Does elite European match-play affect salivary immunoglobulin-A and cortisol in soccer players? The influence of playing status and match outcome.

Introduction: The aims of this study were to: a) investigate salivary immunoglobulin A (s-IgA) and cortisol (s-Cort) responses to nine competitive fixtures in starting and non- starting soccer players; and b) compare s-IgA and s-Cort responses of starters and non-starters considering match outcome. Methods: Saliva from 19 male outfield players from an elite soccer team (mean ± SD, age 26 ± 4 years; weight 80.5 ± 8.1 kg; height 1.83 ± 0.07 m; body-fat 10.8% ± 0.7%) was collected. Saliva samples were taken on the day before each match (MD-1), 60-min before kick-off (MDpre), 30-min post-match (MDpost), and 72-h post-match (MD+3). There were five wins, one draw and three losses. Results: The mean s-IgA value was found to be significantly lower at MD+3 compared to MDpre and MDpost. s-Cort was significantly higher at MDpost compared to MD-1 and MDpre. When compared to MDpre, a statistically significant decrease in s-Cort was observed at MD+3 compared to MDpost. Starters displayed higher s-Cort values across the nine matches. There was a significant group-by-time interaction for s-Cort. There was a significant increase in s-Cort levels at MDpost compared to MD-1 and from MDpre to MDpost in starting players. At MDpost, starters had significantly higher s-Cort values. s-IgA values of starting and non- starting players following successful and unsuccessful matches did not reveal a significant difference. However, similar analysis of s-Cort in successful matches showed a significant difference between starters and non-starters. s-IgA values at MD-1, MDpre, MDpost and MD+3 in starters and non-starters following successful and unsuccessful matches revealed significant differences at MDpre and MDpost in starters, respectively. Furthermore, s-Cort values at MD-1, MDpre, MDpost and MD+3 in starters and non-starters in successful and unsuccessful matches revealed significant differences at MD+3 in starting players. Discussion: The present study suggests that in elite level soccer players, both starting status and match outcome influence s-IgA and s-Cort responses, particularly starters. Specifically, s-IgA was lower for starters before and after the match following successful outcomes. Moreover, higher s-Cort values were found before the match while lower values occurred after the match for starters in successful matches.

Artificial intelligence to assist specialists in the detection of haematological diseases.

Artificial intelligence, particularly the growth of neural network research and development, has become an invaluable tool for data analysis, offering unrivalled solutions for image generation, natural language processing, and personalised suggestions. In the meantime, biomedicine has been presented as one of the pressing challenges of the 21st century. The inversion of the age pyramid, the increase in longevity, and the negative environment due to pollution and bad habits of the population have led to a necessity of research in the methodologies that can help to mitigate and fight against these changes. The combination of both fields has already achieved remarkable results in drug discovery, cancer prediction or gene activation. However, challenges such as data labelling, architecture improvements, interpretability of the models and translational implementation of the proposals still remain. In haematology, conventional protocols follow a stepwise approach that includes several tests and doctor-patient interactions to make a diagnosis. This procedure results in significant costs and workload for hospitals. In this paper, we present an artificial intelligence model based on neural networks to support practitioners in the identification of different haematological diseases using only rutinary and inexpensive blood count tests. In particular, we present both binary and multiclass classification of haematological diseases using a specialised neural network architecture where data is studied and combined along it, taking into account the clinical knowledge of the problem, obtaining results up to 96% accuracy for the binary classification experiment. Furthermore, we compare this method against traditional machine learning algorithms such as gradient boosting decision trees and transformers for tabular data. The use of these machine learning techniques could reduce the cost and decision time and improve the quality of life for both specialists and patients while producing more precise diagnoses.

The use of anthropometrical variables for detection of homeostatic measurement assessment-insulin resistance (HOMA-IR) in female participants of a physical exercise program.

BACKGROUND: The Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) is a recognized and validated method which uses the levels of fasting glucose in blood and insulin of patients to evaluate the insulin resistance. AIMS: The purpose of the present study was to assess the cut-off values for anthropological variables to identify the (HOMA-IR) index in female participants of a physical exercise program. In addition, the association and prediction of insulin resistance by anthropological variables was studied. METHODS: A total of 143 participants (45.64 ± 13.17 years) volunteered for this study. Clinical data were collected by means of a self-reported questionnaire. Body weight and BMI were assessed by bioelectrical impedance analysis and skinfold thickness was taken using a caliper. Girths were assessed with a flexible metallic tape measures and finally, the HOMA-IR was calculated by the formula as follows: fasting plasma insulin ((µU/ml) x fasting plasma glucose (mmol/L). RESULTS: The outcomes of the study indicated that the AUC of anthropometrical variables for identifying HOMA-IR are reflected primarily in weight, waist-to-hip ratio, waist-to-thigh ratio, subscapular skinfold thickness, abdominal skinfold thickness, hip circumference, chest circumference, upper arm muscular girths (tensed and relaxed) (all, p ≤ 0.001), triceps skinfold thickness (p 109 cm (specificity: 99.2  waist circumference > 116 cm (specificity: 99.2 %) and abdomen skinfold < 8.8 (specificity: 97.6 %), predict the HOMA-IR in 35.29 %, 29.41 %, 23.53 % and 23.53 %, respectively. CONCLUSION: The present empirical study demonstrates that hip, chest and waist circumference on the one hand, and abdomen skinfold on the other hand are markers that are relevant to the identification of HOMA-IR index in females (Tab. 3, Ref. 33). Text in PDF www.elis.sk Keywords: insulin resistance, anthropometry, cut-off value, women, HOMA-IR.

One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab.

Ravulizumab every 8 weeks showed non-inferiority to eculizumab every 2 weeks in a 26-week, phase 3, randomized controlled trial in adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on eculizumab (NCT03056040). We report results from the first 26 weeks of the extension period in which patients continued ravulizumab (n = 96) or switched from eculizumab to ravulizumab (n = 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) with ravulizumab-ravulizumab and 5.8% (27%) with eculizumab-ravulizumab from primary evaluation period baseline. During the extension period, four patients (ravulizumab-ravulizumab, n = 3; eculizumab-ravulizumab, n = 1) experienced breakthrough hemolysis, but none associated with serum free C5 ≥ 0.5 µg/mL. Mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores remained stable through week 52. During the extension period, proportions of patients avoiding transfusion remained stable (ravulizumab-ravulizumab, 86.5%; eculizumab-ravulizumab, 83.2%); 81.2% and 81.1%, respectively, had stabilized hemoglobin. All patients maintained serum free C5 levels < 0.5 µg/mL. Adverse events were generally similar between groups, and rates were lower in the extension period. Adults with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy, with consistent efficacy in patients who received eculizumab during the primary evaluation period and then switched to ravulizumab. Ravulizumab was well tolerated.

Patient preferences and quality of life implications of ravulizumab (every 8 weeks) and eculizumab (every 2 weeks) for the treatment of paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Eculizumab has transformed management of paroxysmal nocturnal hemoglobinuria (PNH) since its approval. However, its biweekly dosing regimen remains a high treatment burden. Ravulizumab administered every 8 weeks demonstrated noninferiority to eculizumab in two phase 3 trials. In regions where two PNH treatment options are available, it is important to consider patient preference. OBJECTIVE: The aim of this study was to assess patient preference for ravulizumab or eculizumab. METHODS: Study 302s (ALXN1210-PNH-302s) enrolled PNH patients who participated in the extension period of phase 3 study ALXN1210-PNH-302. In the parent study, eculizumab-experienced adult PNH patients received ravulizumab or eculizumab during a 26-week primary evaluation period. All patients in the extension period received ravulizumab. In study 302s, patient treatment preference was evaluated using an 11-item PNH-specific Patient Preference Questionnaire (PNH-PPQ©). Of 98 patients, 95 completed PNH-PPQ© per protocol for analysis. RESULTS: Overall, 93% of patients preferred ravulizumab whereas 7% of patients either had no preference (6%) or preferred eculizumab (1%) (P < 0.001). For specific aspects of treatment, ravulizumab was preferred (in comparison to no preference or eculizumab) on infusion frequency (98% vs. 0% vs. 2%), ability to plan activities (98% vs. 0% vs. 2%), and overall quality of life (88% vs. 11% vs. 1%), among other aspects. Most participants selected frequency of infusions as the most important factor determining preference (43%), followed by overall quality of life (23%). CONCLUSION: This study shows that a substantial proportion of patients preferred ravulizumab over eculizumab and provides an important patient perspective on PNH treatment when there is more than one treatment option.

Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study.

Ravulizumab, a new complement component C5 inhibitor administered every 8 weeks, was noninferior to eculizumab administered every 2 weeks in complement-inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). This study assessed noninferiority of ravulizumab to eculizumab in clinically stable PNH patients during previous eculizumab therapy. In this phase 3, open-label, multicenter study, 195 PNH patients on labeled-dose (900 mg every 2 weeks) eculizumab for >6 months were randomly assigned 1:1 to switch to ravulizumab (n = 97) or continue eculizumab (n = 98). Primary efficacy end point was percentage change in lactate dehydrogenase (LDH) from baseline to day 183. Key secondary end points included proportion of patients with breakthrough hemolysis, change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, transfusion avoidance, and stabilized hemoglobin. In 191 patients completing 183 days of treatment, ravulizumab was noninferior to eculizumab (P inf < .0006 for all end points), including percentage change in LDH (difference, 9.21% [95% confidence interval (CI), -0.42 to 18.84], P = .058 for superiority), breakthrough hemolysis (difference, 5.1 [95% CI, -8.89 to 18.99]), change in FACIT-Fatigue score (difference, 1.47 [95% CI, -0.21 to 3.15]), transfusion avoidance (difference, 5.5 [95% CI, -4.27 to 15.68]), and stabilized hemoglobin (difference, 1.4 [95% CI, -10.41 to 13.31]). The most frequently reported adverse event was headache (26.8%, ravulizumab; 17.3%, eculizumab). No meningococcal infections or discontinuations due to adverse events occurred. Patients with PNH may be safely and effectively switched from labeled-dose eculizumab administered every 2 weeks to ravulizumab administered every 8 weeks. This trial was funded by Alexion Pharmaceuticals, Inc., and is registered at www.clinicaltrials.gov as #NCT03056040.

Low cardiac output syndrome in the postoperative period of cardiac surgery. Profile, differences in clinical course and prognosis. The ESBAGA study. / Síndrome de bajo gasto cardiaco en el postoperatorio de cirugía cardiaca. Perfil, diferencias en evolución clínica y pronóstico. Estudio ESBAGA.

OBJECTIVES: An analysis is made of the clinical profile, evolution and differences in morbidity and mortality of low cardiac output syndrome (LCOS) in the postoperative period of cardiac surgery, according to the 3 diagnostic subgroups defined by the SEMICYUC Consensus 2012. DESIGN: A multicenter, prospective cohort study was carried out. SETTING: ICUs of Spanish hospitals with cardiac surgery. PATIENTS: A consecutive sample of 2,070 cardiac surgery patients was included, with the analysis of 137 patients with LCOS. INTERVENTIONS: No intervention was carried out. RESULTS: The mean patient age was 68.3±9.3 years (65.2% males), with a EuroSCORE II of 9.99±13. NYHA functional class III-IV (52.9%), left ventricular ejection fraction<35% (33.6%), AMI (31.9%), severe PHT (21.7%), critical preoperative condition (18.8%), prior cardiac surgery (18.1%), PTCA/stent placement (16.7%). According to subgroups, 46 patients fulfilled hemodynamic criteria of LCOS (group A), 50 clinical criteria (group B), and the rest (n=41) presented cardiogenic shock (group C). Significant differences were observed over the evolutive course between the subgroups in terms of time subjected to mechanical ventilation (114.4, 135.4 and 180.3min in groups A, B and C, respectively; P<.001), renal replacement requirements (11.4, 14.6 and 36.6%; P=.007), multiorgan failure (16.7, 13 and 47.5%), and mortality (13.6, 12.5 and 35.9%; P=.01). The mean maximum lactate concentration was higher in cardiogenic shock patients (P=.002). CONCLUSIONS: The clinical evolution of these patients leads to high morbidity and mortality. We found differences between the subgroups in terms of the postoperative clinical course and mortality.

TGFß induces BIGH3 expression and human retinal pericyte apoptosis: a novel pathway of diabetic retinopathy.

PurposeOne of the earliest hallmarks of diabetic retinopathy is the loss of retinal pericytes. However, the mechanisms that promote pericyte dropout are unknown. In the present study, we propose a novel pathway in which pericyte apoptosis is mediated by macrophages, TGFß and pro-apoptotic BIGH3 (TGFß-induced Gene Human Clone 3) protein.Patients and methodsTo elucidate this pathway, we assayed human retinal pericyte (HRP) apoptosis by TUNEL assay, BIGH3 mRNA expression by qPCR, and BIGH3 protein expression by western blot analysis. HRP were treated with BIGH3 protein, TGFß1 and TGFß2 and inhibition assays were carried out by blocking with antibodies against BIGH3. The distribution of BIGH3 and CD68+ macrophages were compared in a post-mortem donor eye with 7-year history of Type II diabetes and histopathogically confirmed non-proliferative diabetic retinopathy (NPDR).ResultsTGFß induced a significant increase in BIGH3 mRNA and protein expression, and HRP apoptosis. BIGH3 treatment showed HRP undergo apoptosis in a dose-dependent manner. At 5 µg/ml, BIGH3 induced 3.5-times more apoptosis in HRP than in retinal endothelial cells. TGFß induced apoptosis was inhibited by blocking with antibodies against BIGH3. In an example of NPDR, BIGH3 accumulated within the walls of the inner retina arterioles. Macrophage infiltrates were frequently associated with these vessels and the inner nuclear layer.ConclusionTogether with our previously published results on macrophage-induced retinal endothelial cell apoptosis, the present study supports a novel inflammatory pathway mediated by macrophages and the BIGH3 protein leading to HRP apoptosis. As shown in human post-mortem globes, these observations are clinically relevant, suggesting a new mechanism underlying pericyte dropout during NPDR.

Update on transcobalamin deficiency: clinical presentation, treatment and outcome.

Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.

Haemoglobinopathies with high oxygen affinity. Experience of Erythropathology Cooperative Spanish Group.

Haemoglobinopathies are the world's most frequently found monogenic disorders. In the cases with high oxygen affinity, the decrease in the liberation of the oxygen determines a secondary erythrocytosis. In this work, we present 17 unrelated families of Caucasian race and of Spanish origin, with ten variants of haemoglobin or haemoglobinopathies with high oxygen affinity which were diagnosed in our laboratory. Of the ten haemoglobinopathies, in four (the Hb San Diego, the Hb Johnstown, the Hb Malmö and the Hb Columbia-Missouri), the change of amino acid affects zones of the contact alpha(1)beta(2); in two variants (the Hb Strasbourg and the Hb Syracuse), it affects the unions with 2,3-DPG in the central cavity; in the other two (the Hb Badalona and the Hb La Coruña), the cavity of contact with the group haem is affected; in one (Hb Bethesda), it affects the zone of contact alpha(1)beta(1;) and in one (Hb Olympia), the position 20 of the chain in the helix B in the surface of the protein is affected. In all cases, the change of amino acid, though of different form, facilitates that the quaternary structure of the haemoglobin becomes stable in its relaxed configuration so the transfer of oxygen and the P(50) value are decreased. All cases were sent to our laboratory because of shown erythrocytosis. In the majority of them, the diagnosis was done during an analysis of routine or for being relatives of the first ones.

[The H63D mutation in the HFE gene is related to the risk of hepatocellular carcinoma]. / La mutacion H63D del gen HFE se asocia con un riesgo aumentado de carcinoma hepatocelular .

AIM: To disclose whether mutations in the HFE gene inducing liver iron overload are related to the risk of hepatocellular carcinoma (HCC) in otherwise predisposed patients. PATIENTS AND METHODS: One hundred and ninety-six patients (161 males) diagnosed with HCC and 181 healthy controls were included in the study. All subjects were white Spaniards.C282Y and H63D mutations in the HFE gene were identified in leucocyte genomic DNA using a polymerase chain reaction (PCR) and specific restriction enzymes. RESULTS (CASES/CONTROLS): 1. Genotype distribution: a) C282Y mutation: homozygotes 1/0, heterozygotes 12/23, wild type 183/158 (p = 0.07, non significant); b) H63D mutation: homozygotes 9/5, heterozygotes 85/52, wild type 102/124 (0dds ratio 2.00, 95% C.I. 1.29-3.12, p = 0.002. Four cases and 6 controls were carriers of heterozygous mixed genotypes. 2. Allele frequencies: a) C282Y mutation: wild type allele 378/339, mutated allele 14/23 (p = 0.11, non significant); b) H63D mutation: wild type allele 289/300, mutated allele 103/62 (0dds ratio 1.72, 95% C.I. 1.19-2.50, p = 0.004). Age at diagnosis, gender and etiology of the underlying liver disease do not influence these findings. CONCLUSION: The C282Y mutation in the HFE gene is not related to the risk of HCC in non-hemochromatosis patients. The H63D mutation is associated with a higher risk of HCC in cirrhotic patients irrespective of their underlying liver disease.

La mutacion H63D del gen HFE se asocia con un riesgo aumentado de carcinoma hepatocelular / The H63D mutation of the HFE gene is related to the risk of hepatocellular carcinoma

Objetivo: comprobar si las mutaciones del gen HFE, que puedeninducir sobrecarga hepática de hierro, guardan relación conel riesgo de desarrollar carcinoma hepatocelular (CHC) en sujetospredispuestos a sufrir este tumor.Material y métodos: se han incluido 196 pacientes (161 varones)diagnosticados de CHC. Ninguno estaba diagnosticado dehemocromatosis. El grupo control estaba constituido por 181 sujetossanos. Todos los sujetos eran españoles de raza blanca.Las mutaciones C282Y y H63D del gen HFE se identificaronmediante reacción en cadena de polimerasa (PCR) sobre ADN genómicoleucocitario utilizando enzimas de restricción específicas.Resultados (casos/controles): 1. Distribución genotípica:a) mutación C282Y: 1/0 homocigotos, 12/23 heterocigotos,183/158 normales (p = 0,07, n.s.); y b) mutación H63D: 9/5homocigotos, 85/52 heterocigotos, 102/124 normales (odds ratio2,00, IC95% 1,29-3,12, p = 0,002). Cuatro casos y seis controleseran heterocigotos compuestos. 2. Frecuencias alélicas: a)mutación C282Y: normales 378/339, mutados 14/23 (p =0,11, n.s.); b) mutación H63D: normales 289/300; mutados103/62 (odds ratio 1,72, IC95% 1,19-2,50, p = 0,004). No seobservaron diferencias en relación con el sexo, la edad o la etiología(VHC, VHB, etílica o mixta) de la hepatopatía previa.Conclusiones: la mutación C282Y no guarda relación con elriesgo de desarrollar CHC en sujetos sin hemocromatosis conocida.La posesión de la mutación H63D se asocia con un riesgo aumentadode desarrollar CHC independientemente de la etiologíade la hepatopatía crónica subyacente

Aim: to disclose whether mutations in the HFE gene inducingliver iron overload are related to the risk of hepatocellular carcinoma(HCC) in otherwise predisposed patients.Patients and methods: one hundred and ninety-six patients(161 males) diagnosed with HCC and 181 healthy controls wereincluded in the study. All subjects were white Spaniards.C282Y and H63D mutations in the HFE gene were identifiedin leucocyte genomic DNA using a polymerase chain reaction(PCR) and specific restriction enzymes.Results (cases/controls): 1. Genotype distribution: a)C282Y mutation: homozygotes 1/0, heterozygotes 12/23, wildtype 183/158 (p = 0.07, non significant); b) H63D mutation: homozygotes9/5, heterozygotes 85/52, wild type 102/124 (0ddsratio 2.00, 95% C.I. 1.29-3.12, p = 0.002. Four cases and 6controls were carriers of heterozygous mixed genotypes. 2. Allelefrequencies: a) C282Y mutation: wild type allele 378/339, mutatedallele 14/23 (p = 0.11, non significant); b) H63D mutation:wild type allele 289/300, mutated allele 103/62 (0dds ratio1.72, 95% C.I. 1.19-2.50, p = 0.004). Age at diagnosis, genderand etiology of the underlying liver disease do not influence thesefindings.Conclusion: the C282Y mutation in the HFE gene is not relatedto the risk of HCC in non-hemochromatosis patients. TheH63D mutation is associated with a higher risk of HCC in cirrhoticpatients irrespective of their underlying liver disease

Receptor sérico de transferrina en niños sanos. Valor diagnóstico en la anemia infecciosa y en la ferropénica / Serum transferrin receptor in healthy children. diagnostic yield in ferropenic and infectious anemia

Antecedentes; El receptor sérico de transferrina (RsTf) ofrece ventajas para evaluar el estado de hierro celular por no alterarse en situaciones de enfermedad aguda o crónica. Objetivo Establecer valores de referencia para nuestro laboratorio del RsTf en niños sanos, conocer la distribución de esta variable en niños con enfermedad aguda y en niños con déficit de hierro, así como evaluar el rendimiento diagnóstico del RsTf para distinguir anemia ferropénica de anemia infecciosa y de sus parámetros relacionados con la ferritina (F): cociente RsTf/F e índice RsTf-F (RsTf/log ferritina).Pacientes y métodos Análisis descriptivo transversal durante un período de 18 meses en 132 niños entre 6 meses y 16 años de edad que fueron divididos en tres grupos: sanos, con enfermedad aguda y con déficit de hierro, estudiando la distribución del RsTf, y evaluando su rendimiento diagnóstico para diferenciar la anemia ferropénica de la anemia que acompaña a enfermedad aguda. Resultados De los 132 pacientes, 30 se excluyeron por no contar con alguno de los parámetros relevantes de este estudio y 19 fueron apartados por ser portadores de rasgo talasémico. En los 30 niños sanos la media del RsTf fue 1,2 mg/l (desviación estándar [DE], 0,36); mediana 1,02 (rango intercuartílico [RIQ], 0,7-1,7). Los 32 niños con enfermedad aguda, con o sin anemia, mostraron valores de RsTf similares a los de niños sanos (p > 0,05). Los valores del RsTf fueron superiores en niños con déficit de hierro (21 niños; RsTf, M 1,67 mg/l; DE, 0,98) que en niños sanos, aunque sin significación estadística (p 0,08). Los valores más altos del RsTf correspondieron a niños con anemia ferropénica (RsTf, M 2,13 mg/l; DE, 1,14), con una diferencia estadísticamente significativa respecto a los niños sanos (p 0,04) y a los niños con ferropenia latente (niños con déficit de hierro pero sin anemia) (p 0,01).El cociente RsTf/F mostró un rendimiento diagnóstico óptimo para distinguir entre anemia ferropénica y anemia por enfermedad aguda. Con valores de este cociente superiores a 80,7 se puede sospechar como causa de la anemia la ferropenia con un valor global de la prueba de 100 por ciento (intervalo de confianza del 95 por ciento [IC 95 por ciento], 75,91-99,42). Conclusiones El RsTf puede ser de utilidad para la evaluación del estado de hierro intracelular en niños. Sus valores no se modifican durante procesos agudos y en combinación con la ferritina ofrece un rendimiento diagnóstico óptimo para distinguir anemia ferropénica de anemia infecciosa (AU)

[Serum transferrin receptor in healthy children. Diagnostic yield in ferropenic and infectious anemia]. / Receptor sérico de transferrina en niños sanos. Valor diagnóstico en la anemia infecciosa y en la ferropénica.

BACKGROUND: The serum transferrin receptor (TfR) presents certain advantages over other parameters of cellular iron status because it does not vary in acute or chronic diseases. OBJECTIVE: To establish reference ranges of TfR in healthy children for our laboratory, to define the distribution of this variable in children with acute illness and in those with iron deficiency, and to evaluate the diagnostic yield of TfR, the transferrin-receptor/ferritin ratio (TfR/F) and the transferrin-receptor-ferritin index (TfR-F) in distinguishing ferropenic from infectious anemia. PATIENTS AND METHODS: A descriptive, cross-sectional analysis was conducted in 132 children aged from 6 months to 16 years for a period of 18 months. The subjects were classified in three groups: healthy children, children with acute illness, and children with iron deficiency. The distribution of TfR and its diagnostic yield were evaluated. RESULTS: Of the 132 subjects, 30 were excluded because they lacked one or more of the parameters under analysis and 19 were excluded because they showed a thalassemic trait. In the 30 healthy children, the mean TfR concentration was 1.2 mg/l (SD 0.36) and the median was 1.02 (IQR 0.7-1.7). In the 32 children with acute illness, with or without anemia, TfR values were similar to those found in healthy children (p > 0.05). TfR values were higher in children with iron deficiency (21 patients; mean TfR value: 1.67 mg/l SD 0:98) than in healthy children but this difference was not statistically significant (p 0.08). The highest TfR values were found in the group with ferropenic anemia (mean TfR value: 2.13 mg/l SD 1.14) with a statistically significant difference between healthy children (p 0.04) and those with iron deficiency without anemia (p 0.01). The TfR/F ratio showed an optimal diagnostic yield in distinguishing ferropenic from acute disease anemia. If this ratio is higher than 80.7 ferropenia can be suspected as the cause of the anemia with a global value of the test of 100 % (95 % CI: 75.91-99.42). CONCLUSIONS: TfR could be useful in evaluating intracellular iron status in children. Acute disease does not alter TfR values and, in combination with ferritin, TfR offers an optimal diagnostical yield in distinguishing ferropenic from acute illness anemia.

Evolution of the visual cycle: the role of retinoid-binding proteins.

The trafficking of retinoids in the retina represents a model to study soluble hormone-binding proteins in a complex system subject to profound evolutionary adaptations. Although a remarkable illustration of convergent evolution, all visual systems detect light in the same way, that is through the photoisomerization of an 11-cis retinoid to a corresponding trans isomer. What is strikingly different between the systems, is the mechanism by which the 11-cis chromophore is reformed and visual pigment regenerated in a process known as the visual cycle. The variations of the cycle address a problem inherent to retinoids themselves. That is, the properties that make these molecules suited for light detection also account for their susceptibility to oxidative and isomeric degradation, and cellular toxicity. The cycle therefore provides an opportunity to examine the role of soluble hormone-binding proteins within an integrative and evolutionary context. The present review focuses on interphotoreceptor retinoid-binding protein (IRBP), a controversial glycolipoprotein that recruits a protein fold common to Cterminal-processing proteases and the crotonase family. This unorthodox retinoid-binding protein is entrapped in the subretinal compartment of those eyes that translocate visual cycle retinoids between the photoreceptors and the retinal pigment epithelium. Recent studies suggest that we should look beyond a strictly carrier function if we are to appreciate the role of IRBP in the visual cycle. Here we draw lessons from other soluble hormone-binding proteins to anticipate avenues of future research likely to provide insight into the structure and function of IRBP in vision.

Trilateral retinoblastoma variant indicative of the relevance of the retinoblastoma tumor-suppressor pathway to medulloblastomas in humans.

Results of recent studies have led investigators to suggest that the retinoblastoma tumor-suppressor (rb) gene plays an underappreciated role in the genesis of brain tumors. Such tumors cause significant rates of mortality in children suffering from hereditary retinoblastoma. It has been assumed that the pineal gland, which is ontogenetically related to the retina, accounts for the intracranial origin of these trilateral neoplasms. To address this issue, the authors describe an unusual trilateral retinoblastoma variant. The authors provide a detailed clinicopathological correlation by describing the case of a child with bilateral retinoblastoma who died of a medulloblastoma. The intraocular and intracranial neoplasms were characterized by performing detailed imaging, histopathological, and postmortem studies. Karyotype analysis and fluorescence in situ hybridization were used to define the chromosomal defect carried by the patient and members of her family. An insertion of the q12.3q21.3 segment of chromosome 13 into chromosome 18 at band q23 was identified in members of the patient's family. This translocation was unbalanced in the proband. The intraocular and cerebellar neoplasms were found to be separate primary neoplasms. Furthermore, the pineal gland was normal and the cerebellar neoplasm arose within the vermis as a medulloblastoma. Finally, the two neoplasms had different and characteristically identifiable cytolological and immunohistochemical profiles. The findings of the present study, taken together with those of recent molecular and transgenic studies, support the emerging concept that rb inactivation is not restricted to central nervous system regions of photoreceptor lineage and that inactivation of this tumor suppressor pathway may be relevant to the determination of etiological factors leading to medulloblastoma in humans.