Increased frequency of light physical activity during midlife and old age buffers against cognitive declines.

Although it is well established that moderate-to-vigorous physical activity (MVPA) buffers against declines in cognitive health, less is known about the benefits of light physical activity (LPA). Research on the role of LPA is crucial to advancing behavioral interventions to improve late life health outcomes, including cognitive functioning, because this form of physical activity remains more feasible and amenable to change in old age. Our study examined the extent to which increases in LPA frequency protected against longitudinal declines in cognitive functioning and whether such a relationship becomes pronounced in old age when opportunities for MVPA are typically reduced. We analyzed 9-year data from the national Midlife in the United States Study (n = 2,229; Mage = 56 years, range = 33-83; 56% female) using autoregressive models that assessed whether change in LPA frequency predicted corresponding changes in episodic memory and executive functioning in middle and later adulthood. Increases in LPA frequency predicted less decline in episodic memory (ß = 0.06, p = .004) and executive functioning (ß = 0.14, p < .001) over the 9-year follow-up period, even when controlling for moderate and vigorous physical activity. Effect sizes for moderate and vigorous physical activity were less than half that observed for LPA. Moderation models showed that, for episodic memory, the benefits of increases in LPA frequency were more pronounced at older ages. Findings suggest that increases in LPA over extended periods of time may help slow age-related cognitive declines, particularly in later life when opportunities for MVPA are often diminished.

Scanning Transmission Electron Microscopy in a Scanning Electron Microscope for the High-Throughput Imaging of Biological Assemblies.

Electron microscopy of soft and biological materials, or "soft electron microscopy", is essential to the characterization of macromolecules. Soft microscopy is governed by enhancing contrast while maintaining low electron doses, and sample preparation and imaging methodologies are driven by the length scale of features of interest. While cryo-electron microscopy offers the highest resolution, larger structures can be characterized efficiently and with high contrast using low-voltage electron microscopy by performing scanning transmission electron microscopy in a scanning electron microscope (STEM-in-SEM). Here, STEM-in-SEM is demonstrated for a four-lobed protein assembly where the arrangement of the proteins in the construct must be examined. STEM image simulations show the theoretical contrast enhancement at SEM-level voltages for unstained structures, and experimental images with multiple STEM modes exhibit the resolution possible for negative-stained proteins. This technique can be extended to complex protein assemblies, larger structures such as cell sections, and hybrid materials, making STEM-in-SEM a valuable high-throughput imaging method.

The estimated prevalence of no reported dementia-related diagnosis in older Americans living with possible dementia by healthcare utilization.

BACKGROUND: Screening for dementia in relevant healthcare settings may help in identifying low cognitive functioning for comprehensive cognitive assessments and subsequent dementia treatment after diagnosis. AIMS: This study sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally-representative sample of older Americans with a cognitive impairment consistent with dementia (CICD) by healthcare utilization. METHODS: The unweighted analytical sample included 1514 Americans aged ≥ 65 years that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010-2016 waves of the Health and Retirement Study. An adapted Telephone Interview of Cognitive Status assessed cognitive functioning. Those with scores ≤ 6 had a CICD. Dementia-related diagnosis was self-reported. Respondents indicated if they visited a physician, received home healthcare, or experienced an overnight nursing home stay in the previous two years. RESULTS: The prevalence of no reported dementia-related diagnosis in persons with a CICD who visited a physician was 89.9% (95% confidence interval (CI): 85.4%-93.1%). Likewise, the prevalence of no reported diagnosis in those with a CICD who received home healthcare was 84.3% (CI: 75.1-90.5%). For persons with a CICD that had an overnight nursing home stay, the prevalence of no reported dementia-related diagnosis was 83.0% (CI: 69.1-91.4%). DISCUSSION: Although the prevalence of no reported dementia-related diagnosis in individuals with a CICD differed across healthcare settings, the prevalence was generally high nonetheless. CONCLUSIONS: We recommend increased awareness and efforts be given to dementia screenings in various clinical settings.

Synthetic Tuning of Domain Stoichiometry in Nanobody-Enzyme Megamolecules.

This paper presents a method to synthetically tune atomically precise megamolecule nanobody-enzyme conjugates for prodrug cancer therapy. Previous efforts to create heterobifunctional protein conjugates suffered from heterogeneity in domain stoichiometry, which in part led to the failure of antibody-enzyme conjugates in clinical trials. We used the megamolecule approach to synthesize anti-HER2 nanobody-cytosine deaminase conjugates with tunable numbers of nanobody and enzyme domains in a single, covalent molecule. Linking two nanobody domains to one enzyme domain improved avidity to a human cancer cell line by 4-fold but did not increase cytotoxicity significantly due to lowered enzyme activity. In contrast, a megamolecule composed of one nanobody and two enzyme domains resulted in an 8-fold improvement in the catalytic efficiency and increased the cytotoxic effect by over 5-fold in spheroid culture, indicating that the multimeric structure allowed for an increase in local drug activation. Our work demonstrates that the megamolecule strategy can be used to study structure-function relationships of protein conjugate therapeutics with synthetic control of protein domain stoichiometry.

Synthesis, Characterization, and Simulation of Four-Armed Megamolecules.

This paper describes the synthesis, characterization, and modeling of a series of molecules having four protein domains attached to a central core. The molecules were assembled with the "megamolecule" strategy, wherein enzymes react with their covalent inhibitors that are substituted on a linker. Three linkers were synthesized, where each had four oligo(ethylene glycol)-based arms terminated in a para-nitrophenyl phosphonate group that is a covalent inhibitor for cutinase. This enzyme is a serine hydrolase and reacts efficiently with the phosphonate to give a new ester linkage at the Ser-120 residue in the active site of the enzyme. Negative-stain transmission electron microscopy (TEM) images confirmed the architecture of the four-armed megamolecules. These cutinase tetramers were also characterized by X-ray crystallography, which confirmed the active-site serine-phosphonate linkage by electron-density maps. Molecular dynamics simulations of the tetracutinase megamolecules using three different force field setups were performed and compared with the TEM observations. Using the Amberff99SB-disp + pH7 force field, the two-dimensional projection distances of the megamolecules were found to agree with the measured dimensions from TEM. The study described here, which combines high-resolution characterization with molecular dynamics simulations, will lead to a comprehensive understanding of the molecular structures and dynamics for this new class of molecules.

Alzheimer's Disease Warning Signs: Gender and Education Influence Modifiable Risk Factors-A Pilot Survey Study.

OBJECTIVE: The aim of this research was to determine the relationships among diabetes, Alzheimer's disease warning signs, and lifestyle factors such as fruit and vegetable intake and physical activity. METHOD: Adults over the age of 50 (N = 147) responded to a survey about their health, family history, and experience of Alzheimer's warning signs in the previous year. RESULTS: Pearson's correlation revealed significant relationships between fruit and vegetable intake and education, gender, and physical activity. Alzheimer's warning signs were associated with relatives having an Alzheimer's disease diagnosis. Other results were nonsignificant. CONCLUSIONS: Diabetes impacts one-third of older adults in the United States and increases the risk of Alzheimer's disease. This survey revealed that women, who are more at risk for Alzheimer's disease, are less likely to engage in physical activity, a behavior that could decrease their risk. Similarly, those with higher education were more likely to consume colorful fruits and vegetables, potentially decreasing their risk of Alzheimer's disease.

Solid-Phase Synthesis of Megamolecules.

This paper presents a solid-phase strategy to efficiently assemble multiprotein scaffolds-known as megamolecules-without the need for protecting groups and with precisely defined nanoscale architectures. The megamolecules are assembled through sequential reactions of linkers that present irreversible inhibitors for enzymes and fusion proteins containing the enzyme domains. Here, a fusion protein containing an N-terminal cutinase and a C-terminal SnapTag domain react with an ethyl p-nitrophenyl phosphonate (pNPP) or a chloro-pyrimidine (CP) group, respectively, to give covalent products. By starting with resin beads that are functionalized with benzylguanine, a series of reactions lead to linear, branched, and dendritic structures that are released from the solid support by addition of TEV protease and that have sizes up to approximately 25 nm.

Keeping Dr. Charles Richard Drew's legacy alive.

The Charles R. Drew University of Medicine and Science (CDU) recently celebrated its fiftieth anniversary. The university was established to honor Dr. Charles Richard Drew, a pioneer in blood banking. As a tribute to the legacy of CDU and Dr. Drew, the CDU Health Sciences Library examined how CDU is keeping Dr. Drew's legacy alive.

Factors Influencing Nurses' Perceptions of the Baccalaureate Degree in Nursing as Minimum Requirement for Professional Practice.

AIM: The purpose of this study was to determine factors influencing nurses' perceptions of the baccalaureate degree in nursing as the minimum requirement for professional practice. BACKGROUND: The associate degree nursing program was created in response to a nursing shortage in the early 1950s. In 1965, the American Nurses Association recommended that the BSN be the minimum to practice professionally as a nurse. METHOD: A quantitative method with a descriptive design was used. An online, Likert-type survey collected data from 61 nurses in southern Michigan and northern Indiana. Two open-ended questions were included to gain perceptions in nurses' own words. RESULTS: Higher education was noted as positive for nurses, but not necessary for becoming an expert nurse. The most common factors influencing advancing education were time and money, followed by career advancement. CONCLUSION: The study supports the idea that if nurses are able, they will continue their education.

Linear Chains of HER2 Receptors Found in the Plasma Membrane Using Liquid-Phase Electron Microscopy.

The spatial distribution of the human epidermal growth factor 2 (HER2) receptor in the plasma membrane of SKBR3 and HCC1954 breast cancer cells was studied. The receptor was labeled with quantum dot nanoparticles, and fixed whole cells were imaged in their native liquid state with environmental scanning electron microscopy using scanning transmission electron microscopy detection. The locations of individual HER2 positions were determined in a total plasma membrane area of 991 µm2 for several SKBR3 cells and 1062 µm2 for HCC1954 cells. Some of the HER2 receptors were arranged in a linear chain with interlabel distances of 40 ± 7 and 32 ± 10 nm in SKBR3 and HCC1954 cells, respectively. The finding was tested against randomly occurring linear chains of six or more positions, from which it was concluded that the experimental finding is significant and did not arise from random label distributions. Because the measured interlabel distance in the HER2 chains is similar to the 36-nm helix-repetition distance of actin filaments, it is proposed that a linking mechanism between HER2 and actin filaments leads to linearly aligned oligomers.

Expanding Library Services and Instruction Through LibGuides.

Beginning in 2012, the Charles R. Drew University (CDU) Health Sciences Library used LibGuides in a number of innovative ways. Librarians constructed e-book databases, in-depth tutorials on technology-related topics, and web pages highlighting special events. To assess similar LibGuides innovation, CDU librarians developed an eight-question survey distributed to health sciences and hospital libraries throughout Southern California and Arizona. Results showed that libraries used LibGuides primarily to deliver access to online resources and to provide supplementary materials supporting instruction. Responses also revealed that many libraries had not yet adopted LibGuides. These findings were analyzed and compared to past and current LibGuides design at CDU.

When and how perceived control buffers against cognitive declines: A moderated mediation analysis.

Although perceived control is a well-established predictor of cognitive aging, less is known about how and under what developmental circumstances these beliefs about personal influence may protect against cognitive declines. Our study examined light physical activity (LPA) as an unexplored mechanism that may link changes in two facets of perceived control (personal mastery, perceived constraints) to longitudinal trajectories of cognitive functioning. We also examined whether mediated pathways were moderated by age (i.e., differed across the adult lifespan). We analyzed two-wave, 9-year data from the national Midlife in the United States Study (n = 2,456; Mage = 56 years, range = 30-84; 56% female) using autoregressive mediation and moderated mediation models. Mediation models showed that changes in personal mastery and perceived constraints predicted episodic memory and executive functioning via self-reported change in LPA. Only the mediated effects of constraints remained significant in a model that included both mastery and constraints as predictors. Moderated mediation models showed that, for episodic memory, the mediated pathways were strongest in old age and emerged only for constraints: For older but not younger adults, declines in constraints were associated with less decline in episodic memory, as mediated by increases in LPA. Results were consistent in sensitivity analyses that controlled for levels and change in moderate-to-vigorous physical activity. Findings inform lifespan theories of control and provide initial evidence that change in a largely overlooked health behavior (LPA) may underlie the link between perceived constraints and cognitive functioning, with this pathway becoming more pronounced in late life. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Meditation modalities for ADHD in minority pediatric populations in the USA: a scoping review.

Background: Roughly 10% of children aged 3 -17 in the USA are diagnosed with attention-deficit hyperactivity disorder (ADHD), and minorities are less likely to initiate common pharmacologic treatment. We conducted a review of the literature to examine meditation as a safe, effective, and low-cost alternative. Methods: We searched PubMed and other journals using "meditation," "mindfulness," "minority," related keywords, and relevant MeSH terms. Eligible studies involved racial/ethnic minorities in the USA, reported quantitative psychosocial outcomes, and were published in a peer-reviewed, English-language journal. Results: Out of 119 "hits," 111 were eliminated as duplicates or were not relevant. A full-text review of the remaining eight revealed that none fully met our eligibility criteria. Besides the obvious lack of studies, those reviewed reported incomplete demographic and clinical data. They also employed different and inconsistent research methodologies, interventions and modalities, and statistical analyses. This hindered understanding exactly which populations may benefit from meditation, and for which specific symptoms. Conclusion: We recommend a socio-ecological model in examining intervention modalities, especially in the context of intrapersonal, interpersonal, organizational, environmental, and policy domains. We also suggest the possible inclusion of research older than 10 years, conducted outside of the USA, on minority and non-minority populations, for supplementary and confirmatory data. We advocate for consistency in study design and data collection, which would help align research conducted in different countries. Searches should also include variations of meditation such as "mindfulness" and "guided imagery," and associated symptoms and comorbidities of ADHD, including "learning disorder" and "behavioral problems."

The Role of Different Weakness Cut-Points for Future Cognitive Impairment in Older Americans.

OBJECTIVES: New absolute and normalized handgrip strength (HGS) cut-points may not yield similar predictive value for cognitive performance. We sought to determine the associations of (1) each absolute and normalized weakness cut-point, and (2) compounding weakness on future cognitive impairment in older Americans. DESIGN: Longitudinal panel. SETTING AND PARTICIPANTS: The analytic sample included 11,116 participants aged ≥65 years from the 2006 to 2018 waves of the Health and Retirement Study. Participants from the Health and Retirement Study completed detailed interviews that included physical measures and core interviews. METHODS: The modified Telephone Interview of Cognitive Status assessed cognitive function and persons scoring <11 were classified as having a cognitive impairment. A handgrip dynamometer measured HGS. Men were considered weak if their HGS was <35.5 kg (absolute), <0.45 kg/kg (body mass normalized), or <1.05 kg (body mass index normalized), whereas women were classified as weak if their HGS was <20.0 kg, <0.337 kg/kg, or <0.79 kg. Compounding weakness included those below 1, 2, or all 3 cut-points. Generalized estimating equations quantified the associations. RESULTS: Persons considered weak under the absolute cut-point had 1.62 (95% CI 1.34-1.96) greater odds for future cognitive impairment, but no significant associations were observed for those classified as weak under the body mass [odds ratio (OR) 1.12, CI 0.91-1.36] and body mass index normalized (OR 1.17, CI 0.95-1.43) cut-points. Older Americans below all 3 weakness cut-points had 1.47 (CI 1.15-1.88) greater odds for future cognitive impairment, but no significant associations were found for persons classified as weak under 1 (OR 1.08, CI 0.83-1.42) or 2 (OR 1.19, CI 0.91-1.55) cut-points. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that each weakness cut-point has differential prognostic value for future cognitive impairment, and aggregating weakness cut-points may improve their predictive utility. Consideration should be given to how weakness categories are uniquely linked to cognitive function.

The Prevalence and Trends of Instrumental Activities of Daily Living Impairments in the United States from 2008-2018.

Background: Instrumental activities of daily living (IADL) are neuropsychological-driven tasks that are linked to cognitive dysfunction. Examining population-based IADL deficits may reveal insights for the presence of these impairments in the United States. Objective: This investigation sought to evaluate the prevalence and trends of IADL impairments in Americans. Methods: A secondary analysis of data from the 2006-2018 waves of the Health and Retirement Study was conducted. The overall unweighted analytic sample included 29,764 Americans aged≥50 years. Respondents indicated their ability to perform six IADLs: manage money, manage medications, use a telephone, prepare hot meals, shop for groceries, and use a map. Persons reporting difficulty or an inability to complete an individual IADL were considered as having a task-specific impairment. Similarly, those indicating difficulty or an inability to perform any IADL were classified as having an IADL impairment. Sample weights were utilized to generate nationally-representative estimates. Results: Having an impairment in using a map (2018 wave: 15.7% (95% confidence interval (CI): 15.0-16.4) had the highest prevalence in individual IADLs regardless of wave examined. The overall prevalence of IADL impairments declined during the study period (p < 0.001) to 25.4% (CI: 24.5-26.2) in the 2018 wave. Older Americans and women had a consistently higher prevalence of IADL impairments compared to middle-aged Americans and men, respectively. The prevalence of IADL impairments was also highest among Hispanics and non-Hispanic Blacks. Conclusion: IADL impairments have declined over time. Continued surveillance of IADLs may help inform cognitive screening, identify subpopulations at risk of impairment, and guide relevant policy.

Sleep and diet patterns of college students during the COVID-19 pandemic lockdowns.

Introduction: College students experience high levels of depression, anxiety, and stress during the academic year as they juggle the competing demands of young adulthood and their studies. The COVID-19 pandemic heightened this experience. Healthful diets and sleep patterns are associated with improved physical and mental well-being. Purpose: The goal of this study was to identify if there was a relationship between changes in sleep and diet during the COVID-19 pandemic. Methods: A group of college students was surveyed online using Qualtrics software during the first two months of lockdown restrictions at a large, midwestern university in the United States. Results: More participants reported no changes in diet and increased hours of sleep than reported declines or improvements in diet, or reductions or retained sleep patterns. Participants who maintained their diet were likely to maintain their current sleep pattern. Conclusion: College students demonstrated resilience in healthful behaviors during the first two months of COVID-19 lockdown.

Undiagnosed Dementia Is Associated with Poor Physical Function in Older Adults.

BACKGROUND: Older adults with a cognitive impairment, including those not yet diagnosed, may have deficits in their physical function. OBJECTIVE: We sought to determine the associations of cognitive impairment consistent with dementia (CICD) diagnosis status on handgrip strength, gait speed, and functional disability in older adults. METHODS: The analytical sample included 8,383 adults aged ≥65-years without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010-2016 waves of the Health and Retirement Study. A handgrip dynamometer measured handgrip strength. Men with handgrip strength <26 kg and women <16 kg were weak. Gait speed was timed across a 2.5-m course and those with slowness had gait speed <0.8 m/s. Participants with difficulty or an inability in completing any basic activities of daily living had a functional disability. The adapted Telephone Interview of Cognitive Status evaluated cognitive function. Persons with scores <7 had a CICD. Healthcare provider dementia-related diagnosis was self-reported. Undiagnosed CICD was defined as no reported dementia-related diagnosis but had CICD, while diagnosed CICD was classified as reporting a dementia-related diagnosis. Covariate-adjusted logistic models were used for the analyses. RESULTS: Persons with undiagnosed CICD had 1.37 (95% confidence interval (CI): 1.04-1.80) greater odds for weakness and 2.02 (CI: 1.39-2.94) greater odds for slow gait speed. Older adults with diagnosed CICD had 2.29 (CI: 1.32-3.97) greater odds for slowness and 1.85 (CI: 1.19-2.90) greater odds for functional disability. CONCLUSION: Screening for CICD could be recommended when defects in physical function are observed in older adults.

Opioid Use after Pediatric Urologic Surgery: Is It Really Needed?

OBJECTIVES: To identify factors associated with opioid use after pediatric urologic surgery, use this data to educate our patients and colleagues on decreasing post-operative opioid use, and assess the effectiveness of this approach. METHODS: From 1/2018 - 12/2019, a written questionnaire asking which pain medications were used after surgery was given to patients' families before routine post-operative appointments. A retrospective review of the surveys and patient charts was performed. Demographic factors were compared between patients who did and did not use opioids with Fisher's exact and t tests. Midway through the study, the results were presented to the urology department in an attempt to reduce opioid use over the next year. The number of opioid prescriptions and patients who used opioids after surgery in 2018 versus 2019 was compared. RESULTS: 1001 patients were included with a mean age of 5 years, 96% male. Patients used a mean of 4.5 doses of opioids and 83% had leftover opioids. Factors significantly associated with not using opioids included age less than 3, penile, and endoscopic surgery. Between 2018 and 2019-despite no significant difference in patient age, gender, or procedure type-the number of patients who were prescribed (61% vs 34%, P < .0001) and who used opioids (55 vs 28%, P < .0001) was significantly decreased. CONCLUSION: After pediatric urologic surgery, many patients do not need opioid prescriptions. Reviewing our own opioid use practices and providing education within our department allowed us to significantly decrease the number of opioids prescribed and used after surgery.

The Seniors' Community Hub: An Integrated Model of Care for the Identification and Management of Frailty in Primary Care.

(1) Background: Integrated models of primary care deliver the comprehensive and preventative approach needed to identify and manage frailty in older people. Seniors' Community Hub (SCH) was developed to deliver person-centered, evidence-informed, coordinated, and integrated care services to older community dwelling adults living with frailty. This paper aims to describe the SCH model, and to present patient-oriented results of the pilot. (2) Methods: SCH was piloted in an academic clinic with six family physicians. Eligible patients were community dwelling, 65 years of age and older, and considered to be at risk of frailty (eFI > 0.12). Health professionals within the clinic received training in geriatrics and interprofessional teamwork to form the SCH team working with family physicians, patients and caregivers. The SCH intervention consisted of a team-based multi-domain assessment with person-centered care planning and follow-up. Patient-oriented outcomes (EQ-5D-5L and EQ-VAS) and 4-metre gait speed were measured at initial visit and 12 months later. (3) Results: 88 patients were enrolled in the pilot from April 2016-December 2018. No statistically significant differences in EQ-5D-5L/VAS or the 4-metre gait speed were detected in 38 patients completing the 12-month assessment. (4) Conclusions: Future larger scale studies of longer duration are needed to demonstrate impacts of integrated models of primary care on patient-oriented outcomes for older adults living with frailty.

Handgrip Weakness and Asymmetry Independently Predict the Development of New Activity Limitations: Results from Analyses of Longitudinal Data from the US Health and Retirement Study.

OBJECTIVES: Examining strength asymmetries in assessments of muscle function may improve screenings for limitations in independent living tasks such as instrumental activities of daily living (IADL). We sought to determine the associations between handgrip strength (HGS) asymmetry and future IADL limitations in aging Americans. DESIGN: Longitudinal panel. SETTING AND PARTICIPANTS: Secondary analyses of data from participants aged at least 50 years from the 2006-2016 waves of the Health and Retirement Study. The analytic sample included 18,235 Americans who identified hand dominance and had measures of HGS for both hands in a single wave. METHODS: Hand dominance was self-reported, and a handgrip dynamometer measured HGS on each hand. The highest HGS values on each hand were used to calculate the HGS asymmetry ratio: (nondominant HGS/dominant HGS). Individuals with HGS asymmetry ratio <0.80 or >1.20 had HGS asymmetry. Persons with HGS asymmetry ratio <0.80 had dominant HGS asymmetry, whereas participants with HGS asymmetry ratio >1.20 had nondominant HGS asymmetry. Persons with HGS asymmetry ratio <1.0 also had their ratio inversed to make all HGS asymmetry ratios ≥1.0. IADL were self-reported. Covariate-adjusted generalized estimating equations were used for the analyses. RESULTS: Participants with HGS asymmetry had 1.12 [95% confidence interval (CI): 1.03-1.20] greater odds for future IADL limitations. Each HGS asymmetry dominance group also had greater odds for future IADL limitations: 1.09 (CI: 1.01-1.18) for individuals with dominant HGS asymmetry and 1.29 (CI: 1.09-1.52) for persons with nondominant HGS asymmetry. Every 0.10 increase in inverted HGS asymmetry ratio was associated with 1.30 (CI: 1.07-1.57) greater odds for future IADL limitations. CONCLUSIONS AND IMPLICATIONS: Assessing HGS asymmetry, as another potential biomarker of impaired muscle function, may provide novel insights for predicting IADL limitations. Future research should continue examining how strength asymmetries, and other aspects of muscle function beyond maximal strength, factor into the disabling cascade.