Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome

The functional relevance of brain-derived neurotrophic factor (BDNF) is beginning to be well appreciated not only in mice, but also in humans. Because reduced levels typically correlate with impaired neuronal function, increasing BDNF levels with well-tolerated drugs diffusing into the central nervous system may help in ameliorating functional deficits. With this objective in mind, we used the sphingosine-1 phosphate receptor agonist fingolimod, a drug that crosses the blood-brain barrier. In addition, fingolimod has recently been introduced as the first oral treatment for multiple sclerosis. In cultured neurons, fingolimod increases BDNF levels and counteracts NMDA-induced neuronal death in a BDNF-dependent manner. Ongoing synaptic activity and MAPK signaling is required for fingolimod-induced BDNF increase, a pathway that can also be activated in vivo by systemic fingolimod administration. Mice lacking Mecp2, a gene frequently mutated in Rett syndrome, show decreased levels of BDNF, and fingolimod administration was found to partially rescue these levels as well as the size of the striatum, a volumetric sensor of BDNF signaling in rodents. These changes correlate with increased locomotor activity of the Mecp2-deficient animals, suggesting that fingolimod may improve the functional output of the nervous system, in addition to its well-documented effects on lymphocyte egress from lymph nodes.     

Serum concentrations of antiphospholipid and anticardiolipin antibodies are higher in HIV-infected women

Manifestations of viral infections like human immune deficiency virus (HIV) differ between women and men. There are some reports due to a higher risk of thrombosis due to antiphospholipid syndrome in HIV-infected women compared with men. The purpose of this study was demonstrating the impact of gender on serum concentration of antiphospholipid and anticardiolipin antibodies in HIV-infected patients. A total of 58 HIV-infected patients and 58 age, sex-matched healthy adults were enrolled. We measured platelets count, hemoglobin, partial thromboplastin time (PTT); prothrombin time (PT), international normalized ratio (INR), antiphospholipid IgG/IgM and anticardiolipin IgG/IgM serotypes in our studied population. Age, male-to-female ratio, hemoglobin level, PT, INR, antiphospholipid IgM isotype, anticardiolipin IgM and IgG isotypes levels were not significantly different between HIV-infected patients and healthy individuals, when CD4+ T-cell count, CD8+ T-cell count, platelet count, and PTT were significantly lower, and antiphospholipid IgG isotype levels was significantly higher in HIV patients. Antiphospholipid IgG isotypes (3.2 [2.8–4.2] vs. 2.5 [2.3–3.1]; P?<?0.001) and anticardiolipin IgG isotypes (2.2 [1.9–2.7] vs. 1.4 [1.4–1.9]; P?<?0.001) were significantly higher in HIV-infected women than in HIV-infected men. Antiphospholipid IgG/IgM and anticardiolipin IgG/IgM were significantly correlated in HIV-infected men and women when they did not had any correlation in controls. We suggest that HIV infection accelerate thrombosis in women more profoundly than in men, as a result of differences in disease progression and response to therapy in these patients.     

Safety and Efficacy of Non-Cemented Femoral Fixation in Patients 75 Years of Age and Older

The aim of this study was to assess peri-operative complications, safety and efficacy of non-cemented femoral fixation in total hip arthroplasty (THA) as compared to cemented femoral fixation in the elderly population. Fifty-two matched pair analysis of patients with 75 years of age and older (104 patients), who underwent primary THA from June 1997 to December 2004, was performed based on age, sex, BMI, and Charnley classification. Mean age was 81 years (75–101) and the average follow up was 3.1 ± 2.9 years (1.2–6.4). There was no difference in peri-operative cardiopulmonary complications, pulmonary failures, deep venous thrombosis, pulmonary embolus, length of stay, or discharge deposition between the two groups. Non-cemented fixation is safe and effective in patients older than 75 years of age.     

The clinical significance of small subarachnoid hemorrhages

With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests that patients may not require as aggressive monitoring as is currently provided for those with tSAH.     

Occupational stress among Swedish audiologists in clinical practice: Reasons for being stressed

Objective: The present study reports on the application of a Swedish translation of the audiologist occupational stress questionnaire (AOSQ) on audiologists working in Sweden. The relations between AOSQ scores and perceived effort, perceived rewards, coping strategies at work, demographic variables such as salary, education length, practise length, and practice type were tested. Design: A cross-sectional e-mail survey using the AOSQ, effort-reward imbalance questionnaire, and demographic questions. Study sample: Four-hundred and four Swedish licensed audiologists working with clients. Results: The Swedish AOSQ translation demonstrated high inter-item correlations and high internal consistency. Several stress factors were identified: time spent at work, accountability, leadership at the workplace, paperwork and practice demands, equipment and clinical protocols, own health concerns, and job control. The outcome on the complete AOSQ questionnaire was related to perceived effort, perceived rewards, coping strategies at work, and age. Conclusions: The Swedish AOSQ translation seems to provide a valid measure of occupational stress among audiologists.     

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11?nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2?mg/mL of QDs) after 24?h indicated low toxicity for the bare QDs and functionalised QDs (about 80–90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.     

Potential Cardioprotective Effects of Sumac Capsule in Patients With Hyperlipidemia: A Triple-Blind Randomized,Placebo-Controlled Crossover Trial

Objective: Alternative medicine and herbal drugs have been taken into account for managing cardiovascular risk factors. Sumac (Rhus coriaria L.) is rich in biologically active ingredients known to improve cardiovascular health. We investigated the effect of sumac on systolic (SBP) and diastolic (DBP) blood pressure, flow-mediated dilation (FMD), body mass index (BMI), and serum concentrations of lipids and fasting blood sugar (FBS) in participants with hyperlipidemia in a triple-blind randomized placebo- controlled crossover trial.

Methods: Thirty adults with dyslipidemia (mild to moderate elevation of plasma total cholesterol and/or triglycerides [TG; total cholesterol ≥ 6.0 mmol/L or TG ≥ 1.7 mmol/L and TG ≤ 5.0 mmol/L]) were assigned randomly to a sumac or a placebo group. Participants in the sumac group received sumac capsules (500 mg/twice daily) for the first 4 weeks, followed by 2 weeks’ washout period; the patients were then switched to a 4-week interval and received placebo for 4 weeks in the second period. The placebo group received these treatments in reverse order. FMD, BMI, SBP, DBP, lipids, and FBS were measured at baseline and after each period.

Results: Differences between placebo group and sumac group (placebo-sumac) were significantly decreased for BMI (0.21 ± 0.075 kg/m²), SBP (1.87 ± 0.83 mm Hg), DBP (1.32 ± 0.46 mm Hg), and total cholesterol (14.42 ± 4.95 mmol/L) and significantly increased for FMD (?0.23% ± 0.065%). Plasma level of TG did not change significantly across the treatment.

Conclusion: Sumac consumption may decrease cardiovascular risk factors in persons with mild to moderate hyperlipidemia.