Development, validation and application of single molecule molecular inversion probe based novel integrated genetic screening method for 29 common lysosomal storage disorders in India.

BACKGROUND: Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. RESULTS: 903 smMIPs were designed to target exon and exon-intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. CONCLUSION: We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

Designing a Clinician-Centered Wearable Data Dashboard (CarePortal): Participatory Design Study.

BACKGROUND: The recent growth of eHealth is unprecedented, especially after the COVID-19 pandemic. Within eHealth, wearable technology is increasingly being adopted because it can offer the remote monitoring of chronic and acute conditions in daily life environments. Wearable technology may be used to monitor and track key indicators of physical and psychological stress in daily life settings, providing helpful information for clinicians. One of the key challenges is to present extensive wearable data to clinicians in an easily interpretable manner to make informed decisions. OBJECTIVE: The purpose of this research was to design a wearable data dashboard, named CarePortal, to present analytic visualizations of wearable data that are meaningful to clinicians. The study was divided into 2 main research objectives: to understand the needs of clinicians regarding wearable data interpretation and visualization and to develop a system architecture for a web application to visualize wearable data and related analytics. METHODS: We used a wearable data set collected from 116 adolescent participants who experienced trauma. For 2 weeks, participants wore a Microsoft Band that logged physiological sensor data such as heart rate (HR). A total of 834 days of HR data were collected. To design the CarePortal dashboard, we used a participatory design approach that interacted directly with clinicians (stakeholders) with backgrounds in clinical psychology and neuropsychology. A total of 8 clinicians were recruited from the Rhode Island Hospital and the University of Massachusetts Memorial Health. The study involved 5 stages of participatory workshops and began with an understanding of the needs of clinicians. A User Experience Questionnaire was used at the end of the study to quantitatively evaluate user experience. Physiological metrics such as daily and hourly maximum, minimum, average, and SD of HR and HR variability, along with HR-based activity levels, were identified. This study investigated various data visualization graphing methods for wearable data, including radar charts, stacked bar plots, scatter plots combined with line plots, simple bar plots, and box plots. RESULTS: We created a CarePortal dashboard after understanding the clinicians' needs. Results from our workshops indicate that overall clinicians preferred aggregate information such as daily HR instead of continuous HR and want to see trends in wearable sensor data over a period (eg, days). In the User Experience Questionnaire, a score of 1.4 was received, which indicated that CarePortal was exciting to use (question 5), and a similar score was received, indicating that CarePortal was the leading edge (question 8). On average, clinicians reported that CarePortal was supportive and can be useful in making informed decisions. CONCLUSIONS: We concluded that the CarePortal dashboard integrated with wearable sensor data visualization techniques would be an acceptable tool for clinicians to use in the future.

Comparative yield of molecular diagnostic algorithms for autism spectrum disorder diagnosis in India: evidence supporting whole exome sequencing as first tier test.

BACKGROUND: Autism spectrum disorder (ASD) affects 1 in 100 children globally with a rapidly increasing prevalence. To the best of our knowledge, no data exists on the genetic architecture of ASD in India. This study aimed to identify the genetic architecture of ASD in India and to assess the use of whole exome sequencing (WES) as a first-tier test instead of chromosomal microarray (CMA) for genetic diagnosis. METHODS: Between 2020 and 2022, 101 patient-parent trios of Indian origin diagnosed with ASD according to the Diagnostic and Statistical Manual, 5th edition, were recruited. All probands underwent a sequential genetic testing pathway consisting of karyotyping, Fragile-X testing (in male probands only), CMA and WES. Candidate variant validation and parental segregation analysis was performed using orthogonal methods. RESULTS: Of 101 trios, no probands were identified with a gross chromosomal anomaly or Fragile-X. Three (2.9%) and 30 (29.7%) trios received a confirmed genetic diagnosis from CMA and WES, respectively. Amongst diagnosis from WES, SNVs were detected in 27 cases (90%) and CNVs in 3 cases (10%), including the 3 CNVs detected from CMA. Segregation analysis showed 66.6% (n = 3 for CNVs and n = 17 for SNVs) and 16.6% (n = 5) of the cases had de novo and recessive variants respectively, which is in concordance with the distribution of variant types and mode of inheritance observed in ASD patients of non-Hispanic white/ European ethnicity. MECP2 gene was the most recurrently mutated gene (n = 6; 20%) in the present cohort. Majority of the affected genes identified in the study cohort are involved in synaptic formation, transcription and its regulation, ubiquitination and chromatin remodeling. CONCLUSIONS: Our study suggests de novo variants as a major cause of ASD in the Indian population, with Rett syndrome as the most commonly detected disorder. Furthermore, we provide evidence of a significant difference in the diagnostic yield between CMA (3%) and WES (30%) which supports the implementation of WES as a first-tier test for genetic diagnosis of ASD in India.

Characterizing the Impedance Properties of Dry E-Textile Electrodes Based on Contact Force and Perspiration.

Biopotential electrodes play an integral role within smart wearables and clothing in capturing vital signals like electrocardiogram (ECG), electromyogram (EMG), and electroencephalogram (EEG). This study focuses on dry e-textile electrodes (E1-E6) and a laser-cut knit electrode (E7), to assess their impedance characteristics under varying contact forces and moisture conditions. Synthetic perspiration was applied using a moisture management tester and impedance was measured before and after exposure, followed by a 24 h controlled drying period. Concurrently, the signal-to-noise ratio (SNR) of the dry electrode was evaluated during ECG data collection on a healthy participant. Our findings revealed that, prior to moisture exposure, the impedance of electrodes E7, E5, and E2 was below 200 ohm, dropping to below 120 ohm post-exposure. Embroidered electrodes E6 and E4 exhibited an over 25% decrease in mean impedance after moisture exposure, indicating the impact of stitch design and moisture on impedance. Following the controlled drying, certain electrodes (E1, E2, E3, and E4) experienced an over 30% increase in mean impedance. Overall, knit electrode E7, and embroidered electrodes E2 and E6, demonstrated superior performance in terms of impedance, moisture retention, and ECG signal quality, revealing promising avenues for future biopotential electrode designs.

iTex Gloves: Design and In-Home Evaluation of an E-Textile Glove System for Tele-Assessment of Parkinson's Disease.

Parkinson's disease (PD) is a neurological progressive movement disorder, affecting more than 10 million people globally. PD demands a longitudinal assessment of symptoms to monitor the disease progression and manage the treatments. Existing assessment methods require patients with PD (PwPD) to visit a clinic every 3-6 months to perform movement assessments conducted by trained clinicians. However, periodic visits pose barriers as PwPDs have limited mobility, and healthcare cost increases. Hence, there is a strong demand for using telemedicine technologies for assessing PwPDs in remote settings. In this work, we present an in-home telemedicine kit, named iTex (intelligent Textile), which is a patient-centered design to carry out accessible tele-assessments of movement symptoms in people with PD. iTex is composed of a pair of smart textile gloves connected to a customized embedded tablet. iTex gloves are integrated with flex sensors on the fingers and inertial measurement unit (IMU) and have an onboard microcontroller unit with IoT (Internet of Things) capabilities including data storage and wireless communication. The gloves acquire the sensor data wirelessly to monitor various hand movements such as finger tapping, hand opening and closing, and other movement tasks. The gloves are connected to a customized tablet computer acting as an IoT device, configured to host a wireless access point, and host an MQTT broker and a time-series database server. The tablet also employs a patient-centered interface to guide PwPDs through the movement exam protocol. The system was deployed in four PwPDs who used iTex at home independently for a week. They performed the test independently before and after medication intake. Later, we performed data analysis of the in-home study and created a feature set. The study findings reported that the iTex gloves were capable to collect movement-related data and distinguish between pre-medication and post-medication cases in a majority of the participants. The IoT infrastructure demonstrated robust performance in home settings and offered minimum barriers for the assessment exams and the data communication with a remote server. In the post-study survey, all four participants expressed that the system was easy to use and poses a minimum barrier to performing the test independently. The present findings indicate that the iTex glove system has the potential for periodic and objective assessment of PD motor symptoms in remote settings.

Textile Knitted Stretch Sensors for Wearable Health Monitoring: Design and Performance Evaluation.

The advancement of smart textiles has led to significant interest in developing wearable textile sensors (WTS) and offering new modalities to sense vital signs and activity monitoring in daily life settings. For this, textile fabrication methods such as knitting, weaving, embroidery, and braiding offer promising pathways toward unobtrusive and seamless sensing for WTS applications. Specifically, the knitted sensor has a unique intermeshing loop structure which is currently used to monitor repetitive body movements such as breathing (microscale motion) and walking (macroscale motion). However, the practical sensing application of knit structure demands a comprehensive study of knit structures as a sensor. In this work, we present a detailed performance evaluation of six knitted sensors and sensing variation caused by design, sensor size, stretching percentages % (10, 15, 20, 25), cyclic stretching (1000), and external factors such as sweat (salt-fog test). We also present regulated respiration (inhale-exhale) testing data from 15 healthy human participants; the testing protocol includes three respiration rates; slow (10 breaths/min), normal (15 breaths/min), and fast (30 breaths/min). The test carried out with statistical analysis includes the breathing time and breathing rate variability. These testing results offer an empirically derived guideline for future WTS research, present aggregated information to understand the sensor behavior when it experiences a different range of motion, and highlight the constraints of the silver-based conductive yarn when exposed to the real environment.

Clinical Characteristics, Molecular Profile, and Outcomes in Indian Patients with Glutaric Aciduria Type 1.

Glutaric acidemia type 1 (GA-1, OMIM 231670) is an autosomal recessive inborn error of metabolism caused by the deficiency of glutaryl-coenzyme A (CoA) dehydrogenase with most children presenting in infancy with encephalopathy, dystonia, and macrocephaly. In this article, we presented the clinical characteristics, molecular profile, and outcomes in 29 unrelated families with affected children (30 cases total). The mean age at onset of illness was 10 months (±14.58), whereas the mean age at referral for molecular diagnosis was 29.44 months (±28.11). Patients were residents of nine different states of India. Clinical presentation varied from acute encephalitis followed by neuroregression and chronic/insidious developmental delay. Neurological sequelae varied from asymptomatic (no sequelae, 2 patients) to moderate (5 patients) and severe (23 patients) sequelae. All patients underwent blood tandem mass spectrometry (TMS on dried blood spots) and/or urine gas chromatography mass spectrometry (GCMS). Neuroimaging demonstrated batwing appearance in 95% cases. Sanger's sequencing of GCDH , covering all exons and exon-intron boundaries, was performed for all patients. Variants identified include 15 novel coding variants: p.Met100Thr, p.Gly107Ser, p.Leu179Val, p.Pro217Ser, p. Phe236Leufs*107, p.Ser255Pro, p.Met266Leufs*2, p.Gln330Ter, p.Thr344Ile, p.Leu345Pro, p.Lys377Arg, p.Leu424Pro, p.Asn373Lys, p.Lys377Arg, p.Asn392Metfs*9, and nine known genetic variants such as p.Arg128Gln, p.Leu179Arg, p.Trp225Ter, p.Met339Val, p.Gly354Ser, p.Arg402Gln, p.Arg402Trp, p.His403Tyr, and p.Ala433Val (Ensembl transcript ID: ENST00000222214). Using in silico analysis, genetic variants were shown to be affecting the residues responsible for homotetramer formation of the glutaryl-CoA dehydrogenase protein. Treatment included oral carnitine, riboflavin, protein-restricted diet, lysine-deficient special formulae, and management of acute crises with intravenous glucose and hydration. However, the mortality (9/30, 27.58%) and morbidity was high in our cohort with only two patients affording the diet. Our study is the largest multicentric, genetic variant-proven series of glutaric aciduria type 1 from India till date.

Feasibility of combining functional near-infrared spectroscopy with electroencephalography to identify chronic stroke responders to cerebellar transcranial direct current stimulation-a computational modeling and portable neuroimaging methodological study.

Feasibility of portable neuroimaging of cerebellar transcranial direct current stimulation (ctDCS) effects on the cerebral cortex has not been investigated vis-à-vis cerebellar lobular electric field strength. We studied functional near-infrared spectroscopy (fNIRS) in conjunction with electroencephalography (EEG) to measure changes in the brain activation at the prefrontal cortex (PFC) and the sensorimotor cortex (SMC) following ctDCS as well as virtual reality-based balance training (VBaT) before and after ctDCS treatment in 12 hemiparetic chronic stroke survivors. We performed general linear modeling (GLM) that putatively associated the lobular electric field strength with the changes in the fNIRS-EEG measures at the ipsilesional and contra-lesional PFC and SMC. Here, fNIRS-EEG measures were found in the latent space from canonical correlation analysis (CCA) between the changes in total hemoglobin (tHb) concentrations (0.01-0.07Hz and 0.07-0.13Hz bands) and log10-transformed EEG bandpower within 1-45 Hz where significant (Wilks' lambda>0.95) canonical correlations were found only for the 0.07-0.13-Hz band. Also, the first principal component (97.5% variance accounted for) of the mean lobular electric field strength was a good predictor of the latent variables of oxy-hemoglobin (O2Hb) concentrations and log10-transformed EEG bandpower. GLM also provided insights into non-responders to ctDCS who also performed poorly in the VBaT due to ideomotor apraxia. Future studies should investigate fNIRS-EEG joint-imaging in a larger cohort to identify non-responders based on GLM fitting to the fNIRS-EEG data.

Investigating the feasibility of cerebellar transcranial direct current stimulation to facilitate post-stroke overground gait performance in chronic stroke: a partial least-squares regression approach.

BACKGROUND: Investigation of lobule-specific electric field effects of cerebellar transcranial direct current stimulation (ctDCS) on overground gait performance has not been performed, so this study aimed to investigate the feasibility of two lobule-specific bilateral ctDCS montages to facilitate overground walking in chronic stroke. METHODS: Ten chronic post-stroke male subjects participated in this repeated-measure single-blind crossover study, where we evaluated the single-session effects of two bilateral ctDCS montages that applied 2 mA via 3.14 cm2 disc electrodes for 15 min targeting (a) dentate nuclei (also, anterior and posterior lobes), and (b) lower-limb representations (lobules VIIb-IX). A two-sided Wilcoxon rank-sum test was performed at a 5% significance level on the percent normalized change measures in the overground gait performance. Partial least squares regression (PLSR) analysis was performed on the quantitative gait parameters as response variables to the mean lobular electric field strength as the predictors. Clinical assessments were performed with the Ten-Meter walk test (TMWT), Timed Up & Go (TUG), and the Berg Balance Scale based on minimal clinically important differences (MCID). RESULTS: The ctDCS montage specific effect was found significant using a two-sided Wilcoxon rank-sum test at a 5% significance level for 'Step Time Affected Leg' (p = 0.0257) and '%Stance Time Unaffected Leg' (p = 0.0376). The changes in the quantitative gait parameters were found to be correlated to the mean electric field strength in the lobules based on PLSR analysis (R2 statistic = 0.6574). Here, the mean electric field strength at the cerebellar lobules, Vermis VIIIb, Ipsi-lesional IX, Vermis IX, Ipsi-lesional X, had the most loading and were positively related to the 'Step Time Affected Leg' and '%Stance Time Unaffected Leg,' and negatively related to the '%Swing Time Unaffected Leg,' '%Single Support Time Affected Leg.' Clinical assessments found similar improvement in the TMWT (MCID: 0.10 m/s), TUG (MCID: 8 s), and BBS score (MCID: 12.5 points) for both the ctDCS montages. CONCLUSION: Our feasibility study found an association between the lobular mean electric field strength and the changes in the quantitative gait parameters following a single ctDCS session in chronic stroke. Both the ctDCS montages improved the clinical outcome measures that should be investigated with a larger sample size for clinical validation. TRIAL REGISTRATION: Being retrospectively registered.

Implications of Physiology-Sensitive Gait Exercise on the Lower Limb Electromyographic Activity of Hemiplegic Post-Stroke Patients: A Feasibility Study in Low Resource Settings.

Background: Stroke is one of the leading causes of disability with ~80% of post-stroke survivors suffering from gait-related deficits. Conventional gait rehabilitation settings are labor-intensive and need rigorous involvement of clinicians (who use their expertise to decide the dosage of exercise intensity based on patient's capability). This demands a technology-assisted individualized exercise platform that can offer varying dosage of exercise intensity based on one's capability. Here, we have used an individualized physiology-sensitive treadmill-assisted gait exercise platform. We wanted to investigate the implications of this platform on one's lower limb muscle strength and muscle fatigue by analyzing surface Electromyogram (sEMG)-related indices and standard gait-related clinical measures. METHODS: We designed a feasibility study involving post-stroke patients (n=9; 44.4(±15)years; post-stroke period=3.1(±3)years) and gave them multiple exposures to this exercise platform. We investigated the Gastrocnemius Lateralis and Tibialis Anterior muscle activation prior to and post multiple exposures to our exercise platform while they walked overground. The feasibility study ended with collecting feedback on the patients' perception on the implications of having gait exercise using such a platform on their ambulation capability. RESULTS: The results showed that repeated exposures to this gait exercise platform can contribute towards gait rehabilitation of post-stroke patients with rehabilitation outcomes measured in terms of group average improvement of (i)~14% in muscle strength and (ii)marginal (~6%) in functional mobility (as in our case). CONCLUSION: Such a physiology-sensitive treadmill-assisted gait exercise platform can hold promise towards contributing to post-stroke gait rehabilitation in low-resource settings with the rehabilitation outcomes being measured in terms of sEMG-based observations.

Deep Cerebellar Transcranial Direct Current Stimulation of the Dentate Nucleus to Facilitate Standing Balance in Chronic Stroke Survivors-A Pilot Study.

OBJECTIVE: Cerebrovascular accidents are the second leading cause of death and the third leading cause of disability worldwide. We hypothesized that cerebellar transcranial direct current stimulation (ctDCS) of the dentate nuclei and the lower-limb representations in the cerebellum can improve functional reach during standing balance in chronic (>6 months' post-stroke) stroke survivors. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) based subject-specific electric field was computed across a convenience sample of 10 male chronic (>6 months) stroke survivors and one healthy MRI template to find an optimal bipolar bilateral ctDCS montage to target dentate nuclei and lower-limb representations (lobules VII-IX). Then, in a repeated-measure crossover study on a subset of 5 stroke survivors, we compared 15minutes of 2mA ctDCS based on the effects on successful functional reach (%) during standing balance task. Three-way ANOVA investigated the factors of interest- brain regions, montages, stroke participants, and their interactions. RESULTS: "One-size-fits-all" bipolar ctDCS montage for the clinical study was found to be PO9h-PO10h for dentate nuclei and Exx7-Exx8 for lobules VII-IX with the contralesional anode. PO9h-PO10h ctDCS performed significantly (alpha = 0.05) better in facilitating successful functional reach (%) when compared to Exx7-Exx8 ctDCS. Furthermore, a linear relationship between successful functional reach (%) and electric field strength was found where PO9h-PO10h montage resulted in a significantly (alpha = 0.05) higher electric field strength when compared to Exx7-Exx8 montage for the same 2mA current. CONCLUSION: We presented a rational neuroimaging based approach to optimize deep ctDCS of the dentate nuclei and lower limb representations in the cerebellum for post-stroke balance rehabilitation. However, this promising pilot study was limited by "one-size-fits-all" bipolar ctDCS montage as well as a small sample size.

Identification of novel variants in a large cohort of children with Tay-Sachs disease: An initiative of a multicentric task force on lysosomal storage disorders by Government of India.

Tay-Sachs disease (TSD) (OMIM) is a neurodegenerative lysosomal storage disorder caused due to mutations in the HEXA gene. To date, nearly 190 mutations have been reported in HEXA gene. Here, we have characterized 34 enzymatically confirmed TSD families to investigate the presence of novel as well as known variants in HEXA gene. Overall study detected 25 variants belonging to 31 affected TSD patients and 3 carrier couples confirmed by enzyme study. Of these 17 patients harbors 15 novel variants, including seven missense variants [p.V206L, p.Y213H, p.R252C, p.F257S, p.C328G, p.G454R, and p.P475R], four nonsense variant [p.S9X, p.E91X, p.W420X, and p.W482X], two splice site variants [c.347-1G>A and c.460-1G>A], and two small deletion [c.1349delC (p.A450VfsX3) and c.52delG (p.G18Dfs*82)]. While remaining 17 patients harbors 10 previously reported variants that includes six missense variants [p.M1T, p.R170Q, p.D322Y, p.D322N, p.E462V, and p.R499C], one nonsense variant [p.Q106X], two splice site variants [c.1073+1G>A and c.459+4A>G] and one 4 bp insertion [c.1278insTATC (p.Y427IfsX5)]. In conclusion, Indian infantile TSD patients provide newer insight into the molecular heterogeneity of the TSD. Combining present study and our earlier studies, we have observed that 67% genotypes found in Indian TSD patients are novel, which are associated with severe infantile phenotypes, while rest 33% genotypes found in our cohort were previously reported in various populations. In addition, higher frequency of the p.E462V and c.1278insTATC mutations in the present study further support and suggest the prevalence of p.E462V mutation in the Indian population.

A child with intellectual disability and dysmorphism due to complex ring chromosome 6: identification of molecular mechanism with review of literature.

BACKGROUND: Ring chromosome 6 (r(6)) is a rare disorder that mainly occurs as a 'de novo' event. Nonetheless, a wide phenotypic spectrum has been reported in r(6) cases, depending on breakpoints, size of involved region, copy number alterations and mosaicism of cells with r(6) and/or monosomy 6 due to loss of r(6). CASE PRESENTATION: An 11-year-old male was referred with developmental delay, intellectual disability and microcephaly. Physical examination revealed additionally short stature and multiple facial dysmorphisms. Banding cytogenetic studies revealed a karyotype of mos 46,XY,r(6)(p25.3q27)[54]/45,XY,-6[13]/46,XY,r(6)(::p25.3→q27::p25.3→q27::)[13]/46,XY[6]/47,XY,r(6)(p25.3q27)×2[2]dn. Additionally, molecular karyotyping and molecular cytogenetics confirmed the breakpoints and characterized a 1.3 Mb contiguous duplication at 6p25.3. CONCLUSION: The present study has accurately identified copy number alterations caused by ring chromosome formation. A review of the literature suggests that hemizygous expression of TBP gene in 6q27~qter, is likely to be the underlying cause of the phenotype. The phenotypic correlation and clinical severity in r(6) cases continue to remain widely diverse in spite of numerous reports of genomic variations.

Design of Instrumented Shoes for Gait Characterization: A Usability Study With Healthy and Post-stroke Hemiplegic Individuals.

Ambulation is a fundamental requirement of human beings for enjoying healthy community life. A neurological disorder such as stroke can significantly affect one's gait thereby restricting one's active community participation. To quantify one's gait, spatiotemporal gait parameters are widely used in clinical context with different tests such as 10 meter walk test, 6 min walk test, etc. Though these conventional observation-based methods are powerful, yet they often suffer from subjectivity, a scarcity of adequately trained therapists and frequent clinical visits for assessment. Researchers have been exploring the technology-assisted solutions for gait characterization. There are laboratory-based stereophotogrammetric methods and walk mats that are powerful tools as far as gait characterization is concerned. However, these suffer from issues with portability, accessibility due to high cost, labor-intensiveness, etc. Faced with these issues, our present research tries to investigate and quantify the gait abnormalities in individuals with neurological disorder by using a portable and cost-effective instrumented shoes (ShoesFSRhenceforth). The in-house developed ShoesFSR comprised of a pair of shoes instrumented with Force Sensing Resistors (FSR) and a wireless data acquisition unit. The real-time FSR data was acquired wirelessly and analyzed by a central console to offer quantitative indices of one's gait. Studies were conducted with 15 healthy participants and 9 post-stroke survivors. The spatiotemporal gait parameters of healthy participants measured using ShoesFSR were validated with standard methods such as stereophotogrammetric system and paper-based setup. Statistical analysis showed good agreement between the gait parameters measured using ShoesFSR and the standard methods. Specifically, the mean absolute error of the spatial parameters measured by the ShoesFSR , in the worst case, was 1.24% and that for the temporal parameters was 1.12% with that measured by standard methods for healthy gait. This research shows the potential of the ShoesFSR to quantify gait abnormality of post-stroke hemiplegic patients. In turn, the results show a promise for the future clinical use of the ShoesFSR .

Identification of deletion-duplication in HEXA gene in five children with Tay-Sachs disease from India.

BACKGROUND: Tay-Sachs disease (TSD) is a sphingolipid storage disorder caused by mutations in the HEXA gene. To date, nearly 170 mutations of HEXA have been described, including only one 7.6 kb large deletion. METHODS: Multiplex Ligation-dependent Probe Amplification (MLPA) study was carried out in 5 unrelated patients for copy number changes where heterozygous and/or homozygous disease causing mutation/s could not be identified in the coding region by sequencing of HEXA gene. RESULTS: The study has identified the presence of a homozygous deletion of exon-2 and exon-3 in two patients, two patient showed compound heterozygosity with exon 1 deletion combined with missense mutation p.E462V and one patient was identified with duplication of exon-1 with novel variants c.1527-2A > T as a second allele. CONCLUSION: This is the first report of deletion/duplication in HEXA gene providing a new insight into the molecular basis of TSD and use of MLPA assay for detecting large copy number changes in the HEXA gene.

Low molecular weight heparin (enoxaparin) reverses pregangrene in a preterm neonate.

A 34-week-old, 1.6 kg preterm boy was admitted for management of mild respiratory distress syndrome. On the third day of life 1 min after an intravenous cannulation attempt at the right cubital fossa, he developed pregangrene bluish discoloration of all fingertips up to the distal interphalangial joint and pallor of right palm. Pulsations on right forearm were reduced. There was no evidence of sepsis.Enoxaparin, a low molecular weight heparin (1.5 mg/kg (standard dose)) was injected subcutaneously in the abdomen in two doses 12 h apart within 2 h of the event. At 6 h after the first dose, brachial artery pulsation was bilaterally symmetrical. After the second dose, bilateral radial artery pulsation became symmetrical. The pregangrene changes returned to normal within 20 h as the distal phalanges became pink and warm. He was discharged on the eighth day of life. Enoxaparin was safe and effective in this preterm infant for reversal of pregangrene.