Broad responses and attitudes to having music in surgery (the BRAHMS study) - a South African perspective.

BACKGROUND: Music is played in operating theatres (OTs) throughout the world, though controversy around its use exists. While some clinicians may find background music favourable to the theatre mood and a way to augment surgical performance, there is concern raised over its distracting and noise-creating properties. METHODS: In this prospective observational study, between August and December 2021, 110 surgeons and registrars in South Africa responded to a survey investigating the way they use music, and their perceptions and attitudes towards its effect on the OT environment. RESULTS: In this cohort, 66% were male, 29% were consultants and the most common age range was 30-39 years old. Eighty per cent of respondents reported that music was played at least "sometimes", with 74% reporting that they enjoyed it. Easy Listening was the most played and preferred genre followed by Top 40/Billboard hits. Overwhelmingly, respondents reported that background music in the OT improved temperament, focus, mood, and performance, though over a quarter felt it worsened communication. Thirty-one per cent of respondents reported that the choice of music depended on the type of operation, and 70% would turn music down or off during crises. Those who enjoyed music in their spare time were significantly more likely to enjoy music in the OT and perceive it positively. CONCLUSION: This study provides a window into the surgeons' use of and attitudes to intraoperative music in South Africa. While overall, music is viewed positively by this cohort, some concerns remain regarding communication and distractedness. Further interventional and qualitative studies would be useful.

Patients' expectation of postoperative course and satisfaction following cardiac surgery.

INTRODUCTION: In patients undergoing cardiac surgery, preoperative concerns, expectations of the impact of surgery, anticipated recovery timelines, and pre- and postoperative education, which impact recovery and quality-of-life, are not well documented. These factors are important with the increase in virtual consultations, the availability of internet-based information and increased use of minimally invasive surgical procedures. METHODS: Patients who underwent cardiac surgery between January 2016 and December 2019 took part in an online survey examining preoperative concerns, information provision, use of digital channels, satisfaction with surgery, impact on health and resumption of daily activity. 80 patients completed the survey. RESULTS: There was a high rate of overall post-surgical satisfaction (86%); 71% of respondents reported an improvement in physical health, 45% in mental health and 70% in their quality-of-life. The usefulness of information provided by the National Health Service varies across different stages of the patient experience. Although approximately 90% of respondents found the information provided at each stage at least 'somewhat' helpful, the proportion who found the information 'very' helpful was lower (68% for pre-procedure; 55% for post-discharge). The majority (79%) said that they felt prepared for their operation. Survey responses highlighted areas of lower understanding, including survival rate, levels of postoperative pain, duration of hospital stay and when the patient could return to normal physical activity. CONCLUSIONS: Levels of satisfaction with the outcomes of heart surgery are high, and the majority of patients report positive health outcomes. However, there is room for improvement in patients' understanding of survival rate and level of pain post-procedure. There is also a clear desire among patients for a more surgical team-based face-to-face consultation.

The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.

Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating ß-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer ß-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.

Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.

South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10-8 to 5.2 × 10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.

Towards disrupting Varroa -honey bee chemosensing: A focus on a Niemann-Pick type C2 transcript.

We focused our study on the 12 recently identified putative odorant carrier proteins in the ectoparasitic mite, Varroa destructor. Here we show, via an exclusion of the chemosensory appendages (forelegs and gnathosoma) that transcripts of five of the 12 genes were significantly lower, suggesting that they are likely involved in carrying host volatiles. Specifically, three transcripts were found to be foreleg-specific while the other two transcripts were expressed in both the forelegs and gnathosoma. We focused on one of the highly expressed and foreleg-specific transcript Vd40090, which encodes a Niemann-Pick disease protein type C2 (NPC2) protein. Effects of dsRNA-mediated silencing of Vd40090 were first measured by quantifying the transcript levels of genes that encode other putative odorant carrier proteins as well as reproduction related proteins. In addition, the impact of silencing on mites behaviour and survival was tested. Silencing of Vd40090 effectively disrupted Varroa host selection, acceptance and feeding and significantly impaired the expression of genes that regulate its reproduction in brood cells, resulting in reduced reproduction and survival.

Big data in vascular surgery: registries, international collaboration and future directions.

Given the increasing availability of large data set, small single-institutional series raise decreasing attention. Rapid expansion of technology from electronic medical records to easily accessible internet access, and widespread use and acceptance of registries in the medical world has allowed for research and quality improvement efforts using 'big data'. Big data, although technically not defined, typically refers to large databases that can be used to investigate common or rare disease processes or outcomes, describe variation in clinical practices across and between different specialties at various practice location, whilst allowing important information about trends over time. Big data have allowed investigators to quickly assimilate cohorts of patients and/or procedures to answer current questions, with more complete population representation and improved generalizability whilst decreasing the likelihood of power problems and type II errors. On the other hand, pitfalls still exist with the growing problem of hypothesis fishing, lack of granularity and the fear by many clinicians that registry transparency may have already gone too far, where surgery groups or individual surgeon outcomes are readily available to patients and referring providers. Within vascular surgery specifically, big data have expanded over the last decade and now includes regional, national and global registries that have major benefits of gathering specific clinical and procedural information within vascular surgery. In this review, we highlight the main vascular surgery registries and recap a few success stories of how the registries have been leveraged to benefit discovery, quality improvement and ultimately patient care. Additionally, we outline future directions that will be imperative for continued expansion, acceptance and adoption of 'big data' utilization inpatients with vascular disease.

Paradigm shifts in abdominal aortic aneurysm management based on vascular registries.

Abdominal aortic aneurysm (AAA) is a relatively common and potentially fatal disease. The management of AAA has undergone extensive changes in the last two decades. High quality vascular surgical registries were established early and have been found to be instrumental in the evaluation and monitoring of these changes, most notably the wide implementation of minimally invasive endovascular surgical technology. Trends over the years showed the increased use of endovascular aneurysm repair (EVAR) over open repair, the decreasing perioperative adverse outcomes and the early survival advantage of EVAR. Also, data from the early EVAR years changed the views on endoleak management and showed the importance of tracking the implementation of new techniques. Registry data complemented the randomized trials performed in aortic surgery by showing the high rate of laparotomy-related reinterventions after open repair. Also, they are an essential tool for the understanding of outcomes in a broad patient population, evaluating the generalizability of findings from randomized trials and analysing changes over time. By using large-scale data over longer periods of time, the importance of centralization of care to high-volume centres was shown, particularly for open repair. Additionally, large-scale databases can offer an opportunity to assess practice and outcomes in patient subgroups (e.g. treatment of AAA in women and the elderly) as well as in rare aortic pathologies. In this review article, we point out the most important paradigm shifts in AAA management based on vascular registry data.

Top 10 candidate aortic disease trials.

Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.

Lack of an effective drug therapy for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo-controlled drug trials in patients with small AAAs. Eleven previously published randomized-controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta-analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure-lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.

Protease-Sensitive Pancreatic Lipase Variants Are Associated With Early Onset Chronic Pancreatitis.

OBJECTIVES: Premature activation of the digestive protease trypsin within the pancreatic parenchyma is a critical factor in the pathogenesis of pancreatitis. Alterations in genes that affect intrapancreatic trypsin activity are associated with chronic pancreatitis (CP). Recently, carboxyl ester lipase emerged as a trypsin-independent risk gene. Here, we evaluated pancreatic lipase (PNLIP) as a potential novel susceptibility gene for CP. METHODS: We analyzed all 13 PNLIP exons in 429 nonalcoholic patients with CP and 600 control subjects from Germany, in 632 patients and 957 controls from France, and in 223 patients and 1,070 controls from Japan by DNA sequencing. Additionally, we analyzed selected exons in further 545 patients with CP and 1,849 controls originating from Germany, United States, and India. We assessed the cellular secretion, lipase activity, and proteolytic stability of recombinant PNLIP variants. RESULTS: In the German discovery cohort, 8/429 (1.9%) patients and 2/600 (0.3%) controls carried a PNLIP missense variant (P = 0.02, odds ratio [OR] = 5.7, 95% confidence interval [CI] = 1.1-38.9). Variants detected in patients were prone to proteolytic degradation by trypsin and chymotrypsin. In the French replication cohort, protease-sensitive variants were also enriched in patients with early-onset CP (5/632 [0.8%]) vs controls (1/957 [0.1%]) (P = 0.04, OR = 7.6, 95% CI = 0.9-172.9). In contrast, we detected no protease-sensitive variants in the non-European populations. In the combined European data, protease-sensitive variants were found in 13/1,163 cases (1.1%) and in 3/3,000 controls (0.1%) (OR = 11.3, 95% CI = 3.0-49.9, P < 0.0001). CONCLUSIONS: Our data indicate that protease-sensitive PNLIP variants are novel genetic risk factors for the development of CP.

Attenuation of adverse effects of noise induced hearing loss on adult neurogenesis and memory in rats by intervention with Adenosine A2A receptor agonist.

Hearing loss and cognitive decline are commonly associated with aging and morbidity. Present clinical interest lies in whether peripheral hearing loss promotes cognitive decline and if prophylaxis with selective adenosine receptor agonist CGS21680 effectively mitigates the adverse effects. In the current study, male Sprague Dawley rats weighing 200-250 g m were randomly allocated into three groups: Group 1) rats exposed to 100 dB SPL white noise, 2 h a day for 15 consecutive days, 2) rats supplemented with an adenosine receptor agonist, CGS21680 at 100 µg/kg/day prior to noise exposure and 3) unexposed control rats. Baseline hearing and cognition assessed by auditory brainstem response (ABR) and water maze respectively was undertaken for all the groups. Phalloidin stain and synaptic ribbons count in cochlea, and, Ki67, DCX and NeuN in hippocampus were observed by immunohistochemistry. It was inferred that noise exposed rats showed elevated thresholds of ABR and poorer performances in spatial working memory when compared with controls. On the contrary, CGS21680 administered group exhibited improved ABR and cognitive functions with shorter mean latency and path-length to reach the platform, significant reduction in the noise induced loss of synaptic ribbons count and increased number of Ki67 and doublecortin (DCX) positive cells compared to their noise exposed counterparts. Pharmacologic intervention with selective A2A receptor agonist CGS21680 provided adequate protection from noise by effectively maintaining hearing threshold levels, cell viability in cochlea and hippocampus & functional/intact reference memory.

Distortion product oto-acoustic emission: a superior tool for hearing assessment than pure tone audiometry.

OBJECTIVE: Hearing plays a crucial role in the performance of a soldier and is important for communication and speech processing. Service personnel are constantly exposed to high levels of noise and hence predisposed to occupational health disabilities, principally noise-induced hearing loss (NIHL) and tinnitus. NIHL is a significantly common impairment in the military and can affect the warfare performances. Parochial awareness about the effects of uproarious noise which exacerbates their hearing, acceptance rate of use of hearing protection devices and follow-up audiological tests have become the major drawback for prevention of NIHL and are less pondered upon. METHOD: The present study focuses on the effects of noise on the hearing of service crew operating and maintaining military equipment and explores the efficacy of DPOAE's to substitute pure tone audiometry as a quick, easy to operate and implementable test technique for monitoring of hearing status. RESULTS: The results suggest that DPOAE test is important and more coherent than audiometry alone for the early detection of cochlear injury due to noise from military operations and efficacious for detecting NIHL.

Treatment of aortic aneurysms registered in Swedvasc: Development reflected in a national vascular registry with an almost 100% coverage.

Swedvasc is a registry for vascular surgical procedures, both open and endovascular. It was started in 1987 and since 1994 the whole population of Sweden is covered, at present around 10 million inhabitants. In a recent external validation, it was found to be highly accurate with abdominal aortic aneurysm surgery correctly reported in >96%. In this paper various factors explaining the almost 100% coverage are discussed, one important being that the registry has been developed and maintained within the profession of vascular surgery and not dictated by authorities. Another factor of importance is the possibility to use data in various research projects and so far 15 PhD theses have used Swedvasc data. To exemplify the practical use of the registry, the treatment of abdominal aortic aneurysms is scrutinized and among the various complications abdominal compartment syndrome is analyzed. Several significant temporal changes have been observed over the almost 25 years of Swedvasc: increasing use of endovascular surgery, treatment of aneurysms detected by screening , decreasing treatment for rupture, improved outcome, increasing treatment of older patients and patients with comorbid conditions. In conclusion, a high quality national vascular registry can be valid with high compliance and can be used to study population-based development of treatment and outcome. It can also be used to perform international comparisons with other registries, thereby getting an indication of the quality of care.