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1.
Space Sci Rev ; 218(4): 28, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574273

RESUMO

Interstellar pickup ions are an ubiquitous and thermodynamically important component of the solar wind plasma in the heliosphere. These PUIs are born from the ionization of the interstellar neutral gas, consisting of hydrogen, helium, and trace amounts of heavier elements, in the solar wind as the heliosphere moves through the local interstellar medium. As cold interstellar neutral atoms become ionized, they form an energetic ring beam distribution comoving with the solar wind. Subsequent scattering in pitch angle by intrinsic and self-generated turbulence and their advection with the radially expanding solar wind leads to the formation of a filled-shell PUI distribution, whose density and pressure relative to the thermal solar wind ions grows with distance from the Sun. This paper reviews the history of in situ measurements of interstellar PUIs in the heliosphere. Starting with the first detection in the 1980s, interstellar PUIs were identified by their highly nonthermal distribution with a cutoff at twice the solar wind speed. Measurements of the PUI distribution shell cutoff and the He focusing cone, a downwind region of increased density formed by the solar gravity, have helped characterize the properties of the interstellar gas from near-Earth vantage points. The preferential heating of interstellar PUIs compared to the core solar wind has become evident in the existence of suprathermal PUI tails, the nonadiabatic cooling index of the PUI distribution, and PUIs' mediation of interplanetary shocks. Unlike the Voyager and Pioneer spacecraft, New Horizon's Solar Wind Around Pluto (SWAP) instrument is taking the only direct measurements of interstellar PUIs in the outer heliosphere, currently out to ∼ 47 au from the Sun or halfway to the heliospheric termination shock.

2.
4.
Anaesthesia ; 73(11): 1337-1344, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30112809

RESUMO

In 2011, the Fourth National Audit Project (NAP4) reported high rates of airway complications in adult intensive care units (ICUs), including death or brain injury, and recommended preparation for airway difficulty, immediately available difficult airway equipment and routine use of waveform capnography monitoring. More than 80% of UK adult intensive care units have subsequently changed practice. Undetected oesophageal intubation has recently been listed as a 'Never Event' in UK practice, with capnography mandated. We investigated whether the NAP4 recommendations have been embedded into paediatric and neonatal intensive care practice by conducting a telephone survey of senior medical or nursing staff in UK paediatric intensive care units (PICUs) and neonatal intensive care units (NICUs). Response rates were 100% for paediatric intensive care units and 90% for neonatal intensive care units. A difficult airway policy existed in 67% of paediatric intensive care units and in 40% of neonatal intensive care units; a pre-intubation checklist was used in 70% of paediatric intensive care units and in 42% of neonatal intensive care units; a difficult intubation trolley was present in 96% of paediatric intensive care units and in 50% of neonatal intensive care units; a videolaryngoscope was available in 55% of paediatric intensive care units and in 29% of neonatal intensive care units; capnography was 'available' in 100% of paediatric intensive care units and in 46% of neonatal intensive care units, and 'always available' in 100% of paediatric intensive care units and in 18% of neonatal intensive care units. Death or serious harm occurring secondary to complications of airway management in the last 5 years was reported in 19% of paediatric intensive care units and in 26% of neonatal intensive care units. We conclude that major gaps in optimal airway management provision exist in UK paediatric intensive care units and especially in UK neonatal intensive care units. Wider implementation of waveform capnography is necessary to ensure compliance with the new 'Never Event' and has the potential to improve airway management.


Assuntos
Manuseio das Vias Aéreas/métodos , Cuidados Críticos/métodos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Pediatria/métodos , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva/estatística & dados numéricos , Terapia Intensiva Neonatal/métodos , Reino Unido
5.
NPJ Parkinsons Dis ; 4: 21, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30003140

RESUMO

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

6.
Epidemiol Infect ; 145(15): 3284-3293, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29032772

RESUMO

Prior studies suggest that the influenza vaccine is protective against some outcomes in hospitalized patients infected with influenza despite vaccination. We utilized surveillance data from Columbus, Ohio to investigate this association over multiple influenza seasons and age groups. Data on laboratory-confirmed influenza-associated hospitalizations were collected as a part of the Influenza Hospitalization Surveillance Project for the 2012-2013, 2013-2014, and 2014-2015 influenza seasons. The association between influenza vaccination status was examined in relation to the outcomes of severe influenza and diagnosis of pneumonia among patients receiving antiviral treatment. Data were analyzed using multivariable logistic regression. We observed no overall association between influenza vaccination status and severe influenza among hospitalized patients. During the 2013-2014 season, those who were vaccinated were 41% less likely to be diagnosed with pneumonia compared with those who were unvaccinated (OR = 0·59 95% CI 0·41-0·86). The influenza vaccine may provide a secondary preventive function against pneumonia among influenza cases requiring hospitalization. However, a protective effect was only observed in 2013-2014, an influenza H1N1 dominant year. Differences in circulating influenza virus strains and vaccine matching to the circulating strains during influenza seasons may impact this association.


Assuntos
Hospitalização/estatística & dados numéricos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Lactente , Influenza Humana/prevenção & controle , Influenza Humana/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Ohio/epidemiologia , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Estudos Retrospectivos , Estações do Ano , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Transl Psychiatry ; 6(9): e893, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27648915

RESUMO

Assessing cognitive abilities in children is challenging for two primary reasons: lack of testing engagement can lead to low testing sensitivity and inherent performance variability. Here we sought to explore whether an engaging, adaptive digital cognitive platform built to look and feel like a video game would reliably measure attention-based abilities in children with and without neurodevelopmental disabilities related to a known genetic condition, 16p11.2 deletion. We assessed 20 children with 16p11.2 deletion, a genetic variation implicated in attention deficit/hyperactivity disorder and autism, as well as 16 siblings without the deletion and 75 neurotypical age-matched children. Deletion carriers showed significantly slower response times and greater response variability when compared with all non-carriers; by comparison, traditional non-adaptive selective attention assessments were unable to discriminate group differences. This phenotypic characterization highlights the potential power of administering tools that integrate adaptive psychophysical mechanics into video-game-style mechanics to achieve robust, reliable measurements.


Assuntos
Transtorno Autístico/psicologia , Transtornos Cromossômicos/psicologia , Cognição , Deficiência Intelectual/psicologia , Jogos de Vídeo , Adolescente , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/psicologia , Estudos de Casos e Controles , Criança , Deleção Cromossômica , Cromossomos Humanos Par 16 , Feminino , Humanos , Deficiência Intelectual/genética , Masculino , Projetos Piloto , Irmãos
8.
Parkinsonism Relat Disord ; 21(10): 1210-3, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26324211

RESUMO

INTRODUCTION: Adult-onset dystonias are often segmental in distribution and preferentially affect the craniocervical muscles. Here we describe an overlooked muscle group involved in craniocervical dystonia - the hyoid muscles. Dystonia of these muscles results in anterior neck tightness, speech changes, and dysphagia. METHODS: For this retrospective study we obtained a list of 55 patients who had received botulinum toxin injections into hyoid muscles between 1998 and 2013. Fifteen patients were identified to have an unusual dystonia affecting the hyoid muscles. RESULTS: Patients presented with a triad of speech resonance changes (100%), anterior neck tightness (86.6%), and dysphagia (73.3%). Ten (66.7%) patients presented with all three symptoms, while fourteen (93.3%) had at least two. Fourteen patients (93.3%) had a concomitant dystonia affecting the face or neck and eleven (73.3%) had a sensory trick. Exam universally showed contracted hyoid muscles. Some patients had professions or hobbies requiring prolonged use of vocal muscles such as teachers, singers, and musicians. Patients were often misdiagnosed and received unnecessary treatments. Patients underwent botulinum toxin injections into various hyoid muscles with benefit in 71% of patients but adverse effects in the same proportion. CONCLUSIONS: Hyoid muscle dystonia is a previously poorly characterized focal dystonia causing the triad of speech changes, anterior neck tightness, and dysphagia. Concomitant dystonia, sensory tricks, and visualization of contracted hyoid muscles were often present. Recognition of this disease may reduce unnecessary testing and treatments, and patients may benefit from botulinum toxin injections.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Distúrbios Distônicos/complicações , Distúrbios Distônicos/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Adulto , Idoso , Transtornos de Deglutição/etiologia , Feminino , Humanos , Osso Hioide , Masculino , Pessoa de Meia-Idade , Músculos do Pescoço/patologia , Estudos Retrospectivos , Distúrbios da Fala/etiologia
9.
Int J Tuberc Lung Dis ; 19(9): 1073-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26260827

RESUMO

>We previously reported on a comparison of the AccuProbe(®) Gen-Probe(®) MTBC assay (AccuProbe) (BioMérieux, Marcy L'Etoile, France) with the Becton Dickinson (BD) MGIT™ TBc Identification (TBc) Test (BD, Franklin Lakes, NJ, USA) in our laboratory. In the period following the shift from the AccuProbe assay to the TBc test, we obtained six false-negative results. On sequencing the mpt64 gene, we found that these false-negative cases had mutations in the mpt64 gene due to deletion, insertion or substitution. Despite the occurrence of false-negative results, we found that the reduced cost and minimal technical expertise, combined with a new testing algorithm, still make this test the preferred option for rapidly identifying Mycobacterium tuberculosis complex in MGIT cultures in a low TB burden country such as New Zealand.


Assuntos
Técnicas Bacteriológicas/métodos , Mycobacterium tuberculosis/genética , Tuberculose/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Reações Falso-Negativas , Feminino , Genes Bacterianos , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Sensibilidade e Especificidade , Adulto Jovem
10.
Brain Imaging Behav ; 7(4): 511-23, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23835929

RESUMO

To examine relationships following adjuvant chemotherapy between circulating pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. 33 breast cancer patients who had completed initial treatment (surgery, ± radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and 1 year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the no chemotherapy group. After 1 year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the 1 year time frame (IL-1ra: peak voxel p < 0.0005; cluster size p < 0.0005, p = 0.001 after correction (medial prefrontal), p < 0.0005; cluster size p = 0.001, p = 0.029 corr. (anterior temporal), sTNF-RII: p < 0.0005; cluster size p = 0.001, p = 0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p < 0.0005; cluster size p < 0.0005, p < 0.0005 corr.) and anterior temporal (p < 0.0005; cluster size p < 0.0005, p = 0.002 corr.) cortices at baseline and 1 year later. Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients.


Assuntos
Antineoplásicos/efeitos adversos , Encéfalo/metabolismo , Neoplasias da Mama/tratamento farmacológico , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Neoplasias da Mama/complicações , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante/efeitos adversos , Cognição/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Distribuição Tecidual , Resultado do Tratamento
11.
Int J Tuberc Lung Dis ; 17(7): 892-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23635796

RESUMO

SETTING: In New Zealand, the lineage genotypes of Mycobacterium tuberculosis clinical isolates and their role in the epidemiology of tuberculosis (TB) are currently unknown. OBJECTIVE: 1) To measure the relative frequency of each phylogenetic lineage of the M. tuberculosis complex in New Zealand, and 2) to examine its relationship with patient demographics and multidrug-resistant TB (MDR-TB). METHODS: All non-duplicate M. tuberculosis complex isolates recovered in 2010 and 2011 underwent large sequence polymorphism and/or single nucleotide polymorphism analyses. Mycobacterial interspersed repetitive units (MIRU) profiling was also performed for cluster identification. RESULTS: New Zealand isolates were dominated by lineage 4 (Euro-American: 37.8%, 95%CI 33.6-42.2), followed by lineage 1 (Indo-Oceanic: 22.6%, 95%CI 19.1-26.5), lineage 2 (East Asian: 19.5%, 95%CI 16.2-23.3) and lineage 3 (East-African Indian, which included Central Asian: 17.7%, 95%CI 14.5-21.3). Lineage 2 accounted for 58.1% of MDR-TB cases from 2002 to 2011. Among immigrants, the predominant lineages corresponded to high prevalence lineages in the country of origin. In New Zealand-born individuals, Maori and NZ Europeans share the same predominant lineage, lineage 4, with a higher proportion of non-unique MIRU types observed in Maori cases. Lineage 3 was more prevalent in Maori than in NZ Europeans. CONCLUSION: In New Zealand, M. tuberculosis complex phylogenetic lineage is associated with TB epidemiology in terms of ethnicity, country of origin and MDR-TB.


Assuntos
Antituberculosos/farmacologia , Emigrantes e Imigrantes , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Técnicas de Tipagem Bacteriana , Análise por Conglomerados , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Nova Zelândia/epidemiologia , Filogenia , Polimorfismo de Nucleotídeo Único , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
12.
Brain Behav Immun ; 30 Suppl: S99-108, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22884417

RESUMO

Post-chemotherapy treated cancer patients frequently report cognitive difficulties. The biology of this phenomenon is poorly understood, with uncertainty about possible direct toxic effects on the brain, secondary effects from systemic inflammation, host factors/genetic predisposition to cognitive complaints, or hormonal changes influencing cognitive function. To elucidate possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors, in 2007 we established a prospective, longitudinal, observational cohort study of early stage breast cancer patients, recruited at the end of initial treatments (primary treatment exposure included surgery, ± radiation, ± chemotherapy), and prior to the initiation of adjuvant endocrine therapy. We assessed cognitive complaints, neuropsychological (NP) test performance, markers of inflammation, and brain imaging at baseline, 6 months and 12 months after enrollment. In this analysis of data from the first 93 patients enrolled in the cohort study, we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure. Among the proinflammatory cytokines tested (IL-1 ra, sTNF-RII, CRP, and IL-6) at baseline, only sTNF-RII was increased among chemotherapy exposed patients, with a significant decline in the year after treatment (p=0.003). Higher baseline sTNF-RII in chemotherapy patients was significantly associated with increased memory complaints. In chemotherapy exposed patients, the longitudinal decline in sTNF-RII was significantly correlated with fewer memory complaints over 12 months (r=-0.34, p=0.04). Higher baseline sTNF-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex (r=-0.55, p=0.02), as well as relatively increased inferior frontal metabolism after 1 year, in chemotherapy-exposed subjects. These preliminary findings suggest that post-chemotherapy increases in TNF-α may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo/metabolismo , Neoplasias da Mama/terapia , Transtornos Cognitivos/induzido quimicamente , Citocinas/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Transtornos Cognitivos/sangue , Transtornos Cognitivos/diagnóstico , Terapia Combinada , Função Executiva , Feminino , Humanos , Inflamação/sangue , Inflamação/psicologia , Estudos Longitudinais , Memória , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Sobreviventes , Aprendizagem Verbal
13.
Psychol Med ; 43(8): 1773-83, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23151405

RESUMO

BACKGROUND: Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset. METHOD: The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991-1993, aged 39-63 years). Fatigue was assessed using the Vitality subscale of the 36-item Short Form Health Survey (SF-36) at phase 3 and phase 4 (1995-1996). RESULTS: During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were identified using the pre-established cut-off score of ≤ 50 on the Vitality subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (≥ 1.0 mg/l) using the Centers for Disease Control/American Heart Association recommendations. Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (≥ 1.5 pg/ml). After full adjustment for sociodemographic and biobehavioral covariates, the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI) 1.09-1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06-1.45, p = 0.008) for high IL-6. Similar results were found when CRP and IL-6 were treated as continuous variables. CONCLUSIONS: Plasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue.


Assuntos
Proteína C-Reativa/biossíntese , Fadiga/sangue , Fadiga/etiologia , Mediadores da Inflamação/sangue , Interleucina-6/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Fadiga/patologia , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/patologia , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Eur J Clin Microbiol Infect Dis ; 31(8): 2057-60, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22271302

RESUMO

Extended spectrum beta-lactamase producing E. coli (ESBL-EC) are an emerging public health issue. In New Zealand (NZ), bla (CTX-M-14) and bla (CTX-M-15) are the most common ESBL genes. Although many studies describe risk factors for ESBL-EC, few describe risk factors for specific ESBL genes. Between January 2006 and December 2007, we characterized 108 consecutive, non-duplicate isolates of ESBL-EC at the Auckland Hospital laboratory. Demographic and clinical data were recorded. Of the 108, 54.6% (59) were CTX-M-15-EC, 26.9% (29) were CTX-M-14-EC and 12.09% were CTX-M-9 (13). The remaining seven isolates carried CTX-M-3 (3; 2.7%), CTX-M-65 (2; 1.8%), CTX-M-27 (1; 0.9%) and CTX-M-57 (1; 0.9%). CTX-M-15-EC were more likely than CTX-M-14-EC to be fluoroquinolone-resistant (86.4% versus 32.4%; p=0.006) and to be non-susceptible to amoxicillin-clavulanate (84.7% versus 41.4%; p=0.0001). Patients with CTX-M-15-EC were more likely to be of Indian ethnicity (34.5% versus 0%; p=0.0012) and to have travelled recently (31.6% versus 4%; p=0.0088). Patients with CTX-M-14-EC were more likely to have Chinese or South-East Asian ethnicity (48.1% versus 5.2%; p<0.0001) and to have no history of either travel or prior hospital admission (44% versus 8.9%; p=0.0006). These data imply that CTX-M-15 and CTX-M-14 producing E. coli are associated with distinct demographic subgroups in NZ.


Assuntos
Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/enzimologia , beta-Lactamases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Demografia , Farmacorresistência Bacteriana , Escherichia coli/isolamento & purificação , Etnicidade , Feminino , Fluoroquinolonas/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Fatores de Risco , Adulto Jovem
15.
Dis Esophagus ; 25(2): 166-74, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21819482

RESUMO

The pathogenesis of eosinophilic esophagitis (EoE) is incompletely understood. In certain eosinophilic diseases, activation of tyrosine kinase after fusion of the Fip1-like-1 and platelet-derived growth factor receptor-α genes (F-P fusion gene) mediates eosinophilia via downstream effectors such as extracellular-regulated kinase (ERK1/2) and signal transducers and activators of transcription (STAT5). This mechanism has not been examined in EoE. Our aim was to detect the F-P fusion gene, pERK1/2, and pSTAT5 in esophageal tissue from patients with EoE, gastroesophageal reflux disease (GERD), and normal controls. We performed a cross-sectional pilot study comparing patients with steroid-responsive and steroid-refractory EoE, to GERD patients and normal controls. EoE cases were defined by consensus guidelines. Fluorescence in situ hybridization (FISH) was performed to detect the F-P fusion gene and immunohistochemistry (IHC) was performed to detect pERK1/2 and pSTAT5 in esophageal biopsies. Twenty-nine subjects (median age 30 years [range 1-59]; 16 males; 24 Caucasians) were included: eight normal, six GERD, and 15 EoE (five steroid-refractory). On FISH, 98%, 99%, and 99% of the nuclei in the normal, GERD, and EoE groups, respectively, were normal (P= 0.42). On IHC, a median of 250, 277, and 479 nuclei/mm(2) stained for pERK 1/2 in the normal, GERD, and EoE groups, respectively (P= 0.07); the refractory EoE patients had the highest degree pERK 1/2 staining (846 nuclei/mm(2); P= 0.07). No trend was seen for pSTAT5. In conclusion, the F-P fusion gene was not detected with increased frequency in EoE. Patients with EoE had a trend toward higher levels of pERK 1/2, but not STAT5, in the esophageal epithelium, with highest levels in steroid-refractory EoE patients.


Assuntos
Esofagite Eosinofílica/metabolismo , Refluxo Gastroesofágico/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Fator de Transcrição STAT5/metabolismo , Adolescente , Adulto , Biomarcadores/metabolismo , Criança , Pré-Escolar , Estudos Transversais , Esofagite Eosinofílica/genética , Feminino , Refluxo Gastroesofágico/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Estudos Retrospectivos , Fator de Transcrição STAT5/genética , Adulto Jovem
16.
Int J Tuberc Lung Dis ; 16(2): 216-20, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22137551

RESUMO

SETTING: Recently, Mycobacterium tuberculosis isolates have been described that test phenotypically susceptible to rifampicin (RMP) yet harbour genotypic rpoB mutations. OBJECTIVE: 1) To investigate the impact of such mutations on clinical outcomes among RMP-susceptible isolates, and 2) to determine the prevalence of rpoB mutations among isoniazid (INH) monoresistant isolates at our laboratory and to describe the association between the presence of these mutations and clinical outcomes. METHODS: M. tuberculosis isolates were screened for mutations in the rpoB gene using the Cepheid Gene-Xpert® MTB/RIF assay. Clinical correlation was made by reviewing patient case notes. RESULTS: Isolates from 94 patients were found to have INH-resistant, RMP-susceptible profiles. Clinical information was available for 52 patients, including three whose isolates had rpoB mutations. All three of these patients had treatment failures, compared to two of 49 patients whose isolates did not have rpoB mutations (P = 0.0005). DISCUSSION: We demonstrate a significant association between the presence of rpoB gene mutations that are not detected at the current RMP critical concentration and treatment failure. We suggest that a review of the current RMP critical concentration is warranted to ensure that RMP is not used inappropriately for the treatment of phenotypically occult multidrug-resistant tuberculosis.


Assuntos
Proteínas de Bactérias/genética , DNA Bacteriano/genética , Mutação , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/genética , Antituberculosos/uso terapêutico , RNA Polimerases Dirigidas por DNA , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo , Estudos Retrospectivos , Análise de Sequência de DNA , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
17.
Phys Rev Lett ; 106(8): 085004, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21405580

RESUMO

We demonstrate the hohlraum radiation temperature and symmetry required for ignition-scale inertial confinement fusion capsule implosions. Cryogenic gas-filled hohlraums with 2.2 mm-diameter capsules are heated with unprecedented laser energies of 1.2 MJ delivered by 192 ultraviolet laser beams on the National Ignition Facility. Laser backscatter measurements show that these hohlraums absorb 87% to 91% of the incident laser power resulting in peak radiation temperatures of T(RAD)=300 eV and a symmetric implosion to a 100 µm diameter hot core.

18.
Parkinsonism Relat Disord ; 17(4): 260-4, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21310646

RESUMO

BACKGROUND: Compulsive behaviors provoked by dopamine agonists often go undetected in clinical series, especially if not specifically inquired about. AIM: To determine the frequency of compulsive behaviors in a Parkinson's disease (PD) clinic where agonist-treated patients were routinely asked about such aberrant behaviors. METHODS: We utilized the Mayo Health Science Research database to ascertain all PD patients taking a dopamine agonist over a two year period (2007-2009). All were seen by a Mayo-Rochester Movement Disorders Staff specialist who routinely inquired about behavior compulsions. RESULTS: Of 321 PD patients taking an agonist, 69 (22%) experienced compulsive behaviors, and 50/321 (16%) were pathologic. However, when the analysis was restricted to patients taking agonist doses that were at least minimally therapeutic, pathological behaviors were documented in 24%. The subtypes were: gambling (25; 36%), hypersexuality (24; 35%), compulsive spending/shopping (18; 26%), binge eating (12; 17%), compulsive hobbying (8; 12%) and compulsive computer use (6; 9%). The vast majority of affected cases (94%) were concurrently taking carbidopa/levodopa. Among those with adequate followup, behaviors completely or partly resolved when the dopamine agonist dose was reduced or ceased. CONCLUSIONS: Dopamine agonist treatment of PD carries a substantial risk of pathological behaviors. These occurred in 16% of agonist-treated patients; however, when assessing patients whose dose was at least minimally in the therapeutic range, the frequency jumped to 24%. Pathological gambling and hypersexuality were most common. Carbidopa/levodopa therapy taken concurrently with a dopamine agonist appeared to be an important risk factor.


Assuntos
Antiparkinsonianos/efeitos adversos , Comportamento Compulsivo/induzido quimicamente , Agonistas de Dopamina/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzotiazóis/efeitos adversos , Feminino , Humanos , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pramipexol
19.
Neurology ; 75(4): 349-57, 2010 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-20660865

RESUMO

OBJECTIVE: It has been suggested that people who develop Parkinson disease (PD) may have a characteristic premorbid personality. We tested this hypothesis using a large historical cohort study with long follow-up. METHODS: We conducted a historical cohort study in the region including the 120-mile radius centered in Rochester, MN. We recruited 7,216 subjects who completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 through 1965 and we considered 5 MMPI scales to measure sensation seeking, hypomania, positive emotionality, social introversion, and constraint. A total of 6,822 subjects (94.5% of the baseline sample) were followed over 4 decades either actively (via interview and examination) or passively (via medical records). RESULTS: During follow-up, 227 subjects developed parkinsonism (156 developed PD). The 3 MMPI scales that we selected to measure the extroverted personality construct (sensation seeking, hypomania, and positive emotionality) did not show the expected pattern of higher scores associated with reduced risk of PD. Similarly, the 2 MMPI scales that we selected to measure the introverted personality construct (social introversion and constraint) did not show the expected pattern of higher scores associated with increased risk of PD. However, higher scores for constraint were associated with an increased risk of all types of parkinsonism pooled together (hazard ratio 1.39; 95% CI 1.06-1.84; p = 0.02). CONCLUSIONS: We suggest that personality traits related to introversion and extroversion do not predict the risk of PD.


Assuntos
Comportamento Exploratório , Introversão Psicológica , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Personalidade , Adulto , Idoso , Estudos de Coortes , Extroversão Psicológica , Feminino , Seguimentos , Humanos , MMPI , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto Jovem
20.
Opt Lett ; 35(13): 2124-6, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20596167

RESUMO

We measure the transmission of IR radiation through double-layer metal films with periodic arrays of subwavelength holes. When the two metal films are placed in sufficiently close proximity, two types of transmission resonances emerge. For the surface plasmon mode, the electromagnetic field is concentrated on the outer surface of the entire metallic layer stack. In contrast, for the guided mode, the field is confined to the gap between the two metal layers. Our measurements indicate that, as the two layers are laterally shifted from perfect alignment, the peak transmission frequency of the guided mode decreases significantly, while that of the surface plasmon mode remains largely unchanged, in agreement with numerical calculations.

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