Glycogen accumulation modulates life span in a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord. Glial cells, including astrocytes and microglia, have been shown to contribute to neurodegeneration in ALS, and metabolic dysfunction plays an important role in the progression of the disease. Glycogen is a soluble polymer of glucose found at low levels in the central nervous system that plays an important role in memory formation, synaptic plasticity, and the prevention of seizures. However, its accumulation in astrocytes and/or neurons is associated with pathological conditions and aging. Importantly, glycogen accumulation has been reported in the spinal cord of human ALS patients and mouse models. In the present work, using the SOD1G93A mouse model of ALS, we show that glycogen accumulates in the spinal cord and brainstem during symptomatic and end stages of the disease and that the accumulated glycogen is associated with reactive astrocytes. To study the contribution of glycogen to ALS progression, we generated SOD1G93A mice with reduced glycogen synthesis (SOD1G93A GShet mice). SOD1G93A GShet mice had a significantly longer life span than SOD1G93A mice and showed lower levels of the astrocytic pro-inflammatory cytokine Cxcl10, suggesting that the accumulation of glycogen is associated with an inflammatory response. Supporting this, inducing an increase in glycogen synthesis reduced life span in SOD1G93A mice. Altogether, these results suggest that glycogen in reactive astrocytes contributes to neurotoxicity and disease progression in ALS.

Nonalcoholic Fatty Liver Disease and the Gut-Liver Axis: Exploring an Undernutrition Perspective.

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition affecting one quarter of the global population. Although primarily linked to obesity and metabolic syndrome, undernutrition and the altered (dysbiotic) gut microbiome influence NAFLD progression. Both undernutrition and NAFLD prevalence are predicted to considerably increase, but how the undernourished gut microbiome contributes to hepatic pathophysiology remains far less studied. Here, we present undernutrition conditions with fatty liver features, including kwashiorkor and micronutrient deficiency. We then review the gut microbiota-liver axis, highlighting key pathways linked to NAFLD progression within both overnutrition and undernutrition. To conclude, we identify challenges and collaborative possibilities of emerging multiomic research addressing the pathology and treatment of undernourished NAFLD.

Gut microbes shape microglia and cognitive function during malnutrition.

Fecal-oral contamination promotes malnutrition pathology. Lasting consequences of early life malnutrition include cognitive impairment, but the underlying pathology and influence of gut microbes remain largely unknown. Here, we utilize an established murine model combining malnutrition and iterative exposure to fecal commensals (MAL-BG). The MAL-BG model was analyzed in comparison to malnourished (MAL mice) and healthy (CON mice) controls. Malnourished mice display poor spatial memory and learning plasticity, as well as altered microglia, non-neuronal CNS cells that regulate neuroimmune responses and brain plasticity. Chronic fecal-oral exposures shaped microglial morphology and transcriptional profile, promoting phagocytic features in MAL-BG mice. Unexpectedly, these changes occurred independently from significant cytokine-induced inflammation or blood-brain barrier (BBB) disruption, key gut-brain pathways. Metabolomic profiling of the MAL-BG cortex revealed altered polyunsaturated fatty acid (PUFA) profiles and systemic lipoxidative stress. In contrast, supplementation with an ω3 PUFA/antioxidant-associated diet (PAO) mitigated cognitive deficits within the MAL-BG model. These findings provide valued insight into the malnourished gut microbiota-brain axis, highlighting PUFA metabolism as a potential therapeutic target.

Certification program of Addiction Centres for hepatitis C virus elimination in Spain. HepCelentes Project. / Programa de certificación de Centros de Adicciones para la eliminación del virus de la hepatitis C en España. Proyecto HepCelentes.

Microelimination strategies for the hepatitis C virus (HCV) in vulnerable populations, such as users of Addiction Centres (AC), are key for the elimination of hepatitis C. The aim of the HepCelentes project was to design a certification program for AC from the generation of a guide with the criteria to favour the prevention, diagnosis, control, and treatment of HCV in Spain. The project was structured in 4 phases: normalisation, implementation, certification, and communication. In the first phase, developed between July and December 2020, a Steering Committee was created (formed by representatives of scientific societies, healthcare professionals from AC, primary care centres and hospital units, and patient associations) that, from of an exhaustive bibliographic review, generated by consensus an accreditation guide for AC. The guide consists of 22 criteria (15 mandatory and 7 recommended) structured based on the requirements to be met by AC, justification for the selection, level of action (management, prevention, diagnosis and treatment/follow-up), measurement of the indicator, objective level to be achieved, evidence of compliance, clarifications to improve understanding, and mandatory / recommendation (depending on their relevance to achieve HCV elimination and its feasibility for implementation in real practice). The development of a certification system for the AC, based on consensus and coordination of multidisciplinary teams, is intended to favour the management of hepatitis C and its elimination in AC users, supporting the international, national, and regional elimination strategies.

Las estrategias de microeliminación del virus de la hepatitis C (VHC) en poblaciones vulnerables, como los usuarios de los centros de adicciones (CA), son fundamentales para lograr la eliminación de la hepatitis C. El objetivo del proyecto HepCelentes fue diseñar un programa de certificación para los CA, a partir de la generación de una guía con los criterios para favorecer la prevención, diagnóstico, control y tratamiento del VHC en España. El proyecto se estructuró en 4 fases: normalización, implementación, certificación y comunicación. En la primera fase, desarrollada entre julio y diciembre de 2020, se creó un Comité de Normalización (formado por representantes de sociedades científicas, profesionales sanitarios de CA, centros de atención primaria, unidades hospitalarias, y asociaciones de pacientes) que, a partir de una revisión bibliográfica exhaustiva, generó por consenso una guía de certificación de los CA. La guía consta de 22 criterios (15 obligatorios y 7 recomendados) estructurados en base a la definición del criterio, justificación de su selección, nivel de actuación (gestión, prevención, diagnóstico y tratamiento/seguimiento), fórmula de medición, nivel objetivo a alcanzar, evidencias de su cumplimiento, aclaraciones para mejorar su comprensión y obligatoriedad/recomendación (en función de la relevancia en la eliminación y capacidad de implementación). El desarrollo de un sistema de certificación para los CA, a partir del consenso y la coordinación de equipos multidisciplinares, pretende favorecer el manejo de la hepatitis C y su eliminación en los usuarios de los CA, apoyando las estrategias de eliminación internacionales, nacionales y autonómicas.

Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study.

Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and age-matched controls. Lipidomic profiles of this subcellular fraction were obtained using liquid chromatography and mass spectrometry. We validated the mechanisms behind presumable lipidomic changes by exploring ALS surrogate models including human motor neurons (derived from ALS lines and controls) subjected to oxidative stress, the hSOD-G93A transgenic mice, and samples from an independent cohort of ALS patients. Among the differential lipid species, we noted 41 potential identities, mostly belonging to phospholipids (particularly ether phospholipids, as plasmalogens), as well as diacylglycerols and triacylglycerides. Decreased expression of alkyldihydroxyacetonephosphate synthase (AGPS)-a critical peroxisomal enzyme in plasmalogen synthesis-is found in motor neuron disease models; this occurs in parallel with an increase in the expression of sterol carrier protein 2 (SCP2) mRNA in ALS and Scp2 levels in G93A transgenic mice. Further, we identified diminished expression of diacylglycerol-related enzymes, such as phospholipase C ßI (PLCßI) and protein kinase CßII (PKCßII), linked to diacylglycerol metabolism. Finally, lipid droplets were recognized in the nuclei, supporting the identification of triacylglycerides as differential lipids. Our results point to the potentially pathogenic role of altered composition of nuclear membrane lipids and lipids in the nucleoplasm in the anterior horn of the spinal cord in ALS. Overall, these data support the usefulness of subcellular lipidomics applied to neurodegenerative diseases.

Age-Related Changes in Lipidome of Rat Frontal Cortex and Cerebellum Are Partially Reversed by Methionine Restriction Applied in Old Age.

Lipids are closely associated with brain structure and function. However, the potential changes in the lipidome induced by aging remain to be elucidated. In this study, we used chromatographic techniques and a mass spectrometry-based approach to evaluate age-associated changes in the lipidome of the frontal cortex and cerebellum obtained from adult male Wistar rats (8 months), aged male Wistar rats (26 months), and aged male Wistar rats submitted to a methionine restriction diet (MetR)-as an anti-aging intervention-for 8 weeks. The outcomes revealed that only small changes (about 10%) were observed in the lipidome profile in the cerebellum and frontal cortex during aging, and these changes differed, in some cases, between regions. Furthermore, a MetR diet partially reversed the effects of the aging process. Remarkably, the most affected lipid classes were ether-triacylglycerols, diacylglycerols, phosphatidylethanolamine N-methylated, plasmalogens, ceramides, and cholesterol esters. When the fatty acid profile was analyzed, we observed that the frontal cortex is highly preserved during aging and maintained under MetR, whereas in the cerebellum minor changes (increased monounsaturated and decreased polyunsaturated contents) were observed and not reversed by MetR. We conclude that the rat cerebellum and frontal cortex have efficient mechanisms to preserve the lipid profile of their cell membranes throughout their adult lifespan in order to maintain brain structure and function. A part of the small changes that take place during aging can be reversed with a MetR diet applied in old age.

Accessibility and adherence to positive airway pressure treatment in patients with obstructive sleep apnea: a multicenter study in Latin America.

PURPOSE: Information on access and adherence to positive airway pressure (PAP) treatment is lacking at the regional level in Latin America. This study characterized access and adherence to PAP in patients with moderate-severe obstructive sleep apnea (OSA) in Latin America. METHODS: Cross-sectional study, conducted at 9 sleep centers across Argentina, Brazil, Chile, Colombia, Mexico, and Peru. Adults diagnosed with moderate-severe OSA (apnea-hypopnea index [AHI] ≥ 15/h) in the previous 12-18 months were eligible. Anthropometrics, health coverage, and OSA severity data were collected. Data on access to therapy, barriers to access, adherence, and factors related to non-compliance were obtained via standardized telephone survey. RESULTS: Eight hundred eighty patients (70% male, 54 ± 13 years, AHI 49 ± 28/h, body mass index 32 ± 7 kg/m2) were included. Four hundred ninety patients (56%) initiated PAP, 70 (14%) discontinued therapy during the first year (mainly due to intolerance), and 420 (48%) were still using PAP when surveyed. Health insurance was private in 36.9% of patients, via the social security system in 31.1%, and via the state in 13.3%, and 18.7% did not have any coverage; 49.5% of patients had to pay all equipment costs. Reasons for not starting PAP were unclear or absent indication (42%), coverage problems (36%), and lack of awareness of OSA burden (14%). Patients with better adherence were older (55.3 ± 13 vs 52 ± 13; p = 0.002) and had more severe OSA (AHI 51.8 ± 27 vs 45.6 ± 27; p = 0.001). CONCLUSIONS: Less than half moderate-severe OSA patients started and continue to use PAP. Unclear or absent medical indication and financial limitations were the most relevant factors limiting access to therapy.

Region-specific vulnerability to lipid peroxidation and evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the healthy adult human central nervous system.

Lipids played a determinant role in the evolution of the brain. It is postulated that the morphological and functional diversity among neural cells of the human central nervous system (CNS) is projected and achieved through the expression of particular lipid profiles. The present study was designed to evaluate the differential vulnerability to oxidative stress mediated by lipids through a cross-regional comparative approach. To this end, we compared 12 different regions of CNS of healthy adult subjects, and the fatty acid profile and vulnerability to lipid peroxidation, were determined by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), respectively. In addition, different components involved in PUFA biosynthesis, as well as adaptive defense mechanisms against lipid peroxidation, were also measured by western blot and immunohistochemistry, respectively. We found that: i) four fatty acids (18.1n-9, 22:6n-3, 20:1n-9, and 18:0) are significant discriminators among CNS regions; ii) these differential fatty acid profiles generate a differential selective neural vulnerability (expressed by the peroxidizability index); iii) the cross-regional differences for the fatty acid profiles follow a caudal-cranial gradient which is directly related to changes in the biosynthesis pathways which can be ascribed to neuronal cells; and iv) the higher the peroxidizability index for a given human brain region, the lower concentration of the protein damage markers, likely supported by the presence of adaptive antioxidant mechanisms. In conclusion, our results suggest that there is a region-specific vulnerability to lipid peroxidation and offer evidence of neuronal mechanisms for polyunsaturated fatty acid biosynthesis in the human central nervous system.

Interplay between TDP-43 and docosahexaenoic acid-related processes in amyotrophic lateral sclerosis.

BACKGROUND: Docosahexaenoic acid (DHA), a key lipid in nervous system homeostasis, is depleted in the spinal cord of sporadic amyotrophic lateral sclerosis (sALS) patients. However, the basis for such loss was unknown. METHODS: DHA synthetic machinery was evaluated in spinal cord samples from ALS patients and controls by immunohistochemistry and western blot. Further, lipid composition was measured in organotypic spinal cord cultures by gas chromatography and liquid chromatography coupled to mass spectrometry. In these samples, mitochondrial respiratory functions were measured by high resolution respirometry. Finally, Neuro2-A and stem cell-derived human neurons were used for evaluating mechanistic relationships between TDP-43 aggregation, oxidative stress and cellular changes in DHA-related proteins. RESULTS: ALS is associated to changes in the spinal cord distribution of DHA synthesis enzymatic machinery comparing ten ALS cases and eight controls. We found increased levels of desaturases (ca 95% increase, p<0.001), but decreased amounts of DHA-related ß-oxidation enzymes in ALS samples (40% decrease, p<0.05). Further, drebrin, a DHA-dependent synaptic protein, is depleted in spinal cord samples from ALS patients (around 40% loss, p<0.05). In contrast, chronic excitotoxicity in spinal cord increases DHA acid amount, with both enhanced concentrations of neuroprotective docosahexaenoic acid-derived resolvin D, and higher lipid peroxidation-derived molecules such as 8-iso-prostaglandin-F2-α (8-iso-PGF2α) levels. Since α-tocopherol improved mitochondrial respiratory function and motor neuron survival in these conditions, it is suggested that oxidative stress could boost motor neuron loss. Cell culture and metabolic flux experiments, showing enhanced expression of desaturases (FADS2) and ß-oxidation enzymes after H2O2 challenge suggest that DHA production can be an initial response to oxidative stress, driven by TDP-43 aggregation and drebrin loss. Interestingly, these changes were dependent on cell type used, since human neurons exhibited losses of FADS2 and drebrin after oxidative stress. These features (drebrin loss and FADS2 alterations) were also produced by transfection by aggregation prone C-terminal fragments of TDP-43. CONCLUSIONS: sALS is associated with tissue-specific DHA-dependent synthetic machinery alteration. Furthermore, excitotoxicity sinergizes with oxidative stress to increase DHA levels, which could act as a response over stress, involving the expression of DHA synthetic enzymes. Later on, this allostatic overload could exacerbate cell stress by contributing to TDP-43 aggregation. This, at its turn, could blunt this protective response, overall leading to DHA depletion and neuronal dysfunction.

Do primary health centres and hospitals contribute equally towards achievement of the transversal clinical competencies of medical students? Performance on the Objective Structured Clinical Examination (OSCE) in competency acquisition.

OBJECTIVES: The adaptation of the educational programmes of European faculties of medicine to the European Higher Education Area guidelines has focused curricula design on competence acquisition. Competencies are defined as the achievements of a predetermined level of efficacy in real-world scenarios. Our objective was to assess whether performance on a common competence evaluation test, the Objective Structured Clinical Examination (OSCE), resulted in different scores for second-year students after a practical medical training course took place in a primary health centre (PHC) or in a hospital. DESIGN: A descriptive study was conducted during the 2010-2014 academic year of the OSCE test scores obtained by all second-year students. LOCATION: Faculty of Medicine at the University of Lleida (Catalonia, Spain). MAIN MEASUREMENTS: We performed a correlation analysis between students who completed their practical medical training at the PHC and hospitals utilising Student's t-test for comparison of means. RESULTS: 423 students who completed internships at the PHC and at hospitals obtained OSCE mean scores of 7.32 (SD; IC) (0.82; 7.18-7.47) points and 7.17 (0.83; 6.07-7.26) points, respectively (p=0.07). CONCLUSIONS: Second-year medical students acquired similar competency levels in the two analysed training scenarios. The two areas both serve their teaching purpose.

Specific lipidome signatures in central nervous system from methionine-restricted mice.

Membrane lipid composition is an important correlate of the rate of aging of animals. Dietary methionine restriction (MetR) increases lifespan in rodents. The underlying mechanisms have not been elucidated but could include changes in tissue lipidomes. In this work, we demonstrate that 80% MetR in mice induces marked changes in the brain, spinal cord, and liver lipidomes. Further, at least 50% of the lipids changed are common in the brain and spinal cord but not in the liver, suggesting a nervous system-specific lipidomic profile of MetR. The differentially expressed lipids includes (a) specific phospholipid species, which could reflect adaptive membrane responses, (b) sphingolipids, which could lead to changes in ceramide signaling pathways, and (c) the physiologically redox-relevant ubiquinone 9, indicating adaptations in phase II antioxidant response metabolism. In addition, specific oxidation products derived from cholesterol, phosphatidylcholine, and phosphatidylethanolamine were significantly decreased in the brain, spinal cord, and liver from MetR mice. These results demonstrate the importance of adaptive responses of membrane lipids leading to increased stress resistance as a major mechanistic contributor to the lowered rate of aging in MetR mice.

Formation of S-(carboxymethyl)-cysteine in rat liver mitochondrial proteins: effects of caloric and methionine restriction.

Maillard reaction contributes to the chemical modification and cross-linking of proteins. This process plays a significant role in the aging process and determination of animal longevity. Oxidative conditions promote the Maillard reaction. Mitochondria are the primary site of oxidants due to the reactive molecular species production. Mitochondrial proteome cysteine residues are targets of oxidative attack due to their specific chemistry and localization. Their chemical, non-enzymatic modification leads to dysfunctional proteins, which entail cellular senescence and organismal aging. Previous studies have consistently shown that caloric and methionine restrictions, nutritional interventions that increase longevity, decrease the rate of mitochondrial oxidant production and the physiological steady-state levels of markers of oxidative damage to macromolecules. In this scenario, we have detected S-(carboxymethyl)-cysteine (CMC) as a new irreversible chemical modification in mitochondrial proteins. CMC content in mitochondrial proteins significantly correlated with that of the lysine-derived analog N (ε)-(carboxymethyl)-lysine. The concentration of CMC is, however, one order of magnitude lower compared with CML likely due in part to the lower content of cysteine with respect to lysine of the mitochondrial proteome. CMC concentrations decreases in liver mitochondrial proteins of rats subjected to 8.5 and 25 % caloric restriction, as well as in 40 and 80 % methionine restriction. This is associated with a concomitant and significant increase in the protein content of sulfhydryl groups. Data presented here evidence that CMC, a marker of Cys-AGE formation, could be candidate as a biomarker of mitochondrial damage during aging.

Comorbidity in patients with chronic obstructive pulmonary disease in family practice: a cross sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequent and often coexists with other diseases. The aim of this study was to quantify the prevalence of COPD and related chronic comorbidity among patients aged over 40 years visiting family practices in an area of Madrid. METHODS: An observational, descriptive, cross-sectional study was conducted in a health area of the Madrid Autonomous Region (Comunidad Autónoma de Madrid). The practice population totalled 198,670 persons attended by 129 Family Physicians (FPs), and the study population was made up of persons over the age of 40 years drawn from this practice population. Patients were deemed to have COPD if this diagnosis appeared on their clinical histories. Prevalence of COPD; prevalence of a further 25 chronic diseases in patients with COPD; and standardised prevalence ratios, were calculated. RESULTS: Prevalence of COPD in family medicine was 3.2% (95% CI 3.0-3.3) overall, 5.3% among men and 1.4% among women; 90% of patients presented with comorbidity, with a mean of 4 ± 2.04 chronic diseases per patient, with the most prevalent related diseases being arterial hypertension (52%), disorders of lipid metabolism (34%), obesity (25%), diabetes (20%) and arrhythmia (15%). After controlling for age and sex, the observed prevalence of the following ten chronic diseases was higher than expected: heart failure; chronic liver disease; asthma; generalised artherosclerosis; osteoporosis; ischaemic heart disease; thyroid disease; anxiety/depression; arrhythmia; and obesity. CONCLUSIONS: Patients with COPD, who are frequent in family practice, have a complex profile and pose a clinical and organisational challenge to FPs.

Non-enzymatic modification of aminophospholipids by carbonyl-amine reactions.

Non-enzymatic modification of aminophospholipids by lipid peroxidation-derived aldehydes and reducing sugars through carbonyl-amine reactions are thought to contribute to the age-related deterioration of cellular membranes and to the pathogenesis of diabetic complications. Much evidence demonstrates the modification of aminophospholipids by glycation, glycoxidation and lipoxidation reactions. Therefore, a number of early and advanced Maillard reaction-lipid products have been detected and quantified in different biological membranes. These modifications may be accumulated during aging and diabetes, introducing changes in cell membrane physico-chemical and biological properties.

Chronic Disease Self-Management of Post-Acute Sequelae of COVID-19 Among Older Adults: A Mixed-Methods Analysis.

Introduction: Approximately 20-30% of individuals who contract acute coronavirus disease (COVID-19) infection develop longer term complications of their initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). PASC is characterized by chronic, varying symptomatology. Methods: Using a mixed methods study design, we aimed to gain insight into individuals' experience with PASC, including cognitive issues, fatigue, and sleep disturbances. We explored whether our previously developed application (app), aimed at improving self-management skills among individuals with chronic diseases, is relevant for individuals with PASC and gained information to adapt the app for individuals with PASC. The study included 19 individuals, aged 40 years and older, recruited from our research participant database, Nova Southeastern University clinics, and community locations. We included this age range because older adults are more likely to have comorbid conditions, allowing us to better understand the impact of COVID-19 infection in these individuals. Participants completed seven standardized self-report questionnaires online, and an individual semi-structured interview via videoconferencing. Quantitative data were assessed using descriptive statistics and calculating individuals' scores in relation to norms. Qualitative data were analyzed using a thematic analysis approach. Triangulation of the data was accomplished by calculating correlations between participants' responses on self-report scales and themes found in semi-structured interviews. Results: Themes included disruption of everyday life, diverse physical symptoms, and cognitive problems including brain fog, fatigue, coping, and emotional upset. Quantitative analysis demonstrated that participants experienced high levels of fatigue, negative mood, cognitive problems, and overall reduction in health-related quality of life (HRQOL). Correlation analyses revealed that individual interview responses were related to participants' self-report of symptoms on standard questionnaires. Discussion: Findings indicate that self-report questionnaires may reflect the experience of individuals with PASC and its impact. Additionally, further efforts to expand our prior mobile app are warranted among individuals with PASC.

A mobile app for chronic disease self-management for individuals with low health literacy: A multisite randomized controlled clinical trial.

Objective: The purpose of this study was to evaluate the effects of a mobile app designed to improve chronic disease self-management in older adult patients with low health literacy and who had at least one chronic health condition, and to assess the impact of delivering information at different levels of reading difficulty. Methods: A randomized controlled trial was completed at two sites. Individuals 40 years of age and older screened for low health literacy who had at least one chronic health condition were randomly assigned to a tailored information multimedia app with text at one of three grade levels. Four primary outcomes were assessed: patient activation, chronic disease self-efficacy, health-related quality of life, and medication adherence. Results: All groups showed overall increases in activation, self-efficacy, and health-related quality of life, but no change in medication adherence. No between-group differences were observed. Conclusions: The mobile app was effective in increasing participants' levels of several psychosocial variables, but reading difficulty level was not significantly related to outcomes.Registered at clinicaltrials.gov NCT02922439.

e-Health Literacy Scale, Patient Attitudes, Medication Adherence, and Internal Locus of Control.

BACKGROUND: Health literacy is related to a variety of health outcomes, including disease control, health-related quality of life, and risk for death. Few studies have investigated the relation of electronic health literacy (e-health literacy) to outcomes or the mechanism by which they may be related. METHODS: Secondary data were drawn from participants in a larger study on chronic disease self-management who were age 40 years and older, had at least one chronic health condition and a health literacy score of 8th grade or below on the validated short form of the Rapid Estimate of Adult Literacy in Medicine. Participants completed the e-Health Literacy Scale (eHEALS), the Multidimensional Health Locus of Control scale, a modified version of the Attitudes Toward Health Care Providers Scale (ATHCPS), the Wake Forest Physician Trust Scale (WFPTS), and the Gonzalez-Lu adherence questionnaire. Hypothesized relations were evaluated in a bootstrapped path analytic model using the Mplus statistical software. KEY RESULTS: Participants included 334 individuals (mean age: 57.5 years; 173 women and 161 men) with Black, Indigenous, and People of Color accounting for 83.3% of the participants and White individuals making up 16.7% of the participants. Model results showed that after controlling for age, education, gender, and race, the eHEALS score was significantly related to the ATHCPS and WFPTS but not to the Gonzalez-Lu adherence questionnaire (p < .05). The eHEALS score was significantly related to the Multidimensional Health Locus of Control scale. Analysis of indirect effects showed that a portion of the relation between e-health literacy and patient attitude and adherence was mediated by internal locus of control (all p < .05). CONCLUSIONS: In this study, e-health literacy was related to important patient attitude and behavior variables via locus of control. This finding has implications for the importance of improving patients' ability to use the internet to access and effectively use health information. [HLRP: Health Literacy Research and Practice. 2023;7(2):e80-e88.].

Increasing Surplus Food Redistribution to Improve Food Access Through a Partnership Between Public Health and a Technology-Based Company.

Redistributing surplus food that would otherwise be discarded represents a viable strategy both for increasing food access and for addressing climate change. This study describes a public-private partnership that scaled such an effort in Los Angeles County. Public health worked with a technology-based company to introduce a mobile app that connected various traditional (e.g., food pantries) and non-traditional (e.g., businesses with surplus food, food rescue organizations, community-based organizations that work in low-income communities) organizations with a countywide surplus food redistribution process. In 11 months, 50 food businesses participated, a total of 43,900 pounds of food were recovered, and surplus food was delivered to 34 community sites, serving 28,400 meals. Lessons from the experience suggest that mobile app use was a key component of the redistribution effort, and that diverting food waste while increasing food access, with a priority towards obtaining food of high nutritional value, was both feasible and practical. It has previously been shown that reducing food loss and waste by at least 50% in the food service sector could help reduce energy use and greenhouse gas emissions.

A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers.

To evaluate senescence mechanisms, including senescence-associated secretory phenotype (SASP), in the motor neuron disease model hSOD1-G93A, we quantified the expression of p16 and p21 and senescence-associated ß-galactosidase (SA-ß-gal) in nervous tissue. As SASP markers, we measured the mRNA levels of Il1a, Il6, Ifna and Ifnb. Furthermore, we explored whether an alteration of alternative splicing is associated with senescence by measuring the Adipor2 cryptic exon inclusion levels, a specific splicing variant repressed by TAR DNA-binding protein (TDP-43; encoded by Tardbp). Transgenic mice showed an atypical senescence profile with high p16 and p21 mRNA and protein in glia, without the canonical increase in SA-ß-gal activity. Consistent with SASP, there was an increase in Il1a and Il6 expression, associated with increased TNF-R and M-CSF protein levels, with females being partially protected. TDP-43 splicing activity was compromised in this model, and the senolytic drug Navitoclax did not alter the disease progression. This lack of effect was reproduced in vitro, in contrast to dasatinib and quercetin, which diminished p16 and p21. Our findings show a non-canonical profile of senescence biomarkers in the model hSOD1-G93A.