Immunomodulation induced by synthetic peptides derived from Staphylococcus aureus protein A

Peptides from 10 to 22 amino acids containing sequences encompassed by Staphylococcus aureus protein A were synthesized. Some of these peptides, when present in cultures of lymphomononuclear cells from healthy donors or from cancer patients (melanoma, breast carcinoma, non-Hodgkin lymphoma and renal cell carcinoma) promoted: (i) changes in the phenotype of the lymphomononuclear population, (ii) stimulation of monocytes (release of IL-1 and TNF-alpha), and (iii) an increase in cytotoxicity against K562, Daudi and HT-29 cells. Isolated monocytes responded also to those peptides with a release of IL-1 and TNF alpha and an increase of cytotoxicity against HT-29 cells. It was found that the active peptides had the following structural pattern: a length of at least 15 amino-acid residues with a proline at position 6, valine, leucine, isoleucine, glycine, alanine or lysine at position 2, and glutamic or aspartic acid at position 11. Replacement of Pro at position 6 with any other residue turned the peptide inactive. Replacement of residues at positions 2 and 11 with amino-acid residues other than those required for activity resulted in compounds with a marked decrease in the immunomodulating properties described, or lacking these properties altogether

Functional connectivity measured with magnetoencephalography identifies persons with HIV disease

There is need for a valid and reliable biomarker for HIV Associated Neurocognitive Disorder (HAND). The purpose of the present study was to provide preliminary evidence of the potential utility of neuronal functional connectivity measures obtained using magnetoencephalography (MEG) to identify HIV-associated changes in brain function. Resting state, eyes closed, MEG data from 10 HIV-infected individuals and 8 seronegative controls were analyzed using mutual information (MI) between all pairs of MEG sensors to ..

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome.

[ES] Introducción El síndrome de déficit del transportador de glucosa cerebral (GLUT1DS) puede presentar fenotipos variados, incluyendo epilepsia, déficit intelectual y trastorno del movimiento. La mayoría presenta hipoglucorraquia y/o defectos en el gen SLC2A1, aunque existen pacientes sin hipoglucorraquia y otros con genética de SLC2A1-negativa, o con defectos en otros genes y fenotipo compatible. Objetivos Describir las características clínicas, bioquímicas y genéticas y realizar un análisis univariante de un grupo de pacientes con fenotipo clínico y bioquímico de GLUT1DS, con o sin genética SLC2A1-positiva. Material y métodos Se incluyeron 13 pacientes con criterios clínico-bioquímicos de GLUT1DS. Se realizó secuenciación de SLC2A1 y MLPA. En los casos negativos se realizó exoma clínico. Resultados Seis presentaron fenotipo clásico, 2 discinesia paroxística, 2 trastornos del movimiento complejo, 2 ausencias precoces y otro presentó epilepsia con ausencias infantiles refractaria a farmacoterapia. Seis fueron SLC2A1-positivos. Y en 5 de los SLC2A1-negativos se identificó otro defecto genético. No hubo diferencias significativas entre los dos grupos en edad de inicio, presentación clínica, microcefalia, discapacidad intelectual ni respuesta a dieta cetogénica. De forma no significativa, los pacientes SCL2A1-positivos presentaron más cambios clínicos en relación con la ingesta (66,7% vs. 28,6%) y mayor persistencia de síntomas motores (66% vs. 28,6%). De forma significativa, presentaron menor glucorraquia (34,5 mg/dl vs. 46 mg/dl, p = 0,04) e índice glucorraquia/glucemia más bajo (0,4 vs. 0,48, p = 0,05) que los SLC2A1-negativos. Conclusiones GLUT1DS puede ser causado por defectos genéticos en otros genes diferentes de SLC2A1 en pacientes con fenotipo compatible, hipoglucorraquia y buena respuesta a dieta cetogénica. [EN] Introduction Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. Aims We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. Material and methods The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. Results Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7% vs. 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs. 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs. 46 mg/dL, P = .04) and CSF/serum glucose ratio (0.4 vs. 0.48, P < .05).S

Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1)

[EN] Introduction: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. Aims: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. Material and methods: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. Results: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7%, vs 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs 0.48, P<.05). Conclusions: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet. [ES] Introducción: El síndrome de déficit del transportador de glucosa cerebral (GLUT1DS) puede presentar fenotipos variados, incluyendo epilepsia, déficit intelectual y trastorno del movimiento. La mayoría presentan hipoglucorraquia y/o defectos en el gen SLC2A1, aunque existen pacientes sin hipoglucorraquia y otros con genética de SLC2A1-negativa, o con defectos en otros genes y fenotipo compatible. Objetivos: Describir las características clínicas, bioquímicas y genéticas y realizar un análisis univariante de un grupo de pacientes con fenotipo clínico y bioquímico de GLUT1DS, con o sin genética SLC2A1-positiva. Material y métodos: Se incluyeron 13 pacientes con criterios clínico-bioquímicos de GLUT1DS. Se realizó secuenciación de SLC2A1 y MLPA. En los casos negativos se realizó exoma clínico. Resultados: Seis presentaron fenotipo clásico, 2 discinesia paroxística, 2 trastornos del movimiento complejo, 2 ausencias precoces y otro presentó epilepsia con ausencias infantiles refractaria a farmacoterapia. Seis fueron SLC2A1-positivos. Y en 5 de los SLC2A1-negativos se identificó otro defecto genético. No hubo diferencias significativas entre los dos grupos en edad de inicio, presentación clínica, microcefalia, discapacidad intelectual ni respuesta a dieta cetogénica. De forma no significativa, los pacientes SCL2A1-positivos presentaron más cambios clínicos en relación con la ingesta (66,7% vs. 28,6%) y mayor persistencia de síntomas motores (66% vs. 28,6%). De forma significativa, presentaron menor glucorraquia (34,5 mg/dl vs. 46 mg/dl, p = 0.04) e índice glucorraquia/glucemia más bajo (0,4 vs. 0,48, p = 0,05) que los SLC2A1-negativos. Conclusiones: GLUT1DS puede ser causado por defectos genéticos en otros genes diferentes de SLC2A1 en pacientes con fenotipo compatible, hipoglucorraquia y buena repuesta a dieta cetogénica.‘‘Identification and clinical and biochemical characterisation of patients with GLUT1DS: treatment monitoring.’’ Translational research project 2017, CIBERER. Coordinator: Dr Luis González Gutiérrez-Solana (GCV6). Participating units: U703 (Artuch); U746 (Pérez); GCV5 (Couce); GCV6 (Gutiérrez-Solana); GCV7 (López Laso); GCV8 (del Toro). Research project: hereditary metabolic disorders.S

Efficacy of the Combination of Pinaverium Bromide 100mg Plus Simethicone 300mg in Abdominal Pain and Bloating in Irritable Bowel Syndrome: A Randomized, Placebo-controlled Trial

Goals: We aimed to evaluate the efficacy and safety of PB+S (pinaverium bromide 100 mg plus simethicone 300 mg) in patients with irritable bowel syndrome (IBS). Background: IBS is a multifactorial disorder; thus, combination therapy with different mechanisms of action is expected to be useful. PB+S has shown effectiveness in an open-label clinical study in IBS. However, there are no placebo-controlled trials. Materials and Methods: IBS-Rome III patients with abdominal pain/discomfort for at least 2 days within the week prior to baseline assessment were included in this 12-week, randomized, doubleblind, placebo-controlled study of PB+S versus placebo, bid. The primary endpoint was overall symptom improvement, evaluated weekly by the patient (Likert Scale). Secondary endpoints included the weekly improvement in the severity of abdominal pain and bloating assessed both by patients (10-cm Visual Analogue Scale) and investigators (Likert Scale); frequency of Bristol Scale stool types (consistency) evaluated by patients and the IBS Quality of Life scores. Results: A total of 285 patients (female: 83%; 36.5±8.9 y old) received at least 1 dose of PB+S (n=140) or placebo (n=145). No difference was observed in overall symptom improvement between the groups (P=0.13). However, PB+S was superior in abdominal pain (effect size: 31%, P=0.038) and bloating (33%, P=0.019). Patients with IBS-C and IBS-M showed the best improvement in the frequency of stool types with PB+S. No differences were observed in IBS Quality of Life scores and adverse events

Low-ionization structures in planetary nebulae: confronting models with observations

Around 50 PNe are presently known to possess "small-scale" low-ionization structures (LISs). We consider here jets, jet-like, symmetrical and non-symmetrical LISs and present a detailed comparison of the existing model predictions with the observational morphological and kinematical properties. We find that nebulae with LISs appear indistinctly spread among all morphological classes of PNe, indicating that the processes leading to the formation of LISs are not necessarily related to those responsible for the asphericity of the large-scale morphological components of PNe. We show that both the observed velocities and locations of most non-symmetrical LISs can be reasonably well reproduced assuming either fossil condensations originated in the AGB wind or in-situ instabilities. The jet models proposed to date (HD and MHD interacting winds or accretion-disk collimated winds) appear unable to account simultaneously for the kinematical ages and the angle between the jet and the symmetry axes of the nebulae. The linear increase in velocity observed in several jets favors MHD confinement compared to pure HD interacting wind models. On the other hand, we find that the formation of jet-like systems characterized by relatively low expansion velocities cannot be explained by any of the existing models. Finally, the knots which appear in symmetrical and opposite pairs of low velocity could be understood as the survival of fossil (symmetrical) condensations formed during the AGB phase or as structures that have experienced substantial slowing down by the ambient medium.Comment: 21 pages including 5 tables. To appear in ApJ 547, Jan 2001. Also available at http://www.iac.es/publicaciones/preprints.htm

Contamination Control and Assay Results for the Majorana Demonstrator Ultra Clean Components

The MAJORANA DEMONSTRATOR is a neutrinoless double beta decay experiment utilizing enriched Ge-76 detectors in 2 separate modules inside of a common solid shield at the Sanford Underground Research Facility. The DEMONSTRATOR has utilized world leading assay sensitivities to develop clean materials and processes for producing ultra-pure copper and plastic components. This experiment is now operating, and initial data provide new insights into the success of cleaning and processing. Post production copper assays after the completion of Module 1 showed an increase in U and Th contamination in finished parts compared to starting bulk material. A revised cleaning method and additional round of surface contamination studies prior to Module 2 construction have provided evidence that more rigorous process control can reduce surface contamination. This article describes the assay results and discuss further studies to take advantage of assay capabilities for the purpose of maintaining ultra clean fabrication and process design.Comment: Proceedings of Low Radioactivity Techniques (LRT May 2017, Seoul