Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term.

BACKGROUND: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). METHODS: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. RESULTS: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25-48) weeks after COVID-19 onset, and they had higher carotid Young's elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P=0.04). Moreover, aPWV (path coefficient: -0.186; P=0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (-9%; P=0.01), incremental Young's elastic modulus (-17%; P=0.03), baroreflex sensitivity (+28%; P=0.049), heart rate variability triangular index (+15%; P=0.01), and subendocardial viability ratio (+12%; P=0.01×10-4) were significantly improved. There was a trend toward improvement in brachial PWV (-6%; P=0.14) and carotid distensibility (+18%; P=0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P=0.04) remained significantly higher in patients with COVID-19 than in control subjects. CONCLUSIONS: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

Associations of Physical Activity and Heart Rate Variability from a Two-Week ECG Monitor with Cognitive Function and Dementia: The ARIC Neurocognitive Study.

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio® XT Patch [aged 72-94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (ß = 0.30, 95% CI: 0.16-0.44) and executive function scores (ß = 0.38, 95% CI: 0.22-0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22-0.67) or dementia (OR = 0.25, 95% CI: 0.08-0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

VLCKD: a real time safety study in obesity.

BACKGROUND: Very Low-Calorie Ketogenic Diet (VLCKD) is currently a promising approach for the treatment of obesity. However, little is known about the side effects since most of the studies reporting them were carried out in normal weight subjects following Ketogenic Diet for other purposes than obesity. Thus, the aims of the study were: (1) to investigate the safety of VLCKD in subjects with obesity; (2) if VLCKD-related side effects could have an impact on its efficacy. METHODS: In this prospective study we consecutively enrolled 106 subjects with obesity (12 males and 94 females, BMI 34.98 ± 5.43 kg/m2) that underwent to VLCKD. In all subjects we recorded side effects at the end of ketogenic phase and assessed anthropometric parameters at the baseline and at the end of ketogenic phase. In a subgroup of 25 subjects, we also assessed biochemical parameters. RESULTS: No serious side effects occurred in our population and those that did occur were clinically mild and did not lead to discontinuation of the dietary protocol as they could be easily managed by healthcare professionals or often resolved spontaneously. Nine (8.5%) subjects stopped VLCKD before the end of the protocol for the following reasons: 2 (1.9%) due to palatability and 7 (6.1%) due to excessive costs. Finally, there were no differences in terms of weight loss percentage (13.5 ± 10.9% vs 18.2 ± 8.9%; p = 0.318) in subjects that developed side effects and subjects that did not developed side effects. CONCLUSION: Our study demonstrated that VLCKD is a promising, safe and effective therapeutic tool for people with obesity. Despite common misgivings, side effects are mild, transient and can be prevented and managed by adhering to the appropriate indications and contraindications for VLCKD, following well-organized and standardized protocols and performing adequate clinical and laboratory monitoring.

Assessment of enthesis in patients with psoriatic arthritis and fibromyalgia using clinical examination and ultrasound.

OBJECTIVES: The primary aim of this study was to compare the prevalence of clinical and particularly ultrasonographic signs of enthesitis in patients with psoriatic arthritis (PsA), fibromyalgia (FM), or both. The secondary aim was to assess the impact of FM on disease activity and clinimetric scores. METHODS: This single-centre, observational cross-sectional study involved 101 consenting patients: 39 with PsA (CASPAR criteria), 23 with FM (2016 criteria), and 39 with both. Standard PsA and FM clinical, laboratory and clinimetric data were recorded, and entheses were assessed using the Leeds Enthesitis Index (LEI) and the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES). All of the patients underwent B mode (grey scale) and Power Doppler (PD) ultrasonography bilaterally at the insertions of the quadriceps tendons, the proximal and distal patellar tendons, the Achilles tendons, and the plantar fascia insertions of the calcaneus, to evaluate the thickness of entheses, the hypoechogenicity, the presence of bony erosions, the enthesophytes, and the bursitis. The US findings were scored using the Glasgow Ultrasound Enthesitis Scoring System (GUESS). The data were statistically analysed using univariate and multivariate analyses, and receiver-operating characteristic (ROC) curves, concentrating on the shared clinical features of the two condition. RESULTS: The mean age of the patients as a whole was 53.6±9.47 years. Females accounted for 64.1% of the PsA patients (disease duration 9.13 years), 95.6% of the FM patients (disease duration 5.09 years), and 92.3% of the patients with PsA-FM (disease duration 7.9 years). There were no between-group differences in the patients' body mass index (BMI). In accordance with the study inclusion criteria, none of the FM subjects had PsA or reported any personal or family history of psoriasis. The mean Psoriasis Area and Severity Index was 2.3±3.1 in the PsA group, and 1.2±2.45 in the PsA-FM group. Clinical evidence of enthesopathy was found in 43% of the patients with PsA, 51.3% of those with PsA-FM, and 50.8% of those with FM, while US entheseal abnormalities were detected in respectively 77%, 74% and 35%. The median Bath Ankylosing Spondylitis Disease Activity Index was significantly higher in the patients with PsA-FM than in those with PsA (7.7 [IQR 2.1] vs. 5.0 [IQR 3.8]; p<0.001), as was the median ESR-assessed Ankylosing Spondylitis Disease Activity Score (3.69 [IQR 1.00] vs. 2.82 [IQR 1.55; p=0.004), or CRP- assessed (median 3.27 [IQR 1.07] vs. 2.66 [IQR 1.26]; p=0.006). There was a correlation between GUESS scores and disease duration in the patients with PsA (rho=0.37; p=0.019, 95% CI 0.10-0.61) or PsA-FM (rho=0.38; p=0.016, 95% CI 0.10-0.61), but not in the FM group, and GUESS scores correlated with BMI (rho=0.2; p=0.05, 95% CI 0.00-0.37) and dyslipidemia (rho=0.34; p=0.006, 95% CI 0.11-0.58) in all three groups. CONCLUSIONS: The use of a clinical examination and clinimetric scores alone may overestimate active enthesitis in FM patients. As US was more frequently positive in patients with PsA and PsA-FM than in those with FM, it may be useful in differentiating pain due to enthesitis from entheseal pain due to FM.

Retrospective evaluation of patient profiling and effectiveness of apremilast in an Italian multicentric cohort of psoriatic arthritis patients.

OBJECTIVES: We aimed to evaluate the baseline characteristics, the reasons for prescription, and the effectiveness/safety profile of real-life apremilast for the treatment of psoriatic arthritis (PsA). METHODS: PsA patients treated with apremilast were retrospectively extracted from an Italian multicentric cohort. Baseline population characteristics and reasons for apremilast prescription were analysed. Clinical response was defined as the proportion of patients achieving Disease Activity in PSoriatic Arthritis (DAPSA) remission/low disease activity (LDA), minimal disease activity (MDA), and very low disease activity (VLDA). Six-month retention rate was computed by the Kaplan-Meier method, with a detailed analysis of reasons for discontinuation. Univariate and multivariate models were developed to examine predictors of clinical response and persistence. RESULTS: The study population included 131 patients mainly with oligoarticular PsA (58%), carrying at least one comorbidity (64.1%, in particular history of malignancies [25.9%] and latent tuberculosis [16.3%]) treated with apremilast as first-line targeted therapy (47.7%) or in biologics failures (52.3%). Contraindication to biologics (60.3%) and lack of poor prognostic factors (27.5%) were the most frequent reason for apremilast prescription. The 6-month retention rate was 72.1%. Inefficacy (n=7), diarrhoea (n=10), nausea (n=3), and headache (n=7) were the most frequent reasons for discontinuation. At 3 months DAPSA LDA/remission, MDA, and VLDA were observed in 40.3, 6.7, and 5.6% of patients, respectively. Female sex was a negative predictor of both retention rate and clinical response. CONCLUSIONS: In our real-life analysis apremilast was mainly used in oligoarticular PsA carrying comorbidities leading to contraindications to biologics. Effectiveness and safety profiles were consistent with clinical trials.

The Human RecQ4 Helicase Contains a Functional RecQ C-terminal Region (RQC) That Is Essential for Activity.

RecQ helicases are essential in the maintenance of genome stability. Five paralogues (RecQ1, Bloom, Werner, RecQ4, and RecQ5) are found in human cells, with distinct but overlapping roles. Mutations in human RecQ4 give rise to three distinct genetic disorders (Rothmund-Thomson, RAPADILINO, and Baller-Gerold syndromes), characterized by genetic instability, growth deficiency, and predisposition to cancer. Previous studies suggested that RecQ4 was unique because it did not seem to contain a RecQ C-terminal region (RQC) found in the other RecQ paralogues; such a region consists of a zinc domain and a winged helix domain and plays an important role in enzyme activity. However, our recent bioinformatic analysis identified in RecQ4 a putative RQC. To experimentally confirm this hypothesis, we report the purification and characterization of the catalytic core of human RecQ4. Inductively coupled plasma-atomic emission spectrometry detected the unusual presence of two zinc clusters within the zinc domain, consistent with the bioinformatic prediction. Analysis of site-directed mutants, targeting key RQC residues (putative zinc ligands and the aromatic residue predicted to be at the tip of the winged helix ß-hairpin), showed a decrease in DNA binding, unwinding, and annealing, as expected for a functional RQC domain. Low resolution structural information obtained by small angle X-ray scattering data suggests that RecQ4 interacts with DNA in a manner similar to RecQ1, whereas the winged helix domain may assume alternative conformations, as seen in the bacterial enzymes. These combined results experimentally confirm the presence of a functional RQC domain in human RecQ4.

Long-Term Consequences of the Chernobyl Radioactive Fallout: An Exploration of the Aggregate Data.

Policy Points Policymakers should invest more on researching the long-term health effects of low-ionizing radiation exposure, as we are far from reaching a consensus on a topic that is of enormous importance for public health and safety. Public policies such as those limiting the import of contaminated food from areas hit by a radioactive disaster or those regulating the resident population's access to such areas should follow a precautionary approach. Neoplasm diagnosis and medical care should be designed in order to take into account the possible role of long-term, low-dose radiation exposure. Health care policies should provide effective screening and prevention strategies with a specific focus on the regions that were hit most severely by the Chernobyl nuclear fallout. Health care expenditure should be targeted, taking into account the geographical dispersion of the fallout in order to attenuate its possible effect on neoplasm incidence. CONTEXT: This study investigates the association between the radioactive 137 Cesium fallout originated by the 1986 Chernobyl nuclear accident and dispersed over Western Europe, as a result of a combination of radioactive cloud passage days and rainy days over a 10-day period, and long-term health patterns and related costs. Since the half-life of 137 Cesium is 30.17 years, part of the radioactivity in the affected regions is still present today, and it is usually still detected in the food chain, although at lower concentration levels. METHODS: We match longitudinal data on neoplasm incidence over the time span 2000-2013 in a number of European regions not immediately adjacent to Chernobyl with the randomly distributed levels of cesium deposition after the nuclear disaster in order to assess whether we can detect an association with the long-term health effects on the European population through a random effects model. FINDINGS: Considering 3 levels of fallout deposition-low, medium, and high-hospital discharges after treatment for neoplasms are, respectively, 0.36, 0.44, and 0.98 discharges over 100 inhabitants higher compared to regions with no fallout, with the population average being around 1.7 hospital discharges by neoplasms over 100 inhabitants. We checked the robustness of our findings to a number of tests including a placebo simulation and different model specifications. CONCLUSIONS: Radioactive fallout is positively associated with a higher incidence of hospital discharges after treatment for neoplasms almost 30 years after its release, with larger effects in regions where the radioactivity was more intense. Our estimates are comparable to the findings of the largest-scale study on the long-term health effects of continuous low levels of radiation exposure among workers in the nuclear industry and suggest that more research is needed on this topic, given its enormous importance for public health and safety.

Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: insights from DNA complex structures.

RecQ helicases are a widely conserved family of ATP-dependent motors with diverse roles in nearly every aspect of bacterial and eukaryotic genome maintenance. However, the physical mechanisms by which RecQ helicases recognize and process specific DNA replication and repair intermediates are largely unknown. Here, we solved crystal structures of the human RECQ1 helicase in complexes with tailed-duplex DNA and ssDNA. The structures map the interactions of the ssDNA tail and the branch point along the helicase and Zn-binding domains, which, together with reported structures of other helicases, define the catalytic stages of helicase action. We also identify a strand-separating pin, which (uniquely in RECQ1) is buttressed by the protein dimer interface. A duplex DNA-binding surface on the C-terminal domain is shown to play a role in DNA unwinding, strand annealing, and Holliday junction (HJ) branch migration. We have combined EM and analytical ultracentrifugation approaches to show that RECQ1 can form what appears to be a flat, homotetrameric complex and propose that RECQ1 tetramers are involved in HJ recognition. This tetrameric arrangement suggests a platform for coordinated activity at the advancing and receding duplexes of an HJ during branch migration.

Corticospinal Modulation of Precision Movements.

Recently we demonstrated a critical role for temporal coding of corticospinal activity in a prehension movement requiring precise forelimb control. Learning of precision isometric pull drives large-scale remodeling of corticospinal motor networks. Optogenetic modulation of corticospinal activity and full transection of the corticospinal tract disrupted critical functions of the network in expert animals resulting in impaired modulation of precise movements. In contrast, we observed more widespread corticospinal co-activation and limited temporal coding on a similar, yet more simplistic prehension task, adaptive isometric pull. Disrupting corticospinal neuron activity had much more limited effects on adaptive isometric pull, which was found to be corticospinal independent by transection of the corticospinal tract. Here we discuss these results in context of known roles for corticospinal and corticostriatal neurons in motor control, as well as some of the questions our study raised.

A second X chromosome improves cognition in aging male and female mice.

Women show resilience to cognitive aging, in the absence of dementia, in many populations. To dissect sex differences, we utilized the FCG and XY* mouse models. Female gonads and sex chromosomes improved cognition in aging mice of both sexes. Further, presence of a second X in male and female mice conferred cognitive resilience while its absence in females blocked it. In the hippocampal proteome of aging female mice, the second X increased proteins involved in synaptogenesis signaling - a potential pathway to improved cognition.

Perceived Fatigability, Fatigue, and Mortality in Mid-to-Late Life in the Baltimore Longitudinal Study of Aging.

INTRODUCTION/PURPOSE: Fatigue is an established prognostic indicator of mortality risk. It remains unknown whether fatigability anchored to a physical task is a more sensitive prognostic indicator and whether sensitivity differs by prevalent chronic conditions. METHODS: A total of 1076 physically well-functioning participants 50 yr or older in the Baltimore Longitudinal Study of Aging self-reported fatigue (unusual tiredness or low energy) and had perceived fatigability assessed after a standardized treadmill walk. All-cause mortality was ascertained by proxy contact and National Death Index linkage. Cox proportional hazards models estimated associations of perceived fatigability and fatigue with all-cause mortality, adjusting for demographic and clinical covariates. Interactions by chronic conditions were also examined. RESULTS: Each 1 SD higher in perceived fatigability, unusual tiredness, or low energy was associated with a higher relative hazard of all-cause mortality after covariate adjustment (fatigability: hazard ratio (HR), 1.18 (95% confidence interval (CI), 1.03-1.36); unusual tiredness: HR, 1.25 (95% CI, 1.08-1.44); low energy: HR, 1.27 (95% CI, 1.10-1.46)). Models had similar discrimination ( P > 0.14 for all). Perceived fatigability was associated with mortality risk among participants free of arthritis or osteoarthritis who otherwise appeared healthy (no arthritis: HR, 1.45 (95% CI, 1.15-1.84); arthritis: HR, 1.09 (95% CI, 0.92-1.30); P -interaction = 0.031). Unusual tiredness was associated with mortality among those with a history of diabetes (no diabetes: HR, 1.16 (95% CI, 0.97-1.38); diabetes: HR, 1.65 (95% CI, 1.22-2.23); P -interaction = 0.045) or pulmonary disease (no pulmonary disease: HR, 1.22 (95% CI, 1.05-1.43); pulmonary disease: HR, 2.15 (95% CI, 1.15-4.03); P -interaction = 0.034). CONCLUSIONS: Higher perceived fatigability and fatigue symptoms were similarly associated with higher all-cause mortality, but utility differed by chronic condition. Perceived fatigability might be useful for health screening and long-term mortality risk assessment for well-functioning adults. Alternatively, self-reported fatigue seems more disease-specific with regard to mortality risk.

Beyond the gut: Investigating the mechanism of formation of ß-casomorphins in human blood.

To evaluate the potential differences in the propensity of ß-casein A1 (ß-CNA1) and A2 (ß-CNA2) from bovine milk to release health-relevant ß-casomorphins (BCMs), food-derived peptides were monitored over time in the blood of eight human volunteers who consumed milk containing both protein variants. Liquid chromatography coupled with high resolution tandem mass spectrometry revealed interindividual variability of milk peptidomic profiles in human blood. BCMs were not detected, whereas BCM precursors originating from both ß-CNA1 and ß-CNA2 were ascertained, with ß-CNA2-derived peptides showing a slightly greater susceptibility to proteolysis. Ten synthetic peptides mimicking circulating BCM precursors from ß-CNA1 and ß-CNA2, which were incubated ex vivo with the blood of two volunteers, showed comparable potential to generate BCMs. The formation of BCMs seemed to depend mainly on the size of the BCM precursors and less on the presence of His67 or Pro67. These findings challenge the belief that BCMs are released exclusively from ß-CNA1 and support the nutritional safety of conventional milk, informing health policies regarding milk consumption.

Sequential extraction of anthropogenic microfibers from the leaves of Pittosporum tobira.

The emission of microfibers (MFs) into all environmental matrices, including biota, is a global concern, but appropriate methodologies aimed at biomonitoring these pollutants are still in an exploratory stage. In this work a new method is presented for the extraction of airborne anthropogenic microfibers (MFs) from the leaves of Pittosporum tobira. The method is a sequential extraction consisting of tape followed by water floating, ethanol extraction, and wet peroxidation, which considered at first outermost MFs, weakly adhering to leaf surface, and deeper MFs partly embedded in waxy cuticle layer. Tape tearing removed the highest fraction of MFs (about 75%), followed by water washing, ethanol and peroxidation. The constant ratio between the MFs collected in the successive extraction steps indicated that the protocol proposed is reliable and reproducible. Moreover, based on the tape tearing step, MFs number was significantly higher on the upper surface of the leaves, whereas MFs were significantly longer on the lower surface. A "reverse" extraction protocol in which tape tearing followed three water-washings demonstrated that a noticeable fraction of MFs still adhered to the leaf after water floating. SEM observation of the leaf surface highlighted the structural changes occurring during the extraction, with leaf surface becoming clearer and smoother at each step. Raman spectroscopy highlighted the presence of different kind of anthropogenic MFs, with microplastics representing 50%, and polyethylene terephthalate 39% of total MFs. Due to reproducible results and easy handling of the leaves, we encourage the use of P. tobira as a biomonitor of airborne MFs and suggest that a simplified extraction method based on tape tearing alone could be a fast and useful alternative to be adopted in biomonitoring protocols.

Goat Milk Supplementation Modulates the Mitochondrial Metabolic Flexibility and Orexin-A Levels Influencing the Inflammatory Pattern in Rats.

Milk and its derivatives are included in a balanced diet of humans as excellent sources of proteins, vitamins, and essential minerals that are functional nutrients. Knowledge about the nutritional benefits or harms due to milk consumption has been expanding in recent years. We previously explored, in rodent models, the metabolic effects of isoenergetic intake of milk derived from cows, donkeys, or humans, while the impact of goat's milk intake has remained unexplored. The aim of this work was to investigate, in an animal model, the effects of dietary supplementation with goat's milk on energy homeostasis and inflammatory state, focusing on the modulation of mitochondrial functions in most metabolically active organs, such as skeletal muscle and the liver. In addition, we highlighted a link between nutrient intake, substrate metabolism, and the orexinergic system. Our results indicate that goat milk improves mitochondrial oxidative capacity and reduces inflammation and oxidative stress in both organs. Notably, goat milk lowers the circulating levels of Orexin-A, a neuropeptide that plays a crucial role in regulating peripheral energy balance and central nervous system mechanisms. These data provide the first evidence that the anti-inflammatory and antioxidant effects of goat milk are mediated by the modulation of mitochondrial functions and orexinergic signaling.

Associations of Physical Activity and Heart Rate Variability from a Two-Week ECG Monitor with Cognitive Function and Dementia: the ARIC Neurocognitive Study.

BACKGROUND: Low physical activity (PA) measured from accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used. These monitors can provide long-term HRV data and, if embedded with an accelerometer, they can also provide PA data. Whether PA or HRV measured from long-term ECG monitors is associated with cognitive function among older adults is unknown. METHODS: Free-living PA and HRV were measured simultaneously over 14-days using the Zio ® XT Patch among 1590 participants in the Atherosclerosis Risk in Communities Study [aged 72-94 years, 58% female, 32% Black]. Total amount of PA was estimated by total mean amplitude deviation (TMAD) from the 14-day accelerometry raw data. HRV indices (SDNN and rMSSD) were measured from the 14-day ECG raw data. Cognitive factor scores for global cognition, executive function, language, and memory were derived using latent variable methods. Dementia or mild cognitive impairment (MCI) status was adjudicated. Linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Models were adjusted for demographic and medical comorbidities. RESULTS: Each 1-unit higher in total amount of PA was significantly associated with 0.30 higher global cognition factor scores (95% CI: 0.16-0.44), 0.38 higher executive function factor scores (95% CI: 0.22-0.53), and 62% lower odds of MCI (OR: 0.38, 95% CI: 0.22-0.67) or 75% lower odds of dementia (OR: 0.25, 95% CI: 0.08-0.74) versus unimpaired cognition. Neither HRV measure was significantly associated with cognitive function or dementia. CONCLUSIONS: PA derived from a 2-week ECG monitor with an embedded accelerometer was significantly associated with higher cognitive test performance and lower odds of MCI/dementia among older adults. By contrast, HRV indices measured over 2 weeks were not significantly associated with cognitive outcomes. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia. CLINICAL PERSPECTIVE: What Is New?: This cross-sectional study evaluated associations between physical activity (PA) and heart rate variability (HRV) measured over 14 days from a wearable ECG monitor with cognitive function.Higher total amount of PA was associated with higher global cognition and executive function, as well as lower odds of mild cognitive impairment or dementia.HRV indices measured over 2 weeks were not significantly associated with cognitive outcomes.What Are the Clinical Implications?: These findings replicate positive associations between PA and cognitive function using accelerometer data from a wearable ECG monitor with an embedded accelerometer.These findings raise the possibility of using wearable ECG monitors (with embedded accelerometers) as a promising tool for digital phenotyping of dementia.

Differences in Daily Physical Activity by Alzheimer's Risk Markers Among Older Adults.

BACKGROUND: Daily physical activity patterns differ by Alzheimer's disease (AD) status and might signal cognitive risk. It is critical to understand whether patterns are disrupted early in the AD pathological process. Yet, whether established AD risk markers (ß-amyloid [Aß] or apolipoprotein E-ε4 [APOE-ε4]) are associated with differences in objectively measured activity patterns among cognitively unimpaired older adults is unclear. METHODS: Wrist accelerometry, brain Aß (+/-), and APOE-ε4 genotype were collected in 106 (Aß) and 472 (APOE-ε4) participants (mean age 76 [standard deviation{SD}: 8.5) or 75 [SD: 9.2] years, 60% or 58% women) in the Baltimore Longitudinal Study of Aging. Adjusted linear and function-on-scalar regression models examined whether Aß or APOE-ε4 status was cross-sectionally associated with activity patterns (amount, variability, or fragmentation) overall and by time of day, respectively. Differences in activity patterns by combinations of Aß and APOE-ε4 status were descriptively examined (n = 105). RESULTS: There were no differences in any activity pattern by Aß or APOE-ε4 status overall. Aß+ was associated with lower total amount and lower within-day variability of physical activity overnight and early evening, and APOE-ε4 carriers had higher total amount of activity in the evening and lower within-day variability of activity in the morning. Diurnal curves of activity were blunted among those with Aß+ regardless of APOE-ε4 status, but only when including older adults with mild cognitive impairment/dementia. CONCLUSIONS: Aß+ in cognitively unimpaired older adults might manifest as lower amount and variability of daily physical activity, particularly during overnight/evening hours. Future research is needed to examine changes in activity patterns in larger samples and by other AD biomarkers.

A Genotyping Method for Detecting Foreign Buffalo Material in Mozzarella di Bufala Campana Cheese Using Allele-Specific- and Single-Tube Heminested-Polymerase Chain Reaction.

Mozzarella di Bufala Campana (MdBC) cheese is a Protected Designation of Origin (PDO) product that is important for the economy and cultural heritage of the Campania region. Food fraud can undermine consumers' trust in this dairy product and harm the livelihood of local producers. The current methods for detecting adulteration in MdBC cheese due to the use of buffalo material from foreign countries could exhibit limitations associated with the required use of expensive equipment, time-consuming procedures, and specialized personnel. To address these limits here, we propose a rapid, reliable, and cost-effective genotyping method that can detect foreign buffalo milk in a counterpart from the PDO area and in MdBC cheese, ensuring the quality and authenticity of the latter dairy product. This method is based on dedicated allele-specific and single-tube heminested polymerase chain reaction procedures. By using allele-specific primers that are designed to detect the nucleotide g.472G>C mutation of the CSN1S1Bbt allele, we distinguished an amplicon of 330 bp in the amplification product of DNA when extracted from milk and cheese, which is specific to the material originating from foreign countries. By spiking foreign milk samples with known amounts of the counterpart from the PDO area, the sensitivity of this assay was determined to be 0.01% v/v foreign to PDO milk. Based on a rough estimate of its simplicity, reliability, and cost, this method could be a valuable tool for identifying adulterated buffalo PDO dairy products.

Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice.

Platelet factors regulate wound healing and can signal from the blood to the brain1,2. However, whether platelet factors modulate cognition, a highly valued and central manifestation of brain function, is unknown. Here we show that systemic platelet factor 4 (PF4) permeates the brain and enhances cognition. We found that, in mice, peripheral administration of klotho, a longevity and cognition-enhancing protein3-7, increased the levels of multiple platelet factors in plasma, including PF4. A pharmacologic intervention that inhibits platelet activation blocked klotho-mediated cognitive enhancement, indicating that klotho may require platelets to enhance cognition. To directly test the effects of platelet factors on the brain, we treated mice with vehicle or systemic PF4. In young mice, PF4 enhanced synaptic plasticity and cognition. In old mice, PF4 decreased cognitive deficits and restored aging-induced increases of select factors associated with cognitive performance in the hippocampus. The effects of klotho on cognition were still present in mice lacking PF4, suggesting this platelet factor is sufficient to enhance cognition but not necessary for the effects of klotho-and that other unidentified factors probably contribute. Augmenting platelet factors, possible messengers of klotho, may enhance cognition in the young brain and decrease cognitive deficits in the aging brain.