Efficient manufacturing of recombinant Adeno-Associated Viral (rAAV) vectors to meet rising clinical demand remains a major hurdle. One of the most significant challenges is the generation of large amounts of empty capsids without the therapeutic genome. There is no standardized analytical method to accurately quantify the viral genes, and subsequently the empty-to-full ratio, making the manufacturing challenges even more complex.
View Article and Find Full Text PDFIntroduction: Venous thromboembolism (VTE) is a recognised postsurgical risk. Current prevention methods involve low molecular weight heparin (LMWH), graduated compression stockings (GCS), and intermittent pneumatic compression devices (IPCDs). Australian guidelines, commonly adopted by surgeons, recommend LMWH with GCS and/or IPCDs.
View Article and Find Full Text PDFBackground: The application of antiseptic skin agents prior to incision minimizes the rate of surgical site infection. Despite their ubiquity, the optimal skin preparation agent remains uncertain. A retrospective economic analysis was conducted to complement the results from the NEWSkin Prep trial which prospectively compared three preparation agents.
View Article and Find Full Text PDFThere remains debate as to the ideal skin preparation agent to prevent surgical site infection (SSI) after clean implant surgery. This study is a subgroup analysis of all patients undergoing implant surgery in the NEWSkin prep trial. The NEWSkin prep trial is a randomized clinical trial (RCT; n = 3300) comparing the three antiseptic skin preparation agents commonly used prior to incisional surgery: chlorhexidine with alcohol (C-Alc), povidone iodine with alcohol (PI-Alc), and aqueous povidone iodine (PI-Aq).
View Article and Find Full Text PDFBackground: Surgical prophylaxis for venous thrombo-embolic disease (VTE) includes risk assessment, chemical prophylaxis and mechanical prophylaxis (graduated compression stockings [GCS] and/or intermittent pneumatic compression devices [IPCD]). Although there is overwhelming evidence for the need and efficacy of VTE prophylaxis in patients at risk, only about a third of those who are at risk of VTE receive appropriate prophylaxis.
Objective: There is debate as to the best combination of VTE prophylaxis following abdominal surgery due to lack of evidence.
Introduction: The Australian population presenting with surgical pathology is becoming older, frailer and more comorbid. Shared decision-making is rapidly becoming the gold standard of care for patients considering high-risk surgery to ensure that appropriate, value-based healthcare decisions are made. Positive benefits around patient perception of decision-making in the immediacy of the decision are described in the literature.
View Article and Find Full Text PDFBackground: Surgical Site Infection (SSI) of the abdominal incision is a dreaded complication following colorectal surgery. Identifying the intraoperative surgical site microbes may provide clarity in the pathogenesis of SSIs. Genomic sequencing has revolutionized the ability to identify microbes from clinical samples.
View Article and Find Full Text PDFIntroduction: Despite advances in achieving low mortality rates with pancreaticoduodenectomy (PD), morbidity remains high. A key contributor to this morbidity is delayed gastric emptying (DGE) occurring with an incidence of up to 30%. The utility of a Braun enteroenterostomy (BE) appears promising to reducing the incidence of DGE, but current research is not definitive.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a clear sex disparity in clinical outcomes. Hence, the interaction between sex hormones, virus entry receptors and immune responses has attracted major interest as a target for the prevention and treatment of SARS-CoV-2 infections. This Review summarizes the current understanding of the roles of androgens, oestrogens and progesterone in the regulation of virus entry receptors and disease progression of coronavirus disease 2019 (COVID-19) as well as their therapeutic value.
View Article and Find Full Text PDFBackground: The benefits of mechanical prophylaxis for the prevention of venous thromboembolism (VTE) in abdominal and pelvic surgery are uncertain, with different guidelines stating that graduated compression stockings (GCS) and intermittent pneumatic compression devices (IPCDs) can be used either alone or in combination. To review the efficacy of IPCDs in preventing VTE following abdominal and pelvic surgery.
Methods: A systematic review was conducted, identifying relevant literature reporting clinical trials conducted in abdominopelvic surgery, comparing the effect of IPCDs alone or in combination with no prophylaxis, GCS and chemical prophylaxis.
CARD19 is a mitochondrial protein of unknown function. While CARD19 was originally reported to regulate TCR-dependent NF-κB activation via interaction with BCL10, this function is not recapitulated ex vivo in primary murine CD8 T cells. Here, we employ a combination of SIM, TEM, and confocal microscopy, along with proteinase K protection assays and proteomics approaches, to identify interacting partners of CARD19 in macrophages.
View Article and Find Full Text PDFObjective: To compare SSI rates between the skin preparation agents: PI-Aq, povidone-iodine with alcohol (PI-Alc), and chlorhexidine with alcohol (C-Alc).
Background: Guidelines suggest that alcohol-containing chlorhexidine solutions are the gold standard for skin preparation before surgery. It remains difficult to determine whether it is the chlorhexidine component or the addition of alcohol that confers the most benefit.
Background: There is much debate surrounding the ideal antiseptic skin preparation agent to reduce postoperative surgical site infection. International guidelines suggest that chlorhexidine- and alcohol-containing compounds have superior efficacy. However, there are minimal clinical trials specifically looking at skin preparation agents for colorectal surgery.
View Article and Find Full Text PDFDeciding whether to delay non-lifesaving orthopaedic trauma surgery to prevent multiple organ failure (MOF) or sepsis is frequently disputed and largely based on expert opinion. We hypothesise that neutrophils and monocytes differentially express activation markers prior to patients developing these complications. Peripheral blood from 20 healthy controls and 162 patients requiring major orthopaedic intervention was collected perioperatively.
View Article and Find Full Text PDFObjective: To test the hypothesis that blood donor demographics are associated with transfused polytrauma patients' post-injury multiple organ failure (MOF) status.
Summary Of Background Data: Traumatic shock and MOF are preventable causes of death and post-traumatic hemorrhage is a frequent indication for transfusion. The role of blood donor demographics on transfusion recipients is not well known.
The adaptive immune response relies on specific apoptotic programs to maintain homeostasis. Conventional effector T cell (Tcon) expansion is constrained by both forkhead box P3 (FOXP3)-regulatory T cells (Tregs) and restimulation-induced cell death (RICD), a propriocidal apoptosis pathway triggered by repeated stimulation through the T-cell receptor (TCR). Constitutive FOXP3 expression protects Tregs from RICD by suppressing SLAM-associated protein (SAP), a key adaptor protein that amplifies TCR signaling strength.
View Article and Find Full Text PDFBackground: No study has examined the prevalence of tobacco, other substance use, and symptoms of anxiety and depression, and rates of comorbidities among the orthopaedic trauma population, despite the impact they have on recovery from surgery. This study aims to 1) describe the rates of symptoms and substance use; 2) compare rates of symptoms and substance use among smokers versus non-smokers; and 3) examine the relationship between symptoms and substance use with smoking status.
Methods: A cross-sectional survey of orthopaedic trauma patients was conducted in two Australian public hospitals.
Background: The potential for the co-existence of genetically disparate cells (microchimerism) and associated cytokine profiles following red blood cell (RBC) transfusion in trauma patients has not been well characterized to date. This study investigated the incidence of surviving donor white blood cells (known as transfused-associated microchimerism (TAM)) and cytokine changes following blood transfusion in trauma patients.
Study Design And Methods: Trauma patients with an injury severity score (ISS) >12 who had been transfused between 2012-2016 with at least 5 units of RBC units over a 4 h period were recruited.
Background: Cell-free mitochondrial DNA (mtDNA) is proinflammatory and has been detected in high concentrations in trauma patients' plasma. Deoxyribonuclease (DNAse) is the free plasma enzyme responsible for the digestion of extracellular DNA. The relationship between mtDNA and DNAse after major trauma is unknown.
View Article and Find Full Text PDFInt J Environ Res Public Health
November 2017
Smoke-free hospital policies are becoming increasingly common to promote good health and quit attempts among patients who smoke. This study aims to assess: staff perceived enforcement and compliance with smoke-free policy; the current provision of smoking cessation care; and the characteristics of staff most likely to report provision of care to patients. An online cross-sectional survey of medical, nursing, and allied staff from two Australian public hospitals was conducted.
View Article and Find Full Text PDFB cell Expansion with NF-κB and T cell Anergy (BENTA) disease is a novel B cell lymphoproliferative disorder caused by germline, gain-of-function mutations in the lymphocyte scaffolding protein CARD11, which drives constitutive NF-κB signaling. Despite dramatic polyclonal expansion of naive and immature B cells, BENTA patients also present with signs of primary immunodeficiency, including markedly reduced percentages of class-switched/memory B cells and poor humoral responses to certain vaccines. Using purified naive B cells from our BENTA patient cohort, here we show that BENTA B cells exhibit intrinsic defects in B cell differentiation.
View Article and Find Full Text PDFSmoking increases the risk of complications associated with orthopaedic trauma surgery, however delivery of care is low. Online interventions may provide needed smoking cessation care and promote abstinence. This study aims to examine the engagement, acceptability, and retention of an online smoking cessation program (Smoke-Free Recovery; SFR) among a sample of orthopaedic trauma patients, as well as themes around the smoking cessation process.
View Article and Find Full Text PDFBackground: eHealth presents opportunities to provide population groups with accessible health interventions, although knowledge about Internet access, peoples' interest in using the Internet for health, and users' characteristics are required prior to eHealth program development.
Objective: This study surveyed hospital patients to examine rates of Internet use, interest in using the Internet for health, and respondent characteristics related to Internet use and interest in using the Internet for health. For patients who smoke, preferences for types of smoking cessation programs for use at home and while in hospital were also examined.