Increase in Frailty in Nursing Home Survivors of Coronavirus Disease 2019: Comparison With Noninfected Residents

ObjectivesInstitutionalized older adults have a high prevalence of frailty and disability, which may make them more vulnerable to the negative consequences of coronavirus disease 2019 (COVID-19). We investigated the impact of COVID-19 on the level of frailty, physical, and cognitive performance in nursing home residents.DesignNested case-control study.Setting and ParticipantsThe study included nursing home residents who were infected with COVID-19 (case group, n = 76), matched by age to a control group (n = 76).MethodsParticipants’ sociodemographic and medical data were collected, and they were also assessed for physical function (handgrip and walking speed), cognitive performance (Mini-Mental State Examination) and frailty (Frail-NH scale) before the first wave of the COVID-19 pandemic (October to December 2019, pre-COVID-19) and after (June to July 2020, post-COVID-19). COVID-19 symptoms and clinical course were recorded for the cases.ResultsBetween the pre- and post-COVID-19 assessments, we found a 19% greater deterioration in handgrip, a 22% greater decrease in walking speed, and a 21% greater increase in Frail-NH scores in cases compared with controls. In both cases and controls, on the other hand, there was a significant 10% decrease in Mini-Mental State Examination scores over the study period. Multivariable logistic regression showed that COVID-19 survivors had a 4-fold increased chance of developing frailty compared with controls (odds ratio 4.95, 95% confidence interval 1.13–21.6, P = .03), but not cognitive decline.Conclusions and ImplicationsCOVID-19 can accelerate the aging process of institutionalized older adults in terms of physical performance and frailty by around 20%. However, we found similar levels of decline in cognitive performance in both cases and controls, likely because of the burden of social isolation and containment measures on neuropsychological health.     

Association of upper gastrointestinal symptoms with functional and clinical charateristics in elderly

AIM: To evaluate the prevalence of upper gastrointestinal symptoms and their association with clinical and functional characteristics in elderly outpatients.METHODS: The study involved 3238 outpatients ≥ 60 years consecutively enrolled by 107 general practitioners. Information on social, behavioral and demographic characteristics, function in the activities of daily living (ADL), co-morbidities and drug use were collected by a structured interview. Upper gastrointestinal symptom data were collected by the 15-items upper gastro-intestinal symptom questionnaire for the elderly, a validated diagnostic tool which includes the following five symptom clusters: (1) abdominal pain syndrome; (2) reflux syndrome; (3) indigestion syndrome; (4) bleeding; and (5) non-specific symptoms. Presence and severity of gastrointestinal symptoms were analyzed through a logistic regression model.RESULTS: 3100 subjects were included in the final analysis. The overall prevalence of upper gastrointestinal symptoms was 43.0%, i.e. cluster (1) 13.9%, (2) 21.9%, (3) 30.2%, (4) 1.2%, and (5) 4.5%. Upper gastrointestinal symptoms were more frequently reported by females (P < 0.0001), with high number of co-morbidities (P < 0.0001), who were taking higher number of drugs (P < 0.0001) and needed assistance in the ADL. Logistic regression analysis demonstrated that female sex (OR = 1.39, 95% CI: 1.17-1.64), disability in the ADL (OR = 1.47, 95% CI: 1.12-1.93), smoking habit (OR = 1.29, 95% CI: 1.00-1.65), and body mass index (OR = 1.06, 95% CI: 1.04-1.08), as well as the presence of upper (OR = 3.01, 95% CI: 2.52-3.60) and lower gastroenterological diseases (OR = 2.25, 95%CI: 1.70-2.97), psychiatric (OR = 1.60, 95% CI: 1.28-2.01) and respiratory diseases (OR = 1.25, 95% CI: 1.01-1.54) were significantly associated with the presence of upper gastrointestinal symptoms.CONCLUSION: Functional and clinical characteristics are associated with upper gastrointestinal symptoms. A multidimensional comprehensive evaluation may be useful when approaching upper gastrointestinal symptoms in older subjects.     

Genome‐Wide Haplotype Association Mapping in Mice Identifies a Genetic Variant in CER1 Associated With BMD and Fracture in Southern Chinese Women

BMD is a heritable trait and risk indicator for osteoporosis. In this study, we used a genome‐wide haplotype association mapping (HAM) approach to identify a haplotype block within Cer1 that partitions inbred mice strains into high and low BMD groups. A cohort of 1083 high and low BMD human subjects were studied, and a nonsynonymous SNP (rs3747532) in human CER1 was identified to be associated with increased risk of both low BMD in premenopausal women (OR: 2.2; 95% CI: 1.0–4.6; p < 0.05) and increased risk of vertebral fractures (OR: 1.82, p = 0.025) in the postmenopausal cohort. We also showed that Cer1 is expressed in mouse bone and growth plate by RT‐PCR, immunohistochemistry, and in situ hybridization, consistent with polymorphisms potentially influencing BMD. Our successful identification of an association with CER1 in humans together with our mouse study suggests that CER1 may play a role in the development of bone or its metabolism. Our study highlights the use of publicly available databases for rapidly surveying the genome for quantitative trait loci.     

Gender differences in depressive symptoms among older adults: a cross-national comparison

OBJECTIVES: To assess country-specific gender differences in depressive symptoms and to explore if exposures and vulnerabilities vary by gender among older men and women from four European countries and Israel. METHODS: Data on 4,449 subjects between 75 and 84 years old were derived from CLESA ("Cross-national determinants of quality of life and health services for the elderly". A ratio score of depressive symptoms derived form the CESD and GDS scales was regressed on education, marital status, living arrangements, comorbidity and disability and all interactions of these factors with gender and country. RESULTS: The prevalence of depressive symptoms is higher in women than in men in every country, except Sweden. Women are more likely to be exposed to socio-structural risks, and have poorer health and more disability than men in most of the countries. However, women are not more vulnerable to these risk factors. CONCLUSIONS: Findings indicate that the female excess in depressive symptoms remains after taking into account the higher prevalence of socio-structural and health-related risk factors and that older women are not more vulnerable than older men to these known risk factors, suggesting the existence of additional pathways linked to gender and/or biological sex.     

Studies on protamine mRNA in epididymal sperm of adenine-induced infertile rats

Objective: To investigate the protamine and protamine mRNA in the epididymal sperm of normal and infertile rats. Methods: Rats were made infertile by adenine treatment. The total nuclear basic protein (TNBP) of epididymal sperm was extracted and analyzed by gel electrophoresis. The total RNA was isolated and the relative amount of protamne mRNA was determined by means of RT-PCR techniques. Results: The content of protamine in the epididymal sperm was much less in the infertile than that in the normal rats. The same results were obtained with protamine mRNA analysis. Conclusion: The relative amount of protamine mRNA in the sperm could reflect the content of sperm protamine. The results may provide a new approach toward the genetic diagnosis for male infertility.     

High-dose intravenous immunoglobulin modifies complement-mediated in vivo clearance

The mechanism of effect of high-dose intravenous immunoglobulin (IVIG) therapy in immune cytopenias is incompletely known. One of the leading theories ascribes the short-term effects of IVIG to the competition of infused IVIG for Fc receptors, thereby inhibiting IgG-mediated clearance. Using a system independent of IgG-Fc receptor interactions, we examined another potential mechanism of IVIG action. Guinea pigs were infused with a human IVIG preparation at 600 mg/kg/day for two consecutive days. Parallel groups of animals were treated with the same volume and/or concentration of saline and albumin. Clearance of IgM- sensitized guinea pig erythrocytes, which is wholly complement dependent, was significantly retarded in animals treated with high-dose IVIG. The effect was specific for IVIG, since human albumin (as a second foreign protein) failed to change the clearance of IgM- sensitized guinea pig erythrocytes. Experiments in which IVIG-treated animals were subjected to pre- and posttreatment clearance studies revealed heterogeneity among individual animals in respect to their response to IVIG infusions. Decrease of available plasma complement components did not account for the effect, since both C3 and CH50 values remained unchanged after IVIG treatment, despite rising levels of IVIG in sera of treated animals. The results of in vitro C3 uptake studies and the effect of IVIG on clearance of preopsonized cells suggest that IVIG produces a kinetic depression of C3 uptake and modifies the process of complement fragment deposition on erythrocytes. A generalized effect on mononuclear phagocytes is less likely but cannot be wholly ruled out. These studies establish another potential mechanism of IVIG action and suggest extension of its use to other complement-mediated diseases.     

Osteoporosis among Italian women at risk: The osteolab study

Objective

The aim of the present study was to identify women at high risk of having osteoporosis according to the clinical judgment of their General Practitioners, but without a previous diagnosis of osteoporosis.

Design

Cross-sectional survey.

Participants

The General Practitioners were asked to select a sample of women aged 65 years or more who could be affected by osteoporosis but had never been diagnosed nor treated: this sample included 8,268. Moreover, 8,956 women asked to be included in the study on a voluntary basis, and were analyzed separately.

Measurements

Participants were referred to a mobile unit equipped with GE Lunar Express Ultras (Achilles), where they were administered a questionnaire and underwent a QUS examination. They were classified at high, moderate or low risk of having osteoporosis according to the 2007 International Society for Clinical Densitometry official position.

Results

The prevalence rate of women at high risk of having osteoporosis was 12.5%; 53% were considered at moderate risk. Logistic regressions revealed that age, early age at menopause, history of fractures, dysthyroidism and smoking were associated with high and moderate risk.

Conclusions

Results suggest that General Practitioners are able to identify women at risk of having osteoporosis, but often do not treat them, suggesting that osteoporosis in Italy is still a neglected condition. The strength of the association of risk factors is similar in women at high and medium risk: this may raise a debate on the validity of this classification in the Italian population.     

Long-distance Axonal Transport of AAV9 Is Driven by Dynein and Kinesin-2 and Is Trafficked in a Highly Motile Rab7-positive Compartment

Adeno-associated virus (AAV) vectors can move along axonal pathways after brain injection, resulting in transduction of distal brain regions. This can enhance the spread of therapeutic gene transfer and improve treatment of neurogenetic disorders that require global correction. To better understand the underlying cellular mechanisms that drive AAV trafficking in neurons, we investigated the axonal transport of dye-conjugated AAV9, utilizing microfluidic primary neuron cultures that isolate cell bodies from axon termini and permit independent analysis of retrograde and anterograde axonal transport. After entry, AAV was trafficked into nonmotile early and recycling endosomes, exocytic vesicles, and a retrograde-directed late endosome/lysosome compartment. Rab7-positive late endosomes/lysosomes that contained AAV were highly motile, exhibiting faster retrograde velocities and less pausing than Rab7-positive endosomes without virus. Inhibitor experiments indicated that the retrograde transport of AAV within these endosomes is driven by cytoplasmic dynein and requires Rab7 function, whereas anterograde transport of AAV is driven by kinesin-2 and exhibits unusually rapid velocities. Furthermore, increasing AAV9 uptake by neuraminidase treatment significantly enhanced virus transport in both directions. These findings provide novel insights into AAV trafficking within neurons, which should enhance progress toward the utilization of AAV for improved distribution of transgene delivery within the brain.