Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus-infected pregnant women.

AIMS: The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)-infected pregnant women receiving epidural anaesthesia for caesarean section. METHODS: Twelve HIV-infected pregnant women (HIV group) were treated long-term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10-20 min after drug administration). RESULTS: The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann-Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th - 75th percentiles) for (+)-(R)-bupivacaine were 0.58 (0.38-0.82) in the HIV group vs. 0.25 (0.18-0.33) in the Control group, and for (-)-(S)-bupivacaine, they were 0.54 (0.34-0.69) in the HIV group vs. 0.25 (0.19-0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups. CONCLUSIONS: This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV-pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section.

PRENACEL - a mHealth messaging system to complement antenatal care: a cluster randomized trial.

BACKGROUND: The aim of this study was to determine whether PRENACEL (a bi-directional, mobile-phone based, short text message service (SMS)) increases the coverage of recommended antenatal care (ANC) practices. METHODS: A parallel, cluster-randomized trial in which 20 public primary Health Care Units (PHCUs) were randomly allocated to the intervention (10 PHCUs) or control (10 PHCUs) group. The study population included pregnant women aged 18 or above with a gestational age of 20 weeks or less. Pregnant women receiving ANC in intervention PHCUs were invited through leaflets and posters to register in PRENACEL. Women who registered in PRENACEL received a weekly set of short text messages with health education and health promotion content related to pregnancy and childbirth and were also able to clarify ANC queries through SMS. All women received routine ANC. The primary outcome was the proportion of women with high ANC Score, a composite measure of coverage of recommended ANC practices. Chi-square or Fisher's exact tests and multivariate log-binomial regression were used to analyze the outcomes. RESULTS: A total of 1210 eligible women received ANC in the participating PHCUs and took part of this study (770 in the intervention group and 440 in the control group). 20.4% (157/770) of intervention-group women registered in PRENACEL, but only 116 read all messages (73.9% of women who registered in PRENACEL, 116/157). The adjusted intention-to-treat analysis suggested no difference between intervention and control groups in the primary outcome (Adjusted Relative Risk (AdjRR): 1.05 (95% Confidence Interval (CI): 1.00-1.09). Both crude and adjusted per-protocol analysis suggested a positive effect of PRENACEL (Crude RR (95% CI): 1.14 (1.06-1.22), AdjRR (95% CI): 1.12 (1.05-1.21). The multivariate analysis also suggests that the PRENACEL group (women who read all SMS) had higher mean ANC score [48.5 (±4.2) vs 45.2 (±8.7), p < 0.01], higher proportion of women with ≥6 ANC visits (96.9% vs. 84.8%, p = 0.01), and higher rates of syphilis testing (40.5% vs. 24.8%, p = 0.03) and HIV testing (46.6% vs. 25.7%, p < 0.01) during ANC. CONCLUSIONS: A bi-directional, mobile-phone based, short text message service is potentially useful to improve the coverage of recommended ANC practices, including syphilis and HIV testing. TRIAL REGISTRATION: Clinical trial registry: RBR-54zf73 , U1111-1163-7761.

Resumo: Introdução: O objetivo deste estudo foi determinar se o PRENACEL, um serviço bidirecional de mensagens curtas de texto (SMS) com base na telefonia celular, aumenta a cobertura das práticas recomendadas de cuidados pré-natais (PN). Métodos: um ensaio paralelo, aleatorizado por conglomerados, no qual 20 unidades básicas de saúde (UBS) foram alocadas aleatoriamente para o grupo de intervenção (10 UBS) ou controle (10 UBS). A população estudada incluiu gestantes com idade igual ou superior a 18 anos com idade gestacional de 20 semanas ou menos. As gestantes que receberam PN em UBS intervenção foram convidadas através de folhetos e cartazes para se inscreverem no PRENACEL. As mulheres que se registraram no PRENACEL receberam um conjunto semanal de SMS com conteúdo de educação e promoção da saúde relacionadas à gravidez e parto e também puderam esclarecer dúvidas relacionadas ao PN através de SMS. Todas as mulheres receberam PN de rotina. O desfecho primário foi a proporção de mulheres com um alto escore de PN, uma medida da cobertura das principais práticas recomendadas no PN. Resultados: um total de 1.210 mulheres participaram deste estudo (770 no grupo de intervenção e 440 no grupo de controle). 20,4% (157/770) das mulheres do grupo de intervenção demonstraram interesse e foram registradas no PRENACEL, mas apenas 116 leram as mensagens (73,9%, 116/157). A análise ajustada de intenção de tratamento sugeriu ausência de efeito da intervenção no desfecho primário (Risco Relativo (RR) ajustado: 1,05, Intervalo de Confiança (IC) de 95%: 1,00-1,09). A análise por protocolo sugeriu um efeito positivo do PRENACEL [RR bruto (IC 95%): 1,14 (1,06-1,22), RR ajustado (IC 95%): 1,12 (1,05-1,21)]. A análise multivariada sugeriu que as mulheres que leram os SMS apresentaram a maior média do escore de PN [48,5 (±4,2) vs 45,2 (±8,7), p < 0,01], maior proporção de mulheres com ≥6 consultas (96,9% vs. 84,8%, p = 0,01) e maiores taxas de teste de sífilis (40,5% vs. 24,8%, p = 0,03) e HIV (46,6% vs. 25,7%, p < 0,01) durante o PN. Conclusões: o sistema PRENACEL é potencialmente útil para melhorar a cobertura das práticas recomendadas de PN, incluindo testes de sífilis e HIV.

Bleeding patterns of HIV-infected women using an etonogestrel-releasing contraceptive implant and efavirenz-based or lopinavir/ritonavir-based antiretroviral therapy.

OBJECTIVES: The use of progestogen-only contraceptives may cause a change in bleeding pattern, which is a common cause of discontinuation of these methods. Co-administration with some antiretroviral therapies (ART) changes the bioavailability of the etonogestrel (ENG)-releasing contraceptive implant, possibly affecting the bleeding pattern. Bleeding patterns were evaluated in HIV-positive users of the ENG implant co-administered with two common ART regimens. METHODS: Forty-five HIV-positive women who wished to use an ENG implant were included in this study: 15 had received zidovudine/lamivudine (AZT/3TC) + lopinavir/ritonavir (LPV/r) for ≥3 months (LPV/r-based ART group), 15 had received AZT/3TC + efavirenz (EFV) for ≥3 months (EFV-based ART group), and 15 had not received ART (non-ART group). Bleeding patterns were evaluated at 3 and 6 months after implant placement using a standard bleeding calendar. RESULTS: Amenorrhoea and infrequent bleeding rates were higher in the LPV/r-based ART group (50% and 36%, respectively) than in the other groups (non-ART group, 36% and 29%, respectively; EFV-based ART group, 7% and 14.5%, respectively; p = 0.01). The EFV-based ART group more frequently had regular bleeding (71.5%) compared with the other groups (LPV/r-based ART group, 7%; non-ART group, 21%; p = 0.01). The proportions of women with frequent and prolonged bleeding were similar (p > 0.05) in the three groups. CONCLUSIONS: The co-administration of EFV-based or LPV/r-based ART with the ENG implant affected the expected bleeding patterns during use of the implant, although unfavourable bleeding (frequent and prolonged) was not associated with the medications under evaluation.

High Incidence Rates of Early-onset Bacterial Sepsis in Infants Born in Two Brazilian Maternities: A 15-Year Retrospective Analysis.

BACKGROUND: Data on the burden and etiology of neonatal early-onset bacterial sepsis (EOBS) in low-to-middle-income countries are scarce. Surveillance is critical for optimizing prevention and treatment strategies. We aimed to estimate the incidence of EOBS in 2 large Brazilian cohorts of neonates. METHODS: Data were retrospectively obtained from 33,794 neonates born between 2009 and 2017 at low-risk (n = 17,981) and high-risk maternity centers (n = 15,813). Blood cultures were taken within 72 hours of life from neonates with perinatal risk factors for EOBS or suspected EOBS. A positive blood culture for a pathogenic microorganism and a compatible clinical evolution confirmed the diagnosis of EOBS. RESULTS: One-third of the infants born from high-risk and 18.5% from low-risk maternities were investigated for EOBS. Overall, EOBS was more incident in neonates born in the high-risk facilities [66 cases or 4.2/1000 (95% CI: 3.2-5.3)] than in the low-risk facilities [24 cases or 1.3/1000 (95% CI: 0.9-2.0)]. The incidence rate of EOBS increased with decreasing gestational age (<32 weeks: 20.5/1000; 32-36 weeks: 5.6/1000; ≥37 weeks: 1.5/1000). Group B Streptococcus (GBS) was the agent more frequently identified in high-risk and low-risk maternities: 1.8/1000 (95% CI: 1.1-2.4) and 0.4/1000 (95% CI: 0.2-0.9), respectively. EOBS's overall case fatality rate was 17.8% for all the agents and 22% for GBS. CONCLUSIONS: EOBS remains unacceptably high and is frequently fatal in preterm and term infants cared for in high- or low-risk maternities. Because GBS has emerged as the most frequent causative agent, preventive strategies are urgently needed.

HPV clearance in postpartum period of HIV-positive and negative women: a prospective follow-up study.

BACKGROUND: HPV persistence is a key determinant of cervical carcinogenesis. The influence of postpartum on HPV clearance has been debated. This study aimed to assess HPV clearance in later pregnancy and postpartum among HIV-positive and negative women. METHODS: We conducted a follow-up study with 151 HPV-positive women coinfected with HIV, in 2007-2010. After baseline assessment, all women were retested for HPV infection using PCR in later pregnancy and after delivery. Multivariable logistic regressions assessed the putative association of covariates with HPV status in between each one of the successive visits. RESULTS: Seventy-one women (47%) have eliminated HPV between the baseline visit and their second or third visits. HIV-positive women took a significantly longer time (7.0 ± 3.8 months) to clear HPV, compared to those not infected by HIV (5.9 ± 3.0 months). HPV clearance was significantly more likely to take place after delivery than during pregnancy (84.5% x 15.5%). CONCLUSIONS: Both HIV-positive and negative women presented a significant reduction in HPV infection during the postpartum period. HIV-positive status was found to be associated with a longer period of time to clear HPV infection in pregnant women.

Seroprevalence of Toxoplasmosis in Puerperal Women Treated at a Tertiary Referral Hospital.

OBJECTIVE: To evaluate the seroprevalence of toxoplasmosis among puerperal women cared for at a tertiary university hospital and the level of understanding of these puerperal women about toxoplasmosis, vertical transmission, and its prophylaxis. METHODS: For this cross-sectional study, we evaluated 225 patients using presential interviews, prenatal documentation, and electronic medical records. Data were stored using Research Electronic Data Capture (REDCap) software. Prevalence rates were estimated by the presence of reactive IgG antibodies against Toxoplasma gondii. Data analysis was performed using the chi-square test and calculation of the odds ratio (OR). Seroreactivity to T. gondii and exposure variables (age, educational level, and parity) were analyzed using a confidence interval (95%CI) and a significance level of 5% (p < 0.05). RESULTS: The seropositivity rate for T. gondii was 40%. There was no association between seroprevalence and age. Primiparity was a protective factor against seropositivity and low education was a risk factor. CONCLUSION: Knowledge of T. gondii infection and its transmission forms was significantly limited, presenting a risk for acute maternal toxoplasmosis and vertical transmission of this protozoan. Increasing the education level regarding the risk of toxoplasmosis during pregnancy could reduce the rates of infection and vertical transmission of this parasite.

OBJETIVO: Avaliar a soroprevalência de toxoplasmose entre puérperas atendidas em um hospital universitário terciário e o nível de compreensão dessas puérperas sobre toxoplasmose, transmissão vertical e sua profilaxia. MéTODOS: Para esse estudo transversal, foram avaliadas 225 pacientes utilizando entrevistas presenciais, documentação de pré-natal e prontuário eletrônico. Os dados foram armazenados usando o software Research Electronic Data Capture (REDCap). As taxas de prevalência foram estimadas pela presença de anticorpos IgG reativos contra o Toxoplasma gondii. A análise dos dados foi realizada por meio do teste do qui-quadrado e cálculo do odds ratio (OR). A sororreatividade ao T. gondii e as variáveis de exposição (idade, escolaridade e paridade) foram analisadas, utilizando-se intervalo de confiança (IC95%) e nível de significância de 5% (p < 0,05). RESULTADOS: A taxa de soropositividade para T. gondii foi de 40%. Não houve associação entre soroprevalência e idade. A primiparidade foi fator de proteção contra a soropositividade e a baixa escolaridade foi fator de risco. CONCLUSãO: O conhecimento da infecção por T. gondii e suas formas de transmissão foi significativamente limitado, apresentando risco para toxoplasmose materna aguda e transmissão vertical desse protozoário. Aumentar o nível de escolaridade quanto ao risco de toxoplasmose durante a gravidez pode reduzir as taxas de infecção e transmissão vertical desse parasita.

Condyloma acuminata: An evaluation of the immune response at cellular and molecular levels.

Condyloma acuminata (CA) is a benign proliferative disease mainly affecting in non-keratinized epithelia. Most cases of CA are caused by low-risk human papillomavirus (HPV), mainly HPV 6 and 11. The aim of the current study was to highlight the candidate genes and pathways associated with immune alterations in individuals who did not spontaneously eliminate the virus and, thus, develop genital warts. Paraffin-embedded condyloma samples (n = 56) were analyzed by immunohistochemistry using antibodies against CD1a, FOXP3, CD3, CD4, CD8, and IFN-γ. The immunomarkers were chosen based on the evaluation of the innate and adaptive immune pathways using qPCR analysis of 92 immune-related genes, applying a TaqMan Array Immune Response assay in HPV 6 or HPV 11 positive samples (n = 27). Gene expression analysis revealed 31 differentially expressed genes in CA lesions. Gene expression validation revealed upregulation of GZMB, IFNG, IL12B, and IL8 and downregulation of NFATC4 and IL7 in CA samples. Immunohistochemical analysis showed increased FOXP3, IFN-γ, CD1a, and CD4 expression in CA than in the control tissue samples. In contrast, CD3 and CD8 expression was decreased in CA lesion samples. Increased levels of pro-inflammatory cytokines in HPV-positive patients compared with HPV-negative patients seem to reflect the elevated immunogenicity of HPV-positive CA lesions. Host defense against HPV begins during the early stages of the innate immune response and is followed by activation of T lymphocytes, which are mainly represented by CD4+ and regulatory T cells. The low CD8+ T cell count in CA may contribute to this recurrent behavior. Additional studies are needed to elucidate the mechanism of host defense against HPV infection in CA.

Is it Necessary to Evaluate Fear of Childbirth in Pregnant Women? A Scoping Review.

OBJECTIVE: To review concepts, definitions, and findings about fear of childbirth (FOC). METHODS: A bibliographic review was carried out through the main scientific databases in 2020. RESULTS: All 32 articles considered potentially relevant were analyzed. A recent study suggests that the global prevalence of FOC can reach up to 14%. Factors such as parity, gestational age, previous birth experience, age and nationality of the woman seem to influence FOC. CONCLUSION: Fear of childbirth could be related to an increased risk of adverse obstetric outcomes such as maternal request for cesarean delivery, preterm birth, prolonged labor, postpartum depression, and post-traumatic stress. These evidence highlight the importance of the discussion regarding this topic.

OBJETIVO: Revisar conceitos, definições e achados sobre medo do parto (MDP). MéTODOS: Foi realizada uma revisão bibliográfica nas principais bases de dados científicas em 2020. RESULTADOS: Foram analisados todos os 32 artigos considerados potencialmente relevantes. Um estudo recente sugere que a prevalência global do MDP pode chegar a 14%. Fatores como paridade, idade gestacional, experiência anterior de parto, idade da mulher e nacionalidade parecem influenciar o MDC. CONCLUSãO: O MDC pode estar relacionado ao aumento do risco de desfechos obstétricos adversos, como solicitação materna de cesariana, parto prematuro, trabalho de parto prolongado, depressão pós-parto e estresse pós-traumático. Estas evidências destacam a importância da discussão sobre este tema.

Applying a physiotherapy protocol to women during the active phase of labor improves obstetrical outcomes: a randomized clinical trial.

BACKGROUND: Labor is a physiological process triggered by mechanical and hormonal events that promote uterine contractions to expel the fetus. OBJECTIVE: This study aimed to evaluate the effectiveness of a nonpharmacologic childbirth care protocol in women in the active phase of labor in improving obstetrical and perinatal outcomes. STUDY DESIGN: This was a randomized trial with concealed allocation, assessor blinding, and intention-to-treat analysis. A total of 80 low-risk primigravida women at the end of pregnancy admitted at the beginning of the active phase of labor participated in the study. The participants were divided into an experimental group (n=40) and a control group (n=40). Women in the experimental group received 4 interventions: ambulation at 4 to 6 cm of cervical dilation, alternation of maternal postures, transcutaneous electrical nerve stimulation at 6 to 7 cm, and a warm shower bath at >7 cm. The control group received only routine obstetrical care during labor. The parturient could request pharmacologic analgesia at any time during the study. The main outcome measures were the duration of the active phase of the first stage of labor, the duration of the expulsive phase of labor, and the prevalence of labor dystocia as assessed by the partograph. The researchers collected other maternal and neonatal data from official birth records. RESULTS: The parturients who received the nonpharmacologic protocol had a shorter active phase of the first stage of labor (444 minutes in the control group and 373 minutes in the experimental group; P=.02), presented rupture of membranes later in labor (7 cm in the control group and 8 cm in the experimental group; P<.01), requested pharmacologic analgesia with more significant cervical dilation (5 cm in the control group and 8 cm in the experimental group; P<.01), requested fewer additional doses of analgesics, and had lower labor dystocia rates than the patients in the control group. In addition, there was no difference in other maternal and perinatal variables between the control group and the experimental group. CONCLUSION: The implementation of a sequential nonpharmacologic protocol composed of ambulation, transcutaneous electrical nerve stimulation with change of upright positions, and warm shower bath has the potential to reduce labor pain, as reflected in decreased and delayed use of pharmacologic analgesia and reduced duration of the active phase of labor and dystocia rates. Maternity hospitals should provide this protocol, and women should be encouraged to request this childbirth care protocol.

Assistance to Victims of Sexual Violence in a Referral Service: A 10-Year Experience.

OBJECTIVE: To evaluate the assistance provided to women victims of sexual violence and their participation in the follow-up treatment after the traumatic event, presenting a sociodemographic profile, gynecological background, and circumstances of the event, and reporting the results, acceptance, and side effects of prophylaxis for sexually transmitted infections (STIs) and pregnancy. METHODS: A retrospective cohort study comprising the period between 2007 and 2016. All women receiving medical care and clinical follow-up after a severe episode of sexual violence were included. Records of domestic violence, male victims, children, and adolescents who reported consensual sexual activity were excluded. The present study included descriptive statistics as frequencies and percentages. RESULTS: A total of 867 medical records were reviewed and 444 cases of sexual violence were included. The age of the victims ranged from 10 to 77 years old, most of them self-declared white, with between 4 and 8 years of education, and denying having a sexual partner. Sexual violence occurred predominantly at night, on public thoroughfare, being committed by an unknown offender. Most victims were assisted at the referral service center within 72 hours after the violence, enabling the recommended prophylaxis. There was high acceptance of antiretroviral therapy (ART), although half of the users reported side effects. Seroconversion to human immunodeficiency virus (HIV) or to hepatitis B virus (HBV) was not detected in women undergoing prophylaxis. CONCLUSION: In the present cohort, the profile of victims of sexual violence was low-educated, young, white women. The traumatic event occurred predominantly at night, on public thoroughfare, being committed by an unknown offender. Assistance within the first 72 hours after sexual violence enables the healthcare center to provide prophylactic interventions against STIs and unwanted pregnancies.

OBJETIVO: Avaliar a assistência prestada às mulheres vítimas de violência sexual e seu acompanhamento após o evento traumático, caracterizando o perfil sociodemográfico, antecedentes ginecológicos e circunstâncias do evento, além de relatar a aceitação e os efeitos colaterais da profilaxia para infecções sexualmente transmissíveis (ISTs) e a ocorrência de gravidez resultante da violência sexual. MéTODOS: Estudo de coorte retrospectivo compreendendo o período entre 2007 e 2016. Foram incluídas todas as mulheres em acompanhamento médico e clínico após episódio de violência sexual. Foram excluídos registros de violência doméstica, vítimas do sexo masculino e crianças e adolescentes que relataram atividade sexual consensual. O estudo incluiu estatísticas descritivas, com frequências e percentuais. RESULTADOS: Foram revisados 867 prontuários e 444 casos de violência sexual foram incluídos. A faixa etária foi 10 a 77 anos; a maioria das vítimas se autodeclarou branca, com entre 4 e 8 anos de escolaridade, e negou ter um parceiro sexual fixo. A violência sexual ocorreu predominantemente à noite, em via pública, por um agressor desconhecido. A maioria foi atendida no serviço de referência em até 72 horas após a violência, possibilitando profilaxias preconizadas. Houve alta aceitação da terapia antirretroviral (TARV), embora metade das usuárias relatasse efeitos colaterais. A soroconversão para o vírus da imunodeficiência humana (HIV, na sigla em inglês) ou para o vírus da hepatite B (HBV, na sigla em inglês) não foi detectada entre as vítimas. CONCLUSãO: Nesta coorte, o perfil das vítimas de violência sexual foi de mulheres brancas, de baixa escolaridade, e jovens. O evento traumático ocorreu predominantemente à noite, em via pública, por um agressor desconhecido. A assistência nas primeiras 72 horas após a violência sexual permite que o serviço de saúde realize intervenções profiláticas contra ISTs e gravidez indesejada.

COVID-19 Vaccines Confer Protection in Hospitalized Pregnant and Postpartum Women with Severe COVID-19: A Retrospective Cohort Study.

The coronavirus disease 2019 (COVID-19) pandemic has had deleterious effects among the obstetric population. Pregnant and postpartum women constitute a high-risk group for severe COVID-19. Vaccination reduces the risk of infection, but it is not known whether women who become infected despite vaccination have a milder course of disease than those who had not been vaccinated. This retrospective cohort study evaluated whether vaccination reduces the severity of COVID-19 infection, as measured by severe maternal morbidity and mortality among hospitalized pregnant and postpartum individuals. A total of 2284 pregnant and postpartum women hospitalized with severe COVID-19 were included. Those who did and who did not receive COVID-19 vaccination were compared. The rates of intensive care unit admission, intubation, and mortality were significantly lower among subjects in the vaccinated group (p < 0.001, p < 0.001 and p < 0.001, respectively). The numbers of patients who needed to be vaccinated to avoid one case of intensive care unit admission, intubation, or death due to COVID-19 were 7, 7, and 9, respectively. The COVID-19 vaccine offers protective effects against intensive care unit admission, intubation, and death in hospitalized pregnant and postpartum women with severe SARS-CoV-2-induced SARS.

Proteases and HPV-Induced Carcinogenesis.

Persistent infection with Human papillomavirus (HPV) is the main etiologic factor for pre-malignant and malignant cervical lesions. Moreover, HPV is also associated with oropharynx and other anogenital carcinomas. Cancer-causing HPV viruses classified as group 1 carcinogens include 12 HPV types, with HPV 16 and 18 being the most prevalent. High-risk HPVs express two oncoproteins, E6 and E7, the products of which are responsible for the inhibition of p53 and pRB proteins, respectively, in human keratinocytes and cellular immortalization. p53 and pRB are pleiotropic proteins that regulate the activity of several signaling pathways and gene expression. Among the important factors that are augmented in HPV-mediated carcinogenesis, proteases not only control processes involved in cellular carcinogenesis but also control the microenvironment. For instance, genetic polymorphisms of matrix metalloproteinase 1 (MMP-1) are associated with carcinoma invasiveness. Similarly, the serine protease inhibitors hepatocyte growth factor activator inhibitor-1 (HAI-1) and -2 (HAI-2) have been identified as prognostic markers for HPV-dependent cervical carcinomas. This review highlights the most crucial mechanisms involved in HPV-dependent carcinogenesis, and includes a section on the proteolytic cascades that are important for the progression of this disease and their impact on patient health, treatment, and survival.

Giant perineal leiomyoma incidentally manifested at a recent episiotomy site: case report.

Benign leiomyomas are common soft tumors, arising especially in the female genital tract; unlike uterine leiomyomas, they rarely occur in perineal regions. They can develop wherever smooth muscle is present. Herein is reported the case of a large perineal leiomyoma in a 36-year-old woman who noted a palpable mass close to the rectum 1 year after she had delivered vaginally, in the same region of as a mediolateral episiotomy. Complete surgical excision was performed. Histopathologic findings were compatible with benign leiomyoma. At postoperative follow-up, no signs of anal dysfunction were noted. There was no pathologic correlation between formation of the leiomyoma and the episiotomy despite a possible association between the presence of fibrosis and development of leiomyomas, which was found during a literature review. Microarray analysis will be necessary to elucidate this hypothesis.

Scale for assessing the quality of life of women with Human Papillomavirus infection.

OBJECTIVES: to develop and validate a scale for assessing the quality of life of women with Human Papillomavirus infection. METHODS: a methodological study to develop the stages of item elaboration, apparent and content validation, semantic validation, pre-test, item allocation in domains, and reliability. RESULTS: 98 items were elaborated and submitted to apparent and content validation (version 2; n=05). In semantic validation, 90.9% of women considered all items clear and understandable (version 3; n=11). In pre-test, the best applicability was in the form of a self-administered questionnaire in relation to the interview (version 4; n=38). The Exploratory Factor Analysis allocated 58 items in 6 domains; (version 5; n=351). For reliability, the general Cronbach's alpha value was 0.883. CONCLUSIONS: the instrument proved to be valid and reliable for assessing the quality of life of women with Human Papillomavirus infection, consisting of 54 items allocated in 6 domains.

Perspectives on administration of COVID-19 vaccine to pregnant and lactating women: a challenge for low- and middle-income countries.

Women who are in the pregnancy-puerperal cycle or are lactating have been deliberately excluded from participating in COVID-19 vaccine clinical trials that aimed to evaluate either the efficacy of the vaccines in inducing the formation of neutralizing antibodies or the investigational products' safety profile. The exclusion of pregnant and lactating women from such studies certainly and inequitably denies these women access to COVID-19 vaccines, since these products have become increasingly available to nonpregnant people and even to those who are pregnant and are in high-income settings. In this clinical opinion article, we discuss some aspects of the prolonged pandemic, the emergence of viral variants, the risks of severe complications of COVID-19 in pregnant women, and the disproportionate impact of the above on low- and middle-income countries. We argue that the decision to receive the COVID-19 vaccine should be a joint decision between the pregnant or lactating women and the healthcare providers, while considering the available data on vaccine efficacy, safety, the risks of SARS-CoV-2 infection in pregnant women, and the women's individual risks for infection and serious illness. The various types of vaccines that are already in use and their safety, effectiveness, and the potential risks and benefits of their administration to pregnant or lactating women are also reviewed.

Downregulation of IL-2 and IL-23 in Cervical Biopsies of Cervical Intraepithelial Lesions: A Cross-Sectional Study.

INTRODUCTION: Persistent infection with high-risk human papillomavirus (HPV) types is associated with high-grade intraepithelial lesions (HSILs) and invasive cervical cancer. The host immune response plays a key role in whether HPV clears or persists. Most studies on local immune response to HPV collect cervical mucus in order to quantify secreted cytokines; however, cells located inside the tissue can release different cytokines associated with HPV infection. OBJECTIVE: This study compared the cytokine levels in cervical biopsy specimens of women with abnormal colposcopic findings according to the histopathological results: low-grade intraepithelial lesion (LSIL), HSIL, and no intraepithelial lesion (NSIL). METHODS: A cross-sectional study enrolling 141 cervical biopsy specimens examined the cytokine profile for interleukin (IL-) 2, IL-4, IL-10, IL-12, IL-17, and IL-23 and interferon-γ, using the Luminex assay/ELISA. Differences in cytokine levels among the cervical lesion groups were assessed using the Kruskal-Wallis test. RESULTS: The 141 specimens included 90 HSILs, 22 LSILs, and 29 NSILs. IL-2 levels were significantly higher in NSIL samples than in LSIL or in HSIL samples (p = 0.0001) and IL-23 levels were significantly higher in NSIL than in HSIL samples (p = 0.003). CONCLUSIONS: Our study shows that in samples from the lesion site point, 2 important pro-inflammatory cytokines, IL-2 and IL-23, are downregulated in HPV lesions.

Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16.

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.

Immunogenicity and safety of the AS04-HPV-16/18 and HPV-6/11/16/18 human papillomavirus vaccines in asymptomatic young women living with HIV aged 15-25 years: A phase IV randomized comparative study.

BACKGROUND: Women living with HIV (WLWH) are at higher risk of acquisition and progression of human papillomavirus (HPV) infection. Evidence on effect of HPV vaccination in this population is limited. METHODS: This phase IV randomized controlled observer-blind study assessed immunogenicity and safety of two HPV vaccines (AS04-HPV-16/18 vs. 4vHPV) given in WLWH (stage 1) and HIV- females aged 15-25 years. Co-primary endpoints were to demonstrate, in WLWH subjects, non-inferiority (and if demonstrated, superiority) of AS04-HPV-16/18 vs. 4vHPV for HPV-16 and HPV-18 by pseudovirion-based neutralization assay (PBNA) at month 7 and safety. Non-inferiority criteria was lower limit (LL) of the 95% confidence interval (CI) of the GMT ratio AS04-HPV-16/18/4vHPV above 0.5, in the according to protocol population. NCT01031069. FINDINGS: Among 873 subjects recruited between 26-Oct-2010 and 14-May-2015, 546 were randomized (1:1) and received at least one vaccine dose (total vaccinated cohort, TVC): 257 were WLWH (129 AS04-HPV-16/18; 128 4vHPV) and 289 were subjects without HIV (144 AS04-HPV-16/18; 145 4vHPV). Baseline CD4 cell count in WLWH was at least 350 cells/mm3.At month 7, AS04-HPV-16/18 showed immunological superiority to 4vHPV in WLWH. Neutralizing anti-HPV-16 and HPV-18 antibody GMTs were 2·74 (95% CI: 1·83; 4·11) and 7·44 (95% CI: 4·79; 11·54) fold higher in AS04-HPV-16/18 vs. 4vHPV (LL of the GMT ratio >1 in TVC, p<0·0001), respectively. Similar results were observed by ELISA up to month 24.Solicited local and general symptoms were in line with product labels. The number of reported serious adverse events (SAEs) was balanced throughout the study. INTERPRETATION: Both vaccines showed an acceptable safety profile in all subjects. Despite the absence of an immunological correlate of protection for HPV, differences in immune responses elicited by the vaccines especially for HPV-18 may translate into longer lasting or more robust protection against cervical cancer with the AS04-HPV-16/18 vaccine in WLWH.

Changes in Cortisol Awakening Response Before and After Development of Posttraumatic Stress Disorder, Which Cannot be Avoided with Use of Cannabidiol: A Case Report.

INTRODUCTION: Previous studies have shown attenuated cortisol awakening response in patients with posttraumatic stress disorder (PTSD). CASE PRESENTATION: A 15-year-old girl, a survivor of acute sexual violence, received a 7-day oral treatment with cannabidiol. She was followed-up from the first 24 hours after the event for 6 months, for assessment of the effects of this treatment on the reconsolidation of memories related to the traumatic event. DISCUSSION: Cannabidiol treatment did not prevent the onset of PTSD. Cortisol awakening responses after the onset of the disorder were attenuated compared with those observed in the same individual before the onset of PTSD, in line with previous evidence from studies comparing groups with and without PTSD.