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Maternal infection and stress exposure, especially during childhood and adolescence, have been implicated as risk factors for schizophrenia. Both insults induce an exacerbated inflammatory response, which could mediate disturbance of neurodevelopmental processes and, ultimately, malfunctioning of neural systems observed in this disorder. Thus, anti-inflammatory drugs, such as PPARγ agonists, may potentially be used to prevent the development of schizophrenia. Microglia culture was prepared from the offspring of saline or poly(I:C)-injected mice. The cells were pretreated with pioglitazone and then, stimulated by LPS. Proinflammatory mediators and phagocytic activity were measured. Also, pregnant rats were injected with saline or poly(I:C) on GD17. The offspring were subjected to footshock during adolescence and subsequently injected with pioglitazone or vehicle. At adulthood, behavior and dopaminergic activity were evaluated. Pioglitazone reduced proinflammatory mediators induced by poly(I:C) microglia stimulated by LPS without affecting their decreased phagocytic activity. The PPARγ agonist also prevented the emergence of social and cognitive impairments, as well as attenuated the increased number of spontaneously active dopamine neurons in the VTA, observed in both males and females from poly(I:C) and stress group. Therefore, pioglitazone could potentially prevent the emergence of the schizophrenia-like alterations induced by the two-hit model via reduction of microglial activation., Competing Interests: Declaration of competing interest AAG received funds from Merck, Newron, Alkermes, Lundbeck, Takeda, Roche, Lyra, Concert, and SynAgile. All other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) is approved for the treatment of patients with platinum-sensitive relapsed ovarian cancer. Nevertheless, there is currently limited information regarding this treatment in elderly patients with ovarian cancer in a real-world setting., Methods: This observational and multicentric study retrospectively evaluated trabectedin plus PLD in a real-world setting treatment of elderly patients diagnosed with platinum-sensitive relapsed ovarian cancer, treated according to the Summary of Product Characteristics (SmPC) from 15 GEICO-associated hospitals. Patients ≥ 70 years old at the time of treatment initiation and platinum-free intervals ≥ 6 months were considered eligible., Results: Forty-three patients with a median age of 74.0 years were treated between January 1st, 2015, and December 31st, 2019 in 15 Spanish centers. Four patients achieved complete response (9.3%), 14 (32.6%) partial response, and 13 (30.2%) stable disease as the best radiological response. In the analysis of biological overall response according to CA125 serum levels (i.e., Rustin criteria), 14 responded to the treatment (32.6%), 11 responded and normalized (25.6%), three patients stabilized (7.0%) and three progressed (7.0%). Median progression-free survival (PFS) and overall survival (OS) in the study population were 7.7 and 19.5 months, respectively. The most common grade 3/4 adverse events were neutropenia (n = 8, 18.7%) and asthenia (n = 5, 11.6%)., Conclusions: This analysis demonstrated that trabectedin combined with PLD is a feasible and effective treatment in elderly patients with platinum-sensitive relapsed ovarian cancer, showing an acceptable safety profile, which is crucial in the palliative treatment of these patients., (© 2024. The Author(s).)

Background: Aldosterone has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The functions of CCL5 (C-C motif chemokine ligand 5) and its receptor CCR5 (C-C motif chemokine receptor 5) are well known in infectious diseases, their contributions to aldosterone-induced vascular injury and hypertension remain unknown., Methods: We analyzed the vascular profile, blood pressure, and renal damage in wild-type (CCR5 +/+ ) and CCR5 knockout (CCR5 -/- ) mice treated with aldosterone (600 µg/kg per day for 14 days) while receiving 1% saline to drink. Vascular function was analyzed in aorta and mesenteric arteries, blood pressure was measured by telemetry and renal injury and inflammation were analyzed via histology and flow cytometry. Endothelial cells were used to study the molecular signaling whereby CCL5 induces endothelial dysfunction., Results: Aldosterone treatment resulted in exaggerated CCL5 circulating levels and vascular CCR5 expression in CCR5 +/+ mice accompanied by endothelial dysfunction, hypertension, and renal inflammation and damage. CCR5 -/- mice were protected from these aldosterone-induced effects. Mechanistically, we demonstrated that CCL5 increased NOX1 (NADPH oxidase 1) expression, reactive oxygen species formation, NFκB (nuclear factor kappa B) activation, and inflammation and reduced NO production in isolated endothelial cells. These effects were abolished by antagonizing CCR5 with Maraviroc. Finally, aorta incubated with CCL5 displayed severe endothelial dysfunction, which is prevented by blocking NOX1, NFκB, or CCR5., Conclusions: Our data demonstrate that CCL5/CCR5, through activation of NFκB and NOX1, is critically involved in aldosterone-induced vascular and renal damage and hypertension placing CCL5 and CCR5 as potential therapeutic targets for conditions characterized by aldosterone excess., Competing Interests: None.

Psoriasis is an inflammatory skin disease characterized by keratinocyte proliferation and inflammatory cell infiltration induced by IL-17. However, the molecular mechanism through which IL-17 signaling in keratinocytes triggers skin inflammation remains not fully understood. Pyruvate kinase M2 (PKM2), a glycolytic enzyme, has been shown to have non-metabolic functions. Here, we report that PKM2 mediates IL-17A signaling in keratinocytes triggering skin psoriatic inflammation. We find high expression of PKM2 in the epidermis of psoriatic patients and mice undergoing psoriasis models. Specific depletion of PKM2 in keratinocytes attenuates the development of experimental psoriasis by reducing the production of pro-inflammatory mediators. Mechanistically, PKM2 forms a complex with Act1 and TRAF6 regulating NF-κB transcriptional signaling downstream of the IL-17 receptor. As IL-17 also induces PKM2 expression in keratinocytes, our findings reveal a sustained signaling circuit critical for the psoriasis-driving effects of IL-17A, suggesting that PKM2 is a potential therapeutic target for psoriasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Over the past few decades, the literature has pointed out pathways to success in co-management processes based on key conditions. Rather than offering prescriptive conclusions for successful co-management in protected areas, in this article, we highlight the importance of the "process" and certain elements that contribute to advancements of formal and informal co-management. We analyzed the trajectory of two protected areas for sustainable use in coastal Brazil - Extractive Reserves of Prainha do Canto Verde and São João da Ponta. Advancements of co-management were understood as processes of shared environmental and territorial governance, with levels of community participation and/or social control. Advancements were observed in both formal co-management arenas, such as deliberative boards for protected area management, and informal spheres, such as the implementation of projects and other actions involving traditional populations and partners. Drawing on Grounded Theory, the advancements were explained based on two categories of inter-related factors: (i) catalytic factors - crises, threats and other factors of social mobilization, emancipatory partnerships, and political identity, and (ii) structural factors, based on resources of community power and citizenship. Beyond diagnoses or rankings of success, the explanatory dimension of these phenomena highlights their inherent complexity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

CD4+ T cells differentiate into subsets that promote immunity or minimize damage to the host. T helper 17 cells (Th17) are effector cells that function in inflammatory responses. T regulatory cells (Tregs) maintain tolerance and prevent autoimmunity by secreting immunosuppressive cytokines and expressing check point receptors. While the functions of Th17 and Treg cells are different, both cell fate trajectories require T cell receptor (TCR) and TGF-β receptor (TGF-βR) signals, and Th17 polarization requires an additional IL-6 receptor (IL-6R) signal. Utilizing high-resolution phosphoproteomics, we identified that both synergistic and additive interactions between TCR, TGF-βR, and IL-6R shape kinase signaling networks to differentially regulate key pathways during the early phase of Treg versus Th17 induction. Quantitative biochemical analysis revealed that CD4+ T cells integrate receptor signals via SMAD3, which is a mediator of TGF-βR signaling. Treg induction potentiates the formation of the canonical SMAD3/4 trimer to activate a negative feedback loop through kinases PKA and CSK to suppress TCR signaling, phosphatidylinositol metabolism, and mTOR signaling. IL-6R signaling activates STAT3 to bind SMAD3 and block formation of the SMAD3/4 trimer during the early phase of Th17 induction, which leads to elevated TCR and PI3K signaling. These data provide a biochemical mechanism by which CD4+ T cells integrate TCR, TGF-β, and IL-6 signals via generation of alternate SMAD3 complexes that control the development of early signaling networks to potentiate the choice of Treg versus Th17 cell fate., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to evaluate frequency and experience in the use of menstrual cycle monitoring applications (apps) by Brazilian women., Methods: A cross-sectional study was performed through an online survey, announced in social media women's groups, among menstruating Brazilian women aged ≥18 years. The instrument collected sociodemographic, sexual, menstrual and technology usage data of all the women who agreed to participate., Results: Of the 1160 participants, 71.2% used a menstrual cycle monitoring app. The principal motivation for using menstrual cycle apps was to track the menstrual cycle (94.3%), followed by pregnancy avoidance (49.5%). Users rated the apps with a mean 4.4 (standard deviation 0.65) stars out of five. There was a greater likelihood of using an app among women who used behavioural contraceptive methods (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2, 2.7; p  = 0.01), barrier methods (OR 1.6; 95% CI 1.1, 2.5; p  = 0.02) and copper- or silver/copper-bearing intrauterine devices (IUDs) (OR 1.9; 95% CI 1.1, 3.5; p  = 0.04) and a lower likelihood among women who used hormonal contraception (OR 0.5; 95% CI 0.3, 0.8; p  = 0.00) and permanent contraception (OR 0.1; 95% CI 0.0, 0.4; p  = 0.00)., Conclusion: The use of menstrual cycle monitoring apps was quite widespread in the studied group. Satisfaction with app use was considered adequate. The use of menstrual cycle apps was associated with the use of behavioural contraceptive and barrier methods as well as IUDs.

While Treg cells are responsible for self-tolerance and immune homeostasis, pathogenic autoreactive Th17 cells produce pro-inflammatory cytokines that lead to tissue damage associated with autoimmunity, as observed in multiple sclerosis. Therefore, the immunological balance between Th17 and Treg cells may represent a promising option for immune therapy. Statin drugs are used to treat dyslipidemia; however, besides their effects on preventing cardiovascular diseases, statins also have anti-inflammatory effects. Here, we investigated the role of pitavastatin on experimental autoimmune encephalomyelitis (EAE) and the differentiation of Treg and Th17 cells. EAE was induced by immunizing C57BL/6 mice with MOG 35-55 . EAE severity was determined by analyzing the clinical score and inflammatory parameters in the spinal cord. Naive CD4 T cells were cultured under Treg and Th17-skewing conditions in vitro in the presence of pitavastatin. We found that pitavastatin decreased EAE development, which was accompanied by a reduction of all parameters investigated. Pitavastatin also reduced the expression of IBA1 and pSTAT3 (Y705 and S727) in the spinal cords of EAE mice. Interestingly, the reduction of Th17 cell frequency in the draining lymph nodes of EAE mice treated with pitavastatin was followed by an increase of Treg cells. Indeed, pitavastatin directly affects T cell differentiation in vitro by decreasing Th17 and increasing Treg cell differentiation. Mechanistically, pitavastatin effects are dependent on mevalonate synthesis. Thus, our data show the potential anti-inflammatory effect of pitavastatin on the pathogenesis of the experimental neuroinflammation by modulating the Th17/Treg axis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Th17 cell differentiation and pathogenicity depend on metabolic reprogramming inducing shifts toward glycolysis. Here, we show that the pyruvate kinase M2 (PKM2), a glycolytic enzyme required for cancer cell proliferation and tumor progression, is a key factor mediating Th17 cell differentiation and autoimmune inflammation. We found that PKM2 is highly expressed throughout the differentiation of Th17 cells in vitro and during experimental autoimmune encephalomyelitis (EAE) development. Strikingly, PKM2 is not required for the metabolic reprogramming and proliferative capacity of Th17 cells. However, T cell-specific PKM2 deletion impairs Th17 cell differentiation and ameliorates symptoms of EAE by decreasing Th17 cell-mediated inflammation and demyelination. Mechanistically, PKM2 translocates into the nucleus and interacts with STAT3, enhancing its activation and thereby increasing Th17 cell differentiation. Thus, PKM2 acts as a critical nonmetabolic regulator that fine-tunes Th17 cell differentiation and function in autoimmune-mediated inflammation., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2020 Damasceno et al.)

Macrophages are highly plastic cells, responding to diverse environmental stimuli to acquire different functional phenotypes. Signaling through MAPKs has been reported to regulate the differentiation of macrophages, but the role of ERK5 in IL-4-mediated M2 macrophage differentiation is still unclear. Here, we showed that the ERK5 signaling pathway plays a critical role in IL-4-induced M2 macrophage differentiation. Pharmacologic inhibition of MEK5, an upstream activator of ERK5, markedly reduced the expression of classical M2 markers, such as Arg-1, Ym-1, and Fizz-1, as well as the production of M2-related chemokines and cytokines, CCL22, CCL17, and IGF-1 in IL-4-stimulated macrophages. Moreover, pharmacologic inhibition of ERK5 also decreased the expression of several M2 markers induced by IL-4. In accordance, myeloid cell-specific Erk5 depletion (Erk5 ∆mye ), using LysM cre /Erk5 f/f mice, confirmed the involvement of ERK5 in IL-4-induced M2 polarization. Mechanistically, the inhibition of ERK5 did not affect STAT3 or STAT6 phosphorylation, suggesting that ERK5 signaling regulates M2 differentiation in a STAT3 and STAT6-independent manner. However, genetic deficiency or pharmacologic inhibition of the MEK5/ERK5 pathway reduced the expression of c-Myc in IL-4-activated macrophages, which is a critical transcription factor involved in M2 differentiation. Our study thus suggests that the MEK5/ERK5 signaling pathway is crucial in IL-4-induced M2 macrophage differentiation through the induction of c-Myc expression., (©2020 Society for Leukocyte Biology.)

Nucleotide oligomerization domain (NOD)-like receptor-12 (NLRP12) has emerged as a negative regulator of inflammation. It is well described that the Th17 cell population increases in patients with early Rheumatoid Arthritis (RA), which correlates with the disease activity. Here, we investigated the role of NLRP12 in the differentiation of Th17 cells and the development of experimental arthritis, using the antigen-induced arthritis (AIA) murine model. We found that Nlrp12 -/ - mice develop severe arthritis characterized by an exacerbated Th17-mediated inflammatory response with increases in the articular hyperalgesia, knee joint swelling, and neutrophil infiltration. Adoptive transfer of Nlrp12 -/ - cells into WT mice recapitulated the hyperinflammatory response seen in Nlrp12 -/ - mice and the treatment with anti-IL-17A neutralizing antibody abrogated arthritis development in Nlrp12 -/ - mice, suggesting that NLRP12 works as an inhibitor of Th17 cell differentiation. Indeed, Th17 cell differentiation markedly increases in Nlrp12 -/- T cells cultured under the Th17-skewing condition. Mechanistically, we found that NLRP12 negatively regulates IL-6-induced phosphorylation of STAT3 in T cells. Finally, pharmacological inhibition of STAT3 reduced Th17 cell differentiation and abrogated hyperinflammatory arthritis observed in Nlrp12 -/ - mice. Thus, we described a novel role for NLRP12 as a checkpoint inhibitor of Th17 cell differentiation, which controls the severity of experimental arthritis., (© 2020 Federation of American Societies for Experimental Biology.)

The Prenatal Care and Birth Humanization Program (PHPN) establishes a minimum number of procedures to be provided to all pregnant women during prenatal care. This study aimed to analyze the quality of prenatal care in Sergipe based on the PHPN recommendations. This is a cross-sectional study, with a descriptive and analytic approach, using survey data from the Birth in Sergipe research, conducted from June 2015 to April 2016 with 768 puerperae proportionally distributed among all state maternity hospitals (n = 11). Data were collected from face-to-face interviews and patients' prenatal care cards. The results showed a high coverage of prenatal care (99.3%; n =763), but little more than half of these women started their prenatal care within 16 weeks of gestation (57%; n =435), and 74.7% (n = 570) had six or more visits. We noted that 16.6% (n = 127) of pregnant women were at high risk for complications and almost half continued monitoring prenatal care with professional nurses. Around 61.3% were advised about the maternity care service of reference for delivery, and 29.4% sought more than one health service for childbirth. We concluded that there was a high prenatal care coverage in Sergipe, however, with issues concerning its adaptation to the PHPN.

Aldosterone excess aggravates endothelial dysfunction in diabetes and hypertension by promoting the increased generation of reactive oxygen species, inflammation, and insulin resistance. Aldosterone activates the molecular platform inflammasome in immune system cells and contributes to vascular dysfunction induced by the mineralocorticoid hormone. It is unclear as to whether the NLRP3 inflammasome associated with the mineralocorticoid receptor contributes to vascular dysfunction in diabetic conditions. Here, we tested the hypothesis that an excess of aldosterone induces vascular dysfunction in type 2 diabetes, via the activation of mineralocorticoid receptors (MR) and assembly of the NLRP3 inflammasome. Mesenteric resistance arteries from control (db/m) and diabetic (db/db) mice treated with vehicle, spironolactone (MR antagonist) or an NLRP3 selective inhibitor (MCC950) were used to determine whether NLRP3 contributes to diabetes-associated vascular dysfunction. Db/db mice exhibited increased vascular expression/activation of caspase-1 and IL-1β, increased plasma IL-1β levels, active caspase-1 in peritoneal macrophages, and reduced acetylcholine (ACh) vasodilation, compared to db/m mice. Treatment of db/db mice with spironolactone and MCC950 decreased plasma IL-1β and partly restored ACh vasodilation. Spironolactone also reduced active caspase-1-positive macrophages in db/db mice, events that contribute to diabetes-associated vascular changes. These data clearly indicate that MR and NLRP3 activation contribute to diabetes-associated vascular dysfunction and pro-inflammatory phenotype.

Objective: To analyze the maternal characteristics and type of prenatal care associated with peregrination before childbirth among pregnant women in a northeastern Brazilian state., Methods: Quantitative and transversal study, with descriptive and analytical approaches, part of the Nascer em Sergipe research held between June 2015 and April 2016. A total of 768 puerperal women proportionally distributed across all maternities of the state (n = 11) were evaluated. Data were collected in interviews and from prenatal records. The associations between antepartum peregrination and the exposure variables were described in absolute and relative frequencies, crude and adjusted odds ratios and their respective confidence intervals., Results: Antepartum peregrination was reported by 29.4% (n = 226) of the interviewees, most of whom sought care in a single service before the current one (87.6%; n = 198). It should be noted that antepartum peregrination was less frequent among women aged ≥ 20 years old (OR = 0.50; 95%CI 0.34-0.71), with high education level (OR = 0.42; 95%CI 0.31-0.59) and a paid job (adjusted OR = 0.59; 95%CI 0.41-0.82), who had been instructed during prenatal care about the referral maternity for childbirth (adjusted OR = 0.88; 95%CI 0.42-0.92), and who used the private service to receive prenatal (adjusted OR = 0.44; 95%CI 0.18-0.86) or childbirth (adjusted OR = 0.96; 95%CI 0.66-0.98) care. No statistical evidence of associations between gestational characteristics and the occurrence of peregrination was observed., Conclusions: Antepartum peregrination suffers interference from the mother's socioeconomic characteristics, the type of prenatal care received and the source of funding for childbirth.

Endometrial tuberculosis is a rare diagnosis in the postmenopausal period, and it can mimic a carcinoma. The present article describes the case of a 54-year-old female patient with weight loss, abdominal pain, and ascites. An ultrasonography showed endometrial thickening, and a video hysteroscopy revealed a uterine cavity with formations with cotton aspect covering the entire endometrial surface and the tubal ostia. An anatomopathological evaluation diagnosed endometrial tuberculosis. The treatment was with a standardized therapeutic scheme (ethambutol, isoniazid, pyrazinamide and rifampicin), and the patient evolved with clinical improvement and normal uterine cavity at hysteroscopy. Considering the lack of pathognomonic hysteroscopic findings of the disorder, it is important to disclose the images of the case., Competing Interests: The authors have no conflicts of interests to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Apical periodontitis is an inflammatory disorder that results from the host immune response to microbial infection through the dental pulp, leading to alveolar bone destruction. The nod-like receptor 12 (NLRP12) is an atypical intracellular sensor of the NLR family that is involved in the negative regulation of several inflammatory conditions and also osteoclastogenesis. However, the role of NLRP12 in the regulation of immune response and bone loss induced by bacterial infection remains unclear. Here we investigated the development of apical periodontitis in wild-type (WT) and NLRP12 knockout (NLRP12 -/- ) mice by using micro-computed tomography together with histological, immunohistochemical, and molecular analyses. We found that NLRP12 -/- mice are highly susceptible to apical periodontitis induced by bacterial infection, which is associated with an elevated infiltration of neutrophils and macrophages, periapical lesion extension, and alveolar bone destruction. Furthermore, NLRP12 -/- mice showed a high expression of inflammatory cytokines ( Il1b, Il6, and Tnfa) and the osteoclastogenic markers ( Rankl and Acp5) in the periapical tissues. Consistent with this observation, NLRP12 -/- mice showed an increased number of tartrate-resistant acid phosphatase-positive cells lining the apical periodontitis site, which was associated with augmented expression of the osteoclast effector genes, Ctsk and Mmp9. Mechanistically, NLRP12-deficient preosteoclasts showed elevated IκB-α degradation and p65 phosphorylation when stimulated with receptor activator of nuclear factor (NF)-κB ligand (RANKL). Similarly, increased IκB-α degradation was observed in the periapical tissue of NLRP12 -/- mice. Furthermore, our in vitro study showed that preosteoclasts from NLRP12 -/- mice exhibited higher RANKL-induced osteoclastogenesis, which was synergistically amplified by interleukin-1β and tumor necrosis factor α (mimicking an inflammatory periapical milieu). In conclusion, our data show that NLRP12 exhibits a protective role in the periapical bone destruction by attenuating inflammation and osteoclastogenesis through negative regulation of the NF-κB pathway.

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis.

Objective: To evaluate the impact of mode of delivery on breastfeeding incentive practices and on neonatal and maternal short and long-term complications., Methods: A cohort study was conducted between June 2015 and April 2016 with 768 puerperal women from 11 maternities in Sergipe, interviewed in the first 24 hours, 45-60 days and 6-8 months after delivery. Associations between breastfeeding incentive practices, neonatal and maternal, both short-term and late complications, and the exposure variables were evaluated by the relative risk (95%CI) and the Fisher exact test., Results: The C-section newborns had less skin-to-skin contact immediately after delivery (intrapartum C-section: 0.18, 95%CI 0.1-0.31 and elective C-section: 0.36, 95%CI 0.27-0.47) and less breastfeeding within one hour of birth (intrapartum C-section: 0.43, 95%CI 0.29-0.63 and elective C-section: 0.44, 95%CI 0.33-0.59). Newborns from elective C-section were less frequently breastfed in the delivery room 0.42 (95%CI 0.2-0.88) and roomed-in less 0.85 (95%CI 0.77-0.95). Women submitted to intrapartum C-section had greater risk of early complications 1.3 (95%CI 1.04-1.64, p = 0.037) and sexual dysfunction 1.68 (95%CI 1.14-2.48, p = 0.027). The frequency of neonatal complications, urinary incontinence and depression according to the mode of delivery was similar., Conclusions: The C-section was negatively associated with breastfeeding incentive practices; in addition, C-section after labor increased the risk of early maternal complications and sexual dysfunction.

The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms. Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis sativa plant, could be a possible therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti-inflammatory and antipsychotic properties and decreases the acute motor effects of classical antipsychotics. The present study investigated if CBD would attenuate orofacial dyskinesia, oxidative stress and inflammatory changes induced by chronic administration of haloperidol in mice. Furthermore, we verified in vivo and in vitro (in primary microglial culture) whether these effects would be mediated by PPARγ receptors. The results showed that the male Swiss mice treated daily for 21 days with haloperidol develop orofacial dyskinesia. Daily CBD administration before each haloperidol injection prevented this effect. Mice treated with haloperidol showed an increase in microglial activation and inflammatory mediators in the striatum. These changes were also reduced by CBD. On the other hand, the levels of the anti-inflammatory cytokine IL-10 increased in the striatum of animals that received CBD and haloperidol. Regarding oxidative stress, haloperidol induced lipid peroxidation and reduced catalase activity. This latter effect was attenuated by CBD. The combination of CBD and haloperidol also increased PGC-1α mRNA expression, a co-activator of PPARγ receptors. Pretreatment with the PPARγ antagonist, GW9662, blocked the behavioural effect of CBD in our TD model. CBD also prevented LPS-stimulated microglial activation, an effect that was also antagonized by GW9662. In conclusion, our results suggest that CBD could prevent haloperidol-induced orofacial dyskinesia by activating PPARγ receptors and attenuating neuroinflammatory changes in the striatum., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To describe practices and interventions used during labor and childbirth and factors associated with such practices in puerperae in the state of Sergipe., Method: A cross-sectional study with 768 postpartum women from 11 maternity hospitals interviewed 6 hours after delivery, and hospital records review. The associations between best practices and interventions used during labor and delivery with exposure variables were described using simple frequencies, percentages, crude and adjusted odds ratio (ORa) with the confidence interval., Results: Of the women in the study, 10.6% received food and 27.8% moved during labor; non-pharmacological methods for pain relief were performed in 26.1%; a partogram was filled in 39.4% of the charts; and an accompanying person was present in 40.6% of deliveries. Oxytocin, amniotomy and labor analgesia were used in 59.1%, 49.3% and 4.2% of women, respectively. Lithotomy position during childbirth was used in 95.2% of the cases, episiotomy in 43.9% and Kristeller maneuver in 31.7%. The variables most associated with cesarean section were private financing (ORa=4.27, 95CI 2.44-7.47), higher levels of education (ORa=4.54, 95CI 2.56-8.3) and high obstetric risk (ORa=1.9, 95CI 1.31-2.74). Women whose delivery was funded privately were more likely to have an accompanying person present (ORa=2.12, 95CI 1.18-3.79) and to undergo labor analgesia (ORa=4.96, 95CI 1.7-14.5)., Conclusion: Best practices are poorly performed and unnecessary interventions are frequent. The factors most associated with c-section were private funding, greater length of education and high obstetric risk.

Attalea speciosa syn Orbignya phalerata Mart. (babassu) has been used in the treatment of inflammatory and infectious diseases. Aim of the study. To investigate the antimicrobial and immunological activity of babassu mesocarp extract (EE). Material and Methods. The in vitro antimicrobial activity was evaluated by disk diffusion assay and by determination of the minimum inhibitory concentration (MIC) to Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). The flavonoids and phenolic acids content were determined by chromatography. The in vivo assays were performed in Swiss mice submitted to sepsis by cecal ligation and puncture (CLP). The mice received EE subcutaneously (125 or 250 mg/Kg), 6 hours after the CLP. The number of lymphoid cells was quantified and the cytokines production was determined by ELISA after 12 h. Results. EE was effective as antimicrobial to E. faecalis, S. aureus, and MRSA. EE is rich in phenolic acids, a class of compounds with antimicrobial and immunological activity. An increased survival can be observed in those groups, possibly due to a significant inhibition of TNF-α and IL-6. Conclusions. The EE showed specific antimicrobial activity in vitro and an important antiseptic effect in vivo possibly due to the antimicrobial and immunomodulatory activity.

Purpose: To investigate the impact of pregnancy on female sexual function., Methods: An analytical, cross-sectional study was conducted on 181 non-pregnant and 177 pregnant women aged 18 to 45 years. The study included premenopausal, sexually active women with a steady partner and excluded those taking antidepressants or with a diagnosis of depression. Eleven of these women (6.2%) were in the first trimester, 50 (28.2%), in the second trimester and 116 (65.5%), in the third trimester of pregnancy. The evaluation consisted of an interview in which the Female Sexual Function Index (FSFI) was applied. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) software, version 16.0. The nonparametric Mann-Whitney test was used to compare the mean FSFI values of pregnant and non-pregnant women., Results: Sexual dysfunction was 40.4% among pregnant women and 23.3% among non-pregnant women, with a significant difference between the scores of the studied groups (p=0.01). The difference in the mean global FSFI values between the groups was also significant (p<0.0001). There were significant differences between pregnant and non-pregnant women regarding desire (p<0.0001), excitation (p=0.003), lubrication (p=0.02), orgasm (p=0.005) and satisfaction (p=0.03). The same was not observed regarding pain., Conclusion: We conclude that pregnancy negatively influences female sexual function, particularly the desire and excitement domains, revealing the importance of addressing the issue by professionals dealing with pregnant women.

Citronellol (CT) is a monoterpenoid alcohol present in the essential oil of many medicinal plants, such as Cymbopogon citratus. We evaluated the antinociceptive effects of CT on orofacial nociception in mice and investigated the central pathway involved in the effect. Male Swiss mice were pretreated with CT (25, 50 and 100 mg/kg, i.p.), morphine (5 mg/kg, i.p.) or vehicle (saline + tween 80 0.2%). Thirty minutes after the treatment, we injected formalin (20 μl, 2%), capsaicin (20 μl, 2.5 μg) or glutamate (40 μl, 25 μM) into the right limb. For the action in the CNS, ninety minutes after the treatment, the animals were perfused, the brains collected, crioprotected, cut in a criostate and submitted in an immunofluorescence protocol for Fos protein. CT produced significant (p < 0.01) antinociceptive effect, in all doses, in the formalin, capsaicin and glutamate tests. The immunofluorescence showed that the CT activated significantly (p < 0.05) the olfactory bulb, the piriform cortex, the retrosplenial cortex and the periaqueductal grey of the CNS. Together, our results provide first-time evidence that this monoterpene attenuates orofacial pain at least, in part, through an activation of CNS areas, mainly retrosplenial cortex and periaqueductal grey., (© 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.)

Purpose: To determine the main contraceptive methods adopted by users of the public and private health sectors in the city of Aracaju (SE), Brazil, with a secondary focus on orientations for their use and reasons for interruption., Methods: A cross-sectional study was conducted on 210 women, 110 from the public service and 100 from the private sector. The data were collected by applying a questionnaire to sexually active patients who agreed to sign a consent form. The software Statistical Package for Social Sciences (SPSS) version 15.0 was used for statistical analysis, with the x² test for categorical variables and the Student's t-test for independent samples., Results: The overall prevalence of contraceptive use in this study was 83.3%. The main methods used in the public and private sectors, were the hormonal (41 and 24%, p=0.008) and permanent (20 and 26%, p=0.1) ones, respectively. The rate of condom use was 17.3% in the public sector and 12% in the private sector, with no significant difference (p=0.12). Medical orientation about the correct use of the method chosen and/or indicated was provided to 37.3% of users from the public sector and to 48% of users from the private sector. Discontinuation of the use of contraceptive methods was 14.5% in the public sector and 12.0% in the private sector, mainly because of side effects and the desire to become pregnant., Conclusions: The main contraceptive methods adopted by users of the public and private sectors were hormonal contraception and permanent contraception. It is important to highlights the low frequency of use of male condoms in the two groups studied.

Purpose: To identify if there is a difference in the prevalence of sexual dysfunction and in the sexual domain scores between a group of women attended at a public service and a group attended at a private service, and to investigate if there is an association between sexual dysfunction, family income and educational status., Methods: Transversal study including 201 sexually active women aged from 18 to 45 years, 90 of them from a public service and 111 from private services. We evaluated age, marital status, use of hormonal contraception, income and educational status, and all women were submitted to the Female Sexual Function Index (FSFI), an instrument for the evaluation of their sexuality. The Statistical Package for Social Sciences, version 15.0, was used for statistical analysis. The chi(2) test was applied for categorical variables and the Student's t-test to independent samples., Results: There was no significant difference regarding the prevalence of sexual dysfunction between groups (public versus private) (20 and 23.4%, p=0.5), or concerning the domain scores, desire (3.9+/-1.3 and 3.8+/-1.0, p=0.6), sexual arousal (4.5+/-0.8 and 4.4+/-0.9, p=0.5), lubrication (5.2+/-1.2 and 5.0+/-0.9, p=0.1), orgasm (5.0+/-1.2 and 4.9+/-1.1, p=0.5), satisfaction (5.2+/-1.2 and 5.1+/-1.0, p=0.9), and pain (5.3+/-1.1 and 5.2+/-1.0, p=0.8). Sexual dysfunction was detected in 28% of the women with income between two and four minimum wages, in 17.5% of those with an income of five wages or more, and in 14.3% among those with an income of one wage or less (p=0,1). The dysfunction occurred in 30.2% of women with elementary education, in 24.2% of those with high school education and in 13.4% of those with higher education (p=0.09)., Conclusions: There was no significant difference in the prevalence of sexual dysfunction or in the sexual domain scores between groups, nor was there an association with income or education status.

The correlation of erythropoietin (EPO) receptor levels with angiogenesis and progression in some cancers has suggested that EPO could acts directly as an angiogenic factor. The purpose of this study was to assess the effect of treatment with human recombinant erythropoietic (rHuEPO) agents in cancer patients with chemotherapy-induced anaemia on endoglin and vascular endothelial growth factor (VEGF) circulating levels as a possible marker of angiogenesis. Endoglin and VEGF were measured in serum samples from 25 cancer patients with chemotherapy-induced anemia before and after 3-4 weeks of treatment with rHuEPO. A group of 28 healthy voluntaries was used as control. VEGF serum levels were significantly higher in cancer patients than in controls. For endoglin, higher levels were observed without reaching statistical significance. No statistically significant differences in endoglin and VEGF serum levels were found between samples obtained before and after treatment with rHuEPO agents. In conclusion, our result do not support that rHuEpo treatment in anaemic cancer patients induce angiogenesis.