Urogenital Symptoms and Pain History as Precursors of Vulvodynia: A Longitudinal Study

Abstract Background: We sought to assess vulvodynia incidence and risk factors among those with and without premorbid urogenital symptoms. Methods: Women's Health Registry members who completed a baseline assessment in 2004 were sent a 2-year and 4-year follow-up survey containing a validated screen for vulvodynia. Subgroup analysis of vulvodynia incidence rates was performed, and risk factors associated with incidence were assessed. Results: Of 1037 original enrollees, 723 (69.7%) completed consecutive surveys (initial and 2-year or initial, 2-year, and 4-year), 660 of whom did not have current or past vulvodynia at baseline. Of these 660, 71 (10.8%) first met criteria for vulvodynia within the 4-year period, for an annual incidence rate of 3.1% (95% confidence interval [CI] 2.5-4.0). Baseline strict controls were less likely to develop criteria for vulvodynia diagnosis (annual incidence rate of 1.4%) compared to those with an intermediate phenotype (presence of dyspareunia or history of short-term vulvar pain), for whom the incidence rate was 5.6% (p<0.001). Risk factors for incident vulvodynia differed between these two groups. Among the strict controls, an increased risk was noted among younger women (incidence rate ratio) [IRR] 3.6). For those with an intermediate phenotype, risk was increased among nonwhite women and those reporting pain with or after intercourse (IRR 2.2, 3.4, and 3.1, respectively). In both control groups, incident vulvodynia risk increased among those reporting urinary burning at enrollment (IRR 4.2 and 2.8 for strict and intermediate phenotype controls, respectively). Conclusions: The annual incidence of vulvodynia is substantial (3.1%) and is greater among women reporting a history of dyspareunia or vulvar pain that did not meet criteria for vulvodynia compared to those without this history, suggesting that generalized urogenital sensitivity may be a common underlying mechanism predating the clinical presentation of vulvodynia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98465/1/jwh%2E2012%2E3566.pd

Clinical trialist perspectives on the ethics of adaptive clinical trials: a mixed-methods analysis

Abstract Background In an adaptive clinical trial (ACT), key trial characteristics may be altered during the course of the trial according to predefined rules in response to information that accumulates within the trial itself. In addition to having distinguishing scientific features, adaptive trials also may involve ethical considerations that differ from more traditional randomized trials. Better understanding of clinical trial experts’ views about the ethical aspects of adaptive designs could assist those planning ACTs. Our aim was to elucidate the opinions of clinical trial experts regarding their beliefs about ethical aspects of ACTs. Methods We used a convergent, mixed-methods design employing a 22-item ACTs beliefs survey with visual analog scales and open-ended questions and mini-focus groups. We developed a coding scheme to conduct thematic searches of textual data, depicted responses to visual analog scales on box-plot diagrams, and integrated findings thematically. Fifty-three clinical trial experts from four constituent groups participated: academic biostatisticians (n = 5); consultant biostatisticians (n = 6); academic clinicians (n = 22); and other stakeholders including patient advocacy, National Institutes of Health, and U.S. Food and Drug Administration representatives (n = 20). Results The respondents recognized potential ethical benefits of ACTs, including a higher probability of receiving an effective intervention for participants, optimizing resource utilization, and accelerating treatment discovery. Ethical challenges voiced include developing procedures so trial participants can make informed decisions about taking part in ACTs and plausible, though unlikely risks of research personnel altering enrollment patterns. Conclusions Clinical trial experts recognize ethical advantages but also pose potential ethical challenges of ACTs. The four constituencies differ in their weighing of ACT ethical considerations based on their professional vantage points. These data suggest further discussion about the ethics of ACTs is needed to facilitate ACT planning, design and conduct, and ultimately better allow planners to weigh ethical implications of competing trial designs.http://deepblue.lib.umich.edu/bitstream/2027.42/111302/1/12910_2015_Article_22.pd

Contemporary trends in development of active substances possessing the pesticidal properties: neonicotinoid insecticides

A new group of insecticides, widely introduced to the agriculture practice since the 90-ies of XX century - neonicotinoides, is discussed. The history of its arise, and insecticidal properties, mode of action, and short characteristics of some of its representatives is presented

Contemporary trends in development of active substances possessing the pesticidal properties: ryanodine-receptor targeting insecticides

The latest developed classes of synthetic insecticides – phthalic acid diamides and antranilic diamides, acting as ryanodine receptor modulators, are discussed. The mode of their activity, the insecticidal properties and characteristics of their representatives is reviewed

Contemporary trends in development of active substances possessing the pesticidal properties: spinosyn insecticides

A new group of insecticides belonging to the category of bio-pesticides, namely – spinosyns, is discussed. The spinosyns are the products of bacterial fermentation by microorganisms Saccharopolyspora spinosa (Actinomycetes group) in a nutrient media. The chemical structures of spinosyns, also those developed by the semi-synthetic and biochemical modifications, as well as their insecticidal properties and mechanism of biological activity, the range of their application in crop protection and the commercially available products based on them, are reviewed

Organogenesis and long-term micropropagation of Polish pea cultivars

The complete protocol for regeneration and long-term micropropagation of several Polish cultivars of pea (Pisum sativum L.) has been elaborated. The shoots were the most likely regenerated via de novo organogenesis. The adventitious buds formed in callus derived from cotyledons tissue adjacent to the axillary meristems of immature embryos. All cultivars' calli regenerated several shoots per explant on the MS medium supplemented with B5 vitamins and 4.5 mgl-1 of BAP, however some differences in regeneration capacity among cultivars were observed. The plantlets were subsequently micropropagated with slightly higher efficiency and preserving a good viability over the long-term culture on a medium containing 2.0 mgl-1 than one with 4.5 mgl-1 of BAP. The additional step of the pre-conditioning culture of multiplicated shoots on a medium with very low BAP concentration i.e. 0.02 mgl-1 was applied and appeared to be beneficial before rooting in vitro or grafting. The modified MS-derived medium with the half-strength of MS macroelements but with the full original dose of calcium and supplemented with B5 vitamins and 1.0 mgl-1 of NAA was developed for effective rooting. The shoots were also sufficiently transferred into ex vitro conditions using grafting. The majority of the regenerated plants had adapted to in vivo conditions in a greenhouse and subsequently has set seeds. The presented protocol provides relatively efficient rate of de novo pea regeneration and would be useful for Agrobacterium-mediated transformation purposes

Ethyl [1S, 2RS]-and [1S,2S]-2-[2-chloro-propanoyloxy]propanoate. Preparation and hydrolysis

Ethyl (1S,2RS)-2-(2-chloropropanoyloxy)propanoate ((1S,2RS)-(I)) was obtained from rac-2-chloropropionyl chloride and ethyl L-lactate. (1S,2S)- (I) was also synthesized from (S)-2-chloropropionyl chloride and ethyl L-lactate with 93% d.e. (I) was undertaken hydrolysis by different media: NaOH/THF-H2O, Na2CO3/THF-H2O, LiOHxH2O/THF-H2O, 25% NaOH/H2O, and weakly acidic ion-exchange resin Amberlite IRC748 dispersion in MeOH. (1S,2RS)-2-(2-Chloropropanoyloxy) propanoic acid (II) diastereomers were identified as products of acidic hydrolysis with the ionic resin. GC/MS, HPLC and HPLC/MS analyses of resulted products are presented