RIG-I contributes to the innate immune response after cerebral ischemia

BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-α are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-α after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP-positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-α signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia

Lithium intoxication related multiple temporary ecg changes: A case report

Lithium is a widely used mood stabilizer, which may cause cardiac side effects. In this article, we present the case of a 39-year-old woman who had presented with pre-syncope and developed multiple ECG abnormalities that are caused by lithium intoxication and are disappeared after hemodialysis

Validation of the PHQ-9 as a screening instrument for depression in diabetes patients in specialized outpatient clinics

Background. For the treatment of depression in diabetes patients, it is important that depression is recognized at an early stage. A screening method for depression is the patient health questionnaire (PHQ-9). The aim of this study is to validate the 9-item Patient Health Questionnaire (PHQ-9) as a screening instrument for depression in diabetes patients in outpatient clinics. Methods. 197 diabetes patients from outpatient clinics in the Netherlands filled in the PHQ-9. Within 2 weeks they were approached for an interview with the Mini Neuropsychiatric Interview. DSM-IV diagnoses of Major Depressive Disorder (MDD) were the criterion for which the sensitivity, specificity, positive- and negative predictive values and Receiver Operator Curves (ROC) for the PHQ-9 were calculated. Results. The cut-off point of a summed score of 12 on the PHQ-9 resulted in a sensitivity of 75.7% and a specificity of 80.0%. Predictive values for negative and positive test results were respectively 93.4% and 46.7%. The ROC showed an area under the curve of 0.77. Conclusions. The PHQ-9 proved to be an efficient and well-received screening instrument for MDD in this sample of diabetes patients in a specialized outpatient clinic. The higher cut-off point of 12 that was needed and somewhat lower sensitivity than had been reported elsewhere may be due to the fact that the patients from a specialized diabetes clinic have more severe pathology and more complications, which could be recognized by the PHQ-9 as depression symptoms, while instead being diabetes symptom

The functional capacity and quality of life of women with advanced breast cancer

The rehabilitation needs of patients with metastatic breast cancer (MBC) are poorly studied. The primary aim of the study was to evaluate the functional capacity of women with MBC and quality of life (QoL). The present study is an open, non-randomized, prospective cross-sectional observation study. The functional capacity of 128 MBC patients with ongoing cancer treatments, were studied in Helsinki University Hospital (HUS): Peak expiratory flow (PEF), dynamic and static balance, 6 minute walking distance (6MWD), 10 meter walking, sit-to-stand test, repeated squat, grip strength, shoulder movement, pain, and QoL by Beck's depression scale (BDI), health assessment questionnaire (HAQ), RAND SF-36 and EORTC QLQ-30 items. The walking capacity was compromised in half and the strength of the lower extremities in one-third of the patients. PEF was below the normal reference in 55 %, static balance in 62 % and dynamic balance in 73 % (= 61 year olds). The grip power was lowered in 44/30 % of the patients (right/left) and the shoulder movement was restricted in 30 %. Some disability in physical functioning experienced 55 % (HAQ) and 37 % felt depressive (BDI). The QoL (RAND SF-36) was poor especially in the field of physical, role and social functioning and bodily pain (<0.001). Pain, depression, and a poor 6MWD results independently determined the physical component of QoL (p <0.001). The functional capacity of patients with MBC was significantly lowered. This, in association with distressing symptoms like pain and depression causes a vicious circle further leading to functional disabilities and impaired QoL.Peer reviewe

Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome

BACKGROUND: Mild traumatic brain injury (MTBI) can sometimes lead to persistent postconcussion symptoms. One well accepted hypothesis claims that chronic PCS has a neural origin, and is related to neurobehavioral deficits. But the evidence is not conclusive. In the attempt to characterise chronic MTBI consequences, the present experiment used a group comparison design, which contrasted persons (a) with MTBI and PCS, (b) MTBI without PCS, and (c) matched controls. We predicted that participants who have experienced MTBI but show no signs of PCS would perform similar to controls. At the same time, a subgroup of MTBI participants would show PCS symptoms and only these volunteers would have poorer cognitive performance. Thereby, the performance deficits should be most noticeable in participants with highest PCS severity. METHOD: 38 patients with a single MTBI that had occurred at least 12 month prior to testing, and 38 matched controls, participated in the experiment. A combination of questionnaires and neuropsychological test batteries were used to assess the extent of PCS and related deficits in neurobehavioral performance. RESULTS: 11 out of 38 MTBI participants (29%) were found to suffer from PCS. This subgroup of MTBI patients performed poorly on neuropsychological test batteries. Thereby, a correlation was found between PCS symptom severity and test performance suggesting that participants with more pronounced PCS symptoms performed worse in cognitive tasks. In contrast, MTBI patients with no PCS showed performed similar to matched control. We further found that loss of consciousness, a key criterion for PCS diagnosis, was not predictive of sustained PCS. CONCLUSION: The results support the idea that MTBI can have sustained consequences, and that the subjectively experienced symptoms and difficulties in everyday situations are related to objectively measurable parameters in neurocognitive function

A study of the diagnostic accuracy of the PHQ-9 in primary care elderly

<p>Abstract</p> <p>Background</p> <p>The diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) for assessment of depression in elderly persons in primary care settings in the United States has not been previously addressed. Thus, the purpose of this study was to evaluate the test performance of the PHQ-9 for detecting major and minor depression in elderly patients in primary care.</p> <p>Methods</p> <p>A prospective study of diagnostic accuracy was conducted in two primary care, university-based clinics in the Pacific Northwest of the United States. Seventy-one patients aged 65 years or older participated; all completed the PHQ-9 and the 15-item Geriatric Depression Scale (GDS) and underwent the Structured Clinical Interview for Depression (SCID). Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, and likelihood ratios (LRs) were calculated for the PHQ-9, the PHQ-2, and the 15-item GDS for major depression alone and the combination of major plus minor depression.</p> <p>Results</p> <p>Two thirds of participants were female, with a mean age of 78 and two chronic health conditions. Twelve percent met SCID criteria for major depression and 13% minor depression. The PHQ-9 had an area under the curve (AUC) of 0.87 (95% confidence interval [CI], 0.74-1.00) for major depression, while the PHQ-2 and the 15-item GDS each had an AUC of 0.81 (95% CI for PHQ-2, 0.64-0.98, and for 15-item GDS, 0.70-0.91; <it>P </it>= 0.551). For major and minor depression combined, the AUC for the PHQ-9 was 0.85 (95% CI, 0.73-0.96), for the PHQ-2, 0.80 (95% CI, 0.68-0.93), and for the 15-item GDS, 0.71 (95% CI, 0.55-0.87; <it>P </it>= 0.187).</p> <p>Conclusions</p> <p>Based on AUC values, the PHQ-9 performs comparably to the PHQ-2 and the 15-item GDS in identifying depression among primary care elderly.</p

Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice

Background and Objective Transcranial low-level laser therapy (LLLT) using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI). In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI. Study Design/Materials and Methods TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm2 for 12-minutes giving a fluence of 36-J/cm2. Neurological severity score (NSS) and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test. Results The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests. Conclusion The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.National Institutes of Health (U.S.) (NIH grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense. Congressionally Directed Medical Research Programs (W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (Military Photomedicine Program (FA9950-04-1-0079))Japan. Ministry of Education, Culture, Sports, Science and TechnologyJapan Society for the Promotion of Scienc

The Role of the Frank–Starling Law in the Transduction of Cellular Work to Whole Organ Pump Function: A Computational Modeling Analysis

We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca2+ sensitivity of tension (Ca50), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca2+ to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca50 and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca50 was caused by an inversion in the regional distribution of strain