Peri-operative treatment of anaemia in major orthopaedic surgery: a practical approach from Spain

In patients undergoing major orthopaedic surgery, pre-operative anaemia, peri-operative bleeding and a liberal transfusion policy are the main risk factors for requiring red blood cell transfusion (RBCT). The clinical and economic disadvantages of RBCT have led to the development and implementation of multidisciplinary, multimodal, individualised strategies, collectively termed patient blood management, which aim to reduce RBCT and improve patients' clinical outcome and safety. Within a patient blood management programme, low pre-operative haemoglobin is one of the few modifiable risk factors for RBCT. However, a survey among Anaesthesia Departments in Spain revealed that, although pre-operative assessment was performed in the vast majority of hospitals, optimisation of haemoglobin concentration was attempted in <40% of patients who may have benefitted from it, despite there being enough time prior to surgery. This indicates that haemoglobin optimisation takes planning and forethought to be implemented in an effective manner. This review, based on available clinical evidence and our experience, is intended to provide clinicians with a practical tool to optimise pre-operative haemoglobin levels, in order to minimise the risk of patients requiring RBCT. To this purpose, after reviewing the diagnostic value and limitations of available laboratory parameters, we developed an algorithm for the detection, classification and treatment of pre-operative anaemia, with a patient-tailored approach that facilitates decision-making in the pre-operative assessment. We also reviewed the efficacy of the different pharmacological options for pre-operative and post-operative management of anaemia. We consider that such an institutional pathway for anaemia management could be a viable, cost-effective strategy that is beneficial to both patients and healthcare systems

Biomaterials-tissue interaction of an injectable collagen-genipin gel in a rodent hemi-resection model of spinal cord injury

Thesis (Ph. D. in Medical Engineering and Medical Physics)--Harvard-MIT Program in Health Sciences and Technology, 2013.Cataloged from PDF version of thesis.Includes bibliographical references.Spinal cord injury (SCI) is a significant health issue resulting in life-long disability and associated secondary complications, affecting approximately 300,000 individuals in the United States. Primary barriers to functional recovery after SCI include the formation of a growth inhibitory astrocyte scar at the lesion border and a lack of a supportive stroma within the defect allowing for axon regeneration. Interestingly, in animals capable of spinal cord regeneration, astrocytes create a tissue bridge across the injury site to facilitate the regeneration of axons through the defect and thus enable functional recovery. The overall goal of this thesis was to develop an injectable collagen-genipin (Col-Gen) hydrogel to facilitate the intrinsic regenerative response after SCI by promoting the population of the defect with astrocytes through a provisional scaffold pennissive of astrocyte migration. The specific aims of the thesis involved: 1) development and materials characterization of an injectable collagen hydrogel for neural tissue regeneration, capable of undergoing covalent crosslinking in vivo; 2) evaluation of the permissiveness of Col-Gen gels with and without Fibroblast growth factor-2 (FGF-2), a known astrocyte chemoattractant, incorporated within lipid microtubules (LMTs) to infiltration by primary astrocytes using an in vitro cellular outgrowth assay; 3) evaluation of select formulations of the gel, based on the in vitro findings, in a standardized hemi-resection defect in the rat spinal cord. Functional, locomotor, and histopathological outcome measures, recorded up to 4 weeks post-SCI were correlated with each other and with micro MRI studies. In vivo, the implantation of Col-Gen gels containing FGF-2 LMTs resulted in the enhancement of astrocyte, blood vessel, and laminin infiltration of the defect; increased the amount of spinal cord tissue spared from secondary degeneration; and increased functional recovery, at four weeks post injury as compared to control or Col-Gen treatment groups. Micro MRI was found to be a suitable modality to nondestructively observe the features of the injury in situ. This work commends an injectable, covalently cross-linkable formulation of collagen gel incorporating FGF-2-releasing LMTs for further investigation for the treatment of SCI.by Daniel J. Macaya.Ph.D.in Medical Engineering and Medical Physic

New and Old Mechanisms Associated with Hypertension in the Elderly

Hypertension is a widely prevalent and important risk factor for cardiovascular diseases that increase with aging. The hallmark of hypertension in the elderly is increased vascular dysfunction. However, the molecular mechanisms by which increased blood pressure leads to vascular injury and impaired endothelial function are not well defined. In the present paper, we will analyze several mechanisms described in the scientific literature involved in hypertension in the elderly as endothelial dysfunction, increased oxygen delivery to tissues, inflammation, cellular apoptosis, and increased concentration of active metabolites. Also, we will focus on new molecular mechanisms involved in hypertension such as telomeres shortening, progenitor cells, circulating microparticles, and epigenetic factors that have appeared as possible causes of hypertension in the elderly. These molecular mechanisms may elucidate different origin for hypertension in the elderly and provide us with new targets for hypertension treatment

Zero-order controlled release of ciprofloxacin-HCl from a reservoir-based, bioresorbable and elastomeric device

A reservoir-based device constructed of a completely biodegradable elastomer can enable several new implantation and insertion options for localized drug therapy, particularly in the case of urological therapies. We performed an in vitro performance evaluation of an implantable, bio-resorbable device that supplies short-term controlled release of ciprofloxacin-HCl (CIP). The proposed device functions through a combination of osmosis and diffusion mechanisms to release CIP for short-term therapies of a few weeks duration. Poly(glycerol-co-sebacic acid) (PGS) was cast in a tubular geometry with solid drug powder packed into its core and a micro-machined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice sizes in which controlled zero-order release was the main form of drug expulsion from the device. It is demonstrated that PGS is sufficiently permeable to water to allow the design of an elementary osmotic pump for drug delivery. Indeed, PGS's water permeability is several orders of magnitude larger than commonly used cellulose acetate for elementary osmotic pumps.Deshpande Center for Technological InnovationSamsung Scholarship Foundatio

Pleiotropic and Epistatic Network-Based Discovery: Integrated Networks for Target Gene Discovery

Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current environmental and epigenetic signals, and, as such, their co-occurrence can be seen as genome-wide correlations in a number of different manners. Biomass recalcitrance (i.e., the resistance of plants to degradation or deconstruction, which ultimately enables access to a plant’s sugars) is a complex polygenic phenotype of high importance to biofuels initiatives. This study makes use of data derived from the re-sequenced genomes from over 800 different Populus trichocarpa genotypes in combination with metabolomic and pyMBMS data across this population, as well as co-expression and co-methylation networks in order to better understand the molecular interactions involved in recalcitrance, and identify target genes involved in lignin biosynthesis/degradation. A Lines Of Evidence (LOE) scoring system is developed to integrate the information in the different layers and quantify the number of lines of evidence linking genes to target functions. This new scoring system was applied to quantify the lines of evidence linking genes to lignin-related genes and phenotypes across the network layers, and allowed for the generation of new hypotheses surrounding potential new candidate genes involved in lignin biosynthesis in P. trichocarpa, including various AGAMOUS-LIKE genes. The resulting Genome Wide Association Study networks, integrated with Single Nucleotide Polymorphism (SNP) correlation, co-methylation, and co-expression networks through the LOE scores are proving to be a powerful approach to determine the pleiotropic and epistatic relationships underlying cellular functions and, as such, the molecular basis for complex phenotypes, such as recalcitrance

Automation Proposal for the Intermediate Steps in the 16S FFPE Samples Analysis Pipeline

Cursos e Congresos, C-155[Abstract] In the day-to-day work of bioinformatics, the use of integrated software packages, which encompass a wide range of tools, enables the development of pipelines for omics data analysis. Within the various existing pipelines, we focus on the analysis of the 16S rRNA gene as it allows for the study of diversity and taxonomy of prokaryotic microorganisms such as Bacteria and Archaea. However, these pipelines often involve a sequence of multiple tools that require intermediate steps before further processing can proceed, as in the case between Cutadapt and DADA2. In fact, in a typical pipeline, the values for DADA2 input arguments ’trunc-len-f’ and ’trunc-len-r’ are extracted from the output of Cutadapt. The best approach for selecting optimal values (aka the trimming positions) is graphically visualizing Cutadapt output and manually selecting the most accurate trimming position length. Therefore, we propose the automation of this specific intermediate step between Cutadapt and DADA2 tools, by selecting values displayed in the graphs that meet the filtering criteria. This automation has been incorporated into a custom pipeline for the analysis of the microbiome in 16S paired-end samples from colorectal cancer patients, and could potentially serve as a standardization approach in these processesThe authors of this paper extend their sincere appreciation to the collaborative efforts and contributions of the meiGAbiome Group, aswell as the entire team of medical and anatomopathologists. Finally, we are deeply grateful to the patients whose selfless donations have made this and numerous other studies possibl

Impact of Puberty in Pediatric Migraine : A Pilot Prospective Study

The short-term evolution of pediatric migraine remains unclear. We aimed to describe the evolution of migraine before and after puberty and its relationship with lifestyle habits. We prospectively selected prepuberal patients from a neuropediatric unit who had a migraine diagnosis. Their medical history, migraine characteristics and impact, and lifestyle habits were recorded at the baseline visit. After 2 years we performed a telephone follow-up assessment. Nineteen patients were recruited (age 10.2±2.9 years, mean±SD; 57.9% female), of whom 27.5% had migraine with aura. The accompanying symptoms had changed at the follow-up, with significantly higher prevalence rates of dizziness (44.4% vs. 88.9%), vertigo (11.1% vs. 66.7%), mood changes (38.9% vs 83.3%), confusion (5.6% vs. 77.8%), and allodynia (27.8% vs. 61.1%). Sleep disturbances (5.6% vs. 38.9%) and schedule changes (0% vs. 38.9%) increased significantly as triggers. Prodromal symptoms became more prevalent (16.7% vs. 50%), with a higher proportion of sleep disturbances reported (50.0% vs. 87.5%). Prodromal symptoms increase in pediatric migraine after 2 years, and some trigger factors for migraine become more prevalent, including sleep disturbances. New accompanying symptoms are also identified. These changes provide information about how migraine changes during puberty along with physical and lifestyle changes, and represent a dynamic physiopathological process that deserves more research

Challenges in the Design and Interpretation of Noninferiority Trials: Insights From Recent Stent Trials.

The noninferiority design is used extensively in current clinical research, but its complex features may hamper the appropriate interpretation of such trials. Thus, understanding the pillars of noninferiority design is indispensable. The authors discuss fundamental concepts regarding the design and interpretation of noninferiority trials and then explore some common methodological criticism by analyzing a sample of contemporary coronary stent trials. Finally, the authors give an overall perspective to enhance the design and conduct of future trials

All-plastic electrochemical transistor for glucose sensing using a ferrocene mediator.

We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT) in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS). The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva