The mutual relationship between heart failure and atrial fibrillation

Atrial fibrillation (AF) and Heart Failure (HF) are evolving epidemies, together responsible for substantial human suffering and health-care expenditure. The simultaneous co-existence of the two conditions is associated with higher mortality rates than those observed in individuals with only one or none of them. Patients with concomitant HF and AF suffer from even worse symptoms and poorer prognosis, yet evidence-based evaluation and management of this group of patients is lacking. In this review, we evaluate the common mechanisms for the development of AF in HF patients and vice versa, focusing on the evidence for potential treatment strategies. Recent data have suggested that these patients may respond differently if compared to those with HF or AF alone. These results highlight the clear clinical need to identify and treat these diseases according to best evidence, in order to prevent adverse outcomes and reduce the huge burden er that HF and AF are expected to have on global healthcare systems in the future

Detection of the United States Neisseria meningitidis urethritis clade in the United Kingdom, August and December 2019 - emergence of multiple antibiotic resistance calls for vigilance.

Since 2015 in the United States (US), the US Neisseria meningitidis urethritis clade (US_NmUC) has caused a large multistate outbreak of urethritis among heterosexual males. Its 'parent' strain caused numerous outbreaks of invasive meningococcal disease among men who have sex with men in Europe and North America. We highlight the arrival and dissemination of US_NmUC in the United Kingdom and the emergence of multiple antibiotic resistance. Surveillance systems should be developed that include anogenital meningococci

Diversity of group B streptococcus serotypes causing urinary tract infection in adults

Serotypes of group B streptococcus (GBS) that cause urinary tract infection (UTI) are poorly characterized. We conducted a prospective study of GBS UTI in adults to define the clinical and microbiological characteristics of these infections, including which serotypes cause disease. Patients who had GBS cultured from urine over a 1-year period were grouped according to symptoms, bacteriuria, and urinalysis. Demographic data were obtained by reviewing medical records. Isolates were serotyped by latex agglutination and multiplex PCRreverse line blotting (mPCR/RLB). Antibiotic susceptibilities were determined by disc diffusion. GBS was cultured from 387/34,367 consecutive urine samples (1.1%): 62 patients had bacteriuria of >10 7 CFU/liter and at least one UTI symptom; of these patients, 31 had urinary leukocyte esterase and pyuria (others not tested), 50 (81%) had symptoms consistent with cystitis, and 12 (19%) had symptoms of pyelonephritis. Compared with controls (who had GBS isolated without symptoms), a prior history of UTI was an independent risk factor for disease. Increased age was also significantly associated with acute infection. Serotyping results were consistent between latex agglutination and mPCR/RLB for 331/387 (85.5%) isolates; 22 (5.7%) and 7 (1.8%) isolates were nontypeable with antisera and by mPCR/RLB, respectively; and 45/56 (80.4%) isolates with discrepant results were typed by mPCR/RLB as belonging to serotype V. Serotypes V, Ia, and III caused the most UTIs; serotypes II, Ib, and IV were less common. Nontypeable GBS was not associated with UTI. Erythromycin (39.5%) and clindamycin (26.4%) resistance was common. We conclude that a more diverse spectrum of GBS serotypes causes UTI than previously recognized, with the exception of nontypeable GBS

Molecular epidemiology of multidrug-resistant Acinetobacter baumannii in a single institution over a 10-year period

The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Acinetobacter baumannii (CRAB) were determined in hospitals in the states of the Cooperation Council for the Arab States of the Gulf (Gulf Cooperation Council [GCC]), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic resistance genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Selected isolates were subjected to multilocus sequence typing (MLST). We investigated 117 isolates resistant to carbapenem antibiotics (either imipenem or meropenem). All isolates were positive for OXA-51. The most common carbapenemases were the OXA-23-type, found in 107 isolates, followed by OXA-40-type (OXA-24-type), found in 5 isolates; 3 isolates carried the ISAba1 element upstream of blaOXA-51-type. No OXA-58-type, NDM-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with 16 clusters of clonally related CRAB. Some clusters involved hospitals in different states. MLST analysis of 15 representative isolates from different clusters identified seven different sequence types (ST195, ST208, ST229, ST436, ST450, ST452, and ST499), as well as three novel STs. The vast majority (84%) of the isolates in this study were associated with health care exposure. Awareness of multidrug-resistant organisms in GCC states has important implications for optimizing infection control practices; establishing antimicrobial stewardship programs within hospital, community, and agricultural settings; and emphasizing the need for establishing regional active surveillance systems. This will help to control the spread of CRAB in the Middle East and in hospitals accommodating transferred patients from this region

The influence of pH, temperature and salt on the ethanolic desolvation of dilute cold water fish skin gelatin from aqueous solution

Gelatin is a heterogeneous mixture of water-soluble proteins of high molecular weight. It is the degradation product of the protein collagen, a long triple-stranded helical rod which is stabilized by non-covalent interactions and covalent crosslinking. A number of studies have been carried on the desolvation of various types of gelatin of mammalian origin.1,2 Cold-water fish skin gelatin (CWFSG) has a different imino acid composition to mammalian gelatin. The number of proline and hydroxylproline groups in CWFSG is lower and this means that there is less hydrogen bonding. This leads to a different secondary structure. Moreover, the differences in the primary structure of the protein would also be expected to cause differences in other physical properties fish gelatin may exhibit. The objective of this work was to determine the response of CWFSG in aqueous solution, to the non- solvent ethanol under different conditions of pH, temperature and concentration.peer-reviewe

Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics

There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen

Interplay between tolerance mechanisms to copper and acid stress in Escherichia coli

Copper (Cu) is a key antibacterial component of the host innate immune system and almost all bacterial species possess systems that defend against the toxic effects of excess Cu. The Cu tolerance system in Gram-negative bacteria is composed minimally of a Cu sensor (CueR) and a Cu export pump (CopA). The cueR and copA genes are encoded on the chromosome typically as a divergent but contiguous operon. In Escherichia coli, cueR and copA are separated by two additional genes, ybaS and ybaT, which confer glutamine (Gln)-dependent acid tolerance and contribute to the glutamate (Glu)-dependent acid resistance system in this organism. Here we show that Cu strongly inhibits growth of a ∆copA mutant strain in acidic cultures. We further demonstrate that Cu stress impairs the pathway for Glu biosynthesis via glutamate synthase, leading to decreased intracellular levels of Glu. Addition of exogenous Glu rescues the ∆copA mutant from Cu stress in acidic conditions. Gln is also protective but this relies on the activities of YbaS and YbaT. Notably, expression of both enzymes is up-regulated during Cu stress. These results demonstrate a link between Cu stress, acid stress, and Glu/Gln metabolism, establish a role for YbaS and YbaT in Cu tolerance, and suggest that subtle changes in core metabolic pathways may contribute to overcoming host-imposed copper toxicity

Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone.

UNLABELLED: Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three (m6)A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for (m6)A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located. IMPORTANCE: DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant E. coli sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined E. coli clone

Electron/pion separation with an Emulsion Cloud Chamber by using a Neural Network

We have studied the performance of a new algorithm for electron/pion separation in an Emulsion Cloud Chamber (ECC) made of lead and nuclear emulsion films. The software for separation consists of two parts: a shower reconstruction algorithm and a Neural Network that assigns to each reconstructed shower the probability to be an electron or a pion. The performance has been studied for the ECC of the OPERA experiment [1]. The $e/\pi$ separation algorithm has been optimized by using a detailed Monte Carlo simulation of the ECC and tested on real data taken at CERN (pion beams) and at DESY (electron beams). The algorithm allows to achieve a 90% electron identification efficiency with a pion misidentification smaller than 1% for energies higher than 2 GeV

Nine-year nationwide environmental surveillance of hepatitis E virus in urban wastewaters in Italy (2011–2019)

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis worldwide. To provide insights into the epidemiology of HEV in Italy, a large-scale investigation was conducted into urban sewage over nine years (2011–2019), collecting 1374 sewage samples from 48 wastewater treatment plants located in all the 20 regions of Italy. Broadly reactive primers targeting the ORF1 and ORF2 regions were used for the detection and typing of HEV, followed by Sanger and next generation sequencing (NGS). Real-time RT-qPCR was also used to attempt quantification of positive samples. HEV RNA detection occurred in 74 urban sewage samples (5.4%), with a statistically significant higher frequency (7.1%) in central Italy. Fifty-six samples were characterized as G3 strains and 18 as G1. While the detection of G3 strains occurred in all the surveillance period, G1 strains were mainly detected in 2011–2012, and never in 2017–2019. Typing was achieved in 2 samples (3f subtype). Viral concentrations in quantifiable samples ranged from 1.2 × 103 g.c./L to 2.8 × 104 g.c./L. Our results suggest the considerable circulation of the virus in the Italian population, despite a relatively small number of notified cases, a higher occurrence in central Italy, and a noteworthy predominance of G3 strains