M2 Cortex Circuitry and Sensory-Induced Behavioral Alterations in Huntington's Disease: Role of Superior Colliculus.

Early and progressive cortico-striatal circuit alterations have been widely characterized in Huntington's disease (HD) patients. Cortical premotor area, M2 cortex in rodents, is the most affected cortical input to the striatum from early stages in patients and is associated to the motor learning deficits present in HD mice. Yet, M2 cortex sends additional long-range axon collaterals to diverse output brain regions beyond basal ganglia. Here, we aimed to elucidate the contribution of M2 cortex projections to HD pathophysiology in mice. Using fMRI, M2 cortex showed most prominent functional connectivity alterations with the superior colliculus (SC) in symptomatic R6/1 HD male mice. Structural alterations were also detected by tractography, although diffusion weighted imaging measurements suggested preserved SC structure and similar electrophysiological responses were obtained in the SC on optogenetic stimulation of M2 cortical axons. Male and female HD mice showed behavioral alterations linked to SC function, including decreased defensive behavioral responses toward unexpected stimuli, such as a moving robo-beetle, and decreased locomotion on an unexpected flash of light. Additionally, GCamp6f fluorescence recordings with fiber photometry showed that M2 cortex activity was engaged by the presence of a randomly moving robo-bettle, an effect absent in HD male mice. Moreover, acute chemogenetic M2 cortex inhibition in WT mice shift behavioral responses toward an HD phenotype. Collectively, our findings highlight the involvement of M2 cortex activity in visual stimuli-induced behavioral responses, which are deeply altered in the R6/1 HD mouse model.SIGNIFICANCE STATEMENT Understanding brain circuit alterations in brain disorders is critical for developing circuit-based therapeutic interventions. The cortico-striatal circuit is the most prominently disturbed in Huntington's disease (HD); and particularly, M2 cortex has a prominent role. However, the same M2 cortical neurons send additional projections to several brain regions beyond striatum. We characterized new structural and functional circuitry alterations of M2 cortex in HD mouse models and found that M2 cortex projection to the superior colliculus (SC) was deeply impaired. Moreover, we describe differential responses to unexpected sensory stimulus in HD mouse models, which relies on SC function. Our data highlight the involvement of M2 cortex in SC-dependent sensory processing and its alterations in HD pathophysiology.

Specific dairy foods and risk of frailty in older women: a prospective cohort study.

BACKGROUND: Dairy contains a complex mixture of lipids, proteins, and micronutrients. Whether habitual dairy consumption is associated with health benefits is not well established. Since dairy is high in nutrients that are potentially protective against frailty, the association between dairy products and the risk of frailty is of interest. METHODS: We analyzed data from 85,280 women aged ≥ 60 years participating in the Nurses' Health Study. Consumption of milk, yogurt, and cheese was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥ 5 chronic illnesses, and a weight loss of ≥ 5%. The occurrence of frailty was assessed every four years from 1992 to 2018. Cox proportional hazard models were used to examine the association between the intake of dairy foods and frailty. RESULTS: During follow-up we identified 15,912 incident cases of frailty. Consumption of milk or yogurt was not associated with the risk of frailty after adjustment for lifestyle factors, medication use, and overall diet quality. Cheese consumption was positively associated with risk of frailty [relative risk (95% confidence interval) for one serving/day increment in consumption: 1.10 (1.05, 1.16)]. Replacing one serving/day of milk, yogurt, or cheese with one serving/day of whole grains, nuts, or legumes was associated with a significant lower risk of frailty, while replacing milk, yogurt, or cheese with red meat or eggs was associated with an increased risk. When milk was replaced with a sugar-sweetened or artificially sweetened beverage, a greater risk of frailty was observed, while replacing milk with orange juice was associated with a lower risk of frailty. CONCLUSIONS: The results suggest that the association between milk, yogurt, and cheese and frailty partly depends on the replacement product. Habitual consumption of milk or yogurt was not associated with risk of frailty, whereas cheese consumption may be associated with an increased risk.

Plant-Based Diets and Risk of Multimorbidity: The Health and Retirement Study.

BACKGROUND: Plant-based diets have gained attention due to their beneficial effects against major chronic diseases, although their association with multimorbidity is mostly unknown. OBJECTIVES: We examined the association between the healthful (hPDI) and unhealthful plant-based diet indices (uPDI) with multimorbidity among middle-aged and older adults from the United States. METHODS: Data on 4262 adults aged >50 y was obtained from the 2012-2020 Health and Retirement Study (HRS) and 2013 Health Care and Nutrition Study (HCNS). Food consumption was collected at baseline with a food frequency questionnaire and 2 PDIs were derived: the hPDI, with positive scores for healthy plant foods and reverse scores for less healthy plant foods and animal foods; and the uPDI, with only positive scoring for less healthy plant foods. Complex multimorbidity, defined as ≥3 coexistent conditions, was ascertained from 8 self-reported conditions: hypertension, diabetes, cancer, chronic lung disease, heart disease, stroke, arthritis, and depression. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 7.8 y, we documented 1202 incident cases of multimorbidity. Compared with the lowest quartile, higher adherence to the hPDI was inversely associated with multimorbidity (HR for quartile 3: 0.77; 95% CI: 0.62, 0.96 and HR for quartile 4: 0.79; 95% CI, 0.63, 0.98; P-trend = 0.02). In addition, a 10-point increment in the hPDI was associated with a 11% lower incidence of multimorbidity (95% CI: 1, 20%). No significant associations were found for the uPDI after adjusting for sociodemographic and lifestyle factors. CONCLUSIONS: Higher adherence to the hPDI was inversely associated with multimorbidity among middle-aged and older adults. Plant-based diets that emphasize consumption of high-quality plant foods may help prevent the development of complex multimorbidity.

A wearable device perspective on the standard definitions of disability progression in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a leading cause of disability among young adults, but standard clinical scales may not accurately detect subtle changes in disability occurring between visits. This study aims to explore whether wearable device data provides more granular and objective measures of disability progression in MS. METHODS: Remote Assessment of Disease and Relapse in Central Nervous System Disorders (RADAR-CNS) is a longitudinal multicenter observational study in which 400 MS patients have been recruited since June 2018 and prospectively followed up for 24 months. Monitoring of patients included standard clinical visits with assessment of disability through use of the Expanded Disability Status Scale (EDSS), 6-minute walking test (6MWT) and timed 25-foot walk (T25FW), as well as remote monitoring through the use of a Fitbit. RESULTS: Among the 306 patients who completed the study (mean age, 45.6 years; females 67%), confirmed disability progression defined by the EDSS was observed in 74 patients, who had approximately 1392 fewer daily steps than patients without disability progression. However, the decrease in the number of steps experienced over time by patients with EDSS progression and stable patients was not significantly different. Similar results were obtained with disability progression defined by the 6MWT and the T25FW. CONCLUSION: The use of continuous activity monitoring holds great promise as a sensitive and ecologically valid measure of disability progression in MS.

New trends in modelling of breakthrough curves to remove pollutants using adsorption on advanced monoliths geometries.

This work proposes a rigorous mathematical model capable of reproducing the adsorption process in dynamic regime on advanced monoliths geometries. For this, four bed geometries with axisymmetric distribution of channels and similar solid mass were proposed. In each geometry a different distribution of channels was suggested, maintaining constant the bed dimensions of 15 cm high and 5 cm radius. The mathematical modeling includes mass and momentum transfer phenomena, and it was solved with the COMSOL Multiphysics software using mass transfer parameters published in the literature. The overall performance of the column was evaluated in terms of breakthrough (CA/CA0 = 0.1) and saturation times (CA/CA0 = 0.9). The mass and velocity distributions obtained from the proposed model show good physical consistency with what is expected in real systems. In addition, the model proved to be easy to solve given the short convergence times required (2-4 h). Modifications were made to the bed geometry to achieve a better use of the adsorbent material which reached up to 80%. The proposed bed geometries allow obtaining different mixing distributions, in such a way that inside the bed a thinning of the boundary layer is caused, thus reducing diffusive effects at the adsorbent solid-fluid interface, given dissipation rates of about 323 × 10-11 m2/s3. The bed geometry composed of intersecting rings deployed the best performance in terms of usage of the material adsorbent, and acceptable hydrodynamical behavior inside the channels (maximum fluid velocity = 35.4 × 10-5 m/s and drop pressure = 0.19 Pa). Based on these results, it was found that it is possible to reduce diffusional effects and delimit the mass transfer zone inside the monoliths, thus increasing the efficiency of adsorbent fixed beds.

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

BACKGROUND: Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored. METHODS: We used two different mouse models of HD, the R6/1 and the HdhQ111 mice, to demonstrate a consistent thalamic Foxp2 reduction in the context of HD. We used in vivo electrophysiological recordings, microdialysis in behaving mice and rabies virus-based monosynaptic tracing to study thalamo-striatal and thalamo-cortical synaptic connectivity in R6/1 mice. Micro-structural synaptic plasticity was also evaluated in the striatum and cortex of R6/1 mice. We over-expressed Foxp2 in the thalamus of R6/1 mice or reduced Foxp2 in the thalamus of wild type mice to evaluate its role in sensory and motor skills deficiencies, as well as thalamo-striatal and thalamo-cortical connectivity in such mouse models. RESULTS: Here, we demonstrate in a HD mouse model a clear and early thalamo-striatal aberrant connectivity associated with a reduction of thalamic Foxp2 levels. Recovering thalamic Foxp2 levels in the mouse rescued motor coordination and sensory skills concomitant with an amelioration of neuropathological features and with a repair of the structural and functional connectivity through a restoration of neurotransmitter release. In addition, reduction of thalamic Foxp2 levels in wild type mice induced HD-like phenotypes. CONCLUSIONS: In conclusion, we show that a novel identified thalamic Foxp2 dysregulation alters basal ganglia circuits implicated in the pathophysiology of HD.

Association between diet quality and malnutrition: pooled results from two population-based studies in older adults.

BACKGROUND: The role of diet quality on malnutrition in older adults is uncertain, due the paucity of the research conducted and the use of use of screening tools that did not consider phenotypic criteria of malnutrition. OBJECTIVE: To evaluate the association of two indices of diet quality, namely the Mediterranean Diet Adherence Screener (MEDAS) and the Alternative Healthy Eating Index (AHEI-2010), with malnutrition among community-dwelling older adults in Spain. METHODS: Cross-sectional analysis of data from 1921 adults aged ≥ 60 years from the Seniors-ENRICA-1 (SE-1) study, and 2652 adults aged ≥ 65 years from the Seniors-ENRICA-2 (SE-2) study. Habitual food consumption was assessed through a validated diet history. Malnutrition was defined according to the Global Leadership Initiative on Malnutrition (GLIM) phenotypic criteria. Statistical analyses were performed with logistic regression with adjustment for socioeconomic and lifestyle variables as well as for total energy and protein intake. RESULTS: The prevalence of malnutrition in the SE-1 study was 9.5% (95% confidence interval: 8.2 to 10.9) and 11.7% (10.5 to 13.9) in the SE-2. Adherence to the MEDAS score was associated with lower prevalence of malnutrition [pooled odds ratio for high (≥ 9 points) vs. low adherence (< 7 points): 0.64 (0.48-0.84); p-trend < 0.001]. Higher adherence to the AHEI-2010 also showed an inverse association with malnutrition (pooled odds ratio for quartile 4 vs. 1: 0.65 (0.49-0.86); p-trend 0.006). Among the individual components, higher consumption of fish and long-chain n-3 fatty acids in MEDAS and AHEI-2010, and of vegetables and nuts and legumes in AHEI-2010, and lower intake of trans-fat and sugar-sweetened beverages and fruit juice in AHEI-2010 were independently associated with lower odds of malnutrition. CONCLUSION: Adherence to high diet-quality patterns was associated with lower frequency of malnutrition among older adults. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT02804672. June 17, 2016.; ClinicalTrials.gov NCT03541135. May 30, 2018.

VPS13A knockdown impairs corticostriatal synaptic plasticity and locomotor behavior in a new mouse model of chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an inherited neurodegenerative movement disorder caused by VPS13A gene mutations leading to the absence of protein expression. The striatum is the most affected brain region in ChAc patients. However, the study of the VPS13A function in the brain has been poorly addressed. Here we generated a VPS13A knockdown (KD) model and aimed to elucidate the contribution of VPS13A to synaptic plasticity and neuronal communication in the corticostriatal circuit. First, we infected primary cortical neurons with miR30-shRNA against VPS13A and analyzed its effects on neuronal plasticity. VPS13A-KD neurons showed a higher degree of branching than controls, accompanied by decreased BDNF and PSD-95 levels, indicative of synaptic alterations. We then injected AAV-KD bilaterally in the frontal cortex and two different regions of the striatum of mice and analyzed the effects of VPS13A-KD on animal behavior and synaptic plasticity. VPS13A-KD mice showed modification of the locomotor behavior pattern, with increased exploratory behavior and hyperlocomotion. Corticostriatal dysfunction in VPS13A-KD mice was evidenced by impaired striatal long-term depression (LTD) after stimulation of cortical afferents, which was partially recovered by BDNF administration. VPS13A-KD did not lead to neuronal loss in the cortex or the striatum but induced a decrease in the neuronal release of CX3CL1 and triggered a microglial reaction, especially in the striatum. Notably, CX3CL1 administration partially restored the impaired corticostriatal LTD in VPS13A-KD mice. Our results unveil the involvement of VPS13A in neuronal connectivity modifying BDNF and CX3CL1 release. Moreover, the involvement of VPS13A in synaptic plasticity and motor behavior provides key information to further understand not only ChAc pathophysiology but also other neurological disorders.

BTLA dysregulation correlates with poor outcome and diminished T cell-mediated antitumor responses in chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) progressively develop marked immunosuppression, dampening innate and adaptive-driven antitumor responses. However, the underlying mechanisms promoting immune exhaustion are largely unknown. Herein, we provide new insights into the role of BTLA/HVEM axis promoting defects in T cell-mediated responses against leukemic cells. Increased expression of BTLA, an inhibitory immune checkpoint, was detected on the surface of CD4 + and CD8 + T lymphocytes in patients with CLL. Moreover, high levels of BTLA on CD4 + T cells correlated with diminished time to treatment. Signaling through BTLA activation led to decreased IL-2 and IFN-γ production ex vivo, whereas BTLA/HVEM binding disruption enhanced IFN-γ + CD8 + T lymphocytes. Accordingly, BTLA blockade in combination with bispecific anti-CD3/anti-CD19 antibody promoted CD8 + T cell-mediated anti-leukemic responses. Finally, treatment with an anti-BLTA blocking monoclonal antibody alone or in combination with ibrutinib-induced leukemic cell depletion in vitro. Altogether, our data reveal that BTLA dysregulation has a prognostic role and is limiting T cell-driven antitumor responses, thus providing new insights about immune exhaustion in patients with CLL.

Long-Term Consumption of Nuts (Including Peanuts, Peanut Butter, Walnuts, and Other Nuts) in Relation to Risk of Frailty in Older Women: Evidence from a Cohort Study.

BACKGROUND: Adherence to a healthy diet is inversely associated with frailty. However, the relationship between nuts, a key food group of Mediterranean diet, and frailty is unclear. OBJECTIVES: This study aimed to evaluate the association between nut consumption and frailty in an aging female population. METHODS: This population-based observational study included nonfrail women (≥60 y old) in the NHS from 11 states of the United States. Outcome was incident frailty, defined as having ≥3 of the FRAIL components (fatigue, lower strength, reduced aerobic capacity, multiple chronic conditions, and significant weight loss) and assessed every 4 y from 1992 to 2016. From 1990 to 2014, FFQs were used to assess the intakes of peanuts, peanut butter, walnuts (added in 1998), and other nuts at 4-y intervals. Exposure was total nut consumption, calculated as the sum of intakes of peanuts, peanut butter, walnuts, and other nuts and categorized into <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk. The relations of intakes of peanuts, peanut butter, and walnuts with frailty were also investigated separately. Cox proportional hazards models were used to assess the associations between nut consumption and frailty after adjusting for age, smoking, BMI, EI, diet quality, and medication use. RESULTS: Among 71,704 participants, 14,195 incident frailty cases occurred over 1,165,290 person-years. The adjusted HR (95% CI) for consuming ≥5 servings/wk of nuts was 0.80 (0.73, 0.87), as compared with <1 serving/mo. Higher intakes of peanuts and walnuts, but not peanut butter, were also inversely associated with frailty. CONCLUSIONS: This large prospective cohort study showed a strong and consistent inverse association between regular nut consumption and incident frailty. This suggests that nut consumption should be further tested as a convenient public health intervention for the preservation of health and well-being in older adults.

Ikzf1 as a novel regulator of microglial homeostasis in inflammation and neurodegeneration.

In the last two decades, microglia have emerged as key contributors to disease progression in many neurological disorders, not only by exerting their classical immunological functions but also as extremely dynamic cells with the ability to modulate synaptic and neural activity. This dynamic behavior, together with their heterogeneous roles and response to diverse perturbations in the brain parenchyma has raised the idea that microglia activation is more diverse than anticipated and that understanding the molecular mechanisms underlying microglial states is essential to unravel their role in health and disease from development to aging. The Ikzf1 (a.k.a. Ikaros) gene plays crucial roles in modulating the function and maturation of circulating monocytes and lymphocytes, but whether it regulates microglial functions and states is unknown. Using genetic tools, here we describe that Ikzf1 is specifically expressed in the adult microglia in brain regions such as cortex and hippocampus. By characterizing the Ikzf1 deficient mice, we observed that these mice displayed spatial learning deficits, impaired hippocampal CA3-CA1 long-term potentiation, and decreased spine density in pyramidal neurons of the CA1, which correlates with an increased expression of synaptic markers within microglia. Additionally, these Ikzf1 deficient microglia exhibited a severe abnormal morphology in the hippocampus, which is accompanied by astrogliosis, an aberrant composition of the inflammasome, and an altered expression of disease-associated microglia molecules. Interestingly, the lack of Ikzf1 induced changes on histone 3 acetylation and methylation levels in the hippocampus. Since the lack of Ikzf1 in mice appears to induce the internalization of synaptic markers within microglia, and severe gliosis we then analyzed hippocampal Ikzf1 levels in several models of neurological disorders. Ikzf1 levels were increased in the hippocampus of these neurological models, as well as in postmortem hippocampal samples from Alzheimer's disease patients. Finally, over-expressing Ikzf1 in cultured microglia made these cells hyporeactive upon treatment with lipopolysaccharide, and less phagocytic compared to control microglia. Altogether, these results suggest that altered Ikzf1 levels in the adult hippocampus are sufficient to induce synaptic plasticity and memory deficits via altering microglial state and function.

Distribution of daily protein intake across meals and all-cause mortality in community-dwelling older adults.

Recent findings suggest that the distribution of protein intake throughout the day has an impact on various health outcomes in older adults, independently of the amount consumed. We evaluated the association between the distribution of dietary protein intake across meals and all-cause mortality in community-dwelling older adults. Data from 3225 older adults aged ≥ 60 years from the Seniors-ENRICA-1 cohort were examined. Habitual dietary protein consumption was collected in 2008-2010 and in 2012 through a validated diet history. Protein distribution across meals was calculated for each participant as the coefficient of variation (CV) of protein intake per meal, in sex-specific tertiles. Vital status was obtained from the National Death Index up to 30 January 2020. Cox proportional hazards regression was performed to determine the hazard ratios (HR) and their 95 % CI for the association between the distribution of daily protein intake across meals and all-cause mortality. Over a median follow-up of 10·6 years, 591 deaths occurred. After adjustment for potential confounders, the CV of total protein intake was not associated with all-cause mortality (HR and 95 % CI in the second and third tertile v. the lowest tertile: 0·94 (0·77, 1·15) and 0·88 (0·72, 1·08); Ptrend = 0·22). Similarly, the HR of all-cause mortality when comparing extreme tertiles of CV for types of protein were 0·89 (0·73, 1·10) for animal-protein intake and 1·02 (0·82, 1·25) for plant-protein intake. Dietary protein distribution across meals was not associated with all-cause mortality, regardless of protein source and amount, among older adults. Further studies should investigate whether this picture holds for specific causes of death.

Vitamin D Status in Children With High-risk Neuroblastoma.

BACKGROUND: Vitamin D deficiency has become a matter of concern in pediatric cancer patients. A relationship between neuroblastoma and Vitamin D signaling pathways has been revealed with interest in the antiproliferative and antiinvasive properties of vitamin D. Our aim is to describe the prevalence of Vitamin D deficiency among children with high-risk neuroblastoma (HR-NB) and to explore its association with disease status. MATERIALS AND METHODS: In all, 182 patients with HR-NB were managed at our center from 2017 to 2021. Serum 25(OH)D levels were tested at the first blood analysis performed and correlated with clinical data and disease status. RESULTS: One hundred forty-eight (81.4%) had low 25(OH)D levels (48.4% categorized as deficiency (25(OH)D below 20 ng/mL) and 33.0% as insufficiency (25(OH)D 20 to 30 ng/mL). Median Vitamin D level was 20.2 ng/mL. Vitamin D levels were not associated with race or sex. Although malnourished patients had lower median 25(OH)D levels(11.1 ng/mL), no statistical association was observed with Vitamin D deficiency. There was no association between Vitamin D levels and disease status. An inverse correlation was found between age and vitamin D levels ( P =0.0040). CONCLUSION: A concerning high prevalence of low Vitamin D levels affects more than two-thirds of patients with HR-NB in our cohort, regardless of the disease status at the time of evaluation. Older children are at a higher risk for deficient levels of vitamin D.

Duration and Quality of Sleep and Risk of Self-reported Hearing Loss: The UK Biobank Study.

OBJECTIVE: The duration and quality of sleep have been associated with multiple health conditions in adults. However, whether sleep duration and quality are associated with hearing loss (HL) is uncertain. The present study investigates the prospective association between duration and quality of sleep and HL. DESIGN: This longitudinal analysis included 231,650 participants aged 38 to 72 years from the UK Biobank cohort, established in 2006-2010 in the United Kingdom. Duration and sleep complaints (snoring at night, daytime sleepiness, sleeplessness, difficulty getting up in the morning, and eveningness preference) were self-reported. HL was self-reported at baseline and during the follow-up. RESULTS: Over a median follow-up of 4.19 (SD: 2.15) years, 6436 participants reported incident HL. In fully adjusted models, in comparison with sleeping between 7 and 8 hours a day, the adjusted hazard ratio (HR) (95% CI) associated with sleeping <7 hours a day was 1.01 (0.95 to 1.07), and for sleeping >8 hours a day was 0.98 (0.88 to 1.08). After adjustment for potential confounders, the HRs (95% confidence interval) of HL associated with having 1, 2, 3, and 4 to 5 vs. 0 sleep complaints were: 1.15 (1.05 to 1.27), 1.16 (1.05 to 1.28), 1.32 (1.19 to 1.47), and 1.49 (1.31 to 1.69), respectively; p for trend: <0.001. An increase in the number of sleep complaints was associated with higher risk of HL among participants with non-optimal sleep duration than among participants with optimal sleep duration. CONCLUSION: In this large population-based study, poor sleep quality was associated with an increased risk of HL; however, sleep duration was not associated with risk.

Multimorbidity Patterns in Older Adults: the Role of Social Variables and Lifestyle Behaviors.

INTRODUCTION: While some condition clusters represent the chance co-occurrence of common individual conditions, others may represent shared causal factors. The aims of this study were to identify multimorbidity patterns in older adults and to explore the relationship between social variables, lifestyle behaviors, and the multimorbidity patterns identified. METHODS: This was a cross-sectional design. Data came from 3,273 individuals aged ≥65 from the Seniors-ENRICA-2 cohort; information on 60 chronic disease categories, categorized according to the 2nd edition of the International Classification of Primary Care and the 10th edition of the International Classification of Diseases, was obtained from clinical record linkage. To identify multimorbidity patterns, an exploratory factor analysis was conducted over chronic disease categories with a prevalence >5%, using Oblimin rotation and Kaiser's eigenvalues-greater-than-one rule. The association between multimorbidity patterns and their potential determinants was assessed with multivariable linear regression. RESULTS: The three-factor solution (Musculoskeletal diseases and mental disorders, Cardiometabolic diseases, and Cardiopulmonary diseases) explained 64.5% of the total variance. Being older, lower occupational category, higher levels of loneliness, lower levels of physical activity, and higher body mass index were associated with higher scores in the multimorbidity patterns identified. Female sex was linked to the Musculoskeletal diseases and mental disorders pattern, while being male was revealed to the two remaining multimorbidity patterns. A high diet quality was inversely related to Cardiometabolic diseases, while optimal sleep duration was inversely related to Cardiopulmonary diseases. CONCLUSION: Three multimorbidity patterns were identified in older adults. Multimorbidity patterns were differently associated with social variables and lifestyles behavioral factors.

Changes in resistome profile of potential probiotic Lactiplantibacillus pentosus in response to edible oil adaptation.

Despite increasing interest to investigate horizontal gene transfer as a leading cause of antibiotic resistance spread, the resistome is not only influenced by the influx and efflux of genes in different environments. Rather, the expression of existing genes under different stress conditions requires special attention. This study determined whether pre-adapting Lactiplantibacillus pentosus strains, isolated from Aloreña green table olives, to vegetable-based edible oils influence their phenotypic and genotypic responses to antibiotics. This has significant diet, food matrix, gut health, and food safety concerns. Pre-adapting L. pentosus strains to oils significantly changed their susceptibility profile to antibiotics. However, results generally differed among the three strains; although changes in the Minimum Inhibitory Concentration (MIC) of antibiotics occurred, it depended on the L. pentosus strain and the oil used for adaptation. The pre-adaptation of L. pentosus strains with olive, sunflower, argan and linseed oils induced gene expressions (e.g., rpsL, recA and uvrB) in several stress responses. Thus, to analyze this fact in-depth, transcriptional changes were reported in the selected potential probiotic L. pentosus CF2-10 adapted with olive or sunflower, rerouting its metabolic pathways to export toxic molecules through efflux pumps and ABC transporters. Pre-adaptation of some lactobacilli with olive or sunflower oils may represent a novel approach for manufacturing probiotic products with improved stability, functionality and robustness.

Automatic Assessment of the 2-Minute Walk Distance for Remote Monitoring of People with Multiple Sclerosis.

The aim of this study was to investigate the feasibility of automatically assessing the 2-Minute Walk Distance (2MWD) for monitoring people with multiple sclerosis (pwMS). For 154 pwMS, MS-related clinical outcomes as well as the 2MWDs as evaluated by clinicians and derived from accelerometer data were collected from a total of 323 periodic clinical visits. Accelerometer data from a wearable device during 100 home-based 2MWD assessments were also acquired. The error in estimating the 2MWD was validated for walk tests performed at hospital, and then the correlation (r) between clinical outcomes and home-based 2MWD assessments was evaluated. Robust performance in estimating the 2MWD from the wearable device was obtained, yielding an error of less than 10% in about two-thirds of clinical visits. Correlation analysis showed that there is a strong association between the actual and the estimated 2MWD obtained either at hospital (r = 0.71) or at home (r = 0.58). Furthermore, the estimated 2MWD exhibits moderate-to-strong correlation with various MS-related clinical outcomes, including disability and fatigue severity scores. Automatic assessment of the 2MWD in pwMS is feasible with the usage of a consumer-friendly wearable device in clinical and non-clinical settings. Wearable devices can also enhance the assessment of MS-related clinical outcomes.

Association between neighborhood physical characteristics and mental health among older adults in Spain.

The aim was to assess the impact of neighborhood physical environment on mental health among non-institutionalized older adults. A cross-sectional analysis was conducted over a representative sample of 5,071 people ≥65 years from the Spanish National Health Survey. The survey included nine items addressing the self-perceived degree of discomfort due to neighborhood physical problems. Participants were categorized into groups with "no problems", "some problems" (somewhat discomfort on 1-4 items) and "many problems" (somewhat discomfort on ≥5 items or very much discomfort on ≥1 item). Mental health status was assessed using the General Health Questionnaire, consisting of 12 items assessing the severity of a psychological distress over the past few weeks. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regressions. A dose-response association (p-trend<0.001) was found between living in neighborhoods with some (OR: 1.41; 95% CI: 1.14-1.75) or many problems (OR: 1.93; 95% CI: 1.55-2.42) affecting the physical environment with poor mental health of community dwelling older adults. Integrating and articulating health considerations into public policymaking regarding housing and the residential environment can have broad implications for healthy aging.

Dietary fat intake and risk of disabling hearing impairment: a prospective population-based cohort study.

PURPOSE: To examine the associations of specific dietary fats with the risk of disabling hearing impairment in the UK Biobank study. METHODS: This cohort study investigated 105,592 participants (47,308 men and 58,284 women) aged ≥ 40 years. Participants completed a minimum of one valid 24-h recall (Oxford Web-Q). Dietary intake of total fatty acids, polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA), and monounsaturated fatty acids (MUFA) was assessed at baseline. Functional auditory capacity was measured with a digit triplet test (DTT), and disabling hearing impairment was defined as a speech reception threshold in noise > - 3.5 dB in any physical exam performed during the follow-up. RESULTS: Over a median follow-up of 3.2 (SD: 2.1) years, 832 men and 872 women developed disabling hearing impairment. After adjustment for potential confounders, including lifestyles, exposure to high-intensity sounds, ototoxic medication and comorbidity, the hazard ratios (HRs), and 95% confidence interval (CI) of disabling hearing function, comparing extreme quintiles of intakes were 0.91 (0.71-1.17) for total fat, 1.09 (0.83-1.44) for PUFA, 0.85 (0.64-1.13) for SFA and 1.01 (0.74-1.36) for MUFA among men. Among women, HRs comparing extreme intakes were 0.98 (0.78-1.24) for total fat, 0.69 (0.53-0.91) for PUFA, 1.26 (0.96-1.65) for SFA, and 0.91 (0.68-1.23) for MUFA. Replacing 5% of energy intake from SFA with an equivalent energy from PUFA was associated with 25% risk reduction (HR: 0.75; 95% CI: 0.74-0.77) among women. CONCLUSIONS: PUFA intake was associated with decreased risk of disabling hearing function in women, but not in men.

Prospective association between dietary magnesium intake and physical performance in older women and men.

PURPOSE: Magnesium is a profuse intracellular cation with a key role in muscle function and cellular senescence. The aim was to examine the prospective association between 5 year changes in dietary intake of magnesium and changes in physical performance among older men and women. METHODS: Prospective study conducted over 863 community-dwellers aged ≥ 65 years from the Seniors-ENRICA cohort (Spain). In 2012 and 2017, a validated computerized face-to-face diet history was used to record the consumption of up to 880 foods. From these data, we estimated changes in dietary magnesium intake. The Short Physical Performance Battery (SPPB) was also conducted in both time points and we obtained changes in the score during follow-up, with positive values indicating physical performance improvement. RESULTS: Over 5 years of follow-up, an increase in magnesium intake was associated with an increment in the SPPB score among older women [multivariate ß (95% confidence interval): 1.01 (0.49; 1.52), p-trend: 0.001]. In addition, changes from non-adherence to adherence to both estimated average requirement and recommended dietary allowance during follow-up period were associated with an increment in SPPB score among older women [1.14 (0.36; 1.92) and 0.84 (0.22; 1.47), respectively]. No significant associations between changes in magnesium intake and changes in SPPB score were observed in men. CONCLUSIONS: Both increase of magnesium intake and change from non-adherence to adherence to dietary reference magnesium intake was prospectively associated with better physical performance among older women, but not among men.