Pioneering the implementation of a precision oncology strategy in Portugal: the Precision Oncology Platform trial.

BACKGROUND AND PURPOSE: The Precision Oncology Platform (POP) trial represents the effort of the Portuguese Oncology Institute of Porto (IPO Porto) for joining other leading European institutions in both 'Personalised Cancer Medicine for all EU citizens' (PCM4EU), and 'PRecisIon Cancer MEdicine RepurpOsing SystEm Using Pragmatic Clinical Trials' (PRIME-ROSE) consortia, enabling the development of the Portuguese version of the Drug Rediscovery Protocol (DRUP)-like Clinical Trial (DLCT), based on the experience of the DRUP trial developed in The Netherlands. PATIENTS/MATERIAL AND METHODS: The POP trial is a phase II, pragmatic multicentric, non-randomised, open-label study, designed entirely like the other DLCTs. Its primary objective is to describe anti-tumour activity of targeted anticancer drugs in patients with advanced malignancies harbouring actionable molecular alterations. The primary endpoint is disease control rate (DCR). Secondary endpoints encompass treatment-related grade ≥3 adverse events, objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory objectives will assess biomarkers, resource use and costs, and patient-reported outcome measures (PROMs). INTERPRETATION: The POP trial will offer access to innovative treatments for patients without further therapeutic options and provide evidence on efficacy and safety of molecularly-guided treatments. Methodologically, it represents a pioneer approach in Portugal, including a pay-for-performance model embedded in the clinical trial. The POP trial represents a unique opportunity to integrate clinical research within cancer care, pursuing an evidence-based precision oncology strategy, and facilitating its rational and cost-effective implementation into the Portuguese healthcare system.

PCM4EU and PRIME-ROSE: Collaboration for implementation of precision cancer medicine in Europe.

BACKGROUND: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. PATIENTS AND METHODS: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. RESULTS: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.

Full-fat corn germ improves the performance and milk fat yield of Girolando cows fed sugarcane bagasse and cactus cladodes as forage sources.

We investigated the effects of replacing ground corn with full-fat corn germ (FFCG) on milk production, milk composition, and nutrient use in cows fed sugarcane bagasse and cactus cladodes. Ten multiparous Girolando cows (average body weight 500 ± 66 kg, 90 ± 15 days in milk) were distributed in a replicated 5 × 5 Latin Square and assigned to five dietary treatments containing 0%, 25%, 50%, 75%, or 100% of full-fat corn germ in substitution to ground corn. Full-fat corn germ increased fat-corrected milk yield by 2.2 kg/day and the synthesis of fat, lactose, and total solids in milk by 94.4, 60.0, and 201.10 g/day, respectively (p < 0.05). Cows fed corn germ quadratically increased (p < 0.05) dry matter intake by 1.01 kg/day, with the intake of crude protein and total digestible nutrients following the same pattern. Conversely, the substitution of corn for full-fat corn germ linearly reduced (p < 0.05) the total non-fiber carbohydrate intake from 5.79 to 4.40 kg/d. Except for ether extract and non-fiber carbohydrates, full-fat corn germ did not alter (p > 0.05) nutrient digestibility. Cows fed corn germ excreted less (p < 0.05) urea-N in milk and urine N. These results demonstrate that full-fat corn germ can partially replace ground corn to enhance the milk production efficiency of crossbred cows fed cactus cladodes and sugarcane bagasse. Furthermore, including sugarcane bagasse in FFCG-supplemented diets prevents milk fat depression in cows fed cactus cladodes.

Brazilian Angiology and Vascular Surgery Society Guidelines for the treatment of extracranial cerebrovascular disease.

Extracranial cerebrovascular disease has been the subject of intense research throughout the world, and is of paramount importance for vascular surgeons. This guideline, written by the Brazilian Society of Angiology and Vascular Surgery (SBACV), supersedes the 2015 guideline. Non-atherosclerotic carotid artery diseases were not included in this document. The purpose of this guideline is to bring together the most robust evidence in this area in order to help specialists in the treatment decision-making process. The AGREE II methodology and the European Society of Cardiology system were used for recommendations and levels of evidence. The recommendations were graded from I to III, and levels of evidence were classified as A, B, or C. This guideline is divided into 11 chapters dealing with the various aspects of extracranial cerebrovascular disease: diagnosis, treatments and complications, based on up-to-date knowledge and the recommendations proposed by SBACV.

Brazilian Society of Angiology and Vascular Surgery 2023 guidelines on the diabetic foot.

The diabetic foot interacts with anatomical, vascular, and neurological factors that challenge clinical practice. This study aimed to compile the primary scientific evidence based on a review of the main guidelines, in addition to articles published on the Embase, Lilacs, and PubMed platforms. The European Society of Cardiology system was used to develop recommendation classes and levels of evidence. The themes were divided into six chapters (Chapter 1 - Prevention of foot ulcers in people with diabetes; Chapter 2 - Pressure relief from foot ulcers in people with diabetes; Chapter 3 -Classifications of diabetic foot ulcers; Chapter 4 - Foot and peripheral artery disease; Chapter 5 - Infection and the diabetic foot; Chapter 6 - Charcot's neuroarthropathy). This version of the Diabetic Foot Guidelines presents essential recommendations for the prevention, diagnosis, treatment, and follow-up of patients with diabetic foot, offering an objective guide for medical practice.

New Approaches in Early-Stage NSCL Management: Potential Use of PARP Inhibitors and Immunotherapy Combination.

Lung cancer is the second most common cancer in the world, being the first cause of cancer-related mortality. Surgery remains the only potentially curative treatment for Non-Small Cell Lung Cancer (NSCLC), but the recurrence risk remains high (30-55%) and Overall Survival (OS) is still lower than desirable (63% at 5 years), even with adjuvant treatment. Neoadjuvant treatment can be helpful and new therapies and pharmacologic associations are being studied. Immune Checkpoint Inhibitors (ICI) and PARP inhibitors (PARPi) are two pharmacological classes already in use to treat several cancers. Some pre-clinical studies have shown that its association can be synergic and this is being studied in different settings. Here, we review the PARPi and ICI strategies in cancer management and the information will be used to develop a clinical trial to evaluate the potential of PARPi association with ICI in early-stage neoadjuvant setting NSCLC.

Brazilian guidelines on diagnosis and management of traumatic vascular injuries.

Trauma is a leading cause of death, permanent disability, and health care cost worldwide. The young and economically active are the most affected population. Exsanguination due to noncompressible torso hemorrhage is one of the most frequent causes of early death, posing a significant challenge to trauma and vascular surgeons. The possibility of limb loss due to vascular injuries must also be considered. In recent decades, the approach to vascular injuries has been significantly modified. Angiotomography has become the standard method for diagnosis, endovascular techniques are currently incorporated in treatment, and damage control, such as temporary shunts, is now the preferred approach for the patients sustaining physiological derangement. Despite the importance of this topic, few papers in the Brazilian literature have offered guidelines on vascular trauma. The Brazilian Society of Angiology and Vascular Surgery has developed Projetos Diretrizes (Guideline Projects), which includes this publication on vascular trauma. Since treating trauma patients is a multidisciplinary effort, the Brazilian Trauma Society (SBAIT) was invited to participate in this project. Members of both societies reviewed the literature on vascular trauma management and together wrote these guidelines on vascular injuries of neck, thorax, abdomen, and extremities.

Guidelines on vascular access for hemodialysis from the Brazilian Society of Angiology and Vascular Surgery.

Chronic kidney disease is a worldwide public health problem, and end-stage renal disease requires dialysis. Most patients requiring renal replacement therapy have to undergo hemodialysis. Therefore, vascular access is extremely important for the dialysis population, directly affecting the quality of life and the morbidity and mortality of this patient population. Since making, managing and salvaging of vascular accesses falls within the purview of the vascular surgeon, developing guideline to help specialists better manage vascular accesses for hemodialysis if of great importance. Thus, the objective of this guideline is to present a set of recommendations to guide decisions involved in the referral, evaluation, choice, surveillance and management of complications of vascular accesses for hemodialysis.

A doença renal crônica é um problema de saúde pública global e em seu estágio terminal está associada à necessidade de terapia dialítica. A grande maioria dos pacientes que necessitam realizar a terapia renal substitutiva, a fazem através da hemodiálise. Portanto, o acesso vascular é de extrema importância para a população dialítica, implicando diretamente na qualidade de vida e na morbimortalidade deste grupo de pacientes. Sendo a confecção, gerenciamento e resgate dos acessos vasculares uma das áreas de atuação do cirurgião vascular, é de grande importância a elaboração de uma diretriz que oriente o especialista no manejo mais adequado do acesso vascular para hemodiálise. Assim, o objetivo desta diretriz é apresentar um conjunto de recomendações para guiar as decisões na referenciação, avaliação, escolha, vigilância e gestão das complicações do acesso vascular para hemodiálise.

Brazilian guidelines on chronic venous disease of the Brazilian Society of Angiology and Vascular Surgery.

The Brazilian Society of Angiology and Vascular Surgery has set up a committee to provide new evidence-based recommendations for patient care associated with chronic venous insufficiency. Topics were divided in five groups: 1. Classification, 2. Diagnosis, 3. Conservative or non-invasive treatment, 4. Invasive treatment and 5. Treatment of small vessels. This last series is closely related to the activities of Brazilian angiologists and vascular surgeons, who are heavily involved in the treatment of small superficial veins. These guidelines are intended to assist in clinical decision-making for attending physicians and health managers. The decision to follow a guideline recommendation should be made by the responsible physician on a case-by-case basis taking into account the patient's specific condition, as well as local resources, regulations, laws, and clinical practice recommendations.

A Sociedade Brasileira de Angiologia e de Cirurgia Vascular organizou uma comissão para fornecer novas recomendações baseadas em evidências sobre questões críticas de atendimento ao paciente com insuficiência venosa crônica. São abordados aqui os temas de classificação, diagnóstico, tratamento conservador, tratamento invasivo e tratamento de pequenos vasos. Esta última série está muito relacionada à atividade de angiologistas e cirurgiões vasculares, que possuem forte atuação no tratamento de pequenas veias superficiais. Estas diretrizes destinam-se a auxiliar na tomada de decisões clínicas de médicos assistentes e gestores de saúde. A decisão de seguir uma recomendação de diretriz deve ser feita pelo médico responsável caso a caso, levando em consideração a condição específica do paciente, bem como recursos locais, regulamentos, leis e recomendações de prática clínica.

Brazilian Society for Angiology and Vascular Surgery guidelines on abdominal aortic aneurysm.

The Brazilian Society of Angiology and Vascular Surgery, through the Guidelines Project, presents new Abdominal Aortic Aneurysm Guidelines, on the subject of care for abdominal aortic aneurysm patients. Its development prioritized descriptive guidelines, using the EMBASE, LILACS, and PubMed databases. References include randomized controlled trials, systematic reviews, meta-analyses, and cohort studies. Quality of evidence was evaluated by a pair of coordinators, aided by the RoB 2 Cochrane tool and the Newcastle Ottawa Scale forms. The subjects include juxtarenal aneurysms, infected aneurysms, and new therapeutic techniques, especially endovascular procedures. The current version of the guidelines include important recommendations for the primary topics involving diagnosis, treatment, and follow-up for abdominal aortic aneurysm patients, providing an objective guide for medical practice, based on scientific evidence and widely available throughout Brazil.

A Sociedade Brasileira de Angiologia e Cirurgia Vascular, por meio do projeto Diretrizes, apresenta as novas Diretrizes de Aorta Abdominal, referentes aos cuidados de pacientes com aneurisma de aorta abdominal. Para sua elaboração, foram priorizadas diretrizes descritivas, utilizando as bases EMBASE, LILACS e PubMed. As referências incluem ensaios clínicos randomizados, revisões sistemáticas, metanálises e estudos de coorte. A qualidade das evidências foi examinada por uma dupla de coordenadores, com auxílio da ferramenta RoB 2 da Colaboração Cochrane e dos formulários da Newcastle Ottawa Scale. Aneurismas justarrenais, infectados e novas técnicas terapêuticas, principalmente no âmbito endovascular, estão entre os temas estudados. A versão atual das Diretrizes apresenta importantes recomendações para os principais itens que envolvem o diagnóstico, tratamento e acompanhamento de pacientes com aneurisma de aorta abdominal, oferecendo um guia objetivo para prática médica, construído a partir de evidências científicas e amplamente acessível em todo o território nacional.

Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin.

Pirfenidone, an antifibrotic drug, has antitumor potential against different types of cancers. Our work explored whether pirfenidone sensitizes non-small cell lung cancer (NSCLC) cell lines to chemotherapeutic treatments. The cytotoxic effect of paclitaxel in combination with pirfenidone against three NSCLC cell lines (A549, NCI-H322 and NCI-H460) was evaluated using the sulforhodamine B assay. The effects of this combination on cell viability (trypan blue exclusion assay), proliferation (BrdU incorporation assay), cell cycle (flow cytometry following PI staining) and cell death (Annexin V-FITC detection assay and Western blot) were analyzed on the most sensitive cell line (NCI-H460). The cytotoxic effect of this drug combination was also evaluated against two non-tumorigenic cell lines (MCF-10A and MCF-12A). Finally, the ability of pirfenidone to sensitize NCI-H460 cells to a combination of paclitaxel plus carboplatin was assessed. The results demonstrated that pirfenidone sensitized NCI-H460 cells to paclitaxel treatment, reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile and causing an increase in the % of cell death. Remarkably, this combination did not increase cytotoxicity in non-tumorigenic cells. Importantly, pirfenidone also sensitized NCI-H460 cells to paclitaxel plus carboplatin. This work highlights the possibility of repurposing pirfenidone in combination with chemotherapy for the treatment of NSCLC.

Assisted total thermal ablation: presentation of the ATTA technique.

Treatment of lower limb chronic venous disease has progressed exponentially over recent decades. The advances achieved have made it possible to develop a proposal for a systematized intravenous laser ablation technique - assisted total thermal ablation (ATTA). The technique constitutes a standardized method for management of axial or tributary veins that are varicosed or esthetically unappealing, whether in the lower limbs or other areas, that can be performed on an outpatient or day-hospital basis. This article describes the processes for preoperative preparation and detailed marking, the materials needed, venous access, anesthesia, calculation of power and energy, the ablation technique itself, follow-up, and adverse events. The ATTA technique is proposed as a tool for treatment of chronic venous disease and of esthetically unappealing veins, suggesting possible extension of the applications for lasers beyond trunk veins to any vein that can be punctured.

External validity of type 2 diabetes clinical trials on cardiovascular outcomes for a multimorbid population.

AIM: To investigate the external validity of recent antihyperglycaemic trials evaluating cardiovascular outcomes in a multimorbid population. MATERIALS AND METHODS: Selection criteria of 15 randomized controlled trials from the 2020 American Diabetes Association Standard of Care statement were applied in a stepwise manner to tertiary care patients with type 2 diabetes. Primary outcomes were the number of patients eligible per individual trial and for the aggregate of trials. Secondary outcomes included patient predictors of trial eligibility. RESULTS: Of 1059 patients, the mean (SD) age was 66 (10.74) years, the median (IQR) Charlson index was 2 (2, 3) and 458 (43%) had documented cardiovascular disease. The median (IQR) number of patients included in individual trials was 263 (174.25-308.75) and 795 (75.1%) of them were eligible for at least one trial. Among those 264 ineligible, 127 (48.1%) had an HbA1c level of 7% or less and no cardiovascular disease; 53.5% and 34.4% of the patients were eligible for two and three different classes of drugs, respectively. The strongest predictor of trial eligibility was cardiovascular disease (risk ratio 2.17, 95% CI 2.01-2.35). CONCLUSIONS: A considerable proportion of multimorbid patients would be eligible for recent antihyperglycaemic trials. This positive finding can be attributed to development guidance in diabetes trials and the different approach we took, in which we evaluated inclusion by trials as an aggregate.

Age-related macular degeneration and resource utilization in the Brazilian public healthcare system: a real-world retrospective study.

BACKGROUND: Age-related macular degeneration (AMD) is a disease that causes damage in the macular region of the retina, leading to irreversible blindness. This study aims to understand the profile and care of patients with AMD and its cost at the Brazilian public health system to identify AMD-care needs. METHODS: This is a retrospective observational study of AMD with real-world data from the Brazilian public healthcare system, using DATASUS claim databases. Patients with AMD were selected from 01/Jan/2014 to 31/Jan/2020; had at least one claim of ICD10 code H35.3 (Degeneration of macula and posterior pole), and were submitted to one of two procedures exclusively available for AMD patients - optical coherence tomography (OCT) and medical treatment of retinal disease (antiangiogenic); aged ≥18 years at first ICD10 claim, and presenting at least 1 year of follow-up in the database. We described patients' characteristics, healthcare resource utilization and cost, and the antiangiogenic intravitreal treatment received by AMD patients, including the number of doses and interval time between them. RESULTS: Patients searching for AMD treatment since 2014 were mostly females (59%), white (61%), and a mean age of 72 years. They were mainly located in the Southeast (87%), and few patients were found in the North (1%) and Central-West (1.5%) regions, probably reflecting where the Brazilian guideline to treat AMD (Protocolo Clínico e Diretrizes Terapêuticas - PCDT) was incorporated as routine care for AMD. The average antiangiogenic dose of 2.5 antiangiogenic therapies within a year was below the expected. Most injections had an interval time of 20 to 40 days between doses, although some patients were treated more than 100 days. Another setback is that patients traveled longer distances for OCT and antiangiogenic treatment than overall AMD-healthcare, between 10 and 100 km. CONCLUSIONS: AMD patients seem to be undertreated, as they receive a mean of 2.5 doses of antiangiogenic treatment within a year. Inequalities among regions are evident, as the Southeast and South regions comprise almost all patients receiving the treatment from the public health system, probably reflecting the region with more access to AMD care according to PCDT recommendations.

Limb ischemia in patients with COVID-19.

This narrative review covers the life-threatening thromboembolic events associated with SARS-CoV-2 infection/COVID-19. It addresses the physical changes that cause vascular and arterial damage to limbs, laboratory management of coagulation, and management of anticoagulation. COVID-19's relationship with deep venous thrombosis and arterial thrombosis is also emphasized. The main thromboembolic events described in the literature are illustrated with examples from our experience with COVID-19 patients.

Esta revisão narrativa abrange os eventos tromboembólicos com risco de vida associados a infecção por SARS-CoV-2/COVID-19. Aborda as mudanças físicas que causam danos vasculares e arteriais aos membros, o manejo laboratorial da coagulação e o manejo da anticoagulação. A relação de COVID-19 com trombose venosa profunda e trombose arterial também é enfatizada. Os principais eventos tromboembólicos descritos na literatura são ilustrados a partir de nossa experiência com pacientes COVID-19.

Early metformin treatment improves pancreatic function and prevents metabolic dysfunction in early overfeeding male rats at adulthood.

NEW FINDINGS: What is the central question of this study? Studies reported the efficacy of metformin as a promising drug for preventing or treating of metabolic diseases. Nutrient stresses during neonatal life increase long-term risk for cardiometabolic diseases. Can early metformin treatment prevent the malprogramming effects of early overfeeding? What is the main finding and its importance? Neonatal metformin treatment prevented early overfeeding-induced metabolic dysfunction in adult rats. Inhibition of early hyperinsulinaemia and adult hyperphagia might be associated with decreased metabolic disease risk in these animals. Therefore, interventions during infant development offer a key area for future research to identify potential strategies to prevent the long-term metabolic diseases. We suggest that metformin is a potential tool for intervention. ABSTRACT: Given the need for studies investigating the possible long-term effects of metformin use at crucial stages of development, and taking into account the concept of metabolic programming, the present work aimed to evaluate whether early metformin treatment might program rats to resist the development of adult metabolic dysfunctions caused by overnutrition during the neonatal suckling phase. Wistar rats raised in small litters (SLs, three pups per dam) and normal litters (NLs, nine pups per dam) were used as models of early overfeeding and normal feeding, respectively. During the first 12 days of suckling, animals from SL and NL groups received metformin, whereas the controls received saline injections. Food intake and body weight were monitored from weaning until 90 days of age, when biometric and biochemical parameters were assessed. The metformin treatment decreased insulin concentrations in pups from SL groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, body weight gain, white fat pad stores and food intake. Low-glucose insulinotrophic effects were observed in pancreatic islets from both NL and SL groups. These results indicate that early postnatal treatment with metformin inhibits early overfeeding-induced metabolic dysfunctions in adult rats.

Malnutrition during late pregnancy exacerbates high-fat-diet-induced metabolic dysfunction associated with lower sympathetic nerve tonus in adult rat offspring.

Objectives: We aimed to assess the effects of a maternal protein-caloric restriction diet during late pregnancy on the metabolism of rat offspring fed a high-fat diet (HFD) during adulthood.Methods: During late pregnancy, rat dams received either a low-protein (4%; LP group) or normoprotein (23%; NP group) diet. After weaning, the offspring were fed a standard diet (Control; C). Male offspring (60 days old) from both groups were then fed either the C diet or HFD until they were 90 days old. The adult offspring and maternal metabolic parameters and autonomic nervous system (ANS) were then evaluated.Results: Dams exhibited low body weight gain and food intake during the LP diet consumption. At lactation, these dams showed high body weight gain, hypoinsulinemia and hyperglycemia. The maternal LP diet resulted in low body weights for the pups. There were also no differences in the metabolic parameters between the adult LP offspring that were fed the C diet and the NP group. Adults of both groups that were fed the HFD developed obesity associated with altered insulin/ glucose homeostasis and altered ANS activity; however, the magnitudes of these parameters were higher in the LP group than in the NP group.Conclusions: Maternal protein malnutrition during the last third of pregnancy malprograms the metabolism of rat offspring, resulting in increased vulnerability to HFD-induced obesity, and the correlated metabolic impairment might be associated with lower sympathetic nerve activity in adulthood.

Nutritional and performance viability of cactus Opuntia-based diets added to concentrate levels for Girolando lactating dairy cows.

OBJECTIVE: The aim of this research was to evaluate the effect of different concentrate levels in diets based on cactus Opuntia Stricta (Haw.) Haw cladodes over the performance of lactating Girolando cows. METHODS: The experiment involved 10 Girolando multiparous dairy cows (512.6 kg of body weight and producing 13.2kg milk/day), allocated into two 5 x 5 Latin squares. The experimental treatments consisted of control diet composed by cactus Nopalea cochenillifera. Salm-Dyck. cladodes (Nopalea), forage sorghum silage and concentrate (20% at DM basis), and four concentrate levels diets (20, 24, 28 and 32%) plus cactus Opuntia stricta (Haw.) Haw. cladodes (Opuntia) and forage sorghum silage. RESULTS: Regarding cows fed control diet, the nutrients intake were greater than for cows fed with cactus Opuntia and concentrate. Regarding concentrate levels, intakes of dry matter (DM), organic matter (OM), crude protein (CP), non-fiber carbohydrates (NFC) and total digestible nutrients (TDN) of cows increased linearly. The OM, CP and NDF digestibilities were similar in between to control diet and cactus Opuntia-based diets. The digestibility of NFC increased linearly when the concentrate was inserted. The N balance was the same for control diet and cactus Opuntia-based diets, irrespective the concentrate levels. CONCLUSION: For cows producing 14 kg/day with 3.5% of fat, it is recommended 32% of concentrate inclusion in cactus Opuntia-based diets, and the increase in concentrate level promotes a linear increase in milk yield.

Leg ulcers in sickle cell disease patients.

Leg ulcers are the most common cutaneous complication of sickle cell disease. These lesions occur mainly in homozygous forms, are slow to heal and often relapse, causing negative physical, emotional, and economic impacts. In this paper, we discuss the clinical presentation, diagnosis, and pathophysiology of sickle cell leg ulcers and their implications for treatment.

Moderate exercise training since adolescence reduces Walker 256 tumour growth in adult rats.

KEY POINTS: Cancer growth, cell proliferation and cachexia index can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins in adolescence. Walker 256 tumour-bearing rats who started exercise training during adolescence did not revert the basal low glycaemia and insulinaemia observed before tumour cell inoculation. The moderate exercise training improved glucose tolerance and peripheral insulin sensitivity only in rats exercised early in adolescence. The chronic effects of our exercise protocol are be beneficial to prevent cancer cachexia and hold clear potential as a nonpharmacological therapy of insulin sensitization. ABSTRACT: We tested the hypothesis that moderate exercise training, performed early, starting during adolescence or later in life during adulthood, can inhibit tumour cell growth as a result of changes in biometric and metabolic markers. Male rats that were 30 and 70 days old performed a treadmill running protocol over 8 weeks for 3 days week-1 , 44 min day-1 and at 55-65% V̇O2max . After the end of training, a batch of rats was inoculated with Walker 256 carcinoma cells. At 15 days after carcinoma cell inoculation, the tumour was weighed and certain metabolic parameters were evaluated. The data demonstrated that physical performance was better in rats that started exercise training during adolescence according to the final workload and V̇O2max . Early or later moderate exercise training decreased the cachexia index, cell proliferation and tumour growth; however, the effects were more pronounced in rats that exercised during adolescence. Low glycaemia, insulinaemia and tissue insulin sensitivity was not reverted in Walker 256 tumour-bearing rats who trained during adolescence. Cancer growth can be attenuated by the beneficial programming effect of moderate exercise training, especially if it begins during adolescence. In addition, improvement in glucose-insulin homeostasis might be involved in this process.