Cognitive Impairment In Children Research Articles

Mucosal vaccination in a murine gnotobiotic model of Giardia lamblia infection.

Giardia lamblia is an important protozoan cause of diarrheal disease worldwide, delayed development and cognitive impairment in children in low- and middle-income countries, and protracted post-infectious syndromes in developed regions. G. lamblia resides in the lumen and at the epithelial surface of the proximal small intestine but is not mucosa invasive. The protozoan parasite is genetically diverse with significant genome differences across strains and assemblages. Animal models, particularly murine models, have been instrumental in defining mechanisms of host defense against G. lamblia, but mice cannot be readily infected with most human pathogenic strains. Antibiotic pretreatment can increase susceptibility, suggesting that the normal microbiota plays a role in controlling G. lamblia infection in mice, but the broader implications on susceptibility to diverse strains are not known. Here, we have used gnotobiotic mice to demonstrate that robust intestinal infection can be achieved for a broad set of human-pathogenic strains of the genetic assemblages A and B. Furthermore, gnotobiotic mice were able to eradicate infection with a similar kinetics to conventional mice after trophozoite challenge. Germ-free mice could also be effectively immunized by the mucosal route with a protective antigen, α1-giardin, in a manner dependent on CD4 T cells. These results indicate that the gnotobiotic mouse model is powerful for investigating acquired host defenses in giardiasis, as the mice are broadly susceptible to diverse G. lamblia strains yet display no apparent defects in mucosal immunity needed for controlling and eradicating this lumen-dwelling pathogen.

Prevalence and co-occurrence of cognitive impairment in children and young people up to 12-months post infection with SARS-CoV-2 (Omicron variant)

BackgroundCognitive impairment is often reported after SARS-CoV-2 infection, yet evidence gaps remain. We aimed to (i) report the prevalence and characteristics of children and young people (CYP) reporting “brain fog” (i.e., cognitive impairment) 12-months post PCR-proven SARS-CoV-2 infection and determine whether differences by infection status exist and (ii) explore the prevalence of CYP experiencing cognitive impairment over a 12-month period post-infection and investigate the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and sleep problems. MethodsThe Omicron CLoCk sub-study, set up in January 2022, collected data on first-time PCR-test-positive and PCR-proven reinfected CYP at time of testing and at 3-, 6- and 12-months post-testing. We describe the prevalence of cognitive impairment at 12-months, indicating when it was first reported. We characterise CYP experiencing cognitive impairment and use chi-squared tests to determine whether cognitive impairment prevalence varied by infection status. We explore the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and trouble sleeping using validated scales. We examine associations at 3-, 6- and 12-months post-testing by infection status using Mann-Whitney U and chi-square tests. ResultsAt 12-months post-testing, 7.0 % (24/345) of first-positives and 7.5 % (27/360) of reinfected CYP experienced cognitive impairment with no difference between infection-status groups (p = 0.78). The majority of these CYP experienced cognitive impairment for the first time at either time of testing or 3-months post-test (no difference between the infection-status groups; p = 0.60). 70.8 % of first-positives experiencing cognitive impairment at 12-months, were 15-to-17-years-old as were 33.3 % of reinfected CYP experiencing cognitive impairment (p < 0.01). Consistently at all time points post-testing, CYP experiencing cognitive impairment were more likely to score higher on all Strengths and Difficulties Questionnaire subscales, higher on the Chalder Fatigue sub-scale for mental fatigue, lower on the Short Warwick-Edinburgh Mental Wellbeing Scale and report more trouble sleeping. ConclusionsCYP have a fluctuating experience of cognitive impairment by 12-months post SARS-CoV-2-infection. Cognitive impairment is consistently correlated with poorer sleep, behavioural and emotional functioning over a 12-month period. Clinicians should be aware of cognitive impairment post-infection and its co-occurring nature with poorer sleep, behavioural and mental health symptoms.

Cognitive impairment in children and adolescents living with perinatal HIV disease in the ART era: a meta-analysis

Cognitive impairment in children and adolescents living with perinatal HIV disease in the ART era: a meta-analysis

Analysis of related factors for neuropsychiatric comorbidities in children with epilepsy

ObjectiveTo analyze the risk factors affecting psychiatric behavior and study the psychobehavioral conditions of children with epilepsy.MethodWe randomly selected and enrolled 294 children with epilepsy who visited and were hospitalized in the pediatric clinic of Hebei General Hospital between January 2017 and January 2022, as the study participants. We comprehensively assessed their cognitive functions using the Gesell development schedule or Wechsler Intelligence Scales. The participants were divided into the study group (n = 123) with cognitive impairment and the control group (n = 171) with normal cognitive functions, for analysis.ResultsThere were statistically significant differences between the two groups in disease course, frequency of epilepsy, status epilepticus, and the number of antiseizure medications (ASMs) used (P < 0.05), while there were no statistically significant differences in age, gender, age of onset, form of onset, interictal epileptiform discharge, history of febrile convulsion, and the time from onset to initial visit (P > 0.05). Based on multivariate logistic regression analysis, the course of disease, frequency of onset, status epilepticus and number of ASMs used were identified as high-risk factors for cognitive impairment in children with epilepsy. Similarly, early onset, long course of disease, known etiology, and combination of multiple drugs have a negative impact on behavioral problems, school education, and social adaptability.ConclusionThe course of disease, the frequency of onset, status epilepticus, and the number of ASMs used are high-risk factors for cognitive impairment in children with epilepsy, which can be prevented and controlled early. When selecting ASMs, their advantages and disadvantages should be weighed. Moreover, the availability of alternative treatment options must be considered. With the help of genomic technology, the causes of epilepsy should be identified as early as possible, and precision medicine and gene therapy for children with epilepsy should be actively developed.

Cognitive function in Indonesian children with type 1 diabetes mellitus

Background Children with type 1 diabetes mellitus (T1DM) are at risk of cognitive impairment. While the pathophysiology is still unclear, cognitive impairment in children with T1DM can result in significant negative effects on quality of life. &#x0D; Objective to evaluate the cognitive function of Indonesian children with T1DM and its association with glycemic control and to identify factors affecting cognitive function in children with T1DM.&#x0D; Methods The cognitive function of children aged 6 years or older with T1DM was measured using the Wechsler Intelligence Scale for Children-Revised (WISC-R). We analyzed for potential associations between cognitive function and glycemic control based on mean HbA1c levels and other factors, such as the age of onset, duration of illness, and maternal educational attainment. We also identified failure to achieve age-appropriate results on any of the WISC-R subtests (cognitive impairment) and associated factors. &#x0D; Results A total of 46 subjects were included in this study, with a mean age of 12.8 (SD 3.4) years. There were 27 (58.7%) girls and 19 (41.3%) boys. Subjects’ mean full-scale IQ (FSIQ) was 91.35 (SD 11.43). A moderate negative correlation was found between FSIQ and mean HbA1c levels (r=-0.43; P&lt;0.01). Children with mothers who had university degrees had significantly higher IQs (mean difference 7.39; 95%CI 3.10 to 13.66; P=0.02) than those with mothers without degrees. Failure of any WISC-R subtest was noted in 34 subjects, consisting of 17 verbal, 1 performance, and 34 verbal and performance subtests. A higher proportion of those with cognitive impairment had mean HbA1c &gt;10%. However, compared to those with mean HbA1c ?10, the difference did not reach a statistical significance (OR 5.0; 95%CI 0.95 to 26.31; P=0.50)&#x0D; Conclusion Glycemic control and maternal educational attainment are associated with cognitive function in Indonesian children with T1DM. Poor glycemic control is also associated with a higher risk of cognitive impairment.

To explore the potential mechanisms of cognitive impairment in children with MRI-negative pharmacoresistant epilepsy due to focal cortical dysplasia: A pilot study from gray matter structure view

ObjectivesTo investigate the characteristics of brain structure in children with focal cortical dysplasia (FCD)-induced pharmacoresistant epilepsy, and explore the potential mechanisms of cognitive impairment from the view of gray matter alteration. Methods25 pharmacoresistant pediatric patients with pathologically confirmed focal cortical dysplasia (FCD), and 25 gender-matched healthy controls were included in this study. 3.0T MRI data and intelligence tests using the Wechsler Intelligence Scale for Children-Forth Edition (WISC-IV) were generated for all subjects. Voxel-based morphometry (VBM)-diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) and surface-based morphometry (SBM) analyses were performed to analyze gray matter volume and cortical structure. Two-sample t-tests were used to compare the differences in gray matter volume (P＜0.05, FWE) and cortical thickness (P＜0.001, FWE) between the two groups. Also, the Spearman rank correlation analyses were employed to determine the relationship between structural alterations and neuropsychological results. ResultsThe WISC-IV scores of the FCD group were significantly lower than those of the HC group in terms of full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) (all P＜0.01). Compared with the HC group, in the FCD group, the gray matter volume (GMV) reduced significantly in the left cerebellum_8, cerebellum_Crus2, and bilateral thalamus (P＜0.05, FWE); the GMV increased in the bilateral medial frontal gyrus, right precuneus, and left inferior temporal gyrus (P＜0.05, FWE), and the cortical thickness increased in the bilateral frontal, parietal, and temporal areas (P＜0.001, FWE). Correlation analyses showed that the age of seizure onset had positive correlations with the WISC-IV scores significantly. Meanwhile, the cortex thicknesses of the left pars opercularis gyrus, left middle temporal gyrus, and right inferior temporal gyrus had negative correlations with the WISC-IV scores significantly. ConclusionFCD patients showed subtle structural abnormalities in multiple brain regions, with significant involvement of the primary visual cortex and language function cortex. And we also demonstrated a crucial correlation between gray matter structural alteration and cognitive impairment.

A Single-Stage Population-Based Study of the Relationship between Cognitive and Somatic Health Parameters in Children of Secondary School Age

Background. One of the four important components of the formation of cognitive functions is somatic health. But to date, there are no population studies that consider the relationship with cognitive functions and school performance of a large range of somatic factors, which allows us to compare the strength of their hypothetical contribution to cognitive functioning with each other. This study is the second part of a population-based study, the first part of which is presented in the previous publication "A Single-Stage Population-Based Study of the Prevalence of Mild Cognitive Impairment in Children of Secondary School Age". Aims — to determine the main patterns in the relationship between cognitive-academic and somatic factors in a cohort of Russian children, 5th grade students at school. Methods. In Russian schoolchildren of the 5th grades of municipalities representing cities of all federal districts of the Russian Federation, the links with integrative cognitive success, the number of subtests performed at the level of mild cognitive impairment, the results of individual cognitive subtests, academic performance and the leading hand factor were analyzed — the following somatic factors: the presence of skin pathology, bronchial asthma, orthopedic, ophthalmological disorders, visual acuity, body mass index, parameters of the study of the function of external respiration, electrocardiography, ultrasound examination of the thyroid gland, laboratory blood tests. Results. The results of the survey of 1036 participants, 51% of them girls, were admitted to the analysis. It has been established that iron content is directly related to integrative cognitive success and school performance, the relationship is especially strong between subgroups of iron content above and below 26.4 mmol/l. Clinical levels of erythrocytes are more strongly associated with integrative cognitive success and individual cognitive functions than other factors: in erythropenia cognitive parameters are worse. The presence of thyroid cysts directly correlates with some of the worst parameters of cognitive activity. High body mass index and low hemoglobin are associated with poorer academic performance. Conclusions. The results of the study for the first time on a cohort of Russian schoolchildren showed a connection with cognitive activity and school performance of a number of somatic factors, including iron content, which requires further in-depth study.

Children's cognitive impairment associated with cassava cyanide in Democratic Republic of the Congo: Burden of disease.

Worldwide, tens of millions of children rely on cassava as a dietary staple throughout their formative years of brain and behavioral development. Recently, it was discovered that cassava cyanide can impair children's neurocognitive development at relatively low exposures. We revisited the World Health Organization's foodborne disease burden estimate of cassava cyanide, focusing on the new health endpoint of children's cognitive impairment in Democratic Republic of the Congo (DRC). The loss of Intelligence Quotient (IQ) scores was used to measure the endpoint of cognitive impairment caused by cassava cyanide exposure, which was estimated based on the concentration-effect relationship between children's IQ scores and cyanide concentrations in flour. We estimated the burden of intellectual disability (ID) associated with cassava cyanide exposure in terms of disability-adjusted life years (DALYs). The median content of cyanide in cassava samples collected from DRC was 12.5 mg/kg, causing a median decrement to children's IQ of 2.37 points. The estimated number of children with ID associated with cassava cyanide exposure was 1,643 cases, although 1,567 of these cases (95%) were mild ID. The burden of cognitive impairment attributable to cassava cyanide in DRC alone was 13,862 DALYs per 100,000 children, or 3.01 million for all children under age 5. The results of the study, showing a significant burden of cassava cyanide-related cognitive impairment in children even at relatively low doses, can contribute to the implementation of cost-effective interventions to make cassava consumption safer for children in high-risk rural areas of DRC.

Neuropsychology and Electroencephalography in Rural Children at Neurodevelopmental Risk: A Scoping Review.

Children from rural areas face numerous possibilities of neurodevelopmental conditions that may compromise their well-being and optimal development. Neuropsychology and electroencephalography (EEG) have shown strong agreement in detecting correlations between these two variables and suggest an association with specific environmental and social risk factors. The present scoping review aims to describe studies reporting associations between EEG features and cognitive impairment in children from rural or vulnerable environments and describe the main risk factors influencing EEG abnormalities in these children. The method for this purpose was based on a string-based review from PubMed, EBSCOhost, and Web of Science, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Qualitative and quantitative analyses were conducted from the outcomes that complied with the selected criteria. In total, 2280 records were identified; however, only 26 were eligible: 15 for qualitative and 11 for quantitative analysis. The findings highlight the significant literature on EEG and its relationship with cognitive impairment from studies in children with epilepsy and malnutrition. In general, there is evidence for the advantages of implementing EEG diagnosis and research techniques in children living under risk conditions. Specific associations between particular EEG features and cognitive impairment are described in the reviewed literature in children. Further research is needed to better describe and integrate the state of the art regarding EEG feature extraction.

A single-stage population-based study of the prevalence of mild cognitive impairment in children of secondary school age.

Background: Various mild cognitive impairments in children are socially significant disorders that are often found in the practice of pediatric neurologists, but the apparent lack of epidemiological data does not allow us to judge the scale of the problem. &#x0D; Aims: The aim of the study was to assess the prevalence of combined mild cognitive disorders in a large cohort of Russian children, 5th grade students at school.&#x0D; Materials and methods: The results of the examination of Russian schoolchildren of municipalities representing cities of all federal districts of the Russian Federation (RF) are analyzed. Cognitive functions were tested, which consisted of six subtests. According to the results of testing, using the method of assessing cognitive functions in population studies, the frequency of assigning participants to a high-risk group of combined mild cognitive impairment and the probability of diagnosis of combined mild cognitive impairment were evaluated. The analysis of the links between the breadth of results performed at the level of mild cognitive impairment, integrative cognitive success, the results of individual cognitive subtests with academic performance and the leading hand factor was carried out. .&#x0D; Results: 1,067 5th grade students at school were included in the study, 1,036 participants completed it, 51% of them girls. Belonging to the cluster of integrative cognitive successes and representation of the leading hand had no gender differences, subtests for visual-spatial perception/memory and constructive practice were better performed by boys (p 0.001 and p = 0.020), and girls, as a rule, performed better subtests for verbal-logical thinking and voluntary activity. attention (p = 0.050 and p = 0.051). According to the results of cognitive testing, a high risk of combined mild cognitive impairment was detected in 30.2% of the examined, and the probability of diagnosis of combined mild cognitive impairment was 7.5%. It was found that of the studied factors, the breadth of the results obtained at the level of moderate cognitive impairment and the effectiveness of the verbal-logical thinking subtest are more related to academic performance. At the same time, the strength of these ties was very moderate. The image of the leading hand was in no way associated with cognitive factors, including academic performance at the level of moderate cognitive impairment, but left-handedness was partially associated with better academic performance in literature.&#x0D; Conclusions: The results of the study, conducted for the first time on a multi-regional cohort of Russian schoolchildren, demonstrated a wide scale of the potential prevalence of mild cognitive impairment in children, and also revealed a number of patterns in the neurobiology of cognitive development.

P009 Time spent with SpO2 below 90% during Sleep is Greater in Children with Down syndrome and OSA than in Typically Developing Children

Abstract Background Children with Down syndrome (DS) have a higher predisposition to obstructive sleep apnoea (OSA) compared to typically developing (TD) children. Children with DS have more frequent dips &amp;lt;90% compared with TD children matched for age, sex and OSA severity. Intermittent hypoxia with repeated desaturations and resaturations is associated with cognitive impairment in children. New methods which calculate the time spent with SpO2 &amp;lt;90% have identified an association with cardiac dysfunction in adults with OSA. We aimed to determine if children with DS and OSA spent longer with SpO2 &amp;lt;90% during sleep compared with TD children. Methods 44 children with DS (3-19 y) and age, sex and OSA severity matched TD children underwent overnight polysomnography. Time spent with SpO2 &amp;lt;90% as a percentage of total sleep time (%TST) was calculated. SpO2 nadir when &amp;lt;90% was recorded. Results SpO2 fell &amp;lt;90% in 32 (73%) children with DS and 15 (34%) TD children. The %TST spent with SpO2 &amp;lt;90% was higher in the DS group (median [IQR] 0.029% [0.004, 0.114]) compared with the TD group (0.000% [0.000, 0.020]; p&amp;lt;0.001). There was no difference in SpO2 nadir between the groups (DS mean±sem 84%±1.1%; TD 85%±1.1) when the SpO2 fell &amp;lt;90%. Conclusion Twice as many children with DS experienced periods of oxygen desaturation below 90% as did TD children matched for age, sex and OSA severity. Although as a %TST, the time spent &amp;lt;90% was small, different physiologically-based metrics to characterise OSA severity and the consequences of recurrent hypoxia in children may be merited.

Diabetic ketoacidosis and cognitive impairment in children and adolescents

The aim of the literature review was to highlight modern scientific sources on the formation and clinical manifestations of cognitive impairment in children and adolescents with type 1 diabetes mellitus (DM) after diabetic ketoacidosis (DKA). Type 1 DM is one of the most prevalent endocrine disorders in childhood and adolescence. DKA is the most common acute complication of type 1 DM that may cause cognitive impairment. Cerebral edema is the main cause of cerebral vascular insufficiency in patients with DKA. However, the mechanisms underlying the development of cognitive dysfunction in DKA have not been fully elucidated.The leading hypotheses include development of neuroinflammation, oxidative stress, disruption of neurogenesis, and neurodegeneration. Hypoxic – ischemic injury and changes in the brain neuroanatomy may also cause cognitive dysfunction. Disruption of some brain structures has been reported after DKA episodes, primarily affecting the white matter. Clinical studies in the pediatric population support the presence of a correlation between the severity and frequency of DKA and the severity of cognitive impairment. Cognitive dysfunction in children and adolescents after a DKA episode can manifest through decreased attention, impaired memory and executive function, and reduced IQ. The earliest possible diagnosis of cognitive impairment in pediatric patients with symptoms of DKA in the context of type 1 DM can improve the treatment prognosis for this endocrinopathy.

The efficacy of statins for improving cognitive impairments in pediatric patients with neurofibromatosis type 1 (NF-1): a meta-analysis.

Given the considerable discrepancies in the evidence concerning the efficacy of statins in ameliorating cognitive impairments in pediatric patients with Neurofibromatosis Type 1 (NF-1), this study conducts a systematic review and meta-analysis to consolidate existing evidence to evaluate the efficacy of statins on cognitive impairments in children with NF-1. This study adhered to the PRISMA statement, and the research protocol was pre-registered on PROSPERO (#CRD: 42022369072). Comprehensive searches of databases including PubMed, Embase, and the Cochrane Library were performed up to March 31, 2023 to identify randomized controlled trials (RCTs) investigating the effects of statins on cognitive impairments in children with NF-1. Statistical analyses were conducted using Review Manager 5.4.1. A fixed- or random-effects model was employed according to the I2 statistic. As all data were continuous, MD [95% CI] was used as the pooled estimate. The final analysis included five RCTs with a total of 364 patients. The meta-analysis indicated that aside from a statistically significant improvement in internalizing problems (MD [95%CI] = 3.61[0.11, 7.10], p = 0.04), Object assembly Test (MD [95%CI] = 0.53[0.12, 0.93], p = 0.01), Cancellation Test (MD [95%CI] = 3.61[0.11, 7.10], p < 0.0001), statins did not exhibit significant efficacy in improving other cognitive aspects in children with NF-1 (p > 0.05). An additional descriptive analysis on indices that cannot be meta-analyzed revealed considerable inconsistency in the therapeutic effect of statins across different studies. Current evidence suggests that statins may not be effective for cognitive performance in children with NF-1.

Preoperative anxiety and associated factors among women admitted for elective obstetric and gynecologic surgery in public hospitals, Southern Ethiopia: a cross-sectional study

BackgroundPreoperative anxiety is a major mental health problem during the preoperative period. Admission of women to surgery is stressful, and a high level of anxiety was associated with increased perioperative morbidity and mortality, poor treatment satisfaction, and bad obstetric outcomes, including long-term cognitive impairment in children. Despite its negative consequences, little is known on this area, particularly in the study area.ObjectiveTo assess preoperative anxiety and associated factors among women admitted for elective obstetrics and gynecologic surgeries in public hospitals in Southern Ethiopia, 2022.Methods and MaterialsAn institution-based cross-sectional study design was conducted among 389 women using structured interviewer-administered samples who were selected by systematic random sampling from May 20th to June 20th, 2022. The Amsterdam preoperative anxiety and information scale (APAIS) was used to assess the level of anxiety. Data were collected electronically using the Open Data Kit version 2022.2.3 and analyzed with the Statistical Package for Social Sciences version 26.0. Bivariate and multivariable logistic regression analyses were done. The strength of the association was declared by using an adjusted odds ratio (AOR) with a 95% confidence interval, and a statistical significance of P < 0.05.ResultsThe magnitude of preoperative anxiety was 57.1% (95% CI = 51.4–61.5), and 48.1% of women required an average amount of information. Being a gynecologic patient (AOR = 2.0, 95% CI = 1.21, 3.32), having previous anesthesia and surgery (AOR = 2.09, 95% CI = 1.10, 3.96), having fear of postoperative pain (AOR = 1.96, 95% CI = 1.08, 3.53), having concern for family (AOR = 2.56, 95% CI = 1.49, 4.37), having poor social support (AOR = 3.75, 95% CI = 1.99, 7.09), and moderate social supports (AOR = 3.27, 95% CI = 1.74, 6.17), and having a high information requirement about anesthesia and surgery (AOR = 4.68, 95%CI = 2.16, 10.13) were statistically associated with preoperative anxiety.ConclusionPreoperative anxiety was often high in the region. Associated factors were the type of surgery, previous anesthesia and surgery, fear of postoperative pain, fear for family, social support, and a high information need. So the national and regional health bureau should develop guidelines and implement strategies to reduce women preoperative anxiety as part of midwifery care. The women should be assessed regularly during the preoperative visits; and appropriate anxiety reduction and information regarding surgery, and anesthesia should be provided.

Blockage of calcium-sensing receptor improves chronic intermittent hypoxia-induced cognitive impairment by PERK-ATF4-CHOP pathway

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is involved in cognitive impairment of children. Chronic intermittent hypoxia (CIH) is considered as the critical pathophysiological mechanism of OSAHS. Calcium sensitive receptor (CaSR) mediated apoptosis in many neurological disease models by endoplasmic reticulum stress (ERS)-related pathway. However, little is known about the role of CaSR in OSAHS-induced cognitive dysfunction. In this study, we explored the effect of CaSR on CIH-induced cognitive impairment and possible mechanisms on regulation of PERK-ATF4-CHOP pathway in vivo and in vitro. CIH exposed for 9 h in PC12 cells and resulted in the cell apoptosis, simulating OSAHS-induced neuronal injury. CIH upregulated the level of CaSR, p-PERK, ATF4 and CHOP, contributing to the cell apoptosis. Treated with CaSR inhibitor (NPS-2143) or p-PERK inhibitor (GSK2656157) before CIH exposure, CIH-induced PC12 cell apoptosis was alleviated via inhibition of CaSR by downregulating p-PERK, ATF4 and CHOP. In addition, we established CIH mice model. With CIH exposure for 4 weeks in mice, more spatial memory errors were observed during 8-arm radial maze test. CIH significantly increased apoptotic cells in hippocampus via upregulating cleaved Caspase-3 and downregulating ratio of Bcl-2 to Bax. Besides, treatment of CaSR inhibitor alleviated the hippocampal neuronal apoptosis following CIH with downregulated p-PERK, ATF4 and CHOP, suggesting that CaSR contributed to CIH-induced neuronal apoptosis in hippocampus via ERS pathway. Sum up, our results demonstrated that CaSR accelerated hippocampal apoptosis via PERK-ATF4-CHOP pathway, holding a critical function on CIH-mediated cognitive impairment. Conversely, inhibition of CaSR suppressed PERK-ATF4-CHOP pathway and alleviated cognitive impairment.

Pre-Adolescent Diet Normalization Restores Cognitive Function in Young Mice.

Mastication is a fundamental function critical for human health. Controlled by the central nervous system (CNS), it influences CNS development and function. A poor masticatory performance causes cognitive dysfunction in both older adults and children. Improving mastication may prevent cognitive decline. However, no study has determined the period of masticatory dysfunction that impairs children's later acquisition of cognitive function. Herein, we developed an animal model wherein a soft diet was switched to a normal diet at early and late time points in young mice. We aimed to investigate the impact of restored mastication on learning and memory function. Behavioral studies were conducted to evaluate learning and memory. Micro-CT was used to evaluate orofacial structural differences, while histological and biochemical approaches were employed to assess differences in the hippocampal morphology and function. Correction to a hard-textured diet before adolescence restored mastication and cognitive function through the stimulation of neurogenesis, extracellular signal-regulated kinases, the cyclic adenosine monophosphate-response element-binding protein pathway, and the brain-derived neurotrophic factor, tyrosine receptor B. In contrast, post-adolescent diet normalization failed to rescue full mastication and led to impaired cognitive function, neuronal loss, and decreased hippocampal neurogenesis. These findings revealed a functional linkage between the masticatory and cognitive function in mice during the juvenile to adolescent period, highlighting the need for adequate food texture and early intervention for mastication-related cognitive impairment in children.

Pattern of Auditory and Cognitive Impairment in Children with Sickle Cell Disease: Single Center Experience

Pattern of Auditory and Cognitive Impairment in Children with Sickle Cell Disease: Single Center Experience

Alterations of brain gray matter volume in children with obstructive sleep apnea.

Obstructive sleep apnea (OSA) seriously affects the children's cognitive functions, but the neuroimaging mechanism of cognitive impairment is still unclear. The purpose of our study was to explore the difference in brain local gray matter volume (GMV) between children with OSA and non-OSA, and the correlation between the difference regions of brain gray matter volume and cognitive, the severity of OSA. Eighty-three children aged 8-13 years were recruited in our study, 52 children were diagnosed as OSA by polysomnography, and 31 as the non-OSA. All the subjects were underwent high-resolution 3-dimensional T1-weighted magnetic resonance images. The voxel-based morphometry (VBM) was be used to analyse the local GMV. The Das-Naglieri cognitive assessment system (DN: CAS) was used to assess the subjects' cognitive. The difference of local GMV between the two groups was analyzed by two-sample T-test. The PSG variables and the scores of DN: CAS between the OSA group and non-OSA group were compared by independent samples t-tests. Pearson correlation was used to calculate the association between the difference areas of gray matter volumes in brain and DN: CAS scores, obstructive apnea/hypopnea index (OAHI, an index of the severity of OSA). The gray matter volume of the right Middle Frontal Gyrus (MFG_R) in OSA children were larger than the non-OSA children, and the OSA children had lower scores of the Word Series in DN: CAS. There was negative correlation between the scores of Expressive Attention in DN: CAS and the gray matter volume of the right middle frontal gyrus, and it was no significantly correlation between OAHI and the gray matter volume of the right middle frontal gyrus. Our results suggest that the development of gray matter volume in frontal cortex, which associated with attention, were sensitive to the effects of OSA, provides neuroimaging evidence for cognitive impairment in children with OSA.

A Critical Review on Human Malaria and Schistosomiasis Vaccines: Current State, Recent Advancements, and Developments.

Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches.

Identification of YWHAH as a Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure during Early Development.

Recently, the long-term use of sedative agents in the neonatal intensive care unit (NICU) has raised concerns about neurodevelopmental outcomes in exposed neonates. Midazolam (MDZ), a common neonatal sedative in the NICU, has been suggested to increase learning disturbances and cognitive impairment in children. However, molecular mechanisms contributing to such outcomes with long-term MDZ use during the early stages of life remain unclear. In this study, we for the first time elucidate the role of brain-derived extracellular vesicles (BDEVs), including mining the BDEV proteome post long-term MDZ exposure during early development. Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient. BDEVs from the control and MDZ groups were then characterized using a ZetaView nanoparticle tracking analyzer and transmission electron microscopy analysis. Next, using RT-qPCR, we examined the expression of key ESCRT-related genes involved in EV biogenesis. Lastly, using quantitative mass spectrometry-based proteomics, we mined the BDEV protein cargo that revealed key differentially expressed proteins and associated molecular pathways to be altered post long-term MDZ exposure. Our study characterized the proteome in BDEV cargo from long-term MDZ exposure at early development. Importantly, we identified and validated the expression of YWHAH as a potential target for further characterization of its downstream mechanism and a potential biomarker for the early onset of neurodevelopment and neurodegenerative diseases. Overall, the present study demonstrated long-term exposure to MDZ at early development stages could influence BDEV protein cargo, which potentially impact neural functions and behavior at later stages of development.