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Stem cell-based treatments have emerged as potentially effective approaches to delay the progression of amyotrophic lateral sclerosis (ALS). This study was designed as a single-center, prospective, and open-label study without a placebo control group to assess the safety and efficacy of concurrent intrathecal (IT) and intravenous (IV) administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS. Autologous BM-MSCs were isolated and expanded under standard conditions. Fifteen patients were neurologically examined before BM-MSCs transplantation (1 × 10 6 cells/kg BW) to evaluate the rate of pre-treatment disease progression. To assess the safety and efficacy, patients were examined at 1, 3, and 6 months following the treatment with BM-MSCs. Adverse reactions were assessed, and the clinical outcome was determined by the evaluation of the ALS functional rating scale-revised (ALSFRS-R) and forced vital capacity (FVC). No serious adverse reaction was observed after combined IT and IV administration of BM-MSCs. The mean ALSFRS-R and FVC values remained stable during the first 3 months of the treatment. However, a significant reduction in ALSFRS-R and FVC levels was observed in these patients 6 months after BM-MSCs administration. Our study revealed that the concurrent IT and IV application of BM-MSCs in patients with ALS is a safe procedure. Furthermore, our data indicate a temporary delay in the progression of ALS after a single combined IT and IV administration of BM-MSCs. Further studies are required to explore if the repeated applications of BM-MSCs could prolong survival and delay the progression of ALS.

Because of reducing the number of spectators of football premier league, this study is seeking for identifying factors put the most impact on this decline. The statistical population consisted of all spectators in Iran football premier league in 2015-16, out of which 395 spectators were randomly selected as the research samples. The data were collected via a researcher-made questionnaire. The first part of the questionnaire included demographic information and the second part, at 6 aspects, includes 35 questions analyzing the reasons for reducing the number of spectators in Iran's football Premier League. For analyzing data, it was used from first and second order confirmatory factor analysis based on structural equations through using SPSS 20 and LISREL 8.8 software. The results of first order confirmatory factor analysis showed that the measurement model of factors affecting on reducing the number of spectators of football premier league is an appropriate model and model parameters are significant. All factors are approved as effective variables on reducing the number of spectators of football premier league. The results also showed that the second order measurement model of effective factors on reducing the number of spectators of football premier league are also appropriate, and economic, facilitative, administrative, technical, cultural-social, and personal-family respectively put the most effects on reducing the number of spectators of football premier league. It is suggested for the sport marketers to analyze identified factors in this research and develop applicable strategies and guidelines for them.

Introduction: Chronic inflammations including infectious disorders such as HIV infection are now considered as risk factors for atherosclerosis. In this study, conducted for the first time on human subjects, human T-lymphotropic virus type 1 (HTLV-1) infection was examined as a potential risk factor for atherosclerosis. Materials and Methods: This is a matched-pair cross-sectional study on 58 HTLV-1-infected cases and 55 healthy control subjects. The subjects did not have any major cerebrovascular risk factors. Carotid intima-media thickness (IMT) was measured for each patient using the standard protocol of the Atherosclerosis Risk in Communities (ARIC) Study. Results: The mean age of the subjects was 42.9 ± 10.52 years, and males made up 33% of the population. The difference between the mean IMT of the infected case group and that of the healthy control group was significant (p < 0.05). Discussion: This study indicated that the HTLV-infected individuals showed a greater carotid IMT than the age- and sex-matched control subjects. Observing no other known risk factor for atherosclerosis, we concluded that this significant difference in IMT might support the hypothesis that HTLV-1 infection is an independent risk factor for atherogenesis.

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability

Membranous calcium-sensing receptors (CaSR) on intestinal epithelial cells are difficult to study, due to fast loss of function following isolation of the cells. We established a chemical isolation process to maintain receptor function, being able to measure receptor-activity in a fluorescence spectrometry setup. In diarrhea, high intracellular concentrations of cyclic nucleotides in intestine epithelial cells lead to net fluid excretion due to enhanced serosal to mucosal fluid-transport. We showed earlier the reversibility of this effect via activation of CaSR with calcimimetic agents including natural and synthetic small molecules such as the compound R-568. Exposure to these allosteric modifiers in the presence of calcium resulted in a cessation of fluid excretion, and enhanced absorption. In the present study we develop a new isolation method for single cells of all intestinal segments and demonstrate that CaSR remains viable and active upon stimulationwith allostericmodifiers or by increasing the extracellular calcium concentration. These results give an important new tool for intestinal transport screening. METHODS We generated functional individual intestinal epithelial cells from the duodenum, jejunum, ileum and colon of female rats and human colon, using EDTA digestion solution and light mechanical force at 37°C for 20 minutes. Cells were loaded with 2nM Fluo-4 and Fluo-8, calcium-sensing fluorescent dyes. After multiple washout-steps and sedimentation for two hours, the activity of the CaSRwas determined, using a fluorescence spectrometer measuring the fluorescent excitation at 516nm. RESULTS We were able to show the functionality of epithelial CaSR on epithelial cells from four sections of the intestine of the rat: duodenum, jejunum, ileum and colon, and also human colon. The CaSR shows a dose dependent activation over a concentration range of 0.125mM to 2.5mM. The EC50 for calcium for the freshly isolated cells was comparable to that previously obtained for intact native tissue. In a separate study isolated cells were exposed to R-568 prior to the calcium dose curve, resulting in a left phase shift of the activation curve indicative of enhanced calcium binding to the receptor. CONCLUSION Our studies demonstrate that it is now possible to develop viable isolated cells from the entire digestive tract that maintain CaSR density. This technique provides an important new screening tool for use in testing pharmacological agents on intestinal epithelia.