Management of patients with cognitive impairment.

The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Issues of diagnostics and therapy of patients with CI and their high mortality during the period of coronavirus infection are discussed. A wide prevalence of patients with mild CI (MCI), an important role of neuropsychological research in establishing CI, and frequent diagnosis of CI only at the stage of dementia were noted. In our country, CI is poorly diagnosed, the most common cause of CI in the elderly - Alzheimer's disease (AD) - is rarely established, patients are observed for a long time with a diagnosis of cerebrovascular disease (CVD). Some non-drug and drug methods can reduce the manifestations of CI, improve the quality of life of both the patients themselves and those around them. In severe CI, socio-psychological methods, stimulating patients to feasible household and social, physical and mental activity, and avoiding prolonged hospitalization are of primary importance. In addition to lifestyle changes, much attention in CI is given to the prevention of stroke, the treatment of arterial hypertension and diabetes mellitus. At the stage of dementia, cholinomimetic drugs (acetylcholinesterase inhibitors, donepezil, rivastigmine, galantamine) and the glutamate receptor blocker memantine are used. The use of choline alfoscerate in CI and the results of the multicenter, placebo-controlled ASCOMALVA study are discussed, in which, in patients with AD and CVD, the addition of choline alfoscerate to donepezil reduced the severity of CI, manifestations of depression, anxiety, and apathy. A new oral form of choline alfoscerate (Cerpechol) is reported that may improve patient compliance and be used in patients with swallowing disorders.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

COVID-19 vaccine related hypermetabolic lymph nodes on PET/CT: Implications of inflammatory findings in cancer imaging.

We observed several patients presenting 2-[18F]FDG uptake in the reactive axillary lymph node at PET/CT imaging, ipsilateral to the site of the COVID-19 vaccine injection. Analog finding was documented at [18F]Choline PET/CT. The aim of our study was to describe this source of false positive cases. All patients examined by PET/CT were included in the study. Data concerning patient anamnesis, laterality, and time interval from recent COVID-19 vaccination were recorded. SUVmax was measured in all lymph nodes expressing tracer uptake after vaccination. Among 712 PET/CT scans with 2-[18F]FDG, 104 were submitted to vaccination; 89/104 patients (85%) presented axillary and/or deltoid tracer uptake, related to recent COVID-19 vaccine administration (median from injection: 11 days). The mean SUVmax of these findings was 2.1 (range 1.6-3.3). Among 89 patients with false positive axillary uptake, 36 subjects had received chemotherapy due to lymph node metastases from somatic cancer or lymphomas, prior to the scan: 6/36 patients with lymph node metastases showed no response to therapy or progression disease. The mean SUVmax value of lymph nodal localizations of somatic cancers/lymphomas after chemotherapy was 7.8. Only 1/31 prostate cancer patients examined by [18F]Choline PET/CT showed post-vaccine axillary lymph node uptake. These findings were not recorded at PET/CT scans with [18F]-6-FDOPA, [68Ga]Ga-DOTATOC, and [18F]-fluoride. Following COVID-19 mass vaccination, a significant percentage of patients examined by 2-[18F]FDG PET/CT presents axillary, reactive lymph node uptake. Anamnesis, low-dose CT, and ultrasonography facilitated correct diagnosis. Semi-quantitative assessment supported the visual analysis of PET/CT data; SUVmax values of metastatic lymph nodes were considerably higher than post-vaccine lymph nodes. [18F]Choline uptake in reactive lymph node after vaccination was confirmed. After the COVID-19 pandemic, nuclear physicians need to take these potential false positive cases into account in daily clinical practice.

Management of patients with cognitive impairment.

The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Issues of diagnostics and therapy of patients with CI and their high mortality during the period of coronavirus infection are discussed. A wide prevalence of patients with mild CI (MCI), an important role of neuropsychological research in establishing CI, and frequent diagnosis of CI only at the stage of dementia were noted. In our country, CI is poorly diagnosed, the most common cause of CI in the elderly - Alzheimer's disease (AD) - is rarely established, patients are observed for a long time with a diagnosis of cerebrovascular disease (CVD). Some non-drug and drug methods can reduce the manifestations of CI, improve the quality of life of both the patients themselves and those around them. In severe CI, socio-psychological methods, stimulating patients to feasible household and social, physical and mental activity, and avoiding prolonged hospitalization are of primary importance. In addition to lifestyle changes, much attention in CI is given to the prevention of stroke, the treatment of arterial hypertension and diabetes mellitus. At the stage of dementia, cholinomimetic drugs (acetylcholinesterase inhibitors, donepezil, rivastigmine, galantamine) and the glutamate receptor blocker memantine are used. The use of choline alfoscerate in CI and the results of the multicenter, placebo-controlled ASCOMALVA study are discussed, in which, in patients with AD and CVD, the addition of choline alfoscerate to donepezil reduced the severity of CI, manifestations of depression, anxiety, and apathy. A new oral form of choline alfoscerate (Cerpechol) is reported that may improve patient compliance and be used in patients with swallowing disorders.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Phospholipase D-Catalyzed Transphosphatidylation for the Synthesis of Rare Complex Phospholipid Species─Hemi-bis(monoacylglycero)phosphate and Bis(diacylglycero)phosphate

Progress in developing synthetic pathways for novel and complex phospholipid species, such as Hemi-bis(monoacylglycero)phosphates (Hemi-BMPs) and bis(diacylglycero)phosphates (BDPs), is essential for expanding the knowledge and availability of rare and uncommon phospholipid species. These structurally complex phospholipid species have recently gained more attention with promising applications, as active pharmaceutical ingredient carriers in multiple COVID-19 vaccines, or biomarkers for numerous lysosomal storage disorders and certain types of cancers. The presented work facilitates the production of a range of structurally diverse Hemi-BMP and BDP products intending to increase the availability and thereby the understanding of the underlying chemistry for these high-valuable compounds. The transphosphatidylation of phosphatidylcholine with a variety of structurally diverse monoacylglycerols and diacylglycerols is proceeded by phospholipase D (PLD) catalysis in a biphasic system. Optimization in regard to enzyme loading (5 U), substrate mole ratio (1:5 mol/mol), temperature (30 °C), and aqueous concentration of (18% v/v) afforded the highest conversion for the model transphosphatidylation of phosphatidylcholine with monoolein, yielding 87% in 2 h. The study additionally proposes a reaction mechanism based on molecular simulation, elegantly elaborating the structural constraints (substrate configuration and character of the fatty acid residues) for access to the active site of PLD accordingly for lower yield of BDPs. The successful system designed for the production of high-valuable Hemi-BMP and BDP-analogues demonstrated in this work promises to enhance the understanding of these complex phospholipids, leading to new scientific breakthroughs. © 2023 American Chemical Society.

Ocular Myasthenia Gravis: A Current Overview.

Ocular myasthenia gravis (OMG) is a neuromuscular disease characterized by autoantibody production against post-synaptic proteins in the neuromuscular junction. The pathophysiological auto-immune mechanisms of myasthenia are diverse, and this is governed primarily by the type of autoantibody production. The diagnosis of OMG relies mainly on clinical assessment, the use of serological antibody assays for acetylcholine receptors (AchR), muscle-specific tyrosine kinase (MusK), and low-density lipoprotein 4 (LPR4). Other autoantibodies against post-synaptic proteins, such as cortactin and agrin, have been detected; however, their diagnostic value and pathogenic effect are not yet clearly defined. Clinical tests such as the ice test and electrophysiologic tests, particularly single-fiber electromyography, have a valuable role in diagnosis. The treatment of OMG is primarily through cholinesterase inhibitors (pyridostigmine), and steroids are frequently required in cases of ophthalmoplegia. Other immunosuppressive therapies include antimetabolites (azathioprine, mycophenolate mofetil, methotrexate) and biological agents such as B-cell depleting agents (Rituximab) and complement inhibitors (eculizumab). Evidence is scarce on the effect of immunosuppressive therapy on altering the natural course of OMG. Clinicians must be vigilant of a myasthenic syndrome in patients using immune-check inhibitors. Reliable and consistent biomarkers are required to assess disease severity and response to therapy to optimize the management of OMG. The purpose of this review is to summarize the current trends and the latest developments in diagnosing and treating OMG.

[Postcovid cognitive impairment]. / Postkovidnye kognitivnye narusheniya.

This review addresses current issues in post-COVID syndrome with a focus on neurocognitive impairment. The results of studies on complications in patients of different ages and health statuses recovered from mild to severe COVID-19 are discussed. Current data on the pathogenetic mechanisms of the development of various post-COVID disorders are presented, including a detailed discussion of central nervous system damage. The paper summarizes data on the relationship between neurocognitive disorders and accelerated cell aging, chronic nonspecific inflammation, and reduced neuroplasticity in the central nervous system. The main pathogenetic ways to prevent COVID-related complications, including neuronal tissue damage and the prospects for managing such patients are discussed. The choice of pathogenetic therapy in patients with neurocognitive impairment in the post-COVID period is assessed. The main benefits of choline alfoscerate therapy for neurocognitive impairment in patients with post-COVID syndrome are discussed.

Pulmonary Phospholipid Components as Promising Natural Inhibitors against COVID-19 Mpro;Molecular Docking Analysis Based Study

The ongoing pandemic of COVID-19 caused by the severe acute respiratory syndrome SARS-CoV-2 has become a global crisis. Phospholipids are structural components of mammalian cell membranes that suppress viral attachment to the plasma membrane and subsequent replication in lung cells. Using the molecular docking approach, the inhibitory activity of phosphatidylcholine, dipalmitoylphosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidyl-inositol, lysobisphosphatidic acid and sphingomyelin against SARS CoV-2 by targeting main protease (Mpro, PDB code: 6LU7) has been investigated. All phospholipids established excellent binding to Mpro active bocket by forming several H-bonds with the catalytic amino acids Cys145 and His4, as well as various amino acids involved in the bocket. Furthermore, a potent binding affinity is increased from -7.01 to -9.16 kcal/mol compared to compound N3 (N-[(5methylisoxazol-3-yl)carbonyl]alanyl-L (where L = valyl-N-1-(1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide), a peptide linker, inhibitor for Covid-19 main protease. Co-crystalline ligand of enzyme 6LU7 of -9.99 kcal/mol. The sphingomyelin has the same binding affinity to main protease when compared to compound N3. These findings implied that the selected compounds have the potential to be developed as novel SARS-CoV-2 inhibitors. Therefore, improved, well-designed, potent and structurally and pharmacokinetically effective drugs are urgently needed. Further investigations should focus on validating and finalizing effective drugs for COVID-19 beyond preliminary in silico and in vivo screening. © 2022 Chemical Publishing Co.. All rights reserved.

COVID-19 vaccination simulating lymph node progression in a patient with prostate cancer.

Several cases of cancer patients with 18-fluorodeoxyglucose (18FDG) Positron Emission Tomography/Computed Tomography (PET/CT) evidence of metabolically active axillary lymph nodes after COVID-19 vaccination have been described, creating a diagnostic dilemma and sometimes leading to further unnecessary examinations. A 62-year-old male, diagnosed with prostate cancer, treated with hormone-therapy and radiotherapy of the prostate 2 years before, underwent fluorine-18 choline (F-FCH) PET/CT for restaging purpose, less than 3 weeks after he had received the second dose of the Pfizer BioNTech-BNT162b2 mRNA COVID-19 vaccine. This exam showed an increased F-FCH uptake and an enlargement of the left axillary, paratracheal, para-aortic, subcarinal, and hilar bilateral lymph nodes. Fourteen weeks later, the patient underwent a new F-FCH PET-CT scan, displaying an almost complete regularization of the FCH uptake in all the previously involved regions. The patient was not treated after the first PET-CT scan, thus, the aforementioned PET/CT findings represented inflammatory vaccine-related lymph nodes. This case highlights the significance of knowing vaccination history to correctly interpret imaging findings and to avoid false-positive reports.

Kombucha - An ancient fermented beverage with desired bioactivities: A narrowed review.

Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

COVID-19 and One-Carbon Metabolism.

Dysregulation of one-carbon metabolism affects a wide range of biological processes and is associated with a number of diseases, including cardiovascular disease, dementia, neural tube defects, and cancer. Accumulating evidence suggests that one-carbon metabolism plays an important role in COVID-19. The symptoms of long COVID-19 are similar to those presented by subjects suffering from vitamin B12 deficiency (pernicious anemia). The metabolism of a cell infected by the SARS-CoV-2 virus is reshaped to fulfill the need for massive viral RNA synthesis, which requires de novo purine biosynthesis involving folate and one-carbon metabolism. Many aspects of host sulfur amino acid metabolism, particularly glutathione metabolism underlying antioxidant defenses, are also taken over by the SARS-CoV-2 virus. The purpose of this review is to summarize recent findings related to one-carbon metabolism and sulfur metabolites in COVID-19 and discuss how they inform strategies to combat the disease.

DEVELOPMENT OF A DIETARY SUPPLEMENT FOR IMPROVING THE COGNITIVE FUNCTIONS AN D LOWERING THE HOMOCYSTEINE LEVELS

Introduction. Hyperhomocysteinemia is a dangerous metabolic disorder that leads to a number of diseases. Problem Statement. Urgent task is to develop pharmaceutical product for lowering the homocysteine levels without causing side effects. Purpose. To develop the dietary supplement for reducing high homocysteine levels, which has a minimum content of components that may cause side effects;to test the supplement effect on the cognitive abilities of animals and to commercialize the product. Materials and Methods. The developed dietary supplement Alfacognitin contains vitamins B6, B9, B12, C, and choline. For modelling experimental hyperhomocysteinemia in rats, the animals are kept on a diet rich in L-methionine. Blood homocysteine concentrations are determined by the ion exchange liquid column chromatography method with the use of an automatic amino acid analyzer. The behavioral responses and cognitive abilities of the rats have been studied with the use of behavioral tests (open field test, fear conditioning test, and social interaction test). The production of Alfacognitin dietary supplement has been launched with Nutrimed Ltd. (Kyiv). Results. Alfacognitin has been shown to reduce homocysteine levels, to improve cognitive abilities, social interaction and communication skills, and to compensate functional memory and learning disorders in animals with hyperhomocysteinemia. Specifications for the dietary supplement have been approved, a pilot technology for obtaining the capsule form of the drug has been developed, and an experimental batch has been manufactured. Conclusions. Alfacognitin may reduce the homocysteine levels. Therefore, it may be used to normalize the functional state of the cardiovascular and nervous systems in patients with hyperhomocysteinemia, as well as to improve the cognitive functions, in particular in patients after COVID-19.

Frequency and Characteristics of Nodal and Deltoid FDG and 11C-Choline Uptake on PET Performed After COVID-19 Vaccination.

BACKGROUND. COVID-19 vaccination may trigger reactive lymphadenopathy, confounding imaging interpretation. There has been limited systematic analysis of PET findings after COVID-19 vaccination. OBJECTIVE. The purpose of this study was to evaluate the frequency and characteristics of abnormal FDG and 11C-choline uptake on PET performed after COVID-19 vaccination. METHODS. This retrospective study included 67 patients (43 men and 24 women; mean [± SD] age, 75.6 ± 9.2 years) who underwent PET examination between December 14, 2020, and March 10, 2021, after COVID-19 vaccination and who had undergone prevaccination PET examination without visible axillary node uptake. A total of 52 patients received the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech; hereafter referred to as the Pfizer-BioNTech vaccine), and 15 received the SARS-CoV-2 mRNA-1273 vaccine (Moderna; hereafter referred to as the Moderna vaccine). Sixty-six of the patients underwent PET/CT, and one underwent PET/MRI. Fifty-four PET examinations used FDG, and 13 used 11C-choline. PET was performed a median of 13 and 10 days after vaccination for patients who had received one (n = 44) and two (n = 23) vaccine doses, respectively. Two nuclear medicine physicians independently reviewed images and were blinded to injection laterality and the number of days since vaccination. Lymph node or deltoid SUVmax greater than the blood pool SUVmax was considered positive. Interreader agreement was assessed, and the measurements made by the more experienced physician were used for subsequent analysis. RESULTS. Positive axillary lymph node uptake was observed in 10.4% (7/67) of patients (7.4% [4/54] of FDG examinations and 23.1% [3/13] of 11C-choline examinations); of the patients with positive axillary lymph nodes, four had received the Pfizer vaccine, and three had received the Moderna vaccine. Injection laterality was documented for five of seven patients with positive axillary lymph nodes and was ipsilateral to the positive node in all five patients. PET was performed within 24 days of vaccination for all patients with a positive node. One patient showed extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). Ipsilateral deltoid uptake was present in 14.5% (8/55) of patients with documented injection laterality, including 42.9% (3/7) of patients with positive axillary lymph nodes. Interreader agreement for SUV measurements (expressed as intraclass correlation coefficients) ranged from 0.600 to 0.988. CONCLUSION. Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after COVID-19 vaccination with the Pfizer-BioNTech or Moderna vaccine. CLINICAL IMPACT. Interpreting physicians should recognize characteristics of abnormal uptake on PET after COVID-19 vaccination to guide optimal follow-up management and reduce unnecessary biopsies.

Maternal nutrients and effects of gestational COVID-19 infection on fetal brain development.

BACKGROUND & AIMS: Maternal gestational infection is a well-characterized risk factor for offsprings' development of mental disorders including schizophrenia, autism, and attention deficit disorder. The inflammatory response elicited by the infection is partly directed against the placenta and fetus and is the putative pathogenic mechanism for fetal brain developmental abnormalities. Fetal brain abnormalities are generally irreversible after birth and increase risk for later mental disorders. Maternal immune activation in animals models this pathophysiology. SARS-CoV-2 produces maternal inflammatory responses during pregnancy similar to previously studied common respiratory viruses. METHOD: Choline, folic acid, Vitamin D, and n-3 polyunsaturated fatty acids are among the nutrients that have been studied as possible mitigating factors for effects of maternal infection and inflammation on fetal development. Clinical and animal studies relevant to their use in pregnant women who have been infected are reviewed. RESULTS: Higher maternal choline levels have positive effects on the development of brain function for infants of mothers who experienced viral infections in early pregnancy. No other nutrient has been studied in the context of viral inflammation. Vitamin D reduces pro-inflammatory cytokines in some, but not all, studies. Active folic acid metabolites decrease anti-inflammatory cytokines. N-3 polyunsaturated fatty acids have no effect. CONCLUSIONS: Vitamin D and folic acid are already supplemented in food additives and in prenatal vitamins. Despite recommendations by several public health agencies and medical societies, choline intake is often inadequate in early gestation when the brain is forming. A public health initiative for choline supplements during the pandemic could be helpful for women planning or already pregnant who also become exposed or infected with SARS-CoV-2.

[Direct and indirect neurological manifestations of COVID-19]. / O pryamykh i kosvennykh nevrologicheskikh proyavleniyakh COVID-19.

OBJECTIVE: To systemize the neurological manifestations of COVID-19. MATERIALS AND METHODS: A systematic computer analysis of all currently available publications on the neurological manifestations of COVID-19 (2374 publications in PUBMED) using algorithms of topological data analysis was performed. RESULTS: A complex of interactions between SARS-CoV-2 infection, metabolic disorders of neurotransmitters (acetylcholine, dopamine, serotonin and GABA), enkephalins and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia and neurodegeneration, including demyelination, was described. The most common neurological manifestation of COVID-19 is anosmia/ageusia arising as a result of ischemia, neurodegeneration, and/or systemic elevation of proinflammatory cytokine levels. COVID-19 provokes ischemic stroke, Guillain-Barré syndrome, polyneuropathy, encephalitis, meningitis and parkinsonism. Coronavirus infection significantly aggravates the course of multiple sclerosis and myopathies. Possible roles of the human virome in the neuropathophysiology of COVID-19 are considered. A case of clinical management of a patient with neurological complications of COVID-19 is described. CONCLUSION: In the long term, COVID-19 stimulates neurodegenerative changes, which require specific programs of neurological rehabilitation. It is advisable to use choline drugs and antihypoxants that are compatible with COVID-19 therapy.

Neuroprotective immunity by essential nutrient "Choline" for the prevention of SARS CoV2 infections: An in silico study by molecular dynamics approach.

Prenatal COVID infection is one of the worst affected and least attended aspects of the COVID-19 disease. Like other coronaviruses, CoV2 infection is anticipated to affect fetal development by maternal inflammatory response on the fetus and placenta. Studies showed that higher prenatal choline level in mother's body can safeguard the developing brain of the fetus from the adverse effects of CoV2 infection. Choline is commonly used as food supplement. By virtual screening, molecular docking and molecular dynamics techniques, we have established a strong inhibitory possibility of choline for SARS 3CLpro protease which may provide a lead for prenatal COVID-19 treatment.

Prospects for improving future mental health of children through prenatal maternal micronutrient supplementation in China.

Prenatal micronutrients in pregnant women's diets, including supplements, have an essential role in fetal brain development and may reduce the risk of mental disorders in offspring. Folic acid, vitamin D, omega-3 fatty acids, and choline have been investigated for this purpose. Folic acid supplementation throughout pregnancy has well-established positive effects. Vitamin D, administered to the mother before birth or to the newborn, has also been shown to reduce the risk of neurodevelopmental disorders. Omega-3 fatty acids during pregnancy have a more uncertain role, with recent trials questioning a beneficial effect on cognition and attention deficit disorder, despite positive effects on prematurity and neonatal wheezing prevention. Choline supplementation is associated with positive effects on cognition and behavior, including early behaviors associated with the development of autism and schizophrenia. There is no experience yet with COVID-19, but adverse effects on fetal brain development of most common coronaviruses are mitigated by higher choline levels. Maternal dietary supplementation of nutrients is a benign and inexpensive intervention in pregnancy to prevent life-long disability from mental illness. Use of dietary supplements in poorer, rural areas of China is below recommendations. Physicians, midwives, and public health officials in China can promote prenatal nutrient supplementation to reduce the future burden of mental illnesses that might be prevented before birth.

Maternal choline and respiratory coronavirus effects on fetal brain development.

Prenatal COVID-19 infection is anticipated by the U.S. Centers for Disease Control to affect fetal development similarly to other common respiratory coronaviruses through effects of the maternal inflammatory response on the fetus and placenta. Plasma choline levels were measured at 16 weeks gestation in 43 mothers who had contracted common respiratory viruses during the first 6-16 weeks of pregnancy and 53 mothers who had not. When their infants reached 3 months of age, mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), which assesses their infants' level of activity (Surgency), their fearfulness and sadness (Negativity), and their ability to maintain attention and bond to their parents and caretakers (Regulation). Infants of mothers who had contracted a moderately severe respiratory virus infection and had higher gestational choline serum levels (≥7.5 mM consistent with U.S. Food and Drug Administration dietary recommendations) had significantly increased development of their ability to maintain attention and to bond with their parents (Regulation), compared to infants whose mothers had contracted an infection but had lower choline levels (<7.5 mM). For infants of mothers with choline levels ≥7.5 µM, there was no effect of viral infection on infant IBQ-R Regulation, compared to infants of mothers who were not infected. Higher choline levels obtained through diet or supplements may protect fetal development and support infant early behavioral development even if the mother contracts a viral infection in early gestation when the brain is first being formed.