Coenzyme Q10 deficiencies: pathways in yeast and humans.

Coenzyme Q (ubiquinone or CoQ) is an essential lipid that plays a role in mitochondrial respiratory electron transport and serves as an important antioxidant. In human and yeast cells, CoQ synthesis derives from aromatic ring precursors and the isoprene biosynthetic pathway. Saccharomyces cerevisiae coq mutants provide a powerful model for our understanding of CoQ biosynthesis. This review focusses on the biosynthesis of CoQ in yeast and the relevance of this model to CoQ biosynthesis in human cells. The COQ1-COQ11 yeast genes are required for efficient biosynthesis of yeast CoQ. Expression of human homologs of yeast COQ1-COQ10 genes restore CoQ biosynthesis in the corresponding yeast coq mutants, indicating profound functional conservation. Thus, yeast provides a simple yet effective model to investigate and define the function and possible pathology of human COQ (yeast or human gene involved in CoQ biosynthesis) gene polymorphisms and mutations. Biosynthesis of CoQ in yeast and human cells depends on high molecular mass multisubunit complexes consisting of several of the COQ gene products, as well as CoQ itself and CoQ intermediates. The CoQ synthome in yeast or Complex Q in human cells, is essential for de novo biosynthesis of CoQ. Although some human CoQ deficiencies respond to dietary supplementation with CoQ, in general the uptake and assimilation of this very hydrophobic lipid is inefficient. Simple natural products may serve as alternate ring precursors in CoQ biosynthesis in both yeast and human cells, and these compounds may act to enhance biosynthesis of CoQ or may bypass certain deficient steps in the CoQ biosynthetic pathway

Functional desensitization of the β 2 adrenoceptor is not dependent on agonist efficacy

© 2015 John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. Chronic treatment with β2 adrenoceptor agonists is recommended as a first-line maintenance therapy for chronic obstructive pulmonary disease (COPD). However, a potential consequence of long-term treatment may be the loss of functional response (tachyphylaxis) over time. In this study, we have investigated the tendency of such agonists, with a range of efficacies, to develop functional desensitization to cAMP responses in primary human bronchial smooth muscle cells following prolonged agonist exposure. The data show that upon repeat exposure, all agonists produced functional desensitization to the same degree and rate. In addition, β2 adrenoceptor internalization and β-arrestin-2 recruitment were monitored using β2·eGFP visualization and the PathHunter™ β-arrestin-2 assay, respectively. All agonists were capable of causing robust receptor internalization and β-arrestin-2 recruitment, the rate of which was influenced by agonist efficacy, as measured in those assays. In summary, although a relationship exists between agonist efficacy and the rate of both receptor internalization and β-arrestin-2 recruitment, there is no correlation between agonist efficacy and the rate or extent of functional desensitization

Vector competence of Aedes aegypti, Culex tarsalis, and Culex quinquefasciatus from California for Zika virus.

Zika virus (ZIKV) has emerged since 2013 as a significant global human health threat following outbreaks in the Pacific Islands and rapid spread throughout South and Central America. Severe congenital and neurological sequelae have been linked to ZIKV infections. Assessing the ability of common mosquito species to transmit ZIKV and characterizing variation in mosquito transmission of different ZIKV strains is important for estimating regional outbreak potential and for prioritizing local mosquito control strategies for Aedes and Culex species. In this study, we evaluated the laboratory vector competence of Aedes aegypti, Culex quinquefasciatus, and Culex tarsalis that originated in areas of California where ZIKV cases in travelers since 2015 were frequent. We compared infection, dissemination, and transmission rates by measuring ZIKV RNA levels in cohorts of mosquitoes that ingested blood meals from type I interferon-deficient mice infected with either a Puerto Rican ZIKV strain from 2015 (PR15), a Brazilian ZIKV strain from 2015 (BR15), or an ancestral Asian-lineage Malaysian ZIKV strain from 1966 (MA66). With PR15, Cx. quinquefasciatus was refractory to infection (0%, N = 42) and Cx. tarsalis was infected at 4% (N = 46). No ZIKV RNA was detected in saliva from either Culex species 14 or 21 days post feeding (dpf). In contrast, Ae. aegypti developed infection rates of 85% (PR15; N = 46), 90% (BR15; N = 20), and 81% (MA66; N = 85) 14 or 15 dpf. Although MA66-infected Ae. aegypti showed higher levels of ZIKV RNA in mosquito bodies and legs, transmission rates were not significantly different across virus strains (P = 0.13, Fisher's exact test). To confirm infectivity and measure the transmitted ZIKV dose, we enumerated infectious ZIKV in Ae. aegypti saliva using Vero cell plaque assays. The expectorated plaque forming units PFU varied by viral strain: MA66-infected expectorated 13±4 PFU (mean±SE, N = 13) compared to 29±6 PFU for PR15-infected (N = 13) and 35±8 PFU for BR15-infected (N = 6; ANOVA, df = 2, F = 3.8, P = 0.035). These laboratory vector competence results support an emerging consensus that Cx. tarsalis and Cx. quinquefasciatus are not vectors of ZIKV. These results also indicate that Ae. aegypti from California are efficient laboratory vectors of ancestral and contemporary Asian lineage ZIKV

Evaluation of a Brief Sodium Screener in Two Samples

The Sodium Screener© (SS©), as developed by NutritionQuest (Berkeley, CA, USA), was designed to reduce the burden of repeated dietary or urinary sodium measurements, but the accuracy of daily sodium intake estimates has not been reported. Associations were examined between sodium intakes derived from the SS© scores and repeated 24-h recalls (24DR) in two studies with different administration modes. In one study, 102 registered dietitians (RD) completed three Automated Self-Administered 24DRs (ASA24©), version 2014, followed by the SS©; both were self-administered and web-based. In the second sample, (the Study of Household Purchasing Patterns, Eating, and Recreation or SHoPPER), trained dietitians conducted 24DR interviews with 69 community-dwelling adults in their homes; all the community adults then completed a paper-based SS© at the final visit. In the RD study, SS©-predicted sodium intakes were 2604 ± 990 (mean ± Standard deviation (SD)), and ASA24© sodium intakes were 3193 ± 907 mg/day. In the SHoPPER sample, corresponding values were 3338 ± 1310 mg/day and 2939 ± 1231 mg/day, respectively. SS© -predicted and recall sodium estimates were correlated in the RD study (r = 0.381, p = 0.0001) and in the SHoPPER (r = 0.430, p = 0.0002). Agreement between the SS© and 24-h recalls was poor when classifying individuals as meeting the dietary sodium guidelines of 2300 mg/day or not (RD study: kappa = 0.080, p = 0.32; SHoPPER: kappa = 0.207, p = 0.08). Based on repeated 24DR either in person or self-reported online as the criterion for estimating daily sodium intakes, the SS© may require additional modifications

Telehealth by Certified Psychiatric Providers Compared to Emergency Department Healthcare Providers on Psychiatric Patient Outcomes: A Scoping Review

Background: Emergency department visits for mental health disorders have increased over the years due to insufficient mental health resources. The number of ED visits for mental health disorders rose from 1.4 to 2.5 million per year in the US. Therefore, mental health patients being seen by ED physicians are more likely to have longer lengths of stay, an increase in hospital admission, and high recidivism rates. Purpose: In this scoping review, we wanted to determine the role of telehealth on ED mental health patients. outcomes regarding how telehealth can reduce the number of admissions, length of stay in the ED, dispositions of patients with mental illness complaints, the cost-effectiveness of telehealth, and patient and staff satisfaction were reviewed. Method: We collected data using The University of Tennessee Health Science Center (UTHSC) online Library, and we obtained articles using CINAHL Complete, Medline, and PubMed. The eligibility criteria were studies conducted in English, subjects greater than 18 years of age, meet DSM criteria for mental health diagnosis, and no limit on gender, race, and ethnicity. Participants must be able to consent. Result: Data from 11 articles published from 2012 to 2020 was collected. Decreased length of stay, improved patient outcomes, decreased healthcare cost, and reduction in readmission/revisit rates were the most frequently reported findings. Implications for Nursing Practice: Results of this scoping review showed improved patient outcomes and decreased readmission/revisit rates when patients with psychiatric illness were seen by a psychiatric physician via telehealth in the Emergency Department. This practice can be standardized and utilized to yield similar results to the literature review. Additional research is necessary to assist in the development of healthcare resources that will provide patients who suffer from mental illness with the care they deserve

Efficacy of a Soft Release Strategy for Translocating Scaled Quail in the Rolling Plains of Texas

Scaled Quail (Callipepla squamata) populations have become locally extinct and spatially fragmented in the Rolling Plains ecoregion of Texas. Translocating Scaled Quail from core to declining populations could augment populations or re-establishing extinct populations. Although translocations of scaled quail have been attempted in Texas, none have been documented and none have attempted to identify best practices. Release strategy (i.e., hard or soft release) is a factor that can influence the success of a translocation. Our objective was to compare daily apparent survival of scaled quail translocated to the Rolling Plains between 2 release treatment groups: hard- and soft-release. We estimated a daily apparent survival rate (DASR) for radio-marked hens during the breeding season as a function of age, release treatment, and a time trend. We found evidence of a positive effect of the soft release treatment and higher DASR in adult hens. Overall, DASR of translocated hens was low compared to reported estimates of survival in established resident populations. Using a soft release strategy and translocating a greater proportion of adults may improve future translocation success for scaled quail

Phenoconversion from probable rapid eye movement sleep behavior disorder to mild cognitive impairment to dementia in a population-based sample

© 2017 The Authors Introduction Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. Methods Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed. Results Over 6.4 ± 2.9 years, six of the 14 participants with MCI developed additional neurodegenerative signs, five of whom had Lewy body disease features. Four of them progressed to dementia at a mean age 84.8 ± 4.9 years, three of whom met the criteria for probable dementia with Lewy bodies. One subject with PD developed MCI, but not dementia. Discussion Our findings from the population-based sample of Olmsted County, Minnesota, residents suggest that a substantial number of RBD patients tend to develop overt synucleinopathy features over time, and RBD patients who develop MCI and subsequent dementia have clinical features most consistent with dementia with Lewy bodies

Experimental Everglades Virus Infection of Cotton Rats (Sigmodon hispidus)

We characterized Everglades virus infection of cotton rats from South Florida to validate their role as reservoir hosts in the enzootic transmission cycle

Human T-follicular helper and T-follicular regulatory cell maintenance is independent of germinal centers.

The monoclonal anti-CD20 antibody rituximab (RTX) depletes B cells in the treatment of lymphoma and autoimmune disease, and contributes to alloantibody reduction in transplantation across immunologic barriers. The effects of RTX on T cells are less well described. T-follicular helper (Tfh) cells provide growth and differentiation signals to germinal center (GC) B cells to support antibody production, and suppressive T-follicular regulatory (Tfr) cells regulate this response. In mice, both Tfh and Tfr are absolutely dependent on B cells for their formation and on the GC for their maintenance. In this study, we demonstrate that RTX treatment results in a lack of GC B cells in human lymph nodes without affecting the Tfh or Tfr cell populations. These data demonstrate that human Tfh and Tfr do not require an ongoing GC response for their maintenance. The persistence of Tfh and Tfr following RTX treatment may permit rapid reconstitution of the pathological GC response once the B-cell pool begins to recover. Strategies for maintaining remission after RTX therapy will need to take this persistence of Tfh into account.This work was funded by a Wellcome Trust Programme Grant (083650/Z/07/Z) and a Lister Prize Fellowship to KGCS and supported by the National Institute of Health Research Cambridge Biomedical Research Center. EFW was supported by an Addenbrooke’s Charitable Trust research fellowship; MAL was supported by a NHMRC Overseas Biomedical Fellowship, then by the Biotechnology and Biological Sciences Research Council.This is the accepted manuscript. The final published version is available from Blood at http://dx.doi.org/10.1182/blood-2014-07-58597