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As women age, they typically experience a progressive decrease in skeletal muscle mass and strength, which can lead to a decline in functional fitness and quality of life. Resistance training (RT) has the potential to attenuate these losses. Although well established for men, evidence regarding the benefits of RT for women is sparse and inconsistent: prior reviews include too few studies with women and do not adequately examine the interactive or additive impacts of workload, modalities, and nutritional supplements on outcomes such as muscle mass (MM), body composition (BC), muscle strength (MS), and functional fitness (FF). The purpose of this review is to identify these gaps. Thirty-eight papers published between 2010 and 2020 (in English) represent 2519 subjects (mean age = 66.89 ± 4.91 years). Intervention averages include 2 to 3 × 50 min sessions across 15 weeks with 7 exercises per session and 11 repetitions per set. Twelve studies (32%) examined the impact of RT plus dietary manipulation. MM, MS, and FF showed positive changes after RT. Adding RT to fitness regimens for peri- to postmenopausal women is likely to have positive benefits.

Walking speed is an important clinical tool in the physical therapy examination of older adults, but not always feasible to measure. Clinicians may be limited by space, a client's functional limitations, or use of telehealth. The Walking Speed Questionnaire (WSQ) can be used to estimate walking speed, but the effects of testing protocols on the accuracy and diagnostic capability of the WSQ have not yet been investigated.The purposes of this study were to compare estimated with recorded walking speed and examine effects of start condition and instructions in healthy older adults.One hundred community dwelling adults 60 years or older were tested. After completing the WSQ, participants performed two trials of six walking conditions that included standing and walking starts under instructions toParticipants averaged 72.4 (9.6) years of age. The WSQ average walking speed was 1.22 (0.16) m/s and was slower than each condition, p-value = 0.001, except for those performed with instructions to walk at usual pace with both standing, 1.23 (0.29) m/s and walking starts, 1.26 (0.30) m/s. Compared to the usual pace walking start condition, the WSQ sensitivity and specificity were 31% and 94% respectively with an 82% accuracy. A modified cutoff of the WSQ to 1.17 m/s improves sensitivity.If walking testing cannot be performed, the WSQ is a reasonable alternative providing an accurate estimate of a client's walking speed when walking at a usual pace.

Social isolation is associated with adverse health outcomes in the general older adult population, but little is known about indicators of social isolation in family caregiver populations. This cross-sectional study examined the prevalence of social isolation in the 2015 National Survey of Caregiving. Using the Convoy Model of social relations, a life-course social support framework, we also examined associations between social isolation and caregiver self-reported health. Using multiple ordinal logistic regression models, we examined social isolation - operationalised with a five-item summative measure and, alternatively, with each social isolation item - as a predictor of self-reported general health status. On the dichotomised summative measure, 24.74% (n = 2,175) were more isolated. Younger caregivers were more isolated (M = 56.77 years, SE = 0.76) compared with those who were not (M = 60.86 years, SE = 0.41). Self-reported general health was as follows: 4.93% poor; 15.67% fair; 25.62% good; 34.81% very good and 18.97% excellent. Less social isolation was associated with higher odds of better self-reported health (Adjusted odds ratio [AOR] = 1.19; CI = 1.05-1.35). Of the individual social isolation indicators, only a lack of community participation was associated with higher odds of worse self-reported health (AOR = 1.57; CI = 1.25-1.97). Social isolation and particularly community participation were associated with caregiver health status. It may be necessary for healthcare providers to consider these factors in caregiver health assessments. Future research is recommended to understand the consequences of various social isolation indicators in diverse samples including younger caregivers.

To follow up on research conducted in several countries, in this paper, we look at the dilemmas middle-class parents face of being “good parents” by choosing the “best” school with a milieu-related environment for their child versus being “good citizens” by choosing a “local” public school with a large proportion of students from a working-class or migrant background. Analyzing semi-structured interviews with parents, the paper explores whether and how parents in Germany’s capital city of Berlin refer to this dilemma concerning primary school choice and how they resolve it and justify their decision. The parents interviewed applied strategies in deciding to be “good parents” or “good citizens” or at least to make it easier to solve the dilemma. All the strategies presented in other studies can be found in our sample as well. In addition, we identified two more parental strategies: the strategy of downward comparison and the strategy of choosing a private school. It is notable that the perceived proportion of children with a migrant background in the neighborhood played a major role in relation to the dilemma and the strategies chosen.

Intestinal permeability and neutrophil activity are closely linked to inflammatory bowel disease (IBD) pathophysiology. Here we discuss two techniques for assessing permeability and neutrophil activity in mouse IBD models using near infrared (NIR) detection. To address the limitation of visible light readouts—namely high background—IRDye 800CW was used to enable rapid, non-terminal measurements of intestinal permeability. The increased sensitivity of NIR readouts for colon permeability is shown using dextran sulfate sodium (DSS) and anti-CD40 murine colitis models in response to interleukin-22 immunoglobulin Fc (IL22Fc) fusion protein and anti-p40 monoclonal antibody treatments, respectively. In addition to enhanced permeability, elevated levels of neutrophil elastase (NE) have been reported in inflamed colonic mucosal tissue. Activatable NIR fluorescent probes have been extensively used for disease activity evaluation in oncologic animal models, and we demonstrate their translatability using a NE-activatable reagent to evaluate inflammation in DSS mice. Confocal laser endomicroscopy (CLE) and tissue imaging allow visualization of spatial NE activity throughout diseased colon as well as changes in disease severity from IL22Fc treatment. Our findings with the 800CW dye and the NE probe highlight the ease of their implementation in preclinical IBD research.

Purpose To image colon-expressed alternatively spliced D domain of tenascin C in preclinical colitis models using near infrared (NIR) labeled targeted molecular imaging agents.Methods Human IgG and scFv fusion proteins specific to the alternatively spliced D domain of tenascin C were generated. Immunohistochemistry identified disease-specific expression of this extracellular matrix in mouse colitis models. Proteins were labeled with the NIR fluorophore IRDye 800CW via amine chemistry and intravenously dosed to evaluate targeting specificity in preclinical rodent and primate colitis models.Results The NIR labeled proteins successfully targeted colonic lesions in a murine model of colitis and appeared as distinct punctate spots. Co-administration of a blocking dose reduced the whole colon standardized uptake of the fluorescent dose >7-fold in mouse models. Estimates suggest local expression at >100 nM in diseased mouse colon. Macroscopic targeting specificity was not observed in diseased primate colon. Cellular level specificity was assessed via microscopy and immunohistochemistry.Conclusion Our imaging data suggest the alternatively spliced D domain of tenascin C is a promising target for delivery-based applications in inflammatory bowel diseases.

Aims: Dual task conditions of the Timed Up-and-Go (TUG) add a cognitive (C-TUG) and a manual (M-TUG) task. The purpose of this study was to determine if balance ability differentially affec...

Background. Stroke is the most common cause of long-term disability in the United States (US). Assisted Cycling Therapy (ACT) at cadences of about 80 rpm has been associated with improvements in motor and clinical function in other clinical populations. The acute effects of ACT on motor function of persons with stroke have not been investigated. Objectives. The primary purpose of this cross-over trial was to compare the effects of ACT, voluntary cycling (VC), and no cycling (NC) on upper (Box and Blocks Test) and lower extremity motor function (Lower Extremity Motor Coordination Test) in adults with chronic stroke (age: 60 ± 16 years; months since stroke: 96 ± 85). The secondary purpose was to examine average cycling cadence and ratings of perceived exertion as predictors of change in motor function following the exercise session. Methods. Twenty-two participants (female = 6, male = 16) completed one 20-min session each of ACT (mean cadence = 79.5 rpm, VC (mean cadence = 51.5 rpm), and NC on separate days in quasi-counterbalanced fashion). Results. Main effects of intervention did not differ between ACT and VC. Within-intervention analyses revealed significant (p < 0.05) pre- to posttest changes in all outcome measures for ACT but only in the Lower Extremity Motor Coordination Test on the non-paretic side for VC. Trend analyses revealed a positive relationship between average ACT cadences and improvements in upper and lower extremity motor function (p < 0.05). A positive relationship between average VC cadences and lower extremity function was also revealed (p < 0.05). Conclusion. ACT and VC produced similar acute improvements in paretic and non-paretic lower extremity motor function whereas changes in upper extremity motor function were more limited. Faster cycling cadences seem to be associated with greater acute effects.

Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder. © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.

The complexity of the lung microenvironment together with changes in cellular composition during disease progression make it exceptionally hard to understand the molecular mechanisms leading to the development of chronic lung diseases. Although recent advances in cell type resolved and single-cell sequencing approaches hold great promise for studying complex diseases, their implementation greatly relies on local access to fresh tissue, as traditional methods to process and store tissue do not allow viable cell isolation. To overcome these hurdles, we developed a novel, versatile workflow that allows long-term storage of human lung tissue with high cell viability, permits thorough sample quality check before cell isolation, and is compatible with next generation sequencing-based profiling, including single-cell approaches. We demonstrate that cryopreservation is suitable for isolation of multiple cell types from different lung locations and is applicable to both healthy and diseased tissue, including COPD and tumor samples. Basal cells isolated from cryopreserved airways retain the ability to differentiate, indicating that cellular identity is not altered by cryopreservation. Importantly, using RNA sequencing (RNA-seq) and Illumina EPIC Array, we show that genome-wide gene expression and DNA methylation signatures are preserved upon cryopreservation, emphasizing the suitability of our workflow for -omics profiling of human lung cells. In addition, we obtained high-quality single-cell RNA sequencing data of cells isolated from cryopreserved human lung, demonstrating that cryopreservation empowers single-cell approaches. Overall, thanks to its simplicity, our cryopreservation workflow is well-suited for prospective tissue collection by academic collaborators and biobanks, opening worldwide access to human tissue.

Physical long-term impacts of Takotsubo Cardiomyopathy (TTC) remain controversial and an underestimation of their severity becomes increasingly evident. Even less is known about mental long-term impacts of TTC. This study aims at a better understanding of the physical and mental long-term effects of TTC in comparison to myocardial infarctions (MI). On average 5years after disease onset, 68 TTC patients and 68 age- and sex-matched MI patients were assessed for disease-related quality of life, depression, anxiety, chronic stress, social support, resilience, and life events prior to disease onset. Scores of TTC and MI patients were compared to each other and to normative references values. Regression analyses were used to evaluate the predictive value of the number of life events prior to disease onset for physical and mental long-term outcomes. Both groups displayed higher scores in depression and anxiety, higher levels of chronic stress, and lower scores in physical and mental quality of life in comparison to norm samples, while social support did not differ from norms. No differences between the two patient groups were observed. Within both groups, the majority of patients (TTC: 69.1%; MI: 60.3%) reported stressful life events prior to disease onset. In TTCs and MIs, the number of events had a significant impact on long-term mental health and chronic stress. Notably, both patient collectives scored higher in resilience than healthy controls. Results suggest negative long-term impacts of TTC on mental and physical wellbeing, comparable to those of MI. Besides a good somatic-medical care, psychotherapeutic support, including the development of functional coping strategies, might be warranted for TTC patients. The long-term impact of TTC should be taken as serious as that of MI.

Background and purpose The mineralocorticoid receptor (MR) contributes to fibrosis in various tissues, and MR antagonists, like eplerenone, are used to prevent fibrosis. The role of MR antagonists in hepatic fibrosis and cirrhosis is unknown. Here, we investigated the role of MRs and eplerenone in cirrhosis development. Experimental approach Liver fibrosis (5 weeks) and cirrhosis, without (8 weeks) and with ascites (12 weeks), were induced by CCl4 in rats and comprehensively analysed. The effect of eplerenone on the development of cirrhosis with ascites was assessed. MR expression, cellular and subcellular distribution and impact of hypoxia were investigated in vivo and ex vivo. Primary rat hepatocytes and cell lines were used to investigate MR trafficking and transcriptional activity mechanistically. Key results In cirrhosis with ascites, MR mRNA and protein expressions were reduced in hepatocytes of hypoxic areas. While in normoxic areas MRs were mainly cytosolic, the remaining MRs in hypoxic areas were mainly localized in the nuclei, indicating activation followed by translocation and degradation. Accordingly, eplerenone treatment prevented nuclear MR translocation and the worsening of cirrhosis. Exposing hepatocytes ex vivo to hypoxia induced nuclear MR translocation and enhanced transcriptional MR activity at response elements of the NF-κB pathway. Conclusions and implications We showed for the first time that hypoxia leads to a pathogenetic ligand-independent activation of hepatic MRs during cirrhosis resulting in their nuclear translocation and transcriptional activation of the NF-κB pathway. Treatment with eplerenone prevented the worsening of cirrhosis by blocking this ligand-independent activation of the MR.

The gastrointestinal (GI) barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous systems. Together they act in concert to control normal gut functions (e.g., digestion, absorption, secretion, immunity, etc.) whereas at the same time provide a barrier from the hostile conditions in the luminal environment. Breakdown of these critical GI functions is a central pathophysiological mechanism in the most serious GI disorders in pigs. This review will focus on the development and functional properties of the GI barrier in pigs and how common early life production stressors, such as weaning, can alter immediate and long-term barrier function and disease susceptibility. Specific stress-related pathophysiological mechanisms responsible for driving GI barrier dysfunction induced by weaning and the implications to animal health and performance will be discussed.

The incidence of hip fractures in patients with Alzheimer’s disease and related dementias (ADRD) is 2.7 times higher than it is in those without ADRD. However, there are no standardized post-acute transition models for patients with ADRD after hip fracture. Additionally, there is a lack of knowledge on how post-acute transitions vary by race/ethnicity. Using 100% Medicare data (2016-2017) for 120,179 older adults with ADRD, we conduct multinomial logistic regression, to examine the association between race and post-acute discharge locations (proportion discharged to skilled nursing facility [SNF], inpatient rehabilitation facility [IRF], and Home with Home Health Care [HHC]), after accounting for patient characteristics. Compared to non-Hispanic Whites, Hispanics have a significantly lower odds ratio for discharge to HHC 0.62 (95%CI=0.53-0.73), IRF 0.44 (CI=0.39-0.51), and SNF 0.26 (CI=0.23-0.30). Improving care in patients with ADRD and reducing racial and ethnic disparities in quality of care and health outcomes will be discussed.

Aim: The purpose of the study was to examine the convergent validity of the Sharpened Romberg (SR) as a measure of balance for older adults. Methods: 100 community-dwelling adults aged 60 and older performed the SR with eyes open and closed, the Berg Balance Scale (BBS), Timed Up-and-Go (TUG), and 10-Meter Walk. Results: The SR eyes open was strongly correlated with the BBS and TUG and moderately correlated with the 10-Meter Walk. For the eyes open test, 73 participants completed 30 s; 19 less than 30 s; and 8 could not attain the position, with significant group differences for all measures. Those who stood for 30 s had better scores than the other two groups in the BBS, TUG, and 10-Meter Walk. Conclusions: The SR eyes open is a valid balance test. Inability to complete the SR eyes open test indicates that further balance testing is warranted.

A quick screening test to determine older adults' fall risk would be beneficial given that the physical therapist has limited time to complete an initial examination. The purpose of this study was to determine whether performance on the sharpened Romberg is associated with fall risk, mobility, and g

Social participation is associated with healthy aging, and although associations have been reported between social participation and demographics, no published studies have examined a relationship between social participation and measures amenable to intervention. The purpose was to explore the association between self-reported social participation and lower extremity strength, balance, and gait speed. A cross-sectional analysis of US adults (n = 2291; n = 1,031 males; mean ± standard deviation age 63.5 ± 0.3 years) from the 2001–2 National Health and Nutrition Examination Survey was conducted. Two questions about self-reported difficulty with social participation were categorized into limited (yes/no). The independent variables included knee extension strength (n = 1537; classified as tertiles of weak, normal, and strong), balance (n = 1813; 3 tests scored as pass/fail), and gait speed (n = 2025; dichotomized as slow [less than 1.0 m/s] and fast [greater than or equal to 1.0 m/s]). Logistic regression, accounting for the complex survey design and adjusting for age, sex, physical activity, and medical conditions, was used to estimate the odds of limitation in social participation with each independent variable. Alpha was decreased to 0.01 due to multiple tests. Slower gait speed was significantly associated with social participation limitation (odds ratio = 3.1; 99% confidence interval: 1.5–6.2). No significant association was found with social participation and lower extremity strength or balance. The odds of having limitation in social participation were 3 times greater in those with slow gait speed. Prospective studies should examine the effect of improved gait speed on levels of social participation., Highlights • Social participation is a component of healthy aging. • Population-based studies can explore associations amenable to intervention. • Walking speed and social participation were significantly associated. • Strength and balance were not associated with social participation.

Social relationships are important for family/informal caregiver health. Due to caregiving commitments caregivers are at risk for social isolation. Social isolation is associated with adverse health outcomes in the general population, but few studies have examined this association among caregivers. Employing the Convoy Model of social relations, we examined associations between caregiver self-reported health and social isolation—operationalized as a measure that included multiple domains and as specific domains modeled independently. Social isolation prevalence was 24.74% (n=2,175); mean health was 3.46 (SE=0.02) on a scale of 1 (poor) to 5 (excellent). In adjusted models, domain-inclusive social isolation was inversely associated with health (β=-.07; CI=-0.14,-0.02, p=0.01). In independent domain adjusted models, only participation in club activities was associated with health (β=-.22; CI=-0.35,-0.10, p

The objectives were to examine social isolation research literature, investigate reports of associations with health, and explore the numerous approaches to operationalize social isolation in gerontological research. While associated with negative health outcomes and mortality, the interpretation of social isolation research is hampered by a lack of conceptual clarity and the use of numerous ad hoc measures of the concept. A systematic search was conducted for published empiric studies regarding social isolation health outcomes in older adult samples. The electronic databases: Medline, CINAHL, and PsycINFO were utilized. Reports including social isolation as an independent variable and health outcomes at the individual level were extracted. Of 2,614 studies initially identified, 14 met study criteria. Study outcomes recognized smoking cessation, sleep disruption, inadequate diet, risk for malnutrition, health-related quality of life, subjective well-being, cognitive function, psychological distress, depression, functional decline, stroke, myocardial infarction, and mortality as related to social isolation. Measurement strategies revealed numerous definitions of social isolation reporting to evaluate objective and subjective social isolation, loneliness, engagement, social disconnectedness, and perceived isolation. Measures utilized: eight ad hoc, three versions of the Lubben Social Network Scale, two versions of the Social Network Index, and one question from the Rand Social Battery. Continuing to develop knowledge regarding the predictive power of social isolation on health is important for the care of older adults. Distinguishing social isolation from related but distinctly different social concepts will facilitate the forward movement of the science. Reliably measuring social isolation will enable the comparison of results across studies.

BACKGROUND: The incidence of hip fracture in patients with Alzheimer’s disease and related dementias (ADRD) is 2.7 times higher than it is in those without ADRD. Care complexity, including extensive post-acute rehabilitation, increases substantially in patients with ADRD after hip fracture. However, there are no standardized post-acute care utilization models for patients with ADRD after hip fracture. Additionally, there is a lack of knowledge on how post-acute utilization varies by race/ethnicity, in this population. OBJECTIVES: To investigate racial differences in post-acute care utilization following hip fracture related hospitalization in patients with ADRD. METHODS: A secondary analysis was conducted on 120,179 older adults with ADRD with incident hip fracture, using 100% Medicare data (2016-2017). The primary outcome was post-acute discharge dispositions (skilled nursing facility [SNF], inpatient rehabilitation facility [IRF], and Home Health Care [HHC]) across various racial groups. Multinomial logistic regression examined the association between race and post-acute discharge dispositions after accounting for patient-level covariates. RESULTS: Compared to non-Hispanic Whites, minority racial groups have significantly lower odds of being discharged to SNF, IRF, or HHC, as compared to home. Adjusted odds ratio for Hispanics discharged to SNF was 0.28 (CI=0.24-0.31), to IRF was 0.46 (CI=0.39-0.52) and HHC was 0.64 (95% CI =0.54-0.75), as compared to home. CONCLUSION: ADRD patients have higher risk of hip fracture. Findings from this study will provide insight on how to reduce racial and ethnic disparities in post-acute care utilization in vulnerable populations and improve quality of care and health outcomes.

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted.

A network of 45 spatially distributed time-lapse cameras was used to carry out a continuous observation of snow processes and snow cover properties throughout three mid-latitude medium elevation mountain catchments in hourly intervals during the winter seasons of 2010/2011 and 2011/2012. A simple technical modification was conducted to enable the deployment of the standard digital cameras in any location. Image analysis software was applied to extract information about snow depth, surface albedo and canopy interception from the digital images. Furthermore, the distributed design of the camera network made it possible to identify the elevation of the snow rain interface for any precipitation event which is very helpful for the interpretation of winter flooding events resulting from snow melt. Exemplary data for all these analyses is presented to show the potential fields of application of this innovative approach. Study results prove that the application of digital time-lapse photography is an appropriate technique to observe the spatial distribution and temporal evolution of seasonal snow covers in a mountainous environment.

The cholinergic system plays a central role in regulating critical gastrointestinal functions, including motility, secretion, barrier and immune function. In rodent models of acute, non-infectious gastrointestinal injury, the cholinergic system functions to inhibit inflammation; however, during inflammation local expression and regulation of the cholinergic system is not well known, particularly during infectious enteritis. The objective of this study was to determine the intrinsic expression of the enteric cholinergic system in pig ileum following an acute challenge with Salmonella enterica serovar Typhimurium DT104 (S. Typhimurium). At 2 d post-challenge, a three-fold reduction in ileal acetylcholine (ACh) levels was observed in challenged animals, compared with controls. Ileal acetylcholinesterase (AChE) activity was decreased (by four-fold) while choline acetyltransferase (ChAT) expression was increased in both the ileum and mesenteric lymph nodes. Elevated ChAT found to localize preferentially to mucosa overlying lymphoid follicles of the Peyers patch in challenged pigs, with more intense labeling for ChAT in S. Typhimurium challenged pigs compared to controls. Ileal mRNA gene expression of muscarinic receptor 1 and 3 was also increased in challenged pigs, while muscarinic receptor 2 and the nicotinic receptor alpha 7 subunit gene expression were unaffected. A positive correlation was observed between ChAT protein expression in the ileum, rectal temperature, and histopathological severity in challenged animals. These data show that inflammation from S. Typhimurium challenge alters enteric cholinergic expression by down-regulating acetylcholine concentration and acetylcholine degrading enzymes while increasing acetylcholine synthesis proteins and receptors. Given the known anti-inflammatory role of the cholinergic system, the divergent expression of cholinergic genes may represent an attempt to limit tissue damage by preserving cholinergic signaling in the face of low ligand availability.

BACKGROUND AND PURPOSE Studies have shown that adults with Alzheimer disease (AD) have gait and balance deficits; however, the focus has been on those with mild to severe disease. The purpose of this study was to determine whether balance and gait deficits are present in those with very mild AD. METHODS Thirteen adults (72.9±4.7 years old) with very mild AD and 13 age-matched (72.6±4.6 years old) and sex-matched (10 males and 3 females) participants in a control group without AD performed balance and gait tests. All participants were living in the community and independent in community ambulation. RESULTS Participants with very mild AD had shorter times in tandem stance with eyes open (P

A longitudinal secondary analysis of 2 years of data from the National Health and Aging Trends Study was undertaken to determine the extent to which social isolation predicts falls in older adults. Social isolation during Year 1 (baseline) was operationalized as a multiple-indicator measure based on Social Network Index participation domains. Falling during the previous year was self-reported using Year 2 data. Logistic regression models revealed social isolation significantly predicted falls (odds ratio [OR] = 1.11; 95% confidence interval [CI] [1.05, 1.17]). The relationship remained significant after adjusting for age, gender, and education (OR = 1.08; 95% CI [1.02, 1.14]). The relationship weakened after adjusting for self-reported general health, depression risk, and worry about falling (OR = 1.02; 95% CI [0.96, 1.08]). Adjusting for Short Physical Performance Battery (SPPB), assistive mobility device, and activities of daily living further weakened the relationship (OR = 0.99; 95% CI [0.94, 1.04]). SPPB demonstrated the strongest correlation with social isolation ( r = −0.42; p < 0.01). Fall prevention intervention studies specifically targeting social isolation may incorporate physical performance as a shorter-term and cost-effective proxy outcome for falls. [ Res Gerontol Nurs. 2018; 11(2):61–70 .]

Background Early life adversity (ELA) is a risk factor for development of gastrointestinal disorders later in life. The underlying mechanisms through which ELA and sex interact to influence disease susceptibility remains poorly understood. Methods Utilizing a porcine early weaning stress (EWS) model to mimic ELA, we investigated the long-term effects of EWS on functional diarrhea, ileal permeability, mast cell activity and mast cell relationship with enteric ganglia. Key Results Juvenile and adult EWS pigs exhibited chronic, functional diarrhea (EWS 43.6% vs late wean control(LWC) 4.8%, P

The objectives of the current study were to describe the development of a social isolation measure based on Berkman and Syme's Social Network Index domains with data from the National Health and Aging Trends Study. A descriptive correlational design was used, establishing convergent and divergent validity of the measure with depression risk and well-being. Depression risk was measured with the Patient Health Questionnaire-2 and an ordinal well-being measure was developed based on measures in MIDUS–Midlife in the U.S.–A Study of National Health and Well-Being. Participants who scored ≥4 (cutoff point) on the social isolation measure represented 21.9% ( N = 7,609) of the sample (95% confidence interval [20.6, 23.3]). Spearman's correlation with depression was 0.23 ( p < 0.001) and −0.24 ( p ≤ 0.001) with well-being. The weighted data complex samples general linear model with depression ( R = 0.22, p ≤ 0.001) and well-being ( R = −0.26, p ≤ 0.001) confirm the relationships. This measure offers conceptual clarity and measurement consistency for developing the components and targets for future social isolation intervention research. [Res Gerontol Nurs. 2017; 10(6):277–287.]

Background High concentrations of methylglyoxal (MGO) cause cytotoxiticy via formation of advanced glycation endproducts (AGEs) and inflammation. MGO is detoxificated enzymatically by glyoxalase-I (Glo-I). The aim of this study was to analyze the role of Glo-I during the development of cirrhosis. Methods In primary hepatocytes, hepatic stellate cells (pHSC) and sinusoidal endothelial cells (pLSEC) from rats with early (CCl4 8wk) and advanced cirrhosis (CCl4 12wk) expression and activity of Glo-I were determined and compared to control. LPS stimulation (24h; 100ng/ml) of HSC was conducted in absence or presence of the partial Glo-I inhibitor ethyl pyruvate (EP) and the specific Glo-I inhibitor BrBzGSHCp2. MGO, inflammatory and fibrotic markers were measured by ELISA and Western blot. Additional rats were treated with CCl4 ± EP 40mg/kg b.w. i.p. from wk 8–12 and analyzed with sirius red staining and Western blot. Results Expression of Glo-I was significantly reduced in cirrhosis in whole liver and primary liver cells accompanied by elevated levels of MGO. Activity of Glo-I was reduced in cirrhotic pHSC and pLSEC. LPS induced increases of TNF-α, Nrf2, collagen-I, α-SMA, NF-kB and pERK of HSC were blunted by EP and BrBzGSHCp2. Treatment with EP during development of cirrhosis significantly decreased the amount of fibrosis (12wk CCl4: 33.3±7.3%; EP wk 8–12: 20.7±6.2%; p

Hourly observations of 65 snow monitoring stations were used to investigate the spatiotemporal variability of the surface energy balance during snowmelt in the Black Forest region of southwestern Germany. The study focuses on two rain-on-snow (ROS) events in December 2012 and a clear sky period at the beginning of March 2013 using the same study locations. ROS and clear sky were chosen since they are completely different snowmelt conditions in terms of energy exchanges and dynamics. The results show that snowmelt was dominated by turbulent exchanges at the open field sites and by both turbulent exchanges and net longwave radiation in the forest during ROS. The energy available for snowmelt can be almost identical at open and forest locations during ROS, and a constant energy flux even during night was directed toward the snowpack. During the clear sky conditions, net shortwave radiation was the dominating term in the open, whereas net shortwave and net longwave radiation were most important in the forest. A diurnal signal with positive energy balance during daylight and negative energy balance in the night was observed, with considerably reduced energy available for snowmelt in the forest. Furthermore, the stratified sampling design revealed the strong influence of the canopy and the topography at the locations on the observed energy fluxes. Elevation, aspect, and leaf area index (LAI) were the most important predictor variables during ROS, whereas aspect and LAI were most influential during the clear sky period. The study highlights the distinct spatial variability of the individual energy balance terms over a relatively small area during the differing snowmelt conditions.

The spatial and temporal dynamics of seasonal snow covers play a critical role for many hydrological, ecological, and climatic processes. This paper presents a new, innovative approach to continuously monitor these dynamics using numerous low-cost, standalone snow monitoring stations (SnoMoS). These stations provide snow and related meteorological data with a high temporal and spatial resolution. Data collected by SnoMoS include: snow depth, surface temperature, air temperature and humidity, total precipitation, global radiation, wind speed, and barometric pressure. A total of 99 sensors were placed over the winters 2010/2011 and 2011/2012 at multiple locations within three 40–180 km2 basins in the Black Forest region of Southern Germany. The locations were chosen to cover a wide range of slopes, elevations, and expositions in a stratified sampling design. Furthermore, “paired stations” located in close proximity to each other, one in the open and one underneath various forest canopies, were set up to investigate the influence of vegetation on snow dynamics. The results showed that considerable differences in snow depth and, therefore, snow water equivalent (SWE) are present within the study area despite its moderate temperatures and medium elevation range (400–1500 m). The relative impact of topographical factors like elevation, aspect, and of different types of forest vegetation were quantified continuously and were found to change considerably over the winter period. The recorded differences in SWE and snow cover duration were large enough that they should be considered in hydrologic and climate models.

Human norovirus (HuNoV) is the major cause of acute nonbacterial gastroenteritis worldwide but has no clear animal reservoir. HuNoV can persist after the resolution of symptoms, and this persistence may be essential for viral maintenance within the population. Many strains of the related murine norovirus (MNV) also persist, providing a tractable animal model for studying norovirus (NoV) persistence. We have used recombinant cDNA clones of representative persistent (CR6) and nonpersistent (CW3) strains to identify a domain within the nonstructural gene NS1/2 that is necessary and sufficient for persistence. Furthermore, we found that a single change of aspartic acid to glutamic acid in CW3 NS1/2 was sufficient for persistence. This same conservative change also caused increased growth of CW3 in the proximal colon, which we found to be a major tissue reservoir of MNV persistence, suggesting that NS1/2 determines viral tropism that is necessary for persistence. These findings represent the first identified function for NoV NS1/2 during infection and establish a novel model system for the study of enteric viral persistence.

Background Diabetic peripheral neuropathy affects nearly half of individuals with diabetes and leads to increased fall risk. Evidence addressing fall risk assessment for these individuals is lacking. Objective The purpose of this study was to identify which of 4 functional mobility fall risk assessment tools best discriminates, in people with diabetic peripheral neuropathy, between recurrent “fallers” and those who are not recurrent fallers. Design A cross-sectional study was conducted. Setting The study was conducted in a medical research university setting. Participants The participants were a convenience sample of 36 individuals between 40 and 65 years of age with diabetic peripheral neuropathy. Measurements Fall history was assessed retrospectively and was the criterion standard. Fall risk was assessed using the Functional Reach Test, the Timed “Up & Go” Test, the Berg Balance Scale, and the Dynamic Gait Index. Sensitivity, specificity, positive and negative likelihood ratios, and overall diagnostic accuracy were calculated for each fall risk assessment tool. Receiver operating characteristic curves were used to estimate modified cutoff scores for each fall risk assessment tool; indexes then were recalculated. Results Ten of the 36 participants were classified as recurrent fallers. When traditional cutoff scores were used, the Dynamic Gait Index and Functional Reach Test demonstrated the highest sensitivity at only 30%; the Dynamic Gait Index also demonstrated the highest overall diagnostic accuracy. When modified cutoff scores were used, all tools demonstrated improved sensitivity (80% or 90%). Overall diagnostic accuracy improved for all tests except the Functional Reach Test; the Timed “Up & Go” Test demonstrated the highest diagnostic accuracy at 88.9%. Limitations The small sample size and retrospective fall history assessment were limitations of the study. Conclusions Modified cutoff scores improved diagnostic accuracy for 3 of 4 fall risk assessment tools when testing people with diabetic peripheral neuropathy.

Akkermansia muciniphila is an intestinal anaerobe which has been proposed as a new functional microbe with probiotic properties. However, the species is not included in the European Union qualified presumption of safety (QPS) list and has not yet been assessed. Moreover, products containing A. muciniphila are not on the market and are thus controlled by the Novel Foods Regulation, which requires extensive safety assessment. This review addresses the safety aspects of the use of A. muciniphila based on published information on its functions in humans and predictions based on its activity in model animals. Further, comprehensive studies related to A. muciniphila and its safety properties have gradually appeared and are summarised here. Many of the criteria required for novel food safety assessment in Europe can thus be fulfilled. However, studies focusing on the toxicological properties of A. muciniphila, including long-term and reproduction studies, have not so far been reported and are discussed in the light of the observation that most, if not all, healthy subjects are known to carry this intestinal anaerobe. As this also applies to other beneficial bacteria found in the human intestinal tract, the A. muciniphila case can be seen as a model for the comprehensive safety evaluations required by the European authorities.