Minería de datos para el descubrimiento de patrones en enfermedades respiratorias en Bogotá, Colombia

Trabajo de InvestigaciónEl presente proyecto se basa en la aplicación de minería de datos mediante el algoritmo de clustering K- means que permita la generación de un modelo descriptivo con el análisis de los datos y con el objetivo de identificar posibles comportamientos en enfermedades respiratorias en la ciudad de Bogotá. El conjunto de clústeres generados por la herramienta RapidMiner es la recopilación de datos de un periodo de cinco años de 2012 a 2016, en donde se contemplan el número de casos asociados a 184 diagnósticos de enfermedades respiratorias y la edad de los pacientes corresponde de 0 a 5 años.Trabajo de Investigación1. GENERALIDADES 2. OBJETIVOS 3. JUSTIFICACIÓN 4. DELIMITACIÓN 5. MARCO REFERENCIAL 6. METODOLOGÍA 7. FUENTES DE EXTRACCIÓN Y SUS VARIABLES 8. DISEÑO 9. SELECCIÓN DE ALGORITMOS DE CLUSTERING 10. RECONOCER PATRONES A PARTIR DE LA INFORMACIÓN RECOPILADA 11. CONCLUSIONES 12. TRABAJOS FUTUROS 13. REFERENCIAS BIBLIOGRÁFICAS 14. ANEXOSPregradoIngeniero de Sistema

Home-administered pre-surgical psychological intervention for knee osteoarthritis (HAPPiKNEES): study protocol for a randomised controlled trial

Background: Knee replacement surgery reduces pain for many people with osteoarthritis (OA). However, surgical outcomes are partly dependent on patients’ moods, and those with depression or anxiety have worse outcomes. Approximately one-third of people with OA have mood problems. Cognitive behavioural therapy (CBT), a psychological therapy, is recommended by the National Institute for Health and Care Excellence for improving mood. However, evidence for the effectiveness of CBT before knee surgery in improving pain, mood, and quality of life following this surgery for people with knee OA is lacking. Methods/Design: This is a multi-centre, mixed-methods feasibility randomised controlled trial to compare treatment as usual (TAU) plus a brief CBT-based intervention with a TAU-only control, for people with knee OA. We will recruit 50 patients with knee OA, listed for knee replacement surgery, with high levels of distress (assessed using a mood questionnaire), and who consent to take part. Participants will be randomly allocated to receive TAU plus intervention or TAU. Up to 10 sessions of CBT will be offered on an individual basis by a psychologist. The assessments and interventions will be completed before surgery. Repeat assessments at 4 and 6 months after randomisation will be sent and received by post. Two patient-partners will conduct feedback interviews with some participants to assess what aspects of the intervention were helpful or unhelpful, the acceptability of randomisation, the experience of being in a control group, and the appropriateness of the measures used. Interviews will be audio-recorded, transcribed, and analysed using the framework approach. We will examine the feasibility and acceptability of patient-partners conducting the interviews by also interviewing the patient-partners. Discussion: Findings from this study will be used to design a definitive study that will examine the clinical and cost-effectiveness of the CBT intervention in improving patient outcomes following knee surgery

The Incidence of Adjacent Segment Degeneration after Cervical Disc Arthroplasty (CDA): A Meta Analysis of Randomized Controlled Trials

Cervical disc arthroplasty is being used as an alternative degenerative disc disease treatment with fusion of the cervical spine in order to preserve motion. However, whether replacement arthoplasty in the spine achieves its primary patient centered objective of lowering the frequency of adjacent segment degeneration is not verified yet.We conducted a meta-analysis according to the guidelines of the Cochrane Collaboration using databases including PubMed, Cochrane Central Register of Controlled Trials and Embase. The inclusion criteria were: 1) Randomized, controlled study of degenerative disc disease of the cervical spine involving single segment or double segments using Cervical disc arthroplasty (CDA) with anterior cervical discectomy and fusion (ACDF) as controls; 2) A minimum of two-year follow-up using imaging and clinical analyses; 3) Definite diagnostic evidences for "adjacent segment degeneration" and "adjacent segment disease"; 4) At least a minimum of 30 patients per population. Two authors independently selected trials; assessed methodological quality, extracted data and the results were pooled.No study has specifically compared the results of adjacent segment degenerative; Two papers describing 140 patients with 162 symptomatic cervical segment disorders and compared the rate of postoperative adjacent segment disease development between CDA and ACDF treatments, three publications describing the rate of adjacent-segment surgery including 1273 patients with symptomatic cervical segments. The result of the meta-analysis indicates that there were fewer the rate of adjacent segment disease and the rate for adjacent-segment surgery comparing CDA with ACDF, but the difference was not statistically significant.Based on available evidence, it cannot be concluded, that CDA can significantly reduce the postoperative rate of the adjacent segment degenerative and adjacent segment disease. However, due to some limitations, the results of this meta-analysis should be cautiously accepted, and further studies are needed

Renal tubular HIF-2α expression requires VHL inactivation and causes fibrosis and cysts.

The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated α-subunits HIF-1α or HIF-2α. Both are regulated by oxygen dependent degradation, which is controlled by the tumor suppressor "von Hippel-Lindau" (VHL), the gatekeeper of renal tubular growth control. HIF appears to play a particular role for the kidney, where renal EPO production, organ preservation from ischemia-reperfusion injury and renal tumorigenesis are prominent examples. Whereas HIF-1α is inducible in physiological renal mouse, rat and human tubular epithelia, HIF-2α is never detected in these cells, in any species. In contrast, distinct early lesions of biallelic VHL inactivation in kidneys of the hereditary VHL syndrome show strong HIF-2α expression. Furthermore, knockout of VHL in the mouse tubular apparatus enables HIF-2α expression. Continuous transgenic expression of HIF-2α by the Ksp-Cadherin promotor leads to renal fibrosis and insufficiency, next to multiple renal cysts. In conclusion, VHL appears to specifically repress HIF-2α in renal epithelia. Unphysiological expression of HIF-2α in tubular epithelia has deleterious effects. Our data are compatible with dedifferentiation of renal epithelial cells by sustained HIF-2α expression. However, HIF-2α overexpression alone is insufficient to induce tumors. Thus, our data bear implications for renal tumorigenesis, epithelial differentiation and renal repair mechanisms

The impact of single and pairwise Toll-like receptor activation on neuroinflammation and neurodegeneration

Background Toll-like receptors (TLRs) enable innate immune cells to respond to pathogen- and host-derived molecules. The central nervous system (CNS) exhibits most of the TLRs identified with predominant expression in microglia, the major immune cells of the brain. Although individual TLRs have been shown to contribute to CNS disorders, the consequences of multiple activated TLRs on the brain are unclear. We therefore systematically investigated and compared the impact of sole and pairwise TLR activation on CNS inflammation and injury. Methods Selected TLRs expressed in microglia and neurons were stimulated with their specific TLR ligands in varying combinations. Cell cultures were then analyzed by immunocytochemistry, FlowCytomix, and ELISA. To determine neuronal injury and neuroinflammation in vivo, C57BL/6J mice were injected intrathecally with TLR agonists. Subsequently, brain sections were analyzed by quantitative real-time PCR and immunohistochemistry. Results Simultaneous stimulation of TLR4 plus TLR2, TLR4 plus TLR9, and TLR2 plus TLR9 in microglia by their respective specific ligands results in an increased inflammatory response compared to activation of the respective single TLR in vitro. In contrast, additional activation of TLR7 suppresses the inflammatory response mediated by the respective ligands for TLR2, TLR4, or TLR9 up to 24 h, indicating that specific combinations of activated TLRs individually modulate the inflammatory response. Accordingly, the composition of the inflammatory response pattern generated by microglia varies depending on the identity and combination of the activated TLRs engaged. Likewise, neuronal injury occurs in response to activation of only selected TLRs and TLR combinations in vitro. Activation of TLR2, TLR4, TLR7, and TLR9 in the brain by intrathecal injection of the respective TLR ligand into C57BL/6J mice leads to specific expression patterns of distinct TLR mRNAs in the brain and causes influx of leukocytes and inflammatory mediators into the cerebrospinal fluid to a variable extent. Also, the intensity of the inflammatory response and neurodegenerative effects differs according to the respective activated TLR and TLR combinations used in vivo. Conclusions Sole and pairwise activation of TLRs modifies the pattern and extent of inflammation and neurodegeneration in the CNS, thereby enabling innate immunity to take account of the CNS diseases’ diversity

Release of Intracellular Calcium Stores Facilitates Coxsackievirus Entry into Polarized Endothelial Cells

Group B coxsackieviruses (CVB) are associated with viral-induced heart disease and are among the leading causes of aseptic meningitis worldwide. Here we show that CVB entry into polarized brain microvasculature and aortic endothelial cells triggers a depletion of intracellular calcium stores initiated through viral attachment to the apical attachment factor decay-accelerating factor. Calcium release was dependent upon a signaling cascade that required the activity of the Src family of tyrosine kinases, phospholipase C, and the inositol 1,4,5-trisphosphate receptor isoform 3. CVB-mediated calcium release was required for the activation of calpain-2, a calcium-dependent cysteine protease, which controlled the vesicular trafficking of internalized CVB particles. These data point to a specific role for calcium signaling in CVB entry into polarized endothelial monolayers and highlight the unique signaling mechanisms used by these viruses to cross endothelial barriers

The Response of the Prostate to Circulating Cholesterol: Activating Transcription Factor 3 (ATF3) as a Prominent Node in a Cholesterol-Sensing Network

Elevated circulating cholesterol is a systemic risk factor for cardiovascular disease and metabolic syndrome, however the manner in which the normal prostate responds to variations in cholesterol levels is poorly understood. In this study we addressed the molecular and cellular effects of elevated and suppressed levels of circulating cholesterol on the normal prostate. Integrated bioinformatic analysis was performed using DNA microarray data from two experimental formats: (1) ventral prostate from male mice with chronically elevated circulating cholesterol and (2) human prostate cells exposed acutely to cholesterol depletion. A cholesterol-sensitive gene expression network was constructed from these data and the transcription factor ATF3 was identified as a prominent node in the network. Validation experiments confirmed that elevated cholesterol reduced ATF3 expression and enhanced proliferation of prostate cells, while cholesterol depletion increased ATF3 levels and inhibited proliferation. Cholesterol reduction in vivo alleviated dense lymphomononuclear infiltrates in the periprostatic adipose tissue, which were closely associated with nerve tracts and blood vessels. These findings open new perspectives on the role of cholesterol in prostate health, and provide a novel role for ATF3, and associated proteins within a large signaling network, as a cholesterol-sensing mechanism