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1.
Scand J Med Sci Sports ; 34(4): e14617, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38566409

RESUMEN

PURPOSE: In Football, the high-intensity running bouts during matches are considered decisive. Interestingly, recent studies showed that peak fat oxidation rates (PFO) are higher in football players than other athletes. This study aimed to investigate whether PFO increases following a pre-season. Secondarily, and due to COVID-19, we investigated whether PFO is related to the physical performance in a subgroup of semi-professional male football players. METHODS: Before and after 8 weeks of pre-season training, 42 sub-elite male football players (18 semi-professionals and 24 non-professionals) had a dual-energy x-ray absorptiometry scan and performed a graded exercise test on a treadmill for the determination of PFO, the exercise intensity eliciting PFO (Fatmax) and peak oxygen uptake (V̇O2peak). Additionally, the semi-professional players performed a Yo-Yo Intermittent Recovery Test level 2 (YYIR2) before and after pre-season training to determine football-specific running performance. RESULTS: PFO increased by 11 ± 10% (mean ± 95% CI), p = 0.031, and V̇O2peak increased by 5 ± 1%, p < 0.001, whereas Fatmax was unchanged (+12 ± 9%, p = 0.057), following pre-season training. PFO increments were not associated with increments in V̇O2peak (Pearson's r2 = 0.00, p = 0.948) or fat-free mass (FFM) (r2 = 0.00, p = 0.969). Concomitantly, YYIR2 performance increased in the semi-professional players by 39 ± 17%, p < 0.001, which was associated with changes in V̇O2peak (r2 = 0.35, p = 0.034) but not PFO (r2 = 0.13, p = 0.244). CONCLUSIONS: PFO, V̇O2peak, and FFM increased following pre-season training in sub-elite football players. However, in a subgroup of semi-professional players, increments in PFO were not associated with improvements in YYIR2 performance nor with increments in V̇O2peak and FFM.


Asunto(s)
Rendimiento Atlético , Carrera , Fútbol , Humanos , Masculino , Prueba de Esfuerzo , Oxígeno , Estaciones del Año
2.
J Clin Immunol ; 43(8): 1927-1940, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37581646

RESUMEN

Genetic variants in cell division cycle 42 (CDC42) can manifest with dysmorphic features, autoinflammation, hemophagocytic lymphohistiocytosis, and thrombocytopenia, whereas defective thymopoiesis is a rare disease manifestation. We report a novel CDC42 missense variant (c.46A > G, p.Lys16Glu) resulting in infection and HPV-driven carcinogenesis in the mosaic mother and impaired thymopoiesis and profound T cell lymphopenia in the heterozygous daughter identified through newborn screening for SCID. We found that surface expression of IL-7Rα (CD127) was decreased, consistent with reduced IL-7-induced STAT5 phosphorylation and accelerated apoptotic T cell death. Consistent with the vital role of IL-7 in regulating thymopoiesis, both patients displayed reduced T cell receptor CDR3 repertoires. Moreover, the CDC42 variant prevented binding to the downstream effector, p21-activated kinase (PAK)1, suggesting this impaired interaction to underlie reduced IL-7Rα expression and signaling. Here, we provide the first report of severely compromised thymopoiesis and perturbed IL-7Rα signaling caused by a novel CDC42 variant and presenting with diverging clinical and immunological phenotypes in patients.


Asunto(s)
Interleucina-7 , Quinasas p21 Activadas , Humanos , Recién Nacido , Apoptosis , Interleucina-7/genética , Receptores de Antígenos de Linfocitos T/genética , Transducción de Señal
3.
Hum Brain Mapp ; 44(2): 762-778, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36250712

RESUMEN

Segmenting deep brain structures from magnetic resonance images is important for patient diagnosis, surgical planning, and research. Most current state-of-the-art solutions follow a segmentation-by-registration approach, where subject magnetic resonance imaging (MRIs) are mapped to a template with well-defined segmentations. However, registration-based pipelines are time-consuming, thus, limiting their clinical use. This paper uses deep learning to provide a one-step, robust, and efficient deep brain segmentation solution directly in the native space. The method consists of a preprocessing step to conform all MRI images to the same orientation, followed by a convolutional neural network using the nnU-Net framework. We use a total of 14 datasets from both research and clinical collections. Of these, seven were used for training and validation and seven were retained for testing. We trained the network to segment 30 deep brain structures, as well as a brain mask, using labels generated from a registration-based approach. We evaluated the generalizability of the network by performing a leave-one-dataset-out cross-validation, and independent testing on unseen datasets. Furthermore, we assessed cross-domain transportability by evaluating the results separately on different domains. We achieved an average dice score similarity of 0.89 ± 0.04 on the test datasets when compared to the registration-based gold standard. On our test system, the computation time decreased from 43 min for a reference registration-based pipeline to 1.3 min. Our proposed method is fast, robust, and generalizes with high reliability. It can be extended to the segmentation of other brain structures. It is publicly available on GitHub, and as a pip package for convenient usage.


Asunto(s)
Encéfalo , Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagen , Redes Neurales de la Computación , Imagen por Resonancia Magnética/métodos
4.
Clin Immunol ; 241: 109070, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35779828

RESUMEN

Functional antibody deficiency is clinically assessed from antibody responses to vaccination. However, diagnostic vaccination is complex and may fail in practice. We hypothesized that the levels of naturally occurring antibodies against galactose-α-1,3-galactose (αGal) may represent alternative markers of functional antibody capacity. We included data from 229 patients with suspected primary immunodeficiency in a retrospective study. Antibody levels against αGal and twelve pneumococcal serotypes were determined with solid-phase immunoassays. Pneumococcal vaccinations and treatment with normal human immunoglobulin were assessed from medical records. Anti-αGal antibody levels correlated positively with anti-pneumococcal antibody levels measured before and after pneumococcal vaccination. Contrary to the anti-pneumococcal antibody levels, the anti-αGal antibody level showed potential for predicting subsequent immunoglobulin treatment - a marker of disease severity. Naturally occurring antibodies may reflect the functional capacity tested by diagnostic vaccination but add more useful clinical data. The clinical utility of this easy test should be evaluated in prospective studies.


Asunto(s)
Anticuerpos Antibacterianos , Enfermedades de Inmunodeficiencia Primaria , Galactosa , Humanos , Inmunoglobulina G , Vacunas Neumococicas , Estudios Prospectivos , Estudios Retrospectivos , Vacunación
5.
Immunology ; 162(4): 434-451, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33340093

RESUMEN

Naturally occurring antibodies are abundant in human plasma, but their importance in the defence against bacterial pathogens is unclear. We studied the role of the most abundant of such antibodies, the antibody against terminal galactose-α-1,3-galactose (anti-αGal), in the protection against pneumococcal infections (Streptococcus pneumonia). All known pneumococcal capsular polysaccharides lack terminal galactose-α-1,3-galactose, yet highly purified human anti-αGal antibody of the IgG class reacted with 48 of 91 pneumococcal serotypes. Anti-αGal was found to contain multiple antibody subsets that possess distinct specificities beyond their general reactivity with terminal galactose-α-1,3-galactose. These subsets in concert targeted a wide range of microbial polysaccharides. We found that anti-αGal constituted up to 40% of the total antibody reactivity to pneumococci in normal human plasma, that anti-αGal drives phagocytosis of pneumococci by human neutrophils and that the anti-αGal level was twofold lower in patients prone to pneumococcal infections compared with controls. Moreover, during a 48-year period in Denmark, the 48 anti-αGal-reactive serotypes caused fewer invasive pneumococcal infections (n = 10 927) than the 43 non-reactive serotypes (n = 18 107), supporting protection on the population level. Our findings explain the broad-spectrum pathogen reactivity of anti-αGal and support that these naturally occurring polyreactive antibodies contribute significantly to human protective immunity.


Asunto(s)
Anticuerpos ampliamente neutralizantes/metabolismo , Epítopos/inmunología , Galactosa/inmunología , Inmunoglobulina G/metabolismo , Neutrófilos/inmunología , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/fisiología , Adulto , Dinamarca/epidemiología , Susceptibilidad a Enfermedades , Femenino , Humanos , Inmunidad Humoral , Masculino , Fagocitosis , Infecciones Neumocócicas/epidemiología , Polisacáridos Bacterianos/inmunología
6.
Clin Exp Immunol ; 206(2): 226-236, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34473350

RESUMEN

Inflammation resulting from ischaemia/reperfusion injury can cause kidney graft dysfunction, increase the risk of delayed graft function and possibly reduce long-term graft survival. Remote ischaemic conditioning may protect against ischaemia/reperfusion injury and mitigate the immunological response to the graft. We investigated the immunological effects of remote ischaemic conditioning on kidney transplantation from deceased donors in the randomized CONTEXT study. Three circulating dendritic cell (DC) subtypes identified in peripheral blood from kidney transplant recipients [myeloid DCs, plasmacytoid DCs and immunoglobulin-like transcript (ILT)3+ DCs] were measured at baseline, days 1, 3 and 5 and 1 and 3 months after transplantation. We also quantified 21 cytokines at baseline, days 1 and 5 and 3 months after transplantation. Neither DC counts nor cytokine levels differed between patients receiving remote ischaemic conditioning and controls; however, several parameters exhibited dynamic and parallel alterations in the two groups over time, reflecting the immunological response to the kidney transplantation and immunosuppression.


Asunto(s)
Citocinas , Células Dendríticas , Precondicionamiento Isquémico , Trasplante de Riñón , Adulto , Recuento de Células , Citocinas/sangre , Citocinas/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
7.
Mov Disord ; 36(2): 360-369, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33103821

RESUMEN

OBJECTIVES: Parkinson's disease (PD) commonly affects visuospatial navigation causing postural instability and falls. Our overarching aim was to examine the visual and vestibular systems governing visuospatial navigation in PD. We hypothesize that PD affects vestibular and visual motion perception but to a different extent. The effects of PD on motion perception are dependent on the severity of the disease. METHODS: The two-alternative-forced-choice task objectively measured the motion perception during two experiments. One experiment examined the vestibular motion perception with en bloc movement of the platform. The second experiment tested the visual motion perception using an immersive virtual reality goggle. RESULTS: We found that accuracy, threshold, and precision of vestibular perception were more impaired in advanced-PD patients compared to those with a mild form of the disease. The parameters also correlated with the disease duration, overall axial motor impairment causing postural instability and falls, and subjective rating of the balance function. Such changes were present but less severe in visual motion perception. CONCLUSION: We conclude that PD affects motion perception in the visual and vestibular domains in a severity-dependent manner. The impact of the disease in the vestibular domain is more severe compared to the visual domain. © 2020 International Parkinson and Movement Disorder Society.


Asunto(s)
Percepción de Movimiento , Enfermedad de Parkinson , Vestíbulo del Laberinto , Accidentes por Caídas , Humanos , Enfermedad de Parkinson/complicaciones , Equilibrio Postural , Percepción Visual
8.
Neuromodulation ; 24(2): 248-258, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33389779

RESUMEN

OBJECTIVE: Subthalamic deep brain stimulation (DBS) is an established therapy for Parkinson's disease. Connectomic DBS modeling is a burgeoning subfield of research aimed at characterizing the axonal connections activated by DBS. This article describes our approach and methods for evolving the StimVision software platform to meet the technical demands of connectomic DBS modeling in the subthalamic region. MATERIALS AND METHODS: StimVision v2 was developed with Visualization Toolkit (VTK) libraries and integrates four major components: 1) medical image visualization, 2) axonal pathway visualization, 3) electrode positioning, and 4) stimulation calculation. RESULTS: StimVision v2 implemented two key technological advances for connectomic DBS analyses in the subthalamic region. First was the application of anatomical axonal pathway models to patient-specific DBS models. Second was the application of a novel driving-force method to estimate the response of those axonal pathways to DBS. Example simulations with directional DBS electrodes and clinically defined therapeutic DBS settings are presented to demonstrate the general outputs of StimVision v2 models. CONCLUSIONS: StimVision v2 provides the opportunity to evaluate patient-specific axonal pathway activation from subthalamic DBS using anatomically detailed pathway models and electrically detailed electric field distributions with interactive adjustment of the DBS electrode position and stimulation parameter settings.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Axones , Humanos , Enfermedad de Parkinson/terapia , Programas Informáticos
9.
Transfusion ; 59(6): 2030-2038, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30828821

RESUMEN

BACKGROUND: Blood donors are at increased risk of developing iron deficiency, and several studies have recommended iron supplementation for this group. The aim of this study was to investigate the effect of oral iron supplementation on risk of infections among healthy blood donors. STUDY DESIGN AND METHODS: We included 82,062 participants from the Danish Blood Donor Study who completed a questionnaire on health-related items including use of oral iron supplementation. Infection outcomes were ascertained by using ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis was used as the statistical model. Risk estimates are presented as crude hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During 19,978 person-years of observation, 6983 donors redeemed at least one prescription of antimicrobials. Similarly, during 19,829 person-years of observation, 242 donors were treated for infection at a hospital. Use of oral iron supplementation was not associated with redeemed prescriptions of antimicrobials in any strata: premenopausal women-HR 1.00, 95% CI 0.91-1.10; postmenopausal women-HR 1.07, 95% CI 0.87-1.32; and men-HR 1.01, 95% CI 0.84-1.21. In addition, use of oral iron supplementation was not associated with risk of hospital-based treatment for infection. CONCLUSION: In a large cohort of blood donors, use of oral iron supplementation was not associated with subsequent short-term risk of infection. These findings are important to help understanding the safety of using oral iron supplementation among blood donors and the general population.


Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Infecciones/epidemiología , Hierro/administración & dosificación , Administración Oral , Adolescente , Adulto , Anciano , Estudios de Cohortes , Dinamarca/epidemiología , Suplementos Dietéticos , Femenino , Humanos , Infecciones/sangre , Infecciones/etiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto Joven
10.
Transfusion ; 59(1): 226-231, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30536387

RESUMEN

BACKGROUND: Blood donors have an increased risk of low hemoglobin (Hb) levels due to iron deficiency. Therefore, knowledge of genetic variants associated with low Hb could facilitate individualized donation intervals. We have previously reported three specific single-nucleotide polymorphisms that were associated with ferritin levels in blood donors. In this study, we investigated the effect of these single-nucleotide polymorphisms on Hb levels in 15,567 Danish blood donors. STUDY DESIGN AND METHODS: We studied 15,567 participants in the Danish Blood Donor Study. The examined genes and single-nucleotide polymorphisms were 1) TMPRSS6, involved in regulation of hepcidin: rs855791; 2) HFE, associated with hemochromatosis: rs1800562 and rs1799945; 3) BTBD9, associated with restless leg syndrome: rs9357271; and 4) TF, encoding transferrin: rs2280673 and rs1830084. Associations with Hb levels and risk of Hb deferral were assessed in multivariable linear and logistic regression models. RESULTS: The HFE,rs1800562 G-allele and the HFE rs1799945 C-allele were associated with lower Hb levels in men and women, and with an increased risk of Hb below 7.8 mmol/L (12.5 g/dL) in women. Only the rs1799945 C-allele increased the risk of Hb below 8.4 mmol/L (13.5 g/dL) in men. In TMPRSS6, the rs855791 T-allele was associated with lower Hb levels in both men and women, and with an increased risk of low Hb among women. CONCLUSION: With this study we demonstrate that HFE and TMPRSS6 are associated with Hb levels and risk of Hb below the limit of deferral. Thus, genetic testing may be useful in a future assay for personalized donation intervals.


Asunto(s)
Donantes de Sangre , Hemoglobinas/metabolismo , Alelos , Dinamarca , Femenino , Proteína de la Hemocromatosis/genética , Hepcidinas/metabolismo , Humanos , Masculino , Proteínas de la Membrana/genética , Serina Endopeptidasas/genética
11.
Int J Mol Sci ; 20(12)2019 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-31200465

RESUMEN

Ischemic preconditioning (IPC) has been protective against ischemia-reperfusion injury (IRI), but the underlying mechanism is poorly understood. We examined whether IPC modulates the early inflammatory response after IRI. Nineteen healthy males participated in a randomised crossover trial with and without IPC before IRI. IPC and IRI were performed by cuff inflation on the forearm. IPC consisted of four cycles of five minutes followed by five minutes of reperfusion. IRI consisted of twenty minutes followed by 15 min of reperfusion. Blood was collected at baseline, 0 min, 85 min and 24 h after IRI. Circulating monocytes, T-cells subsets and dendritic cells together with intracellular activation markers were quantified by flow cytometry. Luminex measured a panel of inflammation-related cytokines in plasma. IRI resulted in dynamic regulations of the measured immune cells and their intracellular activation markers, however IPC did not significantly alter these patterns. Neither IRI nor the IPC protocol significantly affected the levels of inflammatory-related cytokines. In healthy volunteers, it was not possible to detect an effect of the investigated IPC-protocol on early IRI-induced inflammatory responses. This study indicates that protective effects of IPC on IRI is not explained by direct modulation of early inflammatory events.


Asunto(s)
Citocinas/sangre , Precondicionamiento Isquémico/efectos adversos , Daño por Reperfusión/terapia , Adulto , Anciano , Biomarcadores/sangre , Células Dendríticas/inmunología , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Daño por Reperfusión/sangre , Subgrupos de Linfocitos T/inmunología
13.
Eur J Nucl Med Mol Imaging ; 44(3): 449-458, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27785538

RESUMEN

INTRODUCTION: Immune cells utilize acetylcholine as a paracrine-signaling molecule. Many white blood cells express components of the cholinergic signaling pathway, and these are up-regulated when immune cells are activated. However, in vivo molecular imaging of cholinergic signaling in the context of inflammation has not previously been investigated. METHODS: We performed positron emission tomography (PET) using the glucose analogue 18F-FDG, and 11C-donepezil and 18F-FEOBV, markers of acetylcholinesterase and the vesicular acetylcholine transporter, respectively. Mice were inoculated subcutaneously with Staphylococcus aureus, and PET scanned at 24, 72, 120, and 144 h post-inoculation. Four pigs with post-operative abscesses were also imaged. Finally, we present initial data from human patients with infections, inflammation, and renal and lung cancer. RESULTS: In mice, the FDG uptake in abscesses peaked at 24 h and remained stable. The 11C-donepezil and 18F-FEOBV uptake displayed progressive increase, and at 120-144 h was nearly at the FDG level. Moderate 11C-donepezil and slightly lower 18F-FEOBV uptake were seen in pig abscesses. PCR analyses suggested that the 11C-donepezil signal in inflammatory cells is derived from both acetylcholinesterase and sigma-1 receptors. In humans, very high 11C-donepezil uptake was seen in a lobar pneumonia and in peri-tumoral inflammation surrounding a non-small cell lung carcinoma, markedly superseding the 18F-FDG uptake in the inflammation. In a renal clear cell carcinoma no 11C-donepezil uptake was seen. DISCUSSION: The time course of cholinergic tracer accumulation in murine abscesses was considerably different from 18F-FDG, demonstrating in the 11C-donepezil and 18F-FEOBV image distinct aspects of immune modulation. Preliminary data in humans strongly suggest that 11C-donepezil can exhibit more intense accumulation than 18F-FDG at sites of chronic inflammation. Cholinergic PET imaging may therefore have potential applications for basic research into cholinergic mechanisms of immune modulation, but also clinical applications for diagnosing infections, inflammatory disorders, and cancer inflammation.


Asunto(s)
Inhibidores de la Colinesterasa/farmacocinética , Indanos/farmacocinética , Piperidinas/farmacocinética , Radiofármacos/farmacocinética , Infecciones Estafilocócicas/diagnóstico por imagen , Acetilcolinesterasa/metabolismo , Adulto , Anciano , Animales , Radioisótopos de Carbono , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Células Renales/diagnóstico por imagen , Donepezilo , Femenino , Fluorodesoxiglucosa F18 , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Porcinos , Proteínas de Transporte Vesicular de Acetilcolina/metabolismo
14.
Transfusion ; 57(3): 571-577, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27900795

RESUMEN

BACKGROUND: Low hemoglobin (Hb) is associated with poor general health and adverse outcomes in a wide range of diseases. However, a link between Hb levels and the risk of infection among healthy individuals has yet to be investigated. STUDY DESIGN AND METHODS: Using data from the Scandinavian Donations and Transfusions database, 497,390 donors were followed after 5,458,499 donations in health registers. With 1,339,362 person-years of follow-up, Andersen-Gill Cox regression was used to study the association of Hb levels below deferral thresholds, very low Hb levels (in the lowest 0.1 percentile), and declining Hb levels with the risk of infection as measured by hospital or outpatient contact for infection and filling of prescription for antimicrobials, respectively, within 3 months of donation. Analyses were stratified by sex, menopausal status, and frequency of donation. RESULTS: Hb levels below deferral thresholds were not associated with a risk of hospital contact for infection among premenopausal women (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.95-1.14), postmenopausal women (HR, 0.77; 95% CI, 0.54-1.11), or men (HR, 0.97; 95% CI, 0.81-1.16), nor was there any association with hospital contact for very low Hb levels or patterns of declining Hb levels. However, subthreshold Hb levels were associated with a reduced risk of antimicrobial prescriptions among premenopausal women (HR, 0.92; 95% CI, 0.91-0.93), postmenopausal women (HR, 0.93; 95% CI, 0.89-0.97), and men (HR, 0.91; 95% CI, 0.88-0.94). CONCLUSIONS: Neither Hb levels below deferral thresholds nor very low or declining Hb levels were associated with an increased risk of infection. This is reassuring, because blood donation can lead to lower Hb levels.


Asunto(s)
Donantes de Sangre , Hemoglobinas/metabolismo , Sistema de Registros , Adulto , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Infecciones/sangre , Infecciones/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales
15.
Transfusion ; 56(3): 622-7, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26597663

RESUMEN

BACKGROUND: Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN AND METHODS: The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9-associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin < 15 ng/mL). RESULTS: In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION: Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron stores in men.


Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Ferritinas/sangre , Adolescente , Adulto , Anciano , Anemia Ferropénica/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Proteína de la Hemocromatosis , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Modelos Logísticos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas del Tejido Nervioso , Polimorfismo de Nucleótido Simple/genética , Serina Endopeptidasas/genética , Factores de Transcripción/genética , Transferrina/genética , Adulto Joven
16.
Epidemiology ; 26(4): 580-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25978794

RESUMEN

BACKGROUND: It is well known that obesity complicates the course of several diseases. However, it is unknown whether obesity affects the risk of infection among healthy individuals. METHODS: We included 37,808 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. Obesity was defined as a body mass index ≥ 30 kg/m(2). Infections among participants were identified by relevant ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis with age as the underlying timescale was used as the statistical model. RESULTS: During 113,717 person-years of observation, 1,233 participants were treated for infection at a hospital. Similarly, during 58,411 person-years of observation, 15,856 participants filled at least one prescription of antimicrobials. Obesity was associated with risk of hospital-based treatment for infection (women: hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI = 1.2, 1.9). For specific infections, obesity was associated with increased risk of abscesses (both sexes), infections of the skin and subcutaneous tissue (men), and respiratory tract infections and cystitis (women). Similarly, obesity was associated with filled prescriptions of antimicrobials overall (women: HR = 1.22, 95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad-spectrum penicillins. CONCLUSIONS: In a large cohort of healthy individuals, obesity was associated with risk of infection. This result warrants further studies of metabolism and the immune response.


Asunto(s)
Absceso/epidemiología , Donantes de Sangre , Cistitis/epidemiología , Obesidad/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones de los Tejidos Blandos/epidemiología , Absceso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Índice de Masa Corporal , Estudios de Cohortes , Cistitis/tratamiento farmacológico , Dinamarca/epidemiología , Dicloxacilina/uso terapéutico , Femenino , Floxacilina/uso terapéutico , Humanos , Incidencia , Infecciones/tratamiento farmacológico , Infecciones/epidemiología , Macrólidos/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Penicilina V/uso terapéutico , Penicilinas/uso terapéutico , Modelos de Riesgos Proporcionales , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Factores de Riesgo , Factores Sexuales , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Encuestas y Cuestionarios , Adulto Joven
17.
Transfusion ; 55(7): 1752-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25851623

RESUMEN

BACKGROUND: Health-related quality of life (HRQL) represents people's subjective assessment of their mental and physical well-being. HRQL is highly predictive of future health. The effect of iron deficiency without anemia induced by blood donation on HRQL is presently unknown. The aim was to explore the relationship between iron status and self-reported mental component score (MCS; SF-12) and physical component score (PCS; SF-12) in Danish blood donors. STUDY DESIGN AND METHODS: Complete relevant data, including the 12-item short-form health survey (SF-12), plasma ferritin levels, age, body mass index, smoking status, C-reactive protein levels, number of donations in the previous 3 years, and PCS and MCS, were available for 8692 men and 7683 women enrolled from March 1, 2010, to December 31, 2010. Multivariable linear and logistic (cutoff at the 10th percentile) regression analyses were used to assess the relationship between iron deficiency (ferritin < 15 ng/mL) and MCS and PCS, respectively. Analyses were performed separately for men and women. RESULTS: There was no significant relationship between iron deficiency and self-reported mental or physical health. CONCLUSION: This study found no association between iron stores and self-reported HRQL among Danish blood donors.


Asunto(s)
Donantes de Sangre , Ferritinas/sangre , Hierro/sangre , Salud Mental , Calidad de Vida , Autoinforme , Adolescente , Adulto , Factores de Edad , Anciano , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Estudios de Cohortes , Dinamarca , Femenino , Humanos , Deficiencias de Hierro , Masculino , Persona de Mediana Edad
18.
Transfusion ; 55(6): 1303-11, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25647099

RESUMEN

BACKGROUND: It is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels. STUDY DESIGN AND METHODS: Initiated in 2010, the Danish Blood Donor Study is a population-based study and biobank. We performed multivariable linear regression analysis to assess the effects of donation activity, physiologic and lifestyle factors, and diet on Hb levels among 15,197 donors. We also performed multivariable logistic regression to evaluate the effects of these factors on the risk of having low Hb (defined as Hb below the 10th percentile among men and women, respectively) and of a decrease in Hb greater than 0.5 mmol/L (0.8 g/dL) between successive donations. All analyses were performed stratified for sex and smoking status. We also tested a previously used model for the prediction of Hb. RESULTS: The strongest predictors of Hb and risk of low Hb were low ferritin (<15 ng/mL) and current use of iron supplementation (yes/no). No dietary factors were found to be consistently significant in multivariable models predicting Hb levels, risk of having low Hb, or risk of a decrease in Hb greater than 0.5 mmol/L. We found similar effects to previous studies of factors in the predictive model, with little additional effect of including smoking status and ferritin. CONCLUSIONS: As ferritin was the strongest predictor of Hb, this study supports the implementation of regular ferritin measurement as a method of risk assessment among blood donors.


Asunto(s)
Anemia Ferropénica/prevención & control , Donantes de Sangre/estadística & datos numéricos , Hemoglobinas/análisis , Adolescente , Adulto , Anciano , Anemia Ferropénica/etiología , Índice de Masa Corporal , Estudios de Cohortes , Anticonceptivos Orales , Dinamarca , Dieta , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Ferritinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Historia Reproductiva , Factores de Riesgo , Caracteres Sexuales , Fumar/sangre , Encuestas y Cuestionarios , Adulto Joven
19.
Transfusion ; 54(3 Pt 2): 789-96, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24372094

RESUMEN

BACKGROUND: Dietary studies show a relationship between the intake of iron enhancers and inhibitors and iron stores in the general population. However, the impact of dietary factors on the iron stores of blood donors, whose iron status is affected by blood donations, is incompletely understood. STUDY DESIGN AND METHODS: In the Danish Blood Donor Study, we assessed the effect of blood donation frequency, physiologic factors, lifestyle and supplemental factors, and dietary factors on ferritin levels. We used multiple linear and logistic regression analyses stratified by sex and menopausal status. RESULTS: Among high-frequency donors (more than nine donations in the past 3 years), we found iron deficiency (ferritin below 15 ng/mL) in 9, 39, and 22% of men, premenopausal women, and postmenopausal women, respectively. The strongest predictors of iron deficiency were sex, menopausal status, the number of blood donations in a 3-year period, and the time since last donation. Other significant factors included weight, age, intensity of menstruation, iron tablets, vitamin pills, and consumption of meat and wine. CONCLUSION: The study confirms iron deficiency as an important problem, especially among menstruating women donating frequently. The risk of iron depletion was largely explained by sex, menopausal status, and donation frequency. Other factors, including dietary and supplemental iron intake, had a much weaker effect on the risk of iron depletion.


Asunto(s)
Hierro/sangre , Adulto , Donantes de Sangre/estadística & datos numéricos , Dinamarca , Femenino , Humanos , Masculino , Persona de Mediana Edad , Suecia
20.
Scand J Infect Dis ; 46(8): 578-84, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24934989

RESUMEN

OBJECTIVES: The aim of this study was to assess hepatitis B virus (HBV) and hepatitis C virus (HCV) surveillance and management in HIV patients currently followed in an outpatient clinic at a Danish University Hospital. METHODS: Patient data, including demographic characteristics, clinical findings, and hepatitis serology, were reviewed at baseline. Patients with incomplete or non-updated serology within the last 2 y were retested in the next 6 months, and the results were reviewed again at follow-up. RESULTS: At baseline, 84% and 74% of the 574 HIV patients were found to have incomplete and/or non-updated HBV and HCV serology, respectively. At follow-up, updated HBV serology was achieved in 535 (93%) patients; 15 (3%) patients were found to have a chronic active infection and 156 (27%) had a resolved infection, whereas 65 (11%) were vaccinated against HBV and 299 (52%) were non-immune. No patients were found to have developed chronic HBV infection following HIV diagnosis (equal to 3649 patient-y). Updated HCV serology revealed that 25 (4%) had a chronic active HCV infection and 15 (3%) had a resolved HCV infection. The anti-HCV incidence rate was 0.27/100 patient-y. A liver pathology assessment had not been performed within the last 2 y in 80% of the HBV and 32% of the HCV co-infected patients. CONCLUSIONS: Hepatitis screening and assessment had been inadequately performed. New cases of chronic hepatitis seem to occur infrequently. However, a more proactive hepatitis surveillance and management strategy integrated into the overall HIV health care program is warranted.


Asunto(s)
Manejo de Caso , Monitoreo Epidemiológico , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/terapia , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/terapia , Adulto , Instituciones de Atención Ambulatoria , Dinamarca , Femenino , Infecciones por VIH/complicaciones , Investigación sobre Servicios de Salud , Humanos , Masculino , Persona de Mediana Edad
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