Clostridium difficile in south-east Scotland: An analysis of severe, recurrent and community-associated disease with a report on the emergence of PCR ribotype 078

Clostridium difficile infection (CDI) has proven to be a constantly evolving disease periodically posing new diagnostic and clinical dilemmas. Different regions of the world have reported specific local genomic characteristics of the infecting strains, which may be related to variation in disease presentation and outcome. This study was performed to determine the clinical and molecular features of severe, recurrent and community-associated disease in the Lothian region of Scotland, UK among patients diagnosed from August 2010-July 2011. Three hundred and thirty-five patients with laboratory confirmed CDI were studied for epidemiological features, clinical presentation, and laboratory markers. They were followed up for one year to determine recurrence and mortality. Four hundred and thirty-two episodes were recorded. Ribotypes, presence of toxin genes and MLVA subtypes of isolates from these episodes were determined. During the course of the study, PCR ribotype 078 was identified as an important emerging type and concerns of “hypervirulence” were raised when an outbreak was recorded in 2012. This ribotype was studied to compare its clinical and molecular characteristics with other endemic ribotypes and between its own outbreak-related and endemic subtypes. Asymptomatic children were also sampled to determine their role as pools of potential pathogens. Severe episodes accounted for 40.4% of total and 29.3% patients had multiple episodes on record. One-year mortality was 32.8% of which CDI was listed on 25.5% death certificates. Ribotype 078 was confirmed in 6.8% episodes. Community-associated disease was identified in 25.3% patients, which differed significantly from hospital-associated disease in the number of antibiotics and gastrointestinal manipulation prior to CDI. Endemic PCR ribotype 078 caused significantly less recurrent disease and more community- associated disease when compared to the most prevalent ribotype 001. Patients who died from ribotype 078 within 30d had a lower Charlson comorbidity index than ribotype 001 counterparts suggesting that the former may infect healthier patients. MLVA subtyping of ribotype 078 proved useful in identifying epidemiological relationships during the outbreak. CDI had contributed to the death of 50% of all patients infected with the outbreak related ribotype 078 strain compared to 14.3% of those infected with the endemic strains. This study documents the changing epidemiology of CDI in the region and demonstrates differences in epidemic and endemic disease

Synthesis of boron doped C3N4/NiFe2O4 nanocomposite: An enhanced visible light photocatalyst for the degradation of methylene blue

In this paper, we report the synthesis of boron doped C3N4/NiFe2O4 nanocomposite and its application as a visible-light photocatalyst for the degradation of methylene blue (MB). Boron-doped C3N4 (BCN) was prepared by simple thermal condensation of dicyandiamide with boric acid, and NiFe2O4 nanoparticles were prepared by the simple sol-gel method. The as-synthesized nanocomposite materials were characterized and confirmed by the X-ray diffraction spectroscopy, Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, UV-Visible diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The photocatalytic activity of BCN/NiFe2O4 nanocomposite was evaluated towards the degradation of MB in the presence of visible light irradiation. The obtained results confirmed that BCN/NiFe2O4 composite has higher degradation efficiency (98%) than that of BCN and NiFe2O4

Ruxolitinib: A restorative of COVID-19

Despite mass level vaccinations and the launch of several repurposed drugs, the recently emerged SARS CoV-2 Omicron (B.1.1.529) is a variant of concern. New drugs must be discovered with artificial intelligence (AI) assistance. Artificial intelligence (AI) enabled drug repurposing reduces the time and costs of drug discovery. Ruxolitinib (formerly known as INCB018424; Jakavi; Jakafi) is an oral inhibitor of JAK 1 & 2. Ruxolitinib has been approved to treat primary myelofibrosis, polycythemia vera, and hemophagocytic lymphohistiocytosis by the Food and Drug Administration and European Medicines Agency. The analysis of ruxolitinib is done via the CoV-DrugX pipeline. We find that the Ruxolitinib has a 75% probability of being considered a COVID-19 repurposed drug with the help of the CoV-DrugX pipeline. In addition, there is a clinical trial assessing the safety and efficacy of ruxolitinib. Therefore, we believe that Ruxolitinib could be a potent drug against the treatment of COVID-19

Ultrasonically Induced Sulfur-Doped Carbon Nitride/Cobalt Ferrite Nanocomposite for Efficient Sonocatalytic Removal of Organic Dyes

The sulfur-doped carbon nitride/cobalt ferrite nanocomposite (SCN/CoFe2O4) was prepared via ultrasonication and studied for the sonocatalytic degradation of wastewater organic dye pollutants including methylene blue, rhodamine B, and Congo red. The X-ray photoelectron spectroscopy confirmed the presence and atomic ratios of S, C, N, Co, Fe, and O elements and their corresponding bonds with Co2+ and Fe3+ cations. The nanocomposite was found to have aggregated nanoparticles on a sheet-like structure. The bandgap energy was estimated to be 1.85 eV. For the sonocatalytic degradation of 25-ppm methylene blue at 20 kHz, 1 W and 50% amplitude, the best operating condition was determined to be 1 g/L of catalyst dosage and 4 vol % of hydrogen peroxide loading. Under this condition, the sonocatalytic removal efficiency was the highest at 96% within a reaction period of 20 min. SCN/CoFe2O4 outperformed SCN and CoFe2O4 by 2.2 and 6.8 times, respectively. The SCN/CoFe2O4 nanocomposite was also found to have good reusability with a drop of only 7% after the fifth cycle. However, the degradation efficiencies were low when tested with rhodamine B and Congo red due to difference in dye sizes, structural compositions, and electric charges

N-acetylmuramoyl-L-alanine amidase : A competent vaccine candidate against IPSID

Immunoproliferative small intestine disease (IPSID) is a collective name for a range of diseases caused by various microorganisms but the major and persistent organism is Campylobacter Jejuni. IPSID can lead to minor symptoms like diarrhea, nausea, imbalance of electrolytes in the body etc. to major consequences that may lead to death in case of prolonged untreated condition. IPSID leads to infiltration of lymphocytes as a consequence of an immune response to invasion by microbes, which eventually leads to the evolvement of IgA producing bodies and to the selection of a body that produces α heavy chains. Hence, it is also called “α- Heavy chain disease”. Until now there has been no successful development of a vaccine for this disease. N-acetylmuramoyl-L-alanine amidase is one of the proteins in Campylobacter Jejuni ssp. Jejuni which is also a Potential vaccine candidate (PVC) against IPSID as identified by Vaxigen. Here, we are utilizing deep learning softwares i.e, Vaxi-DL and VaxELAN for analyzing the given protein in terms of adhesion, secretory nature, trans-membrane helices, cleavage sites, MHC-I binding, CTL epitope prediction, essential genes, molecular weight, non-bacterial pathogen, non-homology with human genome, virulence factors, allergenicity, cellular localization and probability of being a PVC

The Interactive Effect of <em>SIRT1</em> Promoter Region Polymorphism on Type 2 Diabetes Susceptibility in the North Indian Population

<div><p>Our previous studies have implicated genes mainly involved in the activity of pancreatic β cells in type 2 diabetes (T2D) susceptibility in the North Indian population. Recent literature on the role of <em>SIRT1</em> as a potential master switch modulating insulin secretion and regulating gene expression in pancreatic β cells has warranted an evaluation of <em>SIRT1</em> promoter region polymorphisms in the North Indian population, which is the main focus of the present study. 1542 samples (692 T2D patients and 850 controls) were sequenced for the 1.46 kb region upstream the translation start site of the <em>SIRT1</em> gene. We performed a functional characterization of the <em>SIRT1</em> promoter region polymorphisms using luciferase assay and observed a single-nucleotide polymorphism (SNP), rs12778366, in association with SIRT1 expression. We propose that TT, the high-expressing genotype of SNP rs12778366 in the <em>SIRT1</em> promoter region and present in >80% of the North Indian population, was favored under conditions of feast-famine cycles in evolution, which has turned out to be a cause of concern in the present sedentary lifestyle under <em>ad libitum</em> conditions. Case-control association analysis did not implicate rs12778366 in T2DM per se in the studied population. However, our earlier reported risk genotype combinations of mt-<em>ND3</em>, <em>PGC1α</em>, and <em>UCP2</em>-866, when compared with the protective genotype combinations, in the background of the high-expressing TT genotype of <em>SIRT1</em> SNP rs12778366, showed a very high additive risk [corrected odd ratio (OR) = 8.91; p = 6.5×10⁻¹¹]. The risk level was considerably low in the genotype backgrounds of TX (OR = 6.68; p = 2.71×10⁻¹²) and CX (OR = 3.74; p = 4.0×10⁻³). In addition, we screened other reported T2D-associated polymorphisms: <em>PIK3R1</em> rs3730089, <em>IRS1</em> rs1801278, and <em>PPP1R3</em> rs1799999, which did not show any significant association in North Indian population. The present paper emphasizes the importance of gene interactions in the biological pathways of T2D, a complex lifestyle disease.</p> </div