Lifestyle\u27s influence on community-dwelling older adults\u27 health: A mixed-methods study design

Background: Aging often involves health problems and difficulties, such as physical and psychological impairments, isolation, and loneliness, causing social and existential consequences. Studies have explored aging from different perspectives. However, few studies have examined healthy older adults’ genetic backgrounds, lifestyles, and meaning in life separately or in combination. This study aims to describe how healthy older adults experience aging, health, lifestyles, and meaning in life and explore potential genetic correlations. Methods and Design:The project will comprise three main parts: a quantitative section featuring the development and testing of a lifestyle questionnaire, a quantitative genetic analysis, and a qualitative interview study. Participants will be community-dwelling, healthy, older adults between 70 and 95 years of age. A sample size of 800 older adults will be invited to participate in seminars in collaboration with the national Swedish association Active Seniors. Data will be collected through lifestyle questionnaire, DNA extracted from saliva samples, and interviews. Based on questionnaire responses, profile groups will be created and compared statistically with variations in genetic backgrounds, providing the basis for recruiting participants to the qualitative interviews. Discussion: This study’s expected outcome will be to gain knowledge about variations in genetic backgrounds correlated with individual experiences regarding aging, health, and meaning in life. This knowledge can improve the understanding of motivations for healthy lifestyle changes. The results can reveal potential implications for individual prerequisites to healthy aging and how health-promoting aging and lifestyle counseling can be adjusted to meet individual needs

Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men : the MrOS Sweden cohort

Summary: This study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures. Introduction: Anemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures. Method: Men from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years. Results: Men with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28–3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18–3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06–5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD. Conclusions: Anemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture

HAMLET Interacts with Lipid Membranes and Perturbs Their Structure and Integrity

Background Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure. Methodology/Principal Findings We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral pH and physiological conditions, as shown by fluorophore leakage experiments. These effects did not occur with either native HLA or a constitutively unfolded Cys-Ala HLA mutant (rHLAall-Ala). HAMLET also bound to plasma membrane vesicles formed from intact tumor cells, with accumulation in certain membrane areas, but the complex was not internalized by these vesicles or by the synthetic membrane vesicles. Conclusions/Significance The results illustrate the difference in membrane affinity between the fatty acid bound and fatty acid free forms of partially unfolded HLA and suggest that HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. Furthermore, HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death

Sulfatide Recognition by Colonization Factor Antigen CS6 from Enterotoxigenic Escherichia coli

The first step in the pathogenesis of enterotoxigenic Escherichia coli (ETEC) infections is adhesion of the bacterium to the small intestinal epithelium. Adhesion of ETEC is mediated by a number of antigenically distinct colonization factors, and among these, one of the most commonly detected is the non-fimbrial adhesin coli surface antigen 6 (CS6). The potential carbohydrate recognition by CS6 was investigated by binding of recombinant CS6-expressing E. coli and purified CS6 protein to a large number of variant glycosphingolipids separated on thin-layer chromatograms. Thereby, a highly specific binding of the CS6-expressing E. coli, and the purified CS6 protein, to sulfatide (SO3-3Galβ1Cer) was obtained. The binding of the CS6 protein and CS6-expressing bacteria to sulfatide was inhibited by dextran sulfate, but not by dextran, heparin, galactose 4-sulfate or galactose 6-sulfate. When using recombinantly expressed and purified CssA and CssB subunits of the CS6 complex, sulfatide binding was obtained with the CssB subunit, demonstrating that the glycosphingolipid binding capacity of CS6 resides within this subunit. CS6-binding sulfatide was present in the small intestine of species susceptible to CS6-mediated infection, e.g. humans and rabbits, but lacking in species not affected by CS6 ETEC, e.g. mice. The ability of CS6-expressing ETEC to adhere to sulfatide in target small intestinal epithelium may thus contribute to virulence

Who is publishing in ecology and evolution? the underrepresentation of women and the Global South

Introduction: Most global biodiversity is in developing economies. Decades of capacity building should have built sufficient in-country capacity to develop biodiversity baselines; yet has effort provided the expertise to build these baselines?Methods: Grants and access to research opportunities are often linked to success in publishing, with the H-index providing the main metric of academic success. Recent compilations of “Top Researchers in Ecology and Evolution” included 5,419 researchers, but where these researchers are and how representative they are has not been well studied. We explored the global distribution of “Top Researchers in Ecology and Evolution” and explored the representation of Women, non-Caucasians, and non-Caucasian women, as well as the representation of “local” top researchers in different regions.Results: Over half Top Researchers in Ecology and Evolution are from just three countries (United States, United Kingdom, and Australia), and 83% come from 12 higher-income countries. Even in lower-income economies the majority of the few “high impact” researchers are originally from higher-income economies. Only China had a high proportion of their high-impact non-Caucasian researchers, with the majority of researchers coming from that region. Women were also underrepresented across the globe, only three countries had more than 20% of top-performing ecologists being female.Discussion: Ultimately, despite decades of capacity building, we are still failing to build in-country capacity for research or to provide sufficient support for female ecologists to publish and lead the field. Here we discuss why these issues persist, and how we might improve representation and access to opportunity and support for all groups, and provide the analysis needed to provide solutions to global challenges in biodiversity conservation, which require diverse representation to develop effective, and nuanced solutions

The Expression of BAFF, APRIL and TWEAK Is Altered in Eczema Skin but Not in the Circulation of Atopic and Seborrheic Eczema Patients

The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE

Nanovesicles from Malassezia sympodialis and Host Exosomes Induce Cytokine Responses – Novel Mechanisms for Host-Microbe Interactions in Atopic Eczema

BACKGROUND: Intercellular communication can occur via the release of membrane vesicles. Exosomes are nanovesicles released from the endosomal compartment of cells. Depending on their cell of origin and their cargo they can exert different immunoregulatory functions. Recently, fungi were found to produce extracellular vesicles that can influence host-microbe interactions. The yeast Malassezia sympodialis which belongs to our normal cutaneous microbial flora elicits specific IgE- and T-cell reactivity in approximately 50% of adult patients with atopic eczema (AE). Whether exosomes or other vesicles contribute to the inflammation has not yet been investigated. OBJECTIVE: To investigate if M. sympodialis can release nanovesicles and whether they or endogenous exosomes can activate PBMC from AE patients sensitized to M. sympodialis. METHODS: Extracellular nanovesicles isolated from M. sympodialis, co-cultures of M. sympodialis and dendritic cells, and from plasma of patients with AE and healthy controls (HC) were characterised using flow cytometry, sucrose gradient centrifugation, Western blot and electron microscopy. Their ability to stimulate IL-4 and TNF-alpha responses in autologous CD14, CD34 depleted PBMC was determined using ELISPOT and ELISA, respectively. RESULTS: We show for the first time that M. sympodialis releases extracellular vesicles carrying allergen. These vesicles can induce IL-4 and TNF-α responses with a significantly higher IL-4 production in patients compared to HC. Exosomes from dendritic cell and M. sympodialis co-cultures induced IL-4 and TNF-α responses in autologous CD14, CD34 depleted PBMC of AE patients and HC while plasma exosomes induced TNF-α but not IL-4 in undepleted PBMC. CONCLUSIONS: Extracellular vesicles from M. sympodialis, dendritic cells and plasma can contribute to cytokine responses in CD14, CD34 depleted and undepleted PBMC of AE patients and HC. These novel observations have implications for understanding host-microbe interactions in the pathogenesis of AE

Treatment of cerebral cavernous malformations:a systematic review and meta-regression analysis

Item does not contain fulltextOBJECTIVE: The reported effects of treating cerebral cavernous malformations (CCMs) by neurosurgical excision or stereotactic radiosurgery are imprecise and vary between studies. METHODS: We searched Ovid Medline, EMBASE and The Cochrane Library for peer-reviewed publications of cohort studies describing outcomes of treating 20 or more patients with CCM with at least 80% completeness of follow-up. Two reviewers extracted data to quantify the incidence of a composite outcome (death, non-fatal intracranial haemorrhage, or new/worse persistent focal neurological deficit) after CCM treatment. We explored associations between summary measures of study characteristics and outcome using Poisson meta-regression analyses. RESULTS: We included 63 cohorts, involving 3424 patients. The incidence of the composite outcome was 6.6 (95% CI 5.7 to 7.5) per 100 person-years after neurosurgical excision (median follow-up 3.3 years) and 5.4 (95% CI 4.5 to 6.4) after stereotactic radiosurgery (median follow-up 4.1 years). After neurosurgical excision the incidence of the composite outcome increased with every per cent point increase in patients with brainstem CCM (rate ratio (RR) 1.03, 95% CI 1.01 to 1.05), and decreased with each more recent study midyear (RR 0.91, 95% CI 0.85 to 0.98) and each per cent point increase in patients presenting with haemorrhage (RR 0.98, 95% CI 0.96 to 1.00). We did not find significant associations in studies of stereotactic radiosurgery. CONCLUSIONS: The reported risks of CCM treatment (and the lower risks of neurosurgical excision over time, from recently bled CCMs, and for CCMs outside the brainstem) compare favourably with the risks of recurrent haemorrhage from CCM. Long-term effects, especially important for stereotactic radiosurgery, are unknown

Association of vitamin D status with arterial blood pressure and hypertension risk : a mendelian randomisation study

Peer reviewe