Salinity hazard drives the alteration of occupation, land use and ecosystem service in the coastal areas: Evidence from the south-western coastal region of Bangladesh.

Understanding the salinity effects on the rural livelihood and ecosystems services are essential for policy implications and mitigations. Salinity-driven modulation in land use and land cover, community traditional occupations, and ecosystem service have been elucidated in the present investigation. The study was carried out in the south-western region of Bangladesh as a representative case using focus group discussions, questionnaire survey, and remote sensing techniques. The findings showed that salinity-induced land use changes seriously threatened ecosystem services, employment and livelihoods. Shrimp farming was found to have replaced the majority of agricultural and bare lands, which led to the poor locals losing their land. The increasing land transformation to shrimp ponds as a coping strategy with salinity was not reported to be a viable option as maximum marginal poor people were unable to run the capital-intensive shrimp aquaculture. Eventually, many rich people occupied the cropland for shrimp farming which forced the traditional farmers and fishermen to leave their job and sell their labor. Many of the traditional services derived from the ecosystems were drastically reduced or got lost. The ultimate effect on the traditional livelihoods of the communities increased vulnerability and reduced resilience. The findings could aid in formulating realistic policies and action for ensuring the future resilience of the community through an appropriate adaptation strategy, such as introducing salinity-tolerant crops and integrated farming to safeguard the interest of the poor farmers. Despite the geographical locality of the study, its implications are global given the identical salinity concerns in other emerging nations' coastal regions.

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.

Clinical characteristics of children with infantile epileptic spasms syndrome from a tertiary-care hospital in Dhaka, Bangladesh.

Background: We describe patient characteristics and response to initial treatment in a large case series of children presenting with infantile epileptic spasms syndrome to a tertiary-care hospital with a pediatric neurology service in Bangladesh. The purpose of the study was to add to the growing body of literature on infantile epileptic spasms syndrome in low- and middle-income countries. Methods: We enrolled 212 infants with new-onset infantile epileptic spasms syndrome (IESS) at the time of initial presentation to the National Institute of Neurosciences and Hospital (NINS) in Dhaka, Bangladesh, between January 2019 and August 2021. We collected data about seizure type and frequency, etiology, medication dosage, and available neuroimaging. Results: Median age at initial presentation to NINS was 9 months. Developmental delay and regression prior to presentation were found in 83% and 36%, respectively. Prior to their presentation at NINS, 197 (93%) patients had received anti-seizure medication to treat spasms, of whom only 8 (4%) had received standard therapy with ACTH, prednisolone, or vigabatrin. At NINS, 207 (98%) of patients received standard therapy, most frequently ACTH in 154 (73%). Median time between seizure onset to receipt of first-line therapy was 5 months. Of the 169 patients who were seen in follow-up at average of 5 weeks, 92 (54%) reported absence of clinical epileptic spasms. No serious adverse events requiring hospitalization were reported. Conclusions: This study highlights the long lead times to treatment for IESS in a low- and middle-income country, and the need for early referral of children with suspected epileptic spasms to epilepsy care centers.

Prevalence of COVID-19 vaccine reactogenicity among Bangladeshi physicians.

Increased COVID-19 vaccine hesitancy presents a major hurdle in global efforts to contain the COVID-19 pandemic. This study was designed to estimate the prevalence of adverse events after the first dose of the Covishield (AstraZeneca) vaccine among physicians in Bangladesh. A cross-sectional study was conducted using an online questionnaire for physicians (n = 916) in Bangladesh. Physicians who received at least one dose of the COVID-19 vaccine were included. The study was carried out from April 12 to May 31, 2021. More than 58% of respondents (n = 533) reported one or more adverse events. Soreness of the injected arm (71.9%), tiredness (56.1%), fever (54.4%), soreness of muscles (48.4%), headache (41.5%) and sleeping more than usual (26.8%) were the most commonly reported adverse events. Most vaccine-related reactogenicities were reported by the younger cohorts (<45 years). The majority of respondents reported severity of reactogenicity as "mild," experienced on the day of vaccination, and lasting for 1-3 days. The most common reactogenicity was pain at the injection site; the second most common was tiredness. Almost half (49.2%) of the physicians took acetaminophen (paracetamol) to minimize the effects of vaccine reactogenicity. Multivariate logistic regression analyses showed that physicians with diabetes and hypertension (OR = 2.729 95% CI: 1.282-5.089) and asthma with other comorbidities (OR = 1.885 95% CI: 1.001-3.551) had a significantly higher risk of vaccine-related reactogenicities than physicians without comorbidities. Further safety studies with larger cohorts are required to monitor vaccine safety and provide assurance to potential vaccine recipients.

An Exploration of Physical and Phenotypic Characteristics of Bangladeshi Children with Autism Spectrum Disorder.

This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p < 0.03) larger in ASD males compared with non-ASD males. A trend was also observed for symptom severity, higher in females than males (p = 0.068), with further analyses demonstrating that social reciprocity (p < 0.014) and functional play (p < 0.03) were significantly more impaired in ASD females than males. The findings help understand sex differences in ASD.

Prevalence of epilepsy in Bangladesh: Results from a national household survey.

OBJECTIVE: To determine the prevalence and types of epilepsy in Bangladesh. METHODS: We conducted a nationwide population-based cross-sectional survey among Bangladeshi population of all ages, except children under one month. We surveyed 9839 participants (urban, 4918; rural, 4920) recruited at their households using multistage cluster sampling. Trained physicians with neurology background confirmed the diagnosis of suspected epilepsy cases identified by interviewer-administered questionnaires. We reported the overall and sex, residence, and age groups-specific prevalence of epilepsy per 1000 populations with 95% confidence interval. RESULTS: The national prevalence of epilepsy per 1000 was 8.4 (95% CI 5.6-11.1), urban 8.0 (4.6-11.4), and rural 8.5 (5.60-11.5). The prevalence in adult males and females was 9.2 (5.7-12.6) and 7.7 (3.6-11.7), respectively. The prevalence in children aged <18 years (8.2, 3.4-13.0 was similar to adults (8.5 (5.4-11.4). Among all epilepsy cases, 65.1% had active epilepsy. Their (active epilepsy) prevalence was 5.8 (3.5-8.1). Of them, 63.4% were not receiving treatment. Moreover, those who received allopathy treatment, 72.5% had low adherence leading to a high treatment gap. SIGNIFICANCE: Our findings out of this first-ever national survey were similar to other Asian countries. However, the prevalence of active epilepsy and treatment gap were considerably higher. This study serves useful evidence for tailoring interventions aimed to reduce the burden of epilepsy-primarily through targeted community awareness program-and access to antiepileptic treatment in health facilities in Bangladesh.

Mutation Spectrum in TPO Gene of Bangladeshi Patients with Thyroid Dyshormonogenesis and Analysis of the Effects of Different Mutations on the Structural Features and Functions of TPO Protein through In Silico Approach.

Although thyroid dyshormonogenesis (TDH) accounts for 10-20% of congenital hypothyroidism (CH), the molecular etiology of TDH is unknown in Bangladesh. Thyroid peroxidase (TPO) is most frequently associated with TDH and the present study investigated the spectrum of TPO mutations in Bangladeshi patients and analyzed the effects of mutations on TPO protein structure through in silico approach. Sequencing-based analysis of TPO gene revealed four mutations in 36 diagnosed patients with TDH including three nonsynonymous mutations, namely, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, and one synonymous mutation p.Pro715Pro. Homology modelling-based analysis of predicted structures of MPO-like domain (TPO142-738) and the full-length TPO protein (TPO1-933) revealed differences between mutant and wild type structures. Molecular docking studies were performed between predicted structures and heme. TPO1-933 predicted structure showed more reliable results in terms of interactions with the heme prosthetic group as the binding energies were -11.5 kcal/mol, -3.2 kcal/mol, -11.5 kcal/mol, and -7.9 kcal/mol for WT, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, respectively, implying that p.Ala373Ser and p.Thr725Pro mutations were more damaging than p.Ser398Thr. However, for the TPO142-738 predicted structures, the binding energies were -11.9 kcal/mol, -10.8 kcal/mol, -2.5 kcal/mol, and -5.3 kcal/mol for the wild type protein, mutant proteins with p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro substitutions, respectively. However, when the interactions between the crucial residues including residues His239, Arg396, Glu399, and His494 of TPO protein and heme were taken into consideration using both TPO1-933 and TPO142-738 predicted structures, it appeared that p.Ala373Ser and p.Thr725Pro could affect the interactions more severely than the p.Ser398Thr. Validation of the molecular docking results was performed by computer simulation in terms of quantum mechanics/molecular mechanics (QM/MM) and molecular dynamics (MD) simulation. In conclusion, the substitutions mutations, namely, p.Ala373Ser, p.Ser398Thr, and p.Thr725Pro, had been involved in Bangladeshi patients with TDH and molecular docking-based study revealed that these mutations had damaging effect on the TPO protein activity.

Age-Specific Cut-off Values of Amino Acids and Acylcarnitines for Diagnosis of Inborn Errors of Metabolism Using Liquid Chromatography Tandem Mass Spectrometry.

Liquid Chromatography tandem mass spectrometry (LC-MS/MS) is used for the diagnosis of more than 30 inborn errors of metabolisms (IEMs). Accurate and reliable diagnosis of IEMs by quantifying amino acids (AAs) and acylcarnitines (ACs) using LC-MS/MS systems depend on the establishment of age-specific cut-offs of the analytes. This study aimed to (1) determine the age-specific cut-off values of AAs and ACs in Bangladesh and (2) validate the LC-MS/MS method for diagnosis of the patients with IEMs. A total of 570 enrolled healthy participants were divided into 3 age groups, namely, (1) newborns (1-7 days), (2) 8 days-7 years, and (3) 8-17 years, to establish the age-specific cut-offs for AAs and ACs. Also, 273 suspected patients with IEMs were enrolled to evaluate the reliability of the established cut-off values. Quantitation of AAs and ACs was performed on an automated LC-MS/MS system using dried blood spot (DBS) cards. Then the specimens of the enrolled clinically suspected patients were analyzed by the established method. Nine patients came out as screening positive for different IEMs, including two borderline positive cases of medium-chain acyl-CoA dehydrogenase deficiency (MCAD). A second-tier test for confirmation of the screening positive cases was conducted by urinary metabolic profiling using gas chromatography- mass spectrometry (GC-MS). Out of 9 cases that came out as screening positive by LC-MS/MS, seven cases were confirmed by urinary GC-MS analysis including 3 cases with phenylketonuria, 1 with citrullinemia type II, 1 with methylmalonic acidemia, 1 with isovaleric acidemia and 1 with carnitine uptake defect. Two borderline positive cases with MCAD were found negative by urinary GC-MS analysis. In conclusion, along with establishment of a validated LC-MS/MS method for quantitation of AAs and ACs from the DBS cards, the study also demonstrates the presence of predominantly available IEMs in Bangladesh.

High resolution melting curve analysis enables rapid and reliable detection of G6PD variants in heterozygous females.

BACKGROUND: Like glucose-6-phosphate dehydrogenase (G6PD) deficient hemizygous males and homozygous females, heterozygous females could also manifest hemolytic crisis, neonatal hyperbilirubinemia or kernicterus upon exposure to oxidative stress induced by certain foods such as fava beans, drugs or infections. Although hemizygous males and homozygous females are easily detected by conventional G6PD enzyme assay method, the heterozygous state could be missed by the conventional methods as the mosaic population of both normal and deficient RBCs circulates in the blood. Thus the present study aimed to apply high resolution melting (HRM) curve analysis approach to see whether HRM could be used as a supplemental approach to increase the chance of detection of G6PD heterozygosity. RESULTS: Sixty-three clinically suspected females were evaluated for G6PD status using both enzyme assay and HRM analysis. Four out of sixty-three participants came out as G6PD deficient by the enzyme assay method, whereas HRM approach could identify nine participants with G6PD variants, one homozygous and eight heterozygous. Although only three out of eight heterozygous samples had G6PD enzyme deficiency, the HRM-based heterozygous G6PD variants detection for the rest of the samples with normal G6PD enzyme activities could have significance because their newborns might fall victim to serious consequences under certain oxidative stress. CONCLUSIONS: In addition to the G6PD enzyme assay, HRM curve analysis could be useful as a supplemental approach for detection of G6PD heterozygosity.

Focused cardiac ultrasound as a predictor of readmission in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) is a common reason for admission to the hospital, and readmission is frequent. Multiple factors contribute to rehospitalizations, but inadequate assessment of volume status leading to persistent congestion is an important factor. We sought to determine if focused cardiac ultrasound (FCU) of the inferior vena cava (IVC), as a surrogate of volume status, would predict readmission of ADHF patients after index hospitalization. Patients admitted with a primary diagnosis of ADHF were prospectively enrolled. All patients underwent FCU of the IVC on admission and then daily. 82 patients were enrolled. Patients demonstrated improvement in heart failure physical examination findings and symptoms during the hospitalization. There was a reduction in the size of the IVC and a significant increase in patients with small collapsible vena cava. Logistic regression analysis of physical examination, patient symptoms, and IVC parameters at discharge demonstrated IVC collapsibility and patient reported dyspnea improvement as the only significant variables to predict readmission or emergency department visit. FCU assessment of IVC size and collapsibility may be useful in patients with ADHF to predict risk of being readmitted within 30 days of hospital discharge.

Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city.

The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1-5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality.

Examination of Huntington's disease with atypical clinical features in a Bangladeshi family tree.

Atypical manifestation of Huntington's disease (HD) could inform ongoing research into HD genetic modifiers not present in the primarily European populations studied to date. This work demonstrates that expanding HD genetic testing into under-resourced healthcare settings can benefit both local communities and ongoing research into HD etiology and new therapies.

Outpatient Use of Focused Cardiac Ultrasound to Assess the Inferior Vena Cava in Patients With Heart Failure.

Accurate assessment of volume status is critical in the management of patients with heart failure (HF). We studied the utility of a pocket-sized ultrasound device in an outpatient cardiology clinic as a tool to guide volume assessment. Inferior vena cava (IVC) size and collapsibility were assessed in 95 patients by residents briefly trained in focused cardiac ultrasound (FCU). Cardiologist assessment of volume status and changes in diuretic medication were also recorded. Patients were followed for occurrence of 30-day events. There was a 94% success rate of obtaining IVC size and collapsibility, and agreement between visual and calculated IVC parameters was excellent. Most patients were euvolemic by both FCU IVC and clinical bedside assessment (51%) and had no change in diuretic dose. Thirty-two percent had discrepant FCU IVC and clinical volume assessments. In clinically hypervolemic patients, the FCU evaluation of the IVC suggested that the wrong diuretic management plan might have been made 46% of the time. At 30 days, 14 events occurred. The incidence of events increased significantly with FCU IVC imaging categorization, from 11% to 23% to 36% in patients with normal, intermediate, and plethoric IVCs. By comparison, when grouped in a binary manner, there was no significant difference in event rates for patients who were deemed to be clinically volume overloaded. Assessment of volume status in an outpatient cardiology clinic using FCU imaging of the IVC is feasible in a high percentage of patients. A group of patients were identified with volume status discordant between FCU IVC and routine clinic assessment, suggesting that IVC parameters may provide a valuable supplement to the in-office physical examination.

Efficacy of pyridoxine in early-onset idiopathic intractable seizures in children.

OBJECTIVE: To identify pyridoxine responsive seizures among children with early onset intractable seizures, and to identify pyridoxine-dependency as a subset in this group. METHODS: Patients with neonatal onset idiopathic, intractable seizures were identified over a 6-month period and subjected to a 'pyridoxine trial', at the Pediatric Neurology Clinic of a tertiary-care teaching hospital in New Delhi, India. This consisted of an intravenous infusion of 100 mg of pyridoxine over 10-min with a simultaneous EEG monitoring. This procedure was carried out in the EEG laboratory with all appropriate precautions (including availability of resuscitation equipment and trained personnel). Continuous EEG monitoring was done throughout the infusion and till 20 min later, to look for correction of EEG abnormalities. All patients were then prescribed oral pyridoxine, 10-15 mg/kg/day divided TDS for 6 weeks, in addition to their current anticonvulsant therapy. Patients were reviewed every 15 days regarding compliance and change in seizure frequency. A reduction in seizure frequency by 50% of the baseline was considered as 'response' (significant change), meriting further continuation of pyridoxine therapy. In patients who remained seizure free on pyridoxine therapy, previous anti-epileptics were gradually tapered one by one. RESULTS: 621 children with active epilepsy were seen at the PNC, of which 48 had early-onset, medical intractable epilepsy, and 21 children (13 males and 8 females), aged between 11 month and 38 month were enrolled. The median age at onset of seizure was 5.1 months. The major seizure type was focal in 3 and generalized in 18 (including infantile spasm in 11). No patient had normalization of EEG during the 'trial'. Two patients (9.5%) had a response during the 2 weeks of oral treatment and oral therapy was continued. No toxicity or side-effects of pyridoxine were observed in these two patients over a follow-up of more than 18 months. CONCLUSIONS: Pyridoxine responsive seizures contribute a significant proportion to early-onset idiopathic intractable epilepsy in childhood. Routine use of pyridoxine in the management of early onset resistant seizures would go a long way in identifying these patients early.

Clobazam in refractory childhood epilepsy.

OBJECTIVE: To evaluate the efficacy of clobazam in childhood refractory epilepsy and to characterize the adverse drug reaction profile in the Indian population. METHODS: A cohort of 88 children with 'refractory' epilepsy was started on clobazam as add-on therapy. Diagnosis was established and seizure type recorded. Therapeutic response was recorded as 'complete', 'good', and 'no response'. Observed side effects were classified as 'mild', 'moderate' and 'severe'. RESULTS: Most children were on at least two antiepileptics. Seizures most identified were either partial (36.3%) or generalized tonic-clonic (15.9%). The dose ranged from 0.3-2 mg/kg/day (average 1+0.2 mg/kg/day). Clobazam was effective against all seizure types with complete seizure control seen in 60.2% patients. Tolerance was seen in 5 (5.6%) patients. Side effects were seen in 23 (26%) patients and were 'mild' in 20 (86.9%) of them. Clobazam was stopped in three patients who developed ataxia, which resolved on stopping the drug. CONCLUSION: Clobazam was observed to be an effective broad-spectrum antiepileptic with 'mild' side effects in Indian children.

Zinc concentration in serum and cerebrospinal fluid simultaneously decrease in children with febrile seizure: findings from a prospective study in Bangladesh.

OBJECTIVE: Since the underlying mechanisms of febrile seizure (FS) having multi-factorial aetiology yet remains unclear, we conducted this prospectively designed cross-sectional study to determine if there was any simultaneous change in zinc (Zn) concentration (conc.) in serum and cerebrospinal fluid (CSF) among the FS children in comparison to their matched non-seizure febrile (NSF) peers. METHODS: Zn concentration (level) in both serum (intravenous blood) and CSF (lumber puncture: LP) of 50 children with FS and 30 NSF peers (serving as control) were measured employing graphite furnace atomic absorbance spectrophotometer. Data were analysed to compare Zn level between two groups using appropriate statistical tools employing SPSS/Windows 12.0. RESULTS: Mean Zn conc. in both serum and CSF was less in FS children (464.60 +/- 64.57 and 46.28 +/- 7.46, respectively) than their matched NSF peers (749.33 +/- 73.19 microg/L and 111.28 +/- 19.11 microg/L, respectively) showing significant differences both in serum (p < 0.001) and CSF (p < 0.001). None of serum or CSF-Zn differed significantly with age, degree and duration of fever between FS and NSF peers. CSF-Zn among these children showed an upward trend in LP specimen taken beyond 12 h following FS episodes. CONCLUSION AND RECOMMENDATION: Serum and CSF-Zn simultaneously decreased in FS children in comparison to their matched NSF peers. Further prospectively designed multicentral studies are recommended to conduct in geographically diverse regions involving larger sample to confirm or refute our findings. It remains crucial in standardizing/strengthening national seizure prevention protocol with adequate Zn supplementation.