered approach showing the presence of groups both consistent and inconsistent with the predictions of motivational, social learning, and stress and coping theories highlight the need to identify and target certain college students for prevention and intervention of negative affect-related drinking

fMRI Response During Figural Memory Task Performance in College Drinkers [pre-print]

Rationale: 18-25-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. Objective: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy drinking college students. We predicted that heavy drinkers would show worse memory performance and increased frontal/parietal activation and decreased hippocampal response during encoding. Methods: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, ages 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). Results: There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed: 1) greater BOLD response during correct encoding in right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; 2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and 3) less bilateral insula response during correct recognition (clusters \u3e10,233ul, p Conclusions: This is the first investigation of the neural substrates of figural memory among heavy drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers

Kohn–Sham energy decomposition for molecules in a magnetic field

We study the total molecular electronic energy and its Kohn–Sham components within the framework of magnetic-field density-functional theory (BDFT), an alternative to current-dependent density-functional theory (CDFT) for molecules in the presence of magnetic fields. For a selection of closed-shell dia- and paramagnetic molecules, we investigate the dependence of the total electronic energy and its Kohn–Sham components on the magnetic field. Results obtained from commonly used density-functional approximations are compared with those obtained from Lieb optimizations based on magnetic-field dependent relaxed coupled-cluster singles-and-doubles (CCSD) and second-order Møller–Plesset (MP2) densities. We show that popular approximate exchange–correlation functionals at the generalized-gradient-approximation (GGA), meta-GGA, and hybrid levels of theory provide a good qualitative description of the electronic energy and its Kohn–Sham components in a magnetic field—in particular, for the diamagnetic molecules. The performance of Hartree–Fock theory, MP2 theory, CCSD theory and BDFT with different exchange–correlation functionals is compared with coupled-cluster singles-doubles-perturbative-triples (CCSD(T)) theory for the perpendicular component of the magnetizability. Generalizations of the TPSS meta-GGA functional to systems in a magnetic field work well—the cTPSS functional, in particular, with a current-corrected kinetic-energy density, performs excellently, providing an accurate and balanced treatment of dia- and paramagnetic systems and outperforming MP2 theory

Enhanced Protein Homeostasis Mechanisms in Naked Mole Rats Cells

Phylogenic studies suggest that cells from long-lived species are more resistant to a variety of stressors than short-lived species. However, there is little information on the cellular mechanisms that give rise to increased resistance to stress. Our previous studies have shown that liver proteins from a long-lived species have lower levels of protein ubiquitination which is associated with increased proteasome activity, suggesting that mechanisms of protein quality control could play a critical role in assuring longevity of long-lived species. In this study, we evaluated whether autophagy and heat shock chaperones proteins (HSPs) are associated with longevity in rodents using skin fibroblasts isolated from mice and naked mole rats (NMR); two species that are similar in body size but differ almost 10 fold in longevity. Our results indicate that macroautophagy induced by serum-starvation is significantly enhanced in NMR compared to mouse which correlates with an inhibition of the mTOR pathway and increased LC3 conversion. We also found that several HSPs (e.g., Hsp90, Hsp70, Hsp40, Hsp 27) were significantly higher at both basal and after heat shock conditions. These observations suggest that NMR, a long-lived species, has increased mechanisms to ensure protein quality (autophagy and HSPs) and support the idea that protein homeostasis could play an important role in promoting longevity

SupportPrim-a computerized clinical decision support system for stratified care for patients with musculoskeletal pain complaints in general practice: study protocol for a randomized controlled trial.

BACKGROUND: Musculoskeletal disorders represented 149 million years lived with disability world-wide in 2019 and are the main cause of years lived with disability worldwide. Current treatment recommendations are based on "one-size fits all" principle, which does not take into account the large degree of biopsychosocial heterogeneity in this group of patients. To compensate for this, we developed a stratified care computerized clinical decision support system for general practice based on patient biopsychosocial phenotypes; furthermore, we added personalized treatment recommendations based on specific patient factors to the system. In this study protocol, we describe the randomized controlled trial for evaluating the effectiveness of computerized clinical decision support system for stratified care for patients with common musculoskeletal pain complaints in general practice. The aim of this study is to test the effect of a computerized clinical decision support system for stratified care in general practice on subjective patient outcome variables compared to current care. METHODS: We will perform a cluster-randomized controlled trial with 44 general practitioners including 748 patients seeking their general practitioner due to pain in the neck, back, shoulder, hip, knee, or multisite. The intervention group will use the computerized clinical decision support system, while the control group will provide current care for their patients. The primary outcomes assessed at 3 months are global perceived effect and clinically important improvement in function measured by the Patient-Specific Function Scale (PSFS), while secondary outcomes include change in pain intensity measured by the Numeric Rating Scale (0-10), health-related quality of life (EQ-5D), general musculoskeletal health (MSK-HQ), number of treatments, use of painkillers, sick-leave grading and duration, referral to secondary care, and use of imaging. DISCUSSION: The use of biopsychosocial profile to stratify patients and implement it in a computerized clinical decision support system for general practitioners is a novel method of providing decision support for this patient group. The study aim to recruit patients from May 2022 to March 2023, and the first results from the study will be available late 2023. TRIAL REGISTRATION: The trial is registered in ISRCTN 11th of May 2022: 14,067,965

Sex differential in mortality trends of old-aged Danes: a nation wide study of age, period and cohort effects

Objective Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades. Methods Age-period-cohort study of mortality for all Danish women and men aged 79–98 during the period 1949–2006. Outcome measures Relative risks for deaths and second order differences for exploration of the nonlinear variation. Results Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models. Conclusions Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects

Mouse Cognition-Related Behavior in the Open-Field: Emergence of Places of Attraction

Spatial memory is often studied in the Morris Water Maze, where the animal's spatial orientation has been shown to be mainly shaped by distal visual cues. Cognition-related behavior has also been described along “well-trodden paths”—spatial habits established by animals in the wild and in captivity reflecting a form of spatial memory. In the present study we combine the study of Open Field behavior with the study of behavior on well-trodden paths, revealing a form of locational memory that appears to correlate with spatial memory. The tracked path of the mouse is used to examine the dynamics of visiting behavior to locations. A visit is defined as either progressing through a location or stopping there, where progressing and stopping are computationally defined. We then estimate the probability of stopping at a location as a function of the number of previous visits to that location, i.e., we measure the effect of visiting history to a location on stopping in it. This can be regarded as an estimate of the familiarity of the mouse with locations. The recently wild-derived inbred strain CZECHII shows the highest effect of visiting history on stopping, C57 inbred mice show a lower effect, and DBA mice show no effect. We employ a rarely used, bottom-to-top computational approach, starting from simple kinematics of movement and gradually building our way up until we end with (emergent) locational memory. The effect of visiting history to a location on stopping in it can be regarded as an estimate of the familiarity of the mouse with locations, implying memory of these locations. We show that the magnitude of this estimate is strain-specific, implying a genetic influence. The dynamics of this process reveal that locations along the mouse's trodden path gradually become places of attraction, where the mouse stops habitually