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Purpose: Approximately 45% of anaplastic thyroid cancer (ATC) patients harbor a BRAF V600E mutation and are eligible for target therapy (TT) with BRAF and MEK inhibitors (BRAFi/MEKi), nevertheless, few data advocate for this. Hence, we've conducted a systematic review and meta-analysis investigating the effectiveness and safety of BRAFi/MEKi in BRAF V600E ATC patients., Methods: PubMed, Embase, and the Cochrane Library were systematically searched for BRAFi/MEKi TT in BRAF V600E ATC patients. Outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response (DOR) and adverse events (AEs)., Results: Nine studies with 168 patients were included. Median follow-up ranged from 2.0 to 47.9 months. 75% of patients had stage IVc. In a pooled analysis, ORR was 68.15% (95% CI 55.31-80.99, I 2  = 47%) and DCR was 85.39% (95% CI 78.10-92.68, I 2  = 0), with a median DOR of 14.4 months (95% CI 4.6-14.4) and a median PFS of 6.7 months (95% CI 4.7-34.2). Moreover, 1-year OS rate was 64.97% (95% CI 48.76-81.17, I 2  = 84%) and 2-years OS rate was 52.08% (95% CI 35.71-68.45, I 2  = 79%). Subgroup analysis showed patients in the neoadjuvant setting had higher rates of 1 and 2-years OS and observational studies tended to report higher rates of ORR than clinical trials. No new or unexpected adverse events were found., Conclusions: Our study demonstrated BRAFi/MEKi have a decent activity for BRAF V600E ATC patients, especially in the neoadjuvant setting, with a tolerable safety profile. However, further clinical trials are warranted to investigate these findings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Since the seminal publication of the TCGA consortium in 2013, the molecular classification of endometrial cancer has been widely accepted as a new and powerful tool to better understand the natural history of this malignancy. Adoption of routine molecular classification around the world has been limited. We sought to demonstrate our initial experience in incorporating the four molecular subtypes for endometrioid carcinomas., Methods: This was a retrospective analysis at a single center in Portugal. Molecular classification was determined using immunohistochemical staining for MMR and p53 and Sanger Sequencing to determine POLE mutation status as per published PROMISE method. Descriptive statistics were reported., Results: 20 patients with endometrioid histology were included. Median age of the cohort was 64 years (range 45-76). Median Body Mass Index (kg/m 2 ) was 29.81 (range 21.3-43.1). In terms of tumor grading, 16 (80%) of the endometrial carcinomas of the cohort were low-grade (either grade 1 or grade 2). 16 (80%) of the cases were FIGO stage I. Regarding the molecular classification the tumors were classified as: MMRd [n = 6 (30%)]; p53 abn [n = 2 (10%)]; NSMP (n = 10 (50%)), POLE ultramut [n = 2 (10%)]., Conclusion: Despite the small sample size, we were able to show that molecular classification is feasible. To our knowledge this is the first cohort of endometroid endometrial carcinomas fully characterized according to the TCGA classification in Portugal, from one single center., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Casanova, da Costa, Lopes, Catarino, Nave, Sousa and Lima.)

Background: POLE mutated endometrial carcinomas may represent a subspecific type of tumors harboring a more favorable prognosis. Grade 3 (G3 or high-grade) endometrioid endometrial carcinomas remain a clinical dilemma, with some tumors behaving as the low-grade counterparts and others presenting a more aggressive behavior., Objectives: To determine the association between POLE mutational status and the overall-survival (OS) and progression-free-survival (PFS) of patients with G3 endometrioid endometrial cancer (EC). We also aimed to determine the prevalence of POLE mutations in G3 endometrioid EC., Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD4202340008). We searched the following electronic databases: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. For time-to-event data, the effect of POLE mutation in G3 EC was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Individual patient data for each study was investigated if available from the study authors. If individual patient data were not available, information regarding time-to-event outcomes was extracted using an appropriate methodology. OS and PFS were analyzed using both one-stage and two-stage approaches, the Kaplan-Meier method, and Cox-proportional hazards models., Results: This systematic review and meta-analysis included 19 studies with 3092 patients who had high-grade endometrioid EC. Patients with POLE mutations had lower risks of death (HR = 0.36, 95% CI 0.26 to 0.50, I 2  = 0%, 10 trials) and disease progression (HR = 0.31, 95% CI 0.17 to 0.57, I 2  = 33%, 10 trials). The pooled prevalence of POLE mutation was 11% (95% CI 9 to 13, I 2  = 68%, 18 studies)., Conclusion: POLE mutations in high-grade endometrioid EC are associated with a more favorable prognosis with increased OS and PFS., Competing Interests: Declaration of competing interest Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All the other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The hallmark symptom of heart failure (HF) is severe exercise intolerance. Fortunately, accumulated evidence suggests that exercise programs improve physical performance, enhance autonomy in daily activities and quality of life, and reduce cardiovascular and other hospitalizations. Recently, experimental studies have explored the application of non-invasive brain stimulation techniques, especially transcranial direct current stimulation (tDCS), aiming to improve physical performance due to its ability to modulate brain functioning. The primary objective of the present study is to evaluate the effects of anodal tDCS associated with aerobic exercise on the functional capacity of patients with HF with reduced ejection fraction (HFrEF). Secondary objectives are to compare the effects of tDCS associated with aerobic exercise vs. sham-tDCS associated with aerobic exercise on cardiopulmonary exercise capacity; inflammatory cytokines; and quality of life., Methods: This is a two-arm, prospectively registered, randomized trial with concealed allocation, double-blind, and intention-to-treat analysis. Forty-four patients with HFrEF will be recruited. The experimental group will undertake 25-30 min aerobic exercise training associated with tDCS, for 4 weeks. The control group will undergo the same aerobic exercise training, but with sham-tDCS. The primary outcome will be functional performance by the 6-min walk test. Secondary outcomes will include cardiopulmonary exercise capacity, inflammatory cytokines, and quality of life. Outcomes will be collected by a researcher blinded to group allocation at baseline (T0) and after 4 weeks of intervention (T1)., Discussion: Although previous studies have investigated the combined effect of tDCS on T3 area and physical performance and have suggested that tDCS could have reduced ratings of perceived exertion by affecting the activity of the insular cortex, and therefore increase exercise tolerance, this study is the first to evaluate the effects of the addition of anodal tDCS to aerobic exercise training for improving physical and functional performance, decreasing the perceived exertion, altering the quantification of inflammatory cytokines, and improving the subclinical values of the cardiopulmonary test in patients with HFrEF, which could result in an important advance in cardiac rehabilitation for patients with chronic HF., Trial Registration: Brazilian Registry of Clinical Trials (ReBEC) RBR-10w787j6. Registered on 25 April 2023. https://ensaiosclinicos.gov.br/pesquisador., (© 2023. The Author(s).)

Sixteen triterpenoids with various skeletal types, five phenylpropanoid derivatives, and two flavonoids were isolated from a propolis sample produced by Apis mellifera collected in the Atlantic Forest of Midwest Brazil. Among these compounds, six triterpenes, namely 3β,20R-dihydroxylanost-24-en-3-yl-palmitate, (23E)-25-methoxycycloartan-23-en-3-one, 24-methylenecycloartenone, epi-lupeol, epi-α-amyrin, and epi-β-amyrin are being reported for the first time in propolis, while cycloartenone, (E)-cinnamyl benzoate, and (E)-cinnamyl cinnamate are new findings in Brazilian propolis. The presence of cycloartane- and lanostane-type triterpenoids, the latter being a class of compounds of restricted distribution in propolis worldwide, has not been reported in propolis from Midwest Brazil until now. The ethyl acetate phase obtained from the ethanol extract was effective in preventing biofilm formation by Staphylococcus aureus, with an inhibition rate of about 96 % at 0.5 mg.mL -1 , and with quercetin isolated as one of its active constituents. In contrast, the hexane phase exhibited notable antibacterial activity against Pseudomonas aeruginosa, inhibiting bacterial growth by 92 % at 0.5 mg.mL -1 ; however, none of the triterpenoids isolated from this phase proved active against this pathogen. The ethanol extract was neither toxic nor mutagenic at the concentrations tested, as determined by the in vivo SMART assay on Drosophila melanogaster, even under conditions of high metabolic activation., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The JAK2 V617F variant constitutes a genetic alteration of higher frequency in BCR/ABL1 negative chronic myeloproliferative neoplasms, which is caused by a substitution of a G ˃ T at position 1849 and results in the substitution of valine with phenylalanine at codon 617 of the polypeptide chain. Clinical, morphological and molecular genetic features define the diagnosis criteria of polycythemia vera, essential thrombocythemia and primary myelofibrosis. Currently, JAK2 V617F is associated with clonal hematopoiesis, genomic instability, dysregulations in hemostasis and immune response. JAK2 V617F clones induce an inflammatory immune response and lead to a process of immunothrombosis. Recent research has shown great interest in trying to understand the mechanisms associated with JAK2 V617F signaling and activation of cellular and molecular responses that progressively contribute to the development of inflammatory and vascular conditions in association with chronic myeloproliferative neoplasms. Thus, the aim of this review is to describe the main genetic, hematological and immunological findings that are linked to JAK2 variant signaling in chronic myeloproliferative neoplasms.

Background: The city of Manaus, north Brazil, was stricken by a second epidemic wave of SARS-CoV-2 despite high seroprevalence estimates, coinciding with the emergence of the Gamma (P.1) variant. Reinfections were postulated as a partial explanation for the second surge. However, accurate calculation of reinfection rates is difficult when stringent criteria as two time-separated RT-PCR tests and/or genome sequencing are required. To estimate the proportion of reinfections caused by Gamma during the second wave in Manaus and the protection conferred by previous infection, we identified anti-SARS-CoV-2 antibody boosting in repeat blood donors as a mean to infer reinfection., Methods: We tested serial blood samples from unvaccinated repeat blood donors in Manaus for the presence of anti-SARS-CoV-2 IgG antibodies using two assays that display waning in early convalescence, enabling the detection of reinfection-induced boosting. Donors were required to have three or more donations, being at least one during each epidemic wave. We propose a strict serological definition of reinfection (reactivity boosting following waning like a V-shaped curve in both assays or three spaced boostings), probable (two separate boosting events) and possible (reinfection detected by only one assay) reinfections. The serial samples were used to divide donors into six groups defined based on the inferred sequence of infection and reinfection with non-Gamma and Gamma variants., Results: From 3655 repeat blood donors, 238 met all inclusion criteria, and 223 had enough residual sample volume to perform both serological assays. We found 13.6% (95% CI 7.0-24.5%) of all presumed Gamma infections that were observed in 2021 were reinfections. If we also include cases of probable or possible reinfections, these percentages increase respectively to 22.7% (95% CI 14.3-34.2%) and 39.3% (95% CI 29.5-50.0%). Previous infection conferred a protection against reinfection of 85.3% (95% CI 71.3-92.7%), decreasing to respectively 72.5% (95% CI 54.7-83.6%) and 39.5% (95% CI 14.1-57.8%) if probable and possible reinfections are included., Conclusions: Reinfection by Gamma is common and may play a significant role in epidemics where Gamma is prevalent, highlighting the continued threat variants of concern pose even to settings previously hit by substantial epidemics., (© 2022. The Author(s).)

Different factors are used as predictors of unfavorable clinical outcomes in B-Cell Acute Lymphoblastic Leukemia (B-ALL) patients. However, new prognostic markers are needed in order to allow treatment to be more accurate, providing better results and an improved quality of life. In the present study, we have characterized the profile of bone marrow soluble mediators as possible biomarkers for risk group stratification and minimal residual disease (MRD) detection during induction therapy. The study featured 47 newly-diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients that were categorized into subgroups during induction therapy according to risk stratification at day 15 [Low Risk (LR), Low Risk increasing to High Risk (LR→HR) and High Risk (HR)] and the MRD detection on day 35 (MRD (-) and MRD (+) ). Soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, TNF, IFN-γ, IL-17A, IL-4, IL-5, IL-10 and IL-2) were quantified by cytometric bead array and ELISA. Our findings demonstrated that increased levels of CCL5, IFN-γ and IL-2 at baseline appeared as putative candidates of good prognosis in LR and MRD (-) subgroups, while CCL2 was identified as a consistent late biomarker associated with poor prognosis, which was observed on D35 in HR and MRD (+) subgroups. Furthermore, apparently controversial data regarding IL-17A and TNF did not allow the definition of these molecules as either positive or negative biomarkers. These results contribute to the search for novel prognostic indicators, and indicate the potential of bone marrow soluble mediators in prognosis and follow-up of B-ALL patients during induction therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kerr, Magalhães-Gama, Ibiapina, Hanna, Xabregas, Alves, Pimentel, Carvalho, Tarragô, Teixeira-Carvalho, Martins-Filho, da Costa and Malheiro.)

The COVID-19 pandemic threatens indigenous peoples living in suburban areas of large Brazilian cities and has thus far intensified their pre-existing socio-economic inequalities. We evaluated the epidemiological situation of SARS-CoV-2 infection among residents of the biggest urban multiethnic indigenous community of the Amazonas state, Brazil. Blood samples of 280 indigenous people living in the surrounding area of Manaus were tested for the presence of anti-SARS-CoV-2 IgA or IgG antibodies. The risk factors and sociodemographic information were assessed through an epidemiological questionnaire. We found a total positivity rate of 64.64% (95% CI 59.01-70.28) for SARS-CoV-2 infection. IgA and IgG were detected in 55.71% (95% CI 49.89-61.54) and 60.71% (95% CI 54.98-66.45) of the individuals, respectively. Over 80% of positive individuals were positive for both IgA and IgG.No significant difference in positivity rates between genders or age groups was observed. Moreover, the age group ≥ 60 years old showed the highest antibody ratios (IgA mean ratio = 3.080 ± 1.623; IgG mean ratio = 4.221 ± 1.832), while the age groups 13-19 and 20-29 showed the lowest IgA (mean ratio = 2.268 ± 0.919) and IgG ratios (mean ratio = 2.207 ± 1.246), respectively. Individuals leaving the home more frequently were at higher risk of infection (Odds ratio (OD) 2.61; 95% CI 1.00-1.49; p = 0.048). Five or more individuals per household increased fivefold the risk of virus transmission (OR 2.56; 95% CI 1.09-6.01; p = 0.019). The disproportionate dissemination of SARS-CoV-2 infection observed among the study population might be driven by typical cultural behavior and socioeconomic inequalities. Despite the pandemic threat, this population is not being targeted by public policies and appears to be chronically invisible to the Brazilian authorities., (© 2021. The Author(s).)

Background: The irregular use of antiretroviral therapy (ART) and late diagnosis still account for a large part of HIV-associated mortality in people living with HIV (PLHIV). Herein, we describe HIV-associated morbidity among hospitalised HIV/AIDS patients with advanced immunosuppression and assess the comorbidities, laboratory parameters, and immunological markers associated with mortality., Methods: The cross-sectional study was conducted at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) in Manaus, Brazil. In all, 83 participants aged between 12 and 70 years were enrolled by convenience within 72 h of their hospitalisation. Clinical and laboratory data were obtained from electronic medical records. We prospectively measured the cytokines Th1/Th2/Th17 and inflammatory cytokines IL-8, IL-1β, and IL-12 using cytometric bead array, and the soluble CD14 using in-house enzyme-linked immunosorbent assay., Results: The HIV/AIDS inpatients presented a scenario of respiratory syndromes as the most prevalent comorbidity. Almost all patients had CD4 T counts below 350 cells/mL and the mortality rate was 20.5%. Pulmonary tuberculosis, neurotoxoplasmosis and oropharyngeal-esophageal candidiasis were the most prevalent opportunistic infections. TB and weight loss were more prevalent in HIV/AIDS inpatients who died. The Mann Whitney analysis showed that those who died had higher platelet distribution width (PDW) on admission, which is suggestive for platelet activation. The Poisson multivariate analysis showed the prevalence of TB, digestive syndrome and increases in IL-8 and lactate dehydrogenase (LDH) associated to death., Conclusions: The advanced immunosuppression characterized by the opportunistic infections presented in these HIV/AIDS inpatients was the major factor of mortality. The role of platelet activation in worse outcomes of hospitalisation and the IL-8 associated with the context of advanced immunosuppression may be promising markers in the prediction of mortality in HIV/AIDS patients., (© 2021. The Author(s).)

In the hematopoietic microenvironment, leukemic cells secrete factors that imbalanced chemokine and cytokine production. However, the network of soluble immunological molecules in the bone marrow microenvironment of acute lymphoblastic leukemia (ALL) remains underexplored. Herein, we evaluated the levels of the immunological molecules (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN- γ , IL-17A, IL-4, IL-10, and IL-2) in the bone marrow plasma of 47 recently diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients during induction therapy using cytometric beads arrays. The results demonstrated that B-ALL patients showed high levels of CXCL9, CXCL10, IL-6, and IL-10 at the time of diagnosis, while at the end of induction therapy, a decrease in the levels of these immunological molecules and an increase in CCL5, IFN- γ , and IL-17A levels were observed. These findings indicate that B-ALL patients have an imbalance in chemokines and cytokines in the bone marrow microenvironment that contributes to suppressing the immune response. This immune imbalance may be associated with the presence of leukemic cells since, at the end of the induction therapy, with the elimination and reduction to residual cells, the proinflammatory profile is reestablished, characterized by an increase in the cytokines of the Th1 and Th17 profiles., Competing Interests: FM-G, MWAK, FSAH, LAX, and JCFN have fellowship from FAPEAM and CAPES (Master's student). AT-C is level 2 research fellow from CNPq and research fellow from FAPEAM (PVN-II, PECTI-AM/SAÚDE Program #004/2020). OAM-F is level 1 research fellow from CNPq and a research fellow from FAPEAM (PVN-II, Pŕo-Estado Program-#002/2008, #007/2018 and #005/2019). AM is level 2 research fellow from CNPq. The authors declare no conflicts of interest., (Copyright © 2021 Fábio Magalhães-Gama et al.)

Aims: To investigate the impact of Plasmodium vivax malaria and chloroquine-primaquine chemotherapy on CYP2D6 and CYP2C19 activity in patients from the Brazilian Amazon., Methods: Adult patients (n = 30) were given subtherapeutic doses of CYP2D6 and CYP2C19 phenotypic probes metoprolol (10 mg) and omeprazole (2 mg) in three different stages of vivax malaria illness: acute disease (study phase 1), post chemotherapy (phase 2) and convalescence (stage 3). Plasma concentrations of probes and CYP-hydroxylated metabolites (α-OH metoprolol and 5-OH omeprazole) were measured using LC/MS/MS. Two pharmacokinetic metrics were used to estimate CYP activity: (a) ratio of plasma concentrations of probe/metabolite at 240 minutes after administration of the probes and (b) ratio of areas under the time-concentration curves for probe/metabolite (AUC 0-12h ). For statistical analysis, the pharmacokinetic metrics were normalized to the respective values in phase 3. Taqman assays were used for CYP2D6 and CYP2C19 genotyping. Cytokines levels were measured using cytometric bead array., Results: Both pharmacokinetic metrics for metoprolol and omeprazole, and plasma concentrations of cytokines IL-6, IL-8 and IL-10 varied significantly across the three study phases (ANOVA P < 0.0001). Post hoc tests showed greater metoprolol:α-OH metoprolol ratios in phases 1 and 2 compared to phase 3, larger omeprazole:5-OH omeprazole ratios in phase 1 than in phases 2 and 3, and higher circulating IL-6, IL-8 and IL-10 in phase 1 than in phases 2 and 3., Conclusion: P. vivax malaria and treatment altered CYP2D6 and CYP2C19 metabolic phenotypes. CYP2C19 inhibition is attributed to a higher level of circulating proinflammatory cytokines, while suppression of CYP2D6 is ascribed mainly to chloroquine exposure., (© 2020 British Pharmacological Society.)

Tuberculosis (TB) remains a serious public health burden worldwide. TB is an infectious disease caused by the Mycobacterium tuberculosis Complex. Innate immune response is critical for controlling mycobacterial infection. NOD-like receptor pyrin domain containing 3/ absent in melanoma 2 (NLRP3/AIM2) inflammasomes are suggested to play an important role in TB. NLRP3/AIM2 mediate the release of pro-inflammatory cytokines IL-1β and IL-18 to control M. tuberculosis infection. Variants of genes involved in inflammasomes may contribute to elucidation of host immune responses to TB infection. The present study evaluated single-nucleotide variants (SNVs) in inflammasome genes AIM2 (rs1103577), CARD8 (rs2009373), and CTSB (rs1692816) in 401 patients with pulmonary TB (PTB), 133 patients with extrapulmonary TB (EPTB), and 366 healthy control (HC) subjects with no history of TB residing in the Amazonas state. Quantitative Real Time PCR was performed for allelic discrimination. The SNV of AIM2 (rs1103577) is associated with protection for PTB ( p adj: 0.033, ORadj: 0.69, 95% CI: 0.49-0.97). CTSB (rs1692816) is associated with reduced risk for EPTB when compared with PTB ( p adj: 0.034, ORadj: 0.50, 95% CI: 0.27-0.94). Serum IL-1β concentrations were higher in patients with PTB than those in HCs ( p = 0,0003). The SNV rs1103577 of AIM2 appeared to influence IL-1β release. In a dominant model, individuals with the CC genotype (mean 3.78 ± SD 0.81) appeared to have a higher level of IL-1β compared to carriers of the T allele (mean 3.45 ± SD 0.84) among the patients with PTB ( p = 0,0040). We found that SNVs of AIM2 and CTSB were associated with TB, and the mechanisms involved in this process require further study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Figueira, de Lima, Boechat, Filho, Antunes, Matsuda, Ribeiro, Felix, Gonçalves, da Costa, Ramasawmy, Pontillo, Ogusku and Sadahiro.)

The biological process of wound healing is one of the most complex occurrences during our lives turning a serious public health problem. The rate of healing chronic wounds in humans is relatively uniform, regardless of etiologies, and is estimated to be 0.63-0.65 mm/week for diabetics and non- diabetics [1], respectively, being visually unnoticeable throughout the daily care of a wound. A ruler designed for this purpose using a decal for setting the wound limits, however an area with a lot of irregularity requires a tool that carries out this measurement autonomously through image recognition, making the process feasible for the medical teams responsible for the treatment. The digitized images undergo morphological processes sing on the polygonal line that delimits the wound region. With the region delimited by the polygonal, the area and the perimeter are determined. A comparison with analytical methods demonstrates that this tool has the potential to become gold standard for estimating to estimate the area and the perimeter of wounds in the healing process.

Study Objective: To evaluate the outcomes of extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy., Design: A retrospective study (Canadian Task Force classification III)., Setting: An academic institution., Patients: Twenty-three consecutive patients with gynecologic cancer who presented for para-aortic lymphadenectomy between March 2016 and May 2017 were reviewed retrospectively., Interventions: Extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy was performed., Measurements and Main Results: Of the 23 patients reviewed retrospectively, 10 had cervical cancer, 7 had endometrial cancer, 5 had adnexal cancer, and 1 had vaginal cancer. Data regarding patient characteristics, indication for para-aortic lymphadenectomy, type of surgery (infrarenal or inframesenteric), operative time, surgical complications, number of nodes retrieved, and postoperative hospital length of stay were collected. Two patients were excluded because of early perforation of the peritoneum. In total, 21 para-aortic lymphadenectomies were performed (16 infrarenal and 5 inframesenteric). The median skin-to-skin operating time of infrarenal extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy was 170 minutes (range, 90-225 minutes), the median lymph node count was 18 (range, 11-38), and the median estimated blood loss was 50 mL (range, 10-600 mL). The median skin-to-skin operating time of inframesenteric extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy was 120 minutes (range, 90-220 minutes), the median lymph node count was 10 (range, 7-19), and the median estimated blood loss was 30 mL (range, 10-100). Intraoperative complications included 1 thermal lesion of the left genitofemoral nerve, 1 thermal lesion of the left mesoureter (a ureteral stent was placed to avoid ureteric necrosis and fistula without after effect), and 1 lesion of the inferior vena cava that was sutured by robot-assisted laparoscopy. There were 2 additional cases of perforation of the peritoneum that occurred in the infrarenal group. The median hospital length of stay was 1 day (range, 0-7 days). Three patients were readmitted for symptomatic lymphocysts., Conclusion: Extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy provides good visualization of the operative field without arm conflict. Still, perforation of the peritoneum and symptomatic lymphocysts are a postoperative concern., (Copyright © 2018 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.)

Background: Low serum magnesium (MgS) is a known risk factor for cardiovascular and mineral bone disease. In renal transplant recipients (RTRs), low MgS levels have been related to higher glomerular filtration rates (GFR) and with calcineurin inhibitors, particularly tacrolimus. We aimed to evaluate MgS in renal transplant recipients with over 1 year of follow-up to establish related risk factors and the impact of the use of cyclosporine versus tacrolimus., Methods: Cross-sectional study of 94 RTRs with more than 12 months of follow-up. Hypomagnesemia was defined as serum magnesium level <1.5 mg/dL., Results: Hypomagnesemia was found in 5.3% of patients. MgS showed a negative correlation with creatinine clearance. A positive correlation between MgS with urinary magnesium and phosphorus was found. Cyclosporine versus tacrolimus analysis did not show a significant difference regarding MgS when considering all the population and the subgroup of patients with GFR >45 mL/min/1.73 m 2 . On the subgroup with GFR <45 mL/min/1.73 m 2 , those on tacrolimus had lower MgS than those on cyclosporine, but those same patients presented with significantly different GFR, higher in the tacrolimus subgroup., Conclusions: Hypomagnesemia has a low prevalence in RTRs with more than 1 year of follow-up. MgS levels evidenced a strong correlation with GFR. A significant difference on MgS levels between patients on tacrolimus and cyclosporine was found only when considering GFR <45 mL/min/1.73 m 2 , in which patients on tacrolimus had significantly higher GFR than patients on cyclosporine, which may explain these results., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This work proposes a sequential methodology for selecting variables in classification problems in which the number of predictors is much larger than the sample size. The methodology includes a Monte Carlo permutation procedure that conditionally tests the null hypothesis of no association among the outcomes and the available predictors. In order to improve computing aspects, we propose a new parametric distribution, the Truncated and Zero Inflated Gumbel Distribution. The final application is to find compact classification models with improved performance for genomic data. Results using real data sets show that the proposed methodology selects compact models with optimized classification performances.

Background: Toll-interacting protein is a negative regulator in the TLR signaling cascade, particularly by impeding the TLR2 and, TLR4 pathway. Recently, TOLLIP was shown to regulate human TLR signaling pathways. Two common TOLLIP polymorphisms (rs5743899 and rs3750920) were reported to be influencing IL-6, TNF and IL-10 expression. In this study, TOLLIP variants were investigated to their relation to Plasmodium vivax malaria in the Brazilian Amazon., Methods: This cohort study was performed in the municipalities of Careiro and, Manaus, in Western Brazilian Amazon. A total of 319 patients with P. vivax malaria and, 263 healthy controls with no previous history of malaria were included in the study. Genomic DNA was extracted from blood collected on filter paper, using the QIAamp ® DNA Mini Kit, according to the manufacturer's suggested protocol. The rs5743899 and rs3750920 polymorphisms of the TOLLIP gene were typed by PCR-RFLP., Results: Homozygous individuals for the rs3750920 T allele gene had twice the risk of developing malaria when compared to individuals homozygous for the C allele (OR 2.0 [95% CI 1.23-3.07]; p = 0.004). In the dominant model, carriers the C allele indicates protection to malaria, carriers of the C allele were compared to individuals with the T allele, and the difference is highly significant (OR 0.52 [95% CI 0.37-0.76]; p = 0.0006). The linkage disequilibrium between the two polymorphisms was weak (r 2  = 0.037; D' = 0.27)., Conclusions: These findings suggest that genes involved in the TLRs-pathway may be involved in malaria susceptibility. The association of the TOLLIP rs3750920 T allele with susceptibility to malaria further provides evidence that genetic variations in immune response genes may predispose individuals to malaria.

Hyperacute rejection (HAR) is a rare event that can be prevented by crossmatch tests that detect anti-human leukocyte antigen antibodies against the donor. We present the case of a 43-year-old man who underwent a deceased-donor kidney transplantation with a negative complement-dependent cytotoxicity and a negative flow cytometry crossmatch. Luminex technology detected anti-DQ donor-specific antibodies (DSA) with a mean fluorescence intensity of 11,000. A single plasmapheresis session was carried out, followed by immunosuppression with immunoglobulin, antithymocyte globulin, tacrolimus, and methylprednisolone. Minutes after graft reperfusion, in the presence of clinical evidence of HAR, the patient underwent nephrectomy. The investigation for the presence of anti-major histocompatibility complex class I-related chain A and anti-endothelial antibodies was negative. This case reinforces the importance of DSA, and more specifically, of anti-DQ DSA in the allogeneic response when detected by solid-phase tests, even with a negative crossmatch, assuming they can be responsible for HAR., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The optimal immunosuppressive induction therapy in kidney transplant recipients with low immunologic risk of acute rejection (AR) is still controversial. The use of basiliximab (BSX) has led to a significant decrease of AR with a low side effect profile., Objective: This study sought to evaluate predictive risk factors for AR in low immunologic risk patients subjected to immunosuppressive induction therapy with BSX., Methods: We reviewed all low immunologic risk patients (panel reactive antibody [PRA] level <50%, who had undergone a first deceased-donor transplant) subjected to immunosuppressive induction therapy with BSX, calcineurin inhibitor, mycophenolate mofetil, and prednisolone (n = 346). AR was defined as any rejection occurring until 12 months posttransplantation. Predictive risk factors for AR were evaluated by logistic regression and, to find the best cut-off of PRA related to a higher incidence of AR, receiver-operator characteristic (ROC) curve analysis was performed., Results: The rate of AR was 7.8%. Multivariate logistic regression analysis identified age at the time of transplantation (P = .040) and PRA level (P = .001) as independent risk factors for AR. ROC curve analysis confirmed that PRA >10% was related to an increased incidence of AR (19.2% vs 6.0%, P = .005)., Conclusions: A higher incidence of AR was observed in low immunologic risk kidney transplant patients with a PRA level >10%. These data support the use of more intensive immunosuppressive induction therapy in patients with low immunologic risk and a PRA level >10%., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Plasmodium vivax is the causative agent of human malaria of large geographic distribution, with 35 million cases annually. In Brazil, it is the most prevalent species, being responsible by around 70 % of the malaria cases., Methods: A cross-sectional study was performed in Manaus (Amazonas, Brazil), including 36 adult patients with primary malaria, 19 with recurrent malaria, and 20 endemic controls. The ex vivo phenotypic features of circulating leukocyte subsets (CD4(+) T-cells, CD8(+) T-cells, NK, NKT, B, B1 and Treg cells) as well as the plasmatic cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ) were assessed, aiming at establishing patterns of immune response characteristic of primary malaria vs recurrent malaria as compared to endemic controls., Results: The proportion of subjects with high levels of WBC was reduced in malaria patients as compared to the endemic control. Monocytes were diminished particularly in patients with primary malaria. The proportion of subjects with high levels of all lymphocyte subsets was decreased in all malaria groups, regardless their clinical status. Decreased proportion of subjects with high levels of CD4(+) and CD8(+) T-cells was found especially in the group of patients with recurrent malaria. Data analysis indicated significant increase in the proportion of the subjects with high plasmatic cytokine levels in both malaria groups, characterizing a typical cytokine storm. Recurrent malaria patients displayed the highest plasmatic IL-10 levels, that correlated directly with the CD4(+)/CD8(+) T-cells ratio and the number of malaria episodes., Conclusion: The findings confirm that the infection by the P. vivax causes a decrease in peripheral blood lymphocyte subsets, which is intensified in the cases of "recurrent malaria". The unbalanced CD4(+)/CD8(+) T-cells ratio, as well as increased IL-10 levels were correlated with the number of recurrent malaria episodes. These results suggest that the gradual remodelling of the immune response is dependent on the repeated exposure to the parasite, which involves a strict control of the immune response mediated by the CD4(+)/CD8(+) T-cell unbalance and exacerbated IL-10 secretion.

Background: In this study, we have evaluated the immunological status of hepatitis C virus (HCV)-infected patients aiming at identifying putative biomarkers associated with distinct degrees of liver fibrosis. Peripheral blood and tissue T-cells as well as cytokine levels were quantified by flow cytometry., Results: Data analysis demonstrated higher frequency of circulating CD8(+) T-cells and Tregs along with a mixed proinflammatory/IL-10-modulated cytokine pattern in HCV patients. Patients with severe liver fibrosis presented lower frequency of circulating CD8(+) T-cells, higher levels of proinflammatory cytokines, but lower levels of IL-10, in addition to the higher viral load. Despite the lower frequency of intrahepatic T-cells and scarce frequency of Tregs, patients with severe liver fibrosis showed higher levels of proinflammatory cytokines (TNF and IFN-γ). The tissue proinflammatory cytokine pattern supported further studies of serum cytokines as relevant biomarkers associated with different liver fibrosis scores. Serum cytokine signature showed that mild liver fibrosis is associated with higher IL-10 serum levels as compared to severe liver disease. There was a clear positive connection of IL-10 with the TNF node in patients with mild liver fibrosis, whereas there is an evident inverse correlation between IL-10 with all other cytokine nodes., Conclusions: These results suggest the absence of modulatory events in patients with severe liver damage as opposed to mild fibrosis. Machine-learning data mining pointed out TNF and IL-10 as major attributes to differentiate HCV patients from non-infected individuals with highest performance. In conclusion, our findings demonstrated that HCV infection triggers a local and systemic cytokine ensemble orchestrated by TNF and tuned by IL-10 in such a manner that mirrors the liver fibrosis score, which highly suggests the relevance of these set of biomarkers for clinical investigations.

Aim: To compare transvaginal digital examination performed by residents and attending physicians to transabdominal suprapubic ultrasound in the evaluation of fetal head position in the second stage of labor., Methods: A prospective study was conducted at a tertiary center and included pregnant women at term, with normal singleton cephalic presentation fetuses. All patients had ruptured membranes and were evaluated during the second stage of labor. Fetal head position was assessed consecutively by two clinicians (one resident and one attending physician). Afterwards, transabdominal suprapubic ultrasound was performed by another observer. Examiners were blinded to each other's findings. Cohen's kappa test was used to assess the degree of agreement between the evaluation methods., Results: One-hundred sixty-one women were included. Transvaginal examination was consistent with the ultrasound in 45.0% of cases (95% CI: 37-53%) when the examination was performed by residents (k = 0.349) and in 67% (95% CI: 60-74%) if the attending physician carried out the evaluation (k = 0.604). When considering only the anterior positions, the Cohen's kappa test was 0.426 and 0.709, respectively., Conclusion: Transabdominal suprapubic ultrasound improved the accuracy of the evaluation of fetal head position, namely when transvaginal digital examination was performed by residents. This may be important especially when instrumental deliveries are considered.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules., Objective: The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution., Methods: Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments., Results: Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX., Conclusion: The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.

Introduction: Musculoskeletal pain is one of the most frequent complaints among teachers, compromising their health and quality of life., Objective: To estimate the prevalence of musculoskeletal pain among teachers, assessing their occurrence according to sociodemographic characteristics, general health and well-being at work., Methods: An exploratory cross-sectional study conducted with 525 teachers. During activities of continuing education, the teachers completed a self-administered questionnaire containing questions about sociodemographic factors, general health, well-being at work and musculoskeletal pain., Results: The overall prevalence of musculoskeletal pain was equal to 73.5%. The most common musculoskeletal pains were localized in the shoulders (31.6%), upper back (27.8%), neck (27.2%) and ankles and/or feet (24.0%). Circulatory and respiratory problems and Common Mental Disorders were associated with pain in the shoulders, upper back, neck and ankles and/or feet. Well- being at work is associated with pain in the shoulders, neck and ankles and/or feet., Conclusion: It is necessary to deepen the knowledge about musculoskeletal pain among teachers, exploring the biological, ergonomic, occupational and psychosocial mechanisms of teaching, as well as invest in practices that improve the relationship of coexistence between workers and activities that enhance the comfort and reduce referred pain.

Background: The major issues involved in the decision to donate are the perioperative risk and the risk of chronic kidney disease or even end-stage renal disease. The usual glomerular filtration rate (GFR) in kidney donors after transplantation is approximately 70% of the predonation rate; however, some have a GFR <60 mL/min/1.73 m(2). So after kidney donation, mild to moderate renal insufficiency may occur. Thus, it is important to identify predictor factors of postdonation kidney function., Objectives: To evaluate the influence of predictor factors in the evolution of the remaining kidney function and to quantify nonpredictable and unexpected developments in GFR at 1 year post donation., Methods: We performed a study of the evolution of renal function pre- and postnephrectomy of 55 living donors without perioperative comorbidities and a mean follow-up of 6.03 ± 2.7 years., Results: One year after nephrectomy donor function was 32% lower than the prenephrectomy value and 21% of donors had an eGFR <60 mL/min/1.73 m(2). In multivariate logistic regression a living donor with a predonation eGFR <100 but >80 mL/min/1.73 m(2) had 5.24 times a chance of having an eGFR <60 mL/min/1.73 m(2) at 1 year post donation than if he had an eGFR ≥100 mL/min/1.73 m(2). Among 15 donors with prenephrectomy eGFR ≥80 and <100 mL/min/1.73m(2), 8 (53%), RR = 3.26 (1.517-7.012) had eGFR <60 mL/min/ 1.73 m(2)., Conclusions: The eGFR predonation and donor age influenced the first-year postnephrectomy eGFR. Some donors had a more accelerated eGFR fall, not always related to predonation eGFR and age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Diabetes mellitus (DM) may progress to diabetic nephropathy (DN) in approximately 40% of cases and it accounts for one of the most common causes of end-stage of renal disease (ESRD). The pathogenesis of DN involves complex interactions between metabolic and hemodynamic factors. DM type 1 has a dominant impact on morbidity and mortality after renal transplantation. We report a kidney transplantation patient with DM and DN as the etiology of end-stage renal disease and whose post-transplantation evolution over 19 years was remarkably atypical. DM was diagnosed at the age of 7 years and the patient suffered a rapid and aggressive progression of her disease with early development of DN and diabetic retinopathy. Nineteen years post-transplantation, the patient shows neither deterioration of graft function nor clinical reactivation of DN. There seems to be two quite distinct answers to the same injury supported by a group of factors that led to micro- and macrovascular lesions, all present before transplantation and potentially aggravated through some immunosuppressive therapy. This clinical evolution suggests the hypothesis that not only the graft but also the donor may have inherent characteristics that enabled him to display the resistance to DN despite the genetic susceptibility of the receptor. The answers to these questions would help to explain why some patients with diabetes progress to macro- and microvascular complications and others remain resistant to developing these vascular disorders. In this case, the resistance to DN is apparently a feature related to the donor., (Copyright © 2015 Elsevier Inc. All rights reserved.)

NAF is a breast fluid that is closely related to the tumor microenvironment and a valuable sample for studying breast cancer. To perform an in-depth proteomic analysis of this sample, aliquots of a single NAF digest were analyzed by the following peptide-centric fractionation strategies: a) 30-cm reversed-phase (RP) column on-line with an LTQ-Orbitrap XL; b) off-line strong cation-exchange (SCX) column; and c) pI-based OFFGEL fractionation. All fractions from approaches (b) and (c) were further analyzed on a 10-cm RP column hyphenated to the same mass spectrometer. The RP-30cm, SCX/RP-10cm, and OFFGEL/RP-10cm approaches identified 1676, 2930, and 3240 peptides, which corresponded to 193, 390 and 528 proteins, respectively. In our cumulative dataset, 4466 distinct NAF peptides corresponded to a total of 557 proteins, of which only 34% were identified by all three approaches. No exclusive protein identification was associated to the RP-30cm approach, while SCX/RP-10cm and OFFGEL/RP-10cm contributed to 28 and 166 exclusive identifications, respectively. Each approach provided additional information related to energy metabolism (fermentation process/carbohydrate biosynthesis). In conclusion, the pre-fractionation platforms used were complementary for the comprehensive characterization of NAF and our work provides methodological information for future quantitative cancer-related NAF sample studies., Biological Significance: High-resolution peptide separation is a sine qua non condition for achieving extensive proteome coverage. Various techniques have been employed to improve peptide fractionation prior to LC-MS/MS, thus allowing a comprehensive characterization of complex biological samples. Although fractionation efficiency is very sample-dependent, this issue is commonly overlooked, and a "cookbook" approach is routinely used during this critical step. The present study provides a systematic comparison of analytical information needed for the successful large-scale differential proteomic analysis of NAF samples from breast cancer patients, a precious and volume-limited biological sample. It reinforces the importance of optimizing sample-specific fractionation protocols for information retrieval from mass spectrometric analysis., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The incidence of anal cancer has increased over the past 25 years, and HIV/HPV coinfection is the most important risk factor for anal squamous cell carcinoma. In this study, we demonstrated that the evaluation of systemic and compartmentalized anal mucosa immune response is relevant to differentiating HIV(+) patients at risk of anal intraepithelial neoplasia (AIN)., Methods: A systems biology approach was used to integrate different immunological parameters from anal mucosal tissue and peripheral blood assessed by phenotypic and intracytoplasmic analysis of lymphocytes and dendritic cell subsets., Results: Our data demonstrated that anal mucosal mononuclear cells from AIN(+)HIV(+) patients showed a robust capacity in producing proinflammatory/regulatory cytokines, mainly mTNF-α > IL-4 > IL-10 > IL-6 = IL-17A. Mucosal TNF-α/IFN-γ/IL-17A are selective high-grade squamous intraepithelial lesion (HSIL)-related biomarkers. Higher levels of circulating CD11cCD123cells and CD1a cells along with elevated levels of IFN-γCD4 T cells are major features associated with HSIL in AIN(+)HIV(+) patients. Regardless of the presence of AIN, HIV(+) patients presented a complex biomarker network, rich in negative connections. Among those patients, however, HSIL+ patients displayed stronger positive links between peripheral blood and anal mucosa environments, exemplified by the subnet of IL-17A/TNF-α/CD4IFN-γ/CD11cCD123 cells., Conclusions: The significant association between HSIL and the levels of TNF-α/IL-17A/IFN-γ along with the different subsets of DCs present in the anal mucosa milieu should be studied in more detail as a way to identify and categorize HIV(+) patients vis à vis the high risk of anal cancer outcome.

The aim of this observational study was to assess the degree of patient satisfaction toward implant-supported prostheses. A questionnaire was used with two scales (one consisting of detailed adjectival and the other of numerical responses) regarding chewing, esthetics, speaking, comfort and overall satisfaction. The scales were administered to a sample of 147 patients treated with implants and prostheses. The data were submitted to the Kappa statistic and the Chi-square test to analyze the association between dependent and independent variables. High degrees of satisfaction (greater than 91%) were found for all categories evaluated, regardless of gender, age, number of implants or type of prosthesis. "Comfort" was associated significantly with the number of implants (p = 0.038), and "speaking" was associated significantly with the type of prosthesis (p = 0.029). Positive agreement was found between the scales for all categories evaluated, without statistically significant differences regarding respondent preference (p = 0.735). Patients treated with implant-supported prostheses were highly satisfied with the treatment.

In this study, we demonstrate that G-CSF administration triggers distinct kinetics of stem cell-SC mobilization with early raise of hematopoietic-HSC and late increase of mesenchymal-MSC in bone marrow-BM and peripheral blood-PB. The cytokine microenvironment observed following primary cultures showed an overall G-CSF dose-dependent profile with a clear mixed pro-inflammatory/regulatory pattern. Moreover, primary cultures performed at the peak of MSC/HSC ratio, showed distinct cytokine patterns, with higher IL-10, TNF-α and IL-17A observed for BM and enhanced IL-10, IL-2 and IFN-γ for PB harvested cells. Positive correlation was observed between BM-MSC and the levels of TNF-α, IL-10 and IL-17A whereas negative correlation was found between IL-10 and BM-HSC. An opposite association was observed between IL-10 and PB-HSC. Our results support the hypothesis that MSC and HSC harvested from BM and PB display differential functional properties that should be considered when electing the SC sources available for cell therapy applied in clinical protocols., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients., (Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Background: In Brazil, about two million people living in rural semiarid regions were benefited with the construction of rainwater cement cisterns, as an initiative from the program "One Million Cisterns" (P1MC). Nevertheless, few epidemiological studies have been conducted to assess health risks or protection effects associated with consumption of this water source. The aim of this study was to evaluate whether access to rainwater harvesting cisterns is associated with the decrease in the occurrence of Giardia duodenalis infections in children, compared to other children living in households supplied by other water sources., Methodology/principal Findings: A quasi-experimental study with two concurrent cohorts was developed in two rural municipalities of the semiarid region of Brazil. A sample of 664 children, aged between 4 months and 5 years old, was followed up, of which 332 had access to rainwater cisterns (cistern group) and 332 did not, having water supplied from alternative sources (comparison group). In a period of approximately one year (2010) intestinal parasites were investigated in feces three times. The prevalence of G. duodenalis in children from the cistern group ranged from 4.8 to 10.5%, while the prevalence in the comparison group ranged from 7.6 to 16.7%. Multivariate analysis (GEE) showed a higher risk of G. duodenalis infection in children who did not have access to rainwater cisterns, when compared to children who did (OR 1.72; 95% CI 1.14-2.59). The other variables associated with G. duodenalis infection were: number of rooms per house (OR 0.89; 95% CI 0.80-0.99); family income (OR0.48; 95% CI 0.26-0.88); birth order (OR 1.72; 95% CI 1.17-2.51); preterm children (OR 1.70; 95% CI 1.19-2.43); and improper hand hygiene prior to food preparation (OR 4.78; 95% CI 1.95-11.76)., Conclusions/significance: Ownership of a rainwater cistern is associated with a lower prevalence of G. duodenalis infection in children after adjustment for environmental and family-related factors. Nevertheless, the study suggests the necessity to complement physical interventions with actions related to personal and domestic hygiene to enable further reductions in parasite infections affecting mainly the underprivileged populations.

Fungal endophytes associated with Myrtaceae from Brazil and Argentina were isolated at three levels of nesting: leaf, individual host trees, and site collection. The alternating logistic regression (ALR) was used to model the data because it offers a computationally convenient method for fitting regression structures involving large clusters. The objectives of this study were to determine: (i) whether the colonization pattern is influenced by environmental variables, (ii) if there is some leaf part they prefer to colonize; (iii) if there is some fungal endophyte aggregation between hierarchical levels; (iv) what the distance effect is on the fungal association. The environmental variables were statistically significant only for Xylaria, i.e., when the elevation and water precipitation increase and the temperature decreases, the odds ratio of finding another fungal endophyte of that genus previously found increases. Sordariomycetes, Xylariales, and Xylaria exhibited leaf fragment preference to petiole and tip. Fungal endophytes showed association within leaf. The horizontal transmission mode and the dispersal limitation may explain this association at the leaf level. Moreover, our results suggest that when a fungal endophyte infects a leaf or host tree individual, the odds ratio of dispersal inside them is greater., (Copyright © 2013 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Background: Recent studies have shown that the inflammatory process, including the biomarker production, and the intense activation of innate immune responses are greater in the malaria caused by Plasmodium vivax than other species. Here, we examined the levels of serum biomarkers and their interaction during acute malaria., Material and Methods: Blood samples were collected from P. vivax-infected patients at admission and from healthy donors. Levels of serum biomarkers were measured by Cytometric Bead Assay or ELISA., Results: P. vivax infection triggered the production of both inflammatory and regulatory biomarkers. Levels of IL-6, CXCL-8, IFN-γ, IL-5, and IL-10 were higher in P. vivax-infected patients than in healthy donors. On the other hand, malaria patients produced lower levels of TNF-α, IL-12p70, and IL-2 than healthy individuals. While the levels of IL-10 and IL-6 were found independent on the number of malaria episodes, higher levels of these cytokines were seen in patients with higher parasite load., Conclusion: A mixed pattern of proinflammatory and regulatory biomarkers is produced in P. vivax malaria. Analysis of biomarker network suggests that IL-10 and IL-6 are a robust axis in malaria patients and that this interaction seems to be associated with the parasite load.

The authors discuss in this paper the role of inflammatory, anti-inflammatory, and regulatory cytokines in patients infected with different species of Leishmania in Amazonas State, Brazil. A comparative analysis was made of serum concentrations of these cytokines in the peripheral blood of 33 patients infected with cutaneous leishmaniasis. The isolates were identified as Leishmania guyanensis, L. naiffi, and L. amazonensis. Most (64%) of the patients were male ranging in age from 18 to 58 years. Protein expression profiles of IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17 cytokines were shown to vary significantly between infected and noninfected (control group) individuals and according to the Leishmania species. Infection caused by L. guyanensis accounted for 73% of the cases and patients with this parasite also showed higher concentrations of IL-2, IFN-γ, IL-4, and IL-17 when compared to infection by L. amazonensis. Patients with infection caused by L. naiffi showed higher concentration of the cytokines analyzed when compared to uninfected patients; however, there was no statistically significant difference with the other species analyzed.

Breast cancer is the leading cause of cancer related deaths in women. Most breast cancers stem from mammary ductal cells that secrete nipple aspirate fluid (NAF), a biological sample that contains proteins associated with the tumor microenvironment. In this study, NAF samples from both breasts of 7 Brazilian patients with unilateral breast cancer were analyzed. These samples were systematically compared using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional fluorescence difference gel electrophoresis (2D-DIGE); substantial qualitative individual differences were observed. In general, when NAF samples were compared from both breasts within the same patient their electrophoretic patterns were very similar, regardless of their cancer status. A comparison of all patients identified 2 main NAF protein profiles. The HomEP, homogeneous expression profile, was characterized by typical SDS-PAGE and 2D-DIGE protein patterns that were observed in patients with a good breast cancer prognosis and were similar to previous Type I NAF classifications that used one-dimensional electrophoresis. The HetEP, heterogeneous expression profile, was characterized by distinct protein patterns that have not been reported in previous studies and have been primarily observed in breast cancer patients with a poor prognosis. The NAF samples were rich in metal-dependent proteolytic enzymes, as visualized by SDS-PAGE zymography. They varied qualitatively with respect to their gelatinolytic band distribution. However, there were no correlations between these characteristics and the pathologic features of these tumors. A comparative analysis of NAF samples taken from each breast in a single patient showed conserved zymographic patterns. In conclusion, the present study highlights important distinctions in the protein content of individual NAF samples and provides insight into the composition of the tumor microenvironment. These data reinforce breast cancer as a heterogeneous disease with a diverse natural history, which is becoming increasingly evident through other recent studies.