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1.
Phys Rev Lett ; 130(26): 261801, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37450797

RESUMO

We conduct the first "light-shining-through-wall" (LSW) search for dark photons using two state-of-the-art high-quality-factor superconducting radio frequency (SRF) cavities -Dark SRF-and report the results of its pathfinder run. Our new experimental setup enables improvements in sensitivity over previous searches and covers new dark photon parameter space. We design delicate calibration and measurement protocols to utilize the high-Q setup at Dark SRF. Using cavities operating at 1.3 GHz, we establish a new exclusion limit for kinetic mixing as small as ε=1.6×10^{-9} and provide the world's best constraints on dark photons in the 2.1×10^{-7}-5.7×10^{-6} eV mass range. Our result is the first proof of concept for the enabling role of SRF cavities in LSW setups, with ample opportunities for further improvements. In addition, our data set a competitive lab-based limit on the standard model photon mass by searching for longitudinal photon polarization.


Assuntos
Fótons , Cinética
2.
Osteoarthritis Cartilage ; 27(7): 1043-1047, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30890457

RESUMO

OBJECTIVE: To analyze the age-related changes of the physiological hand joint architecture. METHOD: To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. RESULTS: Bone erosions [median (Q1-Q3), 1 (0-2)] and osteophytes [2 (1-4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03-1.06; osteophytes: 1.03-1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20-11.75), 6.81 (3.08-16.46) and 6.92 (3.11-16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69-4.87), 1.53 (0.59-4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32-4.17), 4.17 (2.38-7.49) and 6.86 (3.97-12.20) for the sixth, seventh and eigth decades, respectively. CONCLUSIONS: Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.


Assuntos
Envelhecimento/fisiologia , Doenças Ósseas/patologia , Articulação da Mão/patologia , Osteófito/patologia , Tomografia Computadorizada por Raios X , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Ósseas/diagnóstico por imagem , Feminino , Alemanha , Articulação da Mão/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Masculino , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação Metacarpofalângica/patologia , Pessoa de Meia-Idade , Osteófito/diagnóstico por imagem , Estudos Prospectivos , Medição de Risco , Fatores Sexuais , Adulto Jovem
3.
Med Teach ; 40(7): 728-735, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29457923

RESUMO

BACKGROUND: Inequalities in healthcare are increasing. Engaging medical students to tackle this urgent challenge alongside clinical sciences can be demanding. This study examines medical student perceptions of a flipped approach to health inequalities co-designed by faculty and sixth-year students. INNOVATION: A flipped learning session was piloted for year 4 medical students combining an online lesson followed by a tutorial with a simulated patient. METHODS: A mixed-methods approach collected questionnaire data using 4-point Likert scales and free text answers. A semi-structured group interview was conducted with six voluntary participants. RESULTS: Two hundred and eighty-nine students completed questionnaires. 85% (n = 246) completed the online lesson. Students agreed the session helped their understanding of key concepts (mean 3.2), was improved by having an actor (mean = 3.6), and was enjoyable (mean = 3.2). Thematic analysis of qualitative questionnaire and interview data revealed three themes: engagement; structure; and attitudes towards social determinants of health. The simulation increased clinical relevance and students gained understanding of the impact of health inequalities upon individuals. CONCLUSIONS: This paper indicates flipped learning can increase clinical relevance and engagement in population health and person-centered care. Further work could assess changes in practice and attitudes of future doctors in tackling such global health challenges.


Assuntos
Atitude do Pessoal de Saúde , Treinamento por Simulação/métodos , Determinantes Sociais da Saúde , Estudantes de Medicina/psicologia , Instrução por Computador , Currículo , Educação de Graduação em Medicina , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Aprendizagem , Inovação Organizacional , Simulação de Paciente , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários
4.
Phytopathology ; 106(9): 1029-37, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27111801

RESUMO

Barley is a near-nonhost to numerous heterologous (nonadapted) rust pathogens because a small proportion of genotypes are somewhat susceptible. We assessed 66 barley accessions and three mapping populations (Vada × SusPtrit, Cebada Capa × SusPtrit, and SusPtrit × Golden Promise) for response to three Swedish oat stem rust (Puccinia graminis f. sp. avenae) fungal isolates and determined that barley is a near-nonhost to P. graminis f. sp. avenae and that resistance was polygenically inherited. The parental genotypes Vada and Golden Promise were immune to all three isolates, whereas Cebada Capa was immune to two isolates and moderately resistant to the third. Phenotypic data from the Vada × SusPtrit mapping population and the barley accessions tested also demonstrated isolate-specific resistance. In particular, the SusPtrit parent and several other accessions allowed sporulation by isolate Ingeberga but were resistant to isolate Evertsholm. Nine chromosomal regions carried quantitative trait loci (QTL) (Rpgaq1 to Rpgaq9) of varying effect, most of which colocated to previously identified QTL for resistance to other heterologous rust pathogens. Rpgaq1 on chromosome 1H (Vada and Golden Promise) was effective toward all isolates tested. Microscopic examination indicated that resistance was prehaustorial in Vada whereas, in SusPtrit, both pre- and posthaustorial mechanisms play a role.


Assuntos
Basidiomycota/fisiologia , Cromossomos de Plantas/genética , Resistência à Doença/genética , Hordeum/genética , Herança Multifatorial/genética , Doenças das Plantas/imunologia , Mapeamento Cromossômico , Genótipo , Hordeum/microbiologia , Fenótipo , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologia , Caules de Planta/microbiologia , Locos de Características Quantitativas/genética
5.
Phys Rev Lett ; 114(6): 062002, 2015 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-25723208

RESUMO

The COMPASS collaboration at CERN has investigated pion Compton scattering, π(-)γ→π(-)γ, at center-of-mass energy below 3.5 pion masses. The process is embedded in the reaction π(-)Ni→π(-)γNi, which is initiated by 190 GeV pions impinging on a nickel target. The exchange of quasireal photons is selected by isolating the sharp Coulomb peak observed at smallest momentum transfers, Q(2)<0.0015 (GeV/c)(2). From a sample of 63,000 events, the pion electric polarizability is determined to be α(π)=(2.0±0.6(stat)±0.7(syst))×10(-4) fm(3) under the assumption α(π)=-ß(π), which relates the electric and magnetic dipole polarizabilities. It is the most precise measurement of this fundamental low-energy parameter of strong interaction that has been addressed since long by various methods with conflicting outcomes. While this result is in tension with previous dedicated measurements, it is found in agreement with the expectation from chiral perturbation theory. An additional measurement replacing pions by muons, for which the cross-section behavior is unambiguously known, was performed for an independent estimate of the systematic uncertainty.

6.
Eur J Clin Microbiol Infect Dis ; 34(10): 2063-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26205665

RESUMO

The objective of this investigation was to identify risk factors for carbapenem-resistant Acinetobacter baumannii (CRAB) and its association with mortality. A population-based matched case-control study using the computerized database of Clalit Health Services (CHS) in the period between 2007 and 2012 was conducted. Hospitalized patients with CRAB colonization or infection were compared to hospitalized patients without evidence of A. baumannii, matched by age, ward of hospitalization, season, Charlson score, and length of hospitalization. Risk factors for CRAB isolation were searched for using multivariate analysis. Association of CRAB and other risk factors with mortality were assessed in the cohort. A total of 1190 patients with CRAB were matched to 1190 patients without CRAB. Low socioeconomic status was independently associated with CRAB isolation and CRAB bacteremia [odds ratio 2.18, 95% confidence interval (CI) 1.02-5]. Other risk factors were invasive procedures and bacteremia with other pathogens prior to CRAB isolation, and various comorbidities. Among all patients, CRAB isolation was independently associated with increased mortality (hazard ratio 2.33, 95% CI 2.08-2.6). Socioeconomic status is associated with health outcomes. Our population-based study revealed an almost doubled risk for CRAB in patients at lower socioeconomic status and an association with healthcare exposure. CRAB was associated with mortality and might become a risk indicator for complex morbidity and mortality.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Israel/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
7.
Phys Rev Lett ; 113(6): 062001, 2014 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-25148317

RESUMO

New data on the polarization observables T, P, and H for the reaction γp→pπ(0) are reported. The results are extracted from azimuthal asymmetries when a transversely polarized butanol target and a linearly polarized photon beam are used. The data were taken at the Bonn electron stretcher accelerator ELSA using the CBELSA/TAPS detector. These and earlier data are used to perform a truncated energy-independent partial wave analysis in sliced-energy bins. This energy-independent analysis is compared to the results from energy-dependent partial wave analyses.

8.
Clin Exp Immunol ; 172(2): 263-79, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23574323

RESUMO

RSV lower respiratory tract infections (LRTI) are among the most common diseases necessitating hospital admission in children. In addition to causing acute respiratory failure, RSV infections are associated with sequelae such as secondary bacterial infections and reactive airway disease. One characteristic host response observed in severe RSV-induced LRTI and/or subsequent development of asthma is increased expression of interleukin (IL)-10. However, contradictory results have been reported regarding whether IL-10 inhibits asthmatic responses or intensifies the disease. We aimed to reconcile these discordant observations by elucidating the role of IL-10 in regulating the host response to RSV LRTI. In this study, we used a lung-specific, inducible IL-10 over-expression (OE) transgenic mouse model to address this question. Our results showed that the presence of IL-10 at the time of RSV infection not only attenuated acute inflammatory process (i.e. 24 h post-infection), but also late inflammatory changes [characterized by T helper type 2 (Th2) cytokine and chemokine expression]. While this result appears contradictory to some clinical observations where elevated IL-10 levels are observed in asthmatic patients, we also found that delaying IL-10 OE until the late immune response to RSV infection, additive effects rather than inhibitory effects were observed. Importantly, in non-infected, IL-10 OE mice, IL-10 OE alone induced up-regulation of Th2 cytokine (IL-13 and IL-5) and Th2-related chemokine [monocyte chemoattractant protein 1 (MCP-1), chemokine (C-C motif) ligand 3 (CCL3) and regulated upon activation normal T cell expressed and secreted (RANTES)] expression. We identified a subset of CD11b(+)CD11c(+)CD49b(+)F4/80(-)Gr-1(-) myeloid cells as a prinicipal source of IL-10-induced IL-13 production. Therefore, the augmented pathological responses observed in our 'delayed' IL-10 over-expression model could be attributed to IL-10 OE alone. Taken together, our study indicated dual roles of IL-10 on RSV-induced lung inflammation which appear to depend upon the timing of when elevated IL-10 is expressed in the lung.


Assuntos
Interleucina-10/metabolismo , Pneumonia/imunologia , Pneumonia/virologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Animais , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/virologia , Quimiocina CCL2/genética , Quimiocina CCL5/metabolismo , Interleucina-13 , Ativação Linfocitária/imunologia , Camundongos , Camundongos Transgênicos , Células Mieloides/metabolismo , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/metabolismo , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Células Th2/imunologia
9.
Plant Dis ; 97(10): 1281-1287, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30722146

RESUMO

Barberry (Berberis spp.) hosts the aecial stage of several rust species, including Puccinia graminis, which causes stem rust on grasses and cereals. The aecial stage of this pathogen has received less attention because it is not as economically important compared with the uredinial and telial stages. The main objective of this study was to identify and describe the rust species that were found on Berberis spp. collected in different parts of Sweden. A morphological study, including spore measurements and aecia descriptions, was conducted, as well as DNA sequence analyses (using the internal transcribed spacer region and the EF1-α gene). Based on spore and aecia morphology as well as the genetic analyses, three different taxa could be distinguished on barberry: P. graminis f. sp. avenae, P. graminis f. sp. tritci/secalis, and P. arrhenatheri. The genetic analysis revealed little or no differentiation between P. graminis f. sp. tritici and P. graminis f. sp. secalis and, thus, this group of samples was denominated P. graminis f. sp. tritici/secalis. Aecial morphology may be used to differentiate between different taxa. In particular, examination of aecial cross-sections may be used to distinguish between P. graminis f. sp. avenae and P. graminis f. sp. tritici/secalis. A clear differentiation in the mode of growth on barberry was also found; P. arrhenatheri always appeared systemic whereas P. graminis always appeared localized.

10.
Clin Oncol (R Coll Radiol) ; 35(4): 262-268, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737311

RESUMO

AIMS: To report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. MATERIALS AND METHODS: In 2003-2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan-Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. RESULTS: Of 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3-7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. CONCLUSION: In low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.


Assuntos
Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Pessoa de Meia-Idade , Braquiterapia/métodos , Estudos Prospectivos , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Dosagem Radioterapêutica
11.
J Chem Phys ; 136(22): 224906, 2012 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-22713072

RESUMO

We carry out a molecular dynamics simulation of the first stages of constrained melting in crystalline polyethylene (PE). When heated, the crystal undergoes two structural phase transitions: from the orthorhombic (O) phase to the monoclinic (M) phase, and then to the columnar (C), quasi-hexagonal, phase. The M phase represents the tendency to the parallel packing of planes of PE zigzags, and the C phase proves to be some kind of oriented melt. We follow both the transitions O→M and M→C in real time and establish that, at their beginning, the crystal tries (and fails) to pass into the partially ordered phases similar to the RI and RII phases of linear alkanes, correspondingly. We discuss the molecular mechanisms and driving forces of the observed transitions, as well as the reasons why the M and C phases in PE crystals substitute for the rotator phases in linear alkanes.


Assuntos
Simulação de Dinâmica Molecular , Polietilenos/química , Temperatura Baixa , Congelamento , Modelos Moleculares , Transição de Fase , Temperatura
12.
Bull Exp Biol Med ; 153(4): 455-8, 2012 Aug.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-22977843

RESUMO

A concept of physicochemical forms of biologically active substances introduced in investigation of the action mechanism of ultra-low doses allows qualitative explanation of the main effects of ultra-low doses, chemical diversity of biologically active substances, and physical boundaries for these effects. Phenazepam was shown to possess activity in ultra-low doses only in disperse state, in the form of nanoparticles with a diameter <100-300 nm; these nanoparticles appear as micelles of surface active substances and solvated. Panavir possesses pharmacological activity in ultra-low doses and appears as nanoparticles with a diameter of 200-300 nm, which have uncompensated negative surface charge and polymer nature.


Assuntos
Benzodiazepinas/química , Benzodiazepinas/farmacologia , Nanopartículas/química , Probucol/química , Probucol/farmacologia , Animais , Relação Dose-Resposta a Droga , Micelas , Peritonite/tratamento farmacológico , Ratos , Tensoativos/química
13.
ESMO Open ; 7(3): 100498, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35642988

RESUMO

BACKGROUND: While side-effects and health-related quality of life (QoL) are routinely assessed in clinical trials, commonly used tools do not measure patients' ability to maintain normal daily activities. QoL can be severely affected directly by the disease, the treatment side-effects and by personal and societal misconceptions promoting avoidance from activities perceived as dangerous for cancer patients. We examined practices of actively treated patients with cancer. METHODS: A questionnaire was designed, assessing daily activities (11 items) and dietary limitations (7 items) distributed between October and December 2019 (before the coronavirus pandemic) among patients treated at the Oncology Division of Tel Aviv Sourasky Medical Center. RESULTS: The study population comprised 208 patients who participated in the survey. The majority reported at least one social-environmental avoidance or dietary limitation (136, 65% and 120, 57.7%, respectively), including abstaining from social contact, avoiding pets, public domains, traveling and maintaining dietary constraints. Adoption of these measures was not associated with clinical, demographic factors and treatment type. The major sources guiding restrictions came from advice of non-medical personnel (55.7%), the Internet (7.2%) and personal choice by the patients themselves (24%). CONCLUSIONS: Most cancer patients reported compromised daily activities, which are likely attributed to misbeliefs about disease and treatment, and have a deleterious impact on QoL, in its wider sense, namely, the ability to conduct a full and meaningful life. These findings call for the development and implementation of tools examining patients' real-life activity, beyond side-effects or health-related QoL (HRQoL). We propose this assessment as an integral part in the evaluation of new drugs and technologies and as an additional endpoint in pivotal clinical trials.


Assuntos
Neoplasias , Qualidade de Vida , Atividades Cotidianas , Humanos , Inquéritos e Questionários
14.
Midwifery ; 57: 1-7, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29128739

RESUMO

OBJECTIVES: to describe topics (1) presented by midwives' during antenatal classes and the amount of time spent on these topics and (2) raised and discussed by first-time parents and the amount of time spent on these topics. DESIGN: qualitative; data were gathered using video or tape recordings and analysed using a three-pronged content analysis approach, i.e., conventional, summative, and directed analyses. SETTING AND PARTICIPANTS: 3 antenatal courses in 2 antenatal units in a large Swedish city; 3 midwives; and 34 course participants. FINDINGS: class content focused on childbirth preparation (67% of the entire antenatal course) and on parenting preparation (33%). Childbirth preparation facilitated parents' understanding of the childbirth process, birthing milieu, the partner's role, what could go wrong during delivery, and pain relief advantages and disadvantages. Parenting preparation enabled parents to (i) plan for those first moments with the newborn; (ii) care for/physically handle the infant; (iii) manage breastfeeding; (iv) manage the period at home immediately after childbirth; and (v) maintain their relationship. During the classes, parents expressed concerns about what could happened to newborns. Parents' questions to midwives and discussion topics among parents were evenly distributed between childbirth preparation (52%) and parenting preparation (48%). KEY CONCLUSIONS: childbirth preparation and pain relief consumed 67% of course time. Parents particularly reflected on child issues, relationship, sex, and anxiety. Female and male participants actively listened to the midwives, appeared receptive to complex issues, and needed more time to ask questions. Parents appreciated the classes yet needed to more information for managing various post-childbirth situations. IMPLICATIONS FOR PRACTICE: while midwifery services vary among hospitals, regions, and countries, midwives might equalise content focus, offer classes in the second trimester, provide more time for parents to talk to each other, allow time in the course plan for parents to bring up new topics, and investigate: (i) ways in which antenatal course development and planning can improve; (ii) measures for evaluating courses; (iii) facilitator training; and (iv) parent satisfaction surveys.


Assuntos
Poder Familiar/psicologia , Parto/psicologia , Educação Pré-Natal/normas , Adulto , Aleitamento Materno/métodos , Feminino , Humanos , Recém-Nascido , Masculino , Pais/educação , Gravidez , Educação Pré-Natal/métodos , Pesquisa Qualitativa , Inquéritos e Questionários , Suécia
15.
Cancer Epidemiol ; 57: 104-109, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30388485

RESUMO

AIMS: This population-based historical cohort study examined whether poor glycemic-control (i.e., high glucose and HbA1c blood levels) in patients with diabetes is associated with cancer-risk. METHODS: From a large healthcare database, patients aged 21-89 years, diagnosed with diabetes before January 2002 (prevalent) or during 2002-2010 (incident), were followed for cancer during 2004-2012 (excluding cancers diagnosed within the first 2 years since diabetes diagnosis). Risks of selected cancers (all-sites, colon, breast, lung, prostate, pancreas and liver) were estimated according to glycemic-control in a Cox regression model with time-dependent covariates, adjusted for age, sex, ethnic origin, socioeconomic status, smoking and parity. Missing glucose or HbA1c values were imputed. RESULTS: Among 440,000 patients included in our analysis, cancer was detected more than 2 years after diabetes diagnosis in 26,887 patients (6%) during the follow-up period. Associations of poor glycemic-control with all-sites cancer and most specific cancers were either null or only weak (hazard ratios (HRs) for a 1% HbA1c or a 30 mg/dl glucose increase between 0.94 and 1.09). Exceptions were pancreatic cancer, for which there was a strong positive association (HRs: 1.26-1.51), and prostate cancer, for which there was a moderate negative association (HRs: 0.85-0.96). CONCLUSION: Overall, poor glycemic-control appears to be only weakly associated with cancer-risk, if at all. A substantial part of the positive association with pancreatic cancer is attributable to reverse causation, with the cancer causing poorer glycemic-control prior to its diagnosis. The negative association with prostate cancer may be related to lower PSA levels in those with poor control.


Assuntos
Complicações do Diabetes/epidemiologia , Neoplasias/complicações , Neoplasias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias da Próstata/epidemiologia , Classe Social , Adulto Jovem
16.
Curr Biol ; 11(11): 836-45, 2001 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-11516644

RESUMO

BACKGROUND: In many cell types, microtubules are thought to direct the spatial distribution of F-actin in cell polarity. Schizosaccharomyces pombe cells exhibit a regulated program of polarized cell growth: after cell division, they grow first in a monopolar manner at the old end, and in G2 phase, initiate growth at the previous cell division site (the new end). The role of microtubule ends in cell polarity is highlighted by the finding that the cell polarity factor, tea1p, is present on microtubule plus ends and cell tips [1]. RESULTS: Here, we characterize S. pombe bud6p/fat1p, a homolog of S. cerevisiae Bud6/Aip3. bud6Delta mutant cells have a specific defect in the efficient initiation of growth at the new end and like tea1Delta cells, form T-shaped cells in a cdc11 background. Bud6-GFP localizes to both cell tips and the cytokinesis ring. Maintenance of cell tip localization is dependent upon actin but not microtubules. Bud6-GFP localization is tea1p dependent, and tea1p localization is not bud6p dependent. tea1Delta and bud6Delta cells generally grow in a monopolar manner but exhibit different growth patterns. tea1(Delta)bud6Delta mutants resemble tea1Delta mutants. Tea1p and bud6p coimmunoprecipitate and comigrate in large complexes. CONCLUSIONS: Our studies show that tea1p (a microtubule end-associated factor) and bud6p (an actin-associated factor) function in a common pathway, with bud6p downstream of tea1p. To our knowledge, bud6p is the first protein shown to interact physically with tea1p. These studies delineate a pathway for how microtubule plus ends function to polarize the actin cytoskeleton through actin-associated polarity factors.


Assuntos
Polaridade Celular , Proteínas do Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Proteínas de Saccharomyces cerevisiae , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces/citologia , Actinas/isolamento & purificação , Actinas/metabolismo , Divisão Celular , Proteínas do Citoesqueleto/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/isolamento & purificação , Proteínas Fúngicas/metabolismo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/isolamento & purificação , Proteínas dos Microfilamentos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Modelos Biológicos , Modelos Estruturais , Mutação , Ligação Proteica
17.
J Clin Invest ; 108(4): 547-56, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11518728

RESUMO

Bronchiolitis obliterans syndrome (BOS) is the major limitation to survival after lung transplantation. Acute rejection, its main risk factor, is characterized by perivascular/bronchiolar leukocyte infiltration. BOS is characterized by persistent peribronchiolar leukocyte recruitment leading to airway fibrosis and obliteration. The specific mechanism(s) by which these leukocytes are recruited are unknown. Because MCP-1, acting through its receptor CCR2, is a potent mononuclear cell chemoattractant, we hypothesized that expression of this chemokine during an allogeneic-response promotes persistent recruitment of leukocytes and, ultimately, rejection. We found that elevated levels of biologically active MCP-1 in human bronchial lavage fluid (BALF) were associated with the continuum from acute to chronic allograft rejection. Translational studies in a murine model of BOS demonstrated increased MCP-1 expression paralleling mononuclear cell recruitment and CCR2 expression. Loss of MCP-1/CCR2 signaling, as seen in CCR2(-/-) mice or in WT mice treated with neutralizing antibodies to MCP-1, significantly reduced recruitment of mononuclear phagocytes following tracheal transplantation and led to attenuation of BOS. Lymphocyte infiltration was not reduced under these conditions. We suggest that MCP-1/CCR2 signaling plays an important role in recruitment of mononuclear phagocytes, a pivotal event in the pathogenesis of BOS.


Assuntos
Bronquiolite Obliterante/etiologia , Quimiocina CCL2/fisiologia , Quimiotaxia de Leucócito/fisiologia , Rejeição de Enxerto/etiologia , Transplante de Coração-Pulmão , Transplante de Pulmão , Complicações Pós-Operatórias/etiologia , Animais , Bronquiolite Obliterante/metabolismo , Líquido da Lavagem Broncoalveolar/química , Quimiocina CCL2/análise , Quimiocina CCL2/genética , Quimiocina CXCL2 , Quimiocinas/análise , Quimiocinas/fisiologia , Estudos de Coortes , Feminino , Rejeição de Enxerto/metabolismo , Humanos , Imunofenotipagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Modelos Animais , Fagocitose , Complicações Pós-Operatórias/metabolismo , RNA Mensageiro/biossíntese , Receptores CCR2 , Receptores de Quimiocinas/biossíntese , Receptores de Quimiocinas/deficiência , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/fisiologia , Transdução de Sinais
18.
Brachytherapy ; 16(4): 679-687, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28237429

RESUMO

PURPOSE: To present an overview of mp MRI techniques necessary for high-resolution imaging of prostate. METHODS: We summarize examples from our clinical experience and concepts from the current literature that illustrate normal prostate anatomy on multiparametric MRI (mp MRI). RESULTS: Our experience regarding optimal mp MRI image acquisition is provided, as well as a summary of prostate and periprostatic anatomy and anatomical variants that pose challenges for BT. CONCLUSIONS: mp MRI provides unparalleled assessment of the prostate and periprostatic anatomy, making it the most appropriate imaging modality to facilitate prostate BT treatment planning, implantation, and followup. This work provides an introduction to prostate mp MR imaging, anatomy, and anatomical variants essential for successful integration mp MRI into prostate brachytherapy practice.

19.
Brachytherapy ; 16(4): 688-697, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28139419

RESUMO

Optimal integration of multiparametric MRI (mp MRI) into prostate brachytherapy practice necessitates an understanding of imaging findings pertinent to prostate cancer detection and staging. This review will summarize prostate cancer imaging findings and tumor staging on mp MRI, including an overview of the Prostate Imaging Reporting and Data System (PIRADS)-structured reporting schema, mp MRI findings observed in the post-therapy setting including cases of post-treatment recurrence, and MRI concepts integral to successful salvage brachytherapy.

20.
Psychoneuroendocrinology ; 17(5): 467-74, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1336607

RESUMO

Neuroendocrine changes associated with performance testing requiring sustained attention were assessed in eight normal male subjects. To verify whether the hormonal pattern was modified by chronic stimulation of opiate receptors, eight heroin addicts also were studied. Reaction times were similar in normal and addict subjects. In normal individuals, consistent and significant increases in plasma ACTH and beta-endorphin and in urinary epinephrine and norepinephrine were observed, whereas serum prolactin (PRL) progressively decreased over the testing period. Despite maintained performance capabilities, heroin addicts showed a blunted response of ACTH and a paradoxical decrease in endorphin levels. As the normal subjects, both epinephrine and norepinephrine in urine showed the same significant increase over baseline values. Serum PRL showed a similar trend towards decreased values over the testing period in both groups.


Assuntos
Nível de Alerta/fisiologia , Atenção/fisiologia , Hormônios/sangue , Sistemas Neurossecretores/fisiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Catecolaminas/urina , Epinefrina/sangue , Dependência de Heroína/sangue , Humanos , Masculino , Testes Neuropsicológicos , Prolactina/sangue , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia
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