A Smad action turnover switch operated by WW domain readers of a phosphoserine code.

When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction. Here we demonstrate that there is an order of events-Smad activation first and destruction later-and that it is controlled by a switch in the recognition of Smad phosphoserines by WW domains in their binding partners. In the BMP pathway, Smad1 phosphorylation by CDK8/9 creates binding sites for the WW domains of YAP, and subsequent phosphorylation by GSK3 switches off YAP binding and adds binding sites for Smurf1 WW domains.

Long-term exposure to duodenal levodopa/carbidopa infusion therapy improves quality of life in relation especially to mobility, activities of daily living, and emotional well-being.

Background: Continuous duodenal levodopa infusion (DLI) is an effective therapy that improves quality of life (QoL) in advanced Parkinson's disease (PD). However, in which aspects improve the patients their QoL has been poorly documented.

Methods: We evaluated 39-item Parkinson's disease Quality of Life Questionnaire Summary Index score (PDQ-39SI) changes analyzing its different domains in nine patients with advanced PD treated with DLI.

Enhancing the algorithm for developmental-behavioral surveillance and screening in children 0 to 5 years.

Objective: To determine if the 2006 American Academy of Pediatrics developmental surveillance and screening algorithm is adequate or if revisions are needed.

Methods: A comprehensive literature search was conducted to investigate a clinician's ability to perform developmental-behavioral surveillance in children 0 to 5 years.

Results: Even when a broad-band developmental screen is typical, pediatricians should refer when they confidently suspect a delay but be far more suspicious about children who seem asymptomatic.

CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening.

Introduction: Cystic fibrosis, the most common autosomal recessive disorder, is caused by defects in the CF transmembrane conductance regulator gene (CFTR) that encodes a chloride channel. To date, over 1,800 mutations have been described related to the causative gene of CF, showing a variable frequency among populations. In a previous extensive analysis of the CFTR locus in 97 Mexican patients, 34 different mutations (75% of CF alleles) were found using several strategies for mutation screening; however, 63% had at least an uncharacterized allele.

Fasting hyperglycaemia and in-hospital mortality in elderly population.

Background: Admission hyperglycaemia has shown to be a marker of poor clinical outcome. The prevalence of admission hyperglycaemia and its relationship with in-hospital mortality in elderly population has not been clearly defined. We assessed the prevalence and prognostic significance of admission fasting hyperglycaemia in aged patients.

Prevalence of human papillomavirus genotypes in cytologic abnormalities from unvaccinated women living in north-western Spain.

Cervical cancer and its precursors low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) are associated with infection by human papillomavirus (HPV), in particular HPV 16 and 18. The distribution of the HPV genotype varies with the severity of cervical disease, age and the geographic location of the patients. We report the results of a population study carried out in a region of north-western (NW) Spain aimed at determining the prevalence of single and multiple infections by 35 types of HPV using low-density microarrays for 113 cases with negative for intraepithelial lesions or malignancies; 588 with atypical squamous cells of undetermined significance (ASCUS)/LSIL; 183 with HSIL; and seven cases of squamous cell carcinomas.

SSTR1- and SSTR3-selective somatostatin analogues.

We prepared the two enantiomers of 3-(3'-quinolyl)-alanine (Qla, 1) in multigram scale by asymmetric hydrogenation. These amino acids, protected as Fmoc derivatives, were then used in the solid-phase synthesis of two new somatostatin 14 (SRIF-14) analogues 8 a and 8 b, tetradecapeptides in which the tryptophan residue (Trp8) is replaced by one of the two enantiomers of 3-(3'-quinolyl)-alanine (Qla8) and therefore lack the N--H bond in residue 8. The selectivity of these new analogues for the somatostatin receptors, SSTR1-5, was measured.

Utility of a combined current procedural terminology and International Classification of Diseases, Ninth Revision, Clinical Modification code algorithm in classifying cervical spine surgery for degenerative changes.

Study Design: Retrospective study.

Objective: To evaluate the sensitivity and specificity of a combined Current Procedural Terminology (CPT) and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm in defining cervical spine surgery in comparison to patient operative reports in the medical record.

Summary Of Background Data: Epidemiological studies of spine surgery often use ICD-9-CM billing codes in administrative databases to study trends and outcome of surgery.

Transcriptional regulation of CDP1 and CYG56 is required for proper NH4+ sensing in Chlamydomonas.

The assimilation of inorganic nitrogen is an essential process for all plant-like organisms. In the presence of ammonium and nitrate as nitrogen sources, Chlamydomonas reinhardtii preferentially assimilates ammonium and represses the nitrate assimilation pathway through an unknown mechanism that in part involves the guanylate cyclase CYG56. It is demonstrated that cells not only respond quantitatively to the NH(4)(+) signal but are also able to sense a balance between both nitrogen sources.

Influence of a fat overload on lipogenic regulators in metabolic syndrome patients.

Several epidemiological studies have related an increase of lipids in the postprandial state to an individual risk for the development of CVD, possibly due to the increased plasma levels of TAG and fatty acids (FA) through enzymes of FA metabolism. The interaction between nutrition and the human genome determines gene expression and metabolic response. The aim of the present study was to evaluate the influence of a fat overload on the gene mRNA levels of lipogenic regulators in peripheral blood mononuclear cells (PBMC) from patients with the metabolic syndrome.

[Experience with continuous levodopa enteral infusion (Duodopa(®)) in patients with advanced Parkinson's disease in a secondary level hospital].

Introduction: Continuous levodopa delivery by enteral infusion (Duodopa(®)) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa(®) therapy in 11 patients with advanced PD.

Methods: We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa(®) was approved for advanced PD treatment in Spain at that date) until April 2010 at the A.

Strengths and limitations of International Classification of Disease Ninth Revision Clinical Modification codes in defining cervical spine surgery.

Study Design: Retrospective study.

Objective: To evaluate the sensitivity and specificity of International Classification of Disease Ninth Revision Clinical Modification (ICD9-CM) hospital discharge codes to define degenerative cervical spine surgery in comparison to patient operative notes in the medical record.

Summary Of Background Data: Population-based studies of spine surgery have often relied on administrative databases as a primary information source, but little is known about the validity of using ICD9-CM codes to identify these operations.

Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade.

The ECS (endocannabinoid system) plays an important role in the onset of obesity and metabolic disorders, implicating central and peripheral mechanisms predominantly via CB1 (cannabinoid type 1) receptors. CB1 receptor antagonist/inverse agonist treatment improves cardiometabolic risk factors and insulin resistance. However, the relative contribution of peripheral organs to the net beneficial metabolic effects remains unclear.

Increased amphiregulin expression as a biomarker of cholesteatoma activity.

Objectives/hypothesis: The purpose of this study was to evaluate human surgical specimens for cholesteatoma-associated changes in amphiregulin expression and determine potential relations to clinical disease variables. Amphiregulin, an epidermal growth factor receptor ligand, has functions in normal epithelial proliferation and aberrant neoplastic cell growth and is proinflammatory (e.g.

Isolation and characterization of true mesenchymal stem cells derived from human term decidua capable of multilineage differentiation into all 3 embryonic layers.

Objective: The objective of the study was to isolate and characterize a population of mesenchymal stem cells (MSCs) from human term placental membranes.

Study Design: We isolated an adherent cell population from extraembryonic membranes. Morphology, phenotype, growth characteristics, karyotype, and immunological and differentiation properties were analyzed.

[Descriptive analysis of the use of atypical antipsychotics under compassionate-use in a health area in Ferrol (La Coruña, Spain)].

Background And Objective: Although atypical antipsychotics (AA) provoke fewer extra-pyramidal symptoms (ES) than classic antipsychotics, their use in patients greater than or equal to 75 years old with dementia must be under compassionate-use. This is an important limitation. We performed a descriptive analysis of the use of atypical antipsychotics under compassionate-use (AACU) in the Ferrol health area.

Validation of a Mexican Spanish version of the Children's Dermatology Life Quality Index.

The Children's Dermatology Quality Index was developed as a tool to evaluate the quality-of-life in children with skin diseases. While a useful, self-administered scale, it has not been validated in Spanish for Mexican children. The aim of this study was to validate a Mexican version.

Anxiety disorders in children and adolescents.

Anxiety disorders are among the most common and functionally impairing mental health disorders to occur in childhood and adolescence. Primary care providers can expect to treat youth who have anxiety disorders frequently, and this article aims to provide the tools necessary to evaluate and manage patients who present with anxiety symptoms during childhood or adolescence. This article discusses the epidemiology of anxiety disorders, including the increased risk of future anxiety disorders and other mental health problems that are associated with having an anxiety disorder in childhood and adolescence.

Serum thyrotropin concentration is an early marker of normalization of low triiodothyronine syndrome in aged hospitalized patients after discharge.

Objectives: To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge.

Methods: A group of 146 patients (mean age±SD 85.9±6.

Implementing developmental screening and referrals: lessons learned from a national project.

Objectives: To assess the degree to which a national sample of pediatric practices could implement American Academy of Pediatrics (AAP) recommendations for developmental screening and referrals, and to identify factors that contributed to the successes and shortcomings of these efforts.

Background: In 2006, the AAP released a policy statement on developmental surveillance and screening that included an algorithm to aid practices in implementation. Simultaneously, the AAP launched a 9-month pilot project in which 17 diverse practices sought to implement the policy statement's recommendations.

Bullying and ostracism experiences in children with special health care needs.

Objective: Bullying experiences are becoming increasingly common in children and can have devastating consequences. Ostracism threatens a child's need for self-esteem, sense of belonging, sense of control, and meaningful existence. Recent literature suggests that children with special health care needs may be at risk for these negative events and consequences.

Detection of piperonal emitted from polymer controlled odor mimic permeation systems utilizing Canis familiaris and solid phase microextraction-ion mobility spectrometry.

Currently, in the field of odor detection, there is generally a wider variation in limit of detections (LODs) for canines than instruments. The study presented in this paper introduces an improved protocol for the creation of controlled odor mimic permeation system (COMPS) devices for use as standards in canine training and discusses the canine detection thresholds of piperonal, a starting material for the illicit drug 3,4-methylenedioxymethamphetamine (MDMA), when exposed to these devices. Additionally, this paper describes the first-ever reported direct comparison of solid phase microextraction-ion mobility spectrometry (SPME-IMS) to canine detection for the MDMA odorant, piperonal.

Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers.

Background: It has been postulated that exercise-induced activation of brain-derived neurotrophic factor (BDNF) may account for improvement of stepping ability in animals after complete spinal cord transection. As we have shown previously, treadmill locomotor exercise leads to up-regulation of BDNF protein and mRNA in the entire neuronal network of intact spinal cord. The questions arise: (i) how the treadmill locomotor training, supplemented with tail stimulation, affects the expression of molecular correlates of synaptic plasticity in spinal rats, and (ii) if a response is related to BDNF protein level and distribution.

Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling.

TGF-beta induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region. TGF-beta-induced linker phosphorylation marks the activated Smad proteins for proteasome-mediated destruction. Here, we identify Nedd4L as the ubiquitin ligase responsible for this step.