Identification and characterization of ERV-W-like sequences in Platyrrhini species provides new insights into the evolutionary history of ERV-W in primates

Background: Endogenous Retroviruses (ERVs) constitute approximately 8% of every human genome and are relics of ancestral infections that affected the germ line cells. The ERV-W group contributed to primate physiology by providing an envelope protein (Syncytin-1) that has been adopted for placenta development in hominoids. Expression of Human ERV-W (HERV-W) sequences is investigated for a pathological role in various human diseases. Results: We previously characterized ERV-W group genomic sequences in human and non-human Catarrhini species. We now investigated ERV-W-like sequences in the parvorder Platyrrhini, especially regarding two species with complete genome assemblies, namely marmoset (Callithrix jacchus) and squirrel monkey (Saimiri boliviensis). We identified in both species proviral sequences, annotated as ERV1-1 in respective genome assemblies, sharing high sequence similarities with Catarrhini ERV-W. A total of 130 relatively intact proviruses from the genomes of marmoset and squirrel monkey were characterized regarding their structural and evolutionarily relationships with Catarrhini ERV-W elements. Platyrrhini ERV-W sequences share several structural features with Catarrhini ERV-W elements and are closely related phylogenetically with the latter as well as with other ERV-W-related gammaretrovirus-like ERVs. The ERV-W group colonized Platyrrhini primates of both Callitrichidae and Atelidae lineages, with provirus formations having occurred mostly between 25 and 15 mya. Two LTR subgroups were associated with monophyletic proviral bodies. A pre-gag region appears to be a sequence feature common to the ERV-W group: it harbors a putative intron sequence that is missing in some ERV-W loci, holding a putative ORF as well. The presence of a long pre-gag portion was confirmed among all gammaretroviral ERV analyzed, suggesting a role in the latter biology. It is noteworthy that, contrary to Catarrhini ERV-W, there was no evidence of L1-mediated mobilization for Platyrrhini ERV-W sequences. Conclusions: Our data establish that ERV-W is not exclusive to Catarrhini primates but colonized both parvorders of Simiiformes, providing further insight into the evolution of ERV-W and the colonization of primate genomes

Bending modes of DNA directly addressed by cryo-electron microscopy of DNA minicircles

We use cryo-electron microscopy (cryo-EM) to study the 3D shapes of 94-bp-long DNA minicircles and address the question of whether cyclization of such short DNA molecules necessitates the formation of sharp, localized kinks in DNA or whether the necessary bending can be redistributed and accomplished within the limits of the elastic, standard model of DNA flexibility. By comparing the shapes of covalently closed, nicked and gapped DNA minicircles, we conclude that 94-bp-long covalently closed and nicked DNA minicircles do not show sharp kinks while gapped DNA molecules, containing very flexible single-stranded regions, do show sharp kinks. We corroborate the results of cryo-EM studies by using Bal31 nuclease to probe for the existence of kinks in 94-bp-long minicircle

Pet ownership and cognitive decline in older people

Animals can have a positive influence on human health. However, it is not yet known whether pet ownership can prevent cognitive decline. Therefore, we aimed to investigate cross-sectional and prospective associations between pet ownership and cognitive function in a large, representative sample of older adults. Data were from the English Longitudinal Study of Ageing (ELSA) using data collected in wave 5 and six years later in wave 8. Pet ownership was categorized as no pet, dog, cat or other pet. Cognitive function was assessed using tests of verbal fluency (assessed by asking how many different animals the participants could name in 60 seconds) and memory (sum of immediate and delayed verbal recall). Multiple linear regression, adjusted for potential confounders, was used to test the associations between pet ownership and cognitive function. A total of 8291 people (mean age: 66.72 years) were included. In cross-sectional analyses, dog owners had better verbal fluency than individuals with no pet, but there was no significant difference between cat or other pet owners and those with no pet. In prospective analyses, dog owners had a significantly larger decline in recall than those with no pet, whilst cat owners had a significantly smaller decline in verbal fluency. These results provide some evidence to suggest that pet ownership may have positive effects on cognition in later life. However, benefits of pet ownership were not unilaterally observed across different types of pet and measures of cognitive function suggesting that further research is required

Patient safety culture in Italian out-ofhours primary care service: a national cross-sectional survey study

Background: Out-of-hours (OOH) services in Italy provide >10 million consultations every year. To the authors' knowledge, no data on patient safety culture (PSC) have been reported. Aim: To assess PSC in the Italian OOH setting. Design & setting: National cross-sectional survey using the Safety Attitudes Questionnaire — Ambulatory Version (SAQ-AV). Method: The SAQ-AV was translated into Italian and distributed in a convenience sample of OOH doctors in 2015. Answers were collected anonymously by Qualtrics. Stata (version 14) was used to estimate Cronbach's alpha, perform exploratory and confirmatory factor analysis, correlate items to doctors' characteristics, and to do item descriptive analysis. Results: Overall, 692 OOH doctors were contacted, with a 71% response rate. In the exploratory factor analysis (EFA), four factors were identified: Communication and Safety Climate (14 items); Perceptions of Management (eight items); Workload and Clinical Risk (six items); and Burnout Risk (four items). These four factors accounted for 68% of the total variance (Kaiser-Meyer-Olkin [KMO] statistic = 0.843). Cronbach's alpha ranged from 0.710-0.917. OOH doctors were often dissatisfied with their job; there is insufficient staff to provide optimal care and there is no training or supervision for new personnel and family medicine trainees. Service managers are perceived as distant, with particular issues concerning the communication between managers and OOH doctors. A large proportion of OOH doctors (56.8%) state that they do not receive adequate support. Conclusion: These findings could be useful for informing policies on how to improve PSC in Italian OOH service

Ethnic Differences in Magnesium Intake in U.S. Older Adults: Findings from NHANES 2005–2016

Magnesium plays a crucial role in hundreds of bodily processes relevant to aging, but consumption of dietary magnesium intake has been shown to be inadequate in a large proportion of older adults. Identifying groups at risk of low magnesium intake is important for informing targeted advice. Using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2016, we examined the association between ethnicity (Caucasian/African American/Hispanic/other) and magnesium intake in a large representative sample of U.S. older adults (≥65 y, n = 5682, mean (SD) 72.9 (0.10) y). Analyses adjusted for total energy intake and a range of relevant covariates. Overall, 83.3% of participants were not meeting the recommended level of dietary magnesium intake, ranging from 78.1% of other ethnic groups to 90.6% of African Americans. In the fully adjusted model, magnesium intake was lower among African American older adults (−13.0 mg/d, 95% CI: −18.8 to −7.2), and higher among Hispanics (14.0 mg/d, 95% CI: 7.5 to 20.5) and those from other ethnic groups (17.2, 95% CI: 3.8 to 30.5) compared with Caucasian older adults. These results highlight the need for targeted interventions to increase magnesium intake in U.S. older adults, with a focus on African Americans, in order to reduce the burden of morbidity and ethnic inequalities in health in later life

Clinical prognostic factors for older people: A systematic review and meta-analysis

Objective: To explore the accuracy and precision of prognostic tools used in older people in predicting mortality, hospitalization, and nursing home admission across different settings and timings. Design: Systematic review and meta-analysis of prospective and retrospective studies. Data sources: A systematic search from database inception until 01st February 2023 was run in Medline, Embase, Cinhal, Cochrane Library. Eligibility criteria: Studies were eligible if they reported accuracy (area under the curve [AUC]) and/or precision (C-index) for the prognostic index in relation to any of the following outcomes: mortality, hospitalization, and nursing home admission. Data extraction and synthesis: Two independent reviewers extracted data. Data were pooled using a random effects model. The risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. If more than three studies for the same setting and time were available, a meta-analysis was performed and evaluated using the GRADE tool; other data were reported descriptively. Results: Among 16,082 studies initially considered, 159 studies with a total of 2398856 older people (mean age: 78 years) were included. The majority of the studies was carried out in hospital or medical wards. In the community setting, only two tools (Health Assessment Tool and the Multidimensional Prognostic Index, MPI) had good precision for long-term mortality. In emergency department setting, Barthel Index had an excellent accuracy in predicting short-term mortality. In medical wards, the MPI had a moderate certainty of the evidence in predicting short-term mortality (13 studies; 11,787 patients; AUC=0.79 and 4 studies; 3915 patients; C-index=0.82). Similar findings were available for MPI when considering longer follow-up periods. When considering nursing home and surgical wards, the literature was limited. The risk of bias was generally acceptable; observed bias was mainly owing to attrition and confounding. Conclusions: Several tools are used to predict poor prognosis in geriatric patients, but only those derived from a multidimensional evaluation have the characteristics of precision and accuracy

Pulmonary stretch and lung mechanotransduction: implications for progression in the fibrotic lung.

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of “squishy balls”, where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity, surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with as34 sociated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review we aim at summarizing the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support

Physical activity and exercise for the prevention and management of mild cognitive impairment and dementia: a collaborative international guideline

Background: Physical activity and exercise have been suggested as effective interventions for the prevention and management of mild cognitive impairment (MCI) and dementia, but there are no international guidelines. Objectives: To create a set of evidence- and expert consensus-based prevention and management recommendations regarding physical activity (any bodily movement produced by skeletal muscles that results in energy expenditure) and exercise (a subset of physical activity that is planned, structured, repetitive), applicable to a range of individuals from healthy older adults to those with MCI/dementia. Methods: Guideline content was developed with input from several scientific and lay representatives’ societies. A systematic search across multidisciplinary databases was carried out until October 2021. Recommendations for prevention and management were developed according to the GRADE and complemented by consensus statements from the expert panels. Recommendations: Physical activity may be considered for the primary prevention of dementia. In people with MCI there is continued uncertainty about the role of physical activity in slowing the conversion to dementia. Mind–body interventions have the greatest supporting evidence. In people with moderate dementia, exercise may be used for maintaining disability and cognition. All these recommendations were based on a very low/low certainty of evidence. Conclusions: Although the scientific evidence on the beneficial role of physical activity and exercise in preserving cognitive functions in subjects with normal cognition, MCI or dementia is inconclusive, this panel, composed of scientific societies and other stakeholders, recommends their implementation based on their beneficial effects on almost all facets of health