Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 µM DXR P<0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P<0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer

A Diabetes Psychosocial Profile

An educational needs assessment instrument for individuals with diabetes has been developed at the Michigan Diabetes Research and Training Center. Responses to the 110-item questionnaire provide subscores on con structs labeled "Control Problems, " "Psychosocial Impact," "Barriers to Compliance, " "Benefits of Regimen, " "Regimen Complexity," and "Risk of Complications." Com bined with demographic and clinical information, these scores form a com prehensive summary of the patient's attitudes, beliefs, behaviors, and knowledge in relation to diabetes. This summary is in the form of an individ ualized graphic profile that highlights possible prob lem areas to be consid ered when developing patient education and management plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68817/2/10.1177_014572178601200210.pd

Segurança da intervenção fisioterápica precoce após o infarto agudo do miocárdio

Introdução: A fisioterapia na fase I da reabilitação cardiovascular (FTCV) pode ser iniciada de 12 a 24 horas após o infarto agudo do miocárdio (IAM), no entanto, é comum o repouso prolongado no leito em razão do receio de instabilização do paciente. Objetivos: Avaliar as respostas autonômicas e hemodinâmicas de pacientes pós-IAM submetidos ao primeiro dia de protocolo de FTCV fase I, bem como sua segurança. Materiais e métodos: Foram estudados 51 pacientes com primeiro IAM não complicado, 55 ± 11 anos, 76% homens. Foram submetidos ao primeiro dia do protocolo de FTCV fase I, em média 24 horas pós-IAM. A frequência cardíaca (FC) instantânea e os intervalos R-R do ECG foram captados pelo monitor de FC (Polar®S810i) e a pressão arterial (PA) aferida pelo método auscultatório. A variabilidade da FC foi analisada nos domínios do tempo (RMSSD e RMSM dos iR-R em ms) e da frequência. A densidade espectral de potência foi expressa em unidades absolutas (ms2/Hz) e normalizada (un) para as bandas de baixa (BF) e alta frequência (AF) e pela razão BF/AF. Resultados: O índice RMSSD, a AF e a AFun apresentaram redução na execução dos exercícios em relação ao repouso pré e pós-exercício (p &lt; 0,05), a BFun e a razão BF/AF aumentaram (p &lt; 0,05). A FC e a PA sistólica apresentaram aumento durante a execução dos exercícios em relação ao repouso (p &lt; 0,05). Não foi observado qualquer sinal e/ou sintoma de intolerância ao esforço. Conclusões: O exercício realizado foi eficaz, pois promoveu alterações hemodinâmicas e na modulação autonômica nesses pacientes, sem ocasionar qualquer intercorrência clínica

Safety of early physical therapy intervention after acute myocardial infarction

INTRODUÇÃO: A fisioterapia na fase I da reabilitação cardiovascular (FTCV) pode ser iniciada de 12 a 24 horas após o infarto agudo do miocárdio (IAM), no entanto, é comum o repouso prolongado no leito em razão do receio de instabilização do paciente. OBJETIVOS: Avaliar as respostas autonômicas e hemodinâmicas de pacientes pós-IAM submetidos ao primeiro dia de protocolo de FTCV fase I, bem como sua segurança. MATERIAIS E MÉTODOS: Foram estudados 51 pacientes com primeiro IAM não complicado, 55 ± 11 anos, 76% homens. Foram submetidos ao primeiro dia do protocolo de FTCV fase I, em média 24 horas pós-IAM. A frequência cardíaca (FC) instantânea e os intervalos R-R do ECG foram captados pelo monitor de FC (Polar®S810i) e a pressão arterial (PA) aferida pelo método auscultatório. A variabilidade da FC foi analisada nos domínios do tempo (RMSSD e RMSM dos iR-R em ms) e da frequência. A densidade espectral de potência foi expressa em unidades absolutas (ms²/Hz) e normalizada (un) para as bandas de baixa (BF) e alta frequência (AF) e pela razão BF/AF. RESULTADOS: O índice RMSSD, a AF e a AFun apresentaram redução na execução dos exercícios em relação ao repouso pré e pós-exercício (p < 0,05), a BFun e a razão BF/AF aumentaram (p < 0,05). A FC e a PA sistólica apresentaram aumento durante a execução dos exercícios em relação ao repouso (p < 0,05). Não foi observado qualquer sinal e/ou sintoma de intolerância ao esforço. CONCLUSÕES: O exercício realizado foi eficaz, pois promoveu alterações hemodinâmicas e na modulação autonômica nesses pacientes, sem ocasionar qualquer intercorrência clínica

Ancient Yersinia pestis and Salmonella enterica genomes from Bronze Age Crete

During the late 3rd millennium BCE, the Eastern Mediterranean and Near East witnessed societal changes in many regions, which are usually explained with a combination of social and climatic factors.1, 2, 3, 4 However, recent archaeogenetic research forces us to rethink models regarding the role of infectious diseases in past societal trajectories.5 The plague bacterium Yersinia pestis, which was involved in some of the most destructive historical pandemics,5, 6, 7, 8 circulated across Eurasia at least from the onset of the 3rd millennium BCE,9, 10, 11, 12, 13 but the challenging preservation of ancient DNA in warmer climates has restricted the identification of Y. pestis from this period to temperate climatic regions. As such, evidence from culturally prominent regions such as the Eastern Mediterranean is currently lacking. Here, we present genetic evidence for the presence of Y. pestis and Salmonella enterica, the causative agent of typhoid/enteric fever, from this period of transformation in Crete, detected at the cave site Hagios Charalambos. We reconstructed one Y. pestis genome that forms part of a now-extinct lineage of Y. pestis strains from the Late Neolithic and Bronze Age that were likely not yet adapted for transmission via fleas. Furthermore, we reconstructed two ancient S. enterica genomes from the Para C lineage, which cluster with contemporary strains that were likely not yet fully host adapted to humans. The occurrence of these two virulent pathogens at the end of the Early Minoan period in Crete emphasizes the necessity to re-introduce infectious diseases as an additional factor possibly contributing to the transformation of early complex societies in the Aegean and beyond.Results and discussion STAR★Method

Safety of early physical therapy intervention after acute myocardial infarction

INTRODUCTION: Physical therapy during phase I of cardiac rehabilitation (CPT) can be started 12 to 24 hours after acute myocardial infarction (AMI), however, it is common to extend the bed rest due to fear of patient?s instability. OBJECTIVES: To assess the hemodynamic and autonomic responses to post-AMI patients when subjected to first day of phase I protocol of CPT, as well as their safety. MATERIALS AND METHODS: We studied 51 patients with first uncomplicated AMI, 55 ± 11 years, 76% men. The patients were subjected to first day protocol phase I CPT, on average, 24 hours after AMI. The Instantaneous heart rate (HR) and RR interval were acquired by HR monitor (Polar?S810i) and blood pressure (BP) checked by auscultation. HR variability was analyzed in the time (RMSSD and RMSM-Ri in ms) and frequency domains. Power spectral density was expressed in absolute (ms²/Hz) and normalized (nu) units for the bands of low (LF) and high frequencies (HF) and as LF/HF ratio. RESULTS: The RMSSD, HF and HFnu have reduced performance of the exercises in relation to rest and post-exercise (p < 0.05), LFnu and LF/HF ratio increased (p < 0.05). HR and systolic BP showed an increase during the execution of the exercises in relation to rest (p < 0.05). There were no any signs and/or symptoms of exercise intolerance. CONCLUSION: The exercise was effective, because it caused changes hemodynamic and autonomic modulation in these patients, without causing any medical complications.INTRODUÇÃO: A fisioterapia na fase I da reabilitação cardiovascular (FTCV) pode ser iniciada de 12 a 24 horas após o infarto agudo do miocárdio (IAM), no entanto, é comum o repouso prolongado no leito em razão do receio de instabilização do paciente. OBJETIVOS: Avaliar as respostas autonômicas e hemodinâmicas de pacientes pós-IAM submetidos ao primeiro dia de protocolo de FTCV fase I, bem como sua segurança. MATERIAIS E MÉTODOS: Foram estudados 51 pacientes com primeiro IAM não complicado, 55 ± 11 anos, 76% homens. Foram submetidos ao primeiro dia do protocolo de FTCV fase I, em média 24 horas pós-IAM. A frequência cardíaca (FC) instantânea e os intervalos R-R do ECG foram captados pelo monitor de FC (Polar®S810i) e a pressão arterial (PA) aferida pelo método auscultatório. A variabilidade da FC foi analisada nos domínios do tempo (RMSSD e RMSM dos iR-R em ms) e da frequência. A densidade espectral de potência foi expressa em unidades absolutas (ms²/Hz) e normalizada (un) para as bandas de baixa (BF) e alta frequência (AF) e pela razão BF/AF. RESULTADOS: O índice RMSSD, a AF e a AFun apresentaram redução na execução dos exercícios em relação ao repouso pré e pós-exercício (p < 0,05), a BFun e a razão BF/AF aumentaram (p < 0,05). A FC e a PA sistólica apresentaram aumento durante a execução dos exercícios em relação ao repouso (p < 0,05). Não foi observado qualquer sinal e/ou sintoma de intolerância ao esforço. CONCLUSÕES: O exercício realizado foi eficaz, pois promoveu alterações hemodinâmicas e na modulação autonômica nesses pacientes, sem ocasionar qualquer intercorrência clínica.153163Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Animal Models of Diabetic Macrovascular Complications: Key Players in the Development of New Therapeutic Approaches

Diabetes mellitus is a lifelong, incapacitating metabolic disease associated with chronic macrovascular complications (coronary heart disease, stroke, and peripheral vascular disease) and microvascular disorders leading to damage of the kidneys (nephropathy) and eyes (retinopathy). Based on the current trends, the rising prevalence of diabetes worldwide will lead to increased cardiovascular morbidity and mortality. Therefore, novel means to prevent and treat these complications are needed. Under the auspices of the IMI (Innovative Medicines Initiative), the SUMMIT (SUrrogate markers for Micro- and Macrovascular hard end points for Innovative diabetes Tools) consortium is working on the development of novel animal models that better replicate vascular complications of diabetes and on the characterization of the available models. In the past years, with the high level of genomic information available and more advanced molecular tools, a very large number of models has been created. Selecting the right model for a specific study is not a trivial task and will have an impact on the study results and their interpretation. This review gathers information on the available experimental animal models of diabetic macrovascular complications and evaluates their pros and cons for research purposes as well as for drug development

Diagnosis of Taenia solium infections based on “mail order” RNA-sequencing of single tapeworm egg isolates from stool samples

Combined community health programs aiming at health education, preventive anti-parasitic chemotherapy, and vaccination of pigs have proven their potential to regionally reduce and even eliminate Taenia solium infections that are associated with a high risk of neurological disease through ingestion of T. solium eggs. Yet it remains challenging to target T. solium endemic regions precisely or to make exact diagnoses in individual patients. One major reason is that the widely available stool microscopy may identify Taenia ssp. eggs in stool samples as such, but fails to distinguish between invasive (T. solium) and less invasive Taenia (T. saginata, T. asiatica, and T. hydatigena) species. The identification of Taenia ssp. eggs in routine stool samples often prompts a time-consuming and frequently unsuccessful epidemiologic workup in remote villages far away from a diagnostic laboratory. Here we present "mail order" single egg RNA-sequencing, a new method allowing the identification of the exact Taenia ssp. based on a few eggs found in routine diagnostic stool samples. We provide first T. solium transcriptome data, which show extremely high mitochondrial DNA (mtDNA) transcript counts that can be used for subspecies classification. "Mail order" RNA-sequencing can be administered by health personnel equipped with basic laboratory tools such as a microscope, a Bunsen burner, and access to an international post office for shipment of samples to a next generation sequencing facility. Our suggested workflow combines traditional stool microscopy, RNA-extraction from single Taenia eggs with mitochondrial RNA-sequencing, followed by bioinformatic processing with a basic laptop computer. The workflow could help to better target preventive healthcare measures and improve diagnostic specificity in individual patients based on incidental findings of Taenia ssp. eggs in diagnostic laboratories with limited resources

Importance of effective collaboration between health professionals for the facilitation of optimal community diabetes care

Diabetes places a significant burden on the individuals concerned, their families and society as a whole. The debilitating sequelae of diabetes can be limited or prevented altogether through strict glycaemic control. Despite the seemingly uncomplicated nature of the disorder, effective management can be elusive, as the impact of having to deal with diabetes on a daily basis can be profound and appropriate professional support is not always readily available. As the roles of general practitioners (GPs) and allied health professionals have evolved, a major issue now facing all is that of developing and maintaining effective collaborative relationships for the facilitation of optimal community diabetes care. Using a simple survey methodology, the present exploratory study investigated the referral patterns of GPs to diabetic educators (DEs) working for a community health service in an Australian town, and reasons for referral and non-referral in order to identify factors that contribute to a sound and sustainable collaborative relationship.The results provide some evidence that GPs and DEs in this town do work collaboratively towards achieving client-centred goals and highlight the need to inform GPs who are new to communities, such as this one, of the available DE services. Most importantly, the study identified that there are many opportunities to strengthen collaboration so as to facilitate optimal community diabetes care. This information is valuable, because there is limited empirical evidence either nationally or internationally about the process of collaboration between health professionals in the management of chronic diseases, such as diabetes