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1.
Nature ; 628(8009): 804-810, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538783

RESUMO

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.


Assuntos
Genoma de Planta , Poliploidia , Saccharum , Cromossomos de Plantas/genética , Genoma de Planta/genética , Haplótipos/genética , Hibridização Genética/genética , Melhoramento Vegetal , Saccharum/classificação , Saccharum/genética , Biotecnologia , Padrões de Referência , DNA de Plantas/genética
2.
Gynecol Oncol ; 165(2): 230-238, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35277281

RESUMO

OBJECTIVE: Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. METHODS: This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. RESULTS: Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLEmut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12-20); with the shortest median time in MMRd patients, with 13 months (95% CI 5-21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P = .042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11-76), compared to 39 months (95% CI 21-57) and 10 months (95% CI 7-13) for the NSMP and p53abn cases respectively (log-rank, P = .001). CONCLUSION: Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients.


Assuntos
Neoplasias do Endométrio , Proteína Supressora de Tumor p53 , Estudos de Coortes , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética
3.
Int J Technol Assess Health Care ; 38(1): e61, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35761433

RESUMO

OBJECTIVES: Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. METHODS: The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. RESULTS: Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. CONCLUSIONS: Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.


Assuntos
Viés de Publicação , Humanos , Rosiglitazona/uso terapêutico
4.
Dermatol Online J ; 28(3)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36259806

RESUMO

In this report, a 55-year-old woman with Graves disease and exophthalmos had a recurrent nodule on the foot. Her initial biopsy and excision specimens were believed to be consistent with spindle cell lipoma, which aligned with her early tumor-like clinical morphology. Her tumor recurred after excision, which is not consistent with spindle cell lipoma. As her condition progressed, her clinical morphology became more consistent with localized myxedema and her biopsies were congruent, securing clinicopathologic correlation. With standard treatment for localized myxedema, she improved significantly. This case emphasizes how clinicians need to have high suspicion for localized myxedema in patients with history of Graves disease and exophthalmos. It also emphasizes how localized myxedema should be included in the histologic differential diagnosis for spindle cell lipoma with prominent myxoid stroma, particularly in those not responding to treatment as anticipated.


Assuntos
Exoftalmia , Doença de Graves , Lipoma , Mixedema , Humanos , Feminino , Pessoa de Meia-Idade , Mixedema/diagnóstico , Recidiva Local de Neoplasia , Lipoma/diagnóstico
5.
Ultrasound Obstet Gynecol ; 58(3): 457-468, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33314410

RESUMO

OBJECTIVE: To evaluate the ability of demographic and sonographic variables and the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) classification to predict preoperatively tumor recurrence or progression in women with endometrial cancer. METHODS: The study included 339 women with histologically confirmed endometrial cancer who underwent expert transvaginal ultrasound in a single center before surgery as part of the prospective International Endometrial Tumor Analysis 4 study or who were evaluated using the same protocol. The tumors were classified according to histotype, FIGO (International Federation of Gynecology and Obstetrics) grade and FIGO stage. In addition, molecular analysis was performed for classification into the four ProMisE subtypes: polymerase-ϵ exonuclease domain mutations (POLE EDM), mismatch repair proteins deficiency (MMR-D), protein 53 wild type (p53 wt) and protein 53 abnormal (p53 abn). Demographic and preoperative sonographic characteristics, tumor recurrence or progression and survival were compared between the ProMisE subgroups. Cox regression analysis was used to identify prognostic factors associated with recurrence or progression, using univariable models to study crude associations and multivariable models to study adjusted associations. Logistic regression and receiver-operating-characteristics (ROC)-curve analysis were used to assess the predictive ability of the preoperative prognostic factors regarding recurrence or progression of cancer within 3 years after surgery, and to compare their predictive ability to that of the European Society for Medical Oncology (ESMO) preoperative (based on depth of myometrial invasion, histotype and grade) and postoperative (based on histotype, grade, surgical stage and lymphovascular space invasion) risk classifications. In a separate subanalysis, cases were stratified according to ProMisE p53 abn status (present vs absent) and sonographic tumor size (anteroposterior (AP) diameter < 2 cm vs ≥ 2 cm). RESULTS: Median follow-up time from surgery was 58 months (interquartile range, 48-71 months; range, 0-102 months). Recurrence or progression of cancer occurred in 51/339 (15%) women, comprising 14% of those with MMR-D, 8% of those with POLE EDM, 9% of those with p53 wt and 45% of those with p53 abn ProMisE subtype. On multivariable analysis, age, waist circumference, ProMisE subtype and tumor extension and AP diameter on ultrasound were associated with tumor recurrence or progression. A multivariable model comprising ProMisE subtype, age, waist circumference and sonographic tumor extension and size (area under the ROC curve (AUC), 0.89 (95% CI, 0.85-0.93)) had comparable ability to predict tumor recurrence/progression to that of a multivariable model comprising histotype, grade, age, waist circumference and sonographic tumor extension and size (AUC, 0.88 (95% CI, 0.83-0.92)), and better predictive ability than both the preoperative (AUC, 0.74 (95% CI, 0.67-0.82); P < 0.01) and postoperative (AUC, 0.79 (95% CI, 0.72-0.86); P < 0.01) ESMO risk classifications. Women with a combination of non-p53 abn subtype and tumor size < 2 cm (164/339 (48%)) had a very low risk (1.8%) of tumor recurrence or progression. CONCLUSIONS: The combination of demographic characteristics, sonographic findings and ProMisE subtype had better preoperative predictive ability for tumor recurrence or progression than did the ESMO classification, supporting their use in the preoperative risk stratification of women with endometrial cancer. The combination of p53 status with ultrasound tumor size has the potential to identify preoperatively a large group of women with a very low risk of recurrence or progression. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.


Assuntos
Neoplasias do Endométrio/classificação , Neoplasias do Endométrio/genética , Tipagem Molecular/estatística & dados numéricos , Recidiva Local de Neoplasia/genética , Ultrassonografia/estatística & dados numéricos , Idoso , Progressão da Doença , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Tipagem Molecular/métodos , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Curva ROC , Medição de Risco , Vagina/diagnóstico por imagem
6.
Phys Rev Lett ; 124(14): 143402, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32338952

RESUMO

Ab initio nuclear physics tackles the problem of strongly interacting four-component fermions. The same setting could foreseeably be probed experimentally in ultracold atomic systems, where two- and three-component experiments have led to major breakthroughs in recent years. Both due to the problem's inherent interest and as a pathway to nuclear physics, in this Letter we study four-component fermions at unitarity via the use of quantum Monte Carlo methods. We explore novel forms of the trial wave function and find one which leads to a ground state of the eight-particle system whose energy is almost equal to that of two four-particle systems. We investigate the clustering properties involved and also extrapolate to the zero-range limit. In addition to being experimentally testable, our results impact the prospects of developing nuclear physics as a perturbation around the unitary limit.

7.
Ultrasound Obstet Gynecol ; 55(1): 115-124, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31225683

RESUMO

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver-operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. CONCLUSIONS: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
8.
BMC Cardiovasc Disord ; 19(1): 37, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744701

RESUMO

BACKGROUND: Interatrial block (IAB) is an ECG indicator of atrial fibrosis related to atrial remodeling and thrombus formation thus leading to embolic stroke and increasing mortality. We aimed to assess weather IAB predicted all-cause mortality during 10 years after ischemic stroke. METHODS: The study sample comprised 235 patients (median age 74 (interquartile range 25-75% 65-81) years, 95 female) included in the Lund Stroke Register in 2001-2002, who had sinus rhythm ECGs at stroke admission. IAB was defined as a P-wave duration ≥120 ms without = partial IAB (n = 56) or with = advanced IAB (n = 41) biphasic morphology (±) in the inferior ECG leads. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register. RESULTS: During follow-up 126 patients died (54%). Advanced IAB, but not partial, was associated with all-cause mortality in univariate Cox regression analysis (hazard ratio (HR) 1.98, 95% CI 1.27-3.09, p = 0.003). After adjustment for age, gender, severity of stroke measured by NIHSS scale and smoking status in patients without additional comorbidities advanced IAB independently predicted all-cause mortality (HR 7.89, 95% CI 2.01-30.98, p = 0.003), while in patients with comorbidities it did not (HR 1.01 95% CI 0.59-1.72, p = 0.966). CONCLUSION: Advanced IAB predicted all-cause mortality after ischemic stroke, but mostly in patients without additional cardiovascular comorbidities.


Assuntos
Isquemia Encefálica/mortalidade , Bloqueio Interatrial/mortalidade , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Remodelamento Atrial , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Causas de Morte , Feminino , Fibrose , Humanos , Bloqueio Interatrial/diagnóstico , Bloqueio Interatrial/fisiopatologia , Masculino , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Suécia/epidemiologia , Fatores de Tempo
10.
BMC Oral Health ; 19(1): 215, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533690

RESUMO

BACKGROUND: Dental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously. METHODS: We performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3-12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance. RESULTS: No loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10- 6) and TUFT1 (rs11805632; p = 5.15 × 10- 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10- 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12-18% of the suggestive loci in adults. CONCLUSIONS: The genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.


Assuntos
Cárie Dentária , Heterogeneidade Genética , Estudo de Associação Genômica Ampla , Adulto , Negro ou Afro-Americano , Animais , Criança , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , beta-Defensinas
11.
Phys Rev Lett ; 120(12): 122502, 2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29694099

RESUMO

We report accurate quantum Monte Carlo calculations of nuclei up to A=16 based on local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We examine the theoretical uncertainties associated with the chiral expansion and the cutoff in the theory, as well as the associated operator choices in the three-nucleon interactions. While in light nuclei the cutoff variation and systematic uncertainties are rather small, in ^{16}O these can be significant for large coordinate-space cutoffs. Overall, we show that chiral interactions constructed to reproduce properties of very light systems and nucleon-nucleon scattering give an excellent description of binding energies, charge radii, and form factors for all these nuclei, including open-shell systems in A=6 and 12.

12.
Ultrasound Obstet Gynecol ; 51(6): 818-828, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28944985

RESUMO

OBJECTIVE: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. RESULTS: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27-98) years, median body mass index was 28.4 (range 16-67) kg/m2 , 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial-myometrial junction (difference of -23%; 95% CI, -27 to -18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). CONCLUSION: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Gradação de Tumores , Ultrassonografia Doppler em Cores/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Conferências de Consenso como Assunto , Estudos Transversais , Neoplasias do Endométrio/classificação , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Terminologia como Assunto
13.
J Dairy Sci ; 101(2): 1777-1784, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29224857

RESUMO

European starlings are an invasive bird species in North America that are known to cause damage to commercial dairies through the consumption of total mixed rations (TMR) destined for dairy cows. We hypothesized that large foraging flocks of starlings alter the physical composition of TMR, and that this change may be significant enough to affect milk production. To better determine if production losses could potentially occur in commercial dairies as a consequence of feed consumption by foraging flocks of starlings, we conducted controlled feeding experiments using a TMR sourced from a commercial dairy that is chronically plagued with seasonal starling damage. European starlings selected the high-energy fraction of the TMR and reduced starch and crude fat availability. Using the dairy National Research Council production model equations, the nutritional changes measured in the controlled feeding experiments could potentially reduce the productivity of dairies. Model output suggests that for Holsteins producing 32 kg of milk/d, total required net energy intake (NEI) was 31.5 Mcal/d. Within the reference TMR, NEI supplied was 29.3 Mcal/d, whereas within the starling-consumed TMR NEI supplied was 27.7 Mcal/d. Following our nutrition experiments, we assessed the efficacy of pelleted feed as a deterrent strategy for bird damage management in commercial dairies. Six different pelleted feed treatments of differing diameter were offered to starlings. All pellets of 0.95 cm diameter or larger inhibited starling consumption by ≥79%.


Assuntos
Ração Animal/análise , Bovinos/metabolismo , Leite/metabolismo , Estorninhos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ingestão de Energia , Comportamento Alimentar , Feminino , Lactação , América do Norte
14.
J Electrocardiol ; 51(2): 282-287, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29203081

RESUMO

BACKGROUND: Cardiac Resynchronization Therapy (CRT) is widely used for treating selected heart failure patients, but patients with myocardial scar respond worse to treatment. The Selvester QRS scoring system estimates myocardial scar burden using 12-lead ECG. This study's objective was to investigate the scores correlation to mortality in a CRT population. METHODS AND RESULTS: Data on consecutive CRT patients was collected. 401 patients with LBBB and available ECG data were included in the study. QuAReSS software was used to perform Selvester scoring. Mean Selvester score was 6.4, corresponding to 19% scar burden. The endpoint was death or heart transplant; outcome was analyzed using Cox proportional hazards models. A Selvester score >8 was significantly associated with higher risk of the combined endpoint (HR 1.59, p=.014, CI 1.09-2.3). CONCLUSION: Higher Selvester scores correlate to mortality in CRT patients with strict LBBB and might be of value in prognosticating survival.


Assuntos
Bloqueio de Ramo/mortalidade , Bloqueio de Ramo/fisiopatologia , Terapia de Ressincronização Cardíaca/mortalidade , Idoso , Eletrocardiografia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Suécia/epidemiologia
15.
Ophthalmic Plast Reconstr Surg ; 34(2): 110-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28350690

RESUMO

PURPOSE: The programmed death-1 pathway negatively regulates the immune system. Previous reports have indicated worse tumor-related outcomes with increased expression of the ligand for this pathway. This study was undertaken to assess the role of the PD pathway in cutaneous malignancies that invade the orbit. METHODS: Immunohistochemical staining for the programmed death-1 receptor and ligand was performed on exenteration specimens of invasive cutaneous orbital malignancies (n = 12) and nodular basal cell carcinoma (n = 10). The numbers of positively-staining cells/40× field were counted across 5 consecutive fields, and statistical analyses were performed to compare the differences between the 2 groups. RESULTS: Programmed death-1 receptor positivity was seen in means of 30.9 cells/40× field and 62.4 cells/40× field for nodular basal cell carcinomas and invasive malignancies, respectively (p = 0.0046). A mean of 4.54 cells/40× field stained positively for the programmed death-1 ligand in nodular basal cell carcinoma, whereas a mean of 46.4 cells/40× field stained positively for programmed cell death ligand-1 in orbital invasive cutaneous carcinomas (p = 0.0015). Both of these differences were statistically significant. CONCLUSIONS: Both the programmed death-1 receptor and its ligand are enriched in invasive cutaneous malignancies. This finding indicates that negative regulation of the immune system likely prohibits tumor surveillance, and facilitates increasing aggressiveness and invasion of cutaneous malignancies.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Basocelular/imunologia , Neoplasias Orbitárias/imunologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Cutâneas/imunologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade
16.
Phys Rev Lett ; 119(22): 223002, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29286794

RESUMO

The properties of cold Bose gases at unitarity have been extensively investigated in the last few years both theoretically and experimentally. In this Letter we use a family of interactions tuned to two-body unitarity and very weak three-body binding to demonstrate the universal properties of both clusters and matter. We determine the universal properties of finite clusters up to 60 particles and, for the first time, explicitly demonstrate the saturation of energy and density with particle number and compare with bulk properties. At saturation in the bulk we determine the energy, density, two- and three-body contacts, and the condensate fraction. We find that uniform matter is more bound than three-body clusters by nearly 2 orders of magnitude, the two-body contact is very large in absolute terms, and yet the condensate fraction is also very large, greater than 90%. Equilibrium properties of these systems may be experimentally accessible through rapid quenching of weakly interacting boson superfluids.

17.
J Cutan Pathol ; 44(4): 328-337, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27987328

RESUMO

BACKGROUND: The expression of TRPM1 (melastatin) mRNA is an independent marker, as measured by radioactive in situ hybridization (RISH), of disease-free survival in primary cutaneous melanoma (PM). The aim of the study was to determine if chromogenic in situ hybridization (CISH) can reproduce results examining diagnostic and prognostic utility of TRPM1 mRNA expression in melanocytic proliferations as measured by RISH. METHODS: The expression of TRPM1 mRNA was detected by CISH in melanocytic nevi (MN, n = 61), PM (n = 145) and metastatic melanomas (MMs, n = 15). RESULTS: A progressive loss of TRPM1 was found moving from MN to PM to MM. The histologic stepwise model of melanoma progression revealed that loss of TRPM1 occurred at the transition of RGP PM to VGP PM. As a diagnostic marker, TRPM1 gradient loss showed 93.8% sensitivity and 52.4% specificity for PM. Loss of TRPM1 mRNA correlated with melanoma aggressiveness markers and was independent predictor of disease-free and overall survival. The corresponding survival curves for degree of melanoma pigmentation matched those for degree of loss of TPRM1 mRNA. CONCLUSION: Loss of TRPM1 mRNA expression appears to be a crucial event in the progression of melanoma to a more malignant, metastatic phenotype.


Assuntos
Melanoma , Proteínas de Neoplasias/biossíntese , Neoplasias Cutâneas , Canais de Cátion TRPM/biossíntese , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Melanoma/metabolismo , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida
18.
Am J Dermatopathol ; 39(7): 493-503, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27898473

RESUMO

The overlap of Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) is more common than it was generally accepted. Both diseases seem to be linked by a mutation in oncogenic BRAFV600E, probably an early event which occurs in bone marrow progenitor cells. In this article are described the clinical and histological findings in 2 cases of ECD-LCH overlap syndrome bearing the BRAFV600E mutation in both ECD and LCH lesions in bone and skin. In one case, lesions of ECD and LCH were situated directly site-to-site in the same bone section leading to the assumption of a common myeloid precursor cell for these diseases. Furthermore, we focus on the histopathological diagnostic criteria of cutaneous involvement in ECD. Lesional tissue shows a dermal infiltrate of lipidized CD68, CD163, CD1a, and langerin histiocytes admixed with Touton giant cells-a xanthogranulomatous phenotype. Often, this pattern of histopathology requires correlation with patterns of systemic involvement to differentiate ECD from other xanthogranulomatous infiltrates. This endeavor is of major importance to determine early diagnosis and treatment, because ECD often shows a poor prognosis compared with its differential diagnoses. Finally, adults who suffer from LCH and develop xanthogranulomatous infiltrates should always be screened for ECD-LCH overlap syndrome.


Assuntos
Doença de Erdheim-Chester/patologia , Histiocitose de Células de Langerhans/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Dermatopatias/patologia , Idoso , Doença de Erdheim-Chester/genética , Feminino , Histiocitose de Células de Langerhans/genética , Humanos , Mutação , Dermatopatias/genética
19.
Am J Dermatopathol ; 39(3): 189-194, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27759693

RESUMO

BACKGROUND: Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect. OBJECTIVES: To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD). METHODS: Case-control study examining clinicopathologic and neuroactive factors (ß-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors. RESULTS: Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more ß-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000). CONCLUSIONS: GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.


Assuntos
Carcinoma Basocelular/patologia , Serotonina/biossíntese , Neoplasias Cutâneas/patologia , beta-Endorfina/biossíntese , Hormônio Adrenocorticotrópico/análise , Hormônio Adrenocorticotrópico/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/psicologia , Estudos de Casos e Controles , Encefalina Metionina/análise , Encefalina Metionina/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Serotonina/análise , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/psicologia , Adulto Jovem , beta-Endorfina/análise
20.
Am J Dermatopathol ; 39(1): 1-13, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28045747

RESUMO

BACKGROUND: Comprehensive genomic profiling of clinical samples by next-generation sequencing (NGS) can identify one or more therapy targets for the treatment of metastatic melanoma (MM) with a single diagnostic test. METHODS: NGS was performed on hybridization-captured, adaptor ligation-based libraries using DNA extracted from 4 formalin-fixed paraffin-embedded sections cut at 10 microns from 30 MM cases. The exons of 182 cancer-related genes were fully sequenced using the Illumina HiSeq 2000 at an average sequencing depth of 1098X and evaluated for genomic alterations (GAs) including point mutations, insertions, deletions, copy number alterations, and select gene fusions/rearrangements. Clinically relevant GAs (CRGAs) were defined as those identifying commercially available targeted therapeutics or therapies in registered clinical trials. RESULTS: The 30 American Joint Committee on Cancer Stage IV MM included 17 (57%) male and 13 (43%) female patients with a mean age of 59.5 years (range 41-83 years). All MM samples had at least 1 GA, and an average of 2.7 GA/sample (range 1-7) was identified. The mean number of GA did not differ based on age or sex; however, on average, significantly more GAs were identified in amelanotic and poorly differentiated MM. GAs were most commonly identified in BRAF (12 cases, 40%), CDKN2A (6 cases, 20%), NF1 (8 cases, 26.7%), and NRAS (6 cases, 20%). CRGAs were identified in all patients, and represented 77% of the GA (64/83) detected. The median and mean CRGAs per tumor were 2 and 2.1, respectively (range 1-7). CONCLUSION: Comprehensive genomic profiling of MM, using a single diagnostic test, uncovers an unexpectedly high number of CRGA that would not be identified by standard of care testing. Moreover, NGS has the potential to influence therapy selection and can direct patients to enter relevant clinical trials evaluating promising targeted therapies.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Melanoma/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biologia Computacional , Bases de Dados Genéticas , Desenho de Fármacos , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
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