Project description:Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. Online supplemental material is available for this article.
Project description:After reading this article, the participant should be able to: 1. Recognize the clinical features associated with five common congenital hand conditions. 2. Describe the indications and appropriate timing for various surgical procedures used to treat congenital hand anomalies. 3. Identify the pearls and pitfalls of these surgical treatments to avoid complications. 4. Understand the expected postoperative outcomes associated with these surgical procedures.This article provides an introduction to congenital hand differences by focusing on practical surgical strategies for treating five commonly encountered conditions, including syndactyly, constriction ring syndrome, duplicated thumb, hypoplastic thumb, and trigger thumb. The accompanying videos demonstrate common and reliable surgical techniques for syndactyly release, duplicated thumb reconstruction, and pollicization for hypoplastic thumb.
Project description:The asthmatic response to the common cold is highly variable, and early characteristics that predict worsening of asthma control following a cold have not been identified. In this prospective multicentric cohort study of 413 adult subjects with asthma, the mini-Asthma Control Questionnaire (mini-ACQ) was used to quantify changes in asthma control and the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) to measure cold severity. Univariate and multivariable models were used to examine demographic, physiological, serological and cold-related characteristics for their relationship to changes in asthma control following a cold. Clinically significant worsening of asthma control was observed following a cold (mean+/-SD increase in mini-ACQ score of 0.69+/-0.93). Univariate analysis demonstrated that season, centre location, cold duration and cold severity measurements were all associated with a change in asthma control. Multivariable analysis of the covariates available within the first 2 days of cold onset revealed that the day 2 and cumulative sum of day 1 and 2 WURSS-21 scores were significant predictors of the subsequent changes in asthma control. In asthmatic subjects, cold severity within the first 2 days can be used to predict subsequent changes in asthma control. This information may help clinicians prevent deterioration in asthma control following a cold.
Project description:Human rhinovirus (RV) is a major risk factor for chronic obstructive pulmonary disease (COPD) and asthma exacerbations. The exploration of RV pathogenesis has been hampered by a lack of disease-relevant model systems. We performed a detailed characterization of host responses to RV infection in human lung tissue ex vivo and investigated whether these responses are disease relevant for patients with COPD and asthma. In addition, impact of the viral replication inhibitor rupintrivir was evaluated. Human precision-cut lung slices (PCLS) were infected with RV1B with or without rupintrivir. At Days 1 and 3 after infection, RV tissue localization, tissue viability, and viral load were determined. To characterize host responses to infection, mediator and whole genome analyses were performed. RV successfully replicated in PCLS airway epithelial cells and induced both antiviral and proinflammatory cytokines such as IFNα2a, CXCL10, CXCL11, IFN-γ, TNFα, and CCL5. Genomic analyses revealed that RV not only induced antiviral immune responses but also triggered changes in epithelial cell-associated pathways. Strikingly, the RV response in PCLS was reflective of gene expression changes described in patients with COPD and asthma. Although RV-induced host immune responses were abrogated by rupintrivir, RV-triggered epithelial processes were largely refractory to antiviral treatment. Detailed analysis of RV-infected human PCLS and comparison with gene signatures of patients with COPD and asthma revealed that the human RV PCLS model represents disease-relevant biological mechanisms that can be partially inhibited by a well-known antiviral compound and provide an outstanding opportunity to evaluate novel therapeutics.
Project description:The cellular environment differs from that of reconstituted materials mainly because of the presence of highly condensed biomacromolecules. To mimic the environment and conditions in living cells, we developed a method to prepare additive-free, highly concentrated cell extracts. First, we verified the requirement for specific salts and buffers for functional cell-free translation extracts. The S30 fraction of Escherichia coli cell extracts without additives exhibited sufficient cell-free protein production. Next, we established a method to accumulate biological components by gradual evaporation by using a vacuum desiccator. Bovine serum albumin, green fluorescent protein, alkaline phosphatase, and a diluted reconstituted protein expression system were successfully condensed in their active forms using this method. The protein concentration of the prepared cell extract was elevated to 180 mg/mL, which was expected to contain approximately 260 mg/mL macromolecules, without the loss of cell-free protein expression activity. Such a condensed cell extract may be useful for investigating the differences between cells and reconstituted materials and may contribute to the development of methods to synthesize cells from cell extracts in the future.
Project description:BackgroundAdverse psychosocial working conditions-in particular poor job decision latitude and poor social support at work-may impair the effective implementation of asthma self-management behaviour at work and may be associated with increased asthma morbidity. In this study, we investigate for the first time the association of job decision latitude and social support at work with (1) four asthma-specific self-management behaviours at work (i.e., physical activity, trigger avoidance, acute symptom management, and communication) and with (2) asthma morbidity.MethodsA total of 221 employees with asthma recruited through three rehabilitation clinics completed questionnaires (response rate = 29.3%). Job decision latitude and social support were measured using items from the Copenhagen Psychosocial Questionnaire. The four asthma self-management behaviours were mainly assessed by self-developed items. We used the Asthma Control Test and the Marks Asthma Quality of Life Questionnaire to measure asthma morbidity. We dichotomized all variables and conducted logistic regression analyses to calculate odds ratios with 95% CIs.ResultsLow job decision latitude and low social support were significantly associated with poorer trigger avoidance (odds ratios ≥ 2.09) and poorer acute symptom management (odds ratios ≥ 2.29); low social support was further related to significantly less communication (odds ratio = 2.82). Low job decision latitude and low social support were also associated with significantly poorer asthma control (odds ratios ≥ 1.95) and poorer asthma-specific quality of life (odds ratios ≥ 2.05). The relationships with asthma morbidity were attenuated after adjustment for the four asthma self-management behaviours (odds ratios ranging from 1.1 to 1.9).ConclusionsAdverse psychosocial working conditions are associated with poorer asthma self-management behaviour at work and with increased asthma morbidity. The latter association may be mediated by asthma self-management behaviour.Trial registration German Clinical Trials Register, registration number: DRK S00011309, date of registration: 22.12.2016.
Project description:MicroRNAs (miRs) are single-stranded RNAs of 18-25 nucleotides. These molecules regulate gene expression at the post-transcriptional level; several of these are differentially expressed in asthma as well as in viral acute respiratory infections (ARIs), the main triggers of acute asthma exacerbations. In recent years, miRs have been studied in order to discover drug targets as well as biomarkers for diagnosis, disease severity and prognosis. We describe recent findings on miR expression and function in asthma and their role in the regulation of viral ARIs, according to cell tissue specificity and asthma severity. By combining the above information, we identify miRs that may be important in virus-induced asthma exacerbations. This is the first attempt to link miR profiles of asthmatic patients and ARI-induced miRs, addressing the question of whether there might be a specific miR deficit in asthmatic subjects that make them more susceptible and/or reactive to infection.
Project description:Public reporting on quality aims to help patients select better hospitals. However, individual quality measures are suboptimal in identifying superior and inferior hospitals based on outcome performance.To combine structure, process, and outcome measures into an empirically derived composite quality measure for heart failure (HF), acute myocardial infarction (AMI), and pneumonia (PNA). To assess how well the composite measure predicts future high and low performers, and explains variance in future hospital mortality.Using national Medicare data, we created a cohort of older patients treated at an acute care hospital for HF (n=1,203,595), AMI (n=625,595), or PNA (n=1,234,299). We ranked hospitals on the basis of their July 2005 to June 2008 performance on the composite. We then estimated the odds of future (July to December 2009) 30-day, risk-adjusted mortality at the worst versus best quintile of hospitals. We repeated this analysis using 2005-2008 performance on existing quality indicators, including mortality.The composite (vs. Hospital Compare) explained 68% (vs. 39%) of variation in future AMI mortality rates. In 2009, if an AMI patient had chosen a hospital in the worst versus best quintile of performance using 2005-2008 composite (vs. Hospital Compare) rankings, he or she would have had 1.61 (vs. 1.39) times the odds of dying in 30 days (P-value for difference <0.001). Results were similar for HF and PNA.Composite measures of quality for HF, AMI, and PNA performed better than existing measures at explaining variation in future mortality and predicting future high and low performers.