Development of an Interdisciplinary Telehealth Model of Provider Training and Comprehensive Care for Hepatitis C and Opioid Use Disorder in a High-Burden Region.

BACKGROUND: Hepatitis C virus (HCV) and the opioid epidemic disproportionately affect the Appalachian region. Geographic and financial barriers prevent access to specialty care. Interventions are needed to address the HCV-opioid syndemic in this region. METHODS: We developed an innovative, collaborative telehealth model in Southwest Virginia featuring bidirectional referrals from and to comprehensive harm reduction (CHR) programs and office-based opioid therapy (OBOT), as well as workforce development through local provider training in HCV management. We aimed to (1) describe the implementation process of provider training and (2) assess the effectiveness of the telehealth model by monitoring patient outcomes in the first year. RESULTS: The provider training model moved from a graduated autonomy model with direct specialist supervision to a 1-day workshop with parallel tracks for providers and support staff followed by monthly case conferences. Forty-four providers and support staff attended training. Eight providers have begun treating independently. For the telehealth component, 123 people were referred, with 62% referred from partner OBOT or CHR sites; 103 (84%) attended a visit, 93 (76%) completed the treatment course, and 61 (50%) have achieved sustained virologic response. Rates of sustained virologic response did not differ by receipt of treatment for opioid use disorder. CONCLUSIONS: Providers demonstrated a preference for an in-person training workshop, though further investigation is needed to determine why only a minority of those trained have begun treating HCV independently. The interdisciplinary nature of this program led to efficient treatment of hepatitis C in a real-world population with a majority of patients referred from OBOTs and CHR programs.

Concern noted: A descriptive study of editorial expressions of concern in PubMed and PubMed Central.

BACKGROUND: An editorial expression of concern (EEoC) is issued by editors or publishers to draw attention to potential problems in a publication, without itself constituting a retraction or correction. METHODS: We searched PubMed, PubMed Central (PMC), and Google Scholar to identify EEoCs issued for publications in PubMed and PMC up to 22 August 2016. We also searched the archives of the Retraction Watch blog, some journal and publisher websites, and studies of EEoCs. In addition, we searched for retractions of EEoCs and affected articles in PubMed up to 8 December 2016. We analyzed overall historical trends, as well as reported reasons and subsequent editorial actions related to EEoCs issued between August 2014 and August 2016. RESULTS: After screening 5,076 records, we identified 230 EEoCs that affect 300 publications indexed in PubMed, the earliest issued in 1985. Half of the primary EEoCs were issued between 2014 and 2016 (52%). We found evidence of some EEoCs that had been removed by the publisher without leaving a record and some were not submitted for PubMed or PMC indexing. A minority of publications affected by EEoCs had been retracted by early December 2016 (25%). For the subset of 92 EEoCs issued between August 2014 and August 2016, affecting 99 publications, the rate of retraction was similar (29%). The majority of EEoCs were issued because of concerns with validity of data, methods, or interpretation of the publication (68%), and 31% of cases remained open. Issues with images were raised in 40% of affected publications. Ongoing monitoring after the study identified another 17 EEoCs to year's end in 2016, increasing the number of EEoCs to 247 and publications in PubMed known to be affected by EEoCs to 320 at the end of 2016. CONCLUSIONS: EEoCs have been rare publishing events in the biomedical literature, but their use has been increasing. Most have not led to retractions, and many remain unresolved. Lack of prominence and inconsistencies in management of EEoCs reduce the ability of these notices to alert the scientific community to potentially serious problems in publications. EEoCs will be made identifiable in PubMed in 2017.

Genetic Ablation, Sensitization, and Isolation of Neurons Using Nitroreductase and Tetrodotoxin-Insensitive Channels.

Advances in genetic technologies enable the highly selective expression of transgenes in targeted neuronal cell types. Transgene expression can be used to noninvasively ablate, silence or activate neurons, providing a tool to probe their contribution to the control of behavior or physiology. Here, we describe the use of the tetrodotoxin (TTX)-resistant voltage-gated sodium channel Nav1.5 for either sensitizing neurons to depolarizing input, or isolating targeted neurons from surrounding neural activity, and methods for selective neuronal ablation using the bacterial nitroreductase NfsB.

Improving HIV Surveillance Data for Public Health Action in Washington, DC: A Novel Multiorganizational Data-Sharing Method.

BACKGROUND: The National HIV/AIDS Strategy calls for active surveillance programs for human immunodeficiency virus (HIV) to more accurately measure access to and retention in care across the HIV care continuum for persons living with HIV within their jurisdictions and to identify persons who may need public health services. However, traditional public health surveillance methods face substantial technological and privacy-related barriers to data sharing. OBJECTIVE: This study developed a novel data-sharing approach to improve the timeliness and quality of HIV surveillance data in three jurisdictions where persons may often travel across the borders of the District of Columbia, Maryland, and Virginia. METHODS: A deterministic algorithm of approximately 1000 lines was developed, including a person-matching system with Enhanced HIV/AIDS Reporting System (eHARS) variables. Person matching was defined in categories (from strongest to weakest): exact, very high, high, medium high, medium, medium low, low, and very low. The algorithm was verified using conventional component testing methods, manual code inspection, and comprehensive output file examination. Results were validated by jurisdictions using internal review processes. RESULTS: Of 161,343 uploaded eHARS records from District of Columbia (N=49,326), Maryland (N=66,200), and Virginia (N=45,817), a total of 21,472 persons were matched across jurisdictions over various strengths in a matching process totaling 21 minutes and 58 seconds in the privacy device, leaving 139,871 uniquely identified with only one jurisdiction. No records matched as medium low or low. Over 80% of the matches were identified as either exact or very high matches. Three separate validation methods were conducted for this study, and they all found ≥90% accuracy between records matched by this novel method and traditional matching methods. CONCLUSIONS: This study illustrated a novel data-sharing approach that may facilitate timelier and better quality HIV surveillance data for public health action by reducing the effort needed for traditional person-matching reviews without compromising matching accuracy. Future analyses will examine the generalizability of these findings to other applications.

Increased functional protein expression using nucleotide sequence features enriched in highly expressed genes in zebrafish.

Many genetic manipulations are limited by difficulty in obtaining adequate levels of protein expression. Bioinformatic and experimental studies have identified nucleotide sequence features that may increase expression, however it is difficult to assess the relative influence of these features. Zebrafish embryos are rapidly injected with calibrated doses of mRNA, enabling the effects of multiple sequence changes to be compared in vivo. Using RNAseq and microarray data, we identified a set of genes that are highly expressed in zebrafish embryos and systematically analyzed for enrichment of sequence features correlated with levels of protein expression. We then tested enriched features by embryo microinjection and functional tests of multiple protein reporters. Codon selection, releasing factor recognition sequence and specific introns and 3' untranslated regions each increased protein expression between 1.5- and 3-fold. These results suggested principles for increasing protein yield in zebrafish through biomolecular engineering. We implemented these principles for rational gene design in software for codon selection (CodonZ) and plasmid vectors incorporating the most active non-coding elements. Rational gene design thus significantly boosts expression in zebrafish, and a similar approach will likely elevate expression in other animal models.

Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses.

Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish.

Structural factors and best practices in implementing a linkage to HIV care program using the ARTAS model.

BACKGROUND: Implementation of linkage to HIV care programs in the U.S. is poorly described in the literature despite the central role of these programs in delivering clients from HIV testing facilities to clinical care sites. Models demonstrating success in linking clients to HIV care from testing locations that do not have co-located medical care are especially needed. METHODS: Data from the Antiretroviral Treatment Access Studies-II project ('ARTAS-II') as well as site visit and project director reports were used to describe structural factors and best practices found in successful linkage to care programs. Successful programs were able to identify recently diagnosed HIV-positive persons and ensure that a high percentage of persons attended an initial HIV primary care provider visit within six months of enrolling in the linkage program. RESULTS: Eight categories of best practices are described, supplemented by examples from 5 of 10 ARTAS-II sites. These five sites highlighted in the best practices enrolled a total of 352 HIV+ clients and averaged 85% linked to care after six months. The other five grantees enrolled 274 clients and averaged 72% linked to care after six months. Sites with co-located HIV primary medical care services had higher linkage to care rates than non-co-located sites (87% vs. 73%). Five grantees continued linkage to care activities in some capacity after project funding ended. CONCLUSIONS: With the push to expand HIV testing in all U.S. communities, implementation and evaluation of linkage to care programs is needed to maximize the benefits of expanded HIV testing efforts.

Allocation from capital and income sources to reproduction shift from first to second clutch in the flesh fly, Sarcophaga crassipalpis.

Understanding how resources are allocated between survival and reproduction is fundamental to the study of the evolution of life histories. Reproductive resources can come from two intrinsic resource pools, stored reserves (capital) acquired before reproduction or income acquired during reproduction. The variety of reproductive strategies in insects is remarkable and reproductive allocation encompasses the complete range of allocation strategies from pure capital breeders to pure income breeders. However, most organisms probably use a blend of capital and income and this blend is likely dynamic, changing between reproductive bouts in response to internal and external conditions. We used stable isotopes to quantify the allocation of capital and income resources to reproduction in the flesh fly, Sarcopha crassipalpis and assessed how allocation patterns change over multiple bouts of reproduction. Sarcophaga crassipalpis shifts from a slight investment of capital in the first clutch to an almost pure income breeder in the second clutch. We discuss the relationship between activity and allocation, and the potential for this system to understand how allocation patterns change in response to environmental stress.

Progestin therapy of complex endometrial hyperplasia with and without atypia.

OBJECTIVE: To assess the likelihood of histologic persistence/progression of complex hyperplasia and atypical hyperplasia among women treated with progestin compared with those not treated, with attention to type, dose, and duration. METHODS: This was a cohort study at an integrated health plan of women, ages 18-85 years, with complex or atypical hyperplasia on independent pathology review with a second endometrial specimen in the 2-6 months after the index diagnosis. Progestin therapy between index diagnosis and follow-up biopsy was determined from the pharmacy database. Medical record abstraction was performed. Relative risks (RRs), adjusted for age and body mass index, were calculated. RESULTS: Among 185 women, average age 55.9 years, follow-up 16.1 weeks, 115 had complex and 70 had atypical hyperplasia. Among women with complex hyperplasia, 28.4% of those treated with progestin and 30.0% of those not treated had persistence/progression (RR 1.20, 95% confidence interval [CI] 0.53-2.72). Among women with atypical hyperplasia, 26.9% of those treated with progestin and 66.7% of those not treated had persistence/progression (RR 0.39, 95% CI 0.21-0.70); there was a suggestion that use of at least a medium dose, or a duration of at least 3 months, was associated with a particularly low probability of persistence/progression. CONCLUSION: Although progestin treatment of women with atypical hyperplasia was associated with a substantial increase in the likelihood of regression of the lesion during the ensuing 2-6 months, persistence/progression was nonetheless present in more than one quarter of treated women. Regression of complex hyperplasia without atypia was common whether progestin had or had not been used.