Accumulation of β-Amyloid (βA) is a key pathogenetic factor in Alzheimer's disease; however, the normal function of βA is unknown. Recent studies have shown that βA can inhibit growth of bacteria and fungi. In this paper we show that βA also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV) in vitro. The 42 amino acid fragment of βA (βA42) had greater activity than the 40 amino acid fragment. Direct incubation of the virus with βA42 was needed to achieve optimal inhibition. Using quantitative PCR assays βA42 was shown to reduce viral uptake by epithelial cells after 45 minutes and to reduce supernatant virus at 24 hours post infection. βA42 caused aggregation of IAV particles as detected by light transmission assays and electron and confocal microscopy. βA42 did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated by IAV. In addition, βA42 increased uptake of IAV by neutrophils. βA42 reduced viral protein synthesis in monocytes and reduced IAV-induced interleukin-6 production by these cells. Hence, we demonstrate for the first time that βA has antiviral activity and modulates viral interactions with phagocytes.

Cerebral volume loss has long been associated with normal aging but whether this is due to aging itself or to age-related diseases including incipient Alzheimer disease (AD) is uncertain. To understand the changes that occur in the aging brain, we examined the cerebral cortex of 27 normal individuals ranging in age from 56 to 103 years. None fulfilled the criteria for the neuropathological diagnosis of AD or other neurodegenerative disease. Seventeen of the elderly participants had cognitive testing an average of 6.7 months prior to death. We used quantitative approaches to analyze cortical thickness, neuronal number, and density. Frontal and temporal neocortical regions had clear evidence of cortical thinning with age but total neuronal numbers in frontal and temporal neocortical regions remained relatively constant over a 50-year age range. These data suggest that loss of neuronal and dendritic architecture, rather than loss of neurons, underlies neocortical volume loss with increasing age in the absence of AD.

Colonization with MDRGN is common in the LTC setting. A diagnosis of advanced dementia is a major risk factor for harboring MDRGN.

Background: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. Objective: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zincdeficient nursing home elderly. Design: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged $65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc ,70 mg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. Results: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with #60 mg serum Zn/dL failed to increase their serum zinc to $70 mg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P , 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. Conclusions: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.Am J Clin Nutr 2016;103:942-51.

Objective To characterize the clinical and molecular epidemiology of multidrug-resistant (MDR) organisms in residents, in healthcare workers (HCWs), and on inanimate surfaces at a long-term care facility (LTCF). Design Point-prevalence study in 4 separate wards at a 600-bed urban LTCF that was conducted from October 31, 2006 through February 5, 2007. Participants One hundred sixty-one LTCF residents and 13 HCWs. Methods Nasal and rectal samples were obtained for culture from each resident, selected environmental surfaces in private and common rooms, and the hands and clothing of HCWs in each ward. All cultures were evaluated for the presence of MDR gram-negative bacteria, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. Clinical and demographic information were collected for each enrolled resident. Molecular typing was performed to identify epidemiologically related strains. Results A total of 37 (22.8%), 1 (0.6%), and 18 (11.1%) residents were colonized with MDR gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant S. aureus, respectively. MDR gram-negative bacteria were recovered from 3 (1.8%) of the 175 environmental samples cultured, all of which were obtained from common areas in LTCF wards. One (7.7%) of the 13 HCWs harbored MDR gram-negative bacteria. Molecular typing identified clonally related MDR gram-negative strains in LTCF residents. After multivariable analysis, length of hospital stay of at least 4 years, fecal incontinence, and antibiotic exposure for at least 8 days were independent risk factors associated with harboring MDR gram-negative bacteria among LTCF residents. Conclusions The prevalence of MDR gram-negative bacteria is high among LTCF residents and exceeds that of vancomycin-resistant enterococci and methicillin-resistant S. aureus. Common areas in LTCFs may provide a unique opportunity for person-to-person transmission of MDR gram-negative bacteria.

An outbreak of acute respiratory disease due to human adenovirus and a resulting increase in mortality occurred in a long-term care facility for the elderly. By use of viral culture and polymerase chain reaction, not a rapid antigen test, the virus was detected. Human adenovirus infection can occur in elderly individuals, but detection by rapid antigen testing may be limited.

Influenza virus infections remain an important cause of morbidity and mortality. Furthermore, a recurrence of pandemic influenza remains a real possibility. There are now effective ways to both prevent and treat influenza. Prevention of infection is most effectively accomplished by vaccination. Vaccination with the inactivated, intramuscular influenza vaccine has been clearly demonstrated to reduce serious morbidity and mortality associated with influenza infection, especially in groups of patients at high risk (e.g. the elderly). However, the inactivated, intramuscular vaccine does not strongly induce cell-mediated or mucosal immune responses, and protection induced by the vaccine is highly strain specific. Live, attenuated influenza vaccines administered intranasally have been studied in clinical trials and shown to elicit stronger mucosal and cell-mediated immune responses. Live, attenuated vaccines appear to be more effective for inducing protective immunity in children or the elderly than inactivated, intramuscular vaccines. Additionally, novel vaccine methodologies employing conserved components of influenza virus or viral DNA are being developed. Preclinical studies suggest that these approaches may lead to methods of vaccination that could induce immunity against diverse strains or subtypes of influenza. Because of the limitations of vaccination, antiviral therapy continues to play an important role in the control of influenza. Two major classes of antivirals have demonstrated ability to prevent or treat influenza in clinical trials: the adamantanes and the neuraminidase inhibitors. The adamantanes (amantadine and rimantadine) have been in use for many years. They inhibit viral uncoating by blocking the proton channel activity of the influenza A viral M2 protein. Limitations of the adamantanes include lack of activity against influenza B, toxicity (especially in the elderly), and the rapid development of resistance. The neuraminidase inhibitors were designed to interfere with the conserved sialic acid binding site of the viral neuraminidase and act against both influenza A and B with a high degree of specificity when administered by the oral (oseltamivir) or inhaled (zanamivir) route. The neuraminidase inhibitors have relatively low toxicity, and viral resistance to these inhibitors appears to be uncommon. Additional novel antivirals that target other phases of the life cycle of influenza are in preclinical development. For example, recombinant collectins inhibit replication of influenza by binding to the viral haemagglutinin as well as altering phagocyte responses to the virus. Recombinant techniques have been used for generation of antiviral proteins (e.g. modified collectins) or oligonucleotides. Greater understanding of the biology of influenza viruses has already resulted in significant advances in the management of this important pathogen. Further advances in vaccination and antiviral therapy of influenza should remain a high priority.

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