Impaired Brain Research Articles

Brain dysfunction during warming is linked to oxygen limitation in larval zebrafish

Understanding the physiological mechanisms that limit animal thermal tolerance is crucial in predicting how animals will respond to increasingly severe heat waves. Despite their importance for understanding climate change impacts, these mechanisms underlying the upper thermal tolerance limits of animals are largely unknown. It has been hypothesized that the upper thermal tolerance in fish is limited by the thermal tolerance of the brain and is ultimately caused by a global brain depolarization. In this study, we developed methods for measuring the upper thermal limit (CTmax) in larval zebrafish (Danio rerio) with simultaneous recordings of brain activity using GCaMP6s calcium imaging in both free-swimming and agar-embedded fish. We discovered that during warming, CTmax precedes, and is therefore not caused by, a global brain depolarization. Instead, the CTmax coincides with a decline in spontaneous neural activity and a loss of neural response to visual stimuli. By manipulating water oxygen levels both up and down, we found that oxygen availability during heating affects locomotor-related neural activity, the neural response to visual stimuli, and CTmax. Our results suggest that the mechanism limiting the upper thermal tolerance in zebrafish larvae is insufficient oxygen availability causing impaired brain function.

Prenatal and Postnatal Zika Intrauterine Infection: Diagnostic Imaging Techniques and Placental Pathology

Introduction: Zika virus (ZIKV) is an arbovirus (arthropod-borne virus) in the genus Flavivirus and Flaviviridae family. In November 2015, several cases of microcephaly in Northeastern of Brazil suggested ZIKV involvement. Case Report: A 33-year-old primigravida developed fever and cutaneous rash at 7th week of gestation (WGA). The ultrasound and MRI examination showed head circumference < 5th centile and enlargement of lateral ventricles. The infant was delivered at 39th WGA with microcephaly. Microscopy of the placenta showed chronic villitis and intervillitis, nodular stromal fibrosis in the stem villi, and vascular thickening. Postnatal CT showed collapsed cranium due to growth impairment of the suprathalamic brain, multiple cerebral calcifications, parenchymal atrophy, and ventricular dilatation. Now, at 6 years old, the child suffers from severe neurologic symptoms, including seizures. Conclusion: This case gathers images of prenatal and postnatal period, and placental histopathology. The long-term follow-up highlights the dramatic neurological sequelae induced by ZIKV.

Association between maternal oxygenation and brain growth in fetuses with left-sided cardiac obstructive lesions.

Impaired brain growth has been observed in fetuses with left-sided obstructive lesions (LSOL). Maternal oxygenation (MO) can alter fetal cerebral oxygenation and vascular reactivity. Our aim was to observe whether brain growth improves during MO in fetuses with LSOL. Forty-six fetuses with LSOL and 23 control fetuses were enrolled in this prospective longitudinal study. Fetuses with LSOL were subgrouped into those with MO (LSOL-MO, n = 23) and those without MO (LSOL-nMO, n = 23). Fetal head circumference (HC) and total intracranial volume (TIV) were evaluated serially at 4-week intervals. Brain biometry and growth were analyzed using linear mixed models adjusted for gestational age and sex. Spearman's correlation coefficients were calculated to identify baseline characteristics predictive of brain growth in the LSOL-MO group. Duration of MO therapy had significant interaction effects on cerebral biometry in fetuses with LSOL. TIV increased more rapidly after 8 weeks of oxygen exposure and HC was larger after 16 weeks of oxygen exposure in the LSOL-MO group compared with the LSOL-nMO group (P &lt; 0.001). The change in TIV at the final time- point relative to the initial timepoint in the LSOL-MO group correlated negatively with the baseline pulsatility index of the middle cerebral artery (r = -0.58, P = 0.003) and baseline myocardial performance index of the left ventricle (r = -0.68, P &lt; 0.001). TIV and HC increased faster in fetuses with LSOL which had MO compared with those that did not. Lower cerebral vascular resistance and preserved left heart function at baseline may predict greater cerebral biometric growth during MO. Additional research, including larger serial studies, is needed to confirm these preliminary findings and evaluate the clinical application of MO in this population. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

ИЗУЧЕНИЕ ВОЗМОЖНОСТИ СОЗДАНИЯ ИНТРАНАЗАЛЬНЫХ ЛЕКАРСТВЕННЫХ ФОРМ С ФИТОКОМПЛЕКСОМ ГИНКГО ДВУЛОПАСТНОГО И ИХ АНАЛИЗ

Abstract. One of the important tasks of modern pharmaceutical technology is the creation of effective and safe medicines that meet modern requirements and realities. And, as a result, having a minimum of side effects. Stressful situations associated with a stressful rhythm of life, past illnesses and many other factors contribute to a significant increase in the number of patients with cerebral circulatory disorders. That is why the search for new effective medicines and more universal dosage forms capable of restoring or compensating for impaired brain functions is timely and relevant. There are enough drugs with such activity, but there are not so many containing phytocomplexes. That is why the choice of objects of plant origin that occupy a special niche in the group and have an impact on cerebral circulation and on the condition of blood vessels seems promising to us Models constructed on the basis of the ginkgo biloba phytocomplex fit into this problem in all indicators – pharmacological, technological and economic. In addition, there is a sufficient raw material base. Analysis of the literature data has shown that drugs in the form of intranasal dosage forms intended to improve cerebral circulation will be promising drugs aimed at a wide range of consumers. Therefore, research in this area is appropriate and will have wide practical application in the future. The purpose of this study is the development of intranasal pharmaceutical farms and their standardization.

Impaired Brain Information Transmission Efficiency and Flexibility in Parkinson's Disease and Rapid Eye Movement Sleep Behavior Disorder: Evidence from Functional Connectivity and Functional Dynamics.

Parkinson's disease (PD) is a common neurodegenerative disorder. Rapid eye movement sleep behavior disorder (RBD) is one of the prodromal symptoms of PD. Studies have shown that brain information transmission is affected in PD patients. Consequently, we hypothesized that brain information transmission is impaired in RBD and PD. To prove our hypothesis, we performed functional connectivity (FC) and functional dynamics analysis of three aspects—based on the whole brain, within the resting-state network (RSN), and the interaction between RSNs—using normal control (NC) (n = 21), RBD (n = 24), and PD (n = 45) resting-state functional magnetic resonance imaging (rs-fMRI) data sets. Furthermore, we tested the explanatory power of FC and functional dynamics for the clinical features. Our results found that the global functional dynamics and FC of RBD and PD were impaired. Within RSN, the impairment concentrated in the visual network (VIS) and sensorimotor network (SMN), and the impaired degree of SMN in RBD was higher than that in PD. On the interaction between RSNs, RBD showed a widespread decrease, and PD showed a focal decrease which concentrated in SMN and VIS. Finally, we proved FC and functional dynamics were related to clinical features. These differences confirmed that brain information transmission efficiency and flexibility are impaired in RBD and PD, and these impairments are associated with the clinical features of patients.

Impaired brain satiety responses after weight loss in children with obesity

Impaired brain satiety responses after weight loss in children with obesity

Machine learning based on Optical Coherence Tomography images as a diagnostic tool for Alzheimer's disease.

We mainly evaluate retinal alterations in Alzheimer's disease (AD) patients, investigate the associations between retinal changes with AD biomarkers, and explore an optimal machine learning (ML) model for AD diagnosis based on retinal thickness. A total of 159 AD patients and 299 healthy controls were enrolled. The retinal parameters of each participant were measured using optical coherence tomography (OCT). Additionally, cognitive impairment severity, brain atrophy, and cerebrospinal fluid (CSF) biomarkers were measured in AD patients. AD patients demonstrated a significant decrease in the average, superior, and inferior quadrant peripapillary retinal nerve fiber layer, macular retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL) thicknesses, as well as total macular volume (TMV) (all p < 0.05). Moreover, TMV was positively associated with Mini-Mental State Examination and Montreal Cognitive Assessment scores, IPL thickness was correlated negatively with the medial temporal lobe atrophy score, and the GCL thickness was positively correlated with CSF Aβ42 /Aβ40 and negatively associated with p-tau level. Based on the significantly decreased OCT variables between both groups, the XGBoost algorithm exhibited the best diagnostic performance for AD, whose four references, including accuracy, area under the curve, f1 score, and recall, ranged from 0.69 to 0.74. Moreover, the macular retinal thickness exhibited an absolute superiority for AD diagnosis compared with other enrolled variables in all ML models. We identified the retinal alterations in AD patients and found that macular thickness and volume were associated with AD severity and biomarkers. Furthermore, we confirmed that OCT combined with ML could serve as a potential diagnostic tool for AD.

Role of SNAP-25 MnlI variant in impaired working memory and brain functions in attention deficit/hyperactivity disorder.

IntroductionAttention deficit/hyperactivity disorder (ADHD) is a hereditary neurodevelopmental disorder characterized by working memory (WM) deficits. The MnlI variant (rs3746544) of the synaptosomal‐associated protein 25 (SNAP‐25) gene is associated with ADHD. In this study, we investigated the role and underlying mechanism of SNAP‐25 MnlI variant in cognitive impairment and brain functions in boys with ADHD.MethodWe performed WM capacity tests using the fourth version of the Wechsler Intelligence Scale for Children (WISC‐IV) and regional homogeneity (ReHo) analysis for the resting‐state functional magnetic resonance imaging data of 56 boys with ADHD divided into two genotypic groups (TT homozygotes and G‐allele carriers). Next, Spearman's rank correlation analysis between the obtained ReHo values and the WM index (WMI) calculated for each participant.ResultsCompared with G‐allele carrier group, there were higher ReHo values for the left medial prefrontal cortex (mPFC) and higher WM capacity in TT homozygote group. Contrary to TT homozygote group, the WM capacity was negatively correlated with the peak ReHo value for the left mPFC in G‐allele carrier group.ConclusionThese findings suggest that SNAP‐25 MnlI variant may underlie cognitive and brain function impairments in boys with ADHD, thus suggesting its potential as a new target for ADHD treatment.

Longitudinal grey matter and metabolic contributions to cognitive changes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is characterized by rapidly evolving cognitive and brain impairments. While previous work revealed structural and functional alterations associated with cognitive decline in patients suffering from amyotrophic lateral sclerosis, the relationships between anatomo-functional changes and both disease’s progression and the evolution of cognitive performance remain largely unexplored. Here, we took advantage of repeated multi-modal acquisitions in patients with amyotrophic lateral sclerosis over 1 year to assess the longitudinal sequence of grey matter atrophy, glucose metabolism and cognitive changes. Results revealed metabolic and structural changes over frontal, thalamic and temporal regions. Both cortical hypermetabolism and hypometabolism (right temporal gyrus and right angular gyrus, respectively) were associated with cognitive performance and thalamic hypometabolism during the follow-up testing session. Furthermore, the inferior frontal gyrus atrophy mediated the relation between early hypometabolism in this region and the subsequent decline of the theory of mind abilities. Marked volume loss was associated with larger hypometabolism and impaired cognitive performance. To our knowledge, this is the first study to longitudinally examine both grey matter volume and metabolic alteration patterns in patients with amyotrophic lateral sclerosis, over a mean follow-up time of 1 year. We identify how changes of the inferior frontal gyrus critically underly later cognitive performance, shedding new light on its high prognostic significance for amyotrophic lateral sclerosis-related changes. These results have important implications for our understanding of structural and functional changes associated with amyotrophic lateral sclerosis and how they underly cognitive impairments.

Association between Long-Term Air Pollution, Chronic Traffic Noise, and Resting-State Functional Connectivity in the 1000BRAINS Study.

Background:Older adults show a high variability in cognitive performance that cannot be explained by aging alone. Although research has linked air pollution and noise to cognitive impairment and structural brain alterations, the potential impact of air pollution and noise on functional brain organization is unknown.Objective:This study examined the associations between long-term air pollution and traffic noise with measures of functional brain organization in older adults. We hypothesize that exposures to high air pollution and noise levels are associated with age-like changes in functional brain organization, shown by less segregated brain networks.Methods:Data from 574 participants (44.1% female, 56–85 years of age) in the German 1000BRAINS study (2011–2015) were analyzed. Exposure to particulate matter (, , and absorbance), accumulation mode particle number (), and nitrogen dioxide () was estimated applying land-use regression and chemistry transport models. Noise exposures were assessed as weighted 24-h () and nighttime () means. Functional brain organization of seven established brain networks (visual, sensorimotor, dorsal and ventral attention, limbic, frontoparietal and default network) was assessed using resting-state functional brain imaging data. To assess functional brain organization, we determined the degree of segregation between networks by comparing the strength of functional connections within and between networks. We estimated associations between air pollution and noise exposure with network segregation, applying multiple linear regression models adjusted for age, sex, socioeconomic status, and lifestyle variables.Results:Overall, small associations of high exposures with lesser segregated networks were visible. For the sensorimotor networks, we observed small associations between high air pollution and noise and lower network segregation, which had a similar effect size as a 1-y increase in age [e.g., in sensorimotor network, (95% CI: , 0.009) per 0.3 increase in absorbance and (95% CI: , ) per 1-y age increase].Conclusion:High exposure to air pollution and noise was associated with less segregated functional brain networks. https://doi.org/10.1289/EHP9737

White Matter Perivascular Space Burden Is Associated With Mild Traumatic Brain Injury History In Soldiers

Mild traumatic brain injury (mTBI) exposure in military Service Members may lead to impaired brain waste clearance which increases neurological disease risk including amyloidopathies. Perivascular spaces (PVS) are part of the glymphatic pathway which support brain waste clearance, especially during sleep. Greater magnetic resonance imaging (MRI)-visible PVS burden has been previously observed in patients with neurodegenerative diseases and animal TBI models. PURPOSE: To determine the association between PVS burden (number and volume) and mTBI history in Special Operations Forces (SOF) combat Soldiers. METHODS: In this cross-sectional study, participants underwent neuroimaging to capture T2-weighted (T2w) whole brain three dimensional volumes obtained on a Siemens 3T Biograph mMR or 3T MAGNETOM Prisma scanner (TR/TE = 3200/400ms, slice thickness = 1mm, FoV = 256mm x 256 mm). The PVS segmentation was performed using a previously validated, multi-scale deep convolutional encoder-decoder neural network. All T2w images were skull stripped and a custom T2w atlas with segmented cerebral white matter and subcortical gray matter labels was registered to each subject using Advanced Normalization Tools to minimize misidentifying thin tubular structures in the skull, brainstem, cerebellum, and cortex as PVS. Only PVS clusters within the white matter mask were quantified for analyses. Binary mTBI history was self-reported (“yes” or “no”). Due to non-normal PVS metric distribution, non-parametric Mann-Whitney U tests were used to determine group differences in PVS outcomes. RESULTS: In total, 223 healthy SOF combat Soldiers (age = 33.1±4.3yrs) were included for analysis and 123 (55.16%) reported mTBI history. Soldiers with mTBI history had greater PVS number (z = 2.506, P = 0.013) and PVS volume (z = 2.419, P = 0.016). CONCLUSIONS: We found mTBI history is associated with increased PVS burden in SOF combat Soldiers that are clinically recovered from mTBI. This may indicate ongoing physiological post-mTBI changes that could lead to impaired waste clearance via the glymphatic system. Future studies should determine how sleep influences PVS burden following mTBI exposure and if PVS number and volume are meaningful neurobiological outcomes for neurodegenerative disease risk. Funded by US Special Operations Command

Common and unique neural activities in subclinical depression and major depressive disorder indicate the development of brain impairments in different depressive stages

BackgroundSubclinical depression (SD) and major depressive disorder (MDD) can be considered as the early and late stages of depression, but the characteristics of intrinsic neural activity in different depressive stages are largely unknown. MethodsTwenty-six SD, 36 MDD subjects and 33 well-matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Voxel-wise regional homogeneity (ReHo) was analyzed to explore the alterations of intrinsic neural activity, and machine learning classification based on ReHo features was performed to assess potential performance for diagnostic classification. ResultsCommon alterations of ReHo in both SD and MDD groups were found in the bilateral middle temporal gyrus and the left middle occipital gyrus. Opposite alterations in SD and MDD groups were found in the right superior cerebellum. Moreover, increased ReHo in the bilateral precuneus was only found in MDD, while increased ReHo in the right middle frontal gyrus and precentral gyrus were unique to SD. The distinct ReHo values correctly identified SD, MDD, and HC by linear support vector machine (SVM) with an accuracy of 77.89 %, which further verified the discrimination ability of altered ReHo in these brain regions. LimitationThe sample size is relatively small. ConclusionCommon and unique ReHo alterations provided insights into the development of brain impairments in depression, and helped to understand the pathophysiology of SD and MDD.

Interhemispheric asymmetry of the brain in patients with type 1 diabetes mellitus and cognitive impairment.

With an ageing of population and a splurging epidemic of diabetes mellitus (DM), the prevalence of complications associated with pathology of the central nervous system are expected to increase, which in the future may have serious consequences for public health. It is known that one of the main manifestations of brain damage in type 1 diabetes is cognitive impairment, which is possibly associated with the peculiarities of vascularization and interhemispheric asymmetry, which requires in-depth analysis using modern neuroimaging methods. The aim of the study is to assess the symmetry of structural, metabolic and neurovascularization changes in the brain in patients with type 1 diabetes and cognitive impairment. The study included 120 patients with type 1 diabetes aged 18 to 45 years suffering from cognitive impairment, and 30 people without cognitive decline and the control group (n=30) healthy people without diabetes. Neuropsychological testing included the Montreal Cognitive Dysfunction Assessment Scale (MoCA test). For neuroimaging methods, standard magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), contrast and non-contrast-enhanced perfusion were used. Statistical processing was carried out using the SPSS Statistic 2020 software. In patients with type 1 diabetes with cognitive impairment, as manifested by impaired memory and/or attention, perfusion imaging revealed the presence of brain asymmetry zones. Standard MRI allowed to demonstrate changes in the white, gray matter and hippocampus in the right hemisphere. The results obtained were refined taking into account the topical localization, so during the perfusion study, regions with asymmetric blood flow were identified - namely, the white matter of the frontal lobe and the gray matter in the occipital lobe. Spectroscopy of the brain revealed that it was in these areas of the brain that the most significant metabolic disorders were noted – in the form of significantly altered ratio of N-acetylaspartate (NAA)/choline (Cho) on the left, along with the asymmetry in phosphocreatine level (Cr 2) on the right. In conclusion, early preclinical predictive diagnostics with the use of modern neuroimaging methods allows for timely detection of impaired vascularization and brain metabolism in this group of patients, However, decreased perfusion in the region within the region of frontal lobe white matter and temporal lobe grey matter, and hippocampal cell metabolism by spectra should be highlighted among the parameters Cr right and NAA/Cho left.

Distinct patterns of functional brain network integration between treatment-resistant depression and non treatment-resistant depression: A resting-state functional magnetic resonance imaging study

BackgroundPrevious neuroimaging has paid little attention to the differences in brain network integration between patients with treatment-resistant depression(TRD) and non-TRD (nTRD), and the relationship between their impaired brain network integration and clinical symptoms has not been elucidated. MethodEighty one major depressive disorder (MDD) patients (40 in TRD, 41 in nTRD) and 40 healthy controls (HCs) were enrolled for the functional magnetic resonance imaging (fMRI) scans. A seed-based functional connectivity (FC) method was used to investigate the brain network abnormalities of default mode network (DMN), affective network (AN), salience network (SN) and cognitive control network (CCN) for the MDD. Finally, the correlation was analyzed between the abnormal FCs and 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores. ResultsCompared with the HC group, the FCs in DMN, AN, SN, CCN were altered in both the TRD and nTRD groups. Compared with the nTRD group, FC alterations in the AN and CCN were more abnormal in the TRD group, and the FC alterations were generally decreased at the SN in the TRD group. In addition, the FC values of right dorsolateral prefrontal cortices and left caudate nucleus in the TRD group and the FC values of right subgenual anterior cingulate cortex and left middle temporal gyrus in the nTRD group were positively correlated with HAMD-17 scale scores. ConclusionsAbnormal FCs are present in four brain networks (DMN, AN, SN, CCN) in both the TRD and nTRD groups. Except of DMN, FCs in AN, SN and CCN maybe underlay the neurobiological mechanism in differentiating TRD from nTRD.

Abnormal cerebral microvascular perfusion and reactivity in female offspring of reduced uterine perfusion pressure (RUPP) mice model

Children born from women with preeclampsia have alterations in cerebral neurovascular development and a high risk for developing cognitive alterations. Because cerebral blood vessels are critical components in cerebrovascular development, we evaluated the brain microvascular perfusion and microvascular reactivity (exposed to external stimuli of warm and cold) in pups born to preeclampsia-like syndrome based on the reduction of uterine perfusion (RUPP). Also, we evaluate the angiogenic proteomic profile in those brains. Pregnant mice showed a reduction in uterine flow after RUPP surgery (−40 to 50%) associated with unfavorable perinatal results compared to sham mice. Furthermore, offspring of the RUPP mice exhibited reduced brain microvascular perfusion at postnatal day 5 (P5) compared with offspring from sham mice. This reduction was preferentially observed in females. Also, brain microvascular reactivity to external stimuli (warm and cold) was reduced in pups of RUPP mice. Furthermore, a differential expression of the angiogenic profile associated with inflammation, extrinsic apoptotic, cancer, and cellular senescence processes as the primary signaling impaired process was found in the brains of RUPP-offspring. Then, offspring (P5) from preeclampsia-like syndrome exhibit impaired brain perfusion and microvascular reactivity, particularly in female mice, associated with differential expression of angiogenic proteins in the brain tissue.

Neuronal Ceroid Lipofuscinoses Presenting as Rett-like Phenotype: A Two-Case Report From Thailand

BackgroundNeuronal ceroid lipofuscinoses (NCLs) (hereafter described as CLN disease) comprise a rare and life-limiting set of genetically inherited neurodegenerative disorders that are characterized by abnormal lysosomal storage. The NCL disorders are, collectively, the most common group of degenerative brain disorders in children. Patient DescriptionsWe report two cases of CLN disease that were diagnosed and treated at the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Both cases of CLN disease (CLN1 and CLN6 diagnosed in 2016 and 2017, respectively) profiled in this report presented with clinical features of Rett syndrome. In the first case, a 2-year-old girl presented with Rett-like clinical features, including global developmental regression and hand-wringing action. Single-gene analysis of the MECP2 gene was negative. However, PPT1 gene sequencing revealed a novel homozygous frameshift mutation, c.629_630dupGT (p.Ile211Valfs∗10). In the second case, a 7.5-year-old girl presented with ataxia, progressive myoclonic epilepsy, and Rett-like hand-wringing. A c.794_796delCCT variant in the CLN6 gene was identified by whole-exome sequencing. Fingerprint bodies from electron microscopy of the skin also supported a diagnosis of CLN disease in our second case. DiscussionPresentation with clinical features of Rett syndrome has only been reported in patients diagnosed with CLN1 and CLN7 disease, and never in those with CLN6. ConclusionsPhysicians should suspect and investigate for CLN disease in patients with Rett-like phenotype who are negative for MECP2 mutation, especially in patients with visual impairment and early prominent brain atrophy.

A-304 Neurocognitive considerations for Fitness for Duty Evaluations and Its Impact on Occupational Functioning in Police Psychology

Abstract Objective: The current abstract sought to examine (1) how neurocognitive impairments may impact occupational functioning in police officers; (2) the relationship between co-morbid disorders and cognitive functions when conducting fitness for duty evaluations; and (3) the need for future research on conducting neuropsychological assessments and fitness for duty evaluations. Data Selection: A systematic review of the literature was utilized. Studies reviewed were empirically valid and focused on neurocognitive impairments, fitness for duty evaluation for police officers, and co-morbid psychological factors that influence cognitive performance in public safety personnel. Data Synthesis: The impact of impaired brain functioning can affect a police officer’s judgment, reasoning, ability to resist impulses as well as their behavior and/or changes in personality (e.g., aggression) (Stephen, E. B., Bina, P., Michael B., 2020). Research has shown that PTSD is associated with mild impairments on several neurocognitive functions among police officers. Further, depression and PTSD appear to have a cumulative negative impact on speed of processing information and cognitive performance (LeBlanc, V. R., Regehr, C., Jelley, R. B., &amp; Barath, I , 2007). Therefore, even mild subclinical cognitive difficulties experienced by police officers may affect their social and occupational functioning. Conclusions: These considerations illustrate that neurocognitive impairments, psychological disorders, behavioral and/or personality changes are often co-morbid conditions. Therefore, there is a need for more research on comprehensive neuropsychological assessments associated with occupational functioning as part of fitness for duty evaluations. Research in this area is necessary for defining best practices in fitness for duty evaluations and is paramount for promoting public safety.

Discharge against medical advice among infants with 24-31 weeks' gestation admitted to Chinese neonatal intensive care units: A multicenter cohort study.

BackgroundPrevious studies demonstrated high rates of discharge against medical advice (DAMA) among very preterm infants (VPIs) in China.ObjectivesThe aim of this study was to investigate the concurrent incidence, variation, and predictors of DAMA, along with the effect of DAMA on mortality of VPIs in China using data from the Chinese Neonatal Network (CHNN).MethodsAll infants born at 24–31 completed weeks’ gestation and admitted to 57 CHNN neonatal intensive care units (NICUs) in 2019 were included for this cohort study, excluding infants with major congenital anomalies. Patient information was prospectively collected using the CHNN database. Multivariable log-linear regression analysis was used to assess the association of perinatal factors and DAMA.ResultsA total of 9,442 infants born at 24–31 completed weeks’ gestation and admitted to 57 CHNN participating sites in 2019 were included in the study. Overall, 1,341 infants (14.2%) were discharged against medical advice. Rates of DAMA decreased with increasing gestational age (GA), and infants with lower GA were discharged earlier. DAMA infants had significantly higher rates of necrotizing enterocolitis, severe brain impairment, and bronchopulmonary dysplasia than non-DAMA infants. A total of 58.2% DAMA infants were predicted to die after discharge. The attributable risk percentage of mortality among DAMA infants was 92.4%. Younger maternal age, lower gestational age, small for gestational age, and Apgar score ≤3 at 5 min were independently associated with an increased risk of DAMA, while infants with antenatal steroids were less likely to be DAMA.ConclusionThe rate of DAMA in preterm infants between 24 and 31 weeks’ gestation remained high in China with a significant impact on the mortality rates. Continuous efforts to reduce DAMA would result in substantial improvement of outcomes for VPIs in China.

High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging.

BackgroundHigh cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.MethodsSeven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a high-fat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.ResultsThe obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.ConclusionThe protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

Brain morphological alterations and their correlation to tumor differentiation and duration in patients with lung cancer after platinum chemotherapy.

ObjectiveChemotherapy-related brain impairments and changes can occur in patients with lung cancer after platinum chemotherapy and have a substantial impact on survivors’ quality of life. Therefore, it is necessary to understand the brain neuropathological alterations and response mechanisms to provide a theoretical basis for rehabilitation strategies. This study aimed to investigate the related brain morphological changes and clarified their correlation with clinical and pathological indicators in patients with lung cancer after platinum chemotherapy.MethodsOverall, 28 patients with chemotherapy, 56 patients without chemotherapy, and 41 healthy controls were categorized in three groups, matched for age, sex, and years of education, and included in the cross-sectional comparison of brain volume and cortical thickness. 14 matched patients before and after chemotherapy were subjected to paired comparison for longitudinal observation of brain morphological changes. Three-dimensional T1-weighted images were acquired from all participants, and quantitative parameters were calculated using the formula of the change from baseline. Correlation analysis was performed to evaluate the relationship between abnormal morphological indices and clinical information of patients.ResultsBrain regions with volume differences among the three groups were mainly distributed in frontal lobe and limbic cortex. Additionally, significant differences in cerebrospinal fluid were observed in most ventricles, and the main brain regions with cortical thickness differences were the gyrus rectus and medial frontal cortex of the frontal lobe, transverse temporal gyrus of the temporal lobe, insular cortex, anterior insula, and posterior insula of the insular cortex. According to the paired comparison, decreased brain volumes in the patients after chemotherapy appeared in some regions of the frontal, parietal, temporal, and occipital lobes; limbic cortex; insular cortex; and lobules VI-X and decreased cortical thickness in the patients after chemotherapy was found in the frontal, temporal, limbic, and insular cortexes. In the correlation analysis, only the differentiation degree of the tumor and duration after chemotherapy were significantly correlated with imaging indices in the abnormal brain regions.ConclusionsOur findings illustrate the platinum-related brain reactivity morphological alterations which provide more insights into the neuropathological mechanisms of patients with lung cancer after platinum chemotherapy and empirical support for the details of brain injury related to cancer and chemotherapy.