atz-1 Influences meiosis to maintain germline chromosomal stability in Caenorhabditis elegans.

Exchange of genetic information during meiosis occurs in all sexually reproducing species to produce haploid gametes from diploid cells. This process involves tight coordination of a meiotic specific cohesin complex, the synaptonemal complex, and DNA damage repair mechanisms. In this study, we describe a putative myosin heavy chain protein orthologous to human myosin 1, F28D1.2, which we named Abnormal Transition Zone (atz-1). Deletion of atz-1 results in embryonic lethality and a depleted transition zone, accompanied by reduced expression of the meiotic cohesin protein, REC-8. atz-1 mutants display disorganized and aggregated chromosomal bodies in diakinetic oocytes. In addition to this, atz-1 mutants are hypersensitive to mild inhibition of DNA damage repair, suggesting that DNA replication in atz-1 mutants is impaired. Moreover, the atz-1 mutant phenotype is germline specific and resupplying somatically expressed atz-1 does not rescue the reproductive defects associated with atz-1 mutants. Overall, our data suggest that atz-1 contributes to meiosis and maintains germline chromosomal stability.

Fluid-structure interaction study for biomechanics and risk factors in Stanford type A aortic dissection.

Aortic dissection is a life-threatening condition with a rising prevalence in the elderly population, possibly as a consequence of the increasing population life expectancy. Untreated aortic dissection can lead to myocardial infarction, aortic branch malperfusion or occlusion, rupture, aneurysm formation and death. This study aims to assess the potential of a biomechanical model in predicting the risks of a non-dilated thoracic aorta with Stanford type A dissection. To achieve this, a fully coupled fluid-structure interaction model was developed under realistic blood flow conditions. This model of the aorta was developed by considering three-dimensional artery geometry, multiple artery layers, hyperelastic artery wall, in vivo-based physiological time-varying blood velocity profiles, and non-Newtonian blood behaviours. The results demonstrate that in a thoracic aorta with Stanford type A dissection, the wall shear stress (WSS) is significantly low in the ascending aorta and false lumen, leading to potential aortic dilation and thrombus formation. The results also reveal that the WSS is highly related to blood flow patterns. The aortic arch region near the brachiocephalic and left common carotid artery is prone to rupture, showing a good agreement with the clinical reports. The results have been translated into their potential clinical relevance by revealing the role of the stress state, WSS and flow characteristics as the main parameters affecting lesion progression, including rupture and aneurysm. The developed model can be tailored for patient-specific studies and utilised as a predictive tool to estimate aneurysm growth and initiation of wall rupture inside the human thoracic aorta.

Frail patients having vascular surgery during the early COVID-19 pandemic experienced high rates of adverse perioperative events and amputation.

BACKGROUND: Frailty predicts adverse perioperative outcomes and increased mortality in patients having vascular surgery. Frailty assessment is a potential tool to inform resource allocation, and shared decision-making about vascular surgery in the resource constrained COVID-19 pandemic environment. This cohort study describes the prevalence of frailty in patients having vascular surgery and the association between frailty, mortality and perioperative outcomes. METHODS: The COVID-19 Vascular Service in Australia (COVER-AU) prospective cohort study evaluates 30-day and six-month outcomes for consecutive patients having vascular surgery in 11 Australian vascular units, March-July 2020. The primary outcome was mortality, with secondary outcomes procedure-related outcomes and hospital utilization. Frailty was assessed using the nine-point visual Clinical Frailty Score, scores of 5 or more considered frail. RESULTS: Of the 917 patients enrolled, 203 were frail (22.1%). The 30 day and 6 month mortality was 2.0% (n = 20) and 5.9% (n = 35) respectively with no significant difference between frail and non-frail patients (OR 1.68, 95%CI 0.79-3.54). However, frail patients stayed longer in hospital, had more perioperative complications, and were more likely to be readmitted or have a reoperation when compared to non-frail patients. At 6 months, frail patients had twice the odds of major amputation compared to non-frail patients, after adjustment (OR 2.01; 95% CI 1.17-3.78), driven by a high rate of amputation during the period of reduced surgical activity. CONCLUSION: Our findings highlight that older, frail patients, experience potentially preventable adverse outcomes and there is a need for targeted interventions to optimize care, especially in times of healthcare stress.