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Background: The cognitive distraction caused by Virtual Reality (VR) seems to cause a decrease both in pain and its perception as in the time spent thinking about possible pain, among anxiety about hysteroscopy procedure. The main objective of this investigation was to evaluate the efficacy of virtual reality for pain relief during outpatient hysteroscopy. Method: A total of 83 patients underwent outpatient diagnostic hysteroscopy in a single-centre, open-label, randomized control trial. Overall, 180 women with medical indication for an outpatient diagnostic hysteroscopy were randomized. Ten were excluded due to the impossibility of entering the endometrial cavity caused by a cervical canal that was not permeable, and 15 did not tolerate the pain at the beginning and during the procedure, excluding themselves from the final model. Finally, 154 were analysed per protocol to use VR (n = 82, study group) or standard treatment (n = 72, control group) assessing the differences between both groups by reduction in pain using Visual Analogue Scale score (VAS: 0–10 cm) and clinical data (arterial pressure, heart rate, and oxygen saturation) at the end of hysteroscopy, at 15 and 30 min after hysteroscopy. Results: Women with VR outpatient diagnostic hysteroscopy experienced less pain at final (VAS score 2.451 vs. 3.972, standard mean difference (SMD) −1.521, 95% CI −2.601 to −0.440; p = 0.006), at 15 min (VAS 1.769 vs. 3.300, SMD −1.531, 95% CI −2.557 to −0.504; p = 0.004), and at 30 min (VAS 1.621 vs. 2.719, SMD −1.099, 95% CI −2.166 to −0.031; p = 0.044) after the ending of the hysteroscopy, compared with no VR. Conclusions: The use of VR during outpatient diagnostic hysteroscopy proved effective in the reduction of pain in this randomized control trial. It shows wide potential role in ambulatory gynaecologic procedures to avoid repeating tests, perform surgeries without anaesthesia, and the use of medication and its side effects.

Introduction Microsatellite instability occurs due to a series of mutations in the DNA pairing error repair (Mismatch repair; MMR) genes, which can affect germ cells as occurs in Lynch syndrome, whose patients are at high risk of developing multiple cancers. The loss of MMR protein is commonly determined by immunohistochemical studies. Although the relation between microsatellite instability and urothelial carcinomas has been widely studied, its evaluation is not currently performed in the analysis of urothelial carcinomas. Methods In this study, the microsatellite status of 139 urothelial carcinomas was analyzed and their clinicopathological characteristics were evaluated. We identified that 10.3% (13 patients) of urothelial carcinomas had loss of MMR protein expression (9 MLH1; 5 MSH2; 2 PMS2; 2 PSH6; n = 139). Results Results suggest that these tumors occur more frequently in males, are more frequently located in the bladder or ureters, and present a high tumor grade with a papillary histological pattern that does not infiltrate the lamina propria or, in the case of infiltrating tumors, that grows into perivesical tissues. Conclusions We identified patients with the aforementioned tumor characteristics as patients with a high probability of presenting loss of MMR protein expression, and consider that only these patients should undergo further immunohistochemical and molecular techniques for proper diagnosis. Therefore, we propose that the clinicopathological characteristics found in the present study could become possible markers to determine which cases should undergo additional tests.

p-Synephrine is deemed a safe and effective substance to increase fat utilization during exercise of low-to-moderate intensity in men but not in women. Additionally, the existence of a diurnal variation in substrate utilization has been documented during exercise with enhanced fat oxidation in the evening compared with early morning. However, it remains unknown whether there is an interaction between the effect of p-synephrine and the time of the day on fat oxidation during exercise. This study aimed to evaluate the effect of the acute ingestion of 3 milligram of p-synephrine per kilogram of body mass (mg/kg) on fat oxidation during exercise of increasing intensity when the exercise is performed in the morning vs. the evening. Using a randomized, double-blind, placebo-controlled experimental design, 16 healthy and active women performed four identical exercise trials after the ingestion of 3 mg/kg of p-synephrine and 3 mg/kg of a placebo (cellulose) both in the morning (8-10 am) and in the evening (5-7 pm). In the exercise trials, the substances were ingested 60 min before an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 80% of maximal oxygen uptake (VO(2)max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. A two-way analysis of variance (time-of-the day x substance) was used to detect differences among the trials. With the placebo, MFO was 0.25 +/- 0.11 g/min in the morning and 0.24 +/- 0.07 g/min in the evening. With p-synephrine, MFO was 0.26 +/- 0.09 g/min in the morning and 0.21 +/- 0.07 g/min in the evening. There was no main effect of substance (p = 0.349), time of day (p = 0.186) and the substance x time of day (p = 0.365) on MFO. Additionally, Fatmax was reached at a similar exercise intensity with the placebo (41.33 +/- 8.34% VO(2)max in the morning and 44.38 +/- 7.37% VO(2)max in the evening) and with p-synephrine (43.33 +/- 7.24% VO(2)max in the morning and 45.00 +/- 7.43% VO(2)max in the evening), irrespective of the time of day with no main effect of substance (p = 0.633), time of day (p = 0.191), or interaction (p = 0.580). In summary, the acute intake of 3 mg/kg of p-synephrine before exercise did not increase MFO and Fatmax, independently of the time of day, in female athletes. This indicates that the time of day is not a factor explaining the lack of effectiveness of this substance to enhance fat oxidation during aerobic exercise in women., Francisco de Vitoria University, grant number UFV-18/2020

p-Synephrine is the principal alkaloid of bitter orange (Citrus aurantium). Several recent investigations have found that the intake of 2-3 mg/kg of p-synephrine raises fat oxidation rate during exercise of low-to-moderate intensity. However, these investigations have been carried out only with samples of male participants or mixed men/women samples. Therefore, the aim of this investigation was to study the effect of p-synephrine intake on fat oxidation during exercise of increasing intensity in healthy women. Using a double-blind, randomized experiment, 18 healthy recreationally active women performed two identical exercise trials after the ingestion of (a) 3 mg/kg of p-synephrine and (b) 3 mg/kg of a placebo (cellulose). The exercise trials consisted of a ramp test (from 30 to 80% of maximal oxygen uptake; VO(2)max) on a cycle ergometer while substrate oxidation rates were measured at each workload by indirect calorimetry. In comparison to the placebo, the intake of p-synephrine increased resting tympanic temperature (36.1 +/- 0.5 vs. 36.4 +/- 0.4 degrees C p = 0.033, d = 0.87) with no effect on resting heart rate (p = 0.111) and systolic (p = 0.994) and diastolic blood pressure (p = 0.751). During exercise, there was no significant effect of p-synephrine on fat oxidation rate (F = 0.517; p = 0.484), carbohydrate oxidation rate (F = 0.730; p = 0.795), energy expenditure rate (F = 0.480; p = 0.833), heart rate (F = 4.269; p = 0.068) and participant's perceived exertion (F = 0.337; p = 0.580). The maximal rate of fat oxidation with placebo was 0.26 +/- 0.10 g/min and it was similar with p-synephrine (0.28 +/- 0.08 g/min, p = 0.449, d = 0.21). An acute intake of 3 mg/kg of p-synephrine before exercise did not modify energy expenditure and substrate oxidation during submaximal aerobic exercise in healthy active women. It is likely that the increase in resting tympanic temperature induced by p-synephrine hindered the effect of this substance on fat utilization during exercise in healthy active women., Francisco de Vitoria University UFV-18/2020

Background: The Mediterranean diet is considered one of the dietary patterns with the most accumulated scientific evidence on health benefits. In children, it has positive effects in the prevention of obesity and cardiovascular diseases, as well as in the prevention of diabetes. We aimed to evaluate the medium-term efficacy of an intervention programme, targeting adherence to the Mediterranean diet among preschool children. Methods: In a randomised, parallel trial of participants aged 3–5 years, a school garden was attended in the experimental group, and in the control group, the usual content on the human body and health were taught. Adherence to the Mediterranean diet was assessed using the KIDMED questionnaire, controlling for weight, height, body mass index (BMI) and socio-demographic variables. Results: A reduction in BMI was found in the experimental group after one year and at the end of the follow-up period. In the overall score obtained in the KIDMED survey, a statistical trend was found between the two groups (p = 0.076). In multivariate analysis, consumption of pulses more than once a week’ was predictive of improved diet quality, with an Odds Ratio (OR) in the experimental group of 1.382 (95% CI 1.126–1.695; p = 0.009). Conclusions: The experimental approach improved the quality of the participants’ diet, increasing adherence to the Mediterranean diet due to increased consumption of plant-based protein. post-print 461 KB

Functional rehabilitation programs in multiple sclerosis have demonstrated their efficacy in improving fatigue. The assessment of functional impairment, however, is more difficult. The purpose is to assess fatigue and disability as a first study measure and to verify their improvement after a specific functional rehabilitation program. An analytical, longitudinal, prospective, and experimental study was carried out with 51 patients aged 18-55 years, with an Expanded Disability Status Scale (EDSS) between 2 and 6.5 who were being followed up in outpatient clinics of the Rehabilitation Service of La Princesa Hospital. The fatigue and disability outcomes before and after a structured exercise training program were evaluated, with each subject acting as their own control. The variables were measured using the Modified Fatigue Impact Scale (MFIS), Barthel Index (BI), and Functional Independence Scale (FIM). Differences according to recurrent or progressive course of the disease are assessed. Improvement in the FIM scale was observed after the retraining program ( p = 0.016 ) and was maintained in the medium term ( p = 0.042 ). This improvement is not statistically significant in Barthel Index. Improvement in MFIS is observed after the program ( p < 0.001 ) and 4-6 months after the end. Both disease courses experience the same improvements with no statistically significant differences between them. The retraining program improves fatigue and multiple sclerosis-related functionality in the short and medium term. There are no differences according to disease course. Both experience the same positive changes with our intervention.

Background: The potential influence of genetics in athletic performance allows the search for genetic profiles associated with muscular work for the orientation of strength training and sports selection. The purpose of the study was to analyze four muscular exercises for effectiveness in improving explosive strength variables, associated to the genetics in Angiotensin Converting Enzyme (ACE) and α-actinin-3 (ACTN3) polymorphisms. Methods: A randomized controlled trial was conducted on a sample of 80 subjects allocated into four groups: concentric muscle work (CMW), eccentric muscle work (EMW), concentric-eccentric muscle (C-EMW) work and isometric muscular work (IMW), by block and gender randomization. Vertical jump, long jump, power jump, and speed were measured to study explosive strength. Genotypic frequencies of ACE (rs4646994) and ACTN3 (rs1815739) were obtained by polymerase chain reaction. Results: ACE gen showed significant improvements regarding the DD genotype in the Sargent test (p = 0.003) and sprint velocity test (p = 0.017). In the ACTN3 gene, the RR variable obtained improvement results with regard to RX and XX variables in long jump (p &lt, 0.001), Sargent test (p &lt, 0.001) and power jump (p = 0.004). Conclusions: The selected genes demonstrated an influence on the muscle work and the improvement in explosive strength variables with a decisive role regarding the type of muscle work performed.

By using deceptive experiments in which participants are informed that they received caffeine when, in fact, they received an inert substance (i.e., placebo), several investigations have demonstrated that exercise performance can be enhanced to a similar degree as a known caffeine dose. This ‘placebo effect’ phenomenon may be part of the mechanisms explaining caffeine’s ergogenicity in exercise. However, there is no study that has established whether the placebo effect of caffeine is also present for other benefits obtained with acute caffeine intake, such as enhanced fat oxidation during exercise. Therefore, the aim of this investigation was to investigate the placebo effect of caffeine on fat oxidation during exercise. Twelve young men participated in a deceptive double-blind cross-over experiment. Each participant completed three identical trials consisting of a step incremental exercise test from 30 to 80% of V.O2max. In the two first trials, participants ingested either 3 mg/kg of cellulose (placebo) or 3 mg/kg of caffeine (received caffeine) in a randomized order. In the third trial, participants were informed that they had received 3 mg/kg of caffeine, but a placebo was provided (informed caffeine). Fat oxidation rates were derived from stoichiometric equations. In received caffeine, participants increased their rate of fat oxidation over the values obtained with the placebo at 30%, 40%, 50%, and 60% of V.O2max (all p &lt, 0.050). In informed caffeine, participants increased their rate of fat oxidation at 30%, 40%, 50% 60%, and 70% of V.O2max (all p &lt, 0.050) over the placebo, while there were no differences between received versus informed caffeine. In comparison to placebo (0.32 ± 0.15 g/min), the rate of maximal fat oxidation was higher in received caffeine (0.44 ± 0.22 g/min, p = 0.045) and in informed caffeine (0.41 ± 0.20 g/min, p = 0.026) with no differences between received versus informed caffeine. However, the intensity at which maximal fat oxidation rate was obtained (i.e., Fatmax) was similar in placebo, received caffeine, and informed caffeine trials (42.5 ± 4.5, 44.2 ± 9.0, and 41.7 ± 10.5% of V.O2max, respectively, p = 0.539). In conclusion, the expectancy of having received caffeine produced similar effects on fat oxidation rate during exercise than actually receiving caffeine. Therefore, the placebo effect of caffeine is also present for the benefits of acute caffeine intake on substrate oxidation during exercise and it may be used to enhance fat oxidation during exercise in participants while reducing any risks to health that this substance may have.

Objective We aimed to analyze risk factors related to the development of delirium, aiming for early intervention in patients with greater risk. Material and methods Observational study, including prospectively collected patients treated in a single general ICU. These were classified into two groups, according to whether they developed delirium or not (screening performed using CAM-ICU tool). Demographics and clinical data were analyzed. Multivariate logistic regression analyses were performed to quantify existing associations. Results 1462 patients were included. 93 developed delirium (incidence: 6.3%). These were older, scored higher on the Clinical Frailty Scale, on the risk scores on admission (SAPS-3 and SOFA), and had a greater number of organ failures (OF). We observed more incidence of delirium in patients who (a) presented more than two OF (20.4%; OR 4.9; CI95%: 2.9–8.2), and (b) were more than 74 years old albeit having Conclusions The highest risk observed for developing delirium clustered in patients who presented more than 2 OF and patients over 74 years old. The detection of patients at high risk for developing delirium could imply a change in management and improved quality of care.

Producción Científica, Background: most of the research concerning the influence of genetics on endurance performance has been carried out by investigating target genes separately. However, endurance performance is a complex trait that can stem from the interaction of several genes. The objective of this study was to compare the frequencies of polymorphisms in target genes involving cardiorespiratory functioning in elite endurance athletes vs. non-athlete controls. Methods: genotypic frequencies were determined in 123 elite endurance athletes and in 122 non-athletes. Genotyping of ACE (rs4340), NOS3 (rs2070744 and rs1799983), ADRA2a (rs1800544 and rs553668), ADRB2 (rs1042713 and rs1042714), and BDKRB2 (rs5810761) was performed by polymerase chain reaction. The total genotype score (TGS: from 0 to 100 arbitrary units; a.u.) was calculated from the genotype score in each polymorphism. Results: the mean TGS in non-athletes (47.72 ± 11.29 a.u.) was similar to elite endurance athletes (46.54 ± 11.32 a.u., p = 0.415). The distribution of TGS frequencies were also similar in non-athletes and elite endurance athletes (p = 0.333). There was no TGS cut-off point to discriminate being elite endurance athletes. Conclusions: the genetic profile in the selected genes was similar in elite endurance athletes and in controls, suggesting that the combination of these genes does not determine endurance performance., Consejo Superior de Deportes de España (CSD) - (grant 15/UPB10/08)

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Previous investigations have found that several genes may be associated with the interindividual variability to the ergogenic response to caffeine. The aim of this study is to analyze the influence of the genetic variations in CYP1A2 (&minus, 163C&thinsp, &gt, A, rs762551, characterized such as &ldquo, fast&rdquo, (AA genotype) and &ldquo, slow&rdquo, caffeine metabolizers (C-carriers)) and ADORA2A (1976T&thinsp, C, rs5751876, characterized by &ldquo, high&rdquo, (TT genotype) or &ldquo, low&rdquo, sensitivity to caffeine (C-carriers)) on the ergogenic response to acute caffeine intake in professional handball players. Thirty-one professional handball players (sixteen men and fifteen women, daily caffeine intake = 60 &plusmn, 25 mg&middot, d&minus, 1) ingested 3 mg&middot, kg&minus, 1&middot, body mass (bm) of caffeine or placebo 60 min before undergoing a battery of performance tests consisting of a countermovement jump (CMJ), a sprint test, an agility test, an isometric handgrip test, and several ball throws. Afterwards, the handball players performed a simulated handball match (2 &times, 20 min) while movements were recorded using inertial units. Saliva samples were analyzed to determine the genotype of each player for the &minus, A polymorphism in the CYP1A2 gene (rs762551) and for the 1976T&thinsp, C polymorphism in the ADORA2A gene (rs5751876). In the CYP1A2, C-allele carriers (54.8%) were compared to AA homozygotes (45.2%). In the ADORA2A, C-allele carriers (80.6%) were compared to TT homozygotes (19.4%). There was only a genotype x treatment interaction for the ball throwing from 7 m (p = 0.037) indicating that the ergogenic effect of caffeine on this test was higher in CYP1A2 AA homozygotes than in C-allele carriers. In the remaining variables, there were no genotype x treatment interactions for CYP1A2 or for ADORA2A. As a whole group, caffeine increased CMJ height, performance in the sprint velocity test, and ball throwing velocity from 9 m (2.8&ndash, 4.3%, p = 0.001&ndash, 0.022, effect size = 0.17&ndash, 0.31). Thus, pre-exercise caffeine supplementation at a dose of 3 mg&middot, bm can be considered as an ergogenic strategy to enhance some neuromuscular aspects of handball performance in professional handball players with low daily caffeine consumption. However, the ergogenic response to acute caffeine intake was not modulated by CYP1A2 or ADORA2A genotypes.

Objective: to analyse maternal physiological changes in several areas (cardiovascular, metabolic, renal and hepatic) related to the regular practice of a supervised exercise program. Methods: This is an unplanned secondary analysis from a randomized controlled trial carried out in a single maternity unit in Madrid, Spain (NCT 02,756,143). From November 2014 to June 2015, 92 women were randomly assigned to perform a mild-moderate supervised exercise program during pregnancy (Intervention group, IG) or to continue with their routine pregnancy care (control group, CG). For the purpose of this study we collected clinical and analytical data (heart blood pressure, weight, blood glucose, AST, ALT, blood Creatinine and blood Uric acid) available from all obstetric visits and examined the differences between groups. Results: We did not find any differences in: pregnancy weight (IG: 11.4 ± 4.4 Kg vs. CG: 10.1 ± 5.3 Kg; p = 0.173); fasting glucose at 10+0–12+6 weeks (IG: 78.48±8.34 vs. CG: 76±13.26, p = 0.305) or at 34+0–36+4 weeks (IG: 73.25±10.27 vs CG: 73.45± 8.29,p = 0.920), and 50 gs glucose tolerance at 24+4–26+6weeks (IG: 116.23±35.07 vs CG: 116.36±25.98, p = 0.984); Aspartate-amino-transferase at 10+0–12+6 weeks (IG: 15.38±4.17 vs CG: 17.33±7.05, p = 0.124) and at 34+0–36+4 weeks (IG: 21.65±5.25 vs CG: 19.53±8.32, p = 0.165) or Alanine-amino- transferase at 10+0–12+6 weeks (IG: 27.50±10.63 vs CG: 28.27±11.77, p = 0.746) or at 34+0–36+4 weeks (IG: 22.93±9.23 vs CG: 20.84±13.49, p = 0.407); blood Creatinine concentrations at 34+0–36+4 weeks (IG: 0.595±0.401 vs CG: 0.575±0.100, p = 0.757) and blood uric acid concentrations at 34+0–36+4 weeks (IG: 3.526 ± 0.787 vs CG: 3.262±0.672, p = 0.218). Heart blood pressure was similar between groups except at 27+0–28+6 weeks, where systolic blood pressure was significantly lower in the CG in comparison to the IG (116.31±10.8 mmHg vs. 120.22 ± 10.3 mmHg, p = 0.010). Conclusion: Regular supervised exercise during pregnancy does not alter normal maternal physiology pre-print 609 KB

Cross-sectional study to know if tracheostomy influences the time on mechanical ventilation and reduces the ICU stay in patients with SARS-CoV2. From February 14 to May 31, 2020, 29 patients: 23 men and 6 women, with an average age (SD) of 66.4 years (±6,2) required tracheostomy. The average intensive care unit (ICU) stay was 36 days [31–56.5]. The average days on mechanical ventilation was 28,5 days (±9.7). Mean time to tracheostomy was 15.2 days (±9.5) with an average disconnection time after procedure of 11.3 days (±7.4). The average hospital stay was 55 days [39–79]. A directly proportional relation between the number of days of MV and the number of days from ICU admission until tracheostomy showed a significant value of p = 0.008. For each day of delay in tracheostomy, the days of mechanical ventilation were increased by 0.6 days. There was no relation between days to tracheostomy and days to disconnection (p = 0.092). PaO2 / FiO2 (PAFI) before tracheostomy and Simplified Acute Physiology Score III (SAPS III) at admission presented a statistical relation with mortality, with an OR of 1.683 (95%CI; 0.926–2.351; p = 0.078) and an OR of 1.312 (CI95%: 1.011–1.703; p = 0.034) respectively. The length of stay in the ICU until the tracheostomy was not related to the risk of death (p = 0.682). PEEP and PaO2/FiO2 (PAFI) at admission and before tracheostomy and APACHE II, SAPS III and SOFA at admission did not show influence over time on MV. We conclude that the delay in tracheostomy increase the days on mechanical ventilation but does not influence stay or mortality., Highlights • For each day of delay in tracheostomy, the days of mechanical ventilation were increased by 0.6 days. • Timing of the tracheostomy did not influence days of disconnection from mechanical ventilation, ICU stay, or mortality. • There was no relationship between days to tracheostomy and days to disconnection. • Respiratory variables (PEEP and PaO2 / FiO2 on admission and before tracheostomy) and patient severity scales (APACHE II, SAPS III and SOFA on admission) did not show influence over time on mechanical ventilation. • The length of stay in the ICU until the tracheostomy was not related to the risk of death.

Introduction Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1 beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL- 6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL- 6, IL- 8 and PaO2 in critical patients. Conclusions While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness., This work has been made by an international team pertaining to the Spanish-Canadian Consortium for the Study of Influenza Immunopathogenesis. The authors would like to thank Lucia Rico and Veronica Iglesias for their assistance in the technical development of the multiplex cytokine assays, to Bego a Nogueira for her technical support, and to Nikki Kelvin for language revision of this article. This work was possible thanks to the financial support obtained from the Ministry of Science of Spain and Consejeria de Sanidad Junta de Castilla y Leon, Programa de investigacion comisionada en gripe, GR09/0021, Programa para favorecer la incorporacion de grupos de investigacion en las Instituciones del Sistema Nacional de Salud, EMER07/050, and Proyectos en Investigacion Sanitaria, PI081236. CIHR, NIH and LKSF-Canada support DJK. This sponsorship made possible reagent acquisition and sample transportation between participant groups.