Accelerated aging in people experiencing homelessness: A rapid review of frailty prevalence and determinants

Introduction: Older people experiencing homelessness (PEH) are a rapidly growing population at risk of accelerated aging and the early onset of geriatric conditions. One construct that shows promise in predicting age-related decline is frailty. Better understanding the rates and causes of frailty in PEH may improve understanding of its antecedents, thereby facilitating more targeted health and aged care service interventions. The aim of this study was to conduct a rapid review on the prevalence and determinants of frailty in adult PEH. Methods: We conducted a rapid review of primary research papers studying PEH and frailty or frailty-related concepts. Results: Fourteen studies were included, which indicate that frailty presents earlier and at higher rates in PEH than community-dwelling cohorts. A notable difficulty for many aging PEH was early-onset cognitive impairment which was associated with a range of negative functional outcomes. Another recurrent theme was the negative impact that drug and alcohol use and dependence can have on the health of PEH. Further, psychosocial and structural determinants such as loneliness, living in an impoverished neighborhood and being female had statistically significant associations with frailty and functional decline in PEH. Discussion and implications: PEH in their 40s and 50s can be frail and experience geriatric conditions, including cognitive impairment. Factors that have important relationships to frailty and functional decline in PEH include cognitive deficits, drug and alcohol dependence and loneliness, as well as upstream determinants such as gender and ethnicity. More targeted data and research on these factors, including cohort studies to better investigate their potentially causal effects, is important for researchers and practitioners assessing and treating frailty in PEH, particularly those interested in early intervention and prevention. Prospero registration ID: CRD42022292549

Femtosecond Photoemission Study of Ultrafast Electron Dynamics in Single-Crystal Au(111) Films

The energy-dependent relaxation of photoexcited electrons has been measured by time-resolved two-photon photoemission spectroscopy on single-crystal Au(111) films with thickness ranging from 150 to 3000 Å. It is found that the energy-dependent relaxation does not show any significant thickness dependence, which indicates that electron transport is a much slower dynamical process in the near-surface region than expected from bulk properties. Furthermore, lifetimes of the photoexcited electrons can be fitted well by the Fermi-liquid theory with a scaling factor plus an effective upper lifetime. This observation enables separation of electron-electron scattering, and to a lesser extent electron-phonon scattering, processes from electron-transport effects on the surface dynamics. ©1998 American Physical Societ

Femtosecond Photoemission Study of Ultrafast Electron Dynamics on Cu(100)

The energy dependence of the relaxation of photoexcited electrons in copper was measured using femtosecond time-resolved photoemission spectroscopy to within 0.3 eV above the Fermi level. By performing lifetime measurements under different surface conditions, several surface dynamical processes were investigated. In particular, an anomalous long lifetime feature, which cannot be explained with Fermi-liquid theory, was observed in the lifetime-energy curve. This feature was found originating from the photoexcitation of the strongly localized Cu 3d electrons. ©1997 American Physical Societ

Quantitative silencing of EGFP reporter gene by self-assembled siRNA lipoplexes of LinOS and cholesterol

[Image: see text] Nonviral siRNA vectors prepared by the direct mixing of siRNA and mixtures of an asymmetric N(4),N(9)-diacyl spermine conjugate, N(4)-linoleoyl-N(9)-oleoyl-1,12-diamino-4,9-diazadodecane (LinOS), with either cholesterol or DOPE, at various molar ratios of the neutral lipids, are reported. The effects of varying the lipid formulation and changing the N/P charge ratio on the intracellular delivery of siRNA to HeLa cells and on the siRNA-mediated gene silencing of a stably expressed reporter gene (EGFP) were evaluated. The presence of either cholesterol or DOPE in the mixture resulted in a marked increase in the delivery of the siRNA as well as enhanced EGFP silencing as evaluated by FACS. A LinOS/Chol 1:2 mixture resulted in the highest siRNA delivery and the most efficient EGFP silencing (reduced to 20%) at N/P = 3.0. Lowering the amount of siRNA from 15 pmol to 3.75 pmol, thus increasing the N/P charge ratio to 11.9, resulted in decreasing the amount of delivered siRNA, while the efficiency of gene silencing was comparable to that obtained with 15 pmol (N/P = 3.0) of siRNA. Mixtures of symmetrical N(4),N(9)-dioleoyl spermine (DOS) with cholesterol at 1:2 molar ratio showed less siRNA delivery than with LinOS/Chol at N/P = 3.0 (15 pmol of siRNA), and comparable delivery at N/P = 11.9 (3.75 pmol of siRNA). The EGFP silencing was comparable with LinOS and with DOS when mixed with cholesterol 1:2 (lipoplexes prepared with 15 pmol of siRNA), but LinOS mixtures showed better EGFP silencing when the siRNA was reduced to 3.75 pmol. Lipoplex particle size determination by DLS of cholesterol mixtures was 106–118 nm, compared to 194–356 nm for lipoplexes prepared with the spermine conjugates only, and to 685 nm for the LinOS/DOPE 1:1 mixture. Confocal microscopy showed successful siRNA delivery of red tagged siRNA and quantitative EGFP knockdown in HeLa EGFP cells; Z-stack photomicrographs showed that the delivered siRNA is distributed intracellularly. Cryo-TEM of siRNA LinOS/Chol 1:2 lipoplexes shows the formation of multilamellar spheres with a size of ∼100 nm, in good agreement with the particle size measured by DLS. The constant distance between lamellar repeats is ∼6 nm, with the electron-dense layers fitting a monolayer of siRNA. AlamarBlue cell viability assay showed that the lipoplexes resulted in cell viability ≥81%, with LinOS/Chol 1:2 mixtures resulting in cell viabilities of 89% and 94% at siRNA 15 nM and 3.75 nM respectively. These results show that lipoplexes of siRNA and LinOS/Chol mixtures prepared by the direct mixing of the lipid mixture and siRNA, without any preceding preformulation steps, result in enhanced siRNA delivery and EGFP knockdown, with excellent cell viability. Thus, LinOS/Chol 1:2 mixture is a promising candidate as a nontoxic nonviral siRNA vector

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

Offering Self-administered Oral HIV Testing as a Choice to Truck Drivers in Kenya: Predictors of Uptake and Need for Guidance While Self-testing

We assessed predictors of choosing self-administered oral HIV testing in the clinic with supervision versus the standard provider-administered blood test when offered the choice among 149 Kenyan truck drivers, described the types of guidance participants needed during self-testing and predictors of needing guidance. Overall, 56.38% of participants chose the self-test, 23.49% the provider-administered test, and 20.13% refused testing. In the adjusted regression models, each additional unit on the fatalism and self-efficacy scales was associated with 0.97 (p = 0.003) and 0.83 (p = 0.008) times lower odds of choosing the self-test, respectively. Overall, 52.38% of self-testers did so correctly without questions, 47.61% asked questions, and 13.10% required unsolicited correction from the provider. Each additional unit on the fatalism scale was associated with 1.07 times higher odds of asking for guidance when self-testing (p\0.001). Self-administered oral HIV testing seems to be acceptable and feasible among Kenyan truck drivers, especially if given the opportunity to ask questions

The α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation

© 2020 The Author(s). Background: Oxygen therapy, using supraphysiological concentrations of oxygen (hyperoxia), is routinely administered to patients who require respiratory support including mechanical ventilation (MV). However, prolonged exposure to hyperoxia results in acute lung injury (ALI) and accumulation of high mobility group box 1 (HMGB1) in the airways. We previously showed that airway HMGB1 mediates hyperoxia-induced lung injury in a mouse model of ALI. Cholinergic signaling through the α7 nicotinic acetylcholine receptor (α7nAChR) attenuates several inflammatory conditions. The aim of this study was to determine whether 3-(2,4 dimethoxy-benzylidene)-anabaseine dihydrochloride, GTS-21, an α7nAChR partial agonist, inhibits hyperoxia-induced HMGB1 accumulation in the airways and circulation, and consequently attenuates inflammatory lung injury. Methods: Mice were exposed to hyperoxia (≥99% O2) for 3 days and treated concurrently with GTS-21 (0.04, 0.4 and 4 mg/kg, i.p.) or the control vehicle, saline. Results: The systemic administration of GTS-21 (4 mg/kg) significantly decreased levels of HMGB1 in the airways and the serum. Moreover, GTS-21 (4 mg/kg) significantly reduced hyperoxia-induced acute inflammatory lung injury, as indicated by the decreased total protein content in the airways, reduced infiltration of inflammatory monocytes/macrophages and neutrophils into the lung tissue and airways, and improved lung injury histopathology. Conclusions: Our results indicate that GTS-21 can attenuate hyperoxia-induced ALI by inhibiting extracellular HMGB1-mediated inflammatory responses. This suggests that the α7nAChR represents a potential pharmacological target for the treatment regimen of oxidative inflammatory lung injury in patients receiving oxygen therapy

Molecular mechanism for kinesin-1 direct membrane recognition

The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1\u2013dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1\u2013mediated organelle transport

The African Women's Protocol: Bringing Attention to Reproductive Rights and the MDGs

Andrew Gibbs and colleagues discuss the African Women's Protocol, a framework for ensuring reproductive rights are supported throughout the continent and for supporting interventions to improve women's reproductive health, including the MDGs

Irrigation of field and orchard crops under semi-arid conditions

Rev. ed