gamma-Diimine palladium(II) based complexes mediated polymerization of methyl methacrylate

The synthesis of new palladium(II) complexes of the type [Pd(A-N=C-ph-C=N-A) Cl-2] (4a-e) (A = cyclohexyl (a), 2-isoprpropyl (b), pyrenyl (c), naphthyl (d), and 2,6-diisopropyl (e)) is described. The isolated gamma-diimine ligands and their corresponding palladium(II) complexes were characterized by their physical properties, elemental analysis, H-1 NMR=, C-13 NMR, and infrared spectroscopy. The palladium(II) complexes (4a-e) were employed successfully as catalysts for atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) in the presence of ethyl-2-bromoisobutyrate (EBIB) as initiator at 90 degrees C. Polymerization with these catalyst systems afforded polymers with low molecular weight distribution (M-w/M-n) and syndio-rich atactic poly (MMA) with relatively higher [rr] diads. (C) 2013 Production and hosting by Elsevier B.V.Peer reviewe

Reduction of guide needle streak artifact in CT-guided biopsy

Purpose: Computed tomography (CT)–guided core needle biopsy (CNB) can be affected by streak artifact obscuring the needle tip. This study investigates factors that influence the occurrence and severity of streak artifact during CNB. Materials and Methods: Eight coaxial guide needles of two sizes from two manufacturers with and without stylets were imaged in a CT phantom, with CT reconstructed with adaptive statistical iterative reconstruction and filtered back projection. CNB-related streak artifact was quantified with profile analysis in an image-processing program. Differences between maximum attenuation at the needle tip and minimum attenuation in the streak artifact were compared for each variable. Diagnostic acceptability and streak artifact were subjectively assessed on each phantom image and on 40 clinical CNB procedures by three independent blinded reviewers following training case review. Results: Artifact was significantly less with the central stylet removed versus in situ (median, 1,145 HU vs 3,390 HU; P < .001) for all needles, and less for 19-gauge needles versus 17-gauge needles (median, 1,334 HU vs 2,780 HU, respectively; P = .006). There were no differences based on manufacturer (P = .906) or reconstruction algorithm (P = .524). Independent reviews found that streak artifact was significantly reduced when the central stylet was removed (κ = 0.875–1.0; P < .001), and needle tip position was better in cases in which the stylet was removed (κ = 0.231–0.711; P < .001). Conclusions: Streak artifact can be reduced and needle tip visualization improved by confirming final biopsy needle position with the central stylet removed on CT and using smaller-gauge guide needles

Targeting neuroinflammation for therapeutic intervention in neurodegenerative pathologies: A role for the peptide analogue of thymulin (PAT)

Introduction: Inflammation has a vital task in protecting the organism, but when deregulated, it can have serious pathological consequences. The central nervous system (CNS) is capable of mounting immune and inflammatory responses, albeit different from that observed in the periphery. Neuroinflammation, however, can be a major contributor to neurodegenerative diseases and constitute a major challenge for medicine and basic research. Areas covered: Both innate and adaptive immune responses normally play an important role in homeostasis within the CNS. Microglia, astrocytes and neuronal cells express a wide array of toll-like receptors (TLR) that can be upregulated by infection, trauma, injuries and various exogenic or endogenic factors. Chronic hyper activation of brain immune cells can result in neurotoxic actions due to excessive production of several pro-inflammatory mediators. Several studies have recently described an important role for targeting receptors such as nicotinic receptors located on cells in the CNS or in other tissues for the control of inflammation. Expert opinion: Thymulin and its synthetic peptide analogue (PAT) appear to exert potent anti-inflammatory effects at the level of peripheral tissues as well as at the level of the brain. This effect involves, at least partially, the activation of cholinergic mechanisms. © 2012 Informa UK, Ltd

Novel palladium(II) and platinum(II) complexes with a fluoropiperazinyl based ligand exhibiting high cytotoxicity and anticancer activity in vitro

cis-Dichloro-palladium(II) and cis-dichloro-platinum(II) complexes (2, 4) of the general formula [M(N-N)Cl2] (M=Pd(II) and Pt(II), N-N= 1,2-diamino-4-fluoro-5-(4-methyl-1-piperazinyl) benzene, (DFMPB)) and the dicationic palladium(II) complex [Pd(N-N)(CH3CN)2](BF4)2 (3) have been prepared and characterized by elemental analysis, 1H-NMR-, mass spectroscopy, and IR spectroscopy. The cytotoxic effect of these complexes against MDA-231 and MCF-7 human breast cancer cell lines and K562 human leukemia cell line has been studied. The influence was dose dependent and varies with cell type. The palladium(II) complex (2) showed superior cytotoxic effect compared with the corresponding platinum(II) complex and the standard, cisplatin, when tested against all the above cell lines. 2016 Kayed A. Abu-Safieh et al.Scopu

Cerebrospinal fluid α-synuclein species in cognitive and movements disorders

Total CSF α-synuclein (t-α-syn), phosphorylated α-syn (pS129-α-syn) and α-syn oligomers (o-α-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of α-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF α-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson’s disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer’s disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-α-syn/α-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower α-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-α-syn levels (p = 0.002; cut-off value: ≤865 pg/mL; sensitivity: 95%, specificity: 69%) and higher pS129-/t-α-syn ratios (p = 0.020; cut-off value: ≥0.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant α-syn species alterations in non-synucleinopathies.This study was supported by Strat-up Funding to OE from Qatar Biomedical Research Institute (SF 2007–007) and Qatar National Research Fund (NPRPNo.: 8–517–3-112)

Factors that influence a patient’s decision to engage in genetic research

IntroductionThe most challenging step in clinical research studies is patient recruitment. Many research studies do not reach their targets because of participant rejection. The purpose of this study was to assess patient as well as the community knowledge, motivation, and barriers to participate in genetic research.MethodsA cross-section study was conducted between September 2018 and February 2020 using face-to-face interviews with candidate patients from outpatient clinics at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia. Additionally, an online survey was conducted to assess the community’s knowledge, motivation and barriers to participate in genetic research studies.ResultsIn total, 470 patients were interviewed for this study, with 341 being successfully recruited for the face to face interview, and the other patients being refused owing to time constraints. The majority percentage of the respondents were females. The respondents’ mean age was 30, and 52.6% reported having a college degree. The survey results from 388 participants illustrated that around 90% of the participants, participated voluntarily due to a good understanding of genetics studies. The majority held positive attitudes toward being part of genetic research, which exceeded the reported motivation score of &gt;75%. The survey indicated that &gt;90% of individuals were willing to participate to acquire therapeutic benefits or to receive continued aftercare. However, 54.6% of survey participants were worried about the side effects and the risks involved in genetic testing. A higher proportion (71.4%) of respondents reported that lack of knowledge about genetic research was one of the barriers to rejecting participation.ConclusionRespondents reported relatively high motivation and knowledge for participation in genetic research. However, study participants reported “do not know enough about genetic research” and “lack of time during clinic visit” as a barrier for participation in genetic research

Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing.

Purpose: Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies. Methods: Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing. Results: Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D). Conclusions: Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics

Detecting autozygosity through runs of homozygosity: A comparison of three autozygosity detection algorithms

<p>Abstract</p> <p>Background</p> <p>A central aim for studying runs of homozygosity (ROHs) in genome-wide SNP data is to detect the effects of autozygosity (stretches of the two homologous chromosomes within the same individual that are identical by descent) on phenotypes. However, it is unknown which current ROH detection program, and which set of parameters within a given program, is optimal for differentiating ROHs that are truly autozygous from ROHs that are homozygous at the marker level but vary at unmeasured variants between the markers.</p> <p>Method</p> <p>We simulated 120 Mb of sequence data in order to know the true state of autozygosity. We then extracted common variants from this sequence to mimic the properties of SNP platforms and performed ROH analyses using three popular ROH detection programs, PLINK, GERMLINE, and BEAGLE. We varied detection thresholds for each program (e.g., prior probabilities, lengths of ROHs) to understand their effects on detecting known autozygosity.</p> <p>Results</p> <p>Within the optimal thresholds for each program, PLINK outperformed GERMLINE and BEAGLE in detecting autozygosity from distant common ancestors. PLINK's sliding window algorithm worked best when using SNP data pruned for linkage disequilibrium (LD).</p> <p>Conclusion</p> <p>Our results provide both general and specific recommendations for maximizing autozygosity detection in genome-wide SNP data, and should apply equally well to research on whole-genome autozygosity burden or to research on whether specific autozygous regions are predictive using association mapping methods.</p

Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes

Retinal dystrophy (RD) is a heterogeneous group of hereditary diseases caused by loss of photoreceptor function and contributes significantly to the etiology of blindness globally but especially in the industrialized world. The extreme locus and allelic heterogeneity of these disorders poses a major diagnostic challenge and often impedes the ability to provide a molecular diagnosis that can inform counseling and gene-specific treatment strategies. In a large cohort of nearly 150 RD families, we used genomic approaches in the form of autozygome-guided mutation analysis and exome sequencing to identify the likely causative genetic lesion in the majority of cases. Additionally, our study revealed six novel candidate disease genes (C21orf2, EMC1, KIAA1549, GPR125, ACBD5, and DTHD1), two of which (ACBD5 and DTHD1) were observed in the context of syndromic forms of RD that are described for the first time

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN