Testosterone and coronary artery disease in men

Coronary artery disease (CAD) is the leading cardiovascular cause of death, and in men, endogenous testosterone concentrations are inversely related to the extent and severity of CAD. Testosterone is known to affect a number of risk factors for CAD and has effects on vascular tone, vasoreactivity and blood flow of blood vessels beyond the reproductive system, indicating that testosterone may be involved in the pathogenesis of CAD. In this review we will present and discuss the actions of endogenous testosterone and testosterone treatment on risk factors for CAD, on the blood vessel wall and blood flow, and on atheroma development and progression, and discuss the potential for testosterone use in men with CAD.     

Statin drugs, metabolic pathways, and asthma: a therapeutic opportunity needing further research

The chance discovery of hydroxymethylglutaryl (HMG)-CoA reductase inhibitors has revolutionized the care of patients with cardiovascular disease. The unexpected finding that these cholesterol-lowering drugs (or 'statins') also possess pleiotropic immunomodulatory properties, has opened a new area of research which investigates the anti-inflammatory and anti-proliferative properties of statins. In this brief commentary, we discuss the potential application of these drugs in asthma, where metabolic pathways pertinent to lung inflammation, in addition to the mevalonate cascade, may be targeted. We review mechanisms of action, discuss the potential therapeutic use of statins in asthma, share some preliminary data from our laboratory, discuss results from recent clinical trials in asthma, and propose a new target asthma subpopulation that could potentially benefit. We conclude our essay by highlighting the mevalonate-dependent and -independent pathways that may be modulated by statins, including the emerging area of cholesterol, sphingolipid, and lipid raft biology in lung disease. In this is an opportunity to develop new treatments for asthma, where innovative therapies are urgently needed to prevent acute exacerbations and alter disease progression.     

Urinary tract infection of mice to model human disease: Practicalities,implications and limitations

Abstract

Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Murine models of human UTI are vital experimental tools that have helped to elucidate UTI pathogenesis and advance knowledge of potential treatment and infection prevention strategies. Fundamentally, several variables are inherent in different murine models, and understanding the limitations of these variables provides an opportunity to understand how models may be best applied to research aimed at mimicking human disease. In this review, we discuss variables inherent in murine UTI model studies and how these affect model usage, data analysis and data interpretation. We examine recent studies that have elucidated UTI host–pathogen interactions from the perspective of gene expression, and review new studies of biofilm and UTI preventative approaches. We also consider potential standards for variables inherent in murine UTI models and discuss how these might expand the utility of models for mimicking human disease and uncovering new aspects of pathogenesis.     

Biplane Correlation Imaging: A Feasibility Study Based on Phantom and Human Data

The objective of this study was to implement and evaluate the performance of a biplane correlation imaging (BCI) technique aimed to reduce the effect of anatomic noise and improve the detection of lung nodules in chest radiographs. Seventy-one low-dose posterior–anterior images were acquired from an anthropomorphic chest phantom with 0.28° angular separations over a range of ±10° along the vertical axis within an 11 s interval. Similar data were acquired from 19 human subjects with institutional review board approval and informed consent. The data were incorporated into a computer-aided detection (CAD) algorithm in which suspect lesions were identified by examining the geometrical correlation of the detected signals that remained relatively constant against variable anatomic backgrounds. The data were analyzed to determine the effect of angular separation, and the overall sensitivity and false-positives for lung nodule detection. The best performance was achieved for angular separations of the projection pairs greater than 5°. Within that range, the technique provided an order of magnitude decrease in the number of false-positive reports when compared with CAD analysis of single-view images. Overall, the technique yielded ~1.1 false-positive per patient with an average sensitivity of 75%. The results indicated that the incorporation of angular information can offer a reduction in the number of false-positives without a notable reduction in sensitivity. The findings suggest that the BCI technique has the potential for clinical implementation as a cost-effective technique to improve the detection of subtle lung nodules with lowered rate of false-positives.     

MDCT of abdominal wall lumbar hernias: anatomical review, pathologic findings and differential diagnosis

Purpose

To review the anatomical landmarks of the abdominal wall lumbar region and its normal appearance on multidetector computed tomography (MDCT) and to briefly describe the MDCT features of lumbar hernias.

Methods

We performed a retrospective search of the imaging report database from November 2007 to October 2011. We retrieved the clinical data and MDCT studies of patients suffering from abdominal wall lumbar hernias. We reviewed the imaging features of abdominal lumbar hernias and compared those with the normal appearance of the lumbar region in asymptomatic individuals.

Results

We classified lumbar wall hernias as diffuse, superior (or Grynfelt–Lesshaft) and inferior (or Petit) lumbar hernias. We briefly describe the imaging features of each subtype and review the anatomy and MDCT appearance of normal lumbar region.

Conclusions

Currently available MDCT provides an excellent opportunity for reviewing the normal anatomy of the wall lumbar region and may be considered a useful modality for evaluating lumbar hernias.     

基于CT影像分析的肺结节计算机辅助检测与诊断技术进展

肺结节是肺部最常见的病变之一,肺结节的早期检测和诊断对于肺癌的早期诊治十分重要.近年来,随着多层螺旋CT(MSCT)、高分辨CT(HRCT)及低剂量胸部CT(LDCT)的应用,计算机辅助诊断(CAD)系统的必要性和重要性也日益显现.由于CAD系统可以明显提高诊断医生的工作效率,为更多的患者服务,因此成为国内外相关领域专家的研究热点,近几年来也取得了一定的成果.就肺结节的CT计算机辅助检测和诊断的基本方法和应用作一综述. Abstract： Lung nodules are one of the most common pathological changes, thus early detection of lung nodule is very important for the diagnosis medical treatment of lung eancer. In recent years, as the application of multi-slice spiral CT(MSCT), high-resolution CT(HRCT) and low-dose chest CTCLDCT), computer-aided diagnosis (CAD) system will be more essential and more important. Since CAD system can improve the working efficiency of doctors and provide service to more patients, has become the research hotspot and achievement has been made in relevant area internationally recently. This review summarizes the basic methods and applieations of computer-aided detection and diagnosis of lung nodule based on CT image.     

Lung nodule detection on thoracic computed tomography images: preliminary evaluation of a computer-aided diagnosis system

We are developing a computer-aided diagnosis (CAD) system for lung nodule detection on thoracic helical computed tomography (CT) images. In the first stage of this CAD system, lung regions are identified by a k-means clustering technique. Each lung slice is classified as belonging to the upper, middle, or the lower part of the lung volume. Within each lung region, structures are segmented again using weighted k-means clustering. These structures may include true lung nodules and normal structures consisting mainly of blood vessels. Rule-based classifiers are designed to distinguish nodules and normal structures using 2D and 3D features. After rule-based classification, linear discriminant analysis (LDA) is used to further reduce the number of false positive (FP) objects. We performed a preliminary study using 1454 CT slices from 34 patients with 63 lung nodules. When only LDA classification was applied to the segmented objects, the sensitivity was 84% (53/63) with 5.48 (7961/1454) FP objects per slice. When rule-based classification was used before LDA, the free response receiver operating characteristic (FROC) curve improved over the entire sensitivity and specificity ranges of interest. In particular, the FP rate decreased to 1.74 (2530/1454) objects per slice at the same sensitivity. Thus, compared to FP reduction with LDA alone, the inclusion of rule-based classification lead to an improvement in detection accuracy for the CAD system. These preliminary results demonstrate the feasibility of our approach to lung nodule detection and FP reduction on CT images.     

Pulmonary group 2 innate lymphoid cells: surprises and challenges

Group 2 innate lymphoid cells (ILC2s) are a recently described subset of innate lymphocytes with important immune and homeostatic functions at multiple tissue sites, especially the lung. These cells expand locally after birth and during postnatal lung maturation and are present in the lung and other peripheral organs. They are modified by a variety of processes and mediate inflammatory responses to respiratory pathogens, inhaled allergens and noxious particles. Here, we review the emerging roles of ILC2s in pulmonary homeostasis and discuss recent and surprising advances in our understanding of how hormones, age, neurotransmitters, environmental challenges, and infection influence ILC2s. We also review how these responses may underpin the development, progression and severity of pulmonary inflammation and chronic lung diseases and highlight some of the remaining challenges for ILC2 biology.     

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management

The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment.     

Forecasting the future of HIV epidemics: the impact of antiretroviral therapies & imperfect vaccines

Mathematical models can be used as health policy tools and predictive tools. Here we review how mathematical models have been used both to predict the consequences of specific epidemic control strategies and to design epidemic control strategies. We review how models have been used to evaluate the potential impact on HIV epidemics of (i) combination antiretroviral therapies (ART) and (ii) imperfect vaccines. In particular, we discuss how models have been used to predict the potential effect of ART on incidence rates, and to predict the evolution of an epidemic of drug-resistant HIV. We also discuss, in detail, how mathematical models have been used to evaluate the potential impact of prophylactic, live-attenuated and therapeutic HIV vaccines. We show how HIV vaccine models can be used to evaluate the epidemic-level impact of vaccine efficacy, waning in vaccine-induced immunity, vaccination coverage level, and changes (increases or decreases) in risky behavior. We also discuss how mathematical models can be used to determine the levels of cross-immunity that vaccines will need to attain if they are to be used to control HIV epidemics in countries where more than one subtype is being transmitted.     

Manipulating the immune system for anti-tumor responses and transplant tolerance via mixed hematopoietic chimerism

Summary: Stem cells (SCs) with varying potentiality have the capacity to repair injured tissues. While promising animal data have been obtained, allogeneic SCs and their progeny are subject to immune-mediated rejection. Here, we review the potential of hematopoietic stem cells (HSCs) to promote immune tolerance to allogeneic and xenogeneic organs and tissues, to reverse autoimmunity, and to be used optimally to cure hematologic malignancies. We also review the mechanisms by which hematopoietic cell transplantation (HCT) can promote anti-tumor responses and establish donor-specific transplantation tolerance. We discuss the barriers to clinical translation of animal studies and describe some recent studies indicating how they can be overcome. The recent achievements of durable mixed chimerism across human leukocyte antigen barriers without graft-versus-host disease and of organ allograft tolerance through combined kidney and bone marrow transplantation suggest that the potential of this approach for use in the treatment of many human diseases may ultimately be realized.     

Lung transplantation: infection, inflammation, and the microbiome

Lung transplantation is the only therapeutic option for patients with end-stage pulmonary disorders. Despite the improvements in surgical techniques and immunosuppressive therapy, allograft function and long-term survival are limited by the development of chronic lung transplant rejection. In this review, we focus on bronchiolitis obliterans syndrome (BOS) which is the major manifestation of chronic lung allograft rejection. We specifically review the effect of infection, a risk factor for BOS, cytokines/chemokines in the pathogenesis of BOS, and the potential link between the allograft microbiome and immune responses that may mediate the development of BOS. Understanding the allograft microbiome and how it relates to the pathologic mechanisms of BOS may suggest targeted therapies to improve long-term survival post-lung transplantation.     

Respiratory impedance measurements for assessment of lung mechanics: focus on asthma

This review discusses the history and current state of the art of the forced oscillation technique (FOT) to measure respiratory impedance. We focus on how the FOT and its interaction with models have emerged as a powerful method to extract out not only clinically relevant information, but also to advance insight on the mechanisms and structures responsible for human lung diseases, especially asthma. We will first provide a short history of FOT for basic clinical assessment either directly from the data or in concert with lumped element models to extract out specific effective properties. We then spend several sections on the more exciting recent advances of FOT to probe the relative importance of tissue versus airway changes in disease, the impact of the disease on heterogeneous lung function, and the relative importance of small airways via synthesis of FOT with imaging. Most recently, the FOT approach has been able to directly probe airway caliber in humans and the distinct airway properties of asthmatics that seem to be required for airway hyperresponsiveness. We introduce and discuss the mechanism and clinical implications of this approach, which may be substantial for treatment assessment. Finally, we highlight important future directions for the FOT, particularly its use to probe specific lung components (e.g., isolated airways, isolated airway smooth muscle, etc.) and relate such data to the whole lung. The intent is to substantially advance an integrated understanding of structure–function relationships in the lung.     

Lung inflammation in the pathogenesis of rheumatoid arthritis

The primary manifestation of rheumatoid arthritis (RA) is articular disease; however, extra-articular disease can also occur. In particular, pulmonary disease is a leading cause of morbidity and mortality in individuals with RA. Herein, we will review the types, prevalence, risk factors, and potential pathophysiology of lung disease in individuals with established RA. We will also discuss the emerging understanding of potential role of the lung in the generation of RA-related autoantibodies during a period of disease development termed “pre-RA.” Finally, we will discuss a research agenda outlining the next steps to improve our understanding and management of lung inflammation and lung disease throughout the natural history of RA.     

Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

Myokines are molecules produced and secreted by skeletal muscle to act in an auto‐, para‐ and endocrine manner to alter physiological function of target tissues. The growing number of effects of myokines on metabolism of distant tissues provides a compelling case for crosstalk between skeletal muscle and other tissues and organs to regulate metabolic homoeostasis. In this review, we summarize and discuss the current knowledge regarding the impact on metabolism of several canonical and recently identified myokines. We focus specifically on myostatin, β‐aminoisobutyric acid, interleukin‐15, meteorin‐like and myonectin, and discuss how these myokines are induced and regulated as well as their overall function. We also review how these myokines may serve as potential prognostic biomarkers that reflect whole‐body metabolism and how they may be attractive therapeutic targets for treating muscle and metabolic diseases.     

GridIMAGE: A Novel Use of Grid Computing to Support Interactive Human and Computer-Assisted Detection Decision Support

This paper describes a Grid-aware image reviewing system (GridIMAGE) that allows practitioners to (a) select images from multiple geographically distributed digital imaging and communication in medicine (DICOM) servers, (b) send those images to a specified group of human readers and computer-assisted detection (CAD) algorithms, and (c) obtain and compare interpretations from human readers and CAD algorithms. The currently implemented system was developed using the National Cancer Institute caGrid infrastructure and is designed to support the identification of lung nodules on thoracic computed tomography. However, the infrastructure is general and can support any type of distributed review. caGrid data and analytical services are used to link DICOM image databases and CAD systems and to interact with human readers. Moreover, the service-oriented and distributed structure of the GridIMAGE framework enables a flexible system, which can be deployed in an institution (linking multiple DICOM servers and CAD algorithms) and in a Grid environment (linking the resources of collaborating research groups). GridIMAGE provides a framework that allows practitioners to obtain interpretations from one or more human readers or CAD algorithms. It also provides a mechanism to allow cooperative imaging groups to systematically perform image interpretation tasks associated with research protocols.     

Interstitial lung disease--the new synergy between radiology and pathology

In the last 30 years, high-resolution computed tomography (HRCT) has been the major advance in diagnosis of diffuse parenchymal lung disease (DPLD). We review the diagnostic accuracy of HRCT and discuss how the gold standard in diagnosis of DPLD has shifted from histopathological diagnosis in isolation to a multidisciplinary approach. This latter process is now accepted as providing the highest levels of diagnostic accuracy in patients with DPLD and lung biopsy is primarily reserved for cases with atypical clinical or radiological presentations.     

The evidence for and against different modes of tumour cell extravasation in the lung: diapedesis,capillary destruction,necroptosis, and endothelialization

The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies. Here, we discuss the literature pertaining to the proposed mechanisms of extravasation and critically compare a recently proposed mechanism (tumour cell‐induced endothelial necroptosis) with the already described extravasation mechanisms in the lung. We also provide novel data that may help to explain the underlying physiological basis for endothelialization as a mechanism of tumour cell extravasation in the lung. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Wavelet method for CT colonography computer-aided polyp detection

Computed tomographic colonography (CTC) computer aided detection (CAD) is a new method to detect colon polyps. Colonic polyps are abnormal growths that may become cancerous. Detection and removal of colonic polyps, particularly larger ones, has been shown to reduce the incidence of colorectal cancer. While high sensitivities and low false positive rates are consistently achieved for the detection of polyps sized 1 cm or larger, lower sensitivities and higher false positive rates occur when the goal of CAD is to identify "medium"-sized polyps, 6-9 mm in diameter. Such medium-sized polyps may be important for clinical patient management. We have developed a wavelet-based postprocessor to reduce false positives for this polyp size range. We applied the wavelet-based postprocessor to CTC CAD findings from 44 patients in whom 45 polyps with sizes of 6-9 mm were found at segmentally unblinded optical colonoscopy and visible on retrospective review of the CT colonography images. Prior to the application of the wavelet-based postprocessor, the CTC CAD system detected 33 of the polyps (sensitivity 73.33%) with 12.4 false positives per patient, a sensitivity comparable to that of expert radiologists. Fourfold cross validation with 5000 bootstraps showed that the wavelet-based postprocessor could reduce the false positives by 56.61% (p <0.001), to 5.38 per patient (95% confidence interval [4.41, 6.34]), without significant sensitivity degradation (32/45, 71.11%, 95% confidence interval [66.39%, 75.74%], p=0.1713). We conclude that this wavelet-based postprocessor can substantially reduce the false positive rate of our CTC CAD for this important polyp size range.     

The diagnostic rules of peripheral lung cancer preliminary study based on data mining technique

Objective: To discuss the clinical and imaging diagnostic rules of peripheral lung cancer by data mining technique, and to explore new ideas in the diagnosis of peripheral lung cancer, and to obtain early-stage technology and knowledge support of computer-aided detecting (CAD). Methods: 58 cases of peripheral lung cancer confirmed by clinical pathology were collected. The data were imported into the database after the standardization of the clinical and CT findings attributes were identified. The data was studied comparatively based on Association Rules (AR) of the knowledge discovery process and the Rough Set (RS) reduction algorithm and Genetic Algorithm(GA) of the generic data analysis tool (ROSETTA), respectively. Results: The genetic classification algorithm of ROSETTA generates 5 000 or so diagnosis rules. The RS reduction algorithm of Johnson's Algorithm generates 51 diagnosis rules and the AR algorithm generates 123 diagnosis rules. Three data mining methods basically consider gender, age,cough, location, lobulation sign, shape, ground-glass density attributes as the main basis for the diagnosis of peripheral lung cancer. Conclusion: These diagnosis rules for peripheral lung cancer with three data mining technology is same as clinical diagnostic rules, and these rules also can be used to build the knowledge base of expert system. This study demonstrated the potential values of data mining technology in clinical imaging diagnosis and differential diagnosis.