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Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction.Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values −4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI.Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10−8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis.Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.

Age-specific resources in human MRI mitigate processing biases that arise from structural changes across the lifespan. There are fewer age-specific resources for preclinical imaging, and they only represent developmental periods rather than adulthood. Since rats recapitulate many facets of human aging, it was hypothesized that brain volume and each tissue's relative contribution to total brain volume would change with age in the adult rat. Data from a longitudinal study of rats at 3, 5, 11, and 17 months old were used to test this hypothesis. Tissue volume was estimated from high resolution structural images using a priori information from tissue probability maps. However, existing tissue probability maps generated inaccurate gray matter probabilities in subcortical structures, particularly the thalamus. To address this issue, gray matter, white matter, and CSF tissue probability maps were generated by combining anatomical and signal intensity information. The effects of age on volumetric estimations were then assessed with mixed-effects models. Results showed that herein estimation of gray matter volumes better matched histological evidence, as compared to existing resources. All tissue volumes increased with age, and the tissue proportions relative to total brain volume varied across adulthood. Consequently, a set of rat brain templates and tissue probability maps from across the adult lifespan is released to expand the preclinical MRI community's fundamental resources.

Objective: Immune checkpoints inhibitors are promising and wide-spread agents in anti-cancer therapy. However, despite their efficacy, these agents could cause cardiotoxicity, a rare but life-threatening event. In addition, there are still no well-described predictive factors for the development of immune-related adverse events and information on high risk groups. According to known experimental studies we hypothesized that cardiovascular diseases may increase myocardial PD-L1 expression, which could be an extra target for Checkpoint inhibitors and a potential basis for complications development.Methods: We studied patterns of myocardial PD-L1 expression in non-cancer-related cardiovascular diseases, particularly ischemic heart disease (n = 12) and dilated cardiomyopathy (n = 7), compared to patients without known cardiovascular diseases (n = 10) using mouse monoclonal anti-PD-L1 antibody (clone 22C3, 1:50, Dako). Correlation between immunohistochemical data and echocardiographic parameters was assessed. Statistical analyses were performed using R Statistical Software—R studio version 1.3.1093.Results: In the myocardium of cardiac patients, we found membranous, cytoplasmic, and endothelial expression of PD-L1 compared to control group. In samples from patients with a history of myocardial infarction, PD-L1 membrane and endothelial expression was more prominent and frequent, and cytoplasmic and intercalated discs staining was more localized. In contrast, samples from patients with dilated cardiomyopathy displayed very faint endothelial staining, negative membrane staining, and more diffuse PD-L1 expression in the cytoplasm and intercalated discs. In samples from the non-cardiac patients, no convincing PD-L1 expression was observed. Moreover, we discovered a significant negative correlation between PD-L1 expression level and left ventricular ejection fraction and a positive correlation between PD-L1 expression level and left ventricular end-diastolic volume.Conclusions: The present findings lay the groundwork for future experimental and clinical studies of the role of the PD-1/PD-L1 pathway in cardiovascular diseases. Further studies are required to find patients at potentially high risk of cardiovascular adverse events associated with immune checkpoint inhibitors therapy.

The COVID-19 pandemic has caused a dramatic reshaping of passenger risk perception for airline industry. The sharp increase in risk aversion by air passenger has caused a disastrous impact on the tourism service industry, particularly airline industry. Although the existing literature has provided a lot of studies on the impact of the pandemic on travel industry, there are very few studies discussing the impact of change in passenger risk perception on the stock market performance of airline industry. This study considers two types of airline companies, full-service and low-cost. In order to overcome the traditional problem of the Chow test, Quandt–Andrews test is used to identify structural change points during the pandemic in the stock prices of United States airline companies. The result shows that an industry-wide structural change in the stock market performance indeed is found to take place during the pandemic for United States airline companies. Meanwhile, no significant difference is found in the structural change date between the two types of airline companies. The selected airline companies are found to be clustered toward the end of 2020 (November and December) in their structural change dates. Although the strike of the COVID-19 pandemic on airline industry has proven to be widespread and profound, our investigation implies that air passengers have gradually adapted to the new normal of travel activities at some level and partly rebuild their sense of safety under the strict epidemic-control measures.

Clinical populations have memory deficits linked to sleep oscillations that can potentially be treated with sleep medications. Eszopiclone and zolpidem (two non-benzodiazepine hypnotics) both enhance sleep spindles. Zolpidem improved sleep-dependent memory consolidation in humans, but eszopiclone did not. These divergent results may reflect that the two drugs have different effects on hippocampal ripple oscillations, which correspond to the reactivation of neuronal ensembles that represent previous waking activity and contribute to memory consolidation. We used extracellular recordings in the CA1 region of rats and systemic dosing of eszopiclone and zolpidem to test the hypothesis that these two drugs differentially affect hippocampal ripples and spike activity. We report evidence that eszopiclone makes ripples sparser, while zolpidem increases ripple density. In addition, eszopiclone led to a drastic decrease in spike firing, both in putative pyramidal cells and interneurons, while zolpidem did not substantially alter spiking. These results provide an explanation of the different effects of eszopiclone and zolpidem on memory in human studies and suggest that sleep medications can be used to regulate hippocampal ripple oscillations, which are causally linked to sleep-dependent memory consolidation.

To study the aging human brain requires significant resources and time. Thus, mice models of aging can provide insight into changes in brain biological functions at a fraction of the time when compared to humans. This study aims to explore changes in dopamine D1 and D2 receptor availability and of gray matter density in striatum during aging in mice and to evaluate whether longitudinal imaging in mice may serve as a model for normal brain aging to complement cross-sectional research in humans. Mice underwent repeated structural magnetic resonance imaging (sMRI), and [11C]Raclopride and [11C]SCH23390 positron emission tomography (PET) was performed on a subset of aging mice. PET and sMRI data were analyzed by binding potential (BPND), voxel- and tensor-based morphometry (VBM and TBM, respectively). Longitudinal PET revealed a significant reduction in striatal BPND for D2 receptors over time, whereas no significant change was found for D1 receptors. sMRI indicated a significant increase in modulated gray matter density (mGMD) over time in striatum, with limited clusters showing decreased mGMD. Mouse [11C]Raclopride data is compatible with previous reports in human cross-sectional studies, suggesting that a natural loss of dopaminergic D2 receptors in striatum can be assessed in mice, reflecting estimates from humans. No changes in D1 were found, which may be attributed to altered [11C]SCH23390 kinetics in anesthetized mice, suggesting that this tracer is not yet able to replicate human findings. sMRI revealed a significant increase in mGMD. Although contrary to expectations, this increase in modulated GM density may be attributed to an age-related increase in non-neuronal cells.

This brief report assessed the psychometric validity and gender invariance of the School Burnout Inventory (SBI) –a measure of students’ exhaustion, cynicism, and inadequacy– in a convenience sample of 972 high school Chilean students ranging between 12 and 18 years old. The results showed that: (1) the SBI produces adequate scores in terms of reliability; (2) two models (one solution of three related factors and one of second-order and three first-order factors) fitted adequately fit to our sample and was invariant across gender; and (3) the SBI scores were significantly related to other related constructs (i.e., study-related emotions, academic psychological capital, and academic engagement). Overall, the SBI was found to be a reliable and valid inventory to assess school burnout in Chilean high school students.

Background: The diagnosis of the behavioral variant of frontotemporal dementia (bvFTD) can be especially challenging and is relatively underdiagnosed. There is scarce information on training and attitudes from care providers facing bvFTD in settings with limited resources. We aim to describe clinical knowledge and attitudes facing bvFTD from neurologists, psychiatrists, and residents in Peru.Methods: Potential participants received invitations by email to complete an online questionnaire. In addition, we reviewed 21 curricula from undergraduate medical schools' programs offered by the main schools of medicine in Peru during 2020 and 2021.Results: A total of 145 participants completed the survey. The responders were neurologists (51%), psychiatrists (25%), and residents in neurology or psychiatry (24%). Only 26% of the respondents acknowledged receiving at least one class on bvFTD in undergraduate medical training, but 66.6% received at least some training during postgraduate study. Participants identified isolated supportive symptoms for bvFTD; however, only 25% identified the possible criteria and 18% the probable bvFTD criteria. They identified MoCA in 44% and Frontal Assessment Battery (39%) as the most frequently used screening test to assess bvFTD patients. Memantine and Acetylcholinesterase inhibitors were incorrectly indicated by 40.8% of participants. Seventy six percentage of participants indicated that they did not provide education and support to the caregiver. The dementia topic was available on 95.2%, but FTD in only 19%.Conclusion: Neuropsychiatry medical specialists in Peru receive limited training in FTD. Their clinical attitudes for treating bvFTD require appropriate training focused on diagnostic criteria, assessment tools, and pharmacological and non-pharmacological management.

Cancer research is deficient in Colombia and efforts and resources diverted due to the COVID-19 pandemic could worsen the situation. We explore the impact of the pandemic on cancer research funding, output, and conduct. We sought information at national level and used the experience of an academic reference center to contrast the impact at institutional level. We searched databases and official documents of national governmental institutions, trial registries, hospital registries, and the Web of Science. We interviewed principal investigators (PIs) to retrieve information on the conduct of cancer research. A decline in resource availability and new proposals was observed at the national level with a shift to COVID-19 related research. However, at institutional level there was no decline in the number of cancer research proposals. The predominance of observational studies as opposed to the preponderance of clinical trials and basic science in high-income countries may be related to the lower impact at institutional level. Nevertheless, we found difficulties similar to previous reports for conducting research during the pandemic. PIs reported long recovery times and a great impact on research other than clinical trials, such as observational and qualitative studies. No significant impact on research output was observed. Alternatives to ensure research continuity such as telemedicine and remote data collection have scarcely been implemented given limited access and low technology literacy. In this middle-income setting the situation shows a notable dependency of international collaborations to develop research on COVID-19 and cancer and to overcome challenges for cancer research during the pandemic.

Background: The Parkinsonian [i.e., Parkinson's disease (PD)] gait disorder represents a therapeutical challenge with residual symptoms despite the use of deep brain stimulation of the subthalamic nucleus (STN DBS) and medical and rehabilitative strategies. The aim of this study was to assess the effect of different DBS modes as combined stimulation of the STN and substantia nigra (STN+SN DBS) and environmental rehabilitative factors as footwear on gait kinematics.Methods: This single-center, randomized, double-blind, crossover clinical trial assessed shod and unshod gait in patients with PD with medication in different DBS conditions (i.e., STIM OFF, STN DBS, and STN+SN DBS) during different gait tasks (i.e., normal gait, fast gait, and gait during dual task) and compared gait characteristics to healthy controls. Notably, 15 patients participated in the study, and 11 patients were analyzed after a dropout of four patients due to DBS-induced side effects.Results: Gait was modulated by both factors, namely, footwear and DBS mode, in patients with PD. Footwear impacted gait characteristics in patients with PD similarly to controls with longer step length, lower cadence, and shorter single-support time. Interestingly, DBS exerted specific effects depending on gait tasks with increased cognitive load. STN+SN DBS was the most efficient DBS mode compared to STIM OFF and STN DBS with intense effects as step length increment during dual task.Conclusion: The PD gait disorder is a multifactorial symptom, impacted by environmental factors as footwear and modulated by DBS. DBS effects on gait were specific depending on the gait task, with the most obvious effects with STN+SN DBS during gait with increased cognitive load.

Bone formation involves a complex crosstalk between endothelial cells (EC) and osteodifferentiating stem cells. This functional interplay is greatly mediated by the paracrine and autocrine action of soluble factors released at the vasculature-bone interface. This study elucidates the molecular and functional responses triggered by this intimate interaction. In this study, we showed that human dermal microvascular endothelial cells (HMEC) induced the expression of pro-angiogenic factors in stem cells from human exfoliated deciduous teeth (SHED) and sustain their osteo-differentiation at the same time. In contrast, osteodifferentiating SHED increased EC recruitment and promoted the formation of complex vascular networks. Moreover, HMEC enhanced anaerobic glycolysis in proliferating SHED without compromising their ability to undergo the oxidative metabolic shift required for adequate osteo-differentiation. Taken together, these findings provide novel insights into the molecular mechanism underlying the synergistic cooperation between EC and stem cells during bone tissue renewal.

Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer’s disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations.Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK’s Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results.Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 > 0.05; weighted median (WM), p = 0.337 > 0.05; inverse variance weighted (IVW), p = 0.471 > 0.05; simple mode, p = 0.454 > 0.05; weighted mode, p = 0.401 > 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 > 0.05; IVW, p = 0.0879 > 0.05; simple mode, p = 0.170 > 0.05; weighted mode, p = 0.110 > 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 < 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis.Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.

Physical activity is an important determinant of a healthy lifestyle. Regular participation in sports-related activities contributes to the maintenance of good psychophysiological and social health. Long-term physical activity has a positive impact on subjective well-being and can reduce stress. Karate is a specific physical activity which focuses on self-regulation and self-development; therefore, it may reduce impulsivity and improve self-control. Good self-control is also related to satisfaction with life and well-being. The presented study aimed to examine the possible intermediate impact of self-control and emotion regulation on the relationship between karate training and satisfaction with life. Fifty-eight karate practitioners and fifty-nine control subjects participated in the research. The Satisfaction With Life Scale and the Brief Self-Control Scale were applied in order to assess life satisfaction and the general level of self-control. The Emotion Regulation Questionnaire was used to assess suppression and reappraisal, both of which are distinct aspects of emotion regulation. The direct and indirect relationships between karate training and satisfaction with life were investigated using a linear regression model that included self-control, suppression and reappraisal as mediating variables. No direct effects of karate training on satisfaction with life were found, whereas karate training was indirectly associated with satisfaction with life via the indirect path that leads through self-control and reappraisal. This indicates that self-control and reappraisal fully mediate the impact of karate training on subjective well-being. Karate training can therefore play an important role in shaping volitional and personality characteristics, both of which contribute to increasing the well-being of trainees.

Vitamin D deficiency is a worldwide public health concern, which can be addressed with voluntary or mandatory food fortification. The aim of this study was to determine if branded food composition databases can be used to investigate voluntary fortification practices. A case study was conducted using two nationally representative cross-sectional datasets of branded foods in Slovenia, collected in 2017 and 2020, and yearly sales data. Using food labeling data we investigated prevalence of fortification and average vitamin D content, while nutrient profiling was used to investigate overall nutritional quality of the foods. In both datasets, the highest prevalence of vitamin D fortification was observed in meal replacements (78% in 2017; 100% in 2020) and in margarine, corresponding to high market share. Other food categories commonly fortified with vitamin D are breakfast cereals (5% in 2017; 6% in 2020), yogurts and their imitates (5% in 2017; 4% in 2020), and baby foods (18% in both years). The highest declared average content of vitamin D was observed in margarine and foods for specific dietary use (7–8 μg/100g), followed by breakfast cereals (4 μg/100g), while the average content in other foods was below 2 μg/100g. Only minor differences were observed between 2017 and 2020. Major food-category differences were also observed in comparison of the overall nutritional quality of the fortified foods; higher overall nutritional quality was only observed in fortified margarine. Our study showed that branded food composition databases are extremely useful resources for the investigation and monitoring of fortification practices, particularly if sales data can also be used. In the absence of mandatory or recommended fortification in Slovenia, very few manufacturers decide to add vitamin D, and even when this is the case, such products are commonly niche foods with lower market shares. We observed exceptions in imported foods, which can be subject to fortification policies introduced in other countries.

Objective: The aim of this study was to present some cases of acute vertigo potentially related to the coronavirus disease 2019 (COVID-19) vaccine and review the available literature about cochleovestibular dysfunction after the COVID-19 vaccination.Methods: In the period from May to July 2021, we evaluated 33 patients (mean age 54.3 ± 14.1) with “acute vertigo” post COVID-19 vaccination. A detailed medical history was taken on comorbidities, types of vaccines received, and symptoms associated. All patients underwent otoneurological evaluation, such as head impulse test, nystagmus evaluation, test of skew (HINTS) examination. Head shaking test-induced nystagmus, hyperventilation-induced nystagmus, and parossistic positional nystagmus were studied to search for vestibular impairment.Results: Symptoms included 16 patients (48.5%) with objective vertigo, 14 patients (42.4%) with subjective vertigo, and 3 patients (9.1%) with dizziness. Of the associated ear, nose, and throat (ENT) symptoms, the most expressed was tinnitus (18.2%). Bedside examination showed absent nystagmus in 7 patients (21.2%), 9 patients (27.3%) had horizontal or rotatory nystagmus, 17 patients (51.5%) had a vertical or oblique nystagmus, negative HST, or “central HINTS.”Discussion and Conclusions: The 9 patients had an evoked nystagmus pathognomonic for benign paroxysmal positional vertigo; in the remaining 17 cases, peripheral vestibular dysfunction could be excluded and central disorder may be suggested. Due to the prevalence of nystagmus of non-peripheral origin, a central nervous system involvement could not be excluded. However, due to the small sample size, a definite cause–effect relationship between vaccination and vertigo cannot be inferred. In light of expected third dose, large-scale and well-designed studies are needed to better define possible adverse reactions of the COVID-19 vaccine.

The present study fills a void in research on passion by examining for the first time the role of passion in physiological responses. The aim of the study was to investigate the role of passion, and the mediating role of cognitive appraisals, in the psychological and physiological responses to a stressful situation related to one’s passion. Students (43 women, 12 men, M age = 27.21 years), who were passionate for their studies, completed the Passion Scale for their studies and the Cognitive Appraisal Scale (assessing perceptions of challenge/threat). Then, they engaged in an education task under stressful conditions, and a subsequent unrelated leisure task under no-stress. Physiological reactivity was measured throughout the entire session and their perceptions of situational vitality and positive and negative emotions were assessed directly after the education task. Results showed that harmonious passion (HP) positively predicted challenge appraisals that, in turn, were positively related to positive emotions, vitality, and positive cardiovascular adaptation while engaging in the stressful education task, but less so with the leisure task (unrelated to one’s passion for academia). On the other hand, obsessive passion (OP) positively predicted threat appraisals. In turn, threat appraisals were positively related to negative emotions, negatively associated with vitality, and not related to cardiovascular reactivity. The present findings suggest that HP creates the onset of an adaptive psychological and physiological response whereas the response is less adaptive with OP.

Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (, Graphical Abstract

Risk-taking behaviors in adolescents have traditionally been analyzed from a psychopathological approach, with an excessive emphasis on their potential costs. From evolutionary theory we propose that risk-taking behaviors can be means through which adolescents obtain potential benefits for survival and reproduction. The present study analyses sex differences in three contexts of risk (i.e., risk propensity, expected benefits and risk perception) in the evolutionary specific domains and the predictive value of these domains over risk-taking behaviors, separately in female and male adolescents. 749 adolescents (females = 370) valued their risk perception, expected benefits and risk propensity through the Evolutionary Domain-Specific Risk Scale, as well as their engagement in risk-taking behaviors through the Risky Behavior Questionnaire. Male adolescents showed lower risk perception in two evolutionary domains, expected higher benefits in two other domains and showed higher risk propensity in six domains. Female adolescents showed lower risk perception in two domains. Additionally, risk perception, expected benefits and risk propensity in the evolutionary domains predicted the engagement in risk-taking behaviors in male adolescents, whereas in female adolescents only expected benefits and risk propensity showed a predictive effect over risk-taking behaviors. These results suggest the potential role of evolutionary mechanisms on risk-taking behaviors in adolescents. Results have practical implications for interventions programs aimed at reducing risk-taking behaviors. In addition to considering sex differences, intervention programs should consider alternative behaviors through which adolescents can reach their evolutionary goals, and handle the risks related to those behaviors that cannot be replaced but have potential benefits for adolescents.

MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.

In adult hippocampal neurogenesis, chromatin modification plays an important role in neural stem cell self-renewal and differentiation by regulating the expression of multiple genes. Histone deacetylases (HDACs), which remove acetyl groups from histones, create a non-permissive chromatin that prevents transcription of genes involved in adult neurogenesis. HDAC inhibitors have been shown to promote adult neurogenesis and have also been used to treat nervous system disorders, such as epilepsy. However, most HDAC inhibitors are not specific and may have other targets. Therefore, it is important to decipher the role of individual HDACs in adult hippocampal neurogenesis. HDACs 1, 2, and 3 have been found expressed at different cellular stages during neurogenesis. Conditional deletion of HDAC2 in neural stem cells impairs neuronal differentiation in adult hippocampus. HDAC3 supports proliferation of adult hippocampal neural stem/progenitor cells. The role of HDAC1 in adult neurogenesis remains still open. Here, we used a conditional knock-out mouse to block HDAC1 expression in neural stem cells (Nestin+ cells) during hippocampal neurogenesis. Our results showed that both HDAC1 and HDAC2 are expressed in all cellular stages during hippocampal neurogenesis. Moreover, we found that deletion of HDAC1 by viral infection of neural stem cells is sufficient to compromise neuronal differentiation in vitro. However, we were unable to reduce the expression of HDAC1 in vivo using Nestin-CreERT2 mice. Understanding the role of HDAC1 may lead to ways to control stem cell proliferation and neuronal regeneration in the adult hippocampus, and to more specific HDAC therapeutics for neurological disorders.

The COVID-19 pandemic has highlighted the need and benefits for all communities to be permitted timely access to on-demand screening for infectious respiratory diseases. This can be achieved with simplified testing approaches and affordable access to core resources. While RT-qPCR-based tests remain the gold standard for SARS-CoV-2 detection due to their high sensitivity, implementation of testing requires high upfront costs to obtain the necessary instrumentation. This is particularly restrictive in low-resource settings. The Ubiquitome Liberty16 system was developed as an inexpensive, portable, battery-operated single-channel RT-qPCR device with an associated iPhone app to simplify assay set-up and data reporting. When coupled with the SalivaDirect protocol for testing saliva samples for SARS-CoV-2, the Liberty16 device yielded a limit of detection (LOD) of 12 SARS-CoV-2 RNA copies/µL, comparable to the upper end of the LOD range for the standard SalivaDirect protocol when performed on larger RT-qPCR instruments. While further optimization may deliver even greater sensitivity and assay speed, findings from this study indicate that small portable devices such as the Liberty16 can deliver reliable results and provide the opportunity to further increase access to gold standard SARS-CoV-2 testing.

Background: Strengthening the sense of meaning in life and psychological well-being brings benefits for mental health. The group particularly vulnerable to mental problems are young adults, therefore the aim of our research was to explore how a gratitude intervention will affect the sense of meaning in life, psychological well-being, general health and perceived stress among them. The research also took into account the issue of expressing gratitude.Method: The study involved 80 young adults (58 women and 22 men) who were randomly assigned to the experimental group that filled out the specially prepared diaries for a week (participants were asked to list three things for which they feel grateful, to whom they are grateful and if and how they expressed their gratitude) or the control group. Participants completed the Meaning in Life Questionnaire (MLQ), the General Health Questionnaire – 28 (GHQ-28), the Perceived Stress Scale (PSS), and the Ryff Scales of Psychological Well-Being (PWBS) twice (before and after intervention).Results: In the experimental group significant increases were observed in three areas of psychological well-being: environmental mastery, relationships with others and purpose in life. The significant decrease was also noted in anxiety/insomnia and depression symptoms as well as in perceived stress. There were no differences in the level of meaning in life. There was a positive relationship between expressing gratitude and meaning in life and psychological well-being.Conclusion: Proposed gratitude intervention has the potential to enhance psychological well-being among young adults, however, it may not be effective in enhancing meaning in life.

In this pilot study we investigated the vocal strategies of Cantonese women when addressing an attractive vs. unattractive male. We recruited 19 young female native speakers of Hong Kong Cantonese who completed an attractiveness rating task, followed by a speech production task where they were presented a subset of the same faces. By comparing the rating results and corresponding acoustic data of the facial stimuli, we found that when young Cantonese women spoke to an attractive male, they were less breathy, lower in fundamental frequency, and with denser formants, all of which are considered to project a larger body. Participants who were more satisfied with their own height used these vocal strategies more actively. These results are discussed in terms of the body size projection principle.

Background and Objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients.Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males: 78 females) and 69 healthy controls (40 males: 29 females) were obtained from the PPMI dataset.Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function.Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.

Stock enhancement is one of the potential management strategies for the fishery. To better understand the impaction of stock enhancement, we simulated an experiment for lined seahorse (Hippocampus erectus) and evaluated the genetic structure after stock enhancement. In this study, we found the numbers of alleles (NA) and heterozygosity (HO) of stock enhancement strains were lower than those of the wild collections, while the inbreeding coefficient (FIS) and relatedness index were higher. Within the 3 generations of stock enhancement strain, the NA, HO and polymorphism information content (PIC) didn’t change significantly. In addition, the FST value indicated that the genetic differentiation between the stock enhancement strains and the first wild collection reached an intermediate level, which could lead to substructuring in wild populations. Overall, these findings revealed a potential genetic risk associated with the release of hatchery strains into wild populations.

As a major public health emergency, the COVID-19 pandemic has had a huge impact on economies all over the world. The experience of post-COVID-19 economic recovery is of great significance for achieving sustainable and high-quality economic development. Taking the economic development of China as an example, based on the theory of resilient economy and related measurement methods, this article selects five major indicators that are generally recognized as closely connected with economic resilience to construct a system of economic resilience indicators. In addition, the autoregressive integrated moving average (ARIMA) model is used to predict gross domestic product (GDP) under the scenario of no epidemic. The actual value of China's GDP is compared with the predicted value in the absence of the epidemic, verifying that strong economic resilience plays an important role in the country's economic response to major shocks. Based on the results, policy recommendations are made for countries to strengthen their economic resilience in the postepidemic era.

Multiple Sclerosis (MS) is a debilitating chronic autoimmune disease of the central nervous system that results in lower quality of life. Medication adherence is important for reducing relapse, disease progression, and MS-related symptoms, particularly during the early stages of MS. However, adherence may be impacted by negative emotional states. Therefore, it is important to identify protective factors. Past research suggests that the ability to discriminate between negative emotional states, also known as negative emotion differentiation (NED), may be protective against enactment of maladaptive risk-related behaviors. However, less is known as to how NED may promote adaptive health behaviors such as medication adherence. Utilizing weekly diaries, we investigated whether NED moderates the association between negative affect and medication adherence rates across 58 weeks among patients (n = 27) newly diagnosed with MS (following McDonald criteria). Results revealed that NED significantly moderated the relationship between negative affect and medication adherence. Specifically, greater negative affect was associated with lower adherence only for individuals reporting low NED. However, this link disappeared for those reporting moderate to high NED. Building upon past research, our findings suggest that NED may promote adaptive health behaviors and have important clinical implications for the treatment and management of chronic illness.

ObjectivesMost non-metastatic cancer patients can harvest a preferable survival after surgical treatment, however, patients sometimes refuse the recommended cancer-directed surgery. It is necessary to uncover the factors associated with patent's decision in taking cancer surgery and explore racial/ethnic disparities in surgery refusal.MethodsBased on the Surveillance, Epidemiology and End Results (SEER)-18 program, we extracted data of non-metastatic cancer patients who didn't undergo surgery. Ten common solid cancers were selected. Four racial/ethnic categories were included: White, black, Hispanic, and Asian/Pacific Islander (API). Primary outcome was patient's refusal of surgery. Multivariable logistic regression models were used, with reported odds ratio (OR) and 95% confidence interval (CI).ResultsAmong 318,318 patients, the incidence of surgery refusal was 3.5%. Advanced age, female patients, earlier cancer stage, uninsured/Medicaid and unmarried patients were significantly associated with higher odds of surgery refusal. Black and API patients were more likely to refuse recommended surgery than white patients in overall cancer (black-white: adjusted OR, 1.18; 95% CI, 1.11–1.26; API-white: adjusted OR, 1.56; 95% CI, 1.41–1.72); those racial/ethnic disparities narrowed down after additionally adjusting for insurance type and marital status. In subgroup analysis, API-white disparities in surgery refusal widely existed in prostate, lung/bronchus, liver, and stomach cancers.ConclusionsPatient's socioeconomic conditions reflected by insurance type and marital status may play a key role in racial/ethnic disparities in surgery refusal. Oncological surgeons should fully consider the barriers behind patient's refusal of recommended surgery, thus promoting patient-doctor shared decision-making and guiding patients to the most appropriate therapy.

Bioreporter systems based on detectable enzyme activity, such as that of beta-galactosidase or luciferase, are key in novel bacterial promoter discovery and study. While these systems permit quantification of gene expression, their use is limited by the toxicity of the expressed reporter enzymes in a given host. Indeed, the most potent promoters may be overlooked if their activity causes a lethal overproduction of the reporter genes when screening for transcriptional activity of potential promoter sequences with the luxCDABE cassette. To overcome this limitation, a variation of the mini-CTX-lux plasmid has been designed which allows reduction of promoter activity via the addition of an adjacent fluoride riboswitch. The riboswitch adds a layer of regulation between the promoter and the reporter gene, allowing cloning of stronger promoters by weakening expression, while giving the potential to induce with fluoride to provide a good signal for weaker promoters, thus circumventing limitations associated with reporter toxicity. We noticed the riboswitch potential portability issues between species, suggesting caution when using riboswitches non-native to the species where it is being used. This study introduces a new molecular biology tool which will allow for the identification of previously unverifiable or uncharacterized potent promoters and also provides a cloning vector for translational fusion with luciferase in a plasmid compatible with many species such as from the genera Burkholderia and Pseudomonas.

The urgency to understand the long-term neuropsychiatric sequala of COVID-19, a part of the Post-Acute COVID-19 Syndrome (PACS), is expanding as millions of infected individuals experience new unexplained symptoms related to mood, anxiety, insomnia, headache, pain, and more. Much research on PACS involves cross sectional surveys which limits ability to understand the dynamic trajectory of this emerging phenomenon. In this secondary analysis, we analyzed data from a 4-week observational digital phenotyping study using the mindLAMP app for 695 college students with elevated stress who specified if they were exposed to COVID-19. Students also completed a biweekly survey of clinical assessments to obtain active data. Additionally, passive data streams like GPS, accelerometer, and screen state were extracted from phone sensors and through features the group built. Three hundred and eighty-second number participants successfully specified their COVID-19 exposure and completed the biweekly survey. From active smartphone data, we found significantly higher scores for the Prodromal Questionnaire (PQ) and the Pittsburgh Sleep Quality Index (PSQI) for students reporting exposure to COVID-19 compared to those who were not (ps < 0.05). Additionally, we found significantly decreased sleep duration as captured from the smartphone via passive data for the COVID-19 exposed group (p < 0.05). No significant differences were detected for other surveys or passive sensors. Smartphones can capture both self-reported symptoms and behavioral changes related to PACS. Our results around changes in sleep highlight how digital phenotyping methods can be used in a scalable and accessible manner toward better capturing the evolving phenomena of PACS. The present study further provides a foundation for future research to implement improving digital phenotyping methods.

Background: In elderly chronic heart failure (HF) patients, activities of daily living (ADLs) require the use of a high proportion of patients’ peak aerobic capacity, heart rate, and ventilation.Objectives: To assess the effects of short-term comprehensive cardiac rehabilitation (CR) on the metabolic requirement of ADLs in elderly patients with chronic HF.Methods: The study population comprised 99 elderly chronic HF patients (mean age 72 ± 5 years, 80% male, 61% ejection fraction Results: After CR, task-related oxygen uptake did not change in any of the domestic ADLs. Notably, there was a significant decrease in the cumulative time required to perform ADLs (ADL 1–4 and ADL6; from 412 ± 147 to 388 ± 141 s, p = 0.001) and a reduction in maximal heart rate in ADL1 and 3 (p = 0.005 and p = 0.027, respectively). Changes occurred in the 6MWT with an increase in oxygen uptake (p = 0.005) and in the distance covered (p p = 0.004).Conclusion: Elderly patients with chronic heart failure who are engaged in a short-term residential CR program improve the performance of routine ADLs.

This study focuses on identifying COVID-19 related exposure, stress, and mental health concerns in the larger Charlotte, North Carolina region, an area with many low-income and under resourced communities. A community-academic partnership conducted a regional COVID-19 needs assessment. Low-income adults (N = 156) completed an online-administered survey of demographic information, COVID-19 exposure, stress, coping-related factors, and mental health. Frequency data showed that common COVID-19 related stressors included job exposure, lost job/income, and increased home responsibilities. Frequency data further showed elevated screening risk rates for mental health concerns were observed for post-traumatic stress (83.3%), depression (52.2%), problematic drinking (50.0%), generalized anxiety (43.0%), and suicide (40.4%). Bivariate correlation and multivariate regression models identified robust mental health risk factors including COVID-19 related stress affecting close persons, fear/worry reaction to the pandemic, and use of venting as a coping strategy; protective factors included active coping and problem-focused coping beliefs. Findings are discussed with respect to informing regional public health efforts during the pandemic.

ObjectiveSpontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication associated with dermatomyositis (DM). This study reported a case series of SIH associated with DM. In addition, the characteristics and prognostic effects for this complication were analyzed based on literature review.MethodsWe reported seven cases of anti-melanoma differentiation-associated gene five positive dermatomyositis (MDA5+DM) complicated by SIH in our single-center cohort, and a comprehensive literature review was performed. Clinical characteristics, treatment, and outcome data of all eligible reported cases were summarized. Potential prognostic effects were identified by comparisons between the deceased and survivors.ResultsAmong cumulatively reported patients with DM patients and SIH, the overall mortality was 60.9% (14/23) (including our cases). Fourteen out of nineteen (73.7%) hemorrhagic events occurred within 6 months of disease onset. Anti-MDA5 antibody predominated in those myositis-specific antibodies available cases (8/10), although patients with positive anti-NXP2 and anti-Mi2 have also been documented. Iliopsoas (52.2%, 12/23) was the most frequently involved bleeding location. Bleeding in deep muscles was identified to be associated with poorer prognosis. The mortality of patients with DM and deep muscular hematoma (non-palpable) (80%, 12/15) was significantly higher than that of patients with only superficial muscular hematoma (palpable) (25%, 2/8) (p =0.023).ConclusionSpontaneous hematoma in non-palpable deep muscles probably leads to excess mortality in dermatomyositis, particularly for those with anti-MDA5 antibody, which often occurs within 6 months of disease onset. Clinicians should be vigilant to this rare but potentially fatal complication and carefully balance the risks and benefits of prophylactic anti-thrombotic treatment.

Introduction: Ibrutinib, a Bruton's tyrosine kinase inhibitor (TKI) used primarily in the treatment of hematologic malignancies, has been associated with increased incidence of atrial fibrillation (AF), with limited data on its association with other tachyarrhythmias. There are limited reports that comprehensively analyze atrial and ventricular arrhythmia (VA) burden in patients on ibrutinib. We hypothesized that long-term event monitors could reveal a high burden of atrial and VAs in patients on ibrutinib.Methods: A retrospective data analysis at a single center using electronic medical records database search tools and individual chart review was conducted to identify consecutive patients who had event monitors while on ibrutinib therapy.Results: Seventy-two patients were included in the analysis with a mean age of 76.9 ± 9.9 years and 13 patients (18%) had a diagnosis of AF prior to the ibrutinib therapy. During ibrutinib therapy, most common arrhythmias documented were non-AF supraventricular tachycardia (n = 32, 44.4%), AF (n = 32, 44%), and non-sustained ventricular tachycardia (n = 31, 43%). Thirteen (18%) patients had >1% premature atrial contraction burden; 16 (22.2%) patients had >1% premature ventricular contraction burden. In 25% of the patients, ibrutinib was held because of arrhythmias. Overall 8.3% of patients were started on antiarrhythmic drugs during ibrutinib therapy to manage these arrhythmias.Conclusions: In this large dataset of ambulatory cardiac monitors on patients treated with ibrutinib, we report a high prevalence of atrial and VAs, with a high incidence of treatment interruption secondary to arrhythmias and related symptoms. Further research is warranted to optimize strategies to diagnose, monitor, and manage ibrutinib-related arrhythmias.

Asprosin physiologically increases in fasting conditions and decreases with refeeding and has been implicated in glucose homeostasis. An alteration of meal-related circadian oscillation of asprosin has been suggested in adults affected by type 2 diabetes mellitus.Aims of this study were to test the hypothesis of an alteration in the meal-related variation of asprosin levels in non-diabetic children and adolescents with obesity and to assess which metabolic variables condition this variation in non-diabetic children and adolescents with obesity. This is a cross-sectional study which included 79 children and adolescents with obesity. Children underwent clinical and biochemical assessments, including oral glucose tolerance test (OGTT), and liver ultrasound evaluation. Asprosin serum levels were measured by an enzyme-linked immunosorbent assay at a fasting state and at the 120-minute OGTT timepoint (2h-postprandial asprosin). Fasting and 2h-postprandial asprosin serum levels did not significantly differ in the entire study population (374.28 ± 77.23 vs 375.27 ± 81.26;p=0.837). 55.7% of patients had a significant increase in 2h-postprandial asprosin compared with fasting levels. The asprosin level increase condition was significantly associated with HOMA-IR (OR,1.41; 95%CI,1.005-1.977; p=0.047), fasting glycaemia (OR,1.073; 95%CI,1.009-1.141;p=0.024) and HOMA-B (OR,0.99; 95%CI,0.984-0.999; p=0.035). Moreover, the IFG condition was associated with the increase in asprosin levels (OR, 3.040; 95%CI, 1.095-8.436; p=0.033), even after adjustment for HOMA-IR, BMI SDS, sex and pubertal stage. Insulin resistance and IFG influence meal-related changes of asprosin serum levels in our study population of obese, non-diabetic, children. Alteration of asprosin circadian secretion might be an early biomarker of impaired glucose regulation in obese children with insulin resistance.

Although it is well-known that care responsibilities are strongly gendered also in later life, the consequences for older women of juggling work and care responsibilities are understudied. This study contributes to fill this gap by focusing on the wellbeing implications for older European women of combining work and grandchild care. The role strain and role enhancement theories guide our theoretical predictions. While the former predicts a lower wellbeing due to the double burden of grandchild care and paid work, the latter posits an increase in wellbeing through the accumulation of social identities or roles. By using longitudinal data from the Survey of Health, Ageing and Retirement in Europe (SHARE), we investigate whether grandmothers who do and those who do not work experience different levels of quality of life, depressive symptoms and life satisfaction. Our statistical model consists in a fixed-effect regression that adjusts for the lagged outcome. Results show that, among grandmothers engaged in paid work, grandchild care is not significantly associated with any of the three outcomes considered. Instead, non-working grandmothers seem to benefit from provision of grandchild care, in terms of higher quality of life and lower number of depressive symptoms. As thus, the provision of grandchild care tends to be beneficial for grandmothers’ wellbeing only if they do not combine this activity with paid work. Juggling paid work and childcare to grandchildren may result in an excessive burden which eliminates the potential benefits of grandchild care on older women’s wellbeing.

Prior reports suggest that affective effects in visual word processing cannot be fully explained by a dimensional perspective of emotions based on valence and arousal. In the current study, we focused on the contribution of approach and avoidance motivational systems that are related to different action components to the processing of emotional words. To this aim, we compared frontal alpha asymmetries and brain oscillations elicited by anger words associated with approach (fighting) motivational tendencies, and fear words that may trigger either avoidance (escaping), approach (fighting) or no (freezing) action tendencies. The participants’ task was to make decisions about approaching or distancing from the concepts represented by words. The results of cluster-based and beamforming analyses revealed increased gamma power band synchronization for fear words relative to anger words between 725 and 750 ms, with an estimated neural origin in the temporal pole. These findings were interpreted to reflect a conflict between different action tendencies underlying the representation of fear words in semantic and emotional memories, when trying to achieve task requirements. These results are in line with the predictions made by the fear-hinders-action hypothesis. Additionally, current data highlights the contribution of motivational features to the representation and processing of emotional words.

Addiction has become a profound societal problem worldwide, and few effective treatments are available. The nematode Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study neurobiological disease states. C. elegans reportedly developed a preference for cues that had previously been paired with addictive drugs, similar to place conditioning findings in rodents. Moreover, several recent studies discovered and reported the existence of an opioid-like system in C. elegans. Still unclear, however, is whether C. elegans exhibits addictive-like behaviors for opioids, such as morphine. In the present study, we found that C. elegans exhibited dose-dependent preference for morphine using the conditioned chemosensory-cue preference (CCP) test. This preference was blocked by co-treatment with the opioid receptor antagonist naloxone. C. elegans also exhibited aversion to naloxone-precipitated withdrawal from chronic morphine exposure. The expression of morphine-induced CCP and morphine withdrawal were abolished in worms that lacked the opioid-like receptor NPR-17. Dopamine-deficient mutant (cat-2 (e1112)) worms also did not exhibit morphine-induced CCP. These results indicate that the addictive function of the opioid system exists in C. elegans, which may serve as a useful model of opioid addiction.

High vocation education is an important foundation for China to cultivate high teaching quality and technical and skilled talents. In the new era, the acceleration of the development of modern vocational education is put in a more prominent position. It is proposed that we should adhere to moral education, closely combine this with the needs of technological change and industrial upgrading, constantly improve the quality of high vocational education teaching, and cultivate more technical and skilled talents with both political integrity and ability for modernization construction. Under the background of social informatization, using artificial intelligent technology to solve these problems can play an important role for improving the teaching quality of high vocational education. This paper proposed a data mining approach in promoting student satisfaction with the teaching quality of high vocational education. We design a questionnaire for Students’ satisfaction with the teaching quality of basic entrepreneurship curriculum. We take the survey data of vocation education as an example and use mining technology analysis software to understand the current status of the teaching quality of basic entrepreneurship curriculum. The results determine the main factors affecting Students’ satisfaction with teaching quality. The results of this paper can be used in student management, education strategy, student education satisfaction, and teaching quality in high vocation college education, and to improve the teaching quality of fundamentals of entrepreneurship curriculum in high vocation education.

To facilitate effective targeted COVID-19 vaccination strategies, it is important to understand reasons for vaccine hesitancy where uptake is low. Artificial intelligence (AI) techniques offer an opportunity for real-time analysis of public attitudes, sentiments, and key discussion topics from sources of soft-intelligence, including social media data. In this work, we explore the value of soft-intelligence, leveraged using AI, as an evidence source to support public health research. As a case study, we deployed a natural language processing (NLP) platform to rapidly identify and analyse key barriers to vaccine uptake from a collection of geo-located tweets from London, UK. We developed a search strategy to capture COVID-19 vaccine related tweets, identifying 91,473 tweets between 30 November 2020 and 15 August 2021. The platform's algorithm clustered tweets according to their topic and sentiment, from which we extracted 913 tweets from the top 12 negative sentiment topic clusters. These tweets were extracted for further qualitative analysis. We identified safety concerns; mistrust of government and pharmaceutical companies; and accessibility issues as key barriers limiting vaccine uptake. Our analysis also revealed widespread sharing of vaccine misinformation amongst Twitter users. This study further demonstrates that there is promising utility for using off-the-shelf NLP tools to leverage insights from social media data to support public health research. Future work to examine where this type of work might be integrated as part of a mixed-methods research approach to support local and national decision making is suggested.

Objective: Gout is a crystal-induced inflammatory arthritis caused by elevated uric acid. Physical activity has the potential to reduce serum uric acid (SUA), thus improving the disease burden of gout. In this study, we examined the association of objectively-measured physical activity and SUA.Methods: A cross-sectional study was conducted using survey, laboratory, and accelerometer data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES). SUA concentrations (mg/dL) were obtained during an initial exam, and then physical activity (kCal/day) was measured with 7 days of ActiGraph accelerometry in participants (n = 3,475) representative of the ambulatory, non-institutionalized US civilian population. Regression, including restricted cubic splines, was used to assess the relation of physical activity and SUA in bivariate and adjusted models. Covariates included age, gender, race/ethnicity, alcohol use, body mass index, renal function, and urate-lowering therapy.Results: In the bivariate model, physical activity was correlated with SUA concentrations and included a non-linear component (p < 0.01). In the adjusted model, linear splines were employed with a node at the SUA nadir of 5.37mg/dL; this occurred at 703 kCal/day of physical activity. The association of physical activity and SUA was negative from 0 to 703 kCal/day (p = 0.07) and positive >703 kCal/day (p < 0.01 for the change in slope).Conclusion: Physical activity and SUA are associated in a non-linear fashion, with a minimum estimated SUA at 703 kCal/day of objectively-measured physical activity. These findings raise intriguing questions about the use of physical activity as a potential adjunctive therapy in patients with gout, and further interventional studies are needed to elucidate the effects of moderate intensity exercise on SUA concentrations.

Substantial evidence from experimental studies has shown that mating motivation increases men’s financial risk-taking behaviors. The present study proposed a new moderator, men’s past relationship experience, for this well-accepted link between mating motivation and financial risk-taking tendency. Heterosexual young men were randomly assigned to the mating condition and control condition, and they completed a set of financial risk-taking tasks and reported their past relationship experience. A significant main effect of mating motivation and a significant interaction effect between experimental conditions (mating group and control group) and relationship experience emerged, suggesting that mating motivation increased financial risk-taking tendency only among men who have never been committed in a romantic relationship, rather than those who have had such experience. This moderating effect was replicated in two experiments. The present study contributed to the understanding of individual differences in the relationship between mating motivation and male financial risk-taking. The present findings also have important implications for financial industry and gambling companies to better target clients and advertise their high-risk products.

Lower-limb exoskeletons have been created for different healthcare needs, but no research has been done on developing a proper protocol for users to get accustomed to moving with one. The user manuals provided also do not include such instructions. A pre-test was conducted with the TWIN (IIT), which is a lower-limb exoskeleton made for persons with spinal cord injury. In the pre-test, two healthy, able-bodied graduate students indicated a need for a protocol that can better prepare able-bodied, first-time users to move with an exoskeleton. TWIN was used in this preliminary study and nine users were divided to receive a tutorial or no tutorial before walking with the exoskeleton. Due to COVID-19 regulations, the study could only be performed with healthy, young-to-middle-aged lab members that do not require walking support. The proposed protocol was evaluated with the System Usability Scale, NASA Raw Task Load Index, and two custom surveys. The members who received the tutorial found it easy to follow and helpful, but the tutorial seemed to come at a price of higher perceived mental and physical demands, which could stem from the longer testing duration and the need to constantly recall and apply the things learned from the tutorial. All results presented are preliminary, and it is recommended to include biomechanical analysis and conduct the experiment with more participants in the future. Nonetheless, this proof-of-concept study lays groundwork for future related studies and the protocol will be adjusted, applied, and validated to patients and geriatric users.

By crossing septin7-floxed mice with Lyz2-Cre mice carrying the Cre recombinase inserted in the Lysozyme-M (Lyz2) gene locus we aimed the specific deletion of septin7 in myeloid cells, such as monocytes, macrophages and granulocytes. Septin7flox/flox:Lyz2-Cre mice show no alterations in the myeloid compartment. Septin7-deleted macrophages (BMDMs) were isolated and analyzed. The lack of Septin7 expression was confirmed and a constitutive double-nucleation was detected in Septin7-deficient BMDMs indicating a defect in macrophage cytokinesis. However, phagocytic function of macrophages as judged by uptake of labelled E. coli particles and LPS-stimulated macrophage activation as judged by induction of TNF mRNA expression and TNF secretion were not compromised. In addition to myeloid cells, Lyz2-Cre is also active in type II pneumocytes (AT2 cells). We monitored lung adenocarcinoma formation in these mice by crossing them with the conditional knock-in Kras-LSL-G12D allele. Interestingly, we found that control mice without septin7 depletion die after 3–5 weeks, while the Septin7-deficient animals survived 11 weeks or even longer. Control mice sacrificed in the age of 4 weeks display a bronchiolo-alveolar hyperplasia with multiple adenomas, whereas the Septin7-deficient animals of the same age are normal or show only a weak multifocal brochiolo-alveolar hyperplasia. Our findings indicate an essential role of Septin7 in macrophage cytokinesis but not in macrophage function. Furthermore, septin7 seems absolutely essential for oncogenic Kras-driven lung tumorigenesis making it a potential target for anti-tumor interventions.

With the change in the location of school education from the classroom to the home during the COVID-19 outbreak, there should be more educational caregiving from children’s parents when children learn online. Parental involvement in children’s online learning including study guide and psychological counseling is the specific content of educational caregiving, which is different from face-to-face learning. More attention should be paid to parental involvement and parents’ satisfaction with the online learning effect. This study therefore conducted a survey on middle school students’ parents to establish a moderating model, exploring the influence of parental involvement on parent satisfaction, and the number of children and parental education level as the moderator variables influencing parental involvement. The results show that there is a significant positive correlation between parental involvement and satisfaction, while the parental education level and the number of children both have a moderating effect on the relationship between parental involvement and parent satisfaction. The moderating effect of the education level of parents shows negative, while the moderating effect of the number of children is positive. An interesting finding is that the number of children has a very low influence on parental involvement.

Canine distemper and canine parvoviral enteritis are infections caused by the canine distemper virus (CDV) and canine parvovirus type 2 (CPV-2), respectively. They are two common infectious diseases that cause high morbidity and mortality in affected dogs. Combination vaccines have been broadly used to protect dogs from infections of CDV, CPV-2, and other viruses. VP2 is the most abundant protein of the CPV-2 capsid. It elicits potent immunity in animals and, therefore, is widely used for designing subunit antigen-based vaccines. In this study, we rescued a recombinant CDV (QN vaccine strain) using reverse genetics. The recombinant CDV (rCDV-VP2) was demonstrated to express stably the VP2 in cells for at least 33 serial passages in vitro. Unfortunately, a nonsense mutation was initially identified in the VP2 open reading frame (ORF) at passage-34 (P34) and gradually became predominant in rCDV-VP2 quasispecies with passaging. Neither test strip detection nor indirect immunofluorescence assay demonstrated the expression of the VP2 at P50. The P50 rCDV-VP2 was subjected to next-generation sequencing, which totally identified 17 single-nucleotide variations (SNVs), consisting of 11 transitions and 6 transversions. Out of the 17 SNVs, 1 and 9 were identified as nonsense and missense mutations, respectively. Since the nonsense mutation arose in the VP2 ORF as early as P34, an earlier rCDV-VP2 progeny should be selected for the vaccination of animals in future experiments.

Flipped learning could improve the learning effectiveness of students. However, some studies have pointed out the limitations related to flipped classrooms because the content of the flipped course does not vary according to the needs of the students. On the other hand, adaptive teaching, which customizes the learning mode according to the individual needs of students, can make up for some of the shortcomings of flipped teaching. This study combines adaptive teaching with flipped teaching and applies it to face-to-face classroom activities. The purpose of this research is to explore whether the implementation of flipping and adaptive learning in a computer programming course can improve the learning effectiveness of students. The experimental subjects of this study are the sophomore students in the Department of Information Management. The flipped classroom with adaptive instruction has been realized in the limited course time. This study uses questionnaires to collect pre- and post-test data on the “learning motivation” of students. The learning effectiveness was evaluated based on the students' previous programming course (C language) and the semester scores of this course. Research results show that the post-test “learning motivation” has improved overall compared with the pre-test, and the learning effect is significant. The results of this research not only prove the effectiveness of modern teaching theories in programming courses but also lay the foundation for future teaching design.

Understanding key socio-demographic variables of 2019 coronavirus disease (COVID-19) vaccine recipients is crucial to improving its acceptance and Nigeria's COVID-19 control strategy. The survey was conducted as a non-probability cross-sectional survey of 2,936 COVID-19 vaccine recipients in Kwara State. Our findings revealed that 74% (n = 2,161) of the vaccine recipients were older than 40 years. Forty percent (n = 1,180) of the vaccine recipients earned a monthly income >100,000 Naira (equivalent to US $200). Most of the vaccine recipients (64%, n = 1,880) had tertiary education, while 15% (n = 440) of them had no formal education. Almost half of the recipients (47%, n = 1,262) were government employees and 28.8% (n = 846) of them had health-related backgrounds. Only 17% (n = 499) of the vaccine recipients have been screened for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), of which 21% (n = 105/499) of them were tested positive. Only 47% (n = 1,378) had been fully immunized. The prevalence of confirmed COVID-19 cases among COVID-19 vaccine recipients in Kwara State was 3.6% (n = 105/2,936). The most recurrent adverse events following immunization (AEFIs) among vaccine recipients were fever (14%, n = 411), pain at injection site (47%, n = 1,409), headache (19%, n = 558), and body weakness (9%, n = 264). The need to protect themselves from the deadly virus was the main reason that prompted people to voluntarily accept the COVID-19 vaccine. There is a high level of COVID-19 vaccine acceptance among respondents across all social classes including those with no formal education, those with very low monthly income (< US $2 per day), and in untested population. Hence, vaccine donors should prioritize equitable distribution to Low-and-Middle-income Countries (LMICs) such as Nigeria, and health authorities should improve vaccine advocacy to focus on vaccine safety and efficacy.

Doxorubicin (DOX) is a successful chemotherapeutic widely used for the treatment of a range of cancers. However, DOX can have serious side-effects, with cardiotoxicity and hepatotoxicity being the most common events. Oxidative stress and changes in metabolism and bioenergetics are thought to be at the core of these toxicities. We have previously shown in a clinically-relevant rat model that a low DOX dose of 2 mg kg–1 week–1 for 6 weeks does not lead to cardiac functional decline or changes in cardiac carbohydrate metabolism, assessed with hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopy (MRS). We now set out to assess whether there are any signs of liver damage or altered liver metabolism using this subclinical model. We found no increase in plasma alanine aminotransferase (ALT) activity, a measure of liver damage, following DOX treatment in rats at any time point. We also saw no changes in liver carbohydrate metabolism, using hyperpolarized [1-13C]pyruvate MRS. However, using metabolomic analysis of liver metabolite extracts at the final time point, we found an increase in most acyl-carnitine species as well as increases in high energy phosphates, citrate and markers of oxidative stress. This may indicate early signs of steatohepatitis, with increased and decompensated fatty acid uptake and oxidation, leading to oxidative stress.