Impact of Deltoid Computer Tomography Image Data on the Accuracy of Machine Learning Predictions of Clinical Outcomes after Anatomic and Reverse Total Shoulder Arthroplasty.

Background: Despite the importance of the deltoid to shoulder biomechanics, very few studies have quantified the three-dimensional shape, size, or quality of the deltoid muscle, and no studies have correlated these measurements to clinical outcomes after anatomic (aTSA) and/or reverse (rTSA) total shoulder arthroplasty in any statistically/scientifically relevant manner. Methods: Preoperative computer tomography (CT) images from 1057 patients (585 female, 469 male; 799 primary rTSA and 258 primary aTSA) of a single platform shoulder arthroplasty prosthesis (Equinoxe; Exactech, Inc., Gainesville, FL) were analyzed in this study. A machine learning (ML) framework was used to segment the deltoid muscle for 1057 patients and quantify 15 different muscle characteristics, including volumetric (size, shape, etc.) and intensity-based Hounsfield (HU) measurements. These deltoid measurements were correlated to postoperative clinical outcomes and utilized as inputs to train/test ML algorithms used to predict postoperative outcomes at multiple postoperative timepoints (1 year, 2-3 years, and 3-5 years) for aTSA and rTSA. Results: Numerous deltoid muscle measurements were demonstrated to significantly vary with age, gender, prosthesis type, and CT image kernel; notably, normalized deltoid volume and deltoid fatty infiltration were demonstrated to be relevant to preoperative and postoperative clinical outcomes after aTSA and rTSA. Incorporating deltoid image data into the ML models improved clinical outcome prediction accuracy relative to ML algorithms without image data, particularly for the prediction of abduction and forward elevation after aTSA and rTSA. Analyzing ML feature importance facilitated rank-ordering of the deltoid image measurements relevant to aTSA and rTSA clinical outcomes. Specifically, we identified that deltoid shape flatness, normalized deltoid volume, deltoid voxel skewness, and deltoid shape sphericity were the most predictive image-based features used to predict clinical outcomes after aTSA and rTSA. Many of these deltoid measurements were found to be more predictive of aTSA and rTSA postoperative outcomes than patient demographic data, comorbidity data, and diagnosis data. Conclusions: While future work is required to further refine the ML models, which include additional shoulder muscles, like the rotator cuff, our results show promise that the developed ML framework can be used to evolve traditional CT-based preoperative planning software into an evidence-based ML clinical decision support tool.

Crisaborole-Enthused Glycerosomal Gel for an Augmented Skin Permeation.

BACKGROUND: Crisaborole (CB), a boron-based compound, is the first topical PDE4 inhibitor to be approved by the US Food and Drug Administration (2016) for the treatment of Atopic Dermatitis. It is marketed as a 2% ointment (Eucrisa, Pfizer). However, CB is insoluble in water; therfore, CB glycersomes were formulated to enhance its permeation flux across the skin. OBJECTIVE: We developed a glycerosomal gel of CB and compared its in vitro release and permeation flux with the 2% conventional ointment. METHODS: Glycerosomes were prepared using a thin film hydration method employing CB, soya phosphatidylcholine, and cholesterol. The formed film was further hydrated employing a mixture of phosphate buffer pH 7.4 /glycerin solution containing varying percentages (20,30, 40, and 50 %) of glycerol. The glycerosomes obtained were characterized by their size, polydispersity index (PDI), and Zeta potential. The entrapment efficiency of the optimized formulation (F 1) was determined. The in vitro release of F1 was compared with its 2% conventional ointment. F1 was further incorporated into carbopol 934 P gel. The gel was characterized by pH, viscosity, spreadability, and drug content. The permeability flux of the glycerosomal gel was compared with its 2% conventional ointment. RESULTS: The optimized CB glycerosomes had a vesicle size of 137.5 ± 50.58 nm, PDI 0.342, and zeta potential -65.4 ± 6.75 mV. CB glycerosomal gel demonstrated a 2.13-fold enhancement in the permeation flux. CONCLUSION: It can thereby be concluded that glycerosomes can be an effective delivery system to enhance the penetration of CB across the skin.

A Comprehensive Review on Polyphenols Based Nanovesicular System for Topical Delivery.

BACKGROUND: Polyphenols are naturally occurring compounds having more than one hydroxy functional group. They are ubiquitous secondary plant metabolites possessing a wide range of pharmacological activity. Brightly colored fruits and vegetables are the natural source of polyphenols. Majorly, they possess antioxidant, anti-inflammatory and antimicrobial properties which make them suitable candidates to target skin related disorders. OBJECTIVE: This study is focused to explore the potential of polyphenols loaded nanovesicles for skin related disorders. The aim of the study is to review the applicability and efficacy of different vesicular systems encapsulated with various classes of polyphenols for skin related disorders, thus opening the opportunity for future studies based on these drug delivery systems. METHOD: Web of Science, PubMed, Scopus database, and the search engine Google Scholar were accessed for the literature search. The results were then filtered based on the titles, abstracts, and accessibility of the complete texts. RESULTS: The expository evaluation of the literature revealed that various nanovesicles like liposomes, niosomes, ethosomes and transferosomes incorporating polyphenol have been formulated to address issues pertaining to delivery across the skin. These developed nano vesicular systems have shown improvement in the physicochemical properties and pharmacological action. CONCLUSION: Polyphenol based nano-vesicular formulations have proved to be an effective system for topical delivery and henceforth, they might curtail the use of other skin therapies having limited applicability.

Crystal structure of a phenoxyl radical complex relevant to the metal site of the galactose oxidase enzyme: A facile one-pot synthesis, evidence for hydrogen atom transfer and DNA cleavage via self-activation.

Copper complexes [Cu(L1H)ClO4] (1) and [Cu(L2)NO3] (2), which are relevant to the metal site of the galactose oxidase enzyme, were synthesized and characterized by different spectroscopic methods. L1H2 and L2H2 [where L1H2 stands for 2,2'-((1E,1'E)(2,2'-(pyridine-2,6-diyl)bis(2-phenylhydrazin-2-yl-1-ylidene))bis(methanylylidene))diphenol and L2H2 stands for 6,6'-((1E,1'E)-(2,2'-(pyridine-2,6-diyl)bis(2-phenylhydrazin-2-yl-1-ylidene))bis(methanylylidene))bis(2,4-di-tert-butylphenol), H stands for dissociable proton] are pentadentate ligands. These ligands provide pyridyl N, two imine N, and two non-innocent phenoxyl and phenolato O donors, forming complex 1 as a non-radical complex, while complex 2 is a phenoxyl radical complex. The molecular structures of complexes 1 and 2 were authenticated by X-ray crystallography. Benzyl alcohol oxidation was investigated, and the conversion of 9,10-dihydroanthracene to anthracene was examined to scrutinize the H-atom abstraction reaction. Nuclease activity with complexes 1 and 2 was investigated by self-activated plasmid DNA (pBR322) cleavage. Non-innocent properties of the ligand-containing phenolato function were investigated by DFT calculations.

Cochlear Implant in cochlear Hypoplasia type 4 with Chiari Malformation- Case Report.

Cochlear hypoplasia type IV is a rare cochlear malformation with hypoplastic middle and apical turns while basal turn develops normally, it often coexist with other genetic mutations. We present a case of 4 year old with chiari malformation type 1 along with bilateral Cochlear hypoplasia type IV who underwent cochlear implantation.

Comparative Study Between Intravenous Patient-Controlled Analgesia Morphine and Computerized Ambulatory Delivery Device Epidural Morphine for Post Operative Analgesia for Nuss Procedure in Pectus Excavatum: A Retrospective Analysis.

BACKGROUND: Pectus deformities are commonly seen in chest wall deformities among the pediatric age group. Pectus deformities occur due to defective growth of the sternum and its surrounding cartilage. The Nuss procedure is the technique of choice for correcting the deformity surgically which includes placing a convex bar under the sternum without resection or injury to costal cartilages. Adequate pain control is utmost to improve wound healing, patient satisfaction, short hospital stays, and decrease the financial burden on attendants. Therefore, it is necessary to investigate which analgesic method is more advantageous for the Nuss procedure. OBJECTIVE: To compare the analgesic effects of intravenous patient-controlled analgesia (IVPCA) morphine versus computerized ambulatory delivery device (CADD) epidural morphine on acute post-operative pain management in Nuss procedures. METHODS: A retrospective study was done at Rajiv Gandhi Cancer and Research Hospital, New Delhi from 2015 to 2020 to assess the efficacy and safety between IVPCA morphine and CADD epidural for post-operative analgesia following pectus excavatum repair. A total of 34 cases of Nuss procedures were taken with 17 cases in each group. Group 1 (intravenous PCA morphine) was given 39 ml normal saline + 6 ml morphine (total 45 ml, 2 mg/ml morphine), set at demand dose 0.5 ml, i.e. 1 mg, lockout interval 7 minutes, doses per hour was six and Group 2 (CADD epidural morphine) was given 42 ml normal saline + 3 ml morphine (1 mg/ml morphine) with continuous infusion at the rate of 0.5 ml/hr. Demand dose 0, lockout interval nil. Visual analog pain scores using a scale of 0-10 and Ramsay Sedation Score (RSS) scores were obtained on arrival at the post-anesthesia care unit, at 12, 24, 48, and 72 hours throughout the subsequent hospital stay. RESULTS: This study yielded positive information about our experience with the pectus post-operative pain management. The mean visual analog scale (VAS) score was lower in Group 1 compared to Group 2 but significantly different at 12 and 72 hours only. The mean RSS score was comparable between groups. The mean hospital stay (days) and requirement of rescue analgesia doses were 3.47±0.51 and 0.12±0.33 in Group 1 and 4.76±0.44, 0.59±1.12 in Group 2. CONCLUSION:  Both IVPCA morphine and CADD morphine were effective in controlling post-surgical pain in the Nuss procedure, but IVPCA morphine was better as compared to CADD morphine in this regard because it was noninvasive, safe, and cost-effective with non-significant complications.

Incidence of SARS-CoV-2 Co-infections During the Second Wave in Sub-Himalayan Region, India.

Introduction The second wave of the coronavirus disease 2019 (COVID-19) pandemic in India, which started from April 2021, has been more severe and deadly than the first wave. The aim of this prospective study was to determine the possibility of other respiratory pathogens contributing towards the severity and hospitalization in the current second wave. Materials and methods Nasopharyngeal and oropharyngeal swab samples were collected and processed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR). These samples were further processed for detection of co-infection in SARS CoV-2 patients by BioFire® Filmarray® 2.0 (bioMérieux, USA). Results We screened 77 COVID-19-positive patients admitted to All India Institute of Medical Sciences (AIIMS), Rishikesh and found cases of co-infections in five (6.49 %) patients. Conclusion Our finding suggests that co-infections had no or minimal role in augmenting the second wave of the COVID-19 pandemic in India, and the emergence of new variants may be the probable cause.

Cochlear implantation in children with congenital inner ear malformations - Our experience.

OBJECTIVE: To share our experience of the surgical challenges faced in cochlear implanted patients with inner ear malformation and to assess the auditory and speech perception outcomes. MATERIAL AND METHOD: Clinical records of 502 cochlear implant procedures were reviewed and data of 122 patients who had inner ear malformations were enrolled in the study. Their auditory and speech performances were evaluated post implantation for 3 years. RESULT: Cerebrospinal fluid gusher was encountered during opening of cochlea in 42 patients (34.4%) and one patient was re-explored within 24 h. In 30.3% of cases facial anomaly was found. Significant improvement in average performance was seen in all malformation types except in cochlear hypoplasia at 12 months postoperatively. CONCLUSION: Surgical challenges can be overcome with expertise and giving special attention to preoperative imaging. Our experience suggests that outcomes are favourable in patients with inner ear malformations too.

The baneful alliance of COVID-19 and mucormycosis: Histopathological concerns.

Background: Mucormycosis, once a rare fungal disease, has now shown a surge in cases, and its epidemiology in India is intriguing. Rising incidence confers the necessity of defining the demography of the population at risk, early diagnosis, and recommendations for the management of mucormycosis in patients with coronavirus disease (COVID-19) infection. Aims: To study the clinico-epidemological profile, risk factors, and histopathological features of COVID-19-associated Mucormycosis (CAM). Setting and Design: This is a retrospective observational study. Material and Methods: Fifty-six biopsy specimens taken from patients of COVID-19 with clinical suspicion of mucormycosis were included. Results: Diabetes mellitus, corticosteroids, and oxygen therapy were the most common risk factors associated with CAM. The mean duration between the onset of symptoms of COVID-19 and onset of CAM was 25.2 ± 15.3 days. Rhino-orbito-cerebral mucormycosis (ROCM) was present in 24.5% of the cases, with a survival rate of 58.3%. Histopathology showed tissue invasion by branching broad-based, pale, fungal hyphae consistent with mucor in 49 (87.5%) cases. Inflammation was acute neutrophilic type in 61.2% of the patients with a survival rate of 63.33%. The survival rate with chronic non-granulomatous and chronic granulomatous was 100% and 81.8%, respectively. Conclusion: Keeping a high index of suspicion for mucormycosis in COVID-19 by all medical fraternities of the health community in the existence of risk factors is the need of the hour for prompt diagnosis. Biopsy of antral necrotic tissue should be performed immediately after suspicion for histopathological study to confirm the diagnosis of mucormycosis and predict prognosis depending on the type of inflammation incited, fungal morphology, load, and necrosis.

Interference of Antinuclear Antibody (ANA) in Indirect Immunofluorescence Assay (IIFA)-Based Perinuclear Antineutrophil Cytoplasmic Antibody (pANCA) Interpretation.

Background: Indirect immunofluorescence assay (IIFA) based on antineutrophil cytoplasmic antibody (ANCA) testing is a commonly employed test for diagnosing autoimmune vasculitis. Antinuclear antibody (ANA) can give rise to a false interpretation of perinuclear-ANCA (pANCA) in ethanol-fixed granulocyte substrates. Analytical interference could frequently occur in setups where ethanol-fixed substrates are used alone. Here, we intend to investigate this ANA interference in pANCA interpretation. Methods: In this retrospective study, we studied anti-MPO-negative but ANA-positive and pANCA (IIFA based) samples. We also correlated immunoblot results (where data were available) and checked the association between grades of blot positivity (an indicator of the concentration of ANA) and frequency of pANCA interpretation. Data were analyzed by appropriate statistical techniques (Chi-square and kappa statistics). Results: About 19.2% of ANA blot (ENA-blot) positive samples displayed a pANCA positive pattern in the ethanol-fixed substrate, while this positivity in ENA-blot negatives was 6.5%. In positive ANA-IIFA samples, about 14.7% yielded pANCA patterns (on ethanol fixed substrates). Out of this, nuclear homogenous pattern yielding samples gave the highest frequency pANCA, that is, in 31.5% followed by speckled (11.1%), DFS (10.3%), and centromere (6.7%).The association of the nuclear homogenous pattern was statistically significant. Conclusions: ANA-positive results may interfere with the interpretation of pANCA as observed in ANA-IIFA and ENA-blot positive samples. ANA-IIFA patterns like nuclear homogenous may strongly associate this pANCA interpretation. This can help laboratories perform ANCA testing more effectively, ruling out ANA interference in ANCA screening.

Disruptions, restorations and adaptations to health and nutrition service delivery in multiple states across India over the course of the COVID-19 pandemic in 2020: An observational study.

BACKGROUND: Modeling studies estimated severe impacts of potential service delivery disruptions due to COVID-19 pandemic on maternal and child nutrition outcomes. Although anecdotal evidence exists on disruptions, little is known about the actual state of service delivery at scale. We studied disruptions and restorations, challenges and adaptations in health and nutrition service delivery by frontline workers (FLWs) in India during COVID-19 in 2020. METHODS: We conducted phone surveys with 5500 FLWs (among them 3118 Anganwadi Workers) in seven states between August-October 2020, asking about service delivery during April 2020 (T1) and in August-October (T2), and analyzed changes between T1 and T2. We also analyzed health systems administrative data from 704 districts on disruptions and restoration of services between pre-pandemic (December 2019, T0), T1 and T2. RESULTS: In April 2020 (T1), village centers, fixed day events, child growth monitoring, and immunization were provided by <50% of FLWs in several states. Food supplementation was least disrupted. In T2, center-based services were restored by over a third in most states. Administrative data highlights geographic variability in both disruptions and restorations. Most districts had restored service delivery for pregnant women and children by T2 but had not yet reached T0 levels. Adaptations included home delivery (60 to 96%), coordinating with other FLWs (7 to 49%), and use of phones for counseling (~2 to 65%). Personal fears, long distances, limited personal protective equipment, and antagonistic behavior of beneficiaries were reported challenges. CONCLUSIONS: Services to mothers and children were disrupted during stringent lockdown but restored thereafter, albeit not to pre-pandemic levels. Rapid policy guidance and adaptations by FLWs enabled restoration but little remains known about uptake by client populations. As COVID-19 continues to surge in India, focused attention to ensuring essential services is critical to mitigate these major indirect impacts of the pandemic.

Recent nanobiotechnological advancements in lignocellulosic biomass valorization: A review.

Increase in human population, rapid industrialization, excessive utilization of fossil fuel utilization and anthropogenic activities have caused serious threats to the environment in terms of greenhouse gas emissions (GHGs), global warming, air pollution, acid rain, etc. This destruction in sustainability can be averted by a paradigm shift in the fuel production from fossil resources to bioenergy. Amongst different forms of bioenergy, lignocellulosic biomass can be utilized as an attractive substrate for the production of several high-value products owing to its renewability, easy availability, and abundance. Additionally, utilization of these waste biomasses reduces the environmental hazards associated with its disposal. Impedance of lignin and crystalline nature of cellulose pose major bottlenecks in biomass based energy. Though, several physio-chemicals processes are recommended as mitigation route but none of them seems to be promising for large scale application. In recent years, a right fusion of biological treatment combined with nanotechnology for efficient pretreatment and subsequent hydrolysis of biomass by ubiquitous enzymes seems to be promising alternative. In addition, to overcome these difficulties, nanotechnology-based methods have been recently adopted in catalytic valorization of lignocellulosic biomass. The present review has critically discussed the application of nano-biotechnology in lignocellulosic biomass valorization in terms of pretreatment and hydrolysis. A detailed discussion on the application of various nanoparticles in these processes, enzyme immobilization and end-production utilization is presented in this review. Finally, the review emphasizes the major challenges of this process along with different routes and recommendations to address the issues.

Designed pincer ligand supported Co(II)-based catalysts for dehydrogenative activation of alcohols: Studies on N-alkylation of amines, α-alkylation of ketones and synthesis of quinolines.

Base-metal catalysts Co1, Co2 and Co3 were synthesized from designed pincer ligands L1, L2 and L3 having NNN donor atoms respectively. Co1, Co2 and Co3 were characterized by IR, UV-Vis. and ESI-MS spectroscopic studies. Single crystal X-ray diffraction studies were investigated to authenticate the molecular structures of Co1 and Co3. Catalysts Co1, Co2 and Co3 were utilized to study the dehydrogenative activation of alcohols for N-alkylation of amines, α-alkylation of ketones and synthesis of quinolines. Under optimized reaction conditions, a broad range of substrates including alcohols, anilines and ketones were exploited. A series of control experiments for N-alkylation of amines, α-alkylation of ketones and synthesis of quinolines were examined to understand the reaction pathway. ESI-MS spectral studies were investigated to characterize cobalt-alkoxide and cobalt-hydride intermediates. Reduction of styrene by evolved hydrogen gas during the reaction was investigated to authenticate the dehydrogenative nature of the catalysts. Probable reaction pathways were proposed for N-alkylation of amines, α-alkylation of ketones and synthesis of quinolines on the basis of control experiments and detection of reaction intermediates.

Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19.

Vitamin D deficiency (VDD) owing to its immunomodulatory effects is believed to influence outcomes in COVID-19. We conducted a prospective, observational study of patients, hospitalized with COVID-19. Serum 25-OHD level < 20 ng/mL was considered VDD. Patients were classified as having mild and severe disease on basis of the WHO ordinal scale for clinical improvement (OSCI). Of the 410 patients recruited, patients with VDD (197,48.2%) were significantly younger and had lesser comorbidities. The levels of PTH were significantly higher in the VDD group (63.5 ± 54.4 vs. 47.5 ± 42.9 pg/mL). The proportion of severe cases (13.2% vs.14.6%), mortality (2% vs. 5.2%), oxygen requirement (34.5% vs.43.4%), ICU admission (14.7% vs.19.8%) was not significantly different between patients with or without VDD. There was no significant correlation between serum 25-OHD levels and inflammatory markers studied. Serum parathormone levels correlated with D-dimer (r 0.117, p- 0.019), ferritin (r 0.132, p-0.010), and LDH (r 0.124, p-0.018). Amongst VDD patients, 128(64.9%) were treated with oral cholecalciferol (median dose of 60,000 IU). The proportion of severe cases, oxygen, or ICU admission was not significantly different in the treated vs. untreated group. In conclusion, serum 25-OHD levels at admission did not correlate with inflammatory markers, clinical outcomes, or mortality in hospitalized COVID-19 patients. Treatment of VDD with cholecalciferol did not make any difference to the outcomes.

High prevalence of diabetes and other comorbidities in hospitalized patients with COVID-19 in Delhi, India, and their association with outcomes.

BACKGROUND AND AIMS: To study the prevalence and impact of diabetes mellitus and other comorbidities among hospitalized patients with COVID-19. METHODS: In a prospective, observational study including consecutive adults hospitalized with COVID-19, clinical outcomes and inflammatory markers were compared in those with and without diabetes. Participants were classified as having mild or severe COVID-19 disease using the WHO ordinal scale. RESULTS: 401 patients (125 females) with median age of 54 years (range 19-92) were evaluated. Of them 189 (47.1%) had pre-existing diabetes and21 (5.2%) had new-onset hyperglycaemia. Overall, 344 (85.8%) and 57 (14.2%) cases had mild and severe COVID-19 disease respectively. The group with diabetes had a higher proportion of severe cases (20.1% vs 9%, p-0.002), mortality (6.3 vs 1.4%, p-0.015), ICU admission (24.3 vs 12.3%, p-0.002), and oxygen requirement (53.4 vs 28.3%, p < 0.001). Baseline Hba1c (n = 331) correlated significantly with outcome severity scores (r 0.136, p-0.013) and 12/15 (80%) of those who succumbed had diabetes. Hypertension, coronary artery disease, and chronic kidney disease were present in 164 (40.9%), 35 (8.7%) and 12 (2.99%) patients respectively. Hypertension was associated with a higher proportion of severe cases, mortality, ICU admission and oxygen administration. CONCLUSIONS: We report a high prevalence of diabetes in a hospitalized COVID-19 population. Patients with diabetes or hypertension had more severe disease and greater mortality.

Video Consultation Versus In-Person Clinic Visit for Glycemic Control in Type 2 Diabetes during COVID-19 Pandemic (VIP-CD Study).

Objectives: To compare the efficacy of video consultation (VC) for prospective glycemic control against that of in-person clinic visit (IPV) in individuals with type 2 diabetes. Materials and Methods: This is a retrospective, cohort study of 96 individuals with type 2 diabetes followed up for a period of ≤6 months. The cohort was divided into two groups depending on the mode of consultation, namely IPV (n = 48) and VC (n = 48). Baseline and follow-up characteristics including glycemic profile and lipid profile were compared. Results: The cohort had a mean age of 55.4 ± 13.8 years, median diabetes duration of 8 (0.3-70) years, a mean body mass index (BMI) of 28.8 ± 5.8 kg/m2, 44 (46.3%) females, and uncontrolled hyperglycemia (HbA1c 8.7% ± 1.9%). Both groups were adequately matched at baseline. At the time of first visit, cessation of previous medications was more frequent in the IPV group (37.5% vs 8.3%; P = 0.001) than in the VC group. Follow-up was earlier in the VC group as compared to the IPV group (43.2 vs 87.9 days; P = 0.000). During the follow-up period, both groups had similar and adequate glycemic (mean HbA1c 7% ± 1%) and lipid profile control. Cox regression model showed that the VC group achieved glycemic control quicker as compared to the IPV group. Conclusions: Telemedicine is an effective mode of consultation for attaining glycemic control during COVID-19 pandemic, possibly owing to the quicker follow-up without the risk of potential in-clinic/hospital exposure to COVID-19.

Novel coronavirus disease (COVID-19): origin, transmission through the environment, health effects, and mitigation strategies-a review.

The novel coronavirus disease (COVID-19), caused by severe acute respiratory coronavirus-2 (SARS-CoV-2), was first identified in China and subsequently spread globally, resulting in a severe pandemic, and officially declared a significant health emergency by World Health Organization (WHO). Genetic analysis of coronavirus isolated from bats, snakes, and Malay pangolins suggested that they could be intermediate hosts for SARS-CoV-2. The transfer of virus from person to person has been confirmed widely, while the actual source of origin is still unknown. COVID-19 is a highly contagious and infectious disease, and the worldwide transmission of coronavirus has intense effects on the lives of human beings. The spread of the virus is observed mainly through close contact with the infected person due to coughing, sniffing or indirectly through the contaminated surfaces. If people touch contaminated surfaces through their hands, mouth, nose, or eye, it enters the body and causes disease. Also, the virus may transmit through air droplets, water, food, fecal-oral transmission, etc. The infection of virus in human beings could be detected by direct symptoms, or different diagnostic tools are available to determine the viral load. Various safety measures are used to contain the virus, including disinfectants, antiviral drugs, vaccines, wearing masks, social distancing, etc. In the present review, we have focused on transmission of COVID-19 through air and wastewater as environmental transmission modes. We have also discussed the origin of the virus, its mode of action, host immune response, vulnerability, varying symptoms and diagnosis, prevention and control. Further, we have discussed the various treatment options to cope with this viral outbreak.

Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme.

INTRODUCTION: Around 9% of India's children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures. METHODS: This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants' GMs twice, that is, within 2 months after birth and at 3-5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12-24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12-24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA. ETHICS AND DISSEMINATION: G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.