Systemic Inflammation and the Breakdown of Intestinal Homeostasis Are Key Events in Chronic Spinal Cord Injury Patients

Our aim was to investigate the subset distribution and function of circulating monocytes, proinflammatory cytokine levels, gut barrier damage, and bacterial translocation in chronic spinal cord injury (SCI) patients. Thus, 56 SCI patients and 28 healthy donors were studied. The levels of circulating CD14^+highCD16⁻, CD14^+highCD16⁺, and CD14^+lowCD16⁺ monocytes, membrane TLR2, TLR4, and TLR9, phagocytic activity, ROS generation, and intracytoplasmic TNF-α, IL-1, IL-6, and IL-10 after lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. Serum TNF-α, IL-1, IL-6 and IL-10 levels were measured by Luminex and LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP) and zonulin by ELISA. SCI patients had normal monocyte counts and subset distribution. CD14^+highCD16⁻ and CD14^+highCD16⁺ monocytes exhibited decreased TLR4, normal TLR2 and increased TLR9 expression. CD14^+highCD16⁻ monocytes had increased LPS-induced TNF-α but normal IL-1, IL-6, and IL-10 production. Monocytes exhibited defective phagocytosis but normal ROS production. Patients had enhanced serum TNF-α and IL-6 levels, normal IL-1 and IL-10 levels, and increased circulating LBP, I-FABP, and zonulin levels. Chronic SCI patients displayed impaired circulating monocyte function. These patients exhibited a systemic proinflammatory state characterized by enhanced serum TNF-α and IL-6 levels. These patients also had increased bacterial translocation and gut barrier damage.     

High-Fat Diet Aggravates Cerebral Infarct,Hemorrhagic Transformation and Neuroinflammation in a Mouse Stroke Model

Background: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. Methods: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. Results: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30–46.7%) vs. 28.45 (IQR 21–30%); p = 0.016) and HT (HFD: 2 (IQR 1–5) vs. ND: 0 (IQR 0–1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. Conclusion: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.     

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

Design trade-offs in self-management technology: the HeartMan case

ABSTRACT

Health self-management technology has the potential to significantly improve the Quality of Life of patients suffering from chronic diseases. However, designing the technology involves numerous highly context-dependent design decisions. In this paper, we analyse a case study of self-monitoring technology in the field of congestive heart failure. We analyse the design process of the technology from the perspective of design trade-offs. Three important trade-offs related to health self-monitoring technology are described in detail, related to patient autonomy, technology appropriation, and patient well-being. For each of the trade-offs, various mediating factors that influence design decisions are described in detail. On a practical level, this analysis can inform future developments in self-management technology. In addition, this design trade-off analysis provides intermediary knowledge that can contribute to a better theoretical understanding of health self-management technology.     

Deep Learning Based Process Analytics Model for Predicting Type 2 Diabetes Mellitus

Process analytics is one of the popular research domains that advanced in the recent years. Process analytics encompasses identification, monitoring, and improvement of the processes through knowledge extraction from historical data. The evolution of Artificial Intelligence (AI)-enabled Electronic Health Records (EHRs) revolutionized the medical practice. Type 2 Diabetes Mellitus (T2DM) is a syndrome characterized by the lack of insulin secretion. If not diagnosed and managed at early stages, it may produce severe outcomes and at times, death too. Chronic Kidney Disease (CKD) and Coronary Heart Disease (CHD) are the most common, long-term and life-threatening diseases caused by T2DM. Therefore, it becomes inevitable to predict the risks of CKD and CHD in T2DM patients. The current research article presents automated Deep Learning (DL)-based Deep Neural Network (DNN) with Adagrad Optimization Algorithm i.e., DNN-AGOA model to predict CKD and CHD risks in T2DM patients. The paper proposes a risk prediction model for T2DM patients who may develop CKD or CHD. This model helps in alarming both T2DM patients and clinicians in advance. At first, the proposed DNN-AGOA model performs data preprocessing to improve the quality of data and make it compatible for further processing. Besides, a Deep Neural Network (DNN) is employed for feature extraction, after which sigmoid function is used for classification. Further, Adagrad optimizer is applied to improve the performance of DNN model. For experimental validation, benchmark medical datasets were used and the results were validated under several dimensions. The proposed model achieved a maximum precision of 93.99%, recall of 94.63%, specificity of 73.34%, accuracy of 92.58%, and F-score of 94.22%. The results attained through experimentation established that the proposed DNN-AGOA model has good prediction capability over other methods.     

靶向抗癌药格列卫与其治疗白血病疗效监测

Gleevec是抑制致癌的融合蛋白BCR-ABL的一种分子靶向治疗药物,BCR-ABL是一种与慢性髓细胞性白血病(CML)有关的酪氨酸激酶抑制剂。用Gleevec选择性地抑制BCR-ABL活性在治疗CML中显示出很好的效果,特别是在CML慢性期,因此,监测疗效非常重要。现就Gleevec的研究进展及如何监测其在CML中的疗效作一简单综述。     

Patterns of discrimination in hiring job applicants with disabilities: The role of disability type, job complexity, and public contact.

Objective: To evaluate the effects of disability type, job complexity, and public contact on hiring decisions. Design and Participants: An Americans With Disabilities Act (ADA; 1990) fact sheet and matched resumes with vocational and medical histories including chronic mental illness, developmental disability, closed head injury, and back injury were provided to 295 undergraduate business-related majors, who rated the applicants' suitability for 2 job positions and work shifts. Results: Findings indicated disparities in ratings of employability as a function of disability type. Paired comparisons yielded complementary findings, with effects of disability type and Disability Type × Job Complexity, but no effects of public contact. Conclusions: Stereotyping and discrimination in employment decisions apparently persist, more than 10 years after the ADA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do changes in cognitive factors influence outcome following multidisciplinary treatment for chronic pain? A cross-lagged panel analysis.

Changes in maladaptive cognitions may constitute therapeutic processes of multidisciplinary pain programs. A cross-lagged panel design was used to determine whether (a) early-treatment cognitive change predicted late-treatment outcome index change, but not vice versa; and (b) these effects remained significant with depression change controlled. Ninety chronic pain patients, in a 4-week multidisciplinary program, completed measures of catastrophizing, pain helplessness, depression, pain, interference, and activity level at pre-, mid-, and posttreatment. With depression changes controlled, early-treatment catastrophizing and pain helplessness changes predicted late-treatment outcome index changes, but not vice versa; early-treatment depression changes predicted late-treatment activity changes, but not vice versa. Findings advance understanding of pain treatment process and suggest that negative cognition changes may indeed affect improvements in treatment outcome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Critical incidents and chronic stressors at work: Their impact on forensic doctors.

Workers in medium- or high-risk professions are often confronted with critical incidents at the workplace. The impact of these acute stressors may be serious and enduring. Many workers also experience chronic job stressors, such as work overload or role conflicts. This study examined the frequently neglected relationship of acute and chronic stressors with self-reported health symptoms, such as posttraumatic responses, fatigue, and burnout. This association was investigated in a sample of forensic doctors in the Netherlands (N = 84). It was found that the more traumatic events the respondents experienced, the more problems they reported in coping with the traumatic events. Chronic job stressors were associated with posttraumatic responses (intrusions and avoidances) and with burnout and fatigue. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypnosis and clinical pain.

Hypnosis has been demonstrated to reduce analogue pain, and studies on the mechanisms of laboratory pain reduction have provided useful applications to clinical populations. Studies showing central nervous system activity during hypnotic procedures offer preliminary information concerning possible physiological mechanisms of hypnotic analgesia. Randomized controlled studies with clinical populations indicate that hypnosis has a reliable and significant impact on acute procedural pain and chronic pain conditions, Methodological issues of this body of research are discussed, as are methods to better integrate hypnosis into comprehensive pain treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)