Notably, bleeding frequency and trough concentrations were higher with 30 mg of edoxaban (half life 10-14 hours) taken twice daily than with 60 mg taken once daily in a phase II study in patients ...with atrial fibrillation. 7 Robust evidence for rivaroxaban in atrial fibrillation has recently been reiterated by the European Medicines Agency and the US Food and Drug Administration. 8 9 The large phase III study, ROCKET-AF, 10 showed non-inferiority to warfarin in the intention-to-treat population and superiority in the "safety, as treated population" and the "during treatment in the intention-to-treat population."
An examination of the therapeutics and diagnostics use of porphyrinoids including phthalocyanines and glycosylated porphyrins is offered. Topics covered include glycosylated phthalocyanines, ...glycosylated chlorins, isobacteriochlorins and bacteriochlorins and glycosylated porphyrazines.
To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent ...normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥ 4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT, MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose: The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug ketoconazole using solid dispersion technique. Methods: Solid dispersions of ...ketoconazole were prepared in ratios of 90 : 10, 70 : 30, 50 : 50, 30 : 70 and 10 : 90 by the melting method using nicotinamide as carrier. These solid dispersions were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy to ascertain if there were any physicochemical interactions between drug and carrier that could affect dissolution. Solubility and dissolution studies were conducted with pure ketoconazole, physical mixtures and solid dispersions. Results: Solubility studies indicated that nicotinamide increased significantly the solubility of ketoconazole in water. The Gibbs free energy (ΔG°tr) values were negative indicating the spontaneous nature of ketoconazole solubilization, and it decreased with increase in concentration of the carrier, demonstrating that the reaction became more favorable as the concentration of the carrier increased. The cumulative release of ketoconazole within 120 min from solid dispersion at a drug-to-nicotinamide ratio of 10 : 90 (w/w) was 6 times higher than the pure drug in phosphate buffer of pH 6.8. Conclusion: Solid state characterization indicated that there is no interaction between ketoconazole and nicotinamide in the solid state. In contrast to the very slow dissolution rate of pure ketoconazole, the dispersion of the drug in nicotinamide considerably enhanced the dissolution rate. The drug dissolution rate was highest at a drug-to-nicotinamide ratio of 10 : 90 (w/w).
Although it is agreed that physicochemical features of molecules determine their perceived odor, the rules governing this relationship remain unknown. A significant obstacle to such understanding is ...the high dimensionality of features describing both percepts and molecules. We applied a statistical method to reduce dimensionality in both odor percepts and physicochemical descriptors for a large set of molecules. We found that the primary axis of perception was odor pleasantness, and critically, that the primary axis of physicochemical properties reflected the primary axis of olfactory perception. This allowed us to predict the pleasantness of novel molecules by their physicochemical properties alone. Olfactory perception is strongly shaped by experience and learning. However, our findings suggest that olfactory pleasantness is also partially innate, corresponding to a natural axis of maximal discriminability among biologically relevant molecules.
Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, ...subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.
Metastasis is the primary cause of cancer mortality. The primary tumors of colorectal cancer (CRC) often metastasize to the liver. In this study, we have collected 122 samples from 45 CRC patients. ...Among them, 32 patients have primary tumors, adjacent normal tissues, and matched liver metastases. Thirteen patients have primary tumors without distant metastasis and matched normal tissues. Characterization of these samples was conducted by whole-exome and RNA sequencing and SNP6.0 analysis. Our results revealed no significant difference in genetic alterations including common oncogenic mutations, whole genome mutations and copy number variations between primary and metastatic tumors. We then assembled gene co-expression networks and identified metastasis-correlated gene networks of immune-suppression, epithelial-mesenchymal transition (EMT) and angiogenesis as the key events and potentially synergistic drivers associated with CRC metastasis. Further independent cohort validation using published datasets has verified that these specific gene networks are up regulated throughout the tumor progression. The gene networks of EMT, angiogenesis, immune-suppression and T cell exhaustion are closely correlated with the poor patient outcome and intrinsic anti-PD-1 resistance. These results offer insights of combinational strategy for the treatment of metastatic CRC.
Anti-EGFR antibodies are effective in therapies for late-stage colorectal cancer (CRC); however, many tumours are unresponsive or develop resistance. We performed genomic analysis of intrinsic and ...acquired resistance to anti-EGFR therapy in prospectively collected tumour samples from 25 CRC patients receiving cetuximab (an EGFR inhibitor). Of 25 CRC patients, 13 displayed intrinsic resistance to cetuximab; 12 were intrinsically sensitive. We obtained six re-biopsy samples at acquired resistance from the intrinsically sensitive patients. NCOA4-RET and LMNA-NTRK1 fusions and NRG1 and GNAS amplifications were found in intrinsic-resistant patients. In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. The comparison between baseline and acquired-resistant tumours revealed an extreme shift in variant allele frequency of somatic variants, suggesting that cetuximab exposure dramatically selected for rare resistant subclones that were initially undetectable. There was also an increase in epithelial-to-mesenchymal transition at acquired resistance, with a reduction in the immune infiltrate. Furthermore, characterization of an acquired-resistant, patient-derived cell line showed that PI3K/mTOR inhibition could rescue cetuximab resistance. Thus, we uncovered novel genomic alterations that elucidate the mechanisms of sensitivity and resistance to anti-EGFR therapy in metastatic CRC patients.
Everyday, tuberculosis hospitals collect enormous amount of sputum containing viable Mycobacterium tuberculosis bacilli, the disposal of which is a challenging task. Chemical (5% phenol) and physical ...(autoclaving) disinfection methods involve cost, space and cause further environmental degradation. Over the years, use of microwave for sterilisation of biomedical waste has become widespread. However, its efficacy to sterilise large volume of M. tuberculosis positive sputum has never been investigated.
To evaluate the effectiveness of microwave in sterilising large volumes of M. tuberculosis positive sputum samples.
226 sputum samples positive for M. tuberculosis were checked by Ziehl-Neelsen staining and liquid culture (MGIT ™) both before and after microwaving. χ2 test was performed, and p-value <0.05 was considered significant.
Before microwaving, samples containing acid fast bacilli (AFB) and live M. tuberculosis bacilli were 93.8% and 95% (≈94.7%) respectively; which came down to 14.2% (32) and <1% (≈0.9%) in post microwave. In the 32 post-microwave AFB positive samples, bacilli appeared apoptotic, decreased in size, fragmented, loosely arranged and were easily missed as stain artefacts. Their beaded appearance was not appreciable. Background pus cells were of smaller size, did not take up methylene blue stain properly, and multilobed nuclear material was missing.
The study shows efficacy of microwave as an alternative sterilisation method for large volume sputum samples containing M. tuberculosis bacilli. Microwave can become an effective sterilisation method, especially for isolated tuberculosis care centres in countries which struggle for disposal of sputum, the biomedical waste.
Introduction: Delhi, India’s capital, witnessed the first Coronavirus Disease 2019 (COVID-19) case on February 10, 2020, and subsequently three waves of the pandemic due to which the government had ...to impose lockdown starting March 25. It led to a decrease in patients seeking health care services for non emergency problems. Janakpuri Super Speciality Hospital (JSSH), a three hundred bedded autonomous institute under Delhi Government, also encountered a decrease in patient footfall. Aim: To identify the changes in trend in Outpatient Department (OPD) registrations and Inpatient Department (IPD) admissions during one year (January 1, 2020 to December 31, 2020) of COVID-19 pandemic in comparison to 2019 and also to analyse the collected data with the publicly available data on daily COVID-19 incidence in Delhi. Materials and Methods: A retrospective study was done by collecting data from the Janakpuri Super Speciality Hospital, Medical Record Department from 1st January 2019 to 31st December 2020, for daily OPD visits and IPD admissions. The collected data was analysed with the publicly available data on daily COVID-19 incidence in Delhi. Statistical analysis was performed using Microsoft Excel 2017. The non parametric exponential smoothening technique (dampening factor= 0.9) was applied over the dot plot graphs. Results: In 2020, compared to 2019, the daily OPD visits decreased by 37%. After an initial fall with March lockdown, there was a gradual increase in daily load. The OPD load peaked near middle of August 2020, The second big fall in OPD footfall occurred near second wave in September 2020, After that, OPD volume remained low till the 31st December 2020. Similarly, IPD admission volume peaked near the first wave in June 2020. The 2020 IPD admission volume also witnessed a massive decrease of 40.67% compared to 2019 and was maximum in gastroenterology admissions (65.63%). Conclusion: The study’s findings suggest that temporal associations between COVID-19 pandemic and hospital OPD and IPD admissions during 2020. The possibility of increased morbidity and mortality amongst non COVID-19 patients due to the unavailability of timely health care cannot be ruled out. The government should do capacity building to guide patients to identify the best doctor, clinic and hospital nearest to them in case of future pandemics.
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