1/f noise in human cognition.

When a person attempts to produce from memory a given spatial or temporal interval, there is inevitably some error associated with the estimate. The time course of this error was measured in a series of experiments where subjects repeatedly attempted to replicate given target intervals. Sequences of the errors in both spatial and temporal replications were found to fluctuate as 1/f noises. 1/f noise is encountered in a wide variety of physical systems and is theorized to be a characteristic signature of complexity.

Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes.

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

Candidiasis oral en el paciente mayor / Oral candidosis in the older patient

La candidiasis o candidosis oral es la enfermedad infecciosa ocasionada por el crecimiento de las colonias de Cándida y la penetración de las mismas en los tejidos orales cuando las barreras físicas y las defensas del huésped se encuentran alteradas. Es una infección frecuente de la cavidad oral de los adultos de edad avanzada. Aunque la incidencia real se desconoce, se sabe que existe una prevalencia aumentada en ciertas ocasiones como ocurre en ancianos, en presencia de prótesis mucosoportadas, xerostomía o en patologías asociadas frecuentemente en los mayores. Los tipos clínicos más característicos son la forma seudomembranosa y la eritematosa (palatina y lingual). Pueden tener evolución aguda o crónica según la persistencia de los factores predisponentes. También son frecuentes procesos bucales comúnmente asociados: estomatitis protética, queilitis angular, glositis romboidal y lengua vellosa. La mayor parte de las candidiasis orales tienen un diagnóstico clínico, pero ha de confirmarse demostrando la penetración de la cándida en la mucosa oral, siendo el frotis la técnica de elección. Antes de comenzar el tratamiento, debemos estar seguros que se trata de una candidiasis oral, el tipo clínico y los factores predisponentes relacionados con la infección. Empezaremos siempre eliminando estos factores predisponentes, en el adulto mayor, la polifarmacología, la xerostomía, enfermedades crónicas y el uso de prótesis mucosoportadas son situaciones frecuentes que habrá que controlar. Instauraremos medidas higiénicas bucales y posteriormente si es necesario, utilizaremos fármacos antifúngicos, comenzando siempre con formas tópicas (AU)

Oral Candidiasis or Candidosis is the infectious disease caused by the growth of colonies of Candida and penetration in the oral tissues when physical barriers and host defenses are altered. It is the most common fungal infection of oral involvement. It is a common infection of the oral cavity in elderly adults. Although the true incidence is unknown, it is known that there is an increased prevalence in certain situations in the elderly: tissue-borne prosthesis, xerostomia or disorders frequently associated. The most characteristic clinical types are pseudomembranous and erythematous (palatal and lingual) form. They may have acute or chronic evolution as the persistence of predisposing factors. They are also frequent mouth commonly associated processes: denture stomatitis, angular cheilitis, rhomboid glossitis and hairy tongue. Most oral candidiasis have a clinical diagnosis, but must be confirmed by demonstrating penetration of candida on the oral mucosa, being the preferred technique smears. Before starting treatment, we must be sure that it is an oral candidiasis, clinical type and predisposing factors associated with infection. Always start eliminating these predisposing factors in the elderly, the polypharmacy, xerostomia, chronic diseases and the use of tissue-borne prostheses are common situations which must be controlled. We will initiate oral hygiene measures and then if necessary, use antifungaldrugs, always starting with topical forms (AU)

Transcriptional regulation of human placental corticotropin-releasing factor by prostaglandins and estradiol.

The mechanism of labor initiation in humans has not been completely elucidated. Prostaglandins, estrogens, and corticotropin-releasing factor (CRF) have all been shown to affect uterine myocytes and enhance uterine contractility. There are also indications that these uterine regulators have additional effects on other sites involved in labor and that they may act in concert or, perhaps, by regulating each other. Therefore, we evaluated the CRF promoter for transcriptional regulation by prostaglandins and estrogens. Human placental choriocarcinoma cell lines were transfected with CRF-luciferase reporter genes and treated with prostaglandins. Prostaglandin E2 (PGE2), but not prostaglandin F2alpha (PGF2alpha), stimulated CRF-luciferase expression in choriocarcinoma cell lines via a cAMP-dependent pathway. A combination of transfections and in vitro binding studies tested for potential regulation of CRF by estrogen receptor (ER). ER neither regulated the CRF promoter nor interacted with steroid response half-sites from the CRF promoter. Our results provide a molecular regulatory link between PGE2 and CRF, two compounds that enhance uterine contractile function. Combined with the stimulation of prostaglandin release by CRF, these data support a potentially important "feed-forward" regulatory loop involving CRF and PGE2 in parturition. In contrast, we found no evidence for direct effects of estrogens or PGF2alpha on CRF transcription.

Characterization of the homeodomain gene EMX2: sequence conservation, expression analysis, and a search for mutations in endometrial cancers.

Previous loss-of-heterozygosity studies in endometrial carcinoma mapped a putative tumor suppressor gene to 10q25.3-26.1. An analysis of genomic sequences for the deletion interval showed several expressed sequence tags and the homeodomain gene EMX2, a homologue of Drosophila melanogaster empty spiracles. Expression studies showed that EMX2 transcripts are abundant in the adult uterus and that message levels seem to be inversely correlated with endometrial proliferation. EMX2 RNA was more abundant in quiescent postmenopausal endometrium than in premenopausal endometrium. We found decreased EMX2 expression in a subset of primary endometrial tumors, and four of six endometrial cancer cell lines investigated failed to express EMX2. The predicted protein showed extensive amino acid conservation with EMX2 sequences from several vertebrates. There was also considerable evolutionary conservation in the 3' untranslated region. To examine the potential function of EMX2 in endometrial tumorigenesis, we investigated 20 primary tumors and 6 endometrial cancer cell lines for mutations. Two primary tumors had mutations. Inactivation or reduced expression of EMX2 in cancers, coupled with increased expression in the quiescent endometrium, indicate that this homeodomain gene is involved in maintenance of the differentiated state.

Dietary ascorbic acid and resistance to experimental renal candidiasis.

Guinea pigs were maintained for various periods of time on low (0.5 mg/day), intermediate (20 mg/day), or high (100 and 500 mg/day) levels of dietary ascorbic acid. Animals in each experimental group were challenged with Candida albicans via cardiac injection, and the course of infection in the kidneys was assessed. The results show that the animals receiving only 0.5 mg of ascorbic acid per day were significantly more susceptible to the infection than animals maintained on any higher level of dietary ascorbic acid. The greater susceptibility of the guinea pigs in the 0.5-mg level group was evident, however, only during "early" stages of the infection (until about day 3). Guinea pigs receiving high levels of dietary ascorbic acid were no more resistant at any time after infection, or with any challenge dose, than those receiving an intermediate dietary level. Although these data suggest that vitamin C may be involved in resistance to candidiasis, tissue levels of ascorbic acid do not change significantly with time after infection. These results indicate that low levels of dietary ascorbic acid increase susceptibility to candidiasis, yet high (or "megadose") levels of dietary vitamin C do not show any effect on resistance to this microorganism.

Toxicity of the herbicides 2,4-D, DEF, propanil and trifluralin to the Dungeness crab, Cancer magister.

Lethal and sublethal responses to the herbicides 2,4-D, DEF, propanil, and trifluralin of various life history stages of the Dungeness crab, Cancer magister, were examined to estimate maximum acceptable toxicant concentrations (MATC) of each compound for this species. Zoeae were found, in long term tests, to be the most sensitive stage. Based on the experiments with this stage, MATCs were concluded to be greater than 0.95, less than 6.9 microgram/L for DEF, greater than or equal to 26, less than 220 microgram/L for trifluralin, greater than or equal to 1,700 microgram/L for propanil, and less than 1,000 microgram/L for the free acid form of 2,4-D.

Photoelectron microscopy: a new approach to mapping organic and biological surfaces.

A general method of imaging organic and biological surfaces based on the photoelectric effect is reported. For the experiments, a photoelectron emission microscope was constructed. It is an ultrahigh vacuum instrument using electrostatic electron lenses, microchannel plate image intensifier, cold stage, hydrogen excitation source, and magnesium fluoride optics. The organic surfaces examined were grid patterns of acridine orange, fluorescein, and benzo(a)pyrene on a Butvar surface. A biological sample, sectioned rat epididymis, was also imaged by the new photoelectron microscope. Good contrast was obtained in these initial low magnification experiments. These data demonstrate the feasibility of mapping biological surfaces according to differences in ionization potentials of exposed molecules. A number of technical difficulties, such as the intensity of the excitation source, must be solved before high resolution experiments are practical. However, it is probable that this approach can be useful, even at low magnifications, in determination of the properties of organic and biological surfaces.

Diagnóstico del liquen plano oral / Diagnosis of the oral lichen planus

El objetivo de este trabajo es presentar los aspectos clínicos y patológicos necesarios para conocer mejor el liquen plano oral y poder diagnosticarlo correctamente. El diagnóstico se obtiene en primer lugar por el aspecto clínico de las lesiones. Se debe realizar siempre biopsia y estudio anatomopatológico para confirmar la sospecha clínica y realizar diagnóstico diferencial con otras entidades de apariencia clínica similar. Los pasos que debemos seguir para realizar un diagnóstico de certeza son: estudio de la clínica (anamnesis y exploración clínica), biopsia para estudio histopatológico y analítica sanguínea y determinación de la tensión arterial, buscando una posible relación con determinados procesos sistémicos. Se hará una inmunofluorescencia directa cuando haya que diferenciarlo de dermatopatías similares (lupus, penfigoide o pénfigo). En ocasiones podremos realizar un análisis estructural y otras pruebas diagnósticas (AU)

The aim of this work is to present the clinical and pathological necessary aspects to know better the oral lichen planus and to be able to diagnose it correctly. The diagnosis is obtained first by the clinical aspect of the injuries. It is necessary to realize always biopsy and histopathologyc evaluation to confirm the clinical suspicion and realize differential diagnosis with other entities of clinical similar appearance. The steps that we must follow to realize a diagnosis of certainty are: study of the clinic (anamnesis and clinical exploration), biopsy for histopathological study and analytical blood and determination of the blood pressure, looking for a possible relation with certain systemic processes. It will become a direct inmunofluorescence when it is necessary to differentiate it of similar disease (lupus, pemphigoid or pemphigus). In occasions we will be able to realize a ultraestructural analysis and other diagnostic tests (AU)

Desórdenes orales potencialmente malignos. Manifestaciones clínicas / Potentially malignant disorders. Clinical aspects

En el año 2005 un Comité de Expertos, coordinado por el Centro Colaborador de la OMS para el Cáncer Oral y Precáncer, establece el concepto y clasificación de los trastornos orales potencialmente malignos. Los más frecuentes en nuestro medio son: la leucoplasia, eritroplasia, liquen plano, queilitis o queratosis actínica del labio y el lupus eritematoso discoide. En este trabajo se describen las manifestaciones clínicas más frecuentes de los dichos trastornos. El conocimiento de sus características clínicas facilita el diagnóstico precoz como medida de prevención del cáncer oral (AU)

In 2005 a committee of experts, coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer, establishes the concept and classification of potentially malignant oral disorders. The most common in our country are: leukoplakia, erythroplakia, lichen planus, actinic keratosis and discoid lupus erythematosus. In this paper we describe the most common clinical manifestations of these disorders. Knowledge of the clinical features facilitates early diagnosis as a measure of oral cancer prevention (AU)

Factores de riesgo y prevención del cáncer oral. Actitud del odontólogo / Risk factors and prevention of oral cancer. The attitude of the dental professional

El cáncer oral constituye un grave problema sanitario en muchos países. No sólo genera una mortalidad significativa, sino que también provoca desfiguración extensa, deterioro funcional, cambios conductuales, y problemas económicos y sociológicos. La OMS predice un continuo aumento de esta enfermedad en todo el mundo. En España, la incidencia del cáncer oral es de 12 a 15 casos/100.000 habitantes/año en varones y de 2 a 4 casos/100.000 habitantes/año en mujeres; estos resultados posicionan a nuestro país en una posición intermedia en lo que se refiere a la incidencia de cáncer oral en la Comunidad Europea. La profesión odontológica tiene un papel importante en la lucha contra el cáncer oral cumpliendo una invalorable tarea en todos los niveles de prevención. El objetivo del presente trabajo es presentar una actualización acerca de la actuación del odontólogo en la prevención primaria, secundaria y terciaria del cáncer oral (AU)

Oral cancer is a serious health problem in many countries. It not only generates significant mortality, but also causes extensive disfigurement, loss of function, behavioral changes and economic and sociological problems. The World Health Organization (WHO) predicts a continuous increase of this disease worldwide. In Spain, the incidence of oral cancer is 12 to 15 cases per 100,000 / year in males and 2-4 cases per 100,000 / year in women, these results positioning Spain in an intermediate position in relation to the incidence of oral cancer in the European Community. The dental profession has an important role in the fight against oral cancer, fulfilling an invaluable task in all levels of prevention. The aim of this paper is to present an update on the performance of the dentist in the primary, secondary and tertiary prevention of oral cancer (AU)