Lindhardtwarren6648

Thus, all steps in sodium taste signaling are voltage driven and independent of Ca2+ signals. This work also reveals ENaC-independent salt attraction. RNA polymerase II (RNAPII) transcription is governed by the pre-initiation complex (PIC), which contains TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, RNAPII, and Mediator. After initiation, RNAPII enzymes pause after transcribing less than 100 bases; precisely how RNAPII pausing is enforced and regulated remains unclear. To address specific mechanistic questions, we reconstituted human RNAPII promoter-proximal pausing in vitro, entirely with purified factors (no extracts). TBR-652 As expected, NELF and DSIF increased pausing, and P-TEFb promoted pause release. Unexpectedly, the PIC alone was sufficient to reconstitute pausing, suggesting RNAPII pausing is an inherent PIC function. In agreement, pausing was lost upon replacement of the TFIID complex with TATA-binding protein (TBP), and PRO-seq experiments revealed widespread disruption of RNAPII pausing upon acute depletion (t = 60 min) of TFIID subunits in human or Drosophila cells. These results establish a TFIID requirement for RNAPII pausing and suggest pause regulatory factors may function directly or indirectly through TFIID. BACKGROUND Rhabdomyosarcoma (RMS) is a rare malignant tumour originating from striated muscle cells; it accounts for only 3% of all soft tissue sarcomas in adults and its metastases can also reach the central nervous system. Only sporadic cases of primary brain RMS (PBRMS) have been reported so far. CASE PRESENTATION We discuss the atypical presentation and diagnostic challenge of PBRMS in a 65-year-old man. He presented with a 3-day history of progressive right hemiparesis caused by an unspecific left fronto-parietal heterogeneously enhancing lesion. Total body CT and Positron Emission Tomography (PET) scans performed at baseline did not reveal other secondarisms. Patient underwent radical excision of the lesion, which allowed to establish the diagnosis, with immunohistochemical staining positive for desmin and myogenin. Stereotactic radiotherapy guaranteed local disease control; nonetheless the patient required also adjuvant chemotherapy when he developed large right lung metastases 6-months postoperatively. CONCLUSIONS PBRMS can be hardly distinguished from other malignant brain tumours during preoperative radiologic workup; only histology can raise the suspicion of primary or metastatic rhabdomyosarcoma, depending on the presence of other distant lesions. Our review of the literature demonstrates that prognosis is poor 44% of patients die within one year from diagnosis. Overall survival seems to correlate with radical resection, tolerance of stereotactic or if necessary full neuraxis radiotherapy and adjuvant chemotherapy. Given the high relapse rate close monitoring and re-staging are imperative. A 56 years old man presented with a history of chronic headaches and dysarthria with tongue deviation to the right. MRI showed a lesion at the craniocervical junction with imaging characteristics compatible with chordoma. Endoscopic endonasal resection was followed by proton beam therapy. Recurrence of the chordoma was subsequently resected via far lateral approach again followed by proton beam therapy accumulating a total dose of 75 grays. Unfortunately, this led to osteoradionecrosis of the skull base resulting in a CSF leak more than one year after treatment. Following multiple failed attempts to seal the defect using local vascularized tissue and free fat grafts, the defect was reconstructed with a vastus lateralis free tissue transfer. Six weeks later, the flap had mucosalized, the patient was pain free and there was no evidence of a CSF leak. In select cases, vascularized free flaps offer a superior reconstruction for osteoradionecrosis, as radiotherapy often compromises the blood supply of local tissues. INTRODUCTION Intracranial arteriovenous malformations (AVMs) have been considered congenital. We present and discuss a case of a child who had no evidence of an AVM at 6 years of age when presenting with parenchymatous hemorrhage due to cavernous angioma and who developed the lesion during 10 years of follow-up. CASE DESCRIPTION A 6-year-old female presented with parenchymatous hemorrhage and was diagnosed with cavernous angioma of the right occipital lobe. She was treated with lesion removal and remained asymptomatic during the initial follow-up. At age 16, she presented to the emergency department with a new-onset headache. A new magnetic resonance imaging scan was performed and revealed an AVM in the right temporal lobe, which was confirmed with digital subtraction angiography (DSA). The AVM had not been present 10 years earlier, as seen on the previous DSA and MRI exams. CONCLUSIONS Based on recent findings of de novo AVMs and on the current theory of a postnatal origin of AVMs, we propose that AVMs cannot always be considered congenital and that several factors can contribute to their pathogenesis. BACKGROUND Numerous randomized controlled trials have shown that endovascular mechanical thrombectomy (MT) is an effective treatment for large vessel ischemic stroke. This study examines variation in rates of MT across the United States by geographical region and urban-rural areas to identify utilization disparities. METHODS Data from the Global Burden of Disease Collaborative Network was used to determine acute ischemic stroke (AIS) incidence by state for 2016. The 2016 National Inpatient Sample (NIS) was accessed to identify patients who underwent MT and patients who were diagnosed with cerebral infarct due to thrombosis or embolism of anterior circulation arteries representing the AIS population of interest. NIS data was used to create national weighted estimates of the size of subject populations, age at admission, length of stay, and discharge status. RESULTS In the US, approximately 13,010 mechanical thrombectomies were performed in 2016, representing 3.1% of the AIS population. Proportions of patients undergoing MT were highest in large central metropolitan areas and lowest in rural settings when compared to the national estimate. East North Central and West South Central regions had significantly lower proportions of MT patients. Discharge destinations, a proxy for clinical outcome, differed significantly by region and urban-rural designation. CONCLUSIONS The number of MTs performed in 2016 increased approximately 1.3 times from 2015. Considering that 10-17% of AIS patient may be MT-eligible, current rates of MT are low across all regions, but the most pronounced disparities and poorer clinical outcomes occur in rural areas, particularly in the northeast/southwest regions of the Midwest.