Miracle-dz/UniFAR-FTUs huggingface dataset:
Antonovsky’s sense of coherence and resistance resources reduce perception of burden in family carers of people with Alzheimer’s disease

Abstract Objectives: Taking care of people with dementia (PWD) has been associated with some degree of burden. The variability of the carer’s burden can be partially explained by their personal characteristics. Antonovsky’s model of health defined the resistance resources (RRs) as essential mechanisms to cope with stressors, and to shape the personal sense of coherence (SOC). This study identifies the RRs related with carer’s SOC, and their implications in the perception of burden in family dementia carers. Methods: A sample of 308 participants from the ‘SOC & DEM study’ (154 carers and 154 PWD) was recruited from two memory clinics. Carer’s personal characteristics of burden, SOC, self-efficacy, coping strategies, perceived social support, and depression were evaluated using standardized instruments. PWD’s degree of dependence and behaviour and psychological symptoms of dementia (BPSD) were assessed too. A path analysis was used to test the relationship between caregiver burden and SOC including the personal RRs of the carers and clinical data of PWD. Results: The path model identified SOC as a major factor related to carer’s burden perception (r = –.327). Self-efficacy (r = .285), two coping strategies, ‘use instrumental support’ (r = –.235) and ‘behavioural disengagement’ (r = –.219), and social support perceived (r = .304) were the main carer’s personal characteristics directly related with SOC. Caring experience (r = –.281) was the main carer factor related with burden while dependence (r = .156) and BPSD (r = .157) were the dementia factors. Conclusion: The SOC has previously related with carer’s burden. The results contributed to identify relevant and modifiable personal characteristics as RRs that could reduce this burden.
Dynamics of Phenotypic Heterogeneity Associated with EMT and Stemness during Cancer Progression

Genetic and phenotypic heterogeneity contribute to the generation of diverse tumor cell populations, thus enhancing cancer aggressiveness and therapy resistance. Compared to genetic heterogeneity, a consequence of mutational events, phenotypic heterogeneity arises from dynamic, reversible cell state transitions in response to varying intracellular/extracellular signals. Such phenotypic plasticity enables rapid adaptive responses to various stressful conditions and can have a strong impact on cancer progression. Herein, we have reviewed relevant literature on mechanisms associated with dynamic phenotypic changes and cellular plasticity, such as epithelial–mesenchymal transition (EMT) and cancer stemness, which have been reported to facilitate cancer metastasis. We also discuss how non-cell-autonomous mechanisms such as cell–cell communication can lead to an emergent population-level response in tumors. The molecular mechanisms underlying the complexity of tumor systems are crucial for comprehending cancer progression, and may provide new avenues for designing therapeutic strategies.
Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity.

The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 weeks (n=9-11/group). Cardiovascular pathology was assessed as the degree of arterial stiffness (aortic pulse wave velocity) and myocardial infarct size following a 45/120 min ex vivo global cardiac ischemia/reperfusion protocol. Gut microbiota was characterized by 16s rDNA sequencing, along with measures of intestinal barrier function and cecal short-chain fatty acid (SCFA) composition. Following CMT, the gut microbiota of recipient mice was altered to resemble that of the donors. Ob CMT to Con mice increased arterial stiffness, left ventricular (LV) mass and myocardial infarct size, which was associated with greater gut permeability and reduced cecal SCFA concentrations. Conversely, Con CMT to Ob mice increased cecal SCFA, reduced LV mass and attenuated myocardial infarct size, with no effects on gut permeability or arterial stiffness. Collectively, these data demonstrate that obesity-related changes in the gut microbiota, independent of dietary manipulation, regulate hallmark measures of cardiovascular pathology in mice, and highlight the potential of microbiota-targeted therapeutics for reducing cardiovascular pathology and risk in obesity.
Validity and Reliability of the Facility List Coder, a New Tool to Evaluate Community Food Environments

A community food environment plays an essential role in explaining the healthy lifestyle patterns of its community members. However, there is a lack of compelling quantitative approaches to evaluate these environments. This study introduces and validates a new tool named the facility list coder (FLC), whose purpose is to assess food environments based on data sources and classification algorithms. Using the case of Mataró (Spain), we randomly selected 301 grids areas (100 m2), in which we conducted street audits in order to physically identify all the facilities by name, address, and type. Then, audit-identified facilities were matched with those automatically-identified and were classified using the FLC to determine its quality. Our results suggest that automatically-identified and audit-identified food environments have a high level of agreement. The intra-class correlation coefficient (ICC) estimates and their respective 95% confidence intervals for the overall sample yield the result “excellent” (ICC ≥ 0.9) for the level of reliability of the FLC.
Reinhard Hoeppli (1893–1973): The life and curious afterlife of a distinguished parasitologist

Reinhard Hoeepli was a Swiss-German physician with a distinguished career as a researcher and historian of medical parasitology. He spent the majority of his career at the Peking Union Medical College in Beijing, China, where he undertook research on host responses to parasitic infections, in particular describing the ‘Splendore-Hoeppli phenomenon’, between 1929 and 1952. During the Second World War, he acted as the Swiss honorary Consul in Japanese-occupied Beijing. After leaving China following the militarization of the College in the wake of the Korean War, he subsequently worked in Singapore and Liberia before retiring to Switzerland. Hoeppli is most widely known for his association with Sir Edmund Backhouse, a controversial and enigmatic Chinese scholar, who was his war-time patient towards the end of his life. With Hoeppli's encouragement, Backhouse wrote two scandalous and unpublishable memoirs which remained in Hoeppli's safe-keeping until his own death in 1973. However, the revelations by the historian Hugh Trevor-Roper in 1976 that Backhouse was a fraudster and fantasist has had a detrimental effect on Hoeppli's posthumous reputation that has overshadowed his many lifetime achievements. Alongside a biography of his life, an examination of the controversies of the Backhouse revelations on Hoeppli's repute is presented.
In situ characterisation of biofilms formed by psychrotrophic meat spoilage pseudomonads

Abstract Psychrotrophic Pseudomonas species form biofilms on meat during refrigerated and temperature abuse conditions. Biofilm growth leads to slime formation on meat which is a key organoleptic degradation characteristic. Limited research has been undertaken characterising biofilms grown on meat during chilled aerobic storage. In this work, biofilms formed by two key meat spoilage organisms, Pseudomonas fragi and Pseudomonas lundensis were studied in situ using five strains from each species. Biofilm structures were studied using confocal microscope images, cellular arrangement, cell counts and biomass quantifications. This work demonstrated that highly dense, compact biofilms are a characteristic of P. fragi strains. P. lundensis formed biofilms with loosely arranged cells. The cells in P. fragi biofilm appear to be vertically oriented whereas this characteristic was absent in P. lundensis biofilms formed under identical conditions. Despite the continued access to nutrients, biofilms formed on meat by proteolytic Pseudomonas species dispersed after a population maximum was reached.
Efficacy and safety of trimethoprim-sulfamethoxazole in HIV-infected patients with cerebral toxoplasmosis in Brazil: a single-arm open-label clinical trial

Cerebral toxoplasmosis continues to cause high morbidity and mortality in developing countries. The association of sulfadiazine and pyrimethamine is considered the standard therapy; however, it has potential disadvantages. This single-arm open-label clinical trial was carried out in a tertiary hospital in São Paulo, Brazil. We included patients of at least 18 years of age, whose HIV infection was confirmed, and clinical and brain computed tomography (CT) findings were compatible with cerebral toxoplasmosis upon admission. Patients received trimethoprim (TMP) 10 mg/kg/day sulfamethoxazole (SMX) 50 mg/kg/day, in two divided doses. Brain CT was performed at study entry and after two weeks. The endpoints of the study were: (i) the proportion of patients with clinical and radiological response after two weeks of TMP-SMX and (ii) the proportion of patients who discontinued TMP-SMX due to adverse events. Forty-six patients were included (23 males, median age 35 years). The main clinical manifestations were headache, hemiparesis and altered mental status. The proportion of patients who obtained clinical and radiological response after two weeks of anti-toxoplasma treatment was 85% (n = 39). Overall, TMP-SMX was safe, with only 2 (4%) discontinuations due to adverse events. In this study, TMP-SMX was effective and safe in the treatment of HIV-related cerebral toxoplasmosis.
Prevalence and Trends of Developmental Disabilities among Children in the United States: 2009–2017

From the 2009 to 2017 NHIS, there was a 9.5% increase in the prevalence of developmental disabilities among children aged 3 to 17. BrightcoveDefaultPlayer10.1542/6063241429001PEDS-VA_2019-0811 Video Abstract OBJECTIVES: To study the national prevalence of 10 developmental disabilities in US children aged 3 to 17 years and explore changes over time by associated demographic and socioeconomic characteristics, using the National Health Interview Survey. METHODS: Data come from the 2009 to 2017 National Health Interview Survey, a nationally representative survey of the civilian noninstitutionalized population. Parents reported physician or other health care professional diagnoses of attention-deficit/hyperactivity disorder; autism spectrum disorder; blindness; cerebral palsy; moderate to profound hearing loss; learning disability; intellectual disability; seizures; stuttering or stammering; and other developmental delays. Weighted percentages for each of the selected developmental disabilities and any developmental disability were calculated and stratified by demographic and socioeconomic characteristics. RESULTS: From 2009 to 2011 and 2015 to 2017, there were overall significant increases in the prevalence of any developmental disability (16.2%–17.8%, P < .001), attention-deficit/hyperactivity disorder (8.5%–9.5%, P < .01), autism spectrum disorder (1.1%–2.5%, P < .001), and intellectual disability (0.9%–1.2%, P < .05), but a significant decrease for any other developmental delay (4.7%–4.1%, P < .05). The prevalence of any developmental disability increased among boys, older children, non-Hispanic white and Hispanic children, children with private insurance only, children with birth weight ≥2500 g, and children living in urban areas and with less-educated mothers. CONCLUSIONS: The prevalence of developmental disability among US children aged 3 to 17 years increased between 2009 and 2017. Changes by demographic and socioeconomic subgroups may be related to improvements in awareness and access to health care.
Tryptophan catabolites as metabolic markers of vitamin B-6 status evaluated in cohorts of healthy adults and cardiovascular patients.

BACKGROUND Vitamin B-6 status is routinely measured as pyridoxal 5'-phosphate (PLP) in plasma. Low concentrations of PLP are associated with rheumatic, cardiovascular, and neoplastic diseases. We have previously shown that vitamin B-6 status affects the kynurenine (Kyn) pathway of tryptophan (Trp) catabolism. OBJECTIVE This study aimed to comprehensively evaluate the use of Kyns as potential markers of functional vitamin B-6 status across 2 large cohorts. METHODS We measured circulating concentrations of the first 6 metabolites in the Trp catabolic pathway by LC-MS-MS in the community-based Hordaland Health Study (HUSK; n = 7017) and cardiovascular patient-based Western Norway Coronary Angiography Cohort (WECAC; n = 4161). Cross-sectional and longitudinal associations of plasma PLP with Kyns were estimated using linear and nonlinear regression-based methods. RESULTS 3'-Hydroxykynurenine (HK), a substrate, and all 4 products formed directly by the PLP-dependent enzymes kynurenine transaminase and kynureninase contributed to the explanation of circulating PLP in multivariable-adjusted regression models. The construct HK:(kynurenic acid + xanthurenic acid + 3'-hydroxyanthranilic acid + anthranilic acid), termed HK ratio (HKr), was related to plasma PLP with standardized regression coefficients (95% CIs) of -0.47 (-0.49, -0.45) and -0.46 (-0.49, -0.43) in HUSK and WECAC, respectively. Across strata of cohort and sex, HKr was 1.3- to 2.7-fold more sensitive, but also 1.7- to 2.9-fold more specific to changes in PLP than a previously proposed marker, HK:xanthurenic acid. Notably, the association was strongest at PLP concentrations < ∼20 nmol/L, a recognized threshold for vitamin B-6 deficiency. Finally, PLP and HKr demonstrated highly sex-specific and corroborating associations with age. CONCLUSIONS The results demonstrate that by combining 5 metabolites in the Kyn pathway into a simple index, HKr, a sensitive and specific indicator of intracellular vitamin B-6 status is obtained. The data also underscore the merit of evaluating alterations in Kyn metabolism when investigating vitamin B-6 and health.
Adults who report difficulty hearing speech in noise: an exploration of experiences, impacts and coping strategies

Abstract Objective: Listening difficulties in noise are common, even in those with clinically normal hearing. There is a suggestion that subjective assessment of hearing difficulties may be more closely associated with listening effort and fatigue rather than objective measures of hearing and/or speech perception. The aim of this study was to better understand these perceptual deficits and experiences of this population. Design: An exploratory survey was distributed to participants with self-reported listening-in-noise difficulties. The primary aim of the survey was to gather information about challenging listening environments, its impact, and preferred rehabilitation strategies. Secondly, responses were compared to their performance on behavioural tasks. Study sample: Fifty adults aged 33–55 (22 females, with normal or near-normal hearing thresholds), completed the survey, and 45 of these performed behavioural tasks. Results: Background noise with conversational content was the most common source of hearing difficulties. Participants expended higher concentration and attention when communicating in noise, and correlations with previously published behavioural data was reported. Social impacts varied, few had sought treatment, and respondents preferred training over devices. Conclusions: Insights gained may provide clinicians and researchers with an understanding of the situations, impacts and non-auditory factors associated with listening-in-noise difficulties, and preferred rehabilitation for these clients.
Impact of Anticoagulant and Antiplatelet Use on Outcomes in Blunt Chest Injury

The aim of this study was to evaluate the impact of prehospital antiplatelet and/or anticoagulant (APAC) use on treatment and outcomes in patients with severe blunt chest injury. Patients with three or more rib fractures and a hospital length of stay (LOS) > three days admitted from 2014 to 2015 were included. Demographics, mortality, complications, injuries, hospital and ICU LOS, use of blood products, and thoracostomy were studied. Of 383 patients, 27.4 per cent were on APAC medication. Patients on APAC were older (P < 0.0001), had higher Glasgow Coma Score (P < 0.0001), and had lower Injury Severity Score (P < 0.0001) and total number of fractures (P = 0.0013) than the non-APAC group. APAC was not a predictor of mortality with or without age adjustment. In multiple linear regressions, APAC did not predict an increased LOS. APAC patients did not demonstrate an increase in admission diagnosis or complication of hemothorax, blood transfusions, tube thoracostomy, tracheostomy, LOS, or mortality rates. Similar findings are present in the subgroup of patients studied with high kinetic energy mechanism of injury. Our study does not support the perceived morbidity of APAC therapy in patients with severe blunt chest injury.
Motor neuron diseases caused by a novel VRK1 variant – A genotype/phenotype study

Motor neuron disorders involving upper and lower neurons are a genetically and clinically heterogenous group of rare neuromuscular disorders with overlap among spinal muscular atrophies (SMAs) and amyotrophic lateral sclerosis (ALS). Classical SMA caused by recessive mutations in SMN1 is one of the most common genetic causes of mortality in infants. It is characterized by degeneration of anterior horn cells in the spinal cord, leading to progressive muscle weakness and atrophy. Non‐SMN1‐related spinal muscular atrophies are caused by variants in a number of genes, including VRK1, encoding the vaccinia‐related kinase 1 (VRK1). VRK1 variants have been segregated with motor neuron diseases including SMA phenotypes or hereditary complex motor and sensory axonal neuropathy (HMSN), with or without pontocerebellar hypoplasia or microcephaly.
Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial

Introduction Morphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness. Methods Multisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, ‘as needed’, immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0–100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms. Results Analysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference −0.15 mm (95% CI −4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation. Conclusion No differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine. Trial registration number ACTRN12609000806268.
The effectiveness and tolerability of imiquimod suppositories to treat extensive intra-anal high-grade squamous intraepithelial lesions/warts in HIV-infected individuals

Topical imiquimod is a potential treatment for intra-anal condyloma and squamous intraepithelial lesions caused by human papillomavirus (HPV). We aimed to assess the effectiveness and tolerability of imiquimod suppositories for the treatment of anal high-grade intraepithelial lesions (HSIL) and condylomas in HIV-infected patients. We conducted a retrospective analysis in a prospectively followed cohort. High-resolution anoscopy was used for diagnosis and assessment following treatment. Patients’ tolerability was assessed with a self-administered survey. Ninety-five patients (94.7% men) were analyzed. All were on combination antiretroviral therapy. Median CD4 T-cell count was 690 cells/µL, 89% had undetectable plasma viral load. Response to imiquimod was seen in 46.3% (complete: 12.5%, partial: 33.8%) in the intent-to-treat analysis, and in 55.2% (complete: 14.9%, partial: 40.3%) in the on-treatment analysis. Higher response rates were observed for anal condyloma compared with HSIL. A significantly poorer response rate was observed in smokers and in individuals with lower nadir CD4 T-cell counts. Imiquimod tolerability was “good” in 57.1% (n = 36), “acceptable” in 33.3% (n = 21), and “poor” in 9.5% (n = 6). Systemic side effects were reported in 20.7% (n = 13). There was no association between treatment effect and tolerability. In conclusion, imiquimod stands as a well-tolerated option for the treatment of HPV-associated intra-anal pathology in HIV-infected individuals.
Who Is Enrolling? The Path to Monitoring in Type 1 Diabetes TrialNet’s Pathway to Prevention

OBJECTIVE To better understand potential facilitators of individual engagement in type 1 diabetes natural history and prevention studies through analysis of enrollment data in the TrialNet Pathway to Prevention (PTP) study. RESEARCH DESIGN AND METHODS We used multivariable logistic regression models to examine continued engagement of eligible participants at two time points: 1) the return visit after screening to confirm an initial autoantibody-positive (Ab+) test result and 2) the initial oral glucose tolerance test (OGTT) for enrollment into the monitoring protocol. RESULTS Of 5,387 subjects who screened positive for a single autoantibody (Ab), 4,204 (78%) returned for confirmatory Ab testing. Younger age was associated with increased odds of returning for Ab confirmation (age <12 years vs. >18 years: odds ratio [OR] 2.12, P < 0.0001). Racial and ethnic minorities were less likely to return for confirmation, particularly nonwhite non-Hispanic (OR 0.50, P < 0.0001) and Hispanic (OR 0.69, P = 0.0001) relative to non-Hispanic white subjects. Of 8,234 subjects, 5,442 (66%) were identified as eligible to be enrolled in PTP OGTT monitoring. Here, younger age and identification as multiple Ab+ were associated with increased odds of returning for OGTT monitoring (age <12 years vs. >18 years: OR 1.43, P < 0.0001; multiple Ab+: OR 1.36, P < 0.0001). Parents were less likely to enroll into monitoring than other relatives (OR 0.78, P = 0.004). Site-specific factors, including site volume and U.S. site versus international site, were also associated with differences in rates of return for Ab+ confirmation and enrollment into monitoring. CONCLUSIONS These data confirm clear differences between successfully enrolled populations and those lost to follow-up, which can serve to identify strategies to increase ongoing participation.