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We report acute Oropouche virus infections in 2 previously healthy women from a nonendemic region of Brazil outside the Amazon Basin. Infections rapidly progressed to hemorrhagic manifestations and fatal outcomes in 4-5 days. These cases highlight the critical need for enhanced surveillance to clarify epidemiology of this neglected disease.

Acidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-β2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-β2 signaling, which in turn favors the formation of lipid droplets (LD) that represent energy stores readily available to support anoikis resistance and cancer cell invasiveness. We find that, in cancer cells of various origins, acidosis-induced TGF-β2 activation promotes both partial epithelial-to-mesenchymal transition (EMT) and fatty acid metabolism, the latter supporting Smad2 acetylation. We show that upon TGF-β2 stimulation, PKC-zeta-mediated translocation of CD36 facilitates the uptake of fatty acids that are either stored as triglycerides in LD through DGAT1 or oxidized to generate ATP to fulfill immediate cellular needs. We also address how, by preventing fatty acid mobilization from LD, distant metastatic spreading may be inhibited.

Bioenergetic preferences of cancer cells foster tumor acidosis that in turn leads to dramatic reduction in glycolysis and glucose-derived acetyl-coenzyme A (acetyl-CoA). Here, we show that the main source of this critical two-carbon intermediate becomes fatty acid (FA) oxidation in acidic pH-adapted cancer cells. FA-derived acetyl-CoA not only fuels the tricarboxylic acid (TCA) cycle and supports tumor cell respiration under acidosis, but also contributes to non-enzymatic mitochondrial protein hyperacetylation, thereby restraining complex I activity and ROS production. Also, while oxidative metabolism of glutamine supports the canonical TCA cycle in acidic conditions, reductive carboxylation of glutamine-derived α-ketoglutarate sustains FA synthesis. Concomitance of FA oxidation and synthesis is enabled upon sirtuin-mediated histone deacetylation and consecutive downregulation of acetyl-CoA carboxylase ACC2 making mitochondrial fatty acyl-CoA degradation compatible with cytosolic lipogenesis. Perturbations of these regulatory processes lead to tumor growth inhibitory effects further identifying FA metabolism as a critical determinant of tumor cell proliferation under acidosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Minimally invasive surgery for rectal cancer (RC) is now widely performed via the laparoscopic approach, but robotic-assisted surgery may overcome some limitations of laparoscopy in RC treatment. We compared the rate of positive circumferential margins between robotic, laparoscopic and open total mesorectal excision (TME) for RC in our institution., Methods: Mid and low rectal adenocarcinoma patients consecutively submitted to robotic surgery were compared to laparoscopic and open approach. From our prospective database, 59 patients underwent robotic-assisted rectal surgery from 2012 to 2015 (RTME group) were compared to our historical control group comprising 200 open TME (OTME group) and 41 laparoscopic TME (LTME group) approaches from July 2008 to February 2012. Primary endpoint was to compare the rate of involved circumferential resection margins (CRM) and the mean CRM between the three groups. Secondary endpoint was to compare the mean number of resected lymph nodes between the three groups., Results: CRM involvement was demonstrated in 20 patients (15.5%) in OTME, 4 (16%) in LTME and 9 (16.4%) in the RTME (p = 0.988). The mean CRM in OTME, LTME and RTME were respectively 0.6 cm (0-2.7), 0.7 cm (0-2.0) and 0.6 cm (0-2.0) (p = 0.960). Overall mean LN harvest was 14 (0-56); 16 (0-52) in OTME, 13 (1-56) in LTME and 10 (0-45) in RTME (p = 0.156)., Conclusion: Our results suggest that robotic TME has the same oncological short-term results when compared to the open and laparoscopic technique, and it could be safely offered for the treatment of mid and low rectal cancer., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Surgery is the standard treatment of rectal cancer after neoadjuvant therapy. Some authors advocate a nonoperative management (NOM) after complete clinical response (cCR) following chemoradiotherapy (CRT). We compare our results with NOM to standard resection in a retrospective analysis., Methods: Rectal adenocarcinomas submitted to NOM after CRT between September 2002 and December 2013 were compared to surgical patients that had pathological complete response (pCR) during the same period. Endpoints were Overall Survival (OS), Disease Free Survival (DFS), Local Relapse (LR) and Distant Relapse (DR)., Results: Forty-two NOM patients compared to 69 pCR patients operated after a median interval of 35 weeks after CRT. NOM tumors were distal (83.3% vs 59.4%, p = 0.011), less obstructive (26.2% vs 54.4%, p = 0.005) and had a lower digital rectal score (p = 0.024). Twelve (28.0%) recurrences in NOM group and eight (11.5%) in the surgical group occurred after a follow-up of 47.7 and 46.7 months respectively. Isolated LR occurred in five (11%) NOM patients and one (1.4%) in the surgical group. Four (80%) LR were surgically salvaged in NOM group. No difference in OS was found (71.6% vs 89.9%, p = 0.316) but there was a higher DFS favoring surgical group (60.9% vs 82.8%, p = 0.011). Distal tumors had worse OS compared to proximal tumors in surgical group (5-year OS of 85.5% vs 96.2%, p = 0.038)., Conclusion: The NOM achieved OS comparable to surgical treatment and spared patients from surgical morbidity but it resulted in more recurrences. This approach cannot be advocated routinely and controlled trials are warranted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The effectiveness of chemotherapy (CT) for select cases of metastatic colorectal cancer (MCRC) has been well established in the literature, however, it provides limited benefits and in many cases constitutes a treatment with high toxicity. The use of specific molecular biological treatments with monoclonal antibodies (MA) has been shown to be relevant, particularly for its potential for increasing the response rate of the host to the tumour, as these have molecular targets present in the cancerous cells and their microenvironment thereby blocking their development. The combination of MA and CT can bring a significant increase in the rate of resectability of metastases, the progression-free survival (PFS), and the global survival (GS) in MCRC patients., Objective: To assess the effectiveness and safety of MA in the treatment of MCRC., Methods: A systematic review was carried out with a meta-analysis of randomised clinical trials comparing the use of cetuximab, bevacizumab, and panitumumab in the treatment of MCRC., Results: Sixteen randomised clinical trials were selected. The quality of the evidence on the question was considered moderate and data from eight randomised clinical trials were included in this meta-analysis. The GS and PFS were greater in the groups which received the MA associated with CT, however, the differences were not statistically significant between the groups (mean of 17.7 months versus 17.1 months; mean difference of 1.09 (CI: 0.10-2.07); p = 0.84; and 7.4 versus 6.9 months. mean difference of 0.76 (CI: 0.08-1.44); p = 0.14 respectively). The meta-analysis was not done for any of the secondary outcomes., Conclusion: The addition of MA to CT for patients with metastatic colorectal cancer does not prolong GS and PFS.

Introduction: Stomach cancer is the third most common cause of death worldwide, mainly affecting people with low socioeconomic status. In Brazil, we expect 20,390 new cases of stomach cancer in 2014, in both sexes, and according to the proportional distribution of the ten most prevalent types of cancer (except non-melanoma skin cancer) expected for 2014, this type of cancer was estimated to be the fourth most common in men and sixth in women., Aim: To investigate and analyse the clinical and epidemiological profile of deaths caused by stomach adenocarcinoma in patients enrolled in the National Cancer Institute, Brazil., Methods: Cross-sectional study, with samples which consisted of data from the medical records of deaths from stomach cancer, enrolled in the period from 1 February 2009 to 31 March 2012 and who had died as of 30 April 2012., Statistical Analysis Used: The Epi Info ®, version 7., Results: We included 264 cases, mostly male. The mean age was 61.7 years. They were smokers, drinkers, white, and married, with elementary education and an income of one minimum salary. They had advanced stage disease (E IV), with symptoms characteristic of this phase, and the majority died within six months., Conclusion: The findings are similar to other studies. The advanced stage of the disease at the time of admission of the patients reflects the difficulty for users of the Unified Health System to access early diagnosis, demonstrating the need for efforts to identify groups and risk factors for the development of gastric cancer. Training of health professionals will facilitate planning and implementation of programmes for the prevention and control of disease, considering socioeconomic conditions, as seen in the sample, which is common among most users.

Two compost formulations based on oat straw (Avena sativa) and brachiaria (Brachiaria sp.) were tested for the cultivation of three Agaricus bisporus strains (ABI-07/06, ABI-05/03, and PB-1). The experimental design was a 2 × 3 factorial scheme (composts × strains) with 6 treatments and 8 repetitions (boxes containing 12 kg of compost). The chemical characterization of the compost (humidity, organic matter, carbon, nitrogen, pH, raw protein, ethereal extract, fibers, ash, cellulose, hemicellulose, and lignin) before and after the cultivation of A. bisporus and the production (basidiomata mass, productivity, and biological efficiency) were evaluated. Data were submitted to variance analysis, and averages were compared by means of the Tukey's test. According to the results obtained, the chemical and production characteristics showed that the best performances for the cultivation of A. bisporus were presented by the compost based on oat and the strain ABI-07/06.

Background: Neuroendocrine tumors (NETs) are rare, comprising nearly 0.49% of all malignancies. The majority occurs in the gastrointestinal tract., Aim: To analyze the demographic factors, clinicopathologic features, treatment employed, prognostic factors and the oncologic results related to colorectal NETs., Methods: Between the period from 1996 to 2010 174 patients were treated. From these, 34 were localized in the colon and rectum. Demographic factors, stage, therapeutics and its results were analyzed. All patients were followed for more than three years with image exams, urinary 5-hydroxyindolacetic acid (5-HIIA), serum chromogranin A and prostatic acid phosphatase., Results: The median age was 54,4 years (22-76), the majority was female (64,7%). Out of the 12 patients with colon NETs, one (8.3%) patient was classified as Stage IA; one (8.3%) as Stage IB; three (25%) as Stage IIIB and seven (58.4%) as Stage IV. Out of the 22 patients with rectum NETs, six (27.3%) were classified as Stage IA; four (18.2%) as IB; three (13.6 %) as IIIA; one (4.5%) as IIIB and eight (36.4%) as IV. Of rectal NETs, nine (41%) were treated with endoscopic resection, six (27.2%) underwent conventional surgical treatment and six (27.2%) were treated with chemotherapy. Eleven patients with colon NETs (91.6%) were surgically treated, seven of them with palliative surgery, one (8.4%) was treated with endoscopic resection and no patient was submitted to chemotherapy. After an average follow-up of 55 months, 19 (55%) patients were alive. Analyzing the overall survival was obtained an average overall survival of 29 months in Stage IA, 62 months in IB, 12 months in IIIA, 31 months in IIIB and 39 months in IV., Conclusion: The treatment of colon and rectal NETs is complex, because it depends of the individuality of each patient. With adequate management, the prognosis can be favorable with long survival, but it is related to the tumor differentiation degree, efficacy of the chosen treatment and to the patient adhesion to the follow-up after treatment.

Background: In Brazil, gastric cancer is the fourth most common malignancy among men and sixth among women. The cause is multivariate and the risks are well known. It has prognosis and treatment defined by the location and staging of the tumor and number of lymph nodes resected and involved., Aim: The Brazilian Consensus on Gastric Cancer promoted by ABCG was designed with the intention to issue guidelines that can guide medical professionals to care for patients with this disease., Methods: Were summarized and answered 43 questions reflecting consensus or not on diagnosis and treatment that may be used as guidance for its multidisciplinary approach. The method involved three steps. Initially, 56 digestive surgeons and related medical specialties met to formulate the questions that were sent to participants for answers on scientific evidence and personal experience. Summaries were presented, discussed and voted in plenary in two other meetings. They covered 53 questions involving: diagnosis and staging (six questions); surgical treatment (35 questions); chemotherapy and radiotherapy (seven questions) and anatomopathology, immunohistochemistry and perspective (five questions). It was considered consensus agreement on more than 70% of the votes in each item., Results: All the answers were presented and voted upon, and in 42 there was consensus., Conclusion: It could be developed consensus on most issues that come with the care of patients with gastric cancer and they can be transformed in guidelines.

Objective: To evaluate the treatment of GIST in INCA., Methods: We conducted a retrospective analysis of all cases of GIST treated at INCA in the period from 1997 to 2009., Results: We analyzed 146 patients with a mean age of 44.5 years and female predominance. The main symptom was abdominal pain. We observed the occurrence of a second primary tumor in 22% of cases and 92% of the immunohistochemistry exams were positive for CD117. The most frequent location was in the stomach and the high-risk group was predominant. Surgery was considered R0 (extensive) in 70% of the cases and the main sites of metastases were liver and peritoneum. Overall survival in two and five years was, respectively, 86% and 59%. There was a significant difference between overall survival (p = 0.29) of the high-risk group versus the other., Conclusion: Our patients presented mainly in the form of high-risk disease, with obvious impact on survival. The use of imatinib improved survival of patients with recurrent and metastatic disease. We should study its use in the setting of adjuvant and neoadjuvant therapy to improve results of the high risk group. The creation of reference centers is a need for the study of rare diseases.

The purpose of this work was to assess the acute toxicity on male mice to a chromated copper arsenate (CCA) solution, a widespread wood preservative used in building industry until 2002. Animals were subcutaneously injected with CCA (7.2mg/kg arsenic and 10.2mg/kg chromium per body weight), CrO(3) (10.2mg/kg), As(2)O(5) (7.2mg/kg) and NaCl (0.9%) per se, during 48h and 96h, for histopathology, histochemistry, chromium and arsenic analysis. The results showed some histopathological changes within renal tubules lumen of CCA exposed animals (during 48h, and 96h), and CrO(3) (for the period of 96h). Furthermore, the renal levels of arsenic and chromium in treated animals were statistically more evident than controls. Although, the same contents of pentavalent arsenic and hexavalent chromium were injected into treated animals with CCA and with the prepared solutions of As(2)O(5) and CrO(3), a different distribution of the pattern of these compounds was observed in kidneys., (Copyright © 2008 Elsevier B.V. All rights reserved.)

The dichloromethane extract of the air-dried leaves of Artemisia vulgaris afforded a new sesquiterpene 1, caryophyllene oxide, phytyl fatty acid esters, squalene, stigmasterol and sitosterol. The structure of 1 was elucidated by extensive one- and two-dimensional nuclear magnetic resonance spectroscopy.

Background: Cr(V) species are formed during the intracellular reduction of Cr(VI), a ubiquitous environmental pollutant. In this study, the acute toxicity of a physiologically stable Cr(V) compound, [CrV-BT](2-) (BT = bis(hydroxyethyl)aminotris(hydroxymethyl)methane) was investigated in the male reproductive system of sexually mature 60-day-old male ICR-CD1 mice., Methods: Eight-week-old animals were subcutaneously injected daily with a dose of ca 8 micromol of Cr/mouse, during 5 days. The control group was injected with 0.5 mL of BT buffer. Testis and epididymis morphology was evaluated using light and transmission electron microscopy. Epididymal sperm counts, motility and acrosome integrity were also assayed using standard methods., Results: Seminiferous epithelium abnormalities were detected in the CrV-BT experimental group, including intraepithelial vacuolation, and remarkable degeneration of Sertoli cells, spermatocytes and spermatids. The premature release of germ cells into the tubular lumen was also evident. Histological evaluation of epididymal compartments revealed apparently normal features. However, the epididymal epithelium presented vacuolation. [CrV-BT](2-) induced a reduction in sperm acrosome integrity. However, sperm motility and density were not significantly affected., Conclusion: This in vivo study using a Cr(V) compound, provides evidence for the potential reproductive hazards caused on male reproductive system by species containing chromium in intermediate oxidation states.

Transport of macromolecules from the interstitial testis tissue to cells at the adlumenal compartment of the seminiferous epithelium occurs naturally through Sertoli cells. In previous studies we have shown that Cr(V) intoxication disturbed spermatogenesis in mice. To test if Sertoli cells are affected by chromium, a well proved carcinogen, the uptake and the horseradish peroxidase transport ability of isolated seminiferous tubules of mice administered with a chromium(V) compound, have been studied. Male CD-R mice were exposed daily for 5 days to [CrV-BT]2- through subcutaneous injection and comparisons were made with groups of vehicle-treated mice. Using an in vitro assay we demonstrated that the seminiferous tubules were able to uptake and transport the tracer, in a much faster way than controls, mainly via intercellular and transcellular pathways, providing evidence that this functional role of Sertoli cells is affected by the Cr(V) compound. These findings might improve the knowledge on the toxicity mechanisms of chromium.

Chromium toxicity is strongly dependent on its oxidation state. Cr(VI) is carcinogenic and mutagenic, although its in vivo and in vitro toxic effects are related to its intracellular fate. Inside the cells, Cr(VI) is rapidly reduced to stable Cr(III). As Cr(V) and Cr(IV) species have been reported to be formed in the Cr(VI) reduction pathways, Cr(VI)-induced damage is thought, at least in part, to arise from these hypervalent species. The study of Cr(VI) reduction mechanisms and the characterization of the effects of each reactive intermediate constitute important steps towards a better understanding of chromium toxicity. The purpose of this work is to enlarge the scope of Cr(VI)-induced alterations in mouse to other chromium species. Our studies have led to the in situ preparation of a new Cr(V) complex, 1Cr(V)-BT](2-), a stable compound at neutral pH, which mimics Cr(VI) reduction intermediates. The effect of Cr(V) on the histology of mice liver is assessed and compared with similar Cr(VI) assays. Liver toxicity was examined after single administrations of Cr(VI) or [Cr(V)-BT](2-) to mice. Both compounds produced reversible hepatic damage in a time-dependent manner. However, Cr(V) toxic effects have proved to be more rapid than with Cr(VI), permitting the role of Cr(VI) intermediates formed during intracellular chromium reduction to be highlighted.

Aim: The functional integrity of the blood-testis barrier (BTB) in male mice exposed to Cr(V) was studied in order to clarify the mechanism underlying testicular injury., Methods: Adult male mice were subcutaneously injected repeated doses of 8.02 micromol (0.5 ml) of Cr/mouse.day for 5 days. Animals receiving a similar volume of bis(hydroxyethyl)-aminotris(hydroxymethyl)methane buffer (BT) were used as controls. The animals were sacrificed on day 6 and small fragments of seminiferous tubules, approximately 8-10 mm length, were incised and sutured at both ends. They were exposed in vitro to horseradish peroxidase-containing culture medium for 10 minutes. Tissues were then fixed and processed for ultrastructural studies., Results: Controls and Cr(V)-treated group resulted in the uptake of the tracer by Sertoli cells. However, the major finding consisted in the permeability of the BTB only in the Cr(V)-group, as evidenced by the presence of the tracer within the junctions between the neighbouring Sertoli cells., Conclusion: The BTB is disrupted in mice submitted to Cr(V). The permeability of the BTB is a crucial feature to be investigated for the understanding of lesions within the seminiferous tubule.

The complexes [Ru([9]aneS(3))(dppz)Cl]Cl 1 and [Ru([12]aneS(4))(dppz)]Cl(2)2 ([9]aneS(3) = 1,4,7- trithiaciclononane and [12]aneS(4) = 1,4,7,10-tetrathiaciclododecane) were synthesised and fully characterised. These complexes belong to a small family of dipyridophenazine complexes with non-polypyridyl ancillary ligands . Interaction studies of these complexes with CT-DNA (UV/Vis titrations, steady-state emission and thermal denaturation) revealed their high affinity for DNA . Intercalation constants determined by UV/Vis titrations are of the same order of magnitude (10(6)) as other dppz metallointercalators, namely [Ru(II)(bpy)(2)dppz]S(2+). Differences between l and2 were identified by steady-state emission and thermal denaturation studies . Emission results are in accordance with structural data, which indicate how geometric distortions and different donor and/or acceptor ligand abilities affect luminescence. The possibility of noncovalent interactions between ancillary ligands and nucleobases by van der Waals contacts and H-bridges is discussed . Furthermore, complex l undergoes aquation under intra-cellular conditions and an equilibrium with the aquated form l' is attained . This behaviour may increase the diversity of available interaction modes.

Cr(VI), the highest oxidation state for chromium, is a carcinogenic and mutagenic agent. In vivo and in vitro Cr(VI) toxic effects are related to its intracellular fate. Once inside the cell it is reduced to stable Cr(III) by cysteine, glutathione and ascorbic acid. Additionally, as Cr(V) and/or Cr(IV) intermediates have been reported in Cr(VI) reactions with biological reductants, chromium damage is thought to originate from these chemical species. This work investigated the morphology of splenic cells after short-term exposure to Cr(VI). A dose of 30 mg of K2CrO4/kg body weight was administered to mice and the effects were studied 24 and 48 h after the injections. Histological results revealed a time-dependency effect of Cr(VI) on splenic cells. Changes included enlargement of the capsule and depletion of the red pulp cells, accompanied by an increase in macrophages, 24 h after injection. Partial restoration of red pulp was noted after 48 h.