Amoebicidal activity of cationic carbosilane dendrons derived with 4-phenylbutyric acid against Acanthamoeba griffini and Acanthamoeba polyphaga trophozoites and cysts.

Amoebae from the genus Acanthamoeba are important pathogens responsible for severe illnesses in humans such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. In the last few decades, AK diagnoses have steadily increased. Most patients suffering from AK were contact lens users and the infection was related to poor hygiene. However, therapy is not yet well established, and treatments may last for several months due to resistance. Moreover, these treatments have been described to generate cytotoxicity. Therefore, there is an urgent need to develop new therapeutic strategies against AK. In this study, the amoebicidal activity of different generation cationic carbosilane dendrons derived with 4-phenylbutyric acid was demonstrated against Acanthamoeba polyphaga and Acanthamoeba griffini trophozoites and cysts. In addition, the combination of chlorhexidine digluconate and the most effective dendron (ArCO2G2(SNMe3I)4) showed an in vitro effect against Acanthamoeba trophozoites and cysts, reducing the minimal trophozoite amoebicidal concentration as well as concentrations with cysticidal activity.

Diaphragmatic weakness related to radiotherapy: 2 cases and a review.

Post-radiation diaphragmatic weakness have rarely been described. We report two cases of post-radiation diaphragmatic weakness from our center, and review the other published cases, computing clinical, electromyography and magnetic resonance imaging data. Including our two cases, seven cases of post-radiation diaphragmatic weakness have been described. Most occurred after mantle-field radiotherapy for Hodgkin lymphoma (5/7), often in associations with chemotherapy (4/7). Other radiations-induced complications were found (5/7) such as brachial plexopathy, cardiac involvement or hypothyroidy. When studied, phrenic nerve conduction studies revealed different profiles, from clearly abnormal responses to limit amplitudes. Imaging can be a useful diagnostic tool, displaying abnormalities with sharp limits matching the radiation field. Data is limited about long-term evolution. Presentation of post-radiation diaphragmatic weakness seems relatively homogeneous. We propose a diagnosis work-up for post-radiation diaphragmatic weakness, to exclude potentially treatable differential diagnoses.

Quistes subglóticos adquiridos: Reporte de tres casos y revisión de la literatura / Acquired subglottic cysts: Report of three cases and review of the literature

Los quistes subglóticos adquiridos son una causa rara de estridor en la infancia, cuyo reporte ha ido en aumento en las últimas décadas. Su aparición se relaciona con la prematurez y la intubación en el periodo neonatal. Histológicamente, se observa una obstrucción de las glándulas mucosas de la subglotis debido una metaplasia escamosa del epitelio respiratorio. Esta es una condición que usualmente requiere de un alto índice de sospecha para llegar al diagnóstico, ya que pueden confundirse con otras patologías como laringitis aguda (croup), laringomalacia o asma. La nasofibroscopía permite sospechar su presencia, pero el gold standard diagnóstico lo constituye la laringo-tra-queo-broncoscopía directa en pabellón. Existen diversas técnicas para su manejo, siendo las más frecuentemente utilizadas la marsupialización con instrumental frío y láser. La recurrencia es frecuente, por lo que algunos autores han utilizado mitomicina C y la terapia antirreflujo para intentar disminuirla. Sin embargo, hasta la fecha falta evidencia de calidad que permita llegar a un consenso respecto al manejo ideal de esta patología. En este trabajo, presentamos tres casos clínico de pacientes con antecedentes de prematurez que fueron diagnosticados con quistes subglóticos adquiridos y manejados en un hospital pediátrico de alta complejidad.

Acquired subglottic cysts are an infrequent cause of stridor in infants, which has been increasingly reported in the last decades. Its appearance is related to prematurity and intubation in the neonatal period. Histologically, findings are characterized by an obstruction of the mucosal glands, due to squamous metaplasia of the respiratory epithelium. This condition usually requires a high index of suspicion to be diagnosed, as it can be misdiagnosed as croup, laryngomalacia or asthma. Flexible nasendoscopy allows an initial exploration of the larynx, but direct laryngo-tracheo-bronchoscopy in the operating room is the diagnostic gold standard. There are several techniques for its management, but the most frequently used are cold-steel marsupialization and laser. Recurrence is common, and some authors have used mitomycin C and antireflux therapy to try to decrease it. However, up to date, there is a lack of high-quality evidence, regarding the ideal management of this pathology, which prevents reaching a consensus. In this article, we present three clinical cases of premature patients who were diagnosed with subglottic cysts, treated in a tertiary pediatric hospital.

Histologic Analysis of Testes from Prepubertal Patients Treated with Chemotherapy Associates Impaired Germ Cell Counts with Cumulative Doses of Cyclophosphamide, Ifosfamide, Cytarabine, and Asparaginase.

Cryopreservation of immature testicular tissue is an experimental strategy for the preservation of fertility in prepubertal boys that will be subjected to a gonadotoxic onset, as is the case of oncologic patients. Therefore, the objective of this study was to assess the impact of chemotherapeutic treatments on the testicular histologic phenotype in prepubertal patients. A total of 56 testicular tissue samples from pediatric patients between 0 and 16 years old (28 with at least one previous chemotherapeutic onset and 28 untreated controls) were histologically analyzed and age-matched compared. At least two 5-µm sections from testis per patient separated by a distance of 100 µm were immunostained for the germ cell marker VASA, the spermatogonial markers UTF1, PLZF, UCHL1, and SALL4, the marker for proliferative cells KI67, and the Sertoli cell marker SOX9. The percentage of tubule cross-sections positive for each marker and the number of positive cells per tubule cross-section were determined and association with the cumulative dose received of each chemotherapeutic drug was statistically assessed. Results indicated that alkylating agents, cyclophosphamide and ifosfamide, but also the antimetabolite cytarabine and asparaginase were associated with a decreased percentage of positive tubules and a lower number of positive cells per tubule for the analyzed markers. Our results provide new evidences of the potential of chemotherapeutic agents previously considered to have low gonadotoxic effects such as cytarabine and asparaginase to trigger a severe testicular phenotype, hampering the potential success of future fertility restoration in experimental programs of fertility preservation in prepubertal boys.

Phase I study of CC-90010, a reversible, oral BET inhibitor in patients with advanced solid tumors and relapsed/refractory non-Hodgkin's lymphoma.

BACKGROUND: Bromodomain and extra-terminal (BET) proteins are epigenetic readers that regulate expression of genes involved in oncogenesis. CC-90010 is a novel, oral, reversible, small-molecule BET inhibitor. PATIENTS AND METHODS: CC-90010-ST-001 (NCT03220347; 2015-004371-79) is a phase I dose-escalation and expansion study of CC-90010 in patients with advanced or unresectable solid tumors and relapsed/refractory (R/R) non-Hodgkin's lymphoma (NHL). We report results from the dose escalation phase, which explored 11 dose levels and four dosing schedules, two weekly (2 days on/5 days off; 3 days on/4 days off), one biweekly (3 days on/11 days off), and one monthly (4 days on/24 days off). The primary objectives were to determine the safety, maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) and schedule. Secondary objectives were to evaluate signals of early antitumor activity, pharmacokinetics, and pharmacodynamics. RESULTS: This study enrolled 69 patients, 67 with solid tumors and two with diffuse large B-cell lymphoma (DLBCL). The median age was 57 years (range, 21-80) and the median number of prior regimens was four (range, 1-9). Treatment-related adverse events (TRAEs) were mostly mild and manageable; grade 3/4 TRAEs reported in more than two patients were thrombocytopenia (13%), anemia, and fatigue (4% each). Six patients had dose-limiting toxicities. MTDs were 15 mg (2 days on/5 days off), 30 mg (3 days on/11 days off), and 45 mg (4 days on/24 days off). The RP2D and schedule selected for expansion was 45 mg (4 days on/24 days off). As of 8 October 2019, one patient with grade 2 astrocytoma achieved a complete response, one patient with endometrial carcinoma had a partial response, and six patients had prolonged stable disease ≥11 months. CONCLUSIONS: CC-90010 is well tolerated, with single-agent activity in patients with heavily pretreated, advanced solid tumors.

[Feedback on clinical oncology pharmacy]. / Retour d'expérience en pharmacie clinique oncologique.

The rising of oral anticancer therapies let more and more patients to be cared at home and improve their quality of life. However the toxicities of these drugs and the distance with health professionals imply that the patient needs to be more autonomous with respect to his treatment. Patients through therapeutic education programs allows them to manage side effects, to be more observant and then to subsequently benefit from the treatment. We report here, oncology clinical pharmacists experiences in some health facilities in France, presented at the 1st day of clinical oncology pharmacy (December 2017, Marseille).

Improvement in body composition following a supervised exercise-training program of adult patients with cystic fibrosis.

OBJECTIVES: Maintenance of optimal nutritional status is a crucial issue for cystic fibrosis (CF) patients. Here, we evaluate the effects of an 8-week exercise training (ET) program on body composition in CF patients. METHODS: This prospective pilot observational study was conducted in adult CF subjects in stable condition following their annual check-up. The ET program consisted of three sessions per week and included aerobic training (≥30min), muscle strengthening, circuit training, and relaxation. Exercise tolerance (6-minute walk test, 6MWT), pulmonary function, quadriceps isometric strength, and body composition (bioelectrical impedance analysis of fat-free mass [FFM], fat mass, and body cell mass) were analyzed before and immediately after the ET program. A control group of CF patients who preferred not to participate in the ET program received the same evaluations. RESULTS: A total of 43 CF patients were enrolled and offered the ET program; 28 accepted (aged 28±5 years, forced expiratory volume in 1s [FEV1] 48.8±19% predicted) and 15 declined the ET program but agreed to be part of the control group (matched for age and CF severity: 30.8±9 years, FEV1 51.8±16.5%). Pulmonary function was unchanged at the end of the ET program, but significant improvements were observed in 6MWT distance (from 520±96m to 562±105m, P<0.001) and muscle strength (331±141N to 379±168N, P<0.001). Although mean body mass index did not change, the ET group showed significantly increased FFM (43.85±8kg to 44.5±9.2kg, P=0.03) and a trend towards increased body cell mass (21.4±6 to 22.1±6.6kg, P=0.06). All other parameters were unchanged by ET. There were no significant correlations between the increase in FFM and the improvements in either 6MWT distance or muscle strength. The CF control group exhibited no significant changes in any parameters between evaluations. CONCLUSIONS: ET significantly improved FFM, but not body mass index, in CF patients. The results illustrate the superiority of bioimpedancemetry for assessing changes in body composition and reveal the importance of ET for improving not only exercise tolerance but also nutritional status in these patients.

Synthesis and in vitro activity of new biguanide-containing dendrimers on pathogenic isolates of Acanthamoeba polyphaga and Acanthamoeba griffini.

The genus Acanthamoeba can cause Acanthamoeba keratitis (AK) and granulomatous amoebic encephalitis (GAE). The treatment of these illnesses is hampered by the existence of a resistance stage that many times causes infection relapses. In an attempt to add new agents to our chemotherapeutic arsenal against acanthamebiasis, two Acanthamoeba isolates were treated in vitro with newly synthesized biguanide dendrimers. Trophozoite viability analysis and ultrastructural studies showed that dendrimers prevent encystment by lysing the cellular membrane of the amoeba. Moreover, one of the dendrimers showed low toxicity when tested on mammalian cell cultures, which suggest that it might be eventually used as an amoebicidal drug or as a disinfection compound in contact lens solutions.

Effects of prenatal exposure to alcohol, tobacco and other drugs of abuse on retinal development. / Efectos de la exposición prenatal a alcohol, tabaco y otras drogas de abuso sobre el desarrollo retiniano.

PURPOSE: To assess structural changes in the retina using optical coherence tomography (OCT) in children prenatally exposed to toxic substances. METHODS: The study included a total of 49 infants, aged between 5 and 18years, exposed to toxic substances during pregnancy. Among the exposed children, 25 were exposed to tobacco, 20 were exposed to alcohol, and 4 children were exposed to other drugs of abuse. All children underwent a complete ophthalmology examination, including an OCT. The results were compared against a control group composed of 25 infants, age matched with controlled pregnancy, and not exposed to toxic substances. RESULTS: Children prenatally exposed to toxic substances showed significantly thinner average retinal nerve fibre layer (RNFL) compared with control children (81.5 vs. 99.7µm; P<.005), as well as RNFL thinning in its four quadrants (superior RNFL: 97.5 vs. 127.5µm; P<.005; nasal RNFL: 61.5 vs. 72.3µm; P<.005; inferior RNFL: 99.8 vs. 128.6µm; P<.005, temporal RNFL: 58.3 vs. 68.2µm; P<.005). Exposed children also exhibited a thinner ganglion cell layer (72.9 vs. 85.9; P<.005). Greater RNFL thinning was observed in children exposed to drugs of abuse (RNFL thinner average=72), followed by children exposed to alcohol (RNFL thinner average=72.9), and finally the least affected were those children exposed to tobacco during pregnancy (RNFL=94.6). CONCLUSION: Toxic substances during pregnancy interfere in retinal development. These results strengthen the evidence about the avoidance of any toxic substance during pregnancy.

Is breast magnetic resonance imaging (MRI) useful for diagnosis of additional sites of disease in patients recently diagnosed with pure ductal carcinoma in situ (DCIS)?

PURPOSE: To determine if breast MRI is useful for detecting additional or invasive sites of disease in patients initially diagnosed with pure DCIS. MATERIALS AND METHODS: A retrospective review of women diagnosed with pure DCIS who underwent a breast MRI for evaluation of extent of disease was performed at a single institution from January 2013 to April 2015. Data analysis included imaging (mammography, ultrasound and MRI) and pathology characteristics (histology and biomarker status) of the primary DCIS as well as descriptors for the additional sites of disease incidentally found by breast MRI. RESULTS: A total of 108 patients were diagnosed with pure DCIS during this time period. A breast MRI for staging was recommended for all patients. 76 patients had an MRI performed, ages ranging from 38 to 79 years old (median, 53 years); sizes ranging from 0.3 to 10cm (mean, 2.2cm). A total of 52 patients (68%) either had suspicious new finding(s) (n=27, 36%) or bigger tumor size than originally visualized on mammography (n=43, 57%). A total of twenty-seven patients (36%) had other MRI findings suspicious for additional sites of disease in either breast (four in the ipsilateral breast and twenty-three in the contralateral breast). From this group of patients, twenty-three (85%) patients underwent MRI-guided biopsy as recommended. The four patients who did not have the recommended MRI guided-biopsy either underwent total mastectomies or refused the biopsy. Six out of the twenty-three patients (26%) were diagnosed with an additional site of cancer (5 DCIS and 1 IDC) (7.9%, CI=3.7%, 16.2%). All of the six patients had contralateral disease (100%) and none had a second site of disease in the ipsilateral breast. The size of the additional sites of disease ranged from 0.4 to 8cm (mean, 3.1cm) and the size of the primary lesion in this selected group ranged from 0.1 to 10.9cm (mean, 5.6cm). Ages ranged from 44 to 63 years old (median, 52.5 years). Five out 6 patients (83%) presented with the first site of disease as pure DCIS with estrogen (ER) and progesterone (PR) receptors positive and one case (17%) was pure DCIS ER/PR- negative. The second incidental lesion found on MRI demonstrated 5 cases of contralateral pure DCIS and 1 case of contralateral invasive disease. From this group, we did not have the data for biomarker analysis for the second site of disease in 2 cases and 3 cases showed concordant biomarker status between the first and second sites of disease. The 1 case that presented with an invasive component in the contralateral side of the initially biopsy-proven pure DCIS had discordant biomarkers compared to the first site of disease: the first site of pure DCIS was ER/PR-negative and the second site of invasive ductal carcinoma (IDC) presented with ER/PR-positive status. CONCLUSION: From a total of 76 patients with recent diagnosis of pure DCIS who underwent staging breast MRI examination for diagnosis of additional sites of disease, approximately 8% (95% confidence interval=3.7%, 16.2%) was diagnosed with an additional site of cancer and 1.3% (95% confidence interval=0.2%, 7%) of the total cases had invasive disease in the additional sites with different biomarker status; changing their management and prognosis.

Relación entre el Nivel de Vitamina D y Urticaria Crónica Espontánea

Antecedentes: Se ha incrementado la evidencia que demuestra la conexión entre la diferencia/insuficiencia de Vitamina D con aumento de la incidencia, severidad y actividad de trastornos inmunes-inflamatorios. La urticaria crónica es un trastorno de la piel caracterizado por ronchas recurrentes durante más de 6 semanas, y se divide en espontánea o inducible por estímulos físicos. El objetivo principal del siguiente trabajo fue estudiar la relación que pueden tener los niveles de Vitamina D en suero de pacientes con diagnóstico de urticaria crónica espontánea (UCE) que asisten al Servicio de Alergia e Inmunología del Hospital Nacional de Clínicas y compararlos con un grupo control de pacientes sin urticaria. Material y Métodos: Es un estudio descriptivo, prospectivo en donde se estudiaron 27 pacientes con diagnóstico de urticaria crónica espontánea. Luego de confeccionar Historia Clínica compatible con el diagnóstico, se les otorgó un test (UAS7) para evaluar la gravedad de la enfermedad, se realizaron prubeas cutáneas con aeroalergénos y alimentos, se realizó test intradérmico de suero autólogo, laboratorio que incluía además el hemograma, el perfil tiroideo y hepático, serología para virus (Hepatitis B y C, VDRL y HIV), se dosaron niveles de Ig A, G, M, E, y de Vitamina D (D2+D3) a todos los pacientes para luego analizar los resultados y comparar con un grupo control de 16 adultos sanos. Resultados: Hubo diferencias significativas entre los valores séricos de Vitamina D del grupo con urticaria crónica con respecto al control p<0,0001. Conclusión: Este estudio encontró que los pacientes con UCE tienen valores séricos disminuidos de Vitamina D. Son necesarios más estudios acerca del rol de la Vitamina D en la patogénesis de la Urticaria Crónica.

Evidence demostrates the connection between vitamin D deficiency/insufficiency with increased incidence, severity and activity of immune-inflammatory disorders. Chronic urticaria is a skin disorder characterized by recurring hives for mores than 6 weeks, and is divided into spontaneous or inducible by physical stimuli. The main objective of this study was to study the relationship that serum vitamin D levels may have in patients diagnosed with Spontaneous Chronic Urticaria (SCU) who attend the Allergy and Immunology Service of the National Hospital of Clinics and compare them with a control group of patients without urticaria. Materla and Methods: This is a prospective descriptive study in which 27 patients with chronic urticaria spontaneously diagnosed were studied. After making clinical history compatible with the diagnosis, they were given a test (UAS7) to evaluate the severity of the disease. In adition to the hemogram, the thyroid and hepatic profile, serology for virus (Hepatitis B, C, VDRL and VIH), serum levels of immunoglobulins A, G, M, E and vitamin D (D2+D3) to all patients and then analyzed the results and compared with a control group of 16 healthy adults. Results: There were significant differences between serum vitamin D levels in the group with chronic urticaria compared to the control group (p<0,0001) Conclusion: This study found that patients with SCU have decreased serum vitamin D values. More studies are needed about the role of vitamin D in the pathogenesis of UC.

Asthma-COPD overlap syndrome (ACOS) vs 'pure' COPD: a distinct phenotype?

BACKGROUND: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is associated with worse outcomes than chronic obstructive pulmonary disease (COPD). The goal of this study was to further explore the clinical characteristics and survival of patients with ACOS identified in a real-life cohort of patients with COPD. METHODS: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency of ACOS defined as a physician diagnosis of asthma before the age of 40 years and to analyze its impact. Univariate analyses were performed to assess the relationship between ACOS and sociodemographic characteristics, risk factors (smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis, dyspnea-modified Medical Research Council scale and baseline dyspnea index), quality of life (QoL), mood disorders, exacerbations, comorbidities, lung function, prescribed treatment, and survival. RESULTS: ACOS was diagnosed in 129 patients (13%). In multivariate analyses, ACOS was associated negatively with cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34], theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No independent association was found with dyspnea, QoL, exacerbations, and mortality. CONCLUSIONS: Compared to 'pure' COPD patients, patients with ACOS exhibit lower cumulative smoking, suffer more from obesity and atopic diseases, and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations, comorbidities) and prognosis (mortality) are not different from 'pure' COPD patients.

Conservación de mango Tommy Atkins mínimamente procesado mediante la aplicación de un recubrimiento de aloe vera (Aloe barbandensis Miller) / Conservation of minimally processed mango Tommy Atkins by applying an aloe vera (Aloe barbandensis Miller) coating

Antecedentes: El mango es una fruta climatérica que puede ver limitada su comercialización debido a la deficiencia en sistemas de procesamiento y conservación que ocasionan pérdidas poscosecha en la cadena agroindustrial. Los frutos mínimamente procesados y tratados con recubrimientos comestibles representan una alternativa para mitigar la perecibilidad del fruto, conservando sus atributos de calidad y ofreciendo al consumidor un producto de fácil consumo y almacenamiento. Objetivos: Conservar y prolongar la vida útil de mango Tommy Atkins mínimamente procesado con la aplicación de un recubrimiento comestible de Aloe vera, evaluando su efectividad mediante el análisis de parámetros físicos, fisicoquímicos, respiratorios, microbiológicos y sensoriales durante almacenamiento refrigerado. Métodos: El recubrimiento comestible fue preparado con gel mucilaginoso de aloe vera en una Concentración de 50 % P/P en dilución y homogenizado con cera carnauba y glicerol, para luego ser aplicado por inmersión en los frutos previamente cortados y secados en estufa. Se diseñaron cuatro tratamientos experimentales: C, R, PreREC y CA, almacenados en refrigeración durante un periodo de 12 de días, en los que se evaluó parámetros como firmeza, color, porcentaje de pérdida de peso, pH, Brix, acidez (%), tasas respiratorias, conteos microbiológicos y descriptores sensoriales por medio de un perfil de aproximación multidimensional. Los datos fueron procesados mediante ANOVA y por el método de comparaciones múltiples LSD. Resultados: Las muestras tratadas con el recubrimiento (R y PreREC) mostraron un retraso en la pérdida de la firmeza, menores cambios de color, una menor pérdida de peso, un aumento menos acelerado del pH y de °Brix y valores más elevados de acidez con respecto a los tratamientos control. Se lograron tasas bajas de consumo de O2 y una producción controlada de CO2 en comparación a las muestras sin tratar. A nivel microbiológico, el recubrimiento disminuyó el crecimiento de mesófilos, mohos y levaduras; mientras que sensorialmente, descriptores como la firmeza, calidad general, olor y sabor característico mostraron una mayor calificación por parte del panel sensorial. Conclusiones: El recubrimiento permitió conservar por 3 días más las muestras de mango mínimamente procesado respecto a los tratamientos control.

Background: Mango is a climacteric fruit which can limit its marketing due to some deficiencies in processing and preservation systems that cause postharvest losses in the agribusiness and value chain. Minimally processed fruits and edible coatings represent an alternative to decrease the perishability of fruits, preserving its quality attributes and offering to consumers an easy product to use and storage. Objetives: The aim of this study was to conserve and extend the shelf life of minimally processed "Tommy Atkins" mango covered by an edible coating made of aloe vera mucilage, assessing its effectiveness by analyzing physical, physicochemical, respiratory, microbiological and sensory parameters during refrigerated storage. Methods: The edible coating was prepared with aloe vera, which is a mucilaginous gel, in a concentration of 50% w/w in dilution and homogenized with carnauba wax and glycerol. Then aloe vera was applied by immersion in the pre-cut fruits and dried in stove. Four experimental treatments were designed: C, R, PreREC and CA, stored under refrigeration for a period of 12 days, in which parameters such as strength, color, percentage weight loss, pH, Brix, acidity (%), respiratory rates, microbiological counts, and sensory descriptors were evaluated by a multidimensional approach profile. Data were analyzed using ANOVA and the LSD multiple comparison method. Results: Samples treated with the edible coating (R y PreREC) showed a delay in the loss of firmness, less color changes, less loss of weight, a less increase in pH and Brix values, and a higher acidity compared to the control treatments. Low rates of O2 consumption and controlled CO2 production compared to untreated samples were achieved. Coating decreased the growth of mesophilic, molds and yeasts; while sensory descriptors as firmness, overall quality, characteristic odor and taste showed a higher rating by the sensory panel. Conclusions: Edible coating made of aloe vera gel allowed to keep for 3 more days samples of minimally processed mango compared to control treatments.

[Treatment of malignant central airways obstruction by rigid bronchoscopy]. / Traitement par bronchoscopie rigide de l'obstruction maligne des voies aériennes centrales.

INTRODUCTION: Endobronchial resection is now the standard treatment for tracheobronchial narrowing due to malignancy. The clinical and functional respiratory improvement has been evaluated previously but only in heterogeneous population. METHODS: Between February 2009 and February 2011, we conducted a prospective single centre study at the University Hospital of Lille. Twenty-five patients with malignant tracheobronchial stenosis received a clinical and functional respiratory evaluation before and after a rigid bronchoscopy procedure to reduce the obstruction followed where appropriate by placement of an endobronchial stent. RESULTS: Thirteen patients (52%) had primary lung cancer and in 12 the tumor had another origin. Nineteen patients (76%) received a stent after bronchial unblocking. Clinically, all patients felt an improvement in their dyspnea estimated by the Borg score with a median improvement of -2 points [-1; -4] following the procedure (P<0.001). In 96% the dyspnea visual analogic scale improved by 40 mm [27; 67] (P<0.0001). The FEV1 increased significantly after unblocking by 9% [-3.5; 28.5] (P<0.05). The Rint decreased significantly by -0.19 kPa/L per second [-0.06; -0.023] (P=0.001). Correlations between scales of dyspnea and spirometric values were not significant (P>0.05). The survival rate at 1 year was 29%. CONCLUSION: Interventional bronchoscopy decreases dyspnea. It modestly improves respiratory function and decreases the Rint. However, lung function and dyspnea scales are not correlated. No spirometry factor can predict clinical dyspnea response but an elevated Borg dyspnea scale might be a good indicator.

[Early detection of COPD in occupational medicine in the Alpes-Maritimes]. / Détection précoce de la BPCO en milieu professionnel dans les Alpes-Maritimes.

INTRODUCTION: This study evaluated a standardized procedure aiming at early detection of COPD in a consecutive population of employees visiting occupational medicine. METHODS: A total of 2818 employees were included by 22 occupational physicians in 5 centers. Respiratory symptoms, smoking status, occupational exposures and socioprofessional categories were collected. Subjects with at least one symptom and/or risk factor underwent spirometry. RESULTS: In this population aged 39±12 years, 2603 patients were free of known asthma or COPD. The presence of at least one symptom was observed in 23.6 % of employees and was significantly associated with smoking status, occupational exposure to organic dust, gas fumes and vapors, and agriculture (P<0.0001). Airflow obstruction (FEV1/FVC < 0.70) was detected in 1.7 % of 1605 employees who underwent spirometry. With the inclusion of known COPD subjects (n=22), the prevalence reached 2.38 %. COPD was significantly associated with smoking intensity. Information on subsequent diagnosis was obtained in only two cases. The quality of spirometry was inadequate in 30 % of cases. Thirty-three percent of detected COPD subjects did not report any respiratory symptoms. CONCLUSION: The strategy used in this study (specific questionnaire plus spirometry) allowed detection of a few cases of previously undiagnosed COPD. Occupational physicians need specific training in spirometry and a better follow-up of care pathways is required to obtain diagnostic confirmation.

Delaying mitotic exit downregulates FLIP expression and strongly sensitizes tumor cells to TRAIL.

Many of the current antitumor therapeutic strategies are based on the perturbation of the cell cycle, especially during mitosis. Antimitotic drugs trigger mitotic checkpoint activation, mitotic arrest and eventually cell death. However, mitotic slippage represents a major mechanism of resistance to these treatments. In an attempt to circumvent the process of slippage, targeting mitotic exit has been proposed as a better strategy to kill tumor cells. In this study, we show that treatments that induce mitotic checkpoint activation and mitotic arrest downregulate FLICE-like inhibitory protein (FLIP) levels and sensitize several tumor cell lines to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-induced apoptosis. Interestingly, we also demonstrate that in absence of mitotic checkpoint activation, mitotic arrest induced either by Cdc20 knockdown or overexpression of nondegradable cyclin B is sufficient to induce both FLIP downregulation and sensitivity to TRAIL. In summary, our data suggest that a combination of antimitotic drugs targeting cyclin B degradation and TRAIL might prevent mitotic slippage and allow tumor cells to reach the threshold for apoptosis induction, thereby facilitating tumor suppression.

[Epidemiology and COPD screening in France. Workshop from the Société de Pneumologie de Langue Française (SPLF)]. / Épidémiologie et dépistage de la BPCO en France. Workshop de la Société de pneumologie de langue française (SPLF).

INTRODUCTION: A workshop has been organized in April 2013 by the Société de Pneumologie de Langue Française about COPD epidemiology and COPD screening in France and other European countries. This article deals with epidemiological data and their consequences on the French screening strategy. STATE-OF-THE-ART: According to the most recent data, spirometric prevalence of COPD in France is 7.5% in individuals over 45 years old. During 2000-2002, COPD was responsible for 1.4% of all causes of death in France and was mentioned to be an associated cause of death in 3% of all death certificates. The average medical costs for one COPD patient is estimated to be 4366 €/year, until 7502 €/year in very severe COPD patients. All clinical studies that have been performed in France show that COPD screening via mini-spirometry is feasible in general practice or in an ambulatory setting; however, a mass screening proved to be difficult to perform. A simple technique like the Piko-6(®) implies a concomitant formalized training. The non-reimbursement by the French Social Security is also a limiting factor, as the absence of medical and economical validation of this strategy. Therefore, COPD screening should be focused to individuals at risk and should include tobacco issues and cessation. CONCLUSION: COPD screening strategies have to be medically evaluated and experiments have to take the specificities of the French health organization into consideration. Any COPD screening strategy should be considered as an overall fight against the tobacco epidemics.

Cytoplasmic interaction of the tumour suppressor protein hSNF5 with dynamin-2 controls endocytosis.

Human SNF5 (hSNF5; INI1, SMARCB1 or BAF47) is a component of the human SWI/SNF chromatin remodelling complex and a tumour suppressor mutated in rhabdoid tumours. It also associates with the integrase of the human immunodeficiency virus (HIV)-1. We show by fluorescence loss in photobleaching that hSNF5 is constantly shuttling between the nucleus and the cytoplasm, raising the question of what the role of hSNF5 is in the cytoplasm. Here, we demonstrate that hSNF5 directly interacts with the GTPase dynamin-2 (DNM2) in the cytoplasm. DNM2 is a large GTPase involved in endocytosis and vesicle dynamics, which has been related to HIV-1 internalization. We show that hSNF5 colocalizes with DNM2 in endocytic vesicles. Depletion of hSNF5, but not of other components of the SWI/SNF complex, destabilizes DNM2 and impairs DNM2-dependent endocytosis. Furthermore, we show that hSNF5 inhibits assembly-stimulated DNM2 GTPase activity but not basal GTPase activity in vitro. Altogether, these results indicate that hSNF5 affects both the stability and the activity of DNM2, uncovering an unexpected role of hSNF5 in modulating endocytosis, and open new perspectives in understanding the role of hSNF5 in tumour genesis.

[Daily physical activity in adult patients with cystic fibrosis]. / Activité physique quotidienne de patients adultes atteints de mucoviscidose.

Assessment of daily physical activity (DPA) is a major element in the development of respiratory rehabilitation. The aim of this study was to evaluate the DPA and the daily energy expenditure (DEE) in adult patients with cystic fibrosis. Thirty adult patients (16 women, 14 men, mean age 27.1±8.4 years) with cystic fibrosis (FVC: 69.2±19%, FEV1: 55.1±24%, BMI: 20.5±3.6kg/m(2)), in stable condition were included in the study. The questionnaire allowed DPA to estimate DEE from the intensity and type of activity. This tool divides the DEE into four intensity levels: less than 1 Metabolic Equivalent Task (MET), greater than 1 and less than 3 METs, 3-5 METs, and greater than 5 METs. A shuttle test for estimating VO(2) peak was performed in all patients. The DEE reached 9478.4±3224.3kJ24h(-1) and was significantly and highly correlated with calculated peak VO(2) (l/min) (r=0.876, P=<0.001); 22% DEE was less than 3 METs, 10% between 3 and 5 METs et 2,5% greater than 5 METs; 65% DEE was less than 1 MET. There was a strong correlation between DEE and BMI (r=0.860, P=<0.001), a low correlation with FVC (r=0.423, P=0.02). This questionnaire is relevant for estimating DPA and DEE in patients with cystic fibrosis and is an interesting test to be used to evaluate changes in patients after pulmonary rehabilitation.