Can ethanol affect the cell structure? A dynamic molecular and Raman spectroscopy study.

The role that tobacco consumption plays in the etiology of oral cancer carcinogenesis, and of alcohol consumption acting as a co-factor, have been well established. However, in recent years, the contribution of alcohol consumption alone to oral cancer has been proposed. In fact, a high percentage of patients who develop oral cancer have both habits (tobacco and alcohol consumption), and other small patient groups only consume alcohol or do not have any other identifiable bad habits. In the present study we demonstrate, using a combination of dynamic molecular modelling and Raman spectroscopy, that ethanol has a significant effect on oral cells in vitro, mainly interacting with the lipids of the cell membrane, changing their conformation. Thus, it is possible to conclude that ethanol can affect the cell permeability, and by consequence serve as a possible trigger in oral carcinogenesis.

In vivo Raman spectroscopic characteristics of different sites of the oral mucosa in healthy volunteers.

OBJECTIVES: Investigate the biochemistry of in vivo healthy oral tissues through Raman spectroscopy. We aimed to characterize the biochemical features of healthy condition in oral subsites (buccal mucosa, lip, tongue, and gingiva) of healthy subjects. More specifically, we investigated Raman spectral characteristics and biochemical content of in vivo healthy tissues on Brazilian population. This characterization can be used to better define normal tissue and improve the detection of oral premalignant conditions in future studies. MATERIALS AND METHODS: For spectroscopic analysis a Raman spectrometer (Kaiser Optical Systems imaging spectrograph Holospec, f / 1.8i-NIR) coupled with a laser 785 nm, 60 mW was used. Raman measurements were obtained by means of an optical fiber (EMVision fiber optic probe) coupled between the laser and the spectrometer. Three spectra per site were acquired from the lip, buccal mucosa, tongue, and gingiva of ten healthy volunteers. This resulted in 30 spectra per oral sub-site and in total 120 spectra. RESULTS: We report detailed biochemical information on these subsites and their relative composition based on deconvolution studies of their spectra. Finally, we also report classification efficiency of 61, 83, 41, and 93% for buccal, gingiva, lip, and tongue respectively after applying multivariate statistical tools. CONCLUSIONS: We quantitated the contribution of various biochemicals in terms of percentage, and this will enable comparison not only across anatomical sites but also across studies. Raman spectroscopy can rapidly probe tissue biochemistry of healthy oral regions. Moreover, the study suggests the possibility of using Raman spectroscopy combined with signal processing and multivariate analysis methods to differentiate the oral sites in healthy conditions and compare with pathological conditions in future studies. CLINICAL RELEVANCE: The spectral characterization of the healthy condition of oral tissues by a noninvasive, label-free, and real-time analytical techniques is important to create a spectral reference for future diagnosis of pathological conditions.

Uso de recursos sanitarios y costes asociados al tratamiento antirretroviral de primera línea en España en la era de los inhibidores de la integrasa / Use of health resources and costs associated to first-line antiretroviral therapy in the era of integrase inhibitors

Introducción: El objetivo fue evaluar el uso de recursos sanitarios y costes asociados durante el primer año de tratamiento antirretroviral (TAR) con las pautas de primera línea prescritas más frecuentemente en los pacientes de la cohorte de la Red Española de Investigación en SIDA en la era de los inhibidores de la integrasa. Métodos: Utilizamos un modelo de evaluación de costes en el que el consumo de recursos sanitarios derivados de iniciar tratamiento con cada pauta se estimó utilizando el método Delphi de dos rondas, mediante cuestionario estructurado, en un panel de 35 expertos en VIH. El coste total incluía los costes de TAR, del manejo clínico y del manejo de efectos adversos (EA). Se aplicó la perspectiva del pagador (Sistema Nacional de Salud), considerando solo costes directos. Resultados: En el análisis por intención de tratar, el coste anual varió entre 8.501 Euros para TDF/FTC/EFV y 12.840 Euros para TDF/FTC+RAL. De media, el coste farmacológico supone el 87,6% del coste total, variando entre 83,8 % para TDF/FTC/EFV y 91,1% para TDF/FTC+RAL. El coste del manejo clínico supone el 11,5% del coste total (8,6% para TDF/FTC+RAL y 13,9% para ABC/3TC/DTG). Sólo el 0,9% del coste de la pauta se debe al manejo de EA, más elevados con TDF/FTC/EFV (2,6%) y TDF/FTC+DRV/r (1,1%). Conclusión: El coste para el sistema sanitario del primer año de TAR se debe, fundamentalmente, al precio de los fármacos. Las pautas con menor coste fueron TDF/FTC/EFV, TDF/FTC/RPV y ABC/3TC/DTG, siendo TDF/FTC/EVG/COBI y TDF/FTC+RAL las de coste superior

Introduction: We aimed to evaluate the usage of health resources and the associated costs during the first year of treatment with the most commonly used first-line antiretroviral regimens (ART) in the Cohort of the Spanish AIDS Research Network in the era of integrase inhibitors. Methods: We used a cost evaluation model in which the use of health resources derived from initiating a regimen was estimated using a two-round Delphi method with a structured questionnaire in a pannel of 35 HIV experts. The cost of initiating a regimen included the costs of ART, clinical management and management of adverse effects (AE). The payer perspective (National Health System) was applied. Thus, only direct costs were considered. Results: In an intention-to-treat analysis, the annual cost ranged from 8,501 Euros for TDF/FTC/EFV to 12,840 Euros for TDF / FTC + RAL. On average, the pharmacological cost accounts for 87.6% varying between 83.8% for TDF/FTC/EFV and 91.1% for TDF/FTC+RAL. The cost of clinical management accounts for 11.5% of the total cost, ranging from 8.6% for TDF/FTC+RAL and 13.9% for ABC / 3TC / DTG. Only 0.9% of the total cost is due to management of AE, higher with the use of TDF/FTC/EFV (2.6%) and TDF/FTC+DRV / r (1.1%). Conclusion: The cost for the health system of the first year of antiretroviral treatment is mainly driven by the price of drugs. The regimens with lowest total cost were TDF/FTC/EFV, TDF/FTC/RPV and ABC/3TC/DTG, and the ones with highest total cost were TDF/FTC/EVG/COBI and TDF/FTC+RAL

Position statement for the management of comorbidities in psoriasis.

BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.

Erratum: Raman spectral post-processing for oral tissue discrimination - a step for an automatized diagnostic system: erratum.

[This corrects the article on p. 5218 in vol. 8, PMID: 29188115.].

Recommendations for the management of comorbidity in hidradenitis suppurativa.

BACKGROUND: The association between hidradenitis suppurativa (HS) and some diseases is becoming relevant in recent years. Providing appropriate management of HS from an early stage requires to include prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat HS potentially related to the onset of a comorbidity. OBJECTIVE: To provide the dermatologist with an accurate, easily used tool that will inform the diagnosis of HS comorbidity, and to facilitate decision-making regarding the referral and treatment of patient with HS-associated comorbidity. METHODS: These recommendations have been developed by a working group composed of seven experts (three dermatologists, a cardiovascular specialist internist, a rheumatologist expert in spondyloarthritis, a gastroenterologist and a psychiatrist) and a team of three methodologist researchers. The expert group selected the HS comorbidities considered in these recommendations through a literature review. The recommendations on diagnostic criteria are based on the relevant clinical practice guidelines for each of the comorbidities and on the recommendations of the experts. The information regarding the repercussion of HS medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: The comorbidities considered in this guide are as follows: cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), inflammatory bowel disease, inflammatory joint disorders and psychological disorders (anxiety and depression). In addition, the association between HS and the consumption of alcohol and tobacco is included. The tables and figures are a precise, easy-to-use tool to systematize the diagnosis of comorbidity in patients with HS and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these recommendations will facilitate the dermatologist practice and benefit HS patients' health and quality of life.

Raman spectral post-processing for oral tissue discrimination - a step for an automatized diagnostic system.

Most oral injuries are diagnosed by histopathological analysis of a biopsy, which is an invasive procedure and does not give immediate results. On the other hand, Raman spectroscopy is a real time and minimally invasive analytical tool with potential for the diagnosis of diseases. The potential for diagnostics can be improved by data post-processing. Hence, this study aims to evaluate the performance of preprocessing steps and multivariate analysis methods for the classification of normal tissues and pathological oral lesion spectra. A total of 80 spectra acquired from normal and abnormal tissues using optical fiber Raman-based spectroscopy (OFRS) were subjected to PCA preprocessing in the z-scored data set, and the KNN (K-nearest neighbors), J48 (unpruned C4.5 decision tree), RBF (radial basis function), RF (random forest), and MLP (multilayer perceptron) classifiers at WEKA software (Waikato environment for knowledge analysis), after area normalization or maximum intensity normalization. Our results suggest the best classification was achieved by using maximum intensity normalization followed by MLP. Based on these results, software for automated analysis can be generated and validated using larger data sets. This would aid quick comprehension of spectroscopic data and easy diagnosis by medical practitioners in clinical settings.

"Levántate y anda", un caso de trastorno conversivo grave en la infancia / "Get up and walk", a case of severe conversion disorder in childhood

Presentamos el caso de una niña de 11 años que ingresa en Pediatría y posteriormente en Psiquiatría Infanto-Juvenil, con sospecha de un cuadro conversivo grave consistente en inmovilidad para la deambulación y negativa activa a la ingesta de sólidos y líquidos. Explicamos el abordaje multidisciplinar del caso, tanto a nivel hospitalario como ambulatorio. La recuperación completa se ha alcanzado un año después del inicio de los síntomas. Además, realizamos una breve revisión y repaso de las características de los trastornos conversivos en niños y adolescentes, poniendo especial atención al pronóstico

We report the case of a 11-year-old girl that was admitted in Paediatrics Unit and later in Childhood and Youth Psychiatry Unit, with a suspected severe conversion disorder which included immobility and refusal to eat and drink. We explain the multidisciplinary approach to the case, both hospital and ambulatory levels. Complete recovery took about a year after the onset of symptoms. Furthermore, we make a brief review about the characteristics of conversion disorders in children and adolescents, with a special focus on the prognosis

Comparative analysis of 2 resonance frequency measurement devices: Osstell Mentor and Osstell ISQ.

OBJECTIVE: Comparing reliability of Osstell Mentor and Osstell ISQ in implant stability measurement, and assessing whether their measurements are comparable. MATERIALS AND METHOD: Implant stability was measured with both devices on 58 implants in 15 patients. Six measurements were completed with each device with 2 different transducers (3 measurements with each transducer), that is, 12 measurements for each implant. RESULTS: Mean implant stability quotient (ISQ) value with Osstell ISQ was 72.59, 72.47, and 73.17 in the first measurements, respectively. With Osstell Mentor, the results were 72.43, 72.60, and 73.26, respectively; mean ranges were 3.37, 3.60, and 3.75, respectively. However, mean value with Osstell ISQ and Osstell Mentor was 72.87 and 72.04, respectively. The intraclass correlation coefficient was 0.98. This means an almost perfect degree of concordance between both devices. CONCLUSIONS: Resonance frequency analysis systems in Osstell Mentor and Osstell ISQ show almost perfect reproducibility and repeatability.

Implant-abutment connections: influence of the design on the microgap and their fatigue and fracture behavior of dental implants.

Microgap between implant and abutment can produce biological and mechanical problems such as peri-implantitis and/or fatigue failures. The aim of this study was to evaluate microgap size and fatigue behavior of external and internal connections. In both systems the torque to tighten the abutment screw of single crown abutments was 45 Ncm. Fifty implants for each connection type were studied. One subgroup (n = 5) was used by the observation and evaluation of the microgap, other (n = 5) was tested for fracture strength and the other (n = 40) was subjected to dynamic loading. The internal connection presents a lower microgap than the external ones. From fatigue results, the external hexagon interface showed superior result compared to the internal hexagon interfaces. The tolerances in the internal connections are better and favour the fatigue behavior but this factor alone is not sufficient to improve the fatigue response in relation to the external connections when the screw is subjected at the same torque. The external system presents a higher value of the area than the internal and it produces a better load distribution. Microgaps and mechanical properties are very important for the long-term behavior of the dental implants and these aspects should be known by the implantologists.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Elaboración mediante el método Delphi de recomendaciones para el manejo coordinado (reumatólogo/dermatólogo) de la artritis psoriásica / Recommendations for the Coordinated Management of Psoriatic Arthritis by Rheumatologists and Dermatologists: A Delphi Study

La artritis psoriásica es una enfermedad inflamatoria crónica que afecta al sistema musculoesquelético, se asocia a psoriasis y suele producir destrucción articular con pérdida de función y calidad de vida. Su presentación clínica es heterogénea, con extremos fenotípicos que pueden solaparse con la artritis reumatoide o la espondilitis anquilosante. La psoriasis suele preceder a la artritis psoriásica, y la consulta de dermatología es el lugar clave para su detección precoz. Muchos tratamientos utilizados en psoriasis también se utilizan en artritis psoriásica, por tanto las recomendaciones terapéuticas para la psoriasis deben realizarse teniendo en cuenta el tipo y la gravedad de la artritis psoriásica, y viceversa. El objetivo de este documento es establecer pautas para el manejo coordinado (reumatólogo/dermatólogo) de la artritis psoriásica. Ha sido elaborado mediante la técnica Delphi por un grupo multidisciplinar (6 reumatólogos, 6 dermatólogos y 2 epidemiólogos) y contiene recomendaciones, tablas y algoritmos para diagnóstico, criterios de derivación y tratamiento de la artritis psoriásica

Psoriatic arthritis, a chronic inflammatory musculoskeletal disease that is associated with psoriasis, causes joint erosions, accompanied by loss of function and quality-of-life. The clinical presentation is variable, with extreme phenotypes that can mimic rheumatoid arthritis or ankylosing spondylitis. Because psoriasis usually presents before psoriatic arthritis, the dermatologist plays a key role in early detection of the latter. As many treatments used in psoriasis are also used in psoriatic arthritis, treatment recommendations should take into consideration the type and severity of both conditions. This consensus paper presents guidelines for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists. The paper was drafted by a multidisciplinary group (6 rheumatologists, 6 dermatologists, and 2 epidemiologists) using the Delphi method and contains recommendations, tables, and algorithms for the diagnosis, referral, and treatment of patients with psoriatic arthritis

Recommendations for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists: a Delphi study.

Psoriatic arthritis, a chronic inflammatory musculoskeletal disease that is associated with psoriasis, causes joint erosions, accompanied by loss of function and quality-of-life. The clinical presentation is variable, with extreme phenotypes that can mimic rheumatoid arthritis or ankylosing spondylitis. Because psoriasis usually presents before psoriatic arthritis, the dermatologist plays a key role in early detection of the latter. As many treatments used in psoriasis are also used in psoriatic arthritis, treatment recommendations should take into consideration the type and severity of both conditions. This consensus paper presents guidelines for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists. The paper was drafted by a multidisciplinary group (6rheumatologists, 6dermatologists, and 2epidemiologists) using the Delphi method and contains recommendations, tables, and algorithms for the diagnosis, referral, and treatment of patients with psoriatic arthritis.

Embarazo y parto en el cine (I): emociones y reflexiones / Pregnancy and childbirth in the movies (I): emotions and reflections

En la mayoría de los lugares del planeta Tierra el embarazo no es una elección, sino una obligación. Cada día nacen en el mundo más de 350 000 niños. No es difícil imaginar que la gran mayoría de nacimientos ocurren en países del Tercer y del Segundo Mundo. Y estos embarazos y partos no ocurren con las condiciones sanitarias y sociales que conocemos en los países desarrollados del Primer Mundo. El embarazo como leitmotiv en el cine ha oscilado entre el tono de tragedia y, principalmente, el tono de comedia. La mayoría de estas últimas producciones se convierten en un fast food cinematográfico bastante llevadero que funciona perfectamente como entretenimiento de bajo nivel. Pero también hay películas que tratan el tema del embarazo y el parto no para entretener, sino para concienciar. Hoy destacamos cuatro películas en este aspecto, las cuatro con carácter de película documental: 1) una película que nos acerca al problema del embarazo en el mundo: la estadounidense No llores mujer (Christy Turlington, 2010); 2) una película que nos acerca al problema del parto en el mundo, la colombiana Nacer-Diario de maternidad (Jorge Caballero, 2012); 3) una película que nos acerca al problema del parto respetado, principalmente en el Primer Mundo, la española Néixer (Ana Victoria Pérez, 2012), y 4) una película que nos acerca al problema de la maternidad como reto, como experiencia transformadora de la mujer y de la familia, la francesa Un feliz acontecimiento (Rémi Bezançon, 2011). De nuevo, el cine como una oportunidad para hablar con arte, ciencia y conciencia de un tema social y sanitario de tal importancia. Y una oportunidad para mejorar la relación profesional-paciente, para mejorar la humanización y para abrir el debate bioético (AU)

Teenage pregnancies are described as early pregnancies, because these women haven’t reached the legal age and are in a situation of dependence on family of origin. Pregnancy in adolescent girls is a serious and prevalent socio-medical problem. For all these reasons and more, the teen pregnancy becomes a “sacred” medical consultation: that is, a medical advice that deserves a friendly, warm, dignified, empathetic, respectful and serene communication with the patient and involve a style of practice that makes fluid the present and future doctor-patient relationship. In this article we invite you to live the emotions and thoughts of motherhood and pregnancy in 16 pregnant adolescents, 16 stories between cinema and reality. Because in “sacred” medical consultation about pregnancy in adolescents, we also believe that it is useful to prescribe movies, at least for the professionals. It helps us to better understand the complexity of this hard situation in this complex stage of life. We dare to advise our “top five” films (in chronological order): A Taste of Honey, Palindromos, Juno, Precious and Blog (AU)

Embarazo y parto en el cine (II): historias de embarazos en adolescentes / Pregnancy and labor in the movies (II): history of pregnancy in adolescents

Los embarazos en adolescentes se describen como embarazos precoces, porque normalmente estas mujeres no han alcanzado la mayoría de edad jurídica y están en situación de dependencia de la familia de origen. El embarazo suele implicar un riesgo en la trayectoria vital de las jóvenes adolescentes, y un serio y prevalente problema médico-social. Por todo ello y por más, el embarazo de la adolescente se convierte en una consulta “sagrada” y que debemos conocer; es decir, una consulta que merece una comunicación amable, cálida, digna, empática, respetuosa y serena con el paciente, y que conlleva un estilo de práctica que hace fluidas las relaciones médico-paciente presentes y futuras. En este artículo os invitamos a vivir las emociones y reflexiones de la maternidad y el embarazo en 16 adolescentes, historias entre el cine y la realidad. Porque en las consultas “sagradas” alrededor de los adolescentes que se enfrentan a un embarazo, también creemos que es útil prescribir películas, al menos para los propios profesionales. Nos sirve para entender mejor la complejidad de este momento en esta, ya de por sí, compleja etapa de la vida. Nos atrevemos a aconsejar nuestro "top five" de películas (por orden cronológico): Un sabor a miel, Palíndromos, Juno, Precious y Blog (AU)

Teenage pregnancies are described as early pregnancy, before these women have reached the legal age and are in a situation of dependence on family of origin. Pregnancy in adolescent girls is a serious and prevalent socio-medical problem. For all these reasons and more, the teen pregnancy becomes a "sacred" medical consultation: that is, a medical advice that deserves a friendly, warm, dignified, empathetic, respectful and serene communication with the patient and involve a style of practice that makes fluid the present and future doctor-patient relationship. In this article we invite you to live the emotions and thoughts of motherhood and pregnancy in 16 pregnant adolescents, 16 stories between cinema and reality. Because in "sacred" medical consultation about pregnancy in adolescent, we also believe that it is useful to prescribe movies, at least for the professionals. It helps us better understand the complexity of this hard situation in this complex stage of life. We dare to advise our "top five" films (in chronological order): A Taste of Honey, Palindromos, Juno, Precious and Blog (AU)

[Share experiment: hospital mobile pharmaceutical teams, a proven concept!]. / Partage d'expérience : les équipes pharmaceutiques mobiles à l'hôpital, un concept qui fait ses preuves !

A few months ago, the pharmacy department of the University Hospital of Poitiers was located in the basement of the hospital; communicating with care units by fax, phone or messenger. Today, drugs and medical devices, are stored in a 3400m(2) logistic platform and most of the delivery activity is robotized. Control and validation of prescriptions and dispensing activities are done by the pharmaceutical teams directly in the care units. Quality indicators allow us to improve our services regularly. A great success and interesting prospects for clinical pharmacy.

Influence of acid-etching after grit-blasted on osseointegration of titanium dental implants: in vitro and in vivo studies.

Rough implant surfaces have shown improved osseointegration rates. In a majority of dental implants, the microrough surfaces are obtained by grit blasting and/or acid-etching. The aim of this contribution was to evaluate the effects of acid-etching, after the grit-blasted treatment in titanium dental implants, on surface wettability, surface energy, osteoblast responses and its osseointegration behavior. Four surfaces were studied: as-machined, acid-etched, micro-rough by grit-blasting and the combination grit-blasted surface with acid-etched. The surfaces with increasing roughness show more osteoblastic adhered cells. This effect was most pronounced on samples blasted and blasted with acid-etching. The roughness obtained by grit-blasting is the main factor in comparison with the acid etching treatment in the biological response. These results were confirmed in vivo tests and histological analysis. The results demonstrated that the combination of the grit-blasted and acid-etched accelerated lightly bone regeneration at the different periods of implantation in comparison with the grit-blasted implants.

Phenotypic and histologic characteristics of cutaneous melanoma in patients with melanocortin-1 receptor polymorphisms.

BACKGROUND: The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. OBJECTIVES: To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. MATERIAL AND METHODS: A total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction. RESULTS: At least one of the following MC1R variants was present in 58% of the patients: V60L, V92M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P=.018) and melanomas located on areas with intermittent sun exposure (P=.019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P=.028). CONCLUSIONS: The results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R.

Características fenotípicas e histológicas de los pacientes con melanoma cutáneo en función de los polimorfismos del MC1R / Phenotypic and Histologic Characteristics of Cutaneous Melanoma in Patients With Melanocortin-1 Receptor Polymorphisms

Introducción: El receptor de la melanocortina-1 (MC1R) es un importante determinante del riesgo de melanoma debido a su función en la producción de melanina en respuesta a la exposición solar. Objetivos: Analizar las características fenotípicas e histológicas de los pacientes con melanoma cutáneo portadores de mutaciones del MC1R asociadas a riesgo de melanoma y la influencia de la exposición solar en la aparición del melanoma. Material y métodos: Se incluyeron 224 pacientes diagnosticados de melanoma atendidos en el Servicio de Dermatología del Hospital General Universitario Gregorio Marañón (septiembre de 2004 -diciembre de 2009). Se realizó la secuenciación genómica del ADN del MC1R mediante PCR. Resultados: El 58% presentaba al menos una de las siguientes variantes de MC1R (V60L, V92M, I155T, R160W, D294H, R163Q). Estos pacientes presentaban antecedentes de quemaduras solares (p=0,018), melanomas localizados en áreas de exposición solar intermitente (p=0,019), con predominio del tipo histológico de extensión superficial. Estas asociaciones fueron especialmente significativas en los portadores de las variantes R160W y D294H. Los portadores de R160W presentaron además melanomas asociados a nevus melanocíticos (p=0,028). Conclusión: Los resultados obtenidos sugieren que puede existir una relación entre la expresión de determinadas variantes de MC1R y los hábitos de exposición solar, antecedentes de quemadura y tipo de piel del paciente, así como una mayor frecuencia de melanomas de extensión superficial y melanomas asociados a nevus en portadores de ciertas mutaciones de MC1R (AU)

Background: The melanocortin-1 receptor (MC1R) is an important risk factor for melanoma due to its role in the production of melanin in response to sun exposure. Objectives: To analyze the phenotypic and histologic characteristics of cutaneous melanoma in patients carrying mutations in MC1R and assess the influence of sun exposure on the occurrence of melanoma. Material and methods: A total of 224 patients with a diagnosis of melanoma seen in the Department of Dermatology at Hospital General Universitario Gregorio Marañón in Madrid, Spain between September 2004 and December 2009 were included in the study. The genomic sequence of MC1R was analyzed by polymerase chain reaction. Results: At least one of the following MC1R variants was present in 58% of the patients: V60L, V92M, I155T, R160W, D294H, and R163Q. Carriers of those variants had a history of sunburn (P=.018) and melanomas located on areas with intermittent sun exposure (P=0.019), and the majority had a diagnosis of superficial spreading melanoma. These associations were especially significant in patients with the R160W and D294H variants. Carriers of R160W also had melanomas associated with melanocytic nevi (P=0.028). Conclusions: The results of our study suggest that there may be a relationship between the expression of certain MC1R variants and sun exposure, history of sunburn, and skin type. They also indicate a higher frequency of superficial spreading melanomas and melanomas associated with melanocytic nevi in patients carrying certain mutations in MC1R (AU)

Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism.

BACKGROUND: Glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 are multifunctional enzymes involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. OBJECTIVES: Single nucleotide polymorphisms (SNPs) in GSTP1 and copy number variants in GSTM1 and GSTT1 may be candidate low-penetrance variants with a role in susceptibility to malignant melanoma (MM). METHODS: In this case-control study, 562 Spanish patients with sporadic MM and 338 cancer-free control subjects were included, and the role of polymorphisms in these GST genes was investigated. Genotypes were established by quantitative real-time polymerase chain reaction for GSTM1 and GSTT1 while TaqMan probes were used to genotype GSTP1 SNPs. RESULTS: The GSTP1 polymorphism rs1695, which encodes the amino acid change p.Ile105Val, was individually associated with MM [odds ratio (OR): 1·32, 95% confidence interval (CI): 1·06-1·63]. Furthermore, individuals carrying one or two MC1R nonsynonymous changes and GSTP1 rs1695 rare allele had an increased risk of developing MM (OR: 3·34, 95% CI: 1·42-8·09 and OR: 20·42, 95% CI: 2·80-417·42, respectively). CONCLUSIONS: This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.