Defining well-being in psoriasis: A Delphi consensus among healthcare professionals and patients.

Psoriasis is a chronic skin disease that negatively impacts on patient's life. A holistic approach integrating well-being assessment could improve disease management. Since a consensus definition of well-being in psoriasis is not available, we aim to achieve a multidisciplinary consensus on well-being definition and its components. A literature review and consultation with psoriasis patients facilitated the design of a two-round Delphi questionnaire targeting healthcare professionals and psoriasis patients. A total of 261 panellists (65.1% patients with psoriasis, 34.9% healthcare professionals) agreed on the dimensions and components that should integrate the concept of well-being: emotional dimension (78.9%) [stress (83.9%), mood disturbance (85.1%), body image (83.9%), stigma/shame (75.1%), self-esteem (77.4%) and coping/resilience (81.2%)], physical dimension (82.0%) [sleep quality (81.6%), pain/discomfort (80.8%), itching (83.5%), extracutaneous manifestations (82.8%), lesions in visible areas (84.3%), lesions in functional areas (85.8%), and sex life (78.2%)], social dimension (79.5%) [social relationships (80.8%), leisure/recreational activities (80.3%), support from family/friends (76.6%) and work/academic life (76.5%)], and satisfaction with disease management (78.5%) [treatment (78.2%), information received (75.6%) and medical care provided by the dermatologist (80.1%)]. This well-being definition reflects patients' needs and concerns. Therefore, addressing them in psoriasis will optimise management, contributing to better outcomes and restoring normalcy to the patient's life.

Artritis paradójica por ixekizumab en un paciente con psoriasis en placas / Paradoxical Arthritis Due to Ixekizumab in a Patient With Plaque Psoriasis

No disponible

Documento de consenso sobre las necesidades psicológicas de los pacientes con enfermedades inflamatorias crónicas dermatológicas / Consensus Statement on the Psychological Needs of Patients With Chronic Inflammatory Skin Diseases

Objetivo: Establecer recomendaciones para conocer, identificar y manejar las necesidades psicológicas y emocionales de los pacientes con enfermedades inflamatorias crónicas dermatológicas en la práctica clínica habitual. Métodos: En una reunión de grupo nominal con expertos dermatólogos y psicólogos, se realizó una discusión guiada sobre las necesidades psicológicas y emocionales de estos pacientes, cómo abordarlas, y cuáles serían los criterios de derivación apropiados. A partir de todo ello, con la ayuda de un grupo focal de pacientes y de una revisión de la literatura, se preparó un documento matriz con las recomendaciones para su discusión, así como una encuesta tipo Delphi para evaluar el grado de acuerdo con las mismas, que se hizo extensiva a más dermatólogos y psicólogos. Resultados: Se establecieron 10 recomendaciones que podrían resumirse en las siguientes: explore la esfera psicológica de los pacientes con preguntas abiertas tanto en el momento del diagnóstico como durante el curso de la enfermedad. Dele explicaciones claras adaptadas a sus preocupaciones e infórmele de la existencia de asociaciones de pacientes. Explore si existen síntomas de ansiedad y depresión, y si se confirman mediantes una puntuación de 11 o más en la Hospital Anxiety and Depression Scale (HADS), valore una derivación a un especialista en salud mental. En las visitas, genere un clima de confianza, empatice con el paciente, consensúe con él los objetivos y opciones terapéuticas, y motívele para conseguir una buena adherencia. Conclusiones: Estas recomendaciones pueden servir a los profesionales sanitarios para que aborden de forma abierta y natural aspectos psicológicos y emocionales del paciente en la consulta diaria

Objective: To establish recommendations to determine, identify, and manage the psychological and emotional needs of patients with chronic inflammatory skin diseases in clinical practice. Methods: A guided discussion was held at meeting of a nominal group of expert dermatologists and psychologists on the psychological and emotional needs of patients with chronic inflammatory skin diseases, how to manage these cases, and which referral criteria to employ. Based on the results of the discussion, and with the aid of a patient focus group and a review of the literature, a master document was drawn up with recommendations for discussion. A Delphi survey was circulated among a larger group of dermatologists and psychologists to assess the level of agreement with the recommendations. Results: Ten recommendations were established and can be summarized as follows: explore the psychological sphere of the patients with open questions at the time of diagnosis and during the course of the disease; provide patients with clear explanations that address their concerns and inform them of the existence of patient associations; investigate symptoms of anxiety and depression and, if confirmed by means of a Hospital Anxiety and Depression score (HADS) of 11 or greater, consider referral to a mental-health specialist; and, during visits, create a climate of trust, empathize with patients, agree goals and treatment options with them, and motivate them to adhere to those treatments. Conclusions: These recommendations may help health care professionals address psychological and emotional aspects of their patients in daily clinical practice

Consensus Statement on the Psychological Needs of Patients With Chronic Inflammatory Skin Diseases. / Documento de consenso sobre las necesidades psicológicas de los pacientes con enfermedades inflamatorias crónicas dermatológicas.

OBJECTIVE: To establish recommendations to determine, identify, and manage the psychological and emotional needs of patients with chronic inflammatory skin diseases in clinical practice. METHODS: A guided discussion was held at meeting of a nominal group of expert dermatologists and psychologists on the psychological and emotional needs of patients with chronic inflammatory skin diseases, how to manage these cases, and which referral criteria to employ. Based on the results of the discussion, and with the aid of a patient focus group and a review of the literature, a master document was drawn up with recommendations for discussion. A Delphi survey was circulated among a larger group of dermatologists and psychologists to assess the level of agreement with the recommendations. RESULTS: Ten recommendations were established and can be summarized as follows: explore the psychological sphere of the patients with open questions at the time of diagnosis and during the course of the disease; provide patients with clear explanations that address their concerns and inform them of the existence of patient associations; investigate symptoms of anxiety and depression and, if confirmed by means of a Hospital Anxiety and Depression score (HADS) of 11 or greater, consider referral to a mental-health specialist; and, during visits, create a climate of trust, empathize with patients, agree goals and treatment options with them, and motivate them to adhere to those treatments. CONCLUSIONS: These recommendations may help health care professionals address psychological and emotional aspects of their patients in daily clinical practice.

Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation.

The binding properties toward the human telomeric G-quadruplex of the two natural alkaloids coptisine and chelerythrine were studied using spectroscopic techniques, molecular modeling, and X-ray diffraction analysis. The results were compared with reported data for the parent compounds berberine and sanguinarine. Spectroscopic studies showed modest, but different rearrangements of the DNA-ligand complexes, which can be explained considering particular stereochemical features for these alkaloids, in spite of the similarity of their skeletons. In fact, the presence of a dioxolo moiety rather than the two methoxy functions improves the efficiency of coptisine and sanguinarine in comparison to berberine and chelerythrine, and the overall stability trend is sanguinarine > chelerythrine ≈ coptisine > berberine. Accordingly, the X-ray diffraction analysis confirmed the involvement of the benzodioxolo groups in the coptisine/DNA binding by means of π···π, O···π, and CH···O interactions. Similar information is provided by modeling studies, which, additionally, evidenced reasons for the quadruplex vs double-helix selectivity shown by these alkaloids. Thus, the analyses shed light on the key role of the benzodioxolo moieties in strengthening the interaction with the G4-folded human telomeric sequence and indicated the superior G4 stabilizing properties of the benzophenanthridine scaffold with respect to the protoberberine one and conversely the better G4 vs dsDNA selectivity profile of coptisine over the other alkaloids.

6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells.

The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Moreover, depletion of PFKFB4-attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4-induced apoptosis in p53-deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment.

Función y respaldo a la asociación de pacientes con psoriasis en España según sus miembros: estudio descriptivo transversal / The Spanish psoriasis patients’ association according to its members: cross-sectional descriptive study of members’ opinions of the association’s functions

INTRODUCCIÓN: Las asociaciones de pacientes son un elemento más del sistema sanitario, sin embargo en España se desconoce la funcionalidad y el respaldo que tienen según sus propios asociados. OBJETIVO: Estudiar la funcionalidad de la principal asociación española de pacientes y familiares afectados por la psoriasis según sus propios socios. MATERIAL Y MÉTODOS: Estudio mediante un cuestionario autoadministrado a una muestra de socios y/o simpatizantes (población total = 26.349 personas). Se estudió la credibilidad, confianza y satisfacción y se comparó con otros agentes sanitarios. El cuestionario de funcionalidad se analizó con un modelo de Rasch, y se examinó si había diferencias entre grupos de participantes con la prueba de ANOVA. RESULTADOS: Participaron 746 socios y/o simpatizantes (tasa de respuesta 2,83%). La credibilidad de la asociación se situó tras la de los especialistas que tratan la psoriasis. El respaldo medio a la función de la asociación fue notable (7,53 en una escala de 0 a 10). Según los socios las funciones mejor puntuadas se relacionaban con acciones colectivas para sensibilizar a la sociedad sobre el problema de la psoriasis, en cambio, tuvieron una menor valoración las acciones relacionadas con los servicios de atención personalizada. Solo hubo diferencias significativas (p < 0,05) en el respaldo a la asociación en función del nivel académico de los participantes. CONCLUSIONES: Las asociaciones son unas instituciones que contribuyen a la difusión de información de la enfermedad, que cuidan y representan a los pacientes. Los profesionales de salud e instituciones deberían tenerlas en cuenta para afrontar la psoriasis y diseñar políticas de salud efectivas

INTRODUCTION: Patient associations form part of health care systems, but little is known about how their members' view the functionality of these associations and whether they endorse their goals and activities. OBJECTIVE: To study how the members of the leading Spanish association of patients with psoriasis and their relatives view the group's functioning. MATERIAL AND METHODS: Survey study using a self-administered questionnaire answered by members of the association (total membership, 26 349 persons). The credibility of the association and respondents' confidence in and satisfaction with it were studied and compared with their attitudes toward other agents in the health care system. A Rasch model was used to analyze respondents' ranking of functions. Analysis of variance was used to study between-group differences. RESULTS: A total of 746 members participated (response rate 2.83%). The association's credibility was rated in second place, after that of specialists who treat psoriasis. Support for the association functions was good (7.53 on a scale of 0 to 10). The function the members rated highest was the raising of societal awareness of psoriasis and its problems. Rated lowest were functions related to personal services for members. Educational level was the only participant factor associated with significant differences in evaluations (P < .05). CONCLUSIONS: The psoriasis association contributes by disseminating information about the disease and patient care, and it serves to represent patients. Health professionals and institutions should take the association into account in their efforts to deal with the disease and in designing effective policies

The Spanish Psoriasis Patients' Association According to Its Members: Cross-Sectional Descriptive Study of Members' Opinions of the Association's Functions. / Función y respaldo a la asociación de pacientes con psoriasis en España según sus miembros: estudio descriptivo transversal.

INTRODUCTION: Patient associations form part of health care systems, but little is known about how their members' view the functionality of these associations and whether they endorse their goals and activities. OBJECTIVE: To study how the members of the leading Spanish association of patients with psoriasis and their relatives view the group's functioning. MATERIAL AND METHODS: Survey study using a self-administered questionnaire answered by members of the association (total membership, 26 349 persons). The credibility of the association and respondents' confidence in and satisfaction with it were studied and compared with their attitudes toward other agents in the health care system. A Rasch model was used to analyze respondents' ranking of functions. Analysis of variance was used to study between-group differences. RESULTS: A total of 746 members participated (response rate 2.83%). The association's credibility was rated in second place, after that of specialists who treat psoriasis. Support for the association functions was good (7.53 on a scale of 0 to 10). The function the members rated highest was the raising of societal awareness of psoriasis and its problems. Rated lowest were functions related to personal services for members. Educational level was the only participant factor associated with significant differences in evaluations (P<.05). CONCLUSIONS: The psoriasis association contributes by disseminating information about the disease and patient care, and it serves to represent patients. Health professionals and institutions should take the association into account in their efforts to deal with the disease and in designing effective policies.

Dermatitis atópica desde la perspectiva del paciente: desencadenantes, cumplimiento de las recomendaciones médicas y control de la enfermedad. Estudio DATOP / Patient Perspectives on Triggers, Adherence to Medical Recommendations, and Disease Control in Atopic Dermatitis: The DATOP Study

INTRODUCCIÓN Y OBJETIVOS: Conocer, desde la perspectiva del paciente, los desencadenantes de la dermatitis atópica (DA), el grado de control percibido y el cumplimiento de las indicaciones médicas y su calidad de vida relacionada con la salud (CVRS). PACIENTES Y MÉTODOS: Estudio epidemiológico, transversal, multicéntrico incluyendo pacientes adultos (> 16 años; n = 125) y pediátricos (entre 2-15 años; n = 116) con DA de intensidad moderada-grave, más de 12 meses de evolución y con episodios de lesiones activas moderados-graves (escala de evaluación global del investigador [IGA] > 2). Se analizaron los desencadenantes informados por los pacientes, el cumplimiento de las recomendaciones y el tratamiento farmacológico (TF), las diferencias en CVRS y el control percibido (U de Mann-Whitney) según la gravedad de la DA (índice SCORAD-SCORing Atopic Dermatitis). RESULTADOS: Los desencadenantes más frecuentes fueron: cosméticos, ropa, ácaros, detergentes/jabones y cambios de temperatura. El 47,2% de los pacientes adultos y el 39,7% de los pediátricos no aplicaban el TF desde el inicio del episodio. El TF, la hidratación y los consejos médicos de cuidado fueron las recomendaciones más seguidas. El 41,6 y el 27,6% (adultos y pediátricos, respectivamente) consideraba que su grado de control era insuficiente y se asoció con la gravedad de la DA en adultos (p = 0,014). CONCLUSIONES: El grado de control actual de la DA es mejorable, especialmente en adultos. Aunque los pacientes indican seguir las recomendaciones médicas, un porcentaje significativo no aplica correctamente los tratamientos. Parece necesario potenciar la educación sobre la enfermedad y su manejo para mejorar el grado de control y potenciar su CVRS

INTRODUCTION AND OBJECTIVES: To analyze the triggers of atopic dermatitis (AD), adherence to medical recommendations, disease control, and health-related quality of life (HRQOL) from the patient's perspective. PATIENTS AND METHODS: This was a multicenter, cross-sectional, epidemiological study with the participation of adults (age > 16 years; n = 125) and children (age, 2-15 years, n = 116). Patients had a history of at least 12 months of moderate to severe AD with a moderate to severe flare (Investigator Global Assessment score > 2) at the time of recruitment. The Mann-Whitney U test was used to evaluate relationships between disease severity, determined according to the Scoring in Atopic Dermatitis index, and triggers reported by patients, adherence to recommendations and pharmacological therapy, HRQOL, and patient-perceived control. RESULTS: The most common triggers were cosmetic products, clothing, mites, detergents/soaps, and changes in temperature. In 47.2% of adults and 39.7% of children, pharmacological therapy was not initiated at flare onset. Adherence was highest to pharmacological therapy, skin moisturizing, and medical care recommendations. Disease control was considered insufficient by 41.6% of adults and 27.6% of pediatric patients and, in adults, this was associated with the severity of AD (P = 0.014). CONCLUSIONS: The therapeutic control of AD is susceptible to improvement, especially in adults. Although patients state that they follow medical recommendations, a significant percentage of patients do not apply recommended treatments correctly. Better education about the disease and its management would appear to be necessary to improve disease control and HRQOL

Patient perspectives on triggers, adherence to medical recommendations, and disease control in atopic dermatitis: the DATOP study.

INTRODUCTION AND OBJECTIVES: To analyze the triggers of atopic dermatitis (AD), adherence to medical recommendations, disease control, and health-related quality of life (HRQOL) from the patient's perspective. PATIENTS AND METHODS: This was a multicenter, cross-sectional, epidemiological study with the participation of adults (age >16 years; n=125) and children (age, 2-15 years, n=116). Patients had a history of at least 12 months of moderate to severe AD with a moderate to severe flare (Investigator Global Assessment score>2) at the time of recruitment. The Mann-Whitney U test was used to evaluate relationships between disease severity, determined according to the Scoring in Atopic Dermatitis index, and triggers reported by patients, adherence to recommendations and pharmacological therapy, HRQOL, and patient-perceived control. RESULTS: The most common triggers were cosmetic products, clothing, mites, detergents/soaps, and changes in temperature. In 47.2% of adults and 39.7% of children, pharmacological therapy was not initiated at flare onset. Adherence was highest to pharmacological therapy, skin moisturizing, and medical care recommendations. Disease control was considered insufficient by 41.6% of adults and 27. 6% of pediatric patients and, in adults, this was associated with the severity of AD (P=.014). CONCLUSIONS: The therapeutic control of AD is susceptible to improvement, especially in adults. Although patients state that they follow medical recommendations, a significant percentage of patients do not apply recommended treatments correctly. Better education about the disease and its management would appear to be necessary to improve disease control and HRQOL.

Cumulative life course impairment: the imprint of psoriasis on the patient's life.

We now realize that moderate to severe psoriasis takes a toll on the patient's overall health beyond the effects on the skin itself, and so we use quality of life (QOL) measures to assess how the individual perceives both the impact of disease and the response to treatment. However, available instruments give us a cross-sectional assessment of QOL at a specific moment, and we lack longitudinal studies of how a disease affects each and every aspect of a patient's life over time-including physical and psychological wellbeing, social and emotional relationships, vocational and employment decisions, and how they change the individual's outlook. A new concept, cumulative life course impairment (CLCI), captures the notion of the ongoing effect of a disease, providing us with a new paradigm for assessing the impact of psoriasis on QOL. Unlike conventional measurement tools and scales, which focus on a specific moment in the patient's life, a CLCI tool investigates the repercussions of disease that accumulate over a lifetime, interfering with the individual's full potential development and altering perspectives that might have been different had psoriasis not been present. The accumulated impact will vary from patient to patient depending on circumstances that interact differently over time as the burden of stigmatization, concomitant physical and psychological conditions associated with psoriasis, coping mechanisms, and external factors come into play and are modulated by the individual's personality.

Calidad de vida relacionada con la salud, satisfacción y cumplimiento de los pacientes con dermatitis atópica moderada-grave que siguen un tratamiento farmacológico de mantenimiento. Estudio CONDA-SAT / Health-Related Quality of Life, Patient Satisfaction, and Adherence to Treatment in Patients With Moderate or Severe Atopic Dermatitis on Maintenance Therapy: The CONDA-SAT Study

Introducción y objetivos: Evaluar la calidad de vida relacionada con la salud (CVRS), la satisfacción y cumplimiento en pacientes con dermatitis atópica (DA) moderada-grave en tratamiento farmacológico de mantenimiento. Material y métodos: Estudio epidemiológico, multicéntrico, nacional, transversal con pacientes adultos y pediátricos diagnosticados de DA moderada o grave de al menos 16 meses de evolución y en tratamiento de mantenimiento. Se aplicó el Índice de Calidad de Vida en Dermatología (DLQI), el Cuestionario Dermatológico de Calidad de Vida Infantil (CDLQI), la versión para menores de 4 años (IDQOL), la Escala de Afectación de la Dermatitis Atópica (EADA), el test de Morisky-Green y escalas visuales analógicas de satisfacción. Se comparó la CVRS entre pacientes con afectación moderada y grave (U de Mann-Whitney) y la duración y número de brotes antes y después de la terapia de mantenimiento (prueba de Wilcoxon). Resultados: Participaron 141 pacientes pediátricos y 141 adultos con DA moderada en el 85,8 y 79,4% de los casos, respectivamente. El impacto en CVRS fue leve-moderado. La duración y número de los brotes disminuyeron desde la aplicación del tratamiento de mantenimiento (p < 0,001). Aunque la satisfacción fue alta en ambos grupos, el cumplimiento fue muy bajo (entre el 18,4-42,6% en pediátricos y entre el 14,9-27,0% en adultos). Conclusiones: Los pacientes con DA moderada o grave que siguen tratamiento farmacológico de mantenimiento presentan una reducción en la duración y número de los brotes y menor afectación de su CVRS. Además, los pacientes están satisfechos con el tratamiento aunque su cumplimiento es mejorable (AU)

Objective: To evaluate health-related quality of life (HRQOL), patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy. Material and methods: We performed a national, multicenter, cross-sectional, epidemiological study in adults and children with moderate or severe atopic dermatitis of at least 16 months’ duration who were receiving maintenance therapy. We used the Dermatology Life Quality Index (DLQI), the children's version of this scale (cDLQI), and the Morisky medication adherence scale. Visual analog scales were used to measure treatment satisfaction. We used the Mann-Whitney U test to compare HRQOL between patients with moderate and severe disease and the Wilcoxon test to compare the frequency and duration of flares before and after the start of maintenance therapy. Results: We studied 141 children and 141 adults; the prevalence of moderate AD in these groups was 85.8% and 79.4%, respectively. The impact of AD on HRQOL was mild to moderate. Maintenance therapy led to a significant decrease in the frequency and duration of flares (P <0 .001). While treatment satisfaction was high in both groups, adherence was poor (18.4%-42.6% in children and 14.9%-27.0% in adults). Conclusions: Patients with moderate and severe AD receiving maintenance therapy experience a reduction in the number and duration of flares and an improvement in HRQOL. While treatment satisfaction is high, adherence rates could be improved (AU)

Health-related quality of life, patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy: the CONDA-SAT study.

OBJECTIVE: To evaluate health-related quality of life (HRQOL), patient satisfaction, and adherence to treatment in patients with moderate or severe atopic dermatitis on maintenance therapy. MATERIAL AND METHODS: We performed a national, multicenter, cross-sectional, epidemiological study in adults and children with moderate or severe atopic dermatitis of at least 16 months' duration who were receiving maintenance therapy. We used the Dermatology Life Quality Index (DLQI), the children's version of this scale (cDLQI), and the Morisky medication adherence scale. Visual analog scales were used to measure treatment satisfaction. We used the Mann-Whitney U test to compare HRQOL between patients with moderate and severe disease and the Wilcoxon test to compare the frequency and duration of flares before and after the start of maintenance therapy. RESULTS: We studied 141 children and 141 adults; the prevalence of moderate AD in these groups was 85.8% and 79.4%, respectively. The impact of AD on HRQOL was mild to moderate. Maintenance therapy led to a significant decrease in the frequency and duration of flares (P < .001). While treatment satisfaction was high in both groups, adherence was poor (18.4%-42.6% in children and 14.9%-27.0% in adults). CONCLUSIONS: Patients with moderate and severe AD receiving maintenance therapy experience a reduction in the number and duration of flares and an improvement in HRQOL. While treatment satisfaction is high, adherence rates could be improved.

Restoration of hepatic glycogen deposition reduces hyperglycaemia, hyperphagia and gluconeogenic enzymes in a streptozotocin-induced model of diabetes in rats.

AIMS/HYPOTHESIS: Glycogen deposition is impaired in diabetes, thus contributing to the development of hyperglycaemia. Several glucose-lowering strategies have attempted to increase liver glycogen deposition by modulating targets, which eventually trigger the activation of liver glycogen synthase (LGS). However, these targets also alter several other biological processes, and therefore their therapeutic use may be limited. Here we tested the approach of directly activating LGS and evaluated the potential of this strategy as a possible treatment for diabetes. METHODS: In this study, we examined the efficacy of directly overproducing a constitutively active form of LGS in the liver to ameliorate streptozotocin-induced diabetes in rats. RESULTS: Activated mutant LGS overproduction in the liver of streptozotocin-induced diabetic rats normalised liver glycogen content, despite low levels of glucokinase and circulating insulin. Moreover, this overproduction led to a decrease in food intake and in the production of the main gluconeogenic enzymes, glucose-6-phosphatase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase. The resulting combined effect was a reduction in hyperglycaemia. CONCLUSIONS/INTERPRETATION: The restoration of liver glycogen ameliorated diabetes and therefore is considered a potential strategy for the treatment of this disease.

The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker.

AIMS/HYPOTHESIS: Transmembrane protein 27 (TMEM27) is a membrane protein cleaved and shed by pancreatic beta cells that has been proposed as a beta cell mass biomarker. Despite reports of its possible role in insulin exocytosis and cell proliferation, its function in beta cells remains controversial. We aimed to characterise the function of TMEM27 in islets and its potential use as a beta cell mass biomarker. METHODS: To determine TMEM27 function, we studied TMEM27 gene expression and localisation in human healthy and diabetic islets, the correlation of its expression with cell cycle and insulin secretion genes in human islets, its expression in tungstate-treated rats, and the effects of its overproduction on insulin secretion and proliferation in a beta cell line and islets. To elucidate its utility as a beta cell mass biomarker, we studied TMEM27 cleavage in a beta cell line, islets and primary proximal tubular cells. RESULTS: TMEM27 mRNA levels in islets are lower in diabetic donors than in controls. Its gene expression correlates with that of insulin and SNAPIN in human islets. TMEM27 expression is downregulated in islets of tungstate-treated rats, which exhibit decreased insulin secretion and increased proliferation. TMEM27 overproduction in a beta cell line and islets significantly enhanced glucose-induced insulin secretion, with modest or no effects on proliferation. Finally, TMEM27 is cleaved and shed by renal proximal tubular cells and pancreatic islets. CONCLUSIONS/INTERPRETATION: Our data support a role for TMEM27 in glucose-induced insulin secretion but not in cell proliferation. The finding that its cleavage is not specific to beta cells challenges the current support for its use as a potential beta cell mass biomarker.

A survey of Cambodian health-care providers' HIV knowledge, attitudes and intentions to take a sexual history.

Cambodia has one of the highest prevalence rates of HIV in Asia and is scaling up HIV testing. We conducted a cross-sectional survey with 358 health care providers in Phnom Penh, Cambodia to assess readiness for voluntary testing and counselling for HIV. We measured HIV knowledge and attitudes, and predictors of intentions to take a sexual history using the Theory of Planned Behaviour. Over 90% of health care providers correctly answered knowledge questions about HIV transmission, but their attitudes were often not positive towards people living with HIV. The Theory of Planned Behaviour constructs explained 56% of the variance in intention to take a sexual history: the control providers perceive they have over taking a sexual history was the strongest contributor (51%), while social pressure explained a further 3%. Attitudes about taking a sexual history did not contribute to intention. Interventions with Cambodian health care providers should focus on improving skills in sexual history-taking.

Acidosis tubular renal inducida portopiramato. A propósito de un caso / No disponible

No disponible