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1.
J Biomech Eng ; 146(3)2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38217114

RESUMO

Head impacts in bicycle accidents are typically oblique to the impact surface and transmit both normal and tangential forces to the head, causing linear and rotational head kinematics, respectively. Traditional expanded polystyrene (EPS) foam bicycle helmets are effective at preventing many head injuries, especially skull fractures and severe traumatic brain injuries (TBIs) (primarily from normal contact forces). However, the incidence of concussion from collisions (primarily from rotational head motion) remains high, indicating need for enhanced protection. An elastomeric honeycomb helmet design is proposed herein as an alternative to EPS foam to improve TBI protection and be potentially reusable for multiple impacts, and tested using a twin-wire drop tower. Small-scale normal and oblique impact tests showed honeycomb had lower oblique strength than EPS foam, beneficial for diffuse TBI protection by permitting greater shear deformation and had the potential to be reusable. Honeycomb helmets were developed based on the geometry of an existing EPS foam helmet, prototypes were three-dimensional-printed with thermoplastic polyurethane and full-scale flat and oblique drop tests were performed. In flat impacts, honeycomb helmets resulted in a 34% higher peak linear acceleration and 7% lower head injury criteria (HIC15) than EPS foam helmets. In oblique tests, honeycomb helmets resulted in a 30% lower HIC15 and 40% lower peak rotational acceleration compared to EPS foam helmets. This new helmet design has the potential to reduce the risk of TBI in a bicycle accident, and as such, reduce its social and economic burden. Also, the honeycomb design showed potential to be effective for repetitive impact events without the need for replacement, offering benefits to consumers.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Traumatismos Craniocerebrais , Humanos , Fenômenos Biomecânicos , Dispositivos de Proteção da Cabeça , Ciclismo/lesões , Traumatismos Craniocerebrais/prevenção & controle , Lesões Encefálicas Traumáticas/prevenção & controle , Aceleração
2.
Ann Biomed Eng ; 50(11): 1689-1700, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36310295

RESUMO

Drop and Impact testing of helmets are used extensively in the design process and eventual certification of helmets. These techniques have traditionally relied heavily on the measurement of the kinematic response to impact, which provides an indirect measurement of the liner response that is subject to interpretation during the design process. In the present work, we introduce an in situ experimental technique that provides a time-resolved measurement of the deformation of the helmet and its components during an impact event. The data collected from a high-speed X-ray imaging system can provide a full description of the deformation at the component level, which provides a helmet designer further insight into the performance of their helmet, while also returning the traditional kinematic metrics. The data presented focuses on the deformation of a commercial hockey helmet subjected to a series of linear impacts with three different impactor caps at speeds ranging from 2.4 to 4.5 m/s. Deformation of the liner was monitored in the midsagittal and a parasagittal plane of the helmet. The results show that there is a clear dependence on the maximum strain achieved in the foam that is dependent on the impact type, the impactor shape, and the resulting strain rate of deformation in the foam liner. These techniques can provide the first data for a direct validation and calibration of finite element helmet deformation models, while also providing a new tool-set to improve the efficacy of helmet design.


Assuntos
Dispositivos de Proteção da Cabeça , Hóquei , Fenômenos Biomecânicos , Aceleração
3.
J Mech Behav Biomed Mater ; 130: 105181, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35405519

RESUMO

Finite element models of thoracic injury often treat the lung as a bulk homogeneous and isotropic material, which reduces the computational costs associated with such investigations. Ignoring the heterogeneous structure of the lung may be computationally expedient, but this simplification may inadvertently fail to capture the true lung strain dynamics. In the present work, a series of direct impact experiments were performed on porcine lungs, inflated to a relevant expiratory pressure, and monitored using high-speed X-ray imaging. The lungs were instrumented with radiopaque markers within the parenchyma and tertiary bronchi to monitor the resulting deformation mechanics. The deformation mechanics demonstrate a high degree of strain localization related to the structural heterogeneity of the lung. The relative motion of the tertiary bronchi was measured during the impact event, and used to estimate the parenchyma tissue strains in the inter-bronchial regions. These were shown to exceed the trans-lobe strains by a factor 3 to 5 times higher in their tensile, compressive, and shear strain responses. Our results demonstrate that the lung parenchyma and bronchial tissues form a heterogeneous structure with a substantial stiffness differential that cannot be appropriately modelled as a homogeneous and isotropic monolithic mass without loss of accuracy and predictive relevance.


Assuntos
Brônquios , Pulmão , Animais , Brônquios/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/fisiologia , Suínos
4.
J Biomech ; 128: 110708, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492445

RESUMO

The biomechanical response of brain tissue to strain and the immediate neural outcomes are of fundamental importance in understanding mild traumatic brain injury (mTBI). The sensitivity of neural tissue to dynamic strain events and the resulting strain-induced changes are considered to be a primary factor in injury. Rodent models have been used extensively to investigate impact-induced injury. However, the lissencephalic structure is inconsistent with the human brain, which is gyrencephalic (convoluted structure), and differs considerably in strain field localization effects. Porcine brains have a similar structure to the human brain, containing a similar ratio of white-grey matter and gyrification in the cortex. In this study, coronal brain slabs were extracted from female pig brains within 2hrs of sacrifice. Slabs were implanted with neutral density radiopaque markers, sealed inside an elastomeric encasement, and dropped from 0.9 m onto a steel anvil. Particle tracking revealed elevated tensile strains in the sulcus. One hour after impact, decreased microtubule associated protein 2 (MAP2) was found exclusively within the sulcus with no increase in cell death. These results suggest that elevated tensile strain in the sulcus may result in compromised cytoskeleton, possibly indicating a vulnerability to pathological outcomes under the right circumstances. The results demonstrated that the observed changes were unrelated to shear strain loading of the tissues but were more sensitive to tensile load.


Assuntos
Lesões Encefálicas , Substância Branca , Animais , Encéfalo , Feminino , Cabeça , Microtúbulos , Suínos
5.
Ann Biomed Eng ; 49(10): 2836-2851, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34528151

RESUMO

The dynamic response of the human brain subjected to impulsive loading conditions is of fundamental importance to the understanding of traumatic brain injuries. Due to the complexity of such measurements, the existing experimental datasets available to researchers are sparse. However, these measurements are used extensively in the validation of complex finite element models used in the design of protective equipment and the development of injury mitigation strategies. The primary objective of this study was to develop a comprehensive methodology to measure displacement in specific anatomical regions of the brain. A state-of-the-art high-speed cineradiography system was used to capture brain motion in post-mortem human surrogate specimens at a rate of 7500 fps. This paper describes the methodology used to capture these data and presents measurements from these tests. Two-dimensional displacement fields are presented and analyzed based on anatomical regions of the brain. These data demonstrated a multi-modal displacement response in several regions of the brain. The full response of the brain consisted of an elastic superposition of a series of bulk rotations of the brain about its centre of gravity. The displacement field could be linked directly to specific anatomical regions. The methods presented mark an improvement in temporal and spatial resolution of data collection, which has implications for our developing understanding of brain trauma.


Assuntos
Lesões Encefálicas Traumáticas/fisiopatologia , Encéfalo/fisiopatologia , Modelos Biológicos , Fenômenos Biomecânicos , Encéfalo/anatomia & histologia , Cadáver , Análise de Elementos Finitos , Humanos
6.
J Biomech Eng ; 143(11)2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34159365

RESUMO

Datasets obtained from cadaveric experimentation are broadly used in validating finite element models of head injury. Due to the complexity of such measurements in soft tissues, experimentalists have relied on tissue-embedded radiographic or sonomicrometry tracking markers to resolve tissue motion caused by impulsive loads. Dynamic coupling of markers with the surrounding tissue has been a previous concern, yet a thorough sensitivity investigation of marker influences on tissue deformation has not been broadly discussed. Technological improvements to measurement precision have bolstered confidence in acquired data; however, precision is often conflated with accuracy; the inclusion of markers in the tissue may alter its natural response, resulting in a loss of accuracy associated with an altered displacement field. To gain an understanding of how marker properties may influence the measured response to impact, we prepared a set of nine marker designs using a Taguchi L9 array to investigate marker design choice sensitivity. Each of these designs was cast into a block of tissue simulant and subjected to repeated drop tests. Vertical displacement was measured and compared to the response of the neat material, which contained massless tracking markers. Medium density and medium stiffness markers yielded the least deviation from the neat material response. The results provide some design guidelines indicating the importance of maintaining marker matrix density ratio below 1.75 and marker stiffness below 1.0 MPa. These properties may minimize marker interference in tissue deformation. Overall, embedded marker properties must be considered when measuring the dynamic response of tissue.


Assuntos
Interpretação de Imagem Assistida por Computador
7.
Sci Rep ; 11(1): 13161, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162992

RESUMO

In this study, we have investigated the relationship between the spherulitic morphology and the dynamic tensile response of polyurethane reinforced with Halloysite nanotubes (HNTs). The polyurethane prepolymer is partially silane end-capped and filled with only 0.8 wt.% of acid-treated Halloysite nanotubes. The resultant nanocomposite material presents a 35% higher spall strength compared to the neat polyurethane and 21% higher fracture toughness. We show evidence that the HNTs are not the toughening phase in the nanocomposite, but rather it is their influence on the resultant spherulitic structures which alters the polymer microstructure and leads to a tougher dynamic response. Microstructural characterization is performed via Scanning Electron Microscopy, Atomic Force Microscopy and Field Emission Scanning Electron Microscopy, and crystallinity examination via X-ray diffraction. The spherulitic structures present a brittle fracture character, while the interspherulitic regions are more ductile and show large deformation. The nanocomposite presents a finer and more rigid spherulitic structure, and a more energy dissipative fracture mechanism characterized by a rougher fracture surface with highly deformed interspherulitic regions.

8.
J Biomech Eng ; 143(6)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625494

RESUMO

This study investigated impact-induced strain fields within brain tissue surrogates having different cortical gyrification. Two elastomeric surrogates, one representative of a lissencephalic brain and the other of a gyrencephalic brain, were drop impacted in unison at four different heights and in two different orientations. Each surrogate contained a radiopaque speckle pattern that was used to calculate strain fields. Two different approaches, digital image correlation (DIC) and a particle tracking method, enabled comparisons of full-field and localized strain responses. The DIC results demonstrated increased localized deviations from the mean strain field in the surrogate with a gyrified cortex. Particle tracking algorithms, defining four-node quadrilateral elements, were used to investigate the differences in the strain response of three regions: the base of a sulcus, the adjacent gyrus, and the internal capsule of the surrogates. The results demonstrated that the strains in the cortex were concentrated at the sulcal base. This mechanical mechanism of increased strain is consistent with neurodegenerative markers observed in postmortem analyses, suggesting a potential mechanism of local damage due to strain amplification at the sulcal bases in gyrencephalic brains. This strain amplification mechanism may be responsible for cumulative neurodegeneration from repeated subconcussive impacts. The observed results suggest that lissencephalic animal models, such as rodents, would not have the same modes of injury present in a gyrencephalic brain, such as that of a human. As such, a shift toward representative mild traumatic brain injury animal models having gyrencephalic cortical structures should be strongly considered.


Assuntos
Concussão Encefálica
9.
Sci Rep ; 10(1): 13805, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796879

RESUMO

In the present work, nanocomposites based on the partially silane-terminated polyurethanes reinforced with sulfuric acid-treated halloysite nanotubes were synthesized and evaluated as a potential candidate for transparent blast resistant configurations. The polyurethane must present high tensile ductility at high strain rates to be able to contain fragments and increase the survivability of the system. Gas-gun spall experiments were conducted to measure the dynamic tensile strength (spall strength) and fracture toughness of the nanocomposite and neat polyurethane. The nanocomposite presented a 35% higher spall strength and 21% higher fracture toughness compared to the neat polyurethane while maintaining transparency. The recovered samples following the spall tests were analysed via scanning electron microscope fractographies. The nanocomposite and neat polyurethane samples were chemically characterized via Fourier transform infrared spectroscopy and melting behaviour via differential scanning calorimetry. The improved properties can be attributed, in large part, to the presence of more rigid spherulitic structures, and a rougher fracture surface constituting of several micro-cracks within the nanocomposite.

11.
Plast Reconstr Surg Glob Open ; 6(10): e1847, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30534480

RESUMO

BACKGROUND: Complex regional pain syndromes (CRPS) is a disease that is poorly understood. It is a chronic pain syndrome characterized by sympathetic disruptions as well as CNS sensitization. Botulinum Toxin-A has been shown to have efficacy in Raynaud's as well as other neuropathic pain disorders. Perhaps BTX-A warrants experimentation in the treatment of CRPS. METHODS: Patients with CRPS refractory to 2 or more regional sympathetic nerve blocks in 2007 were included in the study. Patient's were asked to rank their initial pain on a visual analog scale of 0 to 10 (10 being the worst pain). "Tenderness maps" were marked on patient's areas of most pain in 1 by 1 centimeter grids. Each box on the grid was injected with 10 IU of BTX-A after nerve blocks with 1% lidocaine. Treatment sessions occured on a monthly basis with VAS pain scores being re-assessed immediately before the new treatment. t Test, linear regression, and Cohen's D-test were used to analyze the correlation of the data. RESULTS: Study sample was 20 patients. Etiology of CRPS was 6 amputations, 4 crush injuries, 4 penetrating injuries, and 2 lacerations. Average pain reduction on VAS scale achieved was 2.05 points. Average percentage pain reduction was 22.94%. Cohen's D Test also showed a meaningful difference with a score of 1.01. Linear regression R2 = 0.491. Maximum pain reduction, on average, was achieved by treatment 9. CONCLUSION: Despite the esoteric etiology of CRPS, BTX-A has a well-demonstrated mechanism of effect. BTX-A should be further explored as a treatment modality for CRPS.

12.
Sci Rep ; 8(1): 16480, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30405157

RESUMO

Thin films of layered semiconductors emerge as highly promising materials for energy harvesting and storage, optoelectronics and catalysis. Their natural propensity to grow as oriented crystals and films is one of their distinct properties under recent focal interest. Specifically, the reaction of transition metal films with chalcogen vapor can result in films of vertically aligned (VA) layers, while metal-oxides react with chalcogens in vapor phase to produce horizontally aligned crystals and films. The growth mechanisms of vertically oriented films are not yet fully understood, as well as their dependence on the initial metal film thickness and growth conditions. Moreover, the resulting electronic properties and the role of defects and disorder had not yet been studied, despite their critical influence on catalytic and device performance. In this work, we study the details of oriented growth of MoS2 with complementary theoretical and experimental approaches. We present a general theoretical model of diffusion-reaction growth that can be applied to a large variety of layered materials synthesized by solid-vapor reaction. Moreover, we inspect the relation of electronic properties to the structure of vertically aligned MoS2 and shed light on the density and character of defects in this material. Our measurements on Si-MoS2 p-n hetero-junction devices point to the existence of polarizable defects that impact applications of vertical transition-metal dichalcogenide materials.

13.
Nanoscale ; 10(34): 16211-16216, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30124225

RESUMO

The alkaline hydrogen evolution reaction (HER) plays a key role in photo(electro)catalytic water splitting technologies, particularly in water-alkali electrolyzers. Unfortunately, although transition metal dichalcogenide (TMD) materials, especially MoS2 and MoSe2, are considered efficient, Earth-abundant catalysts for the HER in an acidic electrolyte, they are much less effective under high pH conditions due to a sluggish water dissociation process (Volmer-step) and strong adsorption of the OH- intermediate on their surfaces. Herein we show a novel synergetic effect obtained by tailoring the S/Se ratio in Mo(SxSe1-x)2 alloys. We were able to influence the metal oxidation state and d-band to optimize the catalytic sites for HOH dissociation and OH- desorption while maintaining favourable M-H energetics. The Mo(SxSe1-x)2 (x = 0.58) catalyst exhibited high performance with an onset potential of -43 mV in 0.5 M KOH, i.e., ∼3 and ∼4-fold less than that for MoSe2 and MoS2, respectively. The results obtained in the current study have implications for the rational design of cost-effective electro-catalysts for water reduction based on TMD alloys.

14.
Nanoscale ; 9(37): 13998-14005, 2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-28891569

RESUMO

Layered transition metal dichalcogenides are noble-metal free electrocatalysts for the hydrogen evolution reaction (HER). Instead of using the common hydrothermal synthesis, which requires high pressure and temperature, herein a relatively simple and controlled colloidal synthesis was used to produce an alloy of Mo1-xWxSe2 with nanoflower morphology as a model system for the electrocatalysis of hydrogen evolution in both acidic and alkaline environments. The results show that Mo1-xWxSe2 alloys exhibit better catalytic activity in both acidic and alkaline solutions with low overpotentials compared to pure MoSe2 and WSe2. Moreover, the electrode kinetics was studied using electrochemical impedance spectroscopy (EIS) and the results indicate that the alloys exhibit improved catalytic activity with low Tafel slopes, making them appealing for HER in either environment. Additionally, when MoSe2 nanoflowers (NFs) are prepared by using different metal salts and chalcogenide precursors, changes in the HER catalytic activity were observed, despite the morphology and crystal structure similarities. This finding suggests that different results reported in the literature could originate from different synthetic methods of the TMD, emphasizing that a better understanding of the relationship between the synthetic route and the catalytic performance is still lacking.

15.
BMC Infect Dis ; 16(1): 630, 2016 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-27809805

RESUMO

BACKGROUND: Migrant farmworkers are among the highest-risk populations for latent TB infection (LTBI) in the United States with numerous barriers to healthcare access and increased vulnerability to infectious diseases. LTBI is usually diagnosed on the border using the tuberculin skin test (TST). QuantiFERON-TB Gold In-Tube (QFT-GIT) also measures immune response against specific Mycobacterium tuberculosis antigens. The objective of this study is to assess the comparability of TST and QFT-GIT to detect LTBI among migrant farmworkers on the border, as well as to examine the effects of various demographic and clinical factors on test positivity. METHODS: Participants were recruited using mobile clinics on the San Luis US-Mexico border and tested with QFT-GIT and TST. Demographic profiles and clinical histories were collected. Kappa coefficients assessed agreement between TST and QFT-GIT using various assay cutoffs. Logistic regression examined factors associated with positive TST or QFT-GIT results. RESULTS: Of 109 participants, 59 of 108 (55 %) were either TST (24/71, 34 %) or QFT-GIT (52/106, 50 %) positive. Concordance between TST and QFT-GIT was fair (71 % agreement, ĸ = 0.38, 95 % CI: 0.15, 0.61). Factors associated with LTBI positivity included smoking (OR = 1.26, 95 % CI-1.01-1.58) and diabetes/high blood sugar (OR = 0.70, 95 % CI = 0.51-0.98). DISCUSSION: Test concordance between the two tests was fair, with numerous discordant results observed. Greater proportion of positives detected using QFT-GIT may help avoid LTBI under-diagnosis. Assessment of LTBI status on the border provides evidence whether QFT-GIT should replace the TST in routine practice, as well as identifies risk factors for LTBI among migrant populations.


Assuntos
Fazendeiros/estatística & dados numéricos , Tuberculose Latente/epidemiologia , Migrantes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperglicemia/epidemiologia , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Modelos Logísticos , Masculino , México/etnologia , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologia , Teste Tuberculínico/métodos , Estados Unidos/epidemiologia , Adulto Jovem
16.
ACS Appl Mater Interfaces ; 8(8): 5070-81, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26795060

RESUMO

Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property.


Assuntos
Anti-Infecciosos/química , Proteínas Mutantes Quiméricas/química , Peptídeos/química , Próteses e Implantes/microbiologia , Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Proteínas Mutantes Quiméricas/uso terapêutico , Peptídeos/uso terapêutico , Engenharia de Proteínas , Staphylococcus/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Titânio/química , Titânio/uso terapêutico
17.
J Chem Inf Model ; 55(12): 2507-18, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26553402

RESUMO

Quantitative structure activity relationship (QSAR) or quantitative structure property relationship (QSPR) models are developed to correlate activities for sets of compounds with their structure-derived descriptors by means of mathematical models. The presence of outliers, namely, compounds that differ in some respect from the rest of the data set, compromise the ability of statistical methods to derive QSAR models with good prediction statistics. Hence, outliers should be removed from data sets prior to model derivation. Here we present a new multi-objective genetic algorithm for the identification and removal of outliers based on the k nearest neighbors (kNN) method. The algorithm was used to remove outliers from three different data sets of pharmaceutical interest (logBBB, factor 7 inhibitors, and dihydrofolate reductase inhibitors), and its performances were compared with those of five other methods for outlier removal. The results suggest that the new algorithm provides filtered data sets that (1) better maintain the internal diversity of the parent data sets and (2) give rise to QSAR models with much better prediction statistics. Equally good filtered data sets in terms of these metrics were obtained when another objective function was added to the algorithm (termed "preservation"), forcing it to remove certain compounds with low probability only. This option is highly useful when specific compounds should be preferably kept in the final data set either because they have favorable activities or because they represent interesting molecular scaffolds. We expect this new algorithm to be useful in future QSAR applications.


Assuntos
Algoritmos , Descoberta de Drogas/métodos , Modelos Teóricos , Relação Quantitativa Estrutura-Atividade , Modelos Moleculares
18.
Clin Exp Allergy ; 45(9): 1439-46, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26011047

RESUMO

OBJECTIVES: Wheezing in infancy has been associated with subsequent asthma, but whether cough similarly influences asthma risk has been little studied. We sought to determine whether prolonged cough and cough without cold in the first year of life are associated with childhood asthma. METHODS: Participants in the Infant Immune Study, a non-selected birth cohort, were surveyed 7 times in the first 9 months of life regarding the presence of wheeze and cough. Cough for more than 28 days was defined as prolonged. Parents were asked at 1 year if the child ever coughed without a cold. Asthma was defined as parental report of physician diagnosis of asthma, with symptoms or medication use between 2 and 9 years. Logistic regression was used to assess adjusted odds for asthma associated with cough characteristics. RESULTS: A total of 24% (97) of children experienced prolonged cough and 23% (95) cough without cold in the first 9 months, respectively. Prolonged cough was associated with increased risk of asthma relative to brief cough (OR 3.57, CI: 1.88, 6.76), with the risk being particularly high among children of asthmatic mothers. Cough without cold (OR 3.13, 95% CI: 1.76, 5.57) was also independently associated with risk of childhood asthma. Both relations persisted after adjustment for wheeze and total IgE at age 1. CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged cough in infancy and cough without cold are associated with childhood asthma, independent of infant wheeze. These findings suggest that characteristics of cough in infancy are early markers of asthma susceptibility, particularly among children with maternal asthma.


Assuntos
Asma/epidemiologia , Asma/etiologia , Tosse/complicações , Tosse/epidemiologia , Suscetibilidade a Doenças , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Risco
19.
PLoS Comput Biol ; 11(3): e1004139, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25735005

RESUMO

Founder populations and large pedigrees offer many well-known advantages for genetic mapping studies, including cost-efficient study designs. Here, we describe PRIMAL (PedigRee IMputation ALgorithm), a fast and accurate pedigree-based phasing and imputation algorithm for founder populations. PRIMAL incorporates both existing and original ideas, such as a novel indexing strategy of Identity-By-Descent (IBD) segments based on clique graphs. We were able to impute the genomes of 1,317 South Dakota Hutterites, who had genome-wide genotypes for ~300,000 common single nucleotide variants (SNVs), from 98 whole genome sequences. Using a combination of pedigree-based and LD-based imputation, we were able to assign 87% of genotypes with >99% accuracy over the full range of allele frequencies. Using the IBD cliques we were also able to infer the parental origin of 83% of alleles, and genotypes of deceased recent ancestors for whom no genotype information was available. This imputed data set will enable us to better study the relative contribution of rare and common variants on human phenotypes, as well as parental origin effect of disease risk alleles in >1,000 individuals at minimal cost.


Assuntos
Algoritmos , Efeito Fundador , Modelos Genéticos , Linhagem , Software , Feminino , Genoma Humano , Genômica , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA , South Dakota , População Branca/genética
20.
Hum Pathol ; 46(3): 397-403, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25582501

RESUMO

Documentation of Helicobacter pylori infection and eradication is important, prompting some clinicians and pathologists to request ancillary stains on all gastric samples that do not demonstrate H. pylori on initial histologic review. Studies evaluating the utility of ancillary stains in patients with minimal inflammation are lacking. We used Giemsa, Warthin-Starry, acridine orange, and immunohistochemical stains to search for organisms in 56 patients with biochemical evidence of H. pylori infection (positive Campylobacter-like organism test) and gastric mucosal samples interpreted to be H pylori negative by hematoxylin and eosin (H&E). We correlated the findings with severity of inflammation and patients' histories of medication use. Nineteen (34%) patients had histologically normal mucosae, 22 (39%) had chronic inflammation with or without focal activity, and 15 (27%) had chemical gastropathy. Fifty (89%) cases were negative for H. pylori with additional stains, and 6 contained bacteria that were detected with all 4 ancillary stains and on retrospective review of H&E-stained sections that also showed chronic inflammation. Eleven (20%) patients were taking proton pump inhibitors, and 4 (7%) had previously received H. pylori eradication therapy. We conclude that H&E stains demonstrate H. pylori in most infected patients, so preemptive stain requests are largely unnecessary. Failure to identify bacteria by H&E evaluation generally reflects their absence in biopsy material, even among Campylobacter-like organism test--positive patients. However, organisms may be overlooked in patients with mild inflammation and in those receiving proton pump inhibitor or antibiotic therapy, so one should consider ordering ancillary stains to enhance detection of bacteria in these settings.


Assuntos
Corantes/análise , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/química , Helicobacter pylori/isolamento & purificação , Laranja de Acridina/análise , Biópsia , Doença Crônica , Corantes/classificação , Feminino , Mucosa Gástrica/patologia , Gastrite/patologia , Infecções por Helicobacter/patologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Coloração e Rotulagem
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