Clusters of high-risk, low-risk, and temporal trends of breast and cervical cancer-related mortality in São Paulo, Brazil, during 2000-2016.

PURPOSE: Studying breast and cervical cancers in space and time and verifying divergences of different territorially established socioeconomic profiles. METHODS: Ecological study using spatial scanning (with socioeconomic characterization), space-time, and spatial variation of temporal trends, in order to identify significant clusters of high- and low-risk or temporal trends, of deaths from breast cancer and cervical cancer, in the city of São Paulo, Brazil, during 2000-2016. RESULTS: High-risk spatial clusters were identified in the central areas, and low-risk clusters were identified in the peripheral areas, which were associated with better and worse socioeconomic conditions, respectively. As for cervical cancer, the pattern was the opposite. High-risk space-time clusters occurred in the early years of the study, whereas low-risk clusters occurred in the most recent years. For breast cancer, the central areas showed a temporal trend of decreasing mortality and the peripheral areas showed an increasing trend. While for cervical cancer, in general, the temporal trend was for the identified clusters to fall. CONCLUSIONS: It is expected that this study will provide insights for the formulation of public policies to implement prevention and control measures, in order to reduce mortality and inequalities related to breast and cervical cancers.

EMMPRIN is an emerging protein capable of regulating cancer hallmarks.

EMMPRIN, also known as Basigin or CD147, is a transmembrane glycoprotein member of the immunoglobulin superfamily. It is expressed basally in cells that regulate physiological processes of the cardiovascular, nervous, and immune systems. However, EMMPRIN is also capable of interacting with different proteins, like VEGFR, SMAD4, Integrin, MCT, CyPA, GLUT1, CAIV, Annexin II, Cav-1, CAML, etc., and regulating signaling pathways that stimulate the cell processes of proliferation, apoptosis, metabolism, adhesion, invasion, migration, metastasis, tumor immune response, and angiogenesis processes, which favors the development of different types of cancer. EMMPRIN is the first protein reported that favors cancer development due to its ability to interact with extracellular, intracellular, and membrane proteins. In conclusion, EMMPRIN regulates several proteins associated with the development of tumor processes. Therefore, blocking the expression of EMMPRIN can be a therapeutic target, and the analysis of its expression can be used as an important biomarker in cancer.

Long non-coding RNAs as new players in cervical carcinogenesis: an update.

Cervical cancer (CC) is the fourth most common cancer in women worldwide. Therefore, it is very important to understand cervical carcinogenesis, as well as the molecular mechanisms and signaling pathways involved in this process, in order to develop new strategies that contribute to diagnosis, prognosis and treatment of cervical cancer. Infection by high risk-human papillomavirus (HR-HPV) is a key event in cervical carcinogenesis, as well as, other factors, such as sociodemographics, lifestyle, sexual behavior, etc. In recent years, it has been shown that long non-coding RNA (lncRNA) are involved in CC and can be classified into tumor promoters or suppressors. Currently, several studies have analyzed the molecular mechanisms of some lncRNA in CC that might be acting, such as 1) competing endogenous RNAs (ceRNAs), 2) activators of signaling pathways, and 3) transcriptional regulators of genes. In this review, we summarized the more recent information on lncRNA and their role in the development of CC.

Enteropatía asociada a olmesartán: atención a un fenómeno iatrogénico emergente / Olmesartan-associated enteropathy: attention to an emerging iatrogenic phenomenon

El olmesartán es un antagonista del receptor tipo 1 de la angiotensina II utilizado habitualmente en el tratamiento de pacientes con hipertensión arterial. Recientemente se han descrito varios casos de enteropatía sprue-like asociados al uso de este fármaco, con afectación clínica importante y total remisión tras la retirada del mismo. Se presenta el caso de un varón de 64 años, con antecedentes de hipertensión arterial en tratamiento con olmesartan-amlodipino con clínica de diarrea y pérdida de peso severas, atrofia vellositaria en biopsia duodenal sin criterios de enfermedad celiaca y remisión completa del cuadro tras la supresión del olmesartán. Basado en los hallazgos del caso clínico presentado, se revisan las manifestaciones clínicas e histopatológicas así como el curso evolutivo de una posible causa de enteropatía farmacológica recientemente descrita (AU)

Olmesartan is an angiotensin II type 1 receptor blocker commonly used in the treatment of hypertension. Several cases of sprue-like enteropathy associated with the use of this drug have been described which, even with important signs and limitations for the patient, present a full recovery after discontinuing the use of olmesartan. The case of a 64 year-old patient is presented, diagnosed with hypertension, under treatment with olmesartan- amlodipine, with chronic diarrhoea and villous atrophy on intestinal biopsies without diagnostic criteria for celiac disease and with complete remission after suspending discontinuing the use of olmesartan. Based on the clinical features presented by the case reported, the clinical and anatomopathological findings are described as well as the evolution of drug-induced enteropathy (AU)

Extracellular matrix in epitheliochorial, endotheliochorial and haemochorial placentation and its potential application for regenerative medicine.

A placenta is defined as structural approximation of maternal and foetal tissues to perform physiological exchange. Associated processes of differentiation and the establishment of its cells take place within the extracellular matrix (ECM) that provides a rich environment of collagens, fibronectins, cytokines and other components. Placental ECM is promising for tissue regeneration purposes, because it has immune tolerance capacities that may cause only minimal rejections of transplants with immunological differences between donor and recipient. However, specific characteristics of ECM during evolution of the structurally very diverse mammalian placenta are not yet revealed. We here address the major aspects of placental types, that is non-invasive (epitheliochorial), medium (endotheliochorial)-to-high (haemochorial) invasive nature of the interhemal barrier between the foetal and maternal blood system as well as their main components of ECM with special reference to species that are commonly used as animal models for human placentation and in the potential applications for regenerative medicine.

Brain-derived neurotrophic factor increase during treatment in severe mental illness inpatients.

Meta-analytical evidence suggests that brain-derived neurotrophic factor (BDNF) is altered in various psychiatric disorders. However, meta-analyses may be hampered by the heterogeneity of BDNF assays, lack of BDNF standard values and heterogeneity among the populations included in the studies. To address these issues, our study aimed to test, in a 'true-to-life' setting, the hypothesis that the serum BDNF level is nonspecifically reduced in acute severe mental illness (SMI) patients and increases during inpatient treatment. Consecutive samples of 236 inpatients with SMI and 100 healthy controls were recruited. SMI includes schizophrenia and severe mood disorders, and is characterized in the sample by the presence of at least 2 years of psychiatric treatment and disability. Generalized estimating equations were used to analyze BDNF serum levels at admission and upon discharge controlled by confounding factors. BDNF levels increased significantly between admission and discharge in SMI patients. BDNF levels showed significant reductions compared with controls both at admission and upon discharge. In addition, BDNF levels showed no difference among SMI patient diagnostic subgroups (unipolar depression, bipolar depression, schizophrenia and manic episode). The increase but non-restoration of BDNF levels, even with the general acute improvement of clinical scores, may reflect the progression of the disorder characteristically seen in these patients. BDNF levels could be considered as a marker for the presence of a nonspecific psychiatric disorder and possibly a transdiagnostic and nonspecific marker of disease activity.

Association Between Dyspnea and Severity of Liver Disease in Patients in the Pre-transplantation Period-A Pilot Study.

BACKGROUND: Liver transplantation is indicated at the end stage of chronic liver failure, and severity of disease will determine the precocity of this happening. At this stage, the presence of chronic dyspnea is one of several manifestations of progression of the disease, which leads the patient to inactivity. A rehabilitation program can positively influence the evolution of liver transplant recipients. The objective of this study was to establish an association between the perception of dyspnea and the severity of liver disease in patients at a single center of a Brazilian liver pre-transplantation clinic. METHODS: Measurements were performed at a liver pre-transplantation clinic. The severity of liver disease was assessed with the use of the Model for End-Stage Liver Disease (MELD) score, and dyspnea was assessed with the use of a modified Medical Research Council scale of dyspnea (mMRC). RESULTS: Men had a higher prevalence of viral hepatitis. Dyspnea was reported only during intense exercise. Duration of disease and MELD score showed medians of 49 months and 20, respectively. CONCLUSIONS: We found no correlation between mMRC and the MELD score. In addition, no correlation was found between duration of disease and MELD score or mMRC.

BDNF Val66Met polymorphism and peripheral protein levels in pediatric bipolar disorder and attention-deficit/hyperactivity disorder.

OBJECTIVE: Frontiers between pediatric bipolar disorder (PBD) and attention-deficit/hyperactivity disorder (ADHD) are not well defined. Few studies have addressed potentially different neurobiological factors between the two disorders. Brain-derived neurotrophic factor (BDNF) has been increasingly recognized for its etiologic and prognostic role in adult bipolar disorder (BD) studies. This study aimed to examine the BDNF gene polymorphism and potential alterations in BDNF serum levels in the pediatric ADHD patients with or without comorbid BD illness. METHOD: We assessed the non-synonymous single-nucleotide polymorphism in the BDNF gene (rs6265/Val66Met) and its serum levels in children and adolescents with BD comorbid with ADHD (BD + ADHD) and ADHD alone. Children and adolescents were assessed for psychiatric diagnoses using the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL). RESULTS: Using Analysis of covariance (ancova) we detected a significant group effect (patients with BD + ADHD had higher serum levels than those with ADHD - F80,3 = 8.73, P = 0.005). CONCLUSION: Although the Val66Met polymorphism at the BDNF gene does not seem to play a significant role in children and adolescents with BD or ADHD, BDNF serum levels deserve further attention in future research on neurobiological aspects of BD and ADHD.

Invasive Fungal Infections After Kidney Transplantation: A Single-center Experience.

INTRODUCTION: Invasive fungal infections (IFI) affecting transplant recipients are associated with increased mortality and graft dysfunction. OBJECTIVE: Describe the frequency, clinical features, and outcomes of IFI (except pneumocystis infection) in kidney transplant recipients. METHOD: Single-center descriptive study including every kidney transplant recipient with a culture-proven or probable IFI between 2003 and 2013, according to the EORTC-MSG criteria. RESULTS: We identified 45 IFI. There were 13 cases of invasive candidiasis (C. albicans: 6 and non-C. albicans candidial spp.: 7), 11 cases of pulmonary aspergillosis (A. fumigatus: 9 and A. flavus: 2); 11 cases of subcutaneous mycosis (Alternaria spp.: 9, Paecilomyces spp.: 1, and Pseudallescheria spp.: 1); 7 cases of cryptococcosis; 2 cases of pneumonia by non-Aspergillus molds (Mucor spp.: 1 and Cunninghamella spp.: 1); and 1 case of Geotrichum capitatum pneumonia. All patients were recipients from deceased donors. Six cases occurred in the first 3 months post-transplant, 15 cases between the third and twelfth months, and 21 cases after the twelfth month. Treatment options were fluconazole for Candida infections, voriconazole or caspofungin for aspergillosis, liposomal amphotericin for cryptococcosis, and itraconazole plus excision or cryotherapy for subcutaneous mycosis. Fifteen patients died (33%). Mortality rates were 15% for invasive candidiasis, 45% for aspergillosis, 71% for cryptococcosis, 100% for non-Aspergillus molds and G. capitatum pneumonia, and 0% for subcutaneous mycosis. Six patients who survived (14%) started regular hemodialysis. CONCLUSION: IFI still have a high mortality and morbidity in kidney transplant recipients, as verified in this report. We reinforce the need for a high index of suspicion and prompt treatment.

Malignancy in Kidney Transplantation: A 25-Year Single-center Experience in Portugal.

It is known that the incidence of malignancy in transplant recipients is higher than in the general population, with a more aggressive behavior and a worse outcome. In fact, malignancy is the third most common cause of death among kidney transplant (KT) recipients, after cardiovascular events and infections. The aim of this study was to investigate the incidence and characteristics of malignancies after KT in a single center. A total of 2353 patients who underwent KT between 1987 and 2012 were retrospectively studied. The results were compared with a group without cancer. During the follow-up period leading to August 2014, which included a median duration of 126.3 ± 81.8 months, 223 malignancies (9.4%) were diagnosed, which were the cause of death in 59 patients. Patients with cancer were older, had a longer duration of graft function, and had more episodes of acute rejection (AR), and a higher number of patients were treated with azathioprine and cyclosporine as initial immunosuppressive regime (P = .001). The most frequent malignancy was skin cancer (28.7%), followed by malignant lymphoma (12.1%) and kidney cancer (10.8%). The mean age of patients at diagnosis was 58.0 ± 11.1 years. The average time for development of a cancer was 7.5 ± 5.8 years, with 43.2% detected between 1 and 5 years. Patient survival was significantly lower among subjects with cancer, and censored graft survival was significantly higher in this group (P = .001). Multivariate logistic regression analysis showed that recipients' age and acute rejection episode are risk factors for development of post-kidney transplantation malignancy.

Brain-derived neurotrophic factor and inflammatory markers in school-aged children with early trauma.

OBJECTIVE: The impact of childhood trauma (CT) on brain-derived neurotrophic factor (BDNF) and cytokines levels remains unclear. We investigated the association between CT and changes in BDNF and cytokines plasma levels in children. METHOD: We recruited 36 children with trauma (CT+) and 26 children without trauma (CT-). The presence of CT was based on a clinical interview and by Criteria A of DSM-IV criteria for PTSD. Blood samples were drawn from all children to assess BDNF and cytokines. ancova was performed with psychiatric symptoms and BMI as covariates to evaluate group differences in plasma levels. RESULTS: CT+ showed increased levels of BDNF and TNF-α after excluding children with history of inflammatory disease (P<0.05) when compared with those CT-. IL-12p70, IL-6, IL-8, IL-10, and IL-1ß levels were not statistically different between groups. CONCLUSION: CT+ showed increased BDNF and proinflammatory cytokines levels. The increase in BDNF levels may be an attempt to neutralize the negative effects of CT, while an increase in TNF-a levels be associated with a proinflammatory state after CT. How these changes associated with trauma relate to other biological changes and illness trajectory later in life remain to be further studied.

Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. AIMS: To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. METHODS: Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. RESULTS: No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. CONCLUSIONS: IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.

Ethnic variation of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase (MTHFR) gene in southwestern Mexico.

In this study, we examined the distribution of genotype and allele frequencies of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate-reductase gene (MTHFR) in two ethnic groups in the State of Guerrero, Mexico, which were compared with those of the Mestizo population of the region. A comparative study was conducted on 455 women from two ethnic groups and a group of Mestizo women of the State of Guerrero, Mexico: 135 Nahuas, 124 Mixtecas, and 196 Mestizas. Genotyping of both polymorphisms were performed by using polymerase chain reaction-restriction fragment length polymorphism methods. We found that the 677TT genotype was more frequent in Nahua and Mixteca women compared to Mestiza women (P = 0.008), and the most prevalent genotype in both ethnic groups was the 1298AA genotype (P < 0.001). We also compared the 677T allele frequency obtained from the groups studied with the frequencies reported in other ethnic groups of Mexico (Huichol, Tarahumara, and Purepecha). There were significant differences between the three ethnic groups compared to Nahuas (Huicholes, P = 0.004; Tarahumaras, P < 0.001; Purepechas, P = 0.042). Our results indicated significant differences in the frequencies of the C677T and A1298C polymorphisms between the two ethnic groups and the Mestizo population of the State of Guerrero. In addition, we found strong differences with other ethnic groups in Mexico. These results could be useful for future studies investigating diseases related to folate metabolism, and could help the government to design specific nutrition programs for different ethnic groups.

The integration of HR-HPV increases the expression of cyclins A and E in cytologies with and without low-grade lesions.

BACKGROUND: Cyclin-A and cyclin-E are regulators of G1-S phase of normal cell cycle. Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer. AIM: To determine the expression of cyclin-A and cyclin-E, types of HR-HPV and physical state of DNA in cytologies with the diagnosis of low-grade squamous intraepithelial lesion (LSIL). MATERIALS AND METHODS: 115 cytological specimens in liquid base (liquid-PREP(™)) were analyzed. 25 specimens were with no signs of SIL (NSIL) and without HPV; 30 with NSIL with low-risk HPV (LR-HPV); 30 with NSIL with HR-HPV; and 30 with both LSIL and HR-HPV. The expression of cyclins was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV. The physical state of HPV was evaluated by in situ hybridization with amplification with tyramide. RESULTS: In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens. Among the specimens of NSIL with HR-HPV, 33.3% expressed cyclin-A and 40% cyclin-E, while 100% of the LSILs expressed the 2 cyclins. On the other hand, 100% of the samples NSIL with LR-HPV presented an episomal pattern. Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed. Among the LSILs, 90% were mixed and 10% integrated. CONCLUSIONS: The cyclins A and E are present in the LSILs that occur predominantly in mixed state in the presence of HR-HPV.

Common variants in the CRP gene are associated with serum C-reactive protein levels and body mass index in healthy individuals in Mexico.

Variants in the C-reactive protein (CRP) gene have been found to be associated with various phenotypic traits. We evaluated the effect of four SNPs in the CRP gene on serum levels of protein and body mass index (BMI) in 150 unrelated Mexican subjects from 18 to 25 years old, without hypertension, non-overweight, and without inflammatory diseases, non-smoking and non-consumers of alcohol. Subjects were measured for BMI, waist circumference, blood pressure, and serum glucose and triglycerides. The identification of SNPs was performed by PCR-RFLP. Three of the four SNPs were associated with variation in serum levels of CRP, increased in TT (rs1130864) and GG (rs2794521) genotypes, and decreased in the AA genotype of rs1205. The TT genotype was associated with a significant increase in BMI (ß = 1.1 kg/m², P = 0.04). Two haplotypes were significantly associated with increased serum levels of CRP, but not with BMI. We conclude that variation in the CRP gene affects serum protein levels.

On the increase of portal pressure during the acute and chronic phases of murine schistosomiasis mansoni and its reversibility after treatment with oxamniquine.

The purpose of the present study was to evaluate the effect of treatment with oxamniquine on the portal pressure of mice infected with Schistosoma mansoni. The animals were infected with 30 cercariae and portal pressure was measured with a polygraph at 70 (acute phase) and 160 (chronic phase) days after infection. On days 70 and 160 two other groups of infected mice were treated with 400 mg/kg of oxamniquine and portal pressure was measured 90 days later (160 and 250 days after infection). A group of uninfected mice was used as control. The measured portal pressures, in mmHg, were: matched uninfected control mice 8.7+/-2.1 and acute phase group, measured at day 70, 13.4+/-3.5. Matched uninfected control 7.5+/-0.6 and chronic phase group, measured at day 160 post-infection, 11.6+/-1.5. Matched uninfected mice 6.9+/-0.9 and chronic phase group, measured at day 250, 10.4+/-1.8. Oxamniquine-treated at day 70 and measured at day 160 7.9+/-0.4; oxamniquine-treated at day 160 and measured at day 250, 7.6+/-1.7. The infection of mice with 30 cercariae of S. mansoni induced portal hypertension, both during the acute and chronic phases and treatment with oxamniquine caused portal pressure to return to normal levels.

Hepatic regeneration after partial hepatectomy in mice infected with Schistosoma mansoni, at the acute and chronic phases of the disease.

Outbred male albino mice normal or infected with 30 cercariae of Schistosoma mansoni (LE strain) were submitted to 65% hepatectomy during the acute (70 days) and chronic phase (160 days) phases of the disease. A group of the infected animals was treated with 400 mg/kg of oxamniquine during the acute phase before hepatectomy. Non-infected, infected and treated but not hepatectomized animals were kept as controls. Hepatic regeneration was evaluated by incorporation of tritiated thymidine, intraperitoneally injected into non-hepatectomized and hepatectomized animals, 24 hours after surgery. The results showed that removal of 65% of the hepatic parenchyma, during the acute phase, led to a statistically significant increase of thymidine incorporation, when compared with the uninfected hepatectomized controls. This phenomenon was not observed at the chronic phase. Treatment with oxamniquine administered during the acute phase led to a decrease in thymidine incorporation rate 160 days after infection (90 days after treatment) and 24 hours after hepatectomy. The data suggest that infection with S. mansoni represents a considerable stimulus for the regenerative capacity of the liver during the acute, but not the chronic phase of disease.