Congenital Adrenal Hyperplasia: Classification of Studies Employing Psychological Endpoints

Psychological outcomes in persons with congenital adrenal hyperplasia (CAH) have received substantial attention. The objectives of this paper were to (1) catalog psychological endpoints assessed in CAH outcome studies and (2) classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68%) investigated endpoints related to psychosexual differentiation. The preponderance of studies (76%) examined a direct relationship (i.e., inferring causality) between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Development and validation of the interactive unit start-up procedure as a software tool in the implementation of the operator information support system at the NVNPP

This article is focused on the current issue of developing an operator information support system (OISS) for the Novovoronezh NPP II project. One of the main reasons to raise this topic is the MCR operator’s overload with data due to the greatly increased information flows related to the VVER-1200 Process I&C compared to the serially produced VVER-1000 power units. The other important reason, in the authors’ opinion, is the increased volume of existing procedures in hard copy due to the strengthened requirements for their registration and attempts to describe all possible failures and deviations in the programs and plant evolution sheet, which complicates the work on them. In the era of ubiquitous digitalization, the paper procedures can only distract the attention of the operator, who is overloaded with information even without that. The obvious solution is to create a system providing automatic collection and analysis of information. In addition, the functionality of the operator information support system allows the use of operating experience, thus minimizing the impact of the human factor. The lack of knowledge or experience could be especially challenging with procedures being applied infrequently, for example, for starting up and shutting down the unit. The authors consider the development and functionality of interactive procedures and applicable requirements for them. Particular attention is paid to the ergonomics of the workplace and the convenience of operating personnel working with an interactive procedure. Since the transition from the paper version of the programs can cause problems with reading the procedures and, ultimately, lead to the failure of the unit start-up time, the personnel of the operating station were directly involved in the development of the interactive programs. Based on the review results, conclusions were made about the correctness of the approaches in developing the interactive procedures and validated solutions to be disseminated for all routine operations

El Tlacuache Núm. 10 (2001). 10 Año 1 (2001) septiembre. El Tlacuache

- “Los murmuros del Popocatepetl” por José Tambonero. - El Patojo, una tetera prehispánica por Giselle Canto Aguilar. - Una maqueta de piedra hallada en Xochicalco, Morelos por Jaime Litvak King. - Nuestro patrimonio desconocido por Teresita Loera y Anaite Monterforte. - El Yahutli por Margarita Avilés y Macrina Fuentes. - Más allá de la juventud en éxtasis: hacia otra lectura de los valores en México/II de IV por Ezequiel Maldonado

El Tlacuache Núm. 8 (2001). 8 Año 1 (2001) agosto. El Tlacuache

- Algunos apuntes sobre las creencias alrededor del sol, en Tetelcingo, Morelos po José Tambonero Tlalpa. - El Mogote de Cuernavaca por Barbara Konieczna. - Nuestro patrimonio desconocido por Teresita Loera y Anaite Monterforte. - El Yahutli por Biol. Margarita Avilés y Biol. Macrina Fuentes. - Una figurilla procedente de Xochicalco, en el Museo de Cambridge, Inglaterra por Jaime Litvak K

El Tlacuache Núm. 7 (2001). 7 Año 1 (2001) agosto. El Tlacuache

- Algunos apuntes sobre las creencias alrededor del sol, en Tetelcingo, Morelos po José Tambonero Tlalpa. - El Mogote de Cuernavaca por Barbara Konieczna. - Nuestro patrimonio desconocido por Teresita Loera y Anaite Monterforte. - El Yahutli por Biol. Margarita Avilés y Biol. Macrina Fuentes. - Una figurilla procedente de Xochicalco, en el Museo de Cambridge, Inglaterra por Jaime Litvak K

Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5

Toll-like receptors (TLRs) engage networks of transcriptional regulators to induce genes essential for antimicrobial immunity. We report that NFAT5, previously characterized as an osmostress responsive factor, regulates the expression of multiple TLR-induced genes in macrophages independently of osmotic stress. NFAT5 was essential for the induction of the key antimicrobial gene Nos2 (inducible nitric oxide synthase [iNOS]) in response to low and high doses of TLR agonists but is required for Tnf and Il6 mainly under mild stimulatory conditions, indicating that NFAT5 could regulate specific gene patterns depending on pathogen burden intensity. NFAT5 exhibited two modes of association with target genes, as it was constitutively bound to Tnf and other genes regardless of TLR stimulation, whereas its recruitment to Nos2 or Il6 required TLR activation. Further analysis revealed that TLR-induced recruitment of NFAT5 to Nos2 was dependent on inhibitor of κB kinase (IKK) β activity and de novo protein synthesis, and was sensitive to histone deacetylases. In vivo, NFAT5 was necessary for effective immunity against Leishmania major, a parasite whose clearance requires TLRs and iNOS expression in macrophages. These findings identify NFAT5 as a novel regulator of mammalian anti-pathogen responses.C. López-Rodríguez was supported by the Ramón y Cajal and I3 Researchers Programmes and grants from the Spanish Government (SAF2006-04913 and SAF2009-08066) and European Union (MCIRG516308). J. Aramburu was supported by grants from the Spanish Government (BFU2008-01070 and SAF2011-24268), and Distinció de la Generalitat de Catalunya per a la Promoció de la Recerca Universitària. Research in the laboratories of C. López-Rodríguez and J. Aramburu is also supported by Fundació la Marató TV3 (030230/31, 080730), Spanish Ministry of Health (ISCIII-RETIC RD06/0009-FEDER), and Generalitat de Catalunya (2009 SGR 601). M. Buxadé was supported by a Beatriu de Pinós postdoctoral contract from Generalitat de Catalunya. S. Iborra was supported by a Sara Borrell postdoctoral contract from the Ministry of Health of Spain. J. Minguillón and R. Berga-Bolaños were supported by predoctoral fellowships from the Spanish Government