NGS-driven molecular diagnosis of heterogeneous hereditary neurological disorders reveals novel and known variants in disease-causing genes.

Hereditary neurological disorders (HNDs) are a clinically and genetically heterogeneous group of disorders. These disorders arise from the impaired function of the central or peripheral nervous system due to aberrant electrical impulses. More than 600 various neurological disorders, exhibiting a wide spectrum of overlapping clinical presentations depending on the organ(s) involved, have been documented. Owing to this clinical heterogeneity, diagnosing these disorders has been a challenge for both clinicians and geneticists and a large number of patients are either misdiagnosed or remain entirely undiagnosed. Contribution of genetics to neurological disorders has been recognized since long; however, the complete picture of the underlying molecular bases are under-explored. The aim of this study was to accurately diagnose 11 unrelated Pakistani families with various HNDs deploying NGS as a first step approach. Using exome sequencing and gene panel sequencing, we successfully identified disease-causing genomic variants these families. We report four novel variants, one each in, ECEL1, NALCN, TBR1 and PIGP in four of the pedigrees. In the rest of the seven families, we found five previously reported pathogenic variants in POGZ, FA2H, PLA2G6 and CYP27A1. Of these, three families segregate a homozygous 18 bp in-frame deletion of FA2H, indicating a likely founder mutation segregating in Pakistani population. Genotyping for this mutation can help low-cost population wide screening in the corresponding regions of the country. Our findings not only expand the existing repertoire of mutational spectrum underlying neurological disorders but will also help in genetic testing of individuals with HNDs in other populations.

A characteristic study of Zea mays L. (sweet corn) cobs for synthetic dye degradation from aqueous media.

The current study reports a systematic methodology of Zea mays L. (sweet corn) cobs (ZMLC) for the sequestration of synthetic dye (gentian violet) from aqueous solutions. Adsorbent was scrutinized by using scanning electron microscopy, Fourier transform infra-red spectrometry with pHpzc determination. The impact of various adsorption parameters including pH effect, ZMLC (sorbent) dosage, temperature, concentration and shaking time was examined. The equilibrium sorption isotherms were determined by the batch method from 283 to 303 K at pHpzc. Adsorption data were adjusted to four isothermal models: Langmuir, Freundlich, Dubinin-Radushkevich and Temkin's models, which presented the best adjustment to Freundlich, Dubinin-Radushkevich and Temkin's at 283 K. The kinetic profile fitted well to the pseudo-second order kinetic equation at three distinct concentrations 600, 700, 800 mg/L. Maximum sorption capacity was gained up to 700 mg.g-1 for gentian violet at pH 3, respectively. The adsorption process is endothermic, non-spontaneous, favorable thermodynamically due to positive values of entropy and Gibbs free energy and randomness decreases during the adsorption process. Furthermore, after biosorption onto ZMLC the dye can be desorbed effectively by using mineral base KOH solution. Consequently, the ZMLC is said to be a promising biosorbent to remediate gentian violet-contaminated water as well as wastewater.

Green synthesis of Fe nanoparticles by using Mangifera indica extract and its application in photo-catalytic degradation of dyes.

An exceedingly facile green approach that produces a reliable adsorbent based on a transition metal such as Iron (Fe) using Mangifera indica leaf extract at room temperature is described. A single pot method was used for synthesis with no capping agents, surfactants or other templates. The main intention of this study is to synthesize iron nanoparticles from leaf extract (Mangifera indica) and examine its degradation potential for photo-catalytic removal of dyes (Congo red and brilliant green) from wastewater. Characterization of synthesized nanoparticles was executed by pHpzc, scanning electron microscopy and Fourier transform infrared spectroscopy studies and results confirm the presence of iron nano-sheets with biomolecules. All photo-catalytic experimental results were assessed by sum of squared estimate of errors and simple linear regression R2 with dye concentration, pH, contact time and dose rate as dependent and independent variables. Adsorption experimental data was verified by kinetics and isothermal models. Results showed that Langmuir and pseudo second order models give best fitness towards the photo-catalytic adsorption procedure. Thermodynamics revealed that adsorption mechanism is endothermic, described by the values of changes in Gibbs free energy, enthalpy and entropy, and is chemisorption in nature, with spontaneous processes. Overall photo-catalytic adsorption execution with synthesized iron nanoparticles and simple biomass of Mangifera indica gives satisfactory results for treating dye wastewater.

COVID-19 containment and its unrestrained impact on epilepsy management in resource-limited areas of Pakistan.

The current pandemic of coronavirus disease 2019 (COVID-19) that led to an unprecedented crisis with significant health, social, and economic repercussions presented more serious concerns for those living with some chronic conditions such as epilepsy. This study was aimed to find out impact of the COVID-19 pandemic on management of epilepsy. A cross-sectional study was conducted through telephone interviews, targeting 213 caregivers of pediatric patients with epilepsy, belonging to underserved areas of Faisalabad, Punjab, Pakistan. A simple questionnaire was designed to record the responses of participants relevant to the direct and indirect effects of COVID-19 pandemic and their knowledge about possible ways that can be accessed for the management of epilepsy during an ongoing pandemic. The current study, which holds 77% of the respondents from rural areas and 23% from urban settings, showed that partial measures of lockdown taken to stop or slow the spread of COVID-19 resulted in adverse economic and health outcomes in the said population including cancelation of follow-up visits, worsening of seizures, job loss, burden of antiepileptic drugs (AEDs) costs, and discontinuation of medicines. Furthermore, knowledge about alternative ways to access health facilities was found very poor among caregivers. Income sources of poor people disrupted by lockdown can lead to unintentional nonadherence to medication, which is a clear picture of inequitable distribution of resources. This study highlights the major issues faced by the caregivers during this ongoing pandemic of COVID-19.

Role of Methyl Prednisolone in Longitudinal Extensive Transverse Myelitis (LETM) in Children.

OBJECTIVE: The role of methyl prednisolone in longitudinal extensive transverse myelitis in children is not completely discovered in developing country like Pakistan. So this is the first study which aimed to evaluate the efficacy of methyl prednisolone in longitudinal extensive transverse myelitis in children. METHODS: This is quasi experimental hospital based descriptive prospective study. The data was collected from 34 children admitted in Paediatric Neurology department through Outpatient/emergency department in Children's Hospital and the Institute of Child Health, Lahore for period of one year from January 2018 to December 2018. The children full filling the inclusion criteria were observed before and after giving injection methyl prednisolone 30mg/kg/dose (maximum dose one Gram irrespective of the body weight) once daily for five days in the form of intravenous infusion. RESULTS: Complete recovery was seen in 41.2% while 58.8% showed partial recovery. The correlation of response to treatment (recovery) with gender, area of spinal cord involvement, muscle power and autonomic dysfunction is found at significance level of five percent according to Chi square test. CONCLUSION: Early consideration and administration of methyl prednisolone in longitudinally extensive transverse myelitis in children can be beneficial and can help to reduce the morbidity.

Face mask detection and social distance monitoring system for COVID-19 pandemic.

Coronavirus triggers several respirational infections such as sneezing, coughing, and pneumonia, which transmit humans to humans through airborne droplets. According to the guidelines of the World Health Organization, the spread of COVID-19 can be mitigated by avoiding public interactions in proximity and following standard operating procedures (SOPs) including wearing a face mask and maintaining social distancing in schools, shopping malls, and crowded areas. However, enforcing the adaptation of these SOPs on a larger scale is still a challenging task. With the emergence of deep learning-based visual object detection networks, numerous methods have been proposed to perform face mask detection on public spots. However, these methods require a huge amount of data to ensure robustness in real-time applications. Also, to the best of our knowledge, there is no standard outdoor surveillance-based dataset available to ensure the efficacy of face mask detection and social distancing methods in public spots. To this end, we present a large-scale dataset comprising of 10,000 outdoor images categorized into a binary class labeling i.e., face mask, and non-face masked people to accelerate the development of automated face mask detection and social distance measurement on public spots. Alongside, we also present an end-to-end pipeline to perform real-time face mask detection and social distance measurement in an outdoor environment. Initially, existing state-of-the-art single and multi-stage object detection networks are fine-tuned on the proposed dataset to evaluate their performance in terms of accuracy and inference time. Based on better performance, YOLO-v3 architecture is further optimized by tuning its feature extraction and region proposal generation layers to improve the performance in real-time applications. Our results indicate that the presented pipeline performed better than the baseline version, showing an improvement of 5.3% in terms of accuracy.

Polymorphism in drug transporter gene ABCB1 is associated with drug resistance in Pakistani epilepsy patients.

Despite the best possible medication and treatment protocols, one-third of epilepsy patients have drug resistance which is associated with an elevated risk of mortality and debilitating psychological consequences. P-glycogen encoded by ABCB1 is major drug transporter for a wide variety of AED. To evaluate the complex haplotypic association, genetic and allelic frequency distribution of rs1128503, rs1045642, and rs2032582 polymorphisms of ABCB1 gene with drug resistance in Pakistani pediatric epilepsy patients, we performed this study. A total of 337 individuals including 100 healthy control, 110 drug-resistant patients, and 127 drug-responsive patients were enrolled and genotyped for three polymorphisms. PCR and direct sequencing of DNA were done for genotyping. All the studied SNPs showed a statistically significant association with drug-resistant epilepsy at p < 0.01. In addition, we identified a novel variant at c 0.2678C > A (SCV001712095) position. The haplotype analysis indicated strong linkage disequilibrium between three SNPs. The in-silico analysis indicated that rs2032582 polymorphism at c 0.2677T > A is benign while c 0.2677T > G and c 0.2678C > A are possibly damaging. Our findings showed that pharmacogenetic variants play a key role in disease. Our findings shed light on the pharmacogenomic association of ABCB1 with epilepsy which might facilitate study on pharmacokinetics concerning ethnology.

Clinical Spectrum and Outcome of Cerebral Venous Sinus Thrombosis in Children.

OBJECTIVE: To determine clinical spectrum, neuroimaging finding and outcome of cerebral venous sinus thrombosis (CVST) in children. STUDY DESIGN: Descriptive and cross-sectional study. PLACE AND DURATION OF STUDY: Department of Paediatric Neurology, Children's Hospital and Institute of Child Health, Lahore, from 2015 to 2016. METHODOLOGY: Data was collected in a predesigned proforma by non-probability purposive sampling technique from all enrolled 32 patients fulfilling the inclusion criteria. We analysed descriptively the clinical presentation, neuroimaging findings, associated risk factors and outcome. Chi-square test was used to check the association between demographic variables and findings at five percent level of significance. RESULTS: Out of 32 patients enrolled, 75% (24) patients were male; median age was 2.5 years. Fever was found the most common presentation followed by headache and lethargy. Neuroimaging showed superior sagital sinus thrombosis in all (100%), while 25% (8) have additional thrombosis of internal cerebral veins. Ischemic infarction was found in 11 (35%), while hemorrhagic infarction was found in 9 (29%) patients. Death occurred in 6.25% of children. CONCLUSION: Infections were the common cause of CVST in children followed by anemia and dehydration. Mortality trend was low with earlier diagnosis and aggressive treatment. Anticoagulant treatment along with adequate hydration, antibiotics and correction of anemia can lead to a better outcome. A large local and regional prospective multicenter studies for pediatric cerebral venous sinus thrombosis is suggested to evaluate the risk factors and plan guidelines for managing this condition in children.