Pharmacological Thromboprophylaxis for VTE Post-Endovenous Ablation of Varicose Veins: Network Meta-Analysis.

Objective: Endovenous ablation has revolutionized treatment of varicose vein surgery but is associated with a risk of venous thromboembolism. There is no consensus regarding anticoagulation protocols for these patients. This network meta-analysis (NMA) aims to identify which anticoagulant is optimal in this cohort for clot prevention with minimal risk of adverse bleeding events.

Closantel toxicity.

Closantel is a broad-spectrum antihelminthic agent. It is a veterinary drug used only in animals-usually cattle, sheep and goats. A man in his 60s accidentally ingested approximately 1500 mg closantel.

Optimal Management of Asymptomatic Carotid Artery Stenosis: A Systematic Review and Network Meta-Analysis.

Objective: Management of asymptomatic carotid artery stenosis (ACAS), including carotid endarterectomy (CEA), carotid artery stenting (CAS), and best medical treatment (BMT), remains inconsistent in current practice. Early studies reported a benefit of CEA vs. BMT; however, the current risk-benefit profile of invasive therapy lacks consensus.

The accuracy of breast MRI radiomic methodologies in predicting pathological complete response to neoadjuvant chemotherapy: A systematic review and network meta-analysis.

Background: Achieving pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) improves survival outcomes for breast cancer patients. Currently, conventional histopathological biomarkers predicting such responses are inconsistent. Studies investigating radiomic texture analysis from breast magnetic resonance imaging (MRI) to predict pCR have varied radiomic protocols introducing heterogeneity between results.

Microbial epidemiology and clinical risk factors of carbapenemase-producing Enterobacterales amongst Irish patients from first detection in 2009 until 2020.

Background: Carbapenemase producing Enterobacterales (CPE) are major public health threats.

Aim: To review microbial epidemiology of CPE, as well as clinical risk factors and infections, amongst CPE positive patients over 12 years in an Irish tertiary hospital.

Methods: Retrospective observational study of data extracted from a laboratory CPE database, electronic healthcare records and manual review of patient charts.

Miniature type V-F CRISPR-Cas nucleases enable targeted DNA modification in cells.

Class 2 CRISPR systems are exceptionally diverse, nevertheless, all share a single effector protein that contains a conserved RuvC-like nuclease domain. Interestingly, the size of these CRISPR-associated (Cas) nucleases ranges from >1000 amino acids (aa) for Cas9/Cas12a to as small as 400-600 aa for Cas12f. For in vivo genome editing applications, compact RNA-guided nucleases are desirable and would streamline cellular delivery approaches.

Optimal reconstructive strategies in the setting of post-mastectomy radiotherapy - A systematic review and network meta-analysis.

Background: A third of breast cancer patients require mastectomy. In some high-risk cases postmastectomy radiotherapy (PMRT) is indicated, threatening reconstructive complications. Several PMRT and reconstruction combinations are used.

Biomarkers in delirium: A systematic review.

Background: Delirium is a common neuropsychiatric disorder associated with prolonged hospital stays, and increased morbidity and mortality. Diagnosis is frequently missed due to varying disease presentation and lack of standardized testing. We examined biomarkers as diagnostic or prognostic indicators of delirium, and provide a rational basis for future studies.

Outcomes of Saphenous Vein Intervention in the Management of Superficial Venous Incompetence: A Systematic Review and Network Meta-analysis.

Objective: To determine the most effective modality of intervention to treat saphenous vein insufficiency.

Summary Of Background Data: Endovenous therapies have instigated a paradigm shift in the management of superficial venous incompetence. When compared with open surgery, endovenous interventions (foam sclerotherapy, radiofrequency ablation, endovenous laser ablation (EVLA), mechanochemical ablation, and CAE closure) potentially offer reduced morbidity with similar procedural efficacy.

PAM recognition by miniature CRISPR-Cas12f nucleases triggers programmable double-stranded DNA target cleavage.

In recent years, CRISPR-associated (Cas) nucleases have revolutionized the genome editing field. Being guided by an RNA to cleave double-stranded (ds) DNA targets near a short sequence termed a protospacer adjacent motif (PAM), Cas9 and Cas12 offer unprecedented flexibility, however, more compact versions would simplify delivery and extend application. Here, we present a collection of 10 exceptionally compact (422-603 amino acids) CRISPR-Cas12f nucleases that recognize and cleave dsDNA in a PAM dependent manner.

The repurposing of type I-E CRISPR-Cascade for gene activation in plants.

CRISPR-Cas systems are robust and facile tools for manipulating the genome, epigenome and transcriptome of eukaryotic organisms. Most groups use class 2 effectors, such as Cas9 and Cas12a, however, other CRISPR-Cas systems may provide unique opportunities for genome engineering. Indeed, the multi-subunit composition of class 1 systems offers to expand the number of domains and functionalities that may be recruited to a genomic target.

Youth Homelessness: The Impact of Supportive Relationships on Recovery.

Background Homeless youth are the fastest growing sub-group within the homeless population. They face impaired access to health services and are often left unsupported. They lack social and family support or relationships with service providers.

Prevention of hip displacement in children with cerebral palsy: a systematic review.

Aim: To conduct a systematic review and evaluate the quality of evidence for interventions to prevent hip displacement in children with cerebral palsy (CP).

Method: A systematic review was performed using American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were completed in seven electronic databases.

HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition.

The expression of the E6 protein from certain members of the HPV genus β (β HPV 5 and 8 E6) can disrupt p53 signaling by diminishing the steady state levels of two p53 modifying enzymes, ATR and p300. Here, we show that β-HPV 5 and 8 E6 are also capable of reducing the steady state levels of another p53 modifying enzyme, ATM, and as a result restrict LINE-1 retrotransposition. Furthermore, we show that the reduction of both ATM and LINE-1 retrotransposition is dependent upon the ability of β-HPV 8 E6 to bind and degrade p300.

ERCC1/XPF limits L1 retrotransposition.

Retrotransposons are currently active in the human and mouse genomes contributing to novel disease mutations and genomic variation via de novo insertions. However, little is known about the interactions of non-long terminal repeat (non-LTR) retrotransposons with the host DNA repair machinery. Based on the model of retrotransposition for the human and mouse LINE-1 element, one likely intermediate is an extension of cDNA that is heterologous to the genomic target, a flap intermediate.

Characterization of pre-insertion loci of de novo L1 insertions.

The human Long Interspersed Element-1 (LINE-1) and the Short Interspersed Element (SINE) Alu comprise 28% of the human genome. They share the same L1-encoded endonuclease for insertion, which recognizes an A+T-rich sequence. Under a simple model of insertion distribution, this nucleotide preference would lead to the prediction that the populations of both elements would be biased towards A+T-rich regions.

The human LINE-1 retrotransposon creates DNA double-strand breaks.

Long interspersed element-1 (L1) is an autonomous retroelement that is active in the human genome. The proposed mechanism of insertion for L1 suggests that cleavage of both strands of genomic DNA is required. We demonstrate that L1 expression leads to a high level of double-strand break (DSB) formation in DNA using immunolocalization of gamma-H2AX foci and the COMET assay.

Alu-linked hairpins efficiently mediate RNA interference with less toxicity than do H1-expressed short hairpin RNAs.

RNA interference has become a powerful tool for specific inhibition of gene expression in mammalian cells. Expression constructs allow for the long-term delivery of short interfering RNAs, usually through the expression of Pol III-transcribed hairpins. In some instances, these expression systems have been shown to have side effects, including induction of the interferon response and cytotoxicity.

Assembly of RecA-like recombinases: distinct roles for mediator proteins in mitosis and meiosis.

Members of the RecA family of recombinases from bacteriophage T4, Escherichia coli, yeast, and higher eukaryotes function in recombination as higher-order oligomers assembled on tracts of single-strand DNA (ssDNA). Biochemical studies have shown that assembly of recombinase involves accessory factors. These studies have identified a class of proteins, called recombination mediator proteins, that act by promoting assembly of recombinase on ssDNA tracts that are bound by ssDNA-binding protein (ssb).

Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic recombination.

Two RecA homologs, Rad51 and Dmc1, assemble as cytologically visible complexes (foci) at the same sites on meiotic chromosomes. Time course analysis confirms that co-foci appear and disappear as the single predominant form. A large fraction of co-foci are eliminated in a red1 mutant, which is expected as a characteristic of the interhomolog-specific recombination pathway.

Rad52 associates with RPA and functions with rad55 and rad57 to assemble meiotic recombination complexes.

We show that the Saccharomyces cerevisiae recombination protein Rad52 and the single-strand DNA-binding protein RPA assemble into cytologically detectable subnuclear complexes (foci) during meiotic recombination. Immunostaining shows extensive colocalization of Rad52 and RPA and more limited colocalization of Rad52 with the strand exchange protein Rad51. Rad52 and RPA foci are distinct from those formed by Rad51, and its meiosis-specific relative Dmc1, in that they are also detected in meiosis during replication.

Saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination.

Background: Rad51 and Dmc1 are Saccharomyces cerevisiae homologues of the Escherichia coli recombination protein RecA. Mutant analysis has shown that both proteins are required for normal meiotic recombination, for timely and efficient formation of synaptonemal complex and for normal progression out from meiotic prophase.

Results: We have further characterized rad51 and dmc1 single mutants.