Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

The Mitla Landslide, an Event That Changed the Fate of a Mixteco/Zapoteco Civilization in Mesoamerica

Before the arrival of the Spanish conquerors, Mitla was the second most important city in the valleys of Oaxaca, México. However, the ruins that are visible today do not seem to match the size of a city of more than 10,000 inhabitants. Geological and geophysical studies suggest that part of the city was covered by the deposits of a dry landslide likely to have been caused by an earthquake with a magnitude that could vary between 6 and 7. This landslide is monolithological, which is why two geophysical methods were used in order to evaluate its geometrical characteristics and to suggest the possible existence of archeological remains under the landslide

Comparison of Metabolic, Lifestyle and Mental Health Parameters in People with Diabetes and Relatives with and without Family Support

Ana Cristina García-Ulloa,1 Valeria Miranda-Gil,1 Michelle Díaz-Pineda,1 María Fernanda Garnica-Carrillo,1 Nancy Haydée Serrano-Pérez,1 Maria Sofia Tron-Gomez,2 Grecia Piedad Colorado Báez,3 Christian Alejandro Cruz Madrigal,3 Sergio Hernández-Jiménez1 for the Group of Study CAIPaDi1Centro de Atención Integral del Paciente con Diabetes (CAIPaDi), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Facultad de Ciencias de la Salud, Universidad Anáhuac México Campus Norte, Estado de México, México; 3Escuela de Medicina, Universidad Panamericana, Mexico City, MexicoCorrespondence: Sergio Hernández-Jiménez, Vasco de Quiroga No. 15, Colonia Sección XVI, Tlalpan, Mexico City, 14080, Mexico, Tel +1 52 55 54870900 (5045) ; +1 52 55 55737378, Email [email protected]: To analyze and compare metabolic, lifestyle and mental health parameters in relatives and people-with-T2DM (PDM) with and without support.Patients and Methods: We included 160 patients with < 5 years of diagnosis of T2DM, without disabling complications, and non-smokers, attending a multidisciplinary program for diabetes control, and their accompanying relatives. If the patients or relatives abandoned the program, we contacted them and asked to take laboratory tests and answer surveys regarding anxiety, depression, and perception of their family support. Variables distribution was assessed with the Kolmogorov–Smirnov test. We used ANOVA or Kruskal Wallis Tests, according to variable distribution. Frequencies and percentages are used for categorical values and analyzed with a chi-square test. We separated the participants in four groups: relatives with and without support and PDM with and without support.Results: We included 160 participants, age 51± 10, and 54.3% women. Total cholesterol (188± 36 vs 204± 43 vs 170± 34 vs 181± 35 mg/dL, p=0.001), LDL-cholesterol (113± 35 vs 125± 27 vs 101 ± 30 vs 109± 29, p=0.008), and non-HDL cholesterol (143± 32 vs 154 ± 30 vs 129± 33 vs 135± 35 mg/dL, p=0.010) were higher in the group without support. Although patients without family support had lower values, they did not achieve metabolic goals. Weight (75± 17 vs 77± 19 vs 74.2± 10.5 vs 90.2± 17.3 kg) and body mass index (28.9± 4.8 vs 30.1± 4.7 vs 27.4± 3.3 vs 33± 4.3 kg/m2) were higher in PDM without family support (p< 0.001 for both).Conclusion: Support in PDM and their families is important in metabolic control. However, raising awareness among family members to screen for diabetes and changes in lifestyle are points to improve. Including the evaluation of social and family support will allow a more complete assessment to identify barriers to achieving goals.Keywords: family support, social support, relatives, patients, type 2 diabete

Paleoseismology of the southwestern Morelia-Acambay fault system, central Mexico

El sistema de fallas Morelia–Acambay (MAFS) consiste en una serie de fallas normales de dirección E–W y NE–SW que cortan la parte central del Cinturón Volcánico Transmexicano. El sistema de fallas se asocia a la formación de las depresiones lacustres de Chapala, Zacapu, Cuitzeo, Maravatio y Acambay. Las fallas E–W de MAFS aparecieron hace 7–9 millones de años durante Mioceno temprano. Las fallas NNW–SSE son más viejas y se han reactivado en el tiempo, desplazando y controlando a las depresiones lacustres E–W. Se estimaron las magnitudes sísmicas de las estructuras E–W de la región de Morelia–Cuitzeo asumiendo una ruptura cosismica. Cartografía, geología estructural y paleosismología sugieren que las estructuras de MAFS en la región de Morelia–Cuitzeo han estado activas durante el Holoceno, controlando los terremotos históricos que afectan a paleosuelos con cerámica de las culturas Pirinda–Purepecha. Estos terremotos históricos también están registrados en las fallas E–W del campo geotérmico de Los Azufres. En la región de Pátzcuaro, las estructuras E–W de MAFS también se ligan a sismos fuertes ocurridos durante épocas prehistóricas e históricas. Por ejemplo, la secuencia lacustre de Jarácuaro, en el sector meridional del lago Pátzcuaro ha registrado por lo menos tres sismos importantes (Período de PostClassic, 1845 y 1858). El sismo de 1858 (Magnitud estimada de ~7.3) generó un tsunami de 2 m de altura descrito en los archivos históricos. Un sismo similar en la actualidad devastaría esta zona del estado de Michoacán, la cual está ocupada por las poblaciones de más alta densidad. De hecho, el 17 de octubre de 2007 mientras que este articulo era escrito, ocurrieron tres sismos en la ciudad de Morelia que fueron ligados a la falla normal derecha de la Central o de La Paloma. Este hecho corroboraba la sismicidad potencial de las fallas E–W y NE–SW del TMBV. doi: https://doi.org/10.22201/igeof.00167169p.2009.48.3.2