Human plasmacytoid dendritic cells express the functional purinergic halo (CD39/CD73).

Plasmacytoid dendritic cells (pDCs) are a specialized DC subset mainly associated with sensing viral pathogens and high-type I interferon (IFN-I) release in response to toll-like receptor (TLR)-7 and TLR-9 signaling. Currently, pDC contribution to inflammatory responses is extensively described; nevertheless, their regulatory mechanisms require further investigation. CD39 and CD73 are ectoenzymes driving a shift from an ATP-proinflammatory milieu to an anti-inflammatory environment by converting ATP to adenosine. Although the regulatory function of the purinergic halo CD39/CD73 has been reported in some immune cells like regulatory T cells and conventional DCs, its presence in pDCs has not been examined. In this study, we uncover for the first time the expression and functionality of the purinergic halo in human blood pDCs. In healthy donors, CD39 was expressed in the cell surface of 14.0 ± 12.5% pDCs under steady-state conditions, while CD73 showed an intracellular location and was only expressed in 8.0 ± 2.2% of pDCs. Nevertheless, pDCs stimulation with a TLR-7 agonist (R848) induced increased surface expression of both molecules (43.3 ± 23.7% and 18.6 ± 9.3%, respectively), as well as high IFN-α secretion. Furthermore, exogenous ATP addition to R848-activated pDCs significantly increased adenosine generation. This effect was attributable to the superior CD73 expression and activity because blocking CD73 reduced adenosine production and improved pDC allostimulatory capabilities on CD4 + T cells. The functional expression of the purinergic halo in human pDCs described in this work opens new areas to investigate its participation in the regulatory pDC mechanisms in health and disease.

Results from the Radiation Assessment Detector on the International Space Station: Part 1, the Charged Particle Detector.

We report the results of the first six years of measurements of the energetic particle radiation environment on the International Space Station (ISS) with the Radiation Assessment Detector (ISS-RAD), spanning the period from February 2016 to February 2022. The first RAD was designed and built for MSL, the Mars Science Laboratory rover, also known as Curiosity; it has been operating on Mars since 2012 and is referred to here as MSL-RAD. ISS-RAD combines two sensor heads, one nearly identical to the single MSL-RAD sensor head, the other with greatly enhanced sensitivity to fast neutrons. These two sensor heads are referred to as the Charged Particle Detector (CPD) and Fast Neutron Detector (FND), respectively. Despite its name, the CPD is also capable of measuring high-energy neutrons and γ-rays, as is MSL-RAD. ISS-RAD was flown to the ISS in December 2015 and was deployed in February 2016, initially in the USLab module. RAD was used as a survey instrument from January 2017 through May 2020, when the instrument was positioned in the USLab and set to a zenith-pointing orientation. The energetic particle environment on the ISS is complex and varies on short time scales owing to the orbit, which has a 51.6∘ inclination with respect to the equator and has had an altitude in the 400-440 km range in this time period. The ISS moves continuously through the geomagnetic field, the strength of which varies with latitude, longitude, and altitude. The orbit passes through the South Atlantic Anomaly (SAA) several times a day, where magnetically trapped protons and electrons produce large but transient increases in observed fluxes and absorbed dose rates. The environment inside the ISS is affected by the solar cycle, altitude, and the local shielding, which varies between different ISS modules. We report results for charged particle absorbed dose and dose equivalent rates in various positions in the ISS. In an accompanying paper, we report similar results for neutron dose equivalent rates obtained with the ISS-RAD Fast Neutron Detector.

Results from the Radiation Assessment Detector on the International Space Station, Part 2: The fast neutron detector.

We report the results of the first six years of measurements of so-called fast neutrons on the International Space Station (ISS) with the Radiation Assessment Detector (ISS-RAD), spanning the period from February 2016 to February 2022. ISS-RAD combines two sensor heads, one nearly identical to the single sensor head in the Mars Science Laboratory RAD (MSL-RAD). The latter is described in a companion article to this one. The novel sensor is the FND, or fast neutron detector, designed to measure neutrons with energies in the range from 200 keV to about 8 MeV. ISS-RAD was deployed in February 2016 in the USLAB module, and then served as a survey instrument from March 2017 until May 2020. Data were acquired in Node3, the Japanese Pressurized Module, Columbus, and Node2. At the conclusion of the survey portion of RAD's planned 10-year campaign on ISS, the instrument was stationed in the USLAB; current plans call for it to remain there indefinitely. The radiation environment on the ISS consists of a complex mix of charged and neutral particles that varies on short time scales owing to the Station's orbit. Neutral particles, and neutrons in particular, are of concern from a radiation protection viewpoint, because they are both highly penetrating (since they do not lose energy via direct ionization) and, at some energies, have high biological effectiveness. Neutrons are copiously produced by GCRs and other incident energetic particles when they undergo nuclear interactions in shielding. As different ISS modules have varying amounts of shielding, they also have varying neutron environments. We report results for neutron fluences and dose equivalent rates in various positions in the ISS.

Results from the Radiation Assessment Detector on the International Space Station: Part 3, combined results from the CPD and FND.

The energetic particle radiation environment on the International Space Station (ISS) includes both charged and neutral particles. Here, we make use of the unique capabilities of the Radiation Assessment Detector (ISS-RAD) to measure both of these components simultaneously. The Charged Particle Detector (CPD) is, despite its name, capable of measuring neutrons in the energy range from about 4 MeV to a few hundred MeV. Combined with data from the Fast Neutron Detector (FND) in the 0.2 to 8 MeV range, we present the first broad-spectrum measurements of the neutron environments in various locations within the ISS since an early Bonner-Ball experiment that was conducted before the Station was fully constructed. The data presented here span the time period from February 2016 to February 2022. In addition to presenting broad-spectrum neutron fluence measurements, we show correlations of the measured neutron dose equivalent with charged-particle dose rates. The ratio of charged-particle dose to neutron dose equivalent is found to be relatively stable within the ISS.

[Neuroanatomical and neuropsychological correlates of shopping addiction behaviour. A systematic review]. / Correlatos neuroanatómicos y neuropsicológicos del comportamiento de adicción a las compras. Una revisión sistemática.

INTRODUCTION: The incidence of compulsive buying has increased over the last two decades and it has a substantial negative impact on consumers' overall functioning. However, despite its clinical relevance, the neuropsychological mechanisms and neural correlates underlying this phenomenon are still unknown. Also, compulsive buying behaviour remains unrecognised as a diagnostic category belonging to addictive disorders. AIM: The aim of the study is to systematically analyse the available empirical evidence on compulsive buying in order to identify the underlying neuropsychological variables and neural correlates. MATERIALS AND METHODS: PubMed, Scopus and ScienceDirect were searched for the mechanisms behind this phenomenon. RESULTS: The results show only 11 recent studies that investigate these mechanisms. In addition, the protocol of this systematic review was pre-registered in the international PROSPERO register (registration number CRD42023427497). CONCLUSIONS: The studies reviewed refer to impaired executive functions, decision-making and sensitivity to rewards, and a tendency to reactivity to purchase-related cues. This pattern of behaviour appears to involve a loss of behavioural control linked to dysregulation of structures such as the striatum and frontal regions. The results obtained are examined and similarities with the mechanisms underlying other addictions are discussed.

TITLE: Correlatos neuroanatómicos y neuropsicológicos del comportamiento de adicción a las compras. Una revisión sistemática.Introducción. La incidencia de la compra compulsiva ha aumentado en las últimas dos décadas y supone un impacto negativo sustancial en el funcionamiento general de los consumidores. No obstante, a pesar de su relevancia clínica, todavía se desconocen los mecanismos neuropsicológicos y los correlatos neurales subyacentes a este fenómeno. Asimismo, el comportamiento de compra compulsiva continúa sin reconocerse como una categoría diagnóstica perteneciente a los trastornos adictivos. Objetivo. El objetivo del estudio es analizar de forma sistemática la evidencia empírica disponible sobre la compra compulsiva con la finalidad de identificar las variables neuropsicológicas y los correlatos neurales subyacentes. Materiales y métodos. Se realizó una búsqueda en PubMed, Scopus y ScienceDirect sobre los mecanismos subyacentes a este fenómeno. Resultados. Los resultados muestran únicamente 11 estudios recientes que indagan sobre estos mecanismos. Además, se realizó un registro previo del protocolo de esta revisión sistemática en el registro internacional PROSPERO (número de registro CRD42023427497). Conclusiones. Los estudios analizados aluden a una alteración en la función ejecutiva, en la toma de decisiones y en la sensibilidad a la recompensa, y una tendencia a la reactividad de señales relacionadas con las compras. Este patrón conductual parece implicar una pérdida del control del comportamiento vinculado a la desregulación de estructuras como el estriado y las regiones frontales. Se examinan los resultados obtenidos y se analizan las similitudes existentes con los mecanismos subyacentes a otras adicciones.

Adsorption of azithromycin in agricultural soils of the Bogotá savanna, Colombia.

Azithromycin is one of the most widely used macrolide antibiotics in medical treatment. However, there is little information on studies of the ecotoxicity, persistence and mobility of this type of compounds in the environment, although their presence in surfaces and wastewater has already been detected (Hernández et al., 2015). Based on this approach, the present research performs an analysis of the behavior of the adsorption process of azithromycin in soils of different textural classes, with the intention of establishing a first approach to assess the destination and transport of such substances in the biosphere. From the results of the evaluation of the conditions of adsorption of azithromycin, it is established that the Langmuir model has a better fit for clay soils with correlation coefficients R2 between 0.998 and 0.961. In contrast, the Freundlich model fits the soil with higher sand fraction with a higher correlation, R2 of 0.9892. Finally, based on a correlation analysis between the clay content, the percentage of organic matter and the adsorption coefficient K, it was evident that the adsorption of azithromycin is mainly related to the inorganic fraction of the soil.

[Reliability and validity of the Acquired healthy lifestyle assessment scale (E-VEVSA) in adults from Albacete and Murcia (Spain)]. / Fiabilidad y validez de la Escala de valoración del estilo de vida saludable adquirido (E-VEVSA) en adultos de Albacete y Murcia (España).

BACKGROUND: Lifestyle is a theoretical construct that is formed by the life habits of a subject. The analysis and objective quantification of lifestyle can have a great impact on people's health, as well as on the evolution of its status over the years. The objective of this research has been the validation of the Acquired Healthy Lifestyle Assessment Scale (E-VEVSA) in Spanish adults. METHOD: On an initial sample for the exploratory tests of 248 subjects and a final sample for the confirmatory tests of 780 subjects, aged between 22 and 72 years of age. Exploratory and confirmatory psychometric tests were carried out based on the Cronbach's alpha statistic (reliability) and exploratory factorial analysis with oblique rotation (oblimin) and confirmatory with varimax rotation (construct validity), which resulted in an instrument made up of 52 items and structured in 7 dimensions: individual responsibility in health care (9 items), habits of physical-sports practice (6 items), health habits in social relationships (10 items), habit of tobacco and alcohol consumption (9 items), habit of healthy eating (7 items), psychological health habits (6 items) and daily rest and sleep habits (5 items). RESULTS: All the items explained a total variance of 66.87% and a Cronbach's alpha of .894, with the partial alpha of each dimension or factor being above .700. CONCLUSIONS: The results show psychometric tests that confirm the validity of the E-VEVSA scale as a useful instrument to measure the healthy lifestyle acquired among adults.

Development of a neuropsychological assessment in smoking. / Desarrollo de una batería de evaluación neuropsicológica en fumadores.

INTRODUCTION: Smoking is one of the causes leading to the development of disease and mortality worldwide. One of the focuses of interest in this area is the impact of smoking on neuropsychological health. However, few studies provide instruments to assess executive functioning in smokers. The purpose of this study was to examine the viability of the internal structure of a neuropsychological battery for the assessment of executive function in smokers. SUBJECTS AND METHODS: A total of 171 smokers (Mage= 47.44, SDage= 8.48) were assessed. Executive functions were assessed at baseline with measures of inhibition (go/no go task and five digit test), updating (visual search and attention test and letter-number sequencing) and shifting (delay discounting task and Iowa gambling task). RESULTS: The exploratory factor analysis obtained a three-component solution of 59.6%. Establishing a first factor composed of visual search and attention test and letter-number sequencing, a second factor composed of delay discounting task and go/no go task and a third factor with Iowa gambling task and five digit test. CONCLUSIONS: The analysis of the internal structure reflected three factors which are consistent with the structure proposed by Miyake (2000).

TITLE: Desarrollo de una batería de evaluación neuropsicológica en fumadores.Introducción. El tabaquismo es una de las causas que conducen al desarrollo de enfermedades y a la mortalidad en todo el mundo. Uno de los focos de interés en esta área es el impacto del tabaquismo en la salud neuropsicológica. Sin embargo, son pocos los estudios que proporcionan instrumentos para evaluar el funcionamiento ejecutivo en los fumadores. El propósito de este estudio fue examinar la viabilidad de la estructura interna de una batería neuropsicológica para la evaluación de la función ejecutiva en fumadores. Sujetos y métodos. Se evaluó a un total de 171 fumadores (mediaedad = 47,44; desviación estándaredad = 8,48). Las funciones ejecutivas se evaluaron en la línea de base con medidas de inhibición (tarea go/no go y prueba de los cinco dígitos), actualización (prueba de búsqueda y atención visual, y escala de inteligencia de Wechsler para adultos) y cambio (tarea de descuento por demora y tarea de juego de Iowa). Resultados. El análisis factorial exploratorio obtuvo una solución de tres componentes del 59,6%, y se estableció un primer factor compuesto por la prueba de búsqueda y atención visual y la escala de inteligencia de Wechsler para adultos; un segundo factor, por la tarea de descuento por demora y la tarea go/no go; y un tercer factor, por la tarea de juego de Iowa y la prueba de los cinco dígitos. Conclusiones. El análisis de la estructura interna reflejó tres factores que son consistentes con la estructura propuesta por Miyake (2000).

Nutritional status assessment in Alzheimer disease and its influence on disease progression.

INTRODUCTION: Nutritional deficiencies are frequent in Alzheimer disease (AD), even in early stages. Nutritional impairment (NI) may be associated with faster disease progression. The objective of this study was to describe the frequency of NI and the associated risk factors at the time of diagnosis and to analyse its influence on subsequent progression. METHODS: We performed a prospective, multicentre, observational study of patients recently diagnosed with prodromal AD (pAD) or dementia due to AD (ADd). Two clinical assessments were conducted over a period of 18 months. The Mini Nutritional Assessment test (MNA; score range, 0-30; cut-off point for NI, < 24) was used to estimate nutritional status. Progression was defined as an increase of ≥ 3 points on the Clinical Dementia Rating-sum of boxes test. RESULTS: The sample included 50 patients with pAD (mean [standard deviation] age, 76.1 [5.3] years; 68% women), and 127 with ADd (80 [5.9] years; 72.4% women). A total of 141 (79.7%) completed both evaluations. The prevalence of NI was 28.2% (24% for pAD, 29.9% for ADd; P = .43), with the majority (92%) at risk of malnutrition. NI was associated with female sex (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 1.7-10.5; P < .001) and greater behavioural involvement (OR: 5.8; 95% CI: 2.6-12.7; P < .001). A larger proportion of patients with progression was observed among those with NI than among those with normal nutritional status (50% vs 28.7%, P < .05; ADd: 53.6% vs 31.8%, P < .05; pAD: 41.7% vs 22.9%, P = .21). Greater cognitive impairment (OR: 2.1; 95% CI: 1.03-4.4; P < .05) and NI (OR: 2.4; 95% CI: 1.1-5.1; P < .05) were independent risk factors for disease progression. CONCLUSIONS: NI is highly prevalent in patients with AD. Assessing nutritional status at the time of diagnosis may enable identification of patients at greater risk of disease progression.

Quiste pilonidal del ombligo: presentación de dos casos / Umbilical pilonidal sinus: presentation of two cases

Resumen Introducción: El quiste pilonidal del ombligo (QPO) es una entidad muy infrecuente y por eso no es reconocida precozmente. El objetivo de este manuscrito es dar a conocer esta patología. Reporte de casos: Presentamos dos pacientes referidos por un proceso inflamatorio del ombligo, con descarga de mal olor. El primer paciente, luego de dos meses de tratamiento local sin resolución, es intervenido resecando la lesión umbilical, comprobando en ese momento la existencia de contenido piloso en el quiste. En el segundo paciente se plantea el diagnóstico durante la anamnesis y se confirma con el examen físico. En ambos casos se efectuó una resección parcial del ombligo incluyendo la lesión pilonidal. La biopsia confirmó el diagnóstico. El resultado posoperatorio ha sido satisfactorio y sin recaídas. Discusión y Conclusión: Hay escasa literatura relacionada con el QPO. Se proponen el tratamiento conservador y la opción de resección quirúrgica del quiste. En nuestra limitada experiencia se procedió a resecar la lesión y recomendar la depilación de la región periumbilical. No podemos descartar la alternativa de manejo conservador en futuros casos, antes de proponer la cirugía.

Introduction: Umbilical pilonidal sinus (UPS) is a rare condition and is therefore not detected early. The aim of this document is to discuss this pathology. Case report: We present two patients referred due to an inflammatory process of the navel, with the presence of a malodor. The first patient, after two months of unsuccessful local treatment, was intervened by a resection of the umbilical lesion, verifying hair content in the sinus. In the second patient the diagnosis was evident during anamnesis and confirmed with the physical examination. In both cases, a partial resection of the umbilicus was performed, including the pilonidal sinus. Biopsy confirmed the diagnosis. The postoperative result has been satisfactory, without relapse. Discussion and Conclusion: There are not much literature related to UPS. Conservative treatment or surgical resection of the sinus is proposed. In our limited experience we proceeded to a surgical resection of the lesion and recommend eliminating the hairs of the periumbilical region. We cannot rule out the conservative management option in future cases, before proposing surgery.

Timing of food consumption in Hispanic adolescents with obesity.

BACKGROUND: Little is known about the normal eating time periods in adolescents with obesity and how these patterns change throughout development. As the obesity epidemic continues to rise in adolescence, it becomes imperative to understand developmentally appropriate eating behaviours and to create weight management strategies that build on those innate patterns and preferences. The purpose of this study was to determine the most common habitual eating windows observed in adolescents with obesity. METHODS: Participants were 101 Hispanic adolescents (mean age 14.8 ± 2.1 years; 48 male/53 female) with obesity (BMI ≥95th percentile) who were recruited as part of a larger clinical trial. Dietary intake and meal timing was determined using multiple pass 24-hours recalls. Histograms were utilized to determine the natural distribution of percent consumption of total kilocalories, carbohydrates and added sugar per hour. RESULTS: The majority of total kilocalories (65.4%), carbohydrates (65.3%) and added sugar (59.1%) occurred between 11:00 and 19:00. Adolescents were 2.5 to 2.9 times more likely to consume kilocalories, carbohydrates, and added sugar during the 8-hour window between 11:00 am and 19:00 pm than other time windows examined (all P < .001). The consumption of these calories did not differ between weekdays and weekend (P > .05) or by sex. CONCLUSIONS: In this cohort, more than 60% of calories, carbohydrates and added sugar were consumed between 11:00 am and 19:00 pm, which is concordant with an afternoon/evening chronotype that is common in adolescents. Our findings support this 8-hour period as a practical window for weight loss interventions that target pre-specified eating periods in this population.

Nutritional status assessment in Alzheimer disease and its influence on disease progression. / Evaluación del estado nutricional en la enfermedad de Alzheimer y su influencia en la progresión tras el diagnóstico.

INTRODUCTION: Nutritional deficiencies are frequent in Alzheimer disease (AD), even in early stages. Nutritional impairment (NI) may be associated with faster disease progression. The objective of this study was to describe the frequency of NI and the associated risk factors at the time of diagnosis and to analyse its influence on subsequent progression. METHODS: We performed a prospective, multicentre, observational study of patients recently diagnosed with prodromal AD (pAD) or dementia due to AD (ADd). Two clinical assessments were conducted over a period of 18months. The Mini Nutritional Assessment test (MNA; score range, 0-30; cut-off point for NI, <24) was used to estimate nutritional status. Progression was defined as an increase of ≥3points on the Clinical Dementia Rating-sum of boxes test. RESULTS: The sample included 50 patients with pAD (mean [standard deviation] age, 76.1 [5.3] years; 68% women), and 127 with ADd (80 [5.9] years; 72.4% women). A total of 141 (79.7%) completed both evaluations. The prevalence of NI was 28.2% (24% for pAD, 29.9% for ADd; P=.43), with the majority (92%) at risk of malnutrition. NI was associated with female sex (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 1.7-10.5; P<.001) and greater behavioural involvement (OR: 5.8; 95%CI: 2.6-12.7; P<.001). A larger proportion of patients with progression was observed among those with NI than among those with normal nutritional status (50% vs 28.7%, P<.05; ADd: 53.6% vs 31.8%, P<.05; pAD: 41.7% vs 22.9%, P=.21). Greater cognitive impairment (OR: 2.1; 95%CI: 1.03-4.4; P<.05) and NI (OR: 2.4; 95%CI: 1.1-5.1; P<.05) were independent risk factors for disease progression. CONCLUSIONS: NI is highly prevalent in patients with AD. Assessing nutritional status at the time of diagnosis may enable identification of patients at greater risk of disease progression.

Development and validation of a specific real-time PCR assay for the detection of the parasite Perkinsus olseni.

Perkinsus olseni is a protozoan parasite that infects a wide variety of molluscs worldwide, causing economic losses in the aquaculture sector. In the present study, a quantitative PCR (qPCR) assay was developed for the detection and quantification of P. olseni in clam gill tissue and hemolymph (Ruditapes philippinarum and R. decussatus), and the results were compared with those of the standard diagnostic methods recommended by the O.I.E. (World Organisation for Animal Health): Ray's fluid thioglycollate culture method (RFTM), a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and histopathology. The efficiency, sensitivity and reproducibility of the newly described qPCR assay were also determined. The highest prevalence was detected using the qPCR assay, and the strongest linear correlation was obtained between the RFTM infection levels and the threshold cycle (Ct) number from the gill tissue. Although better results were obtained from gill than from the hemolymph in the qPCR assays, especially with lower infection levels of the parasite, a significant linear correlation was observed between Ct values from the gill and hemolymph. The qPCR assay that was developed in this study showed high sensitivity, specificity and reproducibility for the detection and quantification of P. olseni.

Resección hepática extendida con vena cava inferior por colangiocarcinoma intrahepático: presentación de 2 casos / Extended hepatic resection with inferior cava vein for intrahepatic cholangiocarcinoma: presentation of two cases

Resumen Introducción: El colangiocarcinoma intrahepático (CIH) corresponde al segundo tumor hepático primario y la resección quirúrgica es la única alternativa válida para el tratamiento curativo de esta enfermedad. Reporte de casos: Describimos 2 paciente portadores de CIH con compromiso de vena cava inferior (VCI) que fueron sometidos a resección en Clínica Alemana de Santiago (CAS). Ambas pacientes son de género femenino de 39 y 47 años de edad. Ambas fueron sometidas a resección mayor hepática izquierda, asociada a resección del segmento I y extendida a VCI. La reconstrucción de la VCI fue realizada con parche pericárdico bovino y cierre primario respectivamente. El período desde el posoperatorio hasta el alta, fue de 13 y 23 días respectivamente. Discusión: Aunque la reseccion quirúrgica es la única vía para la curación en el CIH, el compromiso de estructuras vasculares hacen que esto no sea posible. El manejo multidisciplinario asociado a una técnica meticulosa realizada por un equipo quirúrgico experimentado, hacen posible lograr buenos resultados.

Introduction: Intrahepatic cholangiocarcinoma is the second most common primary liver tumor and surgical resection the only valid curative treatment. Case reports: We describe two patients harboring an intrahepatic cholangiocarcinoma with cava vein involvement who underwent resection at Clinica Alemana of Santiago. Both patients were females with ages of 39 and 47 years old. Both patients underwent left liver resection, associated to resection of segment I and of a portion of cava vein. Reconstruction of resected portion of the cava vein was performed by using a pericardium bovine patch and primary closure respectively. Postoperative period was uneventfully being discharged at 13 and 23 days respectively. Discussion: Although surgical resection is the only way to get curativeness, frequent involvement of large vascular structures make treatment unfeasible. A multidisciplinary approach associated with a meticulous technique performed by an experienced surgical team make possible to accomplish the above objective.

Combined mepacrine-hydroxychloroquine treatment in patients with systemic lupus erythematosus and refractory cutaneous and articular activity.

Aim The aim of this study was to evaluate the clinical response to combined therapy with hydroxychloroquine and mepacrine in patients with systemic lupus erythematosus and refractory joint and/or skin disease. Methods Mepacrine was added to 46 systemic lupus erythematosus patients unresponsive to treatment with the following drug combinations: hydroxychloroquine + prednisone + immunosuppressive drugs ( n = 24), hydroxychloroquine + prednisone ( n = 16), hydroxychloroquine + prednisone + retinoids ( n = 2), hydroxychloroquine alone ( n = 1), hydroxychloroquine + one immunosuppressive drug ( n = 1), hydroxychloroquine + prednisone + one immunosuppressive drug + belimumab ( n = 1) or hydroxychloroquine + prednisone + belimumab ( n = 1). The outcome variable was the clinical response, either complete or partial, based on clinical judgement. The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score were additionally used. Results A total of 91% patients showed complete/partial response, with similar rates among those with joint or skin disease. In patients with cutaneous activity, a statistically significant decrease in the CLASI was seen. There also was a statistically significant decrease in the SLEDAI. The mean daily dose of prednisone decreased from 5.8 to 3.4 mg/d ( p = 0.001). Prednisone could be discontinued in 20% of patients. No serious adverse events were seen. Smoking was the only predictor of complete response. Conclusion In the setting of refractory skin and/or joint disease, the addition of mepacrine to previous therapy including hydroxychloroquine was safe and effective in reducing disease activity and decreasing prednisone doses. The fact that smokers responded better opens the door to further studying the combination of mepacrine-hydroxychloroquine as a first-line therapy in such patients.

Which NICS method is most consistent with ring current analysis? Assessment in simple monocycles.

The aromaticity of benzene, Al4 2- cluster, cyclopropane, borazine and planar cyclooctatetraene (COT) was analyzed according to different strategies based on nucleus-independent chemical shift (NICS) computations. The analysis of NICS-components evolution along the main molecular axis seems to be the most adequate and simplest strategy to predict the aromatic or antiaromatic character of the studied systems. Moreover, the analysis of the σ- and π-electron contributions to the out-of-plane component of NICS (NICS zz ) leads to the same qualitative and quantitative conclusions previously obtained by the analysis of the magnetically induced ring current densities.

Skin cancer prevention campaign in childhood: survey based on 3676 children in Brazil.

BACKGROUND AND OBJECTIVES: Primary skin cancer prevention campaigns are essential and more effective among children, not only because of the importance of sun exposure effects during this period, but also because this age is when individuals are developing behaviours. The Brazilian Society of Dermatology - Regional State of Sao Paulo developed and conducted the programme named 'The Sun, Friend of Childhood', a school health education and disease prevention project for children and parents. Our objective was to evaluate the cognitive and behavioural effects of the children and parents before and after an education model-based intervention of sun protection. METHODS: We carried out a study on a school population of Social Service of Industry - Regional State of São Paulo, from the first to the fifth years of the regular course (6-10 years). Our educational project was planned to be based on two children's learning tools (comic magazine and a DVD cartoon). Questionnaires in relation to habits and knowledge in sun exposure were applied to the children (3776) before and (2748) after the intervention. A questionnaire was applied to 3663 parents regarding personal details and habits of their children. RESULTS: According to the McNemar's statistical test, all changes in the children in acquiring new knowledge about good practices for sun exposure were statistically significant. CONCLUSIONS: Educative sun exposure programmes in childhood are a relevant tool to modify the history of life for next generations, to concern the skin cancer and good health practices.

Exploiting electronic strategies to stabilize a planar tetracoordinate carbon in cyclic aromatic hydrocarbons.

A new approach to stabilize compounds containing a planar tetracoordinate carbon (ptC), embedded in aromatic hydrocarbons, is presented herein. This is achieved by using ligands that promote the formation of a 3c-2e σ-bond with the ptC under two conditions: without altering the sp2 hybridization of the aromatic carbons; and containing empty orbitals perpendicular to the aromatic ring to participate in the aromatic π-electronic delocalization.

PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies.

PR1, an HLA-A2-restricted peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 peptide vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.