Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study.

Background: After percutaneous coronary intervention (PCI), clopidogrel resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these ischemic events and improves outcomes among Caribbean Hispanic patients from Puerto Rico, who are underrepresented in clinical pharmacogenomic (PGx)-guided implementation studies. Methods: Individual platelet function testing (PRU) measures, CYP2C19*2 and PON1 rs662 genotypes, clinical and demographic data from 8 medical facilities were included. Patients were separated into standard of care (SoC) and genotype-guided groups (150 each). Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Alternative therapy with ticagrelor was recommended for patients with a high risk score ≥2. Statistical associations between patient time free of MACCEs and predictor variables (i.e., treatment groups, risk scores) were tested in this population using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. Results: Median age of participants is 67 years; BMI: 27.8; 48% women; 14% smokers; 59% with type-2 diabetes mellitus (T2DM). Among patients with high-risk scores who were free from MACCE events 6 months after coronary stenting, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in terms of reducing the incidence rate of atherothrombotic events. Conclusions: The clinical utility of our PGx-driven CDS algorithm to reduce the incidence rate of MACCEs among post-PCI Caribbean Hispanic patients on clopidogrel was externally demonstrated. Clinical Trial Registration Unique Identifier: NCT03419325.

Comparative investigation of Cu(II) complexes with dithiocarbazate: Structural design, theoretical calculation, and in vitro antitumor activity.

The present work reports the synthesis and investigation by semi-empirical Density Functional Theory (DFT), physical chemistry, and spectroscopic methods of two dithiocarbazates, 2-acetylpyridine-S-p-bromobenzyl-dithiocarbazate (HL1) and 2-acetylpyridine-S-p-nitrobenzyl-dithiocarbazate (HL2) and their Cu(II) complexes, [Cu(L1)Cl] (1), [Cu(L1)Br] (2), [Cu(L2)Cl] (3) and [Cu(L2)Br] (4). Single crystal X-ray analyzes showed distorted square planar geometry to the metal centers, which tridentate ligands coordinated by the NNS system and an additional halogen (Cl- or Br-) to complete the coordination sphere. Mass spectrometry data indicated the presence of [Cu(L1)(DMF)]+ and [Cu(L2)(DMF)]+, due to the exchanging of chloride/bromide ions and characteristic fragmentations of the compounds. The DFT composite method B97-3c was employed to optimize the geometries of ligands and complexes and IR spectra were calculated revealing good agreement with experimental data. Hydrogen bonds and π⋅⋅⋅π stacking interactions upon the molecular packing were investigated by Hirshfeld surface and fingerprint plots with the main interactions attributed to the H⋅⋅⋅H contacts. The biological activity of the dithiocarbazates and their Cu(II) complexes were evaluated in vitro against the human glioma U251 cells. Results revealed that the free dithiocarbazates present great in vitro antitumor activity that is increased after the complexation with copper. The measurement of cytotoxicity of the compounds showed biological activity in a low range of concentration, which indicates high efficiency as potential drugs.

Distinct differences in the nanoscale behaviors of the twist-bend liquid crystal phase of a flexible linear trimer and homologous dimer.

We synthesized the liquid crystal dimer and trimer members of a series of flexible linear oligomers and characterized their microscopic and nanoscopic properties using resonant soft X-ray scattering and a number of other experimental techniques. On the microscopic scale, the twist-bend phases of the dimer and trimer appear essentially identical. However, while the liquid crystal dimer exhibits a temperature-dependent variation of its twist-bend helical pitch varying from 100 to 170 Å on heating, the trimer exhibits an essentially temperature-independent pitch of 66 Å, significantly shorter than those reported for other twist-bend forming materials in the literature. We attribute this to a specific combination of intrinsic conformational bend of the trimer molecules and a sterically favorable intercalation of the trimers over a commensurate fraction (two-thirds) of the molecular length. We develop a geometric model of the twist-bend phase for these materials with the molecules arranging into helical chain structures, and we fully determine their respective geometric parameters.

New SmAPF Mesogens Designed for Analog Electrooptics Applications.

We have previously reported the first realization of an orthogonal ferroelectric bent-core SmAPF phase by directed design in mesogens with a single tricarbosilane-terminated alkoxy tail. Given the potentially useful electrooptic properties of this phase, including analog phase-only electrooptic index modulation with optical latching, we have been exploring its "structure space", searching for novel SmAPF mesogens. Here, we report two classes of these-the first designed to optimize the dynamic range of the index modulation in parallel-aligned cells by lowering the bend angle of the rigid core, and the second expanding the structure space of the phase by replacing the tricarbosilane-terminated alkyl tail with a polyfluorinated polyethylene glycol oligomer.

Tratamiento de hematoma subdural: comparación entre drenaje subdural a presión negativa contra otro tipo de drenajes / Treatment of subdural hematoma: comparative analysis between subdural drainage with negative pressure versus other drainages

La ultrasonografía es un método de evaluación rápido y eficaz en los departamentos de emergencias, siempre en manos entrenadas. La lesión vascular periférica es un cuadro que en lo que trauma se refiere, debe tener un veloz diagnóstico y tratamiento por los riesgos que significa: En lesiones abiertas, la hemorragia; y en lesiones cerradas se añade el síndrome compartimental. Lograr la evaluación de la indemnidad o no del árbol vascular en los miembros, se torna importante a la hora de prevenir eventos que requieran intervención quirúrgica (reparación y/o fasciotomía). El objetivo de este trabajo consiste en demostrar la utilidad del conocimiento del árbol vascular periférico y su evaluación mediante doppler para el manejo del trauma vascular periférico, mental (n=77) = 11 (14,78 %). Resolución: lesión vascular = 1 (1,3 %) síndrome compartimental= 1 (1,3 %) con resolución quirúrgica. La utilización de la ultrasonografía y del doppler para la evaluación vascular periférica es útil para el reconocimiento precoz del riesgo a desarrollar desde una lesión vascular simple hasta un síndrome compartimental. La utilización de listas de verificación durante la simulación para la generación del criterio, son útiles en la formación de residentes de cirugía

Report the recurrence rate ofnegative pressure subdural drainage (NPSD) versusto other kind of drains (OD). Design and Methods: Astudy was conducted cross-sectional and weretrospectively analyzed on the database of theneurosurgical service and we looked for all surgicalprocedures recorded from January 2006 to December2015. Procedures with preoperative diagnosis ofsubdural hematoma (SDH) were selected, with a to-tal of 364 interventions, were excluded patients withpostoperative diagnosis different from SDH andeliminated those who did not have complete data,recurrence was identified, a statistical analysis wasperformed describing frequency measurementspercentage and standard deviation, RM and chi-square was obtained by software EPIDAT 3.1. 277 surgeries were performed in 230 patients, Thepopulation was divided into two groups: the first thoseinterventions with negative pressure subduraldrainage versus a second group with other differentdrains, and finally we compared the recurrence ratein each group, 44 surgeries had recurrence of SDH.The proportion of recurrence was found 16 % of thesurgeries, 16 % (n=7) of these were performed withnegative pressure subdural drainage and theremaining 84 % (n=37) by other drainage. The reasonfor prevalence found was 0.36 (95 % CI , 0.15 to0.85), with statistically significant differences (p =0.0165). The chi-square was 5.75 for the SDH withNPSD. It was found that patients treated with NPSDhave a lower risk of recurrence compared with OD,which acts as a protective factor for patients treatedwith this type of drain, this is statistically significant.

[Maxillary trigeminal schwannoma. Presentation of a case and review of literature]. / Schwannoma trigeminal maxilar. Presentación de un caso y revisión de la literatura.

INTRODUCTION: Schwannomas are benign tumours that are relatively common in the head, however the involvement of the sinunasal region is rare and there are only 5 cases reported in the maxilla in current literature, representing less than 1% of bone tumours. CLINICAL CASE: We report the case of a woman with a right maxillary schwannoma who underwent a complete resection of the lesion. Emphasis is placed on the rarity of the lesion in terms of its location and includes a review of clinical behaviour, diagnosis and current treatment options. CONCLUSIONS: Maxillary trigeminal schwannoma must be suspected if vague sinunasal symptoms, paranasal mass or, as in this case, trigeminal neuralgia present. Surgical treatment is indicated, and approaches vary according to location and tumour size.

Abordaje único para aneurismas del círculo arterial cerebral / Unique craniotomy for aneurysms of the cerebral arterial circle

El objetivo del trabajo fue escribir la técnica quirúrgica y reportar la experiencia de nuestro hospital en el uso del abordaje pterional modificado como primera elección para el clipaje de aneurismas del círculo arterial cerebral en cualquier ubicación e incluso múltiples. Realizamos un estudio retrospectivo y reportamos una serie de 37 pacientes (25 mujeres y 12 hombres) con diagnóstico de aneurismas derivados del círculo arterial cerebral de distintas ubicaciones, desde enero del 2012 hasta marzo del 2015. Se presenta la experiencia de 51 aneurismas incluidos 8 casos de aneurismas múltiples y 9 aneurismas gigantes.Todos los aneurismas fueron clipados mediante un abordaje pterional modificado. Se describieron yesquematizaron los pasos del procedimiento quirúrgico secuencialmente. Mediante este análisis se estableceque el abordaje frontotemporoesfenoidal modificado (pterional) permite el acceso quirúrgico para el clipajede estas lesiones vasculares provenientes del círculo arterial cerebral lo cual correlaciona con la evidencia previa. La descripción detallada de la técnica quirúrgica favorece una adecuada comprensión de la anatomía quirúrgica y permite la reproducción de esta técnica.

The objective of the study was to describe our surgical and technical experience by reporting a series of 51 aneurysms treated by a pterional craniotomy as a unique approach foraneurismatic lesions of the cerebral arterial circle (Willis polygon). Retrospective study that reportsa series of 37 patients (25 females and 12 males) with diagnosis of aneurismatic lesions from different localization in the Willis polygon from January 2012 to March 2015. Fifty one (51)aneurismatic lesions were treated by a unique pterional craniotomy, including 8 cases of multiple aneurismatic disease and 9 giant aneurysms. Every lesion was clipped by the same pterional modified approach. Every step of this procedure was described and illustrated sequentally. This analysis establishes that the modified fronto temporoesfenoidal (pterional) craniotomy allows surgical access to the clipping of these vascular lesions, from the circle of Willis which correlates with previous evidence. The detailed description of the surgical technique promotes a proper understanding of surgical anatomy and allows playback of this technique.

Influence of alkalinity and VFAs on the performance of an UASB reactor with recirculation for the treatment of Tequila vinasses.

The main problem linked to the stability of upflow anaerobic sludge blanket (UASB) reactors during the treatment of Tequila vinasse is the high acidity and the null alkalinity present in this effluent. This research evaluates the effect of alkalinity and volatile fatty acids (VFAs) concentration on the performance of an UASB reactor with recirculation of the effluent for removing organic matter and biogas production from Tequila vinasses. Recirculation of the effluent reduces the impact of VFAs and organic matter concentration present in the influent, inducing the stability of the reactor. The UASB reactor was operated during 235 days at organic loading rates from 2.5 to 20.0 kg m(-3) d(-1), attaining a removal efficiency of COD greater than 75% with a methane yield of 335 ml CH4 g(-1) COD at SPT, maintaining a ratio of VFAs/Alk ≤ 0.5. Therefore, an optimal ratio of VFAs/Alk was established for the system operating in stable conditions for the treatment of Tequila vinasses. Under these conditions, the alkalinity was recuperated by the system itself, without the addition of external alkalinity.

Rovibrational energy and spectroscopic constant calculations of CH4⋯CH4, CH4⋯H2O, CH4⋯CHF3, and H2O⋯CHF3 dimers.

In this work, we performed a thorough investigation of potential energy curves, rovibrational spectra, and spectroscopic constants for dimers whose interactions are mediated by hydrogen bonds and other hydrogen interactions. Particularly, we deal with CH4⋯CH4, CH4⋯H2O, CH4⋯CHF3, and H2O⋯CHF 3 dimers by employing accurate electronic energy calculations with two different basis sets at the MP2 level of theory. Following this, the discrete variable representation method was applied to solve the nuclear Schrödinger equation, thus obtaining spectroscopic constants and rovibrational spectra. The harmonic constant, ω e , presents a direct relation to the strength of dimer interactions. As a general rule, it was found that a decrease of interatomic distances is followed by the increase of D e for all dimers. This behavior suggests that the interaction of CH4⋯CH4 is the weakest among all dimers, followed by CH4⋯CHF3, CH4⋯H2O and the strongest interaction given by the H2O⋯CHF 3 dimer.

Momentos históricos de la Facultad de Medicina en Timor Leste / Historical moments of the Medicine Faculty in East Timor

Se realiza un estudio de corte pedagógico, con el objetivo de precisar momentos históricos de la Facultad de Medicina de Timor Leste. Los datos se obtuvieron a través de la observación, entrevista a informantes claves y la revisión documental. Con la participación de los profesionales de la brigada médica cubana en el mencionado país, se ejecutó el nuevo programa de formación de médicos, el cual se había iniciado en la Universidad Barrio Adentro de la República Bolivariana de Venezuela y en las facultades inauguradas para la formación de médicos de Cuba, y el resto del mundo. Con relación al postgrado se logró la formación de 100 residentes cubanos como especialistas en Medicina General Integral y dos versiones del diplomado en Educación Médica.

A pedagogical study was carried out with the objective to determine the historical moments of the Medicine Faculty in East Timor. The data were collected through the observation, interviews and documents review, with the participation of the professionals of the Cuban medical brigade in this country. A new program for the formation of doctors was carried out; it had started in the Inside the Neighborhood University in the Venezuelan Republic and in the faculties for the formation of doctors in Cuba, and in the rest of the world. In relation to the postgraduate, a hundred Cuban specialists were formed as residents in Integral General Medicine and two versions of the specialized course in medical education.

Momentos históricos de la Facultad de Medicina en Timor Leste / Historical moments of the Medicine Faculty in East Timor

Se realiza un estudio de corte pedagógico, con el objetivo de precisar momentos históricos de la Facultad de Medicina de Timor Leste. Los datos se obtuvieron a través de la observación, entrevista a informantes claves y la revisión documental. Con la participación de los profesionales de la brigada médica cubana en el mencionado país, se ejecutó el nuevo programa de formación de médicos, el cual se había iniciado en la Universidad Barrio Adentro de la República Bolivariana de Venezuela y en las facultades inauguradas para la formación de médicos de Cuba, y el resto del mundo. Con relación al postgrado se logró la formación de 100 residentes cubanos como especialistas en Medicina General Integral y dos versiones del diplomado en Educación Médica(AU)

Spontaneous ferroelectric order in a bent-core smectic liquid crystal of fluid orthorhombic layers.

Macroscopic polarization density, characteristic of ferroelectric phases, is stabilized by dipolar intermolecular interactions. These are weakened as materials become more fluid and of higher symmetry, limiting ferroelectricity to crystals and to smectic liquid crystal stackings of fluid layers. We report the SmAP(F), the smectic of fluid polar orthorhombic layers that order into a three-dimensional ferroelectric state, the highest-symmetry layered ferroelectric possible and the highest-symmetry ferroelectric material found to date. Its bent-core molecular design employs a single flexible tail that stabilizes layers with untilted molecules and in-plane polar ordering, evident in monolayer-thick freely suspended films. Electro-optic response reveals the three-dimensional orthorhombic ferroelectric structure, stabilized by silane molecular terminations that promote parallel alignment of the molecular dipoles in adjacent layers.

Theoretical study of CH4-CH4, CHF3-CH4, CH4-H2O, and CHF3-H2O dimers.

We have studied systems with typical hydrogen bonding and others with interaction involving hydrogen. CH(4)-CH(4), CH(4)-H(2)O, CHF(3)-CH(4), and CHF(3)-H(2)O dimers were studied using MPWB1K, PBE1PBE, MP2, and QCISD levels of theory with a large number of basis functions. The Pople 6-31+G(2d), 6-311++G(2d,2p), and 6-311++G(3df,3pd) as well as Dunning augmented aug-cc-pVDZ and aug-cc-pVTZ basis sets were used. The dimer geometries were fully optimized. An optimal basis set was determined for these systems to achieve a suitable compromise between accuracy and computational feasibility. A proper strategy was found for the electronic property calculations of dimers studied: the use of aug-cc-pVDZ as the optimal basis set at MP2 level. Dipole moments, polarizabilities, BSSE effects, and DeltaZPE were also analyzed for these dimers.

QCODES - fast topological descriptors for macromolecules.

A fast iterative algorithm to obtain topological atomic and molecular descriptors, called Qcodes, is presented in this work. Its linear time dependence with the size of the structures and low memory requirement allows practical use for small molecules as well as macromolecular systems. The descriptors are unique and are able to sense small topological changes in atom's neighborhood. These properties make them suitable as atom and molecular identifiers to be used in database searching, force field atom typing, isomorphism, and automorphism algorithms. Examples of descriptors, their convergence behavior, sensitivity, ambiguity, and algorithm's performance are shown in this paper.

Experiencia en el tratamiento de várices esofágicas mediante ligadura endoscópica / Experience in the treatment of esophageal varices by endoscopy subjected to rubber band ligation

El sangrado variceal representa hasta al 30 por ciento de los sangrados de tubo digestivo alto, ocasiona la muerte hasta en una tercera parte de los pacientes que son internados para su tratamiento y se relaciona con complicaciones más severas que las ocasionadas por cualquier otra hemorragia de localización proximal. El manejo endoscópico de estos pacientes básicamente se concretaba a la escleroterapia, sin embargo, actualmente se considera que la ligadura es el método de elección tanto para el control de las várices esofágicas por las ventajas que ofrece sobre sobre la escleroterapia. El objetivo de este estudio fue demostrar si los resultados reportados eran reproductibles en nuestro medio por lo que se tomó una muestra al azar de 20 pacientes con antecedentes de sangrado reciente de origen variceal, a los que se les sometió a ligadura para control de la hemorragia aguda y posteriormente tratamiento para alcanzar la erradicación de las várices esofágicas, obteniéndose control de la hemorragia aguda en 100 por ciento de los casos, erradicación de los paquetes varicosos en el 90 por ciento con un número de sesiones menor que lo esperado con la escleroterapia y con un menor número de complicaciones. No se presentaron eventos de resangrado en ninguno de los pacientes y no hubo decesos relacionados con el procedimiento