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Visceral leishmaniasis derived from Leishmania donovani is transmitted by sand flies (Phlebotomus argentipes) throughout the Indian subcontinent. Although considered anthroponotic, L. donovani infects other mammals susceptible to sand fly bites, including dogs. Aggressive strategies to reduce sand fly populations in India have led to flies seeking nonhuman hosts, so understanding the role of dogs in L. donovani transmission has become critical. Our study investigated L. donovani infection in dogs and the potential for such infections to be transmitted back to sand flies. We performed xenodiagnosis by using P. argentipes on dogs (n = 73) with quantitative PCR–detectible parasitemia in both endemic and outbreak villages. We found that 12% (9/73) of dogs were infectious to sand flies during winter and rainy seasons. Patients with visceral leishmaniasis remain primary sources of L. donovani transmission, but our findings suggest a possible link between canine infection and human exposure.

Abstract Groundwater poisoning by heavy metals has caused serious health hazards in the exposed population globally. Manganese (Mn) poisoning causing human health hazards is very meagerly reported worldwide. The present research elucidates for the first time the catastrophic effect of manganese causing cancer in the Gangetic plains of Bihar (India). The blood samples of n = 1146 cancer patients were voluntarily obtained for the study, after their consent. Their household water samples were also collected for the study. All the samples were analysed for Mn contamination by Atomic Absorption Spectrophotometer. The study indicates high Mn contamination in the cancer patient blood samples with highest content as 6022 µg/L. Moreover, the cancer patient’s household handpump water samples also contained elevated Mn contamination. The correlation coefficient study finds significant association between Mn contamination in blood of cancer patients and their handpump water. The carcinoma group of cancer patients mostly in Stage III & IV had significant Mn contamination in their blood (above WHO/BIS permissible limit). The geospatial study depicts Mn contamination in handpump water in the state of Bihar in correlation with cancer patient’s blood samples. This novel finding is being reported in India for the first time, which correlates cancer with handpump drinking water. The long-term Mn exposure could be one of the causative agents for elevating cancer incidences. However, other confounding risk factors cannot be denied.

Background: Wireless Holter monitors can be a great alternative to the traditional wired holter monitoring potentially giving better patient outcomes. However, the technology is new and less explored for the quality of ECG wave forms. Objective: This study was taken up to compare the quality of electrocardiogram (ECG) and arrhythmia detection using a traditional Holter and a wireless ambulatory smart ECG – Vigo SmartHeart (VSH) that functions with a Mobile application. Materials and Methods: The present study was cross-sectional in nature. We enrolled the patients indicated for continuous ECG monitoring. All the enrolled patients were connected to VSH wireless Holter solution and a conventional Holter monitor simultaneously. The ECGs generated were compared through descriptive statistics such as mean, standard deviation, and correlation by Pearson’s correlation method. Results: Seventy-one patients had simultaneous ECG recordings by both systems. The Pearson correlation for P wave, QRS, PR, QT, and ST was measured as 0.93, 0.93, 0.99, 0.36, and 0.98, respectively. The minimum heart rate (HR), maximum HR, RR interval, P wave, QRS complex, PR, and ST segments showed a statistically significant correlation between Smart Heart and Conventional Holter. 17 ECG events were reported, of which 14 were detected by both. The events missed by conventional Holter and detected by VSH were Atrioventricular block (2), Supraventricular tachycardia (1), and Intraventricular conduction delay (1). Conclusions: The quality of the report generated by both the methods was comparable to ECG wave quality, However, arrhythmia was picked up by the SmartHeart with better precision compared to conventional Holter. Thus, VSH can serve as a viable and potential alternative tool to screen and help in reducing the morbidity and mortality related to arrhythmias.

Introduction: Coeliac Disease (CD) is a systemic immune disorder caused by gluten in genetically susceptible individuals. A serological screening assay for CD has been designed to detect Immunoglobulin A (IgA) and IgG anti-tissue Transglutaminase (a-tTG) and IgA and IgG Deamidated Gliadin Peptide antibodies (a-DGP) simultaneously. The seronegative gap can be closed when these two antigens are combined on a single solid phase. This is primarily because untreated CD children who are negative for antibodies of one of the antigens may exhibit a positive result for the other. Aim: To determine the diagnostic parameters {sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV)} of tTG-IgA and htTG-DGP (Coeliac fusion- a combination of IgA and IgG to human tTG and synthetic DGP) for the diagnosis of CD in clinically symptomatic children. Materials and Methods: This cross-sectional study was conducted at the Paediatric Outpatient Department (OPD) of Santokhba Durlabhji Memorial Hospital, Jaipur, Rajasthan, India from April 2023 to November 2023. The study population comprised 45 children (age >6 months and

Abstract The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat–maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat–maize rotation is the combined use of nano-fertilizers and conventional fertilizers.

Abstract India is the second-highest contributor to the post-2000 global greening. However, with satellite data, here we show that this 18.51% increase in Leaf Area Index (LAI) during 2001–2019 fails to translate into increased carbon uptake due to warming constraints. Our analysis further shows 6.19% decrease in Net Primary Productivity (NPP) during 2001–2019 over the temporally consistent forests in India despite 6.75% increase in LAI. We identify hotspots of statistically significant decreasing trends in NPP over the key forested regions of Northeast India, Peninsular India, and the Western Ghats. Together, these areas contribute to more than 31% of the NPP of India (1274.8 TgC.year−1). These three regions are also the warming hotspots in India. Granger Causality analysis confirms that temperature causes the changes in net-photosynthesis of vegetation. Decreasing photosynthesis and stable respiration, above a threshold temperature, over these regions, as seen in observations, are the key reasons behind the declining NPP. Our analysis shows that warming has already started affecting carbon uptake in Indian forests and calls for improved climate resilient forest management practices in a warming world.

Introduction: Pain from lower abdominal surgeries originates from the abdominal wall incision. The Transversus Abdominis Plane (TAP) is a fascial plane between the internal oblique and the transversus abdominis muscle, which contains the nerve bundles. TAP block involves infiltrating this plane with anaesthetic drugs that block the somatic component of postoperative pain. Traditionally, the TAP block is given by anaesthesiologists as a blind procedure or under Ultrasound (US) guidance. In 2010, an innovative surgical TAP block method was developed, where the surgeon gives TAP block under direct vision before closing the abdomen during abdominal surgery. Many studies have recommended surgical TAP block as an intervention for achieving postoperative pain relief. Aim: To evaluate the efficacy of the surgical TAP block technique for postoperative analgesia following lower abdominal surgeries using Visual Analogue Scale (VAS) scores and by comparing the need for rescue analgesia and the total amount of analgesic drugs utilised within the first 24 hours of surgery. Materials and Methods: This hospital-based prospective interventional study was conducted in the Department of Obstetrics and Gynaecology at The Oxford Medical College Hospital and Research Centre, Bengaluru, Karnataka, India, from January 2022 to December 2022. The study participants included 108 women undergoing lower abdominal surgeries under spinal or epidural or combined regional anaesthesia and belonging to the American Society of Anaesthesiologists (ASA) physical status classification system ASA I or ASA II or ASA IIE. The study group included 54 women who received surgical TAP block with 20 mL 0.25% bupivacaine and 4 mg of dexamethasone, intraoperatively on either side before closure of the abdomen. Postoperative pain was assessed using VAS at regular intervals within 24 hours of surgery. VAS was also recorded whenever the participants demanded rescue analgesia. The control group included 54 women who received intravenous tramadol 50 mg eight hourly for postoperative pain relief, while the study group received rescue analgesia on demand or if the VAS score was recorded as three or more. The time for the first request for rescue analgesia and the total dose of rescue analgesic required in the first 24 hours after surgery were also recorded. Data were analysed using Statistical Package for Social Sciences (SPSS) version 25.0. For inferential statistics, numerical data were analysed by Chi-square test, and for continuous data, the Student’s t-test was used. A p-value

Background: Snakebite envenoming, a neglected tropical disease (NTD), is an important public health problem that is responsible for more than 1 lakh deaths annually across the world. However, the majority of the data in this regard is from health institutions and data from community settings are scarce. The aim of the current study was to develop valid and reliable qualitative tools for assessing the burden of snakebites and the health-seeking behavior of the community. The tools developed thus will serve in creating a community connection and thereby strengthen primary care teams engaged in managing snakebites at the primary care level. Methods: A four-step design was used; (a) review of the available literature on the burden of disease, tools used to assess the burden, and the guidelines on snakebite (b) development, laying out, and contextualization of questions/items for the tools (c) pilot testing and establishment of validity. Results: A focus group discussion guide, key informant interview schedule for health professionals, community leaders, and traditional faith healers were matured for the implementation. Conclusion: A reliable and valid qualitative tool was developed to discern the speculations related to snakebites and its management in rural field settings.

The complex of methyltransferase-like proteins 3 and 14 (METTL3-14) is the major enzyme that deposits N6-methyladenosine (m6A) modifications on messenger RNA (mRNA) in humans. METTL3-14 plays key roles in various biological processes through its methyltransferase (MTase) activity. However, little is known about its substrate recognition and methyl transfer mechanism from its cofactor and methyl donor S-adenosylmethionine (SAM). Here, we study the MTase mechanism of METTL3-14 by a combined experimental and multiscale simulation approach using bisubstrate analogues (BAs), conjugates of a SAM-like moiety connected to the N6-atom of adenosine. Molecular dynamics simulations based on crystal structures of METTL3-14 with BAs suggest that the Y406 side chain of METTL3 is involved in the recruitment of adenosine and release of m6A. A crystal structure with a BA representing the transition state of methyl transfer shows a direct involvement of the METTL3 side chains E481 and K513 in adenosine binding which is supported by mutational analysis. Quantum mechanics/molecular mechanics (QM/MM) free energy calculations indicate that methyl transfer occurs without prior deprotonation of adenosine-N6. Furthermore, the QM/MM calculations provide further support for the role of electrostatic contributions of E481 and K513 to catalysis. The multidisciplinary approach used here sheds light on the (co)substrate binding mechanism, catalytic step, and (co)product release, and suggests that the latter step is rate-limiting for METTL3. The atomistic information on the substrate binding and methyl transfer reaction of METTL3 can be useful for understanding the mechanisms of other RNA MTases and for the design of transition state analogues as their inhibitors.

Intense cultivation with narrow row spacing in wheat, a common practice in the Indo-Gangetic plains of South Asia, renders the crop more susceptible to lodging during physiological maturity. This susceptibility, compounded by the use of traditional crop cultivars, has led to a substantial decline in overall crop productivity. In response to these challenges, a two-year field study on the system of wheat intensification (SWI) was conducted. The study involved three different cultivation methods in horizontal plots and four wheat genotypes in vertical plots, organized in a strip plot design. Our results exhibited that adoption of SWI at 20 cm × 20 cm resulted in significantly higher intercellular CO2 concentration (5.9-6.3%), transpiration rate (13.2-15.8%), stomatal conductance (55-59%), net photosynthetic rate (126-160%), and photosynthetically active radiation (PAR) interception (1.6-25.2%) over the existing conventional method (plant geometry 22.5 cm × continuous plant to plant spacing) of wheat cultivation. The lodging resistance capacity of both the lower and upper 3rd nodes was significantly higher in the SWI compared to other cultivation methods. Among different genotypes, HD 2967 demonstrated the highest recorded value for lodging resistance capacity, followed by HD 2851, HD 3086, and HD 2894. In addition, adoption of the SWI at 20 cm × 20 cm enhanced crop grain yield by 36.9-41.6%, and biological yield by 27.5-29.8%. Significantly higher soil dehydrogenase activity (12.06 μg TPF g-1 soil hr-1), arylsulfatase activity (82.8 μg p-nitro phenol g-1 soil hr-1), alkaline phosphatase activity (3.11 n moles ethylene g-1 soil hr-1), total polysaccharides, soil microbial biomass carbon, and soil chlorophyll content were also noted under SWI over conventional method of the production. Further, increased root volumes, surface root density and higher NPK uptake were recorded under SWI at 20×20 cm in comparison to rest of the treatments. Among the tested wheat genotypes, HD-2967 and HD-3086 had demonstrated notable increases in grain and biological yields, as well as improvements in the photosynthetically active radiation (PAR) and chlorophyll content. Therefore, adoption of SWI at 20 cm ×20 cm (square planting) with cultivars HD 2967 might be the best strategy for enhancing crop productivity and resource-use efficiency under the similar wheat growing conditions of India and similar agro-ecotypes of the globe.

Abstract Background The complement system functions primarily as a first-line host defense against invading microbes, including viruses. However, the interaction of Hepatitis B virus (HBV) with the complement-components during chronic HBV infection remains largely unknown. We investigated the mechanism by which HBV inhibits the formation of cytolytic complement membrane-attack complex (MAC) and studied its impact on MAC-mediated microbicidal activity and disease pathogenesis. Methods Blood/liver tissues were collected from chronically HBV-infected patients and controls. HepG2hNTCP cells were infected with HBV particles and Huh7 cells were transfected with full-length linear HBV-monomer or plasmids containing different HBV-ORFs and expression of complement components or other host genes were evaluated. Additionally, ELISA, Real-time PCR, Western blot, bioinformatics analysis, gene overexpression/knock-down, mutagenesis, chromatin immunoprecipitation, epigenetic studies, immunofluorescence, and quantification of serum HBV-DNA, bacterial-DNA and endotoxin were performed. Results Among the MAC components (C5b-C9), significant reduction was noted in the expression of C9, the major constituent of MAC, in HBV-infected HepG2hNTCP cells and in Huh7 cells transfected with full-length HBV as well as HBX. C9 level was also marked low in sera/liver of chronic hepatitis B (CHB) and Immune-tolerant (IT) patients than inactive carriers and healthy controls. HBX strongly repressed C9-promoter activity in Huh7 cells but CpG-island was not detected in C9-promoter. We identified USF-1 as the key transcription factor that drives C9 expression and demonstrated that HBX-induced hypermethylation of USF-1-promoter is the leading cause of USF-1 downregulation that in turn diminished C9 transcription. Reduced MAC formation and impaired lysis of HBV-transfected Huh7 and bacterial cells were observed following incubation of these cells with C9-deficient CHB sera but was reversed upon C9 supplementation. Significant inverse correlation was noted between C9 concentration and HBV-DNA, bacterial-DNA and endotoxin content in HBV-infected patients. One-year Tenofovir therapy resulted in improvement in C9 level and decline in viral/bacterial/endotoxin load in CHB patients. Conclusion Collectively, HBX suppressed C9 transcription by restricting the availability of USF-1 through hypermethylation of USF-1-promoter and consequently hinder the formation and lytic functions of MAC. Early therapy is needed for both CHB and IT to normalize the aberrant complement profile and contain viral and bacterial infection and limit disease progression.

Background: COVID-19 is an emerging and rapidly evolving situation globally, and it poses additional burden for emergency health care services especially the transfusion medicine and the need of an hour to safeguard our regular blood donors. Aim and Objectives: The study aims to find out the proportion of COVID-19 infection among blood donors and non-blood donors (NBDs) and to assess their behavioral risk factors that predispose to COVID-19. Materials and Methods: A case-control study was conducted among regular blood donors and non-blood donors at the department of transfusion medicine attached to tertiary care hospital with an objective to find out the proportion of COVID-19 status and the risk factors associated with its occurrence. Results: Total of 834 participants involved in our study. Accordingly, we found the proportion of COVID-19 to be 9% among regular blood donors and 2% among NBDs. A significant association was noted with regular going out, co-morbidities, B positive blood group and perceived stress as the risk factors in regular blood donors. Moreover, among NBDs maintaining social distancing and regular washing of hands/use of sanitizers were significant factors. Conclusions: The novelty of this study helps to remake our policies concerned mainly on the protection of our potentially emergency service providers against COVID-19 infection.

Background: The different ambient temperatures of the upper and lower respiratory tract could influence the replication kinetics of the virus. Objective: This study is aimed to evaluate the effect of steam inhalation on clinical progression of COVID-19 and its subsequent impact on viral load that was evaluated in patients. Materials and Methods: A randomized control trial in mildly infected COVID-19 was undertaken. The participants were randomized either to standard treatment plus steam inhalation (test, n = 22) or standard treatment alone (control, n = 22). Steam inhalation was continued for 20 min thrice daily for 10 days. The first reverse transcription polymerase chain reaction swab was collected on day 1 before steam inhalation and the second swab was obtained after its completion on the fourth day. In the control group, the swabs were collected at the matched time-points. The clinical progression of disease and the need of oxygen therapy were observed for 10 days. Reductions in cycle-threshold levels were assessed at the completion of 4 days of steam treatment. Results: Only one patient from the test group and six patients from the control group progressed to moderate disease. No patient from the steam group required oxygen therapy, whereas three patients from the control group needed it. The median cycle-threshold levels pertaining to N-gene, E-gene, and RNA-dependent RNA polymerase, respectively, were nonsignificant. All the patients showed clinical recovery. Conclusions: The clinical trends support the use of steam therapy as add on over standard treatment in mildly infected COVID-19 patients.

Introduction: Vaccination against the global pandemic coronavirus disease 2019 (COVID-19) is a promising way out of the havoc caused by the disease. The clinico-radiological profile of COVID-19 patients in relation to the vaccination status is depicted in the present study. Materials and Methods: This is a retrospective observational imaging and hospital data-based study performed on 214 confirmed and clinically suspicious patients of COVID-19 who underwent high-resolution computed tomography (HRCT) scan of the thorax at the Department of Radio-Diagnosis of a tertiary medical center in the Himalayan foothills. The present study aims to evaluate the effect of vaccination on HRCT findings of COVID-19 populations. Results: Forty-three percent of the non-vaccinated population presented with severe HRCT scores (19–25) in comparison to only 11.5% of the study population who had taken both doses of vaccine (P = 0.018). Two doses of vaccination had a negative Pearson correlation coefficient with severe HRCT scores (–0.146). Co-morbidities had a significant correlation with HRCT severity score, with 61.5% diabetics and 63.33% of hypertensive patients showing scores >19 on HRCT. Conclusion: Vaccination proves to be a game changer in the pandemic with two doses of vaccination having a significant negative correlation with COVID-19-induced severe pneumonitis on HRCT of the thorax.

One of the biggest challenges to be addressed in world agriculture is low nitrogen (N) use efficiency (

Barley is considered as a foundation of the brewing and malting industry. Varieties with superior malt quality traits are required for efficient brewing and distillation processes. Among these, the Diastatic Power (DP), wort-Viscosity (VIS), β-glucan content (BG), Malt Extract (ME) and Alpha-Amylase (AA) are controlled by several genes linked to numerous quantitative trait loci (QTL), identified for barley malting quality. One of the well-known QTL, QTL2, associated with barley malting trait present on chromosome 4H harbours a key gene, called as HvTLP8 that has been identified for influencing the barley malting quality through its interaction with β-glucan in a redox-dependent manner. In this study, we examined to develop a functional molecular marker for HvTLP8 in the selection of superior malting cultivars. We first examined the expression of HvTLP8 and HvTLP17 containing carbohydrate binding domains in barley malt and feed varieties. The higher expression of HvTLP8 prompted us to further investigate its role as a marker for malting trait. By exploring the 1000 bp downstream 3' UTR region of HvTLP8, we found single nucleotide polymorphism (SNP) in between Steptoe (feed variety) and Morex (malt variety), which was further validated by Cleaved Amplified Polymorphic Sequence (CAPS) marker assay. Analysis of 91 individuals from the Steptoe x Morex doubled haploid (DH) mapping population revealed CAPS polymorphism in HvTLP8. Highly significant (p

Introduction: It is a common practice to keep a patient ‘nil’ per oral, till the return of bowel sounds, after any laparotomy. Enhanced Recovery After Surgery (ERAS) society, now recommends evidenced-based guidelines for postoperative early oral feeding after an uncomplicated Caesarean Delivery (CD), as opposed to the delayed (conventional) initiation of oral feeds. Aim: To compare the effects of early feeding versus delayed oral feeding in women undergoing CD. Materials and Methods: This prospective comparative study was conducted in Department of Obstetrics and Gynaecology at MVJ Medical College and Research Hospital, Bengaluru, Karnataka, India, from November 2020 to October 2021. Total of 148 women with uncomplicated singleton pregnancy undergoing CD, under spinal anaesthesia, were allocated into two groups. Early Feeding group (n=70) (EF) where feeding was started within 2-8 hours of surgery and Delayed Feeding group (n=78) (DF) where feeding was started between 18-24 hours of CD. The outcome measures were maternal satisfaction, and the effect on gastrointestinal function (return of bowel sounds, passage of flatus and stool), mobilisation of patient and complications in postoperative period. Student’s t-test and Chi-square test were used as appropriate, and p-value

Objectives We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India.Design A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data.Setting National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status.Participants Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district.Outcome measures We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015.Results The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra.Conclusion TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.

Abstract Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C–C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-μL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson’s trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA.

Background: Sickness absenteeism is a potential epidemiological issue leading to loss of productivity in addition to increasing the cost of health care and provides a major tool in enhancing occupational health care preventive strategies. Aim and Objectives: To determine the prevalence of sickness absenteeism and their associated factors among Industrial Workers of Pharmaceutical Manufacturing industries in Hyderabad. Materials and Methods: A cross sectional study was taken up among 160 Workers at two Pharmaceutical Manufacturing companies in Hyderabad using simple random sampling technique. Data included Individual, Occupational and Organizational factors influencing their sickness absenteeism and general health conditions in the past six months through camp based approach. Data was analysed using descriptive statistics and multinomial logistic regression analysis to predict the variables associated with the outcome. Results: The prevalence of sickness absenteeism was found among 19% of the workers. Common causes were due to sickness among 25(84%) and social responsibilities among 5(16%). On multinomial logistic regression analysis- poor superior relationships, poor co-workers relationship and high mental stress were found to be significant. Conclusion: Sickness absenteeism was found to be high which can be reduced by improving relationships with superiors and co-workers and also by reducing mental stress among the workers.

Abstract Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving $$\hbox {TNF}_{\alpha }$$ TNF α , IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of $$\hbox {TNF}_{\alpha }$$ TNF α , IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of $$\hbox {TNF}_{\alpha }$$ TNF α would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.

The World Health Organization defined palliative care as “an approach that improves the quality of life of patients and their families facing the problems associated with life threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. The patient centric primary care model (PCCM) promises to provide a solution to control these health-care challenges. The model is largely based on the chronic care model (CCM) and the model developed by the Organized Medicine Academic Guild (OMAG) for delivering health care in India.

Introduction Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.Methods and analysis The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery—(extended) pleurectomy decortication—versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.Ethics and dissemination Research ethics approval was granted by London – Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.Trial registration numbers ISRCTN—ISRCTN44351742 and ClinicalTrials.gov—NCT02040272.

We have previously demonstrated that endothelial targeting of gold nanoparticles followed by external beam irradiation can cause specific tumor vascular disruption in mouse models of cancer. The induced vascular damage may lead to changes in tumor physiology, including tumor hypoxia, thereby compromising future therapeutic interventions. In this study, we investigate the dynamic changes in tumor hypoxia mediated by targeted gold nanoparticles and clinical radiation therapy (RT). By using noninvasive whole-body fluorescence imaging, tumor hypoxia was measured at baseline, on day 2 and day 13, post-tumor vascular disruption. A 2.5-fold increase (P

Background: The incidence of coronary artery disease (CAD) has risen considerably in developing world due to industrialization, urbanisation and lifestyle changes, especially among Indians and South Asians. The onset of CAD has been seen to occur at an early age and the severity of the disease and mortality associated with CAD has also increased. The pathology of atherosclerosis needs to be re-evaluated to develop targeted therapy which can contain the disease process at the earliest stage. Aims and Objectives: Most of the morphological studies on atherosclerosis have been done on autopsy cases. In this study, we have analysed the morphological spectrum of atherosclerotic lesions in live patients. Materials and Methods: We retrospectively analysed the histopathology slides of 85 cases whose endarterectomy plaques were received in the Department of Pathology over a period of three and half years (January 2014 to June 2017) and classified the lesions according to Modified American Heart Association classification of atherosclerosis. Results: The average age of patients was 60 years and male to female ratio of 4.3:1. Left anterior descending artery was the commonest vessel involved (52.4%). Majority of the cases had fibrocalcific plaques,followed by fibrous cap atheroma and calcified nodules. Conclusion: Coronary artery plaques were found even in patients less than 40 years old. Aggressive lipid defense therapy needs to be the cornerstone of management of CAD.

Background: Provision of multitude of medical services under one roof is a norm in modern hospitals. However, in many service hospitals, psychiatric services are still confined within the premises of psychiatric wards. Due to the social stigma attached to psychiatric care many psychiatric patients avoid visiting the psychiatric ward for mental health care. The main objective of this study was to improve attendance in the psychiatric outpatient department (OPD) by making it accessible and acceptable for the clientele in a busy multispecialty service hospital. Materials and Methods: This retrospective study was carried out from January 1, 2009, to December 31, 2010. During the 1st year of the study (i.e., 2009), psychiatry OPD services continued in the psychiatry ward. From January 1, 2010, psychiatric OPD was shifted to polyclinic with a new name as “Department of behavioral sciences and deaddiction.” The data for the year 2009 and 2010 were compared using the Chi-square test. Results: There was a significant rise in the total number of new OPD patients from 522 to 1779 (P < 0.05) in 2010. Among various age groups, in 41–50 years of age group (144 [27.6%] vs. 574 [32.26%], P < 0.05) and those above 70 years (12 [2.29%] vs. 96 [5.39%], P < 0.05) the rise was highly significant. There was a significant increase in the number of patients with substance abuse (38 [7.27%] vs. 188 [10.56%], P < 0.05) and childhood and adolescent psychiatric disorders (42 [8.04%] vs. 213 [11.97%], P < 0.05). Conclusion: Amalgamation of psychiatric OPD services with other specialist OPD services in service hospital resulted in better utilization of psychiatric services.

Background: Preference for a male child by the family leading to a sex-selective abortion has been a leading factor for the skewed sex ratio in India. This has long-term social and demographic consequences. The present study was conducted with the aim to assess the awareness and attitudes regarding prenatal sex determination and preconception and prenatal diagnostic technique act (PC-PNDT) among females of reproductive age group (15–45 years) attending a tertiary care teaching hospital in Jammu district of J and K state in North India. Materials and Methods: A hospital-based cross-sectional study was carried out among 210 females of reproductive age group. The study participants were administered a predesigned and pretested questionnaire. Data thus obtained were analyzed using SPSS Version 20.0 and expressed in percentages. Chi-square test was used as test of statistical significance with P < 0.05 taken as statistically significant. Results: Awareness about sex determination among respondents was 94%. Higher proportion of urban respondents knew about ultrasound as the technique for sex determination than their rural counterparts (P < 0.05). Awareness regarding the PC-PNDT act and determination of sex of a child being a crime was higher among urban respondents (P < 0.05). Among the attitude, more rural females would prefer to know the sex of the child (P < 0.05) than their urban counterparts. Conclusion: Respondents had high awareness about sex determination as well as technique used for it. Awareness about PC-PNDT act was on the lower side. Education programs for the women about gender equality and wider publicity of the act in the mass media need to be scaled up.

Background: Studies suggest that approximately half of patients with raised blood pressure (BP) are undetected, that half of those detected are not treated, and that half of those treated are not controlled, famously described as the “rule of halves.” Importantly, the cornerstone of the primary prevention of cardiovascular diseases is early detection and drug treatment (antihypertensive) of patients with high BP. Studies across populations in developed world have shown that awareness and management of high BP levels are far from optimal. The present study was planned with the aim to assess the knowledge, attitude, and practices (KAP) regarding hypertension in hypertensive patients visiting Tertiary Care Hospital in North-West India. Materials and Methods: Already diagnosed hypertensive patients seeking care at the tertiary care center were selected for this study. The participants were recruited using consecutive sampling technique. All participants were interviewed with the help of a semi-structured questionnaire after obtaining a written informed consent. The components of the KAP were recorded using a score sheet. Results: In all, 394 hypertensive patients of whom majority (239/394; 61%) were males, were included in the study. The KAP score among the study subjects was 88.4%, 90.83%, and 95.83%, respectively. Males had higher knowledge about normal BP levels which was statistically significant (P < 0.01). Among the attitude, regular intake of anti-hypertensive drugs, regular investigations, lifestyle changes, avoidance of salt and allopathic medicines being the best for the treatment of hypertension were found to be significant statistically (P < 0.01). Conclusion: The high score among the study population can be attributed to the fact that all study participants were diagnosed patients of hypertension seeking care in a tertiary care hospital.

[This corrects the article DOI: 10.1371/journal.pone.0213702.].

Disconnected interacting protein 2 homolog A (DIP2A) is highly expressed in nervous system and respiratory system of developing embryos. However, genes regulated by Dip2a in developing brain and lung have not been systematically studied. Transcriptome of brain and lung in embryonic 19.5 day (E19.5) were compared between wild type and Dip2a-/- mice. An average of 50 million reads per sample was mapped to the reference sequence. A total of 214 DEGs were detected in brain (82 up and 132 down) and 1900 DEGs in lung (1259 up and 641 down). GO enrichment analysis indicated that DEGs in both Brain and Lung were mainly enriched in biological processes 'DNA-templated transcription and Transcription from RNA polymerase II promoter', 'multicellular organism development', 'cell differentiation' and 'apoptotic process'. In addition, COG classification showed that both were mostly involved in 'Replication, Recombination, and Repair', 'Signal transduction and mechanism', 'Translation, Ribosomal structure and Biogenesis' and 'Transcription'. KEGG enrichment analysis showed that brain was mainly enriched in 'Thyroid cancer' pathway whereas lung in 'Complement and Coagulation Cascades' pathway. Transcription factor (TF) annotation analysis identified Zinc finger domain containing (ZF) proteins were mostly regulated in lung and brain. Interestingly, study identified genes Skor2, Gpr3711, Runx1, Erbb3, Frmd7, Fut10, Sox11, Hapln1, Tfap2c and Plxnb3 from brain that play important roles in neuronal cell maturation, differentiation, and survival; genes Hoxa5, Eya1, Errfi1, Sox11, Shh, Igf1, Ccbe1, Crh, Fgf9, Lama5, Pdgfra, Ptn, Rbp4 and Wnt7a from lung are important in lung development. Expression levels of the candidate genes were validated by qRT-PCR. Genome wide transcriptional analysis using wild type and Dip2a knockout mice in brain and lung at embryonic day 19.5 (E19.5) provided a genetic basis of molecular function of these genes.

BackgroundTo understand the underlying mechanisms of cardiac dysfunction in cancer, we examined cardiac function, protein synthesis, mitochondrial function and gene expression in a model of heart failure in mice injected with Lewis lung carcinoma (LLC1) cells.Experimental designSeven week-old C57BL/J6 male and female mice were injected with LLC1 cells or vehicle. Cardiac ejection fraction, ventricular wall and septal thickness were reduced in male, but not female, tumor-bearing mice compared to vehicle-injected control mice. Cardiac protein synthesis was reduced in tumor-bearing male mice compared to control mice (p = 0.025). Aspect ratio and form factor of cardiac mitochondria from the tumor-bearing mice were increased compared control mice (p = 0.042 and p = 0.0032, respectively) indicating a more fused mitochondrial network in the hearts of tumor-bearing mice. In cultured cardiomyocytes maximal oxygen consumption and mitochondrial reserve capacity were reduced in cells exposed to tumor cell-conditioned medium compared to non-conditioned medium (p = 0.0059, p = 0.0010). Whole transcriptome sequencing of cardiac ventricular muscle from tumor-bearing vs. control mice showed altered expression of 1648 RNA transcripts with a false discovery rate of less than 0.05. Of these, 54 RNA transcripts were reduced ≤ 0.5 fold, and 3 RNA transcripts were increased by ≥1.5-fold in tumor-bearing mouse heart compared to control. Notably, the expression of mRNAs for apelin (Apln), the apelin receptor (Aplnr), the N-myc proto-oncogene, early growth protein (Egr1), and the transcription factor Sox9 were reduced by >50%, whereas the mRNA for growth arrest and DNA-damage-inducible, beta (Gadd45b) is increased >2-fold, in ventricular tissue from tumor-bearing mice compared to control mice.ConclusionsLung tumor cells induce heart failure in male mice in association with reduced protein synthesis, mitochondrial function, and the expression of the mRNAs for inotropic and growth factors. These data provide new mechanistic insights into cancer-associated heart failure that may help unlock treatment options for this condition.

ObjectivesVitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity.Material and methodsPrimary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities.ResultsEighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (ConclusionOn-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short.

Introduction: An extensive search on PubMed reveals very little in terms of evidence regarding the current knowledge, attitude, and practices (KAP) of the population in general and rural population, in particular, in this part of the country. Therefore, a study was conducted with the aim to assess the communities′ knowledge of malaria transmission, recognition of signs and symptoms, treatment seeking. Materials and Methods: A stratified two-stage design was used to conduct a house-to-house survey using a semi-structured questionnaire in RS Pura block of Jammu District of Jammu and Kashmir State in North India. Results: A total of 300 households were included in the study. However, data on 4 households was found to be incomplete at the time of analysis and, therefore, were excluded. Out of 296 study participants interviewed 65.5% were males, while 34.5% females. All of the study participants (100%) had heard of malaria, and the main source of their information was television/newspaper. 92.5% of the study population considered malaria to be a serious health problem, thus reflecting their attitude to the disease. Regarding practices, 71.6% of the study participants preferred going to doctors at government hospitals for malaria treatment, and 56% were willing to seek medical help in

Introduction: Chronic respiratory diseases are an important cause of disability across the globe. The global burden of these diseases is showing a discernible upward trend. It is estimated that 500 million people suffer from them. Materials and Methods: The study was conducted with the aim to estimate the prevalence of chronic obstructive pulmonary disease (COPD) in a rural Indian population. For this, a population-based survey was conducted using modified British Medical Research Council questionnaire. This was followed by subjecting the respondents to Wright's mini peak flow meter to find out the peak expiratory flow rate to diagnose the COPD cases. Results: The prevalence of chronic bronchitis, bronchial asthma, and COPD was found to be 3.36%, 1.18%, and 4.21%, respectively. Conclusions: Chronic respiratory disorders are more prevalent among rural adults hinting to a rural-urban divide. Therefore, the focus of preventive strategies should take into account this difference.

Introduction: Iodine deficiency disorder remains one of the major public health problems, despite it being easily preventable. Initially thought as the disorder of Himalayan goiter belt, the disorder has been found to have a pan-India presence. The study was planned with the aim to assess the prevalence of goiter among 6–12 years school-going children and to identify levels of iodine in salt consumed at the household level in the study area. Materials and Methods: The study was conducted among 3955 school-going (2162 children from Rajouri and 1793 children from Poonch) children age 6–12 years in Rajouri and Poonch districts of Jammu Province. The children were examined clinically to detect and grade the goiter. Salt samples were collected from subsample (n = 400) to estimate iodine content in the salt. Results: The prevalence of goiter in the study population was found to be 18.87% and 9.70% in Rajouri and Poonch districts, respectively. Goiter prevalence was higher in 9–12 years age group as compared to 6–9 years age group and the difference in goiter prevalence in males of these two age groups was statistically significant (P = 0.02). Estimation of iodine content of the salt samples revealed that all of them (100%) had adequate iodine content. Conclusion: Despite the implementation of Universal Iodization Program and adequate content of iodine in salt consumed by the families, the goiter prevalence in both the districts is high. The future research should focus on identifying the reasons for this high prevalence.

Introduction: Dengue and chikungunya are Aedes mosquitoborne viral diseases of major public health concern in India. Recently, there is a gradual rise in number of dengue and chikungunya positive cases in various states of Northern India and a similar emergence and increase of dengue positive cases has been observed in Jammu since 2011. Among the mosquitoborne diseases dengue has become a regular seasonal disease while chikungunya has recently emerged in 2016 and Zika the third aedes borne viral infection is needed to be under surveillance under national guidelines. Aim: To report the emergence of chikungunya and analyse the status and pattern of dengue over a period of one year along with serosurveillance of Zika which was done under Central Government guidelines. Materials and Methods: A total of eight hundred eight (808) samples from patients suspected of dengue infection over a period of one year from January 2016 to December 2016 from all the districts of Jammu Province, were tested serologically at our tertiary care centre for dengue NS1 antigen and IgM anti - dengue antibodies. Besides three clinical suspects of chikungunya, 167 dengue (7 positive and 160 negative) sera were tested by National Institute of Virology (NIV) CHIK IgM Capture ELISA, as there is an overlap of clinical symptoms. For Zika testing, the stored negative samples of dengue and Chikungunya (215) were sent to NIV Pune. Results: Recurring dengue infection with periodic upsurge since last few years and emergence of chikungunya was reported in Jammu region. Of the 808 sera tested for dengue and 170 tested for chikungunya, 17.82% and 18.2% were positive respectively. The results for Zika testing were negative. The association of dengue on the basis of sex was found to be highly significant (p=0.009276). Conclusion: In the absence of specific treatment and vaccine for dengue and chikungunya fever, early diagnosis is important in the management of these infections. This also demands continuous seroepidemiological surveillance of the locally prevalent and emerging arthropod borne infections for timely formulation and implementation of effective arboviral control programme.

Mycobacterium tuberculosis (Mtb) expresses a broad-spectrum β-lactamase (BlaC) that mediates resistance to one of the highly effective antibacterials, β-lactams. Nonetheless, β-lactams showed mycobactericidal activity in combination with β-lactamase inhibitor, clavulanate (Clav). However, the mechanistic aspects of how Mtb responds to β-lactams such as Amoxicillin in combination with Clav (referred as Augmentin [AG]) are not clear. Here, we identified cytoplasmic redox potential and intracellular redox sensor, WhiB4, as key determinants of mycobacterial resistance against AG. Using computer-based, biochemical, redox-biosensor, and genetic strategies, we uncovered a functional linkage between specific determinants of β-lactam resistance (e.g. β-lactamase) and redox potential in Mtb. We also describe the role of WhiB4 in coordinating the activity of β-lactamase in a redox-dependent manner to tolerate AG. Disruption of WhiB4 enhances AG tolerance, whereas overexpression potentiates AG activity against drug-resistant Mtb. Our findings suggest that AG can be exploited to diminish drug-resistance in Mtb through redox-based interventions.

OBJECTIVES:To evaluate the performance and treatment profile of advanced EML4-ALK positive Non-small cell lung cancer (NSCLC) patients in a developing country with potentially restricted access to Crizotinib. MATERIALS AND METHODS:A retrospective analysis of advanced ALK positive NSCLC patients who were treated from June 2012 to September 2015 was conducted. The primary goal was to evaluate outcomes of advanced ALK positive NSCLC in our practice and examine the logistic constraints in procuring Crizotinib. RESULTS:94 patients were available for analysis. 21 (22.3%) patients were started on Crizotinib upfront, 60 (63.8%) on chemotherapy, 10 (10.6%) on Tyrosine kinase inhibitors (in view of poor PS) and 3 (3.2%) patients were offered best supportive care. Reasons for not starting Crizotinib upfront included symptomatic patients needing early initiation of therapy (23.3%), ALK not tested upfront (23.3%) and financial constraints (21.9%). 69 patients (73.4%) received Crizotinib at some stage during treatment. Dose interruptions (> 1 week) with Crizotinib were seen in 20 patients (29%), with drug toxicity being the commonest reason (85%). Median Progression free survival (PFS) on first line therapy for the entire cohort was 10 months, with a significant difference between patients receiving Crizotinib and those who did not ever receive Crizotinib (10 months vs. 2 months, p = 0.028). Median Overall Survival (OS) was not reached for the entire cohort, with 1 year survival being 81.2%. Patients with an ECOG Performance Status (PS) of >2 had a significantly reduced PFS compared to patients with PS < = 2 (1.5 months vs. 11 months, p< 0.001). 47 patients with financial constraints (68.1%) received Crizotinib completely free via various extramural support schemes. CONCLUSION:A majority of our ALK positive NSCLC patients were exposed to Crizotinib through the help of various support mechanisms and these patients had similar outcomes to that reported from previously published literature.

For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of

Disconnected (disco)-interacting protein 2 homolog A is a member of the DIP2 protein family encoded by Dip2a gene. Dip2a expression pattern has never been systematically studied. Functions of Dip2a in embryonic development and adult are not known. To investigate Dip2a gene expression and function in embryo and adult, a Dip2a-LacZ mouse model was generated by insertion of β-Gal cDNA after Dip2a promoter using CRISPR/Cas9 technology. Dip2a-LacZ mouse was designed to be a lacZ reporter mouse as well as a Dip2a knockout mouse. Heterozygous mice were used to study endogenous Dip2a expression and homozygotes to study DIP2A-associated structure and function. LacZ staining indicated that Dip2a is broadly expressed in neuronal, reproductive and vascular tissues, as well as in heart, kidney, liver and lung. Results demonstrate that Dip2a is expressed in ectoderm-derived tissues in developing embryos. Adult tissues showed rich staining in neurons, mesenchymal, endothelial, smooth muscle cells and cardiomyocytes by cell types. The expression pattern highly overlaps with FSTL1 and supports previous report that DIP2A to be potential receptor of FSTL1 and its protective roles of cardiomyocytes. Broad and intense embryonic and adult expression of Dip2a has implied their multiple structural and physiological roles.

Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined.In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)2D, 24,25-dihydroxyvitamin D (24,25(OH)2D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls.Serum Ca and 1,25(OH)2D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)2D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)2D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)2D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)2D, were not observed. 1,25(OH)2D concentrations associated more weakly with FGF-23 in SF compared with C (P

Arteriovenous fistulas (AVFs) used for hemodialysis fail because of venous neointimal hyperplasia (VNH). There are 1,500,000 patients that have end stage renal disease worldwide and the majority requires hemodialysis. In the present study, the role of the intermediate early response gene X-1 (IEX-1), also known as IER-3 in the pathogenesis of VNH was evaluated. In human samples removed from failed AVF, there was a significant increase in IEX-1 expression localized to the adventitia. In Iex-1-/- mice and wild type (WT) controls, chronic kidney disease was induced and an AVF placed 28 days later by connecting the carotid artery to jugular vein. The outflow vein was removed three days following the creation of the AVF and gene expression analysis demonstrated a significant decrease in vascular endothelial growth factor-A (Vegf-A) and monocyte chemoattractant protein-1 (Mcp-1) gene expression in Iex-1-/- mice when compared to WT mice (P

Iron-Sulfur (Fe-S) proteins are involved in many biological functions such as electron transport, photosynthesis, regulation of gene expression and enzymatic activities. Biosynthesis and transfer of Fe-S clusters depend on Fe-S clusters assembly processes such as ISC, SUF, NIF, and CIA systems. Unlike other eukaryotes which possess ISC and CIA systems, amitochondriate Entamoeba histolytica has retained NIF & CIA systems for Fe-S cluster assembly in the cytosol. In the present study, we have elucidated interaction between two proteins of E. histolytica CIA system, Cytosolic Fe-S cluster deficient 1 (Cfd1) protein and Nucleotide binding protein 35 (Nbp35). In-silico analysis showed that structural regions ranging from amino acid residues (P33-K35, G131-V135 and I147-E151) of Nbp35 and (G5-V6, M34-D39 and G46-A52) of Cfd1 are involved in the formation of protein-protein complex. Furthermore, Molecular dynamic (MD) simulations study suggested that hydrophobic forces surpass over hydrophilic forces between Nbp35 and Cfd1 and Van-der-Waal interaction plays crucial role in the formation of stable complex. Both proteins were separately cloned, expressed as recombinant fusion proteins in E. coli and purified to homogeneity by affinity column chromatography. Physical interaction between Nbp35 and Cfd1 proteins was confirmed in vitro by co-purification of recombinant Nbp35 with thrombin digested Cfd1 and in vivo by pull down assay and immunoprecipitation. The insilico, in vitro as well as in vivo results prove a stable interaction between these two proteins, supporting the possibility of its involvement in Fe-S cluster transfer to target apo-proteins through CIA machinery in E. histolytica. Our study indicates that initial synthesis of a Fe-S precursor in mitochondria is not necessary for the formation of Cfd1-Nbp35 complex. Thus, Cfd1 and Nbp35 with the help of cytosolic NifS and NifU proteins can participate in the maturation of non-mitosomal Fe-S proteins without any apparent assistance of mitosomes.

BACKGROUND/AIMS: HBV has been classified into ten genotypes (A-J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura. METHODS: From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes. RESULTS: HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1-D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation. CONCLUSIONS: IndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to North-East India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia.

KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95%CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95%CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95%CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application.