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Enterovirus 71 (EV71)-induced T lymphocyte apoptosis plays an important role in hand, foot, and mouth disease (HFMD), and granzyme B (GZMB) has been shown to be critical for this process. However, the mechanisms underlying GZMB-mediated apoptosis of T lymphocytes remain unknown. In this study, we investigated whether transcription factors and microRNAs (miRNAs) are involved in GZMB-mediated apoptosis of T lymphocytes in response to EV71 infection. Our findings indicated that EV71 infection significantly induced apoptosis in Jurkat cells, a human T lymphocytes cell line, as revealed in flow cytometric analysis. Furthermore, EV71 increased the expression of pro-apoptosis Bcl-2-associated X (Bax) and cleaved caspase 3 but decreased the expression of anti-apoptosis B-cell lymphoma protein 2 (Bcl2). GZMB knockdown decreased cell apoptosis and prevented EV71-induced changes in the expression of Bax, cleaved caspase 3, and Bcl2 in Jurkat cells, highlighting the role of GZMB as a key factor in EV71-induced apoptosis. Our study also indicated that overexpression of the transcription factors GATA binding factor 1 (GATA1) and specificity protein 1 (SP1) significantly increased luciferase activity when this gene was inserted in the GZMB 3' untranslated region (3'UTR). GATA1/SP1 overexpression induced cell apoptosis, increased the expression of Bax and cleaved caspase 3, and decreased the expression of Bcl2. Finally, our results suggested that miR-874 plays an essential role in GZMB-mediated cell apoptosis, since an miR-874 mimic decreases the expression of GZMB by targeting its 3'UTR. Collectively, these data indicated that GATA1/SP1 and miR-874 mediate EV71-induced apoptosis in a granzyme B-dependent manner. This signaling pathway may provide a new pharmacological target for the prevention and treatment of HFMD.
Ligamento-muscular reflex pattern following stimulation of the anterior talofibular ligament (ATFL) was examined.
The peroneus longus (PL), the tibialis anterior (TA), and tibialis posterior (TP) muscles were investigated in sixteen patients with functional ankle instability (FAI) and 16 age- and gender-matched controls. The ATFL was stimulated with a fine wire electrode while electromyographic (EMG) activities were recorded during isometric foot contraction of 20% maximal force in plantarflexion, dorsiflexion, supination and pronation. The complete measurement was repeated after a peroneal block anesthesia.
Statistically significant changes in post-stimulus EMG activity were observed in all three muscles and all four tested foot positions. In supination, the PL showed no reactions in both groups before and after anesthesia. The post-stimulus inhibition of the TA seen after 80 and 180ms disappeared in controls after anesthesia. The TP had similar inhibitory responses in both groups.
Ligamento-muscular reflex pattern is alterated in FAI. While early reactions are essential in protecting the ankle joint in sudden movements, the later responses indicate a supraspinal control of neuromuscular stability of the ankle joint. Proprioceptive rehabilitation of the PL, TA, and TP is crucial in FAI to compensate for post-traumatic ligamentomuscular reflex deficiencies.
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II.The osseous pelvis is a frequent site of metastases. Alteration of bone integrity may lead to pain but also to functional disability and pathological fractures. Percutaneous image-guided minimally invasive procedures, such as cementoplasty and screw fixation, have emerged as a viable option to provide bone reinforcement and fracture fixation, as stand-alone or combined techniques. Understanding the biomechanics of the osseous pelvis is paramount to tailor the treatment to the clinical situation. The purpose of the present review is to present the biomechanics of the osseous pelvis and discuss its implication for the choice of the optimal consolidative treatment.
This was a retrospective case-control study at a single tertiary centre investigating all UFE procedures between January 2013 and December 2018 for symptomatic fibroids. The aim was to determine the clinical, imaging and procedural risk factors which impact upon the risk of post-uterine fibroid embolisation (UFE) intrauterine infection. Cases were patients which developed intrauterine infection post-procedure, and controls were the background UFE population without infection.
Clinical demographics, presenting symptoms, uterine and fibroid characteristics on imaging and procedural variants were analysed. A p value of less than 0.05 was considered statistically significant. The main outcome measures were presence of infection and requirement of emergency hysterectomy.
333 technically successful UFE procedures were performed in 330 patients. Infection occurred after 25 procedures (7.5%). 3 of these patients progressed to overwhelming sepsis and required emergency hysterectomy. Clinical obesity (BMI > 30) (OR 1.53 [1.18-1.99]) and uterine volume > 1000cm3 (2.94 [1.15-7.54]) were found to increase the risk of infection CONCLUSIONS UFE is generally safe in patients with symptomatic fibroids. Obese patients (BMI > 30) and those with large volume uteri (> 1000cm
) are at slight increased risk of developing infection and require appropriate pre-procedural counselling, as well as careful post-UFE follow-up. BMI and uterine volume may be useful to assess before the procedure to help to determine post-UFE infection risk.
1000cm3) are at slight increased risk of developing infection and require appropriate pre-procedural counselling, as well as careful post-UFE follow-up. BMI and uterine volume may be useful to assess before the procedure to help to determine post-UFE infection risk.Globally, increasing demand for rheumatology services has led to a greater reliance on non-physician healthcare professionals (HCPs), such as rheumatology nurse specialists, to deliver care as part of a multidisciplinary team. Across Africa and the Middle East (AfME), there remains a shortage of rheumatology HCPs, including rheumatology nurses, which presents a major challenge to the delivery of rheumatology services, and subsequently the treatment and management of conditions such as rheumatoid arthritis (RA). To further explore the importance of nurse-led care (NLC) for patients with RA and create a set of proposed strategies for the implementation of NLC in the AfME region, we used a modified Delphi technique. A review of the global literature was conducted using the PubMed search engine, with the most relevant publications selected. The findings were summarized and presented to the author group, which was composed of representatives from different countries and HCP disciplines. selleck The authors also drew on their knowledge of the wider literature to provide context.