Unlocking the Potential of High Entropy Alloys in Electrochemical Water Splitting: A Review.

The global pursuit of sustainable energy is focused on producing hydrogen through electrocatalysis driven by renewable energy. Recently, High entropy alloys (HEAs) have taken the spotlight in electrolysis due to their intriguing cocktail effect, broad design space, customizable electronic structure, and entropy stabilization effect. The tunability and complexity of HEAs allow a diverse range of active sites, optimizing adsorption strength and activity for electrochemical water splitting. This review comprehensively covers contemporary advancements in synthesis technique, design framework, and physio-chemical evaluation approaches for HEA-based electrocatalysts. Additionally, it explores design principles and strategies aimed at optimizing the catalytic activity, stability, and effectiveness of HEAs in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. Through an in-depth investigation of these aspects, the complexity inherent in constituent element interactions, reaction processes, and active sites associated with HEAs is aimed to unravel. Eventually, an outlook regarding challenges and impending difficulties and an outline of the future direction of HEA in electrocatalysis is provided. The thorough knowledge offered in this review will assist in formulating and designing catalysts based on HEAs for the next generation of electrochemistry-related applications.

The metabolic landscape of the bacteria Rhodococcus erythropolis used in the biodesulfurization of petroleum products: an emphasis on 2-hydroxybiphenyl.

Microorganisms produce diverse classes of metabolites under various physiological conditions. Many bacterial strains have been reported to carry out the process of desulfurization in a cost-effective manner by converting dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) and then using the 2-HBP as a carbon source for growth and development. Key rate-limiting factors and an increased concentration of 2HBP (400 µM) affect the biodesulfurization activity of bacteria through the produced metabolites. Thus, this study was designed to explore the nature of the metabolites produced by Rhodococcus erythropolis in the presence of DBT and 2HBP supplemented with a culture medium. A total of 330 metabolites were detected, and the key metabolites identified were 11Z-eicosaenoyl-EA, 1-carboxyethylisoleucine, 1(3)-glyceryl-PGF2alpha, taurine, 2-hydroxynicotinic acid, 4,4-dimethyl-14alpha-hydroxymethyl-5alpha-cholest-8-en-3beta-ol, and 10-nitrooleic acid. The supplementation of DBT and DBT-2HBP resulted in the differential regulation of these metabolites, either through downregulation or overexpression. Furthermore, at high concentrations of 2-HBP, 1-carboxyethylisoleucine, taurine, 2-hydroxynicotinic acid, and nicotinic acid were upregulated. This work proposes that the identified metabolites may play a role in bacteria-mediated desulphurization and could be beneficial in developing a cost-effective method of desulphurization for refining petroleum.

Characterization of Salmonella enterica Biofilms and Antibiofilm Effect of Carvacrol and 2-Aminobenzimidazole.

Biofilm-associated foodborne Salmonella infections in poultry have become increasingly challenging for veterinarians, particularly in developing countries, and warrant thorough investigation. We assessed the biofilm-forming tendency of poultry isolates of Salmonella enterica, namely Salmonella Typhimurium (n = 23), Salmonella Infantis (n = 28), and Salmonella Heidelberg (n = 18), in nutrient-rich Rappaport-Vassiliadis Soya (RVS) peptone broth and nutrient-deficient diluted Tryptone Soya Broth (TSB). Seven of the tested isolates exhibited moderate biofilm formation in diluted TSB, whereas two showed such formation in RVS. In addition, the Congo red agar assay revealed curli and cellulose production in seven isolates. Fourteen specific biofilm-associated genes were analyzed identifying sdiA and seqA to be the most prevalent (100%), and glyA the least prevalent (69.5%). The prevalence of the genes bcsA and csgA was significantly lower in moderate and weak biofilm formers, respectively, as compared with nonbiofilm formers in RVS peptone broth. Furthermore, the compounds carvacrol and 2-aminobenzimidazole (2-ABI) effectively inhibited biofilm formation by Salmonella serovars in RVS peptone and TSB media, respectively. Whereas the antibiofilm activity of 2-ABI against Salmonella has not been reported previously, we determined its most effective concentration at 1.5 mM among tested antibiofilm treatments. These findings indicate that Salmonella strains prevalent in poultry farms have the potential to form biofilms, and the tested compounds should be further explored as supportive or alternative antimicrobials.

New paracetamol hybrids as anticancer and COX-2 inhibitors: Synthesis, biological evaluation and docking studies.

Drug repurposing is an emerging field in drug development that has provided many successful drugs. In the current study, paracetamol, a known antipyretic and analgesic agent, was chemically modified to generate paracetamol derivatives as anticancer and anticyclooxygenase-2 (COX-2) agents. Compound 11 bearing a fluoro group was the best cytotoxic candidate with half-maximal inhibitory concentration (IC50 ) values ranging from 1.51 to 6.31 µM and anti-COX-2 activity with IC50 = 0.29 µM, compared to the standard drugs, doxorubicin and celecoxib. The cell cycle and apoptosis studies revealed that compound 11 possesses the ability to induce cell cycle arrest in the S phase and apoptosis in colon Huh-7 cells. These results were strongly supported by docking studies, which showed strong interactions with the amino acids of the COX-2 protein, and in silico pharmacokinetic predictions were found to be favorable for these newly synthesized paracetamol derivatives. It can be concluded that compound 11 could block cell growth and proliferation by inhibiting the COX-2 enzyme in cancer therapy.

Prospective of nanoscale metal organic frameworks [NMOFs] for cancer therapy.

Nano metal organic frameworks (NMOFs) belong to the group of nanoporous materials. Over the decades, the conducted researches explored the area for the potential applications of NMOFs in areas like biomedical, chemical engineering and materials science. Recently, NMOFs have been explored for their potential use in cancer diagnosis and therapeutics. The excellent physico-chemical features of NMOFs also make them a potential candiadate to facilitate drug design, delivery and storage against cancer cells. In this review, we have explored the characterstic features, synthesis methods, NMOFs based drug delivery, diagnosis and imaging in various cancer types. In addition to this, we have also pondered on the stability and toxicological concerns of NMOFs. Despite, a significant research has been done for the potential use of NMOFs in cancer diagonostic and therapeutics, more information regarding the stability, in-vivo clearance, toxicology, and pharmacokinetics is still needed to ehnace the use of NMOFs in cancer diagonostic and therapeutics.

Remodelin, a N-acetyltransferase 10 (NAT10) inhibitor, alters mitochondrial lipid metabolism in cancer cells.

Remodelin is a small molecule inhibitor of N-acetyltransferase 10 (NAT10), reported to reverse the effect of cancer conditions such as epithelial to mesenchymal transition, hypoxia, and drug resistance. We analysed RNA seq data of siNAT10 and found many metabolic pathways were altered, this made us perform unbiased metabolic analysis. Here we performed untargeted metabolomics in Remodelin treated cancer cells using high-performance liquid chromatography-tandem mass spectrometry. Statistical analysis revealed a total number of 138 of which 52 metabolites were significantly modified in Remodelin treated cells. Among the most significantly altered metabolites, we identified metabolites related with mitochondrial fatty acid elongation (MFAE) and mitochondrial beta-oxidation such as lauroyl-CoA, cholesterol, triglycerides, (S)-3-hydroxyhexadecanoyl-CoA, and NAD+ . Furthermore, assessment showed alteration in expression of Enoyl-CoA hydratase, short chain 1, mitochondrial (ECHS1), and Mitochondrial trans-2-enoyl-CoA reductase (MECR) genes, associated with MFAE pathway. We also found statistically significant decrease in total cholesterol and triglycerides in Remodelin treated cancer cells. Overall, our results showed that Remodelin alters mitochondrial fatty acid metabolism and lipid accumulation in cancer cells. Finally, we validated these results in NAT10 knockdown cancer cells and found that NAT10 reduction results in alteration in gene expression associated with mitochondrial fatty acid metabolism, clearly suggesting the possible role of NAT10 in maintaining mitochondrial fatty acid metabolism.

Integron mediated antimicrobial resistance in diarrheagenic Escherichia coli in children: in vitro and in silico analysis.

The exchange of genes between bacterial chromosome and plasmid(s) and their integration into integrons are mainly responsible for acquisition and dissemination of antibiotic resistance. We investigated the role of integrons and their underlying molecular mechanisms leading to development of adaptability in E. coli and eventual resistance to antimicrobials. Escherichia coli isolates (n = 120); including 40 diarrheagenic isolates, an even number of isolates from cases other than diarrhea, and equal number of isolates from healthy children recovered from fresh stool samples were used for identification of integron genes and gene cassettes. The association of integrons with antibiotic resistance was assayed before phylogenetic analysis. DNA sequence analysis revealed class 1 and 2 integrons in 55.83% and 21.66% isolates, respectively. The integron presence was found significantly associated with the probability of antibiotic resistance in E. coli; the association being highest with class 1 integron. Modelling and molecular docking along with molecular dynamics simulation analyses found ceftriaxone and amoxicillin as potential inhibitors of dihydrofolate reductase (DHFR). The class 1 integrons of these pathogenic isolates can serve as prospective therapeutic targets using specific silencing strategies and combinational antimicrobial therapy. The findings may be useful for the development of a potent and versatile drug for DHFR inhibition.

Nutritive vitamins as epidrugs.

Epigenetic modifications play an important role in disease pathogenesis and therefore are a focus of intense investigation. Epigenetic changes include DNA, RNA, and histone modifications along with expression of non-coding RNAs. Various factors such as environment, diet, and lifestyle can influence the epigenome. Dietary nutrients like vitamins can regulate both physiological and pathological processes through their direct impact on epigenome. Vitamin A acts as a major regulator of above-mentioned epigenetic mechanisms. B group vitamins including biotin, niacin, and pantothenic acid also participate in modulation of various epigenome. Further, vitamin C has shown to modulate both DNA methylation and histone modifications while few reports have also supported its role in miRNA-mediated pathways. Similarly, vitamin D also influences various epigenetic modifications of both DNA and histone by controlling the regulatory mechanisms. Despite the information that vitamins can modulate the epigenome, the detailed mechanisms of vitamin-mediated epigenetic regulations have not been explored fully and hence further detailed studies are required to decipher their role at epigenome level in both normal and disease pathogenesis. The current review summarizes the available literature on the role of vitamins as epigenetic modifier and highlights the key evidences for developing vitamins as potential epidrugs.

Impact of exogenously applied trehalose on leaf biochemistry, achene yield and oil composition of sunflower under drought stress.

This study was carried out to assess the influence of trehalose, a non-reducing disaccharide involved in improving plant stress tolerance, on two cultivars (Hysun 33 and FH 598) of sunflower (Helianthus annuus L.) grown under control and drought stress conditions. At pre-flowering stage, varying concentrations (10, 20 and 30 mM) of trehalose were applied to the foliage. Drought stress significantly suppressed the plant growth, total soluble proteins, chlorophyll, achene yield per plant, oil percentage, organic contents, as well as oil palmitic and linoleic acids in both sunflower cultivars. External application of trehalose significantly reduced RMP (relative membrane permeability), and the accumulation of H2 O2 (hydrogen peroxide), while a considerable improvement was recorded in shoot fresh and shoot and root dry weights, total soluble proteins, glycinebetaine, AsA (ascorbic acid), total phenolics, achene yield per plant, oil contents, inorganic and organic contents, and the activities of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) enzymes under water-limited regimes. The cultivar Hysun 33 was superior to the other cultivar in plant growth, RMP, glycinebetaine, proline, achene yield per plant, oil contents, and palmitic and linoleic acids. Overall, foliar-applied trehalose improved plant growth, oxidative defense system, yield and oil composition of sunflower under drought stress conditions.

Progress in oncology biosimilars till 2020: Scrutinizing comparative studies of biosimilar monoclonal antibodies.

Stupendous elevation in the healthcare costs has followed with the inception of the current unconventional options of treatment available for cancer patients. There is a dire need of innovative financing approaches to lessen the financial load on healthcare system. Biosimilars are biological drugs consisting of an active ingredient from a reference biological drug that has a great potential of relieving financial load. Strict requirements from regulatory point of view are required as biosimilars are exceedingly similar to but not identical to the reference product. This provides with a certainty that no consequential differences from clinical point of view as compared to the respective biologics exists with regards to efficacy, safety and purity. Safety and effectiveness of biosimilars have been disclosed since more than 10 years of affirmations. However, there is a need to educate the healthcare professionals to abolish potential misconceptions and coalesce biosimilars into regular clinical practice. The present review focuses on providing an overview of regulatory aspects and requirements for biosimilars, the main challenges in the selection and development of biosimilars and the economic impact and financial savings observed in recent studies carried out in different parts of the world. In addition, we have discussed the different successful comparative studies which have been done in different parts of the world to depict the biosimilarity for monoclonal antibodies such as bevacizumab, trastuzumab and rituximab.

Urolithin A and B Alter Cellular Metabolism and Induce Metabolites Associated with Apoptosis in Leukemic Cells.

Leukemia is persistently a significant cause of illness and mortality worldwide. Urolithins, metabolites of ellagic acid and ellagitannins produced by gut microbiota, showed better bioactive compounds liable for the health benefits exerted by ellagic acid and ellagitannins containing pomegranate and walnuts. Here, we assessed the potential antileukemic activities of both urolithin A and urolithin B. Results showed that both urolithin A and B significantly inhibited the proliferation of leukemic cell lines Jurkat and K562, among which urolithin A showed the more prominent antiproliferative capability. Further, urolithin treatment alters leukemic cell metabolism, as evidenced by increased metabolic rate and notable changes in glutamine metabolism, one-carbon metabolism, and lipid metabolism. Next, we evidenced that both urolithins equally promoted apoptosis in leukemic cell lines. Based on these observations, we concluded that both urolithin A and B alter leukemic cell metabolome, resulting in a halt of proliferation, followed by apoptosis. The data can be used for designing new combinational therapies to eradicate leukemic cells.

Quantifying satisfaction among pharmacists working in Pharmaceutical Sales or Marketing and its inferential relationship with demographics: A Cross-Sectional analysis in Pakistan.

OBJECTIVES: To quantify satisfaction among pharmacists working in pharmaceutical sales or marketing in Pakistan. METHODS: A cross-sectional study was conducted among pharmacists working in pharmaceutical sales and marketing during August to November, 2019. Satisfaction score of pharmacists was considered satisfied (Score > 2.5) and dissatisfied (Score < 2.5). The maximum and minimum satisfaction score was four and one for each question respectively. RESULTS: A total of 250 questionnaires were distributed and 200 were received back yielding a response rate of 80%. Male respondents dominated the cohort and were more satisfied (2.60 ± 0.47) as compared to females (2.31 ± 0.48) with majority were 18-30 years old and 78% had Pharm. D level of education (2.61 ± 0.47). The mean satisfaction score of participant is 2.51 with standard deviation of 0.49. The 53% of the respondents were dissatisfied with their salaries. The study dependent and independent variables are correlated with each other and significant results were seen between them. The factors associated with dissatisfaction are fear of losing job (2.19 ± 0.88), switch job (2.20 ± 0.77) and health condition (2.09 ± 0.89). Factors associated with satisfaction are positive attitude of doctor (2.91 ± 0.60), doctor consider respectful job holder (2.91 ± 0.61), enjoy work (3.01 ± 0.65), job by choice (3.12 ± 0.67) and progress in job (3.00 ± 0.74). CONCLUSIONS: It was concluded that the respondents were dissatisfied due to number of issues including disturbance in their personal life, lack of promotion and incentives among study participants.

In-vitro evaluation of antiproliferative potential of various fractions of Silybum marianum using HeLa and HepG2 cell lines.

Silybum marianum (Milk thistle) has been proven to possess anticancer, lactogenic, neuroprotective, immunomodulatory, hepatoprotective and anti-inflammatory properties. The current study was designed to evaluate the antiproliferative potential of aqueous and various organic fractions (ethanolic, petroleum ether, ethyl acetate, chloroform, n-butanol) of S. marianum against cancerous [HeLa, HepG2] and noncancerous [BHK] cell lines. The MTT assay was performed to access the cytotoxicity of all these fractions and IC50 values were calculated. The cytotoxicity of these fractions was also confirmed through crystal violet and Trypan blue assays. All the tested fractions of S. marianum possessed significant antiproliferative potential. Interestingly, ethyl acetate fraction of S. marianum exhibited the highest antiproliferative activity amongst all the other tested fractions with an IC50 of 13.07 µg/ml, 18.92 µg/ml and 76.15µg/ml against HeLa, HepG2 and BHK cell lines respectively. So it is concluded that S. marianum possess strong anticancer activity against both cervical and liver cancer and low cytotoxicity against normal cell line so it could be used as a source of potent anticancer compounds having high efficacy and minimal side effects.

Association of mutation and low expression of the CTCF gene with breast cancer progression.

BACKGROUND: CTCF encodes 11-zinc finger protein which is implicated in multiple tumors including the carcinoma of the breast. The Present study investigates the association of CTCF mutations and their expression in breast cancer cases. METHODS: A total of 155 breast cancer and an equal number of adjacent normal tissue samples from 155 breast cancer patients were examined for CTCF mutation(s) by PCR-SSCP and automated DNA sequencing. Immunohistochemistry (IHC) method was used to analyze CTCF expression. Molecular findings were statistically analyzed with various clinicopathological features to identify associations of clinical relevance. RESULTS: Of the total, 16.1% (25/155) cases exhibited mutation in the CTCF gene. Missense mutations Gln > His (G > T) in exon 1 and silent mutations Ser > Ser (C > T) in exon 4 of CTCF gene were analyzed. A significant association was observed between CTCF mutations and some clinicopathological parameters namely menopausal status (p = 0.02) tumor stage (p = 0.03) nodal status (p = 0.03) and ER expression (p = 0.04). Protein expression analysis showed 42.58% samples having low or no expression (+), 38.0% with moderate (++) expression and 19.35% having high (+++) expression for CTCF. A significant association was found between CTCF protein expression and clinicopathological parameters include histological grade (p = 0.04), tumor stage (p = 0.04), nodal status (p = 0.03) and ER status (p = 0.04). CONCLUSIONS: The data suggest that CTCF mutations leading to its inactivation significantly contribute to the progression of breast cancer.

Risk prediction of recurrent venous thromboembolism: a multiple genetic risk model.

A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including established and putative SNPs associated with VTE risk, were genotyped in the Malmö thrombophilia study cohort (MATS; n = 1465, follow-up ~ 10 years) by using TaqMan PCR. Out of 22-SNPs, 12 had an association with the risk of VTE recurrence and were included for calculating GRSs. The risk of VTE recurrence was calculated by stratifying patients according to number of risk alleles. In 12-SNP GRS, patients with ≥ 7 risk alleles were associated with higher risk of VTE recurrence compared to patients having ≤ 6 risk alleles. In a simplified model (8-SNP GRS), the discriminative power of 8-SNP GRS was similar to that of 12-SNP GRS based on post-test probabilities (PP). Furthermore, 8-SNP GRS further improved the risk prediction of VTE recurrence in unprovoked VTE and male patients (PP% = 15.4 vs 8.3, 17.1 vs 7.2 and 19.0 vs 7.1 for high risk groups vs low risk groups in whole population, males and unprovoked VTE patients respectively). In addition, we also validated previously described 5-SNP GRS in our cohort and found that the 8-SNP GRS performed better than the 5-SNP GRS in terms of higher PP. Our results show that a multiple SNP GRS consisting of 8-SNPs may be an effective model for prediction of VTE recurrence, particularly in unprovoked VTE and male patients.

Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner.

Recent studies indicate that mitochondrial DNA (mtDNA) dysfunction is a biomarker of oxidative stress and can predict the risk of cardiovascular diseases (CVDs). Genetic variants in PARK2 (rs4708928) and MRPL37 (rs10888838) genes have been shown to be associated with altered levels of mtDNA in a sex-specific manner. However, the role of these genetic variants in risk assessment of recurrent venous thromboembolism (VTE) is unknown. We investigated the role of these polymorphisms in VTE recurrence in patients from the Malmö thrombophilia study (MATS, n = 1465), followed for ~ 10 years. Genotyping was performed by TaqMan polymerase chain reaction. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence (Hazard ratio [HR] = 2.39, 95% confidence interval [CI] 1.09-5.24) and male patients with MRPL37 polymorphism had a significantly higher risk of VTE recurrence (HR = 1.79, 95% CI 1.01-3.17) on multivariate Cox regression analysis. Combined analysis of these polymorphism with factor V Leiden (FVL) showed that female patients with both, FVL and PARK2 polymorphism had even higher risk of VTE recurrence (HR = 4.49, 95% CI 1.58-12.75) compared to FVL or PARK2 polymorphism alone or both wild-type (reference). Similarly, male patients with both FVL and MRPL37 polymorphism had significantly higher risk of VTE recurrence (HR = 2.97, 95% CI 1.45-6.08) compared to those with FVL or MRPL37 polymorphisms alone or the reference group. Polymorphisms in nuclear genome regulating mtDNA together with FVL may be promising biomarkers for predicting VTE recurrence in a sex specific manner. The abstract should be followed by 3-4 bullet points that highlight the major findings. The final bullet point should address future research.

Expression of claudin 1, claudin 4, and claudin 7 in colorectal cancer and its relation with CLDN DNA methylation patterns.

Altered claudin expression has been described in colon, prostatic, ovarian, and breast carcinoma. However, the role of epigenetic modifications in these genes and their role in colorectal cancer is unknown. We aimed our study to investigate whether claudin protein expression and methylation of CLDN can influence the tumorigenesis of colorectal cancer. A total of 31 patients diagnosed with colorectal carcinoma was used in this study. Immunohistochemical staining was used to study protein expression in both tumor and the adjacent nonneoplastic mucosa of claudin 1, 4, and 7. To detect the DNA methylation pattern of CLDN1, 4, and 7, genomic DNA was extracted from both the tumor and the adjacent nonneoplastic mucosa. Methylation analysis was carried out using bisulfite pyrosequencing. Cell membrane staining intensity of all claudins was found significantly lower in colorectal cancer tissues when compared to paired normal mucosa (p ≤ 0.001). For claudin 4, the percentage of cells staining positively was also significantly reduced (p = 0.04). In normal mucosa, cytoplasm showed no staining for claudins in any patient, whereas in paired colorectal cancer tissues, significant cytoplasmic staining appeared both for claudin 1 (p = 0.04) and claudin 4 (p = 0.01). Tumor samples were significantly hypomethylated in CLDN1 (p < 0.05). In conclusion, our results show that CLDN1 is significantly hypomethylated in tumor samples and that the membrane staining intensity for claudin 1, 4, and 7 is significantly lower in colorectal cancer tissues than in adjacent nonneoplastic tissue. Colorectal cancer cells showed dystopic cytoplasmic location of claudins.

Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism.

Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR. From a total of 1465 VTE patients, those who had VTE before inclusion and those who died or had VTE recurrence during anticoagulant treatment were excluded (n = 415). Cox regression analyses were performed on the remaining 1050 VTE patients, including 126 (12.5%) patients that had recurrent VTE during follow-up period. TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 3.46, 95% CI 1.06-11.33) independent of acquired risk factors for VTE, family history, risk of thrombophilia and deep vein thrombosis (DVT) location. Similarly, in unprovoked VTE patients, TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 5.94, 95% CI 1.25-28.13) after adjusting for family history, risk of thrombophilia and DVT location. No association between TLR9 polymorphism and risk of VTE recurrence was found in male patients. Our results suggest that TLR9 rs5743836 polymorphism is an independent risk factor for VTE recurrence in female patients but not in males.

Comparative evaluation of pan-fungal real-time PCR, galactomannan and (1-3)-ß-D-glucan assay for invasive fungal infection in paediatric cancer patients.

Limited specific data and investigations are available for the diagnosis of Invasive Fungal Infection (IFI) in paediatrics cancer patients. Three non-invasive tests; Platelia Aspergillus EIA for galactomannan (GM), ß-D-glucan (BDG) assay and pan-fungal real-time PCR for fungal DNA in blood were evaluated. One hundred twenty-five paediatrics cancer patients at the high risk of IFI were enrolled. Single blood and serum samples were evaluated by all the three methods. Patients were classified into 10 proven, 52 probable and 63 no IFI cases in accordance with EORTC MSG 2008 revised guidelines. The sensitivity, specificity, PPV and NPV of all the three tests in proven, probable and no IFIs cases were analysed singly and in combination. The sensitivity, specificity, PPV and NPV of GM, BDG and pan-fungal real-time PCR were: 87%, 61%, 81%, 69.5% for GM, 88%, 59.5%, 81%, 71.4% for BDG and 89%, 69.2%, 85%, 67.5% for PCR (95% CI). Among different combinations, best combination was found to be GM and PCR with sensitivity, specificity, PPV and NPV of 98.2%, 89.3%, 97.1% and 90% respectively. Single samples must be evaluated by combination of tests.