Increased core body temperature exacerbates defective protein prenylation in mouse models of mevalonate kinase deficiency.

Mevalonate kinase deficiency (MKD) is characterized by recurrent fevers and flares of systemic inflammation, caused by biallelic loss-of-function mutations in MVK. The underlying disease mechanisms and triggers of inflammatory flares are poorly understood because of the lack of in vivo models. We describe genetically modified mice bearing the hypomorphic mutation p.Val377Ile (the commonest variant in patients with MKD) and amorphic, frameshift mutations in Mvk. Compound heterozygous mice recapitulated the characteristic biochemical phenotype of MKD, with increased plasma mevalonic acid and clear buildup of unprenylated GTPases in PBMCs, splenocytes, and bone marrow. The inflammatory response to LPS was enhanced in compound heterozygous mice and treatment with the NLRP3 inflammasome inhibitor MCC950 prevented the elevation of circulating IL-1ß, thus identifying a potential inflammasome target for future therapeutic approaches. Furthermore, lines of mice with a range of deficiencies in mevalonate kinase and abnormal prenylation mirrored the genotype-phenotype relationship in human MKD. Importantly, these mice allowed the determination of a threshold level of residual enzyme activity, below which protein prenylation is impaired. Elevated temperature dramatically but reversibly exacerbated the deficit in the mevalonate pathway and the defective prenylation in vitro and in vivo, highlighting increased body temperature as a likely trigger of inflammatory flares.

Identifying and addressing mental health providers' perceived barriers to clinical video telehealth utilization.

OBJECTIVE: Clinical video telehealth (CVT) is an innovative modality to provide care directly to Veterans' homes. Despite prior training initiatives, CVT remains underutilized. This project sought to better understand barriers to implementation and to compare responses of CVT utilizers versus nonutilizers. METHOD: Mental health staff were invited to complete an online anonymous survey on their use of CVT in clinical practice. RESULTS: A total of 159 mental health staff completed the survey. Although the majority of the sample endorsed personal use of a video chat program, less than half reported using CVT for patient care. Among nonutilizers, lack of training was the most frequently endorsed barrier to CVT use whereas administrative burden was the most frequently endorsed barrier by utilizers. CONCLUSIONS: This study extends existing literature by determining barriers to CVT adoption. It identifies several barriers among utilizers versus nonutilizers. Discussion includes potential guidelines for overcoming barriers to CVT utilization.

Telemental health training in the Veterans Administration Puget Sound Health Care System.

As a pioneer of training in the field of psychology, the Veterans Affairs (VA) HealthCare System serves as a leader in the training in and provision of Telemental Health (TMH) services in the United States. To meet goals toward continued expansion of these services, the VA TMH training program includes both web-based didactic courses and a skills competency test at a basic level with supervision and consultation in TMH for more advanced training and is available to staff psychologists and psychologist trainees. Despite these efforts, barriers for training in and implementation of TMH occur at the provider, system, and patient level. At the national level, the VA is actively working to resolve these barriers and we share site-specific examples implemented by the VA Puget Sound Health Care System promoting access through TMH team to further address barriers to training and implementation.

Gastroesophageal Reflux Disease Symptom Screening in a Dental Setting.

Purpose: Gastroesophageal Reflux Disease (GERD) is a chronic health condition in which the symptoms often go unnoticed. Oral problems accompanying GERD may include non-specific burning sensation, mucosa ulceration and erosion, erythema of the soft/hard palate mucosa and uvula, loss of taste and either xerostomia or increased salivary flow with potential long-term complications such as difficulty swallowing, trouble breathing, esophagitis and potential development of esophageal adenocarcinoma (EAC). The purpose of this study was to assess the feasibility of using a GERD screening in the dental clinic setting to identify and refer patients.Methods: This was a descriptive survey design utilizing a convenience sample of patients (n=227) from two dental hygiene clinics. Students and faculty were calibrated to administer a previously validated, GERD diagnostic screening questionnaire.Results: The prevalence of GERD in the study population was 8.7%; with 10.1% of female reporting symptoms verses 7.0% of male. There were no statistically significant differences in the study population demographics and GERD prevalence.Conclusion: Screening for GERD symptoms should be a routine procedure for oral health care providers, as is oral cancer screening. GERD screening has the potential to identify those at risk and enable referral to medical care in order to decrease the serious complications associated with GERD.

Thiazolidine-Protected ß-Thiol Asparagine: Applications in One-Pot Ligation-Desulfurization Chemistry.

The synthesis of a ß-thiol asparagine derivative bearing a novel (2,4,6-trimethoxyphenyl)thiazolidine protecting group is described. The efficient incorporation of the amino acid into the N-termini of peptides is demonstrated as well as the utility of the ß-thiol asparagine moiety for rapid ligation reactions with peptide thioesters. The streamlined synthesis of native peptide products could be accomplished using a one-pot radical desulfurization of the ß-thiol auxiliary following the ligation event. The utility of the amino acid is highlighted in the efficient one-pot assembly of the HIV entry inhibitor enfuvirtide.