Activating point mutations in the MET kinase domain represent a unique molecular subset of lung cancer and other malignancies targetable with MET inhibitors.

Activating point mutations in the MET tyrosine kinase domain (TKD) are oncogenic in a subset of papillary renal cell carcinomas (PRCC). Here, using comprehensive genomic profiling among >600,000 patients, we identify activating MET TKD point mutations as putative oncogenic driver across diverse cancers, with a frequency of ~0.5%. The most common mutations in the MET TKD defined as oncogenic or likely oncogenic according to OncoKB resulted in amino acid substitutions at positions H1094, L1195, F1200, D1228, Y1230, M1250, and others. Preclinical modeling of these alterations confirmed their oncogenic potential, and also demonstrated differential patterns of sensitivity to type I and type II MET inhibitors. Two patients with metastatic lung adenocarcinoma harboring MET TKD mutations (H1094Y, F1200I) and no other known oncogenic drivers achieved confirmed partial responses to a type I MET inhibitor. Activating MET TKD mutations occur in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors.

Evaluation of GeneXpert and advanced biological laboratories UltraGene HCV diagnostic detection and performance against Roche real time PCR in Myanmar.

BACKGROUND: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar. METHODS: Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses. RESULTS: There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior. CONCLUSION: We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries.

Proprotein convertase subtisilin/kexin 9 levels decline with hepatitis C virus therapy in people with HIV/hepatitis C virus and correlate with inflammation.

BACKGROUND: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9. DESIGN: A prospective, observational cohort study. METHODS: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations. RESULTS: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284 ng/ml, P  = 0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3 weeks after end of therapy [EOT]) and posttreatment 2 (median 43.5 weeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5 ng/ml ( P  = 0.003) and -55.6 ng/ml ( P  = 0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 ( r  = 0.64, P  = 0.002; r  = 0.58, P  = 0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52 weeks. CONCLUSION: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis.

Amplification of Wild-Type RET Represents a Novel Molecular Subtype of Several Cancer Types With Clinical Response to Selpercatinib.

PURPOSE: RET rearrangements and RET activating point mutations represent targetable genomic alterations in advanced solid tumors. However, the frequency and clinicopathologic characteristics of wild-type RET amplification in cancer and its potential role as a targetable oncogenic driver are not well-characterized. METHODS: In two institutional cohorts of patients with solid cancers from the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC) whose tumors underwent next-generation sequencing (NGS), the frequency and clinicopathologic features of wild-type RET amplification in the absence of RET rearrangements or activating mutations was assessed. The findings were validated using merged data from The Cancer Genome Atlas (TCGA), Genomics Evidence Neoplasia Information Exchange (GENIE), and China Pan-Cancer data sets. RESULTS: The frequency of wild-type RET amplification across all solid cancers was 0.08% (26 of 32,505) in the DFCI cohort, 0.05% (26 of 53,152) in the MSKCC cohort, and 0.25% (71 of 28,623) in the cohort from TCGA, GENIE, and China Pan-Cancer. Cancer types with RET amplification included non-small-cell lung cancer (NSCLC), hepatobiliary cancer, prostate cancer, breast cancer, and others. The median RET copy number in RET-amplified cases was 7.5 (range, 6-36) in the DFCI cohort and 5.7 (range, 4-27.7) in the MSKCC cohort. Among 11 RET-amplified NSCLCs, eight had no other concurrent driver mutations. Finally, we report on a 69-year-old man with recurrent NSCLC harboring high-level wild-type RET amplification (22-28 copies) as the only identified putative genomic driver who experienced both a systemic and intracranial confirmed response to the RET inhibitor selpercatinib. CONCLUSION: Amplification of wild-type RET represents a novel, targetable molecular subset of cancer.

Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer.

There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.03) and overall survival (HR 0.50; p=0.03). Tumors with high aneuploidy had a significantly greater incidence of distant metastasis and shorter median distant-metastasis free survival (p=0.04 and p=0.048, respectively), but aneuploidy level did not associate with local-regional outcomes. Multiplexed immunofluorescence analysis in a cohort of NSCLC found increased intratumoral CD8-positive, PD-1-positive cells, double-positive PD-1 CD8 cells, and FOXP3-positive T-cell in low aneuploid tumors. Additionally, in a cohort of 101 patients treated with cCRT alone, tumor aneuploidy did not associate with disease outcomes. These data support the need for upfront treatment intensification strategies in stage III NSCLC patients with high aneuploid tumors and suggest that tumor aneuploidy is a promising predictive biomarker.

Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC.

INTRODUCTION: Although gene-level copy number alterations have been studied as a potential biomarker of immunotherapy efficacy in NSCLC, the impact of aneuploidy burden and chromosomal arm-level events on immune checkpoint inhibitor (ICI) efficacy in NSCLC is uncertain. METHODS: Patients who received programmed cell death protein 1 or programmed death-ligand 1 (PD-L1) inhibitor at two academic centers were included. Across all 22 chromosomes analyzed, an arm was considered altered if at least 70% of its territory was either gained or deleted. Among nonsquamous NSCLCs which underwent targeted next-generation sequencing, we retrospectively quantified aneuploidy using the adjusted fraction of chromosomal arm alterations (FAA), defined as the number of altered chromosome arms divided by the number of chromosome arms assessed, adjusted for tumor purity. RESULTS: Among 2293 nonsquamous NSCLCs identified, the median FAA increased with more advanced cancer stage and decreased with higher PD-L1 tumor proportion score (TPS) levels (median FAA in TPS < 1%: 0.09, TPS 1%-49%: 0.08, TPS ≥ 50%: 0.05, p < 0.0001). There was a very weak correlation between FAA and tumor mutational burden when taken as continuous variables (R: 0.07, p = 0.0005). A total of 765 advanced nonsquamous NSCLCs with available FAA values were treated with ICIs. With decreasing FAA tertiles, there was a progressive improvement in objective response rate (ORR 15.1% in upper tertile versus 23.2% in middle tertile versus 28.4% in lowest tertile, p = 0.001), median progression-free survival (mPFS 2.5 versus 3.3 versus 4.1 mo, p < 0.0001), and median overall survival (mOS 12.5 versus 13.9 versus 16.4 mo, p = 0.006), respectively. In the arm-level enrichment analysis, chromosome 9p loss (OR = 0.22, Q = 0.0002) and chromosome 1q gain (OR = 0.43, Q = 0.002) were significantly enriched in ICI nonresponders after false discovery rate adjustment. Compared with NSCLCs without chromosome 9p loss (n = 452), those with 9p loss (n = 154) had a lower ORR (28.1% versus 7.8%, p < 0.0001), a shorter mPFS (4.1 versus 2.3 mo, p < 0.0001), and a shorter mOS (18.0 versus 9.6 mo, p < 0.0001) to immunotherapy. In addition, among NSCLCs with high PD-L1 expression (TPS ≥ 50%), chromosome 9p loss was associated with lower ORR (43% versus 6%, p < 0.0001), shorter mPFS (6.4 versus 2.6 mo, p = 0.0006), and shorter mOS (30.2 versus 14.3 mo, p = 0.0008) to immunotherapy compared with NSCLCs without 9p loss. In multivariable analysis, adjusting for key variables including FAA, chromosome 9p loss, but not 1q gain, retained a significant impact on ORR (hazard ratio [HR] = 0.25, p < 0.001), mPFS (HR = 1.49, p = 0.001), and mOS (HR = 1.47, p = 0.003). Multiplexed immunofluorescence and computational deconvolution of RNA sequencing data revealed that tumors with either high FAA levels or chromosome 9p loss had significantly fewer tumor-associated cytotoxic immune cells. CONCLUSIONS: Nonsquamous NSCLCs with high aneuploidy and chromosome 9p loss have a distinct tumor immune microenvironment and less favorable outcomes to ICIs.

Treatment outcomes and costs of a simplified antiretroviral treatment strategy for hepatitis C among Hepatitis C Virus and Human Immuno deficiency Virus co-infected patients in Ukraine.

Background and Aim: To demonstrate the use of a standard dose of ledipasvir (LDV) and sofosbuvir (SOF), with or without ribavirin, to treat hepatitis C and hepatitis C/HIV co-infection in Ukraine. Methods: Eligible HCV viraemic adults from two clinics in Kyiv were treated with LDV/SOF with or without weight-based ribavirin for 12 weeks. Clinical assessments were performed at screening and at week 24, and as needed; treatment was dispensed every 4 weeks. The primary outcome was sustained virologic response (SVR) 12 weeks after treatment, with analysis by intention to treat. Cost per patient was estimated in USD (2018) over the 24-week period. Results: Of 868 patients included in the study and initiated on therapy, 482 (55.5%) were co-infected with HIV. The common genotypes were 1 (74.1%) and 3 (22%). Overall, SVR was achieved in 831 of the 868 patients (95.7%). SVR in patients with hepatitis C alone and hepatitis C/HIV co-infection was 98.4% and 93.6%, respectively. Adverse events were infrequent and usually mild. Using generic medication, cost per patient was estimated at US$680. Conclusion: A standard dose of LDV and SOF, with ribavirin as per protocol, resulted in good outcomes for patients with both hepatitis C alone and co-infected with hepatitis C/HIV. Program costs in Ukraine were modest using generic medication.

Treatment outcomes and costs of a simplified antiviral treatment strategy for hepatitis C among monoinfected and HIV and/or hepatitis B virus-co-infected patients in Myanmar.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population.

Barriers to hepatitis C direct-acting antiviral therapy among HIV/hepatitis C virus-coinfected persons.

BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States. METHODS: The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription. RESULTS: Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA. CONCLUSIONS: In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.

Does Dehydroepiandrosterone (DHEA) improve in vitro fertilisation (IVF) outcomes in poor responders?

BACKGROUND: In reproductive medicine poor ovarian response (POR) among women undergoing in vitro fertilisation (IVF) is of great concern. Meta-analysis showed that Dehydroepiandrosterone (DHEA) administration resulted in a significant increase in the number of oocytes retrieved in women with POR. The aim of this study was to assess the effectiveness of DHEA supplementation on IVF outcomes among poor responders undergoing IVF. METHODS: Sixteen patients who were diagnosed with POR scheduled to undergo their second cycle of Intracytoplasmic sperm injection (ICSI)/embryo transfer cycle were enrolled. All enrolled patients had earlier undergone their first ICSI/embryo transfer cycle at least four months prior to this study. All subjects were given DHEA supplementation of 25mg three times daily for at least three months prior to their second ICSI/embryo transfer cycle. Statistical analysis of various ovarian response and ICSI outcomes parameter were compared pre and post DHEA. RESULTS: Sixteen women with the mean age of 35 years were enrolled in the study. The comparative analysis of results showed a significant increase in the number of good quality of embryos obtained (p<0.05). After the treatment with DHEA, there was an improvement in the number of oocytes retrieved, Metaphase II (MII) oocyte (mature) oocytes obtained, fertilised and transferrable embryos and the pregnancy rate. There was no significant effect of DHEA treatment on the number of days of stimulation and cumulative dose of gonadotrophins used. CONCLUSION: Our results is able to show that DHEA supplementation may help to enhance IVF-ICSI outcomes in women with POR especially in those age 35 years and below.

Chemopreventive effect and lack of genotoxicity and mutagenicity of the exopolysaccharide botryosphaeran on human lymphocytes.

Carbohydrate biopolymers of fungal-origin are an important natural resource in the search for new bioagents with therapeutic and nutraceutical potential. In this study the mutagenic, genotoxic, antigenotoxic and antioxidant properties of the fungal exopolysaccharide botryosphaeran, a (1→3)(1→6)-ß-D-glucan, from Botryosphaeria rhodina MAMB-05, was evaluated. The mutagenicity was assessed at five concentrations in Salmonella typhimurium by the Ames test. Normal and tumor (Jurkat cells) human T lymphocyte cultures were used to evaluate the genotoxicity and antigenotoxicity (Comet assay) of botryosphaeran alone and in combination with the mutagen methyl methanesulfonate (MMS). The ability of botryosphaeran to reduce the production of reactive oxygen and nitrogen species (RONS) generated by hydrogen peroxide was assessed using the CM-H2DCFDA probe in lymphocyte cultures under different treatment times. None of the evaluated botryosphaeran concentrations were mutagenic in bacteria, nor induced genotoxicity in normal and tumor lymphocytes. Botryosphaeran protected lymphocyte DNA against damage caused by MMS under simultaneous treatment and post-treatment conditions. However, botryosphaeran was not able to reduce the RONS generated by H2O2. Besides the absence of genotoxicity, botryosphaeran exerted a protective effect on human lymphocytes against genotoxic damage caused by MMS. These results are important in the validation of botryosphaeran as a therapeutic agent targeting health promotion.

Impact of support group intervention on family system strengths of rural caregivers of stroke patients in India.

OBJECTIVE: The objective of this study is to evaluate the impact of support group intervention on family system strengths of rural caregivers of stroke patients. DESIGN: True experimental pretest and post-test design was adopted for the study. SETTING: The study was conducted in Kattankulathur Block, a rural area in Kancheepuram district, India. PARTICIPANTS: Two hundred forty caregivers of stroke patients were selected by simple random sampling technique. INTERVENTION: Enrolment in self-help groups and attending meetings were used as the interventional strategy for the purpose of this study. MAIN OUTCOME MEASURE: The main outcome of the study was to evaluate the impact of support group intervention on family system strengths of rural caregivers of stroke patients. RESULTS: Following intervention, the mean score and the standard deviation of the experimental group increased to 44.73 and 5.83, respectively, the control group mean score remained at 22.08 and the standard deviation was 3.07 at t = 37.58. P value was 0.001, which is statistically significant at the confidence interval of 39.45%. CONCLUSION: It was found that there was a significant and positive increase in the family system strengths of caregivers who participated in the self-help group meetings, thereby suggesting that support group intervention programs are an effective nursing strategy that can be employed for improving the overall well-being of the caregivers of stroke patients.

Unmet need for family planning among married women of reproductive age group in urban Tamil Nadu.

CONTEXT: Unmet need for family planning (FP), which refers to the condition in which there is the desire to avoid or post-pone child bearing, without the use of any means of contraception, has been a core concept in the field of international population for more than three decades. OBJECTIVES: The very objective of this study is to determine the prevalence of "unmet need for FP" and its socio-demographic determinants among married reproductive age group women in Chidambaram. MATERIALS AND METHODS: The study was a community-based cross-sectional study of married women of the reproductive age group, between 15 and 49 years. The sample size required was 700. The cluster sampling method was adopted. Unmarried, separated, divorced and widows were excluded. RESULTS: The prevalence of unmet need for FP was 39%, with spacing as 12% and limiting as 27%. The major reason for unmet need for FP among the married group was 18%, for low perceived risk of pregnancy, 9%, feared the side effects of contraception 5% lacked information on contraceptives, 4% had husbands who opposed it and 3% gave medical reasons. Higher education, late marriage, more than the desired family size, poor knowledge of FP, poor informed choice in FP and poor male participation were found to be associated with high unmet need for FP. CONCLUSION: Unmet need for younger women was spacing of births, whereas for older women, it was a limitation of births. Efforts should be made to identify the issues in a case by case approach. Male participation in reproductive issues should be addressed.

GPS and GPRS Based Telemonitoring System for Emergency Patient Transportation.

Telemonitoring during the golden hour of patient transportation helps to improve medical care. Presently there are different physiological data acquisition and transmission systems using cellular network and radio communication links. Location monitoring systems and video transmission systems are also commercially available. The emergency patient transportation systems uniquely require transmission of data pertaining to the patient, vehicle, time of the call, physiological signals (like ECG, blood pressure, a body temperature, and blood oxygen saturation), location information, a snap shot of the patient, and voice. These requirements are presently met by using separate communication systems for voice, physiological data, and location that result in a lot of inconvenience to the technicians, maintenance related issues, in addition to being expensive. This paper presents design, development, and implementation of such a telemonitoring system for emergency patient transportation employing ARM 9 processor module. This system is found to be very useful for the emergency patient transportation being undertaken by organizations like the Emergency Management Research Institute (EMRI).

Microbiology of the white coat in a dental operatory.

BACKGROUND: It remains important to have a thorough knowledge of the micro-flora harboring the white coats of doctors to minimize cross-contamination and improve patient safety by reducing the risk of nosocomial infections. This study presents the microbiological analysis of the white coats in clinical departments of a dental college and hospital. MATERIALS AND METHODS: The swabs for the study were taken from the white coats of undergraduate students posted in various clinical departments, interns, and the post-graduate students. The microbial contamination was studied by observing and recording the colony morphology on the culture plates, Gram's staining with light microscopic screening of the slides, and the biochemical characterization of the isolates using standard microbiology protocols. RESULTS: Microbiological analysis of swabs taken from the white coats in the dental operatory showed that 100% coats had bacterial contamination. Out of 30 swabs collected, 46 cultures were obtained. 50% cultures showed Gram-positive cocci, making it the major microbial group contaminating the white coats in the dental operatory. CONCLUSION: The presented study highlights the fact that the white coats are a potential source of cross infection. The results of this study mandate a strict audit process and protocols to be set in place for preventing cross-contamination from the white coats in a dental operatory.

Atypical (symplastic) leiomyoma of the uterus--a case report.

A 30-year-old, nulliparous woman presented with a history of subfertility. On examination she was found to have uterine fibroid of 28 weeks size of gravid uterus and subsequently laporatomy myomectomy was performed. Multilobulated masses, with diameters ranging from 22 mm to 160 mm were found. Cut sections of the lobulated masses showed whitish whorled cut surface. One of the multilobulated masses had a cystic cavity, measuring 60x50x35 mm(3). Light microscopic findings of the mass with the cystic cavity showed a well-circumscribed cellular tumour composed of cells exhibiting moderate nuclear atypia which were enlarged, nuclei with prominent chromatin clumping and were distributed in areas. Some tumour cells showed large nuclear pseudoinclusions, multinucleated or multilobated tumour giant cells, smudging and few enlarged nucleoli. Mitotic activity was 4 MFs per 10 HPFs. Occasional cells with intracytoplasmic inclusions resembling rhabdoid - like features were seen. There were no atypical mitoses or tumour necroses were noted. Diagnosis of atypical leiomyoma or symplastic leiomyoma was made. Atypical or symplastic leiomyomas are rare in the region of Malaysia and the present case discusses its incidence in younger age, its morphological features along with diagnosis and clinical outcome.

Detection of enzootic plague foci in peninsular India.

A continuous serological and bacteriological surveillance in rodents was carried out in peninsular India i.e. Andhra Pradesh, Karnataka and Tamil Nadu to detect the role of different species of rodents in the maintenance of active enzootic plague foci. Live rodents were collected from wild and ruderal/peri-domestic situations by digging and trapping for sera and organ samples. During 1989 to 2007 serological evidence of plague was detected in different species of rodents in peninsular India. Plague antibodies were detected in 243 sera samples in three different rodent species. Sero-positivity (0.042 percent) amongst rodents tested were found in Tatera indica cuvieri (Hardwicke) followed by Rattus rattus and Bandicota bengalensis. Regular plague surveillance work enhanced the possibility of detecting and delimiting plague foci and helped in implementing necessary preventive anti plague measures to prevent the occurrence of human plague.

Studies on leptospirosis outbreaks in Peddamandem Mandal of Chittoor district, Andhra Pradesh.

An outbreak of leptospirosis in Peddamandem Mandal, Chittoor district, Andhra Pradesh occurred during Aug to Oct 2005. Out of 86 single human sera samples of suspected cases collected during the investigation, 49 (56.97%) samples from seven villages were found positive for leptospirosis both by DGM tests and IgM antibodies. Out of total 49 positive cases 16 (47.05%) were male and 33 (69.46%) female patients. The mean age of the positive cases were 42.7 years. There was no significant differences in male and female ratio and age groups in affected population. The higher degree of seropositivity was observed in adult females as they were mainly engaged in both domestic and peridomestic works. Geographical clustering of cases was evident. All the 49 positive cases had fever (100%). Myalgia (42.9%), stiffness of calf muscles (55.1%) and headache (32.6%) were the other major clinical features observed. There was only 1 (2.04%) case with conjunctival suffusion. None of the case presented with jaundice. All the suspected cases were tested negative for malaria, typhoid and dengue fever. In Peddamandem, contaminated water stagnation due to heavy rainfall and frequent contact of barefooted villagers with the infected sources registered higher incidence of leptospirosis. Most of the cases were from the contaminated water logged areas of the affected villages. In the affected villages none of the individual occupational category showed a significant association with seropositivity. It indicated that the transmission was from the common single category source in the villages i.e. contaminated stagnant water. The villagers living with livestocks and rodents were significantly associated with seropositivity.

RET mutation status in medullary thyroid cancer(MTC) patients and the significance of genetic screening for mutations in their immediate relatives--a preliminary report.

Multiple Endocrine Neoplasia (MEN) 2A is an inherited disease characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma(PHCH) and hyperparathyroidism(HPT). It has recently been shown to be associated with germline mutations in the RET proto-oncogene. Genetic testing for RET mutations will, therefore allow the identification of people with asymptomatic MEN 2 who can be offered prophylactic thyroidectomy and biochemical screening as preventive measures. No genetic study based on RET mutation detection has been available in India so far. The aim of the present study is to detect the proportion of MTC cases having inherited germline or somatic RET mutations and to identify family members at risk for MEN and, thereby the feasibility of screening for MEN. DNA extracted from the peripheral blood and somatic (tumor) tissues were subjected to PCR using primers for exons 10,11 and 16. A few samples were subjected to direct sequencing. Germline mutations were identified in 3 of 4 MEN 2A patients, 18 of 24 sporadic MTC(SMTC), 2 of 4 children of MEN2A and 8 relatives of SMTC. Common mutation was in exon 10 and 11 (c634). It is recommended that RET mutation analysis and counseling of patients and their immediate relatives be introduced on a regular basis to identify gene carriers.