Autonomic dysfunction in progressive supranuclear palsy

Background: The degree of involvement of the autonomic nervous system in progressive supranuclear palsy (PSP) has been investigated in several studies, often providing conflicting results. There is a need for a better characterization of autonomic dysfunction in PSP, to enhance our understanding of this highly disabling neurodegenerative disease including patients’ needs and possibly be of value for clinicians in the differential diagnosis among Parkinsonian syndromes. Methods: We applied a systematic methodology to review existing literature on Pubmed regarding autonomic nervous system involvement in PSP. Results: PSP reported quite frequently symptoms suggestive of autonomic dysfunction in all domains. Cardiovascular autonomic testing showed in some cases a certain degree of impairment (never severe). There was some evidence suggesting bladder dysfunction particularly in the storage phase. Dysphagia and constipation were the most common gastrointestinal symptoms. Instrumental tests seemed to confirm sudomotor and pupillomotor disturbances. Conclusions: PSP patients frequently reported visceral symptoms, however objective testing showed that not always these reflected actual autonomic impairment. Further studies are needed to better delineate autonomic profile and its prognostic role in PSP

Organocatalysis and beyond: Activating reactions with two catalytic species

Since the beginning of the millennium, organocatalysis has been gaining a predominant role in asymmetric synthesis and it is, nowadays, a foundation of catalysis. Synergistic catalysis, combining two or more different catalytic cycles acting in concert, exploits the vast knowledge acquired in organocatalysis and other fields to perform reactions that would be otherwise impossible. Merging organocatalysis with photo-, metallo- and organocatalysis itself, researchers have ingeniously devised a range of activations. This feature review, focusing on selected synergistic catalytic approaches, aims to provide a flavor of the creativity and innovation in the area, showing ground-breaking examples of organocatalysts, such as proline derivatives, hydrogen bond-mediated, Cinchona alkaloids or phosphoric acids catalysts, which work cooperatively with different catalytic partners

Asymmetric Organocatalysis Accelerated via Self-Assembled Minimal Structures

Self-assembling minimalistic peptides embedded with an organocatalytic moiety were designed. By controlling the formation of fibrils via external intervention, it was shown that the activation is accelerated when the organocatalyst is in its supramolecular state. The effect of the accelerated catalysis was demonstrated in a Michael benchmark reaction

4-Phenyl-1,2,3-triazoles as Versatile Ligands for Cationic Cyclometalated Iridium(III) Complexes

Five cationic iridium(III) complexes (1-5) were synthesized exploiting two triazole-based cyclometalating ligands, namely, 1-methyl-4-phenyl-1H-1,2,3-triazole (A) and the corresponding mesoionic carbene 1,3-dimethyl-4-phenyl-1H-1,2,3-triazol-5-yliclene (B). From the combination of these two ligands and the ancillary one, i.e., 4,4'-di-tert-butyl-2,2'-bipyridine (for 1-3) or tert-butyl isocyanide (for 4 and 5), not only the typical bis-heteroleptic complexes but also the much less explored tris-heteroleptic analogues (2 and 5) could be synthesized. The redox and emission properties of all of the complexes are effectively fine-tuned by the different ligands: (i) cyclometalating ligand A induces a stronger highest occupied molecular orbital (HOMO) stabilization compared to B and leads to complexes with progressively narrower HOMO-lowest unoccupied molecular orbital (LUMO) and redox gaps, and lower emission energy; (ii) complexes 1-3, equipped with the bipyridine ancillary ligand, display fully reversible redox processes and emit from predominantly metal-to-ligand charge transfer (MLCT) states with high emission quantum yields, up to 60% in polymeric matrix; (iii) complexes 4 and 5, equipped with high-field isocyanide ligands, display irreversible redox processes and high-energy emission from strongly ligand-centered triplets with long emission lifetimes but relatively low quantum yields (below 6%, both in room-temperature solution and in solid state). This work demonstrates the versatility of phenyl-triazole derivatives as cyclometalating ligands with different chelation modes (i.e., C<^>N and C<^>C:) for the synthesis of photoactive iridium(III) complexes with highly tunable properties

Evaluating the impact of the community-based health planning and services initiative on uptake of skilled birth care in Ghana

Background: the Community-based Health Planning and Services (CHPS) initiative is a major government policy to improve maternal and child health and accelerate progress in the reduction of maternal mortality in Ghana. However, strategic intelligence on the impact of the initiative is lacking, given the persistent ?problems of patchy geographical access to care for rural women. This study investigates the impact of proximity to CHPS on facilitating uptake of skilled ?birth care in rural areas.Methods and findings: data from the ?2003 and 2008 Demographic and Health Survey, ? on 4,349 births from 463 rural communities were linked to georeferenced data on health facilities, CHPS and topographic data on national road-networks. Distance to nearest health facility and CHPS was computed using the closest facility functionality in ArcGIS 10.1. Multilevel logistic regression was used to examine the effect of proximity to health facilities and CHPS on use of skilled care at birth, adjusting for relevant predictors and clustering within ?communities.? The results show that a substantial proportion of births continue to occur in communities more than 8 km from both ?health facilities and CHPS. Increases in uptake of skilled birth care are more pronounced where both health ?facilities and CHPS compounds are within 8 km, but not in communities within 8 km of CHPS but lack access to health facilities. Where both health facilities and CHPS are within 8 km, the odds of skilled ?birth care is 16% higher than ?where there is only a health facility within 8km. Conclusion: where CHPS compounds are set up near health facilities, there is improved access to care, demonstrating the facilitatory role of CHPS in stimulating access to better care at birth, in areas where health facilities are accessible. <br/

Processing and structural properties of random oriented lead lanthanum zirconate titanate thin films

Polycrystalline lead lanthanum zirconate titanate (PLZT) thin films have been prepared by a polymeric chemical route to understand the mechanisms of phase transformations and map the microstructure and elastic properties at the nanoscale in these films. X-ray diffraction, atomic force microscopy (AFM) and ultrasonic force microscopy (UFM) have been used as investigative tools. On one side, PLZT films with mixed-phase show that the pyrochlore phase crystallizes predominantly in the bottom film-electrode interface while a pure perovskite phase crystallizes in top film surface. On the contrary, pyrochlore-free PLZT films show a non-uniform microstrain and crystallite size along the film thickness with a heterogeneous complex grainy structure leading to different elastic properties at nanoscale

Autonomic dysfunction in progressive supranuclear palsy.

BACKGROUND: The degree of involvement of the autonomic nervous system in progressive supranuclear palsy (PSP) has been investigated in several studies, often providing conflicting results. There is a need for a better characterization of autonomic dysfunction in PSP, to enhance our understanding of this highly disabling neurodegenerative disease including patients' needs and possibly be of value for clinicians in the differential diagnosis among Parkinsonian syndromes. METHODS: We applied a systematic methodology to review existing literature on Pubmed regarding autonomic nervous system involvement in PSP. RESULTS: PSP reported quite frequently symptoms suggestive of autonomic dysfunction in all domains. Cardiovascular autonomic testing showed in some cases a certain degree of impairment (never severe). There was some evidence suggesting bladder dysfunction particularly in the storage phase. Dysphagia and constipation were the most common gastrointestinal symptoms. Instrumental tests seemed to confirm sudomotor and pupillomotor disturbances. CONCLUSIONS: PSP patients frequently reported visceral symptoms, however objective testing showed that not always these reflected actual autonomic impairment. Further studies are needed to better delineate autonomic profile and its prognostic role in PSP

The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

<p>Abstract</p> <p>Background</p> <p>Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector <it>Anopheles gambiae</it>.</p> <p>Results</p> <p>We have identified the <it>Anopheles gambiae vasa</it>-like gene and found its expression to be specifically localized to both the male and female gonads in adult mosquitoes. We have functionally characterised using transgenic reporter lines the regulatory regions required for driving transgene expression in a pattern mirroring that of the endogenous <it>vasa </it>locus. Two reporter constructs indicate the existence of distinct <it>vasa </it>regulatory elements within the 5' untranslated regions responsible not only for the spatial and temporal but also for the sex specific germline expression. <it>vasa </it>driven eGFP expression in the ovary of heterozygous mosquitoes resulted in the progressive accumulation of maternal protein and transcript in developing oocytes that were then detectable in all embryos and neonatal larvae.</p> <p>Conclusion</p> <p>We have characterized the <it>vasa </it>regulatory regions that are not only suited to drive transgenes in the early germline of both sexes but could also be utilized to manipulate the zygotic genome of developing embryos via maternal deposition of active molecules. We have used computational models to show that a homing endonuclease-based gene drive system can function in the presence of maternal deposition and describe a novel non-invasive control strategy based on early <it>vasa </it>driven homing endonuclease expression.</p

Autologous Marrow Mesenchymal Stem Cell Driving Bone Regeneration in a Rabbit Model of Femoral Head Osteonecrosis

Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disease that ultimately requires a total hip replacement. Mesenchymal stromal/stem cells (MSCs), particularly the ones isolated from bone marrow (BM), could be promising tools to restore bone tissue in ONFH. Here, we established a rabbit model to mimic the pathogenic features of human ONFH and to challenge an autologous MSC-based treatment. ON has been originally induced by the synergic combination of surgery and steroid administration. Autologous BM-MSCs were then implanted in the FH, aiming to restore the damaged tissue. Histological analyses confirmed bone formation in the BM-MSC treated rabbit femurs but not in the controls. In addition, the model also allowed investigations on BM-MSCs isolated before (ON-BM-MSCs) and after (ON+BM-MSCs) ON induction to dissect the impact of ON damage on MSC behavior in an affected microenvironment, accounting for those clinical approaches foreseeing MSCs generally isolated from affected patients. BM-MSCs, isolated before and after ON induction, revealed similar growth rates, immunophenotypic profiles, and differentiation abilities regardless of the ON. Our data support the use of ON+BM-MSCs as a promising autologous therapeutic tool to treat ON, paving the way for a more consolidated use into the clinical settings