Androcentric bias in surgical equipment - What challenges do women face?

BACKGROUND: Increasing diversity amongst surgeons results in a wide range of sizes and strengths. There are many types of biases affecting women surgeons. This study evaluates what challenges women surgeons may have with surgical equipment. METHODS: An online survey was distributed to Women in Surgery social media groups in North America and Australasia between April 2022-July 2022. RESULTS: There were 480 respondents across the range of specialties. 453 surgeons were included. Median glove size was 6.5. Difficulty with use of surgical instruments due to size was reported by 89% of surgeons and 71% reported difficulty due to the required grip strength. One hundred and twelve different tools were reported to be problematic. CONCLUSIONS: This study highlights a potential source of androcentric bias which could be addressed to improve equity for women surgeons.

Pre-cleaning of hair is not beneficial in LA-ICP-MS studies of chronic metal exposure.

Chronic exposure to toxic metals is a serious global health concern. However, population-wide biomonitoring is costly and carries several sampling constraints. Though hair sampling can be a useful way to assess environmental exposure, external contamination is a long-standing concern, and a pre-cleaning step prior to metal quantification has long been recommended despite a lack of evidence for its efficacy. In this study, we quantified the spatial distribution of 16 elements in unwashed human hair samples using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS), then tested how two common pre-cleaning treatments (Triton-ethanol, Triton-nitric acid) affected metal content in external and interior layers of hair using LA-ICP-MS. We show that elements differ in their spatial distribution across hair and that pre-cleaning is not consistent in its effect on element concentrations and decreases interior concentrations of some elements. We demonstrate that differences among individuals can be quantified reliably with LA-ICP-MS analysis of interior concentrations of unwashed hair. Our study tests the widespread notion that pre-cleaning is essential in analyses of hair for environmental exposure to metals, and examines the benefits of a unified approach to analysis of metals in hair using LA-ICP-MS.

COVID-19 responses restricted abilities and aspirations for mobility and migration: insights from diverse cities in four continents.

Research on the impacts of COVID-19 on mobility has focused primarily on the increased health vulnerabilities of involuntary migrant and displaced populations. But virtually all migration flows have been truncated and altered because of reduced economic and mobility opportunities of migrants. Here we use a well-established framework of migration decision-making, whereby individual decisions combine the aspiration and ability to migrate, to explain how public responses to the COVID-19 pandemic alter migration patterns among urban populations across the world. The principal responses to COVID-19 pandemic that affected migration are: 1) through travel restrictions and border closures, 2) by affecting abilities to move through economic and other means, and 3) by affecting aspirations to move. Using in-depth qualitative data collected in six cities in four continents (Accra, Amsterdam, Brussels, Dhaka, Maputo, and Worcester), we explore how populations with diverse levels of education and occupations were affected in their current and future mobility decisions. We use data from interviews with sample of internal and international migrants and non-migrants during the 2020 COVID-19 pandemic outbreak to identify the mechanisms through which the pandemic affected their mobility decisions. The results show common processes across the different geographical contexts: individuals perceived increased risks associated with further migration, which affected their migration aspirations, and had reduced abilities to migrate, all of which affected their migration decision-making processes. The results also reveal stark differences in perceived and experienced migration decision-making across precarious migrant groups compared to high-skilled and formally employed international migrants in all settings. This precarity of place is particularly evident in low-income marginalised populations.

Orthopedic Versus Podiatric Care of the Foot and Ankle: A Literature Review.

As the scope of podiatric surgery expands, the relative roles and outcomes of orthopedic surgeons and podiatrists need to be defined. With growing demand for foot and ankle services, the roles of podiatrists and orthopedic surgeons are increasingly overlapping. Few studies have examined the overlapping scope of practice of each of the groups or compared the relative costs and outcomes associated with each.

Exploring and understanding the scope and value of the Parkinson's nurse in the UK (The USP Project): a realist economic evaluation protocol.

INTRODUCTION: There are multiple configurations of specialist nurses working in the field of Parkinson's. Parkinson's Nurse Specialists (PNSs) are recognised as playing a pivotal role; however, there is little published evidence to demonstrate their effectiveness. Further evidence is needed to establish which aspects of the PNSs provide the greatest benefit to people with Parkinson's and their families, and the cost-effectiveness of different models of care. METHODS AND ANALYSIS: Realist approaches explain how and why programmes work (or not) through striving to answer the question: what works, for whom and under what circumstances. This research uses a realist evaluation and aims to integrate an economic analysis within the realist framework. We refer to this as 'realist economic evaluation'. It comprises four phases: (1) developing resource-sensitive initial programme theories (IPTs) using surveys to gain a better understanding of the role and impact (costs and benefits) of the PNSs; (2) testing the IPTs through qualitative interviews and quantitative data analysis; (3) evaluating the cost and resource use implications alongside the benefits associated with the role of the PNSs and (4) iteratively refining the IPTs throughout the project. The IPTs will draw on both quantitative and qualitative data. The result of the study will be a series of refined programme theories, which will explain how specialist nurses work in the field of Parkinson's in the UK, what impact they have on people with Parkinson's and their families and carers, and at what cost. ETHICS AND DISSEMINATION: Northumbria University, the Health Research Authority and Health and Care Research Wales have approved this study. Key findings will be disseminated throughout the duration of the project online and through social media, and via annual and regional Parkinson's meetings and the Parkinson's UK Excellence Network. Academic dissemination will occur through publication and conference presentations.

Author Correction: Leaf nutrients, not specific leaf area, are consistent indicators of elevated nutrient inputs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Analysing Sr isotopes in low-Sr samples such as single insects with inductively coupled plasma tandem mass spectrometry using N2 O as a reaction gas for in-line Rb separation.

RATIONALE: Strontium isotopes are valuable markers of provenance in a range of disciplines. Limited amounts of Sr in low-mass samples such as insects mean that conventional Sr isotope analysis precludes their use for geographic origins in many ecological studies or in applications such as biosecurity. Here we test the viability of using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) with N2 O as a reaction gas for accurately determining Sr isotopes in insects with Sr < 100 ng. METHODS: Strontium isotopes were determined in solution mode using ICP-MS/MS with 0.14 L/min N2 O as a reaction gas to convert Sr+ into SrO+ for in-line separation of 87 Sr from 87 Rb. The Sr isotope reference standards NIST SRM 987, NIST SRM 1570a and NIST SRM 1547 were used to assess accuracy and reproducibility. Ten insect species collected from the wild as a proof-of-principle application were analysed for Sr concentration and Sr isotopes. RESULTS: Using ICP-MS/MS we show for the first time that internal mass bias correction of 87 Sr16 O/86 Sr16 O based on 88 Sr16 O/86 Sr16 O works to give for NIST SRM 987 a 87 Sr/86 Sr ratio of 0.7101 ± 0.012 (RSD = 0.17%) and for NIST SRM 1570a a 87 Sr/86 Sr ratio of 0.7100 ± 0.009 (RSD = 0.12%), which are within error of the accepted values. The first 87 Sr/86 Sr ratio of NIST SRM 1547 is 0.7596 ± 0.0014. Strontium analyses were run on 0.8 mL of 0.25-0.5 ppb Sr, which equates to 2-4 ng of Sr. Strontium isotope analysis with a precision of >99.8% can be achieved with in-line separation of 87 Sr from 87 Rb at least up to solutions with 25 ppb Rb. CONCLUSIONS: A minimum of 5 mg of insect tissue is required for Sr isotope analysis. This new ICP-MS/MS method enables Sr isotope analysis in single insects, allowing population-scale studies to be feasible and making possible applications with time-critical uses such as biosecurity.

Leaf nutrients, not specific leaf area, are consistent indicators of elevated nutrient inputs.

Leaf traits are frequently measured in ecology to provide a 'common currency' for predicting how anthropogenic pressures impact ecosystem function. Here, we test whether leaf traits consistently respond to experimental treatments across 27 globally distributed grassland sites across 4 continents. We find that specific leaf area (leaf area per unit mass)-a commonly measured morphological trait inferring shifts between plant growth strategies-did not respond to up to four years of soil nutrient additions. Leaf nitrogen, phosphorus and potassium concentrations increased in response to the addition of each respective soil nutrient. We found few significant changes in leaf traits when vertebrate herbivores were excluded in the short-term. Leaf nitrogen and potassium concentrations were positively correlated with species turnover, suggesting that interspecific trait variation was a significant predictor of leaf nitrogen and potassium, but not of leaf phosphorus concentration. Climatic conditions and pretreatment soil nutrient levels also accounted for significant amounts of variation in the leaf traits measured. Overall, we find that leaf morphological traits, such as specific leaf area, are not appropriate indicators of plant response to anthropogenic perturbations in grasslands.

High-Throughput Kinetic Analysis for Target-Directed Covalent Ligand Discovery.

Cysteine-reactive small molecules are used as chemical probes of biological systems and as medicines. Identifying high-quality covalent ligands requires comprehensive kinetic analysis to distinguish selective binders from pan-reactive compounds. Quantitative irreversible tethering (qIT), a general method for screening cysteine-reactive small molecules based upon the maximization of kinetic selectivity, is described. This method was applied prospectively to discover covalent fragments that target the clinically important cell cycle regulator Cdk2. Crystal structures of the inhibitor complexes validate the approach and guide further optimization. The power of this technique is highlighted by the identification of a Cdk2-selective allosteric (type IV) kinase inhibitor whose novel mode-of-action could be exploited therapeutically.

Detecting familial hypercholesterolemia: The Jack and the Beanstalk principle.

We report the case of an 8-year-old girl who was fortuitously diagnosed with familial hypercholesterolemia (FH) while being investigated for obesity. She had a fasting total cholesterol of 11.8 mmol/L and a low-density lipoprotein cholesterol level of 10.3 mmol/L. Her mother and maternal grandmother both had a history of hypercholesterolemia and had developed extensive xanthelasma palpebrarum from early adult life. Reverse cascade testing of first-degree and second-degree relatives diagnosed a further 6 individuals with FH within the family. We discuss the benefits of diagnosing FH in childhood, for the individual and the wider family network ("the beanstalk") and present the rationale for implementing a universal screening program for FH in childhood.

Temperature dependency of shelf and thermal stabilities of anthocyanins from corn distillers' dried grains with solubles in different ethanol extracts and a commercially available beverage.

The objective was to determine the shelf and thermal stabilities of anthocyanins from distillers' dried grains with solubles (DDGS) extracted with different ethanol concentrations as well as a semi-purified Maiz Morado (purple corn) anthocyanin extract added to a commercially available beverage. Storage for 6 weeks of DDGS showed an overall reduction of anthocyanins from 6.8 to 73.7%. In DDGS, an ethanol increase from 0 to 25% resulted in less sensitivity of anthocyanin to temperature changes. Acylation resulted in faster degradation and higher reaction rate constants than their corresponding non-acylated forms. Anthocyanin changes were accompanied by an overall increase in lightness and a decrease in redness. Storage of beverage for 12 weeks at 4 °C resulted in a 25.5% reduction of anthocyanin. Results have important implications in selecting colored corn as an economical source of food colorants.

Determination of refractive and volatile elements in sediment using laser ablation inductively coupled plasma mass spectrometry.

Wet-milling protocol was employed to produce pressed powder tablets with excellent cohesion and homogeneity suitable for laser ablation (LA) analysis of volatile and refractive elements in sediment. The influence of sample preparation on analytical performance was also investigated, including sample homogeneity, accuracy and limit of detection. Milling in volatile solvent for 40 min ensured sample is well mixed and could reasonably recover both volatile (Hg) and refractive (Zr) elements. With the exception of Cr (-52%) and Nb (+26%) major, minor and trace elements in STSD-1 and MESS-3 could be analysed within ±20% of the certified values. Comparison of the method with total digestion method using HF was tested by analysing 10 different sediment samples. The laser method recovers significantly higher amounts of analytes such as Ag, Cd, Sn and Sn than the total digestion method making it a more robust method for elements across the periodic table. LA-ICP-MS also eliminates the interferences from chemical reagents as well as the health and safety risks associated with digestion processes. Therefore, it can be considered as an enhanced method for the analysis of heterogeneous matrices such as river sediments.

CT pulmonary angiography and pulmonary embolism following 5809 primary joint arthroplasties.

AIM: Controversy surrounds prevention, detection and clinical relevance of pulmonary embolism (PE) following arthroplasty in orthopaedic patients. We aimed to review the rates of computer tomography pulmonary angiography (CTPA), PE and fatal PE following total joint replacement. METHOD: Mixed retrospective/prospective review of CTPA requests and PE incidence amongst patients undergoing primary knee and hip arthroplasty. RESULTS: The overall PE rate was 112/5809 (1.93%): 38/3473 (1.1%) and 74/2336 (3.5%) following total hip arthroplasty (THA) and total knee arthroplasty (TKA), respectively. Two deaths from PE occurred, both after TKA, a procedural mortality rate of 0.086%; the overall mortality rate was 0.034%. The rate of CTPA requests increased for the initial 7 years as did the rate of PE, in the last 2 years both rates fell. CONCLUSION: The findings are discussed in context of published data and with reference to studies suggesting the high sensitivity of CTPA may over diagnose clinically significant PE following arthroplasty if ordered without a robust method of determining the pre-test probability.

Spore Cortex Hydrolysis Precedes Dipicolinic Acid Release during Clostridium difficile Spore Germination.

UNLABELLED: Bacterial spore germination is a process whereby a dormant spore returns to active, vegetative growth, and this process has largely been studied in the model organism Bacillus subtilis. In B. subtilis, the initiation of germinant receptor-mediated spore germination is divided into two genetically separable stages. Stage I is characterized by the release of dipicolinic acid (DPA) from the spore core. Stage II is characterized by cortex degradation, and stage II is activated by the DPA released during stage I. Thus, DPA release precedes cortex hydrolysis during B. subtilis spore germination. Here, we investigated the timing of DPA release and cortex hydrolysis during Clostridium difficile spore germination and found that cortex hydrolysis precedes DPA release. Inactivation of either the bile acid germinant receptor, cspC, or the cortex hydrolase, sleC, prevented both cortex hydrolysis and DPA release. Because both cortex hydrolysis and DPA release during C. difficile spore germination are dependent on the presence of the germinant receptor and the cortex hydrolase, the release of DPA from the core may rely on the osmotic swelling of the core upon cortex hydrolysis. These results have implications for the hypothesized glycine receptor and suggest that the initiation of germinant receptor-mediated C. difficile spore germination proceeds through a novel germination pathway. IMPORTANCE: Clostridium difficile infects antibiotic-treated hosts and spreads between hosts as a dormant spore. In a host, spores germinate to the vegetative form that produces the toxins necessary for disease. C. difficile spore germination is stimulated by certain bile acids and glycine. We recently identified the bile acid germinant receptor as the germination-specific, protease-like CspC. CspC is likely cortex localized, where it can transmit the bile acid signal to the cortex hydrolase, SleC. Due to the differences in location of CspC compared to the Bacillus subtilis germinant receptors, we hypothesized that there are fundamental differences in the germination processes between the model organism and C. difficile. We found that C. difficile spore germination proceeds through a novel pathway.

Efficient and facile synthesis of acrylamide libraries for protein-guided tethering.

A kinetic template-guided tethering (KTGT) strategy has been developed for the site-directed discovery of fragments that bind to defined protein surfaces, where acrylamide-modified fragments can be irreversibly captured in a protein-templated conjugate addition reaction. Herein, an efficient and facile method is reported for the preparation of acrylamide libraries from a diverse range of amine fragments using a solid-supported quaternary amine base.

Does computer-assisted total knee arthroplasty improve the overall component position and patient function?

PURPOSE: There remains controversy as to whether computer-navigated total knee replacement (TKR) improves the overall prosthesis alignment and patient function. The aim of this study was to determine whether computer-assisted total knee arthroplasty provides superior prosthesis positioning when compared to a conventional jig-assisted total knee replacement and whether this affected the functional outcome. METHODS: This prospective, randomised controlled study compared computer navigated and conventional jig-assisted total knee replacement in 37 patients who underwent bilateral TKR. A quantitative assessment of the spatial positioning of the implant in the 74 total knee replacements was determined using a low-dose dual-beam CT scanning technique. This resulted in six parameters of alignment that were compared. Functional outcomes using the high activity arthroplasty score and Knee Society score were assessed pre-operatively, postoperatively, at three years and at five years. Patients also indicated which knee they felt was subjectively the best. RESULTS: There was no statistically significant difference in the prosthesis alignment between both groups and the number of outliers was not decreased with navigation. All function scores improved from pre-operative to postoperative but there was no statistically significant difference between the groups at five years. At five years, 40.6% of patients thought their jig-assisted knee was the better knee compared with 21.9% their computer assisted knee and 37.5% of patients who felt they were the same. CONCLUSION: Computer-assisted implantation of total knee replacements does not offer a significant advantage in prosthesis alignment. There was no difference in functional outcome or subjective "best knee" between the computer-assisted or jig-assisted knee.

Do larger femoral heads improve the functional outcome in total hip arthroplasty?

Use of larger diameter femoral heads has been popularised in total hip arthroplasty (THA). Recent studies have implicated larger femoral heads in early failure. We evaluated what effect the size of the femoral head had on the early functional outcome in order to determine the optimal head size for the maximal functional outcome. There were 726 patients who underwent elective THA and were divided into 3 groups according to head size then compared with respect to functional outcome scores and dislocation rates. This study failed to show that increasing the size of the femoral head significantly improved the functional outcome at 1 year after total hip arthroplasty but that the use of a 36 mm or greater femoral head did reduce the dislocation rate.

Muricholic acids inhibit Clostridium difficile spore germination and growth.

Infections caused by Clostridium difficile have increased steadily over the past several years. While studies on C. difficile virulence and physiology have been hindered, in the past, by lack of genetic approaches and suitable animal models, newly developed technologies and animal models allow these processes to be studied in detail. One such advance is the generation of a mouse-model of C. difficile infection. The development of this system is a major step forward in analyzing the genetic requirements for colonization and infection. While important, it is equally as important in understanding what differences exist between mice and humans. One of these differences is the natural bile acid composition. Bile acid-mediated spore germination is an important step in C. difficile colonization. Mice produce several different bile acids that are not found in humans. These muricholic acids have the potential to impact C. difficile spore germination. Here we find that the three muricholic acids (α-muricholic acid, ß-muricholic acid and ω-muricholic acid) inhibit C. difficile spore germination and can impact the growth of vegetative cells. These results highlight an important difference between humans and mice and may have an impact on C. difficile virulence in the mouse-model of C. difficile infection.

Synthesis and evaluation of heteroaryl substituted diazaspirocycles as scaffolds to probe the ATP-binding site of protein kinases.

With the success of protein kinase inhibitors as drugs to target cancer, there is a continued need for new kinase inhibitor scaffolds. We have investigated the synthesis and kinase inhibition of new heteroaryl-substituted diazaspirocyclic compounds that mimic ATP. Versatile syntheses of substituted diazaspirocycles through ring-closing metathesis were demonstrated. Diazaspirocycles directly linked to heteroaromatic hinge binder groups provided ligand efficient inhibitors of multiple kinases, suitable as starting points for further optimization. The binding modes of representative diazaspirocyclic motifs were confirmed by protein crystallography. Selectivity profiles were influenced by the hinge binder group and the interactions of basic nitrogen atoms in the scaffold with acidic side-chains of residues in the ATP pocket. The introduction of more complex substitution to the diazaspirocycles increased potency and varied the selectivity profiles of these initial hits through engagement of the P-loop and changes to the spirocycle conformation, demonstrating the potential of these core scaffolds for future application to kinase inhibitor discovery.

Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection.

Clostridium difficile spores must germinate in vivo to become actively growing bacteria in order to produce the toxins that are necessary for disease. C. difficile spores germinate in vitro in response to certain bile acids and glycine. In other sporulating bacteria, proteins embedded within the inner membrane of the spore sense the presence of germinants and trigger the release of Ca⁺⁺-dipicolinic acid (Ca⁺⁺-DPA) from the spore core and subsequent hydrolysis of the spore cortex, a specialized peptidoglycan. Based upon homology searches of known germinant receptors from other spore-forming bacteria, C. difficile likely uses unique mechanisms to recognize germinants. Here, we identify the germination-specific protease, CspC, as the C. difficile bile acid germinant receptor and show that bile acid-mediated germination is important for establishing C. difficile disease in the hamster model of infection. These results highlight the importance of bile acids in triggering in vivo germination and provide the first description of a C. difficile spore germinant receptor. Blocking the interaction of bile acids with the C. difficile spore may represent an attractive target for novel therapeutics.