The Relationship Between Instruction Specificity and Resistiveness to Care During Activities of Daily Living in Persons with Dementia

It is common for persons with dementia to display resistant behaviors during activities of daily living (ADLs) and caregiver communication skills can influence the likelihood of these behaviors. Previous research suggests that the type of instructions issued by caregivers is related to rates of compliance during ADLs in persons with dementia. It is unclear, however, if these instruction types affect the likelihood resistiveness to care (RTC) during ADLs. The purpose of the current study was to examine how the use of different types of instructions relate to instances of RTC during ADLs. Results indicated that vague and ambiguous instructions (i.e., beta instructions) were more likely to precede and follow physical aggression compared to instructions that were more specific, clear and feasible (i.e., alpha instructions). Results also indicated that alpha instructions were more likely to precede verbal agitation. These findings have implications for communication training programs for caregivers working with persons with dementia

Nutrition and Well-Being

The relationship of nutrition-related factors with well-being in people 80 and older has received little attention. Therefore, this chapter explores the relationships of depression and depressive symptoms, as a measure of well-being, with appetite, body weight changes, underweight, and obesity as measures of nutritional status. The sample is from the Georgia Centenarian Study (aged 80 to 89 and 98+ years, see Chapter 9). In bivariate analyses, centenarians with depression consistently had the highest prevalence of underweight when compared to centenarians without depression and all octogenarians (23% to 33% vs. 0% to 16%). When controlled for other demographic factors, clinically relevant depressive symptomatology was associated with appetite loss, while a current diagnosis of depression was associated with recent changes in body weight. However, taking antidepressant medications was not associated with any of the nutrition-related measures. Demographic factors emerged as important predictors of nutritional status. Living in a skilled nursing facility compared to living in the community was associated with a lower risk of appetite loss and higher risk of weight gain; being a centenarian or being female was associated with underweight; and being Black (vs. White) was associated with obesity. Thus, risk factors for poor nutritional status in the oldest may be related to depression as well as to specific demographic factors including age, gender, race, and residence in a skilled nursing facility

Drastic Reductions in Mental Well-Being Observed Globally During the COVID-19 Pandemic: Results From the ASAP Survey

Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 +/- 16.9 to 51.9 +/- 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11-1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16-1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05-1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16-1.44/OR = 1.35, 95% CI: 1.23-1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 +/- 18.7% pre-restrictions to 81.3 +/- 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50-1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18-1.36), and young age (OR = 1.10, 95% CI: 1.03-1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.DJ-P is supported by a grant from the Spanish Ministry of Science and Innovation-MINECO (RYC-2014-16938). The research fellowship of KH was funded by the German Research Foundation (Grant no. HO 6214/2-1)

Cardiovascular Fitness and Executive Functioning in Primary School-aged Children

Previous research in children has shown that higher cardiovascular fitness is related to better executive functioning. However, the available literature is hampered by methodological limitations. The present study investigates the relationship between cardiovascular fitness and executive functioning in a large sample of healthy children (N = 814). Cardiovascular fitness was assessed with estimated VO2Max from 20 m Shuttle Run Test performance. Executive functioning was assessed using a set of computerized neurocognitive tasks aimed at executive functions (working memory, motor inhibition, interference control) and lower-level neurocognitive functions (information processing and attention). Dependent measures derived from the neurocognitive tests were subjected to principal component analysis. Mixed model analyses tested the relation between cardiovascular fitness and neurocognitive functioning components. Results showed that children with higher cardiovascular fitness performed better on the neurocognitive function components Information Processing and Control, Visuospatial Working Memory and Attention Efficiency. The following measures contained in these components contributed to the observed relations: information processing measures, visuospatial working memory, and speed of alerting attention. No relationship was found between cardiovascular fitness and the other components: Verbal Working Memory, Attention Accuracy, and Interference Control. The present study suggests that there is a relationship between cardiovascular fitness and a specific set of executive functions and lower level neurocognitive functions. These findings highlight the importance of cardiovascular fitness for the overall health of school-aged children

Plasma and Serum Metabolite Association Networks: Comparability within and between Studies Using NMR and MS Profiling

Blood is one of the most used biofluids in metabolomics studies, and the serum and plasma fractions are routinely used as a proxy for blood itself. Here we investigated the association networks of an array of 29 metabolites identified and quantified via NMR in the plasma and serum samples of two cohorts of ∼1000 healthy blood donors each. A second study of 377 individuals was used to extract plasma and serum samples from the same individual on which a set of 122 metabolites were detected and quantified using FIA–MS/MS. Four different inference algorithms (ARANCE, CLR, CORR, and PCLRC) were used to obtain consensus networks. The plasma and serum networks obtained from different studies showed different topological properties with the serum network being more connected than the plasma network. On a global level, metabolite association networks from plasma and serum fractions obtained from the same blood sample of healthy people show similar topologies, and at a local level, some differences arise like in the case of amino acids

Roadmap for C9ORF72 in Frontotemporal Dementia and Amyotrophic Lateral Sclerosis: Report on the C9ORF72 FTD/ALS Summit

A summit held March 2023 in Scottsdale, Arizona (USA) focused on the intronic hexanucleotide expansion in the C9ORF72 gene and its relevance in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS; C9ORF72-FTD/ALS). The goal of this summit was to connect basic scientists, clinical researchers, drug developers, and individuals affected by C9ORF72-FTD/ALS to evaluate how collaborative efforts across the FTD-ALS disease spectrum might break down existing disease silos. Presentations and discussions covered recent discoveries in C9ORF72-FTD/ALS disease mechanisms, availability of disease biomarkers and recent advances in therapeutic development, and clinical trial design for prevention and treatment for individuals affected by C9ORF72-FTD/ALS and asymptomatic pathological expansion carriers. The C9ORF72-associated hexanucleotide repeat expansion is an important locus for both ALS and FTD. C9ORF72-FTD/ALS may be characterized by loss of function of the C9ORF72 protein and toxic gain of functions caused by both dipeptide repeat (DPR) proteins and hexanucleotide repeat RNA. C9ORF72-FTD/ALS therapeutic strategies discussed at the summit included the use of antisense oligonucleotides, adeno-associated virus (AAV)-mediated gene silencing and gene delivery, and engineered small molecules targeting RNA structures associated with the C9ORF72 expansion. Neurofilament light chain, DPR proteins, and transactive response (TAR) DNA-binding protein 43 (TDP-43)-associated molecular changes were presented as biomarker candidates. Similarly, brain imaging modalities (i.e., magnetic resonance imaging [MRI] and positron emission tomography [PET]) measuring structural, functional, and metabolic changes were discussed as important tools to monitor individuals affected with C9ORF72-FTD/ALS, at both pre-symptomatic and symptomatic disease stages. Finally, summit attendees evaluated current clinical trial designs available for FTD or ALS patients and concluded that therapeutics relevant to FTD/ALS patients, such as those specifically targeting C9ORF72, may need to be tested with composite endpoints covering clinical symptoms of both FTD and ALS. The latter will require novel clinical trial designs to be inclusive of all patient subgroups spanning the FTD/ALS spectrum

Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes. The soluble bioactive form of the transmembrane protein fibronectin type III domain containing 4 (sFNDC4) has anti-inflammatory effects and improves insulin sensitivity. Here the authors show that liver derived sFNDC4 signals through adipose tissue GPCR GPR116 to promote insulin-mediated glucose uptake.Peer reviewe

Female Genitalia Concealment Promotes Intimate Male Courtship in a Water Strider

Violent coercive mating initiation is typical for animals with sexual conflict over mating. In these species, the coevolutionary arms-race between female defenses against coercive mating and male counter-adaptations for increased mating success leads to coevolutionary chases of male and female traits that influence the mating. It has been controversial whether one of the sexes can evolve traits that allow them to “win” this arms race. Here, we use morphological analysis (traditional and scanning electron micrographs), laboratory experiments and comparative methods to show how females of a species characterized by typical coercive mating initiation appear to “win” a particular stage of the sexual conflict by evolving morphology to hide their genitalia from direct, forceful access by males. In an apparent response to the female morphological adaptation, males of this species added to their typically violent coercive mounting of the female new post-mounting, pre-copulatory courtship signals produced by tapping the water's surface with the mid-legs. These courtship signals are intimate in the sense that they are aimed at the female, on whom the male is already mounted. Females respond to the signals by exposing their hidden genitalia for copulatory intromission. Our results indicate that the apparent victory of coevolutionary arms race by one sex in terms of morphology may trigger evolution of a behavioral phenotype in the opposite sex

Night Shift Work Affects Urine Metabolite Profiles of Nurses with Early Chronotype

Night shift work can have a serious impact on health. Here, we assess whether and how night shift work influences the metabolite profiles, specifically with respect to different chronotype classes. We have recruited 100 women including 68 nurses working both, day shift and night shifts for up to 5 consecutive days and collected 3640 spontaneous urine samples. About 424 waking-up urine samples were measured using a targeted metabolomics approach. To account for urine dilution, we applied three methods to normalize the metabolite values: creatinine-, osmolality- and regression-based normalization. Based on linear mixed effect models, we found 31 metabolites significantly (false discovery rate <0.05) affected in nurses working in night shifts. One metabolite, acylcarnitine C10:2, was consistently identified with all three normalization methods. We further observed 11 and 4 metabolites significantly associated with night shift in early and late chronotype classes, respectively. Increased levels of medium- and long chain acylcarnitines indicate a strong impairment of the fatty acid oxidation. Our results show that night shift work influences acylcarnitines and BCAAs, particularly in nurses in the early chronotype class. Women with intermediate and late chronotypes appear to be less affected by night shift work

Aconitase Regulation of Erythropoiesis Correlates with a Novel Licensing Function in Erythropoietin-Induced ERK Signaling

Erythroid development requires the action of erythropoietin (EPO) on committed progenitors to match red cell output to demand. In this process, iron acts as a critical cofactor, with iron deficiency blunting EPO-responsiveness of erythroid progenitors. Aconitase enzymes have recently been identified as possible signal integration elements that couple erythropoiesis with iron availability. In the current study, a regulatory role for aconitase during erythropoiesis was ascertained using a direct inhibitory strategy.In C57BL/6 mice, infusion of an aconitase active-site inhibitor caused a hypoplastic anemia and suppressed responsiveness to hemolytic challenge. In a murine model of polycythemia vera, aconitase inhibition rapidly normalized red cell counts, but did not perturb other lineages. In primary erythroid progenitor cultures, aconitase inhibition impaired proliferation and maturation but had no effect on viability or ATP levels. This inhibition correlated with a blockade in EPO signal transmission specifically via ERK, with preservation of JAK2-STAT5 and Akt activation. Correspondingly, a physical interaction between ERK and mitochondrial aconitase was identified and found to be sensitive to aconitase inhibition.Direct aconitase inhibition interferes with erythropoiesis in vivo and in vitro, confirming a lineage-selective regulatory role involving its enzymatic activity. This inhibition spares metabolic function but impedes EPO-induced ERK signaling and disturbs a newly identified ERK-aconitase physical interaction. We propose a model in which aconitase functions as a licensing factor in ERK-dependent proliferation and differentiation, thereby providing a regulatory input for iron in EPO-dependent erythropoiesis. Directly targeting aconitase may provide an alternative to phlebotomy in the treatment of polycythemia vera