Prospective, randomized trial comparing fluids and dobutamine optimization of oxygen delivery in high-risk surgical patients [ISRCTN42445141]

INTRODUCTION: Preventing perioperative tissue oxygen debt contributes to a better postoperative recovery. Whether the beneficial effects of fluids and inotropes during optimization of the oxygen delivery index (DO(2)I) in high-risk patients submitted to major surgeries are due to fluids, to inotropes, or to the combination of the two is not known. We aimed to investigate the effect of DO(2)I optimization with fluids or with fluids and dobutamine on the 60-day hospital mortality and incidence of complications. METHODS: A randomized and controlled trial was performed in 50 high-risk patients (elderly with coexistent pathologies) undergoing major elective surgery. Therapy consisted of pulmonary artery catheter-guided hemodynamic optimization during the operation and 24 hours postoperatively using either fluids alone (n = 25) or fluids and dobutamine (n = 25), aiming to achieve supranormal values (DO(2)I > 600 ml/minute/m(2)). RESULTS: The cardiovascular depression was an important component in the perioperative period in this group of patients. Cardiovascular complications in the postoperative period occurred significantly more frequently in the volume group (13/25, 52%) than in the dobutamine group (4/25, 16%) (relative risk, 3.25; 95% confidence interval, 1.22–8.60; P < 0.05). The 60-day mortality rates were 28% in the volume group and 8% in the dobutamine group (relative risk, 3.00; 95% confidence interval, 0.67–13.46; not significant). CONCLUSION: In patients with high risk of perioperative death, pulmonary artery catheter-guided hemodynamic optimization using dobutamine determines better outcomes, whereas fluids alone increase the incidence of postoperative complications

Evaluation of the antibacterial activity and colouring capacity of two Hylocereus spp. Epicarps

Betalains are a group of secondary metabolites named chromoalkaloids that are synthesized from tyrosine. These compounds have gained some attention in the last few years mainly due to their interesting bioactive potential, namely antioxidant, antimicrobial, and other bioactive properties [1]. Their strong and vibrant colours are also one of the characteristics by which these compounds have gained visibility in the food and pharmaceutical industries [2]. Betalains can be divided in two groups regarding the colour range: betaxanthins in the orange to yellow range, and betacyanins in the purple to pink range. Thereby, these compounds can be used as natural colouring agents, providing alternatives to the massively used artificial counterparts [3]. Although there are already some natural options in the market, these are not enough to meet the needs of the food industry, due to the growing concern of consumers regarding what they eat.To FCT and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019); C. Lobo Roriz (SFRH/BD/117995/2016) and T.C.S. Pires (SFRH/BD/129551/2017) grants and National funding by FCT- Foundation for Science and Technology, P.I., through the institutional scientific employment program-contract for L. Barros contract. This work is funded by the European Regional Development Fund (ERDF) through the Regional Operational Program North 2020, within the scope of Project Mobilizador Norte-01-0247-FEDER-024479:ValorNatural®.info:eu-repo/semantics/publishedVersio

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio

A View from the Past Into our Collective Future: The Oncofertility Consortium Vision Statement

Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Gomphrena globosa L.: otimização do processo de extração de corantes, avaliação da sua atividade antimicrobiana e incorporação numa matriz alimentar

Devido à grande preocupação por parte dos consumidores em relação aos aditivos artificiais presentes nos alimentos, a procura de alternativas de origem natural tem vindo a ganhar uma grande importância. Este trabalho, focou-se na otimização de três técnicas de extração, extração assistida por calor (EAC), micro-ondas (EAM) e ultrassons (EAU) de flores de Gomphrena globosa L., aplicando uma metodologia de superfície de resposta (MSR), tendo-se estudado os efeitos das variáveis, tempo de processamento (t), temperatura (T) ou potência (P), concentração de etanol (%Et) e razão sólido/líquido (S/L). Como respostas foram utilizados o rendimento de extração e a concentração total de betacianinas determinadas por LC-DAD-ESI/MS. A técnica de extração que apresentou melhores resultados foi a EAU: t = 22 min, P = 500 W; %Et = 0%, e S/L = 5 g/L, conduzindo a um valor de betacianinas totais de 46,9 ± 4,8 mg/g [1,2]. Após ter sido determinada a melhor técnica de extração foi aplicada novamente a MSR no sentido de obter um extrato rico em betacianinas com elevada atividade antimicrobiana. As respostas foram avaliadas em termos das concentrações de extrato necessárias para obter os melhores valores de MIC (concentração mínima inibitória do crescimento) e MBC (concentração mínima bactericida). Os resultados indicaram as seguintes condições ótimas: t = 10,8 min, P = 410,5 W; %Et = 57,8%, e razão S/L = 5 g/L, fornecendo as seguintes respostas de MIC ~0,15 a 0,35 g/L e MBC ~0,30 a 0,65 g/L [3]. Este extrato rico em betacianinas e com elevada atividade antimicrobiana, foi incorporado num gelado, tendo-se verificado ao longo do tempo de prateleira (60 dias) a coloração desejada e sem alteração do seu perfil nutricional. Desta forma, foi possível com o extrato aquoso de flores de G. globosa atribuir a cor pretendida ao gelado e, simultaneamente, conferi-lhe capacidade antimicrobiana.FCT e FEDER sob o Programa PT2020 pelo apoio financeiro ao CIMO (UID/AGR/00690/2013); bolsa de C.L. Roriz (SFRH/BD/117995/2016) e contrato de L. Barros; Fundo Europeu de Desenvolvimento Regional (FEDER) através do Programa Operacional Regional Norte 2020, no âmbito do Projeto NORTE-01-0145-FEDER-023289: DeCodE e do Projeto Mobilizador Norte-01-0247-FEDER-024479: ValorNatural®.info:eu-repo/semantics/publishedVersio

Dragon fruits as an alternative source of colorants: evaluation of antibacterial activity and colouring capacity

Betalains are a group of secondary metabolites named chromoalkaloids that are synthesized from tyrosine. These compounds have gained some attention in the last few years mainly due to their interesting bioactive potential, namely antioxidant, antimicrobial, and other bioactive properties [1]. Their strong and vibrant colours are also one of the characteristics by which these compounds have gained visibility in the food and pharmaceutical industries [2]. Betalains can be divided in two groups regarding the colour range: betaxanthins in the orange to yellow range, and betacyanins in the purple to pink range. Thereby, these compounds can be used as natural colouring agents, providing alternatives to the massively used artificial counterparts [3]. Although there are already some natural options in the market, these are not enough to meet the needs of the food industry, due to the growing concern of consumers regarding what they eat. Thus, the objectives of this work were to: i) obtain bioactive extracts and with strong colouring capacity from the epicarp of two pitaya varieties, white-fleshed pitaya Hylocereus undatus (Haworth) Britton & Rose (WFP) and red-fleshed pitaya Hylocereus costaricensis (F.A.C.Weber) Britton & Rose (RFP); ii) chemically characterize the betalains’ content through HPLC-DAD-ESI/MS; iii) evaluate the bioactive properties of the extracts, namely antimicrobial activity. The extracts were obtained through a dynamic maceration assisted by heat, and the betacyanins’ profile was characterized by HPLC-DAD-ESI/MS. The antibacterial capacity was determined against a panel of Gram-negative and Gram-positive bacteria using the colorimetric method of rapid detection with p-iodonitrotetrazolium chloride (INT), and the responses obtained were expressed as minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. By the chromatographic analysis of the extracts it was possible to identify six compounds in both samples. For the WFP the major compounds identified were 6'-O-malonylbetanin (phylocactin), followed by 4'-malonyl-betanin, while for the RFP the major compound found was phylocactin. In the evaluation of the antibacterial activity, both extracts showed MIC and MBC values that ranged from 10 to 20 mg/mL. Gram-positive bacteria showed to be more susceptible to both extracts then the negative strains. Further studies need to be conducted to better understand the correlation between the bioactive potential and the betacyanins’ composition. Nevertheless, these natural matrixes proved to be viable alternatives for obtaining colouring extracts with antimicrobial properties.To FCT and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019); C. Lobo Roriz (SFRH/BD/117995/2016) and T.C.S. Pires (SFRH/BD/129551/2017) grants and L. Barros contract. This work is funded by ERDF through the Regional Operational Program North 2020, within the scope of Project NORTE-01-0145-FEDER-023289: DeCodE and project Mobilizador Norte-01-0247-FEDER-024479: ValorNatural®info:eu-repo/semantics/publishedVersio

Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae

Abstract Background Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution. Results In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results. Conclusion The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes) are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity