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OBJECTIVE: There is currently no recommendation on the optimal surgical management for dysthyroid optic neuropathy (DON). The aim of this study is to systematically review the surgical management of DON and its outcome on visual acuity (VA). DATA SOURCES: MEDLINE, Cochrane Library, and clinicaltrials.gov REVIEW METHODS: A systematic review of studies about the surgical management of DON was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Articles were included if preoperative and postoperative VA in logMAR (Logarithm of the Minimum Angle of Resolution) were available. RESULTS: Fifteen articles were included in the study accounting for 669 orbits. The mean VA improvement was of 0.44 logMAR overall, 0.41 logMAR for 1-wall, 0.41 logMAR for 2-wall, and 0.55 logMAR for 3-wall decompressions. The mean reduction in exophthalmos was 4.9 mm overall, 4.3 mm for 1-wall, 4.54 mm for 2-wall, and 6.02 for 3-wall decompressions. The mean new onset diplopia (NOD) rate was 19.84% overall, 19,12% for 1-wall, 20.75% for 2-wall, and 19.83% for 3-wall decompressions. CONCLUSION: The results are limited due to the high number of biases in the included studies. It seems that 3-wall decompression offers the best VA improvement and proptosis reduction although also the highest NOD and complications rate. Two-wall balanced decompression or 1-wall inferomedial decompression seems to be effective with less morbidity.
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Oftalmopatía de Graves , Enfermedades del Nervio Óptico , Humanos , Oftalmopatía de Graves/cirugía , Enfermedades del Nervio Óptico/cirugía , Descompresión Quirúrgica/métodos , Órbita/cirugía , Agudeza Visual , DiplopíaRESUMEN
STUDY QUESTION: Do human granulosa cells (GCs) ingest and destroy apoptotic oocytes? SUMMARY ANSWER: Somatic GCs ingest and destroy apoptotic oocytes and other apoptotic substrates through unconventional autophagy-assisted phagocytosis. WHAT IS KNOWN ALREADY: Most (99%) ovarian germ cells undergo apoptosis through follicular atresia. The mode of cleaning of atretic follicles from the ovary is unclear. Ovarian GCs share striking similarities with testicular Sertoli cells with respect to their origin and function. Somatic Sertoli cells are responsible for the elimination of apoptotic spermatogenic cells through unconventional autophagy-assisted phagocytosis. STUDY DESIGN, SIZE, DURATION: Human GCs were tested for the ability to ingest and destroy the apoptotic oocytes and other apoptotic substrates. A systemic study of the main phagocytosis steps has been performed at different time points after loading of apoptotic substrates into the GC. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary cultures of GC retrieved following controlled ovarian stimulation of five women for IVF/ICSI and a human granulosa KGN cell line were incubated with different apoptotic substrates: oocytes which underwent spontaneous apoptosis during the cultivation of immature germ cells for IVF/ICSI; apoptotic KGN cells; and apoptotic membranes from rat retinas. Cultured GC were analyzed for the presence of specific molecular markers characteristic of different steps of phagocytic and autophagy machineries by immunocytochemistry, confocal microscopy, transmission electron microscopy and western blotting, before and after loading with apoptotic substrates. MAIN RESULTS AND THE ROLE OF CHANCE: Incubation of human GC with apoptotic substrates resulted in their translocation in cell cytoplasm, concomitant with activation of the phagocytosis receptor c-mer proto-oncogene tyrosine kinase MERTK (P < 0.001), clumping of motor molecule myosin II, recruitment of autophagy proteins: autophagy-related protein 5 (ATG5), autophagy-related protein 6 (Beclin1) and the rise of a membrane form of microtubule-associated protein 1 light chain 3 (LC3-II) protein. Ingestion of apoptotic substrates was accompanied by increased expression of the lysosomal protease Cathepsin D (P < 0.001), and a rise of lysosomes in the GCs, as assessed by different techniques. The level of autophagy adaptor, sequestosome 1/p62 (p62) protein remained unchanged. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The number of patients described here is limited. Also the dependence of phagocytosis on reproductive hormone status of patients should be analyzed. WIDER IMPLICATIONS OF THE FINDINGS: Removal of apoptotic oocytes by surrounding GC seems likely to be a physiological mechanism involved in follicular atresia. Proper functioning of this mechanism may be a new strategy for the treatment of ovarian dysfunctions associated with an imbalance in content of germ cells in the ovaries, such as premature ovarian failure and polycystic ovary syndrome. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Rennes Metropole (AIS 2015) and Agence de BioMédecine. This work was supported by funding from Université de Rennes1, Institut National de la Santé et de la Recherche Médicale (INSERM) and CHU de Rennes. A.B. is funded in part by the program Actions Concertées Interpasteuriennes (ACIP) and a research grant from the European Society of Pediatric Endocrinology. This work is supported by the Agence Nationale de la Recherche Grants ANR-17-CE14-0038 and ANR-10-LABX-73. The authors declare no competing interests.
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Atresia Folicular , Células de la Granulosa , Animales , Autofagia , Femenino , Humanos , Masculino , Oocitos , Fagocitosis , Proto-Oncogenes Mas , RatasRESUMEN
AIM: To determine whether pulsed-field gel electrophoresis (PFGE) accurately recognizes isolates belonging to clusters defined by techniques based on whole-genome sequencing (WGS) using Pseudomonas aeruginosa as a model. METHODS: We selected 65 isolates of ST395 P. aeruginosa isolated in seven European hospitals between 1998 and 2012. Isolates were typed by PFGE and sequenced by WGS. A core genome multi-locus sequence typing (cgMLST) analysis based on 3831 genes was performed with a homemade pipeline. FINDINGS: PFGE identified eight pulsotypes and cgMLST differentiated nine clusters and nine singletons. Five cgMLST clusters and pulsotypes (31/65 isolates) coincided perfectly. Isolates without evident epidemiological links grouped by PFGE were separated by cgMLST (16/65 isolates) differentiating cities, suggesting that PFGE should be kept for the investigation of local outbreaks. Importantly, hypermutator isolates still shared the pulsotype with their parents (16/65 isolates), whereas they were not recognized by cgMLST. This shows that PFGE was less affected than WGS-based typing by the accelerated genetic drift that occurs in epidemic P. aeruginosa. CONCLUSIONS: although WGS-based typing has logically become the new reference standard, we show here that the PFGE can be used with confidence for the investigation of local outbreaks caused by P. aeruginosa.
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Técnicas de Tipificación Bacteriana/normas , Electroforesis en Gel de Campo Pulsado/normas , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/genética , Secuenciación Completa del Genoma/normas , Técnicas de Tipificación Bacteriana/métodos , Brotes de Enfermedades , Electroforesis en Gel de Campo Pulsado/métodos , Europa (Continente)/epidemiología , Genoma Bacteriano , Humanos , Tipificación de Secuencias Multilocus , Infecciones por Pseudomonas/diagnóstico , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/clasificación , Reproducibilidad de los Resultados , Secuenciación Completa del Genoma/métodosRESUMEN
Enhanced recovery after surgery (ERAS) in colorectal surgery consists of multidisciplinary, multimodal, and patient-centred care. The implementation of pre-, intra-, and post-operative measures mitigates the surgical stress, the inflammatory reaction, and their consequences. The elements of this protocol are evidence-based medicine. This allows improved and accelerated recovery. Consequently, ERAS reduces the incidence of medical complications by 50 %, including fewer infectious complications, and a possible positive impact on survival after oncologic surgery. Hospital length of stay is shortened. There is no contraindication to ERAS, which must be used for all patients undergoing colorectal surgery. Adaptation of the protocol will nevertheless be necessary in the event of urgent surgery.
La réhabilitation améliorée après chirurgie (RAC) colorectale est une prise en charge multidisciplinaire et multimodale, centrée sur le patient. La mise en place de mesures pré-, per- et postopératoires réduit la réponse au stress chirurgical, la réaction inflammatoire et leurs conséquences. Ce protocole de soins, basé sur des preuves scientifiques, permet une récupération améliorée et accélérée. L'incidence des complications médicales est, secondairement, réduite de 50 %. La réhabilitation améliorée se traduit par une diminution significative de la durée d'hospitalisation, une diminution des complications infectieuses et, probablement, par un impact positif sur la survie après chirurgie oncologique. Il n'y a pas de contre-indication à la RAC qui doit donc être proposée à tous les patients devant subir une chirurgie colorectale. Une adaptation du protocole sera néanmoins nécessaire en cas de chirurgie urgente.
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Cirugía Colorrectal , Procedimientos Quirúrgicos del Sistema Digestivo , Recuperación Mejorada Después de la Cirugía , Humanos , Tiempo de Internación , Atención Perioperativa , Complicaciones PosoperatoriasRESUMEN
INTRODUCTION: Streptococcus suis is responsible for a zoonosis for which Suidae (pigs and wild boars) constitute the reservoir, mainly in Asia, with a much lower prevalence in Europe. The predominant clinical manifestation is meningitis, possibly resulting in deafness. CASE REPORT: We report the case of a woman hospitalised for meningitis complicated by labyrinthitis, occurring several hours after preparing a meal composed of wild boar meat. Despite the presence of intracochlear fibrosis, the patient was managed by sequential bilateral cochlear implants. DISCUSSION: The discussion presents a review of the international literature and describes the mechanisms responsible for hearing loss related to this rare zoonosis.
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Sordera , Meningitis Bacterianas , Streptococcus suis , Animales , Sordera/etiología , Femenino , Humanos , Carne , Sus scrofa , PorcinosRESUMEN
INTRODUCTION: Labyrinthine hemorrhage is a rare cause of sudden deafness and generally concerns only on one side. CASE SUMMARY: An 84-year-old man with a past medical history of myelomonocytic chronic leukemia (CMML) suffered from sudden bilateral hearing loss associated with vertigo. The audiogram revealed a left cophosis and a right profound deafness. Videonystagmography showed a left vestibular deficit. The MRI showed a spontaneous strong T1 weighted signal in the left and right labyrinths, corresponding to a bilateral inner ear hemorrhage (IEH). Dizziness resolved rapidly following vestibular physiotherapy, in contrast to hearing which did not improve at all and let the patient isolated in his environment. The patient successfully underwent cochlear implantation so that he could communicate. DISCUSSION: Most IEHs are unilateral and due to anticoagulants treatments and hematological diseases. Only rare cases have described bilateral labyrinth hemorrhage. This is the first case reported of bilateral labyrinth hemorrhage due to CMML.
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Enfermedades del Oído/complicaciones , Oído Interno , Pérdida Auditiva Bilateral/etiología , Pérdida Auditiva Súbita/etiología , Hemorragia/complicaciones , Anciano de 80 o más Años , Humanos , MasculinoRESUMEN
The Neoproterozoic Era was characterized by rapidly changing paleogeography, global climate changes and especially by the rise and fall of the Ediacaran macro-biota. The correlation between disparate Ediacaran fossil-bearing localities and the tentative reconstruction of their paleoenvironmental and paleogeographic contexts are usually complicated by the lack of precise and accurate age data. For this reason, Neoproterozoic sedimentary sections associating Ediacaran biota fossils and fresh volcanic material are especially valuable for radioisotopic dating. Our research in the Podolya Basin, southwestern Ukraine, revealed the presence of four Neoproterozoic volcanic ash deposits (potassium-bentonite layers) within Ediacaran fossil-bearing siliciclastic rocks of the Mohyliv-Podilskyi Group. We used zircon U-Pb LA-ICPMS and CA-ID-TIMS methods to date two of those layers. The results indicate that a diverse assemblage of body and trace Ediacaran fossils occurred as early as 556.78 ± 0.18 million years (Ma) ago. By combining morphological evidence and new age determinations, we suggest a closer paleobiogeographical relationship between the Ukrainian Ediacaran assemblage and the Avalon paleocontinent than previously estimated.
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The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy.
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Neoplasias de la Próstata/genética , Tolerancia a Radiación , Fase S , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Docetaxel , Fraccionamiento de la Dosis de Radiación , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Tolerancia a Radiación/efectos de los fármacos , Especies Reactivas de Oxígeno , Fase S/efectos de los fármacos , Taxoides/farmacologíaRESUMEN
Microfluidic separation of magnetic particles is based on their capture by magnetized microcollectors while the suspending fluid flows past the microcollectors inside a microchannel. Separation of nanoparticles is often challenging because of strong Brownian motion. Low capture efficiency of nanoparticles limits their applications in bioanalysis. However, at some conditions, magnetic nanoparticles may undergo field-induced aggregation that amplifies the magnetic attractive force proportionally to the aggregate volume and considerably increases nanoparticle capture efficiency. In this paper, we have demonstrated the role of such aggregation on an efficient capture of magnetic nanoparticles (about 80 nm in diameter) in a microfluidic channel equipped with a nickel micropillar array. This array was magnetized by an external uniform magnetic field, of intensity as low as 6-10 kA/m, and experiments were carried out at flow rates ranging between 0.3 and 30 µL/min. Nanoparticle capture is shown to be mostly governed by the Mason number Ma, while the dipolar coupling parameter α does not exhibit a clear effect in the studied range, 1.4 < α < 4.5. The capture efficiency Λ shows a strongly decreasing Mason number behavior, ΛâMa^{-1.78} within the range 32 ≤ Ma ≤ 3250. We have proposed a simple theoretical model which considers destructible nanoparticle chains and gives the scaling behavior, ΛâMa^{-1.7}, close to the experimental findings.
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Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, ß-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.
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Cadherinas/metabolismo , Galectina 3/biosíntesis , Adenoma Hipofisario Secretor de Hormona del Crecimiento/patología , Neoplasias Hipofisarias/patología , Prolactinoma/patología , Proteínas de Unión al ARN/biosíntesis , Securina/biosíntesis , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Proteínas Sanguíneas , Cadherinas/biosíntesis , Niño , Preescolar , Femenino , Galectinas , Adenoma Hipofisario Secretor de Hormona del Crecimiento/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Hipófisis/metabolismo , Neoplasias Hipofisarias/metabolismo , Prolactinoma/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: A 10-year retrospective study investigated factors for survival and laryngeal preservation in advanced laryngeal, hypopharyngeal or epilaryngeal neoplasia. MATERIAL AND METHOD: Two hundred and forty-six patients with advanced cancer of the larynx (17.48%), hypopharynx (48.78%) or epilarynx (33.74%) undergoing primary organ-sparing treatment were included from 1998 to 2008. Treatment comprised chemotherapy followed by radiation therapy for 92.68% of patients, isolated radiation therapy for 1.6% and concomitant or sequential radiation-chemotherapy for 5.7%. General health status, history and tumor status were recorded. Factors influencing survival were analyzed by Kaplan-Meier estimator, log-rank test and Cox models. RESULTS: Median overall survival of the population was 2.3 years and median laryngeal preservation 0.99 years in male patients and 2 years in female patients. Survival correlated significantly with body mass index (BMI; P=0.0004), WHO performance status (P=0.0064), alcohol consumption (P=0.0004) and cessation (P<0.0001) and also T stage (P=0.0038), initial laryngeal mobility (P=0.0002) and post-chemotherapy assessment (P<0.0001). Survival with functional larynx correlated with baseline BMI at first consultation (P=0.016), baseline WHO grade (P=0.0005), laryngeal mobility (P<0.0001), T staging (P=0.0009), and T and/or N chemotherapy response to a classical organ preservation protocol (P<0.0001). CONCLUSION: Over and above established criteria, the present study highlighted the importance of general health and nutritional status during treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas/terapia , Quimioterapia Adyuvante , Neoplasias Laríngeas/terapia , Laringectomía , Tratamientos Conservadores del Órgano , Radioterapia Adyuvante , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Índice de Masa Corporal , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Quimioterapia Adyuvante/métodos , Terapia Combinada , Femenino , Francia , Humanos , Estimación de Kaplan-Meier , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/mortalidad , Masculino , Persona de Mediana Edad , Tratamientos Conservadores del Órgano/métodos , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Factores de Riesgo , Fumar/efectos adversos , Resultado del TratamientoRESUMEN
This study aimed to to evaluate the stability of commonly used endogenous control genes for messenger RNA (mRNA) (N = 16) and miRNAs (N = 3) expression studies in prostate cell lines following irradiation. The stability of endogenous control genes expression in irradiated (6 Gy) versus unirradiated controls was quantified using NormFinder and coefficient of variation analyses. HPRT1 and 18S were identified as most and least stable endogenous controls, respectively, for mRNA expression studies in irradiated prostate cells. SNORD48 and miR16 miRNA endogenous controls tested were associated with low coefficient of variations following irradiation (6 Gy). This study highlights that commonly used endogenous controls can be responsive to radiation and validation is required prior to gene/miRNAs expression studies.
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Perfilación de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Neoplasias de la Próstata/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Humanos , Masculino , MicroARNs/biosíntesis , MicroARNs/efectos de la radiación , Proteínas de Neoplasias/efectos de la radiación , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , ARN Mensajero/biosíntesis , RadiaciónRESUMEN
OBJECTIVE: There is no evidence that a knee arthroscopy is more beneficial to middle-aged patients with meniscal symptoms compared to other treatments. This randomised controlled trial aimed to determine whether an arthroscopic intervention combined with a structured exercise programme would provide more benefit than a structured exercise programme alone for middle-aged patients with meniscal symptoms that have undergone physiotherapy. METHOD: 150 out of 179 eligible patients, aged 45 to 64 (mean:54 ± 5), symptom duration more than 3 months and standing X-ray with Ahlbäck grade 0, were randomised to: (1) a physiotherapy appointment within 2 weeks of inclusion that included instructions for a 3-month exercise programme (non-surgery group); or (2) the same as (1) plus, within 4 weeks of inclusion, knee arthroscopy for resection of any significant meniscal injuries (surgery group). The primary outcome was change in pain at 12 months, assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOSPAIN). RESULTS: In the Intention-To-Treat analysis, pain at 12 months was significantly lower in the surgery than in the non-surgery group. The change in KOOSPAIN was significantly larger in the surgery than in the non-surgery group (between-group difference was 10.6 points of change; 95% CI: 3.4 to 17.7, P = 0.004). The As-Treated analysis results were consistent with the Intention-To-Treat analysis results. CONCLUSION: Middle-aged patients with meniscal symptoms may benefit from arthroscopic surgery in addition to a structured exercise programme. Patients' age or symptom history (i.e., mechanical symptoms or acute onset of symptoms) didn't affect the outcome. TRIAL REGISTRATION: NCT01288768.
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Artroscopía/métodos , Traumatismos de la Rodilla/cirugía , Lesiones de Menisco Tibial , Femenino , Humanos , Masculino , Meniscos Tibiales/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego , Resultado del TratamientoRESUMEN
When a micron-sized magnetizable particle is introduced into a suspension of nanosized magnetic particles, the nanoparticles accumulate around the microparticle and form thick anisotropic clouds extended in the direction of the applied magnetic field. This phenomenon promotes colloidal stabilization of bimodal magnetic suspensions and allows efficient magnetic separation of nanoparticles used in bioanalysis and water purification. In the present work, the size and shape of nanoparticle clouds under the simultaneous action of an external uniform magnetic field and the flow have been studied in detail. In experiments, a dilute suspension of iron oxide nanoclusters (of a mean diameter of 60 nm) was pushed through a thin slit channel with the nickel microspheres (of a mean diameter of 50 µm) attached to the channel wall. The behavior of nanocluster clouds was observed in the steady state using an optical microscope. In the presence of strong enough flow, the size of the clouds monotonically decreases with increasing flow speed in both longitudinal and transverse magnetic fields. This is qualitatively explained by enhancement of hydrodynamic forces washing the nanoclusters away from the clouds. In the longitudinal field, the flow induces asymmetry of the front and the back clouds. To explain the flow and the field effects on the clouds, we have developed a simple model based on the balance of the stresses and particle fluxes on the cloud surface. This model, applied to the case of the magnetic field parallel to the flow, captures reasonably well the flow effect on the size and shape of the cloud and reveals that the only dimensionless parameter governing the cloud size is the ratio of hydrodynamic-to-magnetic forces-the Mason number. At strong magnetic interactions considered in the present work (dipolar coupling parameter α≥2), the Brownian motion seems not to affect the cloud behavior.
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Coloides/química , Coloides/efectos de la radiación , Campos Magnéticos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/efectos de la radiación , Microesferas , Modelos Químicos , Simulación por ComputadorRESUMEN
Hypoxia impairs the muscle fibre-type shift from fast-to-slow during post-natal development; however, this adaptation could be a consequence of the reduced voluntary physical activity associated with hypoxia exposure rather than the result of hypoxia per se. Moreover, muscle oxidative capacity could be reduced in hypoxia, particularly when hypoxia is combined with additional stress. Here, we used a model of muscle regeneration to mimic the fast-to-slow fibre-type conversion observed during post-natal development. We hypothesised that hypoxia would impair the recovery of the myosin heavy chain (MHC) profile and oxidative capacity during muscle regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14 and 28 days under normoxia or hypobaric hypoxia (5,500 m altitude) conditions. Ambient hypoxia did not impair the recovery of the slow MHC profile during muscle regeneration. However, hypoxia moderately decreased the oxidative capacity (assessed from the activity of citrate synthase) of intact muscle and delayed its recovery in regenerated muscle. Hypoxia transiently increased in both regenerated and intact muscles the content of phosphorylated AMPK and Pgc-1α mRNA, two regulators involved in mitochondrial biogenesis, while it transiently increased in intact muscle the mRNA level of the mitophagic factor BNIP3. In conclusion, hypoxia does not act to impair the fast-to-slow MHC isoform transition during regeneration. Hypoxia alters the oxidative capacity of intact muscle and delays its recovery in regenerated muscle; however, this adaptation to hypoxia was independent of the studied regulators of mitochondrial turn-over.
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Hipoxia de la Célula/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Músculo Esquelético/crecimiento & desarrollo , Regeneración , Animales , Femenino , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Músculo Esquelético/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Fenotipo , Ratas , Ratas WistarRESUMEN
Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro, but whether it affects muscle regeneration in vivo following injury remains to be elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass during regeneration. To test this hypothesis, the soleus muscle of female rats was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the formation and growth of new myofibers and enhanced the loss of muscle mass during the first 7 days of regeneration, but did not affect the final recovery of muscle mass at 28 days. The impaired regeneration under hypoxic conditions was associated with a blunted activation of mechanical target of rapamycin (mTOR) signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent of Akt activation. The decrease in mTOR activity with hypoxia was consistent with the increase in AMP-activated protein kinase activity, but not related to the change in regulated in development and DNA response 1 protein content. Hypoxia increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of regeneration, though muscle atrophy F box transcript levels remained unchanged. The increase in MyoD and myogenin mRNA expression with regeneration was attenuated at 7 days with hypoxia. In conclusion, our results support the notion that the enhanced loss of muscle mass observed after 1 week of regeneration under hypoxic conditions could mainly result from the impaired formation and growth of new fibers resulting from a reduction in protein synthesis and satellite cell activity.
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Hipoxia/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Regeneración , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Proteínas Portadoras/metabolismo , Hipoxia de la Célula , Venenos Elapídicos/toxicidad , Femenino , Hipoxia/fisiopatología , Péptidos y Proteínas de Señalización Intracelular , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/patología , Fibras Musculares Esqueléticas/fisiología , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteína MioD/genética , Proteína MioD/metabolismo , Fosfoproteínas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Proteínas Quinasas S6 Ribosómicas/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Factores de Transcripción , Proteínas de Motivos Tripartitos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
AIM: To determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload. METHODS: Plantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3 days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500 m) or normoxia. Muscles were collected after 5, 12 and 56 days of overload (i.e. after 3, 9 and 53 days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte-enriched calcineurin-integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc-1α, NRF1 and Tfam) and degradation (BNIP-3). RESULTS: Hypoxia did not alter the fast-to-slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload-induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP-3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc-1α mRNA and protein contents did not correlate with changes in oxidative capacity. CONCLUSION: Hypoxia is not a critical stimulus to modulate the fast-to-slow MHC transition associated with overload. Thus, the impairment of the fast-to-slow fibre shift often observed during post-natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.
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Adaptación Fisiológica/fisiología , Hipoxia/fisiopatología , Músculo Esquelético/metabolismo , Fenotipo , Soporte de Peso/fisiología , Animales , Calcineurina/metabolismo , Femenino , Modelos Animales , Cadenas Pesadas de Miosina/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Ratas , Ratas Wistar , Estrés Mecánico , Factores de Transcripción/metabolismoRESUMEN
If a suspension of magnetic micrometer-sized and nanosized particles is subjected to a homogeneous magnetic field, the nanoparticles are attracted to the microparticles and form thick anisotropic halos (clouds) around them. Such clouds can hinder the approach of microparticles and result in effective repulsion between them [M. T. López-López, A. Yu. Zubarev, and G. Bossis, Soft Matter 6, 4346 (2010)]. In this paper, we present detailed experimental and theoretical studies of nanoparticle concentration profiles and of the equilibrium shapes of nanoparticle clouds around a single magnetized microsphere, taking into account interactions between nanoparticles. We show that at a strong enough magnetic field, the ensemble of nanoparticles experiences a gas-liquid phase transition such that a dense liquid phase is condensed around the magnetic poles of a microsphere while a dilute gas phase occupies the rest of the suspension volume. Nanoparticle accumulation around a microsphere is governed by two dimensionless parameters--the initial nanoparticle concentration (φ(0)) and the magnetic-to-thermal energy ratio (α)--and the three accumulation regimes are mapped onto a α-φ(0) phase diagram. Our local thermodynamic equilibrium approach gives a semiquantitative agreement with the experiments on the equilibrium shapes of nanoparticle clouds. The results of this work could be useful for the development of the bimodal magnetorheological fluids and of the magnetic separation technologies used in bioanalysis and water purification systems.
Asunto(s)
Coloides/química , Modelos Químicos , Modelos Moleculares , Reología/métodos , Resistencia al Corte , Coloides/efectos de la radiación , Simulación por Computador , Campos Magnéticos , Transición de Fase/efectos de la radiaciónRESUMEN
Patients with acquired immunodeficiency syndrome (AIDS) can develop severe uveitis. Although infectious and autoimmune causes must always be considered, drug induced uveitis is also an important etiology. Herein, we present two case reports illustrating the classical presentation of rifabutin and cidofovir induced uveitis. The first case was a 33 year old woman with AIDS treated with anti-protease and anti-tuberculosis drugs (including rifabutin). She presented with a red painful right eye. There was a strong anterior segment inflammation with fibrinous exudates and a dense vitritis. Rifabutin was stopped and topical steroids and mydriatics were given. Intraocular inflammation and symptoms rapidly resolved. The second patient was a 36 year old woman who presented with a painful decrease of vision in her left eye. She was followed for bilateral CMV retinitis in the setting of AIDS and had recently received 2 systemic injections of cidofovir. Anterior segment inflammation with posterior synechiae in both eyes and folds of Descemet membrane in the left eye were noted. Intraocular pressure was 0 mmHg in the left eye and 10 mmHg in the right eye. Fundus examination disclosed CMV retinitis scars in the right eye and choroidal folds in the macula of the left eye. Cidofovir was discontinued and topical steroids and mydriatics started. Progressively the inflammation decreased and the intraocular pressure returned to normal levels. In conclusion, rifabutin and cidofovir are classical examples of drug induced uveitis with distinct characteristic clinical presentation. Recognition of those entities in AIDS patients can avoid useless and potentially invasive interventions in those fragile people.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/inducido químicamente , Fármacos Anti-VIH/efectos adversos , Citosina/análogos & derivados , Organofosfonatos/efectos adversos , Rifabutina/efectos adversos , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Cidofovir , Retinitis por Citomegalovirus/complicaciones , Citosina/efectos adversos , Femenino , Humanos , Uveítis/inducido químicamente , Uveítis/diagnósticoRESUMEN
From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.