Miracle-dz/UniFAR-FTUs huggingface dataset:
Recreational Centres’ Facilities and Activities to Support Healthy Ageing in Singapore

Objective: This study examined the physical and social environment (facilities and activities) of Singapore’s Recreational Centres (RCs) and female patrons’ (>50 years) perception of the RC facilities and activities. Materials and Methods: A total of 100 RCs were audited, and 22 face-to-face interviews were undertaken. Results: Physical activity classes were the main activity offered (mean = eight classes per month), with walking (29.8%) and aerobics sessions (17.5%) being the most frequent. Nutrition classes and social activities were offered less often (mean = one class per month). The activities were well received by patrons, offering opportunities to interact while participating in physical activity and nutrition classes. However, the need for staff training, consideration of patron’s abilities and the desire to engage in alternative activities were expressed. Conclusion: Overall, RCs’ facilities and activities were well liked by the patrons but opportunities for improvements were identified. Regular reviews of facilities and activities through consultation with the RC patrons and managers are needed to ensure that the facilities and activities remain relevant and practical to the patrons. This will help to support active lifestyles and healthy eating practices among older adults residing within the community.
Dose–response relationship between physical activity and mortality in people with non-communicable diseases: a study protocol for the systematic review and meta-analysis of cohort studies

Introduction This study protocol outlines our planned systematic review and dose-response meta-analysis of postdiagnosis physical activity and mortality in people with non-communicable diseases (NCDs). Methods and analysis This study is based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols. A systematic literature search will be conducted in various databases—namely, PubMed, Scopus and Web of Science—by two researchers in order to identify prospective observational studies that investigate postdiagnosis physical activity or activity-related energy expenditure and mortality in individuals with NCDs. The target population is adults (≥18 years of age) with one of the following nine NCDs: low back pain, type 2 diabetes mellitus, osteoarthritis, depressive disorder, chronic obstructive pulmonary disease, breast cancer, lung cancer, stroke or ischaemic heart disease. We will focus on all-cause mortality as the primary outcome and investigate indication-specific mortality as the secondary outcome. For each study identified as a result of the literature search, we will conduct graphical dose-response analyses of mortality as a function of activity-related energy consumption. If more than two studies are available for one disease, we will perform linear and non-linear dose-response meta-analyses for said disease using random-effects models. We will investigate the heterogeneity of the studies and publication bias. To assess the risk of bias and the quality of the included studies, we will use the Risk Of Bias In Non-randomised Studies - of Interventions tool, which is a Cochrane tool. Ethics and dissemination This systematic review will be conducted in compliance with ethical precepts. As the systematic review is based on published studies, approval from an ethics committee is not required. The systematic review and meta-analysis will be published in a peer-reviewed journal. PROSPERO registration number CRD42018103357
Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine containing bioactive molecules

Morpholine is a heterocycle featured in numerous approved and experimental drugs as well as bioactive molecules. It is often employed in the field of medicinal chemistry for its advantageous physicochemical, biological, and metabolic properties, as well as its facile synthetic routes. The morpholine ring is a versatile and readily accessible synthetic building block, it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities. There are many examples of molecular targets of morpholine bioactive in which the significant contribution of the morpholine moiety has been demonstrated; it is an integral component of the pharmacophore for certain enzyme active‐site inhibitors whereas it bestows selective affinity for a wide range of receptors. A large body of in vivo studies has demonstrated morpholine's potential to not only increase potency but also provide compounds with desirable drug‐like properties and improved pharamacokinetics. In this review we describe the medicinal chemistry/pharmacological activity of morpholine derivatives on various therapeutically related molecular targets, attempting to highlight the importance of the morpholine ring in drug design and development as well as to justify its classification as a privileged structure.
Clock Genes Disruption in the Intensive Care Unit

Background: Intensive care unit (ICU) environment disrupts the circadian rhythms due to environmental and other nonphotic synchronizers. The main purpose of this article is to establish whether critically patients have desynchronization at the molecular level after 1 week of stay in the ICU. Methods: The rhythm of Clock, Bmal1, Cry1, and Per2 genes in neuro-ICU patients (n = 11) on the first day after admission in the unit (1 day) and 1 week later (1 week) was studied, 4 time points throughout the day, at 6, 12, 18, and 24 hours. Human whole blood samples were obtained from neuro-ICU patients. The total RNA was isolated and each sample was reverse transcribed to complementary DNA and quantitative polymerase chain reaction (PCRq) was performed. The possible rhythm was studied using Fourier Series. Results: After 1 week, the clock gene rhythmicity completely disappeared. Messenger RNA (mRNA) expression for the 4 clock genes was shown rhythmicity at the first day after admission in the ICU. Circadian rhythmicity for none of them was observed but rather, ultradian rhythmicity was found. The expression of Clock, Bmal1, and Per2 mRNA after 1 week was similar in the 4-time point studies without significant fluctuation among the 4 time points analyzed. Discussion: Rhythmic mRNA expression is present at the first day after admission in the ICU. However, ICU stay during 1 week affects the molecular machinery of the biological clock generating chronodisruption. Circadian disruption is associated with the risk of several pathologies, thus, it seems to be clear that ICU stay in constant conditions could adversely affect patient evolution and probably, circadian resynchronization restoring clock gene expression could lead to a better clinical evolution of the patient. Conclusions: Clock genes disruption is observed in neuro-ICU patients. Light therapy as well as melatonin treatment could reduce the impact of ICU stay period in biological clock, thereby improving patients’ recovery.
Long-term Survival of a Patient with Small Cell Lung Cancer Secreting ADH and ACTH Simultaneously, Following the Prolonged Use of Amrubicin

Paraneoplastic syndromes are frequently observed in lung cancer, especially in small cell lung cancer (SCLC). Although there have been many reports on paraneoplastic syndromes, few reports have been published on SCLC that simultaneously produces antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH), and these reports described the prognosis of such cases as extremely poor. We herein present a rare case of a Japanese woman with SCLC accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Cushing's syndrome. The survival of the patient was prolonged by the long-term administration of amrubicin.
Sources of Caregiving Burden in Middle-Aged and Older Latino Caregivers

Objective: We aimed to identify sources of caregiver burden in middle-aged and older Latino caregivers of people with Alzheimer disease and related dementia (ADRD). Methods: Participants were recruited through an agreement with the Rush Alzheimer’s Disease Center Clinic Data Repository. We conducted semistructured interviews with 16 middle-aged and older Latinos who were the primary caregiver for a family member diagnosed with ADRD. The interview guide consisted of questions and probes to capture participants’ perceptions of family caregiving. Direct content analysis was performed. Results: Participants were aged 50 to 75 years (n = 16) and a majority female (n = 12). The sources of burden identified were (1) caregiver responsibilities, (2) caregiving-related health decline, (3) lack of support, (4) financial status, (5) vigilance, and (6) concerns about the future. Conclusions: The influence of gender roles seemed to play a role in caregivers’ perceptions of sources of burden, especially on caregiver responsibilities and perceptions of lack of support. Latinos cultural values such as familismo and marianismo likely reinforced gender disparities in family caregiving.
Rifaximin prevents ethanol-induced liver injury in obese KK-Ay mice through modulation of small intestinal microbiota signature.

Exacerbation of alcoholic hepatitis (AH) with comorbid metabolic syndrome is an emerging clinical problem, where microbiota plays a profound role in the pathogenesis. Here, we investigated the effect of rifaximin (RFX) on liver injury following chronic-binge ethanol (EtOH) administration in KK-Ay mice, a rodent model of metabolic syndrome. Female, 8-week-old KK-Ay mice were fed Lieber-DeCarli diet (5% EtOH) for 10 days, following a single EtOH gavage (4 g/kg BW). Some mice were given RFX (0.1 g/L, in liquid diet) orally. Small intestinal contents were collected from mice without binge. Intestinal microbiota was quantified using conventional, aerobic and anaerobic culturing techniques, and further analyzed by 16S rRNA sequencing in detail. EtOH-feeding/binge caused hepatic steatosis, oxidative stress, and induction of inflammatory cytokines in KK-Ay mice, which were markedly prevented by RFX treatment. Hepatic mRNA levels for cluster of differentiation (CD)-14, toll-like receptor (TLR) 4, and TLR2 and NADPH oxidase (NOX) 2 were increased following EtOH-feeding/binge, and administration of RFX completely suppressed their increase. The net amount of small intestinal bacteria was increased over 3-fold after chronic EtOH feeding as expected; however, RFX did not prevent this net increase. Intriguingly, the profile of small intestinal microbiota was dramatically changed following EtOH feeding in the order level, where the Erysipelotrichales predominated in the relative abundance. In sharp contrast, RFX drastically blunted the EtOH-induced increases in the Erysipelotrichales almost completely, with increased proportion of the Bacteroidales. In conclusion, RFX prevents AH through modulation of small intestinal microbiota/innate immune responses in obese KK-Ay mice.
Impact of neighbourhood food environment on diet and obesity in China: a systematic review

Abstract Objective: This study systematically reviewed literature on the neighbourhood food environment in relation to diet and obesity among residents in China. Design: A keyword search of peer-reviewed articles was performed in Cochrane Library, PubMed, and Web of Science. Eligibility criteria include study designs: longitudinal/cohort studies or cross-sectional studies; study participants: people of all ages; exposures: neighbourhood food environment (e.g. restaurants, supermarkets, wet markets, fast-food restaurants, or convenience stores); outcomes: diet and/or body weight status; and country: China. Results: Seventeen studies met all criteria and were included. Among the eight studies that assessed the neighbourhood food environment in relation to diet, six reported at least one statistically significant relationship in the expected direction, whereas the remaining two exclusively reported null effects. Among the eleven studies that assessed the neighbourhood food environment in relation to body weight or overweight/obesity, ten reported a significant association whereas the remaining one reported a null relationship. Variety, density, and proximity of food outlets were positively associated with local residents’ dietary diversity, portion size, and daily caloric intake. Density and proximity of fast-food restaurants and convenience stores were positively associated with local residents’ adiposity in some but not all studies. Evidence linking any specific food outlet type to diet/obesity remains lacking due to the small number of studies and heterogeneities in food environment measures, geographical locations, and population subgroups. Conclusions: The neighbourhood food environment may influence diet and obesity among Chinese residents but the evidence remains preliminary. Future studies adopting an experimental study design and objective/validated environment and dietary measures are warranted.
Pediatric Pulmonology

Funding information National Heart, Lung, and Blood Institute, Grant/Award Number: U54HL096458 Abstract Introduction: The accuracy of primary ciliary dyskinesia (PCD) diagnosis has improved but no single test is diagnostic and some cases remain unsolved. Data regarding the accuracy of pulmonary radioaerosol mucociliary clearance scan (PRMCC) for the diagnosis of PCD are limited to predominantly adults using a 24‐hour test. This study was performed to determine the accuracy of a 60‐minute PRMCC test for diagnosing PCD in children. Methods: Children with suspected PCD and inconclusive clinical diagnostic testing in an expert center were selected for PRMCC testing. Nebulized Tc sulfur colloid was inhaled and dynamic imaging acquired for 60 to 120 minutes. Two independent radiologists blinded to the clinical diagnosis and health records overread PRMCC studies. The PRMCC result was compared with the reference standard diagnosis of PCD made by two physicians using the cumulative health record, blinded to PRMCC results. Results: From 2008 to 2018, 57 patients (6‐17 years) participated, of which 16 met criteria for the reference diagnosis of PCD. The PRMCC test was conclusive in 54 patients (94.7%) and had a sensitivity of 100% (95% confidence interval [CI] = 78.2–100), specificity of 85.7% (95% CI = 69.7–95.2), positive predictive value of 75% (95% CI = 57.1–87.1), negative predictive value of 100% (95% CI = 90.2–100), and accuracy of 90% (95% CI = 78.2–96.7). Conclusion: The 60‐minute PRMCC test is noninvasive and feasible in children with a high negative predictive value for PCD. It may be a helpful adjunctive test to rule out PCD when clinical suspicion remains after guideline recommended first‐line clinical testing.
Development of a family caregiver needs-assessment scale for end-of-life care for senility at home (FADE)

Aim This study aimed to develop a “family caregiver needs-assessment scale for end-of-life care for senility at home” (FADE) and examine its reliability and validity. Method A draft item pool was developed based on a literature review, and simplified to 30 items in four domains. Next, the item pool was reviewed by four visiting nurses and four researchers and refined to 15 items. A cross-sectional study was then conducted using a self-reported questionnaire. Questionnaires were sent to 2703 visiting nurses. The survey questions included participants’ basic demographic information, the importance of each item according to a modified scale, basic demographics for cases of death by senility at home, satisfaction with each item of the modified scale in an example case, and assessment of the case using the Japanese version of the Support Team Assessment Schedule (STAS-J). Internal consistency was assessed using Cronbach’s alpha. Construct validity was confirmed using confirmatory factor analysis, and correlation between the new scale and the STAS-J was used to assess criterion-related validity. Results In total, 461 visiting nurses provided valid responses. The exploratory and confirmatory factor analyses identified 12 items from two factors: “Needs for adaptation to senility bereavement” and “Needs for essential skills in supporting a dignified death by senility. ” The final model showed appropriate index values: standardized root mean residual = 0.057, Tucker–Lewis index = 0.920, Akaike information criterion = 191.6, and Bayesian information criterion = 298.2. Cronbach’s alpha for the entire scale was 0.908, and was above 0.840 for each factor. The correlation coefficient between STAS-J and the entire scale was 0.259–0.427 (p<0.001). Conclusions The FADE scale showed acceptable internal consistency and concurrent validity. The scale can help clarify issues and desires that present themselves at home related to adaptation to senility bereavement and essential skills in supporting a dignified death by senility. Addressing these issues and desires is expected to reduce caregivers’ anxiety and burden, and means the older adults under their care may be respected and enabled to live with dignity and peace.
Shedding of Mycobacterium caprae by wild red deer (Cervus elaphus) in the Bavarian alpine regions, Germany.

The number of natural infections with Mycobacterium caprae in wildlife and in cattle in the Bavarian and Austrian alpine regions has increased over the last decade. Red deer (Cervus elaphus) have been recognized as maintenance reservoir, however, the transmission routes of M. caprae among and from naturally infected red deer are unknown. The unexpected high prevalence in some hot spot regions might suggest an effective indirect transmission of infection. Therefore, this study was undertaken to diagnose the occurrence of M. caprae in feces and secretions of red deer in their natural habitat. A total of 2,806 red deer hunted in this region during 2014 - 2016 was included in this study. After pathological examination, organs (lymph nodes, lung, heart), excretions and secretions (feces, urine, saliva and tonsil swabs) were further investigated by qPCR specific for Mycobacterium tuperculosis complex (MTC), M. bovis and M. caprae. Samples tested positive by qPCR were processed for culturing of mycobacteria. In total, 55 (2.0%) animals were confirmed positive for M. caprae by pathological examination, PCR and culturing of the affected organ material. With the exception of one sample, all of the secretion and excretion samples were negative for mycobacteria of the Mycobacterium tuberculosis complex (MTC). From one red deer, M. caprae could be isolated from the heart sac as well as from the feces. Whole genome sequencing confirmed that both strains were clonally related. This is the first confirmation that M. caprae can be shed with the feces of a naturally infected red deer. However, further studies focusing on a higher number of infected animals, sample standardization and coordinated multiple sampling are necessary to improve the understanding of transmission routes under natural conditions.
Responses of neurons in macaque MT to unikinetic plaids.

Response properties of MT neurons are often studied with "bikinetic" plaid stimuli, which consist of two superimposed sine wave gratings moving in different directions. Oculomotor studies using "unikinetic plaids" in which only one of the two superimposed gratings moves suggest that the eyes first move reflexively in the direction of the moving grating and only later converge on the perceived direction of the moving pattern. MT has been implicated as the source of visual signals that drives these responses. We wanted to know whether stationary gratings, which have little effect on MT cells when presented alone, would influence MT responses when paired with a moving grating. We recorded extracellularly from neurons in area MT and measured responses to stationary and moving gratings, and to their sums: bikinetic and unikinetic plaids. As expected, stationary gratings presented alone had a very modest influence on the activity of MT neurons. Responses to moving gratings and bikinetic plaids were similar to those previously reported, and revealed cells selective for the motion of plaid patterns and of their components (pattern and component cells). When these neurons were probed with unikinetic plaids, pattern cells shifted their direction preferences by roughly 30 deg, revealing the influence of the static grating. Component cell preferences shifted little or not at all. These results support the notion that pattern selective neurons in area MT integrate component motions that differ widely in speed, and that they do so in a way that is consistent with an intersection-of-constraints model.
Reliability and validity of an FFQ for South American children and adolescents from the SAYCARE study

Abstract Objective: The purpose of this study was to analyse the reliability and validity of a semi-quantitative FFQ to assess food group consumption in South American children and adolescents. Design: The SAYCARE (South American Youth/Child cARdiovascular and Environmental) study is an observational, multicentre, feasibility study performed in a sample of 3- to 18-year-old children and adolescents attending private and public schools from six South American countries. Participants answered the FFQ twice with a two-week interval and three 24-h dietary recalls. Intraclass and Spearman’s correlations, weighted Cohen’s kappa (κw), percentage of agreement and energy-adjusted Pearson’s correlation coefficients were calculated. Setting: Seven cities in South America (Buenos Aires, Lima, Medelin, Montevideo, Santiago, Sao Paulo and Teresina). Subjects: A sample of 200 children and 244 adolescents for reliability analyses and 252 children and 244 adolescents for validity analyses were included. Results: Depending on the food group, for children and adolescents, reliability analyses resulted in Spearman’s coefficients from 0·47 to 0·73, intraclass correlation coefficients from 0·66 to 0·99, κw coefficients from 0·35 to 0·63, and percentage of agreement between 72·75 and 83·52 %. In the same way, validity analyses resulted in Spearman’s coefficients from 0·17 to 0·37, energy-adjusted Pearson’s coefficients from 0·17 to 0·61, κw coefficients from 0·09 to 0·24, and percentages of agreement between 45·79 and 67·06 %. Conclusion: The SAYCARE FFQ achieved reasonable reliability and slight-moderate validity for almost all food groups intakes. Accordingly, it can be used for the purpose of ranking the intake of individuals within a population.
Abnormal expression and clinical significance of 25-hydroxyvitamin D and sFlt-1 in patients with preeclampsia

Objective To determine the association between levels of serum 25-hydroxyvitamin D (25[OH]D) and soluble fms-like tyrosine kinase 1 (sFlt-1) in patients with preeclampsia. Methods Clinical and demographic data were collected from patients with preeclampsia and healthy pregnant controls. Serum 25(OH)D and sFlt-1 levels were evaluated by enzyme-linked immunosorbent assay and their correlations were determined using Spearman’s rank correlation coefficient. Associations between serum 25(OH)D and sFlt-1 levels and disease severity and clinical parameters were evaluated. Results Significantly lower serum 25(OH)D and higher sFlt-1 levels were observed in patients with preeclampsia (n = 100) versus controls (n = 100), and 25(OH)D was inversely correlated with sFlt-1 in patients with preeclampsia. Serum 25(OH)D levels were reduced, while sFlt-1 concentration was increased in patients with severe versus mild preeclampsia. Serum 25(OH)D levels were reduced in late-onset versus early-onset severe preeclampsia. Patients with preeclampsia who had lower serum 25(OH)D or elevated sFlt-1 levels showed significantly higher blood pressure indexes versus those with higher 25(OH)D or lower sFlt-1. Conclusions Low serum 25(OH)D and high sFlt-1 may be candidate biomarkers for preeclampsia diagnosis and prognosis.