Persistence and compliance with osteoporosis therapies among postmenopausal women in the UK Clinical Practice Research Datalink.

Gaining full benefits from osteoporosis medications requires long-term treatment. Investigating the real-world persistence of women receiving osteoporosis medications in the UK, we found that most patients stop treatment within a year. To prevent osteoporotic fragility fractures, long-term treatment persistence must be improved. INTRODUCTION: Persistence with osteoporosis therapies has historically been poor. To treat this chronic and progressive disease, it is essential that patients receive the full benefit of these medications. We estimated persistence and compliance with osteoporosis therapies in a large sample of postmenopausal women in the UK. METHODS: Data were obtained from the Clinical Practice Research Datalink for all women aged 50 years and over or women with early menopause, who received at least one prescription in primary care for any licensed osteoporosis therapy between January 1, 2010 and December 31, 2015. Persistence and compliance at 24 months (primary objective) and at 5 years (exploratory objective) were estimated in three patient cohorts: "All Patients," "Naïve Patients," and "Drug-Specific." RESULTS: The All Patients cohort included 72,256 women. Persistence with any therapy was 56.1%, 43.6%, 36.4%, and 31.0% at 6, 12, 18, and 24 months, respectively, and 23.2% and 13.1% at 3 years and 5 years, respectively. Patients were generally more persistent and compliant if evaluated from their first exposure to osteoporosis therapy (Naïve Patients cohort). In the drug-specific analysis, 64% of patients receiving denosumab (administered subcutaneously every 6 months) were persistent at 24 months compared with 28% and 23% of those taking oral bisphosphonates and intravenous bisphosphonates, respectively. CONCLUSIONS: Only about one in three patients who received osteoporosis therapy continued to be on treatment after 2 years. There is a need to improve persistence with osteoporosis therapy, especially for high-risk patients.

Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance.

OBJECTIVE: Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance. DESIGN: We used radioactively labeled triglycerides to measure blood-brain barrier (BBB) penetration, western blots to measure receptor activation, and feeding and cognitive tests to assess behavioral endpoints. RESULTS: Human CSF was determined to contain triglycerides, a finding previously unclear. The radioactive triglyceride triolein readily crossed the BBB and centrally administered triolein and peripherally administered lipids induced in vivo leptin and/or insulin resistance at hypothalamic receptors. Central triolein blocked the satiety effect of centrally administered leptin. Decreasing serum triglycerides with gemfibrozil improved both learning and memory inversely proportionate to triglyceride levels. CONCLUSIONS: Triglycerides cross the blood-brain barrier rapidly, are found in human cerebrospinal fluid, and induce central leptin and insulin receptor resistance, decreasing satiety and cognition.

Isolation of Aspergillus fumigatus from sputum is associated with elevated airborne levels in homes of patients with asthma.

Indoor bioaerosols, such as mold spores, have been associated with respiratory symptoms in patients with asthma; however, dose-response relationships and guidelines on acceptable levels are lacking. Furthermore, a causal link between mold exposure and respiratory infections or asthma remains to be established. The aim of this study was to determine indoor concentrations of Aspergillus fumigatus and a subset of clinically relevant fungi in homes of people with asthma, in relation to markers of airways colonization and sensitization. Air and dust samples were collected from the living room of 58 properties. Fungal concentrations were quantified using mold-specific quantitative PCR and compared with traditional microscopic analysis of air samples. Isolation of A. fumigatus from sputum was associated with higher airborne concentrations of the fungus in patient homes (P = 0.04), and a similar trend was shown with Aspergillus/Penicillium-type concentrations analyzed by microscopy (P = 0.058). No association was found between airborne levels of A. fumigatus and sensitization to this fungus, or dustborne levels of A. fumigatus and either isolation from sputum or sensitization. The results of this study suggest that the home environment should be considered as a potential source of fungal exposure, and elevated home levels may predispose people with asthma to airways colonization.

Phase transitions in the classical simulability of open quantum systems.

We introduce a Langevin unravelling of the density matrix evolution of an open quantum system over matrix product states, which we term the time-dependent variational principle-Langevin equation. This allows the study of entanglement dynamics as a function of both temperature and coupling to the environment. As the strength of coupling to and temperature of the environment is increased, we find a transition where the entanglement of the individual trajectories saturates, permitting a classical simulation of the system for all times. This is the Hamiltonian open system counterpart of the saturation in entanglement found in random circuits with projective or weak measurements. If a system is open, there is a limit to the advantage in simulating its behaviour on a quantum computer, even when that evolution harbours important quantum effects. Moreover, if a quantum simulator is in this phase, it cannot simulate with quantum advantage.

Assessment and Management of Appetite Loss in Older Adults: An ICFSR Task Force Report.

The Appetite loss in older people is an important unmet clinical need in geriatrics. The International Conference on Frailty and Sarcopenia Research (ICFSR) organized a Task Force on April 20th 2022, in Boston, to discuss issues related to appetite loss in older people, in particular, the assessment tools currently available, its evaluation in the primary care setting, and considerations about its management. There is a high heterogeneity in terms of the etiology of appetite loss in older people and a gold standard assessment tool for evaluating this condition is still absent. Although this may render difficult the management of poor appetite in clinical practice, validated assessment tools are currently available to facilitate early identification of appetite loss and support care decisions. As research on biomarkers of appetite loss progresses, assessment tools will soon be used jointly with biomarkers for more accurate diagnosis and prognosis. In addition, efforts to foster the development of drugs with a favorable risk/benefit ratio to combat poor appetite should be strengthened.

Isolation of filamentous fungi from sputum in asthma is associated with reduced post-bronchodilator FEV1.

BACKGROUND: Fungal sensitization is common in severe asthma, but the clinical relevance of this and the relationship with airway colonization by fungi remain unclear. The range of fungi that may colonize the airways in asthma is unknown. OBJECTIVE: To provide a comprehensive analysis on the range of filamentous fungi isolated in sputum from people with asthma and report the relationship with their clinico-immunological features of their disease. METHODS: We recruited 126 subjects with a diagnosis of asthma, 94% with moderate-severe disease, and 18 healthy volunteers. At a single stable visit, subjects underwent spirometry; sputum fungal culture and a sputum cell differential count; skin prick testing to both common aeroallergens and an extended fungal panel; specific IgE to Aspergillus fumigatus. Fungi were identified by morphology and species identity was confirmed by sequencing. Four patients had allergic bronchopulmonary aspergillosis. RESULTS: Forty-eight percent of asthma subjects were IgE-sensitized to one fungal allergen and 22% to ≥ 2. Twenty-seven different taxa of filamentous fungi were isolated from 54% of their sputa, more than one species being detected in 17%. This compared with 3 (17%) healthy controls culturing any fungus (P < 0.01). Aspergillus species were most frequently cultured in isolation followed by Penicillium species. Post-bronchodilator FEV (1) (% predicted) in the subjects with asthma was 71(± 25) in those with a positive fungal culture vs. 83 (± 25) in those culture-negative, (P < 0.01). CONCLUSION AND CLINICAL RELEVANCE: Numerous thermotolerant fungi other than A. fumigatus can be cultured from sputum of people with moderate-to-severe asthma; a positive culture is associated with an impaired post-bronchodilator FEV (1) , which might be partly responsible for the development of fixed airflow obstruction in asthma. Sensitization to these fungi is also common.

Validation of F3ALLS Assessment in Older Adults.

OBJECTIVES: The study aimed to evaluate the brief F3ALLS assessment's validity in screening fall risk. DESIGN: This is a cross sectional and longitudinal study. SETTING: Participants were recruited from outpatient primary care clinics. PARTICIPANTS: Older ambulatory adults ages 65-90 volunteered for this study. MEASUREMENTS: Falls risk was measured with TGBA and F3ALLS questionnaires. A 6-month follow-up period assessed for falls using falls diaries and chart review. RESULTS: Participants (n=97) were older adults ages 73.91±6.4, 68% (n=66) female. 31% of participants reported at least one fall at 6-months. F3ALLS scores were higher in participants who reported 1 or more falls at 6-months follow-up (3.23±1.5). Higher F3ALLS scores were associated with 6-month fall risk (OR=1.463, 95% CI=1.098-1.949). A score > 3 stratified patients as at risk of falling (AUC=0.77, P<.001; Sensitivity=0.65, Specificity=0.71). CONCLUSION: The F3ALLS questionnaire adequately classifies person at risk versus not at risk for falls, and higher (worse) F3ALLS scores are associated with falls over 6 months.

Validation of the Saint Louis University Quality of Life Questionnaire in Older Adults with Alzheimer's Disease.

BACKGROUND/OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia and negatively impacts individuals' quality of life (QOL). One essential component of disease management in older adults with AD is the maintenance and improvement of QOL. The QOL-AD is a tool that can be administered to evaluate QOL in AD patients, but it can take too long to administer in a patient visit. The purpose of this study was to investigate the validity of a more brief, 6-item QOL questionnaire, LIFEAD, comparing it to the QOL-AD in older adults with mild to moderate cognitive dysfunction. DESIGN: Prospective validation study. SETTING: Participants were patients presenting to internal medicine and geriatrics outpatient clinics and a nursing home. PARTICIPANTS: 285 adults 65 and older with mild to moderate cognitive impairment. MEASUREMENTS: QOL was assessed using LIFEAD and the QOL-AD. Demographic data were collected and level of depression was determined through a demographic questionnaire and the PHQ-8, respectively. RESULTS: QOL-AD mean item scores ranged from 2.27-3.32 with an average scale total of 36.28 ± 6.48. LIFEAD mean item scores ranged from 2.26-2.51 with an average scale total of 14.28 ± 2.87. A majority (68%) of patients rated all items on LIFEAD as either average or good. The correlation between LIFEAD and the QOL-AD was 0.71 (p<0.001). Both LIFEAD and the QOL-AD showed strong internal consistency with a Cronbach's alpha of 0.82 and 0.87, respectively. CONCLUSION: This study validated LIFEAD and exhibited LIFEAD can assess QOL in older adults with mild to moderate cognitive dysfunction in the clinic or nursing home. LIFEAD is a short, practical questionnaire and is easily administered in approximately 1 minute. Further research on LIFEAD could be done with larger samples, in different clinical populations, and including persons of other ethnic backgrounds.

Validation of the ALONE Scale: A Clinical Measure of Loneliness.

OBJECTIVES: This study aimed to examine the validity and reliability of a rapid, clinically administrable loneliness screening tool for older adults called the ALONE scale. DESIGN: This was a cross-sectional study. SETTING: Participants were recruited from either ambulatory clinics or a nursing home. PARTICIPANTS: Participants were 65 years of age or older and had SLUMS scores of 14 or greater. MEASUREMENTS: Construct validity of the 5-item ALONE scale was examined through correlation with the previously validated UCLA-20 Loneliness Questionnaire. Divergent validity for discriminating between loneliness and depression was examined through correlation with the PHQ-8 items. Test-retest reliability was assessed by correlation between baseline ALONE scores and those from re-administration in 2-3 weeks. RESULTS: Among ambulatory clinic participants (n=199), the ALONE scale showed strong correlation with the UCLA-20 (r=0.81, p < 0.001). Similar correlation coefficients were seen among demographic subgroups: White Americans (n=123) (r=0.81, p < 0.001), Black Americans (n=66) (r=0.79, p < 0.001), adults ≥ 75 years (n=74) (r=0.86, p < 0.001). Among nursing home patients (n=22), the ALONE scale showed fair correlation with the UCLA-20 (r=0.74, p < 0.001). Test-retest of the ALONE scale showed a strong correlation (r=0.89, p < 0.001). ROC curve analysis determined ALONE scale scores of 8 and greater as optimal for severe loneliness screening. CONCLUSION: This study shows that the ALONE scale has strong validity in assessing older adults for severe loneliness. The brief, comprehensible nature of the ALONE scale reduces adoption burden making it optimal for use in clinical settings.

Appetite Loss and Anorexia of Aging in Clinical Care: An ICFSR Task Force Report.

Appetite loss/anorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio.

Reduced postsynaptic GABAA receptor number and enhanced gaboxadol induced change in holding currents in Purkinje cells of the dystrophin-deficient mdx mouse.

UNLABELLED: Duchenne muscular dystrophy (DMD) is caused by the absence of a functional transcript of the protein dystrophin. DMD is associated with a range of cognitive deficits that are thought to result from a lack of the protein dystrophin in brain structures involved in cognitive functions. The CNS involvement extends to an impairment of cognitive abilities, with many DMD boys having significant reduction in IQ. In the cerebellum, dystrophin is normally localized at the postsynaptic membrane of GABAergic synapses on Purkinje cells. Here, we investigate the effect of an absence of dystrophin on the number of GABA(A) channels located at the synapse in cerebellar Purkinje cells of the dystrophin-deficient mdx mouse. Whole-cell patch-clamp recordings of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) were performed in cerebellar slices from mdx and littermate control mice. Our results showed that the number of receptors at GABAergic synapses in the cerebellar Purkinje cell was significantly reduced in mdx mice (38.38 ± 2.95) compared to littermate controls (53.03 ± 4.11). Furthermore, when gaboxadol was added to the bath, the change in holding current in mdx mice was significantly enhanced (65.01 ± 5.89pA) compared to littermate controls (37.36 ± 3.82pA). The single channel unitary conductance and the rise and decay time of mIPSCs were not significantly different in these two groups of mice, indicating that those GABA(A) channels located at the postsynaptic sites in the mdx mice function normally. CONCLUSION: There is a reduction in the number of functional receptors localized at GABAergic synapses in the cerebellar Purkinje cells of dystrophin-deficient mdx mice and an increase in a gaboxadol induced holding current, which is evidence for an increase in extrasynaptic GABA(A) receptors in mdx mice. We hypothesize that the absence of dystrophin, from mdx Purkinje cells, reduces the number of post-synaptic GABA(A) receptors and as a result there is an increase in extrasynaptic receptors. If similar changes occur in the CNS in boys with DMD, it will impact on the function of neural networks and may contribute to some of the motor, behavioral and cognitive impairment apparent in many boys with DMD.

Testosterone modulates gene expression pathways regulating nutrient accumulation, glucose metabolism and protein turnover in mouse skeletal muscle.

Testosterone regulates energy metabolism and skeletal muscle mass in males, but the molecular mechanisms are not fully understood. This study investigated the response of skeletal muscle to castration and testosterone replacement in 8-week-old male mice. Using microarray analyses of mRNA levels in gastrocnemius muscle, 91 genes were found to be negatively regulated by testosterone and 68 genes were positively regulated. The mRNA levels of the insulin signalling suppressor molecule Grb10 and the glycogen synthesis inhibitors, protein phosphatase inhibitor-1 and phosphorylase kinase-γ, were negatively regulated by testosterone. The insulin-sensitive glucose and amino acid transporters, Glut3 and SAT2, the lipodystrophy gene, Lpin1 and protein targeting to glycogen were positively regulated. These changes would be expected to increase nutrient availability and sensing within skeletal muscle, increase metabolic rate and carbohydrate utilization and promote glycogen accumulation. The observed positive regulation of atrogin-1 (Fbxo32) by testosterone could be explained by the phosphorylation of Akt and Foxo3a, as determined by Western blotting. Testosterone prevented the castration-induced increase in interleukin-1α, the decrease in interferon-γ and the atrophy of the levator ani muscle, which were all correlated with testosterone-regulated gene expression. These findings identify specific mechanisms by which testosterone may regulate skeletal muscle glucose and protein metabolism.

Performance of the Short Physical Performance Battery in Identifying the Frailty Phenotype and Predicting Geriatric Syndromes in Community-Dwelling Elderly.

The early identification of seniors at high risk of geriatric syndromes is fundamental for targeting interventions to those who most need them. To date, the predictive value of the Short Physical Performance Battery (SPPB) for multifactorial clinical conditions has not been clearly established. Thus, the aim of the present study was to determine whether the SPPB could identify frailty and predict geriatric syndromes in community-dwelling older adults. Participants comprised men and women aged 60 years and older who participated in the Health and Well-being and Aging Survey in Colombia 2015 (n=4125, 57.6% women). A structured interview was administered to obtain socio-demographic data which included age, sex, ethnicity, socioeconomic status, and urbanicity. The study included the measurement of body mass, grip strength, SPPB, Lawton´s instrumental ADL scale, specific subjective memory complaints (SSMC), frailty phenotype (Fried and FRAIL Scale), and self-reported falls, geriatric syndromes and/or medical conditions. ROC analysis was used to examine the ability of the SPPB test to predict frailty and geriatric syndromes. The cutoff that maximized both sensitivity and specificity for the frailty phenotype was 8 points or below for men and 7 points or below for women. These cutoff values significantly predicted four geriatric syndromes in descending order: mild dementia (♂ ORajus 3.34, and ♀ ORajus 2.79), low grip strength (♂ ORajus 1.98, and ♀ ORajus 2.45), falls (♂ ORajus 1.39, and ♀ ORajus 1.49), and SSMC (♂ ORajus 1.39). In summary, the main finding of the present study was that SPPB score (i.e., ≤ 8 ♂ and ≤ 7 ♀) seems to be a useful measure for identifying the physical frailty phenotype and predicting geriatric syndromes in community-dwelling older adults.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Ocean planning for species on the move provides substantial benefits and requires few trade-offs.

Societies increasingly use multisector ocean planning as a tool to mitigate conflicts over space in the sea, but such plans can be highly sensitive to species redistribution driven by climate change or other factors. A key uncertainty is whether planning ahead for future species redistributions imposes high opportunity costs and sharp trade-offs against current ocean plans. Here, we use more than 10,000 projections for marine animals around North America to test the impact of climate-driven species redistributions on the ability of ocean plans to meet their goals. We show that planning for redistributions can substantially reduce exposure to risks from climate change with little additional area set aside and with few trade-offs against current ocean plan effectiveness. Networks of management areas are a key strategy. While climate change will severely disrupt many human activities, we find a strong benefit to proactively planning for long-term ocean change.

Sex-specific muscle and metabolic biomarkers associated with gait speed and cognitive transitions in older adults: a 9-year follow-up.

Physical frailty and cognitive frailty share biological mechanisms, but sex-specific biomarkers associated with transitions in gait speed and cognition during ageing are poorly understood.Gait speed, cognition (3MSE), body composition (DXA) and serological biomarkers were assessed annually over 9 years in 216 males (72.7 + 8.07 years) and 384 females (71.1 + 8.44 years). In females, maintaining normal gait speed was associated with lower percent body fat (IRR 0.793, p = 0.001, 95%CI 0.691-0.910) and lower lactate dehydrogenase (LDH) (IRR 0.623, p = 0.00, 95%CI 0.514-0.752), and in males, the association was with higher cholesterol (IRR 1.394, p = 0.001, 95%CI 1.154-1.684). Abnormal to normal gait speed transitions were associated with higher insulin in females (IRR 1.325, p = 0.022, 95%CI 1.041-1.685) and lower creatinine in males (IRR 0.520, p = 0.01, 95%CI 0.310-0.870). Normal to slow gait speed transitions in males were associated with IGF-1 (IRR 1.74, p = 0.022, 95%CI 1.08-2.79) and leptin in females (IRR 1.39, p = 0.043, 95%CI 1.01-1.91.) Maintaining normal cognition was associated with lower LDH in females (IRR 0.276, p = 0.013, 95%CI 0.099-0.765) and higher appendicular skeletal muscle mass in males (IRR 1.52, p = 0.02, 95%CI 1.076-2.135). Improved cognition was associated with higher leptin (IRR 7.5, p = 0.03, 95%CI 1.282-44.34) and lower triglyceride (IRR 0.299, p = 0.017, 95%CI 0.110-0.809) in males. Education was protective against cognitive decline in females (IRR 0.84, p = 0.037, 0.732-0.982). Sex-specific biomarkers of muscle (LDH, Creatinine, IGF-1, APSM) and metabolism (%fat, insulin,cholesterol, leptin, tryglycerides) were associated with gait speed and cognitive transitions. These data suggest that modifiable biomarkers of muscle and metabolism could be targeted for interventions.

Editorial: Diagnostic Testing for SARS-Coronavirus-2 in the Nursing Facility: Recommendations of a Delphi Panel of Long-Term Care Clinicians.

With the COVID-19 pandemic progressing, guidance on strategies to mitigate its devastating effects in nursing facilities (NFs) is critical to preventing additional tragic outcomes. Asymptomatic spread of COVID-19 from nursing facility staff and residents is a major accelerator of infection. Facility-wide point-prevalence testing is an emerging strategy in disease mitigation. Because time is not available to await the results of randomized controlled trials before implementing strategies in this high-risk setting, an expert Delphi panel composed of experienced long-term care medicine professionals has now met to provide testing guidance for SARS-Coronavirus-2 to NFs. After many email and telephone discussions, the panel responded to a questionnaire that included six different scenarios, based on varying availability of Polymerase Chain Reaction (RT-PCR) testing and personal protective equipment (PPE). The panel endorsed facility-wide testing of staff and residents without dissent when diagnostic RT-PCR was available. While the panel recognized the limitations of RT-PCR testing, it strongly recommended this testing for both staff and residents in NFs that were either COVID-19 naive or had limited outbreaks. There was also consensus on testing residents with atypical symptoms in a scenario of limited testing capability. The panel favored testing every 1 to 2 weeks if testing was readily available, reducing the frequency to every month as community prevalence declined or as the collection of additional data further informed clinical critical thinking and decision-making. The panel recognized that frequent testing would have consequences in terms of potential staff shortages due to quarantine after positive tests and increased PPE use. However, the panel felt that not testing would allow new clusters of infection to form. The resulting high mortality rate would outweigh the potential negative consequences of testing. The panel also recognized the pandemic as a rapidly evolving crisis, and that new science and increasing experience might require an updating of its recommendations. The panel hopes that its recommendations will be of value to the long-term care industry and to policy makers as we work together to manage through this challenging and stressful time.

Stress-induced eating is mediated through endogenous opiates.

The interaction of endogenous opiates and stress-induced eating in rats was evaluated by pharmacological manipulation. Eating induced by the tail-pinch method was inhibited by the opitate antagonist naloxone; after being repeatedly stressed over a 10-day period and then given nalozone, the rats behaved in a manner indistinguishable from the "wet-dog" shakes of opiate withdrawal. Thus endogenous opiates may have a role in the control of stress-related eating, a finding that may have therapeutic implications for humans.

Purinergic regulation of food intake.

Inosine peripherally administered to rats markedly suppressed spontaneous food intake and food intake induced by diazepam, muscimol, insulin, and food deprivation. The purines 2-deoxyguanosine and 2-deoxyinosine also suppressed food deprivation-induced feeding, whereas 7-methylinosine, which does not bind to the benzodiazepine binding site in vitro, had no effect on food intake when compared with controls. These results suggest that purines may represent endogenous substances that regulate food intake through interactions with the benzodiazepine receptor.

Modulation of memory processing by cholecystokinin: dependence on the vagus nerve.

Allowing mice access to food immediately after an aversive training session enhances memory retention. Cholecystokinin-octapeptide (CCK-8), which is a gastrointestinal hormone released during feeding, also enhances memory retention when administered intraperitoneally. This memory-enhancing effect of CCK-8 is blocked when the vagus nerve is cut, indicating that CCK-8 may produce its effect on memory retention by activating ascending fibers in the vagus nerve. Thus, CCK-8, a peripherally acting peptide, may mediate the memory-enhancing effects of feeding.