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1.
Clin Lab ; 65(9)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532106

RESUMO

BACKGROUND: Bone marrow core biopsy is a routine component of comprehensive marrow evaluation, and adequacy criteria have been recommended. However, the effectiveness of these adequacy criteria for diagnostic bone marrow evaluation needs to be reassessed in the current era of extensive ancillary testing. We aimed to determine the impact of core biopsy length and intertrabecular area of evaluable bone marrow on overall adequacy for diagnostic marrow evaluation at our tertiary care institution. METHODS: Five hundred sequential cases of iliac crest bone marrow sampling were identified by retrospective re-view at our tertiary care institution. In this cohort, 470 core biopsies were obtained for histologic evaluation. Data including gross core biopsy length, number of intertrabecular 40x high power fields of evaluable marrow, and other pathologic/clinical parameters were compiled. RESULTS: The mean core biopsy length was 1.2 cm, and only 23% measured the recommended ≥ 1.5 cm. However, 96% of the core biopsies were interpretable and contributed to the comprehensive bone marrow evaluation. Notably, 100% of biopsies with ≥ 5.5 intertrabecular areas were contributory. Ancillary testing including immunophenotypic, cytogenetic, and/or molecular studies were performed in > 99% of cases. CONCLUSIONS: When histology was integrated with ancillary testing, the overall diagnosis was substantially limited in only 0.4% of cases and material deemed entirely insufficient in 0.4%. The number of intertrabecular 40x areas of evaluable marrow is a better predictor of adequacy than core biopsy length, and adequacy criteria should be revised in this era of extensive ancillary testing.


Assuntos
Exame de Medula Óssea/métodos , Doenças Hematológicas/diagnóstico , Neoplasias Hematológicas/diagnóstico , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Exame de Medula Óssea/normas , Criança , Pré-Escolar , Feminino , Doenças Hematológicas/sangue , Neoplasias Hematológicas/sangue , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
2.
BMC Genomics ; 16: 210, 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25880765

RESUMO

BACKGROUND: Whole and partial chromosome losses or gains and structural chromosome changes are hallmarks of human tumors. Guanine-rich DNA, which has a potential to form a G-quadruplex (G4) structure, is particularly vulnerable to changes. In Caenorhabditis elegans, faithful transmission of G-rich DNA is ensured by the DOG-1/FANCJ deadbox helicase. RESULTS: To identify a spectrum of mutations, after long-term propagation, we combined whole genome sequencing (WGS) and oligonucleotide array Comparative Genomic Hybridization (oaCGH) analysis of a C. elegans strain that was propagated, in the absence of DOG-1 and MDF-1/MAD1, for a total of 470 generations, with samples taken for long term storage (by freezing) in generations 170 and 270. We compared the genomes of F170 and F470 strains and identified 94 substitutions, 17 InDels, 3 duplications, and 139 deletions larger than 20 bp. These homozygous variants were predicted to impact 101 protein-coding genes. Phenotypic analysis of this strain revealed remarkable fitness recovery indicating that mutations, which have accumulated in the strain, are not only tolerated but also cooperate to achieve long-term population survival in the absence of DOG-1 and MDF-1. Furthermore, deletions larger than 20 bp were the only variants that frequently occurred in G-rich DNA. We showed that 126 of the possible 954 predicted monoG/C tracts, larger than 14 bp, were deleted in unc-46 mdf-1 such-4; dog-1 F470 (JNC170). CONCLUSIONS: Here, we identified variants that accumulated in C. elegans' genome after long-term propagation in the absence of DOG-1 and MDF-1. We showed that DNA sequences, with G4-forming potential, are vulnerable to deletion-formation in this genetic background.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , DNA Helicases/genética , Genoma , Animais , Caenorhabditis elegans/metabolismo , Hibridização Genômica Comparativa , Quadruplex G , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Mutação , Fenótipo , Análise de Sequência de DNA , Deleção de Sequência
3.
Genome Res ; 22(8): 1567-80, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22772596

RESUMO

Curation of a high-quality gene set is the critical first step in genome research, enabling subsequent analyses such as ortholog assignment, cis-regulatory element finding, and synteny detection. In this project, we have reannotated the genome of Caenorhabditis briggsae, the best studied sister species of the model organism Caenorhabditis elegans. First, we applied a homology-based gene predictor genBlastG to annotate the C. briggsae genome. We then validated and further improved the C. briggsae gene annotation through RNA-seq analysis of the C. briggsae transcriptome, which resulted in the first validated C. briggsae gene set (23,159 genes), among which 7347 genes (33.9% of all genes with introns) have all of their introns confirmed. Most genes (14,812, or 68.3%) have at least one intron validated, compared with only 3.9% in the most recent WormBase release (WS228). Of all introns in the revised gene set (103,083), 61,503 (60.1%) have been confirmed. Additionally, we have identified numerous trans-splicing leaders (SL1 and SL2 variants) in C. briggsae, leading to the first genome-wide annotation of operons in C. briggsae (1105 operons). The majority of the annotated operons (564, or 51.0%) are perfectly conserved in C. elegans, with an additional 345 operons (or 31.2%) somewhat divergent. Additionally, RNA-seq analysis revealed over 10 thousand small-size assembly errors in the current C. briggsae reference genome that can be readily corrected. The revised C. briggsae genome annotation represents a solid platform for comparative genomics analysis and evolutionary studies of Caenorhabditis species.


Assuntos
Caenorhabditis/genética , Genoma Helmíntico , Anotação de Sequência Molecular/métodos , Análise de Sequência de RNA/métodos , Transcriptoma , Processamento Alternativo , Animais , Sequência de Bases , Sequência Conservada , Evolução Molecular , Perfilação da Expressão Gênica/métodos , Íntrons , Modelos Genéticos , Óperon , Sítios de Splice de RNA , RNA Líder para Processamento/genética , RNA Líder para Processamento/metabolismo , Alinhamento de Sequência/métodos , Sintenia , Trans-Splicing
4.
Proc Natl Acad Sci U S A ; 108(2): 609-14, 2011 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-21187420

RESUMO

Voltage gating of hyperpolarization-activated cation (HCN) channels is potentiated by direct binding of cAMP to a cytoplasmic cAMP-sensing domain (CSD). When unliganded, the CSD inhibits hyperpolarization-dependent opening of the HCN channel gate; cAMP binding relieves this autoinhibition so that opening becomes more favorable thermodynamically. This autoinhibition-relief mechanism is conserved with that of several other cyclic nucleotide receptors using the same ligand-binding fold. Besides its thermodynamic effect, cAMP also modulates the depolarization-dependent deactivation rate by kinetically trapping channels in an open state. Here we report studies of strong open-state trapping in an HCN channel showing that the well-established autoinhibition-relief model is insufficient. Whereas deletion of the CSD mimics the thermodynamic open-state stabilization usually associated with cAMP binding, CSD deletion removes rather than mimics the kinetic effect of strong open-state trapping. Substitution of different CSD sequences leads to variation of the degree of open-state trapping in the liganded channel but not in the unliganded channel. CSD-dependent open-state trapping is observed during a voltage-dependent deactivation pathway, specific to the secondary open state that is formed by mode shift after prolonged hyperpolarization activation. This hysteretic activation-deactivation cycle is preserved by CSD substitution, but the change in deactivation kinetics of the liganded channel resulting from CSD substitution is not correlated with the change in autoinhibition properties. Thus the liganded and the unliganded forms of the CSD respectively provide the structural determinants for open-state trapping and autoinhibition, such that two distinct mechanisms for cAMP regulation can operate in one receptor.


Assuntos
AMP Cíclico/química , Citoplasma/metabolismo , Sítio Alostérico , Animais , Cátions , Códon , Ativação do Canal Iônico/fisiologia , Cinética , Ligantes , Camundongos , Técnicas de Patch-Clamp , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Termodinâmica , Xenopus
5.
Diagnostics (Basel) ; 14(12)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38928689

RESUMO

The NG-Test CARBA 5 and Carbapenem-resistant K.N.I.V.O. Detection K-Set are lateral flow assays (LFAs) that rapidly detect five carbapenemases (KPC, NDM, IMP, VIM and OXA-48-like). We evaluated the effect of inoculum size on the performance of these two assays using 27 Enterobacterales isolates. Whole-genome sequencing (WGS) was used as the reference method. Using the NG-Test CARBA 5, eight Serratia spp. and six M. morganii isolates showed false-positive NDM results with a high inoculum. Using the Carbapenem-resistant K.N.I.V.O. Detection K-Set, eight M. morganii, four Serratia spp. and one K. pneumoniae isolates showed false-positive NDM and/or OXA-48-like bands at large inoculum sizes, while the other two M. morganii isolates demonstrated false-positive NDM and OXA-48-like results at all inoculum sizes. The false-positive bands varied in intensity. WGS confirmed that no carbapenemase gene was present. No protein sequence with a ≥50% identity to NDM or OXA-48-like enzymes was found. This study emphasizes the importance of assessing inoculum size in the diagnostic evaluation of LFAs.

6.
Children (Basel) ; 10(3)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36979997

RESUMO

Robotic gait training has the potential to improve secondary health conditions for people with severe neurological impairment. The purpose of this study was to describe who is using the Trexo robotic gait trainer, how much training is achieved in the home and community, and what impacts are observed after the initial month of use. In this prospective observational single-cohort study, parent-reported questionnaires were collected pre- and post-training. Of the 70 participants, the median age was 7 years (range 2 to 24), 83% had CP, and 95% did not walk for mobility. Users trained 2-5 times/week. After the initial month, families reported a significant reduction in sleep disturbance (p = 0.0066). Changes in bowel function, positive affect, and physical activity were not statistically significant. These findings suggest that families with children who have significant mobility impairments can use a robotic gait trainer frequently in a community setting and that sleep significantly improves within the first month of use. This intervention holds promise as a novel strategy to impact multi-modal impairments for this population. Future work should include an experimental study design over a longer training period to begin to understand the relationship between training volume and its full potential.

8.
J Autism Dev Disord ; 52(1): 435-446, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33660139

RESUMO

There is currently limited research and a lack of consensus on emotional processing impairments among adults with autism spectrum disorder (ASD). The present pilot study sought to characterize the extent to which adults with ASD are impaired in processing emotions in both words and pictures. Ten adults with ASD rated word and picture stimuli on emotional valence and arousal. Their ratings were compared to normative data for both stimuli sets using item-level correlations. Adults with ASD rank-ordered stimuli similarly to typically developing individuals, demonstrating relatively typical understanding of emotional words and pictures. However, they used a narrower range of the scales which suggests more subtle impairments affecting emotion-processing. Future directions arising from the findings of this pilot study are discussed.


Assuntos
Transtorno do Espectro Autista , Adulto , Nível de Alerta , Emoções , Humanos , Idioma , Projetos Piloto
9.
ScientificWorldJournal ; 11: 1089-100, 2011 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-21623454

RESUMO

With the rapid change to society after the opening of the gaming licensure by the government and the potential attraction to youth caused by the casinos, a well-tested and comprehensive adolescent development program previously established in Hong Kong was adopted and modified to be used in Macau. It is expected to help our adolescents achieve positive growth and be better prepared for future challenges. The aim of this study is to examine the effectiveness of the modified positive youth development program for Secondary 1 Students in Macau. Specifically, two research questions will be asked: (1) How does the positive youth development program affect positive growth for youth in Macau?; and (2) Is youth growth related to different factors such as gender, age, family financial condition, and parents' marital status? A mixed research method with a quantitative approach using a pre- and post-test pre-experimental design, and a qualitative approach using a focus group for the participants is carried out. The study sample included 232 Secondary 1 Students in two schools. The objective outcome evaluation showed that, overall, 123 (53%) of the participants had significant improvement on the total scores of the Chinese Positive Youth Development Scale (CPYDS) and the two composite scores. However, there were some increases in the behavioral intention of alcohol drinking and participation in gambling activities. The "happiness of the family life" was found to have significant differences in the score of the CPYDS, which was shown to be the factor related to youth growth. The focus group interviews revealed that both positive and negative feedback was obtained from the discussion; however, the majority of the participants perceived benefits to themselves from the program. With reference to the principle of triangulation, the present study suggests that, based on both quantitative and qualitative evaluation findings, it should be concluded that there is positive evidence supporting the effectiveness of the Tier 1 Program of the Hong Kong Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes), which was adopted and modified for Macau. In addition, special attention should be paid to the behavioral intention of alcohol drinking and participation in gambling activities in the local context.


Assuntos
Estudantes/psicologia , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Características da Família , Feminino , Grupos Focais , Jogo de Azar/epidemiologia , Jogo de Azar/psicologia , Humanos , Macau , Masculino , Avaliação de Programas e Projetos de Saúde , Instituições Acadêmicas
10.
J Am Coll Emerg Physicians Open ; 1(4): 487-493, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33000075

RESUMO

BACKGROUND: In 2006, the Centers for Disease Control and Prevention (CDC) recommended non-targeted, opt-out HIV screening in all healthcare settings, including emergency departments (EDs). Multiple HIV testing programs have been implemented in EDs across the United States with varying designs and testing platforms. We report findings from a free, non-targeted, rapid HIV testing program in 2 EDs in the Southeastern United States. METHODS: From 2008 to 2012, adults ≥18 years of age were offered free rapid HIV testing using an oral swab test (OraQuick ADVANCE Rapid HIV-1/2 antibody test) in the EDs of a large academic medical center and an affiliated community hospital in Durham, North Carolina. RESULTS: In total, 5443 ED patients were offered HIV testing. The overall acceptance rate was 66.9% (3639/5443). Younger persons were significantly more likely to accept testing (78.2% for 18-29 years old vs 67.1% for ≥30 years old; P < 0.001) as were Black participants (72.6% Black vs 66.5% White; P < 0.001). Acceptance rates improved significantly after opt-out oral consent replaced written consent (71.3% vs 63.1%; P < 0.001). Seven new HIV diagnoses were confirmed during the testing program, resulting in a seropositivity rate of 0.19% (7/3639). There were 8 false-positive rapid oral HIV tests (positive predictive value = 46.7%). CONCLUSIONS: Although the number of new HIV diagnoses was low, implementation of this rapid, non-targeted ED screening program was feasible with high acceptance rates, particularly after introducing the opt-out oral consent approach.

11.
AIDS Res Hum Retroviruses ; 34(11): 929-935, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29984584

RESUMO

Antiretroviral therapy (ART) has prolonged lives of persons living with HIV/AIDS (PLWHA), resulting in greater incidence of aging-related diseases and disability. Physical activity (PA) is recommended for healthy aging, but little is known about PA in older PLWHA. The purpose of this study was to objectively assess PA levels in older PLWHA and the associations with physical function. Twenty-one PLWHA, ≥50 years old, on ART with undetectable HIV-1 viral loads, wore an accelerometer to assess PA, including number of steps, activity intensity, and energy expenditure over 7 days. A physical function performance battery assessing aerobic capacity, strength, and gait speed was also completed. Average age was 66, and 67% were male. An average of 3,442 (interquartile range: 4,613) steps were walked daily, with 254.9 kcals expended. Participants spent most waking hours (75%) sedentary, with minimal hours (24%) in light-intensity activity. Only 5 min per day (35 min per week), on average, were spent in moderate-to-vigorous physical activity (MVPA). Maximal gait speed and 6-min walk test significantly correlated (p < .05) with all PA outcomes. Usual gait speed significantly correlated with all PA outcomes, except for daily kcals and light-intensity activity. Greater PA was associated with better physical performance, while high sedentary time was associated with poorer performance. To our knowledge, this is the first study to objectively measure PA in older PLWHA. Our findings indicate that older PLWHA accumulate substantial sedentary time. Most (86%) do not achieve recommended MVPA levels. This activity profile was associated with poor physical function. Providers should promote PA among PLWHA.


Assuntos
Exercício Físico/fisiologia , Infecções por HIV/fisiopatologia , Acelerometria , Idoso , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral
12.
CJEM ; 20(6): 882-891, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29041997

RESUMO

IntroductionOver 80% of children experience compromise in functioning following a fracture. Digital media may improve caregiver knowledge of managing fracture pain at home. OBJECTIVES: To determine whether an educational video was superior to an interactive web-based module (WBM) and verbal instructions, the standard of care (SOC). METHODS: This randomized trial included caregivers of children 0-17 years presenting to the emergency department (ED) with non-operative fractures. Primary outcome was the gain score (pre-post intervention) on a 21-item questionnaire testing knowledge surrounding pain recognition and management for children with fractures. Secondary outcomes included survey of caregiver confidence in managing pain (five-item Likert scale), number of days with difficulty sleeping, before return to a normal diet, and work/school missed. RESULTS: We analyzed 311 participants (WBM 99; video 108; SOC 104) with a mean (SD) child age of 9.6 (4.2) years, of which 125/311 (40.2%) were female. The video (delta=2.3, 95% CI: 1.3, 3.3; p<0.001) and WBM (delta=1.6; 95% CI: 0.5, 2.6; p=0.002) groups had significantly greater gain scores than the SOC group. The mean video gain score was not significantly greater than WBM (delta=0.7; 95% CI: -0.3, 1.8; p=0.25). There were no significant differences in caregiver confidence (p=0.4), number of absent school days (p=0.43), nights with difficulty sleeping (p=0.94), days before return to a normal diet (p=0.07), or workdays missed (p=0.95). CONCLUSIONS: A web-based module and online video are superior to verbal instructions for improving caregiver knowledge on management of children's fracture pain without improvement in functional outcomes.


Assuntos
Cuidadores/educação , Fraturas Ósseas/complicações , Educação em Saúde/métodos , Internet , Manejo da Dor/métodos , Dor/diagnóstico , Gravação em Vídeo/métodos , Adolescente , Criança , Pré-Escolar , Serviço Hospitalar de Emergência , Feminino , Fraturas Ósseas/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Dor/etiologia , Estudos Retrospectivos
13.
IEEE J Transl Eng Health Med ; 5: 2800206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29018639

RESUMO

The objective of this paper is development of an inexpensive point-of-care sensor for detecting the primary heart failure marker peptide, NT-proBNP. The device technology is based on an antibody sandwich assay, but with three innovative aspects. First, chemical amplification is carried out via oxidation of silver nanoparticles (NPs) attached to signaling antibodies rather than by enzymatic amplification. The electrochemical method is faster and eliminates the need for long-term storage of enzymes. Second, the antibody sandwich is formed on mobile magnetic beads. This enhances the rate of mass transfer of the biomarker and the signaling antibody to the primary detection antibody, which is immobilized on the magnetic beads. Third, the sensor itself is fabricated on a paper platform with screen-printed electrodes. This coupled with assembly by simple paper folding, keeps the cost of the sensor low. Here, we report on two separate assays. The first is based on a simple biotin-streptavidin conjugate, which is a preliminary model for the antibody assay. The results indicate a detection limit of 2.1 pM of silver NPs and an assay time of 7 min. The actual NT-proBNP antibody assay takes somewhat longer, and the dynamic detection range is higher: 2.9-582 nM. On the basis of the results presented in this paper, we conclude that this inexpensive paper-based sensor represents a viable technology for point-of-care testing of NT-proBNP, but nevertheless several challenges remain prior to clinical implementation. These include attaining a lower detection limit and better reproducibility, and optimizing the device for human blood.

14.
PLoS One ; 12(6): e0179874, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28662079

RESUMO

BACKGROUND: As antiretroviral therapy efficacy improves, HIV is gradually being recognized more as a chronic disease within the aging HIV-infected population. While these individuals are surviving into old age, they may, however, be experiencing "accelerated aging" with greater declines in physical function than that observed among comparably matched individuals free of HIV. This decline is not well understood and it remains unclear if physical decline correlates with the degree of immunosuppression based on CD4 lymphocyte nadir. METHODS: In a cross-sectional study of accelerated aging in the older HIV-infected population on antiretroviral therapy (ART), physical performance evaluations were completed on a cohort of 107 HIV-infected subjects, age 50 years or older (with no HIV-1 RNA >200 copies/mL in the prior 12 months), and compared to reference ranges for age- and gender-matched HIV-uninfected persons. Physical performance testing consisted of four validated assessments: the 2.4-meter walk, 30-second chair stand, grip strength and 6-minute walk test. RESULTS: When compared to age- and gender-matched HIV-uninfected reference controls, older HIV-infected persons had diminished physical function. No correlation was found between physical function and degree of immunosuppression as determined by pre-ART CD4 nadir. CONCLUSIONS: Despite improved survival, HIV-infected adults on suppressive ART have diminished physical function compared to HIV-uninfected persons. The degree of HIV-associated immunosuppression does not correlate with the observed degree of physical function decline in older HIV-infected persons, suggesting the decline is mediated by other mechanisms.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/fisiopatologia , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Sudeste dos Estados Unidos
15.
Mol Metab ; 4(9): 643-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26413470

RESUMO

OBJECTIVE: Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatment improves insulin sensitivity and exercise capacity in obese insulin resistant mice and whether skeletal muscle AMPK was important for mediating potential effects. METHODS: Glucose homeostasis, insulin sensitivity, exercise capacity, and electron transport chain content/activity were examined in wildtype (WT) and AMPK ß1ß2 muscle-specific null (AMPK-MKO) mice fed a high-fat diet (HFD) with or without R419 supplementation. RESULTS: There was no change in weight gain, adiposity, glucose tolerance or insulin sensitivity between HFD-fed WT and AMPK-MKO mice. In both HFD-fed WT and AMPK-MKO mice, R419 enhanced insulin tolerance, insulin-stimulated glucose disposal, skeletal muscle 2-deoxyglucose uptake, Akt phosphorylation and glucose transporter 4 (GLUT4) content independently of alterations in body mass. In WT, but not AMPK-MKO mice, R419 improved treadmill running capacity. Treatment with R419 increased muscle electron transport chain content and activity in WT mice; effects which were blunted in AMPK-MKO mice. CONCLUSIONS: Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity.

16.
Cell Cycle ; 13(19): 3089-199, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25486568

RESUMO

Spindle assembly checkpoint (SAC) ensures genome stability by delaying anaphase onset until all the chromosomes have achieved proper spindle attachment. Once correct attachment has been achieved, SAC must be silenced. In the absence of mdf-1/MAD1, an essential SAC component, Caenorhabditis elegans cannot propagate beyond 3 generations. Previously, in a dog-1(gk10)/FANCJ mutator background, we isolated a suppressor of mdf-1(gk2) sterility (such-4) which allowed indefinite propagation in the absence of MDF-1. We showed that such-4 is a Cyclin B3 (cyb-3) duplication. Here we analyze mdf-1 such-4; dog-1, which we propagated for 470 generations, with freezing of samples for long time storage at F170 and F270. Phenotypic analysis of this strain revealed additional suppression of sterility in the absence of MDF-1, beyond the effects of such-4. We applied oligonucleotide array Comparative Genomic Hybridization (oaCGH) and whole genome sequencing (WGS) and identified a further amplification of cyb-3 (triplication) and a new missense mutation in dynein heavy chain (dhc-1). We show that dhc-1(dot168) suppresses the mdf-1(gk2), and is the second cloned suppressor, next to cyb-3 duplication, that does not cause a delay in anaphase onset. We also show that amplification of cyb-3 and dhc-1(dot168) cooperate to increase fitness in the absence of MDF-1.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/genética , Ciclina B/metabolismo , Dineínas do Citoplasma/metabolismo , Proteínas Nucleares/genética , Sequência de Aminoácidos , Anáfase , Animais , Proteínas de Ciclo Celular/metabolismo , Hibridização Genômica Comparativa , Ciclina B/genética , Dineínas do Citoplasma/genética , DNA Helicases/genética , DNA Helicases/metabolismo , Genótipo , Humanos , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/metabolismo , Fenótipo , Alinhamento de Sequência
17.
Am J Gastroenterol ; 102(1): 56-63, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17100979

RESUMO

BACKGROUND: To assess the usefulness of air-inflated magnetic resonance colonography (MRC) in patients with incomplete conventional colonoscopy (CC). METHODS: From September 2001 to December 2004, 51 patients (25 male and 26 female, age range 32 to 85 years) with incomplete colonoscopy were recruited to have MRC performed. Half-fourier single short turbo spin echo (HASTE) axial, coronal, and three dimensional fat suppressed gradient echo sequence (VIBE) coronal images in both the prone and supine positions were performed for each patient. MRC was reviewed by two radiologists for detection of synchronous colonic lesion. The location and size of lesions were recorded and were compared with the findings of CC. Patients were managed according to the clinical situation and intraoperative findings were compared with MRC findings. Follow-up colonoscopy was performed in 29 patients. The follow-up colonoscopy findings were then compared with the MRC findings. RESULTS: Forty-four patients had incomplete colonoscopy because of an obstructing tumor. The other seven patients had incomplete colonoscopy because of excessive bowel looping. Apart from one patient suffering from chronic obstructive airway disease with resulting nondiagnostic MRC, all other patients had MRC successfully performed. Each colon was divided into six bowel segments for analysis. All 300 segments were of diagnostic quality and were assessed by the MRC. MRC correctly identified all 44 obstructing tumors demonstrated by initial CC. Synchronous tumors in proximal colonic segments were identified in two patients by MRC. In addition, MRC identified two colonic tumors located in bowel segments inaccessible by CC because of excessive looping. CONCLUSIONS: MRC is useful for detection of colonic pathology and assessment of proximal colon in patients with colonic cancer after incomplete colonoscopy.


Assuntos
Colo/patologia , Neoplasias do Colo/diagnóstico , Colonoscopia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ar , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade
18.
AJR Am J Roentgenol ; 179(5): 1167-72, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12388493

RESUMO

OBJECTIVE: Plantar fibromatosis is a rare benign fibroproliferative disorder of the plantar fascia that can be evaluated on sonography. Our study details the sonographic appearances of plantar fibromatosis. MATERIALS AND METHODS: We conducted a retrospective review of the clinical presentation, sonographic appearances, and clinical progress in 14 patients (range, 35-85 years; mean age, 53.1 years;) with plantar fibromatosis. Sonography was performed using either a 13-5-MHz multidimensional or 12.5-MHz linear array transducer. The location, sonographic appearances, and size of the plantar fibromatosis nodules were noted and correlated with symptom duration and clinical outcome. RESULTS: A total of 25 fibromatosis nodules in 19 feet were examined. On sonography, plantar fibromatosis was seen as a discrete fusiform nodular thickening of the plantar fascia, separate from the calcaneal insertion. Approximately one third (36%) of lesions were bilateral, and one quarter (26%) were multiple. All lesions were located either medially (60%) or centrally (40%) in the fascia. Most were hypoechoic (76%), were well defined (64%), and showed no acoustic enhancement (80%) or intrinsic vascularity (92%). No correlation was found between the echogenicity and size of plantar fibromatosis nodules or duration of symptoms (p < 0.01). One quarter of the affected feet had coexistent thickening of the plantar fascia at the calcaneal insertion with no related symptoms. CONCLUSION: Although the sonographic appearances of plantar fibromatosis vary, the appearances are characteristic enough to allow a specific diagnosis to be made. No clear relationship was found among the sonographic appearances, duration of symptoms, or clinical outcome.


Assuntos
Fáscia/diagnóstico por imagem , Fibroma/diagnóstico por imagem , Doenças do Pé/diagnóstico por imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia
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