Impaired Performance Research Articles

Night Shift Work and Sleep Experiences in Older Night Shift Nurses

Background: Working at night leads to misalignment between the biological clock and the work/sleep schedule, resulting in sleepiness and impaired performance during the night shift and poor quality, shortened sleep during the day; this is greatly impaired in older individuals. Objective: To describe night work and sleep experiences from the perspective of older (aged 50-65) nurses. Methods: Seven virtual focus groups were formed comprising 19 older nurses who worked regular 8-hour night shifts (at least 6 consecutive hours between midnight and 6 am) to learn about their shift work and sleep experiences. Two facilitators and 2 research assistants independently reviewed and coded the transcripts using qualitative content analysis. Results: Nine themes were identified in 3 domains: (a) night shift challenges and difficulties, including first night shift is most difficult; never feel rested working nights; and personal health concerns and benefits from working nights; (b) sleep challenges and difficulties, including inconsistent sleep timing when switching between nights and days; extended (24+ hours) time awake before and after consecutive nights; difficulty maintaining long and sound daytime sleep; and napping before night shifts for better performance; and (c) family and social challenges and support, including childcare, family, personal obligations, and social activities affect sleep; aging of self and children influences sleep and prioritization of sleep. Conclusions: The findings help understand challenges and struggles to obtain adequate sleep and safe work performance in older night shift nurses. These insignts are critical for designing and implementing feasible and acceptable interventions to improve sleep in this high-risk occupational group.

No effect of grape juice on exercise-induced muscle damage or performance in male runners: a randomized, placebo-controlled, triple-blind clinical trial

This study aimed to verify the effect of grape juice (Vitis Labrusca) intake on exercise-induced muscle damage (EIMD) and exercise performance parameters (5-km running time-trial [TT], running economy, and countermovement jump [CMJ]). Twenty trained male runners were randomized into two blinded groups and consumed either placebo (n=9) or grape juice (n=11) for six consecutive days (600 mL/day). On the fourth day, the participants performed a downhill running (-15%) at speed that elicited 70% V̇O2max for 20 minutes, to induce muscle damage, followed by assessment of running economy, 5-km TT, and CMJ tests. Blood samples were obtained before and after the exercise tests for quantifying total phenols, creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). On the sixth day, blood parameters and CMJ were evaluated. A two-way ANCOVA mixed model was employed for data analysis, the effects were the juice groups, measurement and a interaction between the factors. EIMD was confirmed by increased levels of indirect markers (serum AST and LDH activities) and an impairment in TT and CMJ performances after 48 hours. The 5-km TT, economy, and CMJ were compromised after EIMD, to a similar extent in the groups. Blood concentrations of CK, LDH, AST, and total phenolic compounds presented similar time course behavior between the groups, showing no group × time interaction effects. In conclusion, grape juice consumption over six days did not attenuate EIMD markers or the impairment in running performance in trained male runners. (ReBEC number: RBR-9jkkvbb).

Abstract 4121348: Impairments in Left Atrioventricular Coupling Underpins Reductions in Skeletal Muscle Mass and Function in Ageing Older Adults

Background: Age-related cardiovascular disease (CVD) may manifest with changes in left ventricular (LV) systolic or left atrial (LA) dysfunction. Alterations in functional performance between the LV and LA chambers characterized by LA-LV coupling may be a sensitive marker representative of impairments in global cardiac performance, compared to either chamber alone. The increasing relevance of skeletal muscle function towards cardiac health in ageing, motivated our current work that investigated associations between skeletal muscle function and LA-LV coupling. Aim : Using advanced cardiac magnetic resonance (CMR) that characterizes cardiac volumetric parameters and strain functions, we determined the association between handgrip strength (HGS) and appendicular lean mass (ALM) with left atrioventricular coupling index (LACI). Methods: Community older adults without CVD underwent simultaneous assessment of HGS by hand dynamometer, height-square adjusted ALM by bio-impedance, and LA phasic function (namely reservoir, conduit, booster strain) as well as LA and LV volumetric parameters by CMR feature tracking. LACI is defined as the ratio of the ratio of LA to LV end-diastolic volumes. We performed linear regression and multivariable logistic regression to examine the relationship between HGS/ALM and LACI. Results: Among 251 study participants (mean age: 71 ± 9.1 years, female 44.7%), 149 (59%) had impaired LACI. HGS was linearly associated with LACI (β=-0.004, p=0.003) and LVEDV (β=1.62, p<0.0001), and ALM was linearly associated with LA volume (β=0.55, p=0.018) and LVEDV (β=3.45, p<0.0001) (Figure.1). Participants with impaired LACI (> 25%) had lower HGS (mean=22.8 ± 7.1 kg vs 26.1 ± 6.4 kg, p= 0.0002), lower ALM (16.4 ± 4.2 kg/m2 vs 17.7 ± 3.8 kg/m2, p=0.014), higher LA volume (36.8 ± 15.2 ml vs 22.0 ± 5.5 ml, p < 0.0001) and lower LV end-diastolic volume (101.0 ± 24.2 ml vs 111.9 ± 27.3 ml, p = 0.0011). The association between impaired LA-LV coupling and lower HGS (β=-0.0647, 95%CI -0.0255, -0.1040, p=0.001) and lower ALM (β=-0.0776, 95%CI -0.0107, -0.1444, p=0.011) persisted after adjusting for age. Conclusion: Reduced HGS and ALM among community-dwelling older adults was associated with impaired LA-LV coupling suggestive of underlying early-stage LA remodelling and impairments in left atrioventricular compliance. Detection of reduced HGS and ALM in community cohorts may prompt early identification of older adults at risk of dysfunctional cardiac aging.

Abstract 4141469: Left Ventricular Septum Displacement Implications in the Limited Cardiac Reserve, RV to Pc Uncoupling and Oxygen Uptake During Exercise in Heart Failure

Background: Dyspnea on exertion is cardinal symptom in heart failure (HF) and may be caused by an unfavorable dynamic of ventricular interaction. This concept has been poorly addressed over time and we hypothesized that a careful study of the interventricular septum adaptations during maximal exercise in HF might be implicated in the limited cardiac reserve and uncoupling of right ventricular (RV) to pulmonary circulation (Pc), both yielding to a limited O2 uptake. Aim: To study the pathophysiology behind biventricular interaction during exercise in HF, evaluating the role of septum displacement during exercise and how and whether it would affect peak exercise oxygen consumption (VO 2 peak) through a limited cardiac output (CO) increase and some degrees of RV to PC uncoupling assessed by TAPSE/PASP. Methods: 22 HF performed a combined cardiopulmonary exercise testing imaging (CPET imaging) with RV 3D-imaging analysis and were compared with a control population. 3D imaging of the RV chamber was examined off-line using the 4D RV TomTec software and obtained 3D mesh of the RV model using custom software to obtain the mean curvature value of IVS in 4 regions of: inflow tract (RVIT), outflow tract (RVOT), apical and body. We acquired measurements of curvature during end-diastole (ED) and at end systole (ES) phases and obtained a parametric curvature map. Results: HF patients (mean age 72±12, 27% female) typically showed an abnormal septal curve, with a more leftward configuration either at rest and under exercise (rest =−0.01±0.007 at ED, and −0.01±0.009 at ES; peak exercise= −0.01±0.006 at ED, and −0.01±0.007 at ES) compared to controls (rest=−0.02±0.002 at ED, and −0.02±0.006 at ES; peak exercise −0.02±0.0.006 at ED, and −0.02±0.01 at ES, Figure). Notably, the degree of the IVS curvature showed a linear correlation with an impaired gas exchange performance as indicated by a lower peak VO 2 , a limited CO and impairment of TAPSE/PASP in HF (respectively, r=0.64, p<0.001, r=0.5, p<0.001, r=0.53, p<0.001 at ED during exercise; r=0.61, p<0.001 at ES during exercise; Figure). Conclusions: In HF, the evidence of right to left IVS displacement appears worth of investigation, by intervening strictly to a reduced CO response, and RV-PA uncoupling during exercise. These findings clearly point to the utility of assessing how new and current therapeutic strategies may modulate the negative septum displacement and overall cardiac mechanics.

Abstract 4137985: Impaired Skeletal Muscle Condition and Stroke Volume Reserve Characterize Poor Exercise Performance in Childhood Cancer Survivors

Background: Childhood cancer survivors (CCS) frequently show poor exercise performance, but its pathophysiology and clinical significance are poorly understood. Methods: Poor exercise performers, defined as peak oxygen consumption (VO2)/kg < 80% of predicted maximum VO2/kg, were enrolled, including 40 CCS (20 males, 20 females) and 32 controls (15 males, 17 females) from 79 CCS and 147 age-matched controls, respectively. Peak and submaximal CPET parameters were compared between CCS and controls with poor exercise performance. Submaximal slope parameters represent a trend up to anaerobic threshold (AT). Results: Ages and anthropometric measurements (weight, height, and body mass index) were comparable between CCS and controls in both sexes (Table 1). Both resting and peak heart rate (HR) were significantly higher in CCS than in controls in males. There was no significant difference in peak VO2/kg, peak oxygen pulse (OP)/kg, peak respiratory exchange ratio, or VO2/kg at AT (VAT/kg) between CCS and controls in both sexes. Peak work rate (WR/kg) was significantly lower in CCS compared with that in controls in both sexes, suggesting reduced muscle strength in CCS. Figure 1 demonstrates decreased muscle mass/strength in CCS than in controls. In males, Δ[VO2/kg]/ ΔHR was significantly lower in CCS than in controls, indicating limited stroke volume reserve (SVR) in male CCS. In female, although there was no significant difference in Δ[VO2/kg]/ΔHR between CCS and controls, HR-dependency expressed by ΔHR/Δ[WR/kg] was significantly higher in CCS than in controls, suggesting impaired SVR. ΔVO2/ΔWR, a marker for physical conditioning, was comparable between CCS and controls in both sexes. Conclusions: Poor exercise performance in CCS is characterized mainly by decreased muscle mass/strength and impaired SVR for both sexs. Impaired SVR may be an early sign of subclinical cardiotoxicity. Poor exercise performance in CCS should be improved to prevent future cardiovascular complications.

Abstract 4134685: Cardiopulmonary Exercise Testing for Characterization and Prognostication in Hypertrophic Cardiomyopathy: A Meta-Analysis

Background: Hypertrophic cardiomyopathy (HCM) carries substantial risk of adverse cardiac events. Consequently, detailed physiologic assessment and accurate risk stratification in HCM are of high clinical importance. Aim: To synthesize current evidence on the utility of cardiopulmonary exercise testing (CPET) for characterization and prognostication of HCM. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched for eligible studies from database inception to November 2023. Studies that had at least one CPET performed in HCM patients, with corresponding test data reported, were included. Abstracts with no full-text and studies focused on pediatric populations were excluded. The primary outcome was a composite endpoint of cardiovascular adverse events. Hazard ratios (HR) and 95% confidence interval (CI) from Cox proportional hazard model were meta-analyzed. This study was performed following the PRISMA guidelines and registered under PROSPERO (CRD42023487759). Results: Sixty full-length manuscripts focused on CPETs performed in HCM patients were included, comprising 12,914 patients. Despite male predominance (66%) and average age of 48 years, peak VO 2 was only 6.2 [95% CI, 6.0-6.4] metabolic equivalents (21.8 [20.9-22.6] mL/kg/min), consistent with significant functional limitation. In subanalyses, peak VO 2 was 18.9 [18.0-19.9] mL/kg/min in obstructive HCM and 22.5 [20.8-24.2] mL/kg/min in non-obstructive HCM. Compared to commonly used metrics such as NYHA Class, CPET markedly enhances sensitivity to detect impaired cardiac performance ( Figure ). This meta-analysis highlights several easily-derived CPET variables that consistently predict HCM prognosis. An increase of 1 mL/kg/min in peak VO 2 was associated with a lower HR of 0.83 [0.76-0.90] for adverse cardiac events, while a 1 unit increase in the VE/VCO 2 slope was associated with a higher HR of 1.12 [1.03-1.23]. Abnormal blood pressure response to exercise conferred a 2.5-fold [2.0-3.1] increase in adverse events. Conclusion: CPET is a valuable objective method for multi-dimensional physiologic assessment and prognostication in HCM. With further standardization, CPET is well suited for more widespread clinical utilization in HCM patients.

Acute responses to a potentiation warm-up protocol on sprint and change of direction in female football players: a randomized controlled study

Abstract Objectives To evaluate the acute effect of exposure to a potentiation warm-up protocol compared to a usual warm-up program. Design Randomized parallel control trial. Setting Synthetic grass in the club’s facilities (Portugal). Participants Seventeen female football players (age: 23.9 ± 3.9 years), were randomly allocated to a control (n = 8) and an experimental group (n = 9). To allocate the players, a table was computer-generated by a research team member with no involvement in the trial. Intervention The control group performed their usual warm-up program, while the experimental group performed a potentiation warm-up protocol with jumps combined with sprints with change of direction. Main outcomes measures The players were tested pre- and post-intervention for a 40-m linear sprint and pre-planned change of direction using the T-test. Statistical analysis An intention-to-treat analysis was performed, with all the participants originally randomized being involved. The normal distribution was verified by the Shapiro-Wilk test. The assumption of sphericity was analyzed. Effect sizes were calculated using partial eta squared. Results No significant pre-post differences in the T-test and in the 40-m sprint were detected for any group. However, in the T-test, large effect sizes in time increments were observed within the experimental (0.27 s; p > 0.05, ηp2 = 0.176) and control groups (0.06 s; p > 0.05, ηp2 = 0.176). Also, in the 40-m sprint, large effect sizes in time increments were observed within the experimental (0.05 s; p > 0.05, ηp2 = 0.251) and control groups (0.09 s; p > 0.05, ηp2 = 0.251). Conclusions The performance-enhancing ability of the potentiation method performed at warm-up was not verified when applied to female football players. Thus, the potentiation methods may not improve sprint and COD ability for this population. However, the lack of statistical significance may have been due to reduced statistical power, as three of four effects suggest acute performance impairment after a supposed potentiation-oriented warm-up. Nevertheless, the presence of a statistical type 2 error cannot be ruled out. Registration number (retrospectively registered) NCT06555185; Project URL: https://clinicaltrials.gov/study/NCT06555185.

A Socio-Ecological Approach to Work Performance: A pilot study among Workers with Chronic Skin Diseases

Abstract Objectives Chronic skin diseases (CSD) may lead to productivity losses. This mixed-methods study investigated symptom severity, social challenges, need for workplace accommodation, sick leave and their association with perceived impaired work performance (IWP) among workers with CSD. Methods Data were collected from April to June 2023. Participants (n = 102) completed an online questionnaire sent from the Institute for Occupational Safety and Hygiene and almost 20% were interviewed. The analyses included logistic regression and structural equation models and a thematic analysis. Results Of participants, 72.3% reported perceived IWP. The need for workplace accommodation and sick leave duration were directly associated with IWP. These findings were integrated with common themes based on a socioecological approach. Conclusions By working together to address personal, interpersonal, organizational, and societal aspects associated with CSD, occupational physicians and stakeholders can alleviate perceived IWP.

A new era for stress research: supporting user performance and experience in the digital age

Stress is both a driver of objective performance impairments and a source of negative user experience of technology. This review addresses future directions for research on stress and ergonomics in the digital age. The review is structured around three levels of analysis. At the individual user level, stress is elicited by novel technologies and tasks including interaction with AI and robots, working in Virtual Reality, and operating autonomous vehicles. At the organisational level, novel, potentially stressful challenges include maintaining cybersecurity, surveillance and monitoring of employees supported by technology, and addressing bias and discrimination in the workplace. At the sociocultural level, technology, values and norms are evolving symbiotically, raising novel demands illustrated with respect to interactions with social media and new ethical challenges. We also briefly review the promise of neuroergonomics and emotional design to support stress mitigation. We conclude with seven high-level principles that may guide future work.

Morbidität und Mortalität nach NSCLC-Operationen bei älteren Patienten: Individualisierte Risikobewertung notwendig

Background: Reports from case series suggest that operative outcomes are comparable amongst different age groups following surgery with curative intent for non-small cell lung cancer (NSCLC). The purpose of this study was to compare morbidity and mortality after NSCLC surgery in older patients (≥ 75 years) versus younger patients (< 75 years) and identify independent predictive risk factors. Methods: We identified 2015 patients with postoperative stages IA to IIIA according to AJCC/UICC 7th edition who had undergone NSCLC surgery with curative intent at a single specialized lung cancer center from January 2010 to December 2015. A matched-pair analysis was performed on 227 older patients and corresponding 227 younger patients. Short-term surgical outcomes were postoperative morbidity, length of hospital stay, 30-day and 90-day mortality. Long-term operative outcomes were disease-free and overall survival. Results: 454 patients were included in the matched-pair analysis. 36% of younger patients developed postoperative complications versus 42% in older patients (p = 0.163). Age was not significantly associated with the occurrence of postoperative complications. Median length of hospital stay was 14 days in older patients and 13 days in younger patients (p = 0.185). 90-day mortality was 2.2% in younger patients compared to 4% in older patients (p = 0.424). In patients aged 75 and older impaired performance status (ECOG ≥ 1) was associated with decreased overall survival (HR = 2.15, CI 1.34–3.46), as were preoperative serum C-reactive protein / albumin ratio ≥ 0.3 (HR = 1.95, CI 1.23–3.11) and elevated preoperative serum creatinine levels ≥ 1.1 mg/dl (HR = 1.84, CI 1.15–2.95). In the younger cohort male sex (HR = 2.26, CI 1.17–4.36), postoperative stage III disease (HR 4.61, CI 2.23–9.54) and preoperative anemia (hemoglobin < 12 g/dl) (HR 2.09, CI 1.10–3.96) were associated with decreased overall survival.

Perceived Negative Menstrual Cycle Symptoms, but not Changes in Estrogen or Progesterone, are Associated with Impaired Cycling Race Performance.

Purpose: To examine the relationship between menstrual cycle (MC) phase-dependent fluctuations of estrogen and progesterone and virtual cycling race performance, with a secondary aim of correlating perceived MC-related symptoms with performance.Methods: In a novel observational study design, thirty-seven female cyclists/triathletes not using any hormonal contraception completed one virtual cycling race [19.5 km time trial (TT)] per week across a one-month period (totaling four races). Participants completed MC characterization and tracking, including urinary ovulation kits, across two complete MCs. Venous blood samples were collected within 21 h of racing to determine serum 17-β-estradiol and progesterone concentrations, as well as an assessment of self-reported, perceived race-day MC and gastrointestinal (GI) symptoms, which were all then correlated to race performance.Results: There was no relationship between race completion time and individual estradiol (r = -0.001, p = 0.992) or progesterone (r = -0.023, p = 0.833) concentrations. There was no difference between race time between MC phases (follicular/luteal, p = 0.238), whether MC bleeding or not bleeding (p = 0.619) and ovulating or not ovulating (p = 0.423). The total number of perceived MC symptoms recorded on race day was positively correlated to increased race time [r = 0.268 (95% CI 0.056 to 0.457), p = 0.014], as was the number of GI symptoms of at least "moderate" severity before the race (r = 0.233 [95% CI 0.021 to 0.425], p = 0.031), but not post-race (r = 0.022, p = 0.841).Conclusions: When implementing a novel, virtual cycling race, fluctuations in ovarian hormone concentrations across the MC do not appear to affect real-world cycling performance among trained cyclists, while perceived negative MC and GI symptoms may relate to impaired performance. Therefore, the management of negative MC and GI symptoms appears important for athletic performance enhancement or to mitigate performance decline.

Comparative Analysis of Two Soybean Cultivars Revealed Tolerance Mechanisms Underlying Soybean Adaptation to Flooding

Flooding stress poses a significant challenge to soybean cultivation, impacting plant growth, development, and ultimately yield. In this study, we investigated the responses of two distinct soybean cultivars: flooding-tolerant Nanxiadou 38 (ND38) and flooding-sensitive Nanxiadou 45 (ND45). To achieve this, healthy seedlings were cultivated with the water surface consistently maintained at 5 cm above the soil surface. Our objective was to elucidate the physiological and molecular adaptations of the two cultivars. Under flooding stress, seedlings of both cultivars exhibited significant dwarfing and a notable decrease in root length. While there were no significant differences in the dry weight of aboveground shoots, the dry weight of underground shoots in ND38 was strikingly decreased following flooding. Additionally, total chlorophyll content decreased significantly following flooding stress, indicating impaired photosynthetic performance of the cultivars. Moreover, malondialdehyde (MDA) levels increased significantly after flooding, particularly in the ND45 cultivar, suggesting heightened oxidative stress. Expression analysis of methylation and demethylation genes indicated that MET1 and DME play crucial roles in response to flooding stress in soybeans. Meanwhile, analysis of the hemoglobin family (GLBs), aquaporin family (AQPs), glycolytic pathway-related genes, and NAC transcription factor-related genes identified GLB1-1 and GLB1-2, GLB2-2, PIP2-6, PIP2-7, TIP2-2, TIP4-1, TIP5-1, Gm02G222400 (fructose-bisphosphate aldolase), Gm19G017200 (glucose-6-phosphate isomerase), and Gm04G213900 (alcohol dehydrogenase 1) as key contributors to flooding tolerance in both soybean cultivars. These findings provide crucial insights into the physiological and molecular mechanisms underlying flooding tolerance in soybeans, which could guide future molecular breeding strategies for the development of flooding-tolerant soybean cultivars.

The cross-sectional and longitudinal associations between fruit intake and cognitive performance: the Chinese Healthy Dance Study

ObjectiveTo analyse the association between fruit consumption and cognitive performance in middle-aged and older adults in China. MethodsParticipants were drawn from the Chinese Square Dance Cohort. The cross-sectional dataset included 4316 individuals, with their first visit from August 2020 to August 2023. The longitudinal dataset included 1465 participants, with their first visit from August 2020 to December 2021 and follow-up visits from August 2022 to December 2023. Fruit consumption was assessed using a food frequency questionnaire. Standardised neuropsychological assessments were used to measure composite z-scores of cognitive performance, and prevalent and incident mild cognitive impairment. ResultsIn the cross-sectional analysis, higher quartiles of citrus fruit, drupe, berry, and tropical fruit consumption were associated with higher composite z-scores for cognitive performance and lower odds of prevalent mild cognitive impairment. In the longitudinal analysis, there was a positive association between higher quartiles of citrus fruit intake and the annual rate of change in the composite z-scores for cognitive performance; standardised regression coefficient (95 % confidence interval) for the highest compared with the lowest quartile was 0.05 (0.02–0.08). Moreover, an association between higher quartiles of citrus fruit intake and a lower risk of incident mild cognitive impairment was detected; in the comparison of the highest with the lowest quartile, the risk ratio (95 % confidence interval) was 0.56 (0.36–0.88). ConclusionsThe relationship between fruit consumption and cognition varies across the different categories of fruit. Cognitive benefits of citrus fruit consumption were found for middle-aged and older adults. Ascertaining this association might enhance comprehensive dietary recommendations for fruit consumption.

Exploring geriatric assessment-driven rehabilitation referral patterns and its influence on functional outcomes and survival in older adults with advanced cancer.

Older adults with advanced cancer experience functional disability that warrants rehabilitation services; however, evidence indicates inconsistencies in referral. The purpose was to (1) identify predictors of geriatric assessment (GA)-driven referrals to rehabilitation services and (2) explore associations between referral and change in function, health-related quality of life (HRQoL), and overall survival among older adults with advanced cancer. This was a secondary analysis (NCT020107443, UG1CA189961) of a nationwide GA clinical trial. Patients were older adults with advanced cancer who had at least one GA-defined physical performance or functional status impairment. Primary outcomes were oncologist-initiated discussion about or referral to rehabilitation services after the GA (Aim 1) and decline in activities of daily living (ADL), Instrumental ADL (IADL), and HRQoL within 3 months, and overall survival at 1 year (Exploratory Aims). Analyses included multivariable logistic regression and Cox proportional hazards models. Demographic and clinical factors were controlled for by using 1:1 propensity score matching. In total 265 patients were analyzed. After adjustment, impaired cognition (odds ratio [OR] = 2.25, p = 0.01), Karnofsky score indicating disability (OR = 2.86, p < 0.01), and receipt of monoclonal antibodies (OR = 1.95, p = 0.04) were associated with higher odds of referral. In contrast, polypharmacy was associated with lower odds of referral (OR = 0.31, p < 0.01). Referred patients were less likely to decline in ADL (OR 0.30, p = 0.07) and IADL (OR 0.64, p = 0.35), but more likely to decline in HRQoL (OR 1.20, p = 0.67) and have worse survival (HR 1.18, p = 0.62). Cancer treatment, polypharmacy, cognition, and disability status likely influence oncologists' decision to refer for rehabilitation. Referral was not independently associated with change in functional disability, HRQoL, or survival. Future studies should evaluate patients' utilization of rehabilitation services post-referral and determine whether dose/timing of rehabilitation services influence clinical outcomes.

Speech perception and language comprehension in primary progressive aphasia

Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive loss of speech and language. Although speech perception and language comprehension deficits are observed in individuals with PPA, these deficits have been understudied relative to production deficits. Recent work has examined receptive language processing at sublexical, lexical, and semantic levels in PPA; however, systematic investigation of these levels of processing within a single PPA cohort is lacking. The current study sought to fill this gap. Individuals with logopenic, nonfluent, and semantic variants of PPA and healthy, age-matched controls completed minimal pairs syllable discrimination, auditory lexical decision, and picture-word verification tasks to assess sublexical, lexical, and semantic processing. Distinct profiles were observed across PPA variants. Individuals with logopenic variant PPA had impaired performance on auditory lexical decision and picture-word verification tasks, with a trend toward impaired performance on the syllable discrimination task. Individuals with nonfluent and semantic variant PPA had impaired performance only on auditory lexical decision and picture-word verification. Evaluation of the types of errors made on the picture-word verification task (phonological and semantic) provided further insight into levels of deficits across the variants. Overall, the results indicate deficits in receptive processing at the lexical-phonological, lexical-semantic, and semantic levels in logopenic variant PPA, with a trend toward impaired sublexical processing. Deficits were observed at the lexical-semantic and semantic levels in semantic variant PPA, and lexical-phonological deficits were observed in nonfluent PPA, likely reflecting changes both in lexical-phonological processing as well as changes in predictive coding during perception. This study provides a more precise characterization of the linguistic profile of each PPA subtype for speech perception and language comprehension. The constellation of deficits observed in each PPA subtype holds promise for differential diagnosis and for informing models of intervention.

Investigating the Significance of the Transgenerational Impact of High and Repeated Doses of Ivermectin: Effects on Paternal Testis Histopathology, Pups' Development, and Sexual Behavior

Paternal exposure to environmental challenges is critical for the offspring's future health, and the transmission of acquired traits through generations increases the risk of offspring developing diseases. Ivermectin (IVM) is widely used in veterinary and human medicine to treat parasitosis. Our previous studies showed that IVM acute administration induced disorganization of the germinal epithelium and could cause damage to sperm production. Thus, this study investigated the effects of paternal exposure to repeated high ivermectin doses on paternal testis histology. After mating, their pups' development and sexual behavior in adult rats were examined. Method: Two groups of male rats were treated with IVM or its vehicle once a week for three weeks. We observed these males' body weight, organs and testis histology, and testosterone levels. These rats were mated with females without any treatment: the reproductive performance, the offspring development, and the male and female sexual behavior observed in adulthood. Relative to controls, the IVM paternal testis histology showed hypertrophy and hyperplasia of Leydig cells and increased diameter of the seminiferous tubules—no impairment in reproductive performance. In males and females, the physical and reflexes were modified. In adult age, female rats of the IVM group showed reduced sexual behavior and sexual preferences for the same sex, while male sexual behavior was not altered. Thus, it is possible that paternal exposure to IVM interfered with pups' hormonal and growth factors during development and in adult age. Further studies are needed to explore IVM transgenerational effects identifying possible mechanisms underpinning behavioral effects.

An Adverse Outcome Pathway Approach Linking Retinoid Signaling Disruption to Teratogenicity and Population-Level Outcomes

Recent research efforts in endocrine disruption have focused on evaluating non-EATS (estrogen, androgen, thyroid, and steroidogenesis) pathways. Retinoid signaling disruption is noteworthy because of its teratogenic effects and environmental relevance. However, current environmental risk assessments are limited in their ability to evaluate impacts on individuals and populations. This study characterizes an Adverse Outcome Pathway (AOP) network linking retinoid signaling disruption to teratogenicity and survival in zebrafish. We identified Retinoic Acid Receptor (RAR) overactivation as the molecular initiating event leading to key events including craniofacial (CFM) and tail (TM) malformations, posterior swim bladder (SB) non-inflation, impaired swimming performance, and reduced feeding, ultimately resulting in decreased survival. Our study (1) determines critical sensitivity windows for CFM, posterior SB non-inflation, and TM, (2) provides quantitative measurements for CFM and TM, and (3) defines impacts on higher biological levels including food ingestion, swimming, and survival. Results show that all-trans retinoic acid (ATRA) induces strong teratogenic effects with sensitivity windows between 4-48 hours post fertilization (hpf) for CFM, TM, and posterior SB non-inflation. TM is the most sensitive indicator, with EC50 of 0.2 - 0.26 µg/L across exposure windows 4-48, 4-72, 4-96, and 4-120 hpf. Besides inducing known malformations, ATRA impaired posterior SB inflation with EC50 of 1 - 1.21 µg/L across the same exposure windows. ATRA exposure (1 µg/L) resulted in 50% food ingestion inhibition at 7 days post fertilization (dpf) and 10% survival at 14 dpf. This study provides a regulatory-relevant framework linking developmental effects to population outcomes, highlighting ecological risks and needs for improved risk assessments.

Using machine learning to derive neurobiological subtypes of general psychopathology in late childhood.

Traditional mental health diagnoses rely on symptom-based classifications. Yet this approach can oversimplify clinical presentations as diagnoses often do not adequately map onto neurobiological features. Alternatively, our study used structural imaging data and a semisupervised machine learning technique, heterogeneity through discriminative analysis, to identify neurobiological subtypes in 9- to 10-year-olds with high psychopathology endorsements (n = 9,027). Our model revealed two stable neurobiological subtypes (adjusted Rand index = 0.38). Subtype 1 showed smaller structural properties, elevated conduct problems and attention-deficit/hyperactivity disorder symptoms, and impaired cognitive performance compared to Subtype 2 and typically developing youth. Subtype 2 had larger structural properties, cognitive abilities comparable to typically developing youth, and elevated internalizing symptoms relative to Subtype 1 and typically developing youth. These subtypes remained stable in their neurobiological characteristics, cognitive ability, and associated psychopathology traits over time. Taken together, our data-driven approach uncovered evidence of neural heterogeneity as demonstrated by structural patterns that map onto divergent profiles of psychopathology symptoms and cognitive performance in youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The retrosplenial cortical role in delayed spatial alternation

The retrosplenial cortex (RSC) plays an important role in spatial cognition. RSC neurons exhibit a variety of spatial firing patterns and lesion studies have found that the RSC is necessary for spatial working memory tasks. However, little is known about how RSC neurons might encode spatial memory during a delay period. In the present study, we trained control rats and rats with excitotoxic lesions of the RSC on spatial alternation task with varying delay durations and in a separate group of rats, we recorded RSC neuronal activity as the rats performed the alternation task. We found that RSC lesions significantly impaired alternation performance, particularly at the longest delay duration. We also found that RSC neurons exhibited reliably different firing patterns throughout the delay periods preceding left and right trials, consistent with a working memory signal. These differential firing patterns were absent during the delay periods preceding errors. We also found that many RSC neurons exhibit a large spike in firing rate leading up to the start of the trial. Many of these trial start responses also differentiated left and right trials, suggesting that they could play a role in priming the ‘go left’ or ‘go right’ behavioral responses. Our results suggest that these firing patterns represent critical memory information that underlies the RSC role in spatial working memory.

Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?

Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.