Ultrastructure of spermiogenesis and mature spermatozoon of Skrjabinoporus merops (Cyclophyllidea, Metadilepididae)

The ultrastructure of the mature spermatozoon and the spermiogenesis of a cestode belonging to the family Metadilepididae is described for the first time. The mature spermatozoon of Skrjabinoporus merops is characterized by twisted peripheral microtubules, the presence of a single crested body, periaxonemal sheath and electron-dense rods, and the absence of intracytoplasmic walls and inclusions (glycogen or proteinaceous granules); no peripheral microtubules where nucleus contacts the external plasma membrane. Four morphologically distinct regions of the mature spermatozoon are differentiated. The proximal part (Region I) contains a single crested body, periaxonemal sheath is absent in some (proximal) sections and is present in others situated closer to the nucleus. The central Region II is nucleated, and is followed by Region III that contains a periaxonemal sheath. The distal pole, Region IV, is characterized by disintegration of the axoneme. Spermiogenesis follows the type III pattern (Ba and Marchand 1995) although in S. merops a slight flagellar rotation is observed. The differentiation zone is characterized by the absence of striated roots and intercentriolar body; two centrioles are present, one of which gives rise to a free flagellum. The latter rotates and undergoes proximodistal fusion with the cytoplasmic protrusion of the differentiation zone. Spermiological characters of S. merops are similar to those of the families Taeniidae and Catenotaeniidae. The mature spermatozoon differs from those of the Dilepididae (where the metadilepidid species have previously been classified) by the lack of glycogen.     

Use of oral contraceptives in three European countries: a population-based multi-database study

Objectives: The aim of the study was to assess the prevalence of oral contraceptive (OC) use, user characteristics and prescribing patterns by accessing health care databases of three European countries.

Methods: A retrospective study was performed from 2009 to 2010 in three general practice (GP) databases from the Netherlands, UK and Italy and in one database of linked pharmacy and hospitalisation data in the Netherlands. The presence of selected chronic conditions and diagnoses of diseases associated with OC use were assessed, as were switches, discontinuations and types of OC used during the study period.

Results: Among 2.16 million women aged 15 to 49 years, 16.0% were using an OC on 1 January 2010. The prevalence ranged from 19.7% in a Dutch database to 2.6% in the Italian database. During 2009 and 2010, mainly second-generation progestogens were prescribed in the Netherlands (79.4% and 78.3% of users), both second- (57.9%) and third-generation progestogens (43.6%) were prescribed in the UK, and mainly third-generation progestogens in Italy (61.8%). Most switches were to third- or fourth-generation pills. The prevalence of chronic diseases tended to be higher among OC users, and the proportions of women with a history of disease associated with OC use tended to be lower than among non-users.

Conclusions: Second-generation OCs were most frequently prescribed in the Netherlands. In the UK, and even more so in Italy, many women used third- or fourth-generation OCs. Preparation switches were mainly to third- or fourth-generation OCs. Among OC users, a somewhat higher prevalence of chronic diseases was observed; however, information bias cannot be ruled out.     

Lung morphometry and MMP-12 expression in rats treated with intraperitoneal nicotine.

Nicotine, a toxic tobacco component, plays an important role in the development of cardiovascular and lung diseases in smokers. Our objective was to investigate the effects of the intraperitoneal (i.p.) nicotine treatment in lung morphology. Wistar male rats (3-4 months old) were divided in five groups, a control one, and other groups treated with nicotine (1 mg/kg/day) for 8 days and sacrificed after 24, 48, 96, and 192 h. Morphometry was used to estimate the lung alveolar parenchyme and septal elastic fibers changes, and immunohistochemistry was performed to detect macrophage metalloelastase (MMP-12) and quantify vessels by immunolabelling with alpha-smooth muscle cells. Thickening of the alveolar septa was present in all nicotine groups, and associated with mononuclear cell infiltration, angiogenesis, and irregular areas of collapse. After 96 h, rat lungs showed macrophage, expressing MMP-12, that was also present after 192 h of recovery. Pleural and parenchyma inflammation, fibrosis and macrophage were also seen after 192 h. Intraperitoneal nicotine treated rats exhibited an increase of the volume fraction of alveolar parenchyme, a reduction of volume and surface fraction septal elastic fibers, and an increase of the numerical fraction of microvasculature vessels compared to control ones. MMP-12 was detected in groups of macrophages Wistar rats lung exhibited a progressive morphological damage after 192 hours of recovery, after 8 daily doses of 1 mg/kg body weight on i.p. nicotine.     

HLA Association with hematopoietic stem cell transplantation outcome: the number of mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 is strongly associated with overall survival.

HLA matching between the donor and recipient improves the success of unrelated hematopoietic stem cell transplantation (HSCT). Because many patients in need of an unrelated transplant have only donors with mismatch, information is needed to evaluate the limits of HLA mismatching. We examined the association of survival, acute graft-versus-host disease (aGVHD) and relapse with HLA-A, -B, -C, -DRB, -DQB1, and -DPB1 mismatching in 334 patients coming from 12 French transplant centers and who received a non-T cell-depleted bone marrow graft from an unrelated donor. All patients were prepared with the use of myeloablative conditioning regimens. Our analyses demonstrate negative effects of HLA mismatching for either HLA-A, -B, -C, -DRB1, or -DQB1 loci on survival. Multivariate Cox analyses showed that a single mismatch was associated with a significant decrement in survival (P=.046, hazard ratio [HR]=1.41, confidence interval [CI] 95% 1.1-1.98). The presence of multiple mismatches was worse for survival (P=.003, HR=1.91, CI 95% 1.26-2.91) and severe aGVHD (grade III-IV) (P=.002, HR=2.51, CI95% 1.41-4.46). The cumulative incidences of aGVHD and relapse in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with 2, 1, or 0 DPB1 incompatibilities were 63%, 50%, and 51%, and 12%, 27%, and 20%, respectively, but these differences were not statistically significant. Similar differences of aGVHD and relapse, but not statistically significant, were observed in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with DPB1 disparities classified into permissive or nonpermissive mismatches according to Zino's classification based on a hierarchy of the immunogenicity of the HLA-DP molecules. "Missing killer cell immunoglobulin-like receptor (KIR) ligand" evaluated on the presence of HLA-C1, -C2, and Bw4 groups in the recipients was not associated with aGVHD, survival, and relapse in this cohort of non-T cell-depleted HSCT.     

Fibroblast growth factor-hedgehog interdependence during retina regeneration.

The embryonic chick is able to regenerate the retina after it has been removed. We have previously shown that proliferating stem/progenitor cells present in the ciliary body/ciliary marginal zone (CB/CMZ) of the chick eye are responsible for regeneration, which can be induced by ectopic fibroblast growth factor-2 (FGF2) or Sonic hedgehog (Shh). Here, we reveal the mechanisms showing how FGF2 and Shh signaling are interdependent during retina regeneration. If the FGF pathway is inhibited, regeneration stimulated by Shh is inhibited. Likewise, if the Hedgehog pathway is inhibited, regeneration stimulated by FGF2 is inhibited. We examined early signaling events in the CB/CMZ and found that FGF2 or Shh induced a robust Erk phosphorylation during the early stages of retina regeneration. Shh also up-regulated the expression of several members of the FGF signaling pathway. We show that ectopic FGF2 or Shh overexpression increased the number of phosphohistone 3 (PH3)-positive cells in the CB/CMZ and inhibition of either pathway decreased the number of PH3-positive cells. Additionally, both FGF and Hh signaling are required for cell survival in the CB/CMZ, whereas Hh and not FGF signaling plays a role in maintaining the identity of the retinal progenitor population in this region. Combined, our results support a model where the FGF and Hedgehog pathways work together to stimulate retina regeneration.     

Towards a reconceptualization of mixed states, based on an emotional-reactivity dimensional model

BACKGROUND: DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. METHOD: We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. RESULTS: This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. CONCLUSION: A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies.     

Evaluation of viral load in infants hospitalized with bronchiolitis caused by respiratory syncytial virus

The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.     

PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo

Medulloblastomas are brain tumors that arise in the cerebellum of children and contain stem cells in a perivascular niche thought to give rise to recurrence following radiation. We used several mouse models of medulloblastomas in parallel to better understand how the critical cell types in these tumors respond to therapy. In our models, the proliferating cells in the tumor bulk undergo radiation-induced, p53-dependent apoptotic cell death. Activation of Akt signaling via PTEN loss transforms these cells to a nonproliferating extensive nodularity morphology. By contrast, the nestin-expressing perivascular stem cells survive radiation, activate PI3K/Akt pathway, undergo p53-dependent cell cycle arrest, and re-enter the cell cycle at 72 h. Furthermore, the ability of these cells to induce p53 is dependent on the presence of PTEN. These cellular characteristics are similar to human medulloblastomas. Finally, inhibition of Akt signaling sensitizes cells in the perivascular region to radiation-induced apoptosis.