Predictors of poor neurodevelopmental outcomes in neonates with clinically observed seizures: A prospective observational study in a tertiary care hospital of Bangladesh.

Neonatal seizures can lead to long-term neurodevelopmental problems. This study aims to identify predictors of poor developmental outcomes in neonates with seizures to aid in early intervention and referral for follow-up and rehabilitation. This observational study was conducted in the Department of Neonatology and Institute of Paediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University. Among 75 study cases of neonatal seizure, 23 died, and 46 were followed-up at 6 and 9 months after discharge. EEGs were performed on every patient. A comprehensive neurological examination and developmental evaluation were performed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III). Three-fourths of neonates were born at term (76.1 %), and over half were male (56.5 %). The majority were appropriate for gestational age (79.7 %) and had an average birth weight of 2607 ± 696 g (±SD). Over half of the neonates (52.2 %) had adverse neurodevelopmental outcomes, with global developmental delay being the most common. Recurrent seizures, the number of anticonvulsants needed to control seizures, and abnormal Electroencephalograms were identified as independent predictors of adverse neurodevelopmental outcomes. The study highlights the need for early referral for follow-up and rehabilitation of neonates with seizures having abnormal electroencephalograms, recurrent seizures and requiring more anticonvulsants to control seizures.

Identification of B and T Cell Epitopes to Design an Epitope-Based Peptide Vaccine against the Cell Surface Binding Protein of Monkeypox Virus: An Immunoinformatics Study.

Background: Although the monkeypox virus-associated illness was previously confined to Africa, recently, it has started to spread across the globe and become a significant threat to human lives. Hence, this study was designed to identify the B and T cell epitopes and develop an epitope-based peptide vaccine against this virus's cell surface binding protein through an in silico approach to combat monkeypox-associated diseases. Results: The analysis revealed that the cell surface binding protein of the monkeypox virus contains 30 B cell and 19 T cell epitopes within the given parameter. Among the T cell epitopes, epitope "ILFLMSQRY" was found to be one of the most potential peptide vaccine candidates. The docking analysis revealed an excellent binding affinity of this epitope with the human receptor HLA-B∗15:01 with a very low binding energy (-7.5 kcal/mol). Conclusion: The outcome of this research will aid the development of a T cell epitope-based peptide vaccine, and the discovered B and T cell epitopes will facilitate the creation of other epitope and multi-epitope-based vaccines in the future. This research will also serve as a basis for further in vitro and in vivo analysis to develop a vaccine that is effective against the monkeypox virus.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Autism spectrum disorder among 16- to 30-month-old children in Bangladesh: Observational cross-sectional study.

LAY ABSTRACT: A nationwide survey was done in Bangladesh to assess autism spectrum disorder prevalence in 16- to 30-month-old children at urban-rural distribution and to determine the association with socioeconomic and demographic conditions. A three-stage cluster sampling method was used where districts from all divisions were selected in the first stage, census enumeration areas as blocks of households were selected in the second stage and households (within the blocks) were selected in the third stage. Thereby, it included 38,440 children from 37,982 households (71% rural, 29% urban) aged 16-30 months from 30 districts of eight divisions of Bangladesh. Screening was done with a 'Red Flag' tool and Modified Checklist for Toddlers and a final diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th Edition for autism spectrum disorder. Autism spectrum disorder prevalence was 17 per 10,000 young children - in other words, one in 589 young children. Boys were found at higher risk of autism (one in 423 boys; one in 1026 girls). Prevalence of autism spectrum disorder was higher in urban environments than in rural ones - 25/10,000 and 14/10,000, respectively. More autism spectrum disorder children were found in advanced age groups of parents, especially mothers, and in households with a higher wealth quintile. This survey is significant as it covers both urban and rural areas and specifically targets very young children. The involvement of the Bangladesh Bureau of Statistics, as well as support from the entire healthcare system infrastructure, makes this survey more representative on a national level. Its results will form a database to support the development of an effective early intervention programme in Bangladesh. We hope it will prove useful for researchers, clinicians and frontline healthcare workers, and inform the decisions of policymakers and funders in Bangladesh.

Structural and Functional Annotation and Molecular Docking Analysis of a Hypothetical Protein from Neisseria gonorrhoeae: An In-Silico Approach.

Background: Worldwide, Neisseria gonorrhoeae-related sexually transmitted infections (STIs) continue to be of significant public health concern. This obligate-human pathogen has developed a number of defenses against both innate and adaptive immune responses during infection, some of which are mediated by the pathogen's proteins. Hence, the uncharacterized proteins of N. gonorrhoeae can be annotated to get insight into the unique functions of this organism related to its pathogenicity and to find a more efficient therapeutic target. Methods: In this study, a hypothetical protein (HP) of N. gonorrhoeae was chosen for analysis and an in-silico approach was used to explore various properties such as physicochemical characteristics, subcellular localization, secondary structure, 3D structures, and functional annotation of that HP. Finally, a molecular docking analysis was performed to design an epitope-based vaccine against that HP. Results: This study has identified the potential role of the chosen HP of N. gonorrhoeae in plasmid transfer, cell cycle control, cell division, and chromosome partitioning. Acidic nature, thermal stability, cytoplasmic localization of the protein, and some of its other physicochemical properties have also been identified through this study. Molecular docking analysis has demonstrated that one of the T cell epitopes of the protein has a significant binding affinity with the human leukocyte antigen HLA-B∗15 : 01. Conclusions: The in-silico characterization of this protein will help us understand molecular mechanism of action of N. gonorrhoeae and get an insight into novel therapeutic identification processes. This research will, therefore, enhance our knowledge to find new medications to tackle this potential threat to humankind.

Rural women participation in farm and off-farm activities and household income in Bangladesh.

The present study was mainly an impact of farm and off-farm activities on household income and participation of rural women in the Thakurgaon district of Bangladesh. The specific aim was to compare the rural women's participation considering their socioeconomic characteristics, income contribution to household income, and its influencing factors. An Independent Sample T-test was used to compare socioeconomic differences. Pearson's correlation test was used to determine the relationship between women's personal income and household income. The propensity Score Matching (PSM) model was used for impact evaluation of off-farm activities. The result of the t-test showed that off-farm activities were significantly ahead for women from the farm women in terms of socioeconomic variables. There was positive and a strong correlation between women's personal income from off-farm activities and their household income. The result of PSM shows that off-farm activities have a positive and significant impact on rural women's income. Estimation of the binary Probit model and marginal effects of related explanatory variables revealed that educational status, family size, work experiences, personal income, saving, and training, significantly affected rural women's involvement in off-farm activities. Therefore, to increase the pace of work, the participation of rural women in off-farm activities needs to be made more effective and efficient, for which government and non-government organizations need to take necessary steps in area-based development (such as work environment, credit facilities, communication, infrastructure, etc.).

Classifying etiology of infantile spasms syndrome in resource-limited settings: A study from the South Asian region.

OBJECTIVE: Etiological classification of infantile spasms syndrome (ISS) is important, considering the influence on prognosis based on the presence or absence of a known etiology. This study was performed to describe the limitations and difficulties experienced within the South Asian region when classifying the etiology of ISS according to the current recommendation. METHOD: Data on healthcare indices and facilities related to management of ISS for the nine countries in the South Asian region were gathered by the South Asian West Syndrome Research Group. A Google survey was performed among three hundred and thirty pediatric neurologists in the region. The capacity within each country for investigating etiology of ISS according to current described benchmarks was evaluated. The difficulties experienced in this regard and the potential solutions were investigated. RESULTS: One hundred and sixty pediatric neurologists (response rate 48%) from Bangladesh (19/25), India (94/255), Myanmar (11/11), Nepal (6/8), Pakistan (19/25), and from Sri Lanka (7/8) responded. Three countries had no pediatric neurology services. Fifty-six percent attempted to classify ISS etiology according to classification outlined by International League Against Epilepsy in 2017. The facilities to perform metabolic, genetic, and immunological investigations were very limited. Lack of funding for investigations and poor laboratory support were the two most frequent barriers encountered. Sixty percent indicated that a separate classification is suitable for low-income setting; 78% suggested inclusion of separate category as "incompletely investigated" as an alternative solution to mitigate the barrier of achieving a better understanding of the etiological subtypes seen more frequently in this region. SIGNIFICANCE: The resources in South Asian region are limited to meet the recommendations for investigating etiology of ISS. Including the etiological subcategory "incompletely investigated" is proposed as an alternative to understand the true proportions of children in this region, with a definite known etiology and those with an unknown etiology.

Genetic Diagnosis in Children with Epilepsy and Developmental Disorders by Targeted Gene Panel Analysis in a Developing Country.

BACKGROUND AND PURPOSE: In childhood epilepsy, genetic etiology is increasingly recognized in recent years with the advent of next generation sequencing. This has broadened the scope of precision medicine in intractable epilepsy, particularly epileptic encephalopathy (EE). Developmental disorder (DD) is an integral part of childhood uncontrolled epilepsy. This study was performed to investigate the genetic etiology of childhood epilepsy and DD. METHODS: In this study, 40 children with epilepsy and DD with positive genetic mutation were included retrospectively. It was done in a tertiary care referral hospital of Bangladesh from January 2019 to December 2020. Genetic study was done by next generation sequencing. In all cases electroencephalography, neuroimaging was done and reviewed. RESULTS: In total, 40 children were enrolled and the average age was 41.4±35.850 months with a male predominance (67.5%). Generalized seizure was the predominant type of seizure. Regarding the association, intellectual disability and attention deficit hyperactivity disorder was common. Seventeen cases had genetically identified early infantile EE and common mutations observed were SCN1A (3), SCN8A (2), SLC1A2 (2), KCNT1 (2), and etc. Five patients of progressive myoclonic epilepsy were diagnosed and the mutations identified were in KCTD7, MFSD8, and CLN6 genes. Three cases had mitochondrial gene mutation (MT-ND5, MT-CYB). Some rare syndromes like Gibbs syndrome, Kohlschütter-Tönz syndrome, Cockayne syndrome, Pitt-Hopkins syndrome and cerebral creatine deficiency were diagnosed. CONCLUSIONS: This is the first study from Bangladesh on genetics of epilepsy and DD. This will help to improve the understanding of genetics epilepsy of this region as well as contribute in administering precision medicine in these patients.

Teleneurology based management of infantile spasms during COVID-19 pandemic: A consensus report by the South Asia Allied West syndrome research group.

With telehealth services rescuing patients with chronic neurological disorders during the COVID-19 pandemic, there is a need for simplified teleneurology protocols for neurological disorders in children. Infantile spasms is an epileptic encephalopathy where treatment lag is a significant predictor of outcome. It is one such condition where telemedicine can make a remarkable difference when in-person consultations are delayed or are not possible. However, the adverse effect profile of the first-line therapeutic options, the need for frequent follow-up, underdeveloped telemedicine services, lack of a rational protocol, poor awareness about infantile spasms, a lesser level of parental understanding, and scarcity of pediatric neurologists are the major hurdles in developing countries. This paper provides a teleneurology based approach for the management of infantile spasms in developing countries during the COVID-19 pandemic. The cornerstones of this approach include the fundamental principles of management of infantile spasms, decentralization of patient care to local health providers, efforts for improving sensitivity and specificity of diagnosis, early initiation of first-line therapeutic options, and constant motivation of parents and local health providers to be vigilant for therapeutic response, adverse effects of therapy, and infections.

Pulse Methylprednisolone with Oral Prednisolone versus Adrenocorticotropic Hormone in Children with West Syndrome: a Randomized Controlled Trial.

BACKGROUND AND PURPOSE: West syndrome is an epileptic encephalopathy of infancy. According to guidelines, adrenocorticotrophic hormone (ACTH) is probably effective for the short-term management of infantile spasm, but there is little uniformity in treatment due to variable response. This study has been done to evaluate the efficacy of pulse methylprednisolone as compared to ACTH in children with West syndrome. METHODS: Children between 3 months to 24 months with the diagnosis of West syndrome were included and ACTH and pulse methyl prednisolone followed by oral prednisolone were given after randomization. Total duration of treatment was 6 weeks in both groups. RESULTS: Total 87 children were enrolled; 12 patients lost in follow up. Finally, 43 received ACTH and 32 received pulse methylprednisolone. In pulse methylprednisolone group, 28.13% showed 50-80% response, 28.13% showed 80-99% response and 21.87% patients showed 100% response. In ACTH group, 41.86% showed 50-80% response, 25.58% showed 80-99% response and only 3 (6.97%) patients showed 100% response. Methylprednisolone treatment regimen did not cause significant or persistent adverse effects. CONCLUSIONS: Pulse methylprednisolone followed by oral prednisolone for 6 weeks is as effective as ACTH. Thus, methylprednisolone therapy can be an important alternative to ACTH.

Epilepsy in Children with Tuberous Sclerosis Complex: A Prospective Observational Study in Bangladesh.

BACKGROUND AND PURPOSE: Epilepsy is an important neurologic feature of patients with tuberous sclerosis complex (TSC). Most common seizure types are focal seizure and epileptic spasm. Seizure control often requires multiple antiepileptic drugs. This study has been done to evaluate the seizure types, electro-encephalography (EEG), neuroimaging features, and drug treatment of epilepsy in TSC. METHODS: This prospective observational study has been conducted on epilepsy patients with TSC at Bangabandhu Sheikh Mujib Medical University from 2011 to 2019. RESULTS: Seventy patients with a mean±standard deviation age of 5.64±3.96 years were identified and 57.1% were female. Most common type of seizure was focal seizure (46%). Epileptic spasm occurred in 17% of patients and all of them had seizure onset before 1 year. In 47% of patients EEG showed focal epileptic discharge; hypsarrhythmia was found in most of the patients with epileptic spasm. Majority of the patients needed more than one drug to control seizure. Only 34% of patients were seizure free for at least 12 months and 22.8% had drug resistant epilepsy. CONCLUSIONS: This study highlights the pattern of seizure, treatment pattern, response to drug, and short-time outcome of children with TSC with epilepsy in a developing country like Bangladesh.

Clinicoradiologic Profile and Outcome of Children With Tubercular Meningitis in a Tertiary Care Hospital in Bangladesh.

BACKGROUND: Children are most vulnerable to tubercular meningitis. Neuroimaging is an important initial investigation in tubercular meningitis. OBJECTIVE: This study was done to describe the clinical profile, neuroimaging changes, and clinical outcome in children with tubercular meningitis. METHODOLOGY: This was an observational cohort study on children with tubercular meningitis, between January 2012 and June 2018. Tubercular meningitis was diagnosed on the basis of clinical criteria, cerebrospinal fluid analysis, neuroimaging, and response to antitubercular drug treatment. Preferably magnetic resonance imaging (MRI) with contrast was done. RESULT: Out of 79 pediatric patients, 17 patients were lost during follow-up; thus, a total of 62 patients were studied. Mean age at presentation was 7.040 (±3.99 SD) year, 51.6% children were male. Rural children were more affected. Twenty eight (45.2 patients had contact with a person with tuberculosis. Only 3 (4.8%) patients presented within 10 days of duration of illness. Most of the cases (67.7%) were in stage 2 at the time of diagnosis. The most common clinical feature was fever, seizure, and signs of meningeal irritation (all present in 12.9%). In neuroimaging most common findings were tuberculoma (50%), hydrocephalus (54.8%), and basal meningeal enhancement (33.8%). Regarding outcome, 6 (9.67%) patients expired and 47 (75%) patients had sequelae. The most common complications were hydrocephalus (30.64%) and intellectual disability (12.9 ). Hydrocephalus was the most common neuroimaging finding among the patients who expired (33%). CONCLUSION: Hydrocephalus is the most common neuroimaging finding. Normal neuroimaging is associated with good outcome whereas all the patients who died had abnormal neuroimaging.

SCN8A Mutation in Infantile Epileptic Encephalopathy: Report of Two Cases.

Early infantile epileptic encephalopathy type 13 is a severe form of epilepsy caused by mutations in the sodium channel 8 alpha (SCN8A) gene. This gene encodes the neuronal voltage-gated sodium channel which plays vital role in neuronal excitability. Here we present two cases with SCN8A encephalopathy. Both cases had mutation in p.Arg1872Gin the SCN8A gene, which was detected by targeted next generation sequencing. Case 1 was a 14-month old boy, who had a normal birth history with normal development up to 6 months and then developed repeated generalized seizure, which was nonresponsive to multiple antiepileptic drugs. He also had neuroregression and dystonia. His electroencephalogram (EEG) showed progressive background abnormality with burst suppression pattern. His metabolic panel was normal and had partial response to carbamazepine. The second case was for an 11-month old boy with the onset of seizure at the age of 7 months. Seizure was generalized, resistant to multiple antiepileptic drugs. He had developmental delay from beginning, no movement disorder. EEG showed focal discharge from left temporal and occipital region. He showed partial response to oxcarbazepine. Our cases had similarities with the previously reported cases. The detailed discussion of our cases would contribute to early detection and targeted treatment of SCN8A encephalopathy. This also gives special emphasis on a genetic test in infants with intractable epilepsy, movement disorder and developmental delay.

Neonatal Glycemic Status of Infants of Diabetic Mothers in a Tertiary Care Hospital.

BACKGROUND: Diabetes is a common medical complication during pregnancy that results in significant neonatal morbidities. In infants of diabetic mothers (IDMs), hypoglycemia is a common complication. OBJECTIVE: To study the neonatal hypoglycemia in IDMs in a tertiary care hospital. SETTINGS AND DESIGN: A cross-sectional study was done in postnatal ward in Bangladesh Institute of Research and Rehabilitation in Diabetic, Endocrine and Metabolic Disorders from January to December 2009. SUBJECTS AND METHODS: The data of IDMs were collected from postnatal ward. All IDMs delivered during this period staying in postnatal ward were included in this study. The outcomes were compared between the hypoglycemic and normoglycemic IDMs and between gestational diabetes mellitus (GDM) and pre-GDM in hypoglycemic group using Chi-square test and Fisher's exact test. The data analysis was performed with Epi-enfo7 software. Statistical significance was set at P < 0.05. RESULTS: A total of 363 IDMs were included in this study. Hypoglycemia developed in 38.3% IDMs and 43.2% mothers of hypoglycemic IDMs had GDM and 56.8% had pre-GDM. Duration of maternal diabetes (P = 0.04) and large for gestational age (P = 0.0001) were associated with hypoglycemia. Multigravidae (82.2% vs 68.3%, P = 0.03), prolonged duration of maternal diabetes (45.46 weeks vs 3.23 weeks, P = 0.00001), preterm babies (48.1% vs 28.3% P = 0.009), and control of diabetes by insulin (81% vs 46.7%, P = 0.001) were more in pre-GDM, and statistically significant. About 85% IDMs developed hypoglycemia within 6 h of birth (P-value 0.00001) and majority (68%) were at 2 h of age. Forty percent of hypoglycemic IDMs from postnatal ward were admitted in special care baby unit. CONCLUSION: Hypoglycemia observed in 38.3% IDMs and developed within 6 h of age and maximum were at 2 h. Early recognition and appropriate intervention are needed in IDMs.

Elemental distribution of metals in urban river sediments near an industrial effluent source.

To study the compositional trends associated with the spatial and layer wise distribution of heavy metals as well as the sediment response towards the untreated chemical wastes, we have analyzed river (Buriganga, Bangladesh) sediments by instrumental neutron activation analysis (INAA) and energy dispersive X-ray fluorescence (EDXRF). In nine sediment samples 27 elements were determined where Na, Al, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Zn, As, Rb, Cs, La, Ce, Sm, Dy, Hf, Th and U were determined by INAA and Cu, Sr, Ba, Hg and Pb were determined by EDXRF. Pollution level and the origin of pollutants were evaluated by the aid of geo-accumulation index (Igeo), enrichment factor (EF), pollution load index (PLI) and the inter-element correlation analysis. Major elements are somehow buffered even though the pollution level is severe while the trace metals seem to be highly responsive. Among the heavy metals, Cr is the dominant pollutant, though the pollution level varies systematically with the sampling depth and the distance from the contamination source. Positive linear correlation between Cr and Zn (0.94) ensures the similar anthropogenic source(s) for these two metals, but the sediments of this study respond differently depending upon their geochemical behavior. Rare earth elements (here La, Ce, Sm and Dy), Th and U seem to have crustal origin and the Th/U ratio varies from 2.58 to 4.96.

Development and validation of a RP-HPLC method for simultaneous estimation of naproxen and ranitidinehydrochloride.

A simple, specific and accurate reverse phase liquid chromatographic method has been developed for the simultaneous determination of naproxen and ranitidine HCl. Both the drugs are official with British Pharmacopoeia 2007, but do not involve simultaneous determination of naproxen and ranitidine HCl. The separation was carried out using 4.6 × 250 mm Symmetry Shield TM RP 18 with a particle diameter of 5 µm and mobile phase containing 0.1M orthophosphoric acid: methanol (35:65, pH 3.1) in isocratic mode. The flow rate was 1.00 ml/min and effluent was monitored at 240 nm. The retention times (average) of ranitidine HCl and naproxen were 2.36 min and 12.39 min, respectively. The linearity for naproxen and ranitidine HCl was in the range of 5-35 µg/ml and 1.5-12 µg/ml, respectively. The potencies of naproxen and ranitidine HCl were found 99.40 % and 99.48 %, respectively. The proposed method was validated and successfully applied to the estimation of naproxen and ranitidine HCl in newly formulated combined tablet and in plasma.