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Anthropogenic activities, climate variability and environmental stresses have greatly affected forest ecosystems globally. Thus, monitoring of forest health is essential for proper planning and effective management. The present study employed an integrated approach of remote sensing and fuzzy analytic hierarchy process to assess the forest health in the Valmiki Tiger Reserve in India. Advanced vegetation index, normalized difference vegetation index, normalized difference moisture index, forest fragmentation, rainfall and soil types were derived from remote sensing data. Multiple buffer zones of villages, roads, railways and canals were also determined for analyzing the forest health status. These layers were prepared in the geographical information system. These layers were given weightage using fuzzy analytic hierarchy process. These layers were integrated to prepare forest health map using weighted overlay method. The results revealed that the largest forest area was found under moderately healthy forest (37%) followed by healthy forest (31%) and unhealthy forest (13%). Of the total area of the Reserve, 19% area was under non-forest category. Human-induced disturbances such as encroachment, illegal sand mining, livestock grazing and forest conversion to agriculture have been attributed to the unhealthy forest in the Reserve. The receiver operating characteristic curve value and area under curve (0.792) show reliability of forest health map. The findings of this study may be helpful for forest managers, conservationists and local communities in devising sustainable strategies for effective management of the forest. The methodological framework adopted in this study may be utilized in other geographical regions interested in assessing forest health. [ABSTRACT FROM AUTHOR]

Occupational exposure to excessive level of copper results in many adverse health effects.~Background~To measure pulmonary function, oxidative stress, and extent of DNA damage in workers of a copper processing industry.~Objective~30 men working in a copper processing industry and 30 men matched for age and socioeconomic status (comparison group) were included in this study. Pulmonary function test parameters were measured for all participants. Serum malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), glutathione (GSH) content in RBCs and 8-OHdG were assayed by ELISA. Extent of DNA damage in leucocytes was assayed by comet assay.~Methods~Pulmonary function parameters, FVC, FEV1, PEFR, and MVV measured in workers were significantly (p<0.05) lower than those observed in the comparison group. Compared to the comparison group, MDA was significantly (p=0.002) increased in studied workers; TAOC (p=0.017), and GSH (p=0.020) were significantly lower in workers than the comparison group. There was significant DNA damage in leucocytes in workers compared to the comparison group (difference in olive tail moment p<0.001). PEFR, FEF25-75%, and MEF50% were negatively correlated with MDA.~Results~The observed DNA damage would be due to increased oxidative stress resulting from excessive exposure to copper.~Conclusion [ABSTRACT FROM AUTHOR]

The article discusses the use of educational methodology program for university teachers and trainers to improve their professional performance and effectiveness in teaching complementary and alternative medicine (CAM) course. It mentions that the study was conducted of the teachers affiliated at the CAM institutions of the Rajiv Gandhi University of Health Sciences in Karnataka, India. It also mentions the activities conducted at the contact program.

Rajiv Gandhi University of Health Sciences, Karnataka, India, is established by an Act of Karnataka State Legislature in the year 1996. Its mandate is to provide training and development in health sciences sector. This University has done pioneering work in the field of curriculum designing for all the health sciences courses offered by the affiliated institutions. In this regard, it has taken lead among all the health sciences universities in India. With student strength of more than one lakh, it has now become a necessity to explore all the possible technological options, so as to provide a comprehensive education to the students. In this context, a proposal has been submitted to the executive head of the University to implement the Blended Learning Program. [ABSTRACT FROM AUTHOR]

Ecosystem services provided by wetlands are essential for communities living near wetlands, especially in an underdeveloped semi-arid landscape. The land use land cover changes and ecosystem degradation and water quality change over the past few decades have had immense effects on declining wetland ecosystem services. With the degradation, it is exerting superfluous effects on wetland communities including loss of livelihood, and decline in other wetland services like fishing, aquaculture, fuelwood, fodder, and many more. The present study attempts to assess the changing nature of wetland health, water quality, and declining ecosystem services of Mount Abu wetlands in Rajasthan, India. For assessing the change of wetland extent, we have used the remote sensing-based data for preparation of land use land cover change from 1992 to 2020. The water samples have been collected from the wetland, and different biophysical parameters of the water have been tested in the laboratory. A questionnaire-based household survey has been conducted to understand the perception of the wetland communities on the loss of ecosystem services over three decades. Further, a correlation and cluster assessment has been conducted to understand the degradation of wetland health in the selected wetlands. The study results indicated deteriorating conditions of wetland health and declining ecosystem services in the study area over the time periods. The land use land cover change analysis indicated a decrease in the spatial extent of the wetlands in the study area. Wetland communities are being affected due to the degradation of wetland health. The study recommended executing a wetland management plan for long-term conservation and livelihood management for the Mount Abu wetlands and communities., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This is a study to explore the risk perception among T2DM patients and to compare the pre-test and post-test levels of knowledge and lifestyle changes among T2DM patients at selected hospitals in Chennai. Most diabetics have type 2 diabetes, accounting for 85-90% of cases. Diabetes is a worldwide epidemic disease with distressing human, societal, and economic effects. It affects an estimated 382 million people worldwide in 2021., Patients and Methods: The research design used mixed-method research, such as Exploratory Sequential Design. The phenomenological approach, in that sequential exploratory design for the qualitative and true experimental design for the quantitative study, was chosen. 60 samples of T2DM patients were selected using a simple random sampling technique through the lottery method and divided into experimental and control groups for every 30 samples in quantitative. Five samples were selected using convenient sampling for qualitative., Results: In the quantitative study, the pre-test showed 4 (13.3%), and 5 (16.7%) adequate knowledge and lifestyle changes in both groups. Post-test experimental group showed that 23 (76.7%) had adequate knowledge and 23 (76.7%) changes in lifestyle found a drastic transformation from the pre-test as well as in the control group. The calculated Chi-square value showed a significant difference in the post-test level of lifestyle change among the T2DM patients between the groups at p<0.001 level., Conclusions: This inferred that Competent Based Intervention (CBI) on knowledge and lifestyle changes administered to T2DM patients in the experimental group was found to be effective. Competent Based Intervention is a nursing intervention that is well accepted and adopted by patients and easily implemented by nurses. It can be included in the nursing curriculum. In-service education can be arranged once a month for staff nurses and faculty members regarding Competent Based Intervention. The Nurse educator should encourage the nurses to effectively utilize research evidence-based practice related to Competent Based Intervention for patients with type 2 diabetes mellitus.

Glacier-associated hazards are becoming a common and serious challenge to the high mountainous regions of the world. Glacial lake outburst floods (GLOFs) are one of the most serious unanticipated glacier hazards, with the potential to release a huge amount of water and debris in a short span of time, resulting in the loss of lives, property, and severe damage to downstream valleys. The present study used multi-temporal Landsat and Google earth imageries to analyze the spatio-temporal dynamism of the selected glacial lake (moraine-dammed) in the Satluj basin of Western Himalayas. Furthermore, GLOF susceptibility of the lake was assessed using a multi-criteria decision-based method. The results show that the lake area has increased from 0.11 to 0.26 km 2 over the past 28 years from 1990 to 2018. The susceptibility index value for the lake was calculated as 0.75, which indicates that the lake is highly susceptible to the GLOF. The depth and volume of the lake were estimated to be 16 m and 57 × 10 5 m 3 , respectively, using an empirical formula. HEC-RAS, HECGeo-RAS, and Arc-GIS software were utilized in this study to perform unsteady flow analysis and to determine the GLOF impact on the downstream area. The worst-case GLOF scenario (breach width of 75 m) was revealed during an overtopping failure of the moraine dam, resulted in a peak discharge of 4060 m 3 /s and releasing a total water volume of 57 × 10 5 m 3 . The breach hydrograph has been routed to calculate the spatial and temporal distribution of peak flood, inundation depth, velocity, water surface elevation, and flood peak arrival time along the river channel. The analysis further reveals that the routed flood waves reach the nearest settlement, i.e., Rajpur town, situated at a distance of 102 km in the downstream valley of the lake at 6 h after the beginning of the lake breach event with a peak discharge/flood of 1757 m 3 /s and maximum flow velocity of 1.5 m/s. With the ongoing climate warming and glacier retreat, moraine-dammed lakes are becoming more hazardous and thus increasing the total threat. Therefore, it is mandatory to monitor and assess such lakes at regular intervals of time to lessen the disastrous impacts of GLOFs on the livelihood and infrastructure in the downstream valleys. The findings of this study will aid in the creation of risk management plans, preparatory tactics, and risk reduction techniques for GLOF hazards in the region., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: BCR-ABL Tyrosine kinase inhibitors (TKI's) are most successful of targeted therapies and are currently considered the cornerstone in the management of patients with chronic myeloid leukemia (CML). A recent study reported excellent outcomes of Dasatinib 50mg with better sustained response. Therefore, we aim to evaluate the molecular responses and safety of upfront Dasatinib 50mg in Indian CML-Chronic Phase patients., Methods: It was an observational single-centre study. CML-CP patients started on Dasatinib 50mg daily were offered to participate in this study. Data of imatinib was collected retrospectively as a comparator group., Results: Between June 2020 to Feb 2022, fifty patients were included in the dasatinib 50mg once daily group. Median age was 40 yrs. ranging from (19 to73) years. At a median follow up of 9.2 months, 49 patients completed three months treatment, out of which 48 patients were evaluated as one patient stopped medication after a month due to financial constraints. The response rate at three months for dasatinib 50mg daily and Imatinib were 68.75% and 69.7% respectively. At 12 months, 68% and 66.6% patients achieved major molecular response [MMR] in dasatinib 50mg and imatinib groups respectively., Conclusion: In conclusion, low dose dasatinib is safe and effective as an upfront therapy in CML-CP. Early molecular response [EMR] rates were comparable in low dose dasatinib and imatinib arm but deep molecular responses were significantly higher in low dose dasatinib arm. Dasatinib, taken daily at a dose of 50mg, may offer a new, alternative choice as generic versions are available now for frontline therapy in CML-CP., Competing Interests: Conflict of Interests All authors have no conflict of interest, (Copyright © 2022 Elsevier Inc. All rights reserved.)

Railways are an indispensable component of sustainable transportation systems, but also exact a toll on wildlife. Wild Asian elephants are often killed by trains in Assam, India, where we assess temporal variations in the occurrences of elephant-train collisions (ETCs) and casualties during 1990-2018. This study also assesses spatially varying relationships between elephant-train collision (ETC) rates and elephant and train densities in the adjoining 10 km2 grid cells of 11 prioritized railroad segments using ordinary least squares (OLS) and geographically weighted regression (GWR) models. The temporal analysis indicated that ETCs spiked at certain hours and months. The adult and calf elephant casualties on the railroads were found to be two to fivefold high during the post monsoon season compared to other seasons. During the operation period of meter gauge railroads (1990-1997), the proportions of ETCs and casualties were only 15.6% and 8.7% respectively. However, these increased substantially to 84.4% and 91.3% respectively during the operation of broad gauge railroads (1998-2018). The OLS model indicated that both elephant and train densities explained 37% of the variance of ETC rate, while GWR model showed 83% of the variance of ETC rate. The local coefficient values of GWR indicated that both the predictor variables interplayed significantly and positively to determine ETC rates in the Mariani-Nakachari and Khatkhati-Dimapur railroad segments. However, the relationship between ETC rate and elephant density is significantly negative in the Habaipur-Diphu railroad, implying that the elephant population along this railroad stretch is significantly affected by railways through large scale ETCs. Hence, there is an urgent need to address long-term mitigation strategies so that elephants can be conserved by providing safe passages and survival resources along railway lines., Competing Interests: The authors have declared that no competing interests exist.

Aim: To unveil and evaluate the association and analyze the incidence and pattern of PGR gene polymorphisms (PROGINS insertion and PGR exon 5-C/T polymorphism) in recurrent pregnancy loss (RPL) couples of Kashmir., Methods: In this study, analyses of PGR gene polymorphisms in RPL couples were genotyped by amplification-refractory mutation system polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism., Results: Molecular analysis of PGR gene polymorphisms indicated that the genotypic and allelic frequencies of PROGINS insertion and PGR exon 5 C/T polymorphisms of female group in cases and controls to be significantly different and poses risk in predisposition to RPL. Moreover, haplotype analysis in female group revealed that P1P2/CC and P1P2/CT genotype are significantly associated with RPL., Conclusion: Our data indicate that the PROGINS insertion and exon 5-C/T polymorphism can act as useful genetic markers in the female group, but needs to be replicated in further studies including various other single nucleotide polymorphisms of PGR gene relevant to pregnancy loss which may contribute to novel therapeutic targets with improved conclusions., (© 2021 Japan Society of Obstetrics and Gynecology.)

Plasmablasts represent a specialized class of antibody-secreting effector B cells that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections such as dengue or Ebola that cause hemorrhagic fever. To gain a detailed understanding of human plasmablast responses beyond antibody expression, here, we performed immunophenotyping and RNA sequencing (RNA-seq) analysis of the plasmablasts from dengue febrile children in India. We found that plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues, including skin, mucosa, and intestine, and upregulated the expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated the expression of receptors for several B-cell prosurvival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock than in patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. IMPORTANCE Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody-dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.

India is one of the most affected countries by COVID-19 pandemic; but little is understood regarding immune responses to SARS-CoV-2 in this region. Herein we examined SARS-CoV-2 neutralizing antibodies, IgG, IgM, IgA and memory B cells in COVID-19 recovered individual from India. While a vast majority of COVID-19 recovered individuals showed SARS-CoV-2 RBD-specific IgG, IgA and IgM antibodies (38/42, 90.47%; 21/42, 50%; 33/42, 78.57% respectively), only half of them had appreciable neutralizing antibody titers. RBD-specific IgG, but not IgA or IgM titers, correlated with neutralizing antibody titers and RBD-specific memory B cell frequencies. These findings have timely significance for identifying potential donors for plasma therapy using RBD-specific IgG assays as surrogate measurement for neutralizing antibodies in India. Further, this study provides useful information needed for designing large-scale studies towards understanding of inter-individual variation in immune memory to SARS CoV-2 natural infection for future vaccine evaluation and implementation efforts., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study's objective is to describe unintentional drowning using GBD estimates from 1990 to 2017., Methods: Unintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning., Results: Globally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes., Conclusions: There has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries., Competing Interests: Competing interests: Dr. Franklin reports receiving airfare reimbursement from Royal Life Saving Society - Australia, during the conduct of the study. Dr. Bhaumik reports grants from Royal National Lifeboat Institution, UK, outside the submitted work. Dr. Driscoll reports grants from World Health Organization, during the conduct of the study. Dr. Ivers reports grants from Royal National LifeBoat Institute, outside the submitted work. Dr. Khubchandani reports grants from Merck Research Laboratories, outside the submitted work. Dr. James reports grants from Sanofi Pasteur, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Over the past decade, breast cancer has overtaken cervical cancer to become the most common cancer among women in India, as in most Western nations. In addition to the high incidence, the morbidity and mortality associated with this malignancy are disproportionately higher in India. Although some efforts are being made to increase awareness about this disease, a large majority of Indian patients present with advanced disease. Here, important institutional data and treatment outcomes are reviewed and compared with data from the West. Additionally, we highlight recent efforts in setting up collaborative multicentre trials in breast cancer in India and suggest some ways forward to improve outcomes., (Copyright © 2019. Published by Elsevier Ltd.)

Light chain myeloma (LCM) has a reported worldwide incidence of approximately 15%-20% among all multiple myeloma (MM) patients. Few western studies have shown strong correlation of LCM with anemia, higher International Staging System scores, proclivity to renal failure, elevated lactate dehydrogenase levels, raised serum-free light chain ratio, higher frequency of extramedullary plasmacytomas, and poorer overall survival, attributable probably to lack of differentiation and skeletal destruction. The primary aim of this retrospective observational study was to define the clinical and hematological characteristics as well as prognostic outcome of Indian LCM patients in comparison with the IgG and IgA subtypes. Patients were defined according to the International Myeloma Working Group diagnostic criteria 2016 and staged as per the International Staging System. Out of 104 patients of newly diagnosed MM in which results of serum immunofixation (IFE) were available, 65 were of IgG isotype (62.5%), 15 had IgA (14.4%), and 24 had light chain myelomas (LCMs) (23.1%). It was observed that LCM patients significantly correlated with hypercalcemia and higher serum-free light chain ratios, whereas IgA patients were strongly associated with anemia and lower serum albumin levels. However, no difference was found among the three subgroups in terms of serum lactate dehydrogenase levels, proclivity to renal failure, presence of lytic bone lesions, prognostic scoring, pretransplant chemosensitivity, and progession-free survival (1 year). Thus, it may be concluded that Indian LCM patients have significantly different clinico-hematological profile in comparison with other published studies worldwide. Also, their prognostic outcomes are not worse when compared with patients of other protein isotypes, probably due to standardized treatment regimens applied., Competing Interests: There are no conflicts of interest

Background: The Indian population is facing highest dengue burden worldwide supporting an urgent need for vaccines. For vaccine introduction, evaluation and interpretation it is important to gain a critical understanding of immune memory induced by natural exposure. However, immune memory to dengue remains poorly characterized in this region., Methods: We enumerated levels of dengue specific memory B cells (MBC), neutralizing (NT) and binding antibodies in healthy adults (n=70) from New Delhi., Results: NT-antibodies, binding antibodies and MBC were detectable in 86%, 86.56% and 81.63% of the subjects respectively. Among the neutralizing positive subjects, 58%, 27%, 5% and 10% neutralized all four, any three, any two and any one dengue serotypes respectively. The presence of the neutralizing antibodies was associated with the presence of the MBC and binding antibodies. However, a massive interindividual variation was observed in the levels of the neutralizing antibodies (range, <1:50-1:30,264), binding antibodies (range, 1:3,000-1:134,000,) as well as the MBC (range=0.006%-5.05%)., Conclusion: These results indicate that a vast majority of the adults are immune to multiple dengue serotypes and show massive interindividual variation in neutralizing/binding antibodies and MBCs - emphasizing the importance of monitoring multiple parameters of immune memory in order to properly plan, evaluate and interpret dengue vaccines., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: Although drug-eluting stents (DES) have outclassed the use of bare metal stents, the safety and efficacy of DES at long-term follow-up has still been conflicting because of increased occurrence of late or very late restenosis and stent thrombosis after DES implantation. Hence, the present study was aimed to evaluate the 3-year safety and clinical performance of biodegradable polymer-coated ultra-thin (60 µm) sirolimus-eluting stent (SES) in real-world patients with coronary artery disease (CAD)., Materials and Methods: This was a physician-initiated, retrospective, single-centre, observational study that included 237 consecutive patients who had previously undergone implantation of only Supraflex SES (Sahajanand Medical Technologies Pvt Ltd, Surat, India) for the treatment of CAD. Follow-up was received after 1 year and 3 years of stent implantation. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction (MI) and target lesion revascularisation (TLR). Stent thrombosis was considered as a safety endpoint., Results: The mean age of patients was 64.1 ± 10.2 years, and 192 (81.0%) patients were male. The average stent length and diameter were 24.4 ± 9.0 mm and 3.1 ± 0.4 mm, respectively. The cumulative MACE rate at 3 years follow-up was 6.5% which included 4 (1.8%) cardiac deaths, 6 (2.8%) MI, and 4 (1.8%) TLR. There were 2 (0.9%) cases of stent thrombosis., Conclusion: Treatment of patients with CAD in real-world clinical practice was associated with sustained clinical safety and low rates of restenosis, stent thrombosis and MACE up to 3 years after Supraflex SES implantation.

Background and Objectives: The study aimed to evaluate the diagnostic performance of malaria through microscopy and rapid diagnostic test (RDT) analysis performed locally and the accuracy evaluated by nested polymerase chain reaction (PCR) for diagnosis of Plasmodium falciparum from hotspot regions of North East (NE) India., Materials and Methods: One thousand one hundred and seventy-three blood samples were collected for identification of P. falciparum infection using microscopy and RDT analysis. DNA was extracted from whole blood using QIAamp DNA blood mini kit, and nested PCR was performed to confirm P. falciparum for evaluating sensitivity and specificity from various epidemiological surveys and geographical areas of NE India., Results: Of 1173 symptomatic malaria suspected patients, 15.6% (183/1173) patients were diagnosed as malaria positive by RDT and 67.94% cases (53/78) with microscopy. Of 183 malaria-positive patients, 42.62% (78/183) were diagnosed with P. falciparum and 84.61% (66/78) further confirmed to be P. falciparum positive by nested PCR. High sensitivity (97.9%) and low specificity (2.03%) of the RDT and high sensitivity (99.1%) and low specificity (0.9%) in microscopy against nested PCR results was statistically significant (P < 0.05). Epidemiological comparisons expressed highest incidences in Manipur (51.11%) followed by Meghalaya (48.93%) and Assam (35.16%). Overall incidence rate among the genders was observed to be higher in males than in females., Conclusions: Our findings suggest that PCR, RDT and microscopy can potentially determine hotspots at moderate transmission intensities, but PCR testing has a diagnostic advantage as transmission intensity falls. Therefore, malaria control programs should consider PCR testing when the prevalence of infection is low., Competing Interests: None

Purpose: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized., Methods: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform., Results: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2., Conclusion: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

In prognostic evaluation of breast cancer Immunohistochemical (IHC) markers namely, oestrogen receptor (ER) and progesterone receptor (PR) are widely used. The expert pathologist investigates qualitatively the stained tissue slide under microscope to provide the Allred score; which is clinically used for therapeutic decision making. Such qualitative judgment is time-consuming, tedious and more often suffers from interobserver variability. As a result, it leads to imprecise IHC score for ER and PR. To overcome this, there is an urgent need of developing a reliable and efficient IHC quantifier for high throughput decision making. In view of this, our study aims at developing an automated IHC profiler for quantitative assessment of ER and PR molecular expression from stained tissue images. We propose here to use CMYK colour space for positively and negatively stained cell extraction for proportion score. Also colour features are used for quantitative assessment of intensity scoring among the positively stained cells. Five different machine learning models namely artificial neural network, Naïve Bayes, K-nearest neighbours, decision tree and random forest are considered for learning the colour features using average red, green and blue pixel values of positively stained cell patches. Fifty cases of ER- and PR-stained tissues have been evaluated for validation with the expert pathologist's score. All five models perform adequately where random forest shows the best correlation with the expert's score (Pearson's correlation coefficient = 0.9192). In the proposed approach the average variation of diaminobenzidine (DAB) to nuclear area from the expert's score is found to be 7.58%, as compared to 27.83% for state-of-the-art ImmunoRatio software., (© 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.)

Background: Few studies have assessed placental malaria infections from low transmission areas by histopathology to define their impact and underlying mechanisms., Methods: Peripheral smears and rapid diagnostic tests (RDTs), placental smears and histological samples, birth weight and gestational age were collected from 2,282 deliveries in three hospitals during a one-year (2006-2007) continuous cross-sectional survey in Madhya Pradesh. Placental histopathology included all 50 cases positive by microscopy or RDT plus 456 randomly selected samples of women negative for malaria by microscopy or RDT. Histological examination included parasites, inflammatory cells, pigment in fibrin, and morphological changes., Results: There were 52 histology-positive cases; 38 (73.1%) active (acute and chronic) and 14 past infections. Intervillous parasitaemia was low (60% had < 1% parasitaemia) and monocytosis mostly mild (63%). Compared with uninfected placentas, acute Plasmodium falciparum infections were associated with stillbirth (RR 3.8, 95% CI 1.2-12.1), lower maternal haemoglobin (mean difference: 1.5 g/dL, 95% CI 0.5-2.5), lower birth weight (mean difference 451 g, 95% CI 169-609) and shorter gestation (mean difference 0.8 weeks, 95% CI 0.2-1.4). Chronic or past infections were not associated with these outcomes. Among the 11 peripheral Plasmodium vivax cases, placental parasites were absent, but they were associated with increased placental polymorphonuclear cells., Conclusions: Malaria associated stillbirth and low birth weight in women with low protective immunity may result, at least in part, from a shortened gestation triggered by acute infection, stressing the importance of early malaria detection.

Aim: To explore the views in non-Western cultures about ending the lives of damaged newborns., Method: 254 university students from India and 150 from Kuwait rated the acceptability of ending the lives of newborns with genetic defects in 54 vignettes consisting of all combinations of four factors: gestational age (term or 7 months); severity of genetic defect (trisomy 21 alone, trisomy 21 with serious morphological abnormalities or trisomy 13 with impending death); the parents' attitude about prolonging care (unknown, in favour or opposed); and the procedure used (withholding treatment, withdrawing it or injecting a lethal substance)., Results: Four clusters were identified by cluster analysis and subjected to analysis of variance. Cluster I, labelled 'Never Acceptable', included 4% of the Indians and 59% of the Kuwaitis. Cluster II, 'No Firm Opinion', had little variation in rating from one scenario to the next; it included 38% of the Indians and 18% of the Kuwaitis. In Cluster III, 'Parents' Attitude+Severity+Procedure', all three factors affected the ratings; it was composed of 18% of the Indians and 16% of the Kuwaitis. Cluster IV was called 'Severity+Parents' Attitude' because these had the strongest impact; it was composed of 40% of the Indians and 7% of the Kuwaitis., Conclusions: In accordance with the teachings of Islam versus Hinduism, Kuwaiti students were more likely to oppose ending a newborn's life under all conditions, Indian students more likely to favour it and to judge its acceptability in light of the different circumstances.

This report summarizes recent findings of environmental arsenic (As) contamination and the consequent health effects in a community located near historic gold mining activities in the Mangalur greenstone belt of Karnataka, India. Arsenic contents in water, hair, nail, soil and food were measured by FI-HG-AAS. Elemental analyses of soils were determined by ICP-MS (inductively coupled plasma-mass spectrometry). Of 59 tube-well water samples, 79% had As above 10 μg L(-1) (maximum 303 μg L(-1)). Of 12 topsoil samples, six were found to contain As greater than 2000 mg kg(-1) possibly indicating the impact of mine tailings on the area. All hair and nail samples collected from 171 residents contained elevated As. Arsenical skin lesions were observed among 58.6% of a total 181 screened individuals. Histopathological analysis of puncture biopsies of suspected arsenical dermatological symptoms confirmed the diagnosis in three out of four patients. Based on the time-course of As-like symptoms reported by the community as well as the presence of overt arsenicosis, it is hypothesized that the primary route of exposure in the study area was via contaminated groundwater; however, the identified high As content in residential soil could also be a significant source of As exposure via ingestion. Additional studies are required to determine the extent as well as the relative contribution of geologic and anthropogenic factors in environmental As contamination in the region. This study report is to our knowledge one of the first to describe overt arsenicosis in this region of Karnataka, India as well as more broadly an area with underlying greenstone geology and historic mining activity., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA-identical sibling or family donors. Seventy-six patients were considered "high risk" as per criteria. The graft source included peripheral blood stem cells in 109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low-risk group (n = 45) and 64.0 ± 5.6% in the high-risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long-term survival in patients undergoing HSCT for SAA., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In the Indian context, there is a convention of doing pre-operative screening for HIV, hepatitis B virus and hepatitis C viruses for all patients as a routine pre-intervention investigation. This approach is justified in some instances in the best interest of the patient. However, as routine screening is not the standard care internationally and as there is a significant divergence of views about the merits and demerits of this practice, this issue needs to be debated in a rational manner with an evidence-based approach. The present article is authored by a surgeon and a microbiologist from a new cancer care centre in eastern India, who has attempted to address this contentious issue. The various available options have been explored, and advantages and disadvantages of the different approach have been discussed. An algorithm for infection prevention and control has been presented so that surgeons and medical microbiologists could manage infection control challenges satisfactorily.

Background: In addition to standard risk criteria at diagnosis, minimal residual disease (MRD) following initiation of therapy is a well-recognized risk factor to predict relapse. Literature from developing countries addressing therapeutic or laboratory practices related to MRD, is largely lacking. In a first paper from India, we describe our experience in establishing a flow cytometry-based MRD assay for precursor B lineage ALL (BCP-ALL) with emphasis on the assay standardization and cost., Methods: Normal templates for B cell development were established in 10 control patients using CD45, CD11a, CD38, CD20, CD10, CD19, CD58, CD34, CD123, and CD22. BCP-ALL samples (n = 42) were characterized at diagnosis to identify a suitable marker for follow-up during mid (D+21) and end of induction (D+33). Both, multiparametric immunophenotyping and single marker detection of LAIP were used for data analysis., Results: In 95.2% of BCP-ALL at least two informative markers could be obtained when a minimum of four cocktail combinations were used. The combination CD20, CD10, CD45, and CD19 was the most useful (71.4%) followed by combinations containing CD38 (66.7%), CD22 (57.1%), CD11a (52.4%), and CD58 (33.3%). Using our approach, 60 and 47% of patients had detectable MRD at mid and end induction time points, respectively., Conclusion: We have described a relatively cost effective MRD panel which is applicable to over 90% of patients. We hope that this data would encourage more centers in India and other resource constrained health delivery systems to develop MRD assays., (Copyright © 2012 International Clinical Cytometry Society.)

Background: Chronic myelogenous leukemia (CML) is characterised by the t(9;22)(q34;q11.2) which results in the formation of the BCR/ABL1 fusion gene. Occasionally, the t(9;22) may be associated with submicroscopic deletions of chromosomes 9 and/or 22 which appear to be associated with a worse prognosis. Three or four-way variant t(9;22) may also occur. All these changes as well as gain of the Philadelphia chromosome which represents disease progression can be detected by fluorescence in situ hybridization (FISH) analysis. FISH analysis at presentation is used to determine the number of cells with BCR/ABL1 fusion and establish whether the patterns are typical or atypical. Response to therapy can then be monitored by serial testing., Patients and Methods: The study group consisted of all patients diagnosed or suspected to have CML who had interphase FISH analysis at presentation on peripheral blood/bone marrow using a commercially available BCR/ABL1 dual colour, dual fusion probe. The study was performed at a tertiary hospital in India between 2004 and 2010., Results: There were 1076 diagnostic samples which were positive for BCR/ABL1 fusion. Typical dual fusion signals (two fusions, one red and one green, 2F1R1G) were seen in 801 cases (74 %). Atypical signal patterns were seen in 275 cases (26%). These were: 1F1R2G (4%), 1F2R1G (2.5%) and 1F1R1G (11%) representing deletions of the derivative 9 involving chromosome 9 sequences, chromosome 22 sequences, or both respectively; 3F1R1G (6.5%) usually representing gain of an additional Philadelphia chromosome and 1F2R2G (1%) representing a three- or four-way variant translocation. More than one signal pattern was seen in 1%., Conclusions: Our findings were similar to the literature with respect to the distribution of signal patterns except that we had a lower number of patients with variant translocations. While each signal pattern is typically associated with a particular abnormality, there can be more than one explanation for each pattern. Hence, metaphase FISH analysis is the "gold standard" for the interpretation of signal patterns.

In a first series from India, we report 9 cases of hepatosplenic T cell lymphoma (HSTCL) seen in 23 months accounting for 4.2% of all mature T-non-Hodgkin lymphomas (NHLs) in our institution. All patients presented with organomegaly, cytopenias and had evidence of bone marrow involvement. The tumor cells had a blastic (55%) morphology with predominantly intrasinusoidal (33.3%) or intrasinusoidal with an additional interstitial component (33.3%). On flow cytometry, the classical phenotype (CD3+, CD7+, CD4-, CD8-, CD5-, CD56+/-) was seen only in 4 patients. Unusual variations included CD45 (overexpression), CD7 (dim expression), CD3 (overexpression, heterogeneous and dim), CD2 (overexpression), CD5 (heterogeneous), CD8 (heterogeneous or dim or overexpression) and aberrant expression of CD19. Fluoresvent in situ hybridisation (FISH) and karyotyping was abnormal in 5 out of 7 patients evaluated. All of the 5 cases showed abnormalities in chromosome 7 (ring chromosome or isochromosome 7q). Five patients died of disease and related complications in a span of 1-3 months after diagnosis whereas 4 were alive at their last follow up out of which 2 had documented a relapse. In our series, HSTCL was characterized by typical clinical and variable immunophenotypic features and a dismal clinical outcome.

Inherited heterogeneous defects of platelet function caused by impairment of platelet responses to weak agonists as ADP, epinephrine and others as low concentration collagen and platelet activating factor (PAF) have been described, though quite rarely. We describe here 25 cases of this defect with impairment in response to ADP and epinephrine. Subjects with a history of generalized bleeding and a prolonged bleeding time, PF3 availability or prothrombin consumption index and a normal platelet count, prothrombin time, activated partial thromboplastin time and clot solubility were subjected to platelet aggregation. Those of these which showed a normal aggregation with collagen and arachidonic acid and an absent or reduced aggregation with ADP and epinephrine were included in our study group. Subjects with history or findings suggestive of antiplatelet drug intake or any acquired condition affecting platelet functions were excluded from this study. 76% of the patients had onset of recurrent bleeding manifestations since childhood with a mean age at onset of 9.2 years. A positive family history was present in 36% of the patients. Majority of the patients (88%) presented with mild bleeding manifestations, the commonest symptom being appearance of recurrent ecchymotic spots. We present here a series of patients with a hereditary platelet aggregation defect selectively with ADP and epinephrine.

We studied 57 patients with Budd-Chiari syndrome (BCS) and 48 with portal vein thrombosis (PVT) for underlying inherited prothrombotic defects such as protein C, protein S, and antithrombin III deficiencies. Genetic mutations for factor V Leiden, prothrombin gene 20210A, and methyltetrahydrofolate reductase (MTHFR) C677T were studied in 29 patients in each group. Inherited prothrombotic defects were detected in 16 (28%) of 57 patients with BCS and 7 (15%) of 48 patients with PVT. Factor V Leiden mutation was the most common prothrombotic defect in BCS (5/29 [17%]) followed by protein C deficiency (7/57 [12%]) and protein S deficiency (4/57 [7%]), whereas in PVT, protein C deficiency was the most common inherited prothrombotic defect (4/48 [8%]) followed by protein S deficiency (2/48 [4%]). The factor V Leiden mutation was detected in only 1 (3%) of 29 cases of PVT. The heterozygous MTHFR C677T mutation was detected in 7 (24%) of 29 patients with BCS and 6 (21%) of 29 patients with PVT. Antithrombin III deficiency, homozygous MTHFR C677T mutation, and prothrombin G20210A mutation were not detected in any patients.

Heparin-induced thrombocytopenia (HIT) was looked for in 33 Indian patients undergoing cardiovascular surgery who received unfractionated heparin (UFH). Platelet counts were performed before the initiation of UFH therapy and 5 to 16 days after administration of the therapy. A decrease in patients' platelet count > 35% of the baseline value or < 100,000/microL was considered to be suggestive of HIT syndrome. Heparin-induced platelet aggregation (HIPA) and enzyme-linked immunosorbent assay (ELISA) tests were performed in all the patients to detect antibodies against heparin/PF4 complex. Thrombocytopenia was found to be present in 10 (30%) patients. Of these, two patients were found to be positive as detected by HIPA and ELISA tests. These two patients were considered to have classic HIT syndrome. One of these had bleeding while the other was asymptomatic. Among the 23 non-thrombocytopenic patients and controls, HIT antibodies were not detectable by HIPA test in all but absent by ELISA in only 21 of them. Two of 23 non-thrombocytopenic patients had positive results on the ELISA test. Because the latter had negative test results on HIPA, they were considered to be false-positive results. Thus, HIT syndrome develops in approximately 6% of Indian patients treated with UFH.

Intron 1 and 22 inversions were looked for in 80 severe haemophilia A patients in India using PCR and multiplex Long-Distance Subcycling-PCR, respectively. Intron 1 inversion was seen in 3 (3.75%) and intron 22 inversion was seen in 35 (43.75%) patients. Of severe haemophilics, 47.5% had either of these inversions. It is thus suggested that screening for inversions may be the first step in genetic testing of Indian haemophilics.

The study was designed to evaluate the oxidative stress and modulation of anti-oxidant enzymes in 10 accidental argimone oil poisoning cases admitted in a hospital in Delhi, India during a recent outbreak of epidemic dropsy in 1998. Serum malondialdehyde (MDA) level, oxygen free-radical scavenging enzymes such as superoxide dismutase (SOD) and catalase (CAT), and glutathione (GSH) and related enzymes, e.g. glutathione reductase (GR), glutathione peroxidase (GPx), gamma glutamyl transpeptidase (GGT) and glutathione-S-transferase (GST) in erythrocytes were assayed. The sanguinarine level in serum was measured by high-performance liquid chromatography. The serum MDA level was higher and the GSH level in erythrocytes was lower in argimone oil poisoning cases than those in controls. There was a significant decrease in SOD and GPx activities in erythrocytes of epidemic dropsy cases but no changes were observed in CAT, GR and GST assay. The depletion of GSH in erythrocytes, serum MDA level and clinical severity were dependent on serum sanguinarine level. The results indicate that sanguinarine (argimone oil) poisoning creates an oxidative stress in humans. The oxidative stress and differential modulation of anti-oxidant enzymes by sanguinarine might play a pathogenic role in epidemic dropsy, which suggests the incorporation of anti-oxidant drugs in the treatment protocol of the disease.