Munnherskind9389

BACKGROUND Bcl6 is required for the development of T follicular helper and regulatory (Tfh, Tfr) cells that regulate germinal center responses. Bcl6 also impacts the function of regulatory T (Treg) cells. OBJECTIVE The goal of this study is to define the functions of Bcl6 in Treg cells including Tfr cells in the context of allergic airway inflammation (AAI). METHODS We employed a model of house dust mite (HDM) sensitization to challenge wild type, Bcl6fl/fl Foxp3-Cre and Prdm1(Blimp1)fl/fl Foxp3-Cre mice to study the reciprocal roles of Bcl6 and Blimp1 in AAI. RESULTS In the HDM model, Tfr cells repress the production of IgE and Bcl6+ Treg cells suppress the generation of type 2 cytokine producing cells in the lungs. In mice with Bcl6-deficient Treg cells, twice as many ST2 (IL-33R)+ Tregs develop as observed in wild type mice. ST2+ Tregs in the context of AAI are Blimp1-dependent, express type 2 cytokines, and share features of visceral adipose tissue Treg cells. Bcl6-deficient Tregs are more susceptible, and Blimp1-deficient Tregs are resistant, to acquiring the ST2+ Treg cell phenotype in vitro and in vivo in response to IL-33. Bcl6-deficient ST2+ Tregs but not Bcl6-deficient ST2+ T conventional cells strongly promote AAI when transferred into recipient mice. Lastly, ST2 is required for the exacerbated AAI in Bcl6fl/fl Foxp3-Cre mice. CONCLUSIONS During AAI, Bcl6 and Blimp1 play dual roles in regulating Tfr activity in the germinal center and in the development of ST2+ Tregs that promote type 2 cytokine responses. Most of what is known on vascular brain-derived neurotrophic factor (BDNF) derived from experiments on cultured endothelial cells. Therefore, the present study compared BDNF levels/localization in artery (aorta) vs vein (vena cava) from a same territory in rats either sedentary (SED) or exposed to treadmill exercise (EX) as a mean to stimulate endogenous endothelial nitric oxide (NO) production. In SED rats, for both artery and vein, BDNF was strongly expressed by endothelial cells, while only a faint and scattered expression was observed throughout the media. Endothelial and muscular BDNF staining as vascular BDNF protein levels were however higher in artery than in vein, while BDNF mRNA levels did not differ between vessels. Irrespective of the vessels, EX resulted in an increase (+50%) in BDNF protein levels with no change in BDNF mRNA levels, a selective endothelial BDNF overexpression (x4) and an increase in vascular levels of tropomyosin related kinase B receptors (TrkB) phosphorylated at tyrosine 816 (p-TrkBTyr816). Endothelial expressions of BDNF and p-TrkBTyr816 were positively associated when SED and EX rats were simultaneously examined. The results incite to consider endothelial BDNF as a full and NO-dependent endothelium-derived factor that exerts autocrine effects. BACKGROUND CONTEXT Depression and anxiety are common psychiatric conditions among US adults, and anterior cervical discectomy and fusion (ACDF) is one of the most commonly performed spinal surgeries. Mental health conditions can affect physical health, and thus have the potential to contribute to adverse outcomes after spine surgery; however, a comprehensive assessment of long-term outcomes and the additive economic burden of these conditions in patients undergoing ACDF has not been well described. PURPOSE Our goal was to assess the associations between depression/anxiety and adverse outcomes and health-resource utilization after anterior cervical discectomy and fusion (ACDF). STUDY DESIGN Retrospective database study. Selleck CHIR-98014 PATIENT SAMPLE We retrospectively analyzed a private administrative health claims database to identify patients who underwent ACDF in the United States from 2010-2013. A total of 16,306 patients met our inclusion criteria. Mean (± standard deviation) patient age was 50 ± 7.9 years. Approximatelgnosis of anxiety had higher odds of multiday hospitalization (OR 1.15, 95% CI 1.06-1.25), revision surgery within 2 years (OR 1.33, 95% CI 1.07-1.65), and chronic postoperative opioid use (OR 1.62, 95% CI 1.48-1.77) and an increase of $4,471 in adjusted 2-year health care payments (p less then 0.001). Neither anxiety nor depression was associated with intensive care unit admission, discharge disposition, 30-day readmission, revision surgery within 1 year, 1-year cumulative health care payments, or cumulative postoperative opioid consumption. CONCLUSION Patients with preoperative diagnoses of depression or anxiety have a greater likelihood of adverse outcomes, increased opioid consumption, and increased cumulative health care payments after ACDF compared with patients without depression or anxiety. BACKGROUND CONTEXT Ligamentum flavum (LF) induced lumbar spinal stenosis (LSS) is conditioned not only by its "gathering" but especially by hypertrophy. Previous studies have examined the pathophysiology and biochemical changes that cause the hypertrophy. Some studies have described a link between chronic LF inflammation and neovascularization but others have reported highly hypovascular LF tissue in LSS patients. Currently, there is no practical application for our knowledge of the pathophysiology of the LF hypertrophy. Considerations for future treatment include influencing this hypertrophy at the level of tissue mediators, which may slow the development of LSS. To our knowledge, there is no study of micromechanical properties of native LF to date. PURPOSE 1) To clarify the changes in vascularization, chondroid metaplasia, and the presence of inflammatory cell infiltration in ligamentum flavum associated with lumbar spinal stenosis. 2) To quantify changes in the micromechanical properties associated with LFalthy ligaments were significantly stiffer than LSS ligaments. CLINICAL SIGNIFICANCE Prevention of the loss of LF vascularization during aging may influence stiffness of LF which in turn may slow down the LF degenerative processes and delay onset of LSS. BACKGROUND CONTEXT Following spine surgery, delays in referral to rehabilitation facilities leads to increased length of hospital stay (LOS), increases costs, more risk of hospital acquired complications, and decreased patient satisfaction. PURPOSE We sought to create a prediction calculator to determine the expected LOS after spine surgery and identify patients most likely to need postoperative non-home discharge. The goal would be to facilitate earlier referral to rehabilitation and thereby ultimately shorten LOS, reduce costs, and improve patient satisfaction. STUDY DESIGN Retrospective PATIENT SAMPLE We retrospectively reviewed all adult patients who underwent spine surgery for all indications between January and June 2018. OUTCOME MEASURES Length of stay and discharge disposition METHODS Demographic variables, insurance status, baseline comorbidities, narcotic use, operative characteristics, as well as postoperative length of stay and discharge disposition data were collected. Univariable and multivariable analyses were performed to identify independent predictors of LOS and discharge disposition.