Repurposing Drugs in Small Animal Oncology.

Repurposing drugs in oncology consists of using off-label drugs that are licensed for various non-oncological medical conditions to treat cancer. Repurposing drugs has the advantage of using drugs that are already commercialized, with known mechanisms of action, proven safety profiles, and known toxicology, pharmacokinetics and pharmacodynamics, and posology. These drugs are usually cheaper than new anti-cancer drugs and thus more affordable, even in low-income countries. The interest in repurposed anti-cancer drugs has led to numerous in vivo and in vitro studies, with some promising results. Some randomized clinical trials have also been performed in humans, with certain drugs showing some degree of clinical efficacy, but the true clinical benefit for most of these drugs remains unknown. Repurposing drugs in veterinary oncology is a very new concept and only a few studies have been published so far. In this review, we summarize both the benefits and challenges of using repurposed anti-cancer drugs; we report and discuss the most relevant studies that have been previously published in small animal oncology, and we suggest potential drugs that could be clinically investigated for anti-cancer treatment in dogs and cats.

IL-10 and IL-12 (P70) Levels Predict the Risk of Covid-19 Progression in Hypertensive Patients: Insights From the BRACE-CORONA Trial.

Background: Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients. Methods: The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome. Results: During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model. Conclusions: This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.

Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. Design, Setting, and Participants: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Interventions: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Results: Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Conclusions and Relevance: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04364893.

Predictive factors for positive surgical margins in the treatment of breast ductal carcinoma in situ.

CONTEXT: Surgery is the main form of treatment for ductal carcinoma in situ (DCIS) of the breast. Among other factors, treatment success requires that the surgical margins are free of disease, to reduce the risk of recurrence. AIMS: The purpose of this study was to analyze factors that might be associated with positive margins in patients diagnosed with DCIS. SETTINGS AND DESIGN: A retrospective analysis was performed of hospital databases from the year 2006 to 2014, to identify patients with an initial diagnosis of DCIS made by percutaneous biopsy. SUBJECTS AND METHODS: Age, the presence of disease symptoms, lesion size on mammogram, and the presence of estrogen receptors, and their relationship to the surgical margins were evaluated in 249 patients. STATISTICAL ANALYSIS USED: Shapiro and Wilcoxon-Mann-Whitney tests were used to verify that the data were normally distributed. Chi-squared test was used to verify the independence of the variables. RESULTS: Lesions measuring 1.55 cm or greater had a relative risk of positive margins after conservative surgery of 1.39 (95% confidence interval [95% CI]: 1.02-1.90). The presence of symptoms had a relative risk of positive margins after conservative surgery of 1.54 (95% CI: 1.17-2.02). CONCLUSION: Lesions measuring 1.55 cm or greater and the presence of symptoms are risk factors for positive margins in the treatment of ductal carcinoma in situ. Therefore, these patients need a better surgical planning in order to reduce the risk of positive margins. There is a clear need for large prospective studies to validate our findings and define other factors that might contribute to the success of surgical resection for ductal carcinoma in situ.

Agro-industrial residues as low-price feedstock for diesel-like fuel production by thermal cracking.

Pyrolysis of industrial fatty wastes (soybean soapstock, beef tallow, and poultry industry waste) was carried out in the absence of catalysts. In all cases, organic mixtures of hydrocarbons and oxygenated compounds were obtained. These mixtures were distilled and diesel-like fractions were isolated and characterized by GC-FID, GC-MS and FT-IR, showing the formation of olefins, paraffins, and some oxygenated compounds such as carboxylic acids and esters. The main physical-chemical properties of those isolated diesel-like fuels (density, viscosity, distillation curve, carbon residue, copper corrosion test, cetane index, cold finger plugging point, acid index and heating value) were determined using ASTM standard methods and matched the Brazilian specification for diesel fuel.

[Occurrence of Aedes (Stegomyia) albopictus (Skuse) in urban area of Tocantins state, Brazil]. / Ocorrência de Aedes (Stegomyia) albopictus (Skuse) em área urbana do estado do Tocantins.

This is the first report of the presence of Aedes albopictus (Skuse) in the Tocantins State, Brazil, in urban area of the Mateiros city. Immature specimens (aquatic stages) of this vector were collected in water reservoirs, treeholes, old tires and others. The existence of Ae. albopictus in the metropolitan area poses a potential risk for the interaction of this mosquito species with the urban human population.

Ocorrência de Aedes (Stegomyia) albopictus (Skuse) em área urbana do estado do Tocantins / Occurrence of Aedes (Stegomyia) albopictus (Skuse) in urban area of Tocantins state, Brazil

Pela primeira vez é registrada a presença do Aedes albopictus (Skuse) em Tocantins, em área urbana da cidade de Mateiros. As coletas foram realizadas em criadouros de formas imaturas (caixas d’água, cisternas, tanques, ocos de árvores, lixo, pneus, etc). A presença de Ae. albopictus em área urbana representa um risco potencial do inter-relacionamento dessa espécie de mosquito com a população.

This is the first report of the presence of Aedes albopictus (Skuse) in the Tocantins State, Brazil, in urban area of the Mateiros city. Immature specimens (aquatic stages) of this vector were collected in water reservoirs, treeholes, old tires and others. The existence of Ae. albopictus in the metropolitan area poses a potential risk for the interaction of this mosquito species with the urban human population.

Constraining the topology of neural networks to ensure dynamics with symmetry properties.

This paper addresses the training of network models from data produced by systems with symmetry properties. It is argued that although general networks are global approximators, in practice some properties such as symmetry are very hard to learn from data. In order to guarantee that the final network will be symmetrical, constraints are developed for two types of models, namely, the multilayer perceptron (MLP) network and the radial basis function (RBF) network. In global modeling problems it becomes crucial to impose conditions for symmetry in order to stand a chance of reproducing symmetry-related phenomena. Sufficient conditions are given for MLP and RBF networks to have a set of fixed points that are symmetrical with respect to the origin of the phase space. In the case of MLP networks such conditions reduce to the absence of bias parameters and the requirement of odd activation functions. This turns out to be important from a dynamical point of view since some phenomena are only observed in the context of symmetry, which is not a structurally stable property. The results are illustrated using bench systems that display symmetry, such as the Duffing-Ueda oscillator and the Lorenz system.