The eXtraordinarY BABIES STUDY: EARLY SOCIAL COMMUNICATION SKILLS IN INFANTS WITH SEX CHROMOSOME TRISOMY (SCT)

Purpose of Study: The eXtraordinarY Babies Study is a natural history study of health and neurodevelopment in infants with a prenatal diagnosis of SCT. Given the increased risk for social difficulties and autism in SCT in later childhood and beyond, the study explores trajectories of early social communication development to identify early predictors of outcomes, and relationship of social communication skills to developmental profiles. Methods Used: A subset of 56 participants (XXY=43, XYY=4, XXX=9) from the eXtraordinarY Babies Study completed the Autism Diagnostic Observation Schedule- 2nd edition (ADOS-2), Toddler Module as part of the 12-month visit and The Bayley-3 Scales of Infant and Toddler Development. The ADOS-2 provides ratings of 0 (typical development), 1 (mild atypicality), and 2 (atypical) for communication, social interaction, and other behavior items, and an algorithm classifies total score into categories of: Little-No Concern, Mild-Moderate Concern, Moderate-Severe Concern. Analyses were limited to those who completed the assessment prior to COVID19 mask/shield requirements. Summary of Results: High rates of delayed or atypical development of early social communication skills were identified, with >75% of the sample showing scores of 1 or 2 in frequency of babbling, spontaneous vocalizations, gesture use, and pointing. 58% of the sample showed unusual eye contact and vocalizations. Over 50% received atypical scores on items assessing the quality of eye contact. Participants showed few restricted and repetitive behaviors. Results of ADOS-2 total scores: Little-no concern 50%, Mild-Moderate concern 35.7%, Moderate-severe concern 14.3%. No one was assigned a clinical diagnosis of ASD. For this group, Bayley-3 results showed average Cognitive (scaled score 10.8 sd1.9) and Fine motor skills (9.3 sd2.3), followed by lower Receptive (8.2 sd2.4) and Expressive Language (8.9 sd3.0) and below average Gross Motor skills (7.9 sd2.6). Receptive language scores negatively correlated with ADOS-2 Social Affect (r= -.38, p = < .001) and Overall Total (r= -.41, p = < .001). Conclusion(s): Even at an early age, toddlers with SCT are at increased risk for language, communication, and social interaction delays. While no participants were diagnosed with ASD at 12 months of age, social communication deficits known to be "red flags" for later diagnosis of ASD were seen in a subset of young children with SCT. Prospective follow-up will allow us to determine the trajectory of these deficits and those that may predict higher risk for more significant clinical symptoms.

First in-neonate use of non-invasive transcutaneous auricular vagus nerve stimulation: 18-month neurodevelopmental and sensory follow-up

Objective: Non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) paired with oral feeding is a novel intervention for infants with feeding delays that may improve feeding and help avoid a gastrostomy tube (Gtube). However, the long-term impact of this neurostimulation on infant's development remains unknown. We investigated the neurodevelopmental and sensory outcomes of infants who received taVNS paired with bottle feeding. Method(s): Twenty-one of 35 toddlers who participated in the open label trial of taVNS paired with one or two feeds a day for 2-3 weeks, underwent comprehensive developmental assessments at 18 months of age using Cognitive Adaptive Test, Clinical Linguistics and Auditory Milestone, and Peabody gross motor scores. Twelve of those assessed achieved full oral feeds ('responders') and 9 had G-tube placed for feeds ('non-responders'). Before COVID, 12 toddlers (5 responders, 7 non-responders) were also assessed in the home using the Bayley-III and Sensory Profile (SP-2) assessments. Area deprivation index (ADI) was used to measure resource poor environments and relate to test scores. We used Fishers exact test and Pearson correlation coefficients to compare neurodevelopmental and sensory performance in responders versus non-responders. Result(s): taVNS responders showed significantly better general sensory processing in SP-2 than did non-responders (p =0.04). There were no significant differences in Bayley-III or CAT/CLAMS/ASQ scores in areas of cognition, receptive language, fine motor, and gross motor skills in this small sample size, but are similar to published scores for preterm infants who received G-tubes. ADI was not significantly associated with neurodevelopmental scores. Conclusion(s): These results suggest that taVNS paired with feeding may have a potential long-term positive neurodevelopmental effect on sensory processing in neonates with poor feeding. The current open-label results need testing in randomized controlled trials of taVNS paired with oral feeding in developmentally delayed infants failing oral feeds. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Neurodevelopment, taVNS, feeding, developmental delaysCopyright © 2023

The Role of Microparticles in Polycystic Ovarian Syndrome. An Updated Review

Microparticles (MPs) are vesicles of less than 1 mum in diameter (submicron vesicles) shed from plasma membranes to cell activation, injury, and apoptosis response. They consisted of membrane proteins and cytosolic material from the cell they originated. These vesicles are vital mediators of pathological and physiological cellular processes. Polycystic ovary syndrome (PCOS) is a regular endocrine, menstrual and metabolic condition that affects 10-15% of females in their reproductive period. Numerous researches have described the association between low-grade chronic inflammation and PCOS;however, the relation is not well understood. Chronic low-grade inflammation is reflected as a risk factor for cardiovascular disease, atherosclerosis, and endothelial dysfunction, and it is linked to abdominal obesity and insulin resistance (IR). MPs may be useful biomarkers for the early detection of cardiovascular disease and thrombosis in PCOS patients. In March 2020, the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic, wreaking havoc on healthcare systems worldwide and the global economy. Obesity, diabetes, and cardiovascular disease have all been linked to COVID-19 increased risk of infection. PCOS patients have recently been identified as an underserved and potentially high-risk demographic for COVID-19 problems. This article tried to review and present recent studies that explored the role of microparticles in polycystic ovarian syndrome.Copyright © 2022 International Journal of Pharmaceutical Research and Allied Sciences. All rights reserved.

Neurological Manifestations In COVID-19 Patients: An Imaging Review

Background: The COVID-19 pandemic that started in late 2019, has posed a great health challenge to India rapidly elevating our country to the second most affected nation after the United States. While the respiratory manifestations of COVID-19 are widely-known, there is paucity of information on its neurological manifestations in Indian literature. The imaging features of the diverse neurological presentations such as stroke, encephalitis, demyelination, hemorrhages and vascular involvement are reviewed in this article. Objective of the review is to discuss the spectrum of neuroimaging features in COVID-19. Method(s): Multiple publications from systematic and cohort studies on neuroimaging are reviewed in this article. Due permission was obtained from the publishers to reproduce the illustrations because of lack of adequate neuroimaging data in our country. Result(s): Ischemic infarcts, micro-hemorrhages, parenchymal hematomas and white matter changes, both diffuse and focal were the most common manifestations. Acute necrotizing hemorrhagic encephalitis, features resembling posterior reversible encephalopathy syndrome (PRES) and acute demyelinating encephalomyelitis (ADEM), arterial dissections, dural sinus and deep venous thrombosis were reported. Olfactory bulb and white matter signal ratios were elevated in anosmic patients. Micro-structural changes such as remyelination and neurogenesis indicated processes of repair. Conclusion(s): Ischemic and hemorrhagic lesions are the most common neuroimaging abnormalities in COVID-19 patients, though 40% of the studies are normal. Awareness of the imaging features is essential for management of these patients in the current pandemic. Severity of illness and risk of spread of infection are major constraints for neuroimaging. Copyright © 2022 International Medical Sciences Academy. All rights reserved.

Neurodevelopment in Infants with Antenatal or Early Neonatal Exposure to SARS-CoV-2

Background. Antenatal and neonatal viral exposure may put the developing brain at risk for abnormal neurodevelopment. A clinical follow-up program was created in the Congenital Infection Program at Children's National Hospital to follow infants with in utero or early life exposure to SARS-CoV-2. The aim of this study was to determine if infants with early SARS-CoV-2 exposure have abnormal neurodevelopment in infancy. Methods. We performed a retrospective review of all infants evaluated in the follow-up program between 3/2020 - 11/2021. Demographic details, SARS-CoV-2 infection/ testing data, pregnancy/birth data, and specialty consult and NICU records were extracted from infants' medical charts. Infants were divided into 3 SARS-CoV-2 exposure groups: 1) antenatal exposure to symptomatic mother, 2) antenatal exposure to asymptomatic mother, 3) neonatal infection. All infants received a neurologic exam and developmental screening with the Ages and Stages Questionnaire (ASQ) in 5 domains (Communication, Gross Motor, Fine Motor, Problem Solving, Personal-Social) during their evaluation. The ASQ accounts for prematurity. Outcomes of interest were an abnormal neurologic exam or ASQ scores close to or below suggested cut-offs. Multivariate analysis was used to study correlations between exposure group and neurodevelopmental outcomes. Results. Thirty-five infants were seen for up to 3 outpatient visits. Most infants (83%) were exposed in utero - 16 to symptomatic mothers (Group 1) and 12 to asymptomatic mothers (Group 2);1 chart did not have symptom data. Six were exposed only as a neonate (Group 3). Group 1 had abnormal neurologic exams at mean (SD) age 112 (24) days (Table 1) and ASQ scores close to or below cut-offs for all domains (Fig. 1) more frequently than Groups 2 or 3. Group 1 was more likely to score below any ASQ cutoff compared to Group 2 (P=.04);of the 5 domains, differences were significant for Fine Motor (P=.01) and Personal-Social (P=.02). Conclusion. Early SARS-CoV-2 exposure may impact infant development, especially among those exposed in utero to a symptomatic mother. Vaccination and other precautions to reduce spread and symptoms may protect against early neurodevelopmental delays. Future work should prioritize longitudinal follow-up of children with early SARS-CoV-2 exposure. (Table Presented).

Influenza and schizophrenia: Howcan we shed a light in the new virus from an old association?

Introduction: COVID-19 raises serious concerns regarding its unknown consequences for health, including psychiatric long term outcomes. Historically, influenza virus has been responsible for pandemics associated with schizophrenia. Epidemiological studies showed increased risk for schizophrenia in children of mothers exposed to the 1957 influenza A2 pandemic. Controversy remains concerning the mechanisms of pathogenesis underlying this risk. Objective(s): We aim to review the evidence for the association between influenza infection and schizophrenia risk, the possible pathogenic mechanisms underlying and correlate these findings with the schizophrenia hypothesis of neurodevelopment. Method(s): We reviewed literature regarding evidence from epidemiological, translational animal models and serological studies using medline database. Result(s): The biological mechanisms likely to be relevant account to the effects of infection-induced maternal immune activation, microglial activation, infection-induced neuronal autoimmunity, molecular mimicry of the influenza virus, neuronal surface autoantibodies and psychosis with potential infectious antecedents. Influenza infection may fit into the theory of the neurodevelopment of schizophrenia as a factor that alters the normal maturation processes of the brain (possible second or third hit). Conclusion(s): Influenza infection has multiple pathogenic pathways in both pre and post natal processes that might increase the risk of schizophrenia or psychosis. The existing evidence regarding the relationship between influenza virus and psychosis might help us draw similar long-term concerns of COVID-19.

3D engineered tissue models for studying human-specific infectious viral diseases

Viral infections cause damage to various organ systems by inducing organ-specific symptoms or systemic multi-organ damage. Depending on the infection route and virus type, infectious diseases are classified as respiratory, nervous, immune, digestive, or skin infections. Since these infectious diseases can widely spread in the community and their catastrophic effects are severe, identification of their causative agent and mechanisms underlying their pathogenesis is an urgent necessity. Although infection-associated mechanisms have been studied in two-dimensional (2D) cell culture models and animal models, they have shown limitations in organ-specific or human-associated pathogenesis, and the development of a human-organ-mimetic system is required. Recently, three-dimensional (3D) engineered tissue models, which can present human organ-like physiology in terms of the 3D structure, utilization of human-originated cells, recapitulation of physiological stimuli, and tight cell-cell interactions, were developed. Furthermore, recent studies have shown that these models can recapitulate infection-associated pathologies. In this review, we summarized the recent advances in 3D engineered tissue models that mimic organ-specific viral infections. First, we briefly described the limitations of the current 2D and animal models in recapitulating human-specific viral infection pathology. Next, we provided an overview of recently reported viral infection models, focusing particularly on organ-specific infection pathologies. Finally, a future perspective that must be pursued to reconstitute more human-specific infectious diseases is presented. Copyright © 2022 The Authors

Brain Organoids as a Model to Study Zika Virus and SARS-CoV-2 Infections

In recent years, we are living through different viral pandemics that result in neurological impairments. Given the human-specific nature of brain development, physiology, and pathology, it is imperative to use human models to investigate the neurological impact of viral infections, such as Zika virus and SARS-CoV-2. Brain organoids are powerful in vitro platforms for the analysis of the effects of viral infections on brain development and function, with prospective application to new emerging viral threats. Using brain organoids, it was possible to show that Zika virus infects neural stem cells, disrupting the cell cycle and neurogenesis, leading to microcephaly, a severe reduction of the brain. On the other hand, while it is still under investigation how SARS-CoV-2 might enter and alter the brain, organoid studies are helping to characterize its neurotropism and potential mechanisms of neurovirulence. Here, we describe a method for the infection of human brain organoid cultures with Zika and Sars-CoV-2 viruses that can be used to study neurodevelopmental phenotypes, alteration in neuronal functionality, host-pathogen interactions, as well as for drug testing. Copyright © 2023, Springer Science+Business Media, LLC, part of Springer Nature.

Donepezil Beyond Alzheimer’s Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer’s disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson’s disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer’s and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer’s diseases, and more comprehensive studies are needed.

INFANT DEVELOPMENTAL SCREENING AT 16 TO 18 MONTHS OF AGE AFTER IN-UTERO EXPOSURE TO MATERNAL SARS-COV-2 INFECTION

Purpose of Study Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in pregnant women is associated with increased maternal and neonatal morbidities. The impact of in-utero exposure to maternal SARS-CoV-2 infection on long-term infant neurodevelopment is currently unknown. Objective: The objective of the study was to undertake developmental screening in infants aged 16-18 months born to mothers with confirmed SARS-CoV-2 during pregnancy. Methods Used This was a descriptive prospective cohort study of full-term infants who had in-utero exposure to maternal SARS-CoV-2 infection as assessed by the Ages and Stages Questionnaire- 3rd edition® (ASQ-3®) at 16 to 18 months of life. Subjects were identified via electronic medical record search of full-term infants delivered to mothers with SARSCoV- 2 positive test during hospitalization between 3/1/2020 to 12/31/2020. The families of eligible subjects were contacted via telephone and if they agreed to participate an informed consent was obtained. Infants with prematurity (<37 weeks gestational age), major congenital anomalies or genetic diagnoses were excluded. Data on maternal and neonatal characteristics were extracted from the charts. Summary of Results A total of 31 children were enrolled in the study till date. Seven (23%) were below cutoff in at least one domain of development. Two subjects (6.5%) were below cutoff in more than one domain. Fine motor was identified as delayed among 3 children (10%). While communication, gross motor and problem solving was identified below cutoff in 2 children (6.5%). One child (3%) had delay in personal social domain. Conclusions About one-quarter of children with history of inutero exposure to maternal SARS-CoV-2 infection were below cutoff in at least one domain of development on (ASQ-3®) at 16-18 months. In this currently ongoing study, we intend to enroll larger group of children with in-utero exposure with maternal SARS-CoV-2.

The relationship between nutritional deficiencies and mental health

The objective of this mini review was to discuss the relationship between nutritional deficiencies and mental health, and to present a structure that helps to visualize these associations based on a literature review and the scenarios of the COVID-19 pandemic. The study was conducted to demonstrate the effect of the nutritional deficiencies on the occurrence and/or worsening of mental health problems, mainly related to the most drastic measures of social distance during the COVID-19 pandemic. Studies have already shown that a nutritionally unbalanced diet may be associated with greater chances of mental health problems. Insufficient levels of micronutrients can, by regulating the stress response, immune and oxidative systems, negatively affect brain functions and, consequently, cognitive functions and mental health of individuals. The current pandemic of COVID-19 reveals an increase in food and nutritional insecurity, and a worsening of this situation among already vulnerable populations. Micronutrient deficiencies may be exacerbated in a context of increased food insecurity and the COVID-19 pandemic, which may contribute to increased mental health problems.

POLICIES ON PARENTAL ACCESS RESTRICTION IN NEONATAL UNITS AND MATERNITY WARDS DURING THE SARS-COV-2 PANDEMIC

Background. Since the beginning of the SARS-CoV-2 pandemic, most neonatal units around the world have restricted parents’ access, aiming to protect the staff and the babies against the infection. Objective. To evaluate the side effects of the limitation of parents presence with their babies in neonatal units and those related to restrictions on maternity wards access. Method. Literature review. A search using ‘SARS-CoV-2’ and ‘COVID-19’ as keywords combined to ‘neonatal’, ‘NICU’, ‘parents’, ‘family centered care’ and ‘neurodevelopmental care’. Consultation of websites containing updated and summarized scientific literature about the pandemic and its consequences in newborns has also been performed: www.dontforgetthebubles.com and www.seneo.es. The voice of the families has been mainly obtained through the websites of their associations and the social networks. Results. The family-centered care model has shown positive effects on the health of sick newborns and on premature infants’ neurodevelopment. This model of care is under threat if parental access is limited. It has been shown that these restrictions have also adverse effects on breastfeeding and on caregivers’ psychological wellbeing. Data from different neonatal series report a benign course of COVID-19 infection in neonates and preterm babies. Conclusions. At a crucial moment for the implementation of the developmental centered care model in Catalan neonatal units, and with the available data, it is essential to redesign the policies regarding parents who accompany their babies admitted to the units.