Evaluations of clinical practice guidelines, protocols, and pathways used in rural and remote Australia, Canada, and Aotearoa New Zealand: a scoping review protocol.

Objective: The objective of this review protocol is to scope the extent and type of evidence describing evaluations of clinical practice guidelines, protocols, and pathways that are used in the rural and remote areas of Australia, Canada, and Aotearoa New Zealand.

Introduction: Given the important role that clinical guidance resources can play in minimizing health disparities, it will be useful to understand what resources are being used in rural and remote health contexts and how these are being developed, implemented, and evaluated.

Inclusion Criteria: Records will be included from 3 high-income countries which have rural or remote regions and First Nations populations.

Shaping leaves through TALE homeodomain transcription factors.

The first TALE homeodomain transcription factor gene to be described in plants was maize knotted1 (kn1). Dominant mutations in kn1 disrupt leaf development, with abnormal knots of tissue forming in the leaf blade. kn1 was found to be expressed in the shoot meristem but not in a peripheral region that gives rise to leaves.

VWF-ADAMTS13 axis dysfunction in children with sickle cell disease treated with hydroxycarbamide vs blood transfusion.

Previous studies have reported elevated von Willebrand factor (VWF) levels in patients with sickle cell disease (SCD) and demonstrated a key role for the VWF-ADAMTS13 axis in the pathobiology of SCD vaso-occlusion. Although blood transfusion is the gold standard for stroke prevention in SCD, the biological mechanisms underpinning its improved efficacy compared with hydroxycarbamide are not fully understood. We hypothesized that the improved efficacy of blood transfusion might relate to differences in VWF-ADAMTS13 axis dysfunction.

Adherence to Evidence-Based Outpatient Antimicrobial Prescribing Guidelines at a Tribal Health System.

Background: In 2019, the Tuba City Regional Health Care Corporation on the Navajo Reservation in northeastern Arizona established facility-wide, evidence-based outpatient antimicrobial guidelines. We aimed to evaluate adherence to these guidelines.

Methods: A retrospective chart review of the electronic health record for all ages was conducted from August 1, 2020, to August 1, 2021, to evaluate antimicrobials prescribed for indications covered by the facility prescribing guidelines.

Endothelial cell activation, Weibel-Palade body secretion, and enhanced angiogenesis in severe COVID-19.

Background: Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined.

Objectives: We investigated EC activation in patients with acute COVID-19, and specifically focused on how proteins stored within Weibel-Palade bodies may impact key aspects of disease pathogenesis.

Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor.

Background: Previous studies have reported marked interindividual variation in factor VIII (FVIII) clearance in patients with hemophilia (PWH) and proposed a number of factors that influence this heterogeneity.

Objectives: To investigate the importance of the clearance rates of endogenous von Willebrand factor (VWF) compared with those of other FVIII half-life modifiers in adult PWH.

Methods: The half-life of recombinant FVIII was determined in a cohort of 61 adult PWH.

Plant development: Elementary changes determine leaf shape complexity.

Leaves come in a wide variety of shapes, from simple to lobed to dissected. A new study suggests this variation is determined by a preferred evolutionary genetic pathway that modifies shape by regulating regional growth in the developing leaf.

Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction.

Background: Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance.

Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance.

Increased von Willebrand factor (VWF) clearance plays a key role in the pathogenesis of type 1 and type 2 von Willebrand disease (VWD). However, the pathological mechanisms involved in patients with mild to moderate reductions in plasma VWF:Ag (range, 30-50 IU/dL; low VWF) remain poorly understood. In this study, we investigated the hypothesis that enhanced VWF clearance may contribute to the pathobiology of low VWF.

Single centre, real-world experience of perioperative rFIXFc use in adult patients with haemophilia B undergoing major and minor surgery.

Introduction: Recombinant factor IX fusion protein concentrate (rFIXFc) is increasingly used for prophylaxis in people with haemophilia B (PWHB), but experience in the perioperative setting is limited.

Aims: To evaluate real-world perioperative factor usage, bleeding and complications in PWHB (≥18 years) who received rFIXFc for surgical haemostasis and to describe the treatment regimens used.

Methods: Single centre, retrospective review of all PWHB who underwent a major or minor surgical procedure between June 2017 and July 2020 and received rFIXFc perioperatively for maintenance of surgical haemostasis.

Persistent endotheliopathy in the pathogenesis of long COVID syndrome.

Background: Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this "long COVID" syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) - a novel clinico-pathological entity with heterogeneous clinical presentations.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a novel entity that emerged in March 2021 following reports of unusual thrombosis after ChAdOx1 nCoV-19, (AstraZeneca) vaccination. Following the recognition of this syndrome, multiple consensus guidelines have been released to risk stratify patients presenting with possible symptoms after ChAdOx1 nCoV-19 vaccination. All guidelines rapidly identify VITT in patients with the complete triad of thrombocytopenia, thrombosis and elevated D-dimers after ChAdOx1 nCoV-19 vaccination.

Real-world outcomes with recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis: Longitudinal follow-up in a national adult cohort.

Introduction: In 2017, all people with severe haemophilia B (PWSHB) in Ireland switched from standard half-life (SHL) recombinant FIX (rFIX) to rFIX Fc fusion protein (rFIXFc) prophylaxis.

Aims: To evaluate prophylaxis regimens, bleeding rates and factor usage for two years of rFIXFc prophylaxis in a real-world setting.

Methods: Data collected retrospectively from electronic diaries and medical records of PWSHB for a two-year period on rFIXFc prophylaxis were compared with paired baseline data on SHL rFIX treatment.

Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response.

Background: Persistent fatigue, breathlessness, and reduced exercise tolerance have been reported following acute COVID-19 infection. Although immuno-thrombosis has been implicated in acute COVID-19 pathogenesis, the biological mechanisms underpinning long COVID remain unknown. We hypothesized that pulmonary microvascular immuno-thrombosis may be important in this context.

Management of elective procedures in low von Willebrand factor patients in the LoVIC study.

Background: Most individuals with mild to moderate reductions in plasma von Willebrand factor (VWF) levels do not demonstrate increased bleeding. However, some patients with plasma VWF levels of 30-50 IU/dl do have a significant bleeding phenotype. Management of these "low VWF" patients, who may have significant bleeding scores >10, around times of elective procedures continues to pose a common clinical challenge because of a lack of evidence.

SAW homeodomain transcription factors regulate initiation of leaf margin serrations.

Plant leaves are the main photosynthetic organ of plants and they occur in an array of different shapes. Leaf shape is determined by morphogenesis whereby patterning of the leaf margin can result in interspaced leaf serrations, lobes, or leaflets, depending on the species, developmental stage, and in some instances the environment. In Arabidopsis, mutations in the homeodomain transcription factors SAW1 and SAW2 result in more prominent leaf margin serrations.

COVID19 coagulopathy in Caucasian patients.

Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung-centric coagulopathy may play an important role. Elevated D-dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3-4-fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African-Americans.

Progress in understanding the role of auxin in lateral organ development in plants.

Plants continuously produce lateral organs from the shoot apex such as leaves and flowers, providing an excellent opportunity to study their development. The plant hormone auxin plays a central role in this process by promoting organ formation where it accumulates due to polar auxin transport. Recently, the use of live-imaging, fine perturbation techniques and computational modelling has helped researchers make exciting progress in addressing long-standing questions on plant organogenesis, not only regarding the role of auxin in promoting growth but also on the regulation of morphogenesis and transcriptional control.

Current interventions to promote safe and appropriate pain management.

Purpose: Describe patient-, clinician-, system-, and community-level interventions for pain management developed and employed by 9 healthcare systems across the United States and report on lessons learned from the implementation of these interventions.

Summary: The high cost associated with pain coupled with the frequent use of opioid analgesics as primary treatment options has made novel pain management strategies a necessity. Interventions that target multiple levels within healthcare are needed to help combat the opioid epidemic and improve strategies to manage chronic pain.