Hepatitis C Within a Single Health System: Progression Along the Cascade to Cure Is Higher for Those With Substance Misuse When Linked to a Clinic With Embedded Support Services.

BACKGROUND: Hepatitis C is now curable for most individuals, and national goals for elimination have been established. Transmission persists, however, particularly in nonurban regions affected by the opioid epidemic. To reach goals of elimination, barriers to treatment must be identified. METHODS: In this open cohort of all individuals diagnosed with active hepatitis C from 2010 to 2016 at a large medical center, we identified patient and clinic characteristics associated with our primary outcome, sustained virologic response (SVR). We performed a subgroup analysis for those with documented substance misuse. RESULTS: SVR was achieved in 1544 (41%) of 3790 people with active hepatitis C. In a multivariable Poisson regression model, SVR was more likely in individuals diagnosed outpatient (incident rate ratio [IRR], 1.7; 95% confidence interval [CI], 1.5-2.0), living in close proximity to the medical center (IRR, 1.2; 95% CI, 1.1-1.3), with private insurance (IRR, 1.1; 95% CI, 1.0-1.3), and with cirrhosis (IRR, 1.4; 95% CI, 1.3-1.5). Achieving SVR was less likely in those qualifying as indigent (IRR, 0.8; 95% CI, 0.8-0.9) and those with substance misuse (IRR, 0.8; 95% CI, 0.7-0.9). In the subgroup analysis of those with substance misuse, SVR rates were higher in those linked to the infectious diseases clinic, which has embedded support services, than those linked to the gastroenterology clinic, which does not (IRR, 1.4; 95% CI, 1.1-1.9). CONCLUSIONS: Social determinants of health including proximity to care and poverty impacted achievement of SVR. Those with substance misuse, a high-priority population for treatment of hepatitis C, had better outcomes when receiving care in a clinic with embedded support services.

Diagnostic accuracy of self-collected human papillomavirus specimens as a primary screen for cervical cancer.

The aim of the study was to compare the sensitivity of self-collected with clinician-collected human papillomavirus (HPV) tests and cytology for cervical cancer. A total of 250 non-pregnant, 25-60-year-old women from Leon, Nicaragua, self-collected vaginal specimens for HPV and received a pelvic examination for cytology and reflex HPV. All participants underwent colposcopy and completed questionnaires regarding demographic and medical information. The sensitivities of self-collected brushes, self-collected swabs and clinician-collected HPV tests were 25%, 16.7%, and 16.7%, respectively, with colposcopy as the gold standard and 30%, 22.2% and 40% when cytology was the gold standard. Agreement between self-collection methods was significant (κ=0.84, p<0.001). Although utilisation of colposcopy in every participant resulted in lower sensitivities, the self-collected tests surpassed cytology and significantly agreed with the clinician-collected results. Further clarification of the sensitivity will be required to employ self-collection for cervical cancer screening in low resource areas like rural Nicaragua.

Genetic manipulation of Bacillus methanolicus, a gram-positive, thermotolerant methylotroph.

We report the fist genetic transformation system, shuttle vectors, and integrative vectors for the thermotolerant, methylotrophic bacterium Bacillus methanolicus. By using a polyethylene glycol-mediated transformation procedure, we have successfully transformed B. methanolicus with both integrative and multicopy plasmids. For plasmids with a single BmeTI recognition site, dam methylation of plasmid DNA (in vivo or in vitro) was found to enhance transformation efficiency from 7- to 11-fold. Two low-copy-number Escherichia coli-B, methanolicus shuttle plasmids, pDQ507 and pDQ508, are described. pDQ508 caries the replication origin cloned from a 17-kb endogenous B. methanolicus plasmid, pBM1. pDQ507 carries a cloned B. methanolicus DNA fragment, pmr-1, possibly of chromosomal origin, that supports maintenance of pDQ507 as a circular, extrachromosomal DNA molecule. Deletion analysis of pDQ507 indicated two regions required for replication, i.e., a 90-bp AT-rich segment containing a 46-bp imperfect, inverted repeat sequence and a second region 65% homologous to the B. subtilis dpp operon. We also evaluated two E. coli-B. subtilis vectors, pEN1 and pHP13, for use as E. coli-B. methanolicus shuttle vectors. The plasmids pHP13, pDQ507, and pDQ508 were segregationally and structurally stable in B. methanolicus for greater than 60 generations of growth under nonselective conditions; pEN1 was segregationally unstable. Single-stranded plasmid DNA was detected in B. methanolicus transformants carrying either pEN1, pHP13, or pDQ508, suggesting that pDQ508, like the B. subtilis plasmids, is replicated by a rolling-circle mechanism. These studies provide the basic tools for the genetic manipulation of B. methanolicus.

Sexually dimorphic effects of perinatal alcohol exposure on social interactions and amygdala DNA and DOPAC concentrations.

The hypotheses that exposure of rats to alcohol during a period roughly equivalent to the human third trimester induces changes in social interactions and neurotransmitter and DNA concentrations in the amygdala region were examined. The alcohol exposure was accomplished via an artificial rearing procedure. There were two alcohol-exposed groups (3 and 5 g/kg/day of ethanol) and two control groups (one artificially reared but not exposed to alcohol and one reared normally by dams) in all studies. Active social interactions were reduced in the male 5 g/kg/day group and increased in both female alcohol-exposed groups compared to their respective control groups. Exposure to 5 g/kg/day of alcohol reduced the DNA concentration in the amygdala region of male rats compared to either control group; there were no effects in females. Because some systems have been shown to exhibit alcohol-induced changes only under stressed conditions, noradrenaline, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured in the amygdala region under both nonstressed and stressed conditions. The stress-induced increase in DOPAC concentrations was enhanced in the female high dose group compared to either control group; there were no effects in males. In summary, alcohol exposure during the early postnatal period altered social interactions and DOPAC and DNA concentrations in the amygdala region in a sexually dimorphic manner.