Matzenpearson1892

Chronic ethanol increased CRF1+ neuronal excitability but did not significantly alter phasic or tonic GABA signaling in either CRF1+ or CRF1- cells. Chronic ethanol and withdrawal also did not alter basal extracellular GABA or glutamate transmitter levels in the LA/BLA and did not alter the sensitivity of GABA or glutamate to acute ethanol-induced increases in transmitter release. Together, these results provide the first characterization of the CRF1+ population of LA neurons and suggest mechanisms for differential acute ethanol sensitivity within this region. Copyright © 2020 Agoglia et al.The concept of chronic obstructive pulmonary disease (COPD) control has been proposed to guide treatment decisions in COPD. In this study, we aimed to validate the prospective value of this concept in the SPARK study population. Control was assessed based on COPD stability and impact. Patients with low impact and stability during weeks 1-12 were classified as controlled, and exacerbations were measured during a 52-week follow-up. Of the 2044 patients included a majority were non-controlled (80%), frequently due to high impact. see more During the follow-up, the rate of moderate/severe exacerbations was significantly lower in controlled patients (rate ratio, 0.56, 95% CI 0.48 to 0.65 p less then 0.0001) and time-to-first moderate/severe exacerbation was significantly delayed. This study demonstrated an association between control status and risk of exacerbations. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The FDA has approved tazemetostat for treating epithelioid sarcoma. The drug produced responses in 15% of patients with the disease in a phase II trial, and 67% of the responses lasted at least 6 months. The drug is the first targeted treatment for epithelioid sarcoma. ©2020 American Association for Cancer Research.OBJECTIVE Despite increases in STIs among those over 40, little is known about the social context of STI transmission among people experiencing relationship transition in midlife, and few sexual health promotion initiatives are targeted at this group. This study sought to identify factors shaping STI risk perceptions and practices among midlife individuals either contemplating or having sex with new partners following the end of a long-term relationship. METHODS Participants were purposively selected from respondents to Britain's third National Survey of Sexual Attitudes and Lifestyles, using three eligibility criteria aged 40-59, reported experience of the end of a marital or cohabiting relationship with an opposite-sex partner in the past 5 years, and willingness to participate in a qualitative interview. Qualitative data were generated via face-to-face interviews with 10 women and 9 men and analysed inductively using thematic analysis, with themes then organised using a socioecological framework. RESULTS Pe influences, on the navigation of sexual safety at this stage of life. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Breast cancer is a leading cause of death in women worldwide, but the underlying mechanisms of breast tumorigenesis remain unclear. Fructose-1, 6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor in breast cancer. However, the mechanisms of FBP1 as a tumor suppressor in breast cancer remain to be explored. Here we showed that FBP1 bound to Notch1 in breast cancer cells. Moreover, FBP1 enhanced ubiquitination of Notch1, further leading to proteasomal degradation via FBXW7 pathway. In addition, we found that FBP1 significantly repressed the transactivation of Notch1 in breast cancer cells. Functionally, Notch1 was involved in FBP1-mediated tumorigenesis of breast cancer cells in vivo and in vitro. Totally, these findings indicate that FBP1 inhibits breast tumorigenesis by regulating Notch1 pathway, highlighting FBP1 as a potential therapeutic target for breast cancer. IMPLICATIONS We demonstrate FBP1 as a novel regulator for Notch1 in breast cancer. ©2020 American Association for Cancer Research.A breadth of time, effort, and resources are put into research. Improvement science is an applied science emphasizing rapid-cycle testing to learn about change and produce improvement. Its foundations lie in understanding your system, its parts and their relationships, and the psychology of change, yet the framework of improvement science is analogous to basic research. In basic research you first ask a question, then form a hypothesis based on background research. After testing this hypothesis, a researcher then draws conclusions and shares the results. In improvement science, researchers start the same, with asking a question, and then defining what is considered an improvement. Rapid-cycle tests of change are guided by subject matter experts and the people and processes involved. The data provided from these tests of change allow researchers to show improvement and share results. The success of improvement science is showcased through statistical process control charts, which inform when significant change has occurred. Improvement science can be applied across all fields of medicine; is a natural partner to basic and clinical research, as it plays a vital role in the implementation and adoption of the best evidence. © American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.Acute flaccid myelitis, defined by acute flaccid limb weakness in the setting of grey matter lesions of the spinal cord, became increasingly recognised in 2014 following outbreaks in Colorado and California, temporally associated with an outbreak of enterovirus D68 respiratory disease. Since then, there have been biennial increases in late summer/early fall. A viral infectious aetiology, most likely enteroviral, is strongly suspected, but a definitive connection has yet to be established. Patients typically present with asymmetric weakness, maximal proximally, in the setting of a febrile illness. MRI demonstrates T2/FLAIR abnormalities in the central grey matter of the spinal cord, and cerebrospinal fluid typically shows a lymphocytic pleocytosis with variable elevation in protein. The weakness may be progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder involvement.