Computerized Tailored Interventions to Enhance Prevention and Screening for Hepatitis C Virus Among People Who Inject Drugs: Protocol for a Randomized Pilot Study.

BACKGROUND: Hepatitis C virus (HCV) infection is a growing problem among people who inject drugs. Strategies to reduce disease transmission (eg, syringe exchange programs) and facilitate HCV screening and linkage are available but are under-utilized in many communities affected by injection drug use. Novel approaches to increasing the use of these strategies are needed. OBJECTIVE: The goals of this project are to (1) develop and pilot test a computerized tailored intervention for increasing HCV screening and decreasing risky drug use behavior among people who inject drugs and (2) determine the feasibility of disseminating such an intervention using peer-based referrals in the setting of a community-based syringe exchange program. METHODS: This 2-arm, randomized pilot study is being conducted in a large-volume, multisite syringe exchange program in southern Wisconsin. A social network-based strategy was used to recruit a total of 235 adults who reported past-month injection of opioids, cocaine, or methamphetamine. Network recruiters were identified among clients requesting services from the syringe exchange program and were enlisted to refer eligible peers to the study. All participants completed a computer-adapted questionnaire eliciting information about risk behaviors and their knowledge, attitudes, and prior experiences related to HCV screening. Subjects were then randomly assigned to receive usual care, consisting of standard counseling by syringe exchange staff, or the Hep-Net intervention, which provides algorithm-based, real-time tailored feedback and recommendations for behavior change in the style of motivational interviewing. Changes in drug use behaviors and attitudes will be assessed during a second session between 90 and 180 days after the baseline visit. Frequency of repeat HCV testing and HCV incidence will be assessed through a database search 1 year after study completion. RESULTS: Recruitment for this study was completed in April 2015. Follow-up of enrolled participants is expected to continue until March 2016. Network recruiters were enrolled who referred a total of 195 eligible peers (overall N=235). At baseline, the median age was 34 years; 41.3% (97/235) were non-white; and 86.4% (203/235) reported predominantly injecting heroin. Most participants (161/234, 68.8%) reported sharing injection equipment in the past and of these, 30.4% (49/161) had never been tested for HCV. CONCLUSIONS: This study will provide preliminary evidence to determine whether incorporating computerized behavioral interventions into existing prevention services at syringe exchange programs can lead to adoption of healthier behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02474043; https://clinicaltrials.gov/ct2/show/NCT02474043 (Archived by WebCite at http://www.webcitation.org/6dbjUQG7J)

Compromised NLRP3 and AIM2 inflammasome function in autoimmune NZB/W F1 mouse macrophages

Inflammasomes are protein complexes activated by infection and cellular stress that promote caspase-1 activation and subsequent inflammatory cytokine processing and cell death. It has been anticipated that inflammasome activity contributes to autoimmunity. However, we previously showed that macrophages from autoimmune New Zealand Black (NZB) mice lack NLRP3 inflammasome function, and their AIM2 inflammasome responses are compromised by high expression of the AIM2 antagonist protein p202. Here we found that the point mutation leading to lack of NLRP3 expression occurred early in the NZB strain establishment, as it is shared with the related obese strain NZO, but not with the unrelated New Zealand White (NZW) strain. The first cross progeny of NZB and NZW mice develop more severe lupus nephritis than the NZB strain. We have compared AIM2 and NLRP3 inflammasome function in macrophages from NZB, NZW and NZB/W F1 mice. The NZW parental strain showed strong inflammasome function, whilst the NZB/W F1 have haploinsufficient expression of NLRP3 and show reduced NLRP3 and AIM2 inflammasome responses, particularly at low stimulus strength. It remains to be established whether the low inflammasome function could contribute to loss of tolerance and the onset of autoimmunity in NZB and NZB/W F1. However, with amplifying inflammatory stimuli through the course of disease, the NLRP3 response in the NZB/W F1 may be sufficient to contribute to kidney damage at later stages of disease. This article is protected by copyright. All rights reserved

Glycoproteomics-Compatible MS/MS-Based Quantification of Glycopeptide Isomers

Glycosylation is an essential protein modification occurring on the majority of extracellular human proteins, with mass spectrometry (MS) being an indispensable tool for its analysis, that not only determines glycan compositions, but also the position of the glycan at specific sites via glycoproteomics. However, glycans are complex branching structures with monosaccharides interconnected in a variety of biologically relevant linkages, isomeric properties that are invisible when the readout is mass alone. Here, we developed an LC-MS/MS-based workflow for determining glycopeptide isomer ratios. Making use of isomerically defined glyco(peptide) standards, we observed marked differences in fragmentation behavior between isomer pairs when subjected to collision energy gradients, specifically in terms of the galactosylation/sialylation branching and linkage. These behaviors were developed into component variables that allowed for relative quantification of isomerism within mixtures. Importantly, at least for small peptides, the isomer quantification appeared to be largely independent from the peptide portion of the conjugate, allowing a broad application of the method

Trends, Challenges, and Evidence-Based Strategies for School Dropout Prevention in Virginia

This MERC research and policy brief explores school dropout prevention by focusing on recent trends and research. It addresses the following questions: 1) What are recent trends in school dropout?2) What factors contribute to school dropout?3) What are the consequences and implications of school dropout?4) What are evidence-based strategies for school dropout prevention?5) What are federal, state, and division-level policies related to school dropout prevention in the MERC region? It concludes with a series of key takeaways and recommendations

Examining differential responses to the Take Care of Me trial: A latent class and moderation analysis

Given prevalent alcohol misuse-emotional comorbidities among young adults, we developed an internet-based integrated treatment called Take Care of Me. Although the treatment had an impact on several secondary outcomes, effects were not observed for the primary outcome. Therefore, the goal of the current study was to examine heterogeneity in treatment responses. The initial RCT randomized participants to either a treatment or psychoeducational control condition. We conducted an exploratory latent class analysis to distinguish individuals based on pre-treatment risk and then used moderated regressions to examine differential treatment responses based on class membership. We found evidence for three distinct groups. Most participants fell in the “low severity” group (n = 123), followed by the “moderate severity” group (n = 57) who had a higher likelihood of endorsing a previous mental health diagnosis and treatment and higher symptom severity than the low group. The “high severity” group (n = 42) endorsed a family history of alcoholism, and the highest symptom severity and executive dysfunction. Moderated regressions revealed significant class differences in treatment responses. In the treatment condition, high severity (relative to low) participants reported higher alcohol consumption and hazardous drinking and lower quality of life at follow-up, whereas moderate severity (relative to low) individuals had lower alcohol consumption at follow-up, and lower hazardous drinking at end-of-treatment. No class differences were found for participants in the control group. Higher risk individuals in the treatment condition had poorer responses to the program. Tailoring interventions to severity may be important to examine in future research

Contemporary human H3N2 influenza A viruses require a low threshold of suitable glycan receptors for efficient infection

Recent human H3N2 influenza A viruses have evolved to employ elongated glycans terminating in α2,6-linked sialic acid as their receptors. These glycans are displayed in low abundancies by (humanized) Madin-Darby Canine Kidney cells, which are commonly employed to propagate influenza A virus, resulting in low or no viral propagation. Here, we examined whether the overexpression of the glycosyltransferases β-1,3-N-acetylglucosaminyltransferase and β-1,4-galactosyltransferase 1, which are responsible for the elongation of poly-N-acetyllactosamines (LacNAcs), would result in improved A/H3N2 propagation. Stable overexpression of β-1,3-N-acetylglucosaminyltransferase and β-1,4-galactosyltransferase 1 in Madin-Darby Canine Kidney and "humanized" Madin-Darby Canine Kidney cells was achieved by lentiviral integration and subsequent antibiotic selection and confirmed by qPCR and protein mass spectrometry experiments. Flow cytometry and glycan mass spectrometry experiments using the β-1,3-N-acetylglucosaminyltransferase and/or β-1,4-galactosyltransferase 1 knock-in cells demonstrated increased binding of viral hemagglutinins and the presence of a larger number of LacNAc repeating units, especially on "humanized" Madin-Darby Canine Kidney-β-1,3-N-acetylglucosaminyltransferase cells. An increase in the number of glycan receptors did, however, not result in a greater infection efficiency of recent human H3N2 viruses. Based on these results, we propose that H3N2 influenza A viruses require a low number of suitable glycan receptors to infect cells and that an increase in the glycan receptor display above this threshold does not result in improved infection efficiency.</p

Childhood Maltreatment Influences Autonomic Regulation and Mental Health in College Students

Childhood maltreatment history may influence autonomic reactivity and recovery to stressors. Hypothetically, the maltreatment history may contribute to a retuned autonomic nervous system that is reflected in a novel metric, vagal efficiency (VE), designed to assess the functional efficiency of vagal cardioinhibitory pathways on heart rate. We explored whether VE mediates the well-documented relationship between maltreatment history and psychiatric symptoms. We also investigated the relationship between measures of autonomic regulation in response to the physical and emotional challenges and psychiatric symptoms. Participants (n = 167) completed self-report measures of psychiatric symptoms and had continuous beat-to-beat heart rate monitored before, during, and after physical and emotional stressors. Participants with maltreatment histories exhibited lower VE, which mediated the association of maltreatment history and the psychiatric symptoms of anxiety and depression. Consistent with prior literature, there were significant associations between maltreatment history and autonomic reactivity (i.e., heart rate and respiratory sinus arrhythmia) during emotional and physical challenges; however, when VE was entered as a covariate these associations were no longer statistically significant. Blunted VE may reflect a neural pathway through which maltreatment retunes autonomic regulation and provides a neurophysiological platform that increases mental health risk

Contemporary human H3N2 influenza a viruses require a low threshold of suitable glycan receptors for efficient infection

Recent human H3N2 influenza A viruses (IAV) have evolved to employ elongated glycans terminating in α2,6-linked sialic acid as their receptors. These glycans are displayed in low abundancies by (humanized) Madin-Darby Canine Kidney cells (MDCK and hCK) which are commonly employed to propagate IAV, resulting in low or no viral propagation. Here, we examined whether the overexpression of the glycosyltransferases B3GNT2 and B4GALT1, which are responsible for the elongation of poly-N-acetyllactosamines (LacNAc), would result in improved A/H3N2 propagation. Stable overexpression of B3GNT2 and B4GALT1 in MDCK and hCK cells was achieved by lentiviral integration and subsequent antibiotic selection and confirmed by qPCR and protein mass spectrometry experiments. Flow cytometry and glycan mass spectrometry experiments using the B3GNT2 and/or B4GALT1 knock-in cells demonstrated increased binding of viral hemagglutinins and the presence of a larger number of LacNAc repeating units, especially on hCK-B3GNT2 cells. An increase in the number of glycan receptors did, however, not result in a greater infection efficiency of recent human H3N2 viruses. Based on these results, we propose that H3N2 IAVs require a low number of suitable glycan receptors to infect cells and that an increase in the glycan receptor display above this threshold does not result in improved infection efficiency

The pleiotropic phenotype of FlbA of Aspergillus niger is explained in part by the activity of seven of its downstream-regulated transcription factors

Inactivation of flbA in Aspergillus niger results in thinner cell walls, increased cell lysis, abolished sporulation, and an increased secretome complexity. A total of 36 transcription factor (TF) genes are differentially expressed in ΔflbA. Here, seven of these genes (abaA, aslA, aslB, azf1, htfA, nosA, and srbA) were inactivated. Inactivation of each of these genes affected sporulation and, with the exception of abaA, cell wall integrity and protein secretion. The impact on secretion was strongest in the case of ΔaslA and ΔaslB that showed increased pepsin, cellulase, and amylase activity. Biomass was reduced of agar cultures of ΔabaA, ΔaslA, ΔnosA, and ΔsrbA, while biomass was higher in liquid shaken cultures of ΔaslA and ΔaslB. The ΔaslA and ΔhtfA strains showed increased resistance to H2O2, while ΔaslB was more sensitive to this reactive oxygen species. Together, inactivation of the seven TF genes impacted biomass formation, sporulation, protein secretion, and stress resistance, and thereby these genes explain at least part of the pleiotropic phenotype of ΔflbA of A. niger

One-year prevalence and the impact of migraine and tension-type headache in Turkey: a nationwide home-based study in adults

Several studies have shown that the prevalence of migraine and tension-type headache (TTH) varied between different geographical regions. Therefore, there is a need of a nationwide prevalence study for headache in our country, located between Asia and Europe. This nationwide study was designed to estimate the 1-year prevalence of migraine and TTH and analyse the clinical features, the impact as well as the demographic and socio-economic characteristics of the participant households in Turkey. We planned to investigate 6,000 representative households in 21 cities of Turkey; and a total of 5,323 households (response rate of 89%) aged between 18 and 65 years were examined for headache by 33 trained physicians at home on the basis of the diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II). The electronically registered questionnaire was based on the headache features, the associated symptoms, demographic and socio-economic situation and history. Of 5,323 participants (48.8% women; mean age 35.9 ± 12 years) 44.6% reported recurrent headaches during the last 1 year and 871 were diagnosed with migraine at a prevalence rate of 16.4% (8.5% in men and 24.6% in women), whereas only 270 were diagnosed with TTH at a prevalence rate of 5.1% (5.7% in men and 4.5% in women). The 1-year prevalence of probable migraine was 12.4% and probable TTH was 9.5% additionally. The rate of migraine with aura among migraineurs was 21.5%. The prevalence of migraine was highest among 35–40-year-old women while there were no differences in age groups among men and in TTH overall. More than 2/3 of migraineurs had ever consulted a physician whereas only 1/3 of patients with TTH had ever consulted a physician. For women, the migraine prevalence was higher among the ones with a lower income, while among men, it did not show any change by income. Migraine prevalence was lower in those with a lower educational status compared to those with a high educational status. Chronic daily headache was present in 3.3% and the prevalence of medication overuse headache was 2.1% in our population. There was an important impact of migraine with a monthly frequency of 5.9 ± 6, and an attack duration of 35.1 ± 72 h, but only 4.9% were on prophylactic treatment. The one-year prevalence of migraine estimated as 16.4% was similar or even higher than world-wide reported migraine prevalence figures and identical to a previous nation-wide study conducted in 1998, whereas the TTH prevalence was much lower using the same methodology with the ICHD-II criteria