Prevalence of serious injuries in low risk trauma patients.

OBJECTIVES: Computed tomography (CT) utilization is widespread in contemporary Emergency Departments (EDs). CT overuse leads to radiation exposure, contrast toxicity, overdiagnosis, and incidental findings. This study explores the prevalence of clinically significant injuries in patients identified as low-risk trauma patients (LRTPs) using newly created criteria that account for the patient's age, trauma mechanism, assessability (which relies on level of consciousness, intoxication, and neurologic deficits), vital signs and other evidence of hypoperfusion, bleeding risk, and past medical history. METHODS: This was a 6-month retrospective chart review of all LRTPs presenting to a level 1 trauma center in Queens, New York. Data abstraction was performed independently by two abstractors and discrepancies adjudicated by the senior author. Patients were identified using the hospital trauma registry and two reports, created by the researchers, identifying selected chief complaints and discharge diagnoses. RESULTS: 750 patients were identified of which 352 (46.93%) received one or more CT scans. There were a total of 790 CT scans ordered, of which 731 (92.53%) were negative for acute injury. There were 13 clinically significant injuries of which only one (0.13%) required immediate intervention. There were no mortalities in this LRTP group. CONCLUSION: The prevalence of clinically significant injuries in this population is very low and injuries requiring immediate intervention are even lower. CT utilization in LRTPs should be guided by an explicit consideration of benefit and harm for each patient.

Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India.

Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.

Visceral leishmaniasis diagnosis and reporting delays as an obstacle to timely response actions in Nepal and India.

BACKGROUND: To eliminate visceral leishmaniasis (VL) in India and Nepal, challenges of VL diagnosis, treatment and reporting need to be identified. Recent data indicate that VL is underreported and patients face delays when seeking treatment. Moreover, VL surveillance data might not reach health authorities on time. This study quantifies delays for VL diagnosis and treatment, and analyses the duration of VL reporting from district to central health authorities in India and Nepal. METHODS: A cross-sectional study conducted in 12 districts of Terai region, Nepal, and 9 districts of Bihar State, India, in 2012. Patients were interviewed in hospitals or at home using a structured questionnaire, health managers were interviewed at their work place using a semi-structured questionnaire and in-depth interviews were conducted with central level health managers. Reporting formats were evaluated. Data was analyzed using two-tailed Mann-Whitney U or Fisher's exact test. RESULTS: 92 VL patients having experienced 103 VL episodes and 49 district health managers were interviewed. Patients waited in Nepal 30 days (CI 18-42) before seeking health care, 3.75 times longer than in Bihar (8d; CI 4-12). Conversely, the lag time from seeking health care to receiving a VL diagnosis was 3.6x longer in Bihar (90d; CI 68-113) compared to Nepal (25d; CI 13-38). The time span between diagnosis and treatment was short in both countries. VL reporting time was in Nepal 19 days for sentinel sites and 76 days for "District Public Health Offices (DPHOs)". In Bihar it was 28 days for "District Malaria Offices". In Nepal, 73% of health managers entered data into computers compared to 16% in Bihar. In both countries reporting was mainly paper based and standardized formats were rarely used. CONCLUSIONS: To decrease the delay between onset of symptoms and getting a proper diagnosis and treatment the approaches in the two countries vary: In Nepal health education for seeking early treatment are needed while in Bihar the use of private and non-formal practitioners has to be discouraged. Reinforcement of VL sentinel reporting in Bihar, reorganization of DPHOs in Nepal, introduction of standardized reporting formats and electronic reporting should be conducted in both countries.

Multidrug resistant Vibrio cholerae O1 from clinical and environmental samples in Kathmandu city.

BACKGROUND: Cholera, an infectious disease caused by Vibrio cholerae, is a major public health problem and is a particularly burden in developing countries including Nepal. Although the recent worldwide outbreaks of cholera have been due to V. cholerae El Tor, the classical biotypes are still predominant in Nepal. Serogroup O1 of the V. cholerae classical biotype was the primary cause of a cholera outbreak in Kathmandu in 2012. Thus, this study was designed to know serotypes and biotypes of V. cholerae strains causing recent outbreak with reference to drug resistant patterns. Moreover, we also report the toxigenic strains of V. cholerae from both environmental and clinical specimens by detecting the ctx gene. METHODS: Twenty four V. cholerae (n = 22 from stool samples and n = 2 from water samples) isolated in this study were subjected to Serotyping and biotyping following the standard protocols as described previously. All of the isolates were tested for antimicrobial susceptibility patterns using the modified Kirby-Bauer disk diffusion method as recommended by CLSI guidelines. The screening of the ctx genes (ctxA2-B gene) were performed by PCR method using a pair of primers; C2F (5'-AGGTGTAAAATTCCTTGACGA-3') and C2R (5'-TCCTCAGGGTATCCTTCATC-3') to identify the toxigenic strains of V. cholerae. RESULTS: Among twenty four V. cholerae isolates, 91.7% were clinical and 8.3% were from water samples. Higher rate of V. cholerae infection was found among adults of aged group 20-30 years. All isolates were serogroups O1 of the V. cholerae classical biotype and sub serotype, Ogawa. All isolates were resistant to ampicillin, nalidixic acid and cotrimoxazole. 90.9% were resistant to erythromycin however, tetracycline was found to be the most effective drug for the isolates. All isolates were multidrug resistant (MDR) and possessed a ctx gene of approximately 400 base pairs indicating the toxigenic strains. CONCLUSION: Hundred percent strains of V. cholerae were MDR possessing a ctx gene. It suggests that toxigenic strains be identified and proper antibiotic susceptibility testing be conducted. This will allow effective empirical therapy to be used to treat and control cholera.

Draft Genome Sequence of the Methyl Parathion (Pesticide) Degrading Bacterium Pseudomonas spp. MR3.

Pseudomonas spp. MR3 was isolated from the surrounding soil of pesticide manufacturing industries of Ankleshwar, Gujarat. Under laboratory conditions these microbes were able to degrade up to 500 ppm of methyl parathion within 72 h. Genome sequencing of Pseudomonas spp. MR3 was carried out inIon Torrent (PGM), next generation sequencer. The data obtained revealed 1,268 contigs with genome size of 2.99 Mb and G + C content of 60.9 %. The draft genome sequence of strain MR3 will be helpful in studying the genetic pathways involved in the degradation of several pesticides.

Optic Nerve Schwannoma: A Report of a Rare Case From India and Literature Review.

Optic nerve schwannoma is a very rarely occurring tumor described in the literature. It is due to the fact that the optic nerve is myelinated by oligodendrocytes. Schwannomas are tumors of the peripheral nervous system, hence optic nerve schwannoma is a rare phenomenon. A 34-year-old patient presented in the outpatient department with complaints of gradual painless protrusion of the left eye (LE) for the past one year. There was no history of diminution of vision. On examination, vision in both eyes was 6/6, anterior segment examination in both eyes was normal, and pupils were central, circular, and reacting to light. Intraocular pressure was measured on a noncontact tonometer and was within normal range. Both eyes' optic disc, fundus, and visual fields were normal. On inspection, axial proptosis was noted in the LE. Proptosis measurement (on Hertel exophthalmometer) in the right eye was 17 mm and in the left eye was 21 mm. MRI of the orbit without contrast was done and showed a well-defined, soft tissue lesion of the optic nerve in the intraconal compartment of the left orbit. Surgical excision of the tumor was done by lateral orbitotomy approach and the tumor was removed in total. Histopathological examination of the mass revealed a benign spindle cell neoplasm suggestive of schwannoma. Postoperatively, proptosis was resolved, 17 mm both in the right and left eye (on Hertel exophthalmometer), and vision in LE remained unchanged (6/6). Postoperatively, intraocular pressure (on noncontact tonometer) was within normal range, and the optic disc, fundus, and visual fields were normal.

Conjunctival Intraepithelial Neoplasia Mimicking a Pigmentary Lesion in an HIV-Seropositive Indian Male.

We present the case of a 27-year-old male who presented to our ophthalmology outpatient clinic with a pigmented lesion on the conjunctiva of his right eye. There was no history of ocular trauma or familial ocular complaints, and a thorough evaluation revealed the patient's seropositive status for HIV for the past eight years. The presentation resembled a conjunctival pigmentary lesion, with typical features of ocular surface squamous neoplasia (OSSN) being absent and a demographic incongruent with typical OSSN cases as OSSN typically affects the elderly population. Given the patient's HIV status and the lesion's recent increase in size, a more aggressive treatment approach was warranted. Mass excisional biopsy surgery confirmed conjunctival intraepithelial neoplasia with one positive margin. Adjuvant treatment with mitomycin eye drops (0.04%) resulted in no lesion recurrence at the one-month follow-up. Conjunctival intraepithelial neoplasia can mimic pigmentary lesions in young HIV-positive patients with obvious signs of OSSN being absent. In such cases, the history of seropositivity should be sufficient to suspect it as OSSN and aggressive management measures should be adopted to get best possible outcomes.

Nefarious NTRK oncogenic fusions in pediatric sarcomas: Too many to Trk.

Neurotrophic Tyrosine Receptor Kinase (NTRK) genes undergo chromosomal translocations to create novel open reading frames coding for oncogenic fusion proteins; the N-terminal portion, donated by various partner genes, becomes fused to the tyrosine kinase domain of either NTRK1, NTRK2, or NTRK3. NTRK fusion proteins have been identified as driver oncogenes in a wide variety of tumors over the past three decades, including Pediatric Gliomas, Papillary Thyroid Carcinoma, Spitzoid Neoplasms, Glioblastoma, and additional tumors. Importantly, NTRK fusions function as drivers of pediatric sarcomas, accounting for approximately 15% of childhood cancers including Infantile Fibrosarcoma (IFS), a subset of pediatric soft tissue sarcoma (STS). While tyrosine kinase inhibitors (TKIs), such as larotrectinib and entrectinib, have demonstrated profound results against NTRK fusion-positive cancers, acquired resistance to these TKIs has resulted in the formation of gatekeeper, solvent-front, and compound mutations. We present a comprehensive compilation of oncogenic fusions involving NTRKs focusing specifically on pediatric STS, examining their biological signaling pathways and mechanisms of activation. The importance of an obligatory dimerization or multimerization domain, invariably donated by the N-terminal fusion partner, is discussed using characteristic fusions that occur in pediatric sarcomas. In addition, examples are presented of oncogenic fusion proteins in which the N-terminal partners may contribute additional biological activities beyond an oligomerization domain. Lastly, therapeutic approaches to the treatment of pediatric sarcoma will be presented, using first generation and second-generation agents such as selitrectinib and repotrectinib.

Oral Hygiene Practices and Factors Affecting Oral Health Service Utilization among Children (11-14 Years) of Government School of Nikol Ward of East Zone of Ahmedabad, Gujarat, India.

CONTEXT: Oral hygiene practices and factors affecting oral health service utilization among the children of 10-16 years of age play a vital role in achieving comprehensive dental care. AIMS: This study was done to assess oral hygiene practices, creating oral hygiene awareness, and to analyze the overt hurdles in getting basic and timely dental care among children. MATERIALS AND METHODS: It was a cross-sectional survey conducted among 200 schoolchildren aged 11-14 years using a pretested, semistructured questionnaire, and clinical examination was done to assess dental caries. Convenience sampling method was used, and the sample size for the study was equal to the total number of participants. The logistic regression analysis along with odds ratios with 95% confidence interval and P < 0.05 was also reported. Chi-square test was used for statistical analysis of dental caries prevalence. RESULTS: Around 70% of the study participants had the habit of brushing their teeth once daily, whereas only 30% of them used to brush their teeth twice daily. The prevalence of dental caries shows an upward trend with increasing age from 11 to 14 years. Cost of dental treatment, transportation, and dental taboos followed by fear of dental treatment are the major constraints for the students in accessing dental treatment. CONCLUSION: School-based tooth brushing and oral health education programs should be regularly organized to promote healthy tooth brushing practices. The cost-effective and timely transportation services along with proper oral health education in alleviating fear of dental treatment and dental taboos should be provided to these children for enhancing the utilization of dental services.

IL-6 and ovarian cancer: inflammatory cytokines in promotion of metastasis.

Ovarian cancer is the most fatal gynecological cancer in the USA and the fifth most common cancer-related cause of death in women. Inflammation has been shown to play many roles in ovarian cancer tumor growth, with the proinflammatory cytokine interleukin-6 (IL-6) having been established as a key immunoregulatory cytokine. Ovarian cancer cells continuously secrete cytokines that promote tumorigenicity in both autocrine and paracrine fashions while also receiving signals from the tumor microenvironment (TME). The TME contains many cells including leukocytes and fibroblasts, which respond to proinflammatory cytokines and secrete their own cytokines, which can produce many effects including promotion of chemoresistance, resistance to apoptosis, invasion, angiogenesis by way of overexpression of vascular endothelial growth factor, and promotion of metastatic growth at distant sites. IL-6 and its proinflammatory family members, including oncostatin M, have been found to directly stimulate enhanced invasion of cancer cells through basement membrane degradation caused by the overexpression of matrix metalloproteinases, stimulate promotion of cell cycle, enhance resistance to chemotherapy, and cause epithelial-to-mesenchymal transition (EMT). IL-6 has been shown to activate signaling pathways that lead to tumor proliferation, the most studied of which being the Janus kinase (JAK) and STAT3 pathway. IL-6-induced JAK/STAT activation leads to constitutive activation of STAT3, which has been correlated with enhanced tumor cell growth and resistance to chemotherapy. IL-6 has also been shown to act as a trigger of the EMT, the hypothesized first step in the metastatic cascade. Understanding the important role of IL-6 and its family members' effects on the pathogenesis of ovarian cancer tumor growth and metastasis may lead to more novel treatments, detection methods, and improvement of overall clinical outcomes.

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

BACKGROUND: We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. METHODS: Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. RESULTS: Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. CONCLUSION: It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation.

Comparative study of Plasmodium falciparum erythrocyte membrane protein 1-DBLα domain variants with respect to antigenic variations and docking interaction analysis with glycosaminoglycans.

The variant surface antigen PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1) encoded by the polymorphic multi-copy var gene family plays an important role in parasite biology and the host-parasite interactions. Sequestration and antigenic variation is an essential component in the survival and pathogenesis of Plasmodium falciparum and contributes to chronic infection. The DBLα domain of PfEMP1 is a potential target for immuno-epidemiological studies and has been visualized as a vaccine candidate against severe malaria. Specific host receptors like heparin, heparan sulphate, blood group A and complement receptor 1 have been reported to bind the DBLα domain. Although heparin has been experimentally shown to disrupt the parasite-host interaction and effectively disrupt rosetting, the binding sites for the DBLα domain and the mechanism behind heparin-mediated rosette inhibition have not been elucidated. In this study, 3D structures and epitopes of the DBLα domain in 3D7 and in two Indian isolates have been predicted and compared. We have carried out docking studies on DBLα domains with human GAG receptors (heparin and heparan sulphate) to predict the strength of association between the protein-ligand interactions. The DBLα domain structures showed extensive diversity and polymorphism in their binding sites. The docking results indicate that heparin binds more effectively with high affinity as compared to heparan sulphate with some common interacting residues. These common residues can play an important role in rosetting and will aid in the designing of inhibitors specific to the interactions between DBLα and heparin or heparan sulphate would be important in malaria treatment. Thus it may lead to the development of novel interference strategies to block red blood cell invasion and provide protection against malaria.