Mice with a targeted disruption of the Fgfrl1 gene die at birth due to alterations in the diaphragm

FGFRL1 is a recently discovered member of the fibroblast growth factor receptor family that is lacking the intracellular tyrosine kinase domain. To elucidate the function of the novel receptor, we created mice with a targeted disruption of the Fgfrl1 gene. These mice develop normally until term, but die within a few minutes after birth due to respiratory failure. The respiratory problems are explained by a significant reduction in the size of the diaphragm muscle, which is not sufficient to inflate the lungs after birth. The remaining portion of the diaphragm muscle appears to be well developed and innervated. It consists of differentiated myofibers with nuclei at the periphery. Fast and slow muscle fibers occur in normal proportions. The myogenic regulatory factors MyoD, Myf5, myogenin and Mrf4 and the myocyte enhancer factors Mef2A, Mef2B, Mef2C and Mef2D are expressed at normal levels. Experiments with a cell culture model involving C2C12 myoblasts show that Fgfrl1 is expressed during the late stages of myotube formation. Other skeletal muscles do not appear to be affected in the Fgfrl1 deficient mice. Thus, Fgfrl1 plays a critical role in the development of the diaphragm.

Dimensional ridge alterations following immediate implant placement in molar extraction sites: a six-month prospective cohort study with surgical re-entry

AIM: To assess dimensional ridge alterations following immediate implant placement in molar extraction sites. MATERIAL AND METHODS: Twelve subjects received 12 immediate transmucosal implants in molar extraction sites. Peri-implant defects were treated according to the principles of Guided Bone Regeneration by means of a deproteinized bone substitute and a bioresorbable collagen membrane. Changes in vertical (IS-BD, CREST-BD) and horizontal distances (EC-I, IC-I) of alveolar bony walls to the bottom of the defects (BD) and to the implant surfaces (I) were compared between implant placement and surgical re-entry at 6 months. RESULTS: The implant survival rate at 6 months was 100%. Statistically significant differences (P<0.01) were observed in the mean changes in vertical distances IS-BD and CREST-BD between baseline and re-entry. At re-entry, all peri-implant marginal defects assessed from the internal socket wall to the implant surface (IC-I) were healed. The residual combined thickness of the buccal wall with the newly formed peri-implant bone at sites with an initial thickness of 1 mm was statistically significantly smaller (P<0.05) compared with that of sites with an initial buccal thickness of 2 mm (2.50 +/- 0.76 vs. 4+/-0 mm). CONCLUSIONS: The marginal defects around immediate implants placed in molar extraction sites were completely filled after 6 months of healing through de novo bone formation. Bone resorption was observed from the external aspects of the buccal and oral socket walls. Dimensional changes of the external socket walls were mostly pronounced at the buccal aspects.

[Dyspnea and hemoptysis in a young woman with unclear renal alterations]

We describe the clinical course and treatment of a young woman diagnosed with tuberous sclerosis. Classical as well as atypical clinical findings are discussed with regards to the differential diagnosis. The most important components of the pathogenesis and the criteria necessary for diagnosis are highlighted. In addition the similarities and differences to lymphangioleiomyomatosis are discussed.

Unexplained gonad alterations in whitefish (Coregonus spp.) from Lake Thun, Switzerland: levels of persistent organic pollutants in different morphs

Since 2000, a surprisingly high number of macroscopical gonad alterations has been reported in whitefish (Coregonus spp.) from Lake Thun, Switzerland. This unique phenomenon is still unexplained and has received much public attention. As one possible trigger for these effects, the presence of persistent, bioaccumulative and toxic compounds acting as endocrine disruptors in the lake has been discussed. In this study, concentrations of selected persistent organic pollutants were examined in two morphs of whitefish from Lake Thun and their link to the observed abnormalities was investigated. Analyzed compound classes included polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated naphthalenes, polybrominated diphenyl ethers and hexabromocyclododecanes. The target substances were identified in all samples and concentrations of the analyzed compounds were highly correlated among each other. These correlations show that the analyzed substances have the same distribution pattern throughout the lake and that uptake, accumulation and elimination processes are similar. Significant differences in contaminant levels within the samples existed between the two analyzed morphs of whitefish, most likely due to different age, food patterns and growth rate. No difference in contaminant levels was observed between fish with abnormal gonads and fish with normal gonads, suggesting no causal link between the investigated lipophilic organohalogen compounds present in fish and the observed gonad abnormalities in whitefish from Lake Thun. A comparison to existing data shows that concentrations in Lake Thun whitefish are at the lower bound of contaminant levels in whitefish from Swiss lakes or from European waters.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.

White matter microstructure alterations of the medial forebrain bundle in melancholic depression

BACKGROUND The medial forebrain bundle (MFB) is a key structure of the reward system and connects the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortex (mOFC, lOFC) and the dorsolateral prefrontal cortex (dlPFC). Previous diffusion tensor imaging (DTI) studies in major depressive disorder point to white matter alterations of regions which may be incorporated in the MFB. Therefore, it was the aim of our study to probe white matter integrity of the MFB using a DTI-based probabilistic fibre tracking approach. METHODS 22 patients with major depressive disorder (MDD) (12 melancholic-MDD patients, 10 non-melancholic-MDD patients) and 21 healthy controls underwent DTI scans. We used a bilateral probabilistic fibre tracking approach to extract pathways between the VTA and NACC, mOFC, lOFC, dlPFC respectively. Mean fractional anisotropy (FA) values were used to compare structural connectivity between groups. RESULTS Mean-FA did not differ between healthy controls and all MDD patients. Compared to healthy controls melancholic MDD-patients had reduced mean-FA in right VTA-lOFC and VTA-dlPFC connections. Furthermore, melancholic-MDD patients had lower mean-FA than non-melancholic MDD-patients in the right VTA-lOFC connection. Mean-FA of these pathways correlated negatively with depression scale rating scores. LIMITATIONS Due to the small sample size and heterogeneous age group comparisons between melancholic and non-melancholic MDD-patients should be regarded as preliminary. CONCLUSIONS Our results suggest that the melancholic subtype of MDD is characterized by white matter microstructure alterations of the MFB. White matter microstructure is associated with both depression severity and anhedonia.

Ridge alterations post-extraction in the esthetic zone: a 3D analysis with CBCT

Dimensional alterations of the facial bone wall following tooth extractions in the esthetic zone have a profound effect on treatment outcomes. This prospective study in 39 patients is the first to investigate three-dimensional (3D) alterations of facial bone in the esthetic zone during the initial 8 wks following flapless tooth extraction. A novel 3D analysis was carried out, based on 2 consecutive cone beam computed tomographies (CBCTs). A risk zone for significant bone resorption was identified in central areas, whereas proximal areas yielded only minor changes. Correlation analysis identified a facial bone wall thickness of ≤ 1 mm as a critical factor associated with the extent of bone resorption. Thin-wall phenotypes displayed pronounced vertical bone resorption, with a median bone loss of 7.5 mm, as compared with thick-wall phenotypes, which decreased by only 1.1 mm. For the first time, 3D analysis has allowed for documentation of dimensional alterations of the facial bone wall in the esthetic zone of humans following extraction. It also characterized a risk zone prone to pronounced bone resorption in thin-wall phenotypes. Vertical bone loss was 3.5 times more severe than findings reported in the existing literature.

Influence of platform switching on bone-level alterations: a three-year randomized clinical trial

The concept of platform switching has been introduced to implant dentistry based on clinical observations of reduced peri-implant crestal bone loss. However, published data are controversial, and most studies are limited to 12 months. The aim of the present randomized clinical trial was to test the hypothesis that platform switching has a positive impact on crestal bone-level changes after 3 years. Two implants with a diameter of 4 mm were inserted crestally in the posterior mandible of 25 patients. The intraindividual allocation of platform switching (3.3-mm platform) and the standard implant (4-mm platform) was randomized. After 3 months of submerged healing, single-tooth crowns were cemented. Patients were followed up at short intervals for monitoring of healing and oral hygiene. Statistical analysis for the influence of time and platform type on bone levels employed the Brunner-Langer model. At 3 years, the mean radiographic peri-implant bone loss was 0.69 ± 0.43 mm (platform switching) and 0.74 ± 0.57 mm (standard platform). The mean intraindividual difference was 0.05 ± 0.58 mm (95% confidence interval: -0.19, 0.29). Crestal bone-level alteration depended on time (p < .001) but not on platform type (p = .363). The present randomized clinical trial could not confirm the hypothesis of a reduced peri-implant crestal bone loss, when implants had been restored according to the concept of platform switching.