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1.
Proc Natl Acad Sci U S A ; 121(14): e2318978121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38536755

RESUMEN

Pressure-induced transformations in an archetypal chalcogenide glass (GeSe2) have been investigated up to 157 GPa by X-ray absorption spectroscopy (XAS) and molecular dynamics (MD) simulations. Ge and Se K-edge XAS data allowed simultaneous tracking of the correlated local structural and electronic changes at both Ge and Se sites. Thanks to the simultaneous analysis of extended X-ray absorption fine structure (EXAFS) signals of both edges, reliable quantitative information about the evolution of the first neighbor Ge-Se distribution could be obtained. It also allowed to account for contributions of the Ge-Ge and Se-Se bond distributions (chemical disorder). The low-density to high-density amorphous-amorphous transformation was found to occur within 10 to 30 GPa pressure range, but the conversion from tetrahedral to octahedral coordination of the Ge sites is completed above [Formula: see text] 80 GPa. No convincing evidence of another high-density amorphous state with coordination number larger than six was found within the investigated pressure range. The number of short Ge-Ge and Se-Se "wrong" bonds was found to increase upon pressurization. Experimental XAS results are confirmed by MD simulations, indicating the increase of chemical disorder under high pressure.

2.
Soft Matter ; 19(43): 8318-8328, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37869967

RESUMEN

The deformation of hemispherical sessile bubbles made of ferrofluid soap under vertical uniform magnetic fields was studied using Helmholtz coils. The deformation and the shape of the bubbles were monitored according to the amplitude of the magnetic field, the initial volume of the bubbles and the ferrofluid volume used to create them. The meniscus was found to bear most of the deformation, reshaping into a cylinder, with the remainder of the bubble forming a spherical cap, mainly adapting to the meniscus transformation. The growth of the meniscus height was rationalised using a simple model. More precisely, the meniscus shape depends on the competition between capillary, gravity and magnetic effects. These three ingredients can be rewritten to highlight two characteristic lengths of the system: the capillary and the magnetic lengths. Depending on the magnetic field intensity, the shape of the meniscus is described by one of the two lengths, thus revealing the existence of two distinct regimes.

3.
Am J Respir Crit Care Med ; 206(3): 337-346, 2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-35438610

RESUMEN

Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study (N = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study (N = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P = 4.28 × 10-67), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P = 8.01 × 10-40), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P = 4.01 × 10-36) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Anomalías del Sistema Respiratorio , Predisposición Genética a la Enfermedad , Humanos , Pulmón , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/genética , Estudios Prospectivos , Proteómica , Tomografía Computarizada por Rayos X
4.
Eur Respir J ; 60(2)2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35115336

RESUMEN

BACKGROUND: Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis; however, it is not known if ILA are associated with decreased mean telomere length (MTL). METHODS: Telomere length was measured with quantitative PCR in the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) and Age Gene/Environment Susceptibility Reykjavik (AGES-Reykjavik) cohorts and Southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality. RESULTS: In all three cohorts, ILA were associated with decreased MTL. In the COPDGene and AGES-Reykjavik cohorts, after adjustment there was greater than twofold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (OR 2.2, 95% CI 1.5-3.4, p=0.0001, and OR 2.6, 95% CI 1.4-4.9, p=0.003, respectively). In the FHS, those with ILA had shorter telomeres than those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR 1.3, 95% CI 1.1-1.6, p=0.01) in COPDGene, the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death when comparing the shortest quartile of telomere length in COPDGene and AGES-Reykjavik (HR 0.82, 95% CI 0.4-1.7, p=0.6, and HR 1.2, 95% CI 0.6-2.2, p=0.5, respectively). CONCLUSION: ILA are associated with decreased MTL.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pulmón , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/genética , Telómero/genética , Tomografía Computarizada por Rayos X
5.
Inorg Chem ; 61(14): 5502-5511, 2022 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-35344352

RESUMEN

All-inorganic lead halide perovskites like CsPbBr3, CsPbI3, or RbPbI3 are good replacements for the classical hybrid organic-inorganic perovskites like CH3NH3PbI3, susceptible to fast degradation in the presence of humid air. They also exhibit outstanding light absorption properties suitable for solar energy applications. Here, we describe the synthesis of RbPbI3 by mechanochemical procedures with green credentials, avoiding toxic or expensive organic solvents; this specimen exhibits excellent crystallinity. We report neutron powder diffraction data, essential to revisit some subtle structural features around room temperature (200-400 K). In all these regimes, the orthorhombic Pnma crystal structure is characterized by the presence along the b direction of the crystal of double rows of edge-sharing PbI6 octahedra. The lone electron pairs of Pb2+ ions have a strong stereochemical effect on the PbI6 octahedral distortion. The relative covalency of Rb-I versus Pb-I bonds shows that the Pb-I-related motions are more rigid than Rb-I-related vibrations, as seen in the Debye temperatures from the evolution of the anisotropic displacements. The optical gap, measured by diffuse reflectance UV-vis spectroscopy, is ∼2.51 eV and agrees well with ab initio calculations. The thermoelectric Seebeck coefficient is 3 orders of magnitude larger than that of other halide perovskites, with a value of ∼117,000 µV·K-1 at 460 K.

6.
COPD ; 19(1): 265-273, 2022 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-35639442

RESUMEN

Limited information is available regarding the role of anaerobic metabolism capacity on GOLD 1 and 2 COPD patients during upper limb exercise. We aimed to compare the upper limb anaerobic power capacity, blood lactate concentration, cardiovascular and respiratory responses, in male COPD patients versus healthy subjects during the 30-s Wingate anaerobic test (WAnT). The rate of fatigue and time constant of the power output decay (τ, tau) were also calculated and a regression analysis model was built to assess the predictors of τ in these patients. Twenty-four male COPD patients (post-bronchodilator FEV1 73.2 ± 15.3% of predicted) and 17 healthy subjects (FEV1 103.5 ± 10.1% of predicted) underwent the WAnT. Measurements were performed at rest, at the end of the WAnT, and during 3' and 5' of recovery time. Peak power (p = 0.04), low power (p = 0.002), and mean power output (p = 0.008) were significantly lower in COPD patients than in healthy subjects. Power output decreased exponentially in both groups, but at a significantly faster rate (p = 0.007) in COPD patients. The time constant of power decay was associated with resistance (in ohms) and fat-free mass (r2 = 0.604, adjusted r2 = 0.555, and p = 0.002). Blood lactate concentration was significantly higher in healthy subjects at the end of the test, as well as during 3' and 5' of recovery time (p < 0.01). Compared with healthy subjects, COPD patients with GOLD 1 and 2 presented lower upper limb anaerobic capacity and a faster rate of power output decrease during a maximal intensity exercise. Also, the WAnT proved to be a valid tool to measure the upper limb anaerobic capacity in these patients.


Asunto(s)
Prueba de Esfuerzo , Enfermedad Pulmonar Obstructiva Crónica , Anaerobiosis , Humanos , Ácido Láctico , Masculino , Extremidad Superior
7.
Monaldi Arch Chest Dis ; 92(4)2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35225440

RESUMEN

Fall-related causes in patients with COPD might be associated to functional balance impairments and greater disease severity. We aimed to evaluate the reasons for falls in patients with COPD who had presented any fall during the previous year. This is a cross-sectional study. All COPD's GOLD classifications (mild, moderate, severe, and very severe) patients were recruited. In order to participate, patients ought to be clinically stable and without any exacerbation within 30 days prior to study entry. History of falls was self-reported by patients through an interview. Pre and post bronchodilator (salbutamol 400 µg) spirometry was performed. All patients accomplished postural balance tests such as the Berg Balance Scale, Falls Efficacy Scale-International, Time up and Go, Functional Reach test, Tinetti test and Chalder Scale; furthermore, lower limbs muscle strength (muscle dynamometry) and the COPD Assessment Test (CAT) were assessed. Ninety-six patients with COPD were evaluated and divided into two groups stratified according to any positive history of falls in the previous year. Patients with COPD who had any fall in the previous year presented older age (p=0.01), higher BMI (p=0.04) and worse pulmonary function than those who did not fall. The risk of falls was increased in patients with lower muscle strength in the lower limbs (OR 2.9, CI 95%;1.6 to 3.9), age greater than 65 years (OR 2.7, CI 95%;1.3 to 3.4), BMI greater than 28.8 kg/m2 (OR 3.2, CI 95%;1.1 to 5.6), very severe airway obstruction (OR 3.9, CI 95%;2.2 to 3.9) and fatigue (OR 3.2, CI 95%;1.5 to 5.3). Impaired body balance, reduced lower limb strength, disease severity, presence of fatigue and elevated BMI are important factors for falls in patients with COPD.


Asunto(s)
Accidentes por Caídas , Enfermedad Pulmonar Obstructiva Crónica , Albuterol , Broncodilatadores , Estudios Transversales , Fatiga/complicaciones , Humanos , Extremidad Inferior , Fuerza Muscular/fisiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
8.
Am J Epidemiol ; 190(1): 95-108, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-32803215

RESUMEN

Docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models, but human studies are lacking. We examined associations of circulating levels of DHA and other polyunsaturated fatty acids with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 6,573). We examined cross-sectional associations with CT lung abnormalities in MESA (2000-2012; n = 6,541), the Framingham Heart Study (2005-2011; n = 3,917), and the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik) (2002-2006; n = 1,106). Polyunsaturated fatty acid levels were determined from fasting blood samples and extracted from plasma phospholipids (MESA and AGES-Reykjavik) or red blood cell membranes (Framingham Heart Study). Higher DHA levels were associated with a lower risk of hospitalization due to ILD (per standard-deviation increment, adjusted rate ratio = 0.69, 95% confidence interval (CI): 0.48, 0.99) and a lower rate of death due to ILD (per standard-deviation increment, adjusted hazard ratio = 0.68, 95% CI: 0.47, 0.98). Higher DHA was associated with fewer interstitial lung abnormalities on computed tomography (per natural log increment, pooled adjusted odds ratio = 0.65, 95% CI: 0.46, 0.91). Higher DHA levels were associated with a lower risk of hospitalization and death due to ILD and fewer lung abnormalities on computed tomography in a meta-analysis of data from population-based cohort studies.


Asunto(s)
Ácidos Grasos Omega-3/sangre , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Estudios Transversales , Estudios Epidemiológicos , Ácidos Grasos Insaturados/sangre , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Enfermedades Pulmonares Intersticiales/mortalidad , Masculino , Persona de Mediana Edad , Factores de Riesgo
9.
Inorg Chem ; 60(10): 7413-7421, 2021 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-33900757

RESUMEN

Skutterudite-type compounds based on □Co4Sb12 pnictide are promising for thermoelectric application due to their good Seebeck values and high carrier mobility. Filling the 8a voids (in the cubic space group Im3̅) with different elements (alkali, alkali earth, and rare earth) helps to reduce the thermal conductivity and thus increases the thermoelectric performance. A systematic characterization by synchrotron X-ray powder diffraction of different M-filled Co4Sb12 (M = K, Sr, La, Ce, and Yb) skutterudites was carried out under high pressure in the range ∼0-12 GPa. The isothermal equations of state (EOS) were obtained in this pressure range and the Bulk moduli (B0) were calculated for all the filled skutterudites, yielding unexpected results. A lattice expansion due to the filler elements fails in the description of the Bulk moduli. Topochemical studies of the filler site environment exhibited a slight disturbance and an increased ionic character when the filler is incorporated. The mechanical properties by means of Bulk moduli resulted in being sensitive to the presence of filler atoms inside the skutterudite voids, being affected by the covalent/ionic exchange of the Co-Sb and Sb-Sb bonds.

10.
Eur Respir J ; 56(6)2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32646918

RESUMEN

An increased incidence of lung cancer is well known among patients with idiopathic pulmonary fibrosis. It is not known whether interstitial lung abnormalities, i.e. early fibrotic changes of the lung, are a risk factor for lung cancer in the general population.The study's objective was to assess whether interstitial lung abnormalities were associated with diagnoses of, and mortality from, lung cancer and other cancers. Data from the AGES-Reykjavik study, a cohort of 5764 older Icelandic adults, were used. Outcome data were ascertained from electronic medical records. Gray's tests, Cox proportional hazards models and proportional subdistribution hazards models were used to analyse associations of interstitial lung abnormalities with lung cancer diagnoses and lung cancer mortality as well as diagnoses and mortality from all cancers.There was a greater cumulative incidence of lung cancer diagnoses (p<0.001) and lung cancer mortality (p<0.001) in participants with interstitial lung abnormalities than in others. Interstitial lung abnormalities were associated with an increased hazard of lung cancer diagnosis (hazard ratio 2.77) and lung cancer mortality (hazard ratio 2.89) in adjusted Cox models. Associations of interstitial lung abnormalities with all cancers were found in models including lung cancers but not in models excluding lung cancers.People with interstitial lung abnormalities are at increased risk of lung cancer and lung cancer mortality, but not of other cancers. This implies that an association between fibrotic and neoplastic diseases of the lung exists from the early stages of lung fibrosis and suggests that interstitial lung abnormalities could be considered as a risk factor in lung cancer screening efforts.


Asunto(s)
Neoplasias Pulmonares , Adulto , Detección Precoz del Cáncer , Humanos , Islandia/epidemiología , Pulmón , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Modelos de Riesgos Proporcionales , Tomografía Computarizada por Rayos X
11.
Inorg Chem ; 59(20): 14932-14943, 2020 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-33006896

RESUMEN

Black phosphorus (BP) allotrope has an orthorhombic crystal structure with a narrow bandgap of 0.35 eV. This material is promising for 2D technology since it can be exfoliated down to one single layer: the well-known phosphorene. In this work, bulk BP was synthesized under high-pressure conditions at high temperatures. A detailed structural investigation using neutron and synchrotron X-ray diffraction revealed the occurrence of anisotropic strain effects on the BP lattice; the combination of both sets of diffraction data allowed visualization of the lone electron pair 3s2. Temperature-dependent neutron diffraction data collected at low temperature showed that the a axis (zigzag) exhibits a quasi-temperature-independent thermal expansion in the temperature interval from 20 up to 150 K. These results may be a key to address the anomalous behavior in electrical resistivity near 150 K. Thermoelectric properties were also provided; low thermal conductivity from 14 down to 6 Wm-1K-1 in the range 323-673 K was recorded in our polycrystalline BP, which is below the reported values for single-crystals in literature.

12.
Scand J Clin Lab Invest ; 80(6): 508-514, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32706999

RESUMEN

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present study, we carried out a comprehensive screening, using a next-generation sequencing (NGS) panel, for FH culprit mutations in two Icelandic studies representative of either FH families or the general population. We confirmed all previously known mutations in the FH families, and identified two subjects that had been misdiagnosed clinically at young age. We identified six new mutations in the Icelandic FH families and detected three pathogenic mutations in the general population-based study. The application of the NGS panel revealed substantial diagnostic yields in identifying pathogenic mutations, or 68.2% of those with definite clinical diagnosis of FH in the family material and 5.6-fold enrichment in the population-based genetic testing.


Asunto(s)
Pruebas Genéticas/métodos , Hiperlipoproteinemia Tipo II/diagnóstico , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hiperlipoproteinemia Tipo II/genética , Islandia , Mutación con Pérdida de Función , Mutación , Estudios Prospectivos
13.
Am J Respir Crit Care Med ; 200(2): 175-183, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-30673508

RESUMEN

Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality. Objectives: To determine the role of imaging patterns on the risk of death and ILA progression. Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality. Measurements and Main Results: Over 5 years, 327 (10%) had ILA on at least one computed tomography, and 1,435 (45%) did not have ILA on either computed tomography. Of those with ILA, 238 (73%) had imaging progression, whereas 89 (27%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95% confidence interval, 2.7-25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P = 0.001; hazard ratio, 3.9; 95% confidence interval, 2.3-6.8;P < 0.0001), respectively. Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.


Asunto(s)
Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Factores de Edad , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Islandia , Fibrosis Pulmonar Idiopática/mortalidad , Fibrosis Pulmonar Idiopática/fisiopatología , Modelos Logísticos , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Mucina 5B/genética , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Tomografía Computarizada por Rayos X
14.
Curr Gastroenterol Rep ; 21(8): 36, 2019 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-31289917

RESUMEN

PURPOSE OF REVIEW: Colorectal cancer (CRC) remains the third most commonly diagnosed cancer globally, and its incidence and mortality rates have been on the rise in Asia. In this paper, we summarize the recent trends and screening challenges of CRC in this region. RECENT FINDINGS: In 2018, Asia had the highest proportions of both incident (51.8%) and mortality (52.4%) CRC cases (all genders and ages) per 100,000 population in the world. In addition, there has been a rising trend of this disease across Asia with some regional geographic variations. This rise in CRC can be attributed to westernized dietary lifestyle, increasing population aging, smoking, physical inactivity, and other risk factors. In curbing the rising trend, Japan, South Korea, Singapore, and Taiwan have launched nationwide population-based screening programs. CRC screening across this region has been found to be effective and cost-effective compared with no screening at all. The emergence of new therapies has caused a reduction in case fatality; however, these new options have had a limited impact on cure rates and long-term survival due to the great disparity in treatment capacity/resources and screening infrastructures among Asian countries with different degrees of economic development. CRC is still rising in Asia, and implementation of screening is necessary for moderate- to high-incidence countries and construction of treatment capacity is the priority task in low-incidence and low-income countries. Unless countries in Asia implement CRC screening, the incidence and mortality rates of this disease will continue to rise especially with the rapidly rising population growth, economic development, westernized lifestyle, and increasing aging.


Asunto(s)
Neoplasias Colorrectales/epidemiología , Asia/epidemiología , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Detección Precoz del Cáncer/métodos , Humanos , Incidencia , Tamizaje Masivo/métodos , Vigilancia de la Población/métodos , Pronóstico
15.
BMC Vet Res ; 14(1): 326, 2018 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-30400794

RESUMEN

BACKGROUND: Haemophilus (Glässerella) parasuis is the etiological agent of Glässer's disease in pigs. Control of this disorder has been traditionally based on bacterins. The search for alternative vaccines has focused mainly on the study of outer membrane proteins. This study investigates the transcriptome of H. (G.) parasuis serovar 5 subjected to in vitro conditions mimicking to those existing during an infection (high temperature and iron-restriction), with the aim of detecting the overexpression of genes coding proteins exposed on bacterial surface, which could represent good targets as vaccine candidates. RESULTS: The transcriptomic approach identified 13 upregulated genes coding surface proteins: TbpA, TbpB, HxuA, HxuB, HxuC, FhuA, FimD, TolC, an autotransporter, a protein with immunoglobulin folding domains, another large protein with a tetratricopeptide repeat and two small proteins that did not contain any known domains. Of these, the first six genes coded proteins being related to iron extraction. CONCLUSION: Six of the proteins have already been tested as vaccine antigens in murine and/or porcine infection models and showed protection against H. (G.) parasuis. However, the remaining seven have not yet been tested and, consequently, they could become useful as putative antigens in the prevention of Glässer's disease. Anyway, the expression of this seven novel vaccine candidates should be shown in other serovars different from serovar 5.


Asunto(s)
Antígenos Bacterianos/inmunología , Infecciones por Haemophilus/veterinaria , Vacunas contra Haemophilus/inmunología , Haemophilus parasuis/genética , Enfermedades de los Porcinos/microbiología , Animales , Perfilación de la Expresión Génica/veterinaria , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/prevención & control , Haemophilus parasuis/inmunología , Haemophilus parasuis/metabolismo , Análisis de Secuencia de ARN , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/prevención & control , Transcriptoma/genética
16.
Stroke ; 48(9): 2353-2360, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28765285

RESUMEN

BACKGROUND AND PURPOSE: The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. METHODS: Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. RESULTS: Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4). CONCLUSIONS: Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels.


Asunto(s)
Infarto Encefálico/epidemiología , Disfunción Cognitiva/epidemiología , Demencia/epidemiología , Anciano , Anciano de 80 o más Años , Infarto Encefálico/diagnóstico por imagen , Cerebelo/irrigación sanguínea , Cerebelo/diagnóstico por imagen , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Islandia/epidemiología , Incidencia , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas
17.
Eur Respir J ; 50(3)2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28893869

RESUMEN

The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the MUC5B genotype and ILA in cohorts with extensive imaging characterisation.We performed ILA phenotyping and MUC5B promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively.We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the MUC5B genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8-2.4, p=1×10-26), there was evidence of significant heterogeneity between cohorts (I2=81%). When narrowed to specific radiologic subtypes, (e.g. subpleural ILA), the MUC5B genotype remained strongly associated (OR 2.6, 95% CI 2.2-3.1, p=1×10-30) with minimal heterogeneity (I2=0%). Although there was no evidence that the MUC5B genotype influenced survival, there was evidence that MUC5B genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.The MUC5B promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.


Asunto(s)
Enfermedades Pulmonares Intersticiales/genética , Mucina 5B/genética , Polimorfismo Genético , Regiones Promotoras Genéticas , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Islandia , Modelos Logísticos , Estudios Longitudinales , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Masculino , Curva ROC , Tomografía Computarizada por Rayos X
18.
Nephrol Dial Transplant ; 31(3): 439-47, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26519958

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is common in the elderly, but data are limited on the distribution of glomerular filtration rate (GFR) and albuminuria and the prevalence of CKD and related complications in this population. METHODS: A cross-sectional study of 3173 older Icelandic adults [42% men; mean (standard deviation, SD) age of 80 (5) years] was performed to examine the distribution of estimated glomerular filtration rate (eGFR) from creatinine and cystatin C, the albumin-to-creatinine ratio (ACR), and CKD-related metabolic complications (hyperparathyroidism, anemia, hypoalbuminemia, increased anion gap, acidosis, hyperphosphatemia and hyperkalemia). RESULTS: There was substantial variability in eGFR [mean (SD) 64 (18) mL/min/1.73 m(2)] and ACR [median (interquartile range) 8 (5, 17) mg/g]. The prevalence (95% confidence interval) of reduced eGFR (<60 mL/min/1.73 m(2)), albuminuria (ACR >30 mg/g) and CKD (either reduced eGFR or albuminuria) was 40% (38-41), 14% (12-15) and 45% (43-47), respectively. The prevalence of complications was higher among those with versus without CKD: hyperparathyroidism (38 versus 15%), anemia (26 versus 14%), hypoalbuminemia (19 versus 13%), increased anion gap (9 versus 5%), acidosis (5 versus 1%); (P ≤ 0.02 for all), except hyperphosphatemia (1 versus 1%) and hyperkalemia (0% overall). CONCLUSIONS: The burden of CKD and CKD-related complications is high among community dwelling elderly Icelandic adults. The wide range of eGFR and ACR suggests heterogeneity in processes leading to CKD and that factors beyond aging contribute to the development of CKD in the elderly.


Asunto(s)
Anemia/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Metabólicas/epidemiología , Insuficiencia Renal Crónica/epidemiología , Factores de Edad , Anciano de 80 o más Años , Anemia/sangre , Anemia/etiología , Enfermedades Cardiovasculares/etiología , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Islandia/epidemiología , Masculino , Enfermedades Metabólicas/etiología , Prevalencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo
19.
BMC Infect Dis ; 16(1): 523, 2016 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-27682438

RESUMEN

BACKGROUND: Malaria is one of the leading causes of morbidity and mortality in children and HIV infection as well as other factors may worsen the situation. This study was aimed at determining the factors influencing malaria parasite prevalence and density as well as anaemia in HIV-infected children in Mutengene, Cameroon from November, 2012 to April, 2013. METHODS: A semi-structured questionnaire was used to record information on socio-demographic factors and use of preventive measures by caregivers of HIV-infected children aged 1-15 years and of both sexes. Venous blood was collected; blood films were prepared and Giemsa-stained for parasite detection and speciation. Haemoglobin concentration was measured and the anaemic status determined. Data was analysed using Epi Info 7 software. RESULTS: A total of 234 children were studied. The overall malaria parasite prevalence was 24.8 % (58) and was significantly higher (31.9 %, P = 0 .004) in females, those who did not implement any preventive measure at all (66.7 %, P = 0.03) and children who used antiretroviral therapy (ART) (28.6 %, P = 0.02) when compared with their respective counterparts. Geometric mean parasite density (GMPD) was significantly higher (3098.4, P = 0.02) in children who presented with fever, had CD4 T cells ≥500 cells/µL (491.3, P = 0.003) and those with moderate anaemia (1658.8, P = 0.03) than their respective counterparts. Although there was no significant difference, GMPD was however higher in males (549.0); those not on ART (635.0) and highest in children <5 years old (633.0) than their respective counterparts. The overall prevalence of anaemia was 49.6 % (116). The value was significantly highest (58.3 %, P = 0.01) in the 11-15 years age group; those with CD4 T cell level 200-499 (72.7 %, P = 0.001) and children with fever (85.7 %, P = 0.01). CONCLUSION: Implementation of proper and integrated malaria preventive measures as well as frequent monitoring of anaemia on prescription of ART could likely improve the health conditions of HIV-infected children thus avoiding malaria-related morbidity and mortality.

20.
JAMA ; 315(7): 672-81, 2016 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-26881370

RESUMEN

IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006). EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS: Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE: In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.


Asunto(s)
Causas de Muerte , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Humanos , Masculino , Neoplasias/mortalidad , Prevalencia , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/mortalidad , Radiografía , Fumar/epidemiología
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