Extraction of 2′-O-apiosyl-6′-O-crotonic acid-betanin from the ayrampo seed (Opuntia soehrensii) cuticle and its use as an emitting layer in an organic light-emitting diode

The molecule 2′-O-apiosyl-6′-O-crotonic acid-betanin (called Achkiy) was obtained after an ecofriendly and low-cost purification process of the extract from the ayrampo seed cuticle. Results from EDS give us an idea of the organic elements present in the ayrampo cuticle layer composed of carbon, oxygen and nitrogen. Further characterization analysis of ayrampo extract by Fourier Transform Infrared Spectrophotometry (FTIR) corroborated the presence of characteristic functional groups corresponding to carboxyl, carbonyls, hydroxyls and secondary amines. On the other hand, we have confirmed by absortion peak the glucose, apiosyl, crotonic acid and betanin at 227 nm, 276 nm, 291 nm and 534 nm bands respectively. Mass Spectrometry (MS) characterization was used finally to identify the electroactive Achkiy molecule. This molecule was tested in an Organic Light Emitting Diode (OLED) achieving a luminance of 4.8 Cd m$^{−2}$ when bias voltage of 16.5 V and a current of 34.1 mA was applied. In addition, the irradiance generated by the Achkiy layer reaches a value of ≈ 113.3 μW m$^{−2}$ emitting light with a λ ≈ 390.10 nm. These preliminary results report an interesting molecule extracted from a natural pigment wich emits light in the blue region

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state

© 2015, Journal of NeuroVirology, Inc. Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies have demonstrated that neural precursor cells (NPCs) show the greatest susceptibility to CMV infection in the developing brain. We sought to establish an in vitro model of CMV infection of the developing brain in order to analyze the cellular events associated with invasion by this virus. To this end, we employed two cell lines as a permanent source of NPC, avoiding the continuous use of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an immortalized cell line of human fetal neural origin, hNS-1. We also investigated the effect of the differentiation stage in relation to the susceptibility of these cell lines by comparing the neuroblastoma cell line with the multipotent cell line hNS-1. We found that the effects of the virus were more severe in the neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells, hNS-1-differentiated cells were also susceptible to infection. Viability of differentiated hNS-1 cells decreased after CMV infection in contrast to undifferentiated cells. In addition, differentiated hNS-1 cells showed an extensive cytopathic effect whereas the effect was scarce in undifferentiated cells. We describe some of the effects of CMV in neural stem cells, and our observations suggest that the degree of differentiation is important in the acquisition of susceptibility.CONACYT (CB16782 and #120452), PROMEP (103.5/10/7697), and FAI-UASLP (C12-FAI-03-62.62).Peer Reviewe

A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway

Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains un- known. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n = 168,287) and non-fatal (13 cohorts, n = 27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 10 0,0 0 0 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those esti- mated from cohorts in high-income countries

Process evaluation in the field: global learnings from seven implementation research hypertension projects in low-and middle-income countries

Background Process evaluation is increasingly recognized as an important component of effective implementation research and yet, there has been surprisingly little work to understand what constitutes best practice. Researchers use different methodologies describing causal pathways and understanding barriers and facilitators to implementation of interventions in diverse contexts and settings. We report on challenges and lessons learned from undertaking process evaluation of seven hypertension intervention trials funded through the Global Alliance of Chronic Diseases (GACD). Methods Preliminary data collected from the GACD hypertension teams in 2015 were used to inform a template for data collection. Case study themes included: (1) description of the intervention, (2) objectives of the process evaluation, (3) methods including theoretical basis, (4) main findings of the study and the process evaluation, (5) implications for the project, policy and research practice and (6) lessons for future process evaluations. The information was summarized and reported descriptively and narratively and key lessons were identified. Results The case studies were from low- and middle-income countries and Indigenous communities in Canada. They were implementation research projects with intervention arm. Six theoretical approaches were used but most comprised of mixed-methods approaches. Each of the process evaluations generated findings on whether interventions were implemented with fidelity, the extent of capacity building, contextual factors and the extent to which relationships between researchers and community impacted on intervention implementation. The most important learning was that although process evaluation is time consuming, it enhances understanding of factors affecting implementation of complex interventions. The research highlighted the need to initiate process evaluations early on in the project, to help guide design of the intervention; and the importance of effective communication between researchers responsible for trial implementation, process evaluation and outcome evaluation. Conclusion This research demonstrates the important role of process evaluation in understanding implementation process of complex interventions. This can help to highlight a broad range of system requirements such as new policies and capacity building to support implementation. Process evaluation is crucial in understanding contextual factors that may impact intervention implementation which is important in considering whether or not the intervention can be translated to other contexts

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

<p>Abstract</p> <p>Background</p> <p>We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, <it>i.e. de novo </it>DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages.</p> <p>Results</p> <p>Native lipoprotein-induced <it>de novo </it>DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as <it>de novo </it>DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway.</p> <p>Conclusions</p> <p>Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a <it>de novo </it>DNA methyltransferase independently of canonical <it>de novo </it>enzymes, and show proof of principle that <it>de novo </it>DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.</p

Human resources: the Cinderella of health sector reform in Latin America

Human resources are the most important assets of any health system, and health workforce problems have for decades limited the efficiency and quality of Latin America health systems. World Bank-led reforms aimed at increasing equity, efficiency, quality of care and user satisfaction did not attempt to resolve the human resources problems that had been identified in multiple health sector assessments. However, the two most important reform policies – decentralization and privatization – have had a negative impact on the conditions of employment and prompted opposition from organized professionals and unions. In several countries of the region, the workforce became the most important obstacle to successful reform. This article is based on fieldwork and a review of the literature. It discusses the reasons that led health workers to oppose reform; the institutional and legal constraints to implementing reform as originally designed; the mismatch between the types of personnel needed for reform and the availability of professionals; the deficiencies of the reform implementation process; and the regulatory weaknesses of the region. The discussion presents workforce strategies that the reforms could have included to achieve the intended goals, and the need to take into account the values and political realities of the countries. The authors suggest that autochthonous solutions are more likely to succeed than solutions imported from the outside

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks