Miracle-dz/UniFAR-FTUs huggingface dataset:
The Vessels Contribute to Fibrosis in Systemic Sclerosis.

BACKGROUND Microvascular damage, clinically expressed by Raynaud's phenomenon, is generally the first symptom of the disease and the injured vascular cells, both endothelial and perivascular, may transdifferentiate to myofibroblasts, thus leading to collagen deposition in the tissue and consequent fibrosis. Systemic sclerosis (SSc, scleroderma) is complex disease characterized by autoimmunity, vasculopathy, and fibrosis. It has been shown that microvascular damage may be the first symptom of SSc. Injured endothelial cells and pericytes may transdifferentiate into myofibroblasts, the cells responsible for fibrosis and collagen deposition in the tissue. Based on these factors, the process of myofibroblast generation may link two pivotal events of SSc: microvascular damage and fibrosis. Understanding the development, differentiation, and function of myofibroblasts is therefore crucial to individuate early pathogenetic events and develop new therapeutic target for SSc, a condition in which no disease-modifying agents are available. The aim of this review was to discuss the possible origins of myofibroblasts in SSc, highlighting the process of endothelial mesenchymal transition and pericytes to myofibroblast transition and to show how these events may contribute to pathogenesis of the disease.
Assessing and mapping language, attention and executive multidimensional deficits in stroke aphasia

Despite being potentially crucial for performance, recovery and rehabilitation, non-verbal cognitive functions have not been investigated comprehensively in patients with post-stroke aphasia. By administering a battery of tests of attention and executive function, Schumacher et al. identify six orthogonal non-verbal and language components that are associated with separable structural correlates.
The association between weight stigma and mental health: A meta‐analysis

In recent years, there has been considerable research on the relation between weight stigma and mental health, but no quantitative synthesis of the empirical evidence is available to date. This meta‐analysis (105 studies, 59 172 participants, and 497 effect sizes) fills this gap by quantifying the association between weight stigma and mental health. Age, gender, and factors presumed to exert a protective role (i.e., adaptive coping strategies and perceived social support) were tested as potential moderators. The three‐level meta‐analytic model estimated under a random effects assumption revealed a medium to large negative association between weight stigma and mental health (r = −0.35). The overall association remained significant when controlling for publication year, education, and body weight. There was substantial heterogeneity in effect sizes between studies (I2 = 43%) and within studies (I2 = 56%). Surprisingly, all moderator hypotheses had to be rejected. Body weight was a significant moderator, indicating a stronger association between weight stigma and diminished mental health with increasing body mass index. Future research might focus on explaining the heterogeneity of findings and on testing causality as well as potential underlying mechanisms.
Development of a Postgraduate Community Pharmacist Specialization Program Using CanMEDS Competencies, and Entrustable Professional Activities

Objectives. To develop and implement a postgraduate, workplace-based curriculum for community pharmacy specialists in the Netherlands, conduct a thorough evaluation of the program, and revise any deficiencies found. Methods. The experiences of the Dutch Advisory Board for Postgraduate Curriculum Development for Medical Specialists were used as a guideline for the development of a competency-based postgraduate education program for community pharmacists. To ensure that community pharmacists achieved competence in 10 task areas and seven roles defined by the Canadian Medical Education Directions for Specialists (CanMEDS), a two-year workplace-based curriculum was built. A development path along four milestones was constructed using 40 entrustable professional activities (EPAs). The assessment program consisted of 155 workplace-based assessments, with the supervisor serving as the main assessor. Also, 360-degree feedback and 22 days of classroom courses were included in the curriculum. In 2014, the curriculum was evaluated by two focus groups and a review committee. Results. Eighty-two first-year trainees enrolled in the community pharmacy specialist program in 2012. That number increased to 130 trainees by 2016 (a 59% increase). In 2015, based on feedback from pharmacy supervisors, trainees, and other stakeholders, 22.5% of the EPAs were changed and the number of workplace-based assessments was reduced by 48.5%. Conclusion. Using design approaches from the medical field in the development of postgraduate workplace-based pharmacy education programs proved to be feasible and successful. How to address the concerns and challenges encountered in developing and maintaining competency-based postgraduate pharmacy education programs merits further research.
Diagnostic Tools for the Identification of Babesia sp. in Persistently Infected Cattle

Bovine babesiosis is a tick-borne disease of cattle caused by the protozoan parasites of the genus Babesia. Babesia bovis, Babesia bigemina and Babesia divergens are considered by International health authorities (OIE) as the principal species of Babesia that cause bovine babesiosis. Animals that recover from a babesial primo infection may remain as persistent carriers with no clinical signs of disease and can be the source of infection for ticks that are able to acquire Babesia parasites from infected cattle and to transmit Babesia parasites to susceptible cattle. Several procedures that have been developed for parasite detection and diagnosis of this infectious carrier state constitute the basis for this review: A brief description of the direct microscopic detection of Babesia-infected erytrocytes; PCR-based diagnostic assays, which are very sensitive particularly in detecting Babesia in carrier cattle; in-vitro culture methods, used to demonstrate presence of carrier infections of Babesia sp. ; animal inoculation, particularly for B. divergens isolation are discussed. Alternatively, persistently infected animals can be tested for specific antibabesial antibodies by using indirect serological assays. Serological procedures are not necessarily consistent in identifying persistently infected animals and have the disadvantage of presenting with cross reactions between antibodies to Babesia sp.
A Retrospective Study on Sociodemographic and Clinical Profile of Patients Underwent for Myomectomy.

Background: Leiomyoma is benign tumor of smooth muscle of Uterus. It is also commonest pelvic tumor among women especially in reproductive age and the incidence is about 30% to 70%. The majorities of uterine leiomyomas are asymptomatic and may not require any therapy. Myomectomy is performing among those women who desire to maintain their menstrual and reproductive function. Objectives: 1.To know the prevalence of Fibroid (Leiomyoma) and proportion of myomectomy among them. 2. To know the various clinical presentation among fibroid patients. 3. To know the commonest site and types fibroid. 4. To find the reasons for conservative surgery and outcomes after myomectomy. Methods: A retrospective study was carried out in Obstetrics and Gynecology Department of G.G. Hospital, Jamnagar over a period 6 years from November-2005 to November-2010. In this study 55 cases of fibroid in which myomectomy were performed was reviewed and each of cases was scrutinized for clinico-epidemiological profile and other necessary information. Data were expressed as number (percentage) and appropriate statistical test was applied. P value <0.05 was taken as level of significance and data were entered and analysed by MS excel-2014. Results: In our study the Mean age of patients underwent for myomectomy was 29.52±5.03 S.D. The prevalence of fibroid was 9.04%. The main clinical presentation of fibroid was lower abdominal pain (44.11%). 23.52% patients had infertility due to fibroid. 17.28% of nulliparous women were conceived after myomectomy. Conclusion: A lot of health problems has been attributed to or linked with fibroids in women. Many of younger females are presenting with fibroids and this will affect their fertility also.
CTLA‐4‐competent conventional T cells back up regulatory T cells to restrain memory T‐helper type 2 cell responses

To the Editor, How inhibitory co‐receptors such as CTLA‐4 (cytotoxic T‐lym‐ phocyte‐associated protein 4) prevent undesired Th2 responses still remains incompletely understood. Understanding the underlying mechanisms could therefore facilitate the improvement of ther‐ apeutic treatment of Th2‐driven diseases. CTLA‐4 is differentially expressed on activated conventional T cells (Tconv) and regulatory T cells (Tregs) whereas the latter essentially maintain tolerance against harmless environmental antigens1 and regulate Th2 differentiation especially in allergy.2,3 However, their suppressive capacity does not solely rely on CTLA‐4.4,5 Instead, CTLA‐4 expression on Tconv might be critically involved in the restriction of Th2 responses. Hence, we aimed to dissect the hierarchy and interplay of CTLA‐4‐dependent effects among Tregs and Tconv on Th2‐effector and Th2‐memory differentiation. To investigate distinct roles of Tregs and Tconv on Th2 differen‐ tiation in vivo, various settings of highdose OVA/Alum adjuvanted in vivo immunization were applied including inducible genetic Treg de‐ pletion via diphtheria toxin (DT) and/or serological CTLA‐4 blockade during priming (Figure 1A). Responding CD40L+ Tconv cells revealed significantly higher frequencies of IL‐4 and IL‐13 producers in the absence of Tregs than in the Treg nondepleted control (Figure 1B). Intriguingly, an additional CTLA‐4 blockade further increased fre‐ quencies of IL‐4 and IL‐13 producers compared to those of only Treg depleted. Even upon Treg recovery in the memory response (Figure S1), this paradigm remains long‐lasting for IL‐4 and IL‐13 (Figure 1B). Interestingly, CTLA‐4 blockade did not influence Treg activity and therefore the frequencies of Th2‐cytokine producers. In terms of antigen‐specific expansion, absolute numbers of CD4+CD40L+ cells indicated that the presence of both Tregs and CTLA‐4 competent Tconvs is required for optimal control of primary Th2 cells (Figure 1C). As the quality of Th cells is shaped by their ability to simulta‐ neously produce multiple cytokines,6 we analyzed T‐cell multi‐func‐ tionality. Intriguingly, the respective combined cytokine data of primary single, double, or triple Th2 producers showed that in addi‐ tion to Treg depletion CTLA‐4 blockade further increased their fre‐ quencies (Figure 1D). In the memory response, Treg depletion alone during sensitization significantly increased the fraction of single and triple producers (Figure 1D). However, additional CTLA‐4 blockade of Tconv during priming significantly enhanced the fraction of double Correspondence Shaoheng He, Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. Email: shoahenghe@126.com Xiao Liu, BGI‐Shenzhen, Shenzhen, China. Email: liuxiao@genomics.cn
Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study.

AIMS The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). METHODS AND RESULTS Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. CONCLUSION Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.
Changes of Microbial Community in Treated Peri-implantitis Sites: An Experimental Study in Beagle Dogs.

OBJECTIVE To investigate the changes of the bacterial community in the oral environment of beagle dogs to gain insights on the possible causes of failed therapy in peri-implantitis. METHODS Beagles were used as models for experimental peri-implantitis. Samples from peri-implant soft tissue (supramargin and submargin), ligature and contaminated surface of peri-implantitis sites were collected and analysed by sequencing the bacterial 16S rRNA gene. RESULTS The residual microbial community from the curettes-treated implant surface contained a variety of microorganisms, including periodontal pathogens, which showed no changes in their composition and structure. CONCLUSION It is possible that the residual bacterial community remained unchanged and this was the cause of recurrent episodes of inflammation.
Causal association between periodontitis and hypertension: evidence from Mendelian randomization and a randomized controlled trial of non-surgical periodontal therapy

Abstract Aims Inflammation is an important driver of hypertension. Periodontitis is a chronic inflammatory disease, which could provide a mechanism for pro-hypertensive immune activation, but evidence of a causal relationship in humans is scarce. We aimed to investigate the nature of the association between periodontitis and hypertension. Methods and results We performed a two-sample Mendelian randomization analysis in the ∼750 000 UK-Biobank/International Consortium of Blood Pressure-Genome-Wide Association Studies participants using single nucleotide polymorphisms (SNPs) in SIGLEC5, DEFA1A3, MTND1P5, and LOC107984137 loci GWAS-linked to periodontitis, to ascertain their effect on blood pressure (BP) estimates. This demonstrated a significant relationship between periodontitis-linked SNPs and BP phenotypes. We then performed a randomized intervention trial on the effects of treatment of periodontitis on BP. One hundred and one hypertensive patients with moderate/severe periodontitis were randomized to intensive periodontal treatment (IPT; sub- and supragingival scaling/chlorhexidine; n = 50) or control periodontal treatment (CPT; supragingival scaling; n = 51) with mean ambulatory 24-h (ABPM) systolic BP (SBP) as primary outcome. Intensive periodontal treatment improved periodontal status at 2 months, compared to CPT. This was accompanied by a substantial reduction in mean SBP in IPT compared to the CPT (mean difference of −11.1 mmHg; 95% CI 6.5–15.8; P < 0.001). Systolic BP reduction was correlated to periodontal status improvement. Diastolic BP and endothelial function (flow-mediated dilatation) were also improved by IPT. These cardiovascular changes were accompanied by reductions in circulating IFN-γ and IL-6 as well as activated (CD38+) and immunosenescent (CD57+CD28null) CD8+T cells, previously implicated in hypertension. Conclusion A causal relationship between periodontitis and BP was observed providing proof of concept for development of clinical trial in a large cohort of hypertensive patients. ClinicalTrials.gov: NCT02131922.
Reduction of inappropriate medication in older populations by electronic decision support (the PRIMA-eDS project): a survey of general practitioners’ experiences

Abstract Objective We sought to investigate the experiences of general practitioners (GPs) with an electronic decision support tool to reduce inappropriate polypharmacy in older patients (the PRIMA-eDS [Polypharmacy in chronic diseases: Reduction of Inappropriate Medication and Adverse drug events in older populations by electronic Decision Support] tool) in a multinational sample of GPs and to quantify the findings from a prior qualitative study on the PRIMA-eDS-tool. Materials and Methods Alongside the cluster randomized controlled PRIMA-eDS trial, a survey was conducted in all 5 participating study centers (Bolzano, Italy; Manchester, United Kingdom; Salzburg, Austria; Rostock, Germany; and Witten, Germany) between October 2016 and July 2017. Data were analyzed using descriptive statistics and chi-square tests. Results Ninety-one (n = 160) percent of the 176 questionnaires were returned. Thirty-two percent of the respondents reported that they did not cease drugs because of the medication check. The 68% who had discontinued drugs comprise 57% who had stopped on average 1 drug and 11% who had stopped 2 drugs or more per patient. The PRIMA-eDS tool was found to be useful (69%) and the recommendations were found to help to increase awareness (86%). The greatest barrier to implementing deprescribing recommendations was the perceived necessity of the medication (69%). The majority of respondents (65%) would use the electronic medication check in routine practice if it was part of the electronic health record. Conclusions GPs generally viewed the PRIMA-eDS medication check as useful and as informative. Recommendations were not always followed due to various reasons. Many GPs would use the medication check if integrated into the electronic health record.
Hemodynamic assessment in heart failure

Hemodynamics play a central role in the pathophysiology of heart failure (HF), yet their proper assessment and optimization remains challenging. Heart failure is defined as the inability of the heart to deliver adequate perfusion (cardiac output) to the body at rest or exercise, or to require an elevation in cardiac filling pressures in order to do this. This bedrock definition is important because it relies on measurable quantities (filling pressures and output) that are readily assessed in the cardiac catheterization laboratory. Here we present three cases to illustrate how better understanding of the determinants of cardiac output and stroke volume: preload, afterload, contractility, and lusitropy, as well as the determinants of congestion (high filling pressures) may be used to guide optimization of hemodynamic status. The goal is that the readers will be able to think more critically when evaluating the hemodynamics of their patient in HF and recognize the complex interplay that determines the complex balance between cardiac ejection and filling capabilities, and how this alters symptoms and outcomes for patients with HF.
Evaluation of a Structured Onboarding Process and Tool for Faculty Members in a School of Pharmacy

Objective. To develop and assess the usefulness of a structured onboarding process and tool at a school of pharmacy to improve the overall onboarding experience for new faculty members. Methods. An assessment of a previously existing, informal onboarding process was conducted from January 1 to February 28, 2017. A structured onboarding tool was developed based on interviews with nine recently hired faculty members regarding their experiences with this legacy, unstructured onboarding process. Nine faculty members who onboarded while the legacy onboarding process was in place and six faculty members who onboarded after the new, onboarding tool was in place were included in the study. The experience of the pre-tool cohort was compared to that of the post-tool cohort. Results. More positive responses in the post-tool cohort were obtained compared to the pre-tool cohort in regard to timeline, expectations, and mentorship. More negative responses for the post-tool group were observed for communication. Overall utility of the onboarding tool changed from 56% (pre-tool group) to 80% (post-tool group). Free text feedback included recommendations to rearrange tasks throughout the onboarding process; clarifying mentor responsibilities and expectations; and providing an overview of the checklist to new faculty members on day 1. Conclusion. Overall, a structured onboarding process tool improved the onboarding experience for new faculty members. Given the lack of literature regarding a structured onboarding process in the academic setting, further refinement and analysis of the onboarding tool is needed.
Utilidad de la resonancia magnética en el paciente con infarto del miocardio

* Departamento de Resonancia Magnetica. Instituto Nacional de Cardiologia “Ignacio Chavez”. ** Departamento de Medicina Nuclear. Instituto Nacional de Cardiologia “Ignacio Chavez” y Unidad PET-Ciclotron, Facultad de Medi -cina, UNAM.Correspondencia:Instituto Nacional de Cardiologia “Ignacio Chavez” (INCICH, Juan Badiano No. 1, Col. Seccion XVI, Tlalpan, 14080 Mexico, D.F.). Recibido: 15 de enero de 2003Aceptado: 30 de enero de 2003
The IL‐13–OVOL1–FLG axis in atopic dermatitis

Despite sharing interleukin‐4 receptor α (IL‐4Rα) in their signaling cascades, IL‐4 and IL‐13 have different functions in atopic inflammation. IL‐13 preferentially participates in the peripheral tissues because tissue‐resident group 2 innate lymphoid cells produce IL‐13 but not IL‐4. In contrast, lymph node T follicular helper cells express IL‐4 but not IL‐13 to regulate B‐cell immunity. The dominant microenvironment of IL‐13 is evident in the lesional skin of atopic dermatitis (AD). The IL‐13‐rich local milieu causes barrier dysfunction by down‐regulating the OVOL1–filaggrin (FLG) axis and up‐regulating the periostin–IL‐24 axis. Genome‐wide association studies also point to the crucial involvement of the IL‐13, OVOL1 and FLG genes in the pathogenesis of AD. Biologics targeting IL‐13, such as the anti‐IL‐4Rα antibody dupilumab and the anti‐IL‐13 antibody tralokinumab, successfully improve AD lesions and further highlight the importance of IL‐13 in the pathogenesis of AD.