Shapirowinstead6120

PURPOSE This prospective, non-randomized, interventional phase I-II study investigated the individualization of the elective node irradiation in clinically N0 (cN0) head and neck squamous cell carcinoma (HSNCC) by sentinel lymph node (SLN) mapping with SPECT/CT and its impact on tumor control and radiation-related toxicity. MATERIALS AND METHODS Forty-four cN0 HNSCC patients treated with definitive (chemo-)radiotherapy were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to the four hottest SLN were selected for prophylactic irradiation (CTVn-LS). A comparative virtual planning was performed with the selection of neck levels based on the current international guidelines (CTVn-IG). The regional control was monitored in function of the selected volume. Dosimetric data to the organs-at-risk (OAR) were compared between both plans. Normal tissue complication probability (NTCP) rates were derived for xerostomia, dysphagia and hypothyroidism to predict the cliniticularly in case of unilateral irradiation. Spinal muscular atrophy (SMA) is a severe, inherited disease characterized by the progressive degeneration and death of motor neurons of the anterior horns of the spinal cord, which results in muscular atrophy and weakness of variable severity. Its early-onset form is invariably fatal in early childhood, while milder forms lead to permanent disability, physical deformities and respiratory complications. Recently, two novel revolutionary therapies, antisense oligonucleotides and gene therapy, have been approved, and might prove successful in making long-term survival of these patients likely. BGJ398 clinical trial In this perspective, a deep understanding of the pathogenic mechanisms and of their impact on the interactions between motor neurons and other cell types within the central nervous system (CNS) is crucial. Studies using SMA animal and cellular models have taught us that the survival and functionality of motor neurons is highly dependent on a whole range of other cell types, namely glial cells, which are responsible for a variety of different functions, such as neuronal trophic support, synaptic remodeling, and immune surveillance. Thus, it emerges that SMA is likely a non-cell autonomous, multifactorial disease in which the interaction of different cell types and disease mechanisms leads to motor neurons failure and loss. This review will introduce the different glial cell types in the CNS and provide an overview of the role of glial cells in motor neuron degeneration in SMA. Furthermore, we will discuss the relevance of these findings so far and the potential impact on the success of available therapies and on the development of novel ones. Endocannabinoid system activity contributes to the homeostatic defense against aging and thus may counteract the progression of brain aging. The cannabinoid type 1 (CB1) receptor activity declines with aging in the brain, which impairs neuronal network integrity and cognitive functions. However, the underlying mechanisms that link CB1 activity and memory decline remain unknown. Mitochondrial activity profoundly influences neuronal function, therefore age-dependent mitochondrial activity change is one of the known hallmarks of brain aging. As CB1 receptor is expressed on mitochondria and may regulate neuronal energy metabolism in hippocampus, we hypothesized that CB1 receptors might influence mitochondria in hippocampal neurons. We found that CB1 receptor significantly affected mitochondrial autophagy (mitophagy) and morphology in an age-dependent manner. We also found that Serine 65-phosphorylated ubiquitin, a key marker for mitophagy, was reduced in adult CB1-deficient mice (CB1-KO) compared to those in wild type controls, particularly in CA1 pyramidal cell layer. Transmission electron microscopy (TEM) analysis showed reduced mitophagy-like events in hippocampus of adult CB1-KO. TEM analysis also showed an increase in thin and elongated mitochondria in hippocampal neurons of adult CB1-KO. 3D reconstruction revealed that mitochondrial morphology in adult CB1-KO was altered as represented by an enhanced density of elongated and interconnected mitochondria. Altogether, these findings suggest that reduced CB1 signaling in CB1-KO mice leads to reduced mitophagy and abnormal mitochondrial morphology in hippocampal neurons during aging. These mitochondrial changes might be due to the impairments in mitochondrial quality control system, which links age-related decline in CB1 activity and impaired memory. Hepatitis B virus (HBV) approximately infects 350 million people. Interleukin-17 (IL-17) as a pro-inflammatory cytokine, have been found to modulate the immune system in infectious and inflammatory diseases. Recently, the influence of genetic changes like single nucleotide polymorphisms (SNP) on expression rate and function of cytokine has been widely investigated. This study was performed to determine any possible association between four IL-17 SNPs (rs2397084, rs763780, rs2275913 and rs10484879) and chronic HBV infection. A total of 466 samples were recruited and studied including 199 chronic patients, 172 healthy controls and 95 spontaneous clearance individuals between genotype and allele frequencies. Genomic DNA was extracted from peripheral blood cells and Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) was used to determine the SNPs genotypes. Genotypes frequencies for rs10484879 were 63.8% CC, 31.7% AC, 4.5% AA in chronic group, 54.7% CC, 36.6% AC, 8.7% AA in control and 63.2% CC, 33.7% AC, 5.8% AA in cleared samples. The AC genotype for rs10484879 was significantly associated with a decreased risk of HBV chronicity (Pvalue = 0.031, OR = 2.699, 95%CI 1.097-6.639). The genotype and allele frequencies of rs2397084, rs763780 and rs2275913 did not show significant difference between chronic HBV patients and healthy controls. Indeed, there is no significant difference between clearance and chronic patient's genotypes in four SNPs. Our results suggest that IL-17A rs10484879 single nucleotide polymorphism genotype is probably associated with susceptibility to HBV chronic infection, while no significant differences in IL-17 rs2397084, rs763780 and rs227591 distribution were found between HBV patients and spontaneous clearance individuals and control participants.