Analytic lymph node number establishes staging accuracy by occult tumor burden in colorectal cancer.

BACKGROUND AND OBJECTIVES: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden. METHODS: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category were defined by multivariable polytomous and semi-parametric polytomous logistic regression. RESULTS: Occult tumor burden stratified this pN0 cohort into categories of low (60%; recurrence rate (RR) = 2.3% [95% CI 0.1-4.5%]), intermediate (31%; RR = 33.3% [23.7-44.1%]), and high (9%; RR = 68.0% [46.5-85.1%], P \u3c 0.001) risk of recurrence. Beyond race and T stage, the number of analytic nodes was an independent marker of risk category (P \u3c 0.001). When \u3e12 nodes were analyzed, occult tumor burden almost completely resolved prognostic risk classification of pN0 patients. CONCLUSIONS: The prognostic utility of occult tumor burden assessed by GUCY2C RT-qPCR is dependent on the number of analytic lymph nodes

Magnetization of small lead particles

The magnetization of an ensemble of isolated lead grains of sizes ranging from below 6 nm to 1000 nm is measured. A sharp disappearance of Meissner effect with lowering of the grain size is observed for the smaller grains. This is a direct observation by magnetization measurement of the occurrence of a critical particle size for superconductivity, which is consistent with Anderson's criterion.Comment: 7 pages, 5 figures, Submitted to PR

Geração de modelo digital de terreno hidrologicamente consistente para delimitação de bacia hidrográfica na Amazônia.

O objetivo deste trabalho foi gerar um modelo digital de terreno hidrologicamente consistente (MDTHC) para a delimitação da bacia hidrográfica do rio Taxidermista no município de Alta Floresta, localizado no norte do estado de Mato Grosso, no bioma Amazônia. Essa região é uma das áreas de estudo definidas no projeto ?Construção do conhecimento e sistematização de experiências sobre valoração e pagamento por serviços ecossistêmicos e ambientais no contexto da agricultura familiar amazônica (ASEAM)?. Para a geração do MDTHC, inicialmente foram utilizados dados referentes a pontos cotados, curvas de nível e hidrografia, provenientes de cartas topográficas, utilizando o interpolador Topo to Raster, do software SIG ArcMap (versão 10.8). Em seguida, o MDTHC foi gerado por meio do aprofundamento da drenagem, utilizando a ferramenta Arc Hydro Tools do ArcMap. O MDTHC foi utilizado na delimitação da bacia hidrográfica do rio Taxidermista, na região de Alta Floresta. O modelo digital de terreno (MDT) gerado pelo interpolador Topo to Raster mostrou-se preciso quando comparado à delimitação feita com base em um modelo digita de elevação (MDE) derivado do Shuttle Radar Topography Mission (SRTM). Igualmente, o MDTHC gerado mostrou-se eficaz na delimitação da bacia hidrográfica do rio Taxidermista, no bioma AmazôniaEvento online. CIIC 2021

Snakebites By Bothrops Spp In Children In Campinas, São Paulo, Brazil.

From January, 1984 to March, 1999, 73 children under 15 y old (ages 1-14 y, median 9 y) were admitted after being bitten by snakes of the genus Bothrops. Twenty-six percent of the children were classified as mild envenoming, 50.7% as moderate envenoming and 20.6% as severe envenoming. Two patients (2.7%) showed no signs of envenoming. Most of the patients presented local manifestations, mainly edema (94.5%), pain (94.5%) ecchymosis (73.9%) and blisters (11%). Local and/or systemic bleeding was observed in 28.8% of the patients. Before antivenom (AV) administration, blood coagulation disorders were observed in 60.7% (incoagulable blood in 39.3%) of the 56 children that received AV only in our hospital. AV early reactions, most of which were considered mild, were observed in 44.6% of these cases (in 15/30 patients not pretreated and in 10/26 patients pretreated with hydrocortisone and histamine H1 and H2 antagonists). The main clinical complications observed were local infection (15.1%), compartment syndrome (4.1%), gangrene (1.4%) and acute renal failure (1.4%). No deaths were recorded. There were no significant differences with regard to severity of envenoming versus the frequency of blood coagulation disorders among the three categories of envenoming (p = 0.75) or in the frequency of patients with AV early reactions between the groups that were and were not pretreated (p = 0.55). The frequency of local infection was significantly greater in severe cases (p < 0.001). Patients admitted more than 6 h after the bite had a higher risk of developing severe envenoming (p = 0.04).43329-3

Molecular staging individualizing cancer management

Although the most important prognostic and predictive marker in colorectal cancer is tumor cells in lymph nodes, ∼30% of patients who are node-negative die from occult metastases. Molecular staging employing specific markers and sensitive detection technologies has emerged as a powerful platform to assess prognosis in node-negative colon cancer. Integrating molecular staging into algorithms that individualize patient management will require validation and the definition of relationships between occult tumor cells, prognosis, and responses to chemotherapy. J. Surg. Oncol. 2012; 105:468-474. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.

Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy. Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity of subjects as joint primary outcomes. Results: All patients receiving Ad5-GUCY2C-PADRE completed the study and none developed adverse events greater than grade 1. Antibody responses to GUCY2C were detected in 10% of patients, while 40% exhibited GUCY2C-specific T-cell responses. GUCY2C-specific responses were exclusively CD8+ cytotoxic T cells, mimicking pre-clinical studies in mice in which GUCY2C-specific CD4+ T cells are eliminated by self-tolerance, while CD8+ T cells escape tolerance and mediate antitumor immunity. Moreover, pre-existing neutralizing antibodies (NAbs) to the Ad5 vector were associated with poor vaccine-induced responses, suggesting that Ad5 NAbs oppose GUCY2C immune responses to the vaccine in patients and supported by mouse studies. Conclusions: Split tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector. TRIAL REGISTRATION: This trial (NCT01972737) was registered at ClinicalTrials.gov on October 30th, 2013. https://clinicaltrials.gov/ct2/show/NCT01972737

Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide

Disponibilidade De Antídotos No Município De Campinas, São Paulo

The lack of availability of antidotes in emergency services is a worldwide concern. The aim of the present study was to evaluate the availability of antidotes used for treating poisoning in Campinas (SP). DESIGN AND SETTING: This was a cross-sectional study of emergency services in Campinas, conducted in 2010-2012. METHODS: The availability, amount in stock, place of storage and access time for 26 antidotal treatments was investigated. In the hospitals, the availability of at least one complete treatment for a 70 kg adult over the first 24 hours of admission was evaluated based on stock and access recommendations contained in two international guidelines. RESULTS: 14 out of 17 functioning emergency services participated in the study, comprising pre-hospital services such as the public emergency ambulance service (SAMU; n = 1) and public emergency rooms for admissions lasting ≤ 24 hours (UPAs; n = 3), and 10 hospitals with emergency services. Six antidotes (atropine, sodium bicarbonate, diazepam, phytomenadione, flumazenil and calcium gluconate) were stocked in all the services, followed by 13 units that also stocked activated charcoal, naloxone and diphenhydramine or biperiden. No service stocked all of the recommended antidotes; only the regional Poison Control Center had stocks close to recommended (22/26 antidotal treatments). The 10 hospitals had almost half of the antidotes for starting treatments, but only one quarter of the antidotes was present with stocks sufficient for providing treatment for 24 hours. CONCLUSION: The stock of antidotes for attending poisoning emergencies in the municipality of Campinas is incomplete and needs to be improved. © 2017, Associacao Paulista de Medicina. All rights reserved.13511522FAPEAM, Fundação de Amparo à Pesquisa do Estado do Amazona

Effect of low-level laser therapy (gaaias - λ660 Nm) on muscle function

Introduction: Low-level laser therapy (LLLT) is effective in preventing fatigue and in stimulating the microcirculation and cellular activity. In this study, we examined the effect of LLLT on injured tibial muscle in vivo by assessing muscle function during fatigue. Methods: Twenty-four male mice were used. Each mouse received an injection of sterile 0.9% saline solution (50 µL) in the right tibialis anterior muscle, after which the tendon of the muscle was exposed, connected to an isometric transducer and subjected to a resting tension of 1 g. A bipolar electrode was attached to the tibial nerve for electrical stimulation. The mice were randomly allocated to one of two groups: G1 (control: 3 h - n=8 and 9 h - n=5) and G2 (treated with GaAlAs laser, λ660 nm, 35 mW, 0.6 J, 17 s: 3 h - n=6 and 9 h - n=5). Results: In G1 mice, the amplitude of the tetanic contracture in response to induced fatigue remained unchanged during six consecutive tetani. The amplitude of the tetanic contractions in response to electrical stimulation (4-8 mV) was also unchanged. These results indicated muscle intactness in response to the load imposed by tetanus. In G2 mice, there was an increase in the amplitude of contraction after 3 h and 9 h when compared to G1 at 83% tetanus. Conclusion: These results indicate that exposure of muscle to LLLT enhanced the contractile force and increased the resistance to muscle fatigue without causing morphological damage to cellular structures. © 2015 Sociedade Brasileira de Engenharia Biomedica.Low-level laser therapy (LLLT) is effective in preventing fatigue and in stimulating the microcirculation and cellular activity. In this study, we examined the effect of LLLT on injured tibial muscle in vivo by assessing muscle function during fatigue. Methods: Twenty-four male mice were used. Each mouse received an injection of sterile 0.9% saline solution (50 µL) in the right tibialis anterior muscle, after which the tendon of the muscle was exposed, connected to an isometric transducer and subjected to a resting tension of 1 g. A bipolar electrode was attached to the tibial nerve for electrical stimulation. The mice were randomly allocated to one of two groups: G1 (control: 3 h - n=8 and 9 h - n=5) and G2 (treated with GaAlAs laser, λ660 nm, 35 mW, 0.6 J, 17 s: 3 h - n=6 and 9 h - n=5). Results: In G1 mice, the amplitude of the tetanic contracture in response to induced fatigue remained unchanged during six consecutive tetani. The amplitude of the tetanic contractions in response to electrical stimulation (4-8 mV) was also unchanged. These results indicated muscle intactness in response to the load imposed by tetanus. In G2 mice, there was an increase in the amplitude of contraction after 3 h and 9 h when compared to G1 at 83% tetanus. Conclusion: These results indicate that exposure of muscle to LLLT enhanced the contractile force and increased the resistance to muscle fatigue without causing morphological damage to cellular structures31324124