Increased expression of aggrecan and biglycan mRNA in Achilles tendinopathy

To determine the expression of mRNA encoding the proteoglycans aggrecan, versican, biglycan and decorin in mid-tendon samples of chronic painful Achilles tendinopathy and ruptured Achilles tendons, compared with normal tendons. Total RNA isolated from frozen tendon samples (14 normal, 13 painful, 14 ruptured) was assayed by relative quantitative reverse transcription polymerase chain reaction for aggrecan, versican, biglycan and decorin mRNA, normalized using 18S rRNA. Differences between sample groups were tested by univariate analysis of variance with age as co-variate. In normal tendon samples expression of each of the proteoglycan mRNA decreased with increasing age. Decorin mRNA was the most highly-expressed of the proteoglycan mRNA, while versican mRNA expression was higher (3.8-fold) than that of aggrecan. In painful tendinopathy both aggrecan and biglycan mRNA expression increased (more than 10-fold and 5-fold, respectively) compared with normal tendon samples, but levels of versican and decorin mRNA were not significantly changed. In ruptured tendons the levels of aggrecan, biglycan and versican mRNA were not changed compared with normal tendon samples, but decorin mRNA decreased markedly. Increased aggrecan and biglycan mRNA expression in painful tendinopathy resembles the pattern in fibrocartilaginous regions of tendon, and may reflect an altered mechanical environment at the site of the lesion. Increased aggrecan mRNA expression may underlie the increase in glycosaminoglycan observed in painful tendinopathy

Versican splice variant messenger RNA expression in normal human Achilles tendon and tendinopathies

Versican is the principal large proteoglycan expressed in mid-tendon, but its role in tendon pathology is unknown. Our objective was to define the expression of versican isoform splice variant messenger ribonucleic acid (mRNA) in normal Achilles tendons, in chronic painful tendinopathy and in ruptured tendons. Total RNA isolated from frozen tendon samples (normal n = 14; chronic painful tendinopathy n = 10; ruptured n = 8) was assayed by relative quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for total versican, versican variants V0, V1, V2, V3 and type I collagen a1 mRNA, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Differences between sample groups were tested by Wilcoxon statistics. Painful and ruptured tendons showed a significant decrease (median 2-fold) in the expression of versican mRNA, in contrast to an increased expression (median 8-fold) of type I collagen a1 mRNA in painful tendons. Versican splice variants V0 and V1 mRNA were readily detected in normal samples, V3 levels were substantially lower, and V2 levels were more variable. Each of V1, V2 and V3 mRNA showed significant decreases in expression in painful and ruptured tendons, but V0 was not significantly changed. Changes in versican expression relative to that of collagen, and alterations in the balance of versican splice variants, may contribute to changes in matrix structure and function in tendinopathies

Empirical study of an team-based incentive model in the Day Surgical Department at Huddinge University Hospital

The study shows that a team-based incentive model changed personnel attitude and behaviour and increased the productivity in the Day Surgical Department at Huddinge University Hospital. The aims by introducing a team-based incentive model were to increase the productivity, to recruit personnel, to strengthen the team feeling and to commit the staff to work on continuous improvement. A bonus wage system based on production, financial and patient satisfaction in a balanced scorecard was implemented in October 2000. The results shown in the study cover the first year. Quantitative data on production, personnel administration and financial was collected. A questionnaire on patient satisfaction was given to patients. Qualitative data was collected by focused interviews with all personnel in the department and with key persons outside the department. The productivity measured as the surgical procedures/surgical-room hours increased by 7 per cent and the surgical hours/surgical-room hours also increased by 7 per cent. Net income was positive. Financial measured as total costs/surgical hour decreased despite of increased salaries and bonus. The patient satisfaction index was rated high. More employees were recruited than finished their employment. The qualitative analysis demonstrates that the employees had changed attitude with increased responsibility and teamwork resulting in an increased productivity. The reward system achieved a broad acceptance within as well as outside the department. Knowledge about the financial goals and the incentive model and information about related matters are fields for improvement. The results of increased productivity and the net recruitment of personnel in the study is encouraging. However, the results have to be evaluated over a longer period of time. The future development of the model may include rewards when achieving goals in the work on continuous improvement.Health care; management control; compensation systems; incentive; incentive model; productivity

Management of neonatal central nervous system viral infections: Knowledge gaps and research priorities

Congenital CMV, enteroviruses, human parechovirus and herpes simplex virus are all common causes of severe central nervous system (CNS) infection in neonates. The introduction of screening (i.e. newborn hearing screening programme), integration of molecular syndromic testing (i.e. multiplex polymerase chain reaction assays) and increase in sexually transmitted infections (i.e. anogenital herpes) have contributed to increases in each of these infections over the last decade. However, therapeutic options are highly limited in part due to the lack of epidemiological data informing trials. This review will describe our current understanding of the clinical burden and epidemiology of these severe neonatal CNS infections, outline the novel antiviral and vaccines in the pipeline and suggest future research studies which could help develop new therapeutics

Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

Toward Rational Boundaries of Tort Liability for Injury to the Unborn: Prenatal Injuries, Preconception Injuries and Wrongful Life

Forskning och nya innovationer inom området medieteknik skapar nya möjligheter inom den svenska sjukvården. I denna rapport undersöks fem telemedicinska scenarier från Karolinska Universitetssjukhuset i Stockholm och tre systemkoncept från forskningsgruppen Mediating Presence. Systemkoncepten är: Hydra, Det Medierade Ritbordet och Video Orchestration. Syftet är att utforska potentialen hos dessa systemkoncept i de undersökta sjukvårdsscenarierna.   Genom litteraturstudier, intervjuer och observationer har information samlats om scenarier och systemkoncept. Med detta som grund har ett framework tagits fram för att utvärdera vilken potential dessa tre systemkoncept har i de undersökta sjukvårdsscenarierna. Resultaten är att två av systemkoncepten, Hydra och Video Orchestration, är intressanta att undersöka vidare. För att till fullo utforska eventuella fördelar och nackdelar med varje implementation behöver ytterligare studier och användartester göras. Research and new innovations in the field of media technology brings new possibilities to the Swedish healthcare system. Representatives of these two worlds are Karolinska University Hospital in Stockholm and the European Union--‐funded research group Mediating Presence. Examined in this report are five telemedicine scenarios from Karolinska and three system concepts. The three concepts are: Hydra, the Mediated Sketching Table and Video Orchestration, all distance communication--‐related research projects from the Mediating Presence group. The purpose of this report is to explore the potential of these systems to increase task performance in these healthcare scenarios.   Through literature studies in presence research, along with interviews and observations, information is gathered about the scenarios and system concepts. On this basis, a framework is developed to analyze the potential of implementing these systems in the hospital scenarios. The results from this method are that two of the system concepts, Hydra and Video Orchestration, are interesting for further investigation in a few particular cases. To fully grasp the advantages and disadvantages of each implementation, further studies, including user tests, need to be conducted

Local Interpretable Model-Agnostic Explanations for Neural Ranking Models

Neural Ranking Models have shown state-of-the-art performance in Learning-To-Rank (LTR) tasks. However, they are considered black-box models. Understanding the logic behind the predictions of such black-box models is paramount for their adaptability in the real-world and high-stake decision-making domains. Local explanation techniques can help us understand the importance of features in the dataset relative to the predicted output of these black-box models. This study investigates new adaptations of Local Interpretable Model-Agnostic Explanation (LIME) explanation for explaining Neural ranking models. To evaluate our proposed explanation, we explain Neural GAM models. Since these models are intrinsically interpretable Neural Ranking Models, we can directly extract their ground truth importance scores. We show that our explanation of Neural GAM models is more faithful than explanation techniques developed for LTR applications such as LIRME and EXS and non-LTR explanation techniques for regression models such as LIME and KernelSHAP using measures such as Rank Biased Overlap (RBO) and Overlap AUC. Our analysis is performed on the Yahoo! Learning-To-Rank Challenge dataset

Assessment of factors that students perceive to affect their virtual learning of clinical skills for OSCE

Purpose: Objective Structured Clinical Examination (OSCE) is a vital examination that must be passed to graduate as a qualified doctor. The delivery of OSCE teaching was changed to an online format to accommodate COVID-19 restrictions. Therefore, this study evaluates factors that students perceive to affect their virtual learning of clinical skills for OSCE. Methods: In this cross-sectional study, all medical students from across the world who attended “The Respiratory Station” session delivered by OSCEazy (a medical student organization providing free online medical education) in the academic year 2020– 2021 received an online questionnaire about their perceptions of this learning opportunity. The survey was created on Google™ forms and consisted of 5-point Likert scales as well as free-text boxes. Results: A total of 556 responses were received (mean age: 24, female: 76.6%). Most students agreed that online OSCE teaching offers more flexibility and convenience (median: 5, IQR: 4– 5) but their likeliness to ask questions in either format was similar (median: 4, IQR: 3– 5 vs median: 4, IQR: 3– 4, p value: 0.94). The use of visual aids (median: 5, IQR: 4– 5) and breakout rooms (median: 3, IQR: 2– 4) were thought to enhance the quality of virtual OSCE teaching. The biggest concern about online teaching was access to a stable internet connection (69.1%). Conclusion: The flexibility and convenience of virtual OSCE teaching enables the sharing of knowledge and skills to a wider audience and thus may be a very useful adjunct to face-to-face OSCE teaching in the future

Modeling of prolactin response following dopamine Dreceptor antagonists in rats:can it be translated to clinical dosing?

Prolactin release is a side effect of antipsychotic therapy with dopamine antagonists, observed in rats as well as humans. We examined whether two semimechanistic models could describe prolactin response in rats and subsequently be translated to predict pituitary dopamine D2receptor occupancy and plasma prolactin concentrations in humans following administration of paliperidone or remoxipride. Data on male Wistar rats receiving single or multiple doses of risperidone, paliperidone, or remoxipride was described by two semimechanistic models, the precursor pool model and the agonist-antagonist interaction model. Using interspecies scaling approaches, human D2receptor occupancy and plasma prolactin concentrations were predicted for a range of clinical paliperidone and remoxipride doses. The predictions were compared with corresponding observations described in literature as well as with predictions from published models developed on human data. The pool model could predict D2receptor occupancy and prolactin response in humans following single doses of paliperidone and remoxipride. Tolerance of prolactin release was predicted following multiple doses. The interaction model underpredicted both D2receptor occupancy and prolactin response. Prolactin elevation may be deployed as a suitable biomarker for interspecies translation and can inform the clinical safe and effective dose range of antipsychotic drugs. While the pool model was more predictive than the interaction model, it overpredicted tolerance on multiple dosing. Shortcomings of the translations reflect the need for better mechanistic models

Clinical features and novel presentations of human monkeypox in a central London centre during the 2022 outbreak: descriptive case series

OBJECTIVE: To characterise the clinical features of monkeypox infection in humans. DESIGN: Descriptive case series. SETTING: A regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022. PARTICIPANTS: 197 patients with polymerase chain reaction confirmed monkeypox infection. RESULTS: The median age of participants was 38 years. All 197 participants were men, and 196 identified as gay, bisexual, or other men who have sex with men. All presented with mucocutaneous lesions, most commonly on the genitals (n=111 participants, 56.3%) or in the perianal area (n=82, 41.6%). 170 (86.3%) participants reported systemic illness. The most common systemic symptoms were fever (n=122, 61.9%), lymphadenopathy (114, 57.9%), and myalgia (n=62, 31.5%). 102/166 (61.5%) developed systemic features before the onset of mucocutaneous manifestations and 64 (38.5%) after (n=4 unknown). 27 (13.7%) presented exclusively with mucocutaneous manifestations without systemic features. 71 (36.0%) reported rectal pain, 33 (16.8%) sore throat, and 31 (15.7%) penile oedema. 27 (13.7%) had oral lesions and 9 (4.6%) had tonsillar signs. 70/195 (35.9%) participants had concomitant HIV infection. 56 (31.5%) of those screened for sexually transmitted infections had a concomitant sexually transmitted infection. Overall, 20 (10.2%) participants were admitted to hospital for the management of symptoms, most commonly rectal pain and penile swelling. CONCLUSIONS: These findings confirm the ongoing unprecedented community transmission of monkeypox virus among gay, bisexual, and other men who have sex with men seen in the UK and many other non-endemic countries. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema. These presentations should be included in public health messaging to aid early diagnosis and reduce onward transmission