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Abstract Central areolar choroidal dystrophy is an inherited disorder characterized by progressive choriocapillaris atrophy and retinal degeneration and is usually associated with mutations in the PRPH2 gene. We aimed to generate and characterize a mouse model with the p.Arg195Leu mutation previously described in patients. Heterozygous (Prph2 WT/KI ) and homozygous (Prph2 KI/KI ) mice were generated using the CRISPR/Cas9 system to introduce the p.Arg195Leu mutation. Retinal function was assessed by electroretinography and optomotor tests at 1, 3, 6, 9, 12, and 20 months of age. The structural integrity of the retinas was evaluated at the same ages using optical coherence tomography. Immunofluorescence and transmission electron microscopy images of the retina were also analyzed. Genetic sequencing confirmed that both Prph2 WT/KI and Prph2 KI/KI mice presented the p.Arg195Leu mutation. A progressive loss of retinal function was found in both mutant groups, with significantly reduced visual acuity from 3 months of age in Prph2 KI/KI mice and from 6 months of age in Prph2 WT/KI mice. Decreased amplitudes in the electroretinography responses were observed from 1 month of age in Prph2 KI/KI mice and from 6 months of age in Prph2 WT/KI mice. Morphological analysis of the retinas correlated with functional findings, showing a progressive decrease in retinal thickness of mutant mice, with earlier and more severe changes in the homozygous mutant mice. We corroborated the alteration of the outer segment structure, and we found changes in the synaptic connectivity in the outer plexiform layer as well as gliosis and signs of microglial activation. The new Prph2 WT/KI and Prph2 KI/KI murine models show a pattern of retinal degeneration similar to that described in human patients with central areolar choroidal dystrophy and appear to be good models to study the mechanisms involved in the onset and progression of the disease, as well as to test the efficacy of new therapeutic strategies.

Purpose: The objective of this research is to statistically contrast the initial level of students’ soft skills against the subsequent level after having completed a virtual internship. These online internships took place during the period of social distancing by COVID-19 pandemic. Design/methodology: The methodology consisted of a pre-experimental pretest/post-test design with a single treatment group. Findings: achievement orientation, planning and organization, stress management, decision-making, problem-solving and emotional intelligence skills increased significantly after completing the online internship. Practical Implications: the findings lend themselves useful to guide higher education institutions in updating their curricula to meet the demands of the labour market in terms of soft skills in the so-called new post-pandemic reality. Originality/value: We provide evidence that virtual internships can have positive returns in terms of soft skills training. Previous studies were limited to recommending that internships be implemented on face-to-face mode.

Background: The COVID-19 pandemic poses a significant global health threat, characterized by high morbidity, severity, and the emergence of concerning variants. Latin America has been greatly affected, with high infection and mortality rates. Vaccination plays a crucial role in mitigating severe disease and controlling the pandemic. This study aims to assess the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 severe acute respiratory infections (SARI) in hospitalized vaccination target groups in Ecuador. Methods: This is a test-negative design study. We used data reported through sentinel surveillance of SARI between May 2021 and March 2022 in Ecuador. Patients with case criteria of SARI and hospitalized for a minimum of 24 hours were included in the study. Cases were defined as patients with SARI with a positive RT-qPCR test for SARS-CoV-2 and controls were those with a negative result. Information on vaccination status was obtained from the national vaccination registry, a valid dose of vaccination was considered when it was administered at least 14 days prior to symptom onset. Vaccine effectiveness (VE) (1-OR/OR) was calculated using a logistic regression. Results: A total of 1,277 patients were included in the analysis of VE. The adjusted vaccine effectiveness (aVE) in preventing hospitalization, adjusted for sex, age group, presence of one or more comorbidities, and period of the predominance of the omicron variant, was 44.5% for the partial primary schedule, 74.7% for the complete primary schedule, and 79.9% for the complete primary schedule plus booster doses. The aVE in avoiding ICU admissions was close to 80% with both the complete primary schedule and the booster doses, and in avoiding deaths, the aVE was 89% and 98%, respectively. Conclusions: In Ecuador, COVID-19 vaccination prevents hospitalizations, ICU admissions, and deaths. The effectiveness of the vaccines improves with more doses, offering increased protection across all age groups.

Abstract Background The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration. Methods Human eyes from control (n = 10) and PD (n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas. Results First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells. Conclusions Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.

Abstract Background Different ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters. Methods Retinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) were immunostained. The location of angiotensin-converting enzyme 2 (ACE2) and the morphology of microglial cells, Müller cells, astrocytes, and photoreceptors were analyzed by confocal microscopy. Microglial quantification and the area occupied by them were measured. Correlations among retinal and clinical parameters were calculated. Results ACE2 was mainly located in the Müller cells, outer segment of cones and retinal pigment epithelium. Cell bodies of Müller cells in COVID-19 group showed greater staining of ACE2 and cellular retinaldehyde-binding protein (CRALBP). The 81.3% of COVID-19 patients presented disorganization of honeycomb-like pattern formed by Müller cells. Gliosis was detected in 56.3% of COVID-19 patients compared to controls (40%) as well as epiretinal membranes (ERMs) or astrocytes protruding (50%). Activated or ameboid-shape microglia was the main sign in the COVID-19 group (93.8%). Microglial migration towards the vessels was greater in the COVID-19 retinas (P

An industrial nuclear technique based on the use of an X-ray profiler was implemented to estimate the densities or concentrations of sediments present in an Atlantic maritime zone in the areas subjected to dredging under the governance of the Panama Canal Authority (ACP).The sediment profiles show in most areas there is a concentration of between 1.00-1.15 g/cm³ except for one area in particular, the density starts at 1.20 g/cm³ and even reaches values greater than 1.50 g/cm³; therefore, an already consolidated sediment is present, which, depending on the depth found. Values of 1.265 g/cm³, 1.297 g/cm³, 1.185 g/cm³ obtained by ACP previous studies are within the range of 1.20–1.30 g/cm³ measured with the nucleonic gauge. However, it should be noted that during the tests with the X ray profiler, sediment densities values greater than the aforementioned limit were also obtained that varying according at depths close to 12 m and 18 m with values reached up to 1.513 g/cm³ and 1.60 g/cm³, respectively. This demonstrates that sediment accumulation depends on depth. This nucleonic gauge is feasible technique for the study of the sedimentation phenomenon in channel basins and even in other projects nationwide.

Background: Diarrheal disease remains a significant cause of child mortality, particularly in regions with limited access to healthcare and sanitation. Inappropriate practices, including unjustified medication prescriptions, pose challenges in the management of acute diarrhea (AD), especially in low- and middle-income countries. Objective: This study analyzed antibiotic prescription patterns and assessed compliance with Integrated Management of Childhood Illness (IMCI) guidelines in children under 5 with AD in the Ministry of Public Health (MOPH) Ambulatory Care Centers of Quito city, Ecuador. Methods: A cross-sectional design was used, collecting electronic health records (EHR) of patients diagnosed with AD from 21 health facilities in District 17D03. A probabilistic and stratified sampling approach was applied. Patient characteristics, prescriber characteristics, treatments, and compliance of IMCI guideline recommendations were evaluated. A stepwise logistic regression analysis examined the association between antibiotic prescription and patient and physician characteristics. Results: A total of 359 children under 5 years of age were included, with 58.77% being girls. 85.24% of the cases of AD were attributed to gastroenteritis and colitis of infectious and unspecified origin. Amebiasis and other protozoal intestinal diseases accounted for 13.37% and 1.11% of the cases, respectively. The completion rates of recording various IMCI parameters varied; parameters such as duration of diarrhea, presence of blood in stool, and evidence of sunken eyes had high completion rates (100%, 100%, and 87.47%, respectively), while parameters like state of consciousness, presence of thirst, and type of diarrhea had low completion rates (0.28%, 0.28%, and 0.84%, respectively). None of the cases had all parameters fully recorded. Antimicrobials were prescribed in 38.72% of the cases. Children aged 3 to 5 years had higher odds of receiving antimicrobial prescription for AD (aOR: 4.42, 95% CI 2.13-9.18, P

Coastal flooding and eros-ion caused by extreme events are the main factors responsible for beach hazards. This effect will be exacerbated by the sea level rise induced by climate change. The present work determines the vulnerability to erosion and flooding along 55 beaches grouped in different coastal archetypes, representative of the Catalan coast. The vulnerability assessment has been done through the numerical simulation of different combinations for projected waves and mean water levels under present conditions and the climate change scenarios RCP4.5 and RCP8.5 for the year 2100. A storm event approach has been used to determine coastal flooding and erosion with return periods of 50, 100, and 500 years using the XBeach numerical model. Results show that shoreline retreat is not the best proxy to characterize the erosion. The low-lying nature of the coast, the non-presence of well-developed berms, and the existence of river mouth and torrents govern the coastal flooding. The sea level rise appears to be a dominant variable in coastal hazards.

Complex thermo-kinetic interactions during metal additive manufacturing reduce the homogeneity of the microstructure of the produced samples. Understanding the effect of processing parameters over the resulting mechanical properties is essential for adopting and popularizing this technology. The present work is focused on the effect of laser power, scanning speed, and hatch spacing on the relative density, microhardness, and microstructure of 316L stainless steel processed by laser powder bed fusion. Several characterization techniques were used to study the microstructure and mechanical properties: optical, electron microscopies, and spectrometry. A full-factorial design of experiments was employed for relative density and microhardness evaluation. The results derived from the experimental work were subjected to statistical analysis, including the use of analysis of variance (ANOVA) to determine both the main effects and the interaction between the processing parameters, as well as to observe the contribution of each factor on the mechanical properties. The results show that the scanning speed is the most statistically significant parameter influencing densification and microhardness. Ensuring the amount of volumetric energy density (125 J/mm3) used to melt the powder bed is paramount; maximum densification (99.7%) is achieved with high laser power and low scanning speed, while hatch spacing is not statistically significant.

The growing installation of intermittent renewable energy sources is forcing hydraulic turbines to work more frequently at speed no load when dangerous vaneless space vortex structures and stochastic flow phenomena can occur. An experimental campaign has been performed in a reduced-scale Kaplan turbine model at speed no load for different combinations of guide vane and runner blade angles under non-cavitation and cavitation conditions. Several simultaneous vaneless space vortex structures, all of them inducing torsional rotor vibrations, have been observed. Nonetheless, only one of them has been found to dominate over the rest depending on the blade and guide vane angles. Off-board pressures, torques and vibrations as well as on-board strains have been measured to characterize their nature, intensity, dynamic behavior and induced structural response. Their precession frequencies have been found to depend on the discharge factor, the number of vortices and their location inside the vaneless space. Under cavitation conditions, their dynamic behavior has not been significantly altered but the induced structural response has increased at the low-pressure side of the turbine.

The operation of submerged rotating machines, such as marine current or tidal turbines, can present deleterious fluid phenomena that may provoke extreme structural vibrations. To predict their dynamic responses, it is necessary to know the added modal coefficients of their runners under a whirling motion. For that purpose, a bespoke test rig was designed to investigate the added modal coefficients of a submerged cylinder, which could rotate at different speeds both in air and completely submerged in water inside a cylindrical tank. First, the modes of vibration were experimentally measured by exciting the cylinder with a push-release method during steady tests or with ramps in rotating speed during transient tests. The calculated natural frequencies and damping ratios were then used in a mathematical model of the dynamic system to calculate the added modal coefficients. During steady tests, the natural frequencies and damping ratios of the whirling modes changed significantly as a function of the rotating speed. Additionally, a whirling mode was observed to change its direction at a given rotating speed. During transient tests, rotating speed ramps with high accelerations were found to present lower lock-in amplitude and frequencies. Moreover, fast downward ramps presented lock-in amplitudes four times higher than fast upward ramps. Consequently, the added modal coefficients changed accordingly as a function of the rotating speed, ramp acceleration, and ramp direction. For these reasons, it was confirmed that the modal responses of submerged rotating bodies must be calculated for each operational rotating speed, even at low velocities, and for each transient event in order to precisely predict their vibration behaviors.

Part 2 of this work presents a numerical methodology, validated using the experimental results presented in Part 1, to calculate the added modal coefficients of a submerged cylinder in water both when it oscillates and when it rotates with a whirling motion. The numerical methodology is based on computational fluid dynamic simulations that obtain the added modal forces on the cylinder when it is forced to vibrate with mode shapes calculated using acoustic-structural modal analysis. Then, these forces are processed with a curve-fitting algorithm to extract all the coefficients. Most numerical coefficients presented a close agreement with the corresponding experimental ones, although the added modal damping was overestimated. In general, the added modal mass was found to be independent of both the rotating speed and the whirling frequency except for low whirling frequencies when it increased. The added modal damping was found to depend on both parameters, and the rest of the coefficients were independent of the whirling frequency and only depended on the rotating speed. As a conclusion, this numerical approach has permitted the study of particular conditions that could not be experimentally tested and thus broadened the knowledge of the behavior of the added modal coefficients of rotating submerged cylinders.

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 1013 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA. Periodic monitoring of CSF and blood, clinical and neurological evaluations, and magnetic resonance and ultrasound imaging of target organs demonstrated no toxicity related to treatment. AAV9-mediated gene transfer resulted in detection of sulfamidase activity in CSF throughout the study. Analysis at tissue level showed widespread sulfamidase expression and activity in the absence of histological findings in any region of encephalon, spinal cord, or dorsal root ganglia. Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS.

Mucopolysaccharidosis type IVA (MPSIVA) is a lysosomal storage disorder causing severe skeletal and non-skeletal alterations in patients. Here, the authors generate a MPSIVA rat model that mimics the disabling human pathology and develop an AAV9-Galns gene therapy to treat the disease.

Multiple gene mutations have been associated with inherited retinal dystrophies (IRDs). Despite the spectrum of phenotypes caused by the distinct mutations, IRDs display common physiopathology features. Cell death is accompanied by inflammation and oxidative stress. The vertebrate retina has several attributes that make this tissue vulnerable to oxidative and nitrosative imbalance. The high energy demands and active metabolism in retinal cells, as well as their continuous exposure to high oxygen levels and light-induced stress, reveal the importance of tightly regulated homeostatic processes to maintain retinal function, which are compromised in pathological conditions. In addition, the subsequent microglial activation and gliosis, which triggers the secretion of pro-inflammatory cytokines, chemokines, trophic factors, and other molecules, further worsen the degenerative process. As the disease evolves, retinal cells change their morphology and function. In disease stages where photoreceptors are lost, the remaining neurons of the retina to preserve their function seek out for new synaptic partners, which leads to a cascade of morphological alterations in retinal cells that results in a complete remodeling of the tissue. In this review, we describe important molecular and morphological changes in retinal cells that occur in response to oxidative stress and the inflammatory processes underlying IRDs.

The structural dynamic response of hydraulic turbines needs to be continuously monitored to predict incipient failures and avoid catastrophic breakdowns. Current methods based on traditional off-board vibration sensors mounted on fixed components do not permit inferring loads induced on rotating parts with enough accuracy. Therefore, the present paper assesses the performance of fiber Bragg grating sensors to measure the vibrations induced on a rotating shaft–disc assembly partially submerged in water resembling a hydraulic turbine rotor. An innovative mounting procedure for installing the sensors is developed and tested, which consists of machining a thin groove along a shaft line to embed a fiber-optic array that can pass through the bearings. At the top of the shaft, a rotary joint is used to extract, in real time, the signals to the interrogator. The shaft strain distribution is measured with high spatial resolution at different rotating speeds in air and water. From this, the natural frequencies, damping ratios, and their associated mode shapes are quantified at different operating conditions. Additionally, the change induced in the modes of vibration by the rotation effects is well captured. All in all, these results validate the suitability of this new fiber-optic technology for such applications and its overall better performance in terms of sensitivity and spatial resolution relative to traditional equipment. The next steps will consist of testing this new sensing technology in actual full-scale hydraulic turbines.

Introduction: Studies have shown that pneumococcal disease significantly increases morbidity and mortality rates in children 5 years old and under. These infections constitute the main cause of preventable deaths in the world, considering the availability of vaccination. Considering that Ecuador is in a high incidence region, despite the introduction of the vaccine, this study aims to describe the burden of hospitalized pneumococcal disease and related mortality in our country between 2005 and 2015, to help decision-making processes for the health authorities. Methods: This cross-sectional study analyzes morbidity, mortality, and the situation in Ecuador caused by pneumococcal disease in children 5 years old and under between 2005 and 2015 using national databases. Results: A total of 163,852 cases of children 5 years old and under were reported to have been hospitalized due to pneumococcal-related diseases. Males comprised 54.7% of the cases and females 45.3%. In 36% of the cases, the patients were 1 year old or under. The mortality rate due to pneumococcal disease in Ecuador in children aged 5 and under decreased in 48% during 2005–2015. Conclusion: The decrease in mortality can be related to the introduction of the vaccine and an increase in access to health care by the general population in the country. It is important to study the specific impact of the vaccine in the reduction of morbidity and mortality of children in Ecuador.

Background. Soft-tissue sarcomas (STSs) are rare tumors; they represent 1% of all tumors in adults. There are new diagnostic techniques to differentiate tumor types, and surgery continues to be the most important treatment for STS. Methods. This cross-sectional study analyzed the morbidity and mortality caused by STS in adults between 2010 and 2020 using national databases. Results. A total of 8,393 patients hospitalized due to STS were reported. The total number of deaths in Ecuador due to STS was 7,088 over the last decade, the provinces of Pichincha and Guayas registered the highest number of cases, and the mortality rate was 1.2 to 2.0 per 100,000 people. It is noteworthy that the lowest point of registered cases was in 2012. Conclusion. Soft-tissue sarcomas are rare tumors in Ecuador. The morbidity and mortality caused by these tumors have not changed in the last decade. National studies are needed to determine the prevalence of this illness and study intervention to lower mortality.

ObjectiveThe aim of this study was to estimate the direct medical cost per episode and the annual cost for acute diarrhea (AD) in children under five years of age in Ambulatory Care Centers of the Ministry of Public Health (MOPH) of Ecuador.MethodsA cost of illness study with a provider perspective was carried out through a micro-costing of health resources and valuated in international dollars. Medical consultations and laboratory tests were valued using the tariff framework of services for the National Health System and for the prescribed medications, a reported cost registry of pharmacy purchases made in the year of study was used.ResultsA total of 332 electronic health records of children under five years of age were included in the analysis. Laboratory tests were performed on 37.95% (126/332), medications were prescribed to 93.67% (311/332) of the children, and antimicrobials were prescribed to 37.35% (124/332) of the children, representing an antibiotic prescription rate of 26.51% (88/332) and an antiparasitic prescription rate of 10.84% (36/332). The mean cost of the MOPH per child per episode of AD was US$45.24 (2019 dollars) (95% CI:43.71 to 46.76).ConclusionThe total estimated cost of AD in children under five years of age for the MOPH in 2019 was about US$6,645,167.88 million (2019 dollars) (95% CI: 6,420,430.77 to 6,868,436.12). A high proportion of the direct medical cost of AD in children under five years of age in outpatient settings is due to unnecessary laboratory tests.

The current paper presents an investigation into novel modal testing methods applied to a disk–shaft structure at different rotating speeds in air and water. The structure was excited using three different methods: an instrumented hammer, a piezoelectric PZT patch glued on the disk and a transient ramp-up. The structural response was measured using an accelerometer and strain gauges mounted on board as well as accelerometers and displacement lasers mounted off board. The potential to excite the natural frequencies using each excitation method and to detect natural frequencies with each sensor was analyzed and compared. Numerical structural and acoustic–structural modal and harmonic analyses of the non-rotating disk in air and water were also performed, taking into consideration the PZT patch. The numerical results showed a close agreement with the experimental ones in both air and water. It was found that the rotating speed of the disk modified the detected natural frequencies, depending on the frame of reference of the sensor. Finally, the PZT patch and the transient ramp-up were proven to be reliable methods to excite the natural frequencies of the current test rig and to be potentially applicable in full-scale hydraulic turbines under operating conditions.

Abstract Background Radiography is useful to determine left atrial (LA) size when echocardiography is not available. Recently, the authors have described Radiographic Left Atrial Dimension (RLAD) as a new radiographic measurement to assess LA size. The objective of this study was to assess the clinical usefulness of 2 new radiographic measurements to detect and quantify left atrial enlargement (LAE) compared to RLAD and using left atrium to aortic root (LA/Ao) ratio as gold standard. These new measurements, bronchus-to-spine (Br-Spine) and RLAD-to-spine (RLAD-Spine) may be more precise in cases were LA boundaries are not well defined. Fifty dogs, 25 with and 25 without LAE were recruited. Reference LA/Ao ratio was assessed by 2D echocardiography and LAE was considered if LA/Ao > 1.6. Br-spine was measured as a straight vertical line from the main stem bronchus to the ventral border of the vertebra situated immediately dorsal to the heart base. RLAD-Spine was measured from RLAD endpoint perpendicularly to spine. The correlation of RLAD, Br-Spine and RLAD-Spine methods with LA/Ao and their sensitivity and specificity for detecting LAE were calculated. Receiver Operating Characteristic (ROC) curves were used to estimate the optimal cut-off for each method. Results Correlations between Br-Spine, RLAD-Spine, RLAD and LA/Ao ratio were − 0.66, − 0.76 and 0.89 respectively (P

The rotating vortex rope, which can be decomposed in the rotating and the plunging modes, is the origin of pressure fluctuations in the draft tube cone when hydraulic turbines operate at part load, compromising the structural integrity and limiting the output load. A measurement campaign was carried out in a Kaplan turbine model which is a replica of the experimental 10 MW Porjus U9 prototype machine along a propeller curve to study the rotating vortex rope’s excitation levels and the induced structural responses. A complete set of sensors mounted on-board and off-board was used to measure pressures, forces, torques, accelerations, displacements, and strains. The characteristic frequencies and amplitudes of the pressure fluctuations and of the corresponding induced loads and vibrations associated with the two modes were quantified in a wide range of operating conditions at part load. The two modes are detected at different frequencies depending on the sensor position. Moreover, their frequencies change depending on the discharge and present different amplitudes depending on the mode. Particularly, the rotating mode shows higher amplitudes than the plunging mode in the majority of positions and directions measured.

Abstract Background The dimensions of the left atrium in cases with mitral regurgitation are an indirect measurement of its severity. The objective of this study was to evaluate the value of a new radiographic measurement, the radiographic left atrial dimension (RLAD), for detecting left atrial enlargement (LAE) in dogs. Thirty one dogs without LAE and 46 dogs with LAE were recruited in a prospective fashion. Reference left atrium dimension was measured by standard left atrium to aorta ratio (LA/Ao) by 2D echocardiography. LAE was considered if LA/Ao > 1.6. Left atrium dimension was then quantified on lateral radiographs by measuring RLAD. Vertebral heart size (VHS) was measured and RLAD was obtained by drawing a line bisecting the 90 degrees angle defined by the long and short cardiac axes lines of the VHS, up to the dorsal edge of the left atrium and comparing its length to T4’s vertebral body length. The correlation of VHS and RLAD methods with LA/Ao was estimated, as well as their sensitivity and specificity for detecting LAE. Receiver Operating Characteristic (ROC) curves were used to estimate the optimal decision criteria for each method. Results A positive correlation was observed between RLAD and LA/Ao (r = 0.82). RLAD’s sensitivity and specificity for detecting LAE when evaluated at the optimal cut-off value, 1.8 vertebrae, were 93.5 and 96.8% respectively. RLAD showed high reproducibility and repeatability. Conclusion RLAD appears to be a clinically useful radiographic measurement for evaluating left atrial dimensions. RLAD would provide clinicians with a simple and cost-effective tool for evaluating and monitoring LAE.

BackgroundClinical guidelines (CG) are used to reduce variability in practice when the scientific evidence is sparse or when multiple therapies are available. The development and implementation of evidence-based CG is intended to organize and provide the best available evidence to support clinical decision making in order to improve quality of care. Upper respiratory tract infections (URTI) are the leading cause of misuse of antibiotics and a CG may reduce the unnecessary antibiotic prescription.MethodsThe aim of this quasi-experimental, before-after study was to analyze the short- and long-term effects of the implementation of a CG to decrease the rate of antibiotic prescription in URTI cases in the emergency department of a third level private hospital in Quito, Ecuador. The study included 444 patients with a main diagnosis of URTI. They were distributed in three groups: a baseline cohort 2011 (n = 114), a first post-implementation cohort 2011 (n = 114), and a later post-implementation cohort 2018 (n = 216). The implementation strategy consisted of five key steps: acceptance of the need for implementation of the CG, dissemination of the CG, an educational campaign, constant feedback, and sustainability of the strategy through continuous training.ResultsThe results of this study show a 42.90% of antibiotic prescription rate before the CG implementation. After the implementation of the CG, the prescription rate of antibiotics was significantly reduced by 24.5% (42.9% vs 18.4%, pConclusionsThe implementation of CGs decreases the rate of antibiotic prescription in URTI cases. The results are remarkable after early implementation, but the effect persists over time. The emphasis must shift from guideline development to strategy implementation.

Background Inappropriate prescriptions of antibiotics lead to ineffective and unsafe treatments and worsening of diseases. Medical students may have deficiencies in their prescription skills and they may need further training in the use of antibiotics for their practice. Medical skills in prescribing antibiotics can be improved through continuous medical education. The aim of this study was to assess the current levels of knowledge, attitudes, and practices (KAP) in antibiotic prescription in upper respiratory tract infections (URTI) among postgraduate family medicine students in Ecuador. Methods A cross-sectional study with an on-line survey, based on micro-curricular contents, to evaluate KAPs regarding antibiotic prescription in URTI among postgraduate family medicine students in 5 provinces of Ecuador. Results Two hundred and seventy-three physicians responded (94.1%). Most physicians treated between 1 and 5 URTI cases per day. The odds for inadequate knowledge and inappropriate practices in URTI among postgraduate family medicine students were 8.74 (95%CI, 4.94-15.46, P

Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration of the retina, ultimately leading to loss of visual function. Oxidative stress and inflammation play fundamental roles in the physiopathology of these diseases. Photoreceptor cell death induces an inflammatory state in the retina. The activation of several molecular pathways triggers different cellular responses to injury, including the activation of microglia to eliminate debris and recruit inflammatory cells from circulation. Therapeutical options for IRDs are currently limited, although a small number of patients have been successfully treated by gene therapy. Many other therapeutic strategies are being pursued to mitigate the deleterious effects of IRDs associated with oxidative metabolism and/or inflammation, including inhibiting reactive oxygen species’ accumulation and inflammatory responses, and blocking autophagy. Several compounds are being tested in clinical trials, generating great expectations for their implementation. The present review discusses the main death mechanisms that occur in IRDs and the latest therapies that are under investigation.

Abstract Background Upper respiratory tract infections are the leading cause of misuse of antibiotics, a problem that leads to unnecessary adverse events and antibiotic resistance. Antibiotic prescription in Ecuador was analyzed in order to evaluate the state of antibiotic prescribing for upper respiratory tract infections. Both the appropriateness and adequacy of prescribing was evaluated. Appropriateness represents the percentage of prescriptions that are indicated; adequacy refers to the percentage of patients requiring antibiotics who are treated. Methods The aim of the study is to analyze the appropriateness and adequacy of antibiotic prescription for upper respiratory tract infections in the Ambulatory Health Centers of the Ministry of Public Health of Ecuador. This is a cross-sectional study of patients from one Health Center of the Ministry of Public Health in the District 17D03 in Ecuador during 2015 with upper respiratory tract infection as a primary diagnosis. Results We included a total of 1393 patients in the analysis. Out of the 1393 patients identified, 523 were prescribed antibiotics, constituting an antibiotic prescription rate of 37.5%, and 51 required antibiotics, reflecting a real need of antibiotics of 3.7%. Appropriateness: Of these 523 patients who were treated, 51 required an antibiotic, resulting in an appropriate antibiotic prescription rate of 9.75%. Adequacy: When analyzing each individual case, 33 of these 51 patients received an antibiotic, constituting an adequate prescription rate of 64.7%. Conclusions The results of our study report a 90.25% of inappropriate prescription. The antibiotic prescription, appropriate prescription, and adequate prescription rates show the need for implementation of strategies in order to reduce them. Related aspects regarding prescriber’s behavior and the patient’s expectations should be analyzed.

As is widely known, additive manufacturing (AM) allows very complex parts to be manufactured with porous structures at a relatively low cost and in relatively low manufacturing times. However, it is necessary to determine in a precise way the input values that allow better results to be obtained in terms of microgeometry, form errors, and dimensional error. In an earlier work, the influence of the process parameters on surface roughness obtained in fused filament fabrication (FFF) processes was analyzed. This present study focuses on form errors as well as on dimensional error of hemispherical cups, with a similar shape to that of the acetabular cup of hip prostheses. The specimens were 3D printed in polylactic acid (PLA). Process variables are nozzle diameter, temperature, layer height, print speed, and extrusion multiplier. Their influence on roundness, concentricity, and dimensional error is considered. To do this, adaptive neuro-fuzzy inference systems (ANFIS) models were used. It was observed that dimensional error, roundness, and concentricity depend mainly on the nozzle diameter and on layer height. Moreover, high nozzle diameter of 0.6 mm and high layer height of 0.3 mm are not recommended. A desirability function was employed along with the ANFIS models in order to determine the optimal manufacturing conditions. The main aim of the multi-objective optimization study was to minimize average surface roughness (Ra) and roundness, while dimensional error was kept within the interval Dimensional Error≤0.01. When the simultaneous optimization of both the internal and the external surface of the parts is performed, it is recommended that a nozzle diameter of 0.4 mm be used, to have a temperature of 197 °C, a layer height of 0.1 mm, a print speed of 42 mm/s, and extrusion multiplier of 94.8%. This study will help to determine the influence of the process parameters on the quality of the manufactured parts.

Recent years have witnessed a growing interest in automatic learning mechanisms and applications. The concept of hyper-heuristics, algorithms that either select among existing algorithms or generate new ones, holds high relevance in this matter. Current research suggests that, under certain circumstances, hyper-heuristics outperform single heuristics when evaluated in isolation. When hyper-heuristics are selected among existing algorithms, they map problem states into suitable solvers. Unfortunately, identifying the features that accurately describe the problem state—and thus allow for a proper mapping—requires plenty of domain-specific knowledge, which is not always available. This work proposes a simple yet effective hyper-heuristic model that does not rely on problem features to produce such a mapping. The model defines a fixed sequence of heuristics that improves the solving process of knapsack problems. This research comprises an analysis of feature-independent hyper-heuristic performance under different learning conditions and different problem sets.

Chemodectomas are low prevalence tumors with complex clinical management. Many present as an incidental finding however, in other dogs, they produce pericardial effusion and/or compression, leading to the appearance of severe clinical signs. There are currently several approaches: surgery, radiotherapy, stent placement and chemotherapy. This is the first description of percutaneous echo-guided radiofrequency ablation of aortic body tumors. This minimally invasive treatment is based on high frequency alternating electrical currents from an electrode that produces ionic agitation and generates frictional heat, causing coagulation necrosis. Five dogs with an echocardiographic and cytological diagnosis of chemodectoma underwent percutaneous echo-guided radiofrequency ablation. At the time of presentation, all the dogs showed clinical signs, such as ascites and/or collapse. There were no complications either during the procedure or in the following 24 hours. Rapid clinical improvement associated with a reduction in size and change in sonographic appearance of the mass were achieved with no complications. Six months follow-up was carried out in all dogs. A second percutaneous echo-guided RFA was performed eight months after the first procedure in one dog. Based on our experience, radiofrequency ablation seems to be a feasible and safe technique, making it a potential alternative therapeutic approach in the clinical management of aortic body tumors leading to severe clinical compromise.

Fused filament fabrication (FFF) 3D printing technology allows very complex parts to be obtained at a relatively low cost and in reduced manufacturing times. In the present work, the effect of main 3D printing parameters on roughness obtained in curved surfaces is addressed. Polylactic acid (PLA) hemispherical cups were printed with a shape similar to that of the acetabular part of the hip prostheses. Different experiments were performed according to a factorial design of experiments, with nozzle diameter, temperature, layer height, print speed and extrusion multiplier as variables. Different roughness parameters were measured—Ra, Rz, Rku, Rsk—both on the outer surface and on the inner surface of the parts. Arithmetical mean roughness value Ra and greatest height of the roughness profile Rz are usually employed to compare the surface finish among different manufacturing processes. However, they do not provide information about the shape of the roughness profile. For this purpose, in the present work kurtosis Rku and skewness Rsk were used. If the height distribution in a roughness profile follows a normal law, the Rku parameter will take a value of 3. If the profile distribution is symmetrical, the Rsk parameter will take a value of 0. Adaptive neural fuzzy inference system (ANFIS) models were obtained for each response. Such models are often employed to model different manufacturing processes, but their use has not yet been extended to 3D printing processes. All roughness parameters studied depended mainly on layer height, followed by nozzle diameter. In the present work, as a general trend, Rsk was close to but lower than 0, while Rku was slightly lower than 3. This corresponds to slightly higher valleys than peaks, with a rounded height distribution to some degree.

Rubber bushings and mounts are vastly used in automotive applications as support and interface elements. In suspension systems, they are commonly employed to interconnect the damping structure to the chassis. Therein, the viscoelastic nature of the material introduces a desirable filtering effect to reduce mechanical vibrations. When designing a suspension system, available literature often deals with viscoelastic mounts by introducing a linear or nonlinear stiffness behavior. In this context, the present paper aims at representing the rubber material using a proper viscoelastic model with the selection of different in-wheels motors. Thus, the mount dynamic behavior’s influence in a suspension is studied and discussed thoroughly through numerical simulations and sensitivity analyses. Furthermore, guidelines are proposed to orient the designer when selecting these elements.

Choroidal dystrophies comprise a group of chorioretinal degenerations. However, the different findings observed among these patients make it difficult to establish a correct clinical diagnosis. The objective of this study was to characterize new clinical findings by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in these patients. Four family members with a PRPH2 gene mutation (p.Arg195Leu) were included. OCT was performed at the macula, and the thickness of the outer and inner retina, total retina, and choroid was measured. The features of the vascular network were analyzed by OCTA. Patients showed a decreased outer nuclear layer in the avascular area compared with the controls. Two patients presented greater foveal and parafoveal degeneration of the outer retina, whereas the most degenerated area in the rest was the perifovea. Disruption of the third outer band at the foveola is one of the first-altered outer bands. Slow blood flow areas or capillary dropout were main signs in the deep capillary plexus. Microaneurysms were frequently observed in less degenerated retinas. Vascular loops and intraretinal microvascular abnormalities (IRMAs) were present in the superficial plexus. Extensive degeneration of the choriocapillaris was detected. Phenotypic differences were found between patients: two showed central areolar choroidal dystrophy and the rest had extensive chorioretinal atrophy. These signs observed in OCT and OCTA can help to more appropriately define the clinical disease in patients with choroidal dystrophies.

Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches.

Augmented Reality, Visualization, Educational TechnologyIn order to take advantage of the didactic potential that AugmentedReality (AR) provides we present an educational resource meant to help to transform the teaching and learning of Mathematics, through the creation of graphical representations for mathematical reasoning. The spatial visualization skill is a cross-curriculum content that has been taken for granted, the challenge then is to improve its development. With the design of this AR application we want to help students with this task. The application covers content that belongs to conventional courses of calculus I, II and III at college.

Turbidity, CTD, and temperature and shear microstructure data recorded along a 25 km transect from 8 to 69 m depth across the Ebro Delta shelf (northwestern Mediterranean) are presented. The water column was stratified and prior to the campaign the regional southwest flow was measured to have superimposed diurnal and sub-inertial components. The bottom boundary layer (BBL) at all stations deeper than 20 m has a vertical extension of 3 to 9 m, increasing to 12 m at the deeper stations and even to 14 m at a station at 45 m depth outside the studied transect. The law of the wall was identified at almost all stations with an extension ranging from 40% to 100% of that of the BBL. At some stations high dissipation rates were found in the interior of the bottom layer. The study shows the correspondence between the turbidity contents and the local mixing processes at the BBL and suggests that sub-critical reflection of internal waves could play an important role in boundary mixing. Our data also suggest that during the campaign, after two consecutive short episodes of high winds, the first baroclinic mode shifted to the second one.