Vacuum‐Ultraviolet Photopolymerisation of Amine‐Rich Thin Films

Nitrogen‐rich organic thin films were deposited by VUV‐assisted photochemical polymerisation of flowing C₂H₄/NH₃ mixtures. The fundamental reaction mechanisms of these binary gas mixtures were investigated as a function of the wavelength of two almost monochromatic VUV sources. Compositions of these “UV‐PE:N” films close to the surface were determined by XPS, and the amine concentrations and selectivities were quantified via chemical derivatisation. The UV‐PE:N films were compared with plasma polymers deposited using low‐pressure glow discharges in similar gas flow mixtures, “L‐PPE:N”; it is shown that VUV photochemistry is superior to plasma chemistry in producing almost monofunctional organic thin films.

     

Antithrombotic therapy in TAVI

Transcatheter aortic valve implantation (TAVI) carries a significant thromboembolic and concomitant bleeding risk, not only during the procedure but also during the periprocedural period. Many issues concerning optimal antithrombotic therapy after TAVI are still under debate. In the present review, we aimed to identify all relevant studies evaluating antithrombotic therapeutic strategies in relation to clinical outcomes after the procedure. Four randomized control trials (RCT) were identified analyzing the post-TAVI antithrombotic strategy with all of them utilizing aspirin lifelong plus clopidogrel for 3?6 months. Seventeen registries have been identified, with a wide variance among them regarding baseline characteristics, while concerning antiplatelet therapy, clopidogrel duration was ranging from 3?12 months. Four non-randomized trials were identified, comparing single vs. dual antiplatelet therapy after TAVI, in respect of investigating thromboembolic outcome events over bleeding complications. Finally, limited data from a single RCT and a retrospective study exist with regards to anticoagulant treatment during the procedure and the optimal antithrombotic therapy when concomitant atrial fibrillation. In conclusion, due to the high risk and frailty of the treated population, antithrombotic therapy after TAVI should be carefully evaluated. Diminishing ischaemic and bleeding complications remains the main challenge in these patients with further studies to be needed in this field.     

The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the “metabolic” workgroup of the Fondation Yves Cotrel

Objective

The purpose of this review is to elucidate the metabolic processes involved in the pathogenesis of adolescent idiopathic scoliosis (AIS) in light of research by the present authors as well as current literature.

Methods

Pathogenetic mechanisms involved in AIS were modeled as (a) a form of neuromuscular scoliosis (in conjunction with an adverse mechanical environment such as bipedality), in which hormonal and other chemical factors act as regulators of skeletal muscle tone and function; (b) as a consequence of an abnormality in growth of the spinal column (in conjunction with an adverse mechanical environment such as bipedality), in which hormones and other chemical factors act as regulators of growth; and (c) as a mechanical failure of one side of the vertebral column due to a defect in trabecular formation or mineralization (in conjunction with an adverse mechanical environment such as bipedality); in which hormonal and other chemical factors act as regulators of bone formation, mineralization and/or resorption.

Results and conclusion

Current evidence supporting these models individually or in combination is discussed.     

PARP10 deficiency manifests by severe developmental delay and DNA repair defect

DNA repair mechanisms such as nucleotide excision repair (NER) and translesion synthesis (TLS) are dependent on proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory protein. Recently, homozygosity for p.Ser228Ile mutation in the PCNA gene was reported in patients with neurodegeneration and impaired NER. Using exome sequencing, we identified a homozygous deleterious mutation, c.648delAG, in the PARP10 gene, in a patient suffering from severe developmental delay. In agreement, PARP10 protein was absent from the patient cells. We have previously shown that PARP10 is recruited by PCNA to DNA damage sites and is required for DNA damage resistance. The patient cells were significantly more sensitive to hydroxyurea and UV-induced DNA damage than control cells, resulting in increased apoptosis, indicating DNA repair impairment in the patient cells. PARP10 deficiency joins the long list of DNA repair defects associated with neurodegenerative disorders, including ataxia telangiectasia, xeroderma pigmentosum, Cockayne syndrome, and the recently reported PCNA mutation.     

Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease

A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti‐) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole‐brain resting‐state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within‐scanner motion. Compared to HC, we found attenuated negative STN‐coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN‐coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN‐coupling with the left insula related to severity of motor symptoms and a decline of inter‐hemispheric functional connectivity between left and right STN with progression of PD‐related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well‐known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. Hum Brain Mapp 37:1235–1253, 2016. © 2015 Wiley Periodicals, Inc .     

Ketoconazole-p aminobenzoic cocrystal,an improved antimycotic drug formulation,does not induce skin sensitization on the skin of BALBc mice

Inflammopharmacology - Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole...