Macrophage migration inhibitory factor favors Neospora caninum infection in mice.

Neospora caninum is a protozoan parasite with worldwide incidence, acting as a major cause of reproductive failures in ruminants and neuromuscular symptoms in dogs. Macrophage Migration Inhibitory Factor (MIF) is produced by several cell types and exhibits a central role in immune responses against intracellular pathogens. The present study aimed to comprehend the role of MIF in the relationship between N. caninum and its host. We used in vivo, in vitro and ex vivo experiments in a model of infection based on genetically deficient mice to analyze the infection kinetics and inflammatory markers. MIF production was measured in response to N. caninum during the acute and chronic phases of the infection. While Mif-/- mice survived lethal doses of NcLiv tachyzoites, sublethal infections in these mice showed that parasite burden was controlled in target tissues, alongside with reduced inflammatory infiltrates detected in lung and brain sections. TNF was increased at the initial site of the infection in genetically deficient mice and the MIF-dependent reduction was confirmed in vitro with macrophages and ex vivo with primed spleen cells. In sum, MIF negatively regulated host immunity against N. caninum, favoring disease progression.

Consumption of ultra-processed foods and mental health of pregnant women from the South of Brazil.

The objective of this study is to evaluate the association between the consumption of ultra-processed foods (UPF) and the mental health of pregnant women from the South of Brazil. This is a cross-sectional study carried out in Criciúma, Brazil, through face-to-face interviews, from April to December 2022. Pregnant women aged 18 or older who underwent prenatal care in the forty-eight basic health care units of the municipality and who were in their third trimester of pregnancy were included. High consumption of UPF was considered as six or more items or subgroups of UPF consumed on the day before the interview, using the Nova-UPF screener. The mental health variables were depressive symptoms, stress, sadness and anxiety. Crude and adjusted analyses were conducted using the Fisher's exact test and the Poisson regression with robust variance. In total, 428 pregnant women were studied; most of them were aged between 20 and 25 years and were white. Pregnant women who presented high consumption of UPF were 1·42-fold (95 % CI 1·06, 1·92) more likely to experience anxiety and presented a prevalence 56 % (95 % CI 1·18, 2·07) higher of stress when compared with those who did not present high consumption of UPF. The prevalence of depressive symptoms and feelings of sadness was 1·31-fold (95 % CI 1·08, 1·60) and 3·41-fold (95 % CI 1·77, 6·58) higher among those with high consumption of UPF, respectively. The results suggest that diet quality is associated with the mental health of pregnant women. Promoting joint actions focused on food and nutritional education, and mental health, for pregnant women, is necessary.

Child maltreatment associates with violent victimization in young adulthood: a Brazilian birth cohort study.

BACKGROUND: Maltreatment in childhood may leave people vulnerable to further experiences of violence and more severe effects of stress later in life. Longitudinal studies of risk for violent victimisation after maltreatment are lacking in low- and middle-income countries. The objective of this study was to quantify the risk for violent victimization in the family and community in young adulthood following experiences of childhood maltreatment (experiences of physical, emotional and sexual abuse and neglect) up to age 15 years in an urban Brazilian population. METHODS: 3246 participants in a prospective, population-based birth cohort study in Pelotas, Rio Grande do Sul, Brazil, were assessed at birth, 15 and 22 years. Sociodemographic factors were reported by mothers at birth and adolescents at age 15 years. Maltreatment and violent victimisation were self-reported in confidential questionnaires at 15 and 22, respectively. Multinomial logistic regression analyses estimated the association between having experienced any maltreatment and later experiences of family and community violence in young adulthood (no adult violence, violence only in the family context, only in the community, or both violence in the family and community), adjusting for sociodemographic factors. RESULTS: 39% of females and 27% of males reported any maltreatment up to age 15 years. At 22 years, rates of past year violence in the family or community were 17.6% for females and 20.2% for males. Maltreatment was strongly associated with community violence (Females: OR = 2.96, CI = 1.83-4.80; Males: OR = 2.01, 95%CI = 1.01-4.00) and its co-occurrence with family violence (Females: OR = 2.33, 95%CI = 1.34-4.04; Males: OR = 3.20, 95%CI = 1.82-5.65) in young adulthood, after adjustment for background sociodemographic factors. CONCLUSION: Childhood maltreatment is an important risk factor for later violent victimisation in both the family and community context. The effects of repeated trauma through the life-course needs research and clinical attention.

Th22 cytokines and yellow fever: Possible implications for the immunopathogenesis of human liver infection.

Yellow fever (YF) is an infectious disease considered a public health problem in tropical and subtropical areas. YF has many pathophysiological events that are correlated with the host immune response. In this study, the in situ Th22 cytokine profile was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died of the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical (IHC) analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of interleukin (IL)-22, IL-13, tumour necrosis factor-alpha, and FGF basic (FGF b) in YFV-positive cases than that in flavivirus-negative controls. These results indicate that the response of Th22 cytokines emerges as an alternative for a better understanding of adaptive immunity in the hepatic parenchyma, highlighting the role of cytokines in the repair and suppressive responses in the immunopathogenesis of YFV infection.

Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides.

Mycobacteria are a wide group of organisms that includes strict pathogens, such as Mycobacterium tuberculosis, as well as environmental species known as nontuberculous mycobacteria (NTM), some of which-namely Mycobacterium avium-are important opportunistic pathogens. In addition to a distinctive cell envelope mediating critical interactions with the host immune system and largely responsible for their formidable resistance to antimicrobials, mycobacteria synthesize rare intracellular polymethylated polysaccharides implicated in the modulation of fatty acid metabolism, thus critical players in cell envelope assembly. These are the 6-O-methylglucose lipopolysaccharides (MGLP) ubiquitously detected across the Mycobacterium genus, and the 3-O-methylmannose polysaccharides (MMP) identified only in NTM. The polymethylated nature of these polysaccharides renders the intervening methyltransferases essential for their optimal function. Although the knowledge of MGLP biogenesis is greater than that of MMP biosynthesis, the methyltransferases of both pathways remain uncharacterized. Here, we report the identification and characterization of a unique S-adenosyl-l-methionine-dependent sugar 1-O-methyltransferase (MeT1) from Mycobacterium hassiacum that specifically blocks the 1-OH position of 3,3'-di-O-methyl-4α-mannobiose, a probable early precursor of MMP, which we chemically synthesized. The high-resolution 3D structure of MeT1 in complex with its exhausted cofactor, S-adenosyl-l-homocysteine, together with mutagenesis studies and molecular docking simulations, unveiled the enzyme's reaction mechanism. The functional and structural properties of this unique sugar methyltransferase further our knowledge of MMP biosynthesis and provide important tools to dissect the role of MMP in NTM physiology and resilience.

"Inequalities in access to medicines for diabetes and hypertension across the capitals in different regions of Brazil: a population-based study".

BACKGROUND: To guarantee prevention and adequate treatment, as required for the population to have access to health services and technologies, including medicines. The purpose of this study is to analyse the economic and regional inequalities in access to medicines for diabetes and hypertension among the adult population in Brazil. METHODS: This was a cross-sectional study with adults aged 18 and over from the VIGITEL study conducted in 2019 in all Brazilian regions. Non-access to antidiabetic and antihypertensive drugs was assessed according to formal education and housing macro-region. The slope index of inequality (SII) was used to analyse absolute inequalities. RESULTS: The total number of individuals interviewed was 52,443. Approximately 10.0% of the people with diabetes and/or hypertension reported not having access to drug treatment. The major means for having access to antihypertensive drugs, in all regions, was private pharmacies; for antidiabetics, in the North region, people had greater access through private pharmacies, while in the Northeast, Southeast and South, they had greater access through the public sector. Inequalities were found in the lack of access to medicines according to the region of residence, especially in the North region. CONCLUSION: The lack of access to medicines showed regional disparities, particularly in the most economically vulnerable regions.

Role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high-grade serous ovarian carcinoma.

INTRODUCTION: We analyzed the role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high-grade serous ovarian carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin-paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC-IVB high-grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin-paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression-free and overall survivals were analyzed using the Kaplan-Meier method. RESULTS: Totally, 132 patients with FIGO IIIC-IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4-70.1) and 61.2 (21.4-101.0) months (p = 0.934); the corresponding disease-free survival was 8.1 (6.2-10.1) and 8.3 (5.1-11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence. CONCLUSIONS: Systematic lymphadenectomy after six NACT cycles may have no influence on survival.

Seasonal dynamics of Amblyomma sculptum in two areas of the Cerrado biome midwestern Brazil, where human cases of rickettsiosis have been reported.

Amblyomma sculptum is a common human-biting tick in Brazil, where it plays an important role as a vector of Rickettsia rickettsii, the agent of the Brazilian spotted fever. Herein, we studied the seasonal dynamics of A. sculptum in an urban area of the Cerrado biome in midwestern Brazil, where human rickettsiosis is endemic. Ticks were collected in two sites located within the campus of Federal University of Goiás. The collections were done by dragging, flagging and visual search. In total, 117,685 ticks were collected, including 100,627 Amblyomma spp. larvae, 10,055 nymphs and 6977 adults of A. sculptum, and one nymph and 25 adults of Amblyomma dubitatum. The highest peak of larvae occurred in June 2018 and in July 2019, whereas nymphs peaked in July 2018 and September 2019. Adults reached their highest numbers in March 2018 and November 2019. These data suggest that A. sculptum develops one generation per year in this urban area of the Cerrado biome in midwestern Brazil. Interestingly, the peak of nymphs occurred during the same period of all confirmed cases of rickettsiosis in Goiás, suggesting a possible relationship between the seasonal dynamics of this tick stage and rickettsiosis transmission in this state.

Trait specific modulatory effects of caffeine exposure on compulsive-like behaviors in a spontaneous mouse model of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by recurring intrusive thoughts and repetitive compulsive behaviors, ultimately interfering with their quality of life. The complex heterogeneity of symptom dimensions across OCD patient subgroups impedes diagnosis and treatment. The core and comorbid symptomologies of OCD are thought to be modulated by common environmental exposures such as consumption of the psychostimulant caffeine. The effect of caffeine on the expression of obsessions and compulsions are unexplored. The current study utilized mouse strains (HA) with a spontaneous, predictable, and stable compulsive-like phenotype that have face, predictive, and construct validity for OCD. We demonstrate that an acute high dose (25 mg/kg) of caffeine decreased compulsive-like nest-building behavior in the HA strains in the first hour after injection. However, nest-building scores increased in hours 3, 4, and 5 after administration finally decreasing over a 24 h period. In contrast, a high dose of chronic caffeine (25 mg/kg/d) increased nest-building behavior. Interestingly for compulsive-like digging behavior, acute exposure to a high dose of caffeine decreased the number of marbles buried, while chronic exposure had little effect. An acute high dose of caffeine decreased anxiety-like and motor activity in open field behaviors whereas chronic caffeine administration did not have any overall effect on open field activity. The results, therefore, suggest a complex role of caffeine on compulsive-like, anxiety-like, and locomotor behaviors that is dependent on the duration of exposure.

Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood.

BACKGROUND: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children. OBJECTIVE: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts. METHODS: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex. RESULTS: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (ß -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (ß 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (ß 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations. CONCLUSIONS: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

Psychostimulant Use for Neuroenhancement (Smart Drugs) among College Students in Brazil.

Background: College students are susceptible to using cognitive enhancement drugs, also known as smart drugs. Objectives: estimate the prevalence of smart drug use and investigate the factors related to access and use among undergraduate students. Methods: cross-sectional study performed among all students who entered the university in 2017 using an anonymous, self-administered questionnaire. Smart drug usage was defined as taking methylphenidate, modafinil or piracetam at any point in life and in the preceding 12 months. We characterized the means of obtaining smart drugs, reasons for using and students' residential situation. We asked students who did not use any medication if they were interested in taking it and the reasons for not using. Results: Out of 1865 respondents, 4.2% had used smart drugs in the last 12 months, and the prevalence among law students reached 14.3%. The most commonly used smart drug was methylphenidate. Among the students who did not present ADD diagnosis, the drug was obtained mostly through a friend. More than 300 students reported a desire to use some smart drug, but they did not, mainly due to the fear of side effects. Conclusions: The current study has found a variety of frequency of smart drug use among college students and has also showed that many students are willing to take some kind of cognitive enhancement drug. Therefore, it is important to discuss this issue from a public health perspective.

IKKß Kinase Promotes Stemness, Migration, and Invasion in KRAS-Driven Lung Adenocarcinoma Cells.

KRAS oncogenic mutations are widespread in lung cancer and, because direct targeting of KRAS has proven to be challenging, KRAS-driven cancers lack effective therapies. One alternative strategy for developing KRAS targeted therapies is to identify downstream targets involved in promoting important malignant features, such as the acquisition of a cancer stem-like and metastatic phenotype. Based on previous studies showing that KRAS activates nuclear factor kappa-B (NF-κB) through inhibitor of nuclear factor kappa-B kinase ß (IKKß) to promote lung tumourigenesis, we hypothesized that inhibition of IKKß would reduce stemness, migration and invasion of KRAS-mutant human lung cancer cells. We show that KRAS-driven lung tumoursphere-derived cells exhibit stemness features and increased IKKß kinase activity. IKKß targeting by different approaches reduces the expression of stemness-associated genes, tumoursphere formation, and self-renewal, and preferentially impairs the proliferation of KRAS-driven lung tumoursphere-derived cells. Moreover, we show that IKKß targeting reduces tumour cell migration and invasion, potentially by regulating both expression and activity of matrix metalloproteinase 2 (MMP2). In conclusion, our results indicate that IKKß is an important mediator of KRAS-induced stemness and invasive features in lung cancer, and, therefore, might constitute a promising strategy to lower recurrence rates, reduce metastatic dissemination, and improve survival of lung cancer patients with KRAS-driven disease.

Toll-Like Receptor 3-TRIF Pathway Activation by Neospora caninum RNA Enhances Infection Control in Mice.

Neospora caninum is a protozoan parasite closely related to Toxoplasma gondii and has been studied for causing neuromuscular disease in dogs and abortions in cattle. It is recognized as one of the main transmissible causes of reproductive failure in cattle and consequent economic losses to the sector. In that sense, this study aimed to evaluate the role of Toll-like receptor 3 (TLR3)-TRIF-dependent resistance against N. caninum infection in mice. We observed that TLR3-/- and TRIF-/- mice presented higher parasite burdens, increased inflammatory lesions, and reduced production of interleukin 12p40 (IL-12p40), tumor necrosis factor (TNF), gamma interferon (IFN-γ), and nitric oxide (NO). Unlike those of T. gondii, N. caninum tachyzoites and RNA recruited TLR3 to the parasitophorous vacuole (PV) and translocated interferon response factor 3 (IRF3) to the nucleus. We also observed that N. caninum upregulated the expression of TRIF in murine macrophages, which in turn upregulated IFN-α and IFN-ß in the presence of the parasite. Furthermore, TRIF-/- infected macrophages produced lower levels of IL-12p40, while exogenous IFN-α replacement was able to completely restore the production of this key cytokine. Our results show that the TLR3-TRIF signaling pathway enhances resistance against N. caninum infection in mice, since it improves Th1 immune responses that result in controlled parasitism and reduced tissue inflammation, which are hallmarks of the disease.

Synthesis of d-desthiobiotin-AI-2 as a novel chemical probe for autoinducer-2 quorum sensing receptors.

In processes regulated by quorum sensing (QS) bacteria respond to the concentration of autoinducers in the environment to engage in group behaviours. Autoinducer-2 (AI-2) is unique as it can foster interspecies communication. Currently, two AI-2 receptors are known, LuxP and LsrB, but bacteria lacking these receptors can also respond to AI-2. In this work, we present an efficient and reproducible synthesis of a novel chemical probe, d-desthiobiotin-AI-2. This probe binds both LuxP and LsrB receptors from different species of bacteria. Thus, this probe is able to bind receptors that recognise the two known biologically active forms of AI-2, presenting the plasticity essential for the identification of novel unknown AI-2 receptors. Moreover, a protocol to pull down receptors bound to d-desthiobiotin-AI-2 with anti-biotin antibodies has also been established. Altogether, this work highlights the potential of conjugating chemical signals to biotinylated derivatives to identify and tag signal receptors involved in quorum sensing or other chemical signalling processes.

The use of folic acid, iron salts and other vitamins by pregnant women in the 2015 Pelotas birth cohort: is there socioeconomic inequality?

BACKGROUND: Many low- and middle-income countries recommend micronutrient supplements for pregnant women to improve their nutritional status, prevent possible deficiencies and avoid fetal healgth consequences. This study evaluated the influence of socioeconomic status on the use of folic acid, iron salts and other vitamins and minerals among pregnant women in the 2015 Pelotas Birth Cohort. METHODS: This population-based birth cohort study was carried out with 4270 women. Participants were interviewed during pregnancy and at the maternity hospital about the antenatal period; including the use of iron salts, vitamins and other minerals. Descriptive analyses were performed to characterize the sample. The analyses were adjusted according to socioeconomic variables (maternal education, ethnicity, household income). RESULTS: The overall prevalence of the use of folic acid, iron salts or other vitamins and minerals was 91.0% (95% CI: 90.1-91.8). Specifically, 70.9% (95% CI: 69.5-72.3) used folic acid, 72.9% (95% CI: 71.5-74.3) used iron compounds, and 31.8% (95% CI: 30.3-33.2) used other vitamins or minerals. In the adjusted analysis, the use of iron salts was associated with nonwhite mothers, with ≤4 years of education and whose family income was less than or equal to the monthly minimum wage. The use of folic acid and other vitamins and minerals was associated with white mothers who were more highly educated and had a higher family income. CONCLUSION: Although folic acid and other vitamins and minerals were more frequently used in white, richer and more educated mothers, which indicates inequality, iron supplements were more frequently used in the poorer, less educated nonwhite mothers, suggesting the opposite association for this supplement.

Management of Para-aortic Lymph Node Disease in Patients With Cervical Cancer: What Is the Best Approach?

Cervical cancer remains a prevalent and deadly disease in low-income countries, especially among young and otherwise healthy women. Multimodality treatment has led to a significant improvement in outcomes for patients with locally advanced disease, and this is mainly because of the incorporation of platinum-based chemoradiotherapy in current treatment protocols. However, locally advanced tumors are associated with a greater risk for para-aortic lymph node (PALN) involvement, which is an important adverse prognostic factor. Most staging techniques have low accuracy for detection of disease in this area, which could lead to understaging and undertreatment. Meanwhile, patients with PALN disease are underrepresented in trials addressing the treatment of advanced cervical cancer and a few studies have been directed at this population. The aim of this review is to analyze the current data regarding staging and treatment of cervical cancer with PALN disease to determine which strategy is best when managing these patients.

Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy.

BACKGROUND: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. OBJECTIVES: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. METHODS: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. RESULTS: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). CONCLUSION: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.

Wheezing in tobacco farm workers in southern Brazil.

BACKGROUND: Tobacco workers are exposed to several respiratory occupational sensitizers. METHODS: A representative cross-sectional study was carried out on 2469 tobacco family farming growers. Gender-stratified multivariate analyses evaluated the association between wheezing and socio-demographic, behavioral, and occupational variables. RESULTS: Wheezing prevalence was 11.0% with no difference between genders. Among men, age, smoking, strenuous work, pesticide use, contact with vegetable dust and dried tobacco dust, lifting sticks with tobacco leaves to the curing barns, and green tobacco sickness (GTS) were risk factors for wheezing. Among women, family history of asthma, tying hands of tobacco, strenuous work, contact with chemical disinfectants, and GTS were positively associated with wheezing. Harvesting lower tobacco leaves was a protective factor for the outcome in both genders. CONCLUSIONS: Pesticides, dusts exposure, and GTS were risk factors for wheezing. The synergic effect of these factors needs to be better evaluated to improve prevention.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness.

OBJECTIVE: Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. METHODS: Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. RESULTS: Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. CONCLUSION: Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.

Antiepileptic drug prophylaxis in primary brain tumor patients: is current practice in agreement to the consensus?

The role of antiepileptic drugs (AED) prophylaxis in primary brain tumor (PBT) seizure-naïve patients remains unclear. Additionally, AED are associated with severe side effects, negative impact on cognition and drug interactions. Little is known about current practice regarding prophylactic AED use in PBT. We investigated its use in a tertiary care cancer center. We reviewed medical records of 260 patients registered in our center between 2008 and 2012, focusing on prophylactic AED use. A descriptive analysis was performed with SPSS IBM version 20.0. Median age was 44.5 years (11-83). Most patients had ECOG PS ≤1 (76.4 %). Among 141 seizure-naïve patients, 70.2 % received an AED as primary prophylaxis (PP). Most commonly used drugs as PP were phenytoin (85.9 %), carbamazepine (6.1 %) and phenobarbital (5.1 %). In only 14 patients (14.1 %) AEDs were eventually discontinued, in a median time of 5.9 months (1.1-76.8 m). AED were used as PP in 60 % of low-grade gliomas, 73.3 % of anaplastic gliomas and 93.9 % of glioblastoma patients. Twenty-seven patients (27.3 %) on PP presented seizures, generally associated with tumor progression. Of the 42 seizure-naïve patients not receiving AED prophylaxis, only two presented seizures, which occurred during or within the first week post-radiotherapy. In this cross-sectional study, prophylactic AED use in PBT was extremely high. Postoperatively, AED were discontinued in a minority of patients, mostly after a prolonged period. Current prophylactic AED use patterns in PBT are not in accordance with established guidelines.