Epigenetic histone modification by butyrate downregulates KIT and attenuates mast cell function.

Short-chain fatty acid butyrate is produced from the bacterial fermentation of indigestible fiber in the intestinal lumen, and it has been shown to attenuate lung inflammation in murine asthma models. Mast cells (MCs) are initiators of inflammatory response to allergens, and they play an important role in asthma. MC survival and proliferation is regulated by its growth factor stem cell factor (SCF), which acts through the receptor, KIT. It has previously been shown that butyrate attenuates the activation of MCs by allergen stimulation. However, how butyrate mechanistically influences SCF signalling to impact MC function remains unknown. Here, we report that butyrate treatment triggered the modification of MC histones via butyrylation and acetylation, and inhibition of histone deacetylase (HDAC) activity. Further, butyrate treatment caused downregulation of SCF receptor KIT and associated phosphorylation, leading to significant attenuation of SCF-mediated MC proliferation, and pro-inflammatory cytokine secretion. Mechanistically, butyrate inhibited MC function by suppressing KIT and downstream p38 and Erk phosphorylation, and it mediated these effects via modification of histones, acting as an HDAC inhibitor and not via its traditional GPR41 (FFAR3) or GPR43 (FFAR2) butyrate receptors. In agreement, the pharmacological inhibition of Class I HDAC (HDAC1/3) mirrored butyrate's effects, suggesting that butyrate impacts MC function by HDAC1/3 inhibition. Taken together, butyrate epigenetically modifies histones and downregulates the SCF/KIT/p38/Erk signalling axis, leading to the attenuation of MC function, validating its ability to suppress MC-mediated inflammation. Therefore, butyrate supplementations could offer a potential treatment strategy for allergy and asthma via epigenetic alterations in MCs.

Protein Kinase C α and ß compensate for each other to promote stem cell factor-mediated KIT phosphorylation, mast cell viability and proliferation.

Mast cells (MCs) develop from hematopoietic progenitors and differentiate into mature MCs that reside within connective or mucosal tissues. Though the number of MCs in tissues usually remains constant, inflammation and asthma disturb this homeostasis, leading to proliferation of MCs. Understanding the signaling events behind this proliferative response could lead to the development of novel strategies for better management of allergic diseases. MC survival, proliferation, differentiation, and migration are all maintained by a MC growth factor, stem cell factor (SCF) via its receptor, KIT. Here, we explored how protein kinase C (PKC) redundancy influences MC proliferation in bone marrow-derived MC (BMMC). We found that SCF activates PKCα and PKCß isoforms, which in turn modulates KIT phosphorylation and internalization. Further, PKCα and PKCß activate p38 mitogen activated protein kinase (MAPK), and this axis subsequently regulates SCF-induced MC cell proliferation. To ascertain the individual roles of PKCα and PKCß, we knocked down either PKCα or PKCß or both via short hairpin RNA (shRNA) and analyzed KIT phosphorylation, p38 MAPK phosphorylation, and MC viability and proliferation. To our surprise, downregulation of neither PKCα nor PKCß affected MC viability and proliferation. In contrast, blocking both PKCα and PKCß significantly attenuated SCF-induced cell viability and proliferation, suggesting that PKCα and PKCß compensate for each other downstream of SCF signaling to enhance MC viability and proliferation. Our results not only suggest that PKC classical isoforms are novel therapeutic targets for SCF/MC-mediated inflammatory and allergic diseases, but they also emphasize the importance of inhibiting both PKCα and ß isoforms simultaneously to prevent MC proliferation.

Obesity Education among American Indians: Evaluating a Culturally Appropriate Approach to Health Awareness.

This research focused on a key health issue that significantly affects American Indian community - obesity. We sought to understand how American Indians perceive culturally appropriate an ethnic identity education about obesity as compared with the generic education that is not sensitive to the ethnic identity of American Indians. The project utilizes a survey based observational design where a sample of American Indians is measured for their preference of educational flyers showing American Indian imagery versus generic/Caucasian imagery. The perceived obesity among American Indians was compared with actual bodyweight levels. The American Indian community strongly prefers education that is supported by culturally appropriate imagery. This result provides support to the hypothesis that cultural identity plays a vital role in health education among American Indians and can be an effective strategy in future efforts.

Teaching It Forward: Educating Parents About HPV/HPV Vaccine.

BACKGROUND: Human papillomavirus (HPV) vaccines are available to prevent HPV-associated cancers. However, parents are reluctant to make the decision to immunize their children. Nationally, HPV vaccination rates remain low. OBJECTIVE: The objectives were to improve parents' attitudes and knowledge about HPV/HPV vaccine, increase parental intent to vaccinate, and increase HPV vaccination rates in a primary care office. METHODS: A one-group, pretest/posttest design was used to assess participants' attitude, knowledge, and intent to vaccinate before and after viewing an HPV educational video. Pre-post project HPV vaccination rates were compared. RESULTS: Participants' attitudes toward HPV/HPV vaccine improved while knowledge increased. Intent to vaccine increased by 31% after viewing the HPV educational video. HPV vaccination rates increased 6% (females) and 9% (males). CONCLUSIONS: Primary care providers (PCPs) should look for innovative ways to educate parents about HPV, help parents make informed decisions about the HPV vaccine, and work toward a common goal of preventing HPV-associated cancers. IMPLICATIONS FOR NURSING: Implications are three-fold benefiting parents, PCPs, and society. Parents will be more knowledgeable, providers will understand they are an important key in the vaccine process, and society will benefit from a decrease in HPV-associated cancers.

Law enforcement attitudes towards naloxone following opioid overdose training.

BACKGROUND: Opioid intoxication and overdoses are life-threatening emergencies requiring rapid treatment. One response to this has been to train law enforcement to detect the signs of an opioid overdose and train them to administer naloxone to reverse the effects. Although not a new concept, few studies have attempted to examine this policy. METHODS: At 4 different locations in Indiana, law enforcement personnel were trained to detect the signs of an opioid-related overdose and how to administer naloxone to reverse the effects of the overdose. Pre and post surveys were administered at each location (N = 97). To examine changes in attitudes following training, the authors included items from the Opioid Overdose Attitudes Scale (OOAS), which measures respondents' competency, concerns, and readiness to administer naloxone. RESULTS: Among the full sample, naloxone training resulted in significant increases in competency, concerns, and readiness. Examining changes in attitudes by each location revealed that the training had the greatest effect on competency to administer naloxone and in easing concerns that law enforcement personal might have in administering naloxone. CONCLUSIONS: This study adds to others in showing that law enforcement personnel are receptive to naloxone training and that the OOAS is able to capture these attitudes. This study advances this literature by examining pre-post changes across multiple locations. As the distribution of naloxone continues to proliferate, this study and the OOAS may be valuable towards the development of an evidence-based training model for law enforcement.

Improving quality of life and decreasing readmissions in heart failure patients in a multidisciplinary transition-to-care clinic.

OBJECTIVES: The purpose was to pilot the feasibility and impact of a 4-week transition-to-care program on quality of life for heart failure patients. BACKGROUND: The transition from the acute care to the outpatient setting has been shown to be a critical time with heart failure patients. METHODS: A pre- and post-test design was used. Quality of Life, measured by the Minnesota Living with Heart Failure Questionnaire, and hospital readmissions were the outcomes. A convenience sample of 50 persons was recruited into a multidisciplinary transition-to-care program for heart failure patients following hospitalization. Thirty-six (72%) completed the study. RESULTS: There was a significant improvement in quality of life. Men reported greater improvement in physical symptoms and less emotional distress when compared to women. Only 2 participants were readmitted within 30 days. CONCLUSIONS: Study findings support improved quality of life and decreased readmission rates following a multidisciplinary transition-to care program for heart failure patients.

Telemental health evaluations enhance access and efficiency in a critical access hospital emergency department.

INTRODUCTION: Mentally ill patients in crisis presenting to critical access hospital emergency rooms often face exorbitant wait times to be evaluated by a trained mental health provider. Patients may be discharged from the hospital before receiving an evaluation or boarded in a hospital bed for observation, reducing quality and increasing costs. This study examined the effectiveness of an emergency telemental health evaluation service implemented in a rural hospital emergency room. MATERIALS AND METHODS: Retrospective data collection was implemented to consider patients presenting to the emergency room for 212 days prior to telemedicine interventions and for 184 days after. The study compared measures of time to treatment, length of stay (regardless of inpatient or outpatient status), and door-to-consult time. RESULTS: There were 24 patients seen before telemedicine was implemented and 38 seen using telemedicine. All patients had a mental health evaluation ordered by a physician and completed by a mental health specialist. Significant reductions in all three time measures were observed. Mean and median times to consult were reduced from 16.2 h (standard deviation=13.2 h) and 14.2 h, respectively, to 5.4 h (standard deviation =6.4 h) and 2.6 h. Similar reductions in length of stay and door-to-consult times were observed. By t tests, use of telemedicine was associated with a statistically significant reduction in all three outcome measures. CONCLUSIONS: Telemedicine appears to be an effective intervention for mentally ill patients by providing more timely access to mental health evaluations in rural hospital emergency departments.