BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population.

BACKGROUND: BEECH investigated the efficacy of capivasertib (AZD5363), an oral inhibitor of AKT isoforms 1-3, in combination with the first-line weekly paclitaxel for advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, and in a phosphoinositide 3-kinase, catalytic, alpha polypeptide mutation sub-population (PIK3CA+). PATIENTS AND METHODS: BEECH consisted of an open-label, phase Ib safety run-in (part A) in 38 patients with advanced breast cancer, and a randomised, placebo-controlled, double-blind, phase II expansion (part B) in 110 women with ER+/HER2- metastatic breast cancer. In part A, patients received paclitaxel 90 mg/m2 (days 1, 8 and 15 of a 28-day cycle) with capivasertib taken twice daily (b.i.d.) at two intermittent ascending dosing schedules. In part B, patients were randomly assigned, stratified by PIK3CA mutation status, to receive paclitaxel with either capivasertib or placebo. The primary end point for part A was safety to recommend a dose and schedule for part B; primary end points for part B were progression-free survival (PFS) in the overall and PIK3CA+ sub-population. RESULTS: Capivasertib was well tolerated, with a 400 mg b.i.d. 4 days on/3 days off treatment schedule selected in part A. In part B, median PFS in the overall population was 10.9 months with capivasertib versus 8.4 months with placebo [hazard ratio (HR) 0.80; P = 0.308]. In the PIK3CA+ sub-population, median PFS was 10.9 months with capivasertib versus 10.8 months with placebo (HR 1.11; P = 0.760). Based on the Common Terminology Criteria for Adverse Event v4.0, the most common grade ≥3 adverse events in the capivasertib group were diarrhoea, hyperglycaemia, neutropoenia and maculopapular rash. Dose intensity of paclitaxel was similar in both groups. CONCLUSIONS: Capivasertib had no apparent impact on the tolerability and dose intensity of paclitaxel. Adding capivasertib to weekly paclitaxel did not prolong PFS in the overall population or PIK3CA+ sub-population of ER+/HER2- advanced/metastatic breast cancer patients.ClinicalTrials.gov: NCT01625286.

Magnitudes y unidades para dosimetría del personal ocupacionalmente expuesto en radiodiagnóstico e intervencionismo / Quantities and units for dosimetry of occupationally exposed personnel in diagnostic and interventional radiology

Resumen:Existen diversos documentos y recomendaciones internacionales sobre nombres, conceptos, definiciones y campos de aplicación para diversas magnitudes y unidades utilizadas para monitorear los niveles de radiación ionizante a los que son expuestos los trabajadores durante los procedimientos de Radiodiagnóstico e Intervencionismo. Sin embargo, la legislación nacional, al igual que para la dosimetría de los pacientes, no se encuentra actualizada en este sentido y no contempla en sus documentos un glosario actualizado que permita encontrar en forma rápida y precisa este tipo de información. Por lo anterior, este trabajo de revisión corresponde a un segundo documento guía, complementario a nuestro trabajo publicado en 2015 titulado "Magnitudes y unidades para dosimetría a pacientes en radiodiagnóstico e intervencionismo", que describe de manera didáctica y en un lenguaje sencillo para los profesionales de la salud y áreas afines, las principales magnitudes y unidades que se deben conocer y utilizar en la dosimetría ocupacional de los trabajadores que participan en procedimientos de Radiodiagnóstico e Intervencionismo.

Abstract: There are many documents and international recommendations offer names, concepts, definitions and fields of application for various quantities and units used to monitor the exposure levels of ionising radiation to which workers are exposed during the diagnostic and interventional radiology procedures. However, as in the case of patient dosimetry, national legislation is not up-to-date in this area and nowhere does it establish an up-to-date glossary that would facilitate rapid and precise location of this kind of information. In light of the foregoing, this review paper presents a second guidance document, complementary to our published article in 2015 titled "Quantities and units used in patient dosimetry in radiodiagnostic and intervencional procedures", which describes the principal quantities and units that must be known and used in occupational dosimetry for workers participating in diagnostic and interventional radiology procedures, in a didactical manner and using simple language for professionals in health and similar areas.

Correction: Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications.

Correction for 'Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications' by R. Ravichandran et al., J. Mater. Chem. B, 2016, 4, 318-326.

Novel specific peptides as superior surface stabilizers for silver nano structures: role of peptide chain length.

Three new collagen mimetic peptides containing the CLK motif as anchoring arms were tested for silver nanoparticle surface stabilization. Our experimental and molecular dynamics data indicate that peptide length has an important effect not only in the resulting nanosilver's colloidal stability, but also in the biological performance of the composite.

Nitroxide amide-BODIPY probe behavior in fibroblasts analyzed by advanced fluorescence microscopy.

A novel synthesized nitroxide amide-BODIPY prefluorescent probe was used to study cellular redox balance that modulates nitroxide/hydroxylamine ratio in cultured human fibroblasts. FLIM quantitatively differentiated between nitroxide states of the cytoplasm-localized probe imaged by TIRF, monitoring nitroxide depletion by hydrogen peroxide; eluding incorrect interpretation if only fluorescence intensity is considered.

Regenerative approaches for the cornea.

The cornea is the transparent front part of the eye that transmits light to the back of the eye to generate vision. Loss of corneal transparency, if irreversible, leads to severe vision loss or blindness. For decades, corneal transplantation using human donor corneas has been the only option for treating corneal blindness. Despite recent improvement in surgical techniques, donor cornea transplantation remains plagued by risks of suboptimal optical results and visual acuity, immune rejection and eventually graft failure. Furthermore, the demand for suitable donor corneas is increasing faster than the number of donors, leaving thousands of curable patients untreated worldwide. Here, we critically review the state of the art of biomaterials for corneal regeneration. However, the lessons learned from the use of the cornea as a disease model will allow for extension of the biomaterials and techniques for regeneration of more complex organs such as the heart.

Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.

Despite the broad anti-microbial and anti-inflammatory properties of silver nanoparticles (AgNPs), their use in bioengineered corneal replacements or bandage contact lenses has been hindered due to their intense yellow coloration. In this communication, we report the development of a new strategy to pre-stabilize and incorporate AgNPs with different colours into collagen matrices for fabrication of corneal implants and lenses, and assessed their in vitro and in vivo activity.

Artificial biomembranes stabilized over spin coated hydrogel scaffolds. Crosslinking agent nature induces wrinkled or flat surfaces on the hydrogel.

Hydrogel films possess the ability of retain water and deliver it to a phospholipid bilayer mainly composed by DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine); moisture of the medium favors the stability of an artificial biomembrane when it is subjected to repetitive heating cycles. This hypothesis is valid when the hydrogel film, used as scaffold, present a flat surface morphology and a high ability for water releasing. On the other hand, when the sample presents a wrinkle topography (periodic undulations), free lateral molecular movement of the bilayer becomes lower, disfavoring the occurrence of clear phases/phase transitions according to applied temperature. Hydrogel films were prepared using HEMA (hydroxyethylmetacrylate), different crosslinking agents and initiators. This reaction mixture was spread over hydrophilic silicon wafers using spin coating technique. Resultant films were then exposed to UV light favoring polymeric chain crosslinking and interactions between hydrogel and substrate; this process is also known to generate tensile stress mismatch between different hydrogel strata, producing out-of-plane net force that generate ordered undulations or collapsed crystals at surface level. DPPC bilayers were then placed over hydrogel using Langmuir-Blodgett technique. Surface morphology was detected in order to clarify the behavior of these films. Obtained data corroborate DPPC membrane stability making possible to detect phases/phase transitions by ellipsometric methods and Atomic Force Microscopy due to their high hydration level. This system is intended to be used as biosensor through the insertion of transmembrane proteins or peptides that detect minimal variations of some analyte in the environment; artificial biomembrane stability and behavior is fundamental for this purpose.

Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications.

In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the cross-linking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

Agenesia del lóbulo hepático derecho asociado a agenesia vesicular / Agenesis of the right hepatic lobe associated with gallbladder agenesis

Background: Anatomical abnormalities of the liver are rare and their association with gallbladder agenesis are even more uncommon. Case report: We report a 63 years old man complaining of jaundice, without pain or fever. A magnetic resonance imaging showed a right hepatic lobe agenesis associated with gallbladder agenesis. Jaundice subsided spontaneously.

Introducción: Las anomalías anatómicas del hígado son raras, la asociación a una agenesia vesicular es más infrecuente aún, siendo su diagnóstico generalmente un hallazgo. Caso clínico: Presentamos el caso de un paciente masculino de 63 años que consulta por ictericia, sin dolor ni fiebre, al cual se le realiza diagnóstico por imagen con resonancia magnética de agenesia de lóbulo hepático derecho asociado a agenesia vesicular. Dado que el paciente no tiene litiasis biliar, se decide tratamiento médico.

Magnitudes y unidades para dosimetría a pacientes en radiodiagnóstico e intervencionismo / Quantities and units for patient dosimetry in diagnostic and interventional radiology

Because diagnostic and interventional radiology procedures represent one of the main sources of irradiation by ionizing radiation in the population, it has become a priority to become familiar with the quantities and units that account for patient dosimetry. There are countless documents and international recommendations on names, concepts, definitions and areas of application for various quantities and units used in patient dosimetry, in interventional and diagnostic radiology procedures. However, national legislation is not updated in this regard and does not provide, in any of its documents, an updated glossary that enables finding this type of information quickly and precisely. Therefore, this review paper presents in a didactic way and in plain language, the main quantities and units to be used in the dosimetry of patients undergoing diagnostic and interventional radiology procedures.

Debido a que los procedimientos de radiodiagnóstico e intervencionismo representan una de las principales fuentes de irradiación a la población por radiaciones ionizantes, se vuelve prioritario conocer las magnitudes y unidades que dan cuenta de la dosimetría a los pacientes. Existen innumerables documentos y recomendaciones internacionales sobre nombres, conceptos, definiciones y campos de aplicación para diversas magnitudes y unidades utilizadas en la dosimetría de pacientes en procedimientos de radiodiagnóstico e intervencionismo. Sin embargo, la legislación nacional no se encuentra actualizada en este sentido y no contempla en ninguno de sus documentos, un glosario actualizado que permita encontrar en forma rápida y precisa este tipo de información. Por lo anterior, este trabajo de revisión presenta de manera didáctica y en un lenguaje sencillo, las principales magnitudes y unidades que se deben utilizar en la dosimetría de pacientes sometidos a procedimientos de radiodiagnóstico e intervencionismo.

Orientation relations during the α-ω phase transition of zirconium: in situ texture observations at high pressure and temperature.

Transition metals Ti, Zr, and Hf have a hexagonal close-packed structure (α) at ambient conditions, but undergo phase transformations with increasing temperature and pressure. Of particular significance is the high-pressure hexagonal ω phase which is brittle compared to the α phase. There has been a long debate about transformation mechanisms and orientation relations between the two crystal structures. Here we present the first high pressure experiments with in situ synchrotron x-ray diffraction texture studies on polycrystalline aggregates. We follow crystal orientation changes in Zr, confirming the original suggestion by Silcock for an α→ω martensitic transition for Ti, with (0001)(α)||(1120)(ω), and a remarkable orientation memory when ω reverts back to α.

Detección de genes shv y tem en cepas de Escherichia coli productoras de B-lactamasas de espectro extendido procedentes de dos centros hospitalarios de Chiclayo- Perú: enero- agosto 2011

Describir la frecuencia de distribucion de los genes blaTEM y blaSHV en cepas de Escherichia coli productoras de �À- lactamasas de espectro extendido (BLEE) procedentes de dos centros hospitalarios de Chiclayo. Material y Metodos: Estudio de tipo descriptivo, trasversal. Las cepas de Escherichia coli productoras de BLEE fueron seleccionadas de pacientes con infeccion urinaria internados en los servicios de Cuidados Intensivos, Ginecologia, Medicina Interna y Cirugia de los hospitales Almanzor Aguinaga Asenjo y Las Mercedes. Las cepas fueron confirmadas previamente en los laboratorios de los dos hospitales usando las prueba fenotipica de Jarlier (Hospital Las Mercedes) y el sistema automatizado Vitek 2 (Hospital Nacional Almanzor Aguinaga Asenjo); el analisis de deteccion de los genes blaTEM y blaSHV se hizo por PCR en el Laboratorio de Genetica de la Universidad Catolica Santo Toribio de Mogrovejo. Resultados: Un total de 66 cepas de Escherichia coli recolectadas desde Enero a Agosto del 2011 fueron confirmadas como BLEE; de estas se confirmo que 40 cepas (60,61%) presentaron el gen blaTEM, 8 cepas (12,12%) presentaron el gen blaSHV y 18 cepas (27,27%) no presentaron ninguno de los dos. Ninguna de las cepas presento ambos genes. Conclusión: los genes blaTEM y blaSHV fueron frecuentes en las cepas BLEE de ambos hospitales, siendo más frecuente el gen blaTEM.(AU)

Objective: To describe the distribution frequency of blaTEM and blaSHV genes in extended spectrum À-lactamase producing Escherichia coli strains of two hospitals of Chiclayo.Material and Methods: Transversal, descriptive study.Extended spectrum À- lactamase (ESBL) Escherichia coli strains were initially obtained from urine cultures of patients with urinary tract infection from the services of Internal Medicine, Surgery, Intensive care unit and Urology from two hospitals of Chiclayo. The strains were previously confirmed in the laboratories using Jarlier's phenotypic method (Hospital las Mercedes) and the Vitek 2 automated system (Hospital Nacional Almanzor Aguinaga Asenjo); the genetic detection analysis of blaTEM and blaSHV genes was done by PCR (Polymerase chain reaction) in the Genetics Laboratory of Universidad Catolica Santo Toribio de Mogrovejo. Results: A total of 66 strains of Escherichia coli isolated since January to August 2011 were classified as ESBL; by PCR, the blaTEM gen was found in 40 strains (60.61%), the blaSHV gen in 8 strains (12.12%), and both genes were absent in 18 strains (27.27%).Conclusion: blaTEM and blaSHV genes were frequently detected in ESBL strains from both hospitals; being the blaTEM the most frequent.(AU)

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru.

SETTING: Primary health care centres in Callao, Peru. OBJECTIVES: To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST). DESIGN: Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008. RESULTS: There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P =30.003) was observed in the 2009 cohort. CONCLUSION: Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru.

Evaluation of solute binding to proteins and intra-protein distances from steady state fluorescence measurements.

Steady state fluorescence measurements, due to their relative simplicity and fast and easy implementation, are one of the most employed techniques for evaluating the non-covalent binding of small molecules to proteins. In the present review we discuss the main characteristics of solute binding and the experimental procedures that can be employed for evaluating both, the efficiency of the process and the number of binding sites. It is also discussed the possibility of determining the distance between endogenous fluorophores and non-covalently bound solutes. Albumins (human serum albumin and bovine serum albumin) are considered as model proteins due to their relevance as solute carriers, the extensive available data comprising binding of a large number of solutes, and the reduced number of intrinsic fluorophores which simplifies the data treatment. It is shown that, in spite of the apparent simplicity of the systems, extreme care must be exercised in data treatment and interpretation to avoid misleading results. This applies to the evaluation of binding constants, number of binding sites, and average distance between intrinsic fluorophores and non-covalently bound solutes associated to the proteins.