Buttslattery9076

Our patient presents with a novel presentation of a fungated ulcerated skin lesion as the initial presentation of lung cancer. The literature describes skin metastases from lung cancer as nodular, papular, and zosteriform. Our case is a fungating ulcerated skin lesion which is not widely reported in literature. There is a still a need for more data on the clinical presentation and prognosis of such cases as it will elucidate the diagnostic challenges and treatment management.

We present a case of a 55 year old Caucasian male with a 60-pack-year smoking history initially presenting with a nodule on his right upper back that quickly fungated and ulcerated requiring surgical excision. Biopsy of both the skin lesion and the lung mass confirmed squamous cell carcinoma (SCC) and the lung mass being the primary tumor. The patient's clinical and functional status severely declined during his hospital stay and was later discharged to hospice without therapeutic intervention.He later expired a month after hospice stay.

Although uncommon, this case clearly illustrates that skin metastases can be the initial finding of primary lung cancer and that not all patients with lung cancer will present with bronchopulmonary symptoms. It also illustrates that a fungating ulcerated lesion can be the initial presentation of lung cancer in addition to nodular, papular, and zosteriform presentations noted in the literature.

Although uncommon, this case clearly illustrates that skin metastases can be the initial finding of primary lung cancer and that not all patients with lung cancer will present with bronchopulmonary symptoms. It also illustrates that a fungating ulcerated lesion can be the initial presentation of lung cancer in addition to nodular, papular, and zosteriform presentations noted in the literature.A central event in the pathogenesis of motor neuron disease (MND) is the loss of neuromuscular junctions (NMJs), yet the mechanisms that lead to this event in MND remain to be fully elucidated. Maintenance of the NMJ relies upon neural agrin (n-agrin) which, when released from the nerve terminal, activates the postsynaptic Muscle Specific Kinase (MuSK) signaling complex to stabilize clusters of acetylcholine receptors. Here, we report that muscle from MND patients has an increased proportion of slow fibers and muscle fibers with smaller diameter. Muscle cells cultured from MND biopsies failed to form large clusters of acetylcholine receptors in response to either non-MND human motor axons or n-agrin. Sodium ascorbate chemical Furthermore, levels of expression of MuSK, and MuSK-complex components LRP4, Caveolin-3, and Dok7 differed between muscle cells cultured from MND patients compared to those from non-MND controls. To our knowledge, this is the first time a fault in the n-agrin-LRP4-MuSK signaling pathway has been identified in muscle from MND patients. Our results highlight the n-agrin-LRP4-MuSK signaling pathway as a potential therapeutic target to prolong muscle function in MND.

Renal colic is the pain experienced by a patient when a renal calculus (kidney stone) causes partial or complete obstruction of part of the renal outflow tract. The standard analgesic regimes for renal colic are often ineffective; in some studies, less than half of patients achieve complete pain relief, and a large proportion of patients require rescue analgesia within 4 h. Current analgesic regimes are also associated with significant side effects including nausea, vomiting, drowsiness and respiratory depression. It has been hypothesised that beta adrenoreceptor agonists, such as salbutamol, may reduce the pain of renal colic. They have been shown to impact a number of factors that target the physiological causes of pain in renal colic (ureteric spasm and increased peristalsis, increased pressure at the renal pelvis and prostaglandin release with inflammation). There is biological plausibility and a body of evidence sufficient to suggest that this novel treatment for the pain of renal colic should be takenle indications, extensive staff familiarity and a good side effect profile; therefore, its potential use for pain relief may have significant benefits for patient care.

ISRCTN Registry ISRCTN14552440 . Registered on 22 July 2019.

ISRCTN Registry ISRCTN14552440 . Registered on 22 July 2019.

The COVID-19 pandemic has challenged healthcare systems and research worldwide. Data is collected all over the world and needs to be integrated and made available to other researchers quickly. However, the various heterogeneous information systems that are used in hospitals can result in fragmentation of health data over multiple data 'silos' that are not interoperable for analysis. Consequently, clinical observations in hospitalised patients are not prepared to be reused efficiently and timely. There is a need to adapt the research data management in hospitals to make COVID-19 observational patient data machine actionable, i.e. more Findable, Accessible, Interoperable and Reusable (FAIR) for humans and machines. We therefore applied the FAIR principles in the hospital to make patient data more FAIR.

In this paper, we present our FAIR approach to transform COVID-19 observational patient data collected in the hospital into machine actionable digital objects to answer medical doctors' research questions. Wisis, linkable to other FAIR data such as Linked Open Data, and reusable to develop software applications on top of them for hypothesis generation and knowledge discovery.

Our work demonstrates that a FAIR research data management plan based on ontological models for data and metadata, open Science, Semantic Web technologies, and FAIR Data Points is providing data infrastructure in the hospital for machine actionable FAIR Digital Objects. This FAIR data is prepared to be reused for federated analysis, linkable to other FAIR data such as Linked Open Data, and reusable to develop software applications on top of them for hypothesis generation and knowledge discovery.

The English schools-based human papillomavirus (HPV) vaccination programme is routinely offered to all young people aged 12-13years, to prevent cancers affecting the cervix, vulva, vagina, penis, anus and mouth. Lower uptake among some population groups has been identified, in part, because of unmet information needs among young people. To address these unmet needs we report intervention planning and development processes to co-produce an educational package about the HPV vaccine.

We used co-production research methodologies and the 'person-based approach' involving the following iterative stages (i) collating and analysing primary and secondary evidence, including HPV vaccine communication materials, interviews and workshops; (ii) developing guiding principles; (iii) undertaking a behavioural analysis informed by the Behaviour Change Wheel and the Behaviour Change Technique taxonomy; (iv) development of a preliminary logic model; (v) co-production of resources, and; (vi) refinement of resources informed vention to address young people's information needs about the HPV vaccination programme. The acceptability and persuasiveness of the package has been maximised by working closely with young people and key informants to develop the content. An implementation study to examine how the EDUCATE package is implemented in practice and the impact on uptake of the HPV vaccination programme is underway.

Engagement with young people and key informants was integral to the development of our rigorously developed, theory-based intervention to address young people's information needs about the HPV vaccination programme. The acceptability and persuasiveness of the package has been maximised by working closely with young people and key informants to develop the content. An implementation study to examine how the EDUCATE package is implemented in practice and the impact on uptake of the HPV vaccination programme is underway.

The relationship between online media exposure and disordered eating symptoms has been reported in western regions. Though the prevalence of eating disorders and access to the Internet increased substantially in recent years, relevant evidence is rare in mainland China. This study aims to evaluate the association between online media exposure or weight and fitness management app use and disordered eating symptoms in Chinese mainland young adults, and the mediation effect of disordered eating cognition.

353 Chinese mainland female and 142 male young adults completed online questionnaires consisting of demographic information, Eating Disorder Examination-Questionnaire 6.0 (EDE-Q 6.0), and items relating to online media exposure and weight and fitness management app use. Through correlation analysis, the relationship between online media exposure or weight and fitness management app use and disordered eating symptoms was examined, separately by sex. The mediation effect of disordered eating cognition on the nd scientific guidance of online media are necessary.

Online media exposure and weight and fitness management app use play a crucial role in the generation of disordered eating symptoms in Chinese mainland young adults, especially in females. The mediation analysis suggested the importance of prevention and intervention of disordered eating cognition. Monitoring and scientific guidance of online media are necessary.Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disorder caused by mutations in the Dystrophin gene and for which there is currently no cure. To bridge the gap between preclinical and therapeutic evaluation studies, we have generated a rat model for DMD that carries an exon 52 deletion (R-DMDdel52) causing a complete lack of dystrophin protein. Here we show that R-DMDdel52 animals recapitulated human DMD pathophysiological trajectory more faithfully than the mdx mouse model. We report that R-DMDdel52 rats displayed progressive and severe skeletal muscle loss associated with fibrotic deposition, fat infiltration and fibre type switch. Early fibrosis was also apparent in the cardiac muscle. These histological modifications led to severe muscle, respiratory and cardiac functional impairments leading to premature death around 1 year. Moreover, DMD muscle exhibited systemic inflammation with a mixed M1/M2 phenotype. A comparative single cell RNAseq analysis of the diaphragm muscle was performed, revealing cellular populations alteration and molecular modifications in all muscle cell types. We show that DMD fibroadipogenic progenitors produced elevated levels of cartilage oligomeric matrix protein, a glycoprotein responsible for modulating homeostasis of extracellular matrix, and whose increased concentration correlated with muscle fibrosis both in R-DMDdel52 rats and human patients. Fibrosis is a component of tissue remodelling impacting the whole musculature of DMD patients, at the tissue level but most importantly at the functional level. We therefore propose that this specific biomarker can optimize the prognostic monitoring of functional improvement of patients included in clinical trials.Current understanding of IL-23 biology, with its link to other pro-inflammatory cytokines, for example, IL-17 and granulocyte macrophage-colony stimulating factor (GM-CSF), is primarily focused on T lymphocyte-mediated inflammation/autoimmunity. Pain is a significant symptom associated with many musculoskeletal conditions leading to functional impairment and poor quality of life. While the role of IL-23 in arthritis has been studied in mouse models of adaptive immune-mediated arthritis using targeted approaches (e.g., monoclonal antibody (mAb) neutralization), the literature on IL-23 and arthritis pain is limited. Encouragingly, the anti-IL-23p19 mAb, guselkumab, reduces pain in psoriatic arthritis patients. Recent evidence has suggested a new biology for IL-23, whereby IL-23 is required in models of innate immune-mediated arthritis and its associated pain with its action being linked to a GM-CSF-dependent pathway (the so-called GM-CSF➔CCL17 pathway). This Commentary discusses the current understanding of potential cytokine networks involving IL-23 in arthritis pain and provides a rationale for future clinical studies targeting IL-23p19 in arthritis pain.