Comparison of Transcallosal Inhibition Between Hemispheres and Its Relationship with Motor Behavior in Patients with Severe Upper Extremity Impairment After Subacute Stroke

ObjectiveTo compare corticospinal excitability and transcallosal inhibition between contralesional primary motor cortex (M1) and ipsilesional M1. We also investigated the correlation between transcallosal inhibition and upper extremity motor behavior.Materials and methods19 individuals with unilateral ischemic subacute stroke who had severe upper extremity impairment participated in this study. Corticospinal excitability was assessed by measuring the resting motor threshold, active motor threshold and motor evoked potential amplitude. Transcallosal inhibition was investigated by measuring the duration and depth of the ipsilateral silent period (ISP). The data from the two hemispheres were compared and the relationships of transcallosal inhibition with upper extremity motor impairment, grip strength and pinch strength were analyzed.ResultsResting motor threshold (p = 0.001) and active motor threshold (p = 0.001) were lower and motor evoked potential amplitude was higher (p = 0.001) in the contralesional M1 compared to the ipsilesional M1. However, there were no differences between the two M1s in ISP duration (p = 0.297) or ISP depth (p =0. 229). Transcallosal inhibition from the contralesional M1 was positively associated with motor impairment (ISP duration, p = 0.003; ISP depth, p = 0.017) and grip strength (ISP duration, p = 0.016; ISP depth, p = 0.045).ConclusionsSymmetric transcallosal inhibition between hemispheres and positive association of transcallosal inhibition from contralesional M1 with upper extremity motor behavior indicate that recruitment of contralesional M1 may be necessary for recovery in patients with severe upper extremity impairment after subacute ischemic stroke.     

Prenatal diagnosis of mosaicism for a distal 5p deletion in a single colony at amniocentesis in a pregnancy with a favorable outcome and a review of mosaic distal 5p deletion

ObjectiveWe present prenatal diagnosis of mosaicism for a distal 5p deletion in a single colony at amniocentesis with a favorable outcome, and we review the literature of mosaic distal 5p deletion.Case ReportA 35-year-old primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed the result of 46,XY,del(5)(p13)[1]/46,XY[19]. Among 20 colonies of cultured amniocytes, all four cells in one colony had a karyotype of 46,XY,del(5)(p13) with a distal deletion of 5p13→pter, while the rest 19 colonies had a karyotype of 46,XY. Repeat amniocentesis was performed at 21 weeks of gestation. Conventional cytogenetic analysis revealed a karyotype of 46,XY in all 20 colonies. Simultaneous array comparative genomic hybridization (aCGH) using the DNA extracted from the uncultured amniocytes revealed no genomic imbalance. Prenatal ultrasound findings were unremarkable. At 38 weeks of gestation, a 3621-g male baby was delivered with no phenotypic abnormality. The cord blood had a karyotype of 46,XY. Postnatal urinary cells analysis by interphase fluorescence in situ hybridization (FISH) using a 5p terminal FISH probe detected no abnormal cell in the urine.ConclusionMosaicism for a distal 5p deletion in a single colony at amniocentesis can be associated with a favorable outcome.     

An investigation to determine the normal 1st to 5th metatarsal peak pressure and PTI ratio of the forefoot

BackgroundThe foot support has been described as that of a tripod. Biomechanical studies often report on peak pressures and pressure time integrals under specific areas of the foot. Reference needs to be made to the normal tripod distribution especially in the forefoot. In the forefoot the ratio between the 1st metatarsal and the 5th metatarsal on the medial and lateral columns of the foot respectively provide an excellent reference especially if the normal ratio is known. This study provides conclusive evidence of the 1st to 5th metatarsal ratio for peak pressures and pressure time integrals in the normal foot to be used as a reference.MethodsA group of normal healthy volunteers (n = 12) and a group of patients with unilateral end stage hallux rigidus (n = 17) were recruited. Repeated measures of 1st and 5th metatarsal peak pressures and Pressure time integrals were measured to determine reliability of measurement and to provide a reference normal ratio.ResultsIn the healthy volunteer group, the 1st/5th metatarsal ratio for PTI was very close to 1 while it was just over 1.5 for peak pressure. In patients with unilateral end stage hallux rigidus, in the normal foot the 1st/5th metatarsal ratio for PP and PTI was very close to 1. These ratios were reproduced in the operated foot following 1st MTPJ replacement.ConclusionThis study using normal healthy volunteers and patients undergoing 1st MTPJ replacement has demonstrated that the normal 1st/5th metatarsal peak pressure and pressure time integrals should be close to 1.     

Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms. Using differential centrifugation, EVs were isolated from established sorafenib-resistant RCC cells (786-0 and ACHN), and EVs derived from sorafenib-resistant cells were uptaken by sensitive parental RCC cells and thus promoted drug resistance. Elevated exogenous miR-31-5p within EVs effectively downregulated MutL homolog 1 (MLH1) expression and thus promoted sorafenib resistance in vitro. Mice experiments also confirmed that miR-31-5p could mediate drug sensitivity in vivo. In addition, low expression of MLH1 was observed in sorafenib-resistant RCC cells and upregulation of MLH1 expression restored the sensitivity of resistant cell lines to sorafenib. Finally, miR-31-5p level in circulating EVs of RCC patients with progressive disease (PD) during sorafenib therapy was higher when compared to that in the pretherapy status. In conclusion, EVs shuttled miR-31-5p can transfer resistance information from sorafenib-resistant cells to sensitive cells by directly targeting MLH1, and thus magnify the drug resistance information to the whole tumor. Furthermore, miR-31-5p and MLH1 could be promising predictive biomarkers and therapeutic targets to prevent sorafenib resistance.