Campylobacter devanensis sp. nov., Campylobacter porcelli sp. nov., and Campylobacter vicugnae sp. nov., three novel Campylobacter lanienae-like species recovered from swine, small ruminants, and camelids.

In a previous study characterizing Campylobacter strains deficient in selenium metabolism, 50 strains were found to be similar to, but distinct from, the selenonegative species Campylobacter lanienae. Initial characterization based on multilocus sequence typing and the phylogeny of a set of 20 core genes determined that these strains form three putative taxa within the selenonegative cluster. A polyphasic study was undertaken here to further clarify their taxonomic position within the genus. The 50 selenonegative strains underwent phylogenetic analyses based on the sequences of the 16S rRNA gene and an expanded set of 330 core genes. Standard phenotypic testing was also performed. All strains were microaerobic and anaerobic, Gram-negative, spiral or curved cells with some displaying coccoid morphologies. Strains were motile, oxidase, catalase, and alkaline phosphatase positive, urease negative, and reduced nitrate. Strains within each clade had unique phenotypic profiles that distinguished them from other members of the genus. Core genome phylogeny clearly placed the 50 strains into three clades. Pairwise average nucleotide identity and digital DNA-DNA hybridization values were all below the recommended cut-offs for species delineation with respect to C. lanienae and other related Campylobacter species. The data presented here clearly show that these strains represent three novel species within the genus, for which the names Campylobacter devanensis sp. nov. (type strain RM3662T=LMG 33097T=NCTC 15074T), Campylobacter porcelli sp. nov. (type strain RM6137T=LMG 33098T=CCUG 77054T=NCTC 15075T) and Campylobacter vicugnae sp. nov. (type strain RM12175T=LMG 33099T=CCUG 77055T=NCTC 15076T) are proposed.

Drug-resistant Pantoea agglomerans Causing Bacteremia at a Tertiary Care Hospital in Kolkata, India: First Report of Carbapenem Resistance Mediated by OXA-181.

The spread of antibiotic resistance (ABR) in uncommon human pathogens endangers global public health, escalating morbidity, death, and healthcare expenditures. Pantoea agglomerans, a member of the Erwiniaceae family that rarely infects humans, is emerging as a drug-resistant nosocomial pathogen. Seven P. agglomerans isolates were recovered from bacteremia patients at a tertiary care hospital in Kolkata, West Bengal, between March 2022 and October 2022. The isolates were evaluated for phenotypic resistance, ß-lactamase and plasmid-mediated quinolone resistance (PMQR) genes, plasmid profiling, and clonality assessment. All isolates were resistant to fluoroquinolones and third-generation cephalosporins, with four resistant to carbapenems. The following ß-lactamases and PMQR genes were identified: blaOXA-1 (n = 1), blaTEM (n = 1), blaCTX-M-1 (n = 2), blaNDM (n = 5), blaOXA-181 (n = 1), qnrB (n = 2), and qnrS (n = 4). Six isolates carried up to seven plasmids ranging in size from 2 kb to > 212 kb. IncFI, FII, HI, and X3 plasmid types were detected in three isolates, while the rest remained untypable. Four different genetic patterns were noted. Four isolates were clonally related, with three being clonal. The swap of environmental isolates to human pathogens exacerbates the ABR dilemma, periling patient care and outcomes. This is the first report in India of a carbapenem-resistant P. agglomerans blood isolate carrying blaOXA-181. In-depth genomic research of drug-resistant microbes adapted to the environment-human interfaces might underpin the source-route-containment of ABR.

Can drug-induced sleep endoscopy (DISE) predict compliance with positive airway pressure therapy? A pilot study.

PURPOSE: Drug-induced sleep endoscopy (DISE) has been poorly explored as an examination to assess positive airway pressure (PAP) therapy in patients with obstructive sleep apnea (OSA). The present study aimed to identify by DISE possible characteristics related to low compliance with PAP therapy due to respiratory complaints. METHODS: Patients using PAP for OSA underwent DISE in two conditions: (1) baseline (without PAP) and (2) PAP (with the same mask and airway pressure used at home). We compared patients reporting low compliance to PAP due to respiratory complaints to those well-adapted to therapy. VOTE classification (assessment of velopharynx, oropharynx, tongue base, and epiglottis) and TOTAL VOTE score (the sum of VOTE scores at each anatomical site) were assessed. ROC curve analyzed the accuracy of TOTAL VOTE to predict low compliance due to persistent pharyngeal obstruction in both conditions. RESULTS: Of 19 patients enrolled, all presented multilevel pharyngeal obstruction at baseline condition, with no difference between groups at this study point. When PAP was added, the median VOTE value was higher in the epiglottis (P value=0.02) and tended to be higher at the velum and tongue base in the poorly adapted group; TOTAL VOTE score was also significantly increased in patients with low compliance (P value<0.001). ROC curve demonstrated that patients with TOTAL VOTE scored 2.5 or more during DISE with PAP presented a 4.6-fold higher risk for low compliance with PAP therapy due to pharyngeal obstruction (AUC: 0.88±0.07; P value<0.01; sensitivity: 77%; specificity: 83%). CONCLUSIONS: Adding PAP during a DISE examination may help to predict persistent pharyngeal obstruction during PAP therapy.

Impact of a structured patient education programme on early diagnosis of prosthetic pulmonary valve endocarditis.

BACKGROUND: Infective endocarditis is a major threat after prosthetic pulmonary valve replacement. Early diagnosis may improve outcomes. METHODS: A structured patient education programme for prevention and early diagnosis of infective endocarditis was developed at our institution since 2016. Time delay between onset of symptoms of prosthetic pulmonary valve endocarditis and its diagnosis (defined as initiation of appropriate high-dose intravenous antibiotic treatment) was compared for patients presenting before (cohort 1) and after (cohort 2) initiation of the patient education programme. RESULTS: Between 2008-2019, 26 patients (median age 24.9, range: 16.8-62.0 years, 73% male) were diagnosed with prosthetic pulmonary valve endocarditis, 13 patients (cohort 1) before (1.7 cases/year) and 13 patients (cohort 2) after June 2016 (3.7 cases/year). There were no differences in baseline characteristics or clinical presentation between the study cohorts. Overall, the median delay between onset of symptoms and diagnosis of infective endocarditis was 6 days (range: 0-133 days) with a significantly longer delay among patients in cohort 1, compared to cohort 2 (25 days, range: 5-133 days versus 3 days, range: 0-13 days, p < 0.0001). A delay of >7 days was documented in 11/13 patients (85%) in cohort 1 as compared to 1/13 (8%) in cohort 2 (p < 0.001). Need for urgent valve replacement or permanent deterioration of prosthetic valve function was higher in cohort 1, compared to cohort 2 (11/13, 85% versus 5/13, 39%; p = 0.041). CONCLUSIONS: Prosthetic pulmonary valve endocarditis is increasingly recognised. A structured patient education programme may improve early diagnosis and clinical outcomes.

Characterization of the Anti-Biofilm and Anti-Quorum Sensing Activities of the ß-Adrenoreceptor Antagonist Atenolol against Gram-Negative Bacterial Pathogens.

The development of bacterial resistance to antibiotics is an increasing public health issue that worsens with the formation of biofilms. Quorum sensing (QS) orchestrates the bacterial virulence and controls the formation of biofilm. Targeting bacterial virulence is promising approach to overcome the resistance increment to antibiotics. In a previous detailed in silico study, the anti-QS activities of twenty-two ß-adrenoreceptor blockers were screened supposing atenolol as a promising candidate. The current study aims to evaluate the anti-QS, anti-biofilm and anti-virulence activities of the ß-adrenoreceptor blocker atenolol against Gram-negative bacteria Serratia marcescens, Pseudomonas aeruginosa, and Proteus mirabilis. An in silico study was conducted to evaluate the binding affinity of atenolol to S. marcescens SmaR QS receptor, P. aeruginosa QscR QS receptor, and P. mirabilis MrpH adhesin. The atenolol anti-virulence activity was evaluated against the tested strains in vitro and in vivo. The present finding shows considerable ability of atenolol to compete with QS proteins and significantly downregulated the expression of QS- and virulence-encoding genes. Atenolol showed significant reduction in the tested bacterial biofilm formation, virulence enzyme production, and motility. Furthermore, atenolol significantly diminished the bacterial capacity for killing and protected mice. In conclusion, atenolol has potential anti-QS and anti-virulence activities against S. marcescens, P. aeruginosa, and P. mirabilis and can be used as an adjuvant in treatment of aggressive bacterial infections.

The Role of Antimicrobial Peptides as Antimicrobial and Antibiofilm Agents in Tackling the Silent Pandemic of Antimicrobial Resistance.

Just over a million people died globally in 2019 due to antibiotic resistance caused by ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The World Health Organization (WHO) also lists antibiotic-resistant Campylobacter and Helicobacter as bacteria that pose the greatest threat to human health. As it is becoming increasingly difficult to discover new antibiotics, new alternatives are needed to solve the crisis of antimicrobial resistance (AMR). Bacteria commonly found in complex communities enclosed within self-produced matrices called biofilms are difficult to eradicate and develop increased stress and antimicrobial tolerance. This review summarises the role of antimicrobial peptides (AMPs) in combating the silent pandemic of AMR and their application in clinical medicine, focusing on both the advantages and disadvantages of AMPs as antibiofilm agents. It is known that many AMPs display broad-spectrum antimicrobial activities, but in a variety of organisms AMPs are not stable (short half-life) or have some toxic side effects. Hence, it is also important to develop new AMP analogues for their potential use as drug candidates. The use of one health approach along with developing novel therapies using phages and breakthroughs in novel antimicrobial peptide synthesis can help us in tackling the problem of AMR.

Going virtual: a report from the sixth Young Microbiologists Symposium on 'Microbe Signalling, Organisation and Pathogenesis'.

The sixth Young Microbiologists Symposium on 'Microbe Signalling, Organisation and Pathogenesis' was scheduled to be held at the University of Southampton, UK, in late August 2020. However, due to the health and safety guidelines and travel restrictions as a response to the COVID-19 pandemic, the symposium was transitioned to a virtual format, a change embraced enthusiastically as the meeting attracted over 200 microbiologists from 40 countries. The event allowed junior scientists to present their work to a broad audience and was supported by the European Molecular Biology Organization, the Federation of European Microbiological Societies, the Society of Applied Microbiology, the Biochemical Society, the Microbiology Society and the National Biofilms Innovation Centre. Sessions covered recent advances in all areas of microbiology including: Secretion and transport across membranes, Gene regulation and signalling, Host-microbe interactions, and Microbial communities and biofilm formation. This report focuses on several of the highlights and exciting developments communicated during the talks and poster presentations.

Impact of intraoperative blood salvage and autologous transfusion during liver transplantation for hepatocellular carcinoma.

PURPOSE: Intraoperative blood salvage (IBS) with autologous blood transfusion is controversial in liver transplantation (LT) for hepatocellular carcinoma (HCC). This study evaluated the role of IBS usage in LT for HCC. METHODS: In a retrospective cohort study at a single center from 2002 to 2018, the outcomes of LT surgery for HCC were analyzed. Overall survival and disease-free survival of patients who received IBS were compared with those who did not receive IBS. Cancer recurrence, length of hospital stay, post-transplant complications, and blood loss also were evaluated. The primary aim of this study was to evaluate overall mid-term and long-term survival (4 and 6 years, respectively). RESULTS: Of the total 163 patients who underwent LT for HCC in the study period, 156 had complete demographic and clinical data and were included in the study. IBS was used in 122 and not used in 34 patients. Ninety-five (60.9%) patients were men, and the mean patient age was 58.5 ± 7.6 years. The overall 1-year, 5-year, and 7-year survival in the IBS group was 84.2%, 67.7%, and 56.8% vs. 85.3%, 67.5%, and 67.5% in the non-IBS group (p = 0.77). The 1-year, 5-year, and 7-year disease-free survival in the IBS group was 81.6%, 66.5%, and 55.4% vs. 85.3%, 64.1%, and 64.1% in the non-IBS group (p = 0.74). For patients without complete HCC necrosis (n = 121), the 1-year, 5-year, and 7-year overall survival rates for those who received IBS (n = 95) were 86.2%, 67.7%, and 49.6% vs. 84.6%, 70.0%, and 70.0% for 26 patients without IBS (p = 0.857). For the same patients, the 1-year, 5-year, and 7-year disease-free survival in the IBS group was 84.0%, 66.8%, and 64.0% vs. 88.0%, 72.8%, and 72.8% in the non-IBS group (p = 0.690). CONCLUSION: IBS does not appear to be associated with worse outcomes in patients undergoing LT for HCC, even in the presence of viable HCC in the explant. There seems to be no reason to contraindicate the use of IBS in LT for HCC.

Genomic insights into the phylogeny of Bacillus strains and elucidation of their secondary metabolic potential.

The genus Bacillus constitutes a plethora of species that have medical, environmental, and industrial applications. While genus Bacillus has been the focus of several studies where genomic data have been used to resolve many taxonomic issues, there still exist several ambiguities. Through the use of in-silico genome-based methods, we tried to resolve the taxonomic anomalies of a large set of Bacillus genomes (n = 178). We also proposed species names for uncharacterized strains and reported genome sequence of a novel isolate Bacillus sp. RL. In the hierarchical clustering on genome-to-genome distances, we observed 11 distinct monophyletic clusters and investigated the functional pathways annotated as the property of these clusters and core-gene content of the entire dataset. Thus, we were able to assert the possible outlier strains (n = 17) for this genus. Analyses of secondary metabolite potential of each strain helped us unravel still unexplored diversity for various biosynthetic genes.

Comparative analysis of completeness of death registration, adult mortality and life expectancy at birth in Brazil at the subnational level.

BACKGROUND: Estimates of completeness of death registration are crucial to produce estimates of life tables and population projections and to estimate the burden of disease. They are an important step in assessing the quality of data. In the case of subnational data analysis in Brazil, it is important to consider spatial and temporal variation in the quality of mortality data. There are two main sources of data quality evaluation in Brazil, but there are few comparative studies and how they evolve over time. The aim of the paper is to compare and discuss alternative estimates of completeness of death registration, adult mortality (45q15) and life expectancy estimates produced by the National Statistics Office (IBGE), Institute for Health Metrics and Evaluation (IHME), and estimates presented in Queiroz et al. (2017) and Schmertmann and Gonzaga (2018), for 1980 and 2010. METHODS: We provide a descriptive and comparative analysis of aforementioned estimates from four (4) sources of estimates at subnational level (26 states and one Federal District) in Brazil from two different points in time. RESULTS: We found significant differences in estimates that affect both levels and trends of completeness of adult mortality in Brazil and states. IHME and Queiroz et al. (2017) estimates converge by 2010, but there are large differences when compared to estimates from the National Statistics Office (IBGE). Larger differences are observed for less developed states. We have showed that the quality of mortality data in Brazil has improved steadily overtime, but with large regional variations. However, we have observed that IBGE estimates show the lowest levels of completeness for the Northern of the country compared to other estimates. Choice of methods and approaches might lead to very unexpected results. CONCLUSION: We produced a detailed comparative analysis of estimates of completeness of death registration from different sources and discuss the main results and possible explanations for these differences. We have also showed that new improved methods are still needed to study adult mortality in less developed countries and at a subnational level. More comparative studies are important in order to improve quality of estimates in Brazil.

Liver transplantation in the setting of a spontaneous shunt between superior mesenteric vein and right renal vein.

Shunts between the superior mesenteric vein (SMV) and the right renal vein (RRV) are very rare. Here, we describe and depict the rare case of a liver transplant (LT) in the setting of shunt between SMV and RRV. A 67-year-old white man presenting with Child C cirrhosis secondary to hemochromatosis and persistent encephalopathy was listed for LT. Preoperative abdominal angiotomography revealed the presence of a large spontaneous shunt between the SMV and the RRV. The patient underwent LT by receiving a liver from a 17-year-old brain-dead deceased donor victim of trauma. A large shunt between the SMV and the RRV was confirmed intraoperatively. Although there was no portal vein (PV) thrombosis, the PV was atrophic and had a reduced flow. PV pressure was 22mmHg (an arterial line was inserted inside the PV stump, and this line was connected to a common pressure transducer, the pressure readings was expressed in the anesthesia monitor). After shunt ligation PV pressure increased to 32mmHg. There were no post-transplant vascular complications, and the patient was discharged home in good health. Preoperative study of all LT candidates with angio CT scan is mandatory. Whenever there is PV thrombosis, an attempt to remove the entire thrombus is warranted. After thrombectomy or whenever there is not PV thrombosis, all large shunts should be ligated. PV pressure and flow should be measured before and after shunt ligation. In the absence of PV thrombosis, ligation of the shunt should enable an increase in PV flow and pressure, as reported herein.

Nasal vs. oronasal mask during PAP treatment: a comparative DISE study.

PURPOSE: The present study evaluated the upper airway pattern of obstruction in individuals undergoing drug-induced sleep endoscopy (DISE) exam with positive airway pressure (PAP), and compared this effect through a nasal or oronasal mask. METHODS: Prospective study. Patients requiring PAP due to obstructive sleep apnea (OSA) were evaluated through DISE at three different moments: (1) a baseline condition (without PAP); (2) PAP treatment with a nasal mask; and (3) PAP with an oronasal mask at the same pressure. The conditions were compared intra-individually, following VOTE classification. A TOTAL VOTE score (the sum of VOTE scores observed for each anatomical site) was also applied to compare intra-individual results. RESULTS: Thirteen patients were enrolled in the study. All patients presented multi-level pharyngeal obstruction at baseline condition. In six patients, the pattern of obstruction differed according to the mask. Nasal mask significantly decreased the obstruction score when compared with baseline condition both in velum (P value < 0.05) and oropharynx regions (P value < 0.005). TOTAL VOTE score was also significantly lower during nasal mask evaluation when compared with basal condition (P value < 0.005). Remarkably, oronasal mask with the same pressure was not as effective as nasal masks. Obstruction levels observed at the tongue base or epiglottis levels were more resistant to PAP treatment. CONCLUSIONS: Collapse in velum and oropharyngeal sites is more compliant to PAP than obstruction at lower levels of the pharynx, either with nasal or oronasal masks. Nasal mask is superior to prevent pharyngeal collapse than oronasal devices under the same pressure.

XRCC4 rs28360071 intronic variant is associated with increased risk for infant acute lymphoblastic leukemia with KMT2A rearrangements.

Early age acute leukemia (EAL) shows a high frequency of KMT2A-rearrangements (KMT2A-r). Previous investigations highlighted double-strand breaks arising from maternal exposure to xenobiotics during pregnancy as a risk factor for EAL and KMT2A-r. In this case-control study, we investigated the relationship between EAL and genetic variants of the nonhomologous end-joining (XRCC6 rs5751129, XRCC4 rs6869366 and rs28360071), since they might affect DNA repair capacity, leading to KMT2A-r and leukemogenesis. Samples from 577 individuals (acute lymphoblastic leukemia-ALL, n=164; acute myeloid leukemia-AML, n=113; controls, n=300) were genotyped. No significant association was found for rs5751129 and rs6869366, whereas rs28360071 was associated with an increased risk for ALL with KMT2A-r (IIxID: OR - Odds ratio 2.23, CI 1.17-4.25, p=0.014). Bone marrow samples from ALL patients showed a higher expression of XRCC4 compared to AML patients (p=0.025). Human Splicing Finder 3.1 predicted that the deleted allele of rs28360071 is potentially associated with the activation of a 5' cryptic splice site in intron 3 of XRCC4. The sequencing of cDNA did not show any differences on the splicing process for the rs28360071 genotypes. Our results suggest that the deleted allele for rs28360071 increases the risk for ALL with KMT2A-r, but not by modifying the XRCC4 expression levels or its structure.

Phylogeographic Analysis Reveals Multiple International transmission Events Have Driven the Global Emergence of Escherichia coli O157:H7.

BACKGROUND: Shiga toxin-producing Escherchia coli (STEC) O157:H7 is a zoonotic pathogen that causes numerous food and waterborne disease outbreaks. It is globally distributed, but its origin and the temporal sequence of its geographical spread are unknown. METHODS: We analyzed whole-genome sequencing data of 757 isolates from 4 continents, and performed a pan-genome analysis to identify the core genome and, from this, extracted single-nucleotide polymorphisms. A timed phylogeographic analysis was performed on a subset of the isolates to investigate its worldwide spread. RESULTS: The common ancestor of this set of isolates occurred around 1890 (1845-1925) and originated from the Netherlands. Phylogeographic analysis identified 34 major transmission events. The earliest were predominantly intercontinental, moving from Europe to Australia around 1937 (1909-1958), to the United States in 1941 (1921-1962), to Canada in 1960 (1943-1979), and from Australia to New Zealand in 1966 (1943-1982). This pre-dates the first reported human case of E. coli O157:H7, which was in 1975 from the United States. CONCLUSIONS: Inter- and intra-continental transmission events have resulted in the current international distribution of E. coli O157:H7, and it is likely that these events were facilitated by animal movements (eg, Holstein Friesian cattle). These findings will inform policy on action that is crucial to reduce the further spread of E. coli O157:H7 and other (emerging) STEC strains globally.

Nationwide Stepwise Emergence and Evolution of Multidrug-Resistant Campylobacter jejuni Sequence Type 5136, United Kingdom.

We examined whole-genome-sequenced Campylobacter jejuni and C. coli from 2012-2015 isolated from birds and human stool samples in North East Scotland for the presence of antimicrobial resistance genes. We found that sequence type (ST) 5136 (clonal complex 464) was the most prevalent multidrug-resistant strain of C. jejuni exclusively associated with poultry host reservoirs and recovered from human cases of campylobacteriosis. Tetracycline resistance in ST5136 isolates was due to a tet(O/32/O) mosaic gene, ampicillin resistance was conferred by G → T transversion in the -10 promoter region of blaOXA-193, fluoroquinolone resistance was due to C257T change in gyrA, and aminoglycoside resistance was conferred by aac. Whole-genome analysis showed that the strain ST5136 evolved from ST464. The nationwide emergence of ST5136 was probably due to stepwise acquisition of antimicrobial resistance genes selected by high use of ß-lactam, tetracycline, fluoroquinolone, and aminoglycoside classes of drugs in the poultry industry.

Genomic analysis of a novel Rhodococcus (Prescottella) equi isolate from a bovine host.

Rhodococcus (Prescottella) equi causes pneumonia-like infections in foals with high mortality rates and can also infect a number of other animals. R. equi is also emerging as an opportunistic human pathogen. In this study, we have sequenced the genome of a novel R. equi isolate, B0269, isolated from the faeces of a bovine host. Comparative genomic analyses with seven other published R. equi genomes, including those from equine or human sources, revealed a pangenome comprising of 6876 genes with 4141 genes in the core genome. Two hundred and 75 genes were specific to the bovine isolate, mostly encoding hypothetical proteins of unknown function. However, these genes include four copies of terA and five copies of terD genes that may be involved in responding to chemical stress. Virulence characteristics in R. equi are associated with the presence of large plasmids carrying a pathogenicity island, including genes from the vap multigene family. A BLAST search of the protein sequences from known virulence-associated plasmids (pVAPA, pVAPB and pVAPN) revealed a similar plasmid backbone on two contigs in bovine isolate B0269; however, no homologues of the main virulence-associated genes, vapA, vapB or vapN, were identified. In summary, this study confirms that R. equi genomes are highly conserved and reports the presence of an apparently novel plasmid in the bovine isolate B0269 that needs further characterisation to understand its potential involvement in virulence properties.

L-TRUST: Long-term risk of cancer in patients under statins therapy. A systematic review and meta-analysis.

INTRODUCTION: Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long-term exposure to statins. This meta-analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins. METHODS: Medline, Cochrane library, and clinicaltrials.gov were searched in order to identify studies with a minimum average follow-up of 10 years of exposure to statins and a cancer-related outcome reported. Relative risk (RR) of the primary outcomes and the combined effect was presented using a random-effects model. In the selected randomized control trials (RCT), statin exposure was compared with placebo, and in the selected observational studies, it was compared with no exposure to statins. RESULTS: We retrieved 1627 studies, of which 15 full-papers were included for final review, five RCT, two cohort studies (CSs), and eight case-control studies (CCs), representing a total of 358 544 patients. Five RCT, two cohort studies (CSs), and eight case-control studies (CCs). No significant differences were found regarding risk of cancer occurrence (RR = 1.08, 0.96-1.21) or cancer mortality (RR = 0.91, 0.80-1.04) due to long-term statin exposure. Regarding all-cause mortality, a protective effect was found (RR = 0.93, 0.90-0.97). CONCLUSIONS: According to available and published evidence, statins are not associated with an increased risk of cancer after prolonged exposure. These findings strengthen the role of statins in the primary and secondary prevention of cardiovascular events.

HIV prevalence and risk factors in infants born to HIV positive mothers, measured by dried blood spot real-time PCR assay in Tigray, Northern Ethiopia.

BACKGROUND: Infants infected during pregnancy or while breastfeeding requires early HIV diagnosis at 6 weeks after birth to identify HIV infection and timely treatment. The objective of this work was to determine the prevalence and associated risk factors of HIV among HIV exposed infants in the Tigray regional state, Northern Ethiopia. METHODS: A cross-sectional study was conducted on 350 exposed infants born to HIV seropositive mothers from September 01 to December 30, 2016. Convenient consecutive sampling technique was employed to enroll HIV exposed infants from age 6 weeks to 18 months attending prevention of mother to child transmission (PMCT) clinic at Anti Retroviral Therapy (ART) site facility in Tigray, Ethiopia. Sociodemographic data and associated risk factors were collected using a structured questionnaire. Dried Blood Spot (DBS) samples were collected from each infant and transported by post to Tigray Health Research Institute to detect HIV infection using real-time Polymerase Chain Reaction (PCR). Data were entered into EPI Info version 7, exported and analyzed using Statistical Package for Social Sciences (SPSS) version 22. p-value less than 0.05 was deemed to be statistically significant by Fisher's exact test. RESULTS: Three hundred forty infants (175 males, 165 females) met the criteria for selection during the completion of the study and the overall HIV prevalence was found to be 2.1% (n = 7). The majority of infants were from urban areas (n = 246, 72.4%). 45.5% (5/11, p = 0.001) infants were without ARV prophylaxis, 60% (3/5, p = 0.001) infants born to mothers who did not take maternal PMTCT intervention, 43% (3/7, p = 0.001) infants born to mothers who were not enrolled to ART care, and 6.1% (4/66, p = 0.029) infants of unmarried mothers showed statistically significant difference. CONCLUSIONS: The overall prevalence of HIV among exposed infants was high but lower than the Millennium Development Goal targets. In order to eliminate the mother to child HIV transmission (MTCT) ARV prophylaxis in infants must be strengthened, and enrollment of HIV positive pregnant women to PMTCT and ART care and treatment is needed.

The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model.

BACKGROUND: Phage therapy is the therapeutic use of bacteriophages to treat highly drug resistant bacterial infections. The current surge in bacteriophage therapy is motivated mainly because of the emergence of antibiotic-resistant bacteria in clinics. This study evaluated the therapeutic potential of three bacteriophages isolated against Escherichia coli ec311, Klebsiella pneumoniae kp235 and Enterobacter cloacae el140 strains using Galleria mellonella. The in vitro activity of three different phages belonging to Podoviridae and Myoviridae families was studied by the double agar overlay method against multi-drug resistant strains. Larval survivability studies were performed to evaluate the potential of phages against infection using G. mellonella. RESULTS: All the three phages were found to have potential to infect the host bacterial strains. For in vivo studies it was observed that E. coli and E. cloacae infected larvae, should be treated with three phage doses (20 µL, 104 PFU/mL) at 6 h interval to achieve 100% survival rate. But in the case of K. pneumoniae, a single phage dose treatment showed promising outcome. When mixed bacterial infections (all three bacterial cultures at 108 CFU/mL) were tested, minimum of four doses of phage cocktail (three phages) at 6 h interval was necessary to recover the larvae. All the results were confirmed by enumerating bacteria from the larvae. CONCLUSION: Our data shows that although in vitro studies showed high infectivity of phages, for in vivo models multiple phage doses were required for effective treatment.

EPHX1 rs1051740 T>C (Tyr113His) is strongly associated with acute myeloid leukemia and KMT2A rearrangements in early age.

Experimental and epidemiological data have shown that acute myeloid leukemia in early-age (i-AML) originates prenatally. The risk association between transplacental exposure to benzene metabolites and i-AML might be influenced by genetic susceptibility. In this study, we investigated the relationship between genetic polymorphisms in CYP2E1, EPHX1, MPO, NQO1, GSTM1 and GSTT1 genes, and i-AML risk. The study included 101 i-AMLs and 416 healthy controls. Genomic DNA from study subjects was purified from bone marrow or peripheral blood aspirates and genotyped for genetic polymorphisms by real-time PCR allelic discrimination, Sanger sequencing and multiplex PCR. Crude and adjusted odds ratios (OR, adjOR, respectively) with 95% confidence intervals (95% CI) were assessed using unconditional logistic regression to estimate the magnitude of risk associations. EPHX1 rs1051740 T>C was associated with i-AML risk under the co-dominant (adjOR 3.04, P = 0.003) and recessive (adjOR 2.99, P = 0.002) models. In stratified analysis, EPHX1 rs1051740 was associated with increased risk for i-AML with KMT2A rearrangement (adjOR 3.06, P = 0.045), i-AML with megakaryocytic differentiation (adjOR 5.10, P = 0.008), and i-AML with type I mutation (adjOR 2.02, P = 0.037). EPHX1 rs1051740-rs2234922 C-G haplotype was also associated with increased risk for i-AML (adjOR 2.55, P = 0.043), and for i-AML with KMT2A rearrangement (adjOR 3.23, P = 0.034). Since EPHX1 enzyme is essential in cellular defense against epoxides, the diminished enzymatic activity conferred by the variant allele C could explain the risk associations found for i-AML. In conclusion, EPHX1 rs1051740 plays an important role in i-AML's genetic susceptibility by modulating the carcinogenic effects of epoxide exposures in the bone marrow.