Immunity to Hepatitis B is Undetectable in the Majority of Adolescents and Young Adults Seeking Outpatient Medication Treatment for Opioid Use Disorder.

OBJECTIVE: To assess prevalence and predictors of hepatitis B immune status among adolescents and young adults (AYA) seeking outpatient medication treatment for opioid use disorder (MOUD). STUDY DESIGN: A retrospective medical chart review was conducted of AYA seeking MOUD between January 1, 2013 through December 31, 2015. Inclusion criteria included: diagnosis of opioid use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; received hepatitis serologic testing; and no evidence of prior or current hepatitis B infection. Hepatitis B immunization initiation was defined as a record of at least 1 hepatitis B vaccination; while receipt of at least 3 vaccinations indicated immunization completion. The presence of hepatitis B surface antibody (anti-HBs) was the primary outcome measure. RESULTS: Of the 193 patients that met eligibility criteria, the presence of anti-HBs was evident in 62 (32.1%). Hepatitis B immunization initiation and completion before presenting for MOUD was documented in 102 (52.9%) and 84 (43.5%). In multivariable logistic regression modeling, hepatitis B immunization initiation after infancy was associated with increased odds of having protective anti-HBs relative to immunization series initiation in infancy (OR 8.96, 95% CI 1.57-51.05). Completion of hepatitis B immunization series after infancy as compared to completion in infancy also increased the odds of protective anti-HBs (OR, 6.68, 95% CI 2.10-21.24). CONCLUSIONS: Rates of immunity to hepatitis B were low in AYA seeking MOUD. It is important to immunize patients seeking MOUD for hepatitis B and follow up with checks for seroconversion.

History of DNA Helicases.

Since the discovery of the DNA double helix, there has been a fascination in understanding the molecular mechanisms and cellular processes that account for: (i) the transmission of genetic information from one generation to the next and (ii) the remarkable stability of the genome. Nucleic acid biologists have endeavored to unravel the mysteries of DNA not only to understand the processes of DNA replication, repair, recombination, and transcription but to also characterize the underlying basis of genetic diseases characterized by chromosomal instability. Perhaps unexpectedly at first, DNA helicases have arisen as a key class of enzymes to study in this latter capacity. From the first discovery of ATP-dependent DNA unwinding enzymes in the mid 1970's to the burgeoning of helicase-dependent pathways found to be prevalent in all kingdoms of life, the story of scientific discovery in helicase research is rich and informative. Over four decades after their discovery, we take this opportunity to provide a history of DNA helicases. No doubt, many chapters are left to be written. Nonetheless, at this juncture we are privileged to share our perspective on the DNA helicase field - where it has been, its current state, and where it is headed.

Multifaceted Quality Improvement Initiative Improves Retention in Treatment for Youth with Opioid Use Disorder.

INTRODUCTION: There is a critical need to develop interventions that help adolescents and young adults with opioid use disorders (OUDs) connect with, engage in, and remain consistent with the treatment given that patients who develop long-term OUDs experience long-term medical and mental health sequelae. METHODS: We implemented quality improvement (QI) processes to increase early engagement and 6-month retention within a medication-assisted treatment clinic for youth with OUDs. QI interventions included motivational interviewing (MI) staff training, implementation of reduced initial treatment requirements, reduction of access barriers to treatment, and enhancement of patient treatment motivation. We monitored the impact of the interventions via a p-chart. RESULTS: A statistically significant shift was seen in the 6-month retention rate following both MI staff training and the use of reduced initial treatment requirements. Second visit return rate also experienced a statistically significant shift following transportation support and an incentive program. DISCUSSION: Our data demonstrate that following MI staff training, reduced initial clinic requirements, transportation support, and utilization of an incentive program, the second visit return rate, and 6-month retention rate improved within an outpatient medication-assisted treatment clinic for youth with OUDs.

Mental Health and Substance Use Care Among Young Adults Before and After Affordable Care Act (ACA) Implementation: A Rural and Urban Comparison.

PURPOSE: Rural young adults experience greater unmet need for mental health (MH) and alcohol or drug (AOD) treatment and lower health insurance coverage than urban residents. It is unknown whether Affordable Care Act (ACA) reforms in 2010 (dependent coverage extended to age 26) or 2014 (Medicaid expansion) closed rural/urban gaps in insurance and treatment. The present study compared changes in rates of health insurance, MH treatment, and AOD treatment for rural and urban young adults over a period of ACA reforms. METHODS: Young adult participants (18-25 years) in the National Survey on Drug Use and Health (2008-2014) with past-year psychological distress or AOD abuse were included. Difference-in-differences logistic regression models estimated rural/urban differences in insurance, MH, and AOD treatment pre- versus post-ACA reforms. Analyses adjusted for gender, race, marital status, and health status. RESULTS: Among 39,482 young adults with psychological distress or AOD, adjusted insurance rates increased from 72.0% to 81.9% (2008-2014), but a significant rural/urban difference (5.1%) remained in 2014 (P < .05). Among young adults with psychological distress (n = 23,470), MH treatment rates increased following 2010 reforms from 30.2% to 33.0%, but gains did not continue through 2014. Differences in MH treatment over time did not vary by rural/urban status and there were no significant changes in AOD treatment for either group. CONCLUSIONS: Although rates of insurance increased for all young adults, a significant rural/urban difference persisted in 2014. Meaningful increases in MH and AOD treatment may require targeted efforts to reduce noninsurance barriers to treatment.

Severe Sepsis and Acute Myocardial Dysfunction in an Adolescent with Chlamydia Trachomatis Pelvic Inflammatory Disease: A Case Report.

BACKGROUND: Although generally asymptomatic, severe Chlamydia trachomatis (C. trachomatis) infections have been documented. C. trachomatis has been associated with myocarditis as well as sepsis. CASE: A 19-year-old girl with type 1 diabetes mellitus developed sudden-onset mental status change and shock after resolution of diabetic ketoacidosis. Abdominal and pelvic imaging showed uterine and adnexal inflammation, and pelvic examination confirmed a diagnosis of pelvic inflammatory disease. The patient was intubated, required vasopressor support, and developed severe biventricular myocardial dysfunction. Infectious myocarditis workup was negative. Nucleic acid amplification testing from vaginal discharge was positive for C. trachomatis and Trichomonas vaginalis and negative for Neisseria gonorrhoeae. SUMMARY AND CONCLUSION: C. trachomatis should be considered in the workup of septic shock, particularly in populations at high risk for sexually transmitted infections.

Vulvar Fibroepithelial Polyps in a Female Adolescent: A Case Report.

BACKGROUND: Fibroepithelial polyps (FEPs) are benign tumors, of possibly hormone-dependent nature, found in the vulvovaginal region of women of reproductive age. CASE: A 15-year-old adolescent girl, receiving hormonal contraceptive therapy, who presented with multiple vulvar masses with histopathology consistent with FEP. SUMMARY AND CONCLUSION: The spectrum of the morphology of FEPs might make their diagnosis challenging. We describe a rare presentation of vulvar FEPs in an adolescent girl receiving hormonal contraceptive therapy.

Statewide opioid prescriptions and the prevalence of adolescent opioid misuse in Ohio.

BACKGROUND: Little is known about the relationship between opioid prescribing practices and the prevalence of adolescent opioid misuse. OBJECTIVE: To examine the relationships between both opioid prescriptions filled by adolescents and adults and adolescents seeking treatment for opioid misuse in Ohio. METHODS: Analyses of large statewide databases from 2008 to 2012, including all 88 counties in Ohio. The Ohio Board of Pharmacy provided data regarding prescription opioids filled by adolescents (12-20 years, N = 50,030,820 doses) and adults (>20 years, N = 3,811,288,395 doses) by county of residence. The Ohio Department of Mental Health and Drug Addiction Services provided annual treatment admissions for adolescent opioid misuse by county of residence (N = 6446). RESULTS: Adults filled prescriptions for nearly 100 oral opioid doses per capita annually, while adolescents filled prescriptions for approximately 7 oral opioid doses per capita annually. In Bayesian Poisson modeling examining the effect of annual adult per capita dose on adolescent treatment admissions, adjusted for annual adolescent per capita dose and year, an increase of one in the annual adult per capita opioid dose resulted in an increase of 1.3% (RR = 1.013, 95% HPD CI = [1.008, 1.017]) in the rate of adolescent treatment admissions. This association corresponds to a 99.99% chance that the adolescent treatment rate increases when the annual per capita adult dose is increased by one unit. CONCLUSION: The amount of opioids filled by adults in Ohio, although relatively stable from 2008 to 2012, is approximately 13 times that filled by adolescents and is significantly associated with adolescents seeking treatment for opioid misuse. Efforts to decrease adolescent opioid misuse should also focus on reducing adult opioid prescriptions.

A Signal Detection Analysis of the Effects of Alcohol on Visual Contrast Sensitivity.

Numerous studies have shown that acute ethanol consumption can reduce visual contrast sensitivity when measured using traditional psychophysical methods. However, no consideration has been given to whether nonsensory factors may also play a role. The present study used both traditional techniques and signal detection procedures to evaluate this possibility. In three within-subject experiments, 41 observers (19 Females and 22 Males) were presented with faint, contrast-modulated, visual patterns and asked to say if they had seen them. In Experiment 1, contrast thresholds were measured using a randomly interleaved staircase procedure, and the data confirmed an increase in threshold following alcohol. In Experiment 2, using similar stimuli, but applying a signal detection analysis, we found that sensitivity, as reflected in d', did not change following alcohol. However, participants became more conservative in their response criterion. The third experiment was designed to allow thresholds to be measured directly with a conventional psychophysical procedure while permitting a signal detection analysis to be performed on the same data. The conventional psychophysical task showed an increase in contrast threshold, while the signal detection analysis showed no change in sensitivity, but a shift to a more conservative criterion. These data highlight the importance of taking into account alcohol's effects on cognitive processes, even when assessing basic sensory function.

Biochemical Activities and Genetic Functions of the Drosophila melanogaster Fancm Helicase in DNA Repair.

Repair of DNA damage is essential to the preservation of genomic stability. During repair of double-strand breaks, several helicases function to promote accurate repair and prevent the formation of crossovers through homologous recombination. Among these helicases is the Fanconi anemia group M (FANCM) protein. FANCM is important in the response to various types of DNA damage and has been suggested to prevent mitotic crossovers during double-strand break repair. The helicase activity of FANCM is believed to be important in these functions, but no helicase activity has been detected in vitro We report here a genetic and biochemical study of Drosophila melanogaster Fancm. We show that purified Fancm is a 3' to 5' ATP-dependent helicase that can disassemble recombination intermediates, but only through limited lengths of duplex DNA. Using transgenic flies expressing full-length or truncated Fancm, each with either a wild-type or mutated helicase domain, we found that there are helicase-independent and C-terminal-independent functions in responding to DNA damage and in preventing mitotic crossovers.

Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults.

Objective. To evaluate ego strengths, in the context of Erikson's framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth. Methods. Opioid dependent (n = 51) and non-drug using control (n = 31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson's ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score. Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65 ± 30.39 opioid dependent versus 270.67 ± 30.06 control; p < 0.01). Evaluation of the PIES subscores found significant (p < 0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p < 0.001) independent predictor of total PIES score. Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence.

The UvrD303 hyper-helicase exhibits increased processivity.

DNA helicases use energy derived from nucleoside 5'-triphosphate hydrolysis to catalyze the separation of double-stranded DNA into single-stranded intermediates for replication, recombination, and repair. Escherichia coli helicase II (UvrD) functions in methyl-directed mismatch repair, nucleotide excision repair, and homologous recombination. A previously discovered 2-amino acid substitution of residues 403 and 404 (both Asp → Ala) in the 2B subdomain of UvrD (uvrD303) confers an antimutator and UV-sensitive phenotype on cells expressing this allele. The purified protein exhibits a "hyper-helicase" unwinding activity in vitro. Using rapid quench, pre-steady state kinetic experiments we show the increased helicase activity of UvrD303 is due to an increase in the processivity of the unwinding reaction. We suggest that this mutation in the 2B subdomain results in a weakened interaction with the 1B subdomain, allowing the helicase to adopt a more open conformation. This is consistent with the idea that the 2B subdomain may have an autoregulatory role. The UvrD303 mutation may enable the helicase to unwind DNA via a "strand displacement" mechanism, which is similar to the mechanism used to processively translocate along single-stranded DNA, and the increased unwinding processivity may contribute directly to the antimutator phenotype.

A retrospective study of retention of opioid-dependent adolescents and young adults in an outpatient buprenorphine/naloxone clinic.

OBJECTIVES: Opioid abuse and dependence rates continue to rise among U.S. adolescents. Medication-assisted treatment with buprenorphine/naloxone (BUP/NAL) has been shown to be effective up to 12 weeks. Few data are available regarding extended treatment outcomes. The objective of this study was to describe 1-year retention and compliance of a specific pediatric, outpatient BUP/NAL treatment program for opioid-dependent adolescents and young adults. METHODS: Retrospective chart review was conducted of all opioid-dependent adolescents and young adults (N = 103) who sought treatment from January 12, 2010, to January 9, 2011. Participants were classified as prescription opioid-dependent or combined heroin/prescription opioid-dependent. Opioid abstinence and BUP/NAL compliance were assessed by urine drug screen (UDS) at each visit. A Kaplan-Meier curve was fit to describe patients' retention time over 1 year. RESULTS: Mean age was 19.2 ± 1.6 years, 50.5% male, 98.1% white non-Hispanic, and 31.9% prescription opioid-dependent. Overall rates of opioid abstinence and BUP/NAL compliance were high (85.2% and 86.6%, respectively). Seventy-five percent of patients returned for a second visit. Patient retention was 45% at 60 days and 9% at 1 year. Female sex (P < 0.05), negative UDS for opioids (P < 0.001) or tetrahydrocannabinol (P < 0.001), and positive UDS for BUP/NAL (P < 0.001) were associated with longer retention time. CONCLUSIONS: Although patient retention was the largest barrier to success, a subset of opioid-dependent adolescents and young adults achieved long-term sobriety in our specific clinic program with continued outpatient BUP/NAL therapy. Retention correlated with UDS negative for opioids, negative for tetrahydrocannabinol, and positive for BUP/NAL.

Receipt of prescribed controlled substances by adolescents and young adults prior to presenting for opiate dependence treatment.

Purpose. The objective of this study was to document the number of controlled substance prescriptions filled by adolescents and young adult patients in the 2 years prior to presentation for opiate dependence treatment. Methods. Opiate-dependent youth (N = 125) presenting to our Medication-Assisted Treatment for Addiction program from January 1, 2008 to June 30, 2010 were identified via electronic medical record. Subjects were further classified based on their opiate use as dependent to heroin-only, prescription (Rx) opiate-only, or combined heroin + Rx opiate only. The Ohio Automated Rx Reporting System (OARRS) was used to identify each subject's controlled substance prescription history. Negative binomial regression was used to examine the relationships between patient characteristics and the total number of prescriptions filled. Results. Twenty-five percent of subjects had filled ≥6 prescriptions, and 15% had filled ≥11 prescriptions. The mean number of prescriptions filled was 5 (range: 0-59). Thirteen percent had filled ≥6 opiate/narcotic prescriptions, and 8% had filled ≥11 prescriptions. Conclusions. A subset of opiate-dependent youth had filled multiple opiate/narcotic prescriptions providing some evidence that physician-provided prescriptions may be a source of opiate abuse or diversion for a minority of opiate-dependent adolescents and young adults.

Reconstitution of the very short patch repair pathway from Escherichia coli.

The Escherichia coli very short patch (VSP) repair pathway corrects thymidine-guanine mismatches that result from spontaneous hydrolytic deamination damage of 5-methyl cytosine. The VSP repair pathway requires the Vsr endonuclease, DNA polymerase I, a DNA ligase, MutS, and MutL to function at peak efficiency. The biochemical roles of most of these proteins in the VSP repair pathway have been studied extensively. However, these proteins have not been studied together in the context of VSP repair in an in vitro system. Using purified components of the VSP repair system in a reconstitution reaction, we have begun to develop an understanding of the role played by each of these proteins in the VSP repair pathway and have gained insights into their interactions. In this report we demonstrate an in vitro reconstitution of the VSP repair pathway using a plasmid DNA substrate. Surprisingly, the repair track length can be modulated by the concentration of DNA ligase. We propose roles for MutL and MutS in coordination of this repair pathway.

Investigating the impact of bisphosphonates and structurally related compounds on bacteria containing conjugative plasmids.

Bacterial plasmids propagate through microbial populations via the directed process of conjugative plasmid transfer (CPT). Because conjugative plasmids often encode antibiotic resistance genes and virulence factors, several approaches to inhibit CPT have been described. Bisphosphonates and structurally related compounds (BSRCs) were previously reported to disrupt conjugative transfer of the F (fertility) plasmid in Escherichia coli. We have further investigated the effect of these compounds on the transfer of two additional conjugative plasmids, pCU1 and R100, between E. coli cells. The impact of BSRCs on E. coli survival and plasmid transfer was found to be dependent on the plasmid type, the length of time the E. coli were exposed to the compounds, and the ratio of plasmid donor to plasmid recipient cells. Therefore, these data indicate that BSRCs produce a range of effects on the conjugative transfer of bacterial plasmids in E. coli. Since their impact appears to be plasmid type-dependent, BSRCs are unlikely to be applicable as broad inhibitors of antibiotic resistance propagation.

Adolescents, IUDs, PID, and Enterococcus: a report of two cases.

BACKGROUND: Intrauterine devices are being used more frequently in adolescents requiring long-term reversible contraception. This population of sexually active adolescents is also at risk for pelvic inflammatory disease (PID). CASES: We report two cases of PID in adolescents with IUDs in place, both of whom had symptom resolution with removal of their IUDs, and in whom both IUDs were culture positive for Enterococcus. SUMMARY AND CONCLUSION: Whether these results indicate vaginal contamination or a causative agent for PID is unclear, but one should consider alternative causes of PID in adolescents with IUDs, particularly in those with prolonged symptoms.

Resolving Holliday junctions with Escherichia coli UvrD helicase.

The Escherichia coli UvrD helicase is known to function in the mismatch repair and nucleotide excision repair pathways and has also been suggested to have roles in recombination and replication restart. The primary intermediate DNA structure in these two processes is the Holliday junction. UvrD has been shown to unwind a variety of substrates including partial duplex DNA, nicked DNA, forked DNA structures, blunt duplex DNA and RNA-DNA hybrids. Here, we demonstrate that UvrD also catalyzes the robust unwinding of Holliday junction substrates. To characterize this unwinding reaction we have employed steady-state helicase assays, pre-steady-state rapid quench helicase assays, DNaseI footprinting, and electron microscopy. We conclude that UvrD binds initially to the junction compared with binding one of the blunt ends of the four-way junction to initiate unwinding and resolves the synthetic substrate into two double-stranded fork structures. We suggest that UvrD, along with its mismatch repair partners, MutS and MutL, may utilize its ability to unwind Holliday junctions directly in the prevention of homeologous recombination. UvrD may also be involved in the resolution of stalled replication forks by unwinding the Holliday junction intermediate to allow bypass of the blockage.