Lumateperone Normalizes Pathological Levels of Acute Inflammation through Important Pathways Known to Be Involved in Mood Regulation.

Lumateperone is indicated for the treatment of schizophrenia in adults and for depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate (Calabrese et al., 2021). It is currently under evaluation for the treatment of major depressive disorder (www.ClinicalTrials.gov). Lumateperone acts by selectively modulating serotonin, dopamine, and glutamate neurotransmission in the brain. However, other mechanisms could be involved in the actions of lumateperone, and because of the connection between the immune system and psychiatric health, we hypothesized that lumateperone might improve symptoms of depression, at least in part, by normalizing pathologic inflammation. Here, we show that in male and female C57BL/6 mice subjected to an acute immune challenge, lumateperone reduced aberrantly elevated levels of key proinflammatory cytokines (e.g., IL-1ß, IL-6, and TNF-α) in both brain and serum; lumateperone also reduced proinflammatory cytokines in male mice under acute behavioral stress. Further, we demonstrate that lumateperone altered key genes/pathways involved in maintaining tissue integrity and supporting blood-brain barrier function, such as claudin-5 and intercellular adhesion molecule 1. In addition, in acutely stressed male Sprague Dawley rats, lumateperone conferred anxiolytic- and antianhedonic-like properties while enhancing activity in the mammalian target of rapamycin complex 1 pathway in the PFC. Together, our preclinical findings indicate that lumateperone, in addition to its ability to modulate multiple neurotransmitter systems, could also act by reducing the impact of acute inflammatory challenges.SIGNIFICANCE STATEMENT Lumateperone is indicated in adults to treat schizophrenia and depressive episodes associated with bipolar I or II disorder, as monotherapy and adjunctive therapy with lithium or valproate. Because aberrant immune system activity is associated with increased depressive symptoms, the relationship between lumateperone and immune function was studied. Here, lumateperone reduced the levels of proinflammatory cytokines that were increased following an immune challenge or stress in mice. Additionally, lumateperone altered genes and pathways that maintain blood-brain barrier integrity, restored an index of blood-brain barrier function, reduced anxiety-like behavior in rodents, and enhanced mammalian target of rapamycin complex 1 pathway signaling in the PFC. These results highlight the anti-inflammatory actions of lumateperone and describe how lumateperone may reduce immune pathophysiology, which is associated with depressive symptoms.

Stigma Related to the Non-Medical Use and Diversion of Prescription Stimulant Drugs: Should We Care.

BACKGROUND: Non-medical use (NMU) and diversion of prescription stimulants are prevalent on college campuses. Diversion represents a primary source of acquisition for NMU among young adults. This study examined relationships between stigmatizing beliefs related to NMU and diversion of stimulant medications and engagement in these behaviors, as well as how such perceptions are associated with indicators of psychological distress among those who engage in these behaviors. METHODS: Young adults (N = 384) were recruited from a large US university to participate in this cross-sectional electronic survey-based study. Relationships between stigma variables and NMU and diversion were assessed. Among those who engage in NMU and diversion, we tested relationships between stigma variables and indicators of psychological distress, using validated instruments. RESULTS: Perceived social and personal stigmatic beliefs did not significantly predict NMU. However, perceived social and personal stigma of diversion significantly reduced diversion likelihood. For NMU, associations were found between stigma variables and indicators of psychological distress. Markedly, we found that as stigmatic perceptions of NMU increased, so did depressive, anxiolytic, and suicidal symptomatology among those who engage in NMU. CONCLUSIONS: Stigmatization does not deter NMU; however, stigmatization is positively associated with psychological harm among those who engage in NMU. Interventions should be developed to reduce stigmatization in order to improve psychological health among those who engage in NMU. Stigmatic perceptions of diversion were not predictive of psychological harm, though they are negatively associated with diversion behavior.

Salient Beliefs Associated with Unsanctioned Adult Cannabis Use in an Evolving Socio-Political Environment.

Background: The changing cannabis legal climate in the United States has been associated with increased prevalence of use, more favorable general attitudes, and cultural norms toward its use among young adults. The purpose of this study was to conceptualize salient beliefs governing illicit cannabis use within a state where medical use is legal and adult use remains illegal. Methods: Following an initial qualitative pilot, a prospective study (baseline and a 30-day follow-up) that utilized an electronic survey design was conducted. Students at a large US university (N = 514) completed a baseline assessment of cannabis use and Theory of Planned Behavior (TPB) constructs, and 169 completed the follow-up assessing actual behavior. Results: Roughly 60% reported illicit cannabis use. Attitude and subjective norms accounted for 57% of the variation in intention for cannabis use in the next 30 days, while intention and perceived behavioral control (PBC) explained 51% of the variation in prospective use. The majority of salient beliefs identified exhibited moderate to strong correlations with intention and behavior among the larger sample. Close friends and partners were identified as important referents, outcome expectations of relaxation, improved social functioning, and more enjoyment, as well as environmental factors, such as proximity to use, safe utilization location, and continued illegality of adult use exhibited strong associations to intention and behavior. Conclusions: The practical utility of the salient belief measures identified herein presents a useful foundation for interventions aimed at reducing illicit cannabis utilization among young adults.

Adjunctive lumateperone (ITI-007) in the treatment of bipolar depression: Results from a randomized placebo-controlled clinical trial.

OBJECTIVE: This phase 3, randomized, double-blind, placebo-controlled study (NCT02600507) evaluated the efficacy and safety of lumateperone adjunctive therapy to lithium or valproate in patients with bipolar depression. METHODS: Patients (18-75 years) with bipolar I or bipolar II disorder experiencing a major depressive episode (MDE), with inadequate therapeutic response to lithium or valproate, were randomized 1:1:1 to 6 weeks adjunctive therapy with lumateperone 28 mg (n = 176), lumateperone 42 mg (n = 177), or placebo (n = 176). The primary and key secondary efficacy endpoints were change from baseline to Day 43 in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score and the Clinical Global Impression Scale-Bipolar Version-Severity Scale (CGI-BP-S) depression subscore. Safety assessments included adverse events, laboratory evaluations, vital signs, extrapyramidal symptoms (EPS), and suicidality. RESULTS: Patients treated with adjunctive lumateperone 42 mg showed significantly greater improvement compared with adjunctive placebo in MADRS Total score (LS mean difference vs placebo [LSMD], -2.4; p = 0.02) and CGI-BP-S depression subscore (LSMD, -0.3; p = 0.01), while adjunctive lumateperone 28 mg showed numerical improvement in MADRS Total score (LSMD, -1.7; p = 0.10) and improvement in the CGI-BP-S depression subscore (LSMD, -0.3; p = 0.04). Adjunctive lumateperone treatment was well tolerated; treatment-emergent adverse events reported at rates >5% and twice placebo for lumateperone 42 mg were somnolence (11.3%), dizziness (10.7%), and nausea (8.5%), with minimal risk of EPS, metabolic abnormalities, or increased prolactin. CONCLUSIONS: Lumateperone 42-mg treatment adjunctive to lithium or valproate significantly improved depression symptoms and was generally well tolerated in patients with MDEs associated with either bipolar I or bipolar II disorder.

Analyzing Twitter Chatter About Tobacco Use Within Intoxication-related Contexts of Alcohol Use: "Can Someone Tell Me Why Nicotine is So Fire When You're Drunk?"

INTRODUCTION: Alcohol and tobacco are commonly used together. Social influences within online social networking platforms contribute to youth and young adult substance use behaviors. This study used a sample of alcohol- and tobacco-related tweets to evaluate: (1) sentiment toward co-use of alcohol and tobacco, (2) increased susceptibility to tobacco use when consuming alcohol, and (3) the role of alcohol in contributing to a failed attempt to quit tobacco use. METHODS: Data were collected from the Twitter API from January 1, 2019 through December 31, 2019 using tobacco-related keywords (e.g., vape, ecig, smoking, juul*) and alcohol-related filters (e.g., drunk, blackout*). A total of 78,235 tweets were collected, from which a random subsample (n = 1,564) was drawn for coding. Cohen's Kappa values ranged from 0.66 to 0.99. RESULTS: Most tweets were pro co-use of alcohol and tobacco (75%). One of every ten tweets reported increased susceptibility to tobacco use when intoxicated. Non-regular tobacco users reported cravings for and tobacco use when consuming alcohol despite disliking tobacco use factors such as the taste, smell, and/or negative health effects. Regular tobacco users reported using markedly higher quantities of tobacco when intoxicated. Individuals discussed the role of alcohol undermining tobacco cessation attempts less often (2.0%), though some who had quit smoking for prolonged periods of time reported reinitiating tobacco use during acute intoxication episodes. CONCLUSIONS: Tobacco cessation interventions may benefit from including alcohol-focused components designed to educate participants about the association between increased susceptibility to tobacco use when consuming alcohol and the role of alcohol in undermining tobacco cessation attempts. IMPLICATIONS: Sentiment toward co-use of alcohol and tobacco on Twitter is largely positive. Individuals reported regret about using tobacco, or using more than intended, when intoxicated. Those who had quit smoking or vaping for prolonged periods of time reported reinitiating tobacco use when consuming alcohol. While social media-based tobacco cessation interventions like the Truth Initiative's "Ditch the Juul" campaign demonstrate potential to change tobacco use behaviors, these campaigns may benefit from including alcohol-focused components designed to educate participants about the association between increased susceptibility to tobacco use when consuming alcohol and the role of alcohol in undermining tobacco cessation attempts.

The Association between Weather and Emergency Department Visitation for Diabetes in Roanoke, Virginia.

Diabetes mellitus imposes a significant and increasing health burden on the US population. Our objective is to determine if weather is related to daily variations in emergency department (ED) visits for diabetes mellitus in Roanoke, Virginia. A time series of daily ED visits for diabetes mellitus at the Carilion Clinic in southwestern Virginia is associated with daily minimum temperature from 2010-2017. Associations between ED visits (through a 14-day lag period) and temperature are examined using generalized additive models and distributed lag nonlinear models. Heat and cold waves are identified at low and high thresholds, and ED visitation during these events is compared to prior control periods using a time-stratified case crossover approach. ED visits for diabetes exhibit a U-shaped relationship with temperature, with a higher relative risk (RR) during cold events (RR = 1.05) vs. warm events (RR = 1.02). When minimum temperatures are below freezing, ED visitation peaks starting 2 days afterward, with RRs approaching 1.04. The RR on warm days (minimum temperature > 10 °C) approaches 1.02 but peaks on the day of or the day following the elevated temperatures. Cold waves increase the odds of ED visits by up to 11% (p = 0.01), whereas heat waves exhibit no significant effect (p = 0.07). The increasing health burden linked to diabetes requires new research on environmental factors that might exacerbate related illness. When examined in the context of climate change impacts on local weather variations, these kinds of linkages between environment and disease can aid in facility staffing and public health messaging during extreme weather events.

Selective Phosphodiesterase 1 Inhibition Ameliorates Vascular Function, Reduces Inflammatory Response, and Lowers Blood Pressure in Aging Animals.

Diminished nitric oxide-cGMP-mediated relaxation plays a crucial role in cardiovascular aging, leading to decreased vasodilation, vascular hypertrophy and stiffening, and ultimately, cardiovascular dysfunction. Aging is the time-related worsening of physiologic function due to complex cellular and molecular interactions, and it is at least partly driven by DNA damage. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in Ercc1Δ/- mice provides us an efficient tool to accelerate vascular aging, explore mechanisms, and test potential treatments. Previously, we identified the cGMP-degrading enzyme phosphodiesterase 1 as a potential treatment target in vascular aging. In the present study, we studied the effect of acute and chronic treatment with ITI-214, a selective phosphodiesterase 1 inhibitor on vascular aging features in Ercc1Δ/- mice. Compared with wild-type mice, Ercc1Δ/- mice at the age of 14 weeks showed decreased reactive hyperemia, diminished endothelium-dependent and -independent responses of arteries in organ baths, carotid wall hypertrophy, and elevated circulating levels of inflammatory cytokines. Acute ITI-214 treatment in organ baths restored the arterial endothelium-independent vasodilation in Ercc1Δ/- mice. An 8-week treatment with 100 mg/kg per day ITI-214 improved endothelium-independent relaxation in both aorta and coronary arteries, at least partly restored the diminished reactive hyperemia, lowered the systolic and diastolic blood pressure, normalized the carotid hypertrophy, and ameliorated inflammatory responses exclusively in Ercc1Δ/- mice. These findings suggest phosphodiesterase 1 inhibition would provide a powerful tool for nitric oxide-cGMP augmentation and have significant therapeutic potential to battle arteriopathy related to aging. SIGNIFICANCE STATEMENT: The findings implicate the key role of phosphodiesterase 1 in vascular function and might be of clinical importance for the prevention of mortalities and morbidities related to vascular complications during aging, as well as for patients with progeria that show a high risk of cardiovascular disease.

The agent associated with blue dwarf disease in wheat represents a new phytoplasma taxon, 'Candidatus Phytoplasma tritici'.

Wheat blue dwarf (WBD) is one of the most economically damaging cereal crop diseases in northwestern PR China. The agent associated with the WBD disease is a phytoplasma affiliated with the aster yellows (AY) group, subgroup C (16SrI-C). Since phytoplasma strains within the AY group are ecologically and genetically diverse, it has been conceived that the AY phytoplasma group may consist of more than one species. This communication presents evidence to demonstrate that, while each of the two 16 rRNA genes of the WBD phytoplasma shares >97.5 % sequence similarity with that of the 'Candidatus Phytoplasma asteris' reference strain, the WBD phytoplasma clearly represents an ecologically separated lineage: the WBD phytoplasma not only has its unique transmitting vector (Psammotettix striatus) but also elicits a distinctive symptom in its predominant plant host (wheat). In addition, the WBD phytoplasma possesses molecular characteristics that further manifest its significant divergence from 'Ca. P. asteris'. Such molecular characteristics include lineage-specific antigenic membrane proteins and a lower than 95 % genome-wide average nucleotide identity score with 'Ca. P. asteris'. These ecological, molecular and genomic evidences justify the recognition of the WBD phytoplasma as a novel taxon, 'Candidatus Phytoplasma tritici'.

Inhibition of calcium-calmodulin-dependent phosphodiesterase (PDE1) suppresses inflammatory responses.

A novel, potent, and highly specific inhibitor of calcium-calmodulin-dependent phosphodiesterases (PDE) of the PDE1 family, ITI-214, was used to investigate the role of PDE1 in inflammatory responses. ITI-214 dose-dependently suppressed lipopolysaccharide (LPS)-induced gene expression of pro-inflammatory cytokines in an immortalized murine microglial cell line, BV2 cells. RNA profiling (RNA-Seq) was used to analyze the impact of ITI-214 on the BV2 cell transcriptome in the absence and the presence of LPS. ITI-214 was found to regulate classes of genes that are involved in inflammation and cell migration responses to LPS exposure. The gene expression changes seen with ITI-214 treatment were distinct from those elicited by inhibitors of other PDEs with anti-inflammatory activity (e.g., a PDE4 inhibitor), indicating a distinct mechanism of action for PDE1. Functionally, ITI-214 inhibited ADP-induced migration of BV2 cells through a P2Y12-receptor-dependent pathway, possibly due to increases in the extent of cAMP and VASP phosphorylation downstream of receptor activation. Importantly, this effect was recapitulated in P2 rat microglial cells in vitro, indicating that these pathways are active in native microglial cells. These studies are the first to demonstrate that inhibition of PDE1 exerts anti-inflammatory effects through effects on microglia signaling pathways. The ability of PDE1 inhibitors to prevent or dampen excessive inflammatory responses of BV2 cells and microglia provides a basis for exploring their therapeutic utility in the treatment of neurodegenerative diseases associated with increased inflammation and microglia proliferation such as Parkinson's disease and Alzheimer's disease.

A comparison of the effect of weather and climate on emergency department visitation in Roanoke and Charlottesville, Virginia.

Compared with mortality, the impact of weather and climate on human morbidity is less well understood, especially in the cold season. We examined the relationships between weather and emergency department (ED) visitation at hospitals in Roanoke and Charlottesville, Virginia, two locations with similar climates and population demographic profiles. Using patient-level data obtained from electronic medical records, each patient who visited the ED was linked to that day's weather from one of 8 weather stations in the region based on each patient's ZIP code of residence. The resulting 2010-2017 daily ED visit time series were examined using a distributed lag non-linear model to account for the concurrent and lagged effects of weather. Total ED visits were modeled separately for each location along with subsets based on gender, race, and age. The relationship between the relative risk of ED visitation and temperature or apparent temperature over lags of one week was positive and approximately linear at both locations. The relative risk increased about 5% on warm, humid days in both cities (lag 0 or lag 1). Cold conditions had a protective effect, with up to a 15% decline on cold days, but ED visits increased by 4% from 2 to 5 days after the cold event. The effect of thermal extremes tended to be larger for non-whites and the elderly, and there was some evidence of a greater lagged response for non-whites in Roanoke. Females in Roanoke were more impacted by winter cold conditions than males, who were more likely to show a lagged response at high temperatures. In Charlottesville, males sought ED attention at lower temperatures than did females. The similarities in the ED response patterns between these two hospitals suggest that certain aspects of the response may be generalizable to other locations that have similar climates and demographic profiles.

Veterinarians' attitudes and practices regarding opioid-related vet shopping practices in tri-state Appalachian counties: an exploratory study.

BACKGROUND: The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States. RESULTS: Fourteen veterinarians were asked a set of 13 questions related to vet shopping. Results indicated that 13 veterinarians in the study had heard of the phenomenon of vet shopping and eight veterinarians had personally encountered vet shopping in their practices. Qualitative analysis of the interviews identified six key themes including a need for interprofessional communication and how important a valid veterinary-client-patient-relationship is within the profession. CONCLUSIONS: The study hopefully sheds some light on the how often vet shopping is encountered in practice, concerns of veterinarians regarding vet shopping, and potential areas for improvement.

Examining the diurnal temperature range enigma: why is human health related to the daily change in temperature?

An increasing number of epidemiological studies are finding statistical evidence that diurnal temperature range (DTR) is positively correlated to human morbidity and mortality despite the lack of clear clinical understanding. We examine a 14-year daily time series of emergency department (ED) admissions to the University of Virginia Medical Center in Charlottesville, Virginia, relative to long-term climate records from the Charlottesville/Albemarle County Airport weather station and the Spatial Synoptic Classification. DTR has a consistent strong positive correlation (r ~ 0.5) with maximum temperature in all months but only a weak, negative correlation (r ~- 0.1) with minimum temperature except in late summer (r ~- 0.4). Warm season DTR is highest on dry air mass days with low dew point temperatures. Cool season DTR is unrelated to morning temperature. Using a distributed lag non-linear model with an emphasis on DTR and its seasonal variation, after stratifying the models by season, we find that ED visits are linked to extreme cold events (cold days and nights) and high DTR in the cold season. In the warm season, ED visits are also linked to high DTR, but these are cool, dry, and pleasant days. The existing confusion regarding interpretation of DTR impacts on health might be rectified through a more careful analysis of the underlying physical factors that drive variations in DTR over the course of a year.

Draft Genome Sequence of 'Candidatus Phytoplasma pini'-Related Strain MDPP: A Resource for Comparative Genomics of Gymnosperm-Infecting Phytoplasmas.

'Candidatus Phytoplasma pini'-related strain MDPP, the reference strain of subgroup 16SrXXI-B, is a pathogen associated with witches' broom disease of Pinus spp. in North America. Here, we report the first draft genome sequence of 'Ca. Phytoplasma pini' strain MDPP, which consists of 474,136 bases, with a G + C content of 22.22%. This information will facilitate comparative genomics of gymnosperm-infecting phytoplasmas.

New Symptoms Identified in Phytoplasma-Infected Plants Reveal Extra Stages of Pathogen-Induced Meristem Fate-Derailment.

In flowering plants, the transition of a shoot apical meristem from vegetative to reproductive destiny is a graduated, multistage process that involves sequential conversion of the vegetative meristem to an inflorescence meristem, initiation of floral meristems, emergence of flower organ primordia, and formation of floral organs. This orderly process can be derailed by phytoplasma, a bacterium that parasitizes phloem sieve cells. In a previous study, we showed that phytoplasma-induced malformation of flowers reflects stage-specific derailment of shoot apical meristems from their genetically preprogrammed reproductive destiny. Our current study unveiled new symptoms of abnormal morphogenesis, pointing to derailment of meristem transition at additional stages previously unidentified. We also found that the fate of developing meristems may be derailed even after normal termination of the floral meristem and onset of seed production. Although previous reports by others have indicated that different symptoms may be induced by different phytoplasmal effectors, the phenomenon observed in our experiment raises interesting questions as to (i) whether effectors can act at specific stages of meristem transition and (ii) whether specific floral abnormalities are attributable to meristem fate-derailment events triggered by different effectors that each act at a specific stage in meristem transition. Research addressing such questions may lead to discoveries of an array of phytoplasmal effectors.

Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition.

BACKGROUND: Phosphodiesterase type-1 (PDE1) hydrolyzes cAMP and cGMP and is constitutively expressed in the heart, although cardiac effects from its acute inhibition in vivo are largely unknown. Existing data are limited to rodents expressing mostly the cGMP-favoring PDE1A isoform. Human heart predominantly expresses PDE1C with balanced selectivity for cAMP and cGMP. Here, we determined the acute effects of PDE1 inhibition in PDE1C-expressing mammals, dogs, and rabbits, in normal and failing hearts, and explored its regulatory pathways. METHODS: Conscious dogs chronically instrumented for pressure-volume relations were studied before and after tachypacing-induced heart failure (HF). A selective PDE1 inhibitor (ITI-214) was administered orally or intravenously±dobutamine. Pressure-volume analysis in anesthetized rabbits tested the role of ß-adrenergic and adenosine receptor signaling on ITI-214 effects. Sarcomere and calcium dynamics were studied in rabbit left ventricular myocytes. RESULTS: In normal and HF dogs, ITI-214 increased load-independent contractility, improved relaxation, and reduced systemic arterial resistance, raising cardiac output without altering systolic blood pressure. Heart rate increased, but less so in HF dogs. ITI-214 effects were additive to ß-adrenergic receptor agonism (dobutamine). Dobutamine but not ITI-214 increased plasma cAMP. ITI-214 induced similar cardiovascular effects in rabbits, whereas mice displayed only mild vasodilation and no contractility effects. In rabbits, ß-adrenergic receptor blockade (esmolol) prevented ITI-214-mediated chronotropy, but inotropy and vasodilation remained unchanged. By contrast, adenosine A2B-receptor blockade (MRS-1754) suppressed ITI-214 cardiovascular effects. Adding fixed-rate atrial pacing did not alter the findings. ITI-214 alone did not affect sarcomere or whole-cell calcium dynamics, whereas ß-adrenergic receptor agonism (isoproterenol) or PDE3 inhibition (cilostamide) increased both. Unlike cilostamide, which further enhanced shortening and peak calcium when combined with isoproterenol, ITI-214 had no impact on these responses. Both PDE1 and PDE3 inhibitors increased shortening and accelerated calcium decay when combined with forskolin, yet only cilostamide increased calcium transients. CONCLUSIONS: PDE1 inhibition by ITI-214 in vivo confers acute inotropic, lusitropic, and arterial vasodilatory effects in PDE1C-expressing mammals with and without HF. The effects appear related to cAMP signaling that is different from that provided via ß-adrenergic receptors or PDE3 modulation. ITI-214, which has completed phase I trials, may provide a novel therapy for HF.

A survey of knowledge and use of telehealth among veterinarians.

BACKGROUND: As usage of digital information and communication technologies continues to grow, the incorporation of telehealth and telemedicine has become a topic of interest in the veterinary industry. Veterinary telemedicine presents the opportunity to expand veterinary medicine by increasing access to healthcare services for clients and patients and improving medical quality. The objective of this study was to assess veterinarians' knowledge and utilization of telehealth and telemedicine. RESULTS: Seventy-six veterinarians participated in the study and both qualitative and quantitative analyses were performed on the data collected. Several key themes emerged from the qualitative analysis of open-ended questions, including telecommunication, Doctor of Veterinary Medicine (DVM)-patient services, and remote interaction, among others. Through coding and qualitative analysis, researchers identified a lack of knowledge of the American Veterinary Medical Association (AVMA) definitions of telehealth and telemedicine. Specifically, a notable amount of participants were unaware of the distinction between the two practices per AVMA guidelines. Quantitative analyses revealed that the largest group of respondents reported sometimes utilizing telehealth and telemedicine in practice, with no distinct difference in utilization among the different age demographics of participants. CONCLUSIONS: These observations indicate a need for interventions both in veterinary school and continuing education programs with the purpose of increasing both knowledge and utilization of telehealth and telemedicine among veterinarians. While these recommendations serve as a starting point, future studies are needed to further enhance the understanding of veterinary telehealth and telemedicine in practice.

A sustainable business model for comprehensive medication management in a patient-centered medical home.

OBJECTIVES: To develop a sustainable business model for pharmacist-provided comprehensive medication management services in a patient-centered medical home. Secondarily, to evaluate the impact that the pharmacist had on clinical (glycosylated hemoglobin [A1C], low-density lipoprotein [LDL], and blood pressure) and economic (physician productivity and cost avoidance) outcomes. PRACTICE DESCRIPTION: This pilot project took place at the Palmetto Primary Care Physicians Trident office in North Charleston, South Carolina, from October 2013 to September 2014. At the time, the practice employed 5 physicians and 2 nurse practitioners and served more than 20,000 patients. PRACTICE INNOVATION: The pharmacist targeted patients with diabetes, lipid disorders, hypertension, congestive heart failure, obesity, polypharmacy, and treatment regimen nonadherence for his comprehensive medication management services. The pharmacist was available for immediate consultation or referrals by appointment 5 days per week. Services provided by the pharmacist were billed as medication therapy management or "incident to" physician evaluation and management services codes. EVALUATION: Number of patients seen per day, revenue collected from services rendered by the pharmacist, physician productivity and payment, cost avoidance, and health quality metrics (A1C, LDL, and blood pressure) were measured to determine the financial sustainability and clinical impact of the project. RESULTS AND IMPLICATIONS: The pharmacist was able to see an average of 11 patients per day, which was 72% of his capacity. The practice collected about $7400 per month for services rendered by the pharmacist. The average daily payment for services rendered by the physicians in the practice increased by 20.6%. More than 70% of uncontrolled patients had an improvement in clinical outcomes, such as A1C, LDL, and blood pressure. CONCLUSION: This project demonstrates the sustainable business model for embedding a pharmacist into a patient-centered medical home.

Jikradia olitoria ([Hemiptera]:[Cicadellidae]) Transmits the Sequevar NAGYIIIß Phytoplasma Strain Associated with North American Grapevine Yellows in Artificial Feeding Assays.

North American Grapevine Yellows (NAGY) is a destructive disease of grapevines caused by phytoplasmas, wall-less bacteria that are insect-transmitted and found in plant phloem tissues. Although the disease was recognized in vineyards in the eastern United States since the 1980s, the identities of vectors remain unknown. The objectives of this study were to survey potential phytoplasma vector insects inhabiting Virginia vineyards that expressed NAGY symptoms and to evaluate their ability to transmit phytoplasmas associated with NAGY. Phytoplasmas were identified as 'Candidatus Phytoplasma pruni'-related NAGYIIIß strains and 'Ca. Phytoplasma asteris'-related NAGYI-B strains. To determine the identities of the potential vectors, artificial feeding solution was used to evaluate the ability of leafhopper species to release phytoplasmas during feeding and phytoplasma strains were identified using molecular tools. Out of 49 insect species screened, Jikradia olitoria was the only insect that released phytoplasmas into the feeding solutions; all phytoplasmas, thus, detected were identified as NAGYIIIß strains by nucleotide sequencing of three different genomic regions. No NAGYI-B strain was detected. To our knowledge, this is the first evidence of a potential insect vector of a specific phytoplasma associated with NAGY disease, and it is the first report of J. olitoria being a putative vector of a plant pathogenic phytoplasma.

Respiratory hospital admissions and weather changes: a retrospective study in Charlottesville, Virginia, USA.

In most midlatitude locations, human morbidity and mortality are highly seasonal, with winter peaks driven by respiratory disease and associated comorbidities. But the transition between high and low mortality/morbidity months varies spatially. We use a measure of the thermal biophysical strain imposed on the respiratory system-the Acclimatization Thermal Strain Index (ATSI)-to examine respiratory hospital admissions in Charlottesville, VA. Daily respiratory admissions to the University of Virginia over a 19-year period are compared to ATSI values derived from hourly surface weather data acquired from the Charlottesville airport. Negative ATSI values (associated with transitions from warm (and humid) to cold (and dry) conditions) are related to admission peaks at seasonal and weekly timescales, whereas positive ATSI values (cold to warm) exhibit weaker relationships. This research marks the first application of the ATSI to human morbidity, and results suggest that respiratory strain may account for how people who are acclimated to different climates respond to short-term weather changes.

'Candidatus Phytoplasma luffae', a novel taxon associated with witches' broom disease of loofah, Luffa aegyptica Mill.

The phytoplasma associated with witches' broom disease of loofah [Luffa aegyptica Mill., syn. Luffa cylindrica (L.) M.J. Roem.] in Taiwan was classified in group 16SrVIII, subgroup A (16SrVIII-A), based on results from actual and in silico RFLP analysis of 16S rRNA gene sequences. Nucleotide sequencing of PCR-amplified, cloned DNA segments revealed rrn interoperon sequence heterogeneity in the loofah witches' broom (LfWB) phytoplasma. Whereas the 16S-23S rRNA spacer region of rrnA contained a complete tRNA-Ile gene, the spacer of rrnB contained a nonfunctional remnant of a tRNA gene. Phylogenetic analysis of the rrnA and rrnB 16S rRNA genes revealed that the LfWB phytoplasma represented a distinct lineage within the phytoplasma clade, and the LfWB phytoplasma shared less than 97.5 % nucleotide sequence similarity of 16S rRNA genes with previously described 'CandidatusPhytoplasma' taxa. Based on unique properties of DNA, we propose recognition of loofah witches' broom phytoplasma strain LfWBR as representative of a novel taxon, 'CandidatusPhytoplasma luffae'.