Comparing Sleep Quality, Duration, and Efficiency Among Low-Income Community-Dwelling Older Adults With and Without Physical Disabilities.

PURPOSE: Physical disabilities may exacerbate the natural decline in sleep quality that occurs with aging. In the current study, we assessed sleep quality and medicinal sleep aid use among 87 community-dwelling older adults with (n = 24) and without (n = 63) physical disabilities. METHOD: Sleep quality, duration, and efficiency were assessed subjectively with the Pittsburgh Sleep Quality Index. Sleep duration and efficiency were objectively measured with actigraphy. Participants self-reported medicinal sleep aid use. RESULTS: Significant group differences were observed in sleep duration measured objectively (p = 0.01) and subjectively (p = 0.04). No other group differences were observed for sleep factors (p > 0.05) or medicinal sleep aid use (p = 0.41). CONCLUSION: Findings show that physical disability may be a factor in sleep duration; however, physical disability was not found to be associated with worsened sleep perception or greater reliance on medicinal sleep aids. Future research should consider longer objective actigraphy assessment windows and explore potential subgroup differences in sex and race/ethnicity. [Journal of Gerontological Nursing, 50(7), 12-18.].

Healthcare Encounters and Outcomes of Filipino Patients with Systemic Lupus Erythematosus Managed at a Tertiary COVID-19 Referral Center.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has limited healthcare delivery for patients with chronic diseases, including Systemic Lupus Erythematosus (SLE). This study aims to describe the outcomes of patients with SLE in a national COVID-19 referral center in the Philippines. Methods: A review of records of all adult patients with SLE seen in the University of the Philippines-Philippine General Hospital (UP-PGH) from March 2020 to December 2021 was done. Data about patient characteristics, health encounters, and outcomes before and after the first visit during the study period were extracted. Descriptive statistics were employed. Results: Our population of 403 patients was predominantly young (mean age 34.53 ± 11.14 years), female, and unemployed. This consisted of 370 known cases of SLE, 92 were diagnosed in institutions outside UP-PGH, and 33 new patients. Over the 22-month study period, there were 2,093 medical encounters, most of which were teleconsultations (81.70%). During an average gap of 53.6 ± 26.7 weeks between the last consultation and the first visit within the pandemic study period, 84 patients (22.70%) discontinued at least one of their SLE control medications, 68 (18.38%) patients developed a lupus flare, and 79 (21.35%) were hospitalized for various reasons. On their return to the rheumatology clinic during the pandemic, 37.47% were in lupus flare, 28.29% needed to be hospitalized, and 20 died. However, 86.75% of flares were controlled. During subsequent health encounters, 48 patients had a new flare (43 of these were controlled) and 20 died. The most common reason for hospitalization (n=160) was lupus disease flare and the most common cause of death (n=40) was pneumonia. Sixty patients acquired COVID-19 infection from which most recovered and four died. Conclusion: Audio teleconsultation was the most common method used by our lupus cohort to interact with their doctors during the pandemic. There was an average of a year-long interruption in medical care for 62.70%. More than a third developed a disease flare and 15% acquired COVID-19 but outcomes were good in more than 85%. Despite the challenges posed by the pandemic, the majority of our lupus cohort who were able to continue their treatment had favorable outcomes.

Microcystins in the benthic food-web of the Sacramento-San Joaquin Delta, California.

Harmful cyanobacteria blooms are a growing threat in estuarine waters as upstream blooms are exported into coastal environments. Cyanobacteria can produce potent toxins, one of which-hepatotoxic microcystins (MCs)-can persist and accumulate within the food web. Filter-feeding invertebrates may biomagnify toxins up to 100× ambient concentrations. As such, bivalves can be used as an environmentally relevant and highly sensitive sentinel for MC monitoring. To date there has been little research on cyanotoxin bioaccumulation in estuaries. The Sacramento-San Joaquin Delta (Delta) aquatic food web has undergone a profound change in response to widespread colonization of aquatic invasive species such as Asian clams (Corbicula fluminea) in the freshwater portion of the Delta. These clams are prolific-blanketing areas of the Delta at densities up to 1000 clams/m2 and are directly implicated in the pelagic organism decline of threatened and endangered fishes. We hypothesized that Asian clams accumulate MCs which may act as an additional stressor to the food web and MCs would seasonally be in exceedance of public health advisory levels. MCs accumulation in Delta Asian clams and signal crayfish (Pacifastacus leniusculus) were studied over a two-year period. ELISA and LC-MS analytical methods were used to measure free and protein-bound MCs in clam and crayfish tissues. We describe an improved MC extraction method for use when analyzing these taxa by LC-MS. MCs were found to accumulate in Asian clams across all months and at all study sites, with seasonal maxima occurring during the summer. Although MC concentrations rarely exceeded public health advisory levels, the persistence of MCs year-round still poses a chronic risk to consumers. Crayfish at times also accumulated high concentrations of MCs. Our results highlight the utility of shellfish as sentinel organisms for monitoring in estuarine areas.

While You Are Sleeping: Marital Ambivalence and Blunted Nocturnal Blood Pressure.

Marital relationships offer health benefits, including a lower risk of cardiovascular disease (CVD). However, quality of the relationship matters; ambivalent behaviors may increase CVD risk by affecting blunted nocturnal blood pressure (BP) dipping. This study tracked daytime and nocturnal SBP and DBP in 180 normotensive individuals (90 couples; participant mean age 25.04; 91.58% white) over a 24 h period using ambulatory blood pressure monitors to explore the impact of martial quality. Results showed that perceptions of spousal ambivalence were associated with blunted nocturnal BP dipping. Perceptions of one's own behavior as ambivalent also showed blunted nocturnal dipping. When in an ambivalent relationship, a gender interaction was found such that women were most likely to have blunted SBP dipping, but men were more likely to have blunted nocturnal DBP dipping. Overall, this study found an association between ambivalence and BP dipping, thus uncovering one virtually unexplored pathway by which marital relationships may have adverse effects on health.

Elucidating the Unconventional Binding Mode of a DNA-Encoded Library Hit Provides a Blueprint for Sirtuin 6 Inhibitor Development.

Sirtuin 6 (Sirt6), an NAD+-dependent deacylase, has emerged as a promising target for aging-related diseases and cancer. Advancing the medicinal chemistry of Sirt6 modulators is crucial for the development of chemical probes aimed at unraveling the intricate biological functions of Sirt6 and unlocking its therapeutic potential. A proprietary DNA-encoded library yielded Sirt6 inhibitor 2-Pr, displaying remarkable inhibitory activity and isoform-selectivity, and featuring a chemical structure distinct from reported Sirt6 modulators. In this study, we explore the inhibitory mechanism of 2-Pr, evaluating the impact of chemical modifications and presenting a crystal structure of the Sirt6/ADP-ribose/2-Pr complex. Notably, co-crystal structure analysis reveals an unexpected and unprecedented binding mode of Sirt6, with 2-Pr spanning the acyl channel of the enzyme, extending into the acetyl-lysine binding pocket, and reaching toward the C-site. This unique binding mode guides potential avenues for developing potent and selective Sirt6 inhibitors.

Acute Effects of Breaking up Sitting Time With Isometric Wall Squat Exercise on Vascular Function and Blood Pressure in Sedentary Adults: Randomized Crossover Trial.

PURPOSE: The World Health Organization has recommended breaking up sitting time to improve cardiovascular health. However, whether isometric exercise can be effectively used as a strategy to break up sitting time remains unclear. Thus, the aim of this study was to analyze the acute effects of breaking up prolonged sitting with isometric wall squat exercise (IWSE) on vascular function and blood pressure (BP) in sedentary adults. METHODS: This randomized crossover trial included 17 adults (53% male, 26 ± 6 yr, 22.4 ± 3.6 kg/m2) with high sedentary behavior (≥ 6 hr/d). The participants completed 2 experimental sessions in a randomized order, both sharing a common sitting period of 180 min: Breaks (2-min breaks were incorporated into the IWSE, with participants maintaining their knees at the angle determined by the incremental test, which occurred every 30 min) and Control (sitting for 180 min continuously). Popliteal artery flow-mediated dilation (FMD) and brachial BP were measured before and at 10 and 30 min after the experimental sessions. RESULTS: The results did not indicate significant session vs time interaction effects on popliteal FMD and brachial BP (P > .05). A subanalysis including only participants with popliteal FMD reduction after the Control session (n = 11) revealed that Breaks enhanced popliteal FMD after 10 min (1.38 ± 6.45% vs -4.87 ± 2.95%, P= .002) and 30 min (-0.43 ± 2.48% vs -2.11 ± 5.22%, P= .047). CONCLUSION: Breaking up prolonged sitting with IWSE mitigates impaired vascular function resulting from prolonged sitting but has no effect on BP in sedentary adults.

Schwarzites and Triply Periodic Minimal Surfaces: From Pure Topology Mathematics to Macroscale Applications.

Schwarzites are porous (spongy-like) carbon allotropes with negative Gaussian curvatures. They are proposed by Mackay and Terrones inspired by the works of the German mathematician Hermann Schwarz on Triply-Periodic Minimal Surfaces (TPMS). This review presents and discusses the history of schwarzites and their place among curved carbon nanomaterials. The main works on schwarzites are summarized and are available in the literature. Their unique structural, electronic, thermal, and mechanical properties are discussed. Although the synthesis of carbon-based schwarzites remains elusive, recent advances in the synthesis of zeolite-templates nanomaterials have brought them closer to reality. Atomic-based models of schwarzites are translated into macroscale ones that are 3D-printed. These 3D-printed models are exploited in many real-world applications, including water remediation and biomedical ones.

Can step count be used to identify older adults with high sedentary time and low moderate-to-vigorous physical activity?

INTRODUCTION: Combined high sedentary time (ST) and low moderate-to-vigorous physical activity (MVPA) has been associated with adverse cardiovascular events. However, accurately assessing ST and MVPA in older adults is challenging in clinical practice. PURPOSE: To investigate whether step count can identify older adults with unhealthier movement behavior (high ST/low MVPA) and poorer cardiometabolic profile. METHODS: Cross-sectional study (n = 258; 66 ± 5 years). Step count, ST, and MVPA were assessed by hip accelerometry during 7 days. The cardiometabolic profile was assessed using a continuous metabolic syndrome score (cMetS), including blood pressure, HDL-cholesterol, triglycerides, fasting glucose, and waist circumference. Receiving operating curve analysis was used to test the performance of step count in identifying older adults with unhealthier movement behavior (highest tertile of ST/lowest tertile of MVPA). Healthier movement behavior was defined as lowest tertile of ST/highest tertile of MVPA, with neutral representing the remaining combinations of ST/MVPA. RESULTS: A total of 40 participants (15.5%) were identified with unhealthier movement behavior (ST ≥ 11.4 h/day and MVPA ≤ 10 min/day). They spent ~73% and 0.4% of waking hours in ST and MVPA, respectively. Step count identified those with unhealthier movement behavior (area under the curve 0.892, 0.850-0.934; cutoff: ≤5263 steps/day; sensitivity/specificity: 83%/81%). This group showed a higher cMetS compared with neutral (ß = .25, p = .028) and healthier movement behavior groups (ß = .41, p = .008). CONCLUSION: Daily step count appears to be a practical, simple metric for identifying community-dwelling older adults with concomitant high ST and low MVPA, indicative of unhealthier movement behavior, who have a poorer cardiometabolic profile.

Characteristics associated with responsiveness to isometric handgrip training in medicated hypertensive patients: secondary data analysis.

OBJECTIVE: Isometric handgrip training (IHT) has been shown to reduce blood pressure (BP) in hypertensive patients. However, factors that predict responsiveness to IHT are largely unknown. The aim of this study was to investigate the patient characteristics associated with the antihypertensive response to IHT using a recommended statistical approach for evaluating interindividual responses. METHODS: Data from four randomized controlled trials were combined, totaling 81 patients undergoing IHT (48.8% women; 60 ±â€Š11 years) and 90 control patients (45.6% women; 62 ±â€Š12 years). IHT consisted of 4 × 2 min isometric contractions at 30% of maximal voluntary contraction, performed three times/week for 8-12 weeks. BP was measured at baseline and following IHT and control interventions. The interindividual variation was assessed by the standard deviation of the individual responses (SD ir ), and linear regression analyses were conducted to explore response predictors. RESULTS: IHT significantly decreased both SBP (-5.4; 95% confidence interval (CI) -9.5 to -1.3 mmHg) and DBP (-2.8; 95% CI -5.1 to -0.6 mmHg). The interindividual variation of BP change was moderate for systolic (SD ir  = 5.2 mmHg, 0.30 standardized units) and low for diastolic (SD ir  = 1.7 mmHg, 0.15 standardized units). Sex, age, and BMI were not associated with the antihypertensive effect of IHT. However, a higher baseline SBP ( b  = -0.467, P  < 0.001) and absence of dihydropyridine calcium channel blockers use ( b  = 0.340, P  = 0.001) were associated with greater BP reductions. CONCLUSION: IHT reduced BP in medicated hypertensive patients regardless of age, sex, and BMI. Patients with a higher baseline SBP and those not prescribed dihydropyridine calcium channel blockers were more responsive to IHT.

Effects of additional exercise therapy after a successful vascular intervention for people with symptomatic peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is characterised by obstruction or narrowing of the large arteries of the lower limbs, usually caused by atheromatous plaques. Most people with PAD who experience intermittent leg pain (intermittent claudication) are typically treated with secondary prevention strategies, including medical management and exercise therapy. Lower limb revascularisation may be suitable for people with significant disability and those who do not show satisfactory improvement after conservative treatment. Some studies have suggested that lower limb revascularisation for PAD may not confer significantly more benefits than supervised exercise alone for improved physical function and quality of life. It is proposed that supervised exercise therapy as adjunctive treatment after successful lower limb revascularisation may confer additional benefits, surpassing the effects conferred by either treatment alone. OBJECTIVES: To assess the effects of a supervised exercise programme versus standard care following successful lower limb revascularisation in people with PAD. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, two other databases, and two trial registers, most recently on 14 March 2023. SELECTION CRITERIA: We included randomised controlled trials which compared supervised exercise training following lower limb revascularisation with standard care following lower limb revascularisation in adults (18 years and older) with PAD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were maximum walking distance or time (MWD/T) on the treadmill, six-minute walk test (6MWT) total distance, and pain-free walking distance or time (PFWD/T) on the treadmill. Our secondary outcomes were changes in the ankle-brachial index, all-cause mortality, changes in health-related quality-of-life scores, reintervention rates, and changes in subjective measures of physical function. We analysed continuous data by determining the mean difference (MD) and 95% confidence interval (CI), and dichotomous data by determining the odds ratio (OR) with corresponding 95% CI. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified seven studies involving 376 participants. All studies involved participants who received either additional supervised exercise or standard care after lower limb revascularisation. The studies' exercise programmes varied, and included supervised treadmill walking, combined exercise, and circuit training. The duration of exercise therapy ranged from six weeks to six months; follow-up time ranged from six weeks to five years. Standard care also varied between studies, including no treatment or advice to stop smoking, lifestyle modifications, or best medical treatment. We classified all studies as having some risk of bias concerns. The certainty of the evidence was very low due to the risk of bias, inconsistency, and imprecision. The meta-analysis included only a subset of studies due to concerns regarding data reporting, heterogeneity, and bias in most published research. The evidence was of very low certainty for all the review outcomes. Meta-analysis comparing changes in maximum walking distance from baseline to end of follow-up showed no improvement (MD 159.47 m, 95% CI -36.43 to 355.38; I2 = 0 %; 2 studies, 89 participants). In contrast, exercise may improve the absolute maximum walking distance at the end of follow-up compared to standard care (MD 301.89 m, 95% CI 138.13 to 465.65; I2 = 0 %; 2 studies, 108 participants). Moreover, we are very uncertain if there are differences in the changes in the six-minute walk test total distance from baseline to treatment end between exercise and standard care (MD 32.6 m, 95% CI -17.7 to 82.3; 1 study, 49 participants), and in the absolute values at the end of follow-up (MD 55.6 m, 95% CI -2.6 to 113.8; 1 study, 49 participants). Regarding pain-free walking distance, we are also very uncertain if there are differences in the mean changes in PFWD from baseline to treatment end between exercise and standard care (MD 167.41 m, 95% CI -11 to 345.83; I2 = 0%; 2 studies, 87 participants). We are very uncertain if there are differences in the absolute values of ankle-brachial index at the end of follow-up between the intervention and standard care (MD 0.01, 95% CI -0.11 to 0.12; I2 = 62%; 2 studies, 110 participants), in mortality rates at the end of follow-up (OR 0.92, 95% CI 0.42 to 2.00; I2 = 0%; 6 studies, 346 participants), health-related quality of life at the end of follow-up for the physical (MD 0.73, 95% CI -5.87 to 7.33; I2 = 64%; 2 studies, 105 participants) and mental component (MD 1.04, 95% CI -6.88 to 8.95; I2 = 70%; 2 studies, 105 participants) of the 36-item Short Form Health Survey. Finally, there may be little to no difference in reintervention rates at the end of follow-up between the intervention and standard care (OR 0.91, 95% CI 0.23 to 3.65; I2 = 65%; 5 studies, 252 participants). AUTHORS' CONCLUSIONS: There is very uncertain evidence that additional exercise therapy after successful lower limb revascularisation may improve absolute maximal walking distance at the end of follow-up compared to standard care. Evidence is also very uncertain about the effects of exercise on pain-free walking distance, six-minute walk test distance, quality of life, ankle-brachial index, mortality, and reintervention rates. Although it is not possible to confirm the effectiveness of supervised exercise compared to standard care for all outcomes, studies did not report any harm to participants from this intervention after lower limb revascularisation. Overall, the evidence incorporated into this review was very uncertain, and additional evidence is needed from large, well-designed, randomised controlled studies to more conclusively demonstrate the role additional exercise therapy has after lower limb revascularisation in people with PAD.

Theoretical Investigation of Transient Species Following Photodissociation of Ironpentacarbonyl in Ethanol Solution.

Photodissociation of ironpentacarbonyl [1Fe(CO)5] in solution generates transient species in different electronic states, which we studied theoretically. From ab initio molecular dynamics simulations in ethanol solution, the closed-shell parent compound 1Fe(CO)5 is found to interact weakly with the solvent, whereas the irontetracarbonyl [Fe(CO)4] species, formed after photodissociation, has a strongly spin-dependent behavior. It coordinates a solvent molecule tightly in the singlet state [1Fe(CO)4] and weakly in the triplet state [3Fe(CO)4]. From the simulations, we have gained insights into intersystem crossing in solvated irontetracarbonyl based on the distinct structural differences induced by the change in multiplicity. Alternative forms of coordination between 1Fe(CO)4 and functional groups of the ethanol molecule are simulated, and a quantum chemical investigation of the energy landscape for the coordinated irontetracarbonyl gives information about the interconversion of different transient species in solution. Furthermore, insights from the simulations, in which we find evidence of a solvent exchange mechanism, challenge the previously proposed mechanism of chain walking for under-coordinated metal carbonyls in solution.

Recurring seasonality exposes dominant species and niche partitioning strategies of open ocean picoeukaryotic algae.

Ocean spring phytoplankton blooms are dynamic periods important to global primary production. We document vertical patterns of a diverse suite of eukaryotic algae, the prasinophytes, in the North Atlantic Subtropical Gyre with monthly sampling over four years at the Bermuda Atlantic Time-series Study site. Water column structure was used to delineate seasonal stability periods more ecologically relevant than seasons defined by calendar dates. During winter mixing, tiny prasinophytes dominated by Class II comprise 46 ± 24% of eukaryotic algal (plastid-derived) 16S rRNA V1-V2 amplicons, specifically Ostreococcus Clade OII, Micromonas commoda, and Bathycoccus calidus. In contrast, Class VII are rare and Classes I and VI peak during warm stratified periods when surface eukaryotic phytoplankton abundances are low. Seasonality underpins a reservoir of genetic diversity from multiple prasinophyte classes during warm periods that harbor ephemeral taxa. Persistent Class II sub-species dominating the winter/spring bloom period retreat to the deep chlorophyll maximum in summer, poised to seed the mixed layer upon winter convection, exposing a mechanism for initiating high abundances at bloom onset. Comparisons to tropical oceans reveal broad distributions of the dominant sub-species herein. This unparalleled window into temporal and spatial niche partitioning of picoeukaryotic primary producers demonstrates how key prasinophytes prevail in warm oceans.

Photochemical Formation and Electronic Structure of an Alkane σ-Complex from Time-Resolved Optical and X-ray Absorption Spectroscopy.

C-H bond activation reactions with transition metals typically proceed via the formation of alkane σ-complexes, where an alkane C-H σ-bond binds to the metal. Due to the weak nature of metal-alkane bonds, σ-complexes are challenging to characterize experimentally. Here, we establish the complete pathways of photochemical formation of the model σ-complex Cr(CO)5-alkane from Cr(CO)6 in octane solution and characterize the nature of its metal-ligand bonding interactions. Using femtosecond optical absorption spectroscopy, we find photoinduced CO dissociation from Cr(CO)6 to occur within the 100 fs time resolution of the experiment. Rapid geminate recombination by a fraction of molecules is found to occur with a time constant of 150 fs. The formation of bare Cr(CO)5 in its singlet ground state is followed by complexation of an octane molecule from solution with a time constant of 8.2 ps. Picosecond X-ray absorption spectroscopy at the Cr L-edge and O K-edge provides unique information on the electronic structure of the Cr(CO)5-alkane σ-complex from both the metal and ligand perspectives. Based on clear experimental observables, we find substantial destabilization of the lowest unoccupied molecular orbital upon coordination of the C-H bond to the undercoordinated Cr center in the Cr(CO)5-alkane σ-complex, and we define this as a general, orbital-based descriptor of the metal-alkane bond. Our study demonstrates the value of combining optical and X-ray spectroscopic methods as complementary tools to study the stability and reactivity of alkane σ-complexes in their role as the decisive intermediates in C-H bond activation reactions.

Isometric Exercise Training and Arterial Hypertension: An Updated Review.

Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.

Association of Sports Practice in Childhood and Adolescence with Cardiac Autonomic Modulation in Adulthood: A Retrospective Epidemiological Study.

BACKGROUND: Practicing sports during childhood and adolescence provides benefits to cardiac autonomic modulation (CAM) at these stages of life. However, it is not known whether these benefits to CAM persist into adulthood. Therefore, the objective of this study was to analyze the association of early sports practice (sports practice in childhood and/or adolescence) with CAM in adult life, regardless of habitual moderate-to-vigorous PA. METHODS: The sample of the present study consisted of 242 adults (141 women and 101 men; age: 41.99 ± 16.24). The assessment of CAM was performed using heart rate variability indices. Sports practice in childhood and adolescence was assessed using a questionnaire. The intensity of physical activity was assessed using accelerometry. To analyze the association between previous sports practice (childhood and/or adolescence) and CAM, the Generalized Linear Model was adopted, considering CAM indices as continuous variables and early sports practice as a 3-fold factor (no sports practice; sports practice in childhood or adolescence; and sports practice in both childhood and adolescence) adjusted by sex, age, socioeconomic condition, and moderate to vigorous PA. RESULTS: Sports practice in childhood was associated with the average standard deviation of all normal RR intervals expressed in milliseconds (SDNN): ß = 5.89; 95%CI: 0.25;11.52, and the standard deviation of the long-term intervals between consecutive heartbeats (SD2): ß = 7.63; 95%CI:1.04; 14.23 indices. Sports practice in adolescence was associated in adulthood with the SD2 index: ß = 7.37; 95%CI: 0.71;14.04. Sports practice in at least one of the periods (childhood or adolescence) was significantly associated with the square root of the mean square of the differences between adjacent normal RR intervals for a period of time expressed in milliseconds (RMSSD) (ß = 8.86; 95%CI = 0.71;17.01), and the standard deviation of the instantaneous beat to beat variability (SD1) (ß = 6.21; 95%CI = 0.45;11.97). Sports practice at both stages of life was significantly associated with better SDNN (ß = 7.70; 95%CI = 1.16;14.23) and SD2 (ß = 10.18; 95%CI = 2.51;17.85). CONCLUSION: Early sports practice was associated with better CAM in adulthood, independently of the current physical activity level. Based on these findings, sports practice is encouraged from childhood and adolescence, for benefits to CAM in adult life.

Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation.

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep.

Secondary brain injury (SBI) occurs with a lag of several days post-bleeding in patients with aneurysmal subarachnoid hemorrhage (aSAH) and is a strong contributor to mortality and long-term morbidity. aSAH-SBI coincides with cell-free hemoglobin (Hb) release into the cerebrospinal fluid. This temporal association and convincing pathophysiological concepts suggest that CSF-Hb could be a targetable trigger of SBI. However, sparse experimental evidence for Hb's neurotoxicity in vivo defines a significant research gap for clinical translation. We modeled the CSF-Hb exposure observed in aSAH patients in conscious sheep, which allowed us to assess neurological functions in a gyrencephalic species. Twelve animals were randomly assigned for 3-day bi-daily intracerebroventricular (ICV) injections of either Hb or Hb combined with the high-affinity Hb scavenger protein haptoglobin (Hb-Hp, CSL888). Repeated CSF sampling confirmed clinically relevant CSF-Hb concentrations. This prolonged CSF-Hb exposure over 3 days resulted in disturbed movement activity, reduced food intake, and impaired observational neuroscores. The Hb-induced neurotoxic effects were significantly attenuated when Hb was administered with equimolar haptoglobin. Preterminal magnetic resonance imaging (MRI) showed no CSF-Hb-specific structural brain alterations. In both groups, histology demonstrated an inflammatory response and revealed enhanced perivascular histiocytic infiltrates in the Hb-Hp group, indicative of adaptive mechanisms. Heme exposure in CSF and iron deposition in the brain were comparable, suggesting comparable clearance efficiency of Hb and Hb-haptoglobin complexes from the intracranial compartment. We identified a neurological phenotype of CSF-Hb toxicity in conscious sheep, which is rather due to neurovascular dysfunction than structural brain injury. Haptoglobin was effective at attenuating CSF-Hb-induced neurological deterioration, supporting its therapeutic potential.

Comparing Sensitivity, Specificity, and Accuracy of Fall Risk Assessments in Community-Dwelling Older Adults.

Purpose: The US Centers for Disease Control and Prevention (CDC) has implemented the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative. This initiative provides an algorithm for fall risk screening. However, the algorithm has the potential to overcategorize individuals as high risk for falling upon initial screening, which may burden clinicians with the task of recategorizing individuals after follow-up testing. Therefore, this study aimed to compare the accuracy, sensitivity, and specificity of fall risk appraisal between the STEADI, Short Fall-Efficacy Scale International (FES-I), and portable balance system (BTrackS) assessments in community-dwelling older adults. Patients and Methods: This cross-sectional analysis included 122 community-dwelling older adults, comprising 94 women and 28 men. Center-of-pressure postural sway was assessed using the BTrackS, fear of falling was assessed using the Short FES-I questionnaire, and all participants completed the STEADI checklist. Each assessment categorized participants as either high or low fall risk and fall risk appraisal was compared between groups using McNemar tests. Results: The STEADI checklist (high risk: n = 62; low risk: n = 60) significantly differed in fall risk appraisal compared to the BTrackS (high risk: n = 44; low risk: n = 78; p = 0.014) and the Short FES-I (high risk: n = 42; low risk: n = 80; p = 0.002). Compared to the BTrackS, the STEADI checklist had a specificity of 62.8%, sensitivity of 70.5%, and accuracy of 65.6%. Compared to the Short FES-I, the STEADI checklist had a specificity of 67.5%, sensitivity of 81.0%, and accuracy of 72.1%. Conclusion: The STEADI checklist appears to overcategorize individuals as high fall risk more frequently than direct assessments of postural sway and fear of falling. Further research is needed to examine potential improvements in accuracy when combining the STEADI checklist with direct assessments of postural sway and/or fear of falling.

Fall risk assessments are crucial for preventative care in older adults. However, the demands of clinical practice require an accurate and time-efficient method. The U.S Centers for Disease Control and Prevention (CDC) has implemented a fall risk checklist through the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) initiative. However, the STEADI checklist might cost clinicians more time than expected, as some patients initially classified as high risk for falling may not actually be at high risk. This leads to unnecessary follow-up assessments. In this study, we compared the STEADI checklist to direct measures of postural sway (balance) using the BTrackS system and fear of falling using the Short FES-I survey to determine how they differed in classifying community-dwelling older adults as high versus low fall risk. Our results show that the STEADI checklist classifies older adults as high risk more frequently than the BTrackS and Short FES-I. Considering that the follow-up assessments for a high-risk classification by the STEADI checklist include a balance test, we suggest that combining a balance test such as the BTrackS with a questionnaire or checklist may yield better screening outcomes and accurately identify high-risk individuals in a timely manner. Further research is needed to determine the effectiveness of this combination and to establish a true gold standard method for fall risk appraisal.

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): a population-based study.

BACKGROUND: Typhoid Fever remains a major cause of morbidity and mortality in low-income settings. The Severe Typhoid in Africa programme was designed to address regional gaps in typhoid burden data and identify populations eligible for interventions using novel typhoid conjugate vaccines. METHODS: A hybrid design, hospital-based prospective surveillance with population-based health-care utilisation surveys, was implemented in six countries in sub-Saharan Africa. Patients presenting with fever (≥37·5°C axillary or ≥38·0°C tympanic) or reporting fever for three consecutive days within the previous 7 days were invited to participate. Typhoid fever was ascertained by culture of blood collected upon enrolment. Disease incidence at the population level was estimated using a Bayesian mixture model. FINDINGS: 27 866 (33·8%) of 82 491 participants who met inclusion criteria were recruited. Blood cultures were performed for 27 544 (98·8%) of enrolled participants. Clinically significant organisms were detected in 2136 (7·7%) of these cultures, and 346 (16·2%) Salmonella enterica serovar Typhi were isolated. The overall adjusted incidence per 100 000 person-years of observation was highest in Kavuaya and Nkandu 1, Democratic Republic of the Congo (315, 95% credible interval 254-390). Overall, 46 (16·4%) of 280 tested isolates showed ciprofloxacin non-susceptibility. INTERPRETATION: High disease incidence (ie, >100 per 100 000 person-years of observation) recorded in four countries, the prevalence of typhoid hospitalisations and complicated disease, and the threat of resistant typhoid strains strengthen the need for rapid dispatch and implementation of effective typhoid conjugate vaccines along with measures designed to improve clean water, sanitation, and hygiene practices. FUNDING: The Bill & Melinda Gates Foundation.