Pediatric conjunctival melanoma: A comprehensive case report and literature review.

Purpose: This case report aims to present a rare instance of conjunctival melanoma in a 5-year-old patient and contribute to the limited body of knowledge on pediatric conjunctival melanoma. The purpose is to understand the characteristics, diagnosis, and management of this uncommon malignancy in young individuals. Observations: The case describes a 5-year-old female with a progressively growing pigmented conjunctival lesion. The lesion was observed to be located on the temporal conjunctiva of the right eye and displayed distinctive features, including feeder vessels. Imaging revealed specific dimensions of the lesion and ruled out deeper invasions. Histopathological examination revealed architectural and cytologic atypia, positive immunohistochemical staining for HMB-45, and a Ki67 proliferation index of 20 %, confirming the diagnosis of conjunctival melanoma. Conclusions: Conjunctival melanoma, an uncommon malignancy even more so in pediatric patients, typically presents with pigmented growths and feeder vessels. This case underscores the need for thorough diagnosis and early intervention, as conjunctival melanoma can lead to devastating outcomes. The rarity of such cases limits our understanding of their etiology and progression. This case contributes to the literature on pediatric conjunctival melanoma and reinforces the importance of vigilance in detecting and managing ocular pigmented lesions in children.

Actualizaciones en el abordaje terapéutico en el síndrome de dolor regional complejo / Therapeutic approach in patients with complex regional pain syndrome: an update

Introducción: El síndrome de dolor regional complejo abarca una sintomatología que puede ser autolimitada o terriblemente limitante. Pese al enorme interés que despierta en la comunidad científica, no tenemos claro qué determina su evolución. Actualmente, parece claro que hay que ajustar el tratamiento en base a los mecanismos fisiopatológicos predominantes en cada paciente en función de su estadio evolutivo. Fisiopatología: Se produce a causa de una compleja combinación de diferentes factores que se inician en el momento del traumatismo y que consisten en sensibilización del sistema nervioso, disfunción del sistema autónomo y cambios inflamatorios. Hay, además, un indudable componente inmunológico, con presencia de autoinmunización, una implicación genética y la constatación de que determinados estados psicológicos parecen influir en la progresión de la enfermedad. Prevención: Se recomienda la administración de la vitamina C tras traumatismos o cirugías sobre miembros, sobre todo cuando existen factores de riesgo (fracturas distales de radio). Asimismo, hay que incentivar la movilización precoz y tratar los altos niveles de ansiedad para prevenir su desarrollo. Tratamiento: El tratamiento debe ser precoz, multimodal y coordinado, con el objetivo fundamental no solo de aliviar el dolor, sino de recuperar funcionalmente el miembro afecto. La pieza angular del tratamiento es la rehabilitación. Se debe acompañar de farmacoterapia y de tratamiento psicológico. Dentro de la farmacoterapia, tienen especial relevancia los corticoides (en las fases más agudas), los bifosfonatos y los "free-radical scavengers". En fases avanzadas de la enfermedad, la ketamina intravenosa se plantea como una opción terapéutica.(AU)

Introduction: Complex Regional Pain Syndrome encompasses a symptomatology that can be self-limiting or terribly limiting. Despite the enormous interest it arouses in the scientific community, it is not clear what determines its evolution. Currently, it seems clear that treatment must be adjusted based on the predominant pathophysiological mechanisms in each patient according to its evolutionary stage. Physiopathology: It is caused by a complex combination of different factors that start at the time of the trauma and consist of sensitization of the nervous system, dysfunction of the autonomic system and inflammatory changes. There is also an undoubted immunological component, with the presence of autoimmunization, genetic involvement and the finding that certain psychological states seem to influence the progression of the disease. Prevention: The administration of vitamin C is recommended after trauma or surgery on limbs, especially when there are risk factors (distal radius fractures). Also, early mobilization should be encouraged and high levels of anxiety should be treated to prevent its development. Treatment: Treatment should be early, multimodal and coordinated, with the fundamental objective not only of relieving pain, but also of functionally recovering the affected limb. The cornerstone of treatment is rehabilitation. It should be accompanied by pharmacotherapy and psychological treatment. Within the pharmacotherapy, corticoids (in the most acute phases), bisphosphonates and free-radical scavengers are of special relevance. In advanced stages of the disease, intravenous ketamine is considered as a therapeutic option. Interventional treatments should be considered when the evolution of the syndrome is not optimal, especially sympathetic blocks, in case of predominant sympathetic dysfunction, or neuromodulation, which is the treatment modality with the most scientific evidence.(AU)

Puberty attainment and reproductive performance of yearling Bos indicus-influenced heifers after two sequential treatments with progesterone.

Number of pubertal heifers at time of breeding season initiation is a primary determinant to pregnancy success during the breeding season. It was hypothesized that pre-breeding progesterone (P4) supplementation (induction) would increase the number of heifers pubertal at the time of imposing estrous synchronization treatment regimens and P/AI. Yearling, Bos indicus-influenced (n = 577) or Bos indicus (n = 174) heifers were or were not treated with P4 (CIDR and Non-CIDR, respectively) for 10 d starting on D-23 (D0 = TAI). Presence of a CL on D-33 or D-23 was considered to indicate heifers were pubertal. On D-13, there was a PGF analogue administered. On D-9, there was treatment with GnRH analogue, 6d-CIDR and PGF. There were inseminations based on estrus (D-2 to D0) or TAI on D0 for non-estrous animals. There were 5.2 % and 62.9 % purebred and crossbred heifers pubertal, respectively. Proportion of prepubertal crossbred than purebred heifers with CL on D-3 was greater as a result of imposing the pubertal induction regimen (P < 0.05 and P> 0.10, respectively). Regardless of puberty status, proportion of heifers in estrus prior to AI in the CIDR group was similar to the heifers of the Non-CIDR group for crossbreds and purebreds. Similarly, P/AI of CIDR group was similar to the Non-CIDR group for crossbreds and purebreds. In summary, imposing the pubertal induction regimen hastened attainment of puberty in yearling crossbred, but not purebred heifers. Puberty induction did not affect estrous response, neither fertility after imposing an estrous synchronization treatment regimen.

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans.

BACKGROUND: The "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. METHODS: SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3-9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0-1.2 g/kg body weight, energy intake of 25-30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. RESULTS: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. CONCLUSION: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations.

A Web-Based Multidomain Lifestyle Intervention for Older Adults: The eMIND Randomized Controlled Trial.

Importance/Objective: To describe the feasibility and acceptability of a 6-month web-based multidomain lifestyle training intervention for community-dwelling older people and to test the effects of the intervention on both function- and lifestyle-related outcomes. DESIGN: 6-month, parallel-group, randomized controlled trial (RCT). SETTING: Toulouse area, South-West, France. PARTICIPANTS: Community-dwelling men and women, ≥ 65 years-old, presenting subjective memory complaint, without dementia. INTERVENTION: The web-based multidomain intervention group (MIG) received a tablet to access the multidomain platform and a wrist-worn accelerometer measuring step counts; the control group (CG) received only the wrist-worn accelerometer. The multidomain platform was composed of nutritional advices, personalized exercise training, and cognitive training. Main outcomes and measures: Feasibility, defined as the proportion of people connecting to ≥75% of the prescribed sessions, and acceptability, investigated through content analysis from recorded semi-structured interviews. Secondary outcomes included clinical (eg, cognitive function, mobility, health-related quality of life (HRQOL)) and lifestyle (eg, step count, food intake) measurements. RESULTS: Among the 120 subjects (74.2 ±5.6 years-old; 57.5% women), 109 completed the study (n=54, MIG; n=55, CG). 58 MIG subjects connected to the multidomain platform at least once; among them, adherers of ≥75% of sessions varied across multidomain components: 37 people (63.8% of 58 participants) for cognitive training, 35 (60.3%) for nutrition, and three (5.2%) for exercise; these three persons adhered to all multidomain components. Participants considered study procedures and multidomain content in a positive way; the most cited weaknesses were related to exercise: too easy, repetitive, and slow progression. Compared to controls, the intervention had a positive effect on HRQOL; no significant effects were observed across the other clinical and lifestyle outcomes. CONCLUSIONS AND RELEVANCE: Providing multidomain lifestyle training through a web-platform is feasible and well-accepted, but the training should be challenging enough and adequately progress according to participants' capabilities to increase adherence. Recommendations for a larger on-line multidomain lifestyle training RCT are provided.

Cognitive Function and Amyloid Marker in Frail Older Adults: The COGFRAIL Cohort Study.

BACKGROUND: Frailty and cognitive impairment are common manifestations of the ageing process and are closely related. But the mechanisms linking aging, physical frailty, and cognitive disorders, are complex and remain unclear. OBJECTIVES: We aim to explore the role of cerebral amyloid pathology, but also a range of nutritional, physical, biological or brain-aging marker in the development of cognitive frailty. METHOD: COGFRAIL study is a monocentric prospective study of frail older patients with an objective cognitive impairment (Clinical Dementia Rating Scale global score at 0.5 or 1). Three-hundred-and-twenty-one patients are followed up every 6 months, for 2 years. Clinical assessment at baseline and during follow-up included frailty, physical, mood, sensory, nutritional, and cognitive assessment (with a set of neuropsychological tests). Cerebral amyloid pathology is measured by amyloid Positron Emission Tomography (PET) or amyloid-ß-1-42 level in cerebrospinal fluid. Brain magnetic resonance imaging, measurement of body composition using Dual X Ray Absorptiometry and blood sampling are performed. The main outcome of the study is to assess the prevalence of positive cerebral amyloid status according to amyloid PET or amyloid-ß-1-42 level CSF. Secondary outcomes included biological, nutritional, MRI imaging, cognitive, clinical, physical and body composition markers to better understand the mechanisms of cognitive frailty. PERSPECTIVE: COGFRAIL study will give the opportunity to better understand the link between Gerosciences, frailty, cognitive impairment, and Alzheimer's disease, and to better characterize the physical and cognitive trajectories of frail older adults according to their amyloid status. Understanding the relationship between physical frailty and cognitive impairment is a prerequisite for the development of new interventions that could prevent and treat both conditions.

Black paints covered with multidielectrics: light absorbers.

Black paints are commonly used to provide broadband light absorbers in high-precision optics. We show how multidielectric coatings improve the performances of these absorbers. The coated rough paints still exhibit a quasi-lambertian diffuse reflection, but this scattering pattern can be reduced by several orders of magnitude, which strongly enhances absorption. Predictions are based on an exact electromagnetic theory of light scattering from arbitrary rough multilayers. Results are also compared to useful approximate theories.

Análisis de las condiciones de trabajo de los especialistas en Medicina del Trabajo en 2018 / Working conditions of Occupational Medicine Specialists in 2018

Introducción: Mediante la realización de este estudio se pretende conocer las condiciones en las que trabajan los especialistas en medicina del trabajo en España. Metodología: Desarrollo de una encuesta con 57 preguntas contestadas de manera anónima, que tratan aspectos generales de las condiciones socioeconómicas, demográficas, organizativas, formativas y del entorno psicosocial, en formato digital distribuida mediante correo electrónico entre los especialistas en medicina del trabajo a nivel nacional a través de las diferentes sociedades científicas. Resultados: Obtenidas n = 478 encuestas completas, con reparto homogéneo en relación al sexo (mujeres 51% vs. Hombre 49%) con una edad media de 50,72 años, siendo más del 45% mayor de 55 años. Remuneración media entre 45-50 mil euros bruto/año con distribución en SPA (41%) vs SPP (37%) y con contratos por cuenta ajena estable y fijo en el 84%. En cuanto a las condiciones de trabajo, en más del 27% se han recibido amenazas, vejaciones o exclusión laboral, y un 55% considera que tiene una carga excesiva de trabajo. En relación a la formación, el 64% ha recibido al menos 20 h en el último año, pero solo 21% ha publicado en los últimos 3 años. Conclusiones: Los especialistas en Medicina del trabajo conforman un colectivo envejecido con una edad media de 50 años y con la tasa de reposición más baja de todas las especialidades médicas, que cuenta con condiciones laborales estables y retribuciones medias entre 45-50 mil euros anuales. Encontramos diferencias según la modalidad de servicio de prevención en donde se trabaja. y con contratos por cuenta ajena estable y fijo en el 84%. En cuanto a las condiciones de trabajo, en más del 27% se han recibido amenazas, vejaciones o exclusión laboral, y un 55% considera que tiene una carga excesiva de trabajo. En relación a la formación, el 64% ha recibido al menos 20 h en el último año, pero solo 21% ha publicado en los últimos 3 años. Conclusiones: Los especialistas en Medicina del trabajo conforman un colectivo envejecido con una edad media de 50 años y con la tasa de reposición más baja de todas las especialidades médicas, que cuenta con condiciones laborales estables y retribuciones medias entre 45-50 mil euros anuales. Encontramos diferencias según la modalidad de servicio de prevención en donde se trabaja

Introduction: By perfoming this study it is intended to know the conditions in which Specialists in Occupational Medicine work in Spain. Methodology: Development of a survey with 57 questions answered anonymously, dealing with general aspects of socio-economic, demographic, organizational, training and psychosocial environment, in digital format distributed by email among specialists in occupational medicine nationwide of the different scientific societies. Results: Obtained n = 478 complete surveys, with homogeneous distribution in relation to sex (women 51% vs. Man 49%) with an average age of 50,72 years, being more than 45% over 55 years. Average compensation between 45-50 thousand euros gross / year with distribution in SPA (41%) vs SPP (37%) and with contracts for stable and fixed third-party accounts in 84%. Threats, harassment or labor exclusion have been received in more than 27%, and 55% consider that they have an excessive workload. In relation to training, 64% have received at least 20 hours in the last year, but only 21% have published in the last 3 years. Conclusion: The specialists in Occupational Medicine make up an aged group with an average age of 50 years and with the lowest replacement rate of specialist training, which has stable working conditions and average salaries between 45-50 thousand euros per year. We found differences according to the type of prevention service where you work

Anti-scattering effect analyzed with an exact theory of light scattering from rough multilayers.

First-order theories of light scattering previously revealed the existence of anti-scattering effects in optical multilayers. Here we present an exact electromagnetic theory that is able to complete the scattering analysis when first-order scattering is cancelled. The theory is valid for arbitrary rough multilayers.

Defining Vitality: Associations of Three Operational Definitions of Vitality with Disability in Instrumental Activities of Daily Living and Frailty among Elderly Over a 3-Year Follow-Up (MAPT Study).

OBJECTIVES: This study aimed to examine the associations of three operational definitions of vitality with variation in instrumental activities of daily living (IADL) and frailty over a 3-year follow-up among non-demented, community-dwelling elderly. DESIGN: Observational study. SETTING AND PARTICIPANTS: 1,679 elderly >70y (64.7% female) participants of the Multidomain Alzheimer Preventive Trial (MAPT). MEASUREMENTS: Vitality was defined as a psychological concept using three items from the Geriatric Depression Scale; as a physical construct using the highest quartile for hand grip strength; and as global physiological reservoir using a combination of good physical and cognitive functions. Variables were assessed at baseline, 6, 12, 24 and 36 months of follow-up. RESULTS: Prevalence of high vitality at baseline was 57.1%, 28.5% and 21.6% for psychological, physical, and physiological reservoir, respectively. People with high vitality presented higher IADL scores compared to people with low vitality for all definitions. Analysis from the mixed-effect model found no differences between vitality groups for IADL performance across all definitions. IADL scores improved among subjects with high vitality over time, independent on the definition; while no significant variation was observed among those with low vitality. Participants with low vitality presented 2.0 to 6.1 higher odds of having more frailty components over time (p<0.0001). CONCLUSION: High vitality defined as a concept related to psychological, physical, or physiological reservoir constructs were positively associated with better IADL performance and with reduced likelihood of frailty worsening over time.

Vitamin D, homocysteine and n-3PUFA status according to physical and cognitive functions in older adults with subjective memory complaint: Results from cross-sectional study of the MAPT trial.

OBJECTIVE: The aim of this study was to investigate the nutritional markers (Vitamin D, homocysteine, n-3PUFA) status of older subjects aged 70 years and older with subjective memory complaint, according to their physical and cognitive function. MAIN OUTCOME MEASURES: This study is a secondary analysis of the MAPT study. Subjects were classified into four groups: 1) Physical limitation with cognitive impairment (PLCI), 2) cognitive impairment (CI), 3) physical limitation (PL) and 4) no physical or cognitive deficits (NPCD). Baseline nutritional characteristics of the four groups according to Vitamin D (n = 732), Omega-3 polyunsaturated fatty acid (n-3PUFA) (n = 1537) and plasma total homocysteine (tHcy) (n = 729) status were investigated. Analysis was performed taking continuous and dichotomized value for Vitamin D insufficiency ([25(OH)D] < 30 ng/ml, high homocysteine level (tHcy ≥ 15 µmol/L) and low n-3PUFA (DHA + EPA ≤ 4.82%) nutritional markers for clinical relevance. RESULTS: PLCI group showed the lowest mean level of Vitamin D and highest level tHcy compared to the other groups. In multivariate analysis, taking continuous nutritional markers, only high Vitamin D was associated with reduced likelihood of PLCI (OR 0.97, 95% CI (0.95 to 0.99) P = 0.011). While taking the dichotomized values the group with low levels of n-3PUFA showed higher likelihood of PL only (OR 1.55, 95% CI (1.12 to 2.15), P = 0.009). Furthermore, our sensitivity analysis for Vitamin D with cut-off [25(OH)D] < 20 ng/ml,(i.e., Vitamin D deficiency), showed more likelihood of PL (OR 1.62, 95% CI (1.01 to 2.60) P = 0.046), CI (OR 1.90, 95% CI (1.16 to 3.10) P = 0.010), and highest likelihood of PLCI (OR 1.99, 95% CI (1.21 to 3.28) P = 0.006). CONCLUSION: In older adults with subjective memory complaints, Vitamin D deficiency status may present higher likelihood of functional deficits, including coexisting or separate physical and cognitive decline. While older adults with low level of n-3PUFA were more likely to demonstrate physical decline only.

A web-based multidomain lifestyle intervention with connected devices for older adults: research protocol of the eMIND pilot randomized controlled trial.

BACKGROUND: Multidomain interventions composed of nutritional counseling, exercise and cognitive trainings have shown encouraging results as effective preventive strategies delaying age-related declines. However, these interventions are time- and resource-consuming. The use of Information and Communication Technologies (ICT) might facilitate the translation from research into real-world practice and reach a massive number of people. AIM: This article describes the protocol of the eMIND study, a randomized controlled trial (RCT) using a web-based multidomain intervention for older adults. METHODS: One hundred and twenty older adults (≥ 65 years), with a spontaneous memory complaint, will be randomly assigned to a six-month web-based multidomain (nutritional counseling, physical and cognitive trainings) intervention group with a connected accelerometer (number of steps, energy expenditure), or to a control group with access to general information on healthy aging plus the accelerometer, but no access to the multidomain intervention. The main outcome is the feasibility/acceptability of the web-based intervention. Secondary clinical outcomes include: cognitive functions, physical performance, nutritional status and cost-effectiveness. RESULTS: We expect a high amount of adherers (ie, > 75% compliance to the protocol) to reflect the feasibility. Acceptability, assessed through interviews, should allow us to understand motivators and barriers to this ICT intervention. We also expect to provide data on its effects on various clinical outcomes and efficiency. CONCLUSION AND DISCUSSION: The eMIND study will provide crucial information to help developing a future and larger web-based multidomain lifestyle RCT, which should facilitate the translation of this ICT intervention from the research world into real-life clinical practice for the healthcare of older adults.

From the Cover: Prolonged Exposure to Volatile Anesthetic Isoflurane Worsens the Outcome of Polymicrobial Abdominal Sepsis.

Sepsis continues to result in high morbidity and mortality. General anesthesia is often administered to septic patients, but the impacts of general anesthesia on host defense are not well understood. General anesthesia can be given by volatile and intravenous anesthetics. Our previous in vitro study showed that volatile anesthetic isoflurane directly inhibits leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), critical adhesion molecules on leukocytes. Thus, the role of isoflurane exposure on in vivo LFA-1 and Mac-1 function was examined using polymicrobial abdominal sepsis model in mice. As a comparison, intravenous anesthetic propofol was given to a group of mice. Wild type, LFA-1, Mac-1, and adhesion molecule-1 knockout mice were used. Following the induction of polymicrobial abdominal sepsis by cecal ligation and puncture, groups of mice were exposed to isoflurane for either 2 or 6 h, or to propofol for 6 h, and their outcomes were examined. Bacterial loads in tissues and blood, neutrophil recruitment to the peritoneal cavity and phagocytosis were studied. Six hours of isoflurane exposure worsened the outcome of abdominal sepsis (P < .0001) with higher bacterial loads in tissues, but 2 h of isoflurane or 6 h of propofol exposure did not. Isoflurane impaired neutrophil recruitment to the abdominal cavity by inhibiting LFA-1 function. Isoflurane also impaired bacterial phagocytosis via complement receptors including Mac-1. In conclusion, prolonged isoflurane exposure worsened the outcome of experimental polymicrobial abdominal sepsis and was associated with impaired neutrophil recruitment and bacterial phagocytosis via reduced LFA-1 and Mac-1 function.

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Navarra, Gipuzkoa and La Rioja]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.

AIM: To evaluate the effectiveness and safety of fingolimod in clinical practice in Navarra, Gipuzkoa and La Rioja regions. PATIENTS AND METHODS: We conducted a retrospective multi-centre study with recurrent multiple sclerosis patients treated with fingolimod, following the product data sheet. The following data were evaluated: annualised relapse rate (ARR), percentage of patients free from relapses, disability using the Expanded Disability Status Scale (EDSS) and the percentage of patients without gadolinium-enhancing lesions. RESULTS: A total of 113 patients were treated with fingolimod: 6% were naive, and 58% and 35% were patients previously treated with an immunomodulator and natalizumab, respectively. Fingolimod lowered the ARR after the first (67%; 1 to 0.3; p < 0.0001) and second (89%; 1 to 0.1; p < 0.0001) years of treatment, and thus the number of patients free from relapses during the treatment increased. The baseline EDSS was 3 and after treatment with fingolimod was 2.5 in both years. The percentage of patients without gadolinium-enhancing lesions after the first year of treatment was 77%. Similar results were observed in naive patients and in those previously treated with an immunomodulator. In patients previously treated with natalizumab no changes were observed following the treatment. CONCLUSIONS: The use of fingolimod in clinical practice showed an effectiveness similar to that observed in clinical trials. There were no changes in the ARR after changing from natalizumab, and only one patient presented a 'relapse' after withdrawal of natalizumab. Fingolimod acts like a safe drug, with scarce side effects and a low percentage of drop-outs.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Navarra, Gipuzkoa y La Rioja.Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en las regiones de Navarra, Gipuzkoa y La Rioja. Pacientes y metodos. Estudio retrospectivo y multicentrico de pacientes con esclerosis multiple recurrente tratados con fingolimod, siguiendo la ficha tecnica. Se evaluo la tasa anualizada de brotes (TAB), el porcentaje de pacientes libres de brotes, la discapacidad usando la escala expandida del estado de discapacidad (EDSS) y el porcentaje de pacientes sin lesiones captantes de gadolinio. Resultados. Un total de 113 pacientes fueron tratados con fingolimod: el 6%, naive, y el 58% y 35%, pacientes tratados previamente con inmunomodulador y natalizumab, respectivamente. El fingolimod disminuyo la TAB tras el primer (67%; 1 a 0,3; p < 0,0001) y segundo (89%; 1 a 0,1; p < 0,0001) año de tratamiento, y aumento asi el porcentaje de pacientes libres de brotes durante el tratamiento. La EDSS basal fue 3 y despues del tratamiento con fingolimod fue 2,5 en ambos años. El porcentaje de pacientes sin lesiones captantes de gadolinio tras el primer año de tratamiento fue del 77%. Resultados similares se observaron en los pacientes naive y en los tratados previamente con inmunomodulador. En los pacientes tratados previamente con natalizumab no se observaron cambios tras el tratamiento. Conclusiones. El uso del fingolimod en la practica clinica mostro una efectividad similar a la eficacia observada en ensayos clinicos. No hubo cambios en la TAB al cambiar desde natalizumab, y solo un paciente tras suspender el natalizumab presento 'rebrote'. El fingolimod se comporta como un farmaco seguro, con escasos efectos adversos y con un bajo porcentaje de abandonos.

Predictive model of mortality in patients with spontaneous bacterial peritonitis.

BACKGROUND: Hospital mortality in patients with spontaneous bacterial peritonitis (SBP) is high despite albumin treatment, particularly in those with worse liver and/or renal function. AIM: To determine the independent predictive factors of in-hospital mortality and to create and validate a predictive model of mortality in patients with SBP. METHODS: We analysed all cirrhotic patients with high-risk SBP (serum urea ≥11 mmol/L and/or serum bilirubin ≥68 µmol/L) between 2001 and 2011. We developed a predictive model of in-hospital mortality and validated this in a different cohort. RESULTS: We included 118 high-risk SBP episodes treated with antibiotics and albumin. In-hospital mortality was 33/118 (28%). The independent predictive factors of in-hospital mortality at SBP diagnosis were serum urea, blood leucocyte count, Child-Pugh score and mean arterial pressure. A predictive model including these four variables showed a discrimination accuracy (AUC) of 0.850, 95% CI 0.777-0.922. A cut-off point of 0.245 showed a sensitivity of 0.85 and specificity of 0.75. The in-hospital mortality was 28/49 (57.1%) in patients with a model value ≥0.245, and 5/69 (7.2%) in patients with a model value <0.245 (P < 0.001). The validation series included 161 patients with an in-hospital mortality of 40/161 (24.8%), 30/77 (39.0%) in patients with a model value ≥0.245, and 10/84 (11.9%) in those with a model value <0.245 (P < 0.001). CONCLUSIONS: We developed and validated a predictive model of mortality that includes serum urea, blood leucocyte count, Child-Pugh score and mean arterial pressure in high-risk patients with spontaneous bacterial peritonitis. These findings may help to identify patients who would benefit from additional therapeutic strategies.

Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism.

Adaptive resistance of myeloma to proteasome inhibition represents a clinical challenge, whose biology is poorly understood. Proteasome mutations were implicated as underlying mechanism, while an alternative hypothesis based on low activation status of the unfolded protein response was recently suggested (IRE1/XBP1-low model). We generated bortezomib- and carfilzomib-adapted, highly resistant multiple myeloma cell clones (AMO-BTZ, AMO-CFZ), which we analyzed in a combined quantitative and functional proteomic approach. We demonstrate that proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition, irrespective of a proteasome mutation, and uniformly show an 'IRE1/XBP1-low' signature. Adaptation of myeloma cells to proteasome inhibitors involved quantitative changes in >600 protein species with similar patterns in AMO-BTZ and AMO-CFZ cells: proteins involved in metabolic regulation, redox homeostasis, and protein folding and destruction were upregulated, while apoptosis and transcription/translation were downregulated. The quantitatively most upregulated protein in AMO-CFZ cells was the multidrug resistance protein (MDR1) protein ABCB1, and carfilzomib resistance could be overcome by MDR1 inhibition. We propose a model where proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition owing to metabolic adaptations that favor the generation of reducing equivalents, such as NADPH, which is supported by oxidative glycolysis. Proteasome inhibitor resistance may thus be targeted by manipulating the energy and redox metabolism.

Speckle intensity statistics for chromatic scattering media under partially polarized illumination.

Intensity contrast in a fully developed speckle pattern resulting from the elastic scattering of a partially polarized light from a strongly scattering medium is theoretically and numerically studied. Simple expressions are derived when the illumination bandwidth is much smaller or larger than the chromatic length of the scattering medium.

Analogies between optical propagation and heat diffusion: applications to microcavities, gratings and cloaks.

A new analogy between optical propagation and heat diffusion in heterogeneous anisotropic media has been proposed recently by three of the present authors. A detailed derivation of this unconventional correspondence is presented and developed. In time harmonic regime, all thermal parameters are related to optical ones in artificial metallic media, thus making possible to use numerical codes developed for optics. Then, the optical admittance formalism is extended to heat conduction in multilayered structures. The concepts of planar microcavities, diffraction gratings and planar transformation optics for heat conduction are addressed. Results and limitations of the analogy are emphasized.

Polarization analysis of speckle field below its transverse correlation width : application to surface and bulk scattering.

An experimental method for accurate polarimetric characterization of speckle field below its transverse correlation width is proposed. Using a polarimetric analyzer, the speckle field under investigation is probed by a set of polarimetric projections describing the full Poincaré sphere surface. Spatial polarimetric variations of the speckle field are thus observed with an accuracy of 1% for each Stokes parameter. Moreover, all the experimental data can be guaranteed by a validity criterion. Using white paper sheet and rough metal samples, the method exhibits strong potential to analyze and differentiate speckle fields generated by bulk and surface scattering.