Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Methyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality. Objective The aim of this study was to identify potential biomarkers of BCC response to MAL-PDT. Material and methods Clinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated. Results The retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01). Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8) Conclusion Our finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapyThis project received support from the Instituto de Salud Carlos III and Fondos Feder Europeos, MINECO (FIS PI15/00974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

A Multidisciplinary Vision of the Criminal, Social and Occupational Risk Consequences of the Use of Police Force

(1) Background: The use of force by public and private security forces is currently an issue of great relevance because of the potential injuries caused by any excessive use of force by either active or passive subjects or a deficit in the real mastery of appropriate physical intervention techniques (PITs). For this reason, certain traditionally used physical intervention techniques have been questioned by scientific research studies and punished by justice. On the other hand, certain media have dealt with this matter in a biased and unfair manner by broadcasting videos where the use of force by police officer is displayed out of context. As a consequence, this problem has been brought under the spotlight, causing general uneasiness of the communities and rapidly spreading over social networks while favoring all sorts of parallel judgments. (2) Research method: A suit was equipped with 19 inertial measurement units (IMUs) and a Biomechanics of Bodies software application for Marras analysis of the data collected on trajectory, trunk twisting velocity, sagittal angle, load, and nature and severity of the injuries associated with the different intervention techniques examined. (3) Results: According to the data registered, the implementation of operational tactical procedures (OTPs) reduces the probability of injuries and leads to a more satisfactory outcome. (4) Conclusions: The implementation of operational tactical procedures, together with an awareness of the risks associated with the excessive use of force by public and private security forces and bodies, could reduce the risk of injuries suffered by both officers and citizens.R&D PROJECT DER 2012-35997-C03-03 “Study of police defense materials and possible improvements” financed by the Secretary of State for research, development, and innovation of MINEC

An Analysis of Biomechanical Parameters in OTP Police Physical Intervention Techniques for Occupational Risk Prevention

(1) Background: a set of ergonomic parameters that are relevant for risk assessment methods for the prevention of occupational risks, such as REBA or NIOSH, have been measured by means of inertial sensors that allow capturing the movements of the human body. These methods base their assessment on a number of postural and dynamic parameters. In the case of police physical intervention techniques, trunk, legs, arms, forearms and wrists angles, joint contact force and sheer force at the L5-Pelvic junction, asymmetry (angle and factor), and muscle power are the more relevant parameters to be considered. (2) Method: The data have been collected by means of a motion capture suit equipped with 19 inertial sensors. The large amount of data and the 3-dimensional plots have been managed by a powerful software package specific for ergonomic analysis. The police physical intervention technique used was OTP. (3) Results: Five ergonomic parameters in a traditional police physical intervention technique have been analyzed. REBA scores and ergonomic metrics have been recorded and discussed with some prevention risk limits from the literature. (4) Conclusions: the usage of inertial sensors to capture the movements in OTPs provides a new and quite an efficient viewpoint for occupational risk research studies

OTP-PRL: an app for occupational risk prevention in policing activities

Background: The rapid progress in information and communication technologies has promoted the development of smartphone applications (apps) for a wide variety of purposes including workplace safety. However, no specific apps for occupational risk prevention in the police domain seemingly exist as yet. In this work, an app running under the iOS and Android operating systems was developed to help police officers become acquainted with policing-related occupational risks and to prevent their damaging consequences. Results: The proposed app, which uses an iterative user-centered design to avoid occupational risks in policing activities, was assessed for performance by a group of users and experts through a System Usability Scale (SUS) questionnaire. The mean overall score for the questionnaire was 82.3. The app has backend support to facilitate continual improvement through contributions from users and administrators. A field test revealed increased awareness of policing occupational risks after using the app in many users. Conclusions: A novel product that covers the needs of ORP requirements of police officers has been developed

A Legal and Forensic Medicine Approach to Police Physical Intervention Techniques in High-Risk Situations

Background: The physical intervention techniques (PITs) typically used by the police in troublesome situations are examined in terms of injuring potential depending on whether they target a body zone of high, medium or low vulnerability. Based on legal and forensic considerations, and principles of congruence, opportunity and proportionality, a need exists to favor opponent locking and arrest techniques targeting non-vulnerable zones to minimize the risk of severe damage. Methods: A search of the training manuals for the different kind of law of enforcement officers was carried out. Revision of injuries was available from electronic databases of academic o medical journals. Results: Three different locking and arrest PITs based on operational tactical procedures (OTP) that avoid zones of high or medium vulnerability are proposed. The new techniques use blocking, diverting and grabbing of the upper and lower limbs, followed by dislocation and locking of the same targets. Conclusions: The damaging potential of such PITs was assessed in terms of anatomical region and most were found to have a high risk of severe damage. The alternative PITs proposed here, which rely on OTP, improve in legal and forensic medical terms on existing choices and dramatically reduce the risk of injuring arrestees

Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy

Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT. © 2014 The Society for Investigative DermatologyThe work was supported by MINECO (FIS PI12/01253), and Comunidad de Madrid (S2010/BMD-2359). We recognize the valuable contributions of Javier Suela and Juan Cruz Cigudos

Diseño experiencial ergocromático para proyectos industriales

El entorno construido ha sido creado para dar soporte a las actividades implicadas en el desarrollo humano. Mejora la habitabilidad sobre el planeta a través de construcciones industriales y urbanas con el objetivo de eliminar las dificultades presentes por la adaptación del ser humano al entorno natural. Una de las características del diseño óptimo de ambientes construidos son las dimensiones del confort (física, psicológica y sociocultural) controladas a través de los factores ambientales como son iluminación, cromatismo, ambiente sonoro o variables termohigrométricas. Todos ellos afectan al bienestar y satisfacción de las personas (bien sean usuarios, o en ambientes laborales trabajadores o clientes). En el presente trabajo se propone una metodología para el diseño experiencial ergocromático del entorno construido de ambientes industriales, incluyendo el espacio de trabajo, de forma que al integrar la dimensión cromática conducida desde el diseño de experiencias, posibilite la fruición y confort de los usuarios. Se pretende incorporar una nueva dimensión en los proyectos de ambientes industriales, teniendo en cuenta aspectos no exclusivamente tecnológicos, sino considerando en la fase de conceptualización, una vertiente de diseño industrial que propicie una mayor armonía entre persona y ambiente a través de la gestión de los aspectos cromáticos del entorno.The built environment has been created to support the activities involved in human development. Industrial and urban construction eliminate the difficulties in the human adaptation to the natural environment and they improve the habitability of the planet. One of the characteristics of the optimal design of built environments are the dimensions of comfort (physical, psychological and sociocultural). They are controlled by environmental factors such as light, colours, noise or thermohigrometric variables. All these affect the welfare and satisfaction people (users or workers and clients in work environments). In this paper a methodology for Experiential ergo-chromatic design of industrial environments is proposed. The methodology integrates the chromatic dimension through experience design to achieve the user comfort. This is a new dimension for industrial projects where is essential to take into account not only technological factors but also the aspects and characteristics for encouraging the harmony between people and the environment through the management of environmental chromatic aspectst

Enhancing the hydrogen transfer catalytic activity of hybrid carbon nanotube-based NHC–iridium catalysts by increasing the oxidation degree of the nanosupport

CVD-grown multiwalled carbon nanotubes were purified by applying four different treatments with increasing oxidation severity. The growing severity of the treatment results in progressive oxygen functionalization of the surface along with introduction of an increasing quantity of defects on the carbon nanotube walls. Iridium–N-heterocyclic carbene complexes were covalently anchored to those oxidized surfaces through their surface carboxylic acids via acetyl linkers. The carbon nanotube-based iridium–NHC hybrid materials developed are active in the hydrogen-transfer reduction of cyclohexanone to cyclohexanol with 2-propanol/KOH as hydrogen source but with rather different activity. The catalytic activity of the hybrid catalysts is strongly influenced by the type and amount of oxygenated functionalization resulting from the treatment applied to the support, being the most active and the most oxidized material

Enhancing the hydrogen transfer catalytic activity of hybrid carbon nanotube-based NHC–iridium catalysts by increasing the oxidation degree of the nanosupport

CVD-grown multiwalled carbon nanotubes were purified by applying four different treatments with increasing oxidation severity. The growing severity of the treatment results in progressive oxygen functionalization of the surface along with introduction of an increasing quantity of defects on the carbon nanotube walls. Iridium-N-heterocyclic carbene complexes were covalently anchored to those oxidized surfaces through their surface carboxylic acids via acetyl linkers. The carbon nanotube-based iridium-NHC hybrid materials developed are active in the hydrogen-transfer reduction of cyclohexanone to cyclohexanol with 2-propanol/KOH as hydrogen source but with rather different activity. The catalytic activity of the hybrid catalysts is strongly influenced by the type and amount of oxygenated functionalization resulting from the treatment applied to the support, being the most active and the most oxidized material.The authors thank the Spanish Ministry of Economy and Competitiveness (MINECO/FEDER) (Projects Consolider Ingenio 2010 CSD2009-00050 and CTQ2013-42532-P) and the Diputación General de Aragón (FSE-E07 and FSE-E69) for their financial support. Dr. P. A. thanks MINECO for a Ramón y Cajal contract. M. B. acknowledges his fellowship from MECD (AP2010-0025).Peer Reviewe

Composición del locus de control en dos ciudades latinoamericanas

The locus of control is a personality trait linked to the attribution people make concerning their success and failures. Research in nations and societies has demonstrated that there exist general and particular characteristics about control perception, where culture plays an important role. The initial objective was to know the factorial composition about locus of control in two groups located in Hermosillo, Sonora México (n=600) and João Pessoa, Paraíba. Brazil (n=600); then, to establish the differences of the construct between the groups concerning the attribute variables: age, education level, occupation and city. The results show three dimensions in the two groups: internal, affiliation and external locus of control. The general data suggest that the population samples of the cities make control judgements related with efforts and personal work, affiliation to collectives and groups of interest as the basis for explaining their success and failures. Key words: locus of control, cross-cultural psychology, México, Brazil.El locus de control es un rasgo de personalidad vinculado con la atribución que hacen los individuos acerca de sus éxitos y fracasos. Los estudios en diferentes naciones y sociedades han demostrado que existen características generales y particulares respecto a la percepción de control y donde la cultura juega un papel importante. Se partió del objetivo de conocer la composición factorial del locus de control en dos poblaciones, Hermosillo, Sonora (México) (n=600) y João Pessoa, Paraíba (Brasil) (n=600); y establecer las diferencias en cuanto a dicho constructo en ambas poblaciones con respecto a las variables atributivas: edad, escolaridad, ocupación y ciudad. Los resultados revelan tres dimensiones comunes a las dos poblaciones: locus de control interno, locus de control afiliativo y locus de control externo. Los datos en general hacen ver que las muestras poblacionales de las ciudades hacen juicios de control en relación a los esfuerzos y el trabajo personal, en la afiliación a colectivos y grupos de interés como los fundamentos de explicación para éxitos y fracasos