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Introduction: To test the hypothesis of impaired cholinergic activity in amyotrophic lateral sclerosis (ALS), we studied short- and long-latency afferent inhibition (SAI and LAI). Methods: The ulnar nerve was stimulated at the wrist preceding transcranial magnetic stimulation (TMS), 21 ms for SAI and 200 ms for LAI, in 21 patients and 17 control subjects. Short-interval intracortical inhibition (SICI) and cognitive function was assessed in ALS patients using automatic threshold tracking and the Montreal Cognitive Assessment (MoCA). Results: The SAI paradigm resulted in inhibition in all control subjects, whereas inhibition was observed in 13 of 21 (62%) patients. Mean SAI and LAI values were significantly reduced in ALS. No significant correlation existed between afferent inhibition and other neurophysiological data. The MoCA was normal in all but 1 patient. Discussion: LAI and SAI are both impaired in ALS, probably unrelated to increased cortical excitability or cognitive dysfunction. Muscle Nerve 59:699–704, 2019  相似文献   
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Aim of the workTo investigate promoter methylation of matrix metalloproteinase-3 (MMP-3) and interleukin-16 (IL-16) genes with the expression of miRNA-93-5p and miRNA-4668-5p which target these genes in rheumatoid arthritis (RA), respectively.Patients and methodsThe study included 49 RA patients and 38 healthy controls. Promoter methylation of MMP-3 and IL-16 was analyzed by methylation-specific PCR. The expression of miRNA-93-5p and miRNA-4668-5p were determined. Disease activity score (DAS28) was assessed.ResultsThe 49 patients (38 female, 11 male) mean age was 50.4 ± 10.5 years and disease duration of 9.1 ± 7.4 years. The mean DAS28 was 3.9 ± 1.4. The MMP-3 gene methylation frequency was significantly lower in patients (n = 37;75.5%) compared to control (n = 37;97.4%) (p = 0.004) while they were comparable for IL-16 gene (n = 46;93.9% vs n = 37;97.4%)(p = 0.45). The relative normalized expression of miRNA-93-5p and miRNA-4668-5p were significantly increased (p < 0.001) in patients (2.28 ± 3.71 and 2.47 ± 4.17-fold) compared to controls (1.12 ± 0.18 and 1.28 ± 0.53-fold) and both tended to decrease with high disease activity (r =  ? 0.104, p = 0.52; r = ?0.24, p = 0.15, respectively). There was no significant difference of miRNA-93-5p (p = 0.45), and miRNA-4668-5p (p = 0.26) expressions between patients receiving treatment and those not. A negative correlation was observed between disease activity and change in expression levels of miRNA-93-5p (r = ?0.104, p = 0.52) and miRNA-4668-5p (r = ?0.24, p = 0.15). The ROC curve analysis of target miRNAs showed the diagnostic potential of miRNA-93-5p and miRNA-4668-5p (p = 0.003 and p < 0.001 respectively).ConclusionsThe methylation status of MMP-3 promoter and expression levels of miRNA-93-5p and miRNA-4668-5p could be useful biomarkers for the pathogenesis of RA and might reflect disease activity.  相似文献   
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PurposeTo evaluate the efficacy and toxicity of hypofractionated radiotherapy in non-metastatic soft tissue and bone sarcomas.Patients and methodsThirty patients underwent hypofractionated radiotherapy between 2007 and 2015. Overall, 17 patients underwent primary hypofractionated radiotherapy, nine underwent hypofractionated radiotherapy for reirradiation, and four received a boost dose via hypofractionated radiotherapy after external beam radiotherapy. Most common disease sites were head and neck and retroperitoneum. Hypofractionated radiotherapy was administered with a definitive, adjuvant, or neoadjuvant intent.ResultsMedian age was 37 years (range: 11–82 years). Median hypofractionated radiotherapy dose was 35 Gy (range: 20–50 Gy) in three to five fractions. Median follow-up was 21 months (range: 1–108 months). One- and 2-year overall survival rate was 75% and 52%, respectively. One- and 2-year local recurrence-free survival rate was 59% and 48%, with local recurrence rates of 16% and 33% in 1 and 2 years, respectively. Univariate analysis revealed tumour size (P = 0.04), hypofractionated radiotherapy intent (P = 0.016) and reirradiation (P = 0.001) as prognostic factors for local recurrence-free survival. Severe late toxicity was observed in one patient as grade 3 trismus.ConclusionHypofractionated radiotherapy as the primary treatment or for reirradiation has been shown to be safe in the treatment of bone and soft tissue sarcomas. It can provide relatively good local control and survival rates.  相似文献   
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Context: To evaluate the stability provided by a new bilateral fixation technique using an in vitro investigation for posterior lumbar segmental instrumentation.

Design: Experimental cadaver study. In this study, we propose an alternative technique for a posterior lumbar fixation technique called “inferior-oblique transdiscal fixation” (IOTF).

Setting: Study performed at Engineering Center for Orthopedic Research Exellence (ECORE) in Toledo University-Ohio.

Participants: Six human lumbar cadaveric specimen used in this study.

Interventions: In this study, we propose an alternative technique for a posterior lumbar fixation technique called “inferior-oblique transdiscal fixation” (IOTF). As a novel contribution to the classical technique, the entry point of the screw is the supero-lateral point of the intersecting line drawn between the corpus and the pedicle of the upper vertebra. This approach enables the fixation of two adjacent vertebrae using a single screw on each side without utilizing connecting rods.

Outcome Measures: Flexion (Flex), extension (Ext), right and left lateral bending (LB & RB), and right and left axial rotation (LR & RR), and the position data were captured at each load step using the Optotrak motion measurement system and compared for IOTF and posterior transpedicular stabilization.

Results: The Posterior stabilization system (PSS) and IOTF significantly reduced the ROM of L4-L5 segment compared to intact segment’s ROM. During axial rotation (AR) IOTF fused index segment more than PSS. Besides this, addition of transforaminal lumbar interbody fusion (TLIF) cage improved the stabilization of IOTF system during flexion, extension and lateral bending. Whereas, PSS yielded better fusion results during extension compared to IOTF with and without interbody fusion cages.

Conclusions: We hypothesized that the new posterior bilateral system would significantly decrease motion compared to the intact spine. This cadaver study showed that the proposed new posterior fusion technique IOTF fused the index segment in a similar fashion to the classical pedicle screw fusion technique.  相似文献   
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Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.  相似文献   

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Purpose: To investigate the effects of dehydration due to fasting on diurnal changes of intraocular pressure, anterior segment biometrics, and refraction. Subjects and methods: The intraocular pressures, anterior segment biometrics (axial length: AL; Central corneal thickness: CCT; Lens thickness: LT; Anterior chamber depth: ACD), and refractive measurements of 30 eyes of 15 fasting healthy male volunteers were recorded at 8:00 in the morning and 17:00 in the evening in the Ramadan of 2013 and two months later. The results were compared and the statistical analyses were performed using the Rstudio software version 0.98.501. The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk test) to determine whether or not they were normally distributed. Results: The refractive values remained stable in the fasting as well as in the control period (p?=?0.384). The axial length measured slightly shorter in the fasting period (p?=?0.001). The corneal thickness presented a diurnal variation, in which the cornea measured thinner in the evening. The difference between the fasting and control period was not statistically significant (p?=?0.359). The major differences were observed in the anterior chamber depth and IOP. The ACD was shallower in the evening during the fasting period, where it was deeper in the control period. The diurnal IOP difference was greater in the fasting period than the control period. Both were statistically significant (p?=?0.001). The LT remained unchanged in both periods. Conclusions: The major difference was shown in the anterior chamber shallowing in the evening hours and IOP. Our study contributes the hypothesis that the posterior segment of the eye is more responsible for the axial length alterations and normovolemia has a more dominant influence on diurnal IOP changes.  相似文献   
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