Downregulation of an NfsA-like nitroreductase causes metronidazole resistance in Gardnerella vaginalis.

The purpose of this review is to summarize current evidence for and against the treatment of asymptomatic bacterial vaginosis (BV) in women. Asymptomatic BV is common although its pathogenesis remains incompletely understood. In favor of treating asymptomatic BV is the large body of data supporting that it is sexually transmitted. Along these lines and similar to other STIs, treatment of BV, regardless of symptom status, should be considered to reduce adverse outcomes of infection (i.e. adverse birth outcomes, infertility, post-gynecologic surgery infections, etc.) and prevent further sexual transmission of BV pathogen(s) to sexual partners. One study has found that treatment of women with asymptomatic BV led to a significant reduction in incident chlamydial infections over a 6 month follow-up period, compared to observation-only women. Additionally, some women with asymptomatic BV actually have symptomatic BV but do not recognize these symptoms as an infection. Nevertheless, limitations of the trial regarding treatment of asymptomatic BV as well as the 2020 United States Preventative Task Force recommendation against screening and treatment of asymptomatic BV in pregnant women dampen enthusiasm for recommending treatment in this setting. Treatment of asymptomatic BV remains controversial. Additional studies are needed to further investigate the pathogenesis of BV, which will directly influence advances in its diagnosis, treatment, and prevention.

The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is an important cosmopolitan and extremely polyphagous species capable of causing direct and indirect damage to various crops. Insecticide resistance in melon aphids is of particular concern. To determine the basis of resistance, organophosphate (OP)-resistant strains of A. gossypii were obtained by continuous selection with dimethoate in the laboratory, and resistance mechanisms were investigated along with susceptible strains. Three resistant strains LKR-1, LKR-2, and LKR-3 exhibiting 270-, 243-, and 210-fold resistance obtained after 30 generations of selection with dimethoate, respectively, were utilized in this study. The role of acetylcholinesterase (AChE), a target enzyme for OPs and carbamates (CMs), was investigated. AChE enzyme assay revealed that there was no significant change in the activities of AChE in resistant and susceptible strains. However, AChE inhibitory assay showed that 50% of the enzyme activity in resistant strains was inhibited at significantly higher concentration of dimethoate (131.87, 158.65, and 99.29 µmolL(−1)) as compared with susceptible strains (1.75 and 2.01 µmolL(−1)), indicating AChE insensitivity owing to altered AChE. Molecular diagnostic tool polymerase chain reaction-restriction fragment length polymorphism revealed the existence of two consistent non-synonymous point mutations, single-nucleotide polymorphism, viz., A302S (equivalent to A201 in Torpedo californica Ayres) and S431F (equivalent to F331 in T. californica), in the AChE gene Ace2 of resistant strains. Further, cloning and sequencing of a partial fragment of Ace2 (897 bp) gene from susceptible and resistant strains revealed an additional novel mutation G221A in resistant strains, LKR-1 and LKR-2. Susceptible Ace2 genes shared 99.6 and 98.9% identity at the nucleic acid and amino acid levels with resistant ones, respectively. Functional analysis of these point mutations was assessed by in silico docking studies using the modeled wild-type and naturally mutated AChE2. Computational analysis showed that the conformational changes in AChE2 active site due to structural gene substitutions (A302S, S431F, and G221A) significantly reduced the level of ligand (OP-dimethoate, omethoate, and CM-pirimicarb) binding, suggesting that they are potentially associated with resistance development. These results unambiguously suggested that multiple mutations located in the enzyme active site are responsible for AChE insensitivity to dimethoate and are likely the molecular basis for dimethoate resistance in these selected field populations of A. gossypii.

Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis

Toxicological and biochemical characterization of coumaphos resistance in the San Roman strain of Boophilus microplus (Acari: Ixodidae)

Triazophos resistance mechanisms in the rice stem borer ( Chilo suppressalis Walker)

Background. Bacterial vaginosis (BV) is an important risk factor for preterm birth. BV is detected in 10–30% of pregnant women and is often asymptomatic. Treatment of BV during pregnancy seems to reduce the risk of preterm delivery among high-risk women. We performed a cost-effectiveness analysis of screening and treatment for BV in early pregnancy among asymptomatic women at low risk for preterm delivery. Methods. A decision tree was built with two arms. For the screening (and treatment) arm the probabilities were derived from our earlier randomized trial on screening and treatment for BV, consisting of BV-positive women treated with intravaginal clindamycin cream or placebo and also of BV-negative pregnant women. The probabilities of outcomes among these women were collected from antenatal clinic records and hospital records, and for the no-screening arm mainly from the Finnish Perinatal Statistics. The outcomes considered were preterm delivery, mode of delivery, peripartum infections and postpartum complications. The unit costs associated with these outcomes were mainly based on disease-related groups (DRGs). No-screening was compared with two screening programs (one with clindamycin, the other with metronidazole treatment) and subjected to sensitivity analyses. Results. There was no significant difference between screening and no-screening strategies in the costs and in the rate of preterm deliveries but the screening strategy produced significantly fewer peripartum infections and postpartum complications. Sensitivity analyses suggested that the screening strategy may become cost-saving if the rate of preterm deliveries exceeds 3%. Conclusion. Screening and treatment for BV in early pregnancy may not reduce costs compared to no-screening in a population at low risk for preterm birth but would produce, at the same cost, more health benefits in terms of fewer peripartum infections and postpartum complications. However, it may be cost-saving if the rate of preterm deliveries is higher than 3%.

Bacterial vaginosis (BV) is extremely common among the African population and is associated with the transmission and acquisition of human immunodeficiency virus (HIV) infection. The objective of this study was to determine the prevalence and characteristics of BV among HIV-infected and -uninfected women in rural Eastern Cape province of South Africa. A descriptive cross-sectional study was conducted between September 2017 and March 2018 on women aged 18 years and above (n = 100), attending Nelson Mandela Academic Hospital and Ngangelizwe Community Health Centre with signs and symptoms suggestive of vaginal infection. High vaginal swabs were collected, and BV was diagnosed using Nugent's score. The prevalence rate of BV was 70% irrespective of HIV status. Of the 61 HIV-infected patients, 49 (80.3%) and 12 (19.7%) were BV positive and BV negative, respectively; whilst of the 39 HIV-uninfected women, 21 (53.8%) and 18 (46.2%) were BV positive and BV negative, respectively (OR = 3.5; CI: 1.4–8.5; p=0.005). Women aged above 35 years were highly likely to develop BV (p=0.049). The presence of Mobiluncus species (>25 per high microscopic field) was significantly associated with BV among HIV-infected patients (p=0.030). A recent history of antibiotic use (≤3 months) was significantly associated with BV among HIV-negative patients (p=0.044). This study shows that BV is more prevalent among HIV-positive women than their HIV-negative counterparts, and its occurrence is higher among those aged above 35 years. The predominance of Mobiluncus species in the vagina microbiota of HIV-infected women might play a significant role in the development of BV. These findings suggest that the treatment of BV could restore normal flora and reduce susceptibility to and transmission of HIV.

Fitness in a malathion resistant Tribolium castaneum strain; feeding, growth and digestion

Three cDNAs, cloned from both pyrethroid-susceptible and -resistant strains of Lygus lineolaris, contained a 1548 nucleotide open reading frame encoding a 516 amino acid residue protein. Predicted cytochrome P450s from cDNAs were classified as the first three new members of subfamily CYP6X, CYP6X1v1 for a susceptible strain and CYP6X1v2 and CYP6X1v3 for two resistant strains. Putative cytochrome P450 CYP6X1s from L. lineolaris were highly similar (up to 42% amino acid sequence identity) to several insect CYP6s that are responsible for reduced sensitivity to pyrethroid insecticides. A total of twenty-six nucleotide substitutions were revealed between cDNAs of susceptible and resistant strains. Two nucleotide substitutions resulted in amino acid changes, Asp373 to Ala373 and Ser487 to Ala487, between susceptible and resistant strains. The resistant laboratory strain contained 2.1-fold higher cytochrome P450 mRNA per microgram total RNA than the susceptible laboratory strain. Topical treatment with 10 ng permethrin elevated cytochrome P450 mRNA levels by approximately 2-fold. The results of this study indicated that cytochrome P450 gene mutation, coupled with up-regulation, was present only in the pyrethroid resistant strains, and was possibly related to resistance development in the tarnished plant bug.

The current study aimed at assessing the overall efficacy of probiotics for the treatment of bacterial vaginosis (BV) through the review of relevant studies. A systematic literature review was conducted based largely on the following electronic databases updated to May 2021: Embase, the Cochrane Library, and PubMed, with the use of keywords. The investigators also thoroughly reviewed key pertinent sources in the literature for further inclusion. Eighteen studies including 1651 patients were selected in the present meta-analysis. In comparison with antibiotics, antibiotics plus probiotics significantly decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months and overall analysis). Compared with placebo, probiotics decreased the recurrence rate of BV (at 1-3 months and overall analysis) and increased the cure/remission rate of BV (at 1-3 months). Compared with antibiotics, probiotics significantly decreased the recurrence rate of BV (at <1 month, 1-3 months and overall analysis) as well as the incidence of adverse events (AEs) (at less than 1 month) and increased the cure/remission rate of BV (at 1-3 months). In comparison with short-term probiotics treatment (<1 month), long-term probiotics treatment (1-3 months) yields superior beneficial outcomes and efficacy in the treatment of BV.

Background: Bacterial vaginosis (BV) is thought to be an important risk factor and predictor of preterm labour. Prevention and early detection and treatment of BV can decrease the incidence of preterm labour. Primary objective of this study was to find out correlation of bacterial vaginosis with preterm labour. Secondary objectives were determination of most important criterion among the Amsels criteria and risk factors for BV among literacy, residence and parity.Methods: A Case-control study carried out at a tertiary care hospital in north India. 100 women with preterm labour and 200 women with term labour after fulfilling inclusion criteria were enrolled as cases and controls respectively. Epidemiological and clinical details were recorded. Bacterial vaginosis was diagnosed by Amsels criteria. Prevalence in both groups was calculated. Statistical analysis was then done to find out association between bacterial vaginosis and preterm labour.Results: Among all women enrolled 94 had bacterial vaginosis. The overall prevalence of bacterial vaginosis in both groups combined was 31.33%. It was 42% in cases and 26% in controls. The difference was statistically significant (p=0.007). Whiff test emerged as the strongest criterion if used alone with a sensitivity of 98% and specificity of 81% when compared to whole Amsels criteria. Bacterial vaginosis was found more in illiterate women and those who had given birth previously.Conclusions: Bacterial vaginosis is significantly more prevalent in women with preterm labour. Whiff test can be used alone in centres where the patient load is too high. Illiteracy is a risk factor that can be modified to bring down incidence of bacterial vaginosis.

The isolation and characterization from the sand fly Phlebotomus perniciosus of a Wickerhamomyces anomalus yeast strain (Wa1F1) displaying the killer phenotype was recently reported. In the present work, the killer toxin (KT) produced by Wa1F1 was purified and characterized, and its antimicrobial activity in vitro was investigated against fluconazole- susceptible and -resistant clinical isolates and laboratory strains of Candida albicans and C. glabrata displaying known mutations. Wa1F1-KT showed a differential killing ability against different mutant strains of the same species. The results may be useful for the design of therapeutic molecules based on Wa1F1-KT and the study of yeast resistance mechanisms.

Bacterial vaginosis (BV) is characterized by a vaginal microbiota low in lactobacilli; it affects one-quarter to one-third of reproductive-age cisgender women. 1 Approximately one-half of cases are symptomatic, with abnormal vaginal discharge and/or amine or fishy vaginal odor. 1 BV contributes to adverse sexual and reproductive outcomes, including HIV and/or sexually transmitted infection (STI) acquisition and preterm birth, and symptoms can negatively impact psychosocial well-being and sexual satisfaction. 1The BV treatment landscape has not appreciably changed in decades: in the US, metronidazole and clindamycin are recommended as first-line treatments for symptomatic BV, and secnidazole and tinidazole are used as alternatives.Although these treatments are effective in the short term, up to 60% of women experience BV recurrence within 1 year of treatment. 2Some have frequent recurrences, and options are limited for these individuals and may involve onerous suppressive regimens with twice-weekly application of intravaginal antibiotics for extended time periods.Suppressive vaginal metronidazole fails for 25% of patients and leads to secondary vulvovaginal candidiasis (VVC) in up to 40%, and many patients have BV recurrence after stopping suppressive therapy. 3It is imperative that we expand the toolkit of available BV treatments.Alternatives that are at least as effective as nitroimidazoles and clindamycin would be welcome additions.Treatments that effect a lasting cure would be paradigm-shifting.One option may be dequalinium chloride (DQC), a locally delivered antiseptic with broad antibacterial and antifungal activity. 4Its antibacterial activity is attributed to interaction with the bacterial cytoplasmic membrane and perturbation of cellular permeability, protein denaturation and subsequent alteration of ribosomal protein synthesis, and nucleic acid precipitation. 4A prior trial 5 reported that intravaginal DQC was noninferior to intravaginal clindamycin for BV treatment (discussed later), motivating Raba and colleagues 6 to evaluate its efficacy vs metronidazole.In a European, phase 4, multicenter, triple-blinded, randomized trial including 147 women, Raba et al 6 found that intravaginal DQC (10 mg tablet daily for 6 days) was noninferior to oral metronidazole (500 mg twice daily for 7 days) for treating BV defined by all four Amsel criteria. 6Clinical cure rates in both groups were 92.8% to 93.2% upon completing treatment, and DQC tolerability was significantly higher than for metronidazole. 6Notably, 27.9% of participants had a Nugent score of 3 or lower at enrollment (indicating non-BV microbiota) despite all 4 Amsel criteria being present; although there is some variation in the literature, this discrepancy is greater than the approximately 10% reported in a sentinel study. 7However, these participants were evenly distributed across groups. 6e trial by Raba et al 6 is the second to compare DQC with standard-of-care BV treatment.In 2012, Weissenbacher and colleagues 5 reported that intravaginal DQC was noninferior to intravaginal clindamycin (2% cream for 7 days) in a trial of 315 participants.Like Raba et al, 6 they enrolled women presenting with 4 Amsel criteria from multiple European clinical sites.Clinical cure rates for DQC and antibiotic groups at early and late time points were somewhat lower than in the trial by Raba et al, which may reflect slightly different clinical cure definitions and outcome assessment timing (7 and 20-40 days after starting treatment for Raba et al, 6 and 7 and 25 days after completing treatment for Weissenbacher et al 5 ).It is encouraging that both trials demonstrated noninferiority using the same 15% noninferiority margin and showed 75% to 80% clinical cure up to 5 weeks after DQC. 5,

Calcification occurs frequently in the development of atherosclerotic lesions, and studies in mice have indicated a genetic contribution. We now show that one genetic factor contributing to aortic calcification is the Dyscalc locus, previously shown to contribute to myocardial calcification. Thus, the Dyscalc locus, on proximal mouse Chromosome (Chr) 7, segregated with vascular calcification in a large cross between susceptible strain DBA/2J and resistant strain C57BL/6J. Further evidence was observed by analysis of recombinant inbred strains derived from various susceptible and resistant parental strains. Myocardial and vascular calcifications are importantly influenced by multiple modifier loci as well as the Dyscalc gene, making fine mapping of Dyscalc difficult. In order to allow more detailed genetic and biochemical characterization of Dyscalc, we have identified congenic strains containing the Dyscalc locus from resistant strain C57BL/10 on the background of susceptible strain C3H/DiSnA. The congenic strains exhibit little or no myocardial or vascular calcification, unlike the background HcB C3H strain, and the calcification segregated as a Mendelian factor, allowing finer mapping of Dyscalc.

An integral membrane protein, Claudin 5 (CLDN5), is a critical component of endothelial tight junctions that control pericellular permeability. Breaching of endothelial barriers is a key event in the development of pulmonary edema during acute lung injury (ALI). A major irritant in smoke, acrolein can induce ALI possibly by altering CLDN5 expression. This study sought to determine the cell signaling mechanism controlling endothelial CLDN5 expression during ALI. To assess susceptibility, 12 mouse strains were exposed to acrolein (10 ppm, 24 h), and survival monitored. Histology, lavage protein, and CLDN5 transcripts were measured in the lung of the most sensitive and resistant strains. CLDN5 transcripts and phosphorylation status of forkhead box O1 (FOXO1) and catenin (cadherin-associated protein) beta 1 (CTNNB1) proteins were determined in control and acrolein-treated human endothelial cells. Mean survival time (MST) varied more than 2-fold among strains with the susceptible (BALB/cByJ) and resistant (129X1/SvJ) strains (MST, 17.3 ± 1.9 h vs. 41.4 ± 5.1 h, respectively). Histological analysis revealed earlier perivascular enlargement in the BALB/cByJ than in 129X1/SvJ mouse lung. Lung CLDN5 transcript and protein increased more in the resistant strain than in the susceptible strain. In human endothelial cells, 30 nM acrolein increased CLDN5 transcripts and increased p-FOXO1 protein levels. The phosphatidylinositol 3-kinase inhibitor LY294002 diminished the acrolein-induced increased CLDN5 transcript. Acrolein (300 nM) decreased CLDN5 transcripts, which were accompanied by increased FOXO1 and CTNNB1. The phosphorylation status of these transcription factors was consistent with the observed CLDN5 alteration. Preservation of endothelial CLDN5 may be a novel clinical approach for ALI therapy.