Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis.

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with <15 dysregulated genes. The constitutive cell types that accomplish homeostatic renewal were conserved in DED but were associated with activation of cell states that comprise "adaptive regeneration." We provide global markers that distinguish cell types in homeostatic renewal vs. adaptive regeneration and markers that specifically define DED-elicited proliferating and differentiating cell types. We validate that expression of SPARC, a marker of adaptive regeneration, is also induced in corneal epithelial wound healing and accelerates wound closure in a corneal epithelial cell scratch assay. Finally, we propose a classification system for LSC markers based on their expression fidelity in homeostasis and disease. This transcriptional dissection uncovers the dramatically altered transcriptional landscape of the corneal epithelium in DED, providing a framework and atlas for future study of these ocular surface stem cells in health and disease.

Reductions in Motor Unit Firing are Associated with Clinically Meaningful Leg Extensor Weakness in Older Adults.

Weakness, one of the key characteristics of sarcopenia, is a significant risk factor for functional limitations and disability in older adults. It has long been suspected that reductions in motor unit firing rates (MUFRs) are one of the mechanistic causes of age-related weakness. However, prior work has not investigated the extent to which MUFR is associated with clinically meaningful weakness in older adults. Forty-three community-dwelling older adults (mean: 75.4 ± 7.4 years; 46.5% female) and 24 young adults (mean: 22.0 ± 1.8 years; 58.3% female) performed torque matching tasks at varying submaximal intensities with their non-dominant leg extensors. Decomposed surface electromyographic recordings were used to quantify MUFRs from the vastus lateralis muscle. Computational modeling was subsequently used to independently predict how slowed MUFRs would negatively impact strength in older adults. Bivariate correlations between MUFRs and indices of lean mass, voluntary activation, and physical function/mobility were also assessed in older adults. Weak older adults (n = 14) exhibited an approximate 1.5 and 3 Hz reduction in MUFR relative to non-weak older adults (n = 29) at 50% and 80% MVC, respectively. Older adults also exhibited an approximate 3 Hz reduction in MUFR relative to young adults at 80% MVC only. Our model predicted that a 3 Hz reduction in MUFR results in a strength decrement of 11-26%. Additionally, significant correlations were found between slower MUFRs and poorer neuromuscular quality, voluntary activation, chair rise time performance, and stair climb power (r's = 0.31 to 0.43). These findings provide evidence that slowed MUFRs are mechanistically linked with clinically meaningful leg extensor weakness in older adults.

Predictors for the development of motoric cognitive risk syndrome in older adults.

BACKGROUND: Motoric cognitive risk (MCR) syndrome refers to a condition where both slow gait and memory complaints coexist, which heightens their vulnerability to developing dementia. Considering that the risk factors of MCR are elucidated from cross-sectional studies and also likely vary based on socioeconomic status, we conducted a community-based longitudinal study to determine the predictors of MCR among older adults in Malaysia. METHODS: Out of 1,249 older participants (aged 60 years and above) without MCR at baseline (Wave II of LRGS-TUA cohort study), 719 were successfully followed up after 3.5 years to identify predictors of subsequent MCR development. A comprehensive interview-based questionnaire was administered for sociodemographic information, cognitive function, psychosocial, functional status, and dietary intake. Anthropometric measurements, body composition, and physical performance were assessed. Univariate analyses were performed for each variable, followed by a hierarchical logistic regression analysis to identify the predictors of MCR that accounted for confounding effects between the studied factors. RESULTS: The incidence rate of MCR was 4.0 per 100 person-years. Smoking (Adjusted Odd Ratio (Adj OR) = 1.782; 95% Confidence Interval (CI):1.050-3.024), hypertension (Adj OR = 1.725; 95% CI:1.094-2.721), decreased verbal memory as assessed by the lower Rey Auditory Verbal Learning Test (RAVLT) (Adj OR = 1.891; 95% CI:1.103-3.243), and decreased functional status measured using instrumental activity of daily living (IADL) (Adj OR = 4.710; 95% CI:1.319-16.823), were predictors for MCR incidence. CONCLUSIONS: Our study results provide an initial reference for future studies to formulate effective preventive management and intervention strategies to reduce the growing burden of adverse health outcomes, particularly among Asian older adults.

Comparison of strategies for assessment of rate of torque development in older and younger adults.

There is increasing appreciation of the role of rate of torque development (RTD) in physical function of older adults (OAs). This study compared various RTD strategies and electromyography (EMG) in the knee extensors and focused on discriminating groups with potential limitations in voluntary activation (VA) and associations of different RTD indices with functional tests that may be affected by VA in OAs. Neuromuscular function was assessed in 20 younger adults (YAs, 22.0 ± 1.7 years) and 50 OAs (74.4 ± 7.0 years). Isometric ballistic and peak torque during maximal voluntary contractions (pkTMVC), doublet stimulation and surface EMG were assessed and used to calculate VA during pkTMVC and RTD and rate of EMG rise during ballistic contractions. Select mobility tests (e.g., gait speed, 5× chair rise) were also assessed in the OAs. Voluntary RTD and RTD normalized to pkTMVC, doublet torque, and peak doublet RTD were compared. Rate of EMG rise and voluntary RTD normalized to pkTMVC did not differ between OAs and YAs, nor were they associated with functional test scores. Voluntary RTD indices normalized to stimulated torque parameters were significantly associated with VA (r = 0.319-0.459), and both indices were significantly lower in OAs vs YAs (all p < 0.020). These RTD indices showed significant association with the majority of mobility tests, but there was no clear advantage among them. Thus, voluntary RTD normalized to pkTMVC was ill-suited for use in OAs, while results suggests that voluntary RTD normalized to stimulated torque parameters may be useful for identifying central mechanisms of RTD impairment in OAs.Clinical trial registration number NCT02505529; date of registration 07/22/2015.

An open repository of real-time COVID-19 indicators.

The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: Operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from deidentified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data are available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.

Removing acoustic ringing baseline curvature in 13 C NMR spectra for quantitative analyses.

13 C nuclear magnetic resonance (NMR) is traditionally considered an insensitive technique, requiring long acquisition times to measure dilute functionalities on large polymers. With the introduction of cryoprobes and better electronics, sensitivity has improved in a way that allows measurements to take less than 1/20th the time that they previously did. Unfortunately, a high Q-factor with cryoprobes creates baseline curvature related to acoustic ringing that affects quantitative NMR analyses. Manual baseline correction is commonly used to compensate for the baseline roll, but it is a time-intensive process. The outcome of manual baseline correction can vary depending on processing parameters, especially for complicated spectra. Additionally, it can be challenging to distinguish between broad peaks and baseline rolls. A new anti-ring pulse sequence (zgig_pisp) was previously reported to improve on the incumbent single pulse experiment (zgig). The original report presented limited comparison data with 13 C NMR, but a thorough validation is needed before broader implementation can be considered. In this work, we report the round-robin testing and comparison of zgig_pisp and zgig pulse sequences. During the testing phase, we found that zgig_pisp is practically equivalent to zgig to ±2% for the majority of integrals examined. Additionally, a short broadband inversion pulse (BIP) was demonstrated as an alternative to the originally reported adiabatic CHIRP shaped pulse. The zgig_pisp pulse sequence code for Bruker spectrometers is also simplified.

Maximizing Strength: The Stimuli and Mediators of Strength Gains and Their Application to Training and Rehabilitation.

ABSTRACT: Spiering, BA, Clark, BC, Schoenfeld, BJ, Foulis, SA, and Pasiakos, SM. Maximizing strength: the stimuli and mediators of strength gains and their application to training and rehabilitation. J Strength Cond Res 37(4): 919-929, 2023-Traditional heavy resistance exercise (RE) training increases maximal strength, a valuable adaptation in many situations. That stated, some populations seek new opportunities for pushing the upper limits of strength gains (e.g., athletes and military personnel). Alternatively, other populations strive to increase or maintain strength but cannot perform heavy RE (e.g., during at-home exercise, during deployment, or after injury or illness). Therefore, the purpose of this narrative review is to (a) identify the known stimuli that trigger gains in strength; (b) identify the known factors that mediate the long-term effectiveness of these stimuli; (c) discuss (and in some cases, speculate on) potential opportunities for maximizing strength gains beyond current limits; and (d) discuss practical applications for increasing or maintaining strength when traditional heavy RE cannot be performed. First, by conceptually deconstructing traditional heavy RE, we identify that strength gains are stimulated through a sequence of events, namely: giving maximal mental effort, leading to maximal neural activation of muscle to produce forceful contractions, involving lifting and lowering movements, training through a full range of motion, and (potentially) inducing muscular metabolic stress. Second, we identify factors that mediate the long-term effectiveness of these RE stimuli, namely: optimizing the dose of RE within a session, beginning each set of RE in a minimally fatigued state, optimizing recovery between training sessions, and (potentially) periodizing the training stimulus over time. Equipped with these insights, we identify potential opportunities for further maximizing strength gains. Finally, we identify opportunities for increasing or maintaining strength when traditional heavy RE cannot be performed.

A single-cell guide to retinal development: Cell fate decisions of multipotent retinal progenitors in scRNA-seq.

Recent advances in high throughput single-cell RNA sequencing (scRNA-seq) technology have enabled the simultaneous transcriptomic profiling of thousands of individual cells in a single experiment. To investigate the intrinsic process of retinal development, researchers have leveraged this technology to quantify gene expression in retinal cells across development, in multiple species, and from numerous important models of human disease. In this review, we summarize recent applications of scRNA-seq and discuss how these datasets have complemented and advanced our understanding of retinal progenitor cell competence, cell fate specification, and differentiation. Finally, we also highlight the outstanding questions in the field that advances in single-cell data generation and analysis will soon be able to answer.

Neuromuscular mechanisms of weakness in a mouse model of chronic alcoholic myopathy.

BACKGROUND: Weakness is a common clinical symptom reported in individuals with chronic alcohol use disorder. However, it remains unclear whether low strength in these individuals is directly related to excessive ethanol intake, other deleterious factors (lifestyle, environment, genetics, etc.), or a combination of both. Therefore, we examined whether (and how) ethanol reduces the muscle's force-producing capacity using a controlled in vivo preclinical mouse model of excessive ethanol intake. METHODS: To establish whether chronic ethanol consumption causes weakness, C57BL/6 female mice consumed 20% ethanol for 40 weeks (following a 2-week ethanol ramping period), and various measures of muscular force were quantified. Functional measures included all-limb grip strength and in vivo contractility of the left ankle dorsiflexors and plantarflexors. Once confirmed that mice consuming ethanol were weaker than age-matched controls, we sought to determine the potential neuromuscular mechanisms of muscle dysfunction by assessing neuromuscular excitation, muscle quantity, and muscle quality. RESULTS: Mice consuming chronic ethanol were 13 to 16% weaker (p ≤ 0.016) than controls (i.e., mice consuming 100% water) with the negative impact of ethanol on voluntary grip strength (ƞ2  = 0.603) being slightly larger than that of electrically stimulated muscle contractility (ƞ2  = 0.482). Relative to controls, lean mass and muscle wet masses were 9 to 16% lower in ethanol-consuming mice (p ≤ 0.048, ƞ2  ≥ 0.268). No significant changes were observed between groups for indices of neuromuscular excitation at the level of the motor unit, neuromuscular junction, or plasmalemma (p ≥ 0.259, ƞ2  ≤ 0.097), nor was muscle quality altered after 40 weeks of 20% ethanol consumption (p ≥ 0.695, ƞ2  ≤ 0.012). CONCLUSIONS: Together, these findings establish that chronic ethanol consumption in mice induces a substantial weakness in vivo that we interpret to be primarily due to muscle atrophy (i.e., reduced muscle quantity) and possibly, to a lesser degree, loss of central neural drive.

Discrepancies in hand motor performance and executive function in older adults.

There is increasing interest in using motor function tests to identify risk of cognitive impairment in older adults (OA). This study examined associations among grip strength, with and without adjustment for muscle mass, manual dexterity and Trail Making Test (TMT) A and B in 77 OA (73.4 ± 5.2 years) with globally intact cognition. A subset of OA who exhibited mismatched motor function (e.g., in the highest strength and lowest dexterity tertiles, or vice versa) was identified and analyzed. Dexterity showed stronger associations with TMT-A and -B than grip strength (absolute or adjusted). OA with mismatched motor function scored worse on tests of TMT-B, but not -A than those with matched motor function. Dexterity may have more promise than grip strength for identifying increased risk of cognitive impairment. Intriguing, though limited, data suggest that mismatched motor function (strength vs. dexterity) in OAs might be an even more robust marker of such risk.

Zeb2 regulates the balance between retinal interneurons and Müller glia by inhibition of BMP-Smad signaling.

The interplay between signaling molecules and transcription factors during retinal development is key to controlling the correct number of retinal cell types. Zeb2 (Sip1) is a zinc-finger multidomain transcription factor that plays multiple roles in central and peripheral nervous system development. Haploinsufficiency of ZEB2 causes Mowat-Wilson syndrome, a congenital disease characterized by intellectual disability, epilepsy and Hirschsprung disease. In the developing retina, Zeb2 is required for generation of horizontal cells and the correct number of interneurons; however, its potential function in controlling gliogenic versus neurogenic decisions remains unresolved. Here we present cellular and molecular evidence of the inhibition of Müller glia cell fate by Zeb2 in late stages of retinogenesis. Unbiased transcriptomic profiling of control and Zeb2-deficient early-postnatal retina revealed that Zeb2 functions in inhibiting Id1/2/4 and Hes1 gene expression. These neural progenitor factors normally inhibit neural differentiation and promote Müller glia cell fate. Chromatin immunoprecipitation (ChIP) supported direct regulation of Id1 by Zeb2 in the postnatal retina. Reporter assays and ChIP analyses in differentiating neural progenitors provided further evidence that Zeb2 inhibits Id1 through inhibition of Smad-mediated activation of Id1 transcription. Together, the results suggest that Zeb2 promotes the timely differentiation of retinal interneurons at least in part by repressing BMP-Smad/Notch target genes that inhibit neurogenesis. These findings show that Zeb2 integrates extrinsic cues to regulate the balance between neuronal and glial cell types in the developing murine retina.

Pulse arrival time, a novel sleep cardiovascular marker: the multi-ethnic study of atherosclerosis.

BACKGROUND: Pulse arrival time (PAT) is commonly used to estimate blood pressure response. We hypothesised that PAT response to obstructive respiratory events would be associated with increased cardiovascular risk in people with obstructive sleep apnoea. METHODS: PAT, defined as the time interval between electrocardiography R wave and pulse arrival by photoplethysmography, was measured in the Multi-Ethnic Study of Atherosclerosis Sleep study participants. The PAT response to apnoeas/hypopnoeas was defined as the area under the PAT waveform following respiratory events. Cardiovascular outcomes included markers of subclinical cardiovascular disease (CVD): left ventricular mass, carotid plaque burden score and coronary artery calcification (CAC) (cross-sectional) and incident composite CVD events (prospective). Multivariable logistic and Cox proportional hazard regressions were performed. RESULTS: A total of 1407 participants (mean age 68.4 years, female 47.5%) were included. Higher PAT response (per 1 SD increase) was associated with higher left ventricular mass (5.7 g/m2 higher in fourth vs first quartile, p<0.007), higher carotid plaque burden score (0.37 higher in fourth vs first quartile, p=0.02) and trended to greater odds of CAC (1.44, 95% CI 0.98 to 2.15, p=0.06). A total of 65 incident CVD events were observed over the mean of 4.1 (2.6) years follow-up period. Higher PAT response was associated with increased future CVD events (HR: 1.20, 95% CI 1.02 to 1.42, p=0.03). CONCLUSION: PAT is independently associated with markers of subclinical CVD and incident CVD events. Respiratory-related PAT response is a novel and promising polysomnography metric with cardiovascular implications.

Ldb1- and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in the retina.

Precise control of the relative ratio of retinal neurons and glia generated during development is essential for visual function. We show that Lhx2, which encodes a LIM-homeodomain transcription factor essential for specification and differentiation of retinal Müller glia, also plays a crucial role in the development of retinal neurons. Overexpression of Lhx2 with its transcriptional co-activator Ldb1 triggers cell cycle exit and inhibits both Notch signaling and retinal gliogenesis. Lhx2/Ldb1 overexpression also induces the formation of wide-field amacrine cells (wfACs). In contrast, Rnf12, which encodes a negative regulator of LDB1, is necessary for the initiation of retinal gliogenesis. We also show that Lhx2-dependent neurogenesis and wfAC formation requires Ascl1 and Neurog2, and that Lhx2 is necessary for their expression, although overexpression of Lhx2/Ldb1 does not elevate expression of these proneural bHLH factors. Finally, we demonstrate that the relative level of the LHX2-LDB1 complex in the retina decreases in tandem with the onset of gliogenesis. These findings show that control of Lhx2 function by Ldb1 and Rnf12 underpins the coordinated differentiation of neurons and Müller glia in postnatal retina.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

Handgrip strength asymmetry is associated with future falls in older Americans.

BACKGROUND: Examining handgrip strength (HGS) asymmetry could extend the utility of handgrip dynamometers for screening future falls. AIMS: We sought to determine the associations of HGS asymmetry on future falls in older Americans. METHODS: The analytic sample included 10,446 adults aged at least 65 years from the 2006-2016 waves of the Health and Retirement Study. Falls were self-reported. A handgrip dynamometer measured HGS. The highest HGS on each hand was used for determining HGS asymmetry ratio: (non-dominant HGS/dominant HGS). Those with HGS asymmetry ratio < 1.0 had their ratio inverted to make all HGS asymmetry ratios ≥ 1.0. Participants were categorized into asymmetry groups based on their inverted HGS asymmetry ratio: (1) 0.0-10.0%, (2) 10.1-20.0%, (3) 20.1-30.0%, and (4) > 30.0%. Generalized estimating equations were used for the analyses. RESULTS: Every 0.10 increase in HGS asymmetry ratio was associated with 1.26 (95% confidence interval (CI) 1.07-1.48) greater odds for future falls. Relative to those with HGS asymmetry 0.0-10.0%, participants with HGS asymmetry > 30.0% had 1.15 (CI 1.01-1.33) greater odds for future falls; however, the associations were not significant for those with HGS asymmetry 10.1-20.0% (odds ratio: 1.06; CI 0.98-1.14) and 20.1-30.0% (odds ratio: 1.10; CI 0.99-1.22). Compared to those with HGS asymmetry 0.0-10.0%, participants with HGS asymmetry > 10.0% and > 20.0% had 1.07 (CI 1.01-1.16) and 1.12 (CI 1.02-1.22) greater odds for future falls, respectively. DISCUSSION: Asymmetric HGS, as a possible biomarker of impaired neuromuscular function, may help predict falls. CONCLUSIONS: We recommend that HGS asymmetry be considered in HGS protocols and fall risk assessments.

Sleeping time is associated with functional limitations in a national sample of older Americans.

BACKGROUND: Engaging in healthy behaviors may help to preserve function during aging; however, it is not well understood how sleeping time is associated with functional capacity in older adults. AIMS: We sought to determine the association of sleeping time on functional limitation in a national sample of older Americans. METHODS: The analytical sample included 6020 adults aged at least 65 years who participated in the 2007-2016 waves of the National Health and Nutrition Examination Survey. Respondents indicated their hours of sleep/weeknight and were categorized as < 5, 5-6.5, 7-8, 8.5-9, and > 9 h of sleep/weeknight. Ability to complete 19 functional tasks including basic activities of daily living, instrumental activities of daily living, leisure and social activities, lower extremity mobility activities, and general physical activities were also self-reported. A covariate-adjusted logistic model analyzed the associations between each sleeping time category and functional limitation. RESULTS: Relative to those reporting 7-8 h of sleep/weeknight, older Americans reporting < 5, 5-6.5, 8.5-9, and > 9 h of sleep/weeknight had 1.66 [95% confidence interval (CI): 1.05, 2.62], 1.25 (CI: 1.02, 1.52), 1.59 (CI: 1.19, 2.12), and 2.99 (CI: 1.96, 4.56) greater odds for functional limitation, respectively. DISCUSSION: Sleep should be recognized as a health factor that may reflect functional capacity in older adults. Healthcare providers should discuss the importance of optimal sleep with their older patients and older adults should practice healthy sleeping behaviors for preserving function. CONCLUSIONS: Not meeting optimal sleep recommendations is associated with functional limitations in older Americans.

Addressing social determinants of health in community pharmacy: Innovative opportunities and practice models.

Social determinants of health (SDoH) account for up to 90% of health outcomes, whereas medical care accounts for only 10%-15%; despite this disparity, only 24% of hospitals and 16% of physician practices screen for the 5 social needs. Community-embedded and highly accessible, pharmacies are uniquely positioned to connect individuals to local community and social resources and thereby address SDoH. In this article, we explore novel community pharmacy practice models that address SDoH, provide real-world examples of these models, and discuss pathways for reimbursement and sustainability. A number of innovative community pharmacy practice models that focus on social issues are currently being explored. These include integrating community health workers (CHWs) or SDoH specialists, wherein CHWs are frontline public health workers who can effectively bridge the health care system and their community, whereas SDoH specialists are pharmacy team members trained with substantial SDoH knowledge and how to use it to connect pharmacy patients to community resources. Three community pharmacy networks have implemented pilot programs using either a CHW or SDoH specialist model. An essential component for program success in all cases has been partnership development and increased interdependence between the pharmacies, local community organizations, and the public health sector. New payment models and financial incentives will be necessary to expand and sustain these programs. A potential Approach may be the use of Z codes, a subset of ICD-10-CM codes specific to assessing SDoH. Although opportunities are developing for community pharmacies to play a major role in sustainably addressing SDoH, additional work is needed before there is a widespread acceptance of pharmacies becoming service referral destinations for patients with social needs. Evaluation of these models on a wider scale will be necessary to fully evaluate their effectiveness, costs, and implementation within different community pharmacy settings.

Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults.

BACKGROUND: Approximately 35% of individuals > 70 years have mobility limitations. Historically, it was posited lean mass and muscle strength were major contributors to mobility limitations, but recent findings indicate lean mass and muscle strength only moderately explain mobility limitations. One likely reason is that lean mass and muscle strength do not necessarily incorporate measures globally reflective of motor function (defined as the ability to learn, or to demonstrate, the skillful and efficient assumption, maintenance, modification, and control of voluntary postures and movement patterns). In this study we determined the relative contribution of lean mass, muscle strength, and the four square step test, as an index of lower extremity motor function, in explaining between-participant variance in mobility tasks. METHODS: In community-dwelling older adults (N = 89; 67% women; mean 74.9 ± 6.7 years), we quantified grip and leg extension strength, total and regional lean mass, and time to complete the four square step test. Mobility was assessed via 6-min walk gait speed, stair climb power, 5x-chair rise time, and time to complete a complex functional task. Multifactorial linear regression modeling was used to determine the relative contribution (via semi-partial r2) for indices of lean mass, indices of muscle strength, and the four square step test. RESULTS: When aggregated by sex, the four square step test explained 17-34% of the variance for all mobility tasks (p <  0.01). Muscle strength explained ~ 12% and ~ 7% of the variance in 6-min walk gait speed and 5x-chair rise time, respectively (p <  0.02). Lean mass explained 32% and ~ 4% of the variance in stair climb power and complex functional task time, respectively (p <  0.02). When disaggregated by sex, lean mass was a stronger predictor of mobility in men. CONCLUSION: The four square step test is uniquely associated with multiple measures of mobility in older adults, suggesting lower extremity motor function is an important factor for mobility performance. TRIAL REGISTRATION: NCT02505529 -2015/07/22.

Weakness and cognitive impairment are independently and jointly associated with functional decline in aging Americans.

BACKGROUND: Discovering how certain health factors contribute to functional declines may help to promote successful aging. AIMS: To determine the independent and joint associations of handgrip strength (HGS) and cognitive function with instrumental activities of daily living (IADL) and activities of daily living (ADL) disability decline in aging Americans. METHODS: Data from 18,391 adults aged 50 years and over who participated in at least one wave of the 2006-2014 waves of the Health and Retirement Study were analyzed. A hand-held dynamometer assessed HGS and cognitive functioning was examined with a modified version of the Telephone Interview of Cognitive Status. IADL and ADL abilities were self-reported. Participants were stratified into four distinct groups based on their HGS and cognitive function status. Separate covariate-adjusted multilevel models were conducted for the analyses. RESULTS: Participants who were weak, had a cognitive impairment, and had both weakness and a cognitive impairment had 1.70 (95% confidence interval (CI) 1.57-1.84), 1.97 (CI 1.74-2.23), and 3.13 (CI 2.73-3.59) greater odds for IADL disability decline, respectively, and 2.26 (CI 2.03-2.51), 1.26 (CI 1.05-1.51), and 4.48 (CI 3.72-5.39) greater odds for ADL disability decline, respectively. DISCUSSION: HGS and cognitive functioning were independently and jointly associated with IADL and ADL disability declines. Individuals with both weakness and cognitive impairment demonstrated substantially higher odds for functional decline than those with either risk factor alone. CONCLUSIONS: Including measures of both HGS and cognitive functioning in routine geriatric assessments may help to identify those at greatest risk for declining functional capacity.

Strategies for Improving Nutrition in Inner-City Populations.

PURPOSE OF REVIEW: The social, economic, cultural, and historic reasons for why inner-city communities have struggled with poor nutrition and health outcomes are complex. Creating successful programs to address these problems requires a better understanding of the gaps that exist and formulating solutions to improve access to nutritious food options. RECENT FINDINGS: Studies have demonstrated that aggressive evidence-based nutrition can decrease factors linked to cardiovascular diseases, but improving access to these nutritious resources and prioritizing health literacy and behavior modification related to meal choices are just as essential. Government programs and community interventions have shown promise through creating supermarkets, farmers' markets, and community gardens, but not all inner-city areas have such programs in place. The poor state of inner-city nutrition and health is a true public health crisis. Creation of innovative strategies to improve education on and sustainable access to nutritious foods is essential in order to improve health disparities and outcomes.