Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation.

This study was designed to analyze cytokine levels in bronchoalveolar lavage (BAL) fluid of patients with pulmonary fibrosis (PF) and was performed at a University hospital. Nineteen veterans had mustard gas-induced PF, and 19 normal veterans were used as a control group. Chest roentgenograms, pulmonary function tests (PFTs), the percentage diffusing capacity of carbon monoxide (D(LCO)), high-resolution CT scans of the chest, and analyses of BAL fluids for five cytokines interleukin-8 (IL-8), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-12, and the growth factors transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) were performed in all cases. A transbronchial lung biopsy was done in all patients. There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with PF and healthy controls. TGF-beta, EGF, and IGF-1 levels were also significantly increased in patients with PF compared with controls. A significant negative correlation was observed between the percentage of D(LCO) and IL-8 levels in BAL fluid in patients with PF (r = -0.47, p = 0.04). A significant negative correlation was also seen between the percentage of D(LCO) and TGF-beta (r = 0.53, p = 0.02) in these patients. Except for the percentage and the absolute number of the BAL fluid neutrophils (r = 0.70, p = 0.001 and r = -0.62, p = 0.005, respectively), no correlation was found between D(LCO)% and the other BAL cells. Of all measured cytokines and growth factors, only IL-8 and TGF-beta showed a significant correlation with the degree of fibrosis (p = 0.004, p = 0.04). The increased levels of cytokines and growth factors in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced PF by recruitment of neutrophils and eosinophils into the lung.     

Aetiology of severe mental retardation and further genetic analysis by high‐resolution microarray in a population‐based series of 6‐ to 17‐year‐old children

Aim: To investigate the prevalence, co‐morbidities and aetiologies of severe mental retardation (SMR) in a cohort of Swedish children and to further penetrate aetiologies in the group with undetermined causes by application of updated clinical‐genetic methods. Methods: The study was population‐based and included children living in the County of Halland in western Sweden in 2004 (born 1987–1998; 46 000 children). Patients were identified through habilitation centres, paediatric clinics and school health services. Patients with unclear prenatal aetiology were investigated with single nucleotide polymorphism (SNP)‐array. Results: Severe mental retardation was identified in 133 children from 132 families, corresponding to a prevalence of 2.9 per 1000 children. There were more males than females (90:43).The aetiology was prenatal in 82 (62%), perinatal in 14 (10%) and postnatal in 8 (6%). In 29 (22 %) children, mainly males with autism, the cause could not be related to the time of birth. In the prenatal group, genetic causes dominated, but still 23 children remained undiagnosed; in 5/19 of these patients, a diagnosis could be made after SNP‐array analysis. One or more associated neurological handicaps were found in more than half of the children. Conclusion: Prevalence and co‐morbidity were similar to previous Scandinavian studies. High‐resolution chromosomal micro‐array techniques are valuable diagnostic tools, reducing the number of patients with unexplained SMR.     

Future of combination therapy with dabrafenib and trametinib in metastatic melanoma

Introduction: Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF^V600 mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy.

Areas covered: This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib, and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway.

Expert opinion: Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.     

Cannabidiol promotes neurogenesis in the dentate gyrus during an abstinence period in rats following chronic exposure to methamphetamine

Metabolic Brain Disease - Chronic methamphetamine (meth) abuse can lead to certain deficits in the hippocampal function by affecting the hippocampal neurogenesis and plasticity. To determine...     

Brain Inconspicuous Effect by Local Sinusoidal Extremely Low Frequency Magnetic Exposure Based on Wavelet Packet Analysis: Innovation in Online Passive Neurofeedback Therapy by the Neuro-LSELF System

Neurofeedback (NF) is a training approach that aims to reinforce brain activity by using the information of human electroencephalogram (EEG) rhythms as a feedback. In addition, some studies have reported Extremely Low Frequency (0–300 Hz, intensity < 500 µT) Magnetic Field (ELF MF) effects upon the EEG and its rhythms. The purpose of this study is to determine if an approach that combines the effects of Local Sinusoidal Extremely Low Frequency Magnetic Fields (LSELF MF) with NF yields higher performance on desired NF goals. The NF protocol used in this study consisted of enhancement of the beta rhythm and inhibition of theta and high beta rhythms in exposed and sham groups for the purpose of improving attention. Twenty-four healthy subjects of at least average intelligence attended 10 sessions of NF training. Sixteen of them were exposed to 45 Hz sinusoidal ELF (360 µT) at F3 to lead to the desired LSELF MF effects on Cz. Wavelet packet analysis was used for the detection of changes in EEG rhythms. Results suggest that, compared to sham exposure, LSELF magnetic waves can significantly affect and modulate brainwaves according to this new neurofeedback approach. In comparison to sham exposure, improved ability to attend (as measured by a decrease in the theta-to-beta ratio) was observed when LSELF MF was combined with NF (p < .05). The hypothesis that LSELF MF can affect the theta-to-beta ratio was confirmed. These effects occurred after approximately 10 min of each NF procedure. This study aimed to pilot a new NF system known as the Neuro-ELF system, a method that may allow for more effective control of brainwave activity. However, we suggest that the effects of LSELF-NF require further research.