Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Association of palliative care management and survival after chemotherapy discontinuation in patients with advanced pancreatic adenocarcinoma: A retrospective single-centre observational study.

BACKGROUND: Palliative care (PC) is integrated into standard oncology care. However, its clinical impact at the end of life remains unclear in pancreatic adenocarcinoma (PA). We aimed to describe the end-of-life care pathway and to assess whether PC referral influences survival after chemotherapy discontinuation (CD) among advanced PA patients. METHODS: This retrospective single-centre observational study was conducted among deceased patients with advanced PA who had received chemotherapy between January 1, 2016, and December 31, 2021. Baseline characteristics, the timing of PC referral and events after CD were collected. The primary outcome was time from CD to death. RESULTS: Among the 148 included patients, 53.4% (n = 79) received PC, mostly late after the CD (n = 133, 89.9%), 16.9% (n = 25) received chemotherapy in the last 14 days of life and 75.6% died at the hospital. None received PC in the 8 weeks following the diagnosis. PC referral significantly increased PC department admissions (p < 0.001) and decreased medical unit admissions (p < 0.001). The median survival after the CD was 35 days (IQR: 19-64.5). PC referral was associated with increased survival after CD (HR: 0.65 [0.47-0.90], p = 0.010, Cox) and after adjusting (HR: 0.65 [0.42-0.99], p = 0.045, Cox). CONCLUSION: The study suggests that PC may be associated with longer survival after CD in advanced PA patients. However, PC is underused, and patients are referred late in their care pathway.

Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study.

OBJECTIVES: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. METHODOLOGY: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). RESULTS: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. CONCLUSION: Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP. KEY POINTS: • Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.

Study of the oxidation process of bismuth nanoparticles using NaClO.

Bismuth nanoparticles (NPs) colloids synthesized in deionized water by laser ablation of solids in liquids technique (LASL) were oxidized using NaClO solutions at different concentrations. Oxidized nanomaterials were characterized using several techniques. The crystalline phases of the bismuth compound were determined using Raman microspectroscopy, and the crystallographic structure was identified by x-ray diffraction (XRD). The size and morphology of the obtained nanomaterials were studied by transmission electron microscopy (TEM). The chemical states were determined using x-ray photoelectron spectroscopy (XPS), and the optical properties of the colloids were characterized by UV-vis spectroscopy. The absorption spectra were analyzed using the Tauc method to determine the band gaps of the obtained nanomaterials. Our results showed morphological changes, starting from small nanoparticles to nanosheets and a mixture of nanosheets with hollow nanoparticles. Two kinds of nanomaterials were found depending on the NaClO solution concentration: Bi2O2CO3single phase and a mixture ofδ-Bi2O3and Bi2O2CO3. Some samples were tested as photocatalysts and showed good performance in the degradation of methylene blue in solution. To the best of our knowledge, this is the first study on the oxidation process of bismuth colloidal nanoparticles at room temperature.

Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

[Intensive care during the 2019-coronavirus epidemic]. / Cuidados intensivos durante la epidemia de coronavirus 2019.

On 31 December 2019, the Health Commission of Hubei Province of China first unveiled a group of unexplained cases of pneumonia, which WHO subsequently defined as the new coronavirus of 2019 (SARS-CoV-2). SARS-CoV-2 has presented rapid person-to-person transmission and is currently a global pandemic. In the largest number of cases described to date of hospitalized patients with SARS-CoV-2 disease (2019-nCoViD), 26% required care in an intensive care unit (ICU). This pandemic is causing an unprecedented mobilization of the scientific community, which has been associated with an exponentially growing number of publications in relation to it. This narrative literature review aims to gather the main contributions in the area of intensive care to date in relation to the epidemiology, clinic, diagnosis and management of 2019-nCoViD.

Criterion-related validity of self-report walking time from the EPIC questionnaire in older adults.

Tools for measuring walking time make use of objective and subjective methods. One subjective approach is to administer physical activity questionnaires (PAQ), mainly because they are inexpensive and easy to give to large groups. The European Prospective Investigation into Cancer and Nutrition (EPIC) study has a brief PAQ (EPIC-PAQ) and includes one question referencing walking time. The objective of this study was to assess the validity of the question about time spent walking included in the EPIC-PAQ. The sample included 200 older adults (113 women). To assess daily walking time, participants responded to the EPIC-PAQ in an interview and wore a portable gait analysis system and physical activity monitor for 48 consecutive hours in free-living condition. Results indicated that the mean of bias between the EPIC-PAQ and objetive measurement was -64.6 min/day. Also, the correlation was low compared to an objective measurement (rho = 0.196) and was positively correlated with the time spent at speeds below 2.5 mph but the correlation was low (slow walking rho = 0.154 and pace walking rho = 0.163). The EPIC-PAQ shows low correlations with the objective measurement of walking time, that suggests it may be inaccurate and affecting the estimate of the EPIC-PAQ's PA energy expenditure in this age group.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a direct role.

BACKGROUND: Bronchial vascular remodelling may contribute to the severity of airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated with the most severe asthmatic phenotype but whether it might contribute to vascular remodelling is uncertain. OBJECTIVE: To assess vascular remodelling in severe asthma and whether IL-17A directly or indirectly may cause endothelial cell activation and angiogenesis. METHODS: Bronchial vascularization was quantified in asthmatic subjects, COPD and healthy subjects together with the number of IL-17A+ cells as well as the concentration of angiogenic factors in the sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and endothelial permeability was assessed directly on primary human lung microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and airway smooth muscle cells (ASMC) after IL-17A stimulation. RESULTS: Severe asthmatics have increased vascularity compared to the other groups, which correlates positively with the concentrations of angiogenic factors in sputum. Interestingly, we demonstrated that increased bronchial vascularity correlates positively with the number of subepithelial IL-17A+ cells. However IL-17A had no direct effect on HMVEC-L function but it enhanced endothelial tube formation and cell migration through the production of angiogenic factors by NHBE and ASMC. CONCLUSIONS & CLINICAL RELEVANCE: Our results shed light on the role of IL-17A in vascular remodelling, most likely through stimulating the synthesis of other angiogenic factors. Knowledge of these pathways may aid in the identification of new therapeutic targets.

Epoxy Nanocomposites Filled with Carbon Nanoparticles.

Over the past decades, the development of high performance lightweight polymer nanocomposites and, in particular, of epoxy nanocomposites has become one the greatest challenges in material science. The ultimate goal of epoxy nanocomposites is to extrapolate the exceptional intrinsic properties of the nanoparticles to the bulk matrix. However, in spite of the efforts, this objective is still to be attained at commercially attractive scales. Key aspects to achieve this are ultimately the full understanding of network structure, the dispersion degree of the nanoparticles, the interfacial adhesion at the phase boundaries and the control of the localization and orientation of the nanoparticles in the epoxy system. In this Personal Account, we critically discuss the state of the art and evaluate the strategies to overcome these barriers.

Clinical perspectives into the use of thalidomide for central nervous system tuberculosis.

BACKGROUND AND PURPOSE: Central nervous system (CNS) tuberculosis (TB) accounts for over 4% of all TB notifications in the UK and causes death or significant disability in over half of those affected. Tumour necrosis factor alpha is a critical cytokine involved in the neuropathogenesis of CNS TB. Thalidomide has been trialled in CNS TB due to its immunomodulatory and immune reconstitution effects through the inhibition of tumour necrosis factor alpha. Despite animal models demonstrating dramatic improvement in survival, studies in paediatric patients have been associated with higher levels of mortality. The effects of thalidomide have not yet been studied in adults with CNS TB. This narrative case series guides clinicians through a range of CNS TB clinical cases seen in a large London teaching hospital, serving a region with a high incidence of TB (32 per 100 000) with 55% of TB cases manifesting as extrapulmonary disease. We aimed to illustrate our experiences of using thalidomide to treat a range of severe CNS TB complications. METHODS: Five inpatients at The Royal London Hospital, London, UK treated with thalidomide in addition to standard TB treatment are described in detail. The rationale for treatment initiation with thalidomide is explained. RESULTS: The case examples are used to guide our reflections and lessons learnt regarding the use of thalidomide. Responses to treatment and functional outcomes suggest that thalidomide may be a useful adjunct to standard TB therapy in selected adult cases. CONCLUSIONS: The experience gained from using thalidomide in this small case series may provide evidence leading to more research into using thalidomide to treat severe CNS TB.

Fermented dairy products, diet quality, and cardio-metabolic profile of a Mediterranean cohort at high cardiovascular risk.

BACKGROUND AND AIMS: Fermented dairy products have been associated with a better diet quality and cardio-metabolic profile. However, in Mediterranean populations, these associations have not been well characterized. The aim of this study was to assess the diet quality and the associations between the consumption of total fermented dairy products and their subtypes and the prevalence of Metabolic Syndrome (MetS) components in a Mediterranean population at high cardiovascular risk. METHODS AND RESULTS: Baseline cross-sectional analyses were conducted on 6,572 men and women (mean age: 65 years) with overweight or obesity and MetS recruited into the PREDIMED-Plus cohort. A 143-item Food Frequency Questionnaire (FFQ) was used, and anthropometrical, biochemical, and blood pressure measurements were recorded. Multivariate-adjusted Cox regressions were fitted to analyze the association between quartiles of consumption of fermented dairy products and their subtypes and MetS components to estimate the relative risk (RR) and 95% confidence intervals (95% CIs). Participants who were high consumers of fermented dairy products reported a higher consumption of fruit, vegetables, fish, nuts, and whole bread and a lower consumption of white bread, alcohol, and cookies. Participants in the higher quartile showed a lower prevalence of the low HDL-cholesterol component of the MetS (RR=0.88; 95% CI: 0.78-0.98) than those in the lowest quartile of cheese consumption. Cheese consumption was inversely associated with the prevalence of hypertriglyceridemia. Total fermented dairy products, yogurt, and its types were not associated with any of the MetS components. CONCLUSIONS: Compared to nonconsumers, participants consuming fermented dairy products reported a better diet quality and, particularly, cheese consumers presented a lower prevalence of hypertriglyceridemia and low HDL-cholesterol plasma levels, which are MetS components.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

A Health Services Research Agenda for Bariatric Surgery Within the Veterans Health Administration.

In 2016, the Veterans Health Administration (VHA) held a Weight Management State of the Art conference to identify evidence gaps and develop a research agenda for population-based weight management for veterans. Included were behavioral, pharmacologic, and bariatric surgery workgroups. This article summarizes the bariatric surgery workgroup (BSWG) findings and recommendations for future research. The BSWG agreed that there is evidence from randomized trials and large observational studies suggesting that bariatric surgery is superior to medical therapy for short- and intermediate-term remission of type 2 diabetes, long-term weight loss, and long-term survival. Priority evidence gaps include long-term comorbidity remission, mental health, substance abuse, and health care costs. Evidence of the role of endoscopic weight loss options is also lacking. The BSWG also noted the limited evidence regarding optimal timing for bariatric surgery referral, barriers to bariatric surgery itself, and management of high-risk bariatric surgery patients. Clinical trials of pre- and post-surgery interventions may help to optimize patient outcomes. A registry of overweight and obese veterans and a workforce assessment to determine the VHA's capacity to increase bariatric surgery access were recommended. These will help inform policy modifications and focus the research agenda to improve the ability of the VHA to deliver population-based weight management.

New horizons in anticoagulation: Direct oral anticoagulants and their implications in oral surgery.

BACKGROUND: Thrombotic disorders remain a leading cause of death in the Western World. For decades, vitamin K antagonists used in the prevention of this pathology, such as warfarin or sintrom, were the only oral agents available for long-term anticoagulation, in spite of their disadvantages. MATERIAL AND METHODS: An electronic database search was carried out on MedLine and The Cochrane Library Plus, without restrictions on the type of study nor dates, in English and Spanish. Abstracts were reviewed, and complete articles if necessary, considering all articles that included recommendations on DOACs and oral surgery. RESULTS: In recent years, the so-called "new oral anticoagulants" have been introduced in clinical practice to treat those patients whose medical conditions require long-term anticoagulant treatment, replacing traditional oral anticoagulants. CONCLUSIONS: The new oral anticoagulants represent new therapeutic options, with a number of advantages such as poor interaction with food, minor drug interactions, and do not require periodic dose adjustments or routine controls. The purpose of this review is to establish an update on the new oral anticoagulants: Dabigatran, Rivarozaban, Apixaban and Edoxaban.

Anti-inflammatory effect of dialysable leucocyte extract in a rat model of osteoarthritis: histopathological and molecular characterization.

OBJECTIVES: To evaluate the effect of dialysable leucocyte extract (DLE) on pro- and anti-inflammatory profiles in a rat model of osteoarthritis (OA). METHOD: Forty-eight male Wistar rats were divided into three groups: normal rats without treatment, OA rats treated with placebo, and OA rats treated with DLE. After treatment, the animals were killed to obtain cartilage for histological analysis and to determine the expression of pro- and anti-inflammatory cytokines by reverse transcription multiplex polymerase chain reaction (RT-MPCR) and immunohistofluorescence analyses. RESULTS: Histological analysis revealed that OA cartilage from rats treated with DLE displayed similar characteristics to non-OA cartilage from the control group. The OA cartilage treated with placebo showed alterations in the cellular architecture and in chondrocyte cluster formation. Analysis of cytokine expression by RT-MPCR showed that OA cartilage from DLE-treated rats expressed platelet-derived growth factor (PDGF), interferon (IFN)-γ, and fibroblast growth factor (FGF)-2, similar to non-OA cartilage from the control group. However, OA cartilage from rats treated with placebo expressed interleukin (IL)-1, PDGF, and I kappa B (IκB). Confocal immunodetection of FGF-2, PDGF, and non-phosphorylated IκB showed that they were distributed in the cytoplasm of most chondrocytes in OA cartilage from DLE-treated rats whereas no nuclear factor kappa B (NF-κB) expression was observed in the nuclei. Instead, in OA cartilage from the placebo group, only weak FGF-2 staining was observed, PDGF and IκB were not detected, and NF-κB was strongly observed in both cytoplasm and nuclei. CONCLUSIONS: Our findings suggest that DLE treatment modifies the OA process, promoting the expression of anti-inflammatory cytokines and diminishing the inflammatory effects, avoiding the nuclear translocation of NF-κB in chondrocytes.

A novel multitarget tracking algorithm for Myosin VI protein molecules on actin filaments in TIRFM sequences.

We propose a novel multitarget tracking framework for Myosin VI protein molecules in total internal reflection fluorescence microscopy sequences which integrates an extended Hungarian algorithm with an interacting multiple model filter. The extended Hungarian algorithm, which is a linear assignment problem based method, helps to solve measurement assignment and spot association problems commonly encountered when dealing with multiple targets, although a two-motion model interacting multiple model filter increases the tracking accuracy by modelling the nonlinear dynamics of Myosin VI protein molecules on actin filaments. The evaluation of our tracking framework is conducted on both real and synthetic total internal reflection fluorescence microscopy sequences. The results show that the framework achieves higher tracking accuracies compared to the state-of-the-art tracking methods, especially for sequences with high spot density.