Ennisli5960

CIE exposure increased GluN2B subunit-dependent NMDAR function of PNCs. This was associated with the loss of both ethanol- and CRF-mediated NMDAR inhibition, and loss of stress-induced short-term potentiation of glutamatergic synaptic inputs, which could be reversed by intracellular blockade of NMDARs with MK801. CIE exposure also blunted the hormonal and self-grooming behavioral responses to repeated restraint stress. These findings suggest a cellular mechanism whereby chronic alcohol dysregulates the hormonal and behavioral responses to repetitive stressors by increasing NMDAR function and decreasing CRFR1 function. INTRODUCTION Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare lung disease associated with proliferation of neuroendocrine cells in the lung and multifocal neuroendocrine tumorlets/tumors. Although usually considered an indolent condition, DIPNECH causes chronic, progressive cough and dyspnea which can adversely impact quality of life. There is very limited information on the treatment of this condition. AIMS To assess changes in symptoms as well as pulmonary function tests (PFTs) in response to somatostatin analog (SSA) treatment. METHODS Patients with clinical and/or pathological diagnosis of DIPNECH and chronic respiratory symptoms were treated with SSAs at the Moffitt Cancer Center, Hadassah Medical Center, and Mayo Clinic. Their charts were reviewed to assess changes in symptoms and pulmonary function tests. RESULTS 42 patients were identified who had either chronic cough or dyspnea due to proven or suspected DIPNECH and who had received treatment with an SSA. 33 patients experienced symptomatic improvement. Additionally, 14 out of 15 patients in whom PFTs were checked were noted to have an improvement in FEV1 following treatment. CONCLUSIONS SSA treatment can improve chronic respiratory symptoms and PFTs in patients with DIPNECH. Signs of both motor and sensory nervous lesions have previously been shown in the upper airway of obstructive sleep apnea (OSA) patients and habitual snorers. HYPOTHESIS snoring per se may damage all upper airway neurons over time, thereby causing progression to manifest sleep apnea. To test this, non-snoring subjects, untreated snorers and CPAP-treated patients underwent repeated sensory testing in the soft palate in a prospective long-term study. METHODS Cold detection threshold (CDT) testing at soft palate and lip with a thermode and nocturnal respiratory recordings were performed in 2008/2009 with retesting 6 -7 years later. RESULTS In 25 untreated snorers palatal CDT worsened from median 4.2 °C (3,2 - 5,9) to 11.0 °C (7,0 - 17,4) (p less then 0.001). AHI increased from median 7.0 to 14.0/h (p less then 0.05. In 21 non-snoring control subjects palatal CDT increased from median 3.2 °C to 5.6 °C (p less then 0.005). There was a significant correlation between changes in CDT and AHI. In 19 CPAP-treated patients palatal CDT did not significantly change; 8 patients had improved values. CDT worsened significantly more in the snorers group than in both controls (p less then 0.05) and CPAP patients (p less then 0.001). There was no significant difference between controls and CPAP-patients. CONCLUSIONS CDT worsened considerably over time in untreated snorers, significantly more than non-snoring controls and CPAP-patients. Untreated snorers therefore risk developing poor sensitivity in the upper airway. In contrast, efficient treatment of OSA seems to protect the sensory innervation, since the CPAP-treated group maintained their sensitivity to cold, and in some cases, the sensitivity even improved. Idiopathic inflammatory myopathies are autoimmune processes that are characterized by skeletal muscle inflammation. The lung is the most commonly involved extramuscular organ, and, when present, pulmonary disease drives morbidity and mortality. A subset of patients can present with rapidly progressive hypoxemic respiratory failure due to myositis-related interstitial lung disease. Confirmatory autoantibody testing requires sending samples to a reference laboratory; thus, diagnosis of rapidly progressive myositis-associated interstitial lung disease relies on a high index of suspicion and careful history and physical examination. Although the cornerstone of therapy for these patients remains multimodality immunosuppression, emerging data support a role for advanced therapies (including extracorporeal membrane oxygenation and lung transplantation) in appropriately selected patients. PPAR antagonist It is hoped that greater awareness of the clinical features of this syndrome will allow for appropriate diagnosis and treatment of these potentially treatable patients, as well as raise awareness of the need for multicenter collaboration to prospectively study how to manage this complex disease. CONTEXT Neoadjuvant chemotherapy (NAC) is considered the standard treatment for muscle-invasive bladder cancer (MIBC). However, its overall survival benefit is limited and toxicity is significant; hence, NAC has not been adopted universally. OBJECTIVE To systematically evaluate whether biomarkers can guide the administration of perioperative chemotherapy in MIBC patients. EVIDENCE ACQUISITION A systematic search of the PubMed database was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). In total, 215 papers were screened and 22 were selected to assess the potential clinical value of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in selecting MIBC patients for perioperative chemotherapy. EVIDENCE SYNTHESIS We found that the presence of one or more CTCs before radical cystectomy, as determined by the CellSearch technique, is a robust marker for poor recurrence-free and overall survival. Consequently, whether NAC can be withheld in patients without the presence of CTCs is a subject of ongoing investigation. Studies investigating various approaches to detect cfDNA showed that cfDNA is present in the blood of MIBC patients, but varying results on its prognostic value have been reported. Successful cfDNA-based approaches are likely to encompass at least a multitude of genes using next-generation sequencing, as there are generally few hotspot somatic mutations in MIBC. CONCLUSIONS Liquid biopsies hold promise in selecting MIBC patients for perioperative chemotherapy, but instead of more proof-of-principle studies, prospective studies investigating true clinical applicability for treatment decision making are urgently needed. PATIENT SUMMARY Liquid biopsies appear to be a promising tool to guide the administration of chemotherapy in patients with muscle-invasive bladder cancer; however, the optimal way to implement these remains to be determined.