From Macroscopic to Microscopic: Experimental and Computational Methods to Investigate Bio-tribology

Tribology is an important factor (among other factors) during biological interactions of devices and tissues. The paper discusses how new computational and experimental methods can be used to understand and improve the design and development of medical devices at macro and micro scales to sustain life beyond 50 years. We have used pre-clinical experiments and computational methods to understand interactions between orthopaedic implants at the macro scale. The computational model has been validated with experiments. Now this computational model can predict damage in implants for different patients. One such application was successfully tried and tested in collaboration with University National Autonomous Mexico. This methodology can be used in future to design patient specific, affordable (using 3D printing) and robust implants which will be useful for developing countries like Vietnam, India and Mexico. Improvement of catheter designs is important to reduce damage to the internal tissues while being used for cardiovascular problems. We are developing new experimental techniques (in micro scale) that can be used to understand the interaction of cells with the catheter material. These will help reduce the hospital costs incurred during longer stay of the patients admitted for cardiovascular related problems

Pre-analytical factors affecting whole blood and plasma glucose concentrations in loggerhead sea turtles (Caretta caretta)

Blood glucose is vital for many physiological pathways and can be quantified by clinical chemistry analyzers and in-house point-of-care (POC) devices. Pre-analytical and analytical factors can influence blood glucose measurements. This project aimed to investigate pre-analytical factors on whole blood and plasma glucose measurements in loggerhead sea turtles (Caretta caretta) by evaluating the effects of storage (refrigeration) up to 48h after sampling and of packed cell volume (PCV) on whole blood glucose analysis by POC glucometer (time series n = 13); and by evaluating the effects of storage (room temperature and refrigeration) on plasma glucose concentrations using a dry slide chemistry analyzer (DCA) at various conditions: immediate processing and delayed plasma separation from erythrocytes at 24h and 48h (time series n = 14). The POC glucometer had overall strong agreement with the DCA (CCC = 0.76, r = 0.84, Cb = 0.90), but consistently overestimated glucose concentrations (mean difference: +0.4 mmol/L). The POC glucometer results decreased significantly over time, resulting in a substantial decline within the first 2h (0.41±0.47 mmol/L; 8±9%) that could potentially alter clinical decisions, thereby highlighting the need for immediate analysis using this method. The effects of PCV on glucose could not be assessed, as the statistical significance was associated with one outlier. Storage method significantly affected plasma glucose measurements using DCA, with room temperature samples resulting in rapid decreases of 3.57±0.89 mmol/L (77±9%) over the first 48h, while refrigerated samples provided consistent plasma glucose results over the same time period (decrease of 0.26±0.23 mmol/L; 6±5%). The results from this study provide new insights into optimal blood sample handling and processing for glucose analysis in sea turtles, show the suitability of the POC glucometer as a rapid diagnostic test, and confirm the reliability of plasma glucose measurements using refrigeration. These findings emphasize the need to consider pre-/analytical factors when interpreting blood glucose results from loggerhead sea turtles

Metaphoric coherence: Distinguishing verbal metaphor from `anomaly\u27

Theories and computational models of metaphor comprehension generally circumvent the question of metaphor versus “anomaly” in favor of a treatment of metaphor versus literal language. Making the distinction between metaphoric and “anomalous” expressions is subject to wide variation in judgment, yet humans agree that some potentially metaphoric expressions are much more comprehensible than others. In the context of a program which interprets simple isolated sentences that are potential instances of cross‐modal and other verbal metaphor, I consider some possible coherence criteria which must be satisfied for an expression to be “conceivable” metaphorically. Metaphoric constraints on object nominals are represented as abstracted or extended along with the invariant structural components of the verb meaning in a metaphor. This approach distinguishes what is preserved in metaphoric extension from that which is “violated”, thus referring to both “similarity” and “dissimilarity” views of metaphor. The role and potential limits of represented abstracted properties and constraints is discussed as they relate to the recognition of incoherent semantic combinations and the rejection or adjustment of metaphoric interpretations

Conversation acts in task-oriented spoken dialogue

A linguistic form\u27s compositional, timeless meaning can be surrounded or even contradicted by various social, aesthetic, or analogistic companion meanings. This paper addresses a series of problems in the structure of spoken language discourse, including turn-taking and grounding. It views these processes as composed of fine-grained actions, which resemble speech acts both in resulting from a computational mechanism of planning and in having a rich relationship to the specific linguistic features which serve to indicate their presence. The resulting notion of Conversation Acts is more general than speech act theory, encompassing not only the traditional speech acts but turn-taking, grounding, and higher-level argumentation acts as well. Furthermore, the traditional speech acts in this scheme become fully joint actions, whose successful performance requires full listener participation. This paper presents a detailed analysis of spoken language dialogue. It shows the role of each class of conversation acts in discourse structure, and discusses how members of each class can be recognized in conversation. Conversation acts, it will be seen, better account for the success of conversation than speech act theory alone

Reversible brain edema associated to flow diverter stent procedures: a retrospective single-center study to evaluate frequency, clinical evolution, and possible mechanism

Background Hemorrhage and ischemia after flow diverter stent (FDS) procedures for intracranial aneurysms are the most common complications and have been extensively described. Temporary brain edema (TBE) is an unknown complication that could be associated with particular FDS procedures. Objective To estimate the frequency, clinical presentation, imaging findings, and possible mechanisms associating TBE with FDS. Methods Unruptured aneurysms treated with FDS implantation performed in our service from June 2015 to March 2018 were reviewed. Medical antecedents, endovascular procedure, clinical assessments before and after treatment, aneurysm characteristics, and image records were collected. Artery diameters of patients in whom TEB developed were also calculated to investigate any correlation between TBE and anatomic descriptors. Results A total of 179 FDS procedures in 176 patients were reviewed. Six patients (3.4%) presented with symptomatic TBE, and all TBE patients had undergone FDS implantation from the middle cerebral artery (MCA) to the internal carotid artery (ICA). A Pearson product-moment correlation coefficient (PPCC) found smaller MCA diameters and MCA/ICA ratios in these 6 patients (respectively PPCC = −0.619, P < 0.04; PPCC = −0.647, P < 0.03). Hemorrhagic and ischemic complications were less frequent than TBE (2.3% and 1.1% vs. 3.4%). Conclusions TBE was more frequent than ischemic or hemorrhagic complications after FDS in this study. TBE seemed to be associated with a particular FDS positioning in small arteries, inducing flow changes and disruption of the blood–brain barrier

The Photoreceptor Cell-Specific Nuclear Receptor Gene (PNR ) Accounts for Retinitis Pigmentosa in the Crypto-Jews from Portugal (Marranos), Survivors from the Spanish Inquisition

The last Crypto-Jews (Marranos) are the survivors of Spanish Jews who were persecuted in the late fifteenth century, escaped to Portugal and were forced to convert to save their lives. Isolated groups still exist in mountainous areas such as Belmonte in the Beira-Baixa province of Portugal. We report here the genetic study of a highly consanguineous endogamic population of Crypto-Jews of Belmonte affected with autosomal recessive retinitis pigmentosa (RP). A genome-wide search for homozygosity allowed us to localize the disease gene to chromosome 15q22-q24 (Zmax=2.95 at θ=0 at the D15S131 locus). Interestingly, the photoreceptor cell-specific nuclear receptor (PNR) gene, the expression of which is restricted to the outer nuclear layer of retinal photoreceptor cells, was found to map to the YAC contig encompassing the disease locus. A search for mutations allowed us to ascribe the RP of Crypto-Jews of Belmonte to a homozygous missense mutation in the PNR gene. Preliminary haplotype studies support the view that this mutation is relatively ancient but probably occurred after the population settled in Belmonte

Substrate Micropatterning as a New in Vitro Cell Culture System to Study Myelination

Artículo de publicación ISIMyelination is a highly regulated developmental process whereby oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system ensheathe axons with a multilayered concentric membrane. Axonal myelination increases the velocity of nerve impulse propagation. In this work, we present a novel in vitro system for coculturing primary dorsal root ganglia neurons along with myelinating cells on a highly restrictive and micropatterned substrate. In this new coculture system, neurons survive for several weeks, extending long axons on defined Matrigel tracks. On these axons, myelinating cells can achieve robust myelination, as demonstrated by the distribution of compact myelin and nodal markers. Under these conditions, neurites and associated myelinating cells are easily accessible for studies on the mechanisms of myelin formation and on the effects of axonal damage on the myelin sheath.Regenerative Medicine and Nanomedicine Initiative of the Canadian Institutes of Health Research (CIHR) RMF-7028 FONDECYT 1080252 CIHR Ministry of Industry of Canada Rio Tinto Alcan Molson Foundatio

Development of a risk score for early saphenous vein graft failure: An individual patient data meta-analysis

Objectives: Early saphenous vein graft (SVG) occlusion is typically attributed to technical factors. We aimed at exploring clinical, anatomical, and operative factors associated with the risk of early SVG occlusion (within 12 months postsurgery). Methods: Published literature in MEDLINE was searched for studies reporting the incidence of early SVG occlusion. Individual patient data (IPD) on early SVG occlusion were used from the SAFINOUS-CABG Consortium. A derivation (n = 1492 patients) and validation (n = 372 patients) cohort were used for model training (with 10-fold cross-validation) and external validation respectively. Results: In aggregate data meta-analysis (48 studies, 41,530 SVGs) the pooled estimate for early SVG occlusion was 11%. The developed IPD model for early SVG occlusion, which included clinical, anatomical, and operative characteristics (age, sex, dyslipidemia, diabetes mellitus, smoking, serum creatinine, endoscopic vein harvesting, use of complex grafts, grafted target vessel, and number of SVGs), had good performance in the derivation (c-index = 0.744; 95% confidence interval [CI], 0.701-0.774) and validation cohort (c-index = 0.734; 95% CI, 0.659-0.809). Based on this model. we constructed a simplified 12-variable risk score system (SAFINOUS score) with good performance for early SVG occlusion (c-index = 0.700, 95% CI, 0.684-0.716). Conclusions: From a large international IPD collaboration, we developed a novel risk score to assess the individualized risk for early SVG occlusion. The SAFINOUS risk score could be used to identify patients that are more likely to benefit from aggressive treatment strategies

Promiscuous drugs compared to selective drugs (promiscuity can be a virtue)

BACKGROUND: The word selectivity describes a drug's ability to affect a particular cell population in preference to others. As part of the current state of art in the search for new therapeutic agents, the property of selectivity is a mode of action thought to have a high degree of desirability. Consequently there is a growing activity in this area of research. Selectivity is generally a worthy property in a drug because a drug having high selectivity may have a dramatic effect when there is a single agent that can be targeted against the appropriate molecular-driver involved in the pathogenesis of a disease. An example is chronic myeloid leukemia (CML). CML has a specific chromosomal abnormality, the Philadelphia chromosome, that results in a single gene that produces an abnormal protein DISCUSSION: There is a burgeoning understanding of the cellular mechanisms that control the etiology and pathogeneses of diseases. This understanding both enables and motivates the development of drugs that induce a specific action in a selected cell population; i.e., a targeted treatment. Consequently, drugs that can target distinct molecular targets involved in pathologic/pathogenetic processes, or signal-transduction pathways, are being developed. However, in most cases, diseases involve multiple abnormalities. A disease may be associated with more than one dysfunctional protein and these may be out-of-balance with each other. Likewise a drug might strongly target a protein that shares a similar active domain with other proteins. A drug may also target pleiotropic cytokines, or other proteins that have multi-physiological functions. In this way multiple normal cellular pathways can be simultaneously influenced. Long term experience with drugs supposedly designed for only a single target, but which unavoidably involve other functional effects, is uncovering the fact that molecular targeting is not medically flawless. SUMMARY: We contend that an ideal drug may be one whose efficacy is based not on the inhibition of a single target, but rather on the rebalancing of the several proteins or events, that contribute to the etiology, pathogeneses, and progression of diseases, i.e., in effect a promiscuous drug. Ideally, if this could be done at minimum drug concentration, side effects could be minimized. Corollaries to this argument are that the growing fervor for researching truly selective drugs may be imprudent when considering the totality of responses; and that the expensive screening techniques used to discover these, may be both medically and financially inefficient