RESUMO
Background: Recent advances open the opportunity of altering the course of Alzheimer's disease (AD) through lifestyle-based modifications and novel therapies. Ensuring that society is investing limited budgets in the interventions that have the greatest potential to generate tangible impact will require tools to guide policymakers. Objectives: To build on previous studies to develop an economic model that estimates the societal burden of AD and evaluates the potential impact of novel interventions in six large European countries. Design: AD progression was modelled using a published Markov structure with a 40-year time horizon to estimate lifetime costs and life years in a cohort aged 65 years and above diagnosed with mild cognitive impairment due to AD (MCI-AD) in 2020. Demographic projections were utilized to estimate the prevalence of MCI-AD up to 2100, total corresponding costs and life years. The model allows a comparison of costs associated with the introduction of a hypothetical new disease-modifying therapy that slows disease progression between MCI-AD and all AD-Dementia stages as well as a 'delayed onset' scenario where disease progression is halted at the MCI-AD stage, potentially occurring, for example, through lifestyle-based modifications. Results: The 2022 present value of total lifetime costs for this cohort moving through all disease stages is ~1.2T. Approximately 80% of the present value of lifetime costs in our model are driven by informal care and non-medical direct costs. Our model suggests that a 25% and 50% reduction in disease progression compared to natural history could translate into a present value of cost savings of 33.7B and 72.7B. Halting MCI-AD progression for 3 years with no therapeutic effect thereafter resulted in a present value cost savings of 84.7B in savings. Conclusions: Our data further suggest that early intervention via disease-modifying therapies or lifestyle-based modifications in AD could result in cost savings for society. Additionally, our findings reinforce the importance of accounting for the full value of innovative interventions, management and care paradigms, including their potential impact on direct, indirect and intangible costs impacting patients, their care partners and health and social care systems.
RESUMO
Dogs are reservoir hosts for Leishmania infantum, a protozoan parasite transmitted by phlebotomine sand flies. The anti-feeding and fast-killing efficacy of Scalibor® deltamethrin collars against experimental Phlebotomus perniciosus challenges on dogs was determined over 1 year. Two groups of 8 dogs each were fitted with placebo (control) or deltamethrin collars (treated) on Day 0 and exposed to sand flies approximately every 28 days up to Day 364. After each exposure, anti-feeding and fast-killing efficacy rates were determined by comparing blood-fed or live insects, respectively, in the treated vs. the control group. Blood-fed and live sand flies were significantly less in treated dogs as compared to control dogs at each assessment. The anti-feeding efficacy rate exceeded 90% except on Day 337 (89%) but increased again (96%) on Day 364. Fast killing efficacy was <74% over the study when considering all flies. However, this value increased cumulatively to 98% when only blood-fed flies were compared between groups. Scalibor® collars are highly effective at preventing P. perniciosus blood-feeding and in fast-killing flies taking a blood meal for up to 1 year after application. These strong and long-lasting effects are an important strategic component for L. infantum transmission control.
Assuntos
Doenças do Cão , Leishmania infantum , Phlebotomus , Psychodidae , Piretrinas , Animais , Doenças do Cão/parasitologia , Doenças do Cão/prevenção & controle , Cães , Nitrilas/farmacologia , Phlebotomus/parasitologia , Piretrinas/farmacologiaRESUMO
PURPOSE: This work aims to evaluate the dosimetric consequences of replacing the Anisotropic Analytical Algorithm (AAA) by Acuros XB (AXB), dose-to-water (Dw) or dose-to-medium (Dm), for RapidArc plans of nasopharyngeal carcinomas (NPC). MATERIALS AND METHODS: Seventeen NPC plans created with AAA (v15.6) were recalculated with AXB (v15.6) Dw and Dm. The dose-volume parameters to the planning target volumes (PTV) and relevant organs at risk (OAR) were compared. The high dose PTV was divided into bone, air and tissue components and the comparison was performed for each of them. RESULTS: AXB Dw revealed no significant differences in the PTVs compared to AAA. Lower values were observed to spinal cord, brainstem, oral cavity and parotids (0.5% to 2.3%), and higher values to cochleas (up to 5.4%) and mandible (up to 6.7%). AXB Dm predicted lower values than AAA for all PTVs and OARs (2.0% to 6.1%). For the bone PTV subvolume, AXB Dw and Dm predicted respectively higher (2.4%) and lower (2.2% to 3.4%) values. No significant differences were noted in air. AXB predicted lower values than AAA in soft tissues (0.4% to 1.6%). The largest difference was found to the mandible V60Gy parameter, with median differences of 6.7% for AXB Dw and -6.0% for AXB Dm. CONCLUSION: Significant dose differences are expected when switching from AAA to AXB in NPC cases. The dose prescriptions and the tolerance limits for some OARs, especially those of high density, may need to be adjusted depending on the selected dose calculation algorithm and reporting mode.
Assuntos
Algoritmos , Fracionamento da Dose de Radiação , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Ar , Anisotropia , Humanos , Mandíbula/efeitos da radiação , ÁguaRESUMO
PURPOSE: Gantry collision is a concern in linac-based stereotactic radiosurgery (SRS). Without collision screening, the planner may compromise optimal planning, unnecessary re-planning delays can occur, and incomplete treatments may be delivered. To address these concerns, we developed a software for collision prediction based on simple machine measurements. MATERIALS AND METHODS: Three types of collision were identified; gantry-couch mount, gantry-couch and gantry-patient. Trigonometric formulas to calculate the distance from each potential point of collision to the gantry rotation axis were generated. For each point, collision occurs when that distance is greater than the gantry head to gantry rotational axis distance. The colliding arc for each point is calculated. A computer code incorporating these formulas was generated. The inputs required are the couch coordinates relative to the isocenter, the patient dimensions, and the presence or absence of a circular SRS collimator. The software outputs the collision-free gantry angles, and for each point, the shortest distance to the gantry or the colliding sector when collision is identified. The software was tested for accuracy on a TrueBEAM® machine equipped with BrainLab® accessories for 80 virtual isocenter-couch angle configurations with and without a circular collimator and a parallelepiped phantom. RESULTS: The software predicted the absence of collision for 19 configurations. The mean absolute error between the measured and predicted gantry angle of collision for the remaining 61 cases was 0.86 (0.01-2.49). CONCLUSION: This tool accurately predicted collisions for linac-based intracranial SRS and is easy to implement in any radiotherapy facility.
Assuntos
Acidentes , Irradiação Craniana/instrumentação , Radiocirurgia/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Rotação , Software , Tamanho Corporal , Desenho de Equipamento , Humanos , MatemáticaRESUMO
Dogs are the reservoir host of zoonotic visceral leishmaniasis (VL) caused by Leishmania infantum (Kinetoplastida: Trypanosomatidae). Both subclinically-infected and sick animals can be infectious to competent phlebotomine vectors. The degree and duration of insecticidal efficacy of an oral dose of fluralaner (Bravecto®; Merck Animal Health) was determined in dogs exposed to bites of Phlebotomus perniciosus (Diptera: Psychodidae), a main Mediterranean vector of VL. Twelve dogs allocated to two groups of six animals each were included in a parallel-group designed, negative-controlled, randomized, blinded, single-centre efficacy study. Group 2 was treated with fluralaner on day 0, and sand-fly exposure of both groups was performed on days 1, 28 and 84. Viability of blood-fed females was assessed up to 96 h after exposure and efficacy was measured as the survival rate of specimens fed on Group 2 versus those fed on Group 1. A mortality of 100% was recorded at 24 h in females fed on Group 2 at both days 1 and 28. Significant insecticidal efficacy was still observed on day 84, with > 50% mortality recorded by 48 h post blood meal in Group 2. Fluralaner treatment of dogs represents a promising and affordable method for reducing the pool of infected vectors in endemic settings of zoonotic VL.
Assuntos
Doenças do Cão/prevenção & controle , Controle de Insetos , Insetos Vetores , Inseticidas , Isoxazóis , Leishmaniose Visceral/veterinária , Phlebotomus , Administração Oral , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Leishmania infantum/fisiologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/prevenção & controle , Masculino , Fatores de TempoRESUMO
BACKGROUND: The World Health Organization refers to stroke, the second most frequent cause of death in the world, in terms of pandemic. Present treatments are only effective within precise time windows. Only 10% of thrombolysis patients are eligible. Late assessment of the patient resulting from admission and lack of knowledge of the symptoms is the main explanation of lack of eligibility. METHODS: The aim is the measurement of the time of access to treatment facilities for stroke victims, using ambulances (firemen ambulances or EMS ambulances) and private car. The method proposed analyses the potential geographic accessibility of stroke care infrastructure in different scenarios. The study allows better considering of the issues inherent to an area: difficult weather conditions, traffic congestion and failure to respect the distance limits of emergency transport. RESULTS: Depending on the scenario, access times vary considerably within the same commune. For example, between the first and the second scenario for cities in the north of Rhône county, there is a 10 min difference to the nearest Primary Stroke Center (PSC). For the first scenario, 90% of the population is 20 min away of the PSC and 96% for the second scenario. Likewise, depending on the modal vector (fire brigade or emergency medical service), overall accessibility from the emergency call to admission to a Comprehensive Stroke Center (CSC) can vary by as much as 15 min. CONCLUSIONS: The setting up of the various scenarios and modal comparison based on the calculation of overall accessibility makes this a new method for calculating potential access to care facilities. It is important to take into account the specific pathological features and the availability of care facilities for modelling. This method is innovative and recommendable for measuring accessibility in the field of health care. This study makes possible to highlight the patients' extension of care delays. Thus, this can impact the improvement of patient care and rethink the healthcare organization. Stroke is addressed here but it is applicable to other pathologies.
Assuntos
Serviços Médicos de Emergência/métodos , Sistemas de Informação Geográfica , Acessibilidade aos Serviços de Saúde , Acidente Vascular Cerebral/terapia , Tempo para o Tratamento , Transporte de Pacientes/métodos , Ambulâncias/normas , Serviços Médicos de Emergência/normas , França/epidemiologia , Sistemas de Informação Geográfica/normas , Acessibilidade aos Serviços de Saúde/normas , Humanos , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento/normas , Transporte de Pacientes/normasRESUMO
PURPOSE: Squamous cell carcinomas of the oral cavity occurring in young people represent a specific entity. Its management and prognosis are controversial. We performed a retrospective chart review of all patients aged less than 40 years old and treated at Gustave-Roussy Cancer Centre for a squamous cell carcinomas of the oral cavity between 1999 and 2011. METHODS: Patients and tumour characteristics, type of treatment and follow-up data were collected. Survival data were analysed according to the methods of Kaplan-Meier and both univariate and multivariate analyses were performed to look for prognostic factors regarding overall survival and progression-free survival. RESULTS: Sixty-three patients were identified. Median follow-up was 64 months. Most of the tumours were initially located in the mobile tongue (n=54, 85.7%). Overall 17 patients had died, including 15 from the treated cancer. Overall and progression-free survival rates at 5 years were respectively 79.6% and 68.6%. The corresponding 5 years local, regional and metastatic relapse free survival rates were 80%, 91% and 89% respectively. In the multivariate analysis only the absence of initial surgery (hazard ratio [HR]: 13.5 [2.0; 90.5]; P=0.007) was prognostic for overall survival, while alcohol abuse (HR: 0.37 [0.15; 0.9]; P=0.03) and the absence of surgery (HR: 13.6 [2.5; 74.2]; P=0.002) were associated with a decreased progression-free survival. A younger age (less than 30 year old) was not associated with the risk of recurrence or death. CONCLUSION: Survival rates and tumour control probabilities are relatively high among young patients suffering from squamous cell carcinomas of the oral cavity treated at a tertiary centre. The early identification of patients at risk of relapse is currently difficult. The balance between recurrence and treatment toxicity warrants further studies, both on the clinical level and for the development of prognostic biomarkers.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/terapia , Adulto , Alcoolismo/complicações , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , França/epidemiologia , Humanos , Masculino , Neoplasias Bucais/patologia , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
لقد هدفت هذه الدراسه الى تقييم الالتزام في الوجبات اليوميه التي تقدم لمرضى ارتفاع ضغط الدم ومرضى القلب المنومين في المستشفيات الاردنيه بالدلائل الارشادية لمنظمة الصحه العالميه وبخطط النظام الغذائي الواردة في التغيرات العلاجيه لنمط الحياة وفي النهج الغذائي الهادف الى وقف ارتفاع ضغط الدم ولقد اجري تحليل لقوائم الطعام الدوريه الاسبوعيه التي اخذت من اقسام خدمات الطعام في المستشفيات الكبرى في الاردن ( ع=16)وذلك باستخدام برنامج معالج الطعام إيشا ESHA للحصول على بيانات عن محتواها من المغذيات كبيره المقدار والمغذيات زهيدة المقدار وعن مجموعات الاغذيه الممثله فيها فأظهرت النتائج ان كميات العديد من المغذيات الواردة في القوائم المقدمة ليست ملائمه الى جانب عدم الالتزام - عموما - بخطط النظام الغذائي الواردة في النهج الغذائي الهادف الى وقف ارتفاع ضغط الدم وفي التغييرات العلاجيه لنمط الحياه بالدلائل الارشاديه لمنظمة الصحه العالميه فكان محتوى الوجبات من الصوديم اعلى من الموصى به الى جانب انخفاض محتواها من البوتاسيوم وكانت كميه الاحماض الدهنيه في الغالب خارج المجالات الموصى بها فالوجبات التى تقدم لمرضى القلب في مستشفيات الاردن بحاجة الى مراجعة كي تلبي الدلائل الارشاديه التي وضعت خصيصا لتناسب الظروف الصحيه لهؤلاء المرضى
This study aimed to evaluate the compliance of daily meals served to hypertensive and cardiac inpatients in Jordan according to WHO guidelines and the Therapeutic Lifestyle Changes (TLC) and Dietary Approach to Stop Hypertension (DASH) diets plans. Weekly cycle menus from the food service department of major hospitals in Jordan (n = 16) were analysed using ESHA Food Processor software to obtain data about macroand micronutrient contents and food groups represented. The results showed inappropriate amounts of several nutrients in the menus provided, along with a general noncompliance with the DASH, TLC and WHO guidelines.Meals had higher than recommended sodium content coupled with low potassium content. Fatty acid profiles were often outside the recommended ranges. Meals provided to cardiac inpatients in Jordan need to be revised to meet the guidelines specified for the health conditions of these patients.
La présente étude visait à évaluer dans quelle mesure les repas quotidiens servis aux patients hospitalisés atteints d’hypertension ou de cardiopathie en Jordanie respectaient les recommendations de l'Organisation mondiale de la Santé (OMS) et les régimes alimentaires Therapeutic Lifestyle Changes (TLC) et Dietary Approach toStop Hypertension (DASH). Les cycles hebdomadaires de menus du service de restauration des grands hôpitaux en Jordanie (n = 16) ont été analysés à l’aide du logiciel ESHA Food Processor pour obtenir des données sur la composition en macronutriments et en micronutriments ainsi que sur les groupes d’aliments représentés. Les résultats ont révélé des quantités inadaptées de plusieurs nutriments dans les menus servis, ainsi qu’un non-respect général des recommandations DASH, TLC et de l’OMS. Les repas avaient une composition en sodium trop élevée et un taux de potassium trop faible par rapport aux recommandations. Les profils des acides gras étaient souvent hors des plages recommandées. Les repas fournis aux patients hospitalisés atteints de cardiopathie en Jordanie doivent être revus pour répondre aux recommandations visant leurs pathologies.
Assuntos
Refeições , Hipertensão , Cardiopatias , Política Nutricional , Organização Mundial da Saúde , Pacientes InternadosRESUMO
INTRODUCTION: Acute exacerbations of chronic obstructive pulmonary disease (COPD) patients are major events in the history of this chronic respiratory disease. Their management in French emergency services is unknown, although national guidelines exist. METHODS: This is a descriptive audit study, over a 10 weeks period (12/01-22/03/2009), of the management of COPD exacerbations in the RESUVal (Réseau des Urgences de la Vallée du Rhône, France) network emergency departments. RESULTS: The enrollement of 16 emergency units allowed the analysis of 221 exacerbations of COPD. Measurement of respiratory rate and description of the sputum were mentioned in only 99 (45%) medical records. The rest of the initial assessment was generally satisfactory. Regarding the therapeutic management, 215 (97%) patients received oxygen, beta-2-agonist aerosols were administrated for 209 (95%) patients and anticholinergic aerosols were used for 176 (80%) patients. A systemic corticosteroid and antibiotics were respectively prescribed for 116 (52%) and 123 (56%) patients. Non-invasive ventilation (NIV) was used in only 59% of patients presenting a pH<7.35. CONCLUSIONS: These findings demonstrate that management of exacerbations of COPD could be improved through systematic patients' respiratory rate and sputum characteristics recording or NIV utilization reinforcement.
Assuntos
Auditoria Clínica , Progressão da Doença , Serviços Médicos de Emergência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas Colinérgicos/uso terapêutico , Serviços Médicos de Emergência/normas , Serviços Médicos de Emergência/estatística & dados numéricos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Respiração Artificial/métodosRESUMO
OPINION STATEMENT: Fibrinolysis had long been the reference treatment in patients with ST-Elevation Myocardial Infarction (STEMI). It was associated with a large reduction in mortality as compared with delayed or no reperfusion in patients managed early, within the first 2 hours from the onset of symptoms. Fibrinolysis also had well-known potential complications: cerebral haemorrhage, especially in patients beyond 75 years, and reinfarction. Primary percutaneous intervention (PCI) has overcome most of these limitations, but at a price: PCI-related delays that can reduce the expected benefit of primary PCI compared with fibrinolysis. That primary PCI is today the treatment of choice in patients with STEMI is no longer discussed. However, fibrinolysis should still maintain a role in the management of acute myocardial infarction (AMI) for three reasons. First, fibrinolysis is no longer a stand-alone treatment. Modern fibrinolytic strategies combine immediate fibrinolysis, loading dose of thienopyridines, and transfer to a PCI hospital for rescue or early PCI within 24 hours. These strategies capitalize on the hub-and-spoke networks that have, or should have, been built everywhere to implement primary PCI. The overall clinical results of these modern fibrinolytic strategies are now similar to those of primary PCI. Second, a substantial number of patients cannot be managed with primary PCI within the reasonable time thresholds set by the guidelines. In the case of long PCI-related delays, patients will benefit from fibrinolysis before or during transfer to a PCI hospital. Third, modern fibrinolytic strategies-immediate fibrinolysis followed by rescue or early PCI-may even offer the best results of all in a subset of patients. Patients of less than 75 years, managed within the first 2 hours and who cannot have immediate PCI, will fare better with a modern fibrinolytic strategy than with primary PCI. Guidelines advocate regional networks between hospitals with and without PCI capabilities, an efficient ambulance service and standardization of AMI management through shared protocols. These regional logistics of care are essential to take full advantage of fibrinolysis strategies. In order to check that these strategies are correctly applied, networks need ongoing registries, as well as benchmarking and quality improvement initiatives.
RESUMO
STUDY QUESTION: Does the selection of sperm for ICSI based on their ability to bind to hyaluronan improve the clinical pregnancy rates (CPR) (primary end-point), implantation (IR) and pregnancy loss rates (PLR)? SUMMARY ANSWER: In couples where ≤ 65% of sperm bound hyaluronan, the selection of hyaluronan-bound (HB) sperm for ICSI led to a statistically significant reduction in PLR. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: HB sperm demonstrate enhanced developmental parameters which have been associated with successful fertilization and embryogenesis. Sperm selected for ICSI using a liquid source of hyaluronan achieved an improvement in IR. A pilot study by the primary author demonstrated that the use of HB sperm in ICSI was associated with improved CPR. The current study represents the single largest prospective, multicenter, double-blinded and randomized controlled trial to evaluate the use of hyaluronan in the selection of sperm for ICSI. DESIGN: Using the hyaluronan binding assay, an HB score was determined for the fresh or initial (I-HB) and processed or final semen specimen (F-HB). Patients were classified as >65% or ≤ 65% I-HB and stratified accordingly. Patients with I-HB scores ≤ 65% were randomized into control and HB selection (HYAL) groups whereas patients with I-HB >65% were randomized to non-participatory (NP), control or HYAL groups, in a ratio of 2:1:1. The NP group was included in the >65% study arm to balance the higher prevalence of patients with I-HB scores >65%. In the control group, oocytes received sperm selected via the conventional assessment of motility and morphology. In the HYAL group, HB sperm meeting the same visual criteria were selected for injection. Patient participants and clinical care providers were blinded to group assignment. PARTICIPANTS AND SETTING: Eight hundred two couples treated with ICSI in 10 private and hospital-based IVF programs were enrolled in this study. Of the 484 patients stratified to the I-HB > 65% arm, 115 participants were randomized to the control group, 122 participants were randomized to the HYAL group and 247 participants were randomized to the NP group. Of the 318 patients stratified to the I-HB ≤ 65% arm, 164 participants were randomized to the control group and 154 participants were randomized to the HYAL group. MAIN RESULTS AND THE ROLE OF CHANCE: HYAL patients with an F-HB score ≤ 65% demonstrated an IR of 37.4% compared with 30.7% for control [n = 63, 58, P > 0.05, (95% CI of the difference -7.7 to 21.3)]. In addition, the CPR associated with patients randomized to the HYAL group was 50.8% when compared with 37.9% for those randomized to the control group (n = 63, 58, P > 0.05). The 12.9% difference was associated with a risk ratio (RR) of 1.340 (RR 95% CI 0.89-2.0). HYAL patients with I-HB and F-HB scores ≤ 65% revealed a statistically significant reduction in their PLR (I-HB: 3.3 versus 15.1%, n = 73, 60, P = 0.021, RR of 0.22 (RR 95% CI 0.05-0.96) (F-HB: 0.0%, 18.5%, n = 27, 32, P = 0.016, RR not applicable due to 0.0% value) over control patients. The study was originally planned to have 200 participants per arm providing 86.1% power to detect an increase in CPR from 35 to 50% at α = 0.05 but was stopped early for financial reasons. As a pilot study had demonstrated that sperm preparation protocols may increase the HB score, the design of the current study incorporated a priori collection and analysis of the data by both the I-HB and the F-HB scores. Analysis by both the I-HB and F-HB score acknowledged the potential impact of sperm preparation protocols. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Selection bias was controlled by randomization. Geographic and seasonal bias was controlled by recruiting from 10 geographically unique sites and by sampling over a 2-year period. The potential for population effect was controlled by adjusting for higher prevalence rates of >65% I-HB that naturally occur by adding the NP arm and to concurrently recruit >65% and ≤ 65% I-HB subjects. Monitoring and site audits occurred regularly to ensure standardization of data collection, adherence to the study protocol and subject recruitment. Subgroup analysis based on the F-HB score was envisaged in the study design. GENERALIZABILITY TO OTHER POPULATIONS: The study included clinics using different sperm preparation methods, located in different regions of the USA and proceeded in every month of the year. Therefore, the results are widely applicable.
Assuntos
Ácido Hialurônico/metabolismo , Análise do Sêmen/métodos , Espermatozoides/metabolismo , Adulto , Coeficiente de Natalidade , Método Duplo-Cego , Implantação do Embrião , Feminino , Humanos , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , Espermatozoides/fisiologiaRESUMO
Expression of human Bax, a cardinal regulator of mitochondrial membrane permeabilization, causes death in yeast. We screened a human cDNA library for suppressors of Bax-mediated yeast death and identified human 14-3-3ß/α, a protein whose paralogs have numerous chaperone-like functions. Here, we show that, yeast cells expressing human 14-3-3ß/α are able to complement deletion of the endogenous yeast 14-3-3 and confer resistance to a variety of different stresses including cadmium and cycloheximide. The expression of 14-3-3ß/α also conferred resistance to death induced by the target of rapamycin inhibitor rapamycin and by starvation for the amino acid leucine, conditions that induce autophagy. Cell death in response to these autophagic stimuli was also observed in the macroautophagic-deficient atg1Δ and atg7Δ mutants. Furthermore, 14-3-3ß/α retained its ability to protect against the autophagic stimuli in these autophagic-deficient mutants arguing against so called 'autophagic death'. In line, analysis of cell death markers including the accumulation of reactive oxygen species, membrane integrity and cell surface exposure of phosphatidylserine indicated that 14-3-3ß/α serves as a specific inhibitor of apoptosis. Finally, we demonstrate functional conservation of these phenotypes using the yeast homolog of 14-3-3: Bmh1. In sum, cell death in response to multiple stresses can be counteracted by 14-3-3 proteins.
Assuntos
Proteínas 14-3-3/metabolismo , Apoptose , Proteínas 14-3-3/genética , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína 7 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Cádmio/toxicidade , Cicloeximida/toxicidade , Biblioteca Gênica , Humanos , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Sirolimo/farmacologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Restorative materials have different consequences on the periodontium. The surface of these materials may influence gingival health and cause in some instances gingival inflammation. The purpose of this study was to investigate and compare, in a healthy periodontium, intracrevicular plaque bacteria (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythensis and Treponema denticola), at day 0 and at 6 months, around subgingivally located amalgam, composite and compomer fillings. All the tests were negative (less than 0.1% of the sum of 103 cells), since none of the investigated pathogens were detected. It has been concluded that the material used does not have direct effect on the bacteria species developed around the restorations at this short time period.
Assuntos
Bactérias Anaeróbias/isolamento & purificação , Compômeros , Resinas Compostas , Amálgama Dentário , Restauração Dentária Permanente/métodos , Adulto , Restauração Dentária Permanente/classificação , Feminino , Gengiva/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Colo do Dente , Adulto JovemRESUMO
Combined radical radiation therapy for head and neck carcinoma should be planned with intensity modulated beams to provide a rapid answer to patients' requirements in terms of quality of treatment. The most frequent late toxicity of radiation therapy is xerostomia, which may be prevented by using this technique able to significantly spare salivary glands irradiation. Selection of indications is a very important step. The objective of sparing salivary functions, strongly associated with optimization criteria of quality of life should be considered as a main objective in irradiation of head and neck tumours. The various possibilities offered by this technique allowing to boost a target volume included in prophylactically irradiated regions could offer the possibility to escalate the dose in selected patients. The feasibility of this process is currently validated in prospective studies. Finally, routine implementation of intensity modulated radiation therapy should be performed with strong and robust quality assurance procedures, ensuring that the expected benefit could be increased with the current developments by using rotational techniques.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada/normas , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Tomografia Computadorizada de Feixe Cônico , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estudos Multicêntricos como Assunto , Órgãos em Risco , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Xerostomia/etiologia , Xerostomia/prevenção & controleRESUMO
OBJECTIVE: To investigate the clinical accuracy of magnetic resonance imaging-guided breast vacuum-assisted biopsy (MR-VAB). METHODS: Of 97 scheduled MR-VAB for single MRI lesions (negative second-look sonography) categorised as BI-RADS 4 or 5, 4 were cancelled (undetected lesion = 2, technical problems = 2). Twenty-one patients lost to follow-up were excluded. RESULTS: Twenty-three patients (median age 51 years) were at high risk (BRCA1 = 11, BRCA2 = 7, familial risk = 5), 23 had a suspected local recurrence of breast cancer. Seventy-two imaged lesions (focus = 1, mass enhancement = 32, non-mass-like enhancement = 39) were targeted with a 10-gauge VAB probe using MRI guidance, with a median of 18 specimens per lesion (median procedural time 72 min, range 50-131 min) followed by clip placement. In the case of benignity, MRI follow-up was performed (19 patients, median 389 days, range 33-1,592) or mammography (3 patients, median 420 days, range 372-1,354). According to histopathology results, 29 lesions were benign, 10 were high-risk (papillary = 2, radial scar = 1, atypical epithelial hyperplasia = 7) and 33 malignant (ductal carcinoma in situ = 8, invasive cancers = 25). Three false negative results and 3 complications occurred (1 malaise, 1 skin defect, 1 infection). CONCLUSION: MRI-guided VAB represents an accurate tool for the histological diagnosis of lesions visible only at MRI.
Assuntos
Biópsia , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Mama/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Dactinomicina , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiografia , Estudos Retrospectivos , Carga Tumoral , Vácuo , VimblastinaRESUMO
Aspects of the bionomics of phlebotomine sandflies (Diptera: Psychodidae) were studied from June to November 2005 in three foci of anthroponotic cutaneous leishmaniasis (ACL) in Aleppo Governorate, Syria, where the agent Leishmania tropica (Wright) (Kinetoplastida: Trypanosomatidae) is transmitted by Phlebotomus sergenti Parrot. Syria has been designated by the World Health Organization as one of four countries in the Old World where cutaneous leishmaniasis is hyperendemic, but little is known about the biology of local vector populations. Standard collections by sticky traps showed two peaks in density, in June and late August. In total, 1840 sandflies were caught, comprising five species: Phlebotomus papatasi (Scopoli) (68.0%); P. sergenti (25.4%); Sergentomyia minuta (Rondani) (6.4%); Phlebotomus tobbi Adler & Theodor (0.1%), and Phlebotomus mascittii canaaniticus Adler & Theodor (0.1%). Similar numbers of P. sergenti were caught indoors (246 specimens) and outdoors (222), whereas P. papatasi was significantly more abundant indoors (1096 specimens) than outdoors (156) (chi(2) = 241, P < 0.01). In total, 212 blood-fed females were tested for host blood determination, of which 176 (83.0%) reacted with anti-species reagent. Results from 20 P. sergenti suggest that this species is an opportunistic feeder, imbibing human, ovine, avian, bovine and feline blood, although more bloodmeals were taken from humans and cattle than expected in relation to the relative proportions of potential hosts present (the forage ratio, FR). The bionomics of P. sergenti are discussed in relation to the inefficacy of control campaigns based on indoor spraying with residual insecticides that have been implemented by the Syrian Ministry of Health to control the epidemics of ACL in the Aleppo Governorate.
Assuntos
Insetos Vetores/fisiologia , Leishmaniose Cutânea/epidemiologia , Phlebotomus/fisiologia , Phlebotomus/parasitologia , Animais , Feminino , Humanos , Phlebotomus/classificação , Dinâmica Populacional , Estações do Ano , Especificidade da Espécie , Síria/epidemiologiaAssuntos
Pneumologia/história , Fumar , História do Século XX , História do Século XXI , Humanos , Líbano , Saúde PúblicaRESUMO
PURPOSE: To compare screening breast MRI with conventional screening techniques in high-risk patients with genetic mutation. MATERIALS AND METHODS: Prospective study of 85 patients (mean age of 43 years) with genetic mutation and screening > or = 2 years (mean of 2.7 years, 231 screening examinations). BI-RADS lesions 3-5 were biopsied; isolated BI-RADS 3 lesions on MRI were followed. Results from both techniques were compared. The number of short interval follow-up examinations and biopsy results were reviewed. RESULTS: Eight cancers were diagnosed (3 in situ, 5 invasive carcinomas including an interval cancer, mean size of 14 mm). The sensitivity values for mammography, US and MRI were 12.5%, 50% and 95%, and specificity values were 98.7%, 97.3% and 94.8% respectively. Nineteen short interval follow-up MRI examinations were performed (19%): 14% of patients at initial screening and 5% and 6% at the the second and third screenings. Thirty-two biopsies were performed in 17 patients, including 18 after MRI (PPV of cytology: 30%, and biopsy: 58%). CONCLUSION: Our results confirm the value of MRI for screening of high-risk patients with genetic mutation.