Background We sought to find the therapeutic effect of 5Hz high‐frequency repetitive transcranial magnetic stimulation (rTMS) over the unaffected pharyngeal motor cortex in post‐stroke dysphagic ...patients.
Methods Eighteen patients with unilateral hemispheric stroke oropharyngeal dysphagia that lasted more than 1 month were randomly divided into two groups. They all performed videofluoroscopic swallowing study (VFSS) before rTMS intervention. The experimental group (EG) received 5Hz rTMS over contra‐lesional pharyngeal motor cortex for 10 min per day for 2 weeks. The control group (CG) received sham stimulation under the same condition. Videofluoroscopic swallowing study were performed again just after treatment cessation and 2 weeks afterward. The evaluation was performed using videofluoroscopic dysphagia scale (VDS) and penetration‐aspiration scale (PAS).
Key Results Mean baseline VDS and PAS of EG was 33.6 ± 12.1 and 3.41 ± 2.32 respectively and the scores were reduced to 25.3 ± 9.8 and 1.93 ± 1.52 just after 2 weeks intervention (P < 0.05). This effect lasted for up to 2 weeks after treatment. However, there was no change in the CG. Baseline prevalence of aspiration, pharyngeal residue, delayed triggering of pharyngeal swallowing and abnormal pharyngeal transit time (PTT) in EG was 66.7%, 66.7%, 33.3%, and 44.4%, respectively. After rTMS, the prevalence of aspiration and pharyngeal residue was reduced to 33.3% and 33.3%, respectively. However, the prevalence of delayed triggering and abnormal PTT was not changed.
Conclusions & Inferences A 5Hz high‐frequency rTMS on contra‐lesional pharyngeal motor cortex might be beneficial for post‐stroke dysphagic patients. This intervention can be used as a new treatment method in post‐stroke patients with dysphagia.
This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer ...(NSCLC) patients who have progressed on, or were intolerant to, crizotinib.
ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic ALK-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary end point was investigator-assessed progression-free survival (PFS).
Altogether, 107 patients were randomized (alectinib, n = 72; chemotherapy, n = 35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months 95% confidence interval (CI): 6.9–12.2 with alectinib and 1.4 months (95% CI: 1.3–1.6) with chemotherapy hazard ratio (HR) 0.15 (95% CI: 0.08–0.29); P < 0.001. Independent Review Committee-assessed PFS was also significantly longer with alectinib HR 0.32 (95% CI: 0.17–0.59); median PFS was 7.1 months (95% CI: 6.3–10.8) with alectinib and 1.6 months (95% CI: 1.3–4.1) with chemotherapy. In patients with measurable baseline central nervous system (CNS) disease (alectinib, n = 24; chemotherapy, n = 16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P < 0.001). Grade ≥3 adverse events were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 weeks versus 6.0 weeks).
Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.
ClinicalTrials.gov NCT02604342; Roche study MO29750
In this Letter, we demonstrate highly efficient, polarization-insensitive planar lenses (metalenses) at red, green, and blue wavelengths (λ = 660, 532, and 405 nm). Metalenses with numerical ...apertures (NA) of 0.85 and 0.6 and corresponding efficiencies as high as 60% and 90% are achieved. These metalenses are less than 600 nm-thick and can focus incident light down to diffraction-limited spots as small as ∼0.64λ and provide high-resolution imaging. In addition, the focal spots are very symmetric with high Strehl ratios. The single step lithography and compatibility with large-scale fabrication processes make metalenses highly promising for widespread applications in imaging and spectroscopy.
Tooth extraction results in alveolar bone resorption and is accompanied by postoperative swelling and pain. Maresin 1 (MaR1) is a proresolving lipid mediator produced by macrophages during the ...resolution phase of inflammation, bridging healing and tissue regeneration. The aim of this study was to examine the effects of MaR1 on tooth extraction socket wound healing in a preclinical rat model. The maxillary right first molars of Sprague-Dawley rats were extracted, and gelatin scaffolds were placed into the sockets with or without MaR1. Topical application was also given twice a week until complete socket wound closure up to 14 d. Immediate postoperative pain was assessed by 3 scores. Histology and microcomputed tomography were used to assess socket bone fill and alveolar ridge dimensional changes at selected dates. The assessments of coded specimens were performed by masked, calibrated examiners. Local application of MaR1 potently accelerated extraction socket healing. Macroscopic and histologic analysis revealed a reduced soft tissue wound opening and more rapid re-epithelialization with MaR1 delivery versus vehicle on socket healing. Under micro–computed tomography analysis, MaR1 (especially at 0.05 μg/μL) stimulated greater socket bone fill at day 10 as compared with the vehicle-treated animals, resulting in less buccal plate resorption and a wider alveolar ridge by day 21. Interestingly, an increased ratio of CD206+:CD68+ macrophages was identified in the sockets with MaR1 application under immunohistochemistry and immunofluorescence analysis. As compared with the vehicle therapy, local delivery of MaR1 reduced immediate postoperative surrogate pain score panels. In summary, MaR1 accelerated extraction wound healing, promoted socket bone fill, preserved alveolar ridge bone, and reduced postoperative pain in vivo with a rodent preclinical model. Local administration of MaR1 offers clinical potential to accelerate extraction socket wound healing for more predictable dental implant reconstruction.
Aims
The leucine‐rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a ...gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature.
Methods
We generated PD patient‐specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three‐dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses.
Results
The expression profiles of LK2GS were distinct from those of wild‐type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD‐specific hNESs and hIOs by microarray and qRT‐PCR analysis.
Conclusion
We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids.
Using three dimensional neural and intestinal organoids derived from induced pluripotent stem cells carrying a LRRK2 G2019S mutation and wild‐type controls has demonstrated differential gene expression implicating several cellular pathways in the pathogenesis of Parkinson's disease.
Contact angle hysteresis is an important physical phenomenon. It is omnipresent in nature and also plays a crucial role in various industrial processes. Despite its relevance, there is a lack of ...consensus on how to incorporate a description of contact angle hysteresis into physical models. To clarify this, starting from the basic definition of contact angle hysteresis, we introduce the formalism and models for implementing contact angle hysteresis into relevant physical phenomena. Furthermore, we explain the influence of the contact angle hysteresis in physical phenomena relevant for industrial applications such as sliding drops, coffee stain phenomenon (in general evaporative self-assembly), and curtain and wire coating techniques.
Background and purpose
Patients with the cerebellar variant of multiple system atrophy (MSA‐C) often show cognitive deficits in various cognitive domains. The association between morphometric changes ...in cortical and subcortical structures and cognitive impairments in MSA‐C were investigated to explore the neural correlates responsible for cognitive deficits in MSA‐C patients.
Methods
Using surface‐based morphometry, region‐of‐interest cortical thickness and the volumes and shapes of subcortical structures were examined in 18 patients who fulfilled the criteria of probable MSA‐C and were compared to 50 healthy controls. The association between regional changes and cognitive functions in MSA‐C were investigated by applying linear regression analyses after controlling for confounding factors.
Results
Compared with controls, the patients with MSA‐C showed significant cortical thinning in the fronto‐temporo‐parietal regions and volume reduction in subcortical structures with shape changes. Cerebellar volume had no significant effect on cortical and subcortical volumes. The severity of atrophic changes in the bilateral thalamus, the left cerebellum and the left pericalcarine gyrus were significantly correlated with attentional, executive and visuospatial dysfunctions.
Conclusion
Cognitive impairment in MSA‐C might result from functional disruption of the corticostriatal and pontocerebellar circuit mediated by primary cortical, cerebellar or thalamic pathology.
An international group of neurologists and radiologists developed revised guidelines for standardized brain and spinal cord MR imaging for the diagnosis and follow-up of MS. A brain MR imaging with ...gadolinium is recommended for the diagnosis of MS. A spinal cord MR imaging is recommended if the brain MR imaging is nondiagnostic or if the presenting symptoms are at the level of the spinal cord. A follow-up brain MR imaging with gadolinium is recommended to demonstrate dissemination in time and ongoing clinically silent disease activity while on treatment, to evaluate unexpected clinical worsening, to re-assess the original diagnosis, and as a new baseline before starting or modifying therapy. A routine brain MR imaging should be considered every 6 months to 2 years for all patients with relapsing MS. The brain MR imaging protocol includes 3D T1-weighted, 3D T2-FLAIR, 3D T2-weighted, post-single-dose gadolinium-enhanced T1-weighted sequences, and a DWI sequence. The progressive multifocal leukoencephalopathy surveillance protocol includes FLAIR and DWI sequences only. The spinal cord MR imaging protocol includes sagittal T1-weighted and proton attenuation, STIR or phase-sensitive inversion recovery, axial T2- or T2*-weighted imaging through suspicious lesions, and, in some cases, postcontrast gadolinium-enhanced T1-weighted imaging. The clinical question being addressed should be provided in the requisition for the MR imaging. The radiology report should be descriptive, with results referenced to previous studies. MR imaging studies should be permanently retained and available. The current revision incorporates new clinical information and imaging techniques that have become more available.
We investigate fast-pulse switching of in-plane-magnetized magnetic tunnel junctions (MTJs) within 3-terminal devices in which spin-transfer torque is applied to the MTJ by the giant spin Hall ...effect. We measure reliable switching, with write error rates down to 10–5, using current pulses as short as just 2 ns in duration. This represents the fastest reliable switching reported to date for any spin-torque-driven magnetic memory geometry and corresponds to a characteristic time scale that is significantly shorter than predicted possible within a macrospin model for in-plane MTJs subject to thermal fluctuations at room temperature. Using micromagnetic simulations, we show that in the three-terminal spin-Hall devices the Oersted magnetic field generated by the pulse current strongly modifies the magnetic dynamics excited by the spin-Hall torque, enabling this unanticipated performance improvement. Our results suggest that in-plane MTJs controlled by Oersted-field-assisted spin-Hall torque are a promising candidate for both cache memory applications requiring high speed and for cryogenic memories requiring low write energies.
To determine the immediate and long-term therapeutic efficacies of Gufoni and head-shaking maneuvers in apogeotropic type of benign paroxysmal positional vertigo involving the horizontal semicircular ...canal (HC-BPPV), a randomized, prospective, sham-controlled study was conducted.
In 10 nationwide dizziness clinics in Korea, 157 consecutive patients (95 women, age range: 18-89 years, mean age ± SD = 59.9 ± 13.6) with apogeotropic HC-BPPV were randomized to Gufoni (n = 52), head-shaking (n = 54), or sham maneuver (n = 51). For Gufoni maneuver, patients underwent ipsilesional side-lying and upward head-turn for migration of the debris toward the vestibule. Immediate responses were determined within 1 hour after a maximum of 2 trials of each maneuver and in the following day. The patients also had weekly follow-ups for 1 month after the initial maneuver.
After a maximum of 2 maneuvers on the initial visit day, Gufoni (38/52, 73.1%) and head-shaking (33/53, 62.3%) maneuvers showed better responses than the sham maneuver (17/49, 34.7%). The cumulative therapeutic effects were also better with Gufoni (p < 0.001) and head-shaking (p = 0.026) maneuvers compared with the sham maneuver. However, therapeutic efficacies did not differ between the Gufoni and head-shaking groups in terms of both immediate (p = 0.129) and long-term (p = 0.239) outcomes.
Using a prospective randomized trial, we demonstrated that the Gufoni and head-shaking maneuvers are effective in treating apogeotropic HC-BPPV.
This study provides Class II evidence that Gufoni and head-shaking maneuvers are effective in treating apogeotropic horizontal BPPV up to 1 month after initial treatment.
NCT00810641.
PDF
