Functional Trajectories Research Articles

A prognostic model for predicting functional impairment in youth mental health services.

Functional impairment is a major concern among those presenting to youth mental health services and can have a profound impact on long-term outcomes. Early recognition and prevention for those at risk of functional impairment is essential to guide effective youth mental health care. Yet, identifying those at risk is challenging and impacts the appropriate allocation of indicated prevention and early intervention strategies. We developed a prognostic model to predict a young person's social and occupational functional impairment trajectory over 3 months. The sample included 718 young people (12-25years) engaged in youth mental health care. A Bayesian random effects model was designed using demographic and clinical factors and model performance was evaluated on held-out test data via 5-fold cross-validation. Eight factors were identified as the optimal set for prediction: employment, education, or training status; self-harm; psychotic-like experiences; physical health comorbidity; childhood-onset syndrome; illness type; clinical stage; and circadian disturbances. The model had an acceptable area under the curve (AUC) of 0.70 (95% CI, 0.56-0.81) overall, indicating its utility for predicting functional impairment over 3 months. For those with good baseline functioning, it showed excellent performance (AUC=0.80, 0.67-0.79) for identifying individuals at risk of deterioration. We developed and validated a prognostic model for youth mental health services to predict functional impairment trajectories over a 3-month period. This model serves as a foundation for further tool development and demonstrates its potential to guide indicated prevention and early intervention for enhancing functional outcomes or preventing functional decline.

Functional Impairment Related to ADHD From Preschool to School Age.

Children with ADHD often experience functional impairments across various aspects of daily life. This study addresses the dearth of longitudinal research on functional impairment trajectories from preschool to school age in children with symptoms of ADHD and comorbid disorders. We investigated the extent to which functional impairments were associated with ADHD symptoms, along with behavioral and anxiety symptoms, from age 3.5 to 8 years. Utilizing parent- and teacher-reported data, we analyzed associations between global impairment, and dimension scores (e.g., family; child quality of life (QoL); learning; play/leisure activities; and friends) and symptoms at ages 3.5 and 8 years (n = 783). The mean parent global impairment score increased from 0.31 (standard deviation (SD) = 0.40) to 0.83 (SD = 0.63) from 3.5 to 8 years, while the teacher impairment scores slightly decreased. Specific parent impairment dimension scores, particularly QoL, learning, and friends, significantly increased. Preschool ADHD and comorbid behavioral symptoms reported by parents weakly predicted impairment at 8 years. By age 8 years, impairment and symptoms exhibited moderate to strong correlations for all impairment dimensions. Parents reported greater child impairment during school age across settings compared to preschool, while teachers' impairment profiles remained consistent across ages. These findings suggest that parents perceive impairment as more pronounced at age 8 years and more strongly associated with symptoms of both ADHD and comorbid disorders than at age 3.5 years. Notably, for teachers, a robust correlation between inattention symptoms and learning impairment was observed, with substantially higher impairment scores reported for boys compared to girls.

Association between renal function trajectories and risk of cardiovascular disease: a prospective cohort study

Introduction It is unclear whether changing trajectories of renal function will increase the risk prediction information of cardiovascular disease (CVD). This study aimed to evaluate the trajectory patterns of estimated glomerular filtration rate (eGFR) and the association between eGFR trajectories and CVD risk. Methods A total of 4742 participants were included in the cohort from the 51st Regiment of Xinjiang Production and Construction Corps. The study endpoint was the occurrence of CVD events. eGFR trajectories were identified using a linear mixed-effects model in four distinct patterns. Multivariate Cox proportional hazards models analysed the correlations between eGFR trajectories and CVD. Results During a median follow-up period of 5.7 years, a total of 559 (11.8%) CVD, 404 (8.5%) myocardial infarction (MI), 244 (5.2%) ischemic stroke (IS), and 62 (1.3%) heart failure (HF) incidents occurred. After multivariable adjustment, gradual decline trajectory increased the risk of CVD (HR 1.42, 95% CI 1.16–1.74), MI (HR 1.41, 95% CI 1.11–1.79), and IS (HR 1.41, 95% CI 1.04–1.92); gradual increase trajectory reduced the risk of CVD (HR 0.40, 95% CI 0.25–0.64) and MI (HR 0.49, 95% CI 0.29–0.81). Consistent results were obtained in sensitivity and subgroup analyses. Conclusions Decline and increase of renal function were related to the risk of CVD, MI, and IS in the rural areas of Xinjiang. Monitoring eGFR changing trajectory is of great significance in improving the risk of CVD.

Integrated Whole-Life Cycle Accuracy Valvular Heart Disease Epidemiology Cohort Study (iWAVE): protocol for a prospective cohort study

IntroductionDespite the rapid advancements in cardiovascular surgery in China, the prevalence of valvular heart disease (VHD) continues to rise, particularly among the elderly population. In the resource-constrained western regions, the...

Beyond out-of-sample: robust and generalizable multivariate neuroanatomical patterns of psychiatric problems in youth.

Mapping differential brain structures for psychiatric problems has been challenging due to a lack of regional convergence and poor replicability in previous brain-behavior association studies. By leveraging two independent large cohorts of neurodevelopment, the ABCD and Generation R Studies (total N = 11271), we implemented an unsupervised machine learning technique with a highly stringent generalizability test to identify reliable brain-behavior associations across diverse domains of child psychiatric problems. Across all psychiatric symptoms measured, one multivariate brain-behavior association was found, reflecting a widespread reduction of cortical surface area correlated with higher child attention problems. Crucially, this association showed marked generalizability across different populations and study protocols, demonstrating potential clinical utility. Moreover, the derived brain dimension score predicted child cognitive and academic functioning three years later and was also associated with polygenic scores for ADHD. Our results indicated that attention problems could be a phenotype for establishing promising multivariate neurobiological prediction models for children across populations. Future studies could extend this investigation into different development periods and examine the predictive values for assessment of functioning, diagnosis, and disease trajectory in clinical samples.

A hierarchical intersection system control framework in mixed traffic conditions

Signalized intersections play a crucial role in urban road system and are a significant source of vehicle delays. Conventional intersection control methods struggle to cope with increasingly challenging traffic conditions. Fortunately, the development of artificial intelligence(AI), information communication technology(ICT) and connected and automated vehicle(CAV) technologies has brought new opportunities to enhance traffic performance at intersections. Based on these technologies, in the mixed traffic environment of CAVs and connected human-driven vehicles (CHVs), this paper proposes a hierarchical intersection system control framework, which adopts intersection level distributed control and corridor level centralized control. At the intersection level, considering the impact of CAV-dedicated lanes and using the CAV platoon and “1 + n” platoon consisting of one leading CAV and n following CHVs as control units, the mixed integer quadratic programming problem and optimal control problem are formulated to collaboratively optimize signal timing, lane settings and vehicle trajectories at isolated signalized intersections. At the corridor level, based on the optimization results of the intersection level and the critical path information, the critical path performance function and multi-stage optimal trajectory control formula are constructed to optimize the signal offsets and vehicle trajectories, which are passed to the intersection level, and ultimately minimize vehicle delays in the corridor. Simulation experiments and sensitivity analysis demonstrate the effectiveness and stability of the proposed framework in reducing vehicle delay and improving fuel consumption.

Immune cells and the trajectories of depression, anxiety, and cognitive function among people with amyotrophic lateral sclerosis

BackgroundAmyotrophic lateral sclerosis (ALS) represents a complex syndrome characterized by motor, psychiatric, and cognitive symptoms, where associations between cellular immune features and non-motor manifestations remain unknown. MethodsIn this cohort study, we enrolled 250 incident people with ALS (pwALS) assessed with the Hospital Anxiety and Depression Scale, and 226 pwALS with the Montreal Cognitive Assessment, including 218 overlapping pwALS. All individuals were diagnosed between January 2015 and January 2023 in Stockholm, Sweden. We applied joint latent class models to delineate distinct trajectories of anxiety, depression, and cognition, incorporating survival outcomes. A majority of the pwALS had data on leukocyte counts and flow cytometric analyses using a comprehensive T cell panel. We then used immune cell subtypes measured at diagnosis to predict trajectories of these outcomes following ALS diagnosis. ResultsWe identified two distinct trajectories for anxiety, depression, and cognitive function following ALS diagnosis. PwALS with longer survival displayed more stable trajectories, while those with shorter survival showed decreasing anxiety symptom, increasing depressive symptom, and declining cognitive function. Higher count of leukocytes at the time of ALS diagnosis tended to associate with anxiety and depression trajectories related to shorter survival. Among T cell subpopulations, several CD8+ T cell subsets were associated with a stable trajectory of depressive symptom, and, in turn, better survival. ConclusionALS-associated psychiatric and cognitive trajectories vary significantly between pwALS with different prognosis. Certain T cell subsets measured at diagnosis might be indicative of depression trajectories post-diagnosis.

Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.

We aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate. OMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or 2 years). OMM metrics were also compared with the standard AUC C-peptide. Percentage changes in CD8+ T memory cell and programmed death-1 (PD-1) expression were evaluated in each group. Baseline metabolic characteristics were similar between 28 placebo- and 39 teplizumab-treated participants. Over 12 months, insulin secretion declined in placebo-treated and rose in teplizumab-treated participants. Within groups, placebo slow-progressors (n=14) maintained insulin secretion and sensitivity, while both declined in placebo rapid-progressors (n=14). Teplizumab slow-progressors (n=28) maintained elevated insulin secretion, while teplizumab rapid-progressors (n=11) experienced mild metabolic decline. Compared with rapid-progressor groups, insulin clearancesignificantlydecreased between baseline and 3, 6 and 12 months in the slow-progressor groups in both treatment arms. In aggregate, both higher baseline insulin secretion (p=0.027) and reduced 12 month insulin clearance (p=0.045) predicted slower progression. A >25% loss of insulin secretion at 3 months had specificity of 0.95 (95% CI 0.86, 1.00) to identify rapid-progressors and correctly classified the 2 year risk for progression in 92% of participants, with a sensitivity of 0.19 (95% CI 0.08, 0.30). OMM-estimated insulin secretion outperformed AUC C-peptide to differentiate groups by treatment or to predict progression. Metabolic changes were paralleled by relative frequency of change in PD-1+ CD8+ T effector memory cells. OMM measures characterise the metabolic heterogeneity in stage 2 diabetes, identifying differences between rapid- and slow-progressors, and heterogeneous impacts of immunotherapy, suggesting the need to account for these differences when designing and interpreting clinical trials.

Abstract 4139170: Relationship between hemodynamics and oxygen consumption in hypertrophic cardiomyopathy during maximal stress testing

Background: Hypertrophic cardiomyopathy (HCM) is a global heart disease with great variability in disease severity, which can lead to significant impairment of exercise capacity. In healthy populations, oxygen consumption is related to cardiac output and arteriovenous oxygen difference. We sought to determine the relationship between hemodynamics (cardiac output and stroke volume) and oxygen consumption in HCM compared to healthy controls during maximal stress testing. Aims: To evaluate associations between the trajectories of hemodynamic function and oxygen consumption in HCM compared to healthy controls. Methods: Twenty individuals with HCM (51±15 years old, body mass index (BMI): 28±3 kg/m 2 , females, n=4) and 16 healthy controls (66±7 years old, 27±6 kg/m 2 , females, n=6) were included in the present study. Participants completed a maximal-graded stress test coupled with non-invasive hemodynamic bioreactance (cardiac output, stroke volume) and gas exchange (oxygen consumption, VO 2 ) measurements. Data were analyzed in quartiles (exercise only) and phases (rest, pre-pedalling, exercise and recovery) of the maximal-graded stress test. Results: In HCM, cardiac output declined in the fourth quartile of the exercise phase of the stress test (-0.39 L/min, p <0.001) whilst VO 2 increased (3.86 ml/kg/min, p <0.001). There was a significant difference in the gradient of cardiac output between HCM and controls in the final quartile of the test (-1.6 vs. 18.1 L/min, p<0.001). In coherence, stroke volume declined in the fourth quartile of the test (-18.4 ml, p <0.01) in response to increasing VO 2 in HCM. The rates of recovery were faster in HCM compared to the control group for VO 2 (-4.3 vs -2.6 mL/second, p<0.001), cardiac output (-0.03 vs -0.02 L/second, p<0.001), heart rate (-0.17 vs -0.10 beats/second, p<0.001), and stroke volume (-0.18 vs -0.07 L/second, p<0.001). Conclusions: In HCM, cardiac output declined during the later stages of maximal stress testing whereas in controls it continued to rise, indicating impaired maximal cardiac output responses to exercise. These findings have implications for exercise prescription and training regimens in HCM suggesting avoidance of maximal exercise levels.

Sexual Function and Satisfaction in Young Women with Breast Cancer: A Five-Year Prospective Study.

Young women with breast cancer (YWBC) face unique challenges that can impact their sexual health. This study aimed to identify factors associated with sexual activity, function, and satisfaction in YWBC up to five years post-diagnosis. We conducted a prospective cohort study of 474 women aged ≤40 years diagnosed with non-metastatic breast cancer in Mexico. Sexual function and satisfaction were assessed using the Female Sexual Function Index and the Sexual Satisfaction Inventory, respectively. Factors associated with sexual health outcomes were examined using mixed-effects models. The prevalence of sexual dysfunction increased from 33.6% at baseline to 52.9% at 4-5 years post-diagnosis. Factors associated with worse sexual function included older age (mean predicted FSFI score -1.35, p = .037), treatment-induced amenorrhea (-2.86, p < .001), depression (-4.11, p < .001), and anxiety (-2.13, p < .001). Lower sexual satisfaction was associated with lower educational attainment (mean predicted SSI score -5.61, p = .002), being single (-6.41, p < .001), treatment induced amenorrhea (-3.76, p = .004), bilateral oophorectomy (-8.21, p = .017), depression (-11.29, p < .001), and anxiety (-7.50, p < .001). Quality of life, body image, and systemic therapy side effects significantly impacted both outcomes. Three distinct trajectories of sexual function were identified: high (62.2%), intermediate (24.3%), and markedly declining (13.5%). Four trajectories of sexual satisfaction were found, ranging from intermediate-to-high (57.3%) to progressively worsening (27.5%). Sexual dysfunction is prevalent and persistent among YWBC. Multiple biological, psychological, and social factors influence sexual health outcomes in this population. These findings highlight the importance of routine screening and tailored interventions to address the sexual health of YWBC throughout survivorship.

Senescence Biomarkers and Trajectories of Frailty and Physical Function After Kidney Transplantation.

Cellular senescence is a biological mechanism of aging and age-related diseases. The aim of this study was to examine whether senescence biomarkers are associated with frailty and physical function trajectories in patients undergoing kidney transplantation (KT). We also discussed the relationship between senescence biomarkers and KT function. In this multicenter study, we prospectively assessed plasma levels of senescence biomarkers, frailty as measured by the Physical Frailty Phenotype, and physical function as measured by the Short Physical Performance Battery prior to KT. Frailty, physical function, and KT function were also measured 1 year after KT. Variable associations were assessed using Cox and relaxed least absolute shrinkage and selection operation regression. The cohort consisted of 197 participants (mean age 53 ±13 years, 61.4% male, and 80.2% White race). Higher pre-KT levels of macrophage-derived chemokine (MDC/CCL22) and growth differentiation factor-15 (GDF-15) were independently associated with less improvement in frailty and/or physical function during the first year after KT. Higher pre-KT levels tumor necrosis factor receptor superfamily member 6 (FAS) and MMP-9 levels were independently associated with lower KT function one year after KT. Pre-KT cellular senescence may contribute to frailty, physical function, and kidney function trajectories during the first year after KT.

A Diathesis-Stress Approach to Understanding Partner Maltreatment Perpetration: A Longitudinal Study.

Despite evidence suggesting that partner maltreatment-a concept which represents a wide array of negative, destructive, and abusive behaviors in romantic relationships-is likely to fluctuate over time, the longitudinal trajectory of partner maltreatment is unclear. This study aims to identify the average trajectory of partner maltreatment over a 5-month period before applying an attachment-informed diathesis-stress framework to explain points of escalation or de-escalation in partner maltreatment perpetration. Two hundred and eight individuals completed 5 monthly assessments of partner maltreatment as well as an assessment of adult attachment and perceived stress at baseline. A nonlinear (i.e., quadratic function) trajectory provided optimal fit for partner maltreatment perpetration over time. An interaction between attachment avoidance and perceived stress predicted the trajectory of partner maltreatment perpetration. Specifically, higher attachment avoidance and higher perceived stress predicted a small initial decline followed by a steep increase in partner maltreatment perpetration. No significant associations were found for the interaction between attachment anxiety and stress and partner maltreatment. The findings suggest that perpetration of partner maltreatment fluctuates over time, and that an attachment-informed diathesis-stress framework can be applied to explain levels of partner maltreatment perpetration and points of escalation and de-escalation over time.

Predictive ability of the Cancer and Aging Research Group chemotherapy toxicity calculator in hematologic malignancy

IntroductionChemotherapy toxicity tools are rarely studied in patients with hematologic malignancy (HM). The primary aim of this pilot study was to determine the predictive ability of the Cancer and Aging Research Group (CARG) chemo-toxicity calculator in estimating grade 3–5 toxicity in patients with HM. Materials and MethodsPatients 60 years and older with HM were prospectively evaluated using the CARG chemo-toxicity calculator. Discrimination and calibration were checked by applying the published model in our data. Additionally, a full geriatric assessment (GA), the Short Physical Performance Battery (SPPB), and health related quality of life (HRQoL) were captured longitudinally at the start of treatment and at end of study. Secondary aims explored the association of GA metrics with chemo-related toxicities and survival. ResultsOne hundred forty-five patients were approached, 118 patients consented, and 97 patients were evaluable. Most patients were newly diagnosed (n = 91). The median CARG score was 9 (range 4–18). The CARG score was not validated in our cohort of older patients with HM, with area under the receiver operation characteristic curve being 0.53 (95 % CI: 0.41–0.65). In multivariable analysis, after controlling for disease type, risk factors associated with grade 3–5 toxicity included living alone (hazard ratio [HR] 4.24, 95 %CI: 2.07–8.68, p < 0.001), increase in body mass index (HR 1.06, 95 %CI: 1.01–1.12, p = 0.03) and a higher social activities score (HR 1.27, 95 %CI: 1.06–1.51, p = 0.01). In multivariable analysis of overall survival, the only prognostic factor was an objective marker of physical function (SPPB score HR = 0.85, 95 %CI:0.78–0.93, p < 0.001). DiscussionThe CARG chemo-toxicity calculator was not predictive of grade 3–5 toxicity in patients with hematologic malignancy. The SPPB was associated with overall survival in multivariable analysis, suggesting future use as an objective biomarker in HM. We also report a comprehensive trajectory of function, QoL, psychosocial well-being, and cognition among older adults with HM. The predictive accuracy of the CARG chemo-toxicity calculator may be affected by the diverse range of HM treatment options that are not traditional chemotherapy.

Lung function trajectories in Common Variable Immunodeficiencies: an observational retrospective multicenter study

Respiratory disease is a frequent cause of morbidity and mortality in Common Variable Immunodeficiencies (CVIDs), however lung function trajectories are poorly understood. To determine lung physiology measurements in CVID, their temporal trajectory and association with clinical and immunological parameters. Retrospective study from 5 Italian centres. CVIDs patients with longitudinal Pulmonary Function Tests (PFTs) measurements and available chest CT scan, were included. Applying the ERS/ATS 2021 standard, PFTs were expressed as percentile value (pct) within the normal distribution of healthy individuals, with the 5th pct identified the lower limit of normal (LLN). The association of lung function with clinical and immunological parameters was investigated. 185 CVIDs patients were included. 64% had at least one lung comorbidity (bronchiectasis 41% and Granulomatous Interstitial Lung Diseases 24%). At first spirometry, the median FEV1 was 3.07 L [IQR 2.40 - 3.80], placing at the 32nd pct [6th-61st], and the median FVC was 3.70 L [3.00 - 4.54], placing at the 29th pct [7th-49th]. 23% of patients had an FEV1 < LLN and 21% had an FVC < LLN. Switched-memory B cells <2% were associated with both FEV1<LLN (OR 7.58) and FVC<LLN (OR 3.55). In 112 patients with at least 5 years of PFT follow-up, we found no significant difference between measured and predicted annual decline of FEV1 (25.6 vs 20.7 mL/year) and FVC (15.6 vs 16.2 mL/year). Our findings suggest that lung volumes of the majority of CVID patients placed in the lower third of normal distribution of healthy individuals. After diagnosis the rate of lung decline was not accelerated.

Lung function trajectories in asthmatic children after the onset of omalizumab

Lung function trajectories in asthmatic children after the onset of omalizumab

Blast Exposure, Tinnitus, Hearing Loss, and Postdeployment Quality of Life in U.S. Veterans: A Longitudinal Analysis.

Examine the association between military blast exposure and functional status among veterans with a focus on functional disability as a proxy for quality of life and explore the potential modifying effect of hearing loss on this association. Prospective cohort. Multi-institutional tertiary referral centers. 540 veterans. Self-reported military blast exposure with and without tinnitus; high-frequency hearing loss (yes/no). WHO Disability Assessment Schedule 2.0 questionnaires at baseline and annually over 5 years. The odds of membership into three functional disability trajectory groups: low functional disability, moderate functional disability, and high functional disability. Of 540 veterans, 197 (36.5%) self-reported a blast exposure history, and 106 of 197 (53.8%) reported tinnitus as a direct result of the blast. Blast exposure without tinnitus increased the odds of moderate functional disability compared with low functional disability (odds ratio [OR] = 1.5; 95% confidence interval [CI], 0.92-2.51), which strengthened among those with blast with tinnitus (OR, 3.6; 95% CI, 2.1-6.1). Blast exposure without tinnitus also increased the odds of membership to high functional disability versus low functional disability (OR, 2.2; 95% CI, 1.1-4.8). Hearing loss further increased the odds of reporting functional disability. The probability of low functional disability was approximately 60% if there was no history of blast or hearing loss, dropping to 20% if there was blast, tinnitus, and hearing loss history. Blast exposure negatively affects the quality of life of veterans, especially when compounded with tinnitus and hearing loss.

Dual group-based trajectories of physical activity and cognitive function in aged over 55: a nationally representative cohort study.

As individuals age, they commonly experience reduced physical activity and cognitive decline. While evidence, there is limited trajectory research on their concurrent progression and interrelation in individuals over 55 years old. The data was collected from 5,765 individuals aged over 55 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2020. Physical activity was measured by IPAQ, cognitive function by episodic memory, and mental intactness score. Separate sets of group-based trajectory models were fitted to identify physical activity trajectories and cognitive function trajectories. Multivariate logistic regression was used to estimate the association between baseline characteristics and each set of trajectories. Group-based dual trajectory modeling (GBDTM) was applied to quantify these associations. GBDTM identified three distinct trajectory groups for physical activity and cognitive outcomes. The physical activity trajectories were classified as "Persistently low physical activity" (74.2%), "Decreasing physical activity" (13.7%), and "Rising physical activity" (12.1%). Similarly, cognitive function trajectories were categorized as "Persistently low cognitive function" (22.2%), "Persistently moderate cognitive function" (37.9%), and "Persistently high cognitive function" (39.9%). Notably, 15.6% of participants followed the trajectories of "Persistently low physical activity" and "Persistently low cognitive function." The presence of a severe decline in physical activity was associated with an increased likelihood of poor cognitive function and vice versa. Age, sex, education, residential status, BMI, and visual impairment were identified as significant predictors for physical activity and cognitive decline. This study found that the GBDTM can determine the consistent trajectories of physical activity and cognitive function trajectories that persistently decline in individuals over 55 years. Analyses of predictive factors can be instrumental in promoting physical activity and delaying cognitive decline.

Developmental Changes in Locomotion and Sensorimotor Reflexes Following Spinal Cord Transection.

The developmental trajectory of weight-bearing locomotion and sensorimotor reflexes following a spinal cord injury, as well as the mechanisms for plasticity, remain unclear. In rats, the second postnatal week is a critical period for the development and recovery of spinal sensorimotor function. The purpose of the present study was to characterize developmental changes during this time frame to provide a basis for potential interventions and future research. Rats underwent a complete low-thoracic (T8-T10) spinal cord transection surgery, or sham procedure, on postnatal day (P)1. Spontaneous locomotion and sensorimotor reflexes (surface righting, hindlimb placing, and crossed-extensor reflex) were tested on P7, P14, or P21. Results show that spinal-transected and sham rats exhibited the same amount of spontaneous locomotion, but the degree of relative weight bearing on the hindlimbs was different between groups and changed over time. Reflex findings showed that throughout the neonatal period, the isolated lumbar spinal cord can respond to sensory input and execute coordinated motor output following spinal cord transection. These insights contribute to understanding the developmental trajectory of spinal cord function after injury and provide a foundation for interventions to enhance recovery outcomes.

Child maltreatment and executive function development throughout adolescence and into young adulthood.

Child maltreatment impacts approximately one in seven children in the United States, leading to adverse outcomes throughout life. Adolescence is a time period critical for the development of executive function, but there is little research examining how abuse and neglect may differently affect the developmental trajectories of executive function throughout adolescence and into young adulthood. In the current study, 167 adolescents participated at six time points from ages 14 to 20. At each time point, adolescents completed behavioral tasks measuring the three dimensions of executive function (working memory, inhibitory control, and cognitive flexibility). Neglect and abuse in early life (ages 1-13) were reported at ages 18-19. Unconditional growth curve models revealed age-related improvement in all three executive function dimensions. Conditional growth curve models tested the prospective effects of recalled neglect and abuse on the developmental trajectories of executive function. The results revealed that neglect was associated with developmental changes in working memory abilities, such that greater levels of neglect during ages 1-13 were associated with slower increases in working memory abilities across ages 14-20. These findings highlight the adverse consequences of early neglect experiences shown by delayed working memory development during adolescence into young adulthood.

Unveiling the prognostic journey: renal function trajectories in 'de novo' heart failure with reduced ejection fraction - insights from a cohort study and their impact on patient outcomes

Abstract Background HFrEF poses significant clinical challenges globally. Renal dysfunction frequently coexists with HF, exacerbating prognosis. However, the dynamic trajectory of renal function in 'de novo' HFrEF patients and its prognostic implications remain understudied. Methods We conducted a prospective cohort study involving 370 'de novo' HFrEF patients. Renal function was initially assessed upon admission and re-evaluated at the end of the titration period. The CKD-EPI formula was used for renal function assessment. Patients were followed up for a median of 15 months. Statistical analyses were performed to evaluate predictors of adverse outcomes. Results Baseline renal function significantly influenced outcomes, with eGFR &amp;lt; 45 ml/min associated with higher mortality and heart failure readmissions. Among patients with available renal function data at discharge (n=354), 87 (24.6%) had eGFR &amp;lt; 45 ml/min, while 267 (72.2%) ≥ 45 ml/min. Patients with eGFR &amp;lt; 45 ml/min exhibited older age, higher prevalence of comorbidities, lower haemoglobin levels, and higher creatinine and NT-proBNP levels, both at admission and discharge. Furthermore, they were less likely to receive certain heart failure medications at discharge. During follow-up, 46 deaths (13.0%) and 105 events of combined all-cause death and readmission due to heart failure (29.6%) occurred. Patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.29, p &amp;lt; 0.001) and all-cause death and heart failure readmissions (HR: 0.32, p &amp;lt; 0.001) both in univariate and multivariate analysis (HR: 0.63, p = 0.028 for mortality; HR: 0.53, p = 0.038 for combined endpoint). See Figure 1. Among patients with available renal function data at follow-up (n=304), 240 (78.9%) had eGFR ≥ 45 ml/min (stabilization or improvement), and 64 (21.1%) had eGFR &amp;lt; 45 ml/min (deterioration or previously &amp;lt; 45 ml/min). Patients with eGFR &amp;lt; 45 ml/min at follow-up exhibited older age, lower BMI, higher prevalence of comorbidities, lower haemoglobin levels, and higher NTproBNP levels at admission and discharge. They were also less likely to receive certain crucial heart failure medications at discharge and follow-up (Table 1). During follow-up, 31 deaths (10.1%) and 87 events of combined death and readmission due to heart failure (38.6%) occurred. In univariate analysis, patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.27, p &amp;lt; 0.001) and admissions (HR: 0.30, p &amp;lt; 0.001), which remained significant in multivariate analysis (HR: 0.43, p = 0.048 for mortality; HR: 46, p = 0.014 for admissions). See Figure 1. Conclusion Our findings underscore the importance of integrated heart-kidney care in 'de novo' HFrEF patients. Continuous monitoring of renal function and interventions to prevent deterioration are crucial for optimizing outcomes. Further research is needed to validate these findings and explore targeted therapeutic strategies for renal protection in HFrEF.