Insights into breast health issues in women's rugby.

World RugbyTM supports dedicated women's welfare, injury surveillance and medical/technical interventions, yet breast health has received limited attention. This article aims to provide insights into breast health issues in rugby, including breast impacts and injuries. We discuss how breast anatomy and position may be problematic in rugby. Breast volume relates to body size, which may be increasing in women's rugby, suggesting increased breast surface area and mass, potentially increasing injury risk. Breast health issues in rugby have been reported previously, with 58% of contact footballers (including rugby) experiencing breast injuries. There are damaging effects related to these breast health issues, with breast impacts often causing pain and swelling. Breast impacts may lead to haematomas, cysts and fat necrosis which can calcify over time making them difficult to distinguish from breast carcinoma, causing further investigation and anxiety. In sport, poor bra fit and insufficient support are associated with pain, skin strain and performance decrements. This article reports the potential implications of these breast health issues on performance in rugby. Recent breast-related projects supported by rugby communities may address recommendations identified in the literature for robust breast injury classifications, updated injury surveillance systems and prospective data collection on breast injury prevalence, severity and impact in rugby. These data should inform breast injury care pathways and intervention research, including evidence-based bra design. Understanding the implications of breast impacts on tissue properties, health and wellbeing is vital. Finally, data should inform rugby-specific breast education, raising awareness of this aspect of athlete health.

Spinal joint moment prediction following simulated breast surgery using a female whole-body musculoskeletal model.

This study aimed to use a musculoskeletal model to predict changes in spinal moments following simulated breast surgery. A female full body musculoskeletal model with a fully articulated thoracolumbar spine and independent moveable breast segments was customised for this study. Key findings suggest that the simulated removal of breast tissue (750 g to 1501 g) can reduce the magnitude of lumbar spine extensor moments by >0.05 Nm/kg during walking and jogging. A customised female whole-body musculoskeletal model is capable of providing a first approximation of changes in spinal loading following simulated breast surgery.

A Short Review on Obeticholic Acid: An Effective Modulator of Farnesoid X Receptor.

Farnesoid X receptor (FXR) was identified as an orphan nuclear receptor resembling the steroid receptor in the late '90s. Activation of FXR is a crucial step in many physiological functions of the liver. A vital role of FXR is impacting the amount of bile acids in the hepatocytes, which it performs by reducing bile acid synthesis, stimulating the bile salt export pump, and inhibiting its enterohepatic circulation, thus protecting the hepatocytes against the toxic accumulation of bile acids. Furthermore, FXR mediates bile acid biotransformation in the intestine, liver regeneration, glucose hemostasis, and lipid metabolism. In this review, we first discuss the mechanisms of the disparate pleiotropic actions of FXR agonists. We then delve into the pharmacokinetics of Obeticholic acid (OCA), the first-in-class selective, potent FXR agonist. We additionally discuss the clinical journey of OCA in humans, its current evidence in various human diseases, and its plausible roles in the future.

Single-cell landscape of functionally cured chronic hepatitis B patients reveals activation of innate and altered CD4-CTL-driven adaptive immunity.

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs (peripheral blood mononuclear cells) from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC. METHODS: We combined single-cell transcriptomics (single-cell RNA sequencing) with multiparametric flow cytometry-based immune phenotyping, and multiplexed immunofluorescence to elucidate the immunopathological cell states associated with CHB vs. FC. RESULTS: We found that the intrahepatic environment in CHB and FC displays specific cell identities and molecular signatures that are distinct from those found in matched PBMCs. FC is associated with the emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes, and an activated innate response represented by liver-resident natural killer cells, specific Kupffer cell subtypes and marginated neutrophils. Surprisingly, we found MHC class II-expressing hepatocytes in patients achieving FC, as well as low but persistent levels of covalently closed circular DNA and pregenomic RNA, which may play an important role in FC. CONCLUSIONS: Our study provides conceptually novel insights into the immuno-pathological control of HBV cure, and opens exciting new avenues for clinical management, biomarker discovery and therapeutic development. We believe that the discoveries from this study, as it relates to the activation of an innate and altered immune response that may facilitate sustained, low-grade inflammation, may have broader implications in the resolution of chronic viral hepatitis. IMPACT AND IMPLICATIONS: This study dissects the immuno-pathological cell states associated with functionally cured chronic hepatitis B (defined by the loss of HBV surface antigen or HBsAg). We identified the sustained presence of very low viral load, accessory antigen-presenting hepatocytes, adaptive-memory-like natural killer cells, and the emergence of helper CD4 T cells with cytotoxic or effector-like signatures associated with functional cure, suggesting previously unsuspected alterations in the adaptive immune response, as well as a key role for the innate immune response in achieving or maintaining functional cure. Overall, the insights generated from this study may provide new avenues for the development of alternative therapies as well as patient surveillance for better clinical management of chronic hepatitis B.

Digital consent in gynecology: an evaluation of patient experience.

INTRODUCTION: The surgical consent process is a crucial discussion between patient and surgeon, which is predominantly documented utilizing hand-written forms. The exchange of individualized information allows the patient to make a truly informed decision. Digital consent (also known as electronic consent or e-consent) has been shown to improve accuracy of information provided without increasing the time taken to consent patients. We aimed to evaluate patient experience and effectiveness of digital consent in a gynecology department in a tertiary London Teaching Hospital. METHODS: A questionnaire was designed and completed by 100 patients undergoing gynecological surgery: 50 consented using paper and 50 consented digitally. The questionnaire included 8 statements, with five possible answers to select, ranging from strongly agree to strongly disagree, on a standard five-point Likert Scale. Patients were all female and categorized into age groups (deciles) and asked whether consent was taken digitally or on paper. Data were collected between January and July 2021. RESULTS: Most responses were positive with 87% (694/800) of responses to the questions being either strongly agree or agree. Patients who were consented using paper selected 'strongly agree' 43.5% (174/400) of the time in comparison to 64.8% (259/400) of the time when they were consented digitally. The majority, 86% (43/50), of digitally consented patients received a copy of the consent form in comparison to 18% (9/50) of those consented using paper. On average, the patients consented digitally were older than their paper-consented counterparts (49-58 and 59-68 respectively). The mean scores for the questions relating to the ease of reading the form, ease of understanding the form, understanding of the potential complications, and overall satisfaction were higher in those digitally consented (p < 0.05). DISCUSSION: Overall, patients were satisfied with both methods of consent. However, individuals who were consented digitally reported higher levels of satisfaction throughout the consent process, compared to paper consent. These data suggest that digital consent is an acceptable alternative to paper consent for patients and facilitates adherence to national consent guidance, which stipulates patients should be given the information they request.

The trehalose 6-phosphate phosphatase family in plants.

Trehalose 6-phosphate (Tre6P), the intermediate of trehalose biosynthesis, is an essential signalling metabolite linking plant growth and development to carbon metabolism. While recent work has focused predominantly on the enzymes that produce Tre6P, little is known about the proteins that catalyse its degradation, the trehalose 6-phosphate phosphatases (TPPs). Often occurring in large protein families, TPPs exhibit cell-, tissue- and developmental stage-specific expression patterns, suggesting important regulatory functions in controlling local levels of Tre6P and trehalose as well as Tre6P signalling. Furthermore, growing evidence through gene expression studies and transgenic approaches shows that TPPs play an important role in integrating environmental signals with plant metabolism. This review highlights the large diversity of TPP isoforms in model and crop plants and identifies how modulating Tre6P metabolism in certain cell types, tissues, and at different developmental stages may promote stress tolerance, resilience and increased crop yield.

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.

Clinical utility of axillary nodal markers in breast cancer.

BACKGROUND: De-escalation of axillary surgery for lymph node (LN) positive breast cancer is facilitated by marking involved nodes which, when removed with sentinel nodes constitute risk-adapted targeted axillary dissection (TAD). Whether after chemotherapy or for primary surgery, selected patients with biopsy-proven involvement of nodes may be eligible for axillary conservation. Likewise, impalpable recurrence or stage 4 patients with localised axillary disease may benefit. In these contexts, several devices are used to mark biopsied nodes to facilitate their accurate surgical removal. We report our experience using the paramagnetic MAGSEED (Endomag®, Cambridge, UK). METHODS: Local approval (BR2021_149) was obtained to interrogate a prospective database of all axillary markers. The primary endpoint was successful removal of the marked LN. RESULTS: Of 241 markers (in 221 patients) inserted between October 2018 and July 2022, all were retrieved. Of 74 patients who had Magseeds® inserted after completion of NACT (involved nodes initially marked using an UltraCor™Twirl™ marker), the Magseeds® were found outside the node in neighbouring axillary tissue in 18 (24.3%) patients. When Magseeds® were placed at commencement of NACT in 54 patients, in only 1 (1.8%) was the marker found outside the node - a statistically significantly lower rate (Chi2 10.7581 p = 0.001038). For 'primary TAD' patients and those localised for recurrent or stage IV disease, all 93 had the Magseed® found within the biopsied node. CONCLUSION: This series supports our axillary nodal marking technique as safe and reliable. For TAD following NACT, placement at the start of treatment led to a significantly higher localisation rate.

Blood Loss Following Open Posterior Spinal Fusion in Fractures: Cannulated vs. Solid Pedicle Screws.

We aim to delineate whether there is increased blood loss with the use of cannulated pedicle screws compared to solid pedicle screws in patients undergoing posterior spinal fusion. A single-centre retrospective case-control study was undertaken on patients undergoing PSF for spinal fractures. Cannulated screw fixation was compared with solid screw fixation. Intraoperative blood loss was estimated using pre and postoperative haemoglobin levels, recorded estimated blood loss and cell saver reports. Anticoagulation, blood product administration, operative time and number of levels fused were assessed. A total of 64 cases, 32 in each cohort, were included in the analysis. Overall mean haemoglobin reduction from pre- to post-operative was 2.82 ± 1.85 g/L per screw inserted in the cannulated group, compared to a haemoglobin decrease of 2.81 ± 1.521 g/L per screw inserted in the solid screw group (p = 0.971). Total estimated intraoperative blood loss was 616.3 + 355.4 mL in the cannulated group, compared to 713.6 + 473.5 mL in the solid screw group (p = 0.456). Patients with preoperative thrombocytopenia had a transfusion rate of 0.5 ± 0.71 units/patient compared to 0.04 ± 0.19 units/patient in patients with normal platelet levels (p < 0.005). The differences in blood loss observed between cannulated and solid pedicle screws are non-significant overall. The largest predictor for need of transfusion was pre-operative thrombocytopenia, regardless of the type of screw used.

Comparing shared decision making using a paper and digital consent process. A multi-site, single centre study in a trauma and orthopaedic department.

INTRODUCTION: The importance of shared decision making (SDM) for informed consent has been emphasised in the updated regulatory guidelines. Errors of completion, legibility and omission have been associated with paper-based consent forms. We introduced a digital consent process and compared it against a paper-based process for quality and patient reported involvement in shared decision making. METHODS: 223 patients were included in this multi-site, single centre study. Patient consent documentation was by either a paper consent form or the Concentric digital consent platform. Consent forms were assessed for errors of legibility, completion and accuracy of content. Core risks for 20 orthopaedic operations were pre-defined by a Delphi round of experts and forms analysed for omission of these risks. SDM was determined via the 'collaboRATE Top Score', a validated measure for gold-standard SDM. RESULTS: 72% (n = 78/109) of paper consent forms contained ≥1 error compared to 0% (n = 0/114) of digital forms (P < 0.0001). Core risks were unintentionally omitted in 63% (n = 68/109) of paper-forms compared to less than 2% (n = 2/114) of digital consent forms (P < 0.0001). 72% (n = 82/114) of patients giving consent digitally reported gold-standard SDM compared to 28% (n = 31/109) with paper consent (P < 0.001). CONCLUSION: Implementation of a digital consent process has been shown to reduce both error rate and the omission of core risks on consent forms whilst increasing the quality of SDM. This novel finding suggests that using digital consent can improve both the quality of informed consent and the patient experience of SDM.

Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT/L axis.

Progressive accrual of senescent cells in aging and chronic diseases is associated with detrimental effects in tissue homeostasis. We found that senescent fibroblasts and epithelia were not only refractory to macrophage-mediated engulfment and removal, but they also paralyzed the ability of macrophages to remove bystander apoptotic corpses. Senescent cell-mediated efferocytosis suppression (SCES) was independent of the senescence-associated secretory phenotype (SASP) but instead required direct contact between macrophages and senescent cells. SCES involved augmented senescent cell expression of CD47 coinciding with increased CD47-modifying enzymes QPCT/L. SCES was reversible by interfering with the SIRPα-CD47-SHP-1 axis or QPCT/L activity. While CD47 expression increased in human and mouse senescent cells in vitro and in vivo, another ITIM-containing protein, CD24, contributed to SCES specifically in human epithelial senescent cells where it compensated for genetic deficiency in CD47. Thus, CD47 and CD24 link the pathogenic effects of senescent cells to homeostatic macrophage functions, such as efferocytosis, which we hypothesize must occur efficiently to maintain tissue homeostasis.

Healthcare Practitioners Knowledge of Shoulder Injury Related to Vaccine Administration (SIRVA).

Background: Vaccine pharmacovigilance is at the forefront of the public eye. Shoulder Injuries Related to Vaccine Administration (SIRVA) is a poorly understood Adverse Event Following Immunisation, with iatrogenic origins. Criteria for medicolegal diagnosis of SIRVA is conflicting, current literature and educational materials are lacking, and healthcare practitioner knowledge of the condition is unknown. Methods: A cross-sectional, convenience sampled survey, utilising a validated online questionnaire assessed practitioner knowledge of SIRVA, safe injecting, and upper limb anatomy, and preferred definition for SIRVA. Results: Mean scores were moderate for safe injecting knowledge (69%), and poor for knowledge of anatomy (42%) and SIRVA (55%). Non-immunising healthcare practitioners scored significantly (p = 0.01, and < 0.05, respectively) higher than immunising practitioners for anatomy (2.213 ± 1.52 vs. 3.12 ± 1.50), and safe injecting knowledge (6.70 ± 1.34 vs. 7.14 ± 1.27). Only 52% of authorised vaccinators accurately selected a 40 × 20 mm area recommended for safe injecting. Majority (91.7%) of respondents thought nerve injuries should be included in the diagnostic criteria for SIRVA. Discussion and conclusions: Greater education and awareness of SIRVA is needed in all healthcare disciplines. Consensus regarding SIRVA definition is paramount for accurate reporting and improved future understanding of all aspects of SIRVA.

Gastrointestinal stromal tumor (GIST) presenting as a multilocular cystic intra-abdominal mass in a dog.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is a malignant mesenchymal neoplasm described in humans, dogs, and cats. A hallmark of diagnosis for GISTs is positive immunohistochemical labelling with c-Kit (CD117). The differentiation of GIST from other mesenchymal neoplasms of the gastrointestinal tract is pivotal to allow for initiation of appropriate treatment. In humans, cystic GIST has been described, though this has not been reported in dogs. In humans, the cystic form of GIST has been associated with a favorable prognosis. In the present paper, we report a case of multilocular cystic GIST in a dog, which has not previously been described in this species. CASE PRESENTATION: A ten-year-old, male-entire Maltese terrier mix breed dog presented with a large cystic mural mass of the duoedenum and orad jejunum. Histopathology and positive immunohistochemical staining with CD117 confirmed a diagnosis of GIST. No evidence of metastasis was detected on routine staging with abdominal sonography and thoracic radiography at the time of diagnosis. Surgical resection was performed and toceranib therapy was initiated post-operatively. Metastasis was documented 251 days after surgery on computed tomography. Due to clinical deterioration, the patient was humanely euthanised 370 days after surgical excision. CONCLUSIONS: There are few differential diagnoses for large multilocular cystic intra-abdominal masses in dogs. This case presents a previously undescribed presentation of gastrointestinal stromal tumor in the dog as a predominantly multilocular cystic mass. It remains unclear if the cystic form of GIST may represent a favorable prognosis in dogs.

Adherence to insulin therapy and associated factors among type 1 and type 2 diabetic patients on follow up in Madda Walabu University Goba Referral Hospital, South East Ethiopia.

BACKGROUND: Non-adherence to insulin therapy is a major global public health issue that has a causal relationship with increased diabetic complications that leads to further increase in the health care cost. However, adherence to insulin therapy and associated factors among diabetic mellitus (DM) patients are still not studied adequately in Ethiopia. OBJECTIVE: To assess the adherence to insulin therapy and associated factors among type 1 and type 2 diabetic patients on follow-up at Madda Walabu University-Goba Referral Hospital, South East Ethiopia. METHOD: An institution-based, cross-sectional study was employed among 311 both type 1 and type 2 diabetic patients, Madda Walabu University-Goba Referral Hospital from March 4 to April 30, 2020. Study participants were recruited with simple random sampling method. Adherence to insulin therapy was measured by 8-item Morisky medication adherence scale. Therefore from these 8-items, those who score 6 or more are considered as adherent to insulin therapy. The data were collected through interviewer administered questionnaires by trained graduating class nurse students. The data were entered to Epidata version 3.1, and analyzed with SPSS version 25. Bivariate and multivariable logistic regression analyses were used to identify factors associated with adherence to insulin therapy. Statistical significance were declared at p <0.05. RESULT: A total of 311 patients participate in the study with response rate of 100%. Among these only 38.9% of them were adherent to insulin therapy with a CI of [33.5, 44.3]. Having glucometer (AOR = 3.88; 95% CI [1.46, 10.35]), regular hospital follow-up (AOR = 3.13; 95% CI [1.12, 8.70]), being knowledgeable (AOR = 3.36; 95% CI [1.53, 7.37]), and favorable attitudes (AOR = 4.55; 95%CI [1.68, 12.34]) were the factor associated with adherence to insulin therapy. CONCLUSION: This study concluded that adherence to insulin therapy was low in the study area. Having glucometer, regular hospital follow-up, being knowledgeable, and favorable attitudes were the factor associated with adherence to insulin therapy. Attention should be paid to help diabetic patients on acquiring knowledge regarding the need of consistent adherence to insulin therapy and its complications.