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2.
Klin Onkol ; 37(6): 467-472, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38158236

RESUMO

BACKGROUND: Postoperative oral cancers with close margins belong to medium- to high-risk category for local failure. During re-surgery for close margins, there is sufficient doubt as to whether the re-excised tissue is from the same region as the close margin. Therefore, we planned a retrospective review of these cases of close margins that were re-excised with extra-resection margins (ERMs). MATERIAL AND METHODS: Details of 2011 oral cavity patients resected at our hospital were retrieved. Cases with close margins were segregated and the status of ERMs was noted. The postoperative histopathological details, radiotherapy details, and failure patterns in all these cases were documented. The primary objective of the study was to assess the overall survival (OS) and disease-free survival (DFS) in cases with ERMs. The secondary objective was to assess the local and regional control rates and variation with the number and status of close and ERMs. OS, DFS, and local failure rates were defined from the date of registration. Statistical analysis was performed with the SPSS statistical software package. All survival analyses were performed using the Kaplan-Meier method. Log-rank test was used to test the statistical significance. A P-value of 0.05 was considered statistically significant. RESULTS: Sixty-four cases with a median age of 47 years (range: 29-76) were considered for the final analysis. The median follow-up was 40 months (range: 9.5-56.5). The 2-year OS and DFS rates were 91.5% and 88.5%, respectively. The crude local and regional failure rates were 10.9% and 3.1%, respectively. The 3-year locoregional control rate was 90.2%. The 2-year locoregional control rate for one close margin was significantly better as compared to more than one close margin (P = 0.049). No difference in survival and failure rates was found between the number of ERMs resected (one vs. two) and ≤ vs. > 3 mm close margin status. Two patients developed bone metastases. CONCLUSION: The survival rates and locoregional control rates did not differ much between the groups that had one or more ERMs. However, the locoregional control rates were better in cases with one close margin as compared to those with more than one close margin. A larger study with longer follow-up is needed to detect statistically significant differences in outcomes and identify the factors that portend poor prognosis in these cases with close margins and ERMs.


Assuntos
Margens de Excisão , Neoplasias Bucais , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/radioterapia , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Complicações Pós-Operatórias
3.
Contemp Clin Trials ; 131: 107274, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37380019

RESUMO

BACKGROUND: Poor diet quality is an important risk factor for increased asthma prevalence and poor asthma control. To address the question of whether adults with asthma can benefit from following a healthy diet, this trial will test the efficacy and mechanisms of action of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with sodium reduction among patients with uncontrolled asthma. METHODS: In this 2-arm randomized clinical trial, 320 racially/ethnically and socioeconomically diverse adults with uncontrolled asthma on standard controller therapy will be randomized to either a control or an intervention group and assessed at baseline, 3, 6 and 12 months. Control and intervention participants will receive education on lung health, asthma, and other general health topics; additionally, the intervention group will receive DASH behavioral counseling over 12 months. The primary hypothesis is that the DASH behavioral intervention, compared with the education-only control, will lead to significantly more participants with minimum clinically important improvement (responders) in asthma-specific quality of life at 12 months. Secondary hypotheses will test the intervention effects on other asthma (e.g., asthma control, lung function) and non-asthma outcomes (e.g., quality of life). Additionally, therapeutic (e.g., short chain fatty acids, cytokines) and nutritional biomarkers (e.g., dietary inflammatory index, carotenoids) will be assessed to understand the mechanisms of the intervention effect. CONCLUSION: This trial can substantially advance asthma care by providing rigorous evidence on the benefits of a behavioral dietary intervention and mechanistic insights into the role of diet quality in asthma. CLINICALTRIALS: gov #: NCT05251402.


Assuntos
Asma , Abordagens Dietéticas para Conter a Hipertensão , Hipertensão , Humanos , Adulto , Qualidade de Vida , Dieta , Asma/tratamento farmacológico , Terapia Comportamental/métodos , Hipertensão/epidemiologia , Hipertensão/terapia
4.
ESMO Open ; 7(6): 100641, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36462464

RESUMO

BACKGROUND: Selective tyrosine kinase inhibitors targeting fibroblast growth factor receptor (FGFR) 1-4 genomic alterations are in development or have been approved for FGFR-altered cancers (e.g. bladder cancer and advanced intrahepatic cholangiocarcinoma). Understanding FGFR inhibitor-resistance mechanisms is increasingly relevant; we surveyed the pan-tumor landscape of FGFR1-4 genomic alterations [short variants (SVs), gene rearrangements (REs), and copy number alterations (CNAs)], including their association with tumor mutational burden (TMB) and the genomic comutational landscape. PATIENTS AND METHODS: Comprehensive genomic profiling of 355 813 solid tumor clinical cases was performed using the FoundationOne and FoundationOne CDx assays (Foundation Medicine, Inc.) to identify genomic alterations in >300 cancer-associated genes and TMB (determined on ≤1.1 megabases of sequenced DNA). RESULTS: FGFR1-4 SVs and REs occurred in 9603/355 813 (2.7%), and CNAs in 15 078/355 813 (4.2%) samples. Most common FGFR alterations for bladder cancer, intrahepatic cholangiocarcinoma, and glioma were FGFR3 SVs (1051/7739, 13.6%), FGFR2 REs (618/6641, 9.3%), and FGFR1 SVs (239/11 550, 2.1%), respectively. We found several, potentially clinically relevant, tumor-specific associations between FGFR1-4 genomic alterations and other genomic markers. FGFR3 SV-altered bladder cancers and FGFR1 SV-altered gliomas were significantly less likely to be TMB-high versus unaltered samples. FGFR3 SVs in bladder cancer significantly co-occurred with TERT and CDKN2A/B alterations; TP53 and RB1 alterations were mutually exclusive. In intrahepatic cholangiocarcinoma, FGFR2 REs significantly co-occurred with BAP1 alterations, whereas KRAS, TP53, IDH1, and ARID1A alterations were mutually exclusive. FGFR1 SVs in gliomas significantly co-occurred with H3-3A and PTPN11 alterations, but were mutually exclusive with TERT, EGFR, TP53, and CDKN2A/B alterations. CONCLUSIONS: Overall, our hypothesis-generating findings may help to stratify patients in clinical trials and guide optimal targeted therapy in those with FGFR alterations.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Glioma , Neoplasias da Bexiga Urinária , Humanos , Ductos Biliares Intra-Hepáticos , Biomarcadores Tumorais/genética , Colangiocarcinoma/genética , Genômica , Glioma/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Receptores Proteína Tirosina Quinases/metabolismo
5.
Phys Rev Lett ; 129(16): 162701, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36306775

RESUMO

We have performed the first direct measurement of two resonances of the ^{7}Be(α,γ)^{11}C reaction with unknown strengths using an intense radioactive ^{7}Be beam and the DRAGON recoil separator. We report on the first measurement of the 1155 and 1110 keV resonance strengths of 1.73±0.25(stat)±0.40(syst) eV and 125_{-25}^{+27}(stat)±15(syst) meV, respectively. The present results have reduced the uncertainty in the ^{7}Be(α,γ)^{11}C reaction rate to ∼9.4%-10.7% over T=1.5-3 GK, which is relevant for nucleosynthesis in the neutrino-driven outflows of core-collapse supernovae (νp process). We find no effect of the new, constrained reaction rate on νp-process nucleosynthesis.

6.
Ann Oncol ; 33(12): 1269-1283, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36089135

RESUMO

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Ácidos Nucleicos Livres , Humanos , Ácidos Nucleicos Livres/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias dos Ductos Biliares/genética , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/patologia
7.
Br J Surg ; 108(10): 1180, 2021 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-34308468
8.
IBRO Rep ; 8: 48-55, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32072069

RESUMO

c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family and are derived from three genes, Jnk1-3. These kinases are involved in cellular responses to homeostatic insults, such as inflammation and apoptosis. Furthermore, increased JNK expression and activation are associated with debilitating neurodegenerative diseases, including Alzheimer's and Parkinson's. We previously reported elevated levels of phosphorylated JNK (pJNK), indicative of JNK hyperactivation, in the CA1 hippocampus of chronically epileptic rats. We also showed that pharmacological inhibition of JNK activity reduced seizure frequency in a dose-dependent fashion (Tai TY et al., Neuroscience, 2017). Building on these observations, the objectives of this current study were to investigate the timeline of JNK activation during epileptogenesis, and to identify the JNK isoform(s) that undergo hyperactivation in the chronic epilepsy stage. Western blotting analysis of CA1 hippocampal homogenates showed JNK hyperactivation only during the chronic phase of epilepsy (6-9 weeks post-status epilepticus), and not in earlier stages of epileptogenesis (1 h, 1 day, and 1 week post-status epilepticus). After enrichment for pJNK by immunoprecipitation, we identified JNK2 as the only significantly hyperactivated JNK isoform, with expression of the 54 kDa pJNK2 variant elevated to a greater extent than the 46 kDa pJNK2 variant. Expression of the total amounts of both JNK2 variants (phosphorylated plus non-phosphorylated) was reduced in epilepsy, however, suggesting that activation of upstream phosphorylation pathways was responsible for JNK2 hyperactivation. Since our prior work demonstrated that pharmacological inhibition of JNK activation had an antiepileptic effect, JNK2 hyperactivation is therefore likely a pathological event that promotes seizure occurrences. This investigation provides evidence that JNK2 is selectively hyperactivated in epilepsy and thus may be a novel and selective antiepileptic target.

9.
Pulm Pharmacol Ther ; 60: 101872, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31841698

RESUMO

Zileuton, a 5-lipoxygenase (5LPO) inhibitor exerts a broad influence in the arachidonic acid (AA) pathway by blocking upstream molecules that otherwise would lead to production of an array of inflammatory leukotrienes (LT) A4-E4. Hence, it has the potential to be a drug suitable to treat complicated asthmatics. Studies have shown modest response rates for zileuton in asthmatics. OBJECTIVE: We sought to study our hypothesis that response to zileuton varies across specific asthmatic phenotypes. METHODS: We retrospectively analyzed data from 129 patients with asthma that were prescribed zileuton at the University of Pittsburgh's Comprehensive Lung Clinic. A total of 75 patients from the above population had requisite lung function data and zileuton usage that would help assess a drug response effect. A zileuton responder was defined as having at least or greater than 5% annualized increase in post-bronchodilator FEV1% from baseline. Using a multivariate logistic regression analysis, we determined the association between responder status and the underlying phenotypic characteristics. RESULTS: Using generalized estimating equations (GEE) analysis of 331 individual lung function test data-points as well as logistic regression analysis for predictors of 5% or more annualized increase in FEV1%, 21 of 75 patients (28%) met criteria for having a differential response to zileuton. Severe asthma was associated less often with responder status (OR 0.12; p 0.004). Obesity was less often associated with responder status, however did not reach significance (OR 0.46; p 0.15). CONCLUSION: In this retrospective study, zileuton response varies across asthmatics, with poorer response rates being associated with those with severe asthma and possibly obesity. Although prescription trends for zileuton may predominate amongst severe asthmatics, this tendency does not seem to mirror the actual likelihood to respond. As against the trivial role for zileuton per current GINA algorithms, our study brings forward a notion that zileuton may well be considered along with LTRAs (like montelukast) for non-severe asthma.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Hidroxiureia/análogos & derivados , Inibidores de Lipoxigenase/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Hidroxiureia/uso terapêutico , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fenótipo , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
J Dent Res ; 98(1): 14-26, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30290130

RESUMO

The goal of nonrestorative or non- and microinvasive caries treatment (fluoride- and nonfluoride-based interventions) is to manage the caries disease process at a lesion level and minimize the loss of sound tooth structure. The purpose of this systematic review and network meta-analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2) adverse events. We included parallel and split-mouth randomized controlled trials where patients were followed for any length of time. Studies were identified with MEDLINE and Embase via Ovid, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews. Pairs of reviewers independently conducted the selection of studies, data extraction, risk-of-bias assessments, and assessment of the certainty in the evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Data were synthesized with a random effects model and a frequentist approach. Forty-four trials (48 reports) were eligible, which included 7,378 participants and assessed the effect of 22 interventions in arresting or reversing noncavitated or cavitated carious lesions. Four network meta-analyses suggested that sealants + 5% sodium fluoride (NaF) varnish, resin infiltration + 5% NaF varnish, and 5,000-ppm F (1.1% NaF) toothpaste or gel were the most effective for arresting or reversing noncavitated occlusal, approximal, and noncavitated and cavitated root carious lesions on primary and/or permanent teeth, respectively (low- to moderate-certainty evidence). Study-level data indicated that 5% NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions (low certainty) and that 38% silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface (moderate to high certainty). Preventing the onset of caries is the ultimate goal of a caries management plan. However, if the disease is present, there is a variety of effective interventions to treat carious lesions nonrestoratively.


Assuntos
Cárie Dentária , Metanálise em Rede , Selantes de Fossas e Fissuras , Dentição Permanente , Humanos , Dente Decíduo
12.
Oxf Med Case Reports ; 2018(3): omx105, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29576872

RESUMO

Occurrence of paradoxical arterial embolism may cause the first symptoms in patients with a coexisting hypercoagulable state and patent foramen ovale (PFO). This can result in significant morbidity and mortality depending on the location of the embolism. The risks and benefits of closure of small PFOs have not been well elucidated in prior studies. We describe a patient with a history of Factor V Leiden heterozygosity who presented with left arm pain secondary to arterial embolism. The patient was a 51-year-old male who initially presented to the emergency department after awaking from sleep with progressive, severe, burning left arm pain. He had also noted intermittent shortness of breath over the 2 weeks prior to admission. Temperature was 97.4 F, pulse 86, respiratory rate 20 and blood pressure 121/87. Oxygen saturation was 94% on supplemental oxygen. He had a cool left upper extremity and the patient described subjective paresthesias in this extremity. Left radial pulse was difficult to palpate. Physical exam was otherwise unremarkable. Troponin I was mildly elevated at 0.217 ng/l. White blood cell count was 11.8 and INR 1.1. EKG showed sinus tachycardia with non-specific T abnormalities in the anterior leads. His past medical history was notable for only hypertension and hyperlipidemia. Current recommendation is for antiplatelet or anticoagulation for those with hypercoaguable states who suffer a stroke; there is currently no absolute indication for closure device. We describe the case of a 51-year-old male who had presented with left arm pain and shortness of breath. The computed tomography (CT) angiography of chest showed pulmonary emboli with heavy clot burden bilaterally. Heparin was started, but patient was found to have occlusion along large arteries of the left arm. Emergent left axillary, brachial, radial and ulnar embolectomy for acute critical arm ischemia were performed. The transthoracic echocardiogram done the next day with bubble study was positive for patent foramen ovale. Hypercoaguability showed factor V Leiden heterozygosity. Decision was made for the patient to initiate long-term anticoagulation with rivaroxaban and closure was performed. Patient was advised that closure is off label but opted to proceed with closure in light of hypercoaguable state.

14.
AJNR Am J Neuroradiol ; 37(6): 985-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26869466

RESUMO

BACKGROUND AND PURPOSE: The American College of Radiology-American Society of Neuroradiology-Society for Pediatric Radiology Practice Parameter for a neck CT suggests that coverage should be from the sella to the aortic arch. It also recommends using CT scans judiciously to achieve the clinical objective. Our purpose was to analyze the potential dose reduction by decreasing the scan length of a neck CT and to assess for any clinically relevant information that might be missed from this modified approach. MATERIALS AND METHODS: This retrospective study included 126 children who underwent a neck CT between August 1, 2013, and September 30, 2014. Alteration of the scan length for the modified CT was suggested on the topographic image on the basis of the indication of the study, with the reader blinded to the images and the report. The CT dose index volume of the original scan was multiplied by the new scan length to calculate the dose-length product of the modified study. The effective dose was calculated for the original and modified studies by using age-based conversion factors from the American Association of Physicists in Medicine Report No. 96. RESULTS: Decreasing the scan length resulted in an average estimated dose reduction of 47%. The average reduction in scan length was 10.4 cm, decreasing the overall coverage by 48%. The change in scan length did not result in any missed findings that altered management. Of the 27 abscesses in this study, none extended to the mediastinum. All of the lesions in question were completely covered. CONCLUSIONS: Decreasing the scan length of a neck CT according to the indication provides a significant savings in radiation dose, while not altering diagnostic ability or management.


Assuntos
Pescoço/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X/métodos , Criança , Humanos , Radiologia , Estudos Retrospectivos , Estados Unidos
15.
Aliment Pharmacol Ther ; 42(2): 188-202, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25996351

RESUMO

BACKGROUND: Vedolizumab, an anti-α(4)ß(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. AIMS: To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. METHODS: Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. RESULTS: Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). CONCLUSIONS: Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3).


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/uso terapêutico , Adolescente , Adulto , Idoso , Albuminas/uso terapêutico , Peso Corporal , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Adulto Jovem
16.
Genes Brain Behav ; 14(4): 357-68, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25868909

RESUMO

The nematode Caenorhabditis elegans has been a powerful model system for the study of key muscle genes relevant to human neuromuscular function and disorders. The behavioral robustness of C. elegans, however, has hindered its use in the study of certain neuromuscular disorders because many worm models of human disease show only subtle phenotypes while crawling. By contrast, in their natural habitat, C. elegans likely spends much of the time burrowing through the soil matrix. We developed a burrowing assay to challenge motor output by placing worms in agar-filled pipettes of increasing densities. We find that burrowing involves distinct kinematics and turning strategies from crawling that vary with the properties of the substrate. We show that mutants mimicking Duchenne muscular dystrophy by lacking a functional ortholog of the dystrophin protein, DYS-1, crawl normally but are severely impaired in burrowing. Muscular degeneration in the dys-1 mutant is hastened and exacerbated by burrowing, while wild type shows no such damage. To test whether neuromuscular integrity might be compensated genetically in the dys-1 mutant, we performed a genetic screen and isolated several suppressor mutants with proficient burrowing in a dys-1 mutant background. Further study of burrowing in C. elegans will enhance the study of diseases affecting neuromuscular integrity, and will provide insights into the natural behavior of this and other nematodes.


Assuntos
Comportamento Animal , Caenorhabditis elegans/genética , Movimento , Doenças Neuromusculares/fisiopatologia , Experimentação Animal , Animais , Fenômenos Biomecânicos , Caenorhabditis elegans/fisiologia , Proteínas de Caenorhabditis elegans/genética , Distrofina/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doenças Neuromusculares/genética
17.
Ann R Coll Surg Engl ; 96(1): 88E-90E, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24417851

RESUMO

Gastric duplication cysts are rare cystic neoplasms that are often difficult to distinguish from other entities. We describe a healthy 44-year-old woman who presented with acute right lower quadrant abdominal and flank pain as well as chronic nausea and constipation. Her physical examination was unremarkable but contrasted computed tomography revealed a 6 cm cystic lesion between the stomach and body of the pancreas. Endoscopic ultrasonography and fluid analysis were consistent with a mucinous cyst with a markedly elevated fluid carcinoembryonic antigen level. The patient subsequently underwent a laparoscopic distal pancreatectomy, which was converted to an open procedure when the lesion was noted to be adherent to the coeliac axis. Intraoperative endoscopy revealed no abnormality. Final pathology revealed a gastric duplication cyst. The patient recovered well and was asymptomatic on follow-up. In this report, we discuss the incidence, natural history and management of this rare entity.


Assuntos
Cistos/diagnóstico , Gastropatias/diagnóstico , Estômago/anormalidades , Adulto , Cistos/cirurgia , Diagnóstico Diferencial , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Cisto Pancreático/diagnóstico , Cisto Pancreático/cirurgia , Gastropatias/cirurgia
18.
Clin Neuroradiol ; 24(4): 365-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24477664

RESUMO

PURPOSE: CT hyperattenuation arising from iodinated contrast has a different temporal evolution than that arising due to hemorrhage. This paper presents a method for optimal discrimination between hemorrhage and iodinated contrast in a postintervention CT in stroke patients. METHODS: We analyzed the brain computed tomography (CT) scans of consecutive patients with intraparenchymal hyperattenuation due to hemorrhage (n=41), those due to iodinated contrast alone (n=24), and those due to contrast mixed with hemorrhage after reperfusion therapy (n=14) in stroke patients. The difference between the maximum enhancement in hyperattenuation in the affected area and the corresponding contralateral area, dubbed Relative Maximum Enhancement (RME), was tracked over time. We fitted regression models to the RME changes due to hemorrhage and contrast to describe their temporal decay, and then derived the optimal discriminant curve that distinguishes the two. A computer algorithm coregistered the baseline and follow-up CT scans and performed pixel-by-pixel comparison to determine hemorrhage and iodinated contrast based on the RME changes with respect to the discriminant curve. RESULTS: For both hemorrhage (k= -0.004, R (2) =0.7) and iodinated contrast (k= -0.064, R (2) =0.9), the temporal evolution of RMEs were best fitted by exponential decay curves, with respective half-lives of 192.3 and 10.7 h. An exponential decay model (k= -0.026) for optimal discrimination of hemorrhage vs. contrast was fitted. The computer algorithm implementing this model was successful in predicting the presence of hemorrhage in a hyperdense lesion with sensitivity =93% and specificity =91%. CONCLUSION: Intraparenchymal hemorrhage and contrast have markedly different decay half-lives that can be used to assess hemorrhage in a hyperdense lesion on a CT scan after intra-arterial therapy.


Assuntos
Angiografia Cerebral/efeitos adversos , Angiografia Cerebral/métodos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/prevenção & controle , Procedimentos Endovasculares , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do Tratamento
19.
J Pediatr Urol ; 10(2): 306-11, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24290222

RESUMO

OBJECTIVE: Cumulative summation (CUSUM) charting is a statistical tool that allows an individual surgeon or surgical department to monitor any binary outcome and rapidly detect when complications are outside the acceptable limits. We applied CUSUM statistical analysis to hypospadias repair to utilize the results in our own quality Improvement process. MATERIALS AND METHODS: An institutional review board-approved retrospective review of all patients who underwent hypospadias repair by a single fellowship trained pediatric urologist at a single institution between September 2004 to July 2009 was performed. To graphically represent the complication rates and to assess for unacceptable rates, the use of CUSUM control charting was employed. RESULTS: In our retrospective review, there were a total of 184 patients who underwent a total of 203 surgeries. Using CUSUM analysis, our incidence of major complications was within acceptable limits until approximately the first 150 operations had been performed, at which time the complication rate fell below the lower limit, indicating performance exceeded expectations. CONCLUSION: CUSUM statistical charting was successfully applied to the retrospective monitoring of hypospadias outcomes at our institution. This is the first known publication in which CUSUM charts were used to evaluate complications of hypospadias repair.


Assuntos
Hipospadia/cirurgia , Monitorização Fisiológica/métodos , Melhoria de Qualidade , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Pré-Escolar , Estudos de Coortes , Humanos , Hipospadia/diagnóstico , Lactente , Masculino , Prontuários Médicos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Deiscência da Ferida Operatória/diagnóstico , Deiscência da Ferida Operatória/epidemiologia , Resultado do Tratamento , Estreitamento Uretral/diagnóstico , Estreitamento Uretral/epidemiologia , Procedimentos Cirúrgicos Urológicos/métodos
20.
Phys Rev Lett ; 110(3): 032502, 2013 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-23373915

RESUMO

The (18)F(p,α)(15)O reaction rate is crucial for constraining model predictions of the γ-ray observable radioisotope (18)F produced in novae. The determination of this rate is challenging due to particular features of the level scheme of the compound nucleus, (19)Ne, which result in interference effects potentially playing a significant role. The dominant uncertainty in this rate arises from interference between J(π)=3/2(+) states near the proton threshold (S(p)=6.411 MeV) and a broad J(π)=3/2(+) state at 665 keV above threshold. This unknown interference term results in up to a factor of 40 uncertainty in the astrophysical S-factor at nova temperatures. Here we report a new measurement of states in this energy region using the (19)F((3)He,t)(19)Ne reaction. In stark contrast to previous assumptions we find at least 3 resonances between the proton threshold and E(cm)=50 keV, all with different angular distributions. None of these are consistent with J(π)=3/2(+) angular distributions. We find that the main uncertainty now arises from the unknown proton width of the 48 keV resonance, not from possible interference effects. Hydrodynamic nova model calculations performed indicate that this unknown width affects (18)F production by at least a factor of two in the model considered.

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