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1.
Trends Biochem Sci ; 46(11): 878-888, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112586

RESUMO

Mammalian cells integrate different types of stimuli that govern their fate. These stimuli encompass biochemical as well as biomechanical cues (shear, tensile, and compressive stresses) that are usually studied separately. The phosphatidylinositol 3-kinase (PI3K) enzymes, producing signaling phosphoinositides at plasma and intracellular membranes, are key in intracellular signaling and vesicular trafficking pathways. Recent evidence in cancer research demonstrates that these enzymes are essential in mechanotransduction. Despite this, the importance of the integration of biomechanical cues and PI3K-driven biochemical signals is underestimated. In this opinion article, we make the hypothesis that modeling of biomechanical cues is critical to understand PI3K oncogenicity. We also identify known/missing knowledge in terms of isoform specificity and molecular pathways of activation, knowledge that is needed for clinical applications.


Assuntos
Mecanotransdução Celular , Fosfatidilinositol 3-Quinase , Animais , Mamíferos , Mecanotransdução Celular/fisiologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/fisiologia
2.
Public Health ; 210: 99-106, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35921739

RESUMO

OBJECTIVES: Minority populations in the United States face a disproportionate burden of illness from COVID-19 infection and have lower vaccination rates compared with other groups. This study estimated the equity implications of increased COVID-19 vaccination in the United States, with a focus on the number of cases, hospitalizations, and deaths avoided. STUDY DESIGN: This was an observational real-world modeling study. METHODS: Data from the Centers for Disease Control and Prevention (CDC) were used to identify the remaining unvaccinated US population by county, age, and race as of October 22, 2021. The number of COVID-19 cases, hospitalizations, and deaths avoided were calculated based on case incidence and death data from the CDC, along with data on race- and age-specific hospitalization multipliers, under a scenario in which half of the remaining unvaccinated population per county, race, and age group obtained a full vaccine regimen. RESULTS: Vaccinating half of the remaining unvaccinated population in each age and race subgroup within counties would result in an estimated 22.09 million COVID-19 cases avoided, 1.38 million hospitalizations avoided, and 150,000 deaths avoided over 12 months. Some minority groups, particularly Black and Hispanic/Latino populations, were projected to experience substantial benefits from increased vaccination rates as they face both lower vaccination rates and worse outcomes if infected with COVID-19. CONCLUSIONS: Increasing COVID-19 vaccination in the United States not only benefits the population as a whole but also serves as a potentially useful lever to reduce the disproportionate burden of COVID-19 illness among minority populations.


Assuntos
COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Hospitalização , Humanos , Grupos Raciais , Estados Unidos/epidemiologia , Vacinação
3.
Eat Weight Disord ; 27(6): 2201-2212, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35128621

RESUMO

PURPOSE: Anorexia nervosa (AN) is a serious mental illness. It is frequently accompanied by a history of childhood maltreatment (CM) that may constitute a specific ecophenotype in patients with eating disorders necessitating special assessment and management. This retrospective study tested whether in patients with AN, CM-related chronic stress may manifest through low-grade inflammation reflected by an increase in white blood cell ratios (neutrophil-to-lymphocyte ratio, NLR, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio). METHODS: Participants (N = 206) were enrolled at an eating disorder daycare unit in Montpellier, France, from March 2013 and January 2020. CM was assessed using the childhood trauma questionnaire (CTQ). The Eating Disorder Examination Questionnaire (EDE-Q) and the MINI were used to assess AN severity and the other clinical characteristics, respectively. RESULTS: NLR was higher in patients with AN and history of CM (p = 0.029) and in patients with AN and history of emotional abuse (p = 0.021), compared with patients with AN without history of CM. In multivariate analysis, emotional abuse (ß = 0.17; p = 0.027) contributed significantly to NLR variability. CONCLUSION: In patients with AN, NLR is a low-grade inflammation marker that is influenced by various sociodemographic, clinical and biological factors. It is more directly affected by some CM types, especially emotional abuse, than by the presence/absence of CM history. Future studies should focus on mediators between CM and increased inflammation, such as interoceptive awareness, emotional dysregulation, food addiction, and stress sensitization. LEVEL OF EVIDENCE: III. Evidence obtained from well-designed cohort or case-control analytic studies.


Assuntos
Anorexia Nervosa , Maus-Tratos Infantis , Anorexia Nervosa/psicologia , Criança , Maus-Tratos Infantis/psicologia , Estudos de Coortes , Humanos , Inflamação , Linfócitos , Neutrófilos , Estudos Retrospectivos
4.
Rev Med Liege ; 74(5-6): 349-353, 2019 05.
Artigo em Francês | MEDLINE | ID: mdl-31206279

RESUMO

Alcohol is often considered as a simple co-factor, potentiating the carcinogenic effect of tobacco, in head and neck cancer. However, its own effect is less clear. It has been recognized by the International Agency for Research on Cancer (IARC) as a risk factor for head and neck cancer for many years. It seems that the risk is a function of the importance of consumption, with certain genetic predispositions. This risk can also decrease if consumption stops, with a prolonged interruption. In addition, alcohol consumption may have a negative influence on the prognosis of patients with this type of cancer. A preventive action is therefore essential, among other things via information to the patient provided by health providers.


En cancérologie ORL, l'alcool est souvent considéré comme un simple co-facteur, potentialisant l'effet carcinogène du tabac. Son effet propre est moins clair. Il est pourtant reconnu par le Centre International de Recherche sur le Cancer (CIRC) comme un facteur de risque de cancer ORL depuis de nombreuses années. Il semble que le risque soit fonction de l'importance de la consommation, avec la contribution de certaines prédispositions génétiques. Ce risque peut également diminuer en cas d'arrêt de la consommation, moyennant un arrêt prolongé. Par ailleurs, la consommation d'alcool pourrait avoir une influence néfaste sur le pronostic des patients atteints de ces cancers. Une action préventive est donc primordiale, entre autres interventions, via l'information du patient par le corps médical.


Assuntos
Consumo de Bebidas Alcoólicas , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Humanos , Fatores de Risco , Fumar
5.
Rev Med Liege ; 73(11): 544-549, 2018 Nov.
Artigo em Francês | MEDLINE | ID: mdl-30431242

RESUMO

While commercialized since over 60 years, metformin is still the first-line drug recommended for the management of type 2 diabetes and is thus today the first glucose-lowering agent used worldwide. Despite this long experience, metformin retains its mysteries, especially regarding the underlying mechanisms responsible for its antidiabetic activity and other potential beneficial effects. During the last years, some contra-indications of metformin use have been at least partially withdrawn while new indications have been recognized. Furthermore, interesting prospects have been reported in important, although unexpected, medical areas such as cancer and neurodegenerative diseases. However, promising results in animal studies and observational human studies have now to be confirmed in well conducted randomized controlled trials.


Commercialisée depuis plus de 60 ans, la metformine est recommandée en première intention dans le traitement du diabète de type 2, ce qui en fait, aujourd'hui, le médicament anti-hyperglycémiant le plus prescrit à travers le monde. Malgré cette longue expérience, la metformine garde ses mystères, notamment quant aux mécanismes qui sous-tendent son action antidiabétique et d'autres effets potentiels. Au cours des dernières années, certaines contre-indications à l'utilisation de la metformine ont été, au moins partiellement, levées tandis que de nouvelles indications apparaissent avec, par ailleurs, des perspectives intéressantes dans des domaines aussi importants qu'inattendus, comme le cancer ou les maladies neurodégénératives. Les résultats prometteurs des études animales et des études observationnelles humaines doivent cependant être vérifiés dans des essais d'intervention contrôlés bien conduits.


Assuntos
Hipoglicemiantes/farmacologia , Metformina/farmacologia , Contraindicações de Medicamentos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Cardiopatias/complicações , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/prevenção & controle , Doenças Neurodegenerativas/tratamento farmacológico , Insuficiência Renal/complicações
6.
Osteoporos Int ; 27(1): 135-46, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26245848

RESUMO

UNLABELLED: Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. INTRODUCTION: Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. METHODS: Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. RESULTS: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. CONCLUSIONS: The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit short- and long-term bone demineralisation and hormonal alterations in AN patients.


Assuntos
Adipocinas/sangue , Anorexia Nervosa/fisiopatologia , Glicemia/metabolismo , Remodelação Óssea/fisiologia , Metabolismo Energético/fisiologia , Adolescente , Anorexia Nervosa/sangue , Anorexia Nervosa/complicações , Antropometria/métodos , Biomarcadores/sangue , Peso Corporal/fisiologia , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/fisiopatologia , Estudos de Casos e Controles , Feminino , Homeostase/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Menstruação/fisiologia , Fatores de Tempo , Adulto Jovem
7.
Horm Metab Res ; 48(3): 174-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26418163

RESUMO

Recent experimental data suggest that circulating serotonin interacts with bone metabolism, although this is less clear in humans. This study investigated whether serum serotonin interferes with bone metabolism in young women with anorexia nervosa (AN), a clinical model of energy deprivation. Serum serotonin, markers of bone turnover [osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), type I-C telopeptide breakdown products (CTX)], leptin, soluble leptin receptor (sOB-R), and insulin-like growth factor-1 (IGF-1) and its binding protein (IGFBP-3) were assessed. Whole body, spine, hip, and radius areal bone mineral density BMD (aBMD) were assessed by dual-energy X-ray absorptiometry in 21 patients with AN and 19 age-matched controls. Serum serotonin, leptin, IGF-1, IGFBP-3, OC, PINP, and aBMD at all sites, radius excepted, were significantly reduced in AN whereas CTX and sOB-R were increased compared with controls. Serum serotonin levels were positively correlated with weight, body mass index, whole body fat mass, leptin, and IGF-1, and negatively with CTX for the entire population. Low serum serotonin levels are observed in patients with AN. Although no direct link between low serum serotonin levels and bone mass was identified in these patients, the negative relationship between serotonin and markers of bone resorption found in all population nevertheless suggests the implication of serotonin in bone metabolism. Impact of low serum serotonin on bone in AN warrants further studies.


Assuntos
Anorexia Nervosa/sangue , Reabsorção Óssea/sangue , Serotonina/sangue , Adolescente , Anorexia Nervosa/complicações , Anorexia Nervosa/fisiopatologia , Antropometria , Densidade Óssea , Reabsorção Óssea/complicações , Reabsorção Óssea/fisiopatologia , Estudos de Casos e Controles , Feminino , Hormônios , Humanos
8.
Rev Med Liege ; 71(9): 407-413, 2016 Sep.
Artigo em Francês | MEDLINE | ID: mdl-28383837

RESUMO

Malaises are often attributed to hypoglycaemia in nondiabetic people who don't have any other serious medical problem. However, such a diagnosis is often overused, because not really demonstrated in most instances. The diagnosis of hypoglycaemia should be structured, based upon the Whipple triad. First, the anamnesis must search for adrenergic and neuroglucopenic symptoms that suggest hypoglycaemia. Afterwards, hypoglycaemia must be authentified by a measurement of a low glucose level at the time of a malaise. Finally, if the malaise is due to a hypoglycaemia, it should resume rapidly after the administration of sugar. When the diagnosis is made based upon this triad, the medical interview should precise the severity of the symptoms and focus on the chronology of the malaises, after meal or in the fasting state, which is crucial to differentiate functional reactice hypoglycaemia from hypoglycaemia due to an insulinoma. Finally, additional medical examinations may be performed, first based upon clinical biology followed, if necessary, by medical imaging. They will not only confirm the diagnosis of hypoglycaemia, but also contribute to find the cause of hypoglycaemia, which will help in choosing the therapeutic strategy.


Résumé : La survenue de malaises est souvent attribuée à une hypoglycémie chez des personnes non diabétiques et, a priori, sans autre problème de santé. Ce diagnostic est, cependant, souvent galvaudé, car habituellement non clairement démontré. Le diagnostic d'hypoglycémie doit se faire de façon structurée en se basant sur la triade de Whipple. Tout d'abord, l'anamnèse doit rechercher les symptômes évocateurs d'hypoglycémie, adrénergiques et neuroglucopéniques. Ensuite, l'hypoglycémie doit être authentifiée par une mesure d'une valeur basse au moment d'un malaise. Enfin, s'il s'agit bien d'une hypoglycémie, le malaise doit disparaître rapidement après resucrage. Une fois le diagnostic posé sur la base de cette triade, l'anamnèse doit faire préciser, outre la sévérité des malaises, leur chronologie, après les repas ou à jeun, ce qui oriente vers une hypoglycémie réactive, fonctionnelle, ou vers une hypoglycémie d'origine organique (insulinome). Des examens complémentaires, faisant d'abord appel à la biologie clinique, ensuite éventuellement à l'imagerie médicale, permettront de, non seulement confirmer le diagnostic d'hypoglycémie, mais aussi d'en préciser l'origine, ce qui orientera la stratégie thérapeutique.


Assuntos
Hipoglicemia/diagnóstico , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Síncope/diagnóstico , Adulto , Algoritmos , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Hipoglicemia/etiologia , Insulinoma/complicações , Neoplasias Pancreáticas/complicações , Síncope/etiologia
9.
Opt Lett ; 40(15): 3667-70, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26258384

RESUMO

We report on spatially- and time-resolved emission measurements and observation of transport of indirect excitons in ZnO/MgZnO wide single quantum wells.


Assuntos
Elétrons , Teoria Quântica , Óxido de Zinco/química , Magnésio/química , Análise Espectral , Temperatura
10.
Br J Dermatol ; 173(4): 1015-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26149621

RESUMO

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.


Assuntos
Rearranjo Gênico do Linfócito T/genética , Micose Fungoide/tratamento farmacológico , Neoplasia Residual/genética , Neoplasias Cutâneas/tratamento farmacológico , Administração Cutânea , Corticosteroides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Clonais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Recidiva Local de Neoplasia/genética , Estudos Prospectivos , Neoplasias Cutâneas/genética , Resultado do Tratamento , Adulto Jovem
11.
Diabetes Obes Metab ; 17(8): 720-5, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25924114

RESUMO

Absolute or relative hyperglucagonaemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet α cells is a direct consequence of intra-islet insulin secretory defects. Recent studies have shown that knockout of the glucagon receptor or administration of a monoclonal specific glucagon receptor antibody make insulin-deficient type 1 diabetic rodents thrive without insulin. These observations suggest that glucagon plays an essential role in the pathophysiology of diabetes and that targeting the α cell and glucagon are innovative approaches in the management of diabetes. Despite active research and identification of promising compounds, no one selective glucagon antagonist is presently used in the treatment of diabetes. Interestingly, besides insulin, several drugs used today in the management of diabetes appear to exert their effects, in part, by inhibiting glucagon secretion (glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, α-glucosidase inhibitors and, possibly, sulphonylureas) or glucagon action (metformin). The potential risks associated with total glucagon suppression include α-cell hyperplasia, increased mass of the pancreas, increased susceptibility to hepatosteatosis and hepatocellular injury and increased risk of hypoglycaemia, and these should be considered in the search and development of new compounds reducing glucagon receptor signalling. More than 40 years after its initial description, hyperglucagonaemia in diabetes can no longer be ignored or minimized, and its correction represents an attractive way to improve diabetes management.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Glucagon/antagonistas & inibidores , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Diabetes Mellitus/fisiopatologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glucagon/sangue , Glucagon/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Células Secretoras de Glucagon/metabolismo , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Pâncreas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Compostos de Sulfonilureia/uso terapêutico
13.
Clin Otolaryngol ; 40(1): 29-35, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25269784

RESUMO

OBJECTIVES: ENT surgeons are facing an ever-increasing demand to demonstrate their efficacy. The 22-item Sino-Nasal Outcome Test (SNOT-22) is a fully validated and easy-to-use outcome measure in rhinology. Our goal was to translate and validate the SNOT-22 in a cohort of 422 French-speaking subjects. DESIGN, SETTING AND PARTICIPANTS: The French version of the SNOT-22 was obtained by forward and backward translations by six independent interpreters. Five experienced rhinologists compared the translations to each other, and a group of 12 naive patients selected the most appropriate translation of each item. To evaluate this questionnaire, we conducted a prospective cohort study on 376 rhinological patients and 46 healthy volunteers in three University-affiliated teaching Hospitals. MAIN OUTCOME MEASURES: Reproducibility (test-retest reliability), internal consistency, known-group differences, responsiveness to treatment, validity and correlation to other clinical instruments (visual analogue scale, Nasal Obstruction Symptoms Evaluation score and Lund-Mackay score). RESULTS: The test-retest reliability coefficient was 0.78, indicating a good reliability when administering the instrument on two different occasions. The internal consistency was high with a Cronbach's α value of 0.93. Our questionnaire was able to detect differences between rhinological patients and control subjects (P < 0.0001) and improved significantly after nose and sinus surgery (P < 0.0001), indicating a good responsiveness. There was a relative correlation with visual analogue scale and Nasal Obstruction Symptoms Evaluation (NOSE) score, but no correlation with Lund-Mackay score. CONCLUSION: The SNOT-22 is a reliable and valid tool to assess quality of life in French-speaking patients and correlates well with known indices of disease severity.


Assuntos
Procedimentos Cirúrgicos Nasais , Avaliação de Resultados em Cuidados de Saúde , Doenças dos Seios Paranasais/cirurgia , Qualidade de Vida , Inquéritos e Questionários , Traduções , Adulto , Idoso , Bélgica , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
14.
Nanotechnology ; 25(43): 435203, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25297338

RESUMO

The growth of ordered arrays of InGaN/GaN nanocolumnar light emitting diodes by molecular beam epitaxy, emitting in the blue (441 nm), green (502 nm), and yellow (568 nm) spectral range is reported. The device active region, consisting of a nanocolumnar InGaN section of nominally constant composition and 250 to 500 nm length, is free of extended defects, which is in strong contrast to InGaN (planar) layers of similar composition and thickness. Electroluminescence spectra show a very small blue shift with increasing current (almost negligible in the yellow device) and line widths slightly broader than those of state-of-the-art InGaN quantum wells.

15.
Nanotechnology ; 25(25): 255202, 2014 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-24897432

RESUMO

We report on the growth and microstructure analysis of high Cd content ZnCdO/ZnO multiple quantum wells (MQW) within a nanowire. Heterostructures consisting of ten wells with widths from 0.7 to 10 nm are demonstrated, and show photoluminescence emissions ranging from 3.03 to 1.97 eV. The wells with thicknesses ≦̸2 nm have high radiative efficiencies compared to the thickest ones, consistent with the presence of quantum confinement. However, a nanometric analysis of the Cd profile along the heterostructures shows the presence of Cd diffusion from the ZnCdO well to the ZnO barrier. This phenomenon modifies the band structure and the optical properties of the heterostructure, and is considered in order to correctly identify quantum effects in the ZnCdO/ZnO MQWs.

16.
J Clin Pharm Ther ; 39(6): 663-72, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25252190

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Current guidelines recommend a combination of clopidogrel and aspirin for management of patients who have experienced an acute coronary syndrome (ACS). Additional antiplatelet agents have been recently approved. Few comparative effectiveness studies are available for these new agents. Accordingly, we evaluated effect on time to hospital admission and resource utilization (number of hospitalizations, ER visits and outpatient visits) of prasugrel vs. clopidogrel in prasugrel-treated patients as assessed in a matched cohort. METHODS: Based on the Truven Health Analytics MarketScan database from 01 January 2009 through 31 July 2012, a retrospective prasugrel-clopidogrel matched cohort was created. Inferences for average treatment effect over 1 and 12 months on time to hospitalization and resource utilization were performed by (i) frequentist Kaplan-Meier estimation with a Cox proportional hazard model and Lin's cost history method for censored resource utilization outcomes and (ii) Bayesian discrete-time hazard and negative binomial models. RESULTS AND DISCUSSION: The 10,963 matched pairs were well balanced on baseline characteristics. Frequentist analyses of time to hospital admission over 365 days and mean all-cause resource utilization over 30 and 365 days showed no statistical differences between prasugrel and clopidogrel (P-values > 0·05). Based on Bayesian analysis of time to admission over 12 months, there was positive evidence of equivalence (0·987 probability of equivalence at a 10% equivalence margin and a Bayes factor of 0·611). Although the frequentist analyses for number of all-cause hospitalizations showed a lack of a significant difference at Months 1 and 12, the Bayesian data analysis showed positive evidence of superiority of clopidogrel at Month 1 (Bayes factor: 5·369); however, at Month 12, there was little evidence of superiority of one treatment over the other (Bayes factor: 0·422). WHAT IS NEW AND CONCLUSION: Using frequentist and Bayesian data analyses, in prasugrel-treated patients, clopidogrel was equivalent to prasugrel for time to hospital admission over 12 months and there was positive evidence that it was superior to prasugrel for number of hospitalizations over the first month of treatment.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Piperazinas/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Tiofenos/uso terapêutico , Ticlopidina/análogos & derivados , Idoso , Teorema de Bayes , Clopidogrel , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cloridrato de Prasugrel , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
17.
Rev Neurol (Paris) ; 170(10): 630-41, 2014 Oct.
Artigo em Francês | MEDLINE | ID: mdl-24952924

RESUMO

INTRODUCTION: Interest in studying swallowing disorders in patients with altered consciousness has increased over the past decade. Swallowing deficit is frequently encountered in severe brain-injured patients. STATE OF ART: Results of studies have highlighted different factors such as the delay between the injury and the treatment and the level of consciousness of these patients, as well as the presence or not of tracheotomy, which will determine the feasibility of resuming oral feeding. Nowadays, very few valid and sensitive scales can be used to assess swallowing deficit in patients with disorders of consciousness. The Facial Oral Tract Therapy (FOTT) scale is an inter-professional multidisciplinary approach offering a structured way to evaluate and treat patients with swallowing disorders. In contrast with other scales, patients do not have to follow verbal instructions for the FOTT. PERSPECTIVES: This paper presents a review of existing literature on the assessment and management of swallowing disorders in patients with altered state of consciousness, and a description of the FOTT method. CONCLUSION: The FOTT seems to be an interesting assessment and rehabilitation tool for patients with disorders of consciousness. However, clinical studies are needed to confirm the validity and sensitivity of this technique.


Assuntos
Transtornos da Consciência/complicações , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/terapia , Humanos , Incidência , Modalidades de Fisioterapia
18.
Clin Exp Allergy ; 43(3): 322-31, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23414540

RESUMO

BACKGROUND: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy. OBJECTIVE: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. METHODS: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. RESULTS: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. CONCLUSIONS AND CLINICAL RELEVANCE: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway.


Assuntos
Quimiocina CX3CL1/metabolismo , Quimiocinas CC/metabolismo , Quimiotaxia/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Receptores de Quimiocinas/metabolismo , Alérgenos , Receptor 1 de Quimiocina CX3C , Quimiocina CCL26 , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Proteínas Tirosina Quinases/metabolismo , Rinite/imunologia , Rinite/metabolismo , Sinusite/imunologia , Sinusite/metabolismo
19.
Clin Anat ; 25(3): 340-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21671283

RESUMO

The aim of the current anatomical and clinical study was to audit our cases of patients who presented with secondary and/or accessory middle turbinates during a two-year period. We investigated the incidence and the clinical impact of these variations. Twenty-eight patients, 19 males and 9 females with a mean age of 41.5 years, representing different ethnic origins, were diagnosed with double middle turbinates based on endoscopic examination. Of those, 92.8% had a main symptom of refractory frontal headache. A secondary nasal symptom was sensation of blocked nose. Patients who underwent endoscopic surgery (n = 13) for reduction of the extra turbinate, reported significant symptom scores improvement (P < 0.0001) of frontal headache and blocked nose, from means of 9.07 ± 0.26 and 8.57 ± 1.39 to 1 ± 0.31, and 1.42 ± 0.35, respectively. Our results indicate that double middle turbinates may be encountered in rhinology practice (2%). Clinically they may present with refractory headache and blocked nose. Endoscopic surgical approach seems to be an effective way of improving the symptoms.


Assuntos
Cavidade Nasal/anatomia & histologia , Conchas Nasais/anormalidades , Adulto , Idoso , Anestésicos Locais/uso terapêutico , Feminino , Variação Genética , Cefaleia/etiologia , Cefaleia/patologia , Cefaleia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Descongestionantes Nasais/uso terapêutico , Obstrução Nasal/complicações , Obstrução Nasal/patologia , Obstrução Nasal/terapia , Dor Intratável/etiologia , Dor Intratável/patologia , Dor Intratável/terapia , Radiografia , Sinusite/complicações , Sinusite/patologia , Sinusite/terapia , Conchas Nasais/diagnóstico por imagem , Conchas Nasais/cirurgia , Adulto Jovem
20.
Diabetes Obes Metab ; 13 Suppl 1: 1-4, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21824250

RESUMO

As an introduction to the Symposium, we have reviewed the early steps in glucagon research from its discovery in 1923 to the establishment of the basics of the physiology and pathophysiology of the hormone after the description of a sensitive and specific radioimmunoassay by Unger and his co-workers in 1959.


Assuntos
Pesquisa Biomédica/história , Glucagon/história , Hiperglicemia/história , Radioimunoensaio/história , Animais , Glucagon/isolamento & purificação , História do Século XX , Humanos , Prêmio Nobel
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