Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel

A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine (DPV) - a lead candidate human immunodeficiency virus type 1 (HIV-1) microbicide compound - has recently demonstrated moderate levels of protection in two Phase III clinical studies. Here, next-generation matrix and reservoir-type silicone elastomer vaginal rings are reported for the first time offering simultaneous and continuous in vitro release of DPV and the contraceptive progestin levonorgestrel (LNG) over a period of between 60 and 180days. For matrix-type vaginal rings comprising initial drug loadings of 100, 150 or 200mg DPV and 0, 16 or 32mg LNG, Day 1 daily DPV release values were between 4132 and 6113μg while Day 60 values ranged from 284 to 454μg. Daily LNG release ranged from 129 to 684μg on Day 1 and 2-91μg on Day 60. Core-type rings comprising one or two drug-loaded cores provided extended duration of in vitro release out to 180days, and maintained daily drug release rates within much narrower windows (either 75-131μg/day or 37-66μg/day for DPV, and either 96-150μg/day or 37-57μg/day for LNG, depending on core ring configuration and ignoring initial lag release effect for LNG) compared with matrix-type rings. The data support the continued development of these devices as multi-purpose prevention technologies (MPTs) for HIV prevention and long-acting contraception.

Alteración del PH vaginal e infección genital en pacientes con amenaza de parto pretérmino, en el Hospital Vicente Corral Moscoso, Cuenca 2003

Con el objetivo de demostrar la relación existente entre la elevación del pH vaginal, infección genital y la amenaza de parto pretérmino. Se investigó una muestra total de 100 pacientes con una edad gestacional entre 20 a 36,6 S. 50 pacientes con amenaza de parto pretérmino y 50 asintomáticas atendidas en el Hospital Vicente Corral Moscoso, a quiénes se les realizó la medición del pH vaginal y exámenes de laboratorio encaminados a la búsqueda de microorganismos frecuentemente relacionados con la amenaza de parto pretérmino. Se realiza un estudio de casos y controlos encontrándose los siguiente resultados: El pH vaginal está alterado en el 100de los caso. Teniéndo un OR> 1 que es un factor negativo para el curso del embarazo. Existe a su vez un RR mayor de tener parto prematuro ante la presencia de infección y pH alterado. Los gérmenes aislados más frcuentes en casos y controles fueron Ureoplasma. La sensibilidad del pH para detectar infecciones fue de 86.3. La especificidad 91.7, el valor predictivo positivo de 98.7. Los pacientes con un pH vaginal anormal tienen mayor riesgo de poseer una infección genital y presentar amenaza de parto pretérmino

Intervención dietético-terapéutica en candidiasis intestinal

Antecedentes: Las candidiasis son infecciones oportunistas producidas por levaduras, cuyo agente etiológico implicado más frecuente C.albicans generando problemas a varios niveles. Caso clínico: Mujer de 39 años diagnosticada de Candidiasis intestinal crónica cursando con sintomatología amplia y variada. Tras la valoración se procede a complementar el tratamiento con una alimentación centrada en la eliminación de azúcares simples, levaduras y productos fermentados. Además, se incluyen ácido caprílico, aceite de orégano y L.acidophylus. Conclusiones: Existe un aumento de la actividad inmunológica acompañada de la mejora sintomatológica.

Discovery and validation of serologic biomarkers for the diagnosis and prognosis of invasive candidiasis by computational immunomics

Invasive candidiasis (IC) is an opportunistic systemic mycosis caused by Candida species (commonly Candida albicans) that continues to pose a significant public health problem worldwide. Despite great advances in antifungal therapy and changes in clinical practices, IC remains a major infectious cause of morbidity and mortality in severely immunocompromised or critically ill patients, and further accounts for substantial healthcare costs. Its impact on patient clinical outcome and economic burden could be ameliorated by timely initiation of appropriate antifungal therapy. However, early detection of IC is extremely difficult because of its unspecific clinical signs and symptoms, and the inadequate accuracy and time delay of the currently available diagnostic or risk stratification methods. In consequence, the diagnosis of IC is often attained in advanced stages of infection (leading to delayed therapeutic interventions and ensuing poor clinical outcomes) or, unfortunately, at autopsy. In addition to the difficulties encountered in diagnosing IC at an early stage, the initial therapeutic decision-making process is also hindered by the insufficient accuracy of the currently available tools for predicting clinical outcomes in individual IC patients at presentation. Therefore, it is not surprising that clinicians are generally unable to early detect IC, and identify those IC patients who are most likely to suffer fatal clinical outcomes and may benefit from more personalized therapeutic strategies at presentation. Better diagnostic and prognostic biomarkers for IC are thus needed to improve the clinical management of this life-threatening and costly opportunistic fungal infection...

Candida duobushaemulonii: an emerging rare pathogenic yeast isolated from recurrent vulvovaginal candidiasis in Brazil

The aim of this study was to identify Candida species isolated from women diagnosed with recurrent vulvovaginal candidiasis (RVVC) and their partners; and to evaluate the fluconazole (FLZ) susceptibility of the isolates. In a period of six years, among 172 patients diagnosed with vulvovaginal candidiasis, 13 women that presented RVVC and their partners were selected for this investigation. The isolates were obtained using Chromagar Candida medium, the species identification was performed by phenotypic and molecular methods and FLZ susceptibility was evaluated by E-test. Among 26 strains we identified 14 Candida albicans , six Candida duobushaemulonii, four Candida glabrata , and two Candida tropicalis . Agreement of the isolated species occurred in 100% of the couples. FLZ low susceptibility was observed for all isolates of C. duobushaemulonii (minimal inhibitory concentration values from 8-> 64 μg/mL), two C. glabrata isolates were FLZ-resistant and all C. albicans and C. tropicalis isolates were FLZ-susceptible. This report emphasises the importance of accurate identification of the fungal agents by a reliable molecular technique in RVVC episodes besides the lower antifungal susceptibility profile of this rare pathogen C. duobushaemulonii to FLZ.

Patients prefer subcutaneous progesterone over vaginal administration. Unexpected results of a prospective trial

SIN FINANCIACIÓN

Genomic and functional insights into the interactions between vaginal Lactobacillus strains and pathogens

The vaginal microbiota of healthy pre-menopausal women is typically dominated by one Lactobacillus species among L. crispatus, L. gasseri, L. jensenii and L. iners. Thanks to a series of antimicrobial activities, strains belonging to these species represent the first barrier against infections and maintain niche homeostasis. On the other hands, the increase abundance in pathogen species is associated with the onset of numerous diseases, leading also to an increase risk of other infections acquisition. The deciphering of factors which influence Lactobacillus survival, as well as the interactions between lactobacilli-pathogens and pathogens-pathogens represent an important topic of study for improving woman health and investigating effective probiotic strategies. Here, we investigated environmental factors and genetic traits that lead to the dominance of either L. crispatus or L. gasseri in the vaginal niche and the possible applications of liposomes loaded with L. gasseri biosurfactants for the treatment and prevention of Staphylococcus aureus biofilm infections. Furthermore, considering the increasing relevance acquired by bacterial extracellular vesicles (EVs) we analysed the role of EVs derived from vaginal lactobacilli and pathogens on both bacterial growth and HIV-1 infections. As a result, we reported for the first time i) common and species-specific genotypic and phenotypic features of L. crispatus and L. gasseri ii) significant antibiofilm activity of liposomes loading vaginal Lactobacillus biosurfactants against multi-drug resistant S. aureus strains iii) absence of growth regulation mediated by EVs derived from lactobacilli on pathogen cultures and vice versa iv) anti-HIV-1 activity of protein derived from L. gasseri EVs and unexpected antiviral effect of pathogen-derived EVs on HIV-1 infections in vitro. In conclusion, this PhD thesis explored characteristics and possible applications of vaginal lactobacilli for the human health, as well as promising antiviral effects of both lactobacilli and pathogen derived EVs.

Vaginal immunology and microbiome composition: bacterial vaginosis in a macaque model

Nonhuman primates (NHPs) are important animal models for the study of human health and disease. In particular, the use of NHPs to study the vaginal microbiome and susceptibility to infections (such as HIV and herpesvirus) is exceptionally valuable due to the similarity in anatomy and physiology. An important aspect to this is maintaining a healthy vaginal microbiome which then minimizes colonization by pathogens and resulting inflammation along the mucosa. In women, conditions such as bacterial vaginosis (BV) are frequently treated with antibiotics such as metronidazole or clindamycin. Due to the excessive use of antimicrobials in medicine and agriculture, alternative compounds and therapies are highly desired to treat infections. Approaches that have been developed and used for vaginal infections includes the use of natural antimicrobials such as essential oils, probiotics, and live cultures, which mimic and function like antibiotics but lack development of resistance like classic antibiotics. However, these approaches have been minimally studied in humans and animals. Effectiveness of essential oils are anecdotal at best. Microbiome manipulation on the other hand has been investigated more thoroughly. Novel products are being distributed for medical use and are monotherapies containing Lactobacillus which colonize the vaginal mucosa (Ali et al., 2020; Brichacek et al., 2013; Lagenaur, Sanders-Beer, et al., 2011). Unfortunately, these therapies have limitations due to durability and individual response in women. By evaluating the extent by which the NHP vaginal mucosa can be colonized with exogenously delivered bacteria, this animal model will highlight the NHP for use in translational studies which use essential oils and beneficial microbiome bacteria for vaginal delivery.

New insights into vaginal environment during pregnancy: a multi-omics approach

The present thesis aims to provide a thorough comprehension of the vaginal ecosystem of pregnant women and enhance the knowledge of pregnancy pathophysiology. The first study emphasized the importance of limiting protein intake from animal sources, consuming carbohydrates, and avoiding starting pregnancy overweight to maintain a healthy vaginal environment characterized by lactobacilli and related metabolites. In the second paper, a reduction in bacterial diversity, an increase in Lactobacillus abundance, and a decrease in bacterial vaginosis-related genera were observed during pregnancy. Lactobacillus abundance correlated with higher levels of lactate, sarcosine, and amino acids, while bacterial vaginosis-related genera were associated with amines, formate, acetate, alcohols, and short-chain fatty acids. An association between intrapartum antibiotic prophylaxis for Group B Streptococcus and higher vaginal abundance of Prevotella was found. Moreover, women experiencing a first-trimester miscarriage displayed a higher abundance of Fusobacterium. The third study explored the presence of macrolides and tetracyclines resistance genes in the vaginal environment, highlighting that different vaginal microbiota types were associated with distinct resistance profiles. Lactobacilli-dominated ecosystems showed fewer or no resistance genes, while women with increased bacterial vaginosis-related genera were positive for resistance genes. The last two papers aimed to identify potential biomarkers of vaginal health or disease status. The fourth paper showed that positivity for Torquetenovirus decreased from the first to the third trimester, being more prevalent in women with higher vaginal leukocyte counts. Torquetenovirus-positive samples showed higher levels of cytokines, propionate, and cadaverine. Lactobacillus species decreased in Torquetenovirus-positive samples, while Sneathia and Shuttleworthia increased. The last work pointed out the association between clade 2 of Gardnerella vaginalis and bacterial vaginosis. Moreover, as the number of simultaneously detected G. vaginalis clades increased, bacterial vaginosis-associated bacteria also tended to increase. Additionally, sialidase gene levels negatively correlated with Lactobacillus and positively correlated with Gardnerella, Atopobium, Prevotella, Megasphaera, and Sneathia.

Quais condutas devem ser adotadas frente a uma paciente com sangramento vaginal abundante em uso de método contraceptivo hormonal injetável? É válido o uso de anti-inflamatórios?

Trata das condutas que devem ser adotadas por profissionais da área de enfermagem e/ou agentes comunitários de saúde frente a pacientes com sangramento uterino excessivo (>80 mL/ciclo), conhecido como menorragia, ou prolongado (>7 dias). Esse é um das queixas ginecológicas mais comuns, acometendo todas as faixas etárias, desde a adolescência até a perimenopausa. A história anterior da paciente, suas características menstruais, que constituem o seu padrão individual de sangramento, é o que leva a definição do padrão do sangramento como normal ou anormal.

IMPLEMENTAÇÃO DA ABORDAGEM SINDRÔMICA DE CORRIMENTO VAGINAL EM GESTANTES DO MUNICÍPIO DE MANSIDÃO

Com o intuito de aprimorar o diagnóstico e o tratamento precoce dos principais agentes etiológicos das Doenças Sexualmente Transmissíveis ainda sem requerer de resultados de exames laboratoriais, o Ministério da Saúde no Brasil recomenda a abordagem sindrômica para o correto manejo dos portadores. O desenho do estudo foi transversal e objetivou a implementação desta estratégia nas 69 gestantes com queixa de corrimento vaginal no âmbito das três Unidades Básicas de Saúde do Município de Mansidão, Estado Bahia, no período de maio a agosto de 2014. Os dados se processaram para determinar os valores percentuais com ajuda do Statistical Package for the Social Sciences (SPSS) versão 18.0. Ditos resultados revelaram que as gestantes atendidas são majoritariamente residentes de zona rural (78,2 %), adultas jovens entre 20 e 29 anos de idade (55 %), com nível Secundário (44,9%), lavradoras (71%) e com união estável (44,9%). Verificou-se a adequada cobertura de recursos humanos e suficientes recursos materiais para garantir a atenção nas unidades da síndrome apresentada pela gestante por meio do fluxograma de conduta de corrimento vaginal sem microscopia adotado no país. Observou-se prevalência de 47,8% com candidíase vulvovaginal, 17,3% com vaginose bacteriana e 11,5% com tricomoníase vaginal. A associação destas infecções foi diagnosticada em 15,9% das mulheres; a cervicite em 33,3% e em 7,2% dos casos o conteúdo vaginal foi considerado fisiológico. Se avaliou a eficácia da abordagem sindrómica através da exaustiva revisão das fichas de pré-natal, além da satisfação manifestada pelos profissionais e gestantes pela assistência prestada e recebida respectivamente, relacionadas com o manejo sindrómico. A análise permitiu evidenciar o impacto deste modelo de intervenção o qual se considerou efetivo ao obter após de sua aplicação a cura clínica em 56,5% dos casos de vaginite e no tratamento da cervicites excedeu 50%. Contudo, se constatou, falta de treinamento dos profissionais em abordagem sindrómica. Recomendamos a realização de uma intervenção capacitam-te para todos os profissionais de saúde dos serviços primários envolvidos nesta tarefa.

Intervenção educativa para aumentar o nível de conhecimento sobre a síndrome do fluxo vaginal em pacientes grávidas no posto médico de saúde sede, em Moraújo/CE

O presente trabalho constitui um estudo de intervenção educativa com o objetivo de implementar um programa sobre a síndrome de corrimento vaginal em pacientes grávidas do PSF Sede do município Moraujo, estado Ceará, Brasil. O Sindrome de Currimento Vaginal pode ser generica e clinicamente definido por uma alteração da ecologia microbiana vaginal que geralmente resulta de um ou mais dos seguintes sintomas: corrimento vaginal, fedor, ardor, coceira e dor. O total do universo de mulheres grávidas, está representado por 117 gestantes. De modo que o universo e a amostra são os mesmos. Nesta investigação será utilizado como meio de obter a informação um questionário pra ser aplicado a cada paciente. Uma vez aplicado, o conhecimento será avaliado usando uma escala de classificação. Os tópicos a tratar são conceito, comportamento e etiologia da síndrome de corrimento vaginal, fatores associados à síndrome corrimento vaginal nas grávidas, as complicações clínicas e possíveis dele derivados. como realizar a prevenção do corrimento vaginal e como realizar a prevenção. Posteriormente será aplicada aos pacientes um programa de intervenção educativa e será reaplicado o questionário para avaliar o nível de conhecimento alcançado depois da intervenção. O estudo tem como resultado esperado aumentar o nível de conhecimento das pacientes para contribuir com a prevenção do sindrome nas pacientes grávidas.

[climacteric Syndrome In A Northeastern Brazilian City: A Household Survey].

To assess the prevalence of Climacteric Syndrome (CS) in women from a municipality of Northeastern Brazil which is less developed socioeconomically. A prospective household survey was performed in São Luís, Maranhão, Brazil with 1,210 climacteric women aged 45 to 60 years. Interviews were applied using previously tested standard questionnaires from April to July 2008. The severity of climacteric symptoms was analyzed by circulatory and psychological indexes and the latter were associated with menopausal status. Multiple correspondence analysis was used to assess the relation among climacteric symptoms. Most patients were 55 to 60 years old (35.3%), mulatto (37.9%), with 9-11 years of schooling (39.8%), with a partner (56%), Catholic (73.9%) and belonged to the socioeconomic class C (51.1%). The prevalence of CS was 85.9%, and hot flashes (56.4%) and sweating (50.4%) were the most prevalent symptoms. The most frequent psychological symptoms were nervousness (45%) and emotional liability (44.8%). The severity of vasomotor and psychological symptoms was significantly higher during the peri and postmenopausal period (p<0.05). Vaginal dryness (62.7%) was the most prevalent urogenital complaint. The prevalence of CS was high among women from São Luís, Maranhão, Brazil.

The Effect Of Pelvic Floor Muscle Training Alone Or In Combination With Electrostimulation In The Treatment Of Sexual Dysfunction In Women With Multiple Sclerosis.

Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD.

Evaluation Of Different Treatment Methods Against Denture Stomatitis: A Randomized Clinical Study.

The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.