¿Es calidad, redundancia o inadecuación del modelo? Algunas estrategias para determinarla idoneidad de los ítems altamente discriminativos

When developing new questionnaires, it is traditionally assumed that the items should be as discriminative as possible, as if this was always indicative of their quality. However, in some cases these high discriminations may be masking some problems such as redundancies, shared residuals, biased distributions, or model limitations which may contribute to inflate the discrimination estimates. Therefore, the inspection of these indices may lead to erroneous decisions about which items to keep or eliminate. Toillustrate this problem, two different scenarios with real data are described. The first focuses on a questionnaire that contains an item apparently highly discriminant, but redundant. The second focuses on a clinical questionnaire administered to a community sample, which gives place to highly right-skewed item response distributions and inflated discriminant indices, despite the items do not discriminate well among the majority of participants. We propose some strategies and checks to identify these situations, so that the items that are inappropriate may be identified and removed. Therefore, this article seeks to promote a critical attitude, which may involve going against routine stablished principles when they are not appropriateCuando se desarrollan nuevos cuestionarios, tradicionalmente se asume que los ítems deben ser lo más discriminativos posible, como si esto fuera siempre indicativo de su calidad. Pero en algunos casos estas discriminaciones elevadas pueden estar ocultando algunos problemas como redundancias, residuales compartidos, distribuciones sesgadas o limitaciones del modelo que pueden contribuir a inflar las estimaciones de la discriminación. Por lo tanto, la inspección de estos índices puede llevar a decisiones erróneas sobre qué ítems mantener o eliminar. Para ilustrar este problema, se describen dos escenarios diferentes con datos reales. El primero se centra en un cuestionario que contiene un ítem aparentemente muy discriminante, pero redundante. El segundo se centra en un cuestionario clínico administrado a una muestra comunitaria, lo que da lugar a distribuciones de respuesta de los ítems muy sesgadas y a índices de discriminación inflados, a pesar de que los ítems no discriminan bien entre la mayoría de los sujetos. Proponemos algunas estrategias y comprobaciones para identificar estas situaciones, para facilitar la identificación y eliminación de los ítems inapropiados. Por lo tanto, este artículo pretende promover una actitud crítica, que puede implicar ir en contra de los principios rutinarios establecidos cuando no son apropiado

Tongue carcinoma in an adult Down's syndrome patient: a case report

<p>Abstract</p> <p>Background</p> <p>Cancer of the oral cavity is rare and unusual in Down's syndrome patient. The over all risk is similar to that in adult population.</p> <p>Case presentation</p> <p>This case report describes a 27 years old male with Down's syndrome, non-smoker, who developed a poorly differentiated squamous cell carcinoma of the tongue. The patient underwent a hemiglossectomy without neck dissection followed by a postoperative locoregional radiation therapy to a total tumor-bed dose of 56 Gy and 45 Gy to the neck. Three months later, the patient presented with local tongue recurrence and was treated by Docetaxel and Carboplatin chemotherapy with no significant response. The patient died one month later, 9 months after his initial diagnosis.</p> <p>Conclusion</p> <p>To our knowledge, this is the first case of tongue carcinoma arising in a patient with Down's syndrome. This unique case might not be sufficient to make a significant conclusion on the prognosis and survival of these patients but will increase the awareness about this possibility and will help in the appropriate management of Down's syndrome patients.</p

Libidibia ferrea loaded in bacterial nanocellulose: evaluation of antimicrobial activity and wound care / Libidibia ferrea loaded in bacterial nanocellulose: evaluation of antimicrobial activity and wound care

The effects of Bacterial Nanocellulose (BNC) loaded with Libidibia ferrea (Lf) hydroalcoholic extract were investigated on the healing process of burn in diabetic and non-diabetic animals. In vivo assay was performed with 36 male rats, with streptozotocin-induced diabetes and burns induced by contact. Animals were divided into Nd-BNC (Non-diabetic + Bacterial nanocellulose membranes); Nd-BNC-Lf (Non-diabetic + Bacterial nanocellulose membranes + Libidibia ferrea); D-BNC (Diabetic + Bacterial nanocellulose membranes); D-BNC-Lf (Diabetic + Bacterial nanocellulose membranes + Libidibia ferrea). Wounds were evaluated for 28 days histologically. Lf extract and BNC-Lf extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. The severe degree of infection, granulation and inflammation observed after 14 days in diabetic rats (exposed or not to Lf extract), disappeared after 21 days. On the 28th day, there was no histological difference among the groups. BNC-Lf extract demonstrated to have antimicrobial activity, however as an wound dressing, both BNC or BNC-Lf extract were effective in the healing of second-degree burn wounds

Concurrent Oral 9 - Rheumatoid Arthritis: Aetiopathogenesis [OP59-OP64]: OP59. The Value of Interleukin-17 Serum Level in Rheumatoid Arthritis Immunopathogenesis

Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P < 0.001), tender (16.7 ± 2.0 vs 8.4 ± 1.1; P < 0.01) and swollen (12.3 ± 2.3 vs 3.9 ± 0.8; P < 0.01) joint count, DAS28 (5.0 ± 0.4 vs 2.8 ± 0.2 P < 0.01) were significantly higher compare to group1. It was found that in group2 the higher T-lymphocyte amount (CD3) was due to CD4 higher quantity, at the same time CD8 amount was significantly lower (22.2 ± 1.5% vs 28.4 ± 1.7%, P < 0.05) compare to group1. This caused the immunoregulative index increasing and indicated in the lost of autoimmune process regulation, including B-lymphocytes (CD19) activation. The CD154 expression was significantly lower in the group2 (3.4 ± 0.4% vs 10.8 ± 2.8%, P < 0.05) compare to group1. The difference in autoimmune reaction indices wasn't significant between groups except antibody-producing B-lymphocytes (13.7 ± 1.5% vs 8.5 ± 1.0%, P < 0.05) and IgM RF serum level (2.9 ± 0.3 U/ml vs 1.6 ± 0.5 U/ml, P < 0.05), which were significantly higher in group1. The IL-17 level had a positive correlative connections with DAS28 (r = 0.7; P < 0.05), circulative immune complex level (r = 0.38; P < 0.05), anti-CCP antibodies (r = 0.4; P < 0.05), IgM RF (r = 0.41; P < 0.05), CD4 (r = 0.38; P < 0.05) and negative correlative connection with CD8 (r = -0.39; P < 0.05). Conclusions: The importance of IL-17 value in immuno-inflammatory and autoimmune reactions development through T-lymphocytes activation in RA pathogenesis was confirmed. Thus the influence on T-depended immuno-inflammatory reaction products synthesis could be a new therapeutic target of RA patients' management. Disclosure statement: All authors have declared no conflicts of interes

Lipid Alterations in Experimental Murine Colitis: Role of Ceramide and Imipramine for Matrix Metalloproteinase-1 Expression

BACKGROUND:Dietary lipids or pharmacologic modulation of lipid metabolism are potential therapeutic strategies in inflammatory bowel disease (IBD). Therefore, we analysed alterations of bioactive lipids in experimental models of colitis and examined the functional consequence of the second messenger ceramide in inflammatory pathways leading to tissue destruction. METHODOLOGY/PRINCIPAL FINDINGS:Chronic colitis was induced by dextran-sulphate-sodium (DSS) or transfer of CD4(+)CD62L(+) cells into RAG1(-/-)-mice. Lipid content of isolated murine intestinal epithelial cells (IEC) was analysed by tandem mass spectrometry. Concentrations of MMP-1 in supernatants of Caco-2-IEC and human intestinal fibroblasts from patients with ulcerative colitis were determined by ELISA. Imipramine was used for pharmacologic inhibition of acid sphingomyelinase (ASM). Ceramide increased by 71% in chronic DSS-induced colitis and by 159% in the transfer model of colitis. Lysophosphatidylcholine (LPC) decreased by 22% in both models. No changes were detected for phosphatidylcholine. Generation of ceramide by exogenous SMase increased MMP-1-protein production of Caco-2-IEC up to 7-fold. Inhibition of ASM completely abolished the induction of MMP-1 by TNF or IL-1beta in Caco-2-IEC and human intestinal fibroblasts. CONCLUSIONS/SIGNIFICANCE:Mucosal inflammation leads to accumulation of ceramide and decrease of LPC in the intestinal epithelium. One aspect of ceramide generation is an increase of MMP-1. Induction of MMP-1 by TNF or IL-1beta is completely blocked by inhibition of ASM with imipramine. Therefore, inhibition of ASM may offer a treatment strategy to reduce MMP-1 expression and tissue destruction in inflammatory conditions

The MS4A gene cluster is a key modulator of soluble TREM2 and Alzheimer's disease risk

Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been associated with Alzheimer's disease (AD). TREM2 plays a critical role in microglial activation, survival, and phagocytosis;however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may reveal new pathological mechanisms and lead to the identification of therapeutic targets. We performed a genome-wide association study (GWAS) to identify genetic modifiers of CSF sTREM2 obtained from the Alzheimer's Disease Neuroimaging Initiative. Common variants in the membrane-spanning 4-domains subfamily A (MS4A) gene region were associated with CSF sTREM2 concentrations (rs1582763;P = 1.15 x 10(-15));this was replicated in independent datasets. The variants associated with increased CSF sTREM2 concentrations were associated with reduced AD risk and delayed age at onset of disease. The single-nucleotide polymorphism rs1582763 modified expression of the MS4A4A and MS4A6A genes in multiple tissues, suggesting that one or both of these genes are important for modulating sTREM2 production. Using human macrophages as a proxy for microglia, we found that MS4A4A and TREM2 colocalized on lipid rafts at the plasma membrane, that sTREM2 increased with MS4A4A overexpression, and that silencing of MS4A4A reduced sTREM2 production. These genetic, molecular, and cellular findings suggest that MS4A4A modulates sTREM2. These findings also provide a mechanistic explanation for the original GWAS signal in the MS4A locus for AD risk and indicate that TREM2 may be involved in AD pathogenesis not only in TREM2 risk-variant carriers but also in those with sporadic disease