vgaraujov/thesis-chile huggingface dataset:
Dual-phase whole-heart imaging using image navigation in congenital heart disease

Abstract Background Dual-phase 3-dimensional whole-heart acquisition allows simultaneous imaging during systole and diastole. Respiratory navigator gating and tracking of the diaphragm is used with limited accuracy. Prolonged scan time is common, and navigation often fails in patients with erratic breathing. Image-navigation (iNAV) tracks movement of the heart itself and is feasible in single phase whole heart imaging. To evaluate its diagnostic ability in congenital heart disease, we sought to apply iNAV to dual-phase sequencing. Methods Healthy volunteers and patients with congenital heart disease underwent dual-phase imaging using the conventional diaphragmatic-navigation (dNAV) and iNAV. Acquisition time was recorded and image quality assessed. Sharpness and length of the right coronary (RCA), left anterior descending (LAD), and circumflex (LCx) arteries were measured in both cardiac phases for both approaches. Qualitative and quantitative analyses were performed in a blinded and randomized fashion. Results In volunteers, there was no significant difference in vessel sharpness between approaches (p > 0.05). In patients, analysis showed equal vessel sharpness for LAD and RCA (p > 0.05). LCx sharpness was greater with dNAV (p < 0.05). Visualized length with iNAV was 0.5 ± 0.4 cm greater than that with dNAV for LCx in diastole (p < 0.05), 1.0 ± 0.3 cm greater than dNAV for LAD in diastole (p < 0.05), and 0.8 ± 0.7 cm greater than dNAV for RCA in systole (p < 0.05). Qualitative scores were similar between modalities (p = 0.71). Mean iNAV scan time was 5:18 ± 2:12 min shorter than mean dNAV scan time in volunteers (p = 0.0001) and 3:16 ± 1:12 min shorter in patients (p = 0.0001). Conclusions Image quality of iNAV and dNAV was similar with better distal vessel visualization with iNAV. iNAV acquisition time was significantly shorter. Complete cardiac diagnosis was achieved. Shortened acquisition time will improve clinical applicability and patient comfort.
Dynamic genome-scale metabolic modeling of the yeast Pichia pastoris

Abstract Background Pichia pastoris shows physiological advantages in producing recombinant proteins, compared to other commonly used cell factories. This yeast is mostly grown in dynamic cultivation systems, where the cell’s environment is continuously changing and many variables influence process productivity. In this context, a model capable of explaining and predicting cell behavior for the rational design of bioprocesses is highly desirable. Currently, there are five genome-scale metabolic reconstructions of P. pastoris which have been used to predict extracellular cell behavior in stationary conditions. Results In this work, we assembled a dynamic genome-scale metabolic model for glucose-limited, aerobic cultivations of Pichia pastoris. Starting from an initial model structure for batch and fed-batch cultures, we performed pre/post regression diagnostics to ensure that model parameters were identifiable, significant and sensitive. Once identified, the non-relevant ones were iteratively fixed until a priori robust modeling structures were found for each type of cultivation. Next, the robustness of these reduced structures was confirmed by calibrating the model with new datasets, where no sensitivity, identifiability or significance problems appeared in their parameters. Afterwards, the model was validated for the prediction of batch and fed-batch dynamics in the studied conditions. Lastly, the model was employed as a case study to analyze the metabolic flux distribution of a fed-batch culture and to unravel genetic and process engineering strategies to improve the production of recombinant Human Serum Albumin (HSA). Simulation of single knock-outs indicated that deviation of carbon towards cysteine and tryptophan formation improves HSA production. The deletion of methylene tetrahydrofolate dehydrogenase could increase the HSA volumetric productivity by 630%. Moreover, given specific bioprocess limitations and strain characteristics, the model suggests that implementation of a decreasing specific growth rate during the feed phase of a fed-batch culture results in a 25% increase of the volumetric productivity of the protein. Conclusion In this work, we formulated a dynamic genome scale metabolic model of Pichia pastoris that yields realistic metabolic flux distributions throughout dynamic cultivations. The model can be calibrated with experimental data to rationally propose genetic and process engineering strategies to improve the performance of a P. pastoris strain of interest.
Effect of cholecystectomy on hepatic fat accumulation and insulin resistance in non-obese Hispanic patients : a pilot study

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Experimental studies have shown that cholecystectomy (XGB) increases hepatic fat content in mice and appears associated to NAFLD in large retrospective population-based studies. The aim of this study was to prospectively assess the effects of XGB on hepatic fat content (HFC) and insulin resistance (IR) in non-obese, middle aged Hispanic subjects. Methods Twenty-six gallstone patients undergoing elective XGB and 16 control subjects with normal livers and gallbladders at ultrasonography were prospectively followed 24 months for changes in HFC and IR. Clinical, biochemical determinations and hepatic imaging were performed at baseline and 24 months after surgery. MRI technique quantified HFC in four hepatic segments. IR was assessed by the Homeostasis Model Assessment (HOMA-IR) index. Results Initial body mass index (BMI) was 25.6 ± 0.4 and 24.3 ± 1.0 in the control and XGB groups of subjects, respectively. Serum insulin level increased from 8.1 ± 0.7 to 10.0 ± 1.9 (μU/ml) 24 months after surgery in XGB patients (p < 0.05); no significant changes were detected in control individuals. Median HOMA-IR index increased from 1.31 (interquartile range, 1.01-1.68) to 2.20 (interquartile range, 1.57 - 2.60) 24 months after XGB, (p < 0.003). Median HOMA-IR index of control subjects remained unchanged at the end of the study. Serum apoB concentration increased from 61.5 ± 3.4 to 79.0 ± 7.8 (μg/ml) in XGB patients (p < 0.03). Serum apoB levels remained within normal ranges in both periods of the study in control subjects. HFC significantly increased in 2 of the 4 segments 24 months after XGB: right posterior hepatic lobe (from 5.3 ± 0.2% to 6.0 ± 0.2%, p > 0.04) and right anterior hepatic lobe (from 5.8 ± 0.2% to 6.6 ± 0.3%, p < 0.02). The average HFC of the four hepatic segments studied slightly increased from 5.4 ± 0.2 to 5.8 ± 0.3 2 years after XGB (p < 0.03). No significant changes were found in HFC in the control subjects at the end of the study. Conclusions Elective XGB increases HFC, HOMA-IR index and serum apoB concentration. These results support the notion that XGB is a risk factor non-alcoholic fatty liver disease and other IR – associated disease conditions.
Effectiveness of a normative nutrition intervention (diet, physical activity and breastfeeding) on maternal nutrition and offspring growth : the Chilean maternal and infant nutrition cohort study (CHiMINCs)

Abstract Background Maternal obesity before and during pregnancy predicts maternal and infant risks of obesity and its associated metabolic conditions. Dietary and physical activity recommendations during pregnancy as well as weight monitoring are currently available in the Chilean primary health care system. However some of these recommendations are not updated and most of them are poorly implemented. We seek to assess the effectiveness of an intervention that enhances the implementation of updated nutrition health care standards (diet, physical activity, and breastfeeding promotion) during pregnancy on maternal weight gain and infant growth. Methods Design & Setting: Cluster randomized controlled trial. The cluster units will be 12 primary health care centers from two counties (La Florida and Puente Alto) from the South-East Area of Santiago randomly allocated to: 1) enhanced nutrition health care standards (intervention group) or 2) routine care (control group). Participants: Women seeking prenatal care before 15 weeks of gestation, residing within a catchment area of selected health centers, and who express that they are not planning to change residence will be invited to participate in the study. Pregnant women classified as high risk according to the Chilean norms (i.e age <16 or >40 years, multiple gestation, pre-gestational medical conditions, previous pregnancy-related issues) and/or underweight will be excluded. Intervention: Pregnant women who attend intervened health care centers starting at their first prenatal visit will receive advice regarding optimal weight gain during pregnancy and diet and physical activity counseling-support. Pregnant women who attend control health clinics will receive routine antenatal care according to national guidelines. We plan to recruit 200 women in each health center. Assuming a 20 % loss to follow up, we expect to include 960 women per arm. Main outcome measures: 1) Achievement of adequate weight gain based on IOM 2009 recommendations and adequate glycaemic control at 24-28 weeks of pregnancy according to ADA 2011, and 2) healthy infant growth during the first year of age based on WHO standards. Discussion We expect that the intervention will benefit the participants in achieving adequate weight gain & metabolic control during pregnancy as well as adequate infant growth as a result of an increased impact of standard nutrition and health care practices. Gathered information should contribute to a better understanding of how to develop effective interventions to halt the maternal obesity epidemic and its associated co-morbidities in the Chilean population. Trial registration Clinicaltrials.gov Identifier: NCT01916603
Effects of auditory and socio-demographic variables on discontinuation of hearing aid use among older adults with hearing loss fitted in the Chilean public health sector

Abstract Background The percentage of older adults with hearing loss who stop using their hearing aids and the variables associated with this phenomenon have not been systematically investigated in South America. This problem is relevant to the region since countries such as Colombia, Brazil and Chile have public programmes that provide hearing aids to older adults. The aims of this study were to determine the percentage of older adults fitted with a hearing aid at a public hospital in Chile who subsequently stop using it and the auditory and socio-demographic variables associated with the hazard of discontinuing hearing aid use. Methods A group that included 355 older adults who had been fitted with a hearing aid was studied retrospectively. In a structured interview, participants were asked about socio-demographic variables and answered part of the Chilean National Survey on Health, evaluating self-perceived hearing loss and responding to questions about discontinuation of hearing aid use and their satisfaction with the device. Survival models were applied to determine the hazard of stopping hearing aid use in relation to the variables of interest. Results The rate of discontinuation of hearing aid use reached 21.7%. Older adults stopped using their hearing aids mainly during the first 5–6 months post-fitting, and then this number steadily increased. The income fifth quintile was 2.56 times less likely to stop using the hearing aid compared to the first. Those who self-reported that they could not hear correctly without the hearing aid were 2.62 times less likely to stop using it compared to those who reported normal hearing. The group that was very dissatisfied with the hearing aid was 20.86 times more likely to discontinue use than those who reported satisfaction with the device. Conclusions Socio-demographic variables such as economic income and auditory factors such as self-perceived hearing loss and satisfaction with the device were significantly associated with the hazard of stopping hearing aid use. Self-perceived hearing loss should be considered part of the candidacy criteria for hearing aids in older adults in Chile and other (developing) countries.
Diseño integrado para el desarrollo de infraestructura multipropósito : tren Santiago-Batuco como modelo replicable

Las infraestructuras son la base del funcionamiento de las ciudades e indispensables para el desarrollo productivo, económico y social. La infraestructura ferroviaria trajo consigo un nuevo desarrollo entre regiones y ciudades acortando los tiempos de viaje acercando a personas y mercancías. Con el tiempo el desarrollo de la infraestructura ferroviaria empezó a estructurar la ciudad condicionando su crecimiento, usos de suelo de sus bordes y forma. Los corredores de trenes se transformaron en un efecto barrera en muchos barrios, fracturando el territorio, empobreciendo la experiencia de viaje y la estética. El lanzamiento del “Plan Chile sobre Rieles”, por parte del Gobierno Central, representa el derecho y la libertad que tienen los ciudadanos de circular en medios de transporte que aporten a mejorar la calidad de vida y acercarlos a sus destinos. Lamentablemente el desarrollo de la infraestructura de transporte se enfoca en responder sólo a su función de transporte dejando fuera de su concepción, implementación y gestión una serie de territorios y dinámicas urbanas, naturales y sociales que cruza estos vastos corredores. Dada la transformación del territorio que generan las infraestructuras, es importante visualizar la oportunidad que éstas son para otros ámbitos de desarrollo, planificación y diseño. Una visión de corredores ferroviarios como infraestructura multipropósito permita implementar nuevas estrategias e integrar los entornos construidos bajo la implementación de un diseño integrado. En los últimos años la Arquitectura del Paisaje, ha volcado su mirada en las infraestructuras para reconocer su rol en la ciudad y el paisaje para abordar los problemas que se presentan debido a su implementación. La investigación estudia el diseño e implantación del Tren de pasajeros y carga Santiago – Batuco a realizarse en el norponiente de la ciudad, utiliza la antigua trocha de tren hacia la ciudad de Valparaíso la cual cruza cuatro comunas de la ciudad. La propuesta se construye bajo una visión de infraestructura multipropósitos como un modelo replicable basado en la lectura y análisis del territorial multiescalar; la faja de protección, el barrio, y la cuenca. De esta manera el tren se convierte en un vector que cruza distintas unidades de paisaje, revelando espacios de oportunidad para la implementación de cuatro estrategias de intervención que permitan la transformación de la infraestructura. Es así, como el tren genera una integración con sus contexto y reconoce un paisaje tanto en la posición del usuario, así como de las personas que convive junto a este elemento.
Wnt-5aoccludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons

Abstract Background Soluble amyloid-β (Aβ;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation. Results We report here that the Wnt signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Aβ oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Aβ oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Aβ oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Aβ oligomers inversely modulate postsynaptic components. Conclusion These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.Abstract Background Soluble amyloid-β (Aβ;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. Wnt signaling plays an important role in neural development, including synaptic differentiation. Results We report here that the Wnt signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Aβ oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with Wnt-5a and Aβ oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Aβ oligomers in neuronal cultures. Taken together these results indicate that Wnt-5a and Aβ oligomers inversely modulate postsynaptic components. Conclusion These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.
Wnt-5a-regulated miR-101b controls COX2 expression in hippocampal neurons

Abstract Background Wnt-5a is a member of the WNT family of secreted lipoglycoproteins, whose expression increases during development; moreover, Wnt-5a plays a key role in synaptic structure and function in the adult nervous system. However, the mechanism underlying these effects is still elusive. MicroRNAs (miRNAs) are a family of small non-coding RNAs that control the gene expression of their targets through hybridization with complementary sequences in the 3′ UTR, thereby inhibiting the translation of the target proteins. Several evidences indicate that the miRNAs are actively involved in the regulation of neuronal function. Results In the present study, we examined whether Wnt-5a modulates the levels of miRNAs in hippocampal neurons. Using PCR arrays, we identified a set of miRNAs that respond to Wnt-5a treatment. One of the most affected miRNAs was miR-101b, which targets cyclooxygenase-2 (COX2), an inducible enzyme that converts arachidonic acid to prostanoids, and has been involved in the injury/inflammatory response, and more recently in neuronal plasticity. Consistent with the Wnt-5a regulation of miR-101b, this Wnt ligand regulates COX2 expression in a time-dependent manner in cultured hippocampal neurons. Conclusion The biological processes induced by Wnt-5a in hippocampal neurons, involve the regulation of several miRNAs including miR-101b, which has the capacity to regulate several targets, including COX-2 in the central nervous system.
Miradas al Salvador : interiorización de la mirada médica

Los cambios en la infraestructura hospitalaria producto de los avances científicos y tecnológicos iniciados a mediados del siglo XIX con la aparición de la antisepsia serán estudiados en el modo en que estos redefinieron la concepción de la exterioridad e interioridad en los hospitales. Las relaciones patio, cuerpo, interior serán analizadas a través del modo en que definen el acto de observar: como una experiencia sensorial, de obediencia, de contemplación o experimentación; entendiendo los cambios físicos del hospital como productos de avances técnicos que venían en conjunto con un cambio en el modo de observar. Tres aproximaciones al Hospital Salvador exponen de manera conjunta el proceso de interiorización de la práctica y la redefinición de la relación entre mirada y cuerpo. El patio considerado por definición como un espacio exterior será un objeto cuestionado y puesto en duda, a través del cual se expondrán las redefiniciones de exterioridad que manejó la medicina desde mediados del s XIX hasta la mitad del s XX. A partir del estudio del Hospital el Salvador en Santiago, ejemplo de las ideas higienistas que llegaron a Chile en el siglo XIX, la presente investigación intenta demostrar cómo la modernización de la disciplina médica fue acompañada por un cambio en el paradigma de arquitectura hospitalaria, y con ello, la definición y rol de sus patios. La teoría de los humores y miasmas presentes en los higienistas, la teoría de los gérmenes que daría paso a la asepsia y antisepsia serán la base para entender los parámetros de diseño hospitalario que darían forma al Hospital del Salvador.
Primary and booster vaccination in latin american children with a DTPw-HBV/Hib combination: a randomized controlled trial

Abstract Background Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). Methods This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. Results One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. Conclusions Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. Trial registration http://www.clinicaltrials.gov NCT00332566