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1.
Gastroenterology ; 164(2): 228-240, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36183751

RESUMO

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. METHODS: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. RESULTS: Unfermented dietary ß-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining ß-fructan supplementation. The proinflammatory response to intact ß-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of ß-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. CONCLUSION: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).


Assuntos
Frutanos , Doenças Inflamatórias Intestinais , Adulto , Humanos , Leucócitos Mononucleares , Intestinos , Fibras na Dieta , Inflamação
2.
Curr Microbiol ; 80(11): 363, 2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37807005

RESUMO

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.


Assuntos
Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/microbiologia , Bactérias/genética , Transplante de Microbiota Fecal
3.
J Pept Sci ; 28(1): e3302, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33506586

RESUMO

Mimicking the extracellular matrix (ECM) continues to be a goal in the field of regenerative medicine. Herein, we report a modified trimeric GCN4 coiled-coil sequence containing three ligands for metal ions specifically positioned for crosslinked assembly (TriCross). In the presence of metal ions, TriCross assembles into a three-dimensional (3D) matrix with significant cavities to accommodate cells. The matrix was found to be stable in media with serum, and mild removal of the metal leads to disassembly. By assembling TriCross with a suspension of cells in media, the matrix encapsulates cells during the assembly process leading to high cell viability. Further disassembly under mild conditions allows for the release of cells from the scaffold. As such, this peptide-based material displays many of the characteristics necessary for successful 3D cell culture.


Assuntos
Técnicas de Cultura de Células em Três Dimensões , Encapsulamento de Células , Sequência de Aminoácidos , Peptídeos , Domínios Proteicos
4.
Am J Pathol ; 188(8): 1910-1920, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29879416

RESUMO

E-cadherin is conventionally considered to be a good prognostic marker in cancer. The loss of E-cadherin is one of the key hallmarks of epithelial-to-mesenchymal transition, a biological process that promotes cancer cell invasiveness and metastasis. Recent evidence has cast doubt on the importance of epithelial-to-mesenchymal transition in metastasis. The availability of protein-level data in the Cancer Genome Atlas allows for the quantitative analysis of protein and prognosis. The prognostic values of E-cadherin and ß-catenin were revisited across 19 cancer types, and high E-cadherin was found to correlate with good prognosis in most cancers. Conversely, higher E-cadherin and ß-catenin correlated with shorter survival in invasive breast carcinoma. Stratifying breast cancers by histologic subtype revealed that the poor prognosis of E-cadherin and ß-catenin proteins was characteristic of infiltrating ductal, but not lobular, carcinomas. To further corroborate the protein findings and examine cellular localization, immunohistochemistry was used for E-cadherin and ß-catenin in 163 breast patient samples from the Iowa cohort. Most previous studies showing that reduced or absent E-cadherin and ß-catenin was inversely associated with tumor stages in ductal carcinomas were confirmed. Taken together, these results lead us to question the prognostic values of E-cadherin and ß-catenin in ductal carcinomas and indicate a complicated role of E-cadherin and ß-catenin in breast cancer progression.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Caderinas/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , beta Catenina/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Humanos , Prognóstico , Análise Serial de Proteínas , Taxa de Sobrevida
5.
J Am Chem Soc ; 140(3): 1011-1018, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29313677

RESUMO

Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.


Assuntos
Óxido Nítrico/análise , Técnicas Fotoacústicas/métodos , Animais , Modelos Animais de Doenças , Inflamação/diagnóstico , Inflamação/diagnóstico por imagem , Camundongos , Compostos Nitrosos/química
6.
J Am Chem Soc ; 140(3): 916-918, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-28930454

RESUMO

Proteins in the hedgehog family undergo self-catalyzed endoproteolysis involving nucleophilic attack by a molecule of cholesterol. Recently, a conserved aspartate residue (D303, or D46) of hedgehog was identified as the general base that activates cholesterol during this unusual autoprocessing event; mutation of the catalyzing functional group (D303A) reduces activity by >104-fold. Here we report near total rescue of this ostensibly dead general base mutant by a synthetic substrate, 3ß-hydroperoxycholestane (3HPC) in which the sterol -OH group is replaced by the hyper nucleophilic -OOH group. Other hedgehog point mutants at D303, also unreactive with cholesterol, accepted 3HPC as a substrate with the rank order: WT > D303A ≈ D303N ≫ D303R, D303E. We attribute the revived activity with 3-HPC to the α-effect, where tandem electronegative atoms exhibit exceptionally high nucleophilicity despite relatively low basicity.


Assuntos
Colestanos/metabolismo , Colesterol/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas Hedgehog/metabolismo , Animais , Catálise , Domínio Catalítico , Proteínas de Drosophila/química , Drosophila melanogaster/química , Proteínas Hedgehog/química , Especificidade por Substrato
7.
Cell Physiol Biochem ; 41(1): 193-204, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28132060

RESUMO

BACKGROUND: Nod-like receptor family, pyrin domain containing 3 (NLRP3) is an important cytosolic sensor of cellular stress and infection. Once activated, NLRP3 forms a multiprotein complex (inflammasome) that triggers the maturation and secretion of interleukin (IL)-1ß and IL-18. We aimed to define the consequences of NLRP3 induction, utilizing exogenous adenosine triphosphate (ATP) as an inflammasome activator, to determine if inflammasome activation increases macrophage killing of Citrobacter rodentium and define mechanisms. METHODS: Bacterial survival was measured using a gentamicin protection assay. Inflammasome activation or inhibition in mouse J774A.1 macrophages were assessed by measuring IL-1ß; cytokines and reactive oxygen species (ROS) were measured by ELISA and DCFDA, respectively. RESULTS: Activation of the inflammasome increased bacterial killing by macrophages and its inhibition attenuated this effect with no impact on phagocytosis or cell death. Furthermore, inflammasome activation suppressed pro-inflammatory cytokines during infection, possibly due to more effective bacterial killing. While the infection increased ROS production, this effect was reduced by inflammasome inhibitors, indicating that ROS is inflammasome-dependent. ROS inhibitors increased bacterial survival in the presence of ATP, suggesting that inflammasome-induced bacterial killing is mediated, at least in part, by ROS activity. CONCLUSION: Improving inflammasome activity during infection may increase bacterial clearance by macrophages and reduce subsequent microbe-induced inflammation.


Assuntos
Trifosfato de Adenosina/farmacologia , Citrobacter rodentium/efeitos dos fármacos , Inflamassomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Citrobacter rodentium/patogenicidade , Citocinas/análise , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Interleucina-1beta/análise , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Microscopia de Fluorescência , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fagocitose/efeitos dos fármacos
8.
J Pediatr Gastroenterol Nutr ; 63(6): 644-650, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26933801

RESUMO

OBJECTIVES: Inflammatory bowel diseases (IBD) present commonly in childhood, with unknown etiology, but an important role for the epithelial lining is suggested. Epithelial cell extrusion, measured by counting gaps between epithelial cells, is higher in adult patients with Crohn disease (CD) than in controls. Our objectives were to compare epithelial gaps in the duodenum of IBD and non-IBD pediatric patients, to study the correlation between epithelial gaps, inflammation, and disease activity, and identify potential mechanisms. METHODS: Epithelial gap density of the duodenum was evaluated using probe-based confocal laser endomicroscopy in 26 pediatric patients with IBD (16 CD, 10 ulcerative colitis [UC]) and 17 non-IBD controls during endoscopy. Epithelial gaps were correlated with serum inflammatory markers, disease activity indices, and intraepithelial lymphocytes. A panel of 10 inflammatory cytokines and expression of TNFAIP3 (A20; inhibits NF-κß-induced inflammation) were analyzed in duodenal and ileal biopsies. RESULTS: Confocal imaging showed significantly higher epithelial gap density in patients with IBD, including UC. Interleukin (IL)-2 and IL-8 were higher in duodenal but not ileal biopsies of patients with UC. No significant correlation was present between C-reactive protein, erythrocyte sedimentation rate, disease activity indices, and epithelial gaps in patients with UC. In patients with CD, C-reactive protein positively correlated with epithelial gaps. A20 expression in the duodenum was unchanged among non-IBD and IBD cases. CONCLUSIONS: Duodenal epithelial gaps are increased in pediatric patients with IBD (including UC) but are unrelated to inflammation. This suggests that altered epithelial barrier is an important systemic feature of pediatric IBD and is not only secondary to inflammation.


Assuntos
Colite Ulcerativa/patologia , Colo/patologia , Doença de Crohn/patologia , Duodeno/patologia , Células Epiteliais/patologia , Junções Comunicantes/patologia , Íleo/patologia , Adolescente , Estudos de Casos e Controles , Criança , Epitélio/patologia , Feminino , Humanos , Masculino , Microscopia Confocal , Índice de Gravidade de Doença
9.
Hum Mol Genet ; 22(20): 4084-101, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23736298

RESUMO

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/- SMA mice), and positively impacts neuromuscular pathologies. In 2B/- SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/- SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects.


Assuntos
Endorribonucleases/antagonistas & inibidores , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/patologia , Atrofia Muscular Espinal/fisiopatologia , Quinazolinas/farmacologia , Quinazolinas/farmacocinética , Proteína 2 de Sobrevivência do Neurônio Motor/metabolismo , Administração Oral , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Endorribonucleases/metabolismo , Feminino , Humanos , Camundongos , Camundongos Transgênicos , Atrofia Muscular Espinal/tratamento farmacológico , Quinazolinas/uso terapêutico , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
10.
Lancet ; 383(9931): 1814-23, 2014 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-24856027

RESUMO

BACKGROUND: The administration of intravenous fluid remains the cornerstone treatment for the prevention of contrast-induced acute kidney injury. However, no well-defined protocols exist to guide fluid administration in this treatment. We aimed to establish the efficacy of a new fluid protocol to prevent contrast-induced acute kidney injury. METHODS: In this randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, we assessed the efficacy of a new fluid protocol based on the left ventricular end-diastolic pressure for the prevention of contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. The primary outcome was the occurrence of contrast-induced acute kidney injury, which was defined as a greater than 25% or greater than 0·5 mg/dL increase in serum creatinine concentration. Between Oct 10, 2010, and July 17, 2012, 396 patients aged 18 years or older undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min per 1·73 m(2) or less and one or more of several risk factors (diabetes mellitus, history of congestive heart failure, hypertension, or age older than 75 years) were randomly allocated in a 1:1 ratio to left ventricular end-diastolic pressure-guided volume expansion (n=196) or the control group (n=200) who received a standard fluid administration protocol. Four computer-generated concealed randomisation schedules, each with permuted block sizes of 4, were used for randomisation, and participants were allocated to the next sequential randomisation number by sealed opaque envelopes. Patients and laboratory personnel were masked to treatment assignment, but the physicians who did the procedures were not masked. Both groups received intravenous 0·9% sodium chloride at 3 mL/kg for 1 h before cardiac catheterisation. Analyses were by intention to treat. Adverse events were assessed at 30 days and 6 months and all such events were classified by staff who were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01218828. FINDINGS: Contrast-induced acute kidney injury occurred less frequently in patients in the left ventricular end-diastolic pressure-guided group (6·7% [12/178]) than in the control group (16·3% [28/172]; relative risk 0·41, 95% CI 0·22-0·79; p=0·005). Hydration treatment was terminated prematurely because of shortness of breath in three patients in each group. INTERPRETATION: Left ventricular end-diastolic pressure-guided fluid administration seems to be safe and effective in preventing contrast-induced acute kidney injury in patients undergoing cardiac catheterisation. FUNDING: Kaiser Permanente Southern California regional research committee grant.


Assuntos
Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Hidratação/métodos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cateterismo Cardíaco/métodos , Protocolos Clínicos , Creatinina/sangue , Feminino , Hidratação/efeitos adversos , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal , Método Simples-Cego , Volume Sistólico/fisiologia
11.
J Prosthet Dent ; 114(1): 46-51, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25819358

RESUMO

STATEMENT OF PROBLEM: Unlike conventional loading protocols, the immediate loading of single implants has not been fully investigated. PURPOSE: The purpose of this study was to assess the prosthetic and esthetic periimplant mucosal outcomes of immediately restored dental implants during a 1-year follow-up. MATERIAL AND METHODS: Twenty participants meeting the established inclusion criteria received double-threaded, tapered body dental implants (SuperLine; Dentium). Implants were placed and stabilized at a minimum of 35 Ncm of torque and restored immediately after the surgery with interim restorations. These were replaced with definitive restorations 6 months after implant placement. Clinical measurements at each visit included resonance frequency analysis, the evaluation of the participants' oral health (gingival and plaque indices), and the esthetic outcome of the interim or definitive restoration. RESULTS: Implants placed in this clinical study had a 100% success rate. The oral health and esthetic outcomes were favorable for all participants. CONCLUSIONS: Double-threaded, tapered body dental implants that were placed and immediately restored with fixed interim prostheses and with definitive prostheses after 6 months remained stable and functional after 1 year.


Assuntos
Implantes Dentários para Um Único Dente , Planejamento de Prótese Dentária , Carga Imediata em Implante Dentário/métodos , Densidade Óssea/fisiologia , Coroas , Implantação Dentária Endóssea/métodos , Índice de Placa Dentária , Retenção em Prótese Dentária , Prótese Dentária Fixada por Implante , Restauração Dentária Temporária , Estética Dentária , Seguimentos , Humanos , Mastigação/fisiologia , Osseointegração/fisiologia , Medição da Dor/métodos , Satisfação do Paciente , Índice Periodontal , Fonética , Estudos Prospectivos , Propriedades de Superfície , Torque , Resultado do Tratamento
12.
Evol Dev ; 16(5): 292-305, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25143258

RESUMO

The evolutionary origin of Lissamphibia likely involved heterochrony, as demonstrated by the biphasic lifestyles of most extant orders, differences between Anura (with tadpole-to-froglet metamorphosis) and Urodela (which lack strongly defined metamorphosis), and the appearance of direct development among separate lineages of frogs. Patterns in the timing of appearance of skeletal elements (i.e., ossification sequence data) represent a possible source of information for understanding the origin of Lissamphibia, and with the advent of analytical methods to directly optimize these data onto known phylogenies, there has been a renewed interest in assessing the role of changes in these developmental events. However, little attention has been given to the potential impact of variation in ossification sequence data--this is particularly surprising given that different criteria for collecting these data have been employed. Herein, new and previously published ossification data are compiled and all pairs of data for same-species comparisons are selected. Analyses are run to assess the impact of using data that were collected by different methodologies: (1) wild- versus lab-raised animals; (2) different criteria for recognizing timing of ossification; and (3) randomly selecting ossification sequences for species from which multiple studies have been published, but for which the data were collected by different criteria. Parsimov-based genetic inference is utilized to map ossification sequence data onto an existing phylogeny to reconstruct ancestral sequences of ossification and infer instances of heterochrony. All analyses succeeded in optimizing sequence data on internal nodes and instances of heterochrony were identified. However, among all analyses little congruence was found in reconstructed ancestral sequences or among inferred instances of heterochrony. These results indicate a high degree of variation in timing of ossification, and suggest a cautionary note about use of these data, particularly given that in most instances issues associated with the original sources of data (e.g., wild- vs. lab-raised animals; or criteria for identification of earliest ossification) are not addressed. Potential sources of variation in the original data are discussed and may explain the incongruence observed here.


Assuntos
Anfíbios/classificação , Anfíbios/embriologia , Osteogênese , Anfíbios/genética , Animais , Crânio/embriologia , Fatores de Tempo
13.
Am J Med Genet A ; 164A(3): 691-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24459042

RESUMO

We evaluated 2,083 cases within the Wisconsin Stillbirth Service Program (WiSSP) that had autopsy reports or ultrasound data relevant to the heart. Of these, 167/1,782 (9.4%) stillbirths after 20 weeks and 11/301 (3.7%) miscarriages <20 weeks had congenital heart disease (CHD). Cases were classified by type of heart defect and whether it related to cause of death. Among cardiac anomalies that contributed significantly to fetal death, 125/151 (83%) were associated with underlying conditions or syndromes, nearly half of which were chromosomal. The most common forms of CHD in stillborns were severe cyanotic lesions (3%), then ventricular (2.6%) and atrial (1.9%) septal defects. Compared to livebirths, this represents a shift toward more severe cardiac lesions, although all comparable categories, including non-lethal conditions such as atrial septal defect, are more common in stillbirths. Clinical cardiomyopathy was identified as cause of death in 1.2% of stillborns. Cardiomegaly, occurring in 26.7% of all cases and 76.7% of infants born to diabetic mothers, may represent undiagnosed cardiomyopathy and/or may decrease fetal tolerance of hypoxia. In contrast, 78.5% of Turner syndrome infants, all <32 weeks, had small hearts. More attention to cardiac findings can lead to increased understanding of stillbirth causes. Based on our findings, we recommend chromosome studies on all stillbirths and close attention to the heart during second trimester ultrasounds, with chromosome studies offered if CHD is found. Consideration of heart size can result in prenatal identification of infants at risk for stillbirth, particularly large hearts in fetuses of diabetic mothers in the third trimester, which may identify fetal cardiomyopathy before it becomes life-threatening.


Assuntos
Cardiopatias Congênitas/epidemiologia , Natimorto/epidemiologia , Autopsia , Idade Gestacional , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/etiologia , Humanos , Incidência , Prevalência , Ultrassonografia , Wisconsin/epidemiologia
14.
J Occup Environ Med ; 66(3): 252-262, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38234103

RESUMO

OBJECTIVE: The aim of the study is to describe cost and frequency of work-related musculoskeletal disorders in Kansas. METHODS: Data were provided by the Kansas Department of Labor and included all closed workers' compensation claims entailing indemnity and medical costs from 2014 to 2022. RESULTS: Work-related musculoskeletal disorder claims entailed a median total cost of $20,097. Medical comprised 48.4% of costs, indemnity 46.4%, and legal 5.2%. The most frequently injured and costliest body part was the shoulder. Manufacturing comprised 28.4% of claims, followed by health care and office. Lifting was the most common cause, generating 32.0% of claims. Education, transportation, and mining were among industries with above average claim rates. CONCLUSIONS: Very few studies use workers' compensation data to assess work-related musculoskeletal disorder costs. This study introduces a state not yet analyzed and presents more recent years of data than available in the literature.


Assuntos
Doenças Musculoesqueléticas , Indenização aos Trabalhadores , Humanos , Kansas , Indústrias , Doenças Musculoesqueléticas/epidemiologia , Dor
15.
Work ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306083

RESUMO

BACKGROUND: The American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Values (TLVs) for Lifting is a manual material handling (MMH) assessment method to identify weight limits that nearly all workers may be exposed to without developing work-related low back disorders (LBD). However, this assessment method only applies to lifting with the torso within 30° asymmetry of the sagittal plane. OBJECTIVE: Estimate TLV weight limits while lifting with torso asymmetry greater than 30° beyond the sagittal plane. METHODS: Lifting tasks were performed from various horizontal and vertical locations, at torso asymmetry angles of 0°, 15°, 30°, 45°, 60°, 75° and 90°, using ACGIH identified TLVs. Validated MMH assessment methods (NIOSH Lifting Equation, Ohio State University LBD Risk Model) were utilized to estimate TLVs at torso asymmetries greater than 30°. RESULTS: The current ACGIH TLVs resulted in low- to moderate-risk risk levels for torso asymmetries from 0° to 30°, and the risk incrementally increased as torso asymmetry increased to 90°. With the intention to keep the risk levels to that found at 30° torso asymmetry, lower TLV weight limits in the vertical and horizontal zones investigated were estimated for torso asymmetries from 45° to 90°. The resulting adjusted TLVs were consistent with weight limits identified for similar lifting conditions from other assessment methods that account for torso asymmetry. CONCLUSIONS: This research found current ACGIH-defined TLVs possess less than high-risk for LBD, and provided guidance to practitioners for reduced TLVs when torso asymmetry is greater than 30° from the sagittal plane.

16.
Front Sports Act Living ; 6: 1392809, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887686

RESUMO

Introduction: Initially developed by New Zealand Rugby in 2014, the Blue Card initiative in rugby enables match officials to remove athletes from play if they are suspected to have sustained a concussion. Considerable attention has been paid by sport and health advocates to the possibilities and limitations of this initiative in safeguarding athlete health. However, little if any attention has been paid to the well-being of those responsible for administering the Blue Card (i.e., match officials). The aim of this paper was to examine match officials' experiences with and perspectives on implementing the Blue Card initiative in Ontario, Canada, with focused attention on the tensions around their ability to manage games and participants (e.g., athletes, coaches) while attempting to safeguard athlete well-being. Methods: Using Relational Coordination Theory (RCT) as a guiding framework and qualitative research method, we highlight the rich accounts of 19 match officials' perspectives and experiences regarding sport-related concussion (SRC) management and the Blue Card protocol. Results: Four themes were derived from the data, reflecting latent assumptions embedded within the concussion management process, which include: assumptions of trust, respect, and cooperation; assumptions of shared responsibility; assumptions of shared understanding; and assumptions of harassment-free sport. Discussion: Our findings emphasize the need to attend to social relations in concussion management and provide insight into match officials' fraught experiences on the frontlines of concussion management. We identify factors affecting match official well-being and provide considerations for concussion management initiatives designed to improve athlete safety, such as the Blue Card.

17.
Appl Ergon ; 119: 104313, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38749093

RESUMO

Work-related musculoskeletal disorder of upper extremity multi-task assessment methods (Revised Strain Index [RSI], Distal Upper Extremity Tool [DUET]) and manual handling multi-task assessment methods (Revised NIOSH Lifting Equation [RNLE], Lifting Fatigue Failure Tool [LiFFT]) were compared. RSI and DUET showed a strong correlation (rs = 0.933, p < 0.001) where increasing risk factor exposure resulted in increasing outputs for both methods. RSI and DUET demonstrated fair agreement (κ = 0.299) in how the two methods classified outputs into risk categories (high, moderate or low) when assessing the same tasks. The RNLE and LiFFT showed a strong correlation (rs = 0.903, p = 0.001) where increasing risk factor exposure resulted in increasing outputs, and moderate agreement (κ = 0.574) in classifying the outputs into risk categories (high, moderate or low) when assessing the same tasks. The multi-task assessment methods provide consistent output magnitude rankings in terms of increasing exposure, however some differences exist between how different methods classify the outputs into risk categories.


Assuntos
Ergonomia , Remoção , Doenças Musculoesqueléticas , Doenças Profissionais , Análise e Desempenho de Tarefas , Extremidade Superior , Humanos , Ergonomia/métodos , Extremidade Superior/fisiologia , Extremidade Superior/fisiopatologia , Doenças Profissionais/etiologia , Doenças Musculoesqueléticas/etiologia , Medição de Risco/métodos , Remoção/efeitos adversos , Masculino , Adulto , Feminino , Fatores de Risco , Dor Lombar/etiologia , Estados Unidos , Pessoa de Meia-Idade , National Institute for Occupational Safety and Health, U.S.
18.
Front Sports Act Living ; 6: 1360329, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799030

RESUMO

Introduction: Parents play an important role in preventing and managing sport-related concussions among youth sport participants. Research indicates that parents understand the severity and consequences associated with the injury but gaps exist in their knowledge of its management. Neuropsychological baseline testing (NBT) is a modality that has gained interest in youth sport to purportedly better manage concussion injuries. Little is known about parents' perspectives on the use of NBT in the management process. Methods: The present qualitative study used Protection Motivation Theory as a guiding framework and employed focus groups (N = 2) with parents (N = 11) to gain insight into parents' perceptions and experiences with concussion management, specifically focusing on NBT. Results: Inductive Content Analysis developed a core theme of navigating uncertainty. Participants expressed uncertainty about the nature of concussion and its management process, where concussion was not always easy to identify, youth were not always reliable reporters, and there was no prescribed or proscribed path for recovery. Personal experience and concussion management policy provided participants with a degree of certainty in managing concussions. Participants gave NBT mixed reviews in potentially promoting greater certainty but also held reservations about its usefulness in concussion management. Discussion: We discuss findings relative to existing knowledge and theory in youth sport concussion and identify implications for practice.

19.
Work ; 76(3): 1047-1060, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37125603

RESUMO

BACKGROUND: Work-related low back pain (LBP) increases the workforce disability and healthcare costs. This study evaluated the LBD risk level associated with handling the ACGIH TLVs in lifting tasks corresponding to various horizontal and vertical zones. OBJECTIVE: The aim of this study was to compare the low-risk ACGIH TLV to risk outcomes from various validated lifting assessment methods, including the OSU LBD Risk Model, NIOSH Lifting Equation, and LiFFT. METHODS: Twenty-four subjects were recruited for this study to perform various lifting conditions. The various ergonomic assessment methods were then used to obtain the risk assessment outcomes. RESULTS: The selected assessment methods showed that the ACGIH-defined TLVs are associated with less than high-risk for LBD for all the assessed tasks. The findings showed a moderate agreement (Kendall's W = 0.477) among the various assessment methods risk outcomes. The highest correlation (ρ= 0.886) was observed between the NIOSH Lifting Equation and LiFFT methods risk assessment outcomes. CONCLUSION: The findings showed that ACGIH-defined TLVs possesses less than high-risk for LBD. The outcomes of the selected ergonomic assessment methods moderately agree to each other.


Assuntos
Remoção , Dor Lombar , Estados Unidos , Humanos , Remoção/efeitos adversos , Níveis Máximos Permitidos , Ergonomia/métodos , Dor Lombar/etiologia , National Institute for Occupational Safety and Health, U.S.
20.
Front Immunol ; 14: 1242242, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022505

RESUMO

The severe and chronic inflammatory bowel diseases (IBD), Crohn disease and ulcerative colitis, are characterized by persistent inflammation and gut damage. There is an increasing recognition that the gut microbiota plays a pivotal role in IBD development and progression. However, studies of the complete microbiota composition (bacteria, fungi, viruses) from precise locations within the gut remain limited. In particular, studies have focused primarily on the bacteriome, with available methods limiting evaluation of the mycobiome (fungi) and virome (virus). Furthermore, while the different segments of the small and large intestine display different functions (e.g., digestion, absorption, fermentation) and varying microenvironment features (e.g., pH, metabolites), little is known about the biogeography of the microbiota in different segments of the intestinal tract or how this differs in IBD. Here, we highlight evidence of the differing microbiota communities of the intestinal sub-organs in healthy and IBD, along with method summaries to improve future studies.


Assuntos
Colite Ulcerativa , Doença de Crohn , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Microbiota , Vírus , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Doença de Crohn/microbiologia , Colite Ulcerativa/microbiologia
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