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Gaurav Kaushik,1,2 Richa Vashishtha,2 Chaitenya Verma,3 Shipra Sharma,4 Vinay Kumar5 1School of Allied Health Sciences, Sharda University, Greater Noida, Uttar Pradesh, 201310, India; 2Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India; 3Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH, USA; 4Shri Guru Ram Rai Institute of Medical & Health Sciences, Dehradun, Uttarakhand, 248001, India; 5Pennsylvania State University Hershey Medical Center, 500 University Dr, Hershey, PA, 17033, USACorrespondence: Gaurav Kaushik; Vinay Kumar, Email gaurav.kaushik@sharda.ac.in; vinayktyagi07@gmail.comBackground: Toll-like receptors (TLRs) are identified as one of the key components of the innate immune system. The objective of this study was to explore the influence of genetic variability in these TLRs on human immunodeficiency virus (HIV) disease progression with and without tuberculosis (TB) co-infection.Materials and Methods: This prospective, cross-sectional, and longitudinal study included 373 HIV-positive patients without TB infection. This study aimed to examine the genetic variation in TLRs (TLR2, TLR4, and TLR9) between patients with HIV-1 infection and those who progressed to active TB during the two years of follow-up.Results: During the two year follow-up of 373 positive patients, 98 patients progressed to active TB/AIDS (acquired immunodeficiency syndrome). When comparing 98 HIV patients who developed active TB/AIDS to 275 HIV patients who did not, it was discovered that the frequency of the A allele in TLR9 was considerably higher (p < 0.001) in HIV patients progressed to active TB/AIDS. Ninety eight HIV individuals who advanced to active TB/AIDS showed a significantly higher frequency of the AA genotype in TLR9 than did in HIV patients who had no TB/AIDS (p < 0.001).Conclusion: The increased association of the AA genotype of TLR9 in HIV patients who progressed to active TB during follow-up suggests that HIV-positive patients with the AA genotype of TLR9 have increased susceptibility towards TB during the disease progression.Keywords: toll-like receptors, human immunodeficiency virus, tuberculosis, acquired immunodeficiency syndrome, immune system

The present study aimed to evaluate the concepts of epidemiology, uropathogenic, diagnosis, prevention, and treatment of urinary tract infections (UTI) in humans. One of the most frequent infections that affect people is UTIs. During childhood they are equally common in boys and girls, and after that, they are more common in girls. In both of the general population and hospital environment, women frequently experienced at least one UTI in their lifetime. The existence of bacteriuria and pyuria are the 2 most significant signs of UTIs. Frequent urination, pain during urination, and soreness in the side or lower back are among the main symptoms of UTI. These infections are classified into 3 primary types: asymptomatic bacteriuria, lower UTI (cystitis), and febrile upper UTI (acute pyelonephritis), because such classification supports understanding of the infection‟s etiology. UTI can be diagnosed through a combination of positive urine tests and/or culture and symptoms. Dipstick urinalysis is widely used due to its ease of availability and utility; however, the outcomes must be evaluated by considering the patient‟s pretest probability depending on the characteristics and symptoms. Most UTIs can be treated with antibiotics such as Amoxicillin, cephalexin, and doxycycline. But the Gram-positive bacterium (Enterobacter faecalis) exhibited great resistance to erythromycin, while the Gram-negative bacterium (Escherichia coli) displayed great resistance to ampicillin. So, there is an urgent need for a combination between organic treatments and antibiotics to treat the complicated UTI. For example, the plant-based treatments, such as cranberry juice, are efficient in treating the UTI and can be used as an alternative to combating the bacteria that cause UTI.

Mohamed Saleh Ismail,1,&ast; Diane E Peters,2,3,&ast; Steven P Rowe,4,5,&ast; Ali Salavati,6 Sowmya Sharma,1 Robert A Anders,7 Martin Pomper,2,4,5,&ast; Barbara S Slusher,2,3,8,&ast; Florin M Selaru1,5,&ast; 1Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 2Department of Pharmacology and Molecular Sciences, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 3Johns Hopkins Drug Discovery, Baltimore, MD, USA; 4Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 5The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA; 7The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 8Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA&ast;These authors contributed equally to this workCorrespondence: Florin M Selaru; Barbara S Slusher, Email fselaru1@jhmi.edu; bslusher@jhmi.eduBackground: Prostate-specific membrane antigen (PSMA) is highly and specifically upregulated in active-inflamed mucosa of patients with inflammatory bowel disease (IBD). We hypothesized that this upregulation would be detectable using a PSMA-targeted positron emission tomography/computed tomography (PET/CT) imaging agent, [18F]DCFPyL, enabling non-invasive visualization of inflammation. A noninvasive means of detecting active inflammation would have high clinical value in localization and management of IBD.Study: We performed [18F]DCFPyL imaging in three IBD patients with active disease. Abnormally increased gastrointestinal [18F]DCFPyL uptake was observed in areas with endoscopic, histologic, and immunohistochemical inflammation, demonstrating partial overlap of segments of bowel with abnormal [18F]DCFPyL uptake and active inflammation.Conclusion: This study demonstrates that PSMA-targeted [18F]DCFPyL PET can effectively detect regions of inflamed mucosa in patients with IBD, suggesting its utility as a non-invasive imaging agent to assess location, extent, and disease activity in IBD.Keywords: IBD, disease activity, PSMA, GCPII, [18F]DCFPyL

Divyani Garg,1 Shekeeb Mohammad,2,3 Anju Shukla,4 Suvasini Sharma5 1Department of Neurology, All India Institute of Medical Sciences, New Delhi, India; 2Kids Neuroscience Centre, The Children’s Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; 3TY Nelson Department of Neurology and Neurosurgery, The Children’s Hospital at Westmead, The University of Sydney, Westmead, New South Wales, Australia; 4Department of Medical Genetics, Kasturba Medical College and Hospital, Manipal, India; 5Department of Pediatrics (Neurology Division), Lady Hardinge Medical College and Kalawati Saran Hospital, New Delhi, IndiaCorrespondence: Suvasini Sharma, Department of Pediatrics (Neurology Division), Kalawati Saran Children’s Hospital, New Delhi, 110001, India, Tel +91 9910234344, Email sharma.suvasini@gmail.comAbstract: Episodic or paroxysmal movement disorders (PxMD) are conditions, which occur episodically, are transient, usually have normal interictal periods, and are characterized by hyperkinetic disorders, including ataxia, chorea, dystonia, and ballism. Broadly, these comprise paroxysmal dyskinesias (paroxysmal kinesigenic and non-kinesigenic dyskinesia [PKD/PNKD], paroxysmal exercise-induced dyskinesias [PED]) and episodic ataxias (EA) types 1– 9. Classification of paroxysmal dyskinesias has traditionally been clinical. However, with advancement in genetics and the discovery of the molecular basis of several of these disorders, it is becoming clear that phenotypic pleiotropy exists, that is, the same variant may give rise to a variety of phenotypes, and the classical understanding of these disorders requires a new paradigm. Based on molecular pathogenesis, paroxysmal disorders are now categorized as synaptopathies, transportopathies, channelopathies, second-messenger related disorders, mitochondrial or others. A genetic paradigm also has an advantage of identifying potentially treatable disorders, such as glucose transporter 1 deficiency syndromes, which necessitates a ketogenic diet, and ADCY5-related disorders, which may respond to caffeine. Clues for a primary etiology include age at onset below 18 years, presence of family history and fixed triggers and attack duration. Paroxysmal movement disorder is a network disorder, with both the basal ganglia and the cerebellum implicated in pathogenesis. Abnormalities in the striatal cAMP turnover pathway may also be contributory. Although next-generation sequencing has restructured the approach to paroxysmal movement disorders, the genetic underpinnings of several entities remain undiscovered. As more genes and variants continue to be reported, these will lead to enhanced understanding of pathophysiological mechanisms and precise treatment.Keywords: paroxysmal movement disorders, episodic ataxia, PRRT2, PNKD, KCNA1

Gohar Azhar,1 Shakshi Sharma,1 Onna Lau,1 Bader Alkharisi,1 Anil Anandam,1 Sakiru Isa,2 Priya Mendiratta,1 Amanda K Pangle,1 Karen Coker,1 Jeanne Wei1 1Department of Geriatrics, Donald W. Reynolds Institute of Aging, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN, USACorrespondence: Gohar Azhar, Email azhargohar@uams.eduBackground: Delirium is a common medical condition that is highly prevalent in older adults who are at increased risk for its development with any illness, post-surgery or during hospitalization. The purpose of our study was to evaluate the health literacy of older adult patients and their caregivers about delirium, offer a brief educational intervention, and reevaluate their knowledge post intervention.Materials and Methods: We conducted a quality improvement project, focused on delirium health literacy in older adult patients ≥ 60 years and their caregivers. Delirium knowledge of participants was evaluated in a pre-education survey after which they were given a delirium education booklet to read. A post-education delirium survey was conducted within 2– 3 weeks of the educational intervention. Chi-square test was used to analyze the knowledge base of older adults.Results: The study population consisted of a total of 70 older adults who participated in pre-education (n=35) and post-education (n=35) surveys. Older adult patients and their caregivers had significant knowledge gaps about the potential causes or etiologies, risk factors, symptomatology, and prevention of delirium in the pre-education survey. After the educational intervention, in the post-education survey, there were overall improvements in knowledge base of older adults in differentiating delirium with dementia (43% vs 94%, p< 0.01) recognizing signs and symptoms (77% vs 94%, p< 0.05), complications (76% vs 100%, p< 0.01) and identifying the etiological factors associated with delirium.Conclusion: The quality improvement project demonstrated that older adults and caregivers have significant knowledge deficits about the common condition of delirium. This study also demonstrated that older adults were able to improve their health literacy regarding delirium after the intervention. Appropriate education on delirium for patients and caregivers might help in earlier identification, prevention, and better overall management of delirium.Keywords: delirium, education, aging, healthcare

Though adjuvant radiotherapy has an established role in the treatment of carcinoma breast, there is concern regarding irradiation to heart and lung, more on left sided disease. Intensity Modulated Radiation Therapy (IMRT) modulates the intensity of the radiation beams with better accuracy, sparing surrounding normal organs. But it increases integral dose to normal healthy tissues compared to 3-Dimensional Conformal Radiation Therapy (3DCRT). So, our study was aimed at comparing the dosimetry and acute toxicity profile of 3DCRT and IMRT in post-mastectomy patients. In study arm patients received radiotherapy with IMRT and in control arm with 3DCRT, radiation dose being 50 Gy in 25 fractions for 5 weeks for both the arms. We compared the dosimetric data for Planning Target Volume (PTV) and Organ At-risk (OAR) by both techniques along with acute toxicity profile. Dosimetric parameter of PTV coverage V95 and V107 were significantly better in IMRT than 3DCRT (p-value

Kritika Singh,1,* Upendra Rathore,1,* Mohit Kumar Rai,1 Manas R Behera,2 Neeraj Jain,3 Manish Ora,4 Dharmendra Bhadauria,2 Supriya Sharma,5 Gaurav Pande,6 Sanjay Gambhir,4 Alok Nath,7 Sudeep Kumar,8 Aman Sharma,9 Vikas Agarwal,1 Durga Prasanna Misra1 1Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 2Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 3Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 4Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 5Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 6Department of Medical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 7Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 8Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 9Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India*These authors contributed equally to this workCorrespondence: Durga Prasanna Misra, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, India, Tel +91 5222495273, Fax + 91 522-2668812, Email DurgapMisra@gmail.comPurpose: We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β 1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK).Materials and Methods: We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β 1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26– 45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK.Results: TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β 1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy.Conclusion: Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.Keywords: arteritis, aortic arch syndromes, PD-1 protein, drug resistance, corticosteroid, fibrosis

In the context of enviromental applications, refining enzymes into more minimalist structures could ease production costs, improve stability, and improve reusability. Here, the authors report a single amino acid bionanozyme that can catalyze the rapid oxidation of environmentally toxic phenolic contaminates and serves as a tool to detect biologically important neurotransmitters similar to the laccase enzyme.

Chaitanya Dutt,1 Joao Eduardo Nunes Salles,2 Shashank Joshi,3 Tiny Nair,4 Subhankar Chowdhury,5 Ambrish Mithal,6 Viswanathan Mohan,7 Ravi Kasliwal,8 Satyawan Sharma,9 Jan Tijssen,10 Nikhil Tandon11 1Research and Development, Torrent Pharmaceuticals Ltd, Ahmedabad, Gujarat, India; 2Discipline of Endocrinology, Medical Sciences of Santa Casa de São Paulo, São Paulo, Brazil; 3Department of Endocrinology, Lilavati Hospital, Mumbai, Maharashtra, India; 4Department of Cardiology, PRS Hospital, Thiruvananthapuram, Kerala, India; 5Department of Endocrinology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India; 6Department of Endocrinology & Diabetes, Max Healthcare, New Delhi, India; 7Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India; 8Medanta- The Medicity, Gurgaon, Haryana, India; 9Department of Cardiology, Bombay Hospital and Medical Research Center, Mumbai, Maharashtra, India; 10Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands; 11Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Chaitanya Dutt, Research & Development, Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India, Tel +91 9825606901, Email Cdutt@torrentpharma.comAbstract: The epidemic of obesity or adiposity-based chronic diseases presents a significant challenge with the rising prevalence of morbidities and mortality due to atherosclerotic cardiovascular diseases (ASCVD), especially in low- and middle-income countries (LMIC). The underlying pathophysiology of metabolic inflexibility is a common thread linking insulin resistance to cardiometabolic-based chronic disease (CMBCD), including dysglycemia, hypertension, and dyslipidemia progressing to downstream ASCVD events. The complex CMBCD paradigm in the LMIC population within the socio-economic and cultural context highlights considerable heterogeneity of disease predisposition, clinical patterns, and socio-medical needs. This review intends to summarize the current knowledge of CMBCD. We describe recently established or emerging trends for managing risk factors, assessment tools for evaluating ASCVD risk, and various pharmacological and non-pharmacological measures particularly relevant for LMICs. A CMBCD model positions insulin resistance and β-cell dysfunction at the summit of the disease spectrum may improve outcomes at a lower cost in LMICs. Despite identifying multiple pathophysiologic disturbances constituting CMBCD, a large percentage of the patient at risk for ASCVD remains undefined. Targeting dysglycemia, dyslipidemia, and hypertension using antihypertensive, statins, anti-glycemic, and antiplatelet agents has reduced the incidence of ASCVD. Thus, primordial prevention targeting pathophysiological changes that cause abnormalities in adiposity and primary prevention by detecting and managing risk factors remains the foundation for CMBCD management. Therefore, targeting pathways that address mitochondrial dysfunction would exert a beneficial effect on metabolic inflexibility that may potentially correct insulin resistance, β cell dysfunction and, consequently, would be therapeutically effective across the entire continuum of CMBCD.Keywords: mitochondrial modulator, insulin resistance, diabetes mellitus, dyslipidemia hypertension, non-high-density lipoprotein-cholesterol, triglycerides, apolipoprotein B

Priya Battu,1,* Kaushal Sharma,1,* Rajarathna Thangavel,2 Ramandeep Singh,3 Suresh Sharma,4 Vinod Srivastava,5 Akshay Anand1 1Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 2Department of Ophthalmology, Vasan Eye Care, Chennai, India; 3Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 4Department of Statistics, Panjab University, Chandigarh, India; 5College of Health and Behavioral Sciences, Fort Hays State University, Hays, KS, USA*These authors contributed equally to this workCorrespondence: Akshay Anand, Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India, Tel +911722756094, Email akshay1anand@rediffmail.comBackground: Optical coherence tomography (OCT) parameters like subretinal fluid (SRF), intra retinal fluid (IRF) and retinal detachment (RPED) etc are routinely accessed by ophthalmologists in patients with retinal complaints. Correlation of OCT findings with genotype and phenotype of AMD patients is relatively unexplored. Here, we have investigated the association of OCT parameters’ with genetic variants along with protein expressions and examined their clinical relevance with AREDS (Age-Related Eye Disease Study) criteria in AMD patients.Methods: For this study, samples were recruited from Advanced Eye Centre, PGIMER, Chandigarh, India. Case-only analysis of anonymous imaging data (OCT/Fundus) acquired during the routine clinical evaluation of patients was done to examine the OCT findings in the AMD patients. TaqMan genotyping assays were used to analyze the single nucleotide polymorphisms in these patients. ELISA (enzyme linked immunosorbent assay) was used to estimate the protein levels of these genes in serum. Information pertaining to lifestyle/habits was also collected by administering a standard questionnaire at the time of recruitment of the patients.Results: Intra-retinal fluid (IRF) was associated significantly with the LIPC genotype (p=0.04). Similarly, smoking status and early AMD were also associated with the APOE genotype (p=0.03). Additionally, variants of IER-3 and SLC16A8 were also found to be associated with co-morbidities (p=0.02) and males (p=0.02), respectively. RPED has shown a significant association with AREDS criteria, which demonstrated an area under AUROC around 72%.Conclusion: Results of genotype–phenotype association can give a precise impression of AMD severity and can be beneficial for the early diagnosis of AMD cases.Keywords: age-related macular degeneration, RPE detachment, OCT parameters, TIMP-3, HTRA1, IPC, APOE, anti-VEGF therapy, AREDS

Ella H Leung,1 Sahana Sharma,2 Ana Levie-Sprick,1 Gregory D Lee,1 Hyung Cho,1 Krishna Mukkamala1 1Georgia Retina, Atlanta, GA, USA; 2Vanderbilt University, Nashville, TN, USACorrespondence: Ella H LeungGeorgia Retina, 833 Campbell Hill St NW, Suite 300, Marietta, GA, 30060, USATel +1-770-218-1888Email eleung@garetina.comPurpose: To evaluate the risk factors and fundus findings of patients with potential PPS-associated retinopathy.Patients and Methods: A retrospective chart review was performed of patients exposed to PPS who had a dilated fundus examination at a large retina-only practice from 2018– 21. Multimodal images were evaluated by masked reviewers.Results: A total of 148 patients were included, of whom 33 (22%) had PPS-associated retinopathy, and 115 (78%) did not. The mean age was 60.3 years old, and the mean follow-up was 11.8 months. The PPS-associated retinopathy group had higher mean cumulative doses of PPS (1600g± 849 vs 864g± 852, P < 0.0001, Mann–Whitney test) and longer duration of PPS use (13.6 years vs 7.48, P < 0.0001). There was no statistically significant difference based on a history of kidney or liver disease or the dosage per day for the weight, body mass index, body surface area, or lean body weight. Of the patients with PPS-associated retinopathy whose genetic results were available, 15 of 16 (93%) were heterozygous for variants of uncertain significance.Conclusion: A longer duration of PPS use and higher cumulative dosage of PPS were associated with an increased risk of developing PPS-associated pigmentary retinopathy. The role of genetic mutations in patients exposed to PPS is still to be determined.Keywords: pentosan polysulfate sodium, pigmentary retinopathy, pharmacotoxicity, inherited retinal dystrophies, genetics

Gohar Azhar,1 Shakshi Sharma,1 Onna Lau,1 Bader Alkharisi,1 Anil Anandam,1 Sakiru Isa,2 Priya Mendiratta,1 Amanda K Pangle,1 Karen Coker,1 Jeanne Wei1 1Department of Geriatrics, Donald W. Reynolds Institute of Aging, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN, USACorrespondence: Gohar Azhar, Reynolds Institute on Aging, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR, 72205, USA, Tel +1 501 526-5935, Email azhargohar@uams.edu

Rahul Sangani,1 Andrew Ghio,2 Stacey Culp,3 Zalak Patel,4 Sunil Sharma1 1Section of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, West Virginia University, Morgantown, WV, USA; 2Human Studies Facility, US Environmental Protection Agency, Chapel Hill, NC, USA; 3Department of Biostatistics, West Virginia University, Morgantown, WV, USA; 4Department of Radiology, West Virginia University, Morgantown, WV, USACorrespondence: Andrew GhioHuman Studies Facility, US Environmental Protection Agency, Chapel Hill, NC, USATel +1 919 966-0670Fax +1 919 966-6271Email ghio.andy@epa.govBackground: Disease heterogeneity in idiopathic pulmonary fibrosis (IPF) often complicates the systematic study of disease, management of patients and clinical investigations.Objective: To describe combined pulmonary fibrosis emphysema (CPFE) phenotype in a rural Appalachian IPF cohort with the highest smoking rates in the United States.Methods: CPFE patients (n = 60) in a developed IPF cohort (n = 153) were characterized. Groups (CPFE vs IPF without emphysema) were categorized based on the predominant HRCT patterns of UIP (n = 109). Demographics, clinical variables, and treatment details were recorded. Kaplan–Meier survival and multivariate logistic regression analysis were performed.Results: The prevalence of CPFE in our IPF cohort was 45% (n = 49). The CPFE group was younger (73.9 vs 78.2), had a more extensive smoking history (93.9% vs 53.3%) with greater mean smoking pack years (49.09 vs 15.39) and had lower percentage predicted DLCO on presentation (38.35 vs 51.09) compared to IPF without emphysema group. Both groups shared equivalent higher burden of comorbidities, including pulmonary hypertension (PH) (46.9% vs 33.3%). One-fifth of patients were prescribed antifibrotics and only a subset (5%) of patients underwent lung transplantation. There was a non-significant trend towards reduced survival in CPFE (p = 0.076). Smoking status and DLCO predicted CPFE in our cohort. Body mass index (BMI), PH, and pirfenidone use were significant predictors of mortality.Conclusion: CPFE was highly prevalent in our rural IPF cohort. In contrast to previous studies, CPFE group was older and had higher female (approx. 30%) occurrence. A greater exposure to cigarette smoke and reduced DLCO at diagnosis predicted CPFE. Lower BMI and PH predicted higher mortality whereas use of pirfenidone improved survival in our cohort. This study highlights a complex interaction of cigarette smoking, advanced fibrosis of UIP, PH and potential utility of antifibrotic agents in CPFE phenotype. Substantial burden of comorbidities, older age, and the limited utilization of advanced therapeutics in the cohort emphasize the challenges faced by rural Appalachian patients.Keywords: combined pulmonary fibrosis emphysema; CPFE, cigarette smoking, pulmonary hypertension; PH, pirfenidone, body mass index; BMI, rural population

Donald P Tashkin,1 Ayca Ozol-Godfrey,2 Sanjay Sharma,2 Shahin Sanjar2 1Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA Health Sciences, Los Angeles, CA, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Donald P TashkinDivision of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA Health Sciences, Los Angeles, CA, 90095, USATel +1 310-825-3163Email dtashkin@mednet.ucla.eduBackground: Chronic bronchitis (CB) is one of the conditions that contribute to chronic obstructive pulmonary disease (COPD). Despite its widespread prevalence among patients with COPD and overall negative impact on treatment outcomes, the effect of CB on the efficacy of bronchodilator therapy has not been evaluated. The objective of this post hoc analysis is to assess the effect of nebulized glycopyrrolate (GLY) on lung function and health-related quality of life outcomes in patients with St George’s Respiratory Questionnaire (SGRQ)-defined CB at baseline.Methods: Pooled data from the replicate, 12-week GOLDEN 3 and 4 studies (N=861) were grouped by CB status at baseline. The endpoints reported are changes from baseline in trough forced expiratory volume in 1 second (FEV1), SGRQ and EXAcerbations of Chronic Pulmonary Disease Tool-Respiratory Symptoms (EXACT-RS) scores. Safety of GLY was evaluated by monitoring the incidence of adverse events (AEs).Results: Following 12 weeks of treatment, GLY 25 μg twice-daily (BID) resulted in placebo-adjusted improvements from baseline in FEV1 of 77.1 mL and 124.4 mL in the CB and non-CB groups, respectively (p< 0.0001 vs placebo in both groups). Significant improvements in SGRQ total scores were observed with GLY 25 μg BID compared with placebo, regardless of baseline CB status. Although EXACT-RS improvements were noted in both CB and non-CB groups, significant improvements were observed only in the CB group. GLY 25 μg BID was generally well tolerated through 12 weeks of treatment, with a low incidence of AEs.Conclusion: Treatment with nebulized GLY 25 μg BID for 12 weeks resulted in significant improvements in lung function and SGRQ total scores, compared with placebo. Significant improvements in EXACT-RS total scores were observed only in the CB group. Together, these results support the use of GLY 25 μg BID in patients with COPD, regardless of their CB status.Keywords: chronic bronchitis, COPD, LAMA, nebulized glycopyrrolate

Nirupama Putcha,1 Ayca Ozol-Godfrey,2 Shahin Sanjar,2 Sanjay Sharma2 1Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Nirupama PutchaDivision of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, JHAAC 4B.74, Baltimore, MD, 21224, USATel +1 410-550-0545Email nputcha1@jhmi.eduPurpose: Patients with COPD often have multiple coexisting comorbidities, affecting quality of life, morbidity and mortality. However, the prevalence and impact of comorbidities on the efficacy of bronchodilators in COPD is poorly understood.Patients and Methods: In this post hoc analysis, pooled data from the 12-week, placebo-controlled GOLDEN 3 and 4 studies of nebulized glycopyrrolate (GLY) in individuals with moderate-to-very-severe COPD were used to quantify comorbidities and assess their impact on treatment efficacy and safety.Results: Comorbidities that were most prevalent in the GOLDEN 3 and 4 study population were hypertension, high cholesterol and osteoarthritis. Participants were grouped based on their pre-specified comorbidity count into Group A (≤ 2 comorbidities; n=439) and Group B (> 2 comorbidities; n=854). Treatment with GLY resulted in significant improvements in forced expiratory volume in 1 second (FEV1) and St George’s Respiratory Questionnaire (SGRQ) total scores, independent of comorbidity prevalence. A higher prevalence of cardiovascular disease (CVD) comorbidities was observed among individuals in Group B, compared with Group A. In a sub-analysis based on prevalence of CVD, treatment with GLY resulted in significant FEV1 improvements independent of CVD prevalence, although values were numerically higher in the CVD group. GLY also led to higher improvements in SGRQ scores in the CVD group. GLY was well tolerated regardless of comorbidity or CVD prevalence, with a lower incidence of serious adverse events compared with placebo.Conclusion: A simple comorbidity count demonstrated that a majority of patients with COPD in the GOLDEN 3 and 4 studies had multiple comorbidities, with CVD being common in those with high comorbidity count. Results from this post hoc analysis demonstrate that GLY improved FEV1 and SGRQ scores in individuals with COPD, independent of their comorbidities or CVD status.Keywords: comorbidities, COPD, cardiovascular disease, LAMA, nebulized glycopyrrolate

Suchismita Sarkar, Saroj Sharma, Shashi Raheja Department of Anatomy, Dr Baba Saheb Ambedkar Medical College and Hospital, Rohini, Delhi, IndiaCorrespondence: Suchismita Sarkar B-8, Sai Apartments, Sector-13, Rohini, Delhi, 110085, IndiaTel +91-7678642842Email dr.suchi02@gmail.comPurpose: The application of blended learning approach improves student engagement, active learning and achievement of higher order analytical thinking. Despite that there is still no clear proof that use of computer assisted learning is better than traditional teaching in human anatomy. In this study, a model of collaborative learning strategy is applied, using both online and face-to-face instruction delivery, for the Phase I medical students. The study aimed to innovate a model of blended learning in delivery of gross anatomy lectures and determine the effectiveness of this strategy in comparison to traditional classroom teaching by student’s perception analysis.Methods: Students were provided with PowerPoint lectures, clinical video of patient cases, and lecture summary handouts before the interactive face-to-face lecture session. Learner satisfaction survey was done to validate the student’s perception.Results: The students’ participation in the survey was 90.4%, with the mean of students’ responses on the survey scale was 4.10 ± 0.94 (standard deviation). Highest agreement was 83.1% on the effectiveness of online resources. Students gave minimum agreement of 54.9% about the time allotted for the online materials. Thematic analysis of the perception of student feedback provided with many positive outcomes for this approach.Conclusion: We propose that blended learning is a process that helps in enhancing student involvement and participation, motivation for self-directed learning and promotes deeper learning of educational outcomes.Keywords: blended learning, anatomy, student engagement, online, interactive face to face

Nicola A Hanania,1 Abebaw M Yohannes,2 Ayca Ozol-Godfrey,3 Michael Tocco,3 Thomas Goodin,3 Sanjay Sharma,3 Shahin Sanjar3 1Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, 77030, USA; 2Department of Physical Therapy, Azusa Pacific University, Azusa, CA, USA; 3Sunovion Pharmaceuticals Inc., Marlborough, MA, USACorrespondence: Nicola A HananiaSection of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX, USATel +1 713-873-3454Email hanania@bcm.eduBackground: Anxiety and depression (A/D) are common in patients with chronic obstructive pulmonary disease (COPD) and are often associated with lower adherence to treatment and worse patient-related outcomes. However, studies on the impact of comorbid A/D on responses to bronchodilators are limited.Methods: This post hoc analysis of pooled data (N=861) from the GOLDEN 3 and 4 studies compared the efficacy and safety of nebulized glycopyrrolate (GLY) 25 μg in patients with moderate-to-very-severe COPD, grouped by self-reported A/D. Changes in forced expiratory volume in 1 second (FEV1) and health-related quality of life determined by St George’s Respiratory Questionnaire (SGRQ) scores in patients with or without comorbid A/D (A/D [+] or A/D [–]) were examined following 12 weeks of GLY 25 μg twice-daily (BID) or placebo treatment.Results: A/D (+) patients were predominantly female, younger, included a higher proportion of current smokers, and had higher baseline SGRQ scores compared with the A/D (–) group. At 12 weeks, GLY resulted in placebo-adjusted improvements from baseline in FEV1 of 46.9 mL (p=0.19; not significant) and 106.7 mL (p< 0.0001), in the A/D (+) and A/D (–) groups, respectively. Improvements were observed with GLY compared to placebo in SGRQ scores, regardless of baseline A/D status; the placebo-adjusted least squares mean change from baseline in SGRQ total scores was – 3.16 (p> 0.05) and – 3.34 (p< 0.001), for the A/D (+) and A/D (–) groups, respectively. Despite numerical improvements in SGRQ scores with GLY in the A/D (+) group, a higher response to placebo was observed. GLY was generally well tolerated throughout 12 weeks of treatment; incidence of adverse events was higher in the A/D (+) group compared with the A/D (–) group in both treatment arms.Conclusion: GLY 25 μg BID resulted in numerical improvements in FEV1, SGRQ total scores and SGRQ responder rates in patients with moderate-to-very-severe COPD, regardless of A/D status at baseline; significant improvements were noted only in the A/D (+) group. The results emphasize the importance of considering underlying comorbidities including A/D when evaluating the efficacy of COPD treatments.Keywords: anxiety, COPD, depression, LAMA, nebulized glycopyrrolate

Sheikh Nizamuddin,1,2 Shivendra Dubey,1 Sakshi Singh,1 Saurav Sharma1 ,† Pratheusa Machha,1,3 Kumarasamy Thangaraj1,3,4 1CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India; 2German Cancer Consortium (DKTK) c/o Zentrale Klinische Forschung (ZKF), University Medical Center, Freiburg, Germany; 3AcSIR (Academy of Scientific and Innovative Research), CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India; 4DBT-Centre for DNA Fingerprinting and Diagnostics, Hyderabad 500039, India†Mr Sharma passed away on June 11, 2019.Correspondence: Kumarasamy ThangarajCSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana 500007, IndiaFax +91-40-27160311Email thangs@ccmb.res.inIntroduction: Allelic frequency distribution of drug metabolizing enzyme genes among populations is important to identify risk groups for adverse drug reaction and to select representative populations for clinical trials. Although India emerged as an important hub for clinical trials, information about the pharmacogenetic diversity for this region is still lacking. Here, we investigated genetic diversity of cytochrome-P450-2C9 (CYP2C9) gene which metabolizes wide range of drugs and is highly expressed in the human liver.Methods: In total, 1278 individuals from 36 diverse Indian populations, 210 individuals from in-house data-repository and 489 other South Asian samples from the 1000 Genomes Project were selected. Variants observed in CYP2C9 gene were subjected to various statistical analyses.Results: High frequency of CYP2C9*3 (∼ 13%) and CYP2C9*3/*3 (∼ 1%) was observed among South Asians, compared to 21 populations living outside the Indian subcontinent. The allelic/genotypic frequency does not correlate with geographical location or linguistic affiliation, except populations speaking Tibeto-Burmans language, who have lower frequency of CYP2C9*3 and CYP2C9*3/*3. Since, South Asians practice strict endogamy, presence of unique mutation and high frequency of homozygous genotypes not surprising. CYP2C9*3 has been associated with therapeutic response.The effect of CYP2C9*3/*3 is more pronounced compared to heterozygous and wild type homozygous genotypes as evident in many in vitro studies. As South Asians have high frequency, it would be interesting to explore potential of CYP2C9*3 as a marker for personalized therapy. Our study revealed several rare functional variants, which form eight novel and rare haplotypes of CYP2C9 (CYP2C9*63–*70). Of which, CYP2C9*64, *65, *66, *68, *69 and *70 haplotypes are South Asian-specific.Conclusion: Overall, we find high genetic heterogeneity within South Asians and identified South Asian-specific putative functional CYP2C9 haplotypes. High frequency of CYP2C9*3 and CYP2C9*3/*3 was observed in South Asian populations. Taken together, current study greatly enriches the knowledge of naturally occurring CYP2C9 variants and its diversity in South Asia, which are relevant to further CYP2C9-related functional research and for personalized medicine.Keywords: pharmacogenetics, CYP2C9, South Asians, genetic diversity

Chung-Shien Lee,1,2 Sandhya Sharma,3 Emily Miao,4 Cheryl Mensah,5 Kevin Sullivan,2 Nagashree Seetharamu2 1Department of Clinical Health Professions, St. John’s University, College of Pharmacy and Health Sciences, Queens, NY 11439, USA; 2Division of Medical Oncology and Hematology, Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY 11042, USA; 3Department of Hematology and Oncology, Denver Health, Denver, CO 80204, USA; 4Albert Einstein College of Medicine, Bronx, NY, USA; 5Weil Cornell School of Medicine, Department of Hematology and Oncology, Weill Cornell of Medicine, New York, NY, USACorrespondence: Nagashree SeetharamuDivision of Medical Oncology and Hematology, Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 450 Lakeville Road, Lake Success, NY 11042, USATel +1 516-734-8855Email nseetharamu@northwell.eduAbstract: Mutations in the epidermal growth factor receptor (EGFR) are common amongst those with non-small cell lung cancer and represent a major factor in treatment decisions, most notably in the advanced stages. Small molecule tyrosine kinase inhibitors (TKIs) that target the EGFR, such as erlotinib, gefitinib, icotinib, afatinib, dacomitinib and osimertinib, have all shown to be effective in this setting. Osimertinib, a third-generation EGFR TKI, is a favorable option, but almost all patients develop resistance at some time point. There are no effective treatment options for patients who progress on osimertinib, but ongoing trials will hopefully address this unmet need. The aim of this review is to provide a comprehensive review of the data with EGFR TKIs, management of the toxicities and the ongoing trials with this class of agents.Keywords: non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

Bhupesh Singh,1 Sourabh Sharma,2 Neha Bharti,3 Richa Ranjan,3 Sudhank Bharti1 1Cornea Department, Bharti Eye Foundation and Hospital, New Delhi, India; 2Glaucoma Department, Bharti Eye Foundation and Hospital, New Delhi, India; 3Vitreoretina Department, Bharti Eye Foundation and Hospital, New Delhi, IndiaCorrespondence: Sourabh SharmaBharti Eye Foundation and Hospital, New Delhi, IndiaTel +91-9910790540Email dr_sourabh@rediffmail.comAbstract: We report a rare case of bilateral keratoglobus with hypermature intumescent cataract in a 55-year-old woman. Clinical examination and corneal topography confirmed generalized corneal bulging and global corneal thinning. A Pentacam® (Oculus Optikgerate, Wetzlar, Germany) demonstrated bilateral diffuse corneal thinning (368 μm in the right eye and 371 μm in the left eye). Phacoemulsification was performed in the right eye after thorough workup and modification of the surgical technique. This case report helps in better understanding of the challenges of cataract surgery and intraocular lens selection in a keratoglobus patient, and stresses the need for both thorough preoperative planning and intraoperative surgical modifications.Keywords: keratoglobus, intumescent cataract, corneal ectasia

Raba Thapa,1 Sanyam Bajimaya,1 Eli Pradhan,1 Sanjita Sharma,1 BalBahadur Kshetri,2 Govinda Paudyal1 1Vitreo-Retina Specialist, Vitreo-Retina Service, Tilganga Institute of Ophthalmology, Bagmati Bridge, Kathmandu, Nepal; 2Tilganga Institute of Ophthalmology, Bagmati Bridge, Kathmandu, NepalCorrespondence: Raba ThapaVitreo-Retina Specialist, Tilganga Institute of Ophthalmology, Bagmati Bridge, Kathmandu, NepalTel +977-1-4493775Fax + 977-1-4474937Email rabathapa@live.comIntroduction: Diabetic retinopathy (DR) is the emerging cause of blindness in developing countries. This study aimed to assess the accuracy of grading retinal findings of patients with diabetes using fundus photographs by allied medical personnel (AMP) when compared to an ophthalmologist.Materials and Methods: Six AMPs were enrolled for grading fundus photographs of patients with diabetes after three and six months of training twice at two weeks interval. The total number of fundus photographs graded were 1,344. Grading by a retina specialist was used as the gold standard. Intra-rater and inter-rater agreement was assessed using the kappa coefficient (k).Results: The intra-rater agreement of half of the AMPs in both three months and six months was almost perfect for grading of any retinal abnormalities, and substantial for retinal hemorrhages. In three months, the overall inter-rater agreement at the second rating was moderate for any retinal abnormalities (k=0.60) and retinal hemorrhage (k=0.48) and was fair for macular exudates (k=0.35). The overall inter-rater agreement of AMPs in six months at the second rating was substantial for any retinal abnormalities (k=0.61), fair for retinal hemorrhage (k=0.30), and moderate for macular exudates (k=0.49). The overall inter-rater agreement at first rating was almost similar to the second rating in both three months and six months.Conclusion: Intra-rater agreement of AMPs was almost perfect for any retinal abnormalities and substantial for retinal hemorrhage. The inter-rater agreement of AMP was substantial for any retinal abnormalities and moderate for retinal hemorrhages and macular exudates. The agreement results were almost similar at three months and six months. AMPs could be utilized in screening of DR and other retinal pathologies for timely referral to reduce the blindness in low-resource settings.Keywords: inter-rater agreement, retinal pathologies, allied medical personnel; AMP, ophthalmologist, diabetic retinopathy; DR

Background: Spontaneous intracranial haemorrhage (ICH) is the most severe type of stroke with high mortality rates. This entity accounts for 17 to 33% of all strokes and is associated with a higher mortality rate. Approximately, 35–50% of patients with ICH die within the 30 days after event. Long-term survivors are often remaining with permanent deficits, with up to 75% suffering permanent disability and only 12% to 39% of the survivors have favourable outcomes. Several studies aiming to explore the efficacy of surgery for patients with ICH have been carried out. However, the results were inconclusive. To provide evidence for clinical practice, here we present a retrospective study to explore the effect of surgery for patients with spontaneous basal ganglia haemorrhage. Methods: The present study was conducted in the Neurosurgery Department of a tertiary care hospital in the Northern part of India from January 2018 to March 2020. Sixty-one patients aged between 20-70 years of basal ganglia haemorrhage who presented within 24 hours of ictus and operated were included in this study. Results: A total of 61 patients underwent surgical intervention consisting of 49 (80%) males and 12 (20%) females. Their age varied from 27 to 70 with mean age ± SD 51.93 ± 13.19 years. Thirty-six patients were ≥ 50 years of age, out of which 72% patients had unfavourable outcomes (GOS 1-3) and 28% had favourable outcome (GOS 4-5). There were 31 patients with GCS 5-8. Most patients (81%) had GOS 1-3(at the time of discharge). Out of 25 patients with GCS 9-12; 64% had GOS 4-5. The patients with volume of haematoma 40-60 ml, 82% patients had GOS 4-5. The patients with midline shift > 5 mm; 78% patients had GOS 1-3. Patients with midline shift < 5 mm; 82% had GOS 4-5 (P=0.005). The mean hospital stays of unfavourable outcomes group was 28.71 ± 10.25 days and of favourable outcomes group was 22.07 ± 6.32 days (0.000). Conclusions: Early surgery (within 6 hours) along with multi-modality medical management has definite positive role in the outcome of patients with spontaneous basal ganglionic haemorrhage. Patients ≥ 50 years, signs of brain herniation, volume of haematoma ≥ 60ml, hydrocephalic dilatation due the intraventricular haemorrhage, midline shift > 5 mm, and GCS ≤ 8 at presentation had poor prognosis.

Santosh Kumar Yadav, 1, 2 Rajshree Bhujel, 2 Pradip Hamal, 3 Shyam Kumar Mishra, 2 Sangita Sharma, 2 Jeevan Bahadur Sherchand 2 1Department of Microbiology, Rajarshi Janak University, Janakpurdham, Nepal; 2Department of Clinical Microbiology, Institute of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal; 3Department of Pathology, B.P. Koirala Memorial Cancer Hospital, Bharatpur, NepalCorrespondence: Santosh Kumar YadavDepartment of Microbiology, Rajarshi Janak University, Janakpurdham, NepalEmail santooshydv@gmail.comIntroduction: Acinetobacter baumannii has emerged as a significant multidrug-resistant (MDR) nosocomial pathogen worldwide and is responsible for various healthcare-associated infections. The MDR strains have been reported increasingly during the last decades in hospitalized patients. They have developed resistance to most of the available antibiotics and are known to produce various acquired β-lactamases. The β-lactamase producing strains have a potential for rapid dissemination in hospital settings, as it is often plasmid-mediated. The Infectious Diseases Society of America (ISDA) stated A. baumannii as one of the “red alert” pathogens that greatly threatens the utility of our current antibacterial armamentarium. The study attempted to investigate the spectrum and antimicrobial resistance among MDR A. baumannii and their potential implications in hospitalized patients in a tertiary care hospital of Nepal.Methods: This study was conducted at Tribhuvan University Teaching Hospital (TUTH), Nepal from January 2017 to December 2017. A total of 177 A. baumannii isolated from hospitalized patients were included in the study. The AST was performed by disc diffusion method. The MDR strains were identified by the criteria of Magiorakos et al, ESBL production by CLSI guidelines, and AmpC β-lactamase production by the AmpC disc test. MBL and KPC production were detected as per the method of Tsakris et al.Results: Out of 177 A. baumannii, 91.0% were MDR isolates. Among the MDR isolates, the majority were isolated from respiratory tract specimens and were isolated from ICU patients. Most of the MDR isolates were resistant to all first-line antibiotics and all were completely sensitive to only polymyxin B and colistin sulfate. MBL (67.7%) was the common β-lactamase production among MDR isolates.Conclusion: Acinetobacter baumannii can cause a vast variety of infections in hospitalized patients. The highly resistant MDR strains are common in tertiary care hospitals. This bacteria lead to high morbidity and mortality as we are left with the only option of treating them by potentially toxic antibiotics like colistin sulfate and polymyxin B. Detection of drug resistance and rational use of antibiotics play a crucial role in the fight against this MDR pathogen.Keywords: Acinetobacter baumannii, hospitalized patients, multidrug resistant, metallo-β-lactamase

Jyotindra Narayan Goswami,1 Suvasini Sharma2 1Department of Pediatrics, Army Hospital (Research & Referral), New Delhi 110010, India; 2Neurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, New Delhi 110001, IndiaCorrespondence: Suvasini SharmaNeurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children’s Hospital, Connaught Place 110001, New Delhi Tel +91-9910234344Email sharma.suvasini@gmail.comAbstract: Drug-refractory epilepsy is a commonly prevalent pediatric neurological illness of global significance. Ketogenic diet (KD) is a time-tested therapeutic modality for refractory epilepsy, which has reemerged as a robust alternative to anti-epileptic pharmacotherapy. There is a growing body of evidence which supports the anti-seizure efficacy, safety profile and feasibility of KD use in childhood epilepsy. In addition, this modality has been recognized to reduce anti-epileptic exposure, improve cognition and behavioral profile of patients as well as improve the quality-of-life of care-givers. Current indications of KD include refractory epilepsy syndromes, selected metabolic disorders (such as pyruvate dehydrogenase deficiency) and a host of varied neurological entities. KD research has broadened the knowledge-base about its mechanisms of action. Four types of KD are in vogue currently with varying nutritional constitution, palatability, administration protocols and comparable efficacy. KD initiation and maintenance are the result of concerted effort of a team of pediatric neurologist/epileptologist, nutritionist and patient’s primary care-giver. Consensus is being formulated about various practical aspects of KD such as patient-selection, parental counseling, baseline work-up, dietary prescription, nutritional supplementation, concurrent anti-epileptic drug administration, follow-up and treatment-duration. Novel applications of KD include its use in neonatal epilepsy and super-refractory status epilepticus and tailor-made formulations such as cooking oil-based KD in predominantly rice-fed populations. Increasing body of clinical experience, improved nutritional designs and translational research are promoting KD as a major therapeutic modality. Currently, KD forms a core essence in the armamentarium against refractory epilepsy. In this review, we summarize the recent advances and current perspectives in the use of KD in refractory epilepsy.Keywords: Modified Atkins Diet, low glycemic index diet, ketosis, intractable epilepsy, epileptic encephalopathies, ketogenic diet, epilepsy

An experiment on eleven rice genotypes was designed at field of Institute of Agriculture and Animal Science, Lamjung, under randomized complete block design with three replications from June-October, 2018 to study genetic variability and character association. Analysis of variance showed significant difference among the genotypes for all the characters studied except for grain yield and fertility percent which indicates the existence of sufficient genetic variability and potential for selection and further improvement. Grain yield was significantly positively correlated with panicle length while positively and non-significantly correlated with days of flowering, leaf area and straw yield except for plant height, SPAD60, fertility percent, thousand grain weight and effective tillers. Leaf area had maximum positive direct effect on grain yield followed by panicle length, thousand grain weight and effective tillers which indicates help for selection and improvement of rice genotypes. The higher value of correlation between panicle length and grain yield is due to the direct effect of panicle length which exhibit true relationship between them. The variability study showed that there was high genotypic coefficient of variation (GCV) and phenotypic coefficient of variation (PCV) for thousand grain weight. High heritability estimates coupled with high genetic advance as per percentage of mean (GAM) was found for thousand grain weight, days of flowering, leaf area and effective tillers which indicate the control of additive gene of action and a greater scope of selection for crop improvement.

S Sharma,1 N Oli,2 B Thapa31Department of Nursing, Kathmandu Medical College Teaching Hospital, Kathmandu, Nepal; 2Department of Community Medicine, Kathmandu Medical College Teaching Hospital, Kathmandu, Nepal; 3Department of Nursing, Nepalgunj Nursing Campus, Nepalgunj, NepalBackground: The Internet has become a major source of health-related information. In order to provide better health services and health-care education to society, nurses should have acceptable electronic health (eHealth) literacy.Objective: The main aim was to measure eHealth-literacy skills among nursing students of Kathmandu Medical College Teaching Hospital, Nepal.Methods: A cross-sectional study was conducted among 152 Bachelor of Science nursing students at the hospital. Data were collected using the self-administered eHealth Literacy Scale. This is an eight-item tool that is assessed on 5-point likert scale to measure consumers’ perceived skills at finding, evaluating, and applying eHealth information to health problems. Demographical and personal variables were collected to explore their relationship with eHealth literacy.Results: A total of 152 nursing students with mean age of 19.84±1.62 years participated in the study. While 44.7% perceived that they had average Internet skills, 65.1% found the Internet useful in helping them make decisions about their health. Nursing students had a moderate self-perceived level of eHealth literacy (median 3.69, IQR 0.87). Related factors included students’ Internet skills, frequency of using the Internet for health related purposes, and self-perception of the usefulness and importance of the Internet.Conclusion: This study represents a baseline reference for eHealth literacy among nursing students. Students have some basic necessary skills, while other skills still need to be improved. There is a need to pay attention to eHealth-literacy needs of nursing students.Keywords: digitization, health literacy, Internet, nursing students, technology

Jill A Ohar,1 Alyssa Bowling,2 Thomas Goodin,2 Barry Price,2 Ayca Ozol-Godfrey,2 Sanjay Sharma,2 Shahin Sanjar2 1Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Sunovion Pharmaceuticals Inc, Marlborough, MA, USA Purpose: Bronchodilator reversibility has been reported in patients with COPD, although correlations between reversibility and treatment response are unclear. The effect of reversibility on lung function, health status, and dyspnea was assessed in patients with moderate-to-severe COPD receiving glycopyrrolate (GLY) 15.6 µg twice daily vs placebo in the Glycopyrrolate Effect on syMptoms and lung function 1 and 2 (GEM1 and GEM2) replicate, 12-week, placebo-controlled studies. Patients and methods: Reversibility was defined as a post-bronchodilator increase of ≥12% and ≥0.200 L in FEV1. FEV1 area under the curve from 0 to 12 hours (AUC0–12 h), trough FEV1, St George’s Respiratory Questionnaire (SGRQ) total score, COPD Assessment Test (CAT™) score, Transition Dyspnea Index (TDI) focal score, daily symptom scores, and rescue medication use were assessed by reversibility status. Incidences of adverse events and serious adverse events were also assessed. Results: Data from 846 patients enrolled in GEM1 and GEM2 with known reversibility status were pooled for post hoc analysis. GLY significantly improved FEV1 AUC0–12 h, trough FEV1, SGRQ and CAT total scores, and rescue medication use compared with placebo in reversible and nonreversible patients. Significant improvements in TDI focal score and daily symptom scores with GLY over placebo were observed only among reversible patients. Improvements in FEV1 AUC0-12 h (0.165 vs 0.078 L; P

Saurab Sharma,1,2 Anupa Pathak,1,3 Jyoti Jha,1,4 Mark P Jensen5 1Department of Physiotherapy, Kathmandu University School of Medical Sciences, Dhulikhel, Nepal; 2Center for Musculoskeletal Outcomes Research, Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; 3School of Physiotherapy, University of Otago, Dunedin, New Zealand; 4Department of Physiotherapy, Grande International Hospital, Kathmandu, Nepal; 5Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA Background: Both socioeconomic and psychological factors have been shown to predict patient function in samples of individuals with chronic pain in Western countries. However, little is known about their role as predictors of function in individuals with chronic pain from developing countries. Purpose: The purpose of this study was to examine the associations between measures of socioeconomic factors (income, education) and psychological factors (catastrophizing and resilience) and measures of function in a sample of individuals with chronic pain from rural Nepal. In addition, we sought to evaluate the moderating effects of socioeconomic factors on the associations between the psychological variables and function. Methods: We interviewed 143 adults with chronic musculoskeletal pain from rural areas of Nepal to assess income, education level, pain intensity, catastrophizing, resilience, physical function, and depression. We performed two regression analyses to evaluate the direct and unique effects of the socioeconomic and psychological variables and pain intensity as predictors of patient function, as well as the moderating influence of income, education level, and pain intensity on the associations between the psychological variables and function. Results: Education and income both predicted physical function, but only income predicted depression. In addition, pain catastrophizing, but not resilience, evidenced a direct and significant independent association with depression. Neither catastrophizing nor resilience made independent and significant direct contributions to the prediction of physical function. The association between resilience and physical function was moderated by pain intensity and income, and income (but not education or pain intensity) moderated the associations between both 1) resilience and depression and 2) catastrophizing and depression. Conclusion: The results suggest the possibility that cultural differences may influence the role that psychosocial factors play in chronic pain adjustment. These findings have important implications regarding how psychosocial pain interventions should be adapted by individuals in developing countries. Keywords: chronic pain, musculoskeletal pain, culture, depression, resilience, pain catastrophizing

Sumitra Sharma,1 Bhuvan KC,2 Asmita Khatri3 1Department of Nursing, Kathmandu Medical College Teaching Hospital, Kathmandu, Nepal; 2School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia; 3Bachelor of Science in Nursing, Department of Nursing, Kathmandu Medical College Teaching Hospital, Kathmandu, Nepal Introduction: Male involvement in reproductive health is an essential component in promoting maternal and family health. In Nepal, men are not actively engaged in most maternal and child health (MCH) services nor in other reproductive health programs. There is a need to know about the understanding of key professionals in such practices. This study explores gendered perspectives among teachers and health professionals to understand the factors contributing to male involvement in reproductive health.Methods: The data were collected through two focus group discussions (FGDs) and seven key informant interviews (KIIs). FGDs were held among male teachers of selected schools, and KIIs were conducted with health professionals of the health post of Bungamati, Lalitpur. An unstructured interview guide was used to explore their experiences and perceptions. All KIIs and FGDs were recorded, translated and transcribed verbatim.Results: Findings show limited male involvement in reproductive health. Participants reported several hindering and challenging factors such as sociocultural and psychological norms, lack of education, and misinformation and dominance of female as health care providers in many MCH clinics. Perceived motivating factors included positive attitude in men, literacy and awareness, inclusion of reproductive health in school curriculum and certain incentives. Participants also recommended a range of strategies for increasing men’s involvement in reproductive health in Nepal.Conclusion: Men’s education and attitude, knowledge and awareness, sociocultural factors, psychological factors, health system factors, and policies play important roles in male involvement in reproductive health. Programs on effective implementation of men involvement in reproductive health initiatives should address the barriers and challenges to men’s supportive activities. This study also suggests increasing literacy of reproductive health among men that enhances their positivity and motivates them to participate in reproductive health services. Keywords: male participation, maternal and child health, reproductive health

Shubham Sharma Faculty of Medicine, Imperial College, London, UKCorrespondence: Shubham SharmaFaculty of Medicine, Imperial College, London Tel +44 780 243 8995Email shubham.sharma16@imperial.ac.uk View the original paper by Dr Dhingra and colleagues

Saurab Sharma,1,2 Pascal Thibault,3 J Haxby Abbott,2 Mark P Jensen41Department of Physiotherapy, Kathmandu University School of Medical Sciences, Dhulikhel, Nepal; 2Centre for Musculoskeletal Outcomes Research, Dunedin School of Medicine, University of Otago, Dunedin, Otago, New Zealand; 3Department of Psychology, McGill University, Montreal, Québec, Canada; 4Department of Rehabilitation Medicine, University of Washington, Seattle, USABackground: Pain catastrophizing is an exaggerated negative cognitive response related to pain. It is commonly assessed using the Pain Catastrophizing Scale (PCS). Translation and validation of the scale in a new language would facilitate cross-cultural comparisons of the role that pain catastrophizing plays in patient function. Purpose: The aim of this study was to translate and culturally adapt the PCS into Nepali (Nepali version of PCS [PCS-NP]) and evaluate its clinimetric properties. Methods: We translated, cross-culturally adapted, and performed an exploratory factor analysis (EFA) of the PCS-NP in a sample of adults with chronic pain (N=143). We then confirmed the resulting factor model in a separate sample (N=272) and compared this model with 1-, 2-, and 3-factor models previously identified using confirmatory factor analyses (CFAs). We also computed internal consistencies, test–retest reliabilities, standard error of measurement (SEM), minimal detectable change (MDC), and limits of agreement with 95% confidence interval (LOA95%) of the PCS-NP scales. Concurrent validity with measures of depression, anxiety, and pain intensity was assessed by computing Pearson’s correlation coefficients. Results: The PCS-NP was comprehensible and culturally acceptable. We extracted a two-factor solution using EFA and confirmed this model using CFAs in the second sample. Adequate fit was also found for a one-factor model and different two- and three-factor models based on prior studies. The PCS-NP scores evidenced excellent reliability and temporal stability, and demonstrated validity via moderate-to-strong associations with measures of depression, anxiety, and pain intensity. The SEM and MDC for the PCS-NP total score were 2.52 and 7.86, respectively (range of PCS scores 0–52). LOA95% was between -15.17 and +16.02 for the total PCS-NP scores. Conclusion: The PCS-NP is a valid and reliable instrument to assess pain catastrophizing in Nepalese individuals with chronic pain. Keywords: measurement error, outcome measure, Bland–Altman plot, reliability, measurement properties, pain assessment