ABSTRACT
Pilomyxoid astrocytoma is a rare form of pediatric CNS malignancy first classified in 2007 by the World Health Organization. The tumors are similar to pilocytic astrocytomas, sharing both some imaging and histologic traits. However, pilomyxoid astrocytomas portend a more ominous prognosis, with more aggressive local tendencies and a greater proclivity for leptomeningeal spread. Although tissue sampling is ultimately required to differentiate pilocytic astrocytomas and pilomyxoid astrocytomas, some imaging features can be used to suggest a pilomyxoid astrocytoma, including homogeneous enhancement, leptomeningeal seeding, and lack of intratumoral cysts. In this article, a case of a hypothalamic pilomyxoid astrocytoma is described, in which the presenting disorder was profound generalized lipodystrophy. The aforementioned imaging characteristics of pilomyxoid astrocytomas are reviewed, as are the pathologic features of such tumors, including their angiocentric cellular arrangement and myxoid background.
Subject(s)
Astrocytoma , Brain Neoplasms , Lipodystrophy , Astrocytoma/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Child , Humans , Magnetic Resonance Imaging , PrognosisABSTRACT
Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.
Subject(s)
Alphapapillomavirus , Carcinoma, Squamous Cell , Carcinoma, Squamous Cell/drug therapy , Humans , Immunotherapy , Papillomaviridae , Prospective StudiesABSTRACT
Retinoblastoma is the most common primary intraocular tumor of childhood. Accurate diagnosis at an early stage is important to maximize patient survival, globe salvage, and visual acuity. Management of retinoblastoma is individualized based on the presenting clinical and imaging features of the tumor, and a multidisciplinary team is required to optimize patient outcomes. The neuroradiologist is a key member of the retinoblastoma care team and should be familiar with characteristic diagnostic and prognostic imaging features of this disease. Furthermore, with the adoption of intra-arterial chemotherapy as a standard of care option for globe salvage therapy in many centers, the interventional neuroradiologist may play an active role in retinoblastoma treatment. In this review, we discuss the clinical presentation of retinoblastoma, ophthalmic imaging modalities, neuroradiology imaging features, and current treatment options.
Subject(s)
Retinal Neoplasms , Retinoblastoma , Humans , Infusions, Intra-Arterial , Melphalan , Neoplasm Seeding , Retinal Neoplasms/drug therapy , Retinal Neoplasms/therapy , Retinoblastoma/drug therapy , Retinoblastoma/therapy , Retrospective Studies , Salvage TherapyABSTRACT
BACKGROUND AND PURPOSE: Prior studies have suggested an association between the presence of cervicofacial venous malformations and intracranial developmental venous anomalies. We reviewed our institutional cohort of patients with cervicofacial venous malformations and examined the spectrum of intracranial venous anomalies, including developmental venous anomalies, cavernous malformations, and dural venous sinus abnormalities. MATERIALS AND METHODS: Consecutive patients who presented to our institution with cervicofacial venous malformations and underwent postcontrast MR imaging were studied. Three neuroradiologists reviewed brain MRIs for the presence of developmental venous anomalies, dural venous sinus ectasia, and cavernous malformations. The prevalence of developmental venous anomalies in this patient population was compared with an age- and sex-matched control group without venous malformations at a ratio of 1:2. Categoric variables were compared with χ2 tests. RESULTS: Sixty-three patients with venous malformations met the inclusion criteria with a mean age of 38.3 ± 24.0 years. The overall presence of developmental venous anomalies in patients with venous malformations was 36.5% (23/63) compared with 7.9% (10/126) in controls (P < .001). The prevalence of dural venous sinus ectasia was 9.5% (6/63) compared with 0% for controls (P = .002). One patient with a venous malformation had a cavernous malformation compared with 1 patient in the control group (P = .62). In 73.9% of patients (17/23), developmental venous anomalies were along the same metamere; and in 82.6% of patients, developmental venous anomalies were ipsilateral to the venous malformations. CONCLUSIONS: Our case-control study demonstrated a significant association between cervicofacial venous malformations and cerebral developmental venous anomalies as well as between cervicofacial venous malformations and dural venous sinus abnormalities. Our findings suggest that venous malformations may be the result of a segmental in utero insult to cells involved in cerebrofacial venous development.
Subject(s)
Intracranial Arteriovenous Malformations/epidemiology , Vascular Malformations/complications , Adolescent , Adult , Case-Control Studies , Child , Face/pathology , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prevalence , Retrospective Studies , Young AdultABSTRACT
The round window serves to decompress acoustic energy that enters the cochlea via stapes movement against the oval window. Any inward motion of the oval window via stapes vibration leads to outward motion of the round window. Occlusion of the round window is a cause of conductive hearing loss because it increases the resistance to sound energy and consequently dampens energy propagation. Because the round window niche is not adequately evaluated by otoscopy and may be incompletely exposed during an operation, otologic surgeons may not always correctly identify associated pathology. Thus, radiologists play an essential role in the identification and classification of diseases affecting the round window. The purpose of this review is to highlight the developmental, acquired, neoplastic, and iatrogenic range of pathologies that can be encountered in round window dysfunction.
Subject(s)
Round Window, Ear/pathology , Female , Humans , Male , Round Window, Ear/abnormalities , Round Window, Ear/surgeryABSTRACT
Desmoplastic infantile tumors are rare supratentorial brain tumors that occur in pediatric patients. Desmoplastic infantile tumors are made up of 2 subtypes: desmoplastic infantile gangliogliomas and desmoplastic infantile astrocytomas. Desmoplastic infantile tumors are often identifiable on imaging on the basis of multiple characteristics. Nevertheless, pathologic analysis is required to confirm the diagnosis, particularly when the imaging features are atypical. Here, the radiology findings, surgical approach and subsequent management, and pathology of a desmoplastic infantile ganglioglioma are described.
Subject(s)
Brain Neoplasms/pathology , Ganglioglioma/pathology , Brain Neoplasms/surgery , Female , Ganglioglioma/surgery , Humans , InfantABSTRACT
In winter 2016-2017, highly pathogenic avian influenza (HPAI) H5N8 virus spread in France, causing an unprecedented epizootic. During the epidemic, southwest France, where most outbreaks were reported, experienced severe weather, with three consecutive storms (Leiv, Kurt, and Marcel) from 3 to 5 February 2017. Although little information is available, one hypothesis is that the spread of HPAI-H5N8 from an infected poultry holding could have been passively facilitated by prevailing wind during the risk period. The aim of this study was therefore to assess the contribution of the wind-borne route to the spatial distribution of HPAI H5N8 outbreaks during the risk period at the beginning of February 2017. The PERLE model, an atmospheric dispersion model (ADM) developed by Météo-France, the French meteorological agency, was used to generate the predicted area at risk of infection from a suspected point source. Model outputs show that the spatial pattern of dust-particle deposition was directed east-southeast in accordance with wind direction. This contrasted with the spatial distribution of HPAI H5N8 outbreaks, which spread westward. These observations suggest that the wind-borne route alone was insufficient to explain the spatial distribution of outbreaks over large distances in southwest France at the beginning of February 2017. Finally, this study illustrates the relevance of close collaboration between governmental authorities, veterinary research institutes, and meteorological agencies involving interdisciplinary research for successful outbreak investigations.
Nota de investigación- Exploración de la propagación por el viento del virus de la influenza aviar altamente patógena H5N8 durante la epizootia entre los años 20162017 en Francia. En el invierno 2016-2017, el virus de la influenza aviar altamente patógena subtipo H5N8 se propagó en Francia y causó una epizootia sin precedentes. Durante la epidemia, en el suroeste de Francia, donde se registraron la mayoría de los brotes, se registró clima severo, con tres tormentas consecutivas (Leiv, Kurt y Marcel) del 3 al 5 de febrero del 2017. Aunque hay poca información disponible, una hipótesis es que la propagación del virus de influenza aviar de alta patogenicidad H5N8 desde una explotación avícola infectada podría haberse facilitado pasivamente por los vientos dominantes durante el período de riesgo. El objetivo de este estudio fue, por lo tanto, evaluar la contribución de la ruta del viento en la distribución espacial de los brotes de influenza aviar de alta patogenicidad H5N8 durante el período de riesgo a principios de febrero del 2017. El modelo PERLE, un modelo de dispersión atmosférica (ADM) desarrollado por la agencia meteorológica francesa Météo-France, fue utilizado para generar el área pronosticada en riesgo de infección a partir de una fuente sospechosa. Los resultados del modelo muestran que el patrón espacial de la deposición de partículas de polvo se dirigió al este-sureste de acuerdo con la dirección del viento. Esto contrastó con la distribución espacial de los brotes de influenza aviar de alta patogenicidad H5N8, que se extendieron hacia el oeste. Estas observaciones sugieren que la ruta por el viento por sí sola no fue suficiente para explicar la distribución espacial de los brotes en grandes distancias en el suroeste de Francia a principios de febrero de 2017. Finalmente, este estudio ilustra la relevancia de la estrecha colaboración entre las autoridades gubernamentales, los institutos de investigación veterinaria y agencias meteorológicas, que se involucren en investigación interdisciplinaria para la investigación exitosa de los brotes.
Subject(s)
Disease Outbreaks/veterinary , Influenza A Virus, H5N8 Subtype/physiology , Influenza in Birds/epidemiology , Poultry Diseases/epidemiology , Poultry , Wind , Animals , France/epidemiology , Influenza in Birds/virology , Poultry Diseases/virologyABSTRACT
In winter 2016-2017, Highly Pathogenic Avian Influenza (HPAI) H5N8 virus spread across Europe, causing unprecedented epizootics. France was massively affected, resulting in the culling of over 6 million poultry. Boosted regression tree (BRT) models were used to quantify the association between spatial risk factors and HPAI H5N8 infection in poultry holdings and to generate predictive maps for HPAI infection. Three datasets were combined to build the model: a dataset of the reported outbreaks in poultry, a dataset of the poultry holdings where the virus has not been reported and a set of relevant spatial risk factors, including poultry production and trade, and water bird habitat. Results identified key associations between the 'foie gras' production systems and HPAI H5N8 risk of occurrence and indicate that strengthening surveillance of fattening duck production systems and making the transportation of fattening ducks more secure would be key priority options for HPAI prevention and control.
Subject(s)
Ducks/virology , Influenza A Virus, H5N8 Subtype/isolation & purification , Influenza in Birds/epidemiology , Poultry Diseases/epidemiology , Animal Husbandry , Animals , France/epidemiology , Influenza in Birds/virology , Poultry Diseases/virology , Risk FactorsABSTRACT
The range of foods featuring lactic acid bacteria (LAB) with potential associated health benefits has expanded over the years from traditional dairy products to meat, cereals, vegetables and fruits, chocolate, etc. All these new carriers need to be compared for their efficacy to protect, carry, and deliver LAB, but because of their profusion and the diversity of methods this remains difficult. This review points out the advantages and disadvantages of the main food matrix types, and an additional distinction between dairy and nondairy foods is made. The food matrix impact on LAB viability during food manufacturing, storage, and digestion is also discussed. The authors propose an ideal hypothetical food matrix that includes structural and physicochemical characteristics such as pH, water activity, and buffering capacities, all of which need to be taken into account when performing LAB food matrix design. Guidelines are finally provided to optimize food matrix design in terms of effective LAB delivery.
Subject(s)
Food , Lactobacillales , Probiotics , Food Microbiology , Food StorageABSTRACT
The purpose of this study was to investigate the relationship between the proportion of sperm chromatin linked to remaining histone and assisted reproductive technology (ART) outcome. A prospective cohort study was performed on couples undergoing ART process at the Department of Reproduction Medicine (HFME, Bron, France). The histone-to-protamine ratio (HPR) was measured using the method described by Wykes & Krawetz (2003) J Biol Chem 278, 29471. The correlations with sperm DFI, blastocyst formation, pregnancy rate, and delivery rate were investigated. A total of 291 ART cycles were included (42 c-IVF and 249 ICSI procedures): 3870 oocytes were punctured and 2211 embryos were obtained, among which 507 were transferred and 336 frozen. The mean HPR was 18.9%. A significant negative correlation was found between HPR and DFI (r = -0.12, p < 0.05). Regarding the type of ART procedure (c-IVF or ICSI), the same kind of relationship between HPR and ART parameters was observed. Regardless of the type of ART procedure used, when the HPR was within the range [6%; 26%], the blastocyst formation rate was higher: 87.8% vs. 71.2% (HPR<6%; p < 0.01) and 74.6% (HPR >26%; p < 0.01). The highest delivery rate (DR; 24.5%) was obtained for HPR within the range [6%; 26%]; DR was 21.9% for HPR<6% and 18.3% for HPR>26%; however, the differences were not statistically significant. The procedure described in this study seems to be a reliable evaluation of the HPR. The HPR parameter seems to be correlated to embryonic development up to the blastocyst stage, but its involvement in clinical pregnancy/delivery could not be confirmed. HPR should be further investigated for confirming the relationship with blastocyst formation. After this, the next step will be to investigate the etiologies of HPR alterations for improving the sperm nucleus quality for increasing the chance of pregnancy.
Subject(s)
Chromatin , Embryonic Development , Histones , Protamines , Reproductive Techniques, Assisted , Spermatozoa , Adult , Chromatin/metabolism , Chromatin/pathology , Cohort Studies , Female , Histones/metabolism , Humans , Male , Pregnancy , Pregnancy Rate , Prospective Studies , Protamines/metabolism , Spermatozoa/metabolism , Spermatozoa/pathologyABSTRACT
Cranial neural crest cells (CNCCs) delaminate from embryonic neural folds and migrate to pharyngeal arches, which give rise to most mid-facial structures. CNCC dysfunction plays a prominent role in the etiology of orofacial clefts, a frequent birth malformation. Heterozygous mutations in SPECC1L have been identified in patients with atypical and syndromic clefts. Here, we report that in SPECC1L-knockdown cultured cells, staining of canonical adherens junction (AJ) components, ß-catenin and E-cadherin, was increased, and electron micrographs revealed an apico-basal diffusion of AJs. To understand the role of SPECC1L in craniofacial morphogenesis, we generated a mouse model of Specc1l deficiency. Homozygous mutants were embryonic lethal and showed impaired neural tube closure and CNCC delamination. Staining of AJ proteins was increased in the mutant neural folds. This AJ defect is consistent with impaired CNCC delamination, which requires AJ dissolution. Further, PI3K-AKT signaling was reduced and apoptosis was increased in Specc1l mutants. In vitro, moderate inhibition of PI3K-AKT signaling in wildtype cells was sufficient to cause AJ alterations. Importantly, AJ changes induced by SPECC1L-knockdown were rescued by activating the PI3K-AKT pathway. Together, these data indicate SPECC1L as a novel modulator of PI3K-AKT signaling and AJ biology, required for neural tube closure and CNCC delamination.
Subject(s)
Adherens Junctions/metabolism , Neural Crest/embryology , Neural Crest/metabolism , Phosphoproteins/deficiency , Animals , Apoptosis/genetics , Biomarkers , Cell Adhesion Molecules/metabolism , Cell Lineage/genetics , Gene Expression , Gene Knockout Techniques , Humans , Mice , Models, Biological , Mutation , Neural Tube Defects/genetics , Neural Tube Defects/pathology , Phenotype , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal TransductionABSTRACT
A patient with a history of squamous cell carcinoma of the right upper lung lobe treated 14 years before by concomitant chemo-radiotherapy was referred on account of dyspnea. Bronchial endoscopy revealed complete obstruction of the right main bronchus highly suggestive of a tumor recurrence. However, biopsy samples only showed inflammatory and necrotic tissue with no evidence of malignancy. Despite complete tissue resection by rigid bronchoscopy, a rapid and complete recurrence occurred requiring the placement of a Y-shaped bronchial prosthesis. Repeat histological, bacteriological and mycological analyses were negative. The patient was soon readmitted to hospital for a lung infection due to recurrence of obstruction inside and around the prosthesis. Bacterial examination of biopsy samples identified Actinomyces meyeri. Appropriate antibiotic therapy led to a complete regression of the bronchial obstruction. Unfortunately, the patient died a few months later due to massive hemoptysis after the removal of the prosthesis. Autopsy examination showed a fistula between the right main bronchus and pulmonary artery, with no evidence of neoplastic recurrence nor the persistence of lesions associated with actinomycosis.
Subject(s)
Actinomycosis/diagnosis , Lung Diseases, Fungal/diagnosis , Aged , Airway Obstruction/etiology , Airway Obstruction/surgery , Biopsy , Bronchial Fistula/etiology , Bronchoscopy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , Device Removal/adverse effects , Diagnosis, Differential , Fatal Outcome , Hemoptysis/etiology , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Male , Necrosis , Neoplasm Recurrence, Local/diagnosis , Postoperative Complications/etiology , Prosthesis Implantation , Pulmonary Artery , Time Factors , Vascular Fistula/etiologyABSTRACT
PURPOSE: The safe medication practices at the hospital constitute a major public health problem. Drug supply chain is a complex process, potentially source of errors and damages for the patient. SHAM insurances are the biggest French provider of medical liability insurances and a relevant source of data on the health care complications. METHODS: The main objective of the study was to analyze the type and cause of medication errors declared to SHAM and having led to a conviction by a court. We did a retrospective study on insurance claims provided by SHAM insurances with a medication error and leading to a condemnation over a 6-year period (between 2005 and 2010). RESULTS: Thirty-one cases were analysed, 21 for scheduled activity and 10 for emergency activity. Consequences of claims were mostly serious (12 deaths, 14 serious complications, 5 simple complications). The types of medication errors were a drug monitoring error (11 cases), an administration error (5 cases), an overdose (6 cases), an allergy (4 cases), a contraindication (3 cases) and an omission (2 cases). Intravenous route of administration was involved in 19 of 31 cases (61%). The causes identified by the court expert were an error related to service organization (11), an error related to medical practice (11) or nursing practice (13). Only one claim was due to the hospital pharmacy. CONCLUSION: The claim related to drug supply chain is infrequent but potentially serious. These data should help strengthen quality approach in risk management.
Subject(s)
Insurance, Liability/statistics & numerical data , Medication Errors , Drug Hypersensitivity , Drug Monitoring , Drug Overdose , France , Humans , Insurance Claim Review , Pharmacy Service, Hospital/statistics & numerical data , Retrospective StudiesABSTRACT
BACKGROUND: Pseudomonas aeruginosa is a major nosocomial pathogen in intensive care units (ICUs); however, endogenous versus exogenous origin of contamination remains unclear. AIM: To identify individual and environmental ICU risk factors for P. aeruginosa acquisition. METHODS: A five-month prospective multicentric study was performed in ten French ICUs. Adult patients hospitalized in ICU for ≥ 24 h were included and screened for P. aeruginosa colonization on admission, weekly and before discharge. P. aeruginosa acquisition was defined by a subsequent colonization or infection if screening swabs on admission were negative. Water samples were obtained weekly on water taps of the ICUs. Data on patient characteristics, invasive devices exposure, antimicrobial therapy, P. aeruginosa water and patient colonization pressures, and ICU characteristics were collected. Hazard ratios (HRs) were estimated using multivariate Cox model. FINDINGS: Among the 1314 patients without P. aeruginosa on admission, 201 (15%) acquired P. aeruginosa during their ICU stay. Individual characteristics significantly associated with P. aeruginosa acquisition were history of previous P. aeruginosa infection or colonization, cumulative duration of mechanical ventilation and cumulative days of antibiotics not active against P. aeruginosa. Environmental risk factors for P. aeruginosa acquisition were cumulative daily ward 'nine equivalents of nursing manpower use score' (NEMS) [hazard ratio (HR): 1.47 for ≥ 30 points; 95% confidence interval (CI): 1.06-2.03] and contaminated tap water in patient's room (HR: 1.76; CI: 1.09-2.84). CONCLUSION: Individual risk factors and environmental factors for which intervention is possible were identified for P. aeruginosa acquisition.
Subject(s)
Cross Infection/etiology , Drug Resistance, Bacterial , Equipment Contamination , Intensive Care Units , Pseudomonas Infections/etiology , Respiration, Artificial/adverse effects , Water Microbiology , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Cross Infection/microbiology , Female , France/epidemiology , Humans , Male , Middle Aged , Prospective Studies , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Risk FactorsABSTRACT
Silica-coated gold nanorods functionalized with grafted fluorescent and photochromic derivatives were synthesized and characterized. Spectroscopic investigations demonstrated that cross-coupled interactions between plasmonic, photochromic, and fluorescence properties play a major role in such nanosystems, depending on the thickness of the silica spacer, leading to multi-signal photoswitchability.
Subject(s)
Fluorescent Dyes/chemistry , Nanostructures , Microscopy, Electron, ScanningABSTRACT
The French bio ethical law published in 2004 did not authorize the transfer of embryos submitted to a research program, or even issued from gametes concerned by an experimentation. Vitrification process was still considered as an "experimental" technique; thus it was impossible to vitrify either oocytes or embryos, whereas numerous international studies emphasized the interest of this technique for both oocytes and embryos, in particular if they were vitrified at the blastocyst stage. The new revised law (7/7/2011), clearly authorizes oocyte vitrification; moreover, studies intended to improve ART efficiency, are now permitted, enabling vitrification of embryos.
Subject(s)
Bioethical Issues/legislation & jurisprudence , Cryopreservation/ethics , Embryo, Mammalian , Oocytes , Blastocyst , Cryopreservation/trends , Embryo Research/ethics , Embryo Research/legislation & jurisprudence , Embryo Transfer/ethics , Female , France , Humans , Male , Reproductive Techniques, Assisted/ethics , Reproductive Techniques, Assisted/legislation & jurisprudenceABSTRACT
INTRODUCTION: The early diagnosis of COPD in general practice is not satisfactory. OBJECTIVES: To evaluate the impact of different diagnostic tools (Piko-6, Software) in general practice (GP). METHODS: A multicentre, randomised, controlled study in GP assessing the effect of the tested strategies on the rate of referrals for spirometry and the rate of detection of airflow obstruction. RESULTS: One thousand one hundred and three patients (55 years old, 60% males, 31 years of smoking habits) were included by 248 GP. The rates of referal to a pneumologist were significantly higher in the Software (50% of patients), and Piko/Software (47%) groups than in the Control (22%) and Piko groups (28%). A high proportion (44%) of lung function tests recommended by the GP were not performed, often because of patient refusal. The confirmation rates were lower in the Software and Piko/Software groups (47% and 43%, respectively) compared with the Piko and Control groups (68% and 79%, respectively). Concordance between PFT and Piko-6 for the diagnosis of airflow obstruction was poor (about 50%). CONCLUSIONS: The use of software in association or not with the Piko-6 was useful for GPs to identify patients to refer for further lung function testing, but did not improve the confirmation of the obstructive syndrome, mainly due to reluctance of patients to go on to have further lung function tests. The use of a diagnostic tool (software and/or mini-spirometry) does however seem to improve early COPD detection.
Subject(s)
Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Referral and Consultation/statistics & numerical data , Software , Diagnosis, Differential , Early Diagnosis , Female , Humans , Male , Middle Aged , Primary Health Care , Pulmonary Disease, Chronic Obstructive/physiopathology , Spirometry , Surveys and QuestionnairesABSTRACT
A farm of meat turkeys was affected by a condition, clinically characterized by unilateral inflammation of the orbital region and progressive crossing of the beak, observed in three successive flocks in 2010. While no toxic, genetic, technical, or diet causes could be found, pathologic and bacteriologic analyses were conducted to investigate the case. Pathologic analyses of the heads of affected birds showed blepharitis and exudative sinusitis as well as severe chronic osteomyelitis of all skull bones and mandibula. Staphylococcus aureus was consistently isolated from these lesions. It is supposed that the severe bacterial osteomyelitis induced deviation of some bones, thereby leading to deviation of the beak. Further investigations remain to be carried out to explain these successive outbreaks of staphylococcal osteomyelitis in skull bones.
Subject(s)
Disease Outbreaks/veterinary , Orbital Cellulitis/veterinary , Osteomyelitis/veterinary , Poultry Diseases/pathology , Staphylococcal Infections/veterinary , Staphylococcus aureus/isolation & purification , Turkeys , Animals , Female , France/epidemiology , Jaw Diseases/epidemiology , Jaw Diseases/microbiology , Jaw Diseases/pathology , Jaw Diseases/veterinary , Male , Orbital Cellulitis/epidemiology , Orbital Cellulitis/microbiology , Orbital Cellulitis/pathology , Osteomyelitis/epidemiology , Osteomyelitis/microbiology , Osteomyelitis/pathology , Poultry Diseases/epidemiology , Poultry Diseases/microbiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Staphylococcus aureus/physiologyABSTRACT
STUDY QUESTION: What is the methylation status of the Nanog and Oct4 promoters in human gametes and ICSI embryos and is abnormal reprogramming of their methylation associated with developmental failure of ICSI embryos? SUMMARY ANSWER: Developmental failure of human ICSI embryos is associated with high methylation of the Oct4 promoter. WHAT IS KNOWN ALREADY: Nanog and Oct4 genes play critical roles in the establishment and maintenance of pluripotency during normal early embryonic development, and both are negatively regulated through the methylation of their promoters. STUDY DESIGN, SIZE AND DURATION: We analysed the methylation profile of Nanog and Oct4 promoters in 5 control sperm from normally fertile men, 70 metaphase II oocytes, 21 4-cell control ICSI embryos, 7 control blastocysts and 45 ICSI embryos arrested at 2- to 8-cell stage following prolonged culture. PARTICIPANTS, MATERIALS, SETTING AND METHODS: Embryos and gametes were donated for research by patients from the Department of Reproductive Medicine at the Hôpital Femme Mère Enfant (Bron, France) and the Clinique du Tonkin (Villeurbanne, France) after giving their informed consent. MAIN RESULTS: For both promoters, high methylation was observed in sperm cells. Although, in general, the promoters were unmethylated in oocytes, the methylation of some alleles was observed, particularly in oocytes from women with known infertility. Both gene promoters were hypomethylated in control blastocyst ICM (inner cell mass) and in control 2-8-cells embryos obtained from 6 out of 8 couples. However, they appeared highly methylated in embryos obtained from the other two couples. In most arrested ICSI embryos, the Nanog promoter was unmethylated while the Oct4 promoter was highly methylated. High methylation of the Oct4 promoter was significantly more pronounced in embryos from couples where a male factor was the only known cause of infertility. When the embryos were heterozygous for a G/A single nucleotide polymorphism, both alleles could be methylated, each likely representing a paternally inherited or a maternally inherited copy. LIMITATIONS AND REASONS FOR CAUTION: The study was done on a limited number of oocytes and embryos and the gametes of the couples were not available. WIDER IMPLICATIONS OF THE FINDINGS: These results provide new insight regarding the roles of epigenetic abnormalities in early developmental failure in humans. STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There was no competing interest.
Subject(s)
DNA Methylation , Embryonic Development/genetics , Homeodomain Proteins/genetics , Octamer Transcription Factor-3/genetics , Promoter Regions, Genetic , Female , Gene Expression Regulation, Developmental , Homeodomain Proteins/metabolism , Homeodomain Proteins/physiology , Humans , Male , Nanog Homeobox Protein , Octamer Transcription Factor-3/metabolism , Octamer Transcription Factor-3/physiology , Sperm Injections, IntracytoplasmicABSTRACT
The aim of this study was to evaluate the incidence of spermatic aneuploidies in men with severe teratozoospermia and to determine an eventual relation between aneuploidies and a specific morphology of spermatozoa. Fluorescence in situ hybridisation (FISH) using a probe cocktail containing the alpha satellite for the centromeric region of chromosome X, Y and 18 was performed on decondensed spermatozoa from fresh ejaculates of thirty patients with severe teratozoospermia (abnormal forms >80%) and 15 fertile men with normal semen profiles. The mean frequency of teratozoospermia in patients was 91 ± 6.99%. There was statistically a significantly increased frequency of 1818, XY, XX and YY disomies in sperm with severe teratozoospermia compared with normal sperm (1.24% versus 0.08%, 1.42% versus 0.31%, 1.13% versus 0.19% and 1.11% versus 0.24%, respectively, P < 0.001 in all comparisons). The rate of total diploidy was significantly increased in patients compared with controls (1.46% versus 0.16%, P < 0.001). There was a correlation between macrocephalic spermatozoa and diploidy (r = 0.37, P < 0.05). Our data add further evidence that patients with severe teratozoospermia have an increased sperm aneuploidy rate and that this is particularly high in macrocephalic spermatozoa; FISH analysis on sperm could help to improve risk assessment and reproductive counselling in these individuals who are frequently candidates for intracytoplasmic sperm injection (ICSI) as a treatment of their infertility, as the use of ICSI has created consequential debate concerning the genetic risk for the offspring.