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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth most frequent disease globally, and its worldwide prevalence is projected to increase in the following decades. Health-related quality of life (HRQOL) of COPD patients depends on multiple factors. OBJECTIVE: The aim of this study was to identify the most important risk factors affecting HRQOL of COPD patients and to measure how specific clinical parameters can predict HRQOL. METHODS: A questionnaire-based cross-sectional study combined with clinical data was conducted among patients diagnosed with COPD (n = 321, 52.6% females, mean age 66.4 ± 9.5) at the National Koranyi Institute for Pulmonology, Budapest in 2019-2020. The inclusion criteria were age ≥40 years and existing COPD. Multivariate linear regression analyses were conducted on three components of the COPD-specific Saint George's Respiratory Questionnaire (SGRQ-C) and on the physical (PCS) and mental component scales (MCS) of the 36-Item Short Form Health Survey (SF-36). Multiple linear regression analysis was performed to evaluate the effects of patient and disease characteristics on COPD Assessment Test (CAT) scores. RESULTS: We found that frequent exacerbations, multiple comorbidities and tobacco smoking were associated with worse HRQOL. Engaging in more frequent physical activity and better 6-minute walking distance results were associated with better HRQOL. CONCLUSIONS: Our results indicate that the complex therapy of COPD should focus not only on improving lung functions and preventing exacerbation, but also on treating comorbidities, encouraging increased physical activity, and supporting smoking cessation to assure better HRQOL for patients.
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Sentinel lymph node biopsy (SLNB) is a standard procedure for regional lymph node staging and still has the most important prognostic value for the outcome of patients with thin melanoma. In addition to ulceration, SLNB had to be considered even for a single mitotic figure in thin (<1 mm) melanoma according to AJCC7th guideline, therefore, a retrospective review was conducted involving 403 pT1 melanoma patients. Among them, 152 patients suffered from pT1b ulcerated or mitotic rate ≥ 1/ mm2 melanomas according to the AJCC7th staging system. SLNB was performed in 78 cases, of which nine (11.5%) showed SLN positivity. From them, interestingly, we found a relatively high positive sentinel rate (6/78-8%) in the case of thin primary melanomas Ë0.8 mm. Moreover, the presence of regression increased the probability of sentinel positivity by 5.796 fold. After reassessing pT stage based on the new AJCC8th, 37 pT1b cases were reordered into pT1a category. There was no significant relation between other characteristics examined (age, gender, Breslow, Clark level, and mitosis index) and sentinel node positivity. Based on our data, we suggest that mitotic rate alone is not a sufficiently powerful predictor of SLN status in thin melanomas. If strict histopathological definition criteria are applied, regression might be an additional adverse feature that aids in identifying T1 patients most likely to be SLN-positive. After reassessing of pT1b cases according to AJCC8th regression proved to be independent prognostic factor on sentinel lymph node positivity. Our results propose that sentinel lymph node biopsy might also be considered at patients with regressive thin (Ë0.8 mm) melanomas.
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Melanoma/diagnóstico , Melanoma/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
Hypoxia is a driver of cell movement in processes such as development and tumor progression. The cellular response to hypoxia involves a transcriptional program mediated by hypoxia-inducible factors, but translational control has emerged as a significant contributor. In this study, we demonstrate that a cell-cell adhesion molecule, cadherin-22, is upregulated in hypoxia via mTORC1-independent translational control by the initiation factor eIF4E2. We identify new functions of cadherin-22 as a hypoxia-specific cell-surface molecule involved in cancer cell migration, invasion and adhesion. Silencing eIF4E2 or cadherin-22 significantly impaired MDA-MB-231 breast carcinoma and U87MG glioblastoma cell migration and invasion only in hypoxia, while reintroduction of the respective exogenous gene restored the normal phenotype. Cadherin-22 was evenly distributed throughout spheroids and required for their formation and support of a hypoxic core. Conversely, E-cadherin translation was repressed by hypoxia and only expressed in the oxygenated cells of U87MG spheroids. Furthermore, immunofluorescence on paraffin-embedded human tissue from 40 glioma and 40 invasive ductal breast carcinoma patient specimens revealed that cadherin-22 expression colocalized with areas of hypoxia and significantly correlated with tumor grade and progression-free survival or stage and tumor size, respectively. This study broadens our understanding of tumor progression and metastasis by highlighting cadherin-22 as a potential new target of cancer therapy to disable hypoxic cancer cell motility and adhesion.
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Neoplasias da Mama/patologia , Caderinas/genética , Carcinoma Ductal de Mama/patologia , Glioma/patologia , Proteínas de Ligação ao Cap de RNA/metabolismo , Antígenos CD , Neoplasias da Mama/genética , Caderinas/metabolismo , Carcinoma Ductal de Mama/genética , Adesão Celular/genética , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Fator de Iniciação 4E em Eucariotos , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Glioma/genética , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Gradação de Tumores , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Proteínas de Ligação ao Cap de RNA/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Esferoides Celulares , Regulação para CimaRESUMO
Aspergillus section Aspergillus (formerly the genus Eurotium) includes xerophilic species with uniseriate conidiophores, globose to subglobose vesicles, green conidia and yellow, thin walled eurotium-like ascomata with hyaline, lenticular ascospores. In the present study, a polyphasic approach using morphological characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of this section. Over 500 strains from various culture collections and new isolates obtained from indoor environments and a wide range of substrates all over the world were identified using calmodulin gene sequencing. Of these, 163 isolates were subjected to molecular phylogenetic analyses using sequences of ITS rDNA, partial ß-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) genes. Colony characteristics were documented on eight cultivation media, growth parameters at three incubation temperatures were recorded and micromorphology was examined using light microscopy as well as scanning electron microscopy to illustrate and characterize each species. Many specific extrolites were extracted and identified from cultures, including echinulins, epiheveadrides, auroglaucins and anthraquinone bisanthrons, and to be consistent in strains of nearly all species. Other extrolites are species-specific, and thus valuable for identification. Several extrolites show antioxidant effects, which may be nutritionally beneficial in food and beverages. Important mycotoxins in the strict sense, such as sterigmatocystin, aflatoxins, ochratoxins, citrinin were not detected despite previous reports on their production in this section. Adopting a polyphasic approach, 31 species are recognized, including nine new species. ITS is highly conserved in this section and does not distinguish species. All species can be differentiated using CaM or RPB2 sequences. For BenA, Aspergillus brunneus and A. niveoglaucus share identical sequences. Ascospores and conidia morphology, growth rates at different temperatures are most useful characters for phenotypic species identification.
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The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.
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Anisomicina/farmacologia , Apoptose/efeitos dos fármacos , Proteína Supressora de Tumor p53/fisiologia , Animais , Western Blotting , Sobrevivência Celular , Fragmentação do DNA , Fator de Iniciação 2 em Eucariotos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Células PC12 , Fosforilação , Biossíntese de Proteínas/efeitos dos fármacos , RatosRESUMO
BACKGROUND: There are conflicting data on the occurrence of subclinical myocardial dysfunction in psoriatic patients and on the impact of long-term tumour necrosis factor-alpha (TNF-α) inhibitor therapy on cardiac function. OBJECTIVE: In this study, we explored whether there are any signs of subclinical cardiovascular disease (echocardiographic abnormalities) in severe psoriatic patients without clinically overt heart disease. As a second objective, the influence of long-term treatment with TNF-α inhibitors on the ventricular functions of psoriatic patients was also investigated. METHODS: Clinical and echocardiographic data from 44 psoriatic patients and 45 age- and sex-matched controls were processed. As a first step, the echocardiographic parameters of psoriatic patients obtained before anti-TNF-α treatment were compared with controls. As a second step, to detect the effect of long-term anti-TNF-α treatment on echocardiographic parameters, data of patients before and after therapy were analysed. RESULTS: The right ventricular Tei index was higher (P < 0.001), whereas the tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall peak systolic velocity were lower (P < 0.001 and P < 0.0001, respectively) in the psoriatic patients than in the controls. Following treatment with TNF-α inhibitors, TAPSE and right ventricular free wall peak systolic velocity significantly improved (P < 0.0001 for both parameters). The Tei index of both ventricles improved during biological therapy; however, this change did not reach statistical significance. CONCLUSION: Patients with severe psoriasis exhibit signs of subclinical cardiovascular disease compared to control, and prolonged anti-TNF-α therapy has a potentially beneficial effect on these signs.
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Doenças Cardiovasculares/complicações , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Doenças Cardiovasculares/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/complicaçõesRESUMO
Aspergillus is one of the economically most important fungal genera. Recently, the ICN adopted the single name nomenclature which has forced mycologists to choose one name for fungi (e.g. Aspergillus, Fusarium, Penicillium, etc.). Previously two proposals for the single name nomenclature in Aspergillus were presented: one attributes the name "Aspergillus" to clades comprising seven different teleomorphic names, by supporting the monophyly of this genus; the other proposes that Aspergillus is a non-monophyletic genus, by preserving the Aspergillus name only to species belonging to subgenus Circumdati and maintaining the sexual names in the other clades. The aim of our study was to test the monophyly of Aspergilli by two independent phylogenetic analyses using a multilocus phylogenetic approach. One test was run on the publicly available coding regions of six genes (RPB1, RPB2, Tsr1, Cct8, BenA, CaM), using 96 species of Penicillium, Aspergillus and related taxa. Bayesian (MrBayes) and Ultrafast Maximum Likelihood (IQ-Tree) and Rapid Maximum Likelihood (RaxML) analyses gave the same conclusion highly supporting the monophyly of Aspergillus. The other analyses were also performed by using publicly available data of the coding sequences of nine loci (18S rRNA, 5,8S rRNA, 28S rRNA (D1-D2), RPB1, RPB2, CaM, BenA, Tsr1, Cct8) of 204 different species. Both Bayesian (MrBayes) and Maximum Likelihood (RAxML) trees obtained by this second round of independent analyses strongly supported the monophyly of the genus Aspergillus. The stability test also confirmed the robustness of the results obtained. In conclusion, statistical analyses have rejected the hypothesis that the Aspergilli are non-monophyletic, and provided robust arguments that the genus is monophyletic and clearly separated from the monophyletic genus Penicillium. There is no phylogenetic evidence to split Aspergillus into several genera and the name Aspergillus can be used for all the species belonging to Aspergillus i.e. the clade comprising the subgenera Aspergillus, Circumdati, Fumigati, Nidulantes, section Cremei and certain species which were formerly part of the genera Phialosimplex and Polypaecilum. Section Cremei and the clade containing Polypaecilum and Phialosimplex are proposed as new subgenera of Aspergillus. The phylogenetic analysis also clearly shows that Aspergillus clavatoflavus and A. zonatus do not belong to the genus Aspergillus. Aspergillus clavatoflavus is therefore transferred to a new genus Aspergillago as Aspergillago clavatoflavus and A. zonatus was transferred to Penicilliopsis as P. zonata. The subgenera of Aspergillus share similar extrolite profiles indicating that the genus is one large genus from a chemotaxonomical point of view. Morphological and ecophysiological characteristics of the species also strongly indicate that Aspergillus is a polythetic class in phenotypic characters.
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The fallopian tubes represent a highly important structure for ovarian carcinogenesis. They provide the passage of eutopic endometrium from the uterus, as well as metastatic cells from the ovaries. A direct source of tumor cells for ovarian cancer was also recently confirmed in the fallopian tubes. The authors present a case report of an incidental tubal endometrioid carcinoma with the coexistence of adenomyosis.
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Adenomiose/patologia , Carcinoma Endometrioide/patologia , Neoplasias das Tubas Uterinas/patologia , Adenomiose/cirurgia , Carcinoma Endometrioide/cirurgia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Species belonging to Aspergillus section Cervini are characterised by radiate or short columnar, fawn coloured, uniseriate conidial heads. The morphology of the taxa in this section is very similar and isolates assigned to these species are frequently misidentified. In this study, a polyphasic approach was applied using morphological characters, extrolite data, temperature profiles and partial BenA, CaM and RPB2 sequences to examine the relationships within this section. Based on this taxonomic approach the section Cervini is resolved in ten species including six new species: A. acidohumus, A. christenseniae, A. novoguineensis, A. subnutans, A. transcarpathicus and A. wisconsinensis. A dichotomous key for the identification is provided.
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Aspergillus section Nidulantes includes species with striking morphological characters, such as biseriate conidiophores with brown-pigmented stipes, and if present, the production of ascomata embedded in masses of Hülle cells with often reddish brown ascospores. The majority of species in this section have a sexual state, which were named Emericella in the dual name nomenclature system. In the present study, strains belonging to subgenus Nidulantes were subjected to multilocus molecular phylogenetic analyses using internal transcribed spacer region (ITS), partial ß-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) sequences. Nine sections are accepted in subgenus Nidulantes including the new section Cavernicolus. A polyphasic approach using morphological characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of section Nidulantes. Based on this approach, section Nidulantes is subdivided in seven clades and 65 species, and 10 species are described here as new. Morphological characters including colour, shape, size, and ornamentation of ascospores, shape and size of conidia and vesicles, growth temperatures are important for identifying species. Many species of section Nidulantes produce the carcinogenic mycotoxin sterigmatocystin. The most important mycotoxins in Aspergillus section Nidulantes are aflatoxins, sterigmatocystin, emestrin, fumitremorgins, asteltoxins, and paxillin while other extrolites are useful drugs or drug lead candidates such as echinocandins, mulundocandins, calbistrins, varitriols, variecolins and terrain. Aflatoxin B1 is produced by four species: A. astellatus, A. miraensis, A. olivicola, and A. venezuelensis.
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Laparoscopia/métodos , Técnicas de Sutura , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , SuturasRESUMO
Aspergillus section Circumdati or the Aspergillus ochraceus group, includes species with rough walled stipes, biseriate conidial heads, yellow to ochre conidia and sclerotia that do not turn black. Several species are able to produce mycotoxins including ochratoxins, penicillic acids, and xanthomegnins. Some species also produce drug lead candidates such as the notoamides. A polyphasic approach was applied using morphological characters, extrolite data and partial calmodulin, ß-tubulin and ITS sequences to examine the evolutionary relationships within this section. Based on this approach the section Circumdati is revised and 27 species are accepted, introducing seven new species: A. occultus, A. pallidofulvus, A. pulvericola, A. salwaensis, A. sesamicola, A. subramanianii and A. westlandensis. In addition we correctly apply the name A. fresenii (≡ A. sulphureus (nom. illeg.)). A guide for the identification of these 27 species is provided. These new species can be distinguished from others based on morphological characters, sequence data and extrolite profiles. The previously described A. onikii and A. petrakii were found to be conspecific with A. ochraceus, whilst A. flocculosus is tentatively synonymised with A. ochraceopetaliformis, despite extrolite differences between the two species. Based on the extrolite data, 13 species of section Circumdati produce large amounts of ochratoxin A: A. affinis, A. cretensis, A. fresenii, A. muricatus, A. occultus, A. ochraceopetaliformis (A. flocculosus), A. ochraceus, A. pseudoelegans, A. pulvericola, A. roseoglobulosus, A. sclerotiorum, A. steynii and A. westerdijkiae. Seven additional species produce ochratoxin A inconsistently and/or in trace amounts: A. melleus, A. ostianus, A. persii, A. salwaensis, A. sesamicola, A. subramanianii and A. westlandensis. The most important species regarding potential ochratoxin A contamination in agricultural products are A. ochraceus, A. steynii and A. westerdijkiae.
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Aspergillus comprises a diverse group of species based on morphological, physiological and phylogenetic characters, which significantly impact biotechnology, food production, indoor environments and human health. Aspergillus was traditionally associated with nine teleomorph genera, but phylogenetic data suggest that together with genera such as Polypaecilum, Phialosimplex, Dichotomomyces and Cristaspora, Aspergillus forms a monophyletic clade closely related to Penicillium. Changes in the International Code of Nomenclature for algae, fungi and plants resulted in the move to one name per species, meaning that a decision had to be made whether to keep Aspergillus as one big genus or to split it into several smaller genera. The International Commission of Penicillium and Aspergillus decided to keep Aspergillus instead of using smaller genera. In this paper, we present the arguments for this decision. We introduce new combinations for accepted species presently lacking an Aspergillus name and provide an updated accepted species list for the genus, now containing 339 species. To add to the scientific value of the list, we include information about living ex-type culture collection numbers and GenBank accession numbers for available representative ITS, calmodulin, ß-tubulin and RPB2 sequences. In addition, we recommend a standard working technique for Aspergillus and propose calmodulin as a secondary identification marker.
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We report a case of a 30-year-old woman with an intrauterine device (IUD) improperly inserted deep within the myometrium, with a muscularis layer injury of the recto-sigmoid colon resulting of a uterine perforation and presented as abdomino-pelvic pain and dyspareunia. The ultrasonographic control of the IUD after the insertion (performed seven months before) was not checked. Cervical examination showed the strings of the IUD. The ultrasonographic exploration identified an intra-myometrial IUD with fundus perforation of the uterus. A laparoscopic exploration permitting the removal of the IUD revealed an insertion through the bowel wall. The lessons to draw of about this case report are discussed through a brief review of the literature.
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Dispositivos Intrauterinos/efeitos adversos , Perfuração Uterina/etiologia , Dor Abdominal , Adulto , Colo Sigmoide/lesões , Dispareunia , Feminino , Humanos , Laparoscopia , Miométrio , Dor Pélvica , Reto/lesões , Ultrassonografia , Perfuração Uterina/diagnóstico por imagemRESUMO
OBJECTIVES: We demonstrate a case report of the patient who suffered from advanced gastric cancer and was treated by means of surgery and HIPEC. BACKGROUND: Gastric cancer is a therapeutic challenge in the European countries due to late diagnosis, advanced stages of the disease in time of diagnosis and early recurrence in cases where a radical surgery is possible. METHOD: The patient with an advanced gastric cancer (pT3N2M1 - peritoneal and ovarian metastases) was treated by means of radical surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). Surgical treatment was followed by a standard chemotherapy. Due to recurrence, there was the second look surgery one year later again with HIPEC procedure. RESULTS: Patient survived 32 months after diagnosis and despite intraperitoneal recurrence she never developed clinically significant ascites and she never suffered from intestinal obstruction. CONCLUSION: This case demonstrate a potential benefit of new oncosurgical approach -radical surgery + HIPEC + EPIC in the treatment of gastric cancers (Tab. 2, Fig. 6, Graph 4, Ref. 18). Text in PDF www.elis.sk.
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Antineoplásicos/administração & dosagem , Gastrectomia/métodos , Hipertermia Induzida/métodos , Cuidados Paliativos/métodos , Neoplasias Gástricas/terapia , Adulto , Evolução Fatal , Feminino , Seguimentos , Humanos , Injeções Intraperitoneais , Período Intraoperatório , Estadiamento de Neoplasias , Neoplasias Gástricas/diagnósticoRESUMO
Despite an accurate classification, the borderline category of ovarian tumors is one of the most controversial topics in gynecologic oncology and is confusing to both clinicians and patients. The treatment is often confronted with the necessity of a fertility-sparing approach, although under-treatment increases the risk of disease recurrence. The clear definition of a group of patients with low or high risk of relapse requiring more or less extensive treatment is lacking. Currently, the main criteria affecting the treatment extent include histopathological features, particularly the presence of microinvasion, and invasive implants. Expansion of knowledge about genetic nature of the tumor characteristics may more closely specify the scope of therapeutic approach for individual patients. The authors report a case report of serous borderline ovarian tumor patient with tumor cell dispersion into the gastrointestinal tract. The genes of tumor vascular markers GPM6B and DR6 were also studied and compared to a group of healthy patients.
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Testes Genéticos , Neoplasias Ovarianas/genética , Adulto , Feminino , Humanos , Glicoproteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Neoplasias Ovarianas/patologia , Receptores do Fator de Necrose Tumoral/genéticaRESUMO
Restructuring the surgery and gynecology-obstetrics departments taking place now raise many interrogations. It appears as a mandatory necessity to some people and as a tribute to financial strategies to others to the detriment of quality and accessibility of care. Its effect is to clarify a good amount of socioeconomical and medical indicators. The plans of perinatality for the obstetrical aspect and the thresholds of activity for the surgical aspect constitute the major lines of these restructurings. A survey soliciting all the French public hospitals was used to assess the state of obstetrics and gynecology departments in the light of these recent restructurings. Medical demography, preserving and improving the quality and continuity of care, efficiency of the technical supports are discriminating criteria of the involved challenges. Such restructurings have an impact on the doctor's lives, which looks globally positive and a good omen to complete this remodeling process. The activity was safeguarded by a redistribution and a refocusing of institutions. One should not minimize the social impact of these changes, with a potential deterioration of working conditions (internal professional reclassifications, mobility obligation towards other sites). It thus appears that the deep changes which affect the small size institutions will be able to achieve well only if they are clearly done (information) and truly integrated in their medical project.