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Objective: Pharmacogenomics plays an important role in drug metabolism. A stable anticoagulation is important for primary and secondary prevention of cardioembolic stroke and cerebral venous sinus thrombosis (CVST). We report the role of cytochrome P450 (CYP2C9*2/*3) and vitamin K epoxide reductase subunit 1 (VKORC1) genotypes and acquired causes in maintaining stability of anticoagulation following acenocoumarin in cardioembolic stroke and CVST. Methods: The study comprised 157 individuals with cardioembolic stroke and CVST who were on acenocoumarin. Their comorbidities, comedication, and dietary habits were noted. Prothrombin time and international normalized ratio (INR) were measured during follow-up, and the coagulation status was categorized as stable (>50% occasions in therapeutic range) and unstable (>50% below and above therapeutic range). Genotyping of VKORC1, CYP2C9*2, and CYP2C9*3 was done by polymerase chain reaction-restriction fragment length polymorphism. Bleeding and embolic complications were noted. The predictors of unstable INR were evaluated using multivariate analysis. Results: INR was stable in 47.8% and unstable in 52.2% of patients. Patients with mutant genotypes required low dose of acenocoumarin. The predictors of unstable INR were metallic valve (odds ratio [OR] 4.07, 95% confidence interval [CI] 1.23-13.49, P = 0.02), use of digoxin (OR 0.031, 95% CI 0.13-0.74, P = 0.09), proton pump inhibitor (OR 0.23, 95% CI 0.06-0.91, P = 0.037), sodium valproate (OR 0.22, 95% CI 0.05-0.85, P = 0.029), and CYP2C9*2 genotype (OR 5.57, 95% CI 1.19-26.06, P = 0.02). Conclusions: Variant genotypes of VKORC1, CYP2C9*2, and CYP2C9*3 required lower dose of acenocoumarin, and CYP2C9*2 was associated with unstable INR. Comedication is a modifiable risk factor that needs attention. [ABSTRACT FROM AUTHOR]

A diagnosis of autism typically depends on clinical assessments by highly trained professionals. This high resource demand poses a challenge in low-resource settings. Digital assessment of neurodevelopmental symptoms by non-specialists provides a potential avenue to address this challenge. This cross-sectional case-control field study establishes proof of principle for such a digital assessment. We developed and tested an app, START, that can be administered by non-specialists to assess autism phenotypic domains (social, sensory, motor) through child performance and parent reports. N = 131 children (2–7 years old; 48 autistic, 43 intellectually disabled and 40 non-autistic typically developing) from low-resource settings in Delhi-NCR, India were assessed using START in home settings by non-specialist health workers. The two groups of children with neurodevelopmental disorders manifested lower social preference, greater sensory interest and lower fine-motor accuracy compared to their typically developing counterparts. Parent report further distinguished autistic from non-autistic children. Machine-learning analysis combining all START-derived measures demonstrated 78% classification accuracy for the three groups. Qualitative analysis of the interviews with health workers and families of the participants demonstrated high acceptability and feasibility of the app. These results provide feasibility, acceptability and proof of principle for START, and demonstrate the potential of a scalable, mobile tool for assessing neurodevelopmental conditions in low-resource settings. Autism is diagnosed by highly trained professionals– but most autistic people live in parts of the world that harbour few or no such autism specialists and little autism awareness. So many autistic people go undiagnosed, misdiagnosed, and misunderstood. We designed an app (START) to identify autism and related conditions in such places, in an attempt to address this global gap in access to specialists. START uses computerised games and activities for children and a questionnaire for parents to measure social, sensory, and motor skills. To check whether START can flag undiagnosed children likely to have neurodevelopmental conditions, we tested START with children whose diagnoses already were known: Non-specialist health workers with just a high-school education took START to family homes in poor neighbourhoods of Delhi, India to work with 131 two-to-seven-year-olds. Differences between typically and atypically developing children were highlighted in all three types of skills that START assesses: children with neurodevelopmental conditions preferred looking at geometric patterns rather than social scenes, were fascinated by predictable, repetitive sensory stimuli, and had more trouble with precise hand movements. Parents' responses to surveys further distinguished autistic from non-autistic children. An artificial-intelligence technique combining all these measures demonstrated that START can fairly accurately flag atypically developing children. Health workers and families endorsed START as attractive to most children, understandable to health workers, and adaptable within sometimes chaotic home and family environments. This study provides a proof of principle for START in digital screening of autism and related conditions in community settings. [ABSTRACT FROM AUTHOR]

Introduction: Covid-19 patients can have both regional and global ventricular dysfunction. We aim to study the spectrum of myocardial involvement in Covid-19 patients on echocardiography. Methods: This is a single center, observational study where wall motion abnormality patterns were studied in Covid-19 patients along with global and regional longitudinal strain analysis (GLS). Results: 30 Covid-19 patients were included in the study, with a mean age of 35.3±6.4 years. Echocardiography revealed characteristic wall motion abnormality involving hypokinesia of anterolateral and apical segments, which produced an operculum like appearance in all patients. Strain derived ejection fraction(EF) was lower in 4 chamber as compared to 2 chamber indicating regional myocardial dysfunction. Reduced GLS values in presence of normal EF indicates global systolic function impairment. Endocardial effacement was also noted in these segments along with stretching of interventricular septum. Conclusion: Specific myocardial involvement pattern can be detected on echocardiography, thus helping in diagnosis of Covid myocarditis. [ABSTRACT FROM AUTHOR]

Background: Environmentally sustainable diets are represented in the EAT‐Lancet recommendations developed by the Lancet Commission on Planetary Health in 2019. Very few studies have compared Indian diets with the EAT‐Lancet recommendations. The present study performed such a comparison using primary dietary consumption data from adults in north and south India. Methods: Data from 8762 adults (52.4 ± 11.7 years) residing in Sonipat and Vizag India were collected on sociodemographic characteristics, wealth index (household assets) and dietary intake (food frequency questionnaire: nine food groups). The quantity consumed and energy from each food group was compared with the EAT‐Lancet recommendations. We investigated the likelihood of deficit or excess in consumption compared to the EAT‐Lancet recommendations by different sociodemographic factors. Results: Half of the participants were women and half resided in rural areas. Vegetables and fruits were consumed in lower quantity, whereas dairy and added fats were consumed in higher quantity than recommended by the EAT‐Lancet recommendations. For whole grains, female gender and poorest wealth index were the factors associated with deficit or no consumption, whereas, for vegetables and fruits, it was poorest wealth index and residence in rural areas (p < 0.05, all). Rural residence and poorest wealth index were associated with excess consumption of dairy and added fats (p < 0.05, all). Conclusions: The diets of the study participants were mainly plant‐based, and high in dairy but lacking in nutrient‐rich foods such as vegetables and fruits. Appropriate policy actions for making healthy sustainable diets and micronutrient‐rich foods available and affordable to all with a particular focus on the poor and rural populations are warranted. Very few studies have compared Indian diets with the EAT‐Lancet dietary recommendations. The present study performed such a comparison using primary dietary consumption data, finding that Indian diets were mainly plant‐based, being high in dairy but lacking in nutrient‐rich foods such as vegetables and fruits. Highlights: Compared with the EAT‐Lancet recommendations, Indian diets were deficit in fruits and vegetables consumption but exceeded in dairy and added fats.Female gender, rural residence and poorest wealth index were associated with lower nutrient rich foods consumption.To ensure sustainable and healthy diets in India, the EAT‐Lancet recommendations should be adopted considering Indian Council of Medical Research guidelines.Urgent policy actions are needed to make healthy and sustainable diets locally available accessible and affordable to all. [ABSTRACT FROM AUTHOR]

Background: Thyroid dysfunction is the leading endocrine disorder worldwide. Iodine deficiency disorders, which were once the major etiology of thyroid dysfunctions, now have been succeeded by autoimmune thyroid diseases with the rise in aberrant salt ionization protocols. This study endeavors to access the level of thyroid autoantibodies viz. anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (TGA), and anti-thyroid stimulating hormone receptor (TRAb) in individuals with subnormal thyroid profiles. Methods: This hospital-based cross-sectional study was conducted at the Department of Clinical Biochemistry, Tribhuvan University for a period of six months. Using non-probability (purposive) sampling method, a total of 60 patients were enrolled with subnormal thyroid profiles to include the population who have not yet started medication. Thyroid hormones (free T3, free T4, TSH) and thyroid antibodies (anti-TPO, TGA, and TRAb) were measured. For non-parametric data, Chi-square test and Kruskal-Wallis test were used. Spearman's correlation was done to determine the association between variables. Results: Out of 60 participants, the majority of the population between 25 and 44 years were diagnosed with thyroid dysfunction with female preponderance. Among all, 40% (n = 24) had subclinical hyperthyroid states while, 60% (n = 36) had subclinical hypothyroid states, and 75% (n = 45) of the total exhibited positive thyroid antibodies. In subclinical hypothyroid patients with TSH above 10 µIU/ml, anti TPO (58.5%) and TGA (66.7%) positivity were highly prevalent. On the other hand, TRAb was exclusively positive in hyperthyroid condition (50% among the group) which is by far the first of its kind reported in Nepal. Conclusion: The rise in autoimmune thyroid disease among the Nepalese population infers that addressing iodine deficiency simply through salt iodinization may not be adequate to deal with the rising burden of thyroid disorders, especially in iodine-depleted areas. Also, the increasing prevalence of thyroid autoantibodies positivity in subclinical hypothyroidism in the Nepalese population accounts for the arduous screening and monitoring of autoimmune thyroid disorders in Nepal. [ABSTRACT FROM AUTHOR]

Objective: The study investigated adherence with MMF treatment among patients attending rheumatology clinics at University Hospitals Coventry and Warwickshire NHS Trust (UHCW) with Autoimmune inflammatory rheumatic diseases (AIIRDs). Methods: This retrospective study collated hospital pharmacy data in patients who requested the prescription for MMF between January 2015 and December 2018. Clinical data were obtained from paper and electronic notes. Data were analysed using Microsoft Excel. Ethical approval was obtained through Coventry University. Results: We recruited 144 patients into this study with age range from 18 to 91 years, including 100 females and 44 males. There were 112 White patients, 22 of South Asian origin, 3 East Asian and 4 black patients. SLE (56), scleroderma (18), mixed connective tissue disease (15), myositis (13), vasculitis (13) were the commonest diagnoses. Overall adherence with Mycophenolate mofetil was 62%. The adherence rates were below 80% for all age groups with ∼60% of patients having adherence levels of >60%. Poor adherence with MMF correlated with 3‐fold increase in risk of flares compared to good adherence (p = 0.002). We also found a significant difference between Asian patients (mean adherence 47%) and White patients (mean adherence 65%, p < 0.001). Conclusion: Adherence with MMF has improved considerably compared to historical studies, although these remain suboptimal. Certain population groups such as young adults, elderly and Asian patients continue to have lower adherence and higher risk of flares. Strategies are needed to improve adherence levels overall and specifically in the high‐risk groups to reduce risk of flares and organ damage. [ABSTRACT FROM AUTHOR]

Aims: To study the respiratory variation of right atrial (RA) pressures at baseline and during atrioventricular nodal reentry tachycardia (AVNRT). Methods: Of the 23 patients screened, 16 participants with typical AVNRT were included in the study. After ensuring adequate hydration, baseline RA pressures were measured as the height of 'a' and 'v' waves. The patients were asked to take deep breaths, and the measurements were taken in both inspiration and expiration. Results: Of the 16 participants, 14(87.5%) showed a normal fall in the height of 'a' and 'v' waves with inspiration, 1(6.25%) showed no change and 1(6.25%) showed a rise in height at baseline, p <0.01. During induced AVNRT, the 'a' and 'v' wave heights increased in 8(50%), remained same in 6(37.5%) and showed a normal fall in 2(12.5%), p = 0.07 for 'a' waves and p = 0.09 for 'v' waves. When the magnitude and direction of change in 'a' and 'v' wave height at baseline was compared with AVNRT, it showed a significant difference with 13(81.25%) participants demonstrating positive Pseudo-Kussmaul's sign, p <0.01. Mean age was numerically higher in those with a more considerable inspiratory rise in RA pressures but was not statistically significant, χ2(2) = 3.1, p = 0.21. Conclusions: Pseudo-Kussmaul's sign does occur in a substantial number of patients during AVNRT. Clinical appreciation of this phenomenon is possible in half to three-fourth of patients, provided the mean RA pressures are low enough for the variation to be visible in the neck. [ABSTRACT FROM AUTHOR]

Context: The Upanishads are primary texts of Yoga philosophy and practices. Various Yoga Upanishads have given detailed description of various yogic practices along with their spiritual and physical benefits. This study aims to assess the effect of one Pranayama practice from Trishikhbrahmana Upanishad on sleep quality in adults. Aim: The aim of the study was to assess the effect of a Pranayama technique (described in the Trishikhbrahmana Upanishad) on sleep quality in adults. Settings and Design: An experimental study was conducted on volunteer participants from North India. Subjects and Methods: A pretest-posttest control group study was designed where the participants (n = 30) were randomized into study (n = 15) and control (n = 15) groups. The study group was given the Pranayama intervention for 30 days whereas the control group was not given any intervention throughout the study. The sleep quality was assessed by using the Pittsburgh Sleep Quality Index (PSQI). Statistical Analysis Used: GraphPad Instat Software was used to carry out independent t-test. The mean and standard deviation were also calculated. Results: The results showed a significant improvement in the postglobal PSQI score in the study group (P < 0.001) whereas there was no significant change in the pre- and postglobal PSQI score in the control group (P = 0.941). Conclusion: The results suggest that the Pranayama technique from the text and its effects are true in improving the sleep quality in adults but future studies with a larger sample size and some other physiological parameter assessments may further support the textual claim. [ABSTRACT FROM AUTHOR]

Background: Bi-spectral index (BIS) has been traditionally used to monitor the depth of anesthesia, with the forehead being the usual site for electrode placement. When the manufacturer-recommended site is itself an operative field or the placement interferes with the surgery, the search for an alternative position of electrode placement is warranted. In our endeavor to do so, we conducted this study to compare BIS scores derived from frontal and supralabial electrode placement. Methods: A cross-sectional study was conducted on a group of 50 patients using two BIS Quatro sensors attached to the frontal and supralabial regions of each patient and connected to two different sets of monitors. BIS values, electromyography (EMG) values, and signal quality index (SQI) were noted from both sites every 15 min during the maintenance phase of anesthesia. Collected data were analyzed using the Bland-Altman analysis. Results: Data analysis of BIS values showed negative bias at most time points with a minimum negative bias of 0.2 with a limit of agreement of -3.67/3.27 and a maximum negative bias of 1.14 with a limit of agreement of -7.61/5.33. The overall 95% limit of agreement for pooled BIS data ranged from -6.63 to 6.1. Conclusion: BIS sensor placement at the supralabial site can be used as an alternative to the frontal placement in scenarios where the frontal position is the surgical site or is inaccessible during the maintenance of general anesthesia as in neurosurgery with particular emphasis on skin preparation and proper positioning of BIS electrodes to improve the signal quality. [ABSTRACT FROM AUTHOR]

BACKGROUND- The laparoscopic cholecystectomy procedure is typically carried out under general anaesthesia, but regional techniques, such as low thoracic isobaric spinal anaesthesia, have been used to manage patients with significant medical problem like coexisting systemic disease, who are deemed to be high risk in general anaesthesia. Segmental spinal anaesthesia has great outcomes in terms of post-operative discomfort, the need for analgesics, relatively fewer complications, and shorter hospital stays. Thus the aim of this study to avoid and minimize the risk of general anaesthesia who does not have any significant comorbidity. So it might be a substitute for a standard laparoscopic cholecystectomy. MATERIAL AND METHODS- Total 60 adult patient with ASA1 &II, 18-60 years,with normal coagulation profile, is divided into 2 groups. Group IS (Isobaric)--given 2.5 ml of isobaric preservative free bupivacaine 0.5% (levobupivacaine) + 0.5 mg of Fentanyl at T9- T10/T10-T11 into sub arachnoid space. Group GA -- given general anaesthesia using propofol, fentanyl citrate and atracurium besylate. After intubation, ventilation was controlled and balanced anaesthesia was continued with isoflurane. After completion, neuromuscular block was anatagonized neostigmine methyl-sulfate and glycopyrrolate at the end of surgery. RESULTS- Isobaric spinal anaesthesia showed good control in intraoperative as well as postoperative pain control as compared to general anaesthesia. In few patients, there were minor degrees of nausea, vomiting, abdominal pain, shoulder pain, patient anxiety or itching which were treated with standard medication like fentanyl and midazolam. All patients can resume oral intake on the day of surgery. CONCLUSIONS- In conclusion, this study provide evidence that segmental spinal anaesthesia can be used in place of general anaesthesia in healthy individuals also. [ABSTRACT FROM AUTHOR]

Introduction: Quantitative analysis of cardiac biomarkers, troponin I and CPK-MB, estimates the extent of myocardial injury while extent of benefit from coronary collateral circulation (CCC) to protect myocardium during acute myocardial infarction (AMI) needs validation. We analysed if the extent of collaterals had impact on baseline biomarkers at the time of coronary angiogram. Methods: We analysed 3616 consecutive patients who presented with AMI and underwent invasive coronary angiography (CAG) with intent to revascularisation with biomarkers assessment at the time of CAG. CCC to Infarct related artery (IRA) were graded as per Rentrop grading viz. poorly-developed CCC (Grade 0/1 as Group A) and well-developed CCC (Grade 2/3 as Group B). Results: Both groups (A and B) were matched for demographics, traditional risk factors, SYNTAX 1 Score, time to CAG from onset of angina and eGFR. 36.59% of patients had Non-ST segment elevation myocardial infarction (NSTEMI) as compared to 63.41% ST -segment elevation infarction (STEMI). Overall Troponin I (P =0.01, P =0.01) and CPK MB (P =0.00, P =0.002) values were lower in group B in both NSTEMI and STEMI groups respectively. Troponin I and CPK-MB were significantly lower in group B [with NSTEMI for SVD (Single vessel disease) (P =0.05) and DVD (Double vessel disease) (P =0.04),but not for TVD (Triple vessel disease) and with STEMI in SVD (P =0.01), DVD (P =0.01) and TVD (P =0.001)]. Conclusion: Patients with well-developed coronary collaterals had a lower rise in biomarkers in AMI as compared to those with poor collaterals amongst both NSTEMI and STEMI groups. [ABSTRACT FROM AUTHOR]

Objective To compare the synovial phenylalanine/tyrosine (Phe/Tyr) ratio between ReA/uSpA and RA and OA by NMR spectroscopy. Methods Paired SF and serum of 30 patients with ReA/uSpA were collected and analysed using a 1D 1H Carr Purcell Meiboom Gill NMR spectra recorded on 800 MHz NMR spectrometer equipped with a TCI Cryoprobe (at 300 K). Phe and Tyr were quantified. SF from 25 patients with RA fulfilling ACR classification criteria and 21 patients with OA were taken as inflammatory and non-inflammatory controls. Results The synovial Phe/Tyr ratio was significantly higher in ReA/uSpA compared with RA and OA. Synovial Phe/Tyr ratios were comparable in RA and OA patients. Compared with serum, the Phe/Tyr was significantly higher in the SF in ReA/uSpA. The Phe/Tyr ratio was also found to be positively correlated between serum and SF samples, with a regression coefficient (r2) of 0.287. Conclusions This NMR-based metabolomics study demonstrates that the synovial Phe/Tyr ratio is specifically elevated in ReA/uSpA. [ABSTRACT FROM AUTHOR]

Background: The pattern of post-stroke aphasia in speakers of Bengali language has not previously been reported in the literature. Furthermore, the inter-relationship between age, gender, and level of education and aphasia typology has remained unsettled thus far. Aims: To investigate the incidence and type of aphasia in first-ever acute stroke patients who were speakers of Bengali language. Methods & Procedures: Bengali version of Western Aphasia Battery was used for language assessment in our study participants. Lesion localization was done by using magnetic resonance imaging(3T) for ischemic stroke (if not contraindicated) and computed tomography for hemorrhagic stroke. Among 515 screened cases of first-ever acute stroke, 208 presented with aphasia. Language assessment was done between 7 and 14 days in all study participants. Outcomes & Results: The incidence of post-stroke aphasia in our sample was found at 40.39%. Types of aphasia were – Broca's (38.5%) followed by global (27.9%); Wernicke's (12.5%); transcortical motor (9.6%); anomic (4.3%); transcortical sensory (3.8%); isolation (1.9%); and conduction (1.4%). Mean number of years of formal education was significantly higher in fluent aphasia group in comparison with non-fluent group (10.51 years versus 7.01 years, p = 0.003). In logistic regression analysis, location of lesion (posterior perisylvian) (p = 0.007, OR = 5.406, 95% CI, 1.602–18.240) and education (p = 0.044, OR = 1.097, 95% CI, 1.003–1.199) were two independent predictors favoring fluent aphasia. Conclusions: Aphasia among post-stroke Bengali patients is quite frequent. The commonest type of aphasia in our sample was Broca's aphasia. Bengali-speaking people with higher education were more likely to present fluent aphasia. [ABSTRACT FROM AUTHOR]

The recently proposed Social Motivation theory (Chevallier et al., Trends in cognitive sciences 16(4):231-239, 2012) suggests that social difficulties in Autism Spectrum Condition (ASC) might be caused by a difference in the motivation to engage with other people. Here we compared adolescents with (N = 31) and without (N = 37) ASC on the Choose-a-Movie paradigm that measures the social seeking. The results showed a preference for viewing objects over smiling faces in ASC, which is in line with the theory of low social motivation. However, typical adolescents did not show any stimuli preferences, raising questions about developmental changes in social motivation. Age was found to play a significant role in moderating the choice behaviour of the participants. We discuss the implications of these findings in detail. [ABSTRACT FROM AUTHOR]

Microprocessor prosthetic knees (MPKs) have advanced technologically, offering new features to decrease impairment and activity limitations for persons with transfemoral amputation (TFA). The Genium knee is functionally untested, and functional differences between it and intact knees are unknown. This study sought to determine whether Genium use improves functional performance compared with the C-Leg. A randomized experimental crossover design was used, with a cross-section of five nonamputee controls for comparison to normal. Twenty community-ambulating persons with TFA were trained and tested for accommodation with study components. All subjects (n = 25) were assessed using the Continuous-Scale Physical Functional Performance-10 (CS-PFP10) assessment. Subjects with TFA used both MPK systems. Genium use improved upper-body flexibility, balance, and endurance domain scores (7.0%-8.4%, p