Resveratrol Mobilizes Endogenous Copper in Human Peripheral Lymphocytes Leading to Oxidative DNA Breakage: A Putative Mechanism for Chemoprevention of Cancer

Plant polyphenols are important components of human diet, and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring anti-oxidants but also act as pro-oxidants catalyzing DNA degradation in the presence of metal ions such as copper. The plant polyphenol resveratrol confers resistance to plants against fungal agents and has been implicated as a cancer chemopreventive agent. Of particular interest is the observation that resveratrol has been found to induce apoptosis in cancer cell lines but not in normal cells. Over the last few years, we have shown that resveratrol is capable of causing DNA breakage in cells such as human lymphocytes. Such cellular DNA breakage is inhibited by copper specific chelators but not by iron and zinc chelating agents. Similar results are obtained by using permeabilized cells or with isolated nuclei, indicating that chromatin-bound copper is mobilized in this reaction. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and resveratrol to generate reactive oxygen species responsible for DNA cleavage. The results are in support of our hypothesis that anti-cancer mechanism of plant polyphenols involves mobilization of endogenous copper and the consequent pro-oxidant action. Such a mechanism better explains the anti-cancer effects of resveratrol, as it accounts for the preferential cytotoxicity towards cancer cells.     

Mycobacterial cervical lymphadenitis

Mycobacterial cervical lymphadenitis remains a diagnostic challenge for many clinicians despite current advances in diagnostic laboratory techniques. Although much has been done to prevent tuberculosis, cases of mycobacterial disease in endemic form still occur. Six hundred and forty-five patients with tuberculosis were diagnosed and treated at the American University of Beirut Medical Center during the period from 1970 to 1985. Twenty-nine (4.5%) of these patients had proven mycobacterial cervical lymphadenitis. We stress histopathologic examination as the single most important means for diagnosing mycobacterial cervical lymphadenitis. Operation in combination with antituberculous chemotherapy remain the treatments of choice.     

Norstephalagine and atherospermidine: two smooth muscle relaxant aporphines from Artabotrys maingayi

Nine isoquinoline alkaloids have been isolated from the bark of Artabotrys maingayi: four noraporphines (norstephalagine, 3-hydroxynornuciferine, anonaine, and nornuciferine), one 7-hydroxyaporphine (ushinsunine), three oxoaporphines (atherospermidine, liriodenine, and lysicamine), and one protoberberine (discretamine). The effects of the main alkaloids, norstephalagine and atherospermidine, have been studied on the Ca-dependent contractile activity of smooth muscle (uterus). Both norstephalagine and atherospermidine show relaxing activity on rat uterine contractions induced by KCl or rhythmic contractions induced by oxytocin in the presence of Ca, but only atherospermidine can relax oxytocin- or vanadate-induced contractions in a Ca-free medium.     

Infusion aspiration mismatch during 25-gauge vitrectomy with conversion to 20-gauge vitrector.

We report intraoperative hypotony throughout the 25G vitrectomy procedure of an elderly patient with dense vitreous hemorrhage when switching to a 20G cutter. This was due to fluidic mismatch between the 25G infusion and 20G aspiration systems. No leakage from the sclerotomy sites or choroidal effusion was noted.     

Automated Classification of Rheumatoid Arthritis,Osteoarthritis, and Normal Hand Radiographs with Deep Learning Methods

Rheumatoid arthritis and hand osteoarthritis are two different arthritis that causes pain, function limitation, and permanent joint damage in the hands. Plain hand radiographs are the most commonly used imaging methods for the diagnosis, differential diagnosis, and monitoring of rheumatoid arthritis and osteoarthritis. In this retrospective study, the You Only Look Once (YOLO) algorithm was used to obtain hand images from original radiographs without data loss, and classification was made by applying transfer learning with a pre-trained VGG-16 network. The data augmentation method was applied during training. The results of the study were evaluated with performance metrics such as accuracy, sensitivity, specificity, and precision calculated from the confusion matrix, and AUC (area under the ROC curve) calculated from ROC (receiver operating characteristic) curve. In the classification of rheumatoid arthritis and normal hand radiographs, 90.7%, 92.6%, 88.7%, 89.3%, and 0.97 accuracy, sensitivity, specificity, precision, and AUC results, respectively, and in the classification of osteoarthritis and normal hand radiographs, 90.8%, 91.4%, 90.2%, 91.4%, and 0.96 accuracy, sensitivity, specificity, precision, and AUC results were obtained, respectively. In the classification of rheumatoid arthritis, osteoarthritis, and normal hand radiographs, an 80.6% accuracy result was obtained. In this study, to develop an end-to-end computerized method, the YOLOv4 algorithm was used for object detection, and a pre-trained VGG-16 network was used for the classification of hand radiographs. This computer-aided diagnosis method can assist clinicians in interpreting hand radiographs, especially in rheumatoid arthritis and osteoarthritis.

     

Timothy Grass Pollen Induces Spatial Reorganisation of F-Actin and Loss of Junctional Integrity in Respiratory Cells

Inflammation - Grass pollens have been identified as mediators of respiratory distress, capable of exacerbating respiratory diseases including epidemic thunderstorm asthma (ETSA). It is...     

Electroencephalogram complexity analysis in children with attention-deficit/hyperactivity disorder during a visual cognitive task

Objective: The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Method: Thirty 7–12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM–5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel–Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. Results: The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Conclusion: Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.     

Altered Integration of Structural Covariance Networks in Young Children With Type 1 Diabetes

Type 1 diabetes mellitus (T1D), one of the most frequent chronic diseases in children, is associated with glucose dysregulation that contributes to an increased risk for neurocognitive deficits. While there is a bulk of evidence regarding neurocognitive deficits in adults with T1D, little is known about how early‐onset T1D affects neural networks in young children. Recent data demonstrated widespread alterations in regional gray matter and white matter associated with T1D in young children. These widespread neuroanatomical changes might impact the organization of large‐scale brain networks. In the present study, we applied graph‐theoretical analysis to test whether the organization of structural covariance networks in the brain for a cohort of young children with T1D (N = 141) is altered compared to healthy controls (HC; N = 69). While the networks in both groups followed a small world organization—an architecture that is simultaneously highly segregated and integrated—the T1D network showed significantly longer path length compared with HC, suggesting reduced global integration of brain networks in young children with T1D. In addition, network robustness analysis revealed that the T1D network model showed more vulnerability to neural insult compared with HC. These results suggest that early‐onset T1D negatively impacts the global organization of structural covariance networks and influences the trajectory of brain development in childhood. This is the first study to examine structural covariance networks in young children with T1D. Improving glycemic control for young children with T1D might help prevent alterations in brain networks in this population. Hum Brain Mapp 37:4034–4046, 2016. © 2016 Wiley Periodicals, Inc .     

Symptom clusters in cancer patients with bone metastases

Purpose The purpose of this study is to explore whether bone pain “clusters” with other symptoms in patients with bone metastases. Materials and methods Patients with bone metastases referred to a palliative radiotherapy clinic were asked to rate their symptom distress using the Edmonton Symptom Assessment Scale (ESAS). Analgesic consumption during the previous 24 h was captured at initial consultation. To determine interrelationships between symptoms, a principal component analysis (PCA) with “varimax rotation” was performed on the nine ESAS symptoms. This study defined a “symptom cluster” as two or more symptoms that occur together, are stable, and are relatively independent of other clusters. Patients were followed 1, 2, 4, 8, and 12 weeks post-radiation treatment by telephone. Statistical analysis was performed at each time point for both responders and nonresponders to radiation (response was defined in accordance to the International Bone Metastases Consensus Working Party). Results Five hundred eighteen patients with bone metastases provided complete baseline data using the ESAS. The four most prevalent symptoms were poor sense of well-being (93.5%), fatigue (92.3%), pain (84.1%), and drowsiness (81.8%). Three clusters were identified and accounted for 66% of the total variance at baseline. Cronbach’s alpha coefficient demonstrated high internal reliability in the clusters, with a coefficient ranging from 0.61 to 0.81. It was observed that the clusters changed post-radiation in both responders and nonresponders and that pain clustered with different symptoms (or remained a separate symptom in responders). In nonresponders, three symptom clusters were consistently present, except in week 8. Conclusion Radiotherapy influenced the structure of symptom clusters in both responders and nonresponders. There was evidence that pain clustered out in responders of radiation to pain. It was found that pain clustered with fatigue, drowsiness, and poor sense of well-being at baseline. However, these findings must be heeded with caution, as more work is needed to clearly define symptom clusters and to understand the effects of radiation in the symptom experience of patients with bone metastases.