The BLISTER Score: A Novel, Externally Validated Tool for Predicting Cardiac Implantable Electronic Device Infections, and Its Cost-Utility Implications for Antimicrobial Envelope Use.

BACKGROUND: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology. METHODS: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation. RESULTS: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9-6.1]; P<0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4-6.4]; P=0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6-17.9]; P<0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6-4.1]; P=0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P=0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P=0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P=0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P=0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446). CONCLUSIONS: The BLISTER score (https://qxmd.com/calculate/calculator_876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients.

Identification of the tail assembly chaperone genes of T4-Like phages suggests a mechanism other than translational frameshifting for biogenesis of their encoded proteins.

Tape measure (TM) proteins are essential for the formation of long-tailed phages. TM protein assembly into tails requires the action of tail assembly chaperones (TACs). TACs (e.g. gpG and gpT of E. coli phage lambda) are usually produced in a short (TAC-N) and long form (TAC-NC) with the latter comprised of TAC-N with an additional C-terminal domain (TAC-C). TAC-NC is generally synthesized through a ribosomal frameshifting mechanism. TAC encoding genes have never been identified in the intensively studied Escherichia coli phage T4, or any related phages. Here, we have bioinformatically identified putative TAC encoding genes in diverse T4-like phage genomes. The frameshifting mechanism for producing TAC-NC appears to be conserved in several T4-like phage groups. However, the group including phage T4 itself likely employs a different strategy whereby TAC-N and TAC-NC are encoded by separate genes (26 and 51 in phage T4).

Delayed presentation of anorectal malformations in a tertiary care hospital in India.

AIM: To study delayed presentation of ARMs, management and its effect on surgical and functional complications. METHODS: It is a retrospective study from March 2015 to March 2020. All the patients satisfying the criteria of delayed ARMs, i.e., presenting 7 days after birth were included. Information regarding type of ARM, mode of presentation, time of presentation, associated anomalies, management strategy, postoperative complications and functional outcome was noted. Minimum follow-up period was 6 months. RESULTS: Out of 102 patients with ARM, 44 patients presented late. Among the 44 patients, 9 were males and 35 were females. Associated comorbidities observed are low birth weight (n = 9) and preterm (n = 13). Associated anomalies observed were cardiac (n = 18), renal (n = 8), other gastrointestinal (n = 5) and skeletal (n = 1). (1) Male: rectourethral fistula-2 (staged repair), anal stenosis-3 (anoplasty) and anocutaneous fistula-4 (anoplasty). (2) Female: vestibular fistula: 15 (6 primary definitive surgery + 9 staged repair), ectopic anus: 3 (staged repair), anal stenosis: 2 (anoplasty), urogenital sinus: 4 (staged repair), H-type ARM: 8 (staged repair) and persistent cloaca: 3 (staged repair). Primary repair was done in 15 patients (34%), and staged repair was done in 29 patients (65.9%). Anoplasty was done in 9 patients, ASARP (modified tsuchida's procedure) in 8 patients and PSARP in 27 patients. Postoperative complications observed were constipation (n = 21, 47.7%), fecal incontinence (n = 12, 27.27%) with perianal excoriation in 2 patients, anal stenosis (n = 3, 6.8%) and rectal mucosal prolapse (n = 2, 4.5%) CONCLUSION: Delayed presentation of ARMs is not uncommon and is more common in females. Management is almost similar to those who present early. Those who present with chronic constipation and megarectum require staged repair. Complications were more frequent with delayed presentation. Hence, every newborn should have careful examination of perineum and screened for ARM to avoid possible morbidity and mortality.

Extrachromosomal circular elements targeted by CRISPR-Cas in Dehalococcoides mccartyi are linked to mobilization of reductive dehalogenase genes.

Dehalococcoides mccartyi are obligate organohalide-respiring bacteria that play an important detoxifying role in the environment. They have small genomes (~1.4 Mb) with a core region interrupted by two high plasticity regions (HPRs) containing dozens of genes encoding reductive dehalogenases involved in organohalide respiration. The genomes of eight new strains of D. mccartyi were closed from metagenomic data from a related set of enrichment cultures, bringing the total number of genomes to 24. Two of the newly sequenced strains and three previously sequenced strains contain CRISPR-Cas systems. These D. mccartyi CRISPR-Cas systems were found to primarily target prophages and genomic islands. The genomic islands were identified either as integrated into D. mccartyi genomes or as circular extrachromosomal elements. We observed active circularization of the integrated genomic island containing vcrABC operon encoding the dehalogenase (VcrA) responsible for the transformation of vinyl chloride to non-toxic ethene. We interrogated archived DNA from established enrichment cultures and found that the CRISPR array acquired three new spacers in 11 years. These data provide a glimpse into dynamic processes operating on the genomes distinct to D. mccartyi strains found in enrichment cultures and provide the first insights into possible mechanisms of lateral DNA exchange in D. mccartyi.

Interactomic and pharmacological insights on human sirt-1.

Sirt-1 is defined as a nuclear protein involved in the molecular mechanisms of inflammation and neurodegeneration through the de-acetylation of many different substrates even if experimental data in mouse suggest both its cytoplasmatic presence and nucleo-cytoplasmic shuttling upon oxidative stress. Since the experimental structure of human Sirt-1 has not yet been reported, we have modeled its 3D structure, highlighted that it is composed by four different structural regions: N-terminal region, allosteric site, catalytic core and C-terminal region, and underlined that the two terminal regions have high intrinsic disorder propensity and numerous putative phosphorylation sites. Many different papers report experimental studies related to its functional activators because Sirt-1 is implicated in various diseases and cancers. The aim of this article is (i) to present interactomic studies based human Sirt-1 to understand its most important functional relationships in the light of the gene-protein interactions that control major metabolic pathways and (ii) to show by docking studies how this protein binds some activator molecules in order to evidence structural determinants, physico-chemical features and those residues involved in the formation of complexes.