HPV16 induces penile intraepithelial neoplasia and squamous cell carcinoma in transgenic mice: first mouse model for HPV-related penile cancer.

Penile cancer is an under-studied disease that occurs more commonly in developing countries and 30-50% of cases show high-risk human papillomavirus (HPV) infection. Therapeutic advances are slow, largely due to the absence of animal models for translational research. Here, we report the first mouse model for HPV-related penile cancer. Ten-week-old mice expressing all the HPV16 early genes under control of the cytokeratin 14 (Krt14) gene promoter and matched wild-type controls were exposed topically to dimethylbenz(a)anthracene (DMBA) or vehicle for 16 weeks. At 30 weeks of age, mice were sacrificed for histological analysis. Expression of Ki67, cytokeratin 14, and of the HPV16 oncogenes E6 and E7 was confirmed using immunohistochemistry and quantitative PCR, respectively. HPV16-transgenic mice developed intraepithelial lesions including condylomas and penile intraepithelial neoplasia (PeIN). Lesions expressed cytokeratin 14 and the HPV16 oncogenes E6 and E7 and showed deregulated cell proliferation, demonstrated by Ki67-positive supra-basal cells. HPV16-transgenic mice exposed to DMBA showed increased PeIN incidence and squamous cell carcinoma. Malignant lesions showed varied histological features closely resembling those of HPV-associated human penile cancers. Wild-type mice showed no malignant or pre-malignant lesions even when exposed to DMBA. These observations provide the first experimental evidence to support the etiological role of HPV16 in penile carcinogenesis. Importantly, this is the first mouse model to recapitulate key steps of HPV-related penile carcinogenesis and to reproduce morphological and molecular features of human penile cancer, providing a unique in vivo tool for studying its biology and advancing basic and translational research. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Trichomonas vaginalis as a risk factor for human papillomavirus: a study with women undergoing cervical cancer screening in a northeast region of Brazil.

BACKGROUND: Human papillomavirus (HPV) and Trichomonas vaginalis (TV) infections are the most common sexually transmitted infections (STIs) globally. The latter has contributed to a variety of adverse outcomes for both sexes. Moreover, in Brazil, epidemiological studies on patients with STIs are limited. Therefore, this study aimed to determine the prevalence of TV and its association with HPV in women undergoing cervical cancer screening. METHODS: Women with a normal cervix were recruited from a community-based cervical cancer screening program. Gynecological examinations were conducted, and questionnaires were provided. Vaginal canal and uterine cervix samples were collected for cytological examinations (reported using the 2001 Bethesda System) and tested for the presence of TV and HPV DNA. RESULTS: In total, 562 women who attended public primary healthcare were included in the study. The T. vaginalis was present in 19.0% (107) and HPV DNA was present in 46.8% (263) of women. Among the women of TV 73.8% (79) had a co-infection with HPV (p = 0.001). CONCLUSIONS: We concluded that a TV infection is associated with an HPV infection of the cervix as well as with the cervical cytological abnormalities. Further studies could reveal the mechanisms by which these two organisms interact at the cellular level, with control for shared behavioral risk factors.

Role of HPV 16 variants among cervical carcinoma samples from Northeastern Brazil.

BACKGROUND: Cervical cancer is the fourth most common type of cancer affecting women globally. In Brazil, it is the third most frequent type of cancer in women and HPV is present in approximately 90% of cases. Evidence suggests that variants of HPV 16 can interfere biologically and etiologically during the development of cervical cancer. METHODS: Cervix tumor fragments were collected, their DNA was extracted, and nested PCR was used to detect HPV. Positive samples were sequenced to determine the viral genotype. To characterize the HPV 16 strains, positive samples PCR was used to amplify the LCR and E6 regions of the HPV 16 virus. RESULTS: Data from 120 patients with cervical cancer were analyzed. Most women were between 41 and 54 years of age, had schooling until primary school, a family income between 1 and 2 times the minimum wage and were married/in a consensual union. There was no statistically significant association between HPV or socio-demographic variables and risk factors for cervical cancer (P <  0.05). HPV was present in 88 women (73%). The most prevalent types were HPV 16 (53.4%), HPV 18 (13.8%), HPV 35 (6.9%) and HPV 45 (5.7%). Of the 47 HPV 16 positive cases, variant A (49%) was present in 23 samples, followed by variant D in 20 cases (43%), and variants B and C in 2 cases each (4%). The most prevalent histological type of HPV 16 tumors was squamous cell carcinoma, followed by adenocarcinoma. There was a statistically significant association between HPV 16 variants and the tumors' histological types (P <  0.001). CONCLUSIONS: Knowledge of HPV 16 variants will provide data on their influence on the pathological and oncogenic aspects of cervical lesions.

Açaí (Euterpe oleracea Mart) Consumption and Prevention of Chronic Diseases: Is There an Association? A Preliminary Study.

BACKGROUND: Flavonoids from a variety of fruits, including açaí, have beneficial antioxidant activity in several diseases, including cancer. Breast cancer is the second most prevalent cancer among Brazilian women. Studies have shown the action of flavonoids on neoplastic cells, as well as on diabetes and neurodegenerative and cardiovascular diseases. OBJECTIVE: To analyze the relationship between the consumption of açaí and the presence of chronic diseases in women residing in the rural area of São Luís, Maranhão. METHODS: A convenience sample of 150 women residing in the Maracanã neighborhood in São Luís, Maranhão, was used; the collected data included sociodemographic characteristics, habits, sexual and reproductive history, consumption of açaí, and history of cancer and other chronic diseases. The sample was divided into women who consumed açaí at least once a week (cases) and women who did not consume açaí (controls). Statistical analysis was performed to assess the relationships between those variables and the consumption of açaí. RESULTS: A total of 141 women (94%) consumed açaí. Among these, 79.3% were aged between 20 and 50 years, 78.67% were farmers or housewives, 64.67% were Pardo (mixed race), 76.67% were nonsmokers, 70% were not receiving hormonal therapy, 40.67% had already undergone mammography, 28% had already undergone breast ultrasound, and 27.33% had a family history of cancer, with breast cancer being the second most prevalent cancer. There was a higher prevalence of hypertension among women who did not consume açaí than that among those who did; however, previous cancer, family history of cancer, heart disease, and diabetes were more prevalent among the consumers of açaí. There were no statistically significant relationships. CONCLUSION: Flavonoids are known to have a beneficial effect on some types of neoplastic cells and other diseases; therefore, larger studies are necessary to better evaluate the beneficial effects of consuming foods containing flavonoids on these diseases.

Human Papillomavirus and Coronary Artery Disease in Climacteric Women: Is There an Association?

BACKGROUND: Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. OBJECTIVE: To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. METHODS: The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. RESULTS: Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). CONCLUSION: These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.

Prevalence of human papillomavirus infection among women from quilombo communities in northeastern Brazil.

BACKGROUND: Human papillomavirus (HPV) is a member of the Papillomaviridae family. The prevalence of HPV genotypes may vary according to the region and the population studied. Quilombo communities are ethnic and racial groups with difficult access to health services compared to the general population in Brazil. The aim of this study was to identify specific HPV types correlating with sociodemographic/behavioral characteristics and cervical smear cytological abnormalities in Quilombola women. METHODS: This cross-sectional study included 395 Quilombola women users of the Unified Health System of the Municipalities of Maranhão for the screening of cervical cancer. The samples were analyzed for the presence of cytological abnormalities by conventional methods and tested for 37 HPV genotypes using polymerase chain reaction with primers PGMY09/11 followed by reverse line blot hybridization performed with the Linear Array HPV Genotyping Test kit by Roche Molecular System®. The association between HPV types and cytological diagnosis was investigated according to the different age groups. RESULTS: HPV infection was detected in 12.6% (50/395) of the women. Infections by high-risk HPV types were more frequent. Genotypes 68 (26.0%); 58 and 52 (20.0%); 31 (10.0%) and 62 (8.0%) were the most prevalent. The highest prevalence (42.0%) of HPV infection occurred in women diagnosed with high-grade squamous intraepithelial lesion. There was a statistically significant association between HPV infection and the detection of cytological abnormalities in all age groups except in women over 60 years. There was a statistically significant association between the municipality of origin and the number of partners with HPV infection. CONCLUSIONS: It is important to incorporate new cervical cancer screening techniques incorporating the cervical-vaginal cytology. For further studies, it is necessary to determine the level of knowledge of Quilombola population on health-related issues including HPV infection and cervical cancer. This will contribute to the continuous improvement of healthcare coverage among the population and enhance the implementation of cancer care in the state of Maranhão.

Importance of lipid accumulation product index as a marker of CVD risk in PCOS women.

BACKGROUND: The polycystic ovary syndrome (PCOS) is considered the most common endocrine disease during the woman's reproductive life, with prevalence ranging from 5 to 10% of women of reproductive age. There is a paucity of studies regarding the use of the lipid accumulation product (LAP) as a risk marker for the development of cardiovascular disease (CVD). METHODS: A cross-sectional study was conducted on 78 women aged 18 to 42 years seen at University Hospital of Maranhão, with a diagnosis of polycystic ovary syndrome according to the Rotterdam criteria. The following variables of interest were recorded on a protocol form: sociodemographic and behavioral data, body mass index, waist circumference, fasting glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, high-density lipoprotein cholesterol, and systolic and diastolic blood pressure. RESULTS: Logistic regression showed that, except for HDL, all cardiovascular risk markers presented a higher chance of being altered when the lipid accumulation product was above the cut off value of 37.9 cm.mmol/L. CONCLUSION: The lipid accumulation product seems to be sufficient to indicate a risk of cardiovascular diseases in women with polycystic ovary syndrome.

Prevalence of human papillomavirus in penile malignant tumors: viral genotyping and clinical aspects.

BACKGROUND: The human papillomavirus (HPV) prevalence in males has been reported to be between 3.6% and 84%, depending specially on the socioeconomic status. HPV infection has been related as a risk factor for penile cancer. This is a rare tumor, and other risk factors include lack of personal hygiene and men who have not undergone circumcision. Penile cancer is less than 1% of cancers in men in the United States, however, is much more common in some parts of Asia, Africa, and South America, where it accounts for up to 10% of cancers in men. This study aimed to determine the prevalence of HPV-DNA in penile cancers in São Luís, Brazil and to correlate the virus presence to histopathological factors. METHODS: Tumor paraffin samples of 76 patients with penile carcinoma were tested in order to establish the prevalence and distribution of genotypic HPV using PCR/Nested and automated sequencing. To evaluate the association between HPV types and other clinical and morphological variables, a nonparametric ANOVA was performed using a Kruskal Wallis test, and statistical significance was determined to a value of p < 0.05. RESULTS: The average age of patients at the time of diagnosis was 66 years ± 17.10. Regarding location, 65.79% of the tumors were located in the glans, and the most common types were vegetative (34.21%) and squamous (98.68%). Most of the lesions ranged in size from 2.1 to 5.0 cm, presenting Jackson I stage and Broders II degree. It was observed that 32 patients had at least one invaded and/or infiltrated structure. Lymph node involvement was observed in 19.76% of the patients, and 21.05% showed an inflammatory process. In the molecular evaluation, HPV infection was observed in 63.15% of the lesions, and the most common type was HPV 16. CONCLUSIONS: From the statistical analysis, it can be verified that the variables were not associated with infection by the HPV virus. Although penile cancer can result from various risk factors that act in synergy, an HPV virus infection is important for the development of such neoplasm.

The influence of hormone replacement therapy on the salivary flow of post-menopausal women.

The aim of this study is to investigate the influence of hormone therapy on salivary flow in menopausal women. It is a case-control study involving 86 post-menopausal women. The case group consisted of 47 women undergoing estroprogestative or estrogen hormone replacement therapy (HRT), and the control group consisted of 39 women who did not receive any HRT. All patients were submitted to a standard questionnaire, followed by total stimulated sialometry and determination of body mass index (BMI). The salivary flow was classified as follows: normal (1.0-3.0 mL/min), low (0.7-1.0 mL/min), and hyposalivation (<0.7 mL/min). The results were analyzed statistically by the chi-square test, logistic regression model, and linear regression (p < 0.05). The HRT group presented an association of protection, even after adjusting the analysis, for low salivary flow (Adjusted OR = 0.22; 95% CI = 0.05-0.88; p = 0.034), and hyposalivation (Adjusted OR = 0.30; 95% CI = 0.10-0.92; p = 0.036). The results suggest that estroprogestative therapy (ß = + 0.53; p = 0.022) has greater influence on the increase of salivary flow than estrogen therapy (ß = +0.35; p = 0.137). The study concludes stating salivary flow was influenced by HRT on the post-menopausal women studied.

Association between oral DNA-HPV and genital DNA-HPV.

BACKGROUND: Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases worldwide and is observed in both men and women. The presence of the virus is often associated with benign and malignant neoplasms of the oral cavity. We wished to investigate whether HPV infection in the genitalia was associated with HPV infection in the oral mucosa. METHODS: The prevalence of HPV in the oral cavity and genitalia was evaluated by DNA extraction from genital and oral cavity samples of 105 women, followed by nested PCR. RESULTS AND CONCLUSIONS: The prevalence of HPV in the oral cavity was significantly higher in women who had genital HPV (P < 0.0001). Oral sex, alcohol, and tobacco consumption were not associated with the oral HPV infection.

Uterine leiomyoma: understanding the impact of symptoms on womens' lives.

BACKGROUND: Most women report negative experience about the symptoms of uterine leiomyoma (UL) in their lives, such as abnormal uterine bleeding and pelvic pain. Many studies have been conducted about efficacy of UL treatment, but little research has been performed about womens health related quality of life (HRQL). METHODS: This is a semi-structured, descriptive, observational, qualitative study that was performed during eight months. Focus group (FG) interviews were performed with women attending at a tertiary hospital in Brazil, who were consecutively included in the study. Seventy women with symptomatic UL were recruited to this study. FG duration was one hour with mediators with 5-6 women at each group. Collected data from discussions was processed according to thematic analysis and stored at a qualitative software. RESULTS: Women were negatively influenced by the presence of symptomatic UL. The major themes that were noticed during analysis were: beliefs and attitudes towards UL; limitation to social and professional activities; sensation of fear/unfairness/discouragement towards the symptoms and adverse effects during treatment with GnRH analogs. CONCLUSIONS: Symptomatic UL has a negative impact on womens HRQL. Health providers should consider such impact when counseling women on their treatment options, since it may have an important influence in these patients' decision-making process. While current pharmacological treatments may improve disease specific outcomes, such as bleeding intensity and tumor volume, they fail on actually improving quality of life.

NK1 receptor mediates cerebral cellular and extracellular morphological changes during the LPS-induced febrile response.

Fever elicited by bacterial lypopolyssacharide (LPS) is mediated by pro-inflammatory cytokines, which activate central mediators and regulate the hypothalamic temperature setpoint. This response is often accompanied by morphological changes involving the extracellular matrix, neurons and glial cells, with significant health impacts. The NK1 receptor is involved in the febrile response induced by LPS but its effects over the extracellular matrix in the context of neuroinflammation remain unknown. The present work aims to clarify the extracellular changes associated with NK1 signaling in LPS-induced fever. Male Wistar rats were exposed to LPS intraperitoneally. Experimental groups were pre-treated intracerebroventricularly with the NK1 selective inhibitor SR140333B or saline. Histological changes involving the brain extracellular matrix were evaluated using hematoxylin and eosin, Mason's trichrome, picrosirius, alcian blue, periodic acid Schiff's stains. The expression of matrix metalloproteinase 9 (MMP9) was studied using confocal microscopy. Fever was accompanied by edema, perivascular lymphoplamacytic and neutrophylic infiltration, spongiosis and MMP9 overexpression. SR140333B significantly reduced LPS-induced fever (p < 0.0001), MMP9 overexpression (p < 0.01) and associated histological changes. These results contribute to characterize cerebral extracellular matrix changes associated with LPS-induced fever. Overall, the present work supports a role for NK1 receptor in these neuroinflammatory changes, involving MMP9 overexpression, edema and leukocytic infiltration.

Stress urinary incontinence in climacteric women in a northeastern Brazilian municipality: a household survey.

INTRODUCTION AND HYPOTHESIS: Low socioeconomic factors may influence the development of stress urinary incontinence (SUI). Thus far, there is little research available on SUI in developing countries. We aimed to determine whether the prevalence of SUI in a northeastern Brazilian municipality was higher or lower than in the general female population. METHODS: Cross-sectional household cluster study of 1,180 climacteric women in the São Luís municipality (Maranhão state, Brazil) was conducted using a standardized questionnaire that was previously tested in a pilot study and administered by interviewers to obtain socioeconomic and cultural information, climacteric aspects, and life habits related to SUI. RESULTS: From this population, 15.34% (n = 181) had SUI; this prevalence did not change with age. More than half (57.92%) of the patients replied that they had not consulted a physician for their SUI. The presence of SUI was not associated with any socioeconomic or gynecological variables after multivariate analysis. CONCLUSIONS: The prevalence of SUI in São Luís was similar to the rates observed in the general global female population. Socioeconomic and gynecological variables were not associated with SUI.

Comparison of the outcomes of the sling technique using a commercial and hand-made polypropylene sling.

PURPOSE: To compare the outcomes and costs of stress urinary incontinence (SUI) surgery using a hand-made sling (Marlex®) versus a commerciallyavailable suburethral polypropylene sling (Advantage®). MATERIALS AND METHODS: Thirty-nine women with SUI due to bladder neck hypermobility and/or sphincter incompetence diagnosed by clinical examination and urodynamic studies were divided into two groups: group 1 (n = 19) consisted of patients from an academic center (Department of Urology, University Hospital of Federal University of Maranhao, and group 2 (n = 20) patients from private practice. The hand-made polypropylene suburethral sling was used in group 1 and the commercial sling in group 2. The patients were evaluated 30, 60 and 90 days after surgery. RESULTS: The mean duration of surgery was 43 min. in group 1 and 51 min. in group 2. No postoperative voiding difficulties were observed in group 1 (100%), as well as, in 94.7% of patients of group 2. A bladder catheter was not required in any of the patients of the two groups at the end of the study. The level of satisfaction was 100% in group 1, whereas, one patient of group 2 considered the surgery to be unsuccessful. Urodynamic studies showed low amplitude uninhibited contraction in 11.1% of patients of group 1 and 10.5% of group 2. No complications were observed in either group. CONCLUSION: The hand-made polypropylene mesh (Marlex®) can be used for sling procedures, saving costs and yielding results similar to that obtained with commercial sling systems.

Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis.

BACKGROUND/AIM: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world and human papillomavirus (HPV) is an important risk factor for this neoplasm. Recent studies showed an association between sex hormone receptors and pathogenesis and/or prognosis in patients with HNSCC. The aim of this study was to clarify the expression patterns of sex hormone receptors in HPV-positive and HPV-negative HNSCC and their associations with tumour biopathology and biological behaviour. MATERIALS AND METHODS: Scientific literature indexed in PubMed about sex hormone receptors in HNSCC was retrieved and critically analyzed, to obtain an overview of expression patterns and their possible implications for tumour biopathology and prognosis. RESULTS: Sex hormone receptors were more frequently detected in oropharyngeal tumours compared with HNSCC from other locations. ERα was associated with HPV-positive tumours. The androgen and progesterone receptors were associated with poor patient prognosis. Estrogen receptor alpha (ERα) is implicated in the biopathology of HNSCC in different ways, by promoting DNA hypermutation and facilitating HPV integration thus contributing to an immunogenic phenotype, but also by cooperating with the epithelial growth factor receptor (EGFR) to promote resistance to therapy. CONCLUSION: The expression of sex hormone receptors may be of prognostic value in specific tumour subgroups, but the use of hormonal therapies for HNSCC is still not in close sight.

Urinary Incontinence in Climacteric Women With or Without Depressive Symptoms: A Cross-Sectional Study.

OBJECTIVE: This study aimed to investigate whether the occurrence of urinary incontinence (UI) is associated with increased odds of depression in perimenopausal and postmenopausal women. METHODS: This cross-sectional study included 208 women with depressive symptoms, confirmed by the Beck Depression Inventory, and 247 patients without depression. All participants were perimenopausal or postmenopausal women aged 35 to 65 years who attended an outpatient clinic from a tertiary-academic hospital in Northeastern Brazil. Urinary incontinence symptoms were assessed using patient's self-report and the validated versions of the International Consultation on Incontinence Questionnaire-Short Form and the Questionnaire for Urinary Incontinence Diagnosis. To investigate the severity of climacteric symptoms, the Blatt-Kupperman Index was used, and menopause-related quality of life was analyzed using the Utian Quality of Life Questionnaire. RESULTS: In univariate analysis, the Beck Depression Inventory-II mean scores for UI and non-UI women were, respectively, 15.5 (95% confidence interval, 14.28-16.72) and 11.83 (10.52-13.13; P < 0.05). Patients with moderate and severe scores of depression reported higher International Consultation on Incontinence Questionnaire-Short Form and Questionnaire for Urinary Incontinence Diagnosis scores when compared with women with mild depression scores and women without depression (P < 0.001). Conversely, in multivariate analysis, having UI was not associated with having depression (odds ratio [OR], 0.85; 0.52-1.37; P = 0.50), after adjusting for confounders. Older age (>55 years) was associated with decreased odds of depression (OR, 0.43; 0.21-0.88; P = 0.02), whereas moderate (OR, 2.28; 1.40-3.71; P = 0.001) and severe (OR, 7.70; 2.79-21.23) intensities of menopause symptoms were associated with increased odds of depression. CONCLUSION: Urinary incontinence was not associated with depression within climacteric women after multivariate analysis.

Differential Incidence of Tongue Base Cancer in Male and Female HPV16-Transgenic Mice: Role of Female Sex Hormone Receptors.

A growing proportion of oropharyngeal squamous cell carcinomas (OPSCC) are associated with infection by high-risk human papillomavirus (HPV). For reasons that remain largely unknown, HPV+OPSCC is significantly more common in men than in women. This study aims to determine the incidence of OPSCC in male and female HPV16-transgenic mice and to explore the role of female sex hormone receptors in the sexual predisposition for HPV+ OPSCC. The tongues of 30-weeks-old HPV16-transgenic male (n = 80) and female (n = 90) and matched wild-type male (n = 10) and female (n = 10) FVB/n mice were screened histologically for intraepithelial and invasive lesions in 2017 at the Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Portugal. Expression of estrogen receptors alpha (ERα) and beta (ERß), progesterone receptors (PR) and matrix metalloproteinase 2 (MMP2) was studied immunohistochemically. Collagen remodeling was studied using picrosirius red. Female mice showed robust ERα and ERß expression in intraepithelial and invasive lesions, which was accompanied by strong MMP2 expression and marked collagen remodeling. Male mice showed minimal ERα, ERß and MMP2 expression and unaltered collagen patterns. These results confirm the association of HPV16 with tongue base cancer in both sexes. The higher cancer incidence in female versus male mice contrasts with data from OPSCC patients and is associated with enhanced ER expression via MMP2 upregulation.

Evidence of Zika virus circulation in asymptomatic pregnant women in Northeast, Brazil.

BACKGROUND: Zika virus (ZIKV) is a flavivirus associated with microcephaly and other fetal anormalities. However, evidence of asymptomatic ZIKV infection in pregnant women is still scarce. This study investigated the prevalence of Zika infection in asymptomatic pregnant women attending two public maternities in Maranhão state, Northeast Brazil. METHODS: A total of 196 women were recruited at the time of delivery by convenience sampling from two maternity clinics in São Luís, Maranhão, Brazil, between April 2017 and June 2018. Venous blood, umbilical cord blood and placental fragments from maternal and fetal sides were collected from each subject. ZIKV infection was determined by reverse transcription polymerase chain reaction (RT-qPCR) for ZIKV and by serology (IgM and IgG). Nonspecific laboratory profiles (TORCH screen) were obtained from medical records. RESULTS: The participants were mostly from São Luís and were of 19-35 years of age. They had 10-15 years of schooling and they were of mixed race, married, and Catholic. ZIKV was identified in three umbilical cord samples and in nine placental fragments. Mothers with positive ZIKV RT-qPCR were in the age group older than 19 years. Of the 196 women tested by ZIKV rapid test, 6 and 117 women were positive for anti-ZIKV IgM and anti-ZIKV IgG antibodies, respectively. Placental Immunohistochemistry study detected ZIKV in all samples positive by RT-PCR. The newborns did not show any morphological and/or psychomotor abnormalities at birth. CONCLUSIONS: Asymptomatic ZIKV infection is frequent, but it was not associated to morphological and/or psychomotor abnormalities in the newborns up to 6 months post-birth. Although pathological abnormalities were not observed at birth, we cannot rule out the long term impact of apparent asymptomatic congenital ZIKV infection.

Immune-mediated febrile response in female rats: Role of central hypothalamic mediators.

Lipopolysaccharide (LPS) induces fever through cytokines like receptor-activator of nuclear factor κB ligand (RANKL), triggering mediators like prostaglandins (PG), endothelin-1 (ET-1), corticotrophin-releasing factor (CRF), substance P (SP) and endogenous opioids. LPS-induced fever is reduced in females compared with males except in ovariectomized (OVX) females which show increased fever mediated by PG. The present study aimed to identify the mediators involved in fever in intact and OVX female rats. Fever was induced with LPS (50 µg/kg) intraperitoneally or CRF (2.5 µg), ET-1 (1 pg), morphine (10 µg) and SP (500 ng) intracerebroventricularly in sham-operated and OVX rats. The role of RANKL was evaluated with osteoprotegerin (OPG, 1 µg, intracerebroventricularly). Expression of RANK, CRFI/II, ETB, µ-opioid (MOR) and NK1 receptors was evaluated by confocal microscopy. Besides LPS, only morphine induced fever in OVX rats while all mediators induced fever in sham-operated animals. OPG abolished LPS-induced fever in OVX but not sham-operated animals. Overall, fever involves similar central mediators in cycling females and males but only morphine induced fever in OVX females. Importantly, RANK/RANKL participates in LPS-induced fever in OVX females, as in males but not in cycling females.

Randomized double-blind placebo-controlled trial of the effect of Morus nigra L. (black mulberry) leaf powder on symptoms and quality of life among climacteric women.

OBJECTIVE: To test the efficacy of Morus nigra L. (MN) leaf powder for treating climacteric symptoms by comparison with hormone therapy (HT) and placebo. METHODS: A randomized controlled trial among 62 climacteric women attending Hospital of the Federal University of Maranhão, Brazil. Women were divided into MN, HT, and placebo groups, and received 250 mg of MN leaf powder, 1 mg of estradiol, or placebo for 60 days. Primary outcomes were the Blatt-Kupperman index (BKI) for climacteric symptoms and SF-36 health questionnaire scores. RESULTS: Baseline sociodemographic variables, BKI scores, symptoms, and SF-36 domains did not differ among the groups. There was a reduction in mean BKI in the MN (17.5 vs 9.7, P<0.001), HT (15.4 vs 8.6, P=0.001), and placebo (16.1 vs 12.4, P=0.040) groups. Analysis of quality of life (QoL) showed that functional capacity (P=0.006), vitality (P=0.031), mental health (P=0.017), and social aspect (P<0.01) improved after treatment in the MN group. The HT group showed improvement in emotional limitation (P=0.040), and the placebo group showed better functional capacity (P=0.030) after treatment. CONCLUSIONS: Climacteric symptoms and QoL improved after administration of 250 mg of MN leaf powder for 60 days, similar to the effects of HT. The trial is registered in the Brazilian Registry of Clinical Trials (REBEC) under registration number RBR-9t4xxk.