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Introduction: Among the increasing number of cancer cases, colorectal cancer (CRC) cases are rising globally. The association of zinc in the neoplastic process of CRC is a major research avenue, yet the published reports have not provided any definitive conclusion. Objectives: We examined the association between serum zinc levels and CRC to test the potential of zinc dysregulation as a CRC susceptibility factor. Methods: In this systemic review and meta-analysis, we extensively searched EBSCOhost, EMBASE, Cochrane Library, ProQuest, PubMed/MEDLINE, Scopus, and Web of Science as well as manual screening by subject experts for studies reporting serum/plasma/blood zinc levels in CRC patients and control subjects till 27th August 2023. Based on a random effect model, we estimated the mean difference in serum/plasma/blood zinc levels between CRC cases and control subjects. Subgroup differences and publication bias were also investigated, along with a critical appraisal of included studies. Results: Eighteen studies with 8330 participants were included. The difference in serum zinc between CRC patients and control subjects was –5.01 µg/dl [95 % CI: −21.76 to 11.74; p = 0.56]. Omitting a highly influential outlier study, made this difference statistically significant at –13.28 µg/dl [95 % CI: −20.66 to -5.90, p < 0.01]. The difference between study effects could not be explained by the difference in analytical methods for zinc assessment, or type of blood samples. Conclusion: CRC patients had lower serum zinc levels. Some factors, such as different tumor grades of CRC, adenomas, and colonic polyps need to be further considered for a more conclusive association between serum zinc levels and risk for CRC.

Summary: We have purified Peptidase M84 from Bacillus altitudinis in an effort to isolate anticancer proteases from environmental microbial isolates. This metallo-protease had no discernible impact on normal cell survival, but it specifically induced apoptosis in ovarian cancer cells. PAR-1, a GPCR which is reported to be overexpressed in ovarian cancer cells, was identified as a target of Peptidase M84. We observed that Peptidase M84 induced PAR-1 overexpression along with activating its downstream signaling effectors NF-κB and MAPK to promote excessive reactive oxygen species (ROS) generation. This evoked apoptotic death of the ovarian cancer cells through the intrinsic route. In in vivo set-up, weekly intraperitoneal administration of Peptidase M84 in syngeneic mice significantly diminished ascites accumulation, increasing murine survival rates by 60%. Collectively, our findings suggested that Peptidase M84 triggered PAR-1-mediated oxidative stress to act as an apoptosis inducer. This established Peptidase M84 as a drug candidate for receptor mediated targeted-therapy of ovarian cancer.

BackgroundHuman monkeypox (mpox) disease is a multicountry outbreak driven by human–human transmission which has resulted in an international public health emergency. However, there is limited evidence on the positivity rate of skin lesions for mpox viral DNA. We aim to fill this gap by estimating the pooled positivity rate of skin samples with mpox viral DNA from mpox patients globally.MethodsIn this systematic review and meta-analysis, seven databases and several preprint servers have been extensively searched until 17 January 2023 according to a prospectively registered protocol (PROSPERO: CRD42023392505). Articles including the positivity rate of skin samples with mpox viral DNA in mpox-confirmed patients were considered eligible. After a quality assessment, a random-effect meta-analysis was used for pooled prevalence. To explore and resolve heterogeneity, we used statistical methods for outlier detection, influence analysis, and sensitivity analysis.FindingsAmong the 331 articles retrieved after deduplication, 14 studies were finally included. The pooled positivity rate of the skin samples was 98.77% (95% CI: 94.74%–99.72%). After the removal of an influential outlier, I2 for heterogeneity dropped from 92.5% to 10.8%. Meta-regression did not reveal any significant moderator.Conclusion/interpretationThe present findings reinforce that skin lesions act as a reservoir of mpox viral DNA and contribute to a high infectivity risk. This may be a prevailing basis of prompt transmission during the current multicountry outbreak and also needs further investigation. The present imperative outcome may benefit in producing valuable preventive and management procedures in an appropriate health strategy.

Introduction: Musculoskeletal tuberculosis is a significant form of extra pulmonary tuberculosis (EPTB) which has substantial consequences if not diagnosed and treated early. Reliable and rapid confirmation of the diagnosis is now possible by advent of Polymerase Chain Reaction (PCR), Cartridge Based Nucleic Acid Amplification Test (CB-NAAT/Gene-Xpert) and radiometric method (BACTEC) However, most of these sensitive technologies are not available at places with constrained resources. Hence, diagnosis of tuberculosis at these places, continues to rely on smear microscopy using Ziehl-Neelsen (ZN) staining. Specificity of ZN staining and microscopy is high, but its overall sensitivity is variable (20-53%). Despite of low sensitivity, it is still an easy, cheap, efficient and accessible tool due to its high specificity. Aim: Aim of the present study was to assess the role of ZN staining in diagnosis of extra-spinal musculoskeletal tuberculosis in resource limited settings. Material and methods: A retrospective study was done from 1st January 2016 to 31st December 2019 on specimens received in microbiology laboratory for ZN staining from clinico-radiologically suspected cases of extra-spinal musculoskeletal tuberculosis. The clinical information of the cases was noted from the Orthopaedics Department case files, while results of ZN microscopy were retrieved from the records maintained in Microbiology Department. Results: Specimens from 95 patients with clinico-radiologically suspected extra-spinal musculoskeletal tuberculosis were examined for Acid Fast Bacillus (AFB) by ZN staining technique. Out of 95 patients; 11 patients (11.58 %) were found to be AFB positive. Conclusion: Owing to low yield percentage of ZN staining in extra spinal musculoskeletal tuberculosis; ZN stain alone cannot be used as a tool for diagnosis of this form of tuberculosis.

Despite monkeypox (mpox) being a public health emergency, there is limited knowledge about the risk of infectivity from skin viral loads during mpox infection. Thus, the aim of this study was to estimate cutaneous viral loads among mpox patients globally. Several databases, including Cochrane, EBSCOHost, EMBASE, ProQuest, PubMed, Scopus, and Web of Science, and preprint servers were searched concerning skin mpox viral loads in confirmed mpox subjects. In this systematic review and meta-analysis, a total of 331 articles were initially screened after the removal of duplicate entries. A total of nine articles were included in the systematic review and meta-analysis for the overall estimation of viral loads (Ct) using a random-effect model. The pooled cutaneous mpox viral load (lower Ct) was 21.71 (95% CI: 20.68–22.75) with a majority of positivity rates being 100%, highlighting a higher infectivity risk from skin lesions. The current results strongly support that skin mpox viral loads may be a dominant source of rapid transmission during current multi-national outbreaks. This important finding can help in constructing useful measures in relevant health policy.

Reactive oxygen species (ROS) play a key role in the neurodegeneration processes. Increased oxidative stress damages lipids, proteins, and nucleic acids in brain tissue, and it is tied to the loss of biometal homeostasis. For this reason, attention has been focused on transition metals involved in several biochemical reactions producing ROS. Even though a bulk of evidence has uncovered the role of metals in the generation of the toxic pathways at the base of Alzheimer’s disease (AD), this matter has been sidelined by the advent of the Amyloid Cascade Hypothesis. However, the link between metals and AD has been investigated in the last two decades, focusing on their local accumulation in brain areas known to be critical for AD. Recent evidence revealed a relation between iron and AD, particularly in relation to its capacity to increase the risk of the disease through ferroptosis. In this review, we briefly summarize the major points characterizing the function of iron in our body and highlight why, even though it is essential for our life, we have to monitor its dysfunction, particularly if we want to control our risk of AD.

The world's largest randomized control trial against COVID-19 using remdesivir, hydroxychloroquine, lopinavir and interferon-β1a appeared to have little or no effect on hospitalized COVID-19 patients. This has again led to search for alternate re-purposed drugs and/or effective “add-on” nutritional supplementation, which can complement or enhance the therapeutic effect of re-purposed drug. Focus has been shifted to therapeutic targets of severe acute respiratory syndrome coronavirus (SARS-CoV-2), which includes specific enzymes and regulators of lipid metabolism. Very recently, fenofibrate (cholesterol-lowering drug), suppressed the SARS-CoV-2 replication and pathogenesis by affecting the pathways of lipid metabolism in lung cells of COVID-19 patients. A preclinical study has shown synergistic effect of quercetin (a flavonoid) and fenofibrate in reducing the cholesterol content, which might be useful in COVID-19 treatment. Based on the scientific literature, use of quercetin and fenofibrate in COVID-19 seems meaningful in pharmaceutical and biomedical research, and warrants basic, experimental and clinical studies. In this article, we have summarized the contemporary findings about drug fenofibrate and its effect on membrane synthesis of COVID-19 virus along with emphasizing on possible synergistic effects of quercetin with fenofibrate.

Evidence of copper’s (Cu) involvement in Alzheimer’s disease (AD) is available, but information on Cu involvement in microglia and astrocytes during the course of AD has yet to be structurally discussed. This review deals with this matter in an attempt to provide an updated discussion on the role of reactive glia challenged by excess labile Cu in a wide picture that embraces all the major processes identified as playing a role in toxicity induced by an imbalance of Cu in AD.

Abstract Arsenic (As) contamination in rice leads to yield decline and causes carcinogenic risk to human health. Although the role of nitric oxide (NO) in reducing As toxicity is known, NO-mediated genetic modulation in the plant during arsenic toxicity has not yet been established. We analyzed the key components of NO metabolism and the correlations between NO interaction and arsenic stress using rice as a relevant model plant. Illumina sequencing was used to investigate the NO-mediated genome-wide temporal transcriptomic modulation in rice root upon AsIII exposure during 12 days (d) of the growth period. Sodium nitroprusside (SNP) was used as NO donor. SNP supplementation resulted in marked decrease in ROS, cell death and As accumulation during AsIII stress. NO was found to modulate metal transporters particularly NIP, NRAMP, ABC and iron transporters, stress related genes such as CytP450, GSTs, GRXs, TFs, amino acid, hormone(s), signaling and secondary metabolism genes involved in As detoxification. We detected NO-mediated change in jasmonic acid (JA) content during AsIII stress. The study infers that NO reduces AsIII toxicity through modulating regulatory networks involved in As detoxification and JA biosynthesis.

Zinc therapy is normally utilized for treatment of Wilson disease (WD), an inherited condition that is characterized by increased levels of non-ceruloplasmin bound (‘free’) copper in serum and urine. A subset of patients with Alzheimer’s disease (AD) or its prodromal form, known as Mild Cognitive Impairment (MCI), fail to maintain a normal copper metabolic balance and exhibit higher than normal values of non-ceruloplasmin copper. Zinc’s action mechanism involves the induction of intestinal cell metallothionein, which blocks copper absorption from the intestinal tract, thus restoring physiological levels of non-ceruloplasmin copper in the body. On this basis, it is employed in WD. Zinc therapy has shown potential beneficial effects in preliminary AD clinical trials, even though the studies have missed their primary endpoints, since they have study design and other important weaknesses. Nevertheless, in the studied AD patients, zinc effectively decreased non-ceruloplasmin copper levels and showed potential for improved cognitive performances with no major side effects. This review discusses zinc therapy safety and the potential therapeutic effects that might be expected on a subset of individuals showing both cognitive complaints and signs of copper imbalance.

Introduction: Blood Pressure (BP) measurement is the basis of diagnosis and treatment of hypertension. Automatic BP monitors are available for self-measurement of BP at home and it helps in adaptation of treatment strategy. However, proper measurement procedures are of paramount importance for credible BP readings. Aim: To ascertain the level of competency in Home Blood Pressure Monitoring (HBPM) among patients and their family members (i.e., operators) and to find the effect of a simple educational program on improvement in the competency in HBPM. Materials and Methods: A cross-sectional survey was conducted with patients or their family members who measure BP at home. Procedure of HBPM, as practiced by the participants was observed by the surveyor physician and competency was scored on 17 item survey questionnaire. Then, an educational tool was used to educate the participants. Summative assessment was conducted after the training program by another session of HBPM. The data was tested statistically by chi-square and paired t-test with α=0.05. Results: A total of 125 respondents of mean age 34.51±12.32 years participated in the survey. Among 17 items, overall competency score in HBPM before training program was 4.63±4.59. The competency score (16.31±2.53) significantly (p

Introduction: Based on the diversity of surface O antigen Vibrio cholerae can be classified into 206 serogroups. Vibrio cholerae is the causative agent of cholera and extra intestinal infections like, septicemia, wound infection and haemorrhagic reactions. Pathogenic factors of V. cholerae extra-intestinal infection are yet to be explored. Aim: To identify the pathogenic factor associated with V. cholerae extra-intestinal infection. Materials and Methods: This study was carried out between April, 2007 to October 2007 in National Institute of Cholera and Enteric Diseases (NICED). Haemagglutinin Protease (HAP), a major secreted proteolytic enzyme, was purified from the culture supernatant of Vibrio cholerae O1 strain C6709 after removal of outer membrane vesicles using a single step ion-exchange chromatography. Function of HAP was characterized by animal model, like, subcutaneous mouse assay, basement membrane component’s degradation assays and tissue culture assays. Results: When suckling mouse was subcutaneously injected with culture supernatant of C6709 strain or purified HAP in both cases, distinct in vivo haemorrhagic response along with histopathological changes like necrosis of the capillaries and muscle layer, acute myofibre degeneration as well as moderate number of erythrocyte scattered through the skin, capillary necrosis, acute myofiber degeneration and necrosis of muscle layer were found. When Tryptic Soy Broth (TSB) media was used, the haemorrhagic effects in suckling mouse were not detectable. The major protein components, laminin and collagen, of basement membrane comprising of vascular endothelial cells, were degraded by HAP. Purified HAP showed cell rounding effects on Int 407 cells. Conclusion: Result indicates that HAP may be a causative agent of Vibrio cholerae mediated extra-intestinal infection. This study confirms that Vibrio cholera as a sole pathogen can cause the extra-intestinal infection. This information is important for public health notification. Besides this, result indicates appropriate testing for Vibrio cholerae and intervention are important for the patient management.

OBJETIVO: Comparar uma técnica composta de dacriocistorrinotomia (DCR) endoscópica à técnica convencional. MÉTODO: Foi realizado um estudo prospectivo no Departamento de Otorrinolaringologia da Faculdade de Medicina Maulana Azad. Trinta pacientes selecionados para DCR endoscópica foram divididos em dois grupos, um submetido à DCR endoscópica convencional e outro tratado com uma técnica mais nova com o uso de cautere, instrumentação fria e laser em diferentes etapas da DCR endoscópica. Os pacientes foram seguidos por nove meses. RESULTADOS/CONCLUSÃO: Com o uso do cautere, instrumentação fria e laser em diferentes etapas da DCR endoscópica, fomos capazes de obter taxa de sucesso de cerca de 94% com a técnica composta em comparação a 83,3% da DCR endoscópica convencional.AIM: To compare a composite technique of Endoscopic Dacrocystorhinostomy with the conventional technique. METHODS: A randomised prospective study was carried in the department of Otolaryngology Maulana Azad Medical College. Thirty patient selected for Endoscopic DCR were divided into two groups, one of which underwent conventional Endoscopic DCR and the other group were treated with a newer technique using cautery, cold instrumentation and laser at different steps of Endoscopic DCR. The patients were followed up for Nine months. RESULTS/CONCLUSION: By using cautery, cold instrumentation and laser at different steps of Endoscopic DCR we were able to achieve a success rate of around 94% with this composite technique as compared to 83.3% in conventional Endoscopic DCR surgery.

Nitric oxide is a gaseous signalling molecule and has a profound impact on plant growth and development. It is reported to serve as pro oxidant as well as antioxidant in plant system. In present study, we evaluated the protective role of nitric oxide against AsV toxicity in rice plants. Arsenate exposure has hampered the plant growth, reduced the chlorophyll content and enhanced the oxidative stress while the exogenous NO supplementation has reverted these symptoms. Nitric oxide supplementation has reduced the As accumulation in root as well as shoot. Nitric oxide supplementation to AsV exposed plants has reduced the gene expression level of OsLsi1 and OsLsi2. Arsenate stress significantly impacted thiol metabolism, it reduced GSH content and GSH/GSSG ratio and enhanced the level of PCs. Nitric oxide supplementation maintained the GSH/GSSG ratio and reduced the level of PCs. Nitric oxide supplementation reverted AsV induced iron deficiency in shoot and had significant impact of gene expression level of various iron transporters (OsYSL2, OsFRDL1, OsIRT1 and OsIRO2). Conclusively, exogenous application of nitric oxide could be advantageous against AsV toxicity and could confer the tolerance to AsV stress in rice.

Arsenic (As) is posing serious health concerns in South East Asia where rice, an efficient accumulator of As, is prominent crop. Salicylic acid (SA) is an important signalling molecule and plays a crucial role in resistance against biotic and abiotic stress in plants. In present study, ameliorative effect of SA against arsenate (AsV) toxicity has been investigated in rice (Oryza sativa L.). Arsenate stress hampered the plant growth in terms of root, shoots length and biomass as well as it enhanced the level of H2O2 and MDA in dose dependent manner in shoot. Exogenous application of SA, reverted the growth and oxidative stress caused byAsV and significantly decreased As translocation to the shoots. Level of As in shoot was positively correlated with the expression of OsLsi2, efflux transporter responsible for root to shoot translocation of arsenic in the form of arsenite (AsIII). Salicylic acid also overcame AsV induced oxidative stress and modulated the activities of antioxidant enzymes in a differential manner in shoots. Arsenic treatment hampered the translocation of Fe in the shoot which was compensated by the SA treatment. The level of Fe in root and shoot was positively correlated with the transcript level of transporters responsible for the accumulation of Fe,OsNRAMP5 and OsFRDL1, in the root and shoot respectively. Co-application of SA was more effective than pre-treatment for reducing As accumulation as well as imposed toxicity.

We investigated the prevalence of Shiga toxin-producing Escherichia coli (STEC) in hospitalized diarrhea patients in Calcutta, India, as well as in healthy domestic cattle and raw beef samples collected from the city's abattoir. Multiplex polymerase chain reaction using primers specific for stx1 and stx2 detected STEC in 18% of cow stool samples, 50% of raw beef samples, and 1.4% and 0.6% of bloody and watery stool samples, respectively, from hospitalized diarrhea patients. Various virulence genes in the STEC isolates indicated that stx1 allele predominated. Plasmid-borne markers, namely, hlyA, katP, espP, and etpD, were also identified. Bead enzyme-linked immunosorbent assay and Vero cell assay were performed to detect and evaluate the cytotoxic effect of the Shiga toxins produced by the strains. STEC is not an important cause of diarrhea in India; however, its presence in domestic cattle and beef samples suggests that this enteropathogen may become a major public health problem in the future.

Outer membrane vesicles (OMVs) released from Gram-negative bacteria can serve as vehicles for the translocation of virulence factors. Vibrio cholerae produce OMVs but their putative role in translocation of effectors involved in pathogenesis has not been well elucidated. The V. cholerae cytolysin (VCC), is a pore-forming toxin that lyses target eukaryotic cells by forming transmembrane oligomeric β-barrel channels. It is considered a potent toxin that contributes to V. cholerae pathogenesis. The mechanisms involved in the secretion and delivery of the VCC have not been extensively studied.OMVs from V. cholerae strains were isolated and purified using a differential centrifugation procedure and Optiprep centrifugation. The ultrastructure and the contents of OMVs were examined under the electron microscope and by immunoblot analyses respectively. We demonstrated that VCC from V. cholerae strain V:5/04 was secreted in association with OMVs and the release of VCC via OMVs is a common feature among V. cholerae strains. The biological activity of OMV-associated VCC was investigated using contact hemolytic assay and epithelial cell cytotoxicity test. It showed toxic activity on both red blood cells and epithelial cells. Our results indicate that the OMVs architecture might play a role in stability of VCC and thereby can enhance its biological activities in comparison with the free secreted VCC. Furthermore, we tested the role of OMV-associated VCC in host cell autophagy signalling using confocal microscopy and immunoblot analysis. We observed that OMV-associated VCC triggered an autophagy response in the target cell and our findings demonstrated for the first time that autophagy may operate as a cellular defence mechanism against an OMV-associated bacterial virulence factor.Biological assays of OMVs from the V. cholerae strain V:5/04 demonstrated that OMV-associated VCC is indeed biologically active and induces toxicity on mammalian cells and furthermore can induce autophagy.

BackgroundColon cancers are the frequent causes of cancer mortality worldwide. Recently bacterial toxins have received marked attention as promising approaches in the treatment of colon cancer. Thermostable direct hemolysin (TDH) secreted by Vibrio parahaemolyticus causes influx of extracellular calcium with the subsequent rise in intracellular calcium level in intestinal epithelial cells and it is known that calcium has antiproliferative activity against colon cancer.Key resultsIn the present study it has been shown that TDH, a well-known traditional virulent factor inhibits proliferation of human colon carcinoma cells through the involvement of CaSR in its mechanism. TDH treatment does not induce DNA fragmentation, nor causes the release of lactate dehydrogenase. Therefore, apoptosis and cytotoxicity are not contributing to the TDH-mediated reduction of proliferation rate, and hence the reduction appears to be caused by decrease in cell proliferation. The elevation of E-cadherin, a cell adhesion molecule and suppression of β-catenin, a proto-oncogene have been observed in presence of CaSR agonists whereas reverse effect has been seen in presence of CaSR antagonist as well as si-RNA in TDH treated cells. TDH also triggers a significant reduction of Cyclin-D and cdk2, two important cell cycle regulatory proteins along with an up regulation of cell cycle inhibitory protein p27(Kip1) in presence of CaSR agonists.ConclusionTherefore TDH can downregulate colonic carcinoma cell proliferation and involves CaSR in its mechanism of action. The downregulation occurs mainly through the involvement of E-cadherin-β-catenin mediated pathway and the inhibition of cell cycle regulators as well as upregulation of cell cycle inhibitors.

BACKGROUND: In our earlier studies 34 kDa outer membrane protein (OMP) of Shigella flexneri 2a has been identified as an efficient immunostimulant. KEY RESULTS: In the present study MALDI-TOF MS analysis of the purified 34 kDa OMP of Shigella flexneri 2a shows considerable sequence homology (Identity 65%) with the OmpA of S. flexneri 2a. By using the specific primers, the gene of interest has been amplified from S. flexneri 2a (N.Y-962/92) genomic DNA, cloned in pET100/D-TOPO® vector and expressed using induction with isopropyl thiogalactoside (IPTG) for the first time. Immunogenicity and protective efficacy of the recombinant OmpA has been evaluated in an intranasally immunized murine pulmonary model. The recombinant protein induces significantly enhanced protein specific IgG and IgA Abs in both mucosal and systemic compartments and IgA secreting cells in the systemic compartment (spleen). The mice immunized with OmpA have been protected completely from systemic challenge with a lethal dose of virulent S. flexneri 2a. Immunization with the protein causes mild polymorphonuclear neutrophil infiltration in the lung, without inducing the release of large amounts of proinflammatory cytokines. CONCLUSION: These results suggest that the OmpA of S. flexneri 2a can be an efficacious mucosal immunogen inducing protective immune responses. Our findings also demonstrate that antibodies and Th1 immune response may be associated with the marked protective efficacy of immunized mice after intranasal shigellae infection.

Two well-characterized proteases secreted by Vibrio cholerae O1 strains are hemagglutinin protease (HAP) and V. cholerae protease (PrtV). The hapA and prtV knock out mutant, V. cholerae O1 strain CHA6.8ΔprtV, still retains residual protease activity. We initiated this study to characterize the protease present in CHA6.8ΔprtV strain and study its role in pathogenesis in rabbit ileal loop model (RIL). We partially purified the residual protease secreted by strain CHA6.8ΔprtV from culture supernatant by anion-exchange chromatography. The major protein band in native PAGE was identified by MS peptide mapping and sequence analysis showed homology with a 59-kDa trypsin-like serine protease encoded by VC1649. The protease activity was partially inhibited by 25 mM PMSF and 10 mM EDTA and completely inhibited by EDTA and PMSF together. RIL assay with culture supernatants of strains C6709 (FA ratio 1.1+/-0.3 n = 3), CHA6.8 (FA ratio 1.08+/-0.2 n = 3), CHA6.8ΔprtV (FA ratio 1.02+/-0.2 n = 3) and partially purified serine protease from CHA6.8ΔprtV (FA ratio 1.2+/-0.3 n = 3) induced fluid accumulation and histopathological studies on rabbit ileum showed destruction of the villus structure with hemorrhage in all layers of the mucosa. RIL assay with culture supernatant of CHA6.8ΔprtVΔVC1649 strain (FA ratio 0.11+/-0.005 n = 3) and with protease incubated with PMSF and EDTA (FA ratio 0.3+/-0.05 n = 3) induced a significantly reduced FA ratio with almost complete normal villus structure. Our results show the presence of a novel 59-kDa serine protease in a ΔhapAΔprtV V. cholerae O1 strain and its role in hemorrhagic response in RIL model.