New insights from nanotechnology in SARS-CoV-2 detection, treatment strategy, and prevention.

The recent outbreak of SARS-CoV-2 resulted into the deadly COVID-19 pandemic, which has made a profound impact on mankind and the world health care system. SARS-CoV-2 is mainly transmitted within the population via symptomatic carriers, enters the host cell via ACE2 and TMPSSR2 receptors and damages the organs. The standard diagnostic tests and treatment methods implemented lack required efficiency to beat SARS-CoV-2 in the race of its spreading. The most prominently used diagnostic test,reverse transcription-polymerase chain reaction (a nucleic acid-based method), has limitations including a prolonged time taken to reveal results, limited sensitivity, a high rate of false negative results, and lacking specificity due to a homology with other viruses. Furthermore, as part of the treatment, antiviral drugs such as remdesivir, favipiravir, lopinavir/ritonavir, chloroquine, daclatasvir, atazanavir, and many more have been tested clinically to check their potency for the treatment of SARS-CoV-2 but none of these antiviral drugs are the definitive cure or suitable prophylaxis. Thus, it is always required to combat SARS-CoV-2 spread and infection for a better and precise prognosis. This review answers the above mentioned challenges by employing nanomedicine for the development of improved detection, treatment, and prevention strategies for SARS-CoV-2. In this review, nanotechnology-based detection methods such as colorimetric assays, photothermal biosensors, molecularly imprinted nanoparticles sensors, electrochemical nanoimmunosensors, aptamer-based biosensors have been discussed. Furthermore, nanotechnology-based treatment strategies involving polymeric nanoparticles, metallic nanoparticles, lipid nanoparticles, and nanocarrier-based antiviral siRNA delivery have been depicted. Moreover, SARS-CoV-2 prevention strategies, which include the nanotechnology for upgrading personal protective equipment, facemasks, ocular protection gears, and nanopolymer-based disinfectants, have been also reviewed. This review will provide a one-site informative platform for researchers to explore the crucial role of nanomedicine in managing the COVID-19 curse more effectively.

Insulin Resistance in children on Sodium Valproate - A hospital based cross-sectional study in Indian children.

Our objective was to compare the point prevalence of insulin resistance (IR) in children taking sodium valproate (VPA) and phenytoin sodium (PS) monotherapy for >1 year. 150 children, aged 6-18 years, were categorized (50 each) into - group A (VPA), group B (PS) and group C (healthy controls age-sex matched with group A). Groups were compared for metabolic complications and risk factors assessed. The point prevalence of IR and non-alcoholic fatty liver disease was significantly higher in children on VPA (12% and 34% respectively) than on PS and healthy controls, regardless of age, sex, pubertal and nutritional status. The presence of central obesity, acanthosis, hypertension, dyslipidaemia was significantly associated with IR but none showed an independent association on multivariate analysis. Therapy with VPA makes children susceptible to metabolic complications. Close monitoring will facilitate early detection and timely intervention.

Indian Guidelines on Nebulization Therapy.

Inhalational therapy, today, happens to be the mainstay of treatment in obstructive airway diseases (OADs), such as asthma, chronic obstructive pulmonary disease (COPD), and is also in the present, used in a variety of other pulmonary and even non-pulmonary disorders. Hand-held inhalation devices may often be difficult to use, particularly for children, elderly, debilitated or distressed patients. Nebulization therapy emerges as a good option in these cases besides being useful in the home care, emergency room and critical care settings. With so many advancements taking place in nebulizer technology; availability of a plethora of drug formulations for its use, and the widening scope of this therapy; medical practitioners, respiratory therapists, and other health care personnel face the challenge of choosing appropriate inhalation devices and drug formulations, besides their rational application and use in different clinical situations. Adequate maintenance of nebulizer equipment including their disinfection and storage are the other relevant issues requiring guidance. Injudicious and improper use of nebulizers and their poor maintenance can sometimes lead to serious health hazards, nosocomial infections, transmission of infection, and other adverse outcomes. Thus, it is imperative to have a proper national guideline on nebulization practices to bridge the knowledge gaps amongst various health care personnel involved in this practice. It will also serve as an educational and scientific resource for healthcare professionals, as well as promote future research by identifying neglected and ignored areas in this field. Such comprehensive guidelines on this subject have not been available in the country and the only available proper international guidelines were released in 1997 which have not been updated for a noticeably long period of over two decades, though many changes and advancements have taken place in this technology in the recent past. Much of nebulization practices in the present may not be evidence-based and even some of these, the way they are currently used, may be ineffective or even harmful. Recognizing the knowledge deficit and paucity of guidelines on the usage of nebulizers in various settings such as inpatient, out-patient, emergency room, critical care, and domiciliary use in India in a wide variety of indications to standardize nebulization practices and to address many other related issues; National College of Chest Physicians (India), commissioned a National task force consisting of eminent experts in the field of Pulmonary Medicine from different backgrounds and different parts of the country to review the available evidence from the medical literature on the scientific principles and clinical practices of nebulization therapy and to formulate evidence-based guidelines on it. The guideline is based on all possible literature that could be explored with the best available evidence and incorporating expert opinions. To support the guideline with high-quality evidence, a systematic search of the electronic databases was performed to identify the relevant studies, position papers, consensus reports, and recommendations published. Rating of the level of the quality of evidence and the strength of recommendation was done using the GRADE system. Six topics were identified, each given to one group of experts comprising of advisors, chairpersons, convenor and members, and such six groups (A-F) were formed and the consensus recommendations of each group was included as a section in the guidelines (Sections I to VI). The topics included were: A. Introduction, basic principles and technical aspects of nebulization, types of equipment, their choice, use, and maintenance B. Nebulization therapy in obstructive airway diseases C. Nebulization therapy in the intensive care unit D. Use of various drugs (other than bronchodilators and inhaled corticosteroids) by nebulized route and miscellaneous uses of nebulization therapy E. Domiciliary/Home/Maintenance nebulization therapy; public & health care workers education, and F. Nebulization therapy in COVID-19 pandemic and in patients of other contagious viral respiratory infections (included later considering the crisis created due to COVID-19 pandemic). Various issues in different sections have been discussed in the form of questions, followed by point-wise evidence statements based on the existing knowledge, and recommendations have been formulated.

Ultramini-percutaneous nephrolithotomy versus retrograde intrarenal surgery in the treatment of 10-30 mm calculi: a randomized controlled trial.

The surgical management of renal stones 10-30 mm is usually performed with percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS). Standard form of percutaneous nephrolithotomy has paved the way for miniaturized PCNL in many centres. We wanted to evaluate the efficacy, safety and the cost-effectiveness of ultramini-percutaneous nephrolithotomy (UMP) versus RIRS in the treatment of renal stones with stone burden 10-30 mm. Patients with renal stone burden 10-30 mm were prospectively randomized into either UMP or RIRS. The demographic data, stone characteristic, operative time and cost of the equipment were recorded. The stone free status, analgesic requirement, deterioration of the renal function and hemoglobin and the postoperative complications as per Clavein-Dindo grade were recorded. One hundred and fifty patients met inclusion criteria. Out of these 98 underwent UMP and 46 RIRS. Six withdrew the consent before the procedure. Mean stone size was comparable in either of the groups. Mean laser time and stone extraction time was significantly less for UMP compared to RIRS (41.17 min versus 73.58 min p < 0.0001). Mean consumable costs in the UMP group were considerably less at US$45.73 compared to the RIRS group at $423.11 (p < 0.0001). The stone free rates at 1 month of follow-up were 100% for UMP group and 73% for RIRS group. There were insignificant changes to mean hemoglobin and glomerular filtration rate (GFR) in all patients and the average length of the stay was similar in both the groups. The postoperative complications revealed Grade I and II rate of 10% in the UMP group and 35% in the RIRS group, respectively. We concluded that UMP to be safe, effective and more economical to the RIRS for renal stones up to 3 cm in size.Trial registered with ISRCTN registry ID ISRCTN20935105, Retrospective.

Psychiatric morbidity and substance use in migrant workers: A population based study.

BACKGROUND: The prevalence of mental health problems and substance abuse in the migrant population is higher than the general population. AIMS AND OBJECTIVES: To assess the prevalence and pattern of mental health issues and substance use in the migrant population and highlight the association with the reverse migration of migrant workers. METHODOLOGY: The field staff visited the shelter homes for migrant population in four cities of Northern India (Chandigarh (UT), Bhatinda (Punjab), Panchkula (Haryana) and Jaipur (Rajasthan). After maintaining the social distance and wearing masks by the staff and migrants, written informed consent was taken for participation in the study. The socio-demographic details of reverse migrants were noted down and Hindi version of Patient Health Questionnaire (PHQ-9) for mental health problems and screening tool for pattern of substance abuse was administered. Geographically matched undisplaced were also administered these tools. RESULTS: A total of 275 reverse migrants and 276 undisplaced were included in the study. The prevalence of ever use for all the substances among reverse migrants was 44.4% (122/275) and among undisplaced, it was 45.3%. The prevalence of alcohol, tobacco and cannabis was higher than the general population. The prevalence of at least one diagnosis on PHQ-9 is 13.45% (reverse migrants 19.3% and undisplaced 7.6) and the prevalence of other depressive disorder is significantly higher in reverse migrants (17.1%) than undisplaced (4.0%). CONCLUSION: The study concludes that prevalence of mental health issues and substance abuse in migrant population is significantly higher than the general population and the prevalence of at least one diagnosis and other depressive disorder is significantly higher in reverse migrants than undisplaced.

Factors Leading to Reverse Migration Among Migrant Workers During the COVID-19 Pandemic: A Multicenter Study From Northwest India.

OBJECTIVE: To examine the various psychosocial factors associated with reverse migration among migrant workers during the coronavirus disease 2019 (COVID-19) lockdown in India. METHODS: A cross-sectional multicenter study was conducted at 4 sites in Northwest India. The migrant workers were recruited from various shelter homes, and information was gathered from reverse migrant workers and controls using various tools including a sociodemographic profile; knowledge, attitudes, and practices questionnaire; and reasons for migration and reverse migration questionnaires. A total of 275 reverse migrant workers and 276 controls participated in the study. RESULTS: There was a considerable difference between reverse migrant workers and controls regarding the question of whether it was safe to travel during lockdown (76.0% vs 26.4%, respectively). The most common route of spread of COVID-19 infection was through touching and sneezing, and symptoms were fever, dry cough, and sore throat in both groups. Reverse migrant workers had low self-esteem and were reluctant to participate in customs of their migration city. A large number of reverse migrant workers reported that they had no money to survive, worried about family back home at their village, felt pressured by family members to come back to the village, and had been terminated from their job. CONCLUSIONS: Reverse migrant workers had the attitude that it was safe to travel during the lockdown. About one-fifth of the reverse migrant workers reported no place to live and fear of getting an infection. The reverse migrant workers also reported feeling low and gloomy, restless, and uncertain about the future and fear of death. Lack of jobs was a major factor driving migrant workers from their native homes.

Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.

BACKGROUND: Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE: To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN: In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS: An interim analysis reflected earlier and better culture conversion rates: 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION: The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.

Guidelines for diagnostic flexible bronchoscopy in adults: Joint Indian Chest Society/National College of chest physicians (I)/Indian association for bronchology recommendations.

Flexible bronchoscopy (FB) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. However, bronchoscopy practices vary widely across India and worldwide. The three major respiratory organizations of the country supported a national-level expert group that formulated a comprehensive guideline document for FB based on a detailed appraisal of available evidence. These guidelines are an attempt to provide the bronchoscopist with the most scientifically sound as well as practical approach of bronchoscopy. It involved framing appropriate questions, review and critical appraisal of the relevant literature and reaching a recommendation by the expert groups. The guidelines cover major areas in basic bronchoscopy including (but not limited to), indications for procedure, patient preparation, various sampling procedures, bronchoscopy in the ICU setting, equipment care, and training issues. The target audience is respiratory physicians working in India and well as other parts of the world. It is hoped that this document would serve as a complete reference guide for all pulmonary physicians performing or desiring to learn the technique of flexible bronchoscopy.

Gender differences in obsessive-compulsive disorder: Findings from a multicentric study from India.

Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous. Gender is an important factor mediating this heterogeneity. We examined gender differences in a large sample (n = 945) of OCD patients under a multi-centric study in India. Cross-sectional assessments were done on consecutive adult (>18 years) treatment-seeking patients with a DSM-5 diagnosis of OCD. Subjects were assessed on Structured Clinical Interview for DSM-5-Research Version for comorbid psychiatric illnesses, Yale Brown Obsessive Compulsive Scale for OCD phenomenology and symptom severity, Brown Assessment of Beliefs Scale for insight, Beck's Depression Inventory for severity of depressive symptoms, and the Obsessive Beliefs Questionnaire. On multivariate backward Wald logistic regression analysis, males (59.7%) had more years of education, had a higher rate of checking compulsions and comorbid substance use disorders. Women were more likely to be married, more commonly reported precipitating factors, had a higher rate of hoarding compulsions and comorbid agoraphobia. Findings from this large study validate gender as an important mediator of phenotypic heterogeneity in OCD. The mechanistic basis for these differences might involve complex interactions between biological, cultural and environmental factors.

Small intestine strictures in opium addicts: An unrecognized cause of intestinal obstruction.

Strictures of the small intestine have been attributed many causes of Crohn's disease, nonsteroidal anti-inflammatory drugs, neoplastic, post-surgical, and corrosive ingestion. Opium as a cause of small intestine strictures has not been described. Six cases of opium addicts diagnosed with small intestine strictures were selected after excluding the possible etiology of strictures. Investigations like upper gastrointestinal endoscopy, colonoscopy (in patients with small intestinal obstruction), barium meal follow-through, and histopathology of strictures were done in all patients. Among the six cases, two patients were diagnosed with small intestinal obstruction and four patients with gastric outlet obstruction. Histopathology of the strictures revealed marked thickening of submucosa with infiltration by lymphocytes, plasma cells, and plenty of eosinophils. There was dilatation of vessels and lymphatics. The granulomatous reaction was not seen. These histological features are suggestive of concentric fibrous thickening in submucosa with stricture formation possibly as a result of drug abuse like opioids and opioid-like products resulting in transient ischemia of the small intestine leading to fibrosis. Patients were managed by surgery and deaddiction treatment was given to prevent further complications. Opium and opioid-like drugs can cause small intestinal strictures causing ulceration and fibrosis in opioid-dependent patients.

Serum Levels of Neuroactive Steroids in First-episode Antipsychotic-naïve Schizophrenic Patients and Its Correlation with Aggression: A Case-control Study.

BACKGROUND: The evidence of hypothalamic-pituitary-adrenal axis dysfunction in schizophrenia has been reviewed in the context of the stress-diathesis model. Overactivation of this axis leads to altered blood levels of cortisol and dehydroepiandrosterone sulfate (DHEA-S). These neurosteroids in turn act on the hippocampus and interact with gamma-aminobutyric acid and N-methyl-D-aspartate receptors leading to neurotoxicity and may be involved in the neurobiology of aggression. This study aimed to explore the blood level of these neurosteroids and ascertain its correlation with state aggression and psychopathology in first-episode antipsychotic-naïve schizophrenic patients. METHODS: A total of 30 patients with first-episode schizophrenia along with 20 age- and gender-matched healthy controls participated in the study. Both groups were subjected to serum cortisol and DHEA-S measurement after assessment of psychopathology and aggression on a standardised psychometric scale. RESULTS: Serum DHEA-S level was significantly higher in the patient group (p = 0.001). No difference was noted between males and females in the patient group (p = 0.93) but female controls had a significantly lower serum DHEA-S level than male controls (p < 0.01). Serum DHEA-S inversely correlated with scores on Modified Overt Aggression Scale (p = 0.01) but not with Positive and Negative Syndrome Scale (p = 0.39) or Clinical Global Impression Scale (p = 0.28). CONCLUSION: The first-episode antipsychotic-naïve schizophrenic patients showed a significantly higher blood level of DHEA-S compared with healthy controls. Serum DHEA-S level has an inverse relationship with aggression and may serve as a biological adaptive mechanism to antagonise the neuronal damage caused by cortisol.

Anisotropy in the thermal hysteresis of resistivity and charge density wave nature of single crystal SrFeO3-δ: X-ray absorption and photoemission studies.

The local electronic and atomic structures of the high-quality single crystal of SrFeO3-δ (δ~0.19) were studied using temperature-dependent x-ray absorption and valence-band photoemission spectroscopy (VB-PES) to investigate the origin of anisotropic resistivity in the ab-plane and along the c-axis close to the region of thermal hysteresis (near temperature for susceptibility maximum, Tm~78 K). All experiments herein were conducted during warming and cooling processes. The Fe L 3,2-edge X-ray linear dichroism results show that during cooling from room temperature to below the transition temperature, the unoccupied Fe 3d e g states remain in persistently out-of-plane 3d 3z2-r2 orbitals. In contrast, in the warming process below the transition temperature, they change from 3d 3z2-r2 to in-plane 3d x2-y2 orbitals. The nearest-neighbor (NN) Fe-O bond lengths also exhibit anisotropic behavior in the ab-plane and along the c-axis below Tm. The anisotropic NN Fe-O bond lengths and Debye-Waller factors stabilize the in-plane Fe 3d x2-y2 and out-of-plane 3d 3z2-r2 orbitals during warming and cooling, respectively. Additionally, a VB-PES study further confirms that a relative band gap opens at low temperature in both the ab-plane and along the c-axis, providing the clear evidence of the charge-density-wave nature of SrFeO3-δ (δ~0.19) single crystal.

Endoxifen, a New Treatment Option for Mania: A Double-Blind, Active-Controlled Trial Demonstrates the Antimanic Efficacy of Endoxifen.

The protein kinase C (PKC) signaling system plays a role in mood disorders and PKC inhibitors such as endoxifen may be an innovative medicine for bipolar disorder (BP) patients. In this study we show for the first time the antimanic properties of endoxifen in patients with bipolar I disorder (BPD I) with current manic or mixed episode. In a double-blind, active-controlled study, 84 subjects with BPD I were randomly assigned to receive endoxifen (4 mg/day or 8 mg/day) or divalproex in a 2:1 ratio. Patients orally administered 4 mg/day or 8 mg/day endoxifen showed significant improvement in mania assessed by the Young Mania Rating Scale as early as 4 days. The effect remained significant throughout the 21-day period. At study end point, response rates were 44.44% and 64.29% at 4 mg/day and 8 mg/day of endoxifen treatment, respectively. Thus, endoxifen has been shown as a promising novel antimanic or mood stabilizing agent.

Brain abscess due to Streptococcus oralis in an immunocompetent patient.

A bacteriologically proven case of brain abscess, due to Streptococcus oralis is being reported in a 12-year-old girl who is a known case of congenital heart disease. The patient presented with fever, headache and vomiting. Pus cultures yielded S. oralis.

Outcomes of Category III DOTS treatment in immunocompetent patients with tuberculosis pleural effusion.

OBJECTIVES: To study the efficacy and safety of Category III DOTS treatment (intermittent thrice-weekly rifampicin [RMP], isoniazid [INH] and pyrazinamide for 2 months, followed by RMP and INH for 4 months) under India's Revised National Tuberculosis Control Programme in patients with uncomplicated small unilateral pleural effusion (<1500 ml). DESIGN: This prospective, multicentre, observational study recruited 351 patients between 2006 and 2010. Patients were regularly followed up clinically as well as with ultrasound examination of the chest. RESULTS: Successful outcome (clinical response with complete resolution on ultrasound examination at 6 months) was seen in 274 patients (78.1%). Efficacy was 88.9% (excluding defaulters), and 94% among those completing follow-up as per protocol. None of the patients received corticosteroids. Other outcomes included treatment extension (n = 26, 7.4%), default (n = 43, 12.2%), treatment failure (n = 3, 0.9%) and death (n = 3, 0.9%). Seventy-nine mild/moderate adverse events and one treatment-related serious adverse event were noted; one patient developed recurrent drug-induced hepatotoxicity. Two patients (0.7%) had relapse/re-infection at 24 months follow-up. CONCLUSION: Intermittent thrice-weekly treatment for 6 months with three drugs in the intensive phase is effective and safe for unilateral small pleural effusion in immunocompetent patients. Although Category III no longer exists in the programme, the results are reassuring for intermittent treatment in extra-pulmonary TB under programme conditions.

Identification of vulnerability among first-degree relatives of patients with schizophrenia.

OBJECTIVES: To evaluate the status of schizotypy, neurological soft signs, and cognitive functions as vulnerability markers for schizophrenia and to investigate the potential value of their combination for early identification of people at high risk for schizophrenia. METHODS: A cross-sectional study was conducted. Subjects were drawn from first-degree relatives of inpatients and outpatients with schizophrenia (n = 50). Controls (n = 30) were recruited by word-of-mouth from hospital staff and attendants of hospitalised patients. Subjects who met inclusion criteria on screening were subjected to selected measures for assessment, including Schizotypal Personality Questionnaire-Brief Version, the Cambridge Neurological Inventory, digit span test, paired associate learning test, and visuospatial working memory matrix. Statistical analysis was completed using the independent t test and significance (p value), as well as calculation of effect size (Cohen's d). Discriminant function analysis was used to determine the effect of combining assessment measures. RESULTS: First-degree relatives showed higher schizotypy scores (Cohen's d = 0.88) and neurological soft signs (Cohen's d = 1.55). They scored significantly worse on all neurocognitive measures (Cohen's d = -1.27). Discriminant function analysis showed that Schizotypal Personality Questionnaire-Brief Version, neurological soft signs, and total cognitive index (the sum of weighted scores on individual cognitive scales) in combination better discriminated between the first-degree relative and control groups (Wilks' λ = 0.54). CONCLUSION: Use of multiple vulnerability markers could enhance the specificity of measures used to determine risk for schizophrenia.

Filarial dance--sonographic sign of filarial infection.

A 17-year-old boy presented with a 3-month history of swelling and vague pain in the scrotum. US revealed multiple anechoic cyst-like lesions in the body of left epididymis. These cysts showed tubular echogenic internal structures with peculiar twirling motion. This was recognised as the sonographic filarial dance-sign of live adult filarial worms. The boy subsequently underwent needle aspiration of the lesion, which microscopically demonstrated microfilaria of Wuchereria bancrofti. Our report includes an online video clip that will help familiarise readers with the filarial dance.

Bilateral multicystic dysplastic kidneys -- an unusual case diagnosed on antenatal ultrasound.

While it is true that unilateral multicystic dysplastic kidney is commonly associated with abnormalities in the contralateral kidney, it is not widely known that the condition may be bilateral. The recognition of the bilaterality of the multicystic dysplastic kidney by ultrasound has grave prognostic implications as this condition is uniformly fatal. High resolution ultrasound examination of the foetus enables early detection of congenital malformations of the urinary tract. This information is of value in determining foetalprognosis, in deciding the method of delivery, and in alerting the paediatricians to supportive and corrective measures which may need to be taken in postnatal period.