Environmental factors modulated ancient mitochondrial DNA variability and the prevalence of rheumatic diseases in the Basque Country.

Among the factors that would explain the distribution of mitochondrial lineages in Europe, climate and diseases may have played an important role. A possible explanation lies in the nature of the mitochondrion, in which the energy generation process produces reactive oxygen species that may influence the development of different diseases. The present study is focused on the medieval necropolis of San Miguel de Ereñozar (13th-16th centuries, Basque Country), whose inhabitants presented a high prevalence of rheumatic diseases and lived during the Little Ice Age (LIA). Our results indicate a close relationship between rheumatic diseases and mitochondrial haplogroup H, and specifically between spondyloarthropathies and sub-haplogroup H2. One possible explanation may be the climate change that took place in the LIA that favoured those haplogroups that were more energy-efficient, such as haplogroup H, to endure lower temperatures and food shortage. However, it had a biological trade-off: the increased risk of developing rheumatic diseases.

[Oxytocin and postpartum depression]. / L'ocytocine et la dépression du post-partum.

INTRODUCTION: Postpartum depression (PPD) is prevalent (about 10%) with a major impact on the mother and child health. At the hormonal level, poor regulation of oxytocin rate has a key role in depression. Recently, oxytocin has been used on psychiatric therapy, intranasal or intravenously, particularly in mood disorders. But, in obstetrics, this molecule is administered during childbirth. The objective of this study was to determine if intravenous administration of oxytocin could influence thymic state of the mother in the postpartum period. METHODS: Literature review, after consultation of Pubmed and Sciencedirect databases, with the following keywords: oxytocin, postpartum depression, pregnancy, social behavior. RESULTS: The effects of oxytocin in the PPD are part of a multifactorial mechanism (hormonal and social) that influences the hormonal effects of oxytocin. Oxytocin use in therapeutic was able to give conclusive results in psychiatry, the way and the optimal method of administration are not known. PPD is associated with administrated oxytocin during labour. Physiopathology remains unknown. CONCLUSION: It is possible that oxytocin administered during childbirth is related with the onset or worsening of the PPD without defining if it's a cause or a consequence.

The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa.

After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage) of the Pestera Muierii 1 individual (PM1) from Romania (35 ky cal BP) we present in this article corresponds fully to Homo sapiens, whilst exhibiting a mosaic of morphological features related to both modern humans and Neandertals. We have identified the PM1 mitogenome as a basal haplogroup U6*, not previously found in any ancient or present-day humans. The derived U6 haplotypes are predominantly found in present-day North-Western African populations. Concomitantly, those found in Europe have been attributed to recent gene-flow from North Africa. The presence of the basal haplogroup U6* in South East Europe (Romania) at 35 ky BP confirms a Eurasian origin of the U6 mitochondrial lineage. Consequently, we propose that the PM1 lineage is an offshoot to South East Europe that can be traced to the Early Upper Paleolithic back migration from Western Asia to North Africa, during which the U6 lineage diversified, until the emergence of the present-day U6 African lineages.

[Prevalence of burnout among obstetrics and gynecology residents]. / Prévalence du syndrome d'épuisement professionnel parmi les internes de gynécologie-obstétrique et facteurs associés.

OBJECTIVES: Prevalence assessment of burnout among obstetrics and gynecology residents and predisposing factors. PATIENTS AND METHODS: Multicentric cross-sectional survey based on a questionnaire sent by email to the residents including demographics data and Maslach Burnout Inventory. RESULTS: Mean burnout scores were 19.67±10.19 for emotional exhaustion, 33.94±5.01 for personal accomplishment and 8.72±6.10 for depersonalization, corresponding to a moderate burnout for each category. High scores of burnout were seen on 19.45 % of residents for emotional exhaustion, 33.33 % for depersonalization and 11.11 % for personal accomplishment. 36.11 % of residents showed evidence of high burnout in emotional exhaustion or depersonalization, and 5.55 % in the three dimensions. The number of semesters is correlated with depersonalization (P=0.01). CONCLUSION: There is a strong personal accomplishment among obstetrics and gynecology residents; however, burnout and emotional exhaustion remains a reality during obstetrics and gynecology residency.

Genetic diversity in northern Spain (Basque Country and Cantabria): GM and KM variation related to demographic histories.

Genetic diversity in Northern Spain (SW Europe) was assessed through the analysis of the GM and KM immunoglobulin markers in 505 individuals using a set of 17 allotypes, including the G2M(23) allotype which has been infrequently used before now. The individuals were representative of three anthropologically well-defined populations belonging to two geographically and archaeologically distinct areas in the Basque Country (Guipúzcoa and Alava provinces) and to the mountainous region of Montes de Pas in the province of Cantabria. Gene frequency distributions indicated a high genetic divergence between Montes de Pas and the Basque Country, and a relative degree of heterogeneity between the two Basque regions. The genetic differentiation of Montes de Pas, which is consistent with previous classical polymorphism analyses, suggests a considerable genetic variation range within the Iberian Peninsula, possibly higher than that often polarised around the Basque versus non-Basque variation. Analyses of genetic structure show that the major differentiation of Montes de Pas could be related to the historically documented mixed origin of this population. The moderate genetic distances between regions in the Spanish Basque Country could be explained by differential systematic pressures acting through a stronger gene flow in the South than in the more isolated Northern areas. The comparisons with neighbouring populations from the French Pyrenees suggest that the present genetic variation revealed by lg polymorphisms in SW Europe can be related to historical demographic processes including gene flow and/or low population sizes.

Comparative in vivo and in vitro models to approach the cellular basis of endotoxic shock. The role of sinusoidal liver cells.

During endotoxic shock, the liver exerts a lipopolysaccharide (LPS) clearance function with the participation of both parenchymal and sinusoidal cells. Liver damage could be caused by LPS direct action, hypoxia and/or inflammatory mediators released by Kupffer cells. The aim of this study is to establish an experimental model that could allow us to understand the direct E. coli 011:B4 LPS action on sinusoidal cells. A comparative study was carried out, in vivo and in vitro, using either a rat reversible endotoxic shock model or sinusoidal cell cultures. The LPS was found to induce important and similar morphological alterations both in vivo and in vitro, specially in Kupffer cells. These cells present mitochondrial damage, nuclear membrane swelling, and increased number of phagosomes, including lamellar bodies. An immunocolloidal gold technique shows, in vitro, the LPS mainly located on Kupffer cell membrane and in phagosomes. The LPS binding to membrane, as a primary step of Kupffer cell activation, increases the phagocytosis. This effect could be related to a decrease of fluidity on the external membrane portion.

Calbindin-D28k- and astroglial protein-immunoreactivities, and ultrastructural differentiation in the prenatal rat cerebral cortex and hippocampus are affected by maternal adrenalectomy.

Maternal adrenal steroid hormones have been proven to be crucial for lung and adrenal prenatal maturation. These hormones mediate the effects of prenatal stress crossing the placenta and influencing the development of the hypothalamus-pituitary-adrenal axis of fetuses. In the present study, we have compared the prenatal development of fetuses from adrenalectomized mothers (ADX group) and from sham-operated mothers. We have used immunohistochemistry for calcium binding-protein Calbindin-D28k, astroglial proteins vimentin and glial fibrillary acidic protein (GFAP), and the ultrastructural differentiation of the cerebral cortex and hippocampus to measure putative differences. The ontogeny of the Calbindin-D28k immunoreactivity was delayed, as transient Calbindin-positive neuronal populations in the ADX group disappeared later during development as compared to that of control animals both in cerebral cortex and hippocampus; cell counts revealed that ADX animals had a significantly higher number of Calbindin-positive cells than controls in the cerebral cortex, while that number was lower in ADX fetuses' hippocampus. Cerebral cortex of ADX animals also had a scattered distribution of stained cells compared with controls, while the hippocampi of the ADX animals had an impaired migration of marginal zone interneurons. No GFAP immunoreactivity was found in the studied prenatal stages. Instead, vimentin-immunoreactivity appeared more profusely distributed throughout the cerebral cortex, in the ADX group than in control animals. At the ultrastructural level, no remarkable differences were found before E20, when a higher undifferentiation in the ADX group, in both cerebral cortex and hippocampus, was evident. The results show for the first time the vulnerability of the prenatal rat brain to maternal adrenalectomy and the necessity of maternal glucocorticoids for encephalic development.

Maternal adrenalectomy affects development of adrenal medulla.

This work investigates the effects of maternal adrenalectomy (ADX) on the development of the adrenal medulla. Adrenal catecholamines (AC) were measured at postnatal day (PN) 1, 8, 12 and 22 in rat offspring of ADX dams and in pups of control dams. The pups of ADX rats showed a reduction in AC concentrations in the adrenal medulla at PN 1, 12 and 22, although these were higher than in the pups of sham dams at PN 8. Further, in the pups of control mothers, there was an increase in ACs during the first two weeks of life whereas pups of ADX mothers only showed increases in noradrenaline, dopamine and adrenaline levels at day 8. These results suggest that maternal absence of corticosterone affects the medulla catecholamine content during development. These data support the idea that a maternal glucocorticoids are involved in the differentiation or/and maturation of the adrenal medulla.

Influence of maternal adrenalectomy and glucocorticoid administration on the development of rat cerebral cortex.

In order to determine the incidence of maternal glucocorticoids on morphological parameters in fetal development, we performed optic and electron microscopic analysis of the cerebral cortex of fetuses of 16 and 20 days of gestation, from control (C) and pregnant rats bilaterally adrenalectomized on day 1 of gestation (ADX). We also studied fetuses 20 days old from pregnant rats betamethasone-injected on days 15, 16 and 17 (BET), and adrenalectomized on day 1 and betamethasone-injected on days 15, 16 and 17 (ADX+BET). Absence of maternal glucocorticoids during gestation caused, in fetuses 16 and 20 days old, a marked increase of cellular density, laxity of tissue and lower cellular maturation in comparison with the control group. Beta-methasone injected into sham-operated animals (BET) caused a slight advance in relation to controls in developmental parameters such as cellular density, maturation and synapse formation. Betamethasone injection into adrenalectomized animals prevented the lower degree of maturation characteristic of the adrenalectomized group, although an increase of cellular density could be detected. The cerebral cortex from fetuses of 16 days of gestation from adrenalectomized mothers also showed an increase of cellular density as compared with the control group. These results show that glucocorticoids participate in prenatal rat brain in control mechanisms of cellular division and maturation.

Ultrastructural variations of the rat fetal adrenal cortex after maternal bilateral adrenalectomy and exogen glucocorticoid administration.

Rat fetal adrenal cortex ultrastructure was studied in fetuses of 20 days of gestation coming from control (C) pregnant rats and from mothers undergoing two experimental conditions: maternal bilateral adrenalectomy on day 1 of gestation (ADX) and maternal bilateral adrenalectomy plus posterior dexamethasone administration the days 15, 16 and 17 of gestation (A+D). Our results show ultrastructural changes in the ADX rat fetal adrenal cortex, consisting of hyperactive steroidogenical features as response to the absence of maternal glucocorticoids, and the restoration of the control structural characteristics after dexamethasone administration to adrenalectomized animals.

Effects of endogenous and exogenous glucocorticoids on liver differentiation.

The effects of maternal bilateral adrenalectomy on day 1 of gestation and betamethasone treatment on fetal liver development were compared, in terms of biochemical and morphological parameters. For fetuses 20 days old (E20), absence of maternal glucocorticoids during gestation caused an increase in the number of nuclei in whole livers, and a significantly decrease of both body weight and protein content per nucleus, in comparison with the control group (C). Betamethasone injection on days 15, 16 and 17 of gestation into adrenalectomized pregnant rats (ADX + BET) did not completely prevent these effects. The electron microscopic analysis of the ADX fetal liver (E20) showed some hepatocyte lesions such as loss of cytoplasmic organelles, increase in hematopoietic cell number as well as a lower cellular maturation in comparison with the control group. The fetal liver from ADX + BET mothers 20 days after gestation displayed a noticeable involution of the hematopoietic component in spite of its relatively immature stage. However, there was no significant change in the degree of fetal hepatocyte lesions. Therefore, supply of maternal glucocorticoids from the beginning of gestation is essential for maintenance of the integral structure of the rat fetal hepatic parenchyma, for the correct maturation of the blood strains and for the beginning of involution of the hematopoietic tissue at the end of gestation.

[Reliability of imaging modalities for preoperative assessment of patients with endometrial carcinoma]. / Pertinence de l'imagerie dans l'évaluation préopératoire des patientes avec cancer endométrial.

OBJECTIVES: To investigate the value of transvaginal sonography, computed tomography and magnetic resonance imaging for the preoperative staging of endometrial cancer. PATIENTS AND METHODS: The patient group consisted of consecutive women undergoing surgery for endometrial cancer in our institution between January 2000, and September 2012. Clinical data included comorbidities, BMI (kg/m(2)), preoperative imaging findings, surgical procedures, surgical International Federation of Gynecology and Obstetrics stage, histological grade, relevant prognostic factors. The pathological data from surgical staging were compared with the preoperative imaging results. RESULTS: Two hundred and forty-four patients with the final diagnosis of endometrial cancer were enrolled. Hundred and ninety-six had preoperative transvaginal ultrasonography, 56 preoperative computed tomography and 158 preoperative MRI assessment. In our analysis, MRI had better sensitivity and specificity for all imaging criteria but lymph node assessment where MRI and CT-scan are equivalent (MRI: Se=45.45 %, Sp=79.52 %; CT: Se=50 %, Sp=80 %). DISCUSSION AND CONCLUSION: In patients with endometrial cancer, preoperative MRI may not accurately diagnose absence of myometrial invasion. This data should be kept in mind before planning the operative treatment modality and particularly before choosing patients for conservative endometrial carcinoma treatment.

Evaluation of lumpectomy surgical specimen radiographs in subclinical, in situ and invasive breast cancer, and factors predicting positive margins.

PURPOSE: To determine the diagnostic performance of radiological evaluation of the margins of surgical specimens from lumpectomies for subclinical malignant breast lesions. MATERIALS AND METHODS: Retrospective study in two French hospitals including all patients who had a non-palpable in situ (ISDC) or invasive (IDC) ductal carcinoma treated by lumpectomy after radiological localisation. For the analysis, the lesions were divided into two groups depending on the majority component in the definitive histological examination: ISDC or IDC. The radiological margin considered was 10mm. RESULTS: For the 178 lumpectomies studied, the sensitivity of the radiographs of the surgical specimen was 33.3% for ISDC and 50% for IDC. The surgical revision rate was 27.41% for ISDC and 12.64% for IDC. The significant predictive factors for positive margins were the radiological size of the lesions (>10mm) for ISDC (P=0.02) and radiologically positive margins for IDC (P=0.01). Correlation was found between the histological and radiological sizes of the lesion for IDC, but not for ISDC. CONCLUSION: Radiological examination of surgical specimens does not provide a satisfactory evaluation of the histological margins, in particular for ISDC, even with a radiological threshold of 10mm.

Influence of metyrapone treatment during pregnancy on the development and maturation of brain monoaminergic systems in the rat.

AIM: This study examines the effect of reducing the corticosterone levels of gestating rat dams on the postnatal development and maturation of monoaminergic systems in their offspring's brains. METHODS: Metyrapone, an inhibitor of CORT synthesis, was administered to pregnant rats from E0 to E17 of gestation. Monoamine concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in the hippocampus, hypothalamus and striatum. RESULTS: Reducing maternal corticosterone (mCORT) during gestation led to alterations in dopamine and serotonin levels in all three brain areas studied at PN 23. Alterations persisted until at least PN 90 in the serotonergic systems; the dopamine content of the hippocampus also remained modified. Reduced mCORT during gestation also led to alterations in the development and maturation of the hypothalamic noradrenergic systems. Sexually dimorphic responses were observed in all these monoaminergic systems at different times. CONCLUSION: These results suggest that while they are still developing, brain monoaminergic systems are particularly sensitive to epigenetic influences. An adequate foetal level of CORT is required for the normal ontogeny of brain monoaminergic systems. The present data also provide that during the critical period of brain development, maternal CORT plays an important role in the sexual differentiation of monoaminergic systems, with particular influence on brain serotonergic neurones.

Temporal mitochondrial DNA variation in the Basque Country: influence of post-neolithic events.

The Basque population has been considered an outlier in a large number of genetic studies, due to its hypothesized antiquity and greater genetic isolation. The present paper deals with an analysis of the mtDNA variability of the historical population of Aldaieta (VI-VII c. AD; Basque Country) which, together with genetic data existing for other prehistoric populations of the Basque Country (4,500-5,000 YBP), permits an appraisal of the hypotheses proposed for the origin of the genetic differentiation of the Basque population. Given that this is an aDNA study, application has been made both of standard precautions, to avoid contamination, and of authentication criteria (analysis of duplicates, replication in an independent laboratory, quantification of target DNA, sequencing and cloning of PCR products). The variability of the mtDNA haplogroups of the historical population of Aldaieta falls within the range of the present-day populations of Europe's Atlantic fringe, whereas the prehistoric populations of the Basque Country display clear differentiation in relation to all others. Consequently, we suggest that between 5,000-1,500 YBP approximately, there may have been gene flow amongst the western European populations that homogenised mtDNA lineages.

An mtDNA analysis in ancient Basque populations: implications for haplogroup V as a marker for a major paleolithic expansion from southwestern europe.

mtDNA sequence variation was studied in 121 dental samples from four Basque prehistoric sites, by high-resolution RFLP analysis. The results of this study are corroborated by (1) parallel analysis of 92 bone samples, (2) the use of controls during extraction and amplification, and (3) typing by both positive and negative restriction of the linked sites that characterize each haplogroup. The absence of haplogroup V in the prehistoric samples analyzed conflicts with the hypothesis proposed by Torroni et al., in which haplogroup V is considered as an mtDNA marker for a major Paleolithic population expansion from southwestern Europe, occurring approximately 10,000-15,000 years before the present (YBP). Our samples from the Basque Country provide a valuable tool for checking the previous hypothesis, which is based on genetic data from present-day populations. In light of the available data, the most realistic scenario to explain the origin and distribution of haplogroup V suggests that the mutation defining that haplogroup (4577 NlaIII) appeared at a time when the effective population size was small enough to allow genetic drift to act-and that such drift is responsible for the heterogeneity observed in Basques, with regard to the frequency of haplogroup V (0%-20%). This is compatible with the attributed date for the origin of that mutation (10,000-15, 000 YBP), because during the postglacial period (the Mesolithic, approximately 11,000 YBP) there was a major demographic change in the Basque Country, which minimized the effect of genetic drift. This interpretation does not rely on migratory movements to explain the distribution of haplogroup V in present-day Indo-European populations.

Maternal adrenalectomy at the early onset of gestation impairs the postnatal development of the rat hippocampal formation: effects on cell numbers and differentiation, connectivity and calbindin-D28k immunoreactivity.

The possible role of the maternal glucocorticoids on the postnatal development of the hippocampus was tested with bilateral adrenalectomy of pregnant rats. Surgery was performed 24 hr after sperm-positiveness was determined. The offspring from adrenalectomized mothers, compared with animals from control sham-operated mothers, showed decreased body weight and increased brain weight. The CA1 field of the hippocampus of these animals showed lower number of both Nissl-stained and Calbindin-immunoreactive cells, whereas the granule cell layer of the dentate gyrus showed higher number of both populations. Both types of cell numbers were statistically similar from postnatal Day 21, however, suggesting some compensatory mechanism. The neuronal populations of adrenalectomized animals appeared with a delay in the development of their dendritic trees, cytoplasmic differentiation, and synaptic connections. In the same way, both septohippocampal and hippocamposeptal projections appeared delayed in the adrenalectomized animals with respect to control ones by several days, mainly with regard to regressive events typical of the first 8 days of age. The ultrastructural study showed that every ADX postnatal group appeared more immature than the corresponding control group. These results suggest that gestational levels of maternal glucocorticoids (that were removed by adrenalectomy) influence the normal postnatal development of the hippocampus as reflected in neuron numbers and cell maturation, as well as in the developmental timing of the pattern of connectivity, and that this effect must be accomplished both in neuroepithelium and post-mitotic cells before the endogenous fetal hormones are secreted and reach concentrations capable to produce a response.

Effects of maternal bilateral adrenalectomy and betamethasone administration on fetal rat encephalic development.

The present study examined the effects of maternal bilateral adrenalectomy and betamethasone treatment on fetal encephalic development, in terms of fetal body weight, brain weight, DNA, protein and lipid content and morphological development. Both influenced the developmental time patterns of fetal brain and cerebellum. Fetuses of adrenalectomized rats had decreased body weights, whereas brain weight was not affected. Maternal adrenalectomy produces in fetal brain a decreased number of cells and increased cell size, while betamethasone treatment of adrenalectomized rats increased cell number, which was not different from control values; cell size remained lower than in control fetuses. Lipid content was increased in the fetuses of betamethasone-treated rats. In terms of morphological development, laminated structures (hippocampus and brain and cerebellar cortex) were the ones most affected.