Circadian time- and sleep-dependent modulation of cortical parvalbumin-positive inhibitory neurons.

Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.

DDID: a comprehensive resource for visualization and analysis of diet-drug interactions.

Diet-drug interactions (DDIs) are pivotal in drug discovery and pharmacovigilance. DDIs can modify the systemic bioavailability/pharmacokinetics of drugs, posing a threat to public health and patient safety. Therefore, it is crucial to establish a platform to reveal the correlation between diets and drugs. Accordingly, we have established a publicly accessible online platform, known as Diet-Drug Interactions Database (DDID, https://bddg.hznu.edu.cn/ddid/), to systematically detail the correlation and corresponding mechanisms of DDIs. The platform comprises 1338 foods/herbs, encompassing flora and fauna, alongside 1516 widely used drugs and 23 950 interaction records. All interactions are meticulously scrutinized and segmented into five categories, thereby resulting in evaluations (positive, negative, no effect, harmful and possible). Besides, cross-linkages between foods/herbs, drugs and other databases are furnished. In conclusion, DDID is a useful resource for comprehending the correlation between foods, herbs and drugs and holds a promise to enhance drug utilization and research on drug combinations.

Cloud transition across the daily cycle illuminates model responses of trade cumuli to warming.

The response of trade cumulus clouds to warming remains a major source of uncertainty for climate sensitivity. Recent studies have highlighted the role of the cloud-convection coupling in explaining this spread in future warming estimates. Here, using observations from an instrumented site and an airborne field campaign, together with high-frequency climate model outputs, we show that i) over the course of the daily cycle, a cloud transition is observed from deeper cumuli during nighttime to shallower cumuli during daytime, ii) the cloud evolution that models predict from night to day reflects the strength of cloud sensitivity to convective mass flux and exhibits many similarities with the cloud evolution they predict under global warming, and iii) those models that simulate a realistic cloud transition over the daily cycle tend to predict weak trade cumulus feedback. Our findings thus show that the daily cycle is a particularly relevant testbed, amenable to process studies and anchored by observations, to assess and improve the model representation of cloud-convection coupling and thus make climate projections more reliable.

Severity-Dependent Interhemispheric White Matter Connectivity Predicts Poststroke Neglect Recovery.

Left-sided spatial neglect is a very common and challenging issue after right-hemispheric stroke, which strongly and negatively affects daily living behavior and recovery of stroke survivors. The mechanisms underlying recovery of spatial neglect remain controversial, particularly regarding the involvement of the intact, contralesional hemisphere, with potential contributions ranging from maladaptive to compensatory. In the present prospective, observational study, we assessed neglect severity in 54 right-hemispheric stroke patients (32 male; 22 female) at admission to and discharge from inpatient neurorehabilitation. We demonstrate that the interaction of initial neglect severity and spared white matter (dis)connectivity resulting from individual lesions (as assessed by diffusion tensor imaging, DTI) explains a significant portion of the variability of poststroke neglect recovery. In mildly impaired patients, spared structural connectivity within the lesioned hemisphere is sufficient to attain good recovery. Conversely, in patients with severe impairment, successful recovery critically depends on structural connectivity within the intact hemisphere and between hemispheres. These distinct patterns, mediated by their respective white matter connections, may help to reconcile the dichotomous perspectives regarding the role of the contralesional hemisphere as exclusively compensatory or not. Instead, they suggest a unified viewpoint wherein the contralesional hemisphere can - but must not necessarily - assume a compensatory role. This would depend on initial impairment severity and on the available, spared structural connectivity. In the future, our findings could serve as a prognostic biomarker for neglect recovery and guide patient-tailored therapeutic approaches.

CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping.

Circadian rhythms are a pervasive property of mammalian cells, tissues and behaviour, ensuring physiological adaptation to solar time. Models of cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are therefore considered essential components of the cellular clock mechanism, supported by behavioural arrhythmicity of CRY-deficient (CKO) mice under constant conditions. Challenging this interpretation, we find locomotor rhythms in adult CKO mice under specific environmental conditions and circadian rhythms in cellular PER2 levels when CRY is absent. CRY-less oscillations are variable in their expression and have shorter periods than wild-type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and period determination by CK1δ/ε activity to be maintained. In the absence of CRY-mediated feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post-translational.

CrossFuse-XGBoost: accurate prediction of the maximum recommended daily dose through multi-feature fusion, cross-validation screening and extreme gradient boosting.

In the drug development process, approximately 30% of failures are attributed to drug safety issues. In particular, the first-in-human (FIH) trial of a new drug represents one of the highest safety risks, and initial dose selection is crucial for ensuring safety in clinical trials. With traditional dose estimation methods, which extrapolate data from animals to humans, catastrophic events have occurred during Phase I clinical trials due to interspecies differences in compound sensitivity and unknown molecular mechanisms. To address this issue, this study proposes a CrossFuse-extreme gradient boosting (XGBoost) method that can directly predict the maximum recommended daily dose of a compound based on existing human research data, providing a reference for FIH dose selection. This method not only integrates multiple features, including molecular representations, physicochemical properties and compound-protein interactions, but also improves feature selection based on cross-validation. The results demonstrate that the CrossFuse-XGBoost method not only improves prediction accuracy compared to that of existing local weighted methods [k-nearest neighbor (k-NN) and variable k-NN (v-NN)] but also solves the low prediction coverage issue of v-NN, achieving full coverage of the external validation set and enabling more reliable predictions. Furthermore, this study offers a high level of interpretability by identifying the importance of different features in model construction. The 241 features with the most significant impact on the maximum recommended daily dose were selected, providing references for optimizing the structure of new compounds and guiding experimental research. The datasets and source code are freely available at https://github.com/cqmu-lq/CrossFuse-XGBoost.

Women and Men are the Barometers of Relationships: Testing the Predictive Power of Women's and Men's Relationship Satisfaction.

There is a longstanding belief in relationship science and popular opinion that women are the barometers in mixed-gender relationships such that their perceptions about the partnership carry more weight than men's in predicting future relationship satisfaction, but this idea has yet to be rigorously tested. We analyze data from two studies to test within-person links between men's and women's relationship satisfaction on their own and their partner's next-day and next-year satisfaction. Study 1 combined nine daily diary datasets from Canada and the United States with 901 mixed-gender couples who provided 29,541 daily reports of relationship satisfaction. Study 2 analyzed five annual waves of data from the German Family Panel (pairfam) that surveyed 3,405 mixed-gender couples who provided 21,115 relationship satisfaction reports. Latent curve models with structured residuals (LCM-SR) revealed that in both studies, men's and women's relationship satisfaction significantly predicted their own and their partner's relationship satisfaction, with no gender differences in the magnitude of these effects. Results underscore the interdependence of romantic partners' satisfaction and indicate that both men and women jointly shape romantic relationship satisfaction.

Orchestrated translation specializes dinoflagellate metabolism three times per day.

Many cells specialize for different metabolic tasks at different times over their normal ZT cycle by changes in gene expression. However, in most cases, circadian gene expression has been assessed at the mRNA accumulation level, which may not faithfully reflect protein synthesis rates. Here, we use ribosome profiling in the dinoflagellate Lingulodinium polyedra to identify thousands of transcripts showing coordinated translation. All of the components in carbon fixation are concurrently regulated at ZT0, predicting the known rhythm of carbon fixation, and many enzymes involved in DNA replication are concurrently regulated at ZT12, also predicting the known rhythm in this process. Most of the enzymes in glycolysis and the TCA cycle are also regulated together, suggesting rhythms in these processes as well. Surprisingly, a third cluster of transcripts show peak translation at approximately ZT16, and these transcripts encode enzymes involved in transcription, translation, and amino acid biosynthesis. The latter has physiological consequences, as measured free amino acid levels increase at night and thus represent a previously undocumented rhythm in this model. Our results suggest that ribosome profiling may be a more accurate predictor of changed metabolic state than transcriptomics.

Thromboxane biosynthesis and future events in diabetes: the ASCEND trial.

BACKGROUND AND AIMS: Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-TXB2 (U-TXM), a stable metabolite reflecting the whole-body TXA2 biosynthesis, is reduced by ∼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation and is enhanced in patients with diabetes. This study assessed whether U-TXM is associated with the risk of future serious vascular events or revascularizations (SVE-R), major bleeding, or cancer in patients with diabetes. METHODS: The U-TXM was measured pre-randomization to aspirin or placebo in 5948 people with type 1 or 2 diabetes and no cardiovascular disease, in the ASCEND trial. Associations between log U-TXM and SVE-R (n = 618), major bleed (n = 206), and cancer (n = 700) during 6.6 years of follow-up were investigated by Cox regression; comparisons of these associations with the effects of randomization to aspirin were made. RESULTS: Higher U-TXM was associated with older age, female sex, current smoking, type 2 diabetes, higher body size, urinary albumin/creatinine ratio of ≥3 mg/mmol, and higher estimated glomerular filtration rate. After adjustment for these, U-TXM was marginally statistically significantly associated with SVE-R and major bleed but not cancer [hazard ratios per 1 SD higher log U-TXM (95% confidence interval): 1.09 (1.00-1.18), 1.16 (1.01-1.34), and 1.06 (0.98-1.14)]. The hazard ratio was similar to that implied by the clinical effects of randomization to aspirin for SVE-R but not for major bleed. CONCLUSIONS: The U-TXM was log-linearly independently associated with SVE-R in diabetes. This is consistent with the involvement of platelet TXA2 in diabetic atherothrombosis.

Acquired Human Immunodeficiency Virus Type 1 Drug Resistance in Rhode Island, USA, 2004-2021.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART). METHODS: We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors. RESULTS: Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options. CONCLUSIONS: Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations.

The impact of hypoglycaemia on daily functioning among adults with diabetes: a prospective observational study using the Hypo-METRICS app.

AIMS/HYPOTHESIS: The aim of this work was to examine the impact of hypoglycaemia on daily functioning among adults with type 1 diabetes or insulin-treated type 2 diabetes, using the novel Hypo-METRICS app. METHODS: For 70 consecutive days, 594 adults (type 1 diabetes, n=274; type 2 diabetes, n=320) completed brief morning and evening Hypo-METRICS 'check-ins' about their experienced hypoglycaemia and daily functioning. Participants wore a blinded glucose sensor (i.e. data unavailable to the participants) for the study duration. Days and nights with or without person-reported hypoglycaemia (PRH) and/or sensor-detected hypoglycaemia (SDH) were compared using multilevel regression models. RESULTS: Participants submitted a mean ± SD of 86.3±12.5% morning and 90.8±10.7% evening check-ins. For both types of diabetes, SDH alone had no significant associations with the changes in daily functioning scores. However, daytime and night-time PRH (with or without SDH) were significantly associated with worsening of energy levels, mood, cognitive functioning, negative affect and fear of hypoglycaemia later that day or while asleep. In addition, night-time PRH (with or without SDH) was significantly associated with worsening of sleep quality (type 1 and type 2 diabetes) and memory (type 2 diabetes). Further, daytime PRH (with or without SDH), was associated with worsening of fear of hyperglycaemia while asleep (type 1 diabetes), memory (type 1 and type 2 diabetes) and social functioning (type 2 diabetes). CONCLUSIONS/INTERPRETATION: This prospective, real-world study reveals impact on several domains of daily functioning following PRH but not following SDH alone. These data suggest that the observed negative impact is mainly driven by subjective awareness of hypoglycaemia (i.e. PRH), through either symptoms or sensor alerts/readings and/or the need to take action to prevent or treat episodes.

Associations between daily step count classifications and continuous glucose monitoring metrics in adults with type 1 diabetes: analysis of the Type 1 Diabetes Exercise Initiative (T1DEXI) cohort.

AIMS/HYPOTHESIS: Adults with type 1 diabetes should perform daily physical activity to help maintain health and fitness, but the influence of daily step counts on continuous glucose monitoring (CGM) metrics are unclear. This analysis used the Type 1 Diabetes Exercise Initiative (T1DEXI) dataset to investigate the effect of daily step count on CGM-based metrics. METHODS: In a 4 week free-living observational study of adults with type 1 diabetes, with available CGM and step count data, we categorised participants into three groups-below (<7000), meeting (7000-10,000) or exceeding (>10,000) the daily step count goal-to determine if step count category influenced CGM metrics, including per cent time in range (TIR: 3.9-10.0 mmol/l), time below range (TBR: <3.9 mmol/l) and time above range (TAR: >10.0 mmol/l). RESULTS: A total of 464 adults with type 1 diabetes (mean±SD age 37±14 years; HbA1c 48.8±8.1 mmol/mol [6.6±0.7%]; 73% female; 45% hybrid closed-loop system, 38% standard insulin pump, 17% multiple daily insulin injections) were included in the study. Between-participant analyses showed that individuals who exceeded the mean daily step count goal over the 4 week period had a similar TIR (75±14%) to those meeting (74±14%) or below (75±16%) the step count goal (p>0.05). In the within-participant comparisons, TIR was higher on days when the step count goal was exceeded or met (both 75±15%) than on days below the step count goal (73±16%; both p<0.001). The TBR was also higher when individuals exceeded the step count goals (3.1%±3.2%) than on days when they met or were below step count goals (difference in means -0.3% [p=0.006] and -0.4% [p=0.001], respectively). The total daily insulin dose was lower on days when step count goals were exceeded (0.52±0.18 U/kg; p<0.001) or were met (0.53±0.18 U/kg; p<0.001) than on days when step counts were below the current recommendation (0.55±0.18 U/kg). Step count had a larger effect on CGM-based metrics in participants with a baseline HbA1c ≥53 mmol/mol (≥7.0%). CONCLUSIONS/INTERPRETATION: Our results suggest that, compared with days with low step counts, days with higher step counts are associated with slight increases in both TIR and TBR, along with small reductions in total daily insulin requirements, in adults living with type 1 diabetes. DATA AVAILABILITY: The data that support the findings reported here are available on the Vivli Platform (ID: T1-DEXI; https://doi.org/10.25934/PR00008428 ).

The effects of daily dose of intense exercise on cardiac responses and atrial fibrillation.

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia that is strongly associated with cardiovascular (CV) disease and sedentary lifestyles. Despite the benefits of exercise on overall health, AF incidence in high-level endurance athletes rivals that of CV disease patients, suggesting a J-shaped relationship with AF. To investigate the dependence of AF vulnerability on exercise, we varied daily swim durations (120, 180 or 240 min day-1 ) in 7-week-old male CD1 mice. We assessed mice after performing equivalent amounts of cumulative work during swimming (i.e. ∼700 L O2  kg-1 ), as determined from O2 consumption rates ( V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ ). The mean V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ during exercise increased progressively throughout the training period and was indistinguishable between the swim groups. Consistent with similar improvements in aerobic conditioning induced by swimming, skeletal muscle mitochondria content increased (P = 0.027) indistinguishably between exercise groups. Physiological ventricular remodelling, characterized by mild hypertrophy and left ventricular dilatation, was also similar between exercised mice without evidence of ventricular arrhythmia inducibility. By contrast, prolongation of daily swim durations caused progressive and vagal-dependent heart rate reductions (P = 0.008), as well as increased (P = 0.005) AF vulnerability. As expected, vagal inhibition prolonged (P = 0.013) atrial refractoriness, leading to reduced AF vulnerability, although still inducible in the 180 and 240 min swim groups. Accordingly, daily swim dose progressively increased atrial hypertrophy (P = 0.003), fibrosis (P < 0.001) and macrophage accumulation (P = 0.006) without differentially affecting the ventricular tissue properties. Thus, increasing daily exercise duration drives progressively adverse atrial-specific remodelling and vagal-dependent AF vulnerability despite robust and beneficial aerobic conditioning and physiological remodelling of ventricles and skeletal muscle. KEY POINTS: Previous studies have suggested that a J-shaped dose-response relationship exists between physical activity and cardiovascular health outcomes, with moderate exercise providing protection against many cardiovascular disease conditions, whereas chronic endurance exercise can promote atrial fibrillation (AF). We found that AF vulnerability increased alongside elevated atrial hypertrophy, fibrosis and inflammation as daily swim exercise durations in mice were prolonged (i.e. ≥180 min day-1 for 6 weeks). The MET-h week-1 (based on O2  measurements during swimming) needed to induce increased AF vulnerability mirrored the levels linked to AF in athletes. These adverse atria effects associated with excessive daily exercise occurred despite improved aerobic conditioning, skeletal muscle adaptation and physiological ventricular remodelling. We suggest that atrial-specific changes observed with exercise arise from excessive elevations in venous filling pressures during prolonged exercise bouts, which we argue has implications for all AF patients because elevated atrial pressures occur in most cardiovascular disease conditions as well as ageing which are linked to AF.

Outside the Laboratory Assessment of Upper Limb Laterality in Patients With Stroke: A Cross-Sectional Study.

BACKGROUND: The rehabilitation of upper limb sensorimotor performance after stroke requires the assessment of daily use, the identification of key levels of impairment, and monitoring the course of recovery. It needs to be answered, how laboratory-based assessments and everyday behavior are connected, which dimension of metrics, that is, volume, intensity, or quality, is most sensitive to reduced function, and what sensor, that is, gyroscope or accelerometer, is best suited to gather such data. METHODS: Performance in laboratory-based sensorimotor tests, as well as smartwatch-derived kinematic data of everyday life relative upper limb activity, during 1 day of inpatient neurorehabilitation (Germany, 2022) of 50 patients with stroke, was cross-sectionally assessed and resulting laterality indices (performance ratios) between the limbs were analyzed using ANCOVAs and principal component analysis. RESULTS: Laboratory-based tests revealed the strongest laterality indices, followed by smartwatch-based (intensity>quality>volume) metrics. Angular velocity-based metrics revealed higher laterality indices than acceleration-based ones. Laterality indices were overall well associated; however, a principal component analysis suggested upper limb impairments to be unidimensional. CONCLUSIONS: Our findings suggest that the use of sensors can deliver valid information of stroke-related laterality. It appeared that commonly used metrics that estimate the volume of use (ie, energy expenditure) are not the most sensitive. Especially reached intensities could be well used for monitoring, because they are more dependent on the performance of the sensorimotor system and less on confounders like age. The unidimensionality of the upper limb laterality suggests that an impaired limb with reduced movement quality and the inability to reach higher intensities will be used less in everyday life, especially when it is the nondominant side.

Socioeconomic Differences in Patient Reported Outcome Measures 3 Months After Stroke: A Nationwide Swedish Register-Based Study.

BACKGROUND: There is a well-known association between low socioeconomic status (SES), poor survival, and clinician-reported outcomes after stroke. We aimed to assess socioeconomic differences in Patient Reported Outcome Measures 3 months after stroke. METHODS: This nationwide cohort study included patients registered with acute stroke in the Swedish Stroke Register 2015-2017. Patient Reported Outcome Measures included activities of daily living (mobility, toileting, and dressing), and poststroke symptoms (low mood, fatigue, pain, and poor general health). Information on SES prestroke was retrieved from Statistics Sweden and defined by a composite measure based on education and income tertiles. Associations between SES and Patient Reported Outcome Measures were analyzed using logistic regression adjusting for confounders (sex and age) and additionally for potential mediators (stroke type, severity, cardiovascular disease risk factors, and living alone). Subgroup analyses were performed for stroke type, men and women, and younger and older patients. RESULTS: The study included 44 511 patients. Of these, 31.1% required assistance with mobility, 18% with toileting, and 22.2% with dressing 3 months after stroke. For poststroke symptoms, 12.3% reported low mood, 39.1% fatigue, and 22.7% pain often/constantly, while 21.4% rated their general health as poor/very poor. Adjusted for confounders, the odds of needing assistance with activities of daily living were highest for patients with low income and primary school education, for example, for mobility, odds ratio was 2.06 (95% CI, 1.89-2.24) compared with patients with high income and university education. For poststroke symptoms, odds of poor outcome were highest for patients with low income and university education (eg, odds ratio, 1.79 [95% CI, 1.49-2.15] for low mood). Adjustments for potential mediators attenuated but did not remove associations. The associations were similar in ischemic and hemorrhagic strokes and more pronounced in men and patients <65 years old. CONCLUSIONS: There are substantial SES-related differences in Patient Reported Outcome Measures poststroke. The more severe outcome associated with low SES is more pronounced in men and in patients of working age.

Moderating Effects of Informal Care on the Relationship Between ADL Limitations and Adverse Outcomes in Stroke Survivors.

BACKGROUND: Stroke survivors with limitations in activities of daily living (ADL) have a greater risk of experiencing falls, hospitalizations, or physical function decline. We examined how informal caregiving received in hours per week by stroke survivors moderated the relationship between ADL limitations and adverse outcomes. METHODS: In this retrospective cohort, community-dwelling participants were extracted from the National Health and Aging Trends Study (2011-2020; n=277) and included if they had at least 1 formal or informal caregiver and reported an incident stroke in the prior year. Participants reported the amount of informal caregiving received in the month prior (low [<5.8], moderate [5.8-27.1], and high [27.2-350.4] hours per week) and their number of ADL limitations (ranging from 0 to 7). Participants were surveyed 1 year later to determine the number of adverse outcomes (ie, falls, hospitalizations, and physical function decline) experienced over the year. Poisson regression coefficients were converted to average marginal effects and estimated the moderating effects of informal caregiving hours per week on the relationship between ADL limitations and adverse outcomes. RESULTS: Stroke survivors were 69.7% White, 54.5% female, with an average age of 80.5 (SD, 7.6) years and 1.2 adverse outcomes at 2 years after the incident stroke. The relationships between informal caregiving hours and adverse outcomes and between ADL limitations and adverse outcomes were positive. The interaction between informal caregiving hours per week and ADL limitations indicated that those who received the lowest amount of informal caregiving had a rate of 0.12 more adverse outcomes per ADL (average marginal effect, 0.12 [95% CI, 0.005-0.23]; P=0.041) than those who received the highest amounts. CONCLUSIONS: Informal caregiving hours moderated the relationship between ADL limitations and adverse outcomes in this sample of community-based stroke survivors. Higher amounts relative to lower amounts of informal caregiving hours per week may be protective by decreasing the rate of adverse outcomes per ADL limitation.

Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

BACKGROUND: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes. METHODS: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions. RESULTS: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P<0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P=0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P=0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P=0.291). CONCLUSIONS: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719.

Comparative transcriptome analysis reveals the impact of daily temperature difference on male sterility in photo-thermo-sensitive male sterile wheat.

BACKGROUND: Photo-thermo-sensitive male sterility (PTMS), which refers to the male sterility triggered by variations in photoperiod and temperature, is a crucial element in the wheat two-line hybrid system. The development of safe production and efficient propagation for male sterile lines holds utmost importance in two-line hybrid wheat. Under the stable photoperiod condition, PTMS is mainly induced by high or low temperatures in wheat, but the effect of daily temperature difference (DTD) on the fertility conversion of PTMS lines has not been reported. Here, three BS type PTMS lines including BS108, BS138, and BS366, as well as a control wheat variety J411 were used to analyze the correlation between fertility and DTD using differentially sowing tests, photo-thermo-control experiments, and transcriptome sequencing. RESULTS: The differentially sowing tests suggested that the optimal sowing time for safe seed production of the three PTMS lines was from October 5th to 25th in Dengzhou, China. Under the condition of 12 h 12 °C, the PTMS lines were greatly affected by DTD and exhibited complete male sterility at a temperature difference of 15 °C. Furthermore, under different temperature difference conditions, a total of 20,677 differentially expressed genes (DEGs) were obtained using RNA sequencing. Moreover, through weighted gene co-expression network analysis (WGCNA) and KEGG enrichment analysis, the identified DEGs had a close association with "starch and sucrose metabolism", "phenylpropanoid biosynthesis", "MAPK signaling pathway-plant", "flavonoid biosynthesis", and "cutin, and suberine and wax biosynthesis". qRT-PCR analysis showed the expression levels of core genes related to KEGG pathways significantly decreased at a temperature difference of 15 ° C. Finally, we constructed a transcriptome mediated network of temperature difference affecting male sterility. CONCLUSIONS: The findings provide important theoretical insights into the correlation between temperature difference and male sterility, providing guidance for the identification and selection of more secure and effective PTMS lines.

Daily routine disruptions and psychiatric symptoms amid COVID-19: a systematic review and meta-analysis of data from 0.9 million individuals in 32 countries.

BACKGROUND: There is currently a deficit of knowledge about how to define, quantify, and measure different aspects of daily routine disruptions amid large-scale disasters like COVID-19, and which psychiatric symptoms were more related to the disruptions. This study aims to conduct a systematic review and meta-analysis on the probable positive associations between daily routine disruptions and mental disorders amid the COVID-19 pandemic and factors that moderated the associations. METHODS: PsycINFO, Web of Science, PubMed, and MEDLINE were systematically searched up to April 2023 (PROSPERO: CRD42023356846). Independent variables included regularity, change in frequency, and change in capability of different daily routines (i.e., physical activity, diet, sleep, social activities, leisure activities, work and studies, home activities, smoking, alcohol, combined multiple routines, unspecified generic routines). Dependent variables included symptoms and/or diagnoses of mental disorders (i.e., depression, anxiety, post-traumatic stress disorder, and general psychological distress). RESULTS: Fifty-three eligible studies (51 independent samples, 910,503 respondents) were conducted in five continents. Daily routine disruptions were positively associated with depressive symptoms (r = 0.13, 95% CI = [0.06; 0.20], p < 0.001), anxiety symptoms (r = 0.12, 95% CI = [0.06; 0.17], p < 0.001), and general psychological distress (r = 0.09, 95% CI = [0.02; 0.16], p = 0.02). The routine-symptom associations were significant for physical activity, eating, sleep, and smoking (i.e., type), routines that were defined and assessed on regularity and change in capability (i.e., definition and assessment), and routines that were not internet-based. While the positive associations remained consistent across different sociodemographics, they were stronger in geo-temporal contexts with greater pandemic severity, lower governmental economic support, and when the routine-symptom link was examined prospectively. CONCLUSIONS: This is one of the first meta-analytic evidence to show the positive association between daily routine disruptions and symptoms of mental disorders among large populations as COVID-19 dynamically unfolded across different geo-temporal contexts. Our findings highlight the priority of behavioral adjustment for enhancing population mental health in future large-scale disasters like COVID-19.

The experience of albinism in France: a qualitative study on dyads of parents and their adult child with albinism.

BACKGROUND: To date, almost no research on the psychosocial implications of albinism has been conducted in France and an exploration of albinism-related experiences could be beneficial, in order to better understand this condition. The aim of this study was to examine how French people with albinism and their parents live with and adapt to this condition in all the areas of their lives. METHODS: Semi-structured phone interviews were conducted with 9 parent-child dyads, each participating separately. Participants were recruited by convenience sampling, thanks to the combined efforts of a patient association (Genespoir) and professionals from the partner medical referral centers involved in the project. Dyads in which the individual with albinism had any comorbidity were excluded. The interviews were then transcribed and subjected to in-depth thematic analysis. Two codebooks were constructed in a mirrored process: one for people with albinism; the other for their parents. They were finally merged at the end of the coding step. RESULTS: Four main categories were identified: personal perceptions and social representations of albinism, difficulties and obstacles encountered by people with albinism, resources and facilitators, and the importance of parent-child functioning. The results indicated that experiences of stigmatization during childhood and adolescence are common and that people with albinism face challenges in adapting to certain obstacles related to their visual impairments (VI) (e.g., inability to drive a car; eye strain...). Parents emerged as one, if not as the main, source of support for people with albinism throughout their development. Although external support systems exist to assist them in various aspects of their lives, some of them primarily rely on their own personal resources to cope. CONCLUSIONS: This research highlights the importance of a systemic and transdisciplinary approach to make sure families receive the support that best meets their needs.