Osteoinductive 3D scaffolds prepared by blend centrifugal spinning for long-term delivery of osteogenic supplements

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems.     

Extra-ostial pulmonary venous isolation: use of epicardial ablation to eliminate a point of conduction breakthrough

Epicardial RFA to Achieve Electrical PV Isolation. During catheter ablation of atrial fibrillation, ablation within the pulmonary veins is undesirable due to the risk of pulmonary venous stenosis and the possibility of leaving residual cuffs of arrhythmogenic tissue proximal to the ablation lesion set. An extra-ostial pulmonary vein isolation strategy may circumvent these limitations, but achieving electrical isolation can be technically challenging, even with the use of saline-irrigated radiofrequency energy technology. This report describes the successful use of epicardial radiofrequency ablation in a patient in whom endocardial irrigated radiofrequency ablation failed to achieve extra-ostial pulmonary vein isolation.     

Craniovascular traits and braincase morphology in craniosynostotic human skulls

Middle meningeal vessels, dural venous sinuses, and emissary veins leave imprints and canals in the endocranium, and thus provide evidence of vascular patterns in osteological samples. This paper investigates whether craniovascular morphology undergoes changes in craniosynostotic human skulls, and if specific alterations may reflect structural and functional relationships in the cranium. The analyzed osteological sample consists of adult individuals with craniosynostoses generally associated with dolichocephalic or brachycephalic proportions, and a control sample of anatomically normal adult skulls. The pattern and dominance of the middle meningeal artery, the morphology of the confluence of the sinuses, and the size and number of the emissary foramina were evaluated. Craniovascular morphology was more diverse in craniosynostotic skulls than in anatomically normal skulls. The craniosynostotic skulls often displayed enlarged occipito-marginal sinuses and more numerous emissary foramina. The craniosynostotic skulls associated with more brachycephalic morphology often presented enlarged emissary foramina, while the craniosynostotic skulls associated with dolichocephalic effects frequently displayed more developed posterior branches of the middle meningeal artery. The course and morphology of the middle meningeal vessels, dural venous sinuses, and emissary veins in craniosynostotic skulls can be related to the redistribution of growth forces, higher intracranial pressure, venous hypertension, or thermal constraints. These functional and structural changes are of interest in both anthropology and medicine, involving epigenetic traits that concern the functional and ontogenetic balance between soft and hard tissues.     

White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis

ObjectiveDespite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations.MethodsTwenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls.ResultsFocal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T₂ signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities.ConclusionWhite matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T₂ signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T₂ signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.     

A familial case of alveolar capillary dysplasia with misalignment of pulmonary veins supports paternal imprinting of FOXF1 in human

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare developmental lung disorder that is uniformly lethal. Affected infants die within the first few weeks of their life despite aggressive treatment, although a few cases of late manifestation and longer survival have been reported. We have shown previously that mutations and deletions in FOXF1 are a cause of this disorder. Although most of the cases of ACD/MPV are sporadic, there have been infrequent reports of familial cases. We present a family with five out of six children affected with ACD/MPV. DNA analysis identified a missense mutation (c.416G>T; p.Arg139Leu) in the FOXF1 gene that segregated in the three affected siblings tested. The same variant is also present as a de novo mutation in the mother and arose on her paternally derived chromosome 16. The two tested affected siblings share the same chromosome 16 haplotype inherited from their maternal grandfather. Their single healthy sibling has a different chromosome 16 haplotype inherited from the maternal grandmother. The results are consistent with paternal imprinting of FOXF1 in human.     

Detection of Leishmania donovani and L. tropica in Ethiopian wild rodents

Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts.