Biomechanical and ergonomic risks associated with cervical musculoskeletal dysfunction amongst surgeons: A systematic review.

INTRODUCTION: Surgeons are at high risk of developing musculoskeletal symptoms due to a range of factors including, maladaptive positioning and surgical ergonomics. Cervical muscle strain and biomechanical load is most prevalent due to repetitive motions and prolonged static neck positioning. This issue is apparent through reports of prevalence between 10 and 74.4% among surgeons. The aim of this systematic review is to provide an objective assessment of the clinical evidence available and a descriptive analysis of the effects of kinematics and surgical ergonomics on the prevalence of surgeons' cervical musculoskeletal pain. METHODS: This is PRISMA-compliant systematic review of clinical studies assessing the prevalence of cervical musculoskeletal dysfunction in surgeons by searching PUBMED and Ovid EMBASE databases from inception to 19th October 2023. Study quality was graded according to the National Institutes of Health study quality assessment tools. RESULTS: A total of 9 studies were included in the final qualitative analysis. The use of loupes, open surgery and excessive neck flexion (>30°) were associated with cervical dysfunction. Comparison of study outcomes was challenging due to heterogeneity within study methods and the paucity of methodological quality. CONCLUSION: The current literature assessing ergonomic and biomechanical factors predisposing surgeons to cervical musculoskeletal dysfunction is insufficient to provide reliable guidance for clinicians. Although the literature identifies factors contributing to work-related cervical dysfunction, few attempt to evaluate interventions for improved surgical ergonomics. An objective assessment of interventions that prompt postural correction with the aim to improve neck pain in surgeon cohorts is warranted.

Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

A potential biomarker of radiosensitivity in metastatic hormone sensitive prostate cancer patients treated with combination external beam radiotherapy and radium-223.

PURPOSE: The ADRRAD trial reported the safety and feasibility of the combination of external beam radiotherapy and radium-223 in the treatment of de novo bone metastatic prostate. This study aimed to determine if any biomarkers predictive of response to these treatments could be identified. EXPERIMENTAL DESIGN: 30 patients with newly diagnosed bone metastatic hormone sensitive prostate cancer were recruited to the ADRRAD trial. Blood samples were taken pre-treatment, before cycles 2 to 6 of radium-223, and 8 weeks and 6 months after treatment. Mononuclear cells were isolated and DNA damage was assessed at all timepoints. RESULTS: DNA damage was increased in all patients during treatment, with bigger increases in foci observed in patients who relapsed late compared to those who relapsed early. Increases in DNA damage during the radium-223 only cycles of treatment were specifically related to response in these patients. Analysis of hematology counts also showed bigger decreases in red blood cell and hemoglobin counts in patients who experienced later biochemical relapse. CONCLUSIONS: While some patients responded to this combination treatment, others relapsed within one year of treatment initiation. This study identifies a biomarker based approach that may be useful in predicting which patients will respond to treatment, by monitoring both increases in DNA damage above baseline levels in circulating lymphocytes and decreases in red blood cell and hemoglobin counts during treatment.

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A.

Chromothripsis, the process of catastrophic shattering and haphazard repair of chromosomes, is a common event in cancer. Whether chromothripsis might constitute an actionable molecular event amenable to therapeutic targeting remains an open question. We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ∼25% of patients ('chr21amp'). We report that chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. The chr21amp event is highly clonal and present throughout the hematopoietic hierarchy. DYRK1A , a serine threonine kinase and transcription factor, is the only gene in the 2.7Mb minimally amplified region which showed both increased expression and chromatin accessibility compared to non-chr21amp BP-MPN controls. We demonstrate that DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development, including DNA repair, STAT signalling and BCL2 overexpression. DYRK1A is essential for BP-MPN cell proliferation in vitro and in vivo , and DYRK1A inhibition synergises with BCL2 targeting to induce BP-MPN cell apoptosis. Collectively, these findings define the chr21amp event as a prognostic biomarker in BP-MPN and link chromothripsis to a druggable target.

Enhanced wave overtopping simulation at vertical breakwaters using machine learning algorithms.

Accurate prediction of wave overtopping at sea defences remains central to the protection of lives, livelihoods, and infrastructural assets in coastal zones. In addressing the increased risks of rising sea levels and more frequent storm surges, robust assessment and prediction methods for overtopping prediction are increasingly important. Methods for predicting overtopping have typically relied on empirical relations based on physical modelling and numerical simulation data. In recent years, with advances in computational efficiency, data-driven techniques including advanced Machine Learning (ML) methods have become more readily applicable. However, the methodological appropriateness and performance evaluation of ML techniques for predicting wave overtopping at vertical seawalls has not been extensively studied. This study examines the predictive performance of four ML techniques, namely Random Forest (RF), Gradient Boosted Decision Trees (GBDT), Support Vector Machines-Regression (SVR), and Artificial Neural Network (ANN) for overtopping discharge at vertical seawalls. The ML models are developed using data from the EurOtop (2018) database. Hyperparameter tuning is performed to curtail algorithms to the intrinsic features of the dataset. Feature Transformation and advanced Feature Selection methods are adopted to reduce data redundancy and overfitting. Comprehensive statistical analysis shows superior performance of the RF method, followed in turn by the GBDT, SVR, and ANN models, respectively. In addition to this, Decision Tree (DT) based methods such as GBDT and RF are shown to be more computationally efficient than SVR and ANN, with GBDT performing simulations more rapidly that other methods. This study shows that ML approaches can be adopted as a reliable and computationally effective method for evaluating wave overtopping at vertical seawalls across a wide range of hydrodynamic and structural conditions.

Juvenile idiopathic arthritis-associated genetic loci exhibit spatially constrained gene regulatory effects across multiple tissues and immune cell types.

Juvenile idiopathic arthritis (JIA) is an autoimmune, inflammatory joint disease with complex genetic etiology. Previous GWAS have found many genetic loci associated with JIA. However, the biological mechanism behind JIA remains unknown mainly because most risk loci are located in non-coding genetic regions. Interestingly, increasing evidence has found that regulatory elements in the non-coding regions can regulate the expression of distant target genes through spatial (physical) interactions. Here, we used information on the 3D genome organization (Hi-C data) to identify target genes that physically interact with SNPs within JIA risk loci. Subsequent analysis of these SNP-gene pairs using data from tissue and immune cell type-specific expression quantitative trait loci (eQTL) databases allowed the identification of risk loci that regulate the expression of their target genes. In total, we identified 59 JIA-risk loci that regulate the expression of 210 target genes across diverse tissues and immune cell types. Functional annotation of spatial eQTLs within JIA risk loci identified significant overlap with gene regulatory elements (i.e., enhancers and transcription factor binding sites). We found target genes involved in immune-related pathways such as antigen processing and presentation (e.g., ERAP2, HLA class I and II), the release of pro-inflammatory cytokines (e.g., LTBR, TYK2), proliferation and differentiation of specific immune cell types (e.g., AURKA in Th17 cells), and genes involved in physiological mechanisms related to pathological joint inflammation (e.g., LRG1 in arteries). Notably, many of the tissues where JIA-risk loci act as spatial eQTLs are not classically considered central to JIA pathology. Overall, our findings highlight the potential tissue and immune cell type-specific regulatory changes contributing to JIA pathogenesis. Future integration of our data with clinical studies can contribute to the development of improved JIA therapy.

A rare case of intralesional haemorrhage of a benign aqueductal cyst after CSF diversion treatment. A case report and review of literature.

Benign cysts within the pure aqueductal region are a rare entity. Their critical location within the ventricular system presents a risk of potentially catastrophic outcomes. We present a case of a 68-year-old female who was transferred to our unit with an acute obstructive triventricular hydrocephalus caused by a benign cyst within the cerebral aqueduct. She became unconscious and had an urgent endoscopic third ventriculostomy (ETV). Post-operatively, the patient was recovering well but then developed a sudden onset severe headache accompanied by vomiting. Imaging revealed intracystic haemorrhage with expansion of lesion but there was no obstructive hydrocephalus due to CSF diversion performed 9 d prior. She was treated conservatively and continued to improve.

Current trends in craniofacial reconstruction.

Reconstruction of the head and neck continues to pose a variety of difficult functional and aesthetic challenges to the plastic surgeon. While the surgical treatment for midfacial and skull base tumours continues to advance, the three-dimensional reconstruction predicaments continue to increase in complexity. Reconstructive strategies of the head and neck require the restoration of intricate skeletal architecture and large volumes of both internal and external soft tissue envelopes that can withstand adjuvant therapies. Vascularized bone grafts in combination with microsurgical techniques is the current trend of most reconstruction and has replaced local and pedicle flaps as the preferred modality for large defects. This article will focus on concise areas of difficulty in craniofacial reconstruction, including mandibular, midfacial, scalp and base of skull reconstruction. As our goals now move from flap survival to refinement, more complex and innovative reconstructions are executed. The problems with each modality are examined, and the frontiers of head and neck reconstruction are explored. With the potential combination of virtual surgery and tissue engineered biotechnology, we may someday be able to expand our reconstructive capabilities beyond free tissue transfer.

Radial Artery Aneurysm Arising from the Stump of a Ligated Arteriovenous Fistula in a Kidney Transplant Patient.

While aneurysm and pseudoaneurysm are common complications to arteriovenous (AV) fistula, the development of aneurysm from the stump of a ligated AV fistula is unusual. The involvement of radial artery after AV fistula ligation is an extremely rare entity with only two cases reported in the literature. In this report, we describe a 40-year-old kidney transplant patient who presented with a radial artery aneurysm after radiocephalic fistula ligation which was managed by the plastic surgery team using autologous vein graft reconstruction, and we compare our case to the two cases described in the literature in the presentations, timelines, and management options.

New insights in the probability distributions of wave-by-wave overtopping volumes at vertical breakwaters.

Advances in the development of prediction tools for wave overtopping allow now for overtopping volumes to be estimated with good accuracy, with the combined use of mean overtopping rates and maximum wave by wave overtopping volumes in a sequence of wave overtopping events. While previous literature has tended to focus on mean overtopping rates at coastal structures, limited studies have investigated the wave by wave overtopping volumes at coastal sea defences; in particular, a paucity of studies have focussed on the prediction of the shape parameter in the Weibull distribution (i.e., Weibull b) of overtopping volumes. This study provides new insights on the probability distribution of individual wave overtopping volumes at plain vertical seawalls by analysing the measured Weibull b values derived from a series of laboratory experiments on seawalls performed on a wide range of wave conditions and crest freeboards. The influence of wave conditions (wave steepness, significant wave height), structural parameters (crest freeboard, toe water depth), impulsiveness, probability of overtopping waves, and overtopping discharge on Weibull b parameter were examined, and then compared with the well-established empirical formulae. For the conditions covered within this study, it was found that the probability distribution of wave-by-wave overtopping volumes follow a 2-parameter Weibull distribution. No apparent differences in Weibull b values were reported with the variation of incident wave steepness and impulsiveness parameter. Results of this study revealed that Weibull b values at vertical walls, subjected to non-impulsive wave conditions, can be predicted reasonably well using relative freeboard and relative overtopping rates. A new unified formula is proposed for the estimation of Weibull b values at vertical walls under impulsive and non-impulsive wave attack.

Association Between Ex Vivo Human Ulcerative Colitis Explant Protein Secretion Profiles and Disease Behaviour.

BACKGROUND: The clinical course of ulcerative colitis (UC) is variable. There is an unmet clinical need for biomarkers of UC disease behaviour. We aimed to evaluate the association between ex vivo human UC explant conditioned media (explant-CM) secreted protein profiles and UC disease behaviour. METHODS: UC patients undergoing endoscopy were prospectively recruited. Endoscopic biopsies were collected and explant-CM generated. Association between explant-CM protein secretion profiles and disease progression was evaluated. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent. Association between explant-CM secreted protein profiles and anti-TNF failure status was also evaluated. p values < 0.05 were considered significant in analyses. RESULTS: Twenty-four UC patients were included (age [median, range]) 55 [21-72] years; 50% female. Disease progression during follow-up occurred in twelve (50%) patients. Multivariate analysis, including endoscopic remission status, demonstrated reduced IL-2 secretion to be independently associated with UC disease progression, p = 0.01. In univariate analysis, anti-TNF failure status was associated with significantly increased IL-17A/F (p = 0.015) and IL-12 / IL-23p40 (p = 0.044) concentrations. In multivariate analysis, there was a trend towards an association between IL-17A/F and anti-TNF failure status (p = 0.069); FLT-1 was demonstrated to be independently associated with anti-TNF failure status (p = 0.016). CONCLUSION: Reduced explant-CM secreted IL-2 is associated with UC disease progression. Increased secretion of IL-23 pathway-associated cytokines was observed in anti-TNF failure status consistent with previous reports. Ex vivo human UC explants, generated from endoscopic biopsies, have potential as precision medicine tools in inflammatory bowel disease.

Modification of hurling helmets causing penetrating upper limb injury: A case series demonstrating opportunity for improved player safety.

BACKGROUND: The games of hurling and camogie involve fast ball movement and a substantial physical contact with opposing players. The wearing of protective helmets with faceguards became obligatory 10 years ago and resulted in a significant reduction of craniofacial injuries. However since then a trend has emerged of players modifying helmets to improve comfort and vision. As officials are not yet required to perform pre-match checks, many players enter competition with defective protective equipment which poses a risk to both themselves and others. METHODS: We present 4 cases of penetrating upper limb injury in hurlers sustained as a result of helmet faceguards. These injuries were sustained during competitive play and the affected patients presented with portions of the faceguards embedded in their wounds. Each patient required admission to hospital and exploration of their wounds under general anaesthetic. CONCLUSIONS: This case series demonstrates the dangers of modification and damage to protective helmet faceguards used in hurling and camogie. We encourage helmet manufacturers to re-engage with players to ensure that current safety equipment meets the functional demands of the modern player while adhering to approved manufacturing standards. Mandatory helmet checks before competitive games would reduce the likelihood of penetrating upper limb injury to players.

A challenging case of sporadic melanocytoma of the jugular foramen.

BACKGROUND: The jugular foramen (JF) can be the site of several tumours. Paragangliomas, schwannomas and meningiomas are the most commonly reported. We describe a case of melanocytoma originating from the JF and presenting with an accessory nerve palsy. ILLUSTRATIVE CASE: A 48-year-old woman presented with a 6-month history of cervical and left shoulder pain with wasting and weakness of the left trapezius. A Magnetic Resonance Imaging (MRI) showed a T1-hyperintense, T2-isointense, heterogeneously enhancing lesion involving the left JF and extending into the cerebello-medullary and cerebello-pontine cisterns. A retrosigmoid craniotomy was performed and a near-total removal achieved. The accessory nerve was involved by tumour and could not be preserved. Given the diagnostic uncertainty between melanotic schwannoma, metastatic melanoma and meningeal melanocytoma, next generation sequencing and genome-wide DNA methylation arrays were performed, documenting a mutation in GNA11 (c.6226A>T, p. Gln209Leu) and a methylation profile consistent with melanocytoma. The patient underwent adjuvant fractionated radiotherapy of the tumour remnant. A follow-up MRI 4 years after surgery did not show any tumour recurrence. CONCLUSIONS: The differential diagnosis of skull base pigmented tumours can be challenging, particularly when they occur in unusual locations such as the JF. They can be misdiagnosed given their similar clinical, neuroradiological and pathological features if anatomy of the site of origin is not carefully considered and molecular tests are not performed, leading to erroneous treatment and follow-up planning.

Absolute quantification of eleven A, D, E and K vitamers in human plasma using automated extraction and UHPLC-Orbitrap MS.

Fat-Soluble Vitamers [FSV] deficiencies and hypervitaminosis are associated with lifestyle diseases such as cardiovascular disease, diabetes, and cancer. Quantification of FSV and their metabolites in plasma has proved to be one of the most demanding analytical chemistry challenges. Current FSV quantification methods are compromises between breadth of coverage and sensitivity across the physiological range. Here, we developed and validated a sensitive, robust, semi-automated method using liquid-liquid extraction coupled with LC-ESI-MS/MS to quantify 11 FSV across their physiological concentrations in plasma. The addition of Phree® phospholipid removal plates as the last step in the extraction process reduced matrix effects, improving precision, recoveries, and the method's final sensitivity. This method can detect and quantify: retinol, retinoic acid, retinyl palmitate, 25 hydroxyvitamin D3 [25-OH-D3], 1-α-25-dihydroxy-D3, α-tocopherol, γ-tocopherol, α-tocotrienol, phylloquinone [K1], Menatetrenone [MK-4], and menaquinone-7 [MK-7].The Instrument Quantitation Limit [IQL]s for retinol (64.1 ng/mL), 25-OH-D3 (10.2 ng/mL), and α-tocopherol (3000 ng/mL) can detect clinical deficiencies. Our automated method will assist in the understanding of the complex interaction between these compounds and their possible role in health and disease.

Understanding the impact of SNPs associated with autism spectrum disorder on biological pathways in the human fetal and adult cortex.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by significant and complex genetic etiology. GWAS studies have identified genetic variants associated with ASD, but the functional impacts of these variants remain unknown. Here, we integrated four distinct levels of biological information (GWAS, eQTL, spatial genome organization and protein-protein interactions) to identify potential regulatory impacts of ASD-associated SNPs (p < 5 × 10-8) on biological pathways within fetal and adult cortical tissues. We found 80 and 58 SNPs that mark regulatory regions (i.e. expression quantitative trait loci or eQTLs) in the fetal and adult cortex, respectively. These eQTLs were also linked to other psychiatric disorders (e.g. schizophrenia, ADHD, bipolar disorder). Functional annotation of ASD-associated eQTLs revealed that they are involved in diverse regulatory processes. In particular, we found significant enrichment of eQTLs within regions repressed by Polycomb proteins in the fetal cortex compared to the adult cortex. Furthermore, we constructed fetal and adult cortex-specific protein-protein interaction networks and identified that ASD-associated regulatory SNPs impact on immune pathways, fatty acid metabolism, ribosome biogenesis, aminoacyl-tRNA biosynthesis and spliceosome in the fetal cortex. By contrast, in the adult cortex they largely affect immune pathways. Overall, our findings highlight potential regulatory mechanisms and pathways important for the etiology of ASD in early brain development and adulthood. This approach, in combination with clinical studies on ASD, will contribute to individualized mechanistic understanding of ASD development.

Contemporary Ross procedure outcomes: medium- to long-term results in 214 patients.

OBJECTIVE: Our goal was to present 2 decades of our experience with the Ross procedure and its sequential modifications, adopted since 2010, to improve the reoperation rate. METHODS: We performed a single-centre, retrospective review of database information and medical notes about the implantation technique: the freestanding root. We compared era 1 (1997-2009) and era 2 (2010-2019). RESULTS: Between 1997 and 2019, a total of 214 Ross procedures were performed (71% men, median age 24 years) [interquartile range (IQR) 15-38]. Of these, 87% had various forms of congenital-dysplastic aortic valves. The median cross-clamping and bypass times were 173 (IQR 148-202) and 202 (IQR 182-244) min. The median postoperative stay was 6 days (2-77). Thirty-day mortality was 0.5%. The median follow-up time was 8.2 years (IQR 3.9-13.2). Survival at 10 and 20 years was 97% and 95%; freedom from greater than moderate aortic regurgitation or aortic valve intervention was 91% and 80%; and 93% of the patients were in New York Heart Association functional class I. Twenty (21%) patients operated on during era 1 and 6 (9%) during era 2 underwent autograft reoperations. The median follow-up time was 14.3 (IQR 11.5-17.4) and 4.8 (IQR 2.5-7) years. Freedom from autograft reoperation was 87% and 69% at 10 and 20 years, with no significant difference between eras. Freedom from homograft reoperation was 96% and 76% at 10 and 20 years. The presence of aortic regurgitation, infective endocarditis and era 1 were predictors of autograft reoperation. Male gender and era 1 were predictors of neoaortic root dilatation. CONCLUSIONS: The contemporary modified Ross procedure continues to deliver excellent results and should remain part of the strategy to treat children and young adults requiring aortic valve replacement.

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800.

AIMS: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. METHODS AND RESULTS: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. CONCLUSIONS: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

LC-MS/MS quantification of fat soluble vitamers - A systematic review.

Fat soluble vitamers (FSV) are several biochemically diverse micronutrients essential for healthy development, growth, metabolism, and cell regulation. We cannot synthesize FSV completely or at the required concentrations. Deficiency or excess of FSV can result in many health problems. Plasma is the most accessible sample matrix for the quantification of FSV. However, due to its complexity and other analytical challenges (e.g., FSV sensitivity to light, oxygen, heat, pH, chemical heterogeneity, standard availability), developing a method for the simultaneous quantification of multiple FSV at physiological concentrations has been challenging. In this systematic review, we examine the parameters and criteria used in existing Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) methods for FSV quantification to the extraction method, chromatographic resolution, matrix effects, and method validation as critical to a sensitive and robust method. We conclude that the final FSV method sensitivity is predominantly based on aforementioned criteria and future method development using LC-MS/MS will benefit from the application of this systematic review.