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The vaginal microbiota in bacterial vaginosis (BV) typically has low abundance of lactic acid producing lactobacilli. Lactic acid has properties that may make it effective for treating BV and/or restoring an optimal lactobacillus-dominated vaginal microbiota. We conducted a systematic review to describe the effect of intravaginal lactic acid-containing products on BV cure, and their impact on vaginal microbiota composition (PROSPERO registration: CRD42018115982). PubMed, Embase and OVID were searched from inception to November 2019 to identify eligible studies. Included studies evaluated an intravaginal lactic acid-containing product and reported BV cure using established diagnostic methods, and/or vaginal microbiota composition using molecular methods. Studies were independently screened and assessed, and the proportion of women cured post-treatment was calculated. Study results were described in a qualitative manner. We identified 1,883 articles and assessed 57 full-texts for eligibility. Seven different lactic acid-containing products were evaluated and differed with respect to excipients, lactic acid concentration and pH. Most studies had medium or high risk of bias. Three trials compared the efficacy of a lactic acid-containing product to metronidazole for BV cure. One study found lactic acid to be equivalent to metronidazole and two studies found lactic acid to be significantly inferior to metronidazole. Two studies included a control group receiving a placebo or no treatment. One reported lactic acid to be superior than no treatment and the other reported lactic acid to be equivalent to placebo. Lactic acid-containing products did not significantly impact the vaginal microbiota composition. There is a lack of high-quality evidence to support the use of lactic acid-containing products for BV cure or vaginal microbiota modulation. However, adequately powered and rigorous randomised trials with accompanying vaginal microbiota data are needed to evaluate the efficacy of lactic acid as a BV treatment strategy.

RationaleA subset of male rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) have unusually high levels of drug intake; however, factor(s) that influence this behavior (e.g., reinforcement history and sex) are unknown.ObjectivesCharacterize the reinforcing potency and effectiveness of MDPV in female rats to determine whether (1) a subset of females also develop high levels of MDPV self-administration (i.e., a high-responder phenotype) and (2) the degree to which the high-responder phenotype is influenced by various reinforcement histories (i.e., responding for cocaine or food).MethodsFemale Sprague Dawley rats initially responded for MDPV (0.032 mg/kg/infusion), cocaine (0.32 mg/kg/infusion), or food (45-mg grain pellet) under fixed ratio (FR) 1 and FR5 schedules of reinforcement. After 20 sessions, the cocaine- and food-history rats responded for MDPV for 20 additional sessions. Dose-response curves for MDPV were generated under FR5 and progressive ratio (PR) schedules of reinforcement.ResultsA subset of rats responding for MDPV developed high levels of MDPV intake. A history of responding for cocaine, but not food, inhibited the development of high levels of MDPV intake. Large individual differences were observed in the level of self-administration when MDPV was available under an FR5, but not PR, schedule of reinforcement.ConclusionsMDPV functions as a powerful reinforcer in female rats, as has been previously reported in male rats. The substantial variability in MDPV self-administration between subjects may be related to individual differences in human drug-taking behavior.

Nkx2.2 Regulates β-Cell Function in the Mature Islet Michelle J. Doyle and Lori Sussel From the Program in Molecular Biology, Department of Biochemistry and Genetics, University of Colorado Health Sciences Center, Aurora, Colorado Address correspondence and reprint requests to Lori Sussel, Biochemistry and Molecular Genetics, Mail Stop 8101, 12801 E. 17th Ave., Room 10101, P.O. Box 6511, Aurora, CO 80045. E-mail: lori.sussel{at}uchsc.edu Abstract Nkx2.2 is a homeodomain transcription factor that is critical for pancreatic endocrine cell specification and differentiation in the developing mouse embryo. The purpose of this study was to determine whether Nkx2.2 is also required for the maintenance and function of the mature β-cell in the postnatal islet. We have demonstrated previously that a repressor derivative of Nkx2.2 can functionally substitute for endogenous Nkx2.2 to fully restore α- and immature β-cells in the embryonic islet; however, Nkx2.2 activator functions appear to be required to form a functional β-cell. In this study, we have created transgenic mouse lines to express the Nkx2.2-repressor derivative in the mature β-cell in the presence of endogenous Nkx2.2. The transgenic mice were assessed for β-cell function, overall islet structure, and expression of β-cell–specific markers. Using this transgenic approach, we have determined that the Nkx2.2-repressor derivative disrupts endogenous Nkx2.2 expression in adult mice and causes downregulation of the mature β-cell factors, MafA and Glut2. Consistently, the Nkx2.2-repressor mice display reduced insulin gene expression and pancreatic insulin content and impaired insulin secretion. At weaning, the male Nkx2.2-repressor mice are overtly diabetic and all Nkx2.2-repressor transgenic mice exhibit glucose intolerance. Furthermore, the loss of β-cell function in the Nkx2.2-repressor transgenic mice is associated with disrupted islet architecture. These studies indicate a previously undiscovered role for Nkx2.2 in the maintenance of mature β-cell function and the formation of normal islet structure. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 24 April 2007. DOI: 10.2337/db06-1766. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted April 22, 2007. Received December 23, 2006. DIABETES

Rationale Social defeat stress results in escalation of cocaine taking and long-term neural adaptations in rats. How the intensity and timing of social defeat stress determine these effects, particularly in mice, have not been well characterized. Objective This study investigated the effects of mild vs. moderate intensities and durations of social stress on intravenous cocaine self-administration as well as on dopamine (DA) release in the nucleus accumbens shell (NAcSh) by using in vivo microdialysis. Methods Adult male Swiss Webster (CFW) mice experienced 10 days of social defeat stress, either mild (15 attack bites in ca. 1.8 min) or moderate (30 attack bites in ca. 3.6 min), and compared to controls that were handled daily. Subsequently, the socially stressed mice were assessed for either (1) intravenous cocaine self-administration, using several unit doses (0, 0.3, 0.6, 1.0 mg/kg/infusion) under limited access conditions, or (2) neural sensitization, as determined by in vivo microdialysis of DA in the NAcSh in response to acute d -amphetamine challenge. Results Social defeat stress resulted in escalated cocaine self-administration in both mild and moderate socially stressed groups. In addition, social defeat stress led to increased DA release after d -amphetamine challenge. Conclusions These data suggest that both mild and moderate socially stressed mice exhibit increased cocaine taking compared to controls, and this increase is associated with escalated dopaminergic responses in the NAcSh.

Antimicrobial-resistant Mycoplasma genitalium is becoming increasingly common and creating major treatment challenges. We present early data on combination therapy with doxycycline and sitafloxacin to treat highly resistant M. genitalium. We found the regimen was well tolerated and cured 11/12 infections that had failed prior regimens with moxifloxacin and pristinamycin.

Recurrence of BV following standard treatment is unacceptably high. Posttreatment recurrence is distressing for women, and it imposes a considerable burden on the health care system. Up to 50% of women receiving first-line antibiotics for bacterial vaginosis (BV) experience recurrence within 12 weeks. Evidence suggests that reinfection from an untreated regular sexual partner contributes to recurrence. We conducted a pilot study of 34 heterosexual couples to describe the impact of concurrent partner treatment on the composition of the genital microbiota over a 12-week period. We also determined the acceptability and tolerability of concurrent partner treatment and obtained preliminary estimates of the efficacy of the intervention to inform a randomized controlled trial (RCT). Women received first-line antibiotic treatment for BV (i.e., oral metronidazole or intravaginal clindamycin), and their male partner received oral metronidazole, 400 mg, and 2% clindamycin cream applied topically to penile skin, both twice daily for 7 days. The genital microbiota was characterized at three anatomical sites (women, vaginal; men, cutaneous penile and first-pass urine [representing the urethra]) using 16S rRNA gene sequencing. Immediately posttreatment, concurrent partner treatment significantly reduced the abundance of BV-associated bacteria (false-discovery rate [FDR] corrected P value < 0.05) and altered the overall microbiota composition of all three anatomical sites ( P  = 0.001). Suppression of BV-associated bacteria was sustained in the majority (81%) of women over the 12-week period (FDR P value < 0.05), despite BV-associated bacteria reemerging at both genital sites in men. In this cohort of women at high risk for recurrence, five recurred within 12 weeks of treatment (17%; 95% confidence interval [CI], 6 to 34%). Importantly, men tolerated and adhered to combination therapy. Our findings provide support for an RCT of combined oral and topical male partner treatment for BV. IMPORTANCE Recurrence of BV following standard treatment is unacceptably high. Posttreatment recurrence is distressing for women, and it imposes a considerable burden on the health care system. Recurrences result in multiple presentations to clinical services and repeated antibiotic use, and the associated obstetric and gynecological sequelae are significant. New treatments to improve long-term BV cure are urgently needed. Here, we used 16S rRNA gene sequencing to investigate changes in the microbiota composition at three genital sites (vagina, penile skin, and male urethra) of heterosexual couples undergoing concurrent partner treatment for bacterial vaginosis (BV). We found that concurrent partner treatment immediately and significantly altered the composition of the genital microbiota of both partners, with a reduction in BV-associated bacteria seen at all three sites. BV cure at 12 weeks posttreatment was higher than expected. These microbiological data provide evidence for continued investigation of partner treatment as a strategy to improve BV cure.

Bacterial vaginosis (BV) is a common vaginal infection among women of reproductive age. Increasing evidence suggests BV may be sexually transmitted indicating a potential role for the treatment of sexual partners. If partner treatment reduces BV recurrence in women, real-world success will depend on sexual partners' willingness to accept it. However, a lack of data exists on the acceptability of partner treatment among sexual partners, and no data exists on male partners' experience of BV specifically. The aim of this study was to explore male partners' views and experience of BV and their attitudes toward associated partner treatment. A social constructionist approach informed the framework of this study. Semi structured interviews were conducted with eleven men who participated in a BV partner treatment trial. Interviews were transcribed verbatim and analysed thematically. In the absence of symptoms in themselves, BV had little impact on men beyond their concerns for their partner's health and self-esteem. Acceptance of treatment was largely a demonstration of care and support. While all participants had accepted treatment, men surmised the primary reasons other men may reject treatment as being: if they felt BV had \"nothing to do with them\", which was related to not wanting to be viewed as having a 'problem' and exacerbated by norms of masculinity and STI-related stigma; lack of a diagnostic test to indicate if a male \"had BV\"; and a casual or less established relationship. Men's attitudes to BV and partner treatment were primarily influenced by the nature of their relationships. The ambiguous aetiology of BV appears to attenuate STI related stigma and questions of infidelity.

Rationale Recent studies in rodents suggest that non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may promote tobacco consumption—either through their own pharmacological effects or by augmenting the effects of nicotine. However, there is scant information on the behavioral pharmacology of minor tobacco alkaloids in primate species. Objective The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine, anabasine, anatabine, myosmine, and cotinine exhibit nicotine-like behavioral effects in squirrel monkeys. Methods Initial experiments were conducted to determine the effects of nicotine (0.032–1.0 mg/kg) and the minor tobacco alkaloids nornicotine (1–1.8 mg/kg), anabasine (0.1–1.0 mg/kg), anatabine (10–32 mg/kg), myosmine (0.32–1.8 mg/kg), and cotinine (10–180 mg/kg) on food-maintained performance ( n  = 4). Next, the ability of tobacco alkaloids to substitute for the α4β2-selective nicotinic agonist (+)-epibatidine in drug discrimination experiments was evaluated in a separate group of monkeys ( n  = 4). Results Results show that nicotine and each minor tobacco alkaloid except cotinine (a) produced dose-related decreases in food-maintained responding; (b) substituted for (+)-epibatidine and, in additional experiments, produced additive effects when combined with nicotine; (c) induced emesis or tremor at doses that reduced food-maintained responding and had (+)-epibatidine-like discriminative-stimulus effects; and (d) based on correlation with reported receptor binding affinities, likely produced their behavioral effects through α4β2 receptor mechanisms. Conclusion Selected minor tobacco alkaloids have nicotinic-like effects that may contribute to tobacco consumption and addiction.

In the era of increasing macrolide- and quinolone-resistant Mycoplasma genitalium (MG), we report the efficacy of 2 nonquinolone antimicrobials in patients with limited treatment options. Pristinamycin + doxycycline cured 75% (95% CI, 64%–85%), and minocycline cured 71% (95% CI, 54%–85%) of cases. These data provide useful estimates to inform clinical practice.