Análisis espacial del patio en la vivienda mexicalense

Peer Reviewe

Adverse drug reactions associated with amitriptyline - protocol for a systematic multiple-indication review and meta-analysis

Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including <100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations

Transcending conventional biometry frontiers: Diffusive Dynamics PPG Biometry

In the first half of the 20th century, a first pulse oximeter was available to measure blood flow changes in the peripheral vascular net. However, it was not until recent times the PhotoPlethysmoGraphic (PPG) signal used to monitor many physiological parameters in clinical environments. Over the last decade, its use has extended to the area of biometrics, with different methods that allow the extraction of characteristic features of each individual from the PPG signal morphology, highly varying with time and the physical states of the subject. In this paper, we present a novel PPG-based biometric authentication system based on convolutional neural networks. Contrary to previous approaches, our method extracts the PPG signal's biometric characteristics from its diffusive dynamics, characterized by geometric patterns image in the (p, q)-planes specific to the 0-1 test. The diffusive dynamics of the PPG signal are strongly dependent on the vascular bed's biostructure, which is unique to each individual, and highly stable over time and other psychosomatic conditions. Besides its robustness, our biometric method is anti-spoofing, given the convoluted nature of the blood network. Our biometric authentication system reaches very low Equal Error Rates (ERRs) with a single attempt, making it possible, by the very nature of the envisaged solution, to implement it in miniature components easily integrated into wearable biometric systems.Comment: 18 pages, 6 figures, 4 table

The mechanisms of potassium loss in acute myocardial ischemia: New insights from computational simulations

: Acute myocardial ischemia induces hyperkalemia (accumulation of extracellular potassium), a major perpetrator of lethal reentrant ventricular arrhythmias. Despite considerable experimental efforts to explain this pathology in the last decades, the intimate mechanisms behind hyperkalemia remain partially unknown. In order to investigate these mechanisms, we developed a novel computational model of acute myocardial ischemia which couples a) an electrophysiologically detailed human cardiomyocyte model that incorporates modifications to account for ischemia-induced changes in transmembrane currents, with b) a model of cardiac tissue and extracellular K + transport. The resulting model is able to reproduce and explain the triphasic time course of extracellular K + concentration within the ischemic zone, with values of [K+]o close to 14&nbsp;mmol/L in the central ischemic zone after 30&nbsp;min. In addition, the formation of a [K+]o border zone of approximately 1.2&nbsp;cm 15&nbsp;min&nbsp;after the onset of ischemia is predicted by the model. Our results indicate that the primary rising phase of [K+]o is mainly due to the imbalance between K + efflux, that increases slightly, and K + influx, that follows a reduction of the NaK pump activity by more than 50%. The onset of the plateau phase is caused by the appearance of electrical alternans (a novel mechanism identified by the model), which cause an abrupt reduction in the K + efflux. After the plateau, the secondary rising phase of [K+]o is caused by a subsequent imbalance between the K + influx, which continues to decrease slowly, and the K + efflux, which remains almost constant. Further, the study shows that the modulation of these mechanisms by the electrotonic coupling is the main responsible for the formation of the ischemic border zone in tissue, with K + transport playing only a minor role. Finally, the results of the model indicate that the injury current established between the healthy and the altered tissue is not sufficient to depolarize non-ischemic cells within the healthy tissue

The influence of floral traits on specialisation and modularity of plant-pollinator networks in a biodiversity hotspot in the Peruvian Andes

Background and Aims: Modularity is a ubiquitous and important structural property of ecological networks which describes the relative strengths of sets of interacting species and gives insights into the dynamics of ecological communities. However, this has rarely been studied in species-rich, tropical plant–pollinator networks. Working in a biodiversity hotspot in the Peruvian Andes we assessed the structure of quantitative plant–pollinator networks in nine valleys, quantifying modularity among networks, defining the topological roles of species and the influence of floral traits on specialization. Methods: A total of 90 transects were surveyed for plants and pollinators at different altitudes and across different life zones. Quantitative modularity (QuanBiMo) was used to detect modularity and six indices were used to quantify specialization. Key Results: All networks were highly structured, moderately specialized and significantly modular regardless of size. The strongest hubs were Baccharis plants, Apis mellifera, Bombus funebris and Diptera spp., which were the most ubiquitous and abundant species with the longest phenologies. Species strength showed a strong association with the modular structure of plant–pollinator networks. Hubs and connectors were the most centralized participants in the networks and were ranked highest (high generalization) when quantifying specialization with most indices. However, complementary specialization d' quantified hubs and connectors as moderately specialized. Specialization and topological roles of species were remarkably constant across some sites, but highly variable in others. Networks were dominated by ecologically and functionally generalist plant species with open access flowers which are closely related taxonomically with similar morphology and rewards. Plants associated with hummingbirds had the highest level of complementary specialization and exclusivity in modules (functional specialists) and the longest corollas. Conclusions: We have demonstrated that the topology of networks in this tropical montane environment was non-random and highly organized. Our findings underline that specialization indices convey different concepts of specialization and hence quantify different aspects, and that measuring specialization requires careful consideration of what defines a specialist

BASIS FOR TARGETING MET ACTIVATION MEDIATED RESISTANCE TO PI3K INHIBITION IN BREAST CANCER

The identification of resistance mechanisms to emerging therapies, such as those targeting the PI3K pathway and the MET receptor, has the potential to benefit a significant number of patients with breast cancer. In this study we hypothesized that concurrent aberrations in PI3K and MET will render breast cancers resistant to therapies targeting each pathway, and that combination therapy targeting the PI3K and MET pathway will optimize therapy-effect by preventing the acquisition of resistance. We analyzed cMET and phospho-cMET levels in 257 breast cancer samples and found that high levels of both the proteins were seen in all breast cancer subtypes, which correlated with poor prognosis.(1) We also analyzed DNA from 971 FFPE early breast tumors, and showed that MET and PIK3CA are frequently co-amplified, and a high copy number of either gene is associated with poorer prognostic features and the triple negative disease.(2) Additionally, we determined the effect of MET-T1010I, MET-Y1253D and MET overexpression, found in breast cancers, on the activity of the two most common breast cancer PIK3CA mutations (E545K and H1047R), in a model of breast epithelial cells (MCF-10A) and a cell line breast cancer model (HCC1954). Our results suggest that tumors with concurrent aberrations in MET and PIK3CA are likely to be more aggressive and resistant to therapies targeting each pathway, and that combinatorial therapy (with MET and PI3K pathway inhibitors) could circumvent this resistance. This is the first study to investigate the significance of differential expression of cMET and p-cMET in different breast cancer subtypes, to report p-cMET levels as a prognostic factor in breast cancer, and also, the first to report MET gene copy number, its distribution by tumor subtype, and correlation with patient outcome.(2) Our study is also unique for showing that the presence of MET aberrations enhances the tumorigenic effects induced by the PIK3CA mutations in breast cancer/epithelial cells; results from our tumor xenograft models corroborate with these in vitro findings. Moreover, we are the first to provide evidence for the potential activity of combinatorial therapy using MET and PI3K pathway inhibitors against breast cancer

Film-forming thermoresponsive nanogels for dermal protein delivery

Thermoresponsive nanogels (NGs) have great potential as nanocarriers because of their high in aqueous solutions, elevated biocompatibility, high loading capacity, controlled release of an active component, fast response to temperature change, and design flexibility. In this scenario, a NG dispersion with a film forming ability could be useful for designing a dermal platform for drugs delivery, where the delivering film/patch could be previously obtained or directly formed onto the surface where the release is required. Please click Additional Files below to see the full abstract

Star Formation Under the Outflow: The Discovery of a Non-Thermal Jet from OMC-2 FIR 3 and its Relationship to the Deeply Embedded FIR 4 Protostar

We carried out multiwavelength (0.7-5 cm), multiepoch (1994-2015) Very Large Array (VLA) observations toward the region enclosing the bright far-IR sources FIR 3 (HOPS 370) and FIR 4 (HOPS 108) in OMC-2. We report the detection of 10 radio sources, seven of them identified as young stellar objects. We image a well-collimated radio jet with a thermal free-free core (VLA 11) associated with the Class I intermediate-mass protostar HOPS 370. The jet presents several knots (VLA 12N, 12C, 12S) of non-thermal radio emission (likely synchrotron from shock-accelerated relativistic electrons) at distances of ~7,500-12,500 au from the protostar, in a region where other shock tracers have been previously identified. These knots are moving away from the HOPS 370 protostar at ~ 100 km/s. The Class 0 protostar HOPS 108, which itself is detected as an independent, kinematically decoupled radio source, falls in the path of these non-thermal radio knots. These results favor the previously proposed scenario where the formation of HOPS 108 has been triggered by the impact of the HOPS 370 outflow with a dense clump. However, HOPS 108 presents a large proper motion velocity of ~ 30 km/s, similar to that of other runaway stars in Orion, whose origin would be puzzling within this scenario. Alternatively, an apparent proper motion could result because of changes in the position of the centroid of the source due to blending with nearby extended emission, variations in the source shape, and /or opacity effects.Comment: 16 pages, 4 figures, accepted for publication in The Astrophysical Journa