One-pot synthesis of a PtPd dendritic nanocube cage superstructure on graphenes as advanced catalysts for oxygen reduction

NASA Astrophysics Data System (ADS)

Zheng, Yuanyuan; Qiao, Junhua; Yuan, Junhua; Shen, Jianfeng; Wang, Ai-Jun; Gong, Peijun

2018-03-01

How to use Pt economically and efficiently in the oxygen reduction reaction (ORR) is of theoretical and practical significance for the industrialization of the proton-exchange membrane fuel cells. In order to minimize Pt consumption and optimize the ORR performance, the ORR catalysts are recommended to be designed as a porous nanostructure. Herein, we report a one-pot solvothermal strategy to prepare PtPd dendritic nanocube cages via a galvanic replacement mechanism triggered by an I- ion. These PtPd alloy crystals are nanoporous, and uniformly dispersed on reduced graphene oxides (RGOs). The size of the PtPd dendritic nanocube cages can be easily tuned from 20-80 nm by controlling their composition. Their composition is optimized to be 1:5 Pt/Pd atomic ratio for these RGO-supported PtPd dendritic nanocages. This catalyst shows superior ORR performance with a specific activity of 2.01 mA cm-2 and a mass activity of 4.45 A mg-1 Pt, far above those for Pt/C catalysts (0.288 mA cm-2 for specific activity, and 0.21 A mg-1 Pt for mass activity). In addition to ORR activity, it also exhibits robust durability with almost negligible decay in ORR mass activity after 10 000 voltammetric cycling.

Decision-making impairments in Parkinson's disease as a by-product of defective cost-benefit analysis and feedback processing.

PubMed

Ryterska, Agata; Jahanshahi, Marjan; Osman, Magda

2014-01-01

Studies examining decision-making in people with Parkinson's disease (PD) show impaired performance on a variety of tasks. However, there are also demonstrations that patients with PD can make optimal decisions just like healthy age-matched controls. We propose that the reason for these mixed findings is that PD does not produce a generalized impairment of decision-making, but rather affects sub-components of this process. In this review we evaluate this hypothesis by considering the empirical evidence examining decision-making in PD. We suggest that of the various stages of the decision-making process, the most affected in PD are (1) the cost-benefit analysis stage and (2) the outcome evaluation stage. We consider the implications of this proposal for research in this area.

Mono and bimetallic nanoparticles of gold, silver and palladium-catalyzed NADH oxidation-coupled reduction of Eosin-Y

NASA Astrophysics Data System (ADS)

Santhanalakshmi, J.; Venkatesan, P.

2011-02-01

Mono metallic (Au, Ag, Pd) and bimetallic (Au-Ag, Ag-Pd, Au-Pd) with 1:1 mol stoichiometry, nanoparticles are synthesized using one-pot, temperature controlled chemical method using cetyltrimethylammonium bromide (CTAB) as the capping agent. The particle sizes (Au = 5.6, Ag = 5.0, Pd = 6.0, Au-Ag = 9.2, Ag-Pd = 9.6, Au-Pd = 9.4 nm) are characterized by UV-Vis, HRTEM, and XRD measurements, respectively. CTAB bindings onto mono and bimetallic nanoparticles are analyzed by FTIR spectra. The catalytic activities of mono and bimetallic nanoparticles are tested on the reaction between NADH oxidation and Eosin-Y reduction. The effects of base, pH, ionic strength, nature of mono and bimetallic catalysts are studied and the reaction conditions are optimized. Bimetallic nanoparticles exhibited better catalysis than the mono metallic nanoparticles, which may be due to the electronic effects of the core to shell metal atoms.

Design of PdAg Hollow Nanoflowers through Galvanic Replacement and Their Application for Ethanol Electrooxidation.

PubMed

Bin, Duan; Yang, Beibei; Zhang, Ke; Wang, Caiqin; Wang, Jin; Zhong, Jiatai; Feng, Yue; Guo, Jun; Du, Yukou

2016-11-07

In this study, galvanic replacement provides a simple route for the synthesis of PdAg hollow nanoflower structures by using the Ag-seeds as sacrificial templates in the presence of l-ascorbic acid (reductant) and CTAC (capping agent). Transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and EDS mapping were used to characterize the as-prepared PdAg hollow nanoflower catalysts, where they were alloyed nanoflower structures with hollow interiors. By maneuvering the Pd/Ag ratio, we found that the as-prepared Pd 1 Ag 3 hollow nanoflower catalysts had the optimized performance for catalytic activity toward ethanol oxidation reaction. Moreover, these as-prepared PdAg hollow nanoflower catalysts exhibited noticeably higher electrocatalytic activity as compared to pure Pd and commercial Pd/C catalysts due to the alloyed Ag-Pd composition as well as the hollow nanoflower structures. It is anticipated that this work provides a rational design of other architecturally controlled bimetallic nanocrystals for application in fuel cells. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Detection of gene mutation in glucose-6-phosphate dehydrogenase deficiency by RT-PCR sequencing].

PubMed

Lyu, Rong-Yu; Chen, Xiao-Wen; Zhang, Min; Chen, Yun-Sheng; Yu, Jie; Wen, Fei-Qiu

2016-07-01

Since glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary hemolytic erythrocyte enzyme deficiency, most cases have single nucleotide mutations in the coding region, and current test methods for gene mutation have some missed detections, this study aimed to investigate the feasibility of RT-PCR sequencing in the detection of gene mutation in G6PD deficiency. According to the G6PD/6GPD ratio, 195 children with anemia of unknown cause or who underwent physical examination between August 2013 and July 2014 were classified into G6PD-deficiency group with 130 children (G6PD/6GPD ratio <1.00) and control group with 65 children (G6PD/6GPD ratio≥1.00). The primer design and PCR amplification conditions were optimized, and RT-PCR sequencing was used to analyze the complete coding sequence and verify the genomic DNA sequence in the two groups. In the G6PD-deficiency group, the detection rate of gene mutation was 100% and 13 missense mutations were detected, including one new mutation. In the control group, no missense mutation was detected in 28 boys; 13 heterozygous missense mutations, 1 homozygous same-sense mutation (C1191T) which had not been reported in China and abroad, and 14 single nucleotide polymorphisms of C1311T were detected in 37 girls. The control group showed a high rate of missed detection of G6PD deficiency (carriers) in the specimens from girls (35%, 13/37). RT-PCR sequencing has a high detection rate of G6PD gene mutation and a certain value in clinical diagnosis of G6PD deficiency.

Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease: A report of 12 cases.

PubMed

Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

2016-12-01

Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change.

Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease

PubMed Central

Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

2016-01-01

Abstract Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. Methods: We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. Results: We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. Conclusions: ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have unsatisfactory control of PD symptoms or stimulation-induced side effects after multiple treatments with conventional stimulation. A return to conventional stimulation may be required if ILS induces new side effects or the needs of the patient change. PMID:27930569

Associative reinstatement memory measures hippocampal function in Parkinson's Disease.

PubMed

Cohn, Melanie; Giannoylis, Irene; De Belder, Maya; Saint-Cyr, Jean A; McAndrews, Mary Pat

2016-09-01

In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Depression in Parkinson's disease: symptom improvement and residual symptoms after acute pharmacologic management.

PubMed

Dobkin, Roseanne DeFronzo; Menza, Matthew; Bienfait, Karina L; Gara, Michael; Marin, Humberto; Mark, Margery H; Dicke, Allison; Friedman, Jill

2011-03-01

Parkinson's disease (PD) is frequently complicated by depression and there is a paucity of controlled research that can inform the management of this disabling nonmotor complaint. A randomized controlled trial of nortriptyline, paroxetine, and placebo for the treatment of depression in PD (dPD) was recently completed. The purpose of this article is to describe the baseline pattern of depressive symptom presentation in PD, the specific symptoms of dPD that improve with pharmacotherapy, and the residual symptoms that remain in patients who meet a priori criteria for response or remission after acute treatment (8 weeks). The Departments of Psychiatry and Neurology at Robert Wood Johnson Medical School, New Jersey. : Fifty-two depressed patients (major depression or dysthymia based on Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria) with Parkinson's disease (by research criteria). A randomized controlled trial of nortriptyline, paroxetine, and placebo. The four subscales (core mood, anxiety, insomnia, and somatic) and individual items from the Hamilton Rating Scale for Depression-17 were the focus of this study. These measures were assessed at baseline and Week 8. Baseline depressive symptoms were unrelated to motor functioning. Treatment response was associated with significant improvements in the core mood, anxiety, insomnia, and somatic symptoms seen in dPD. Residual symptoms, such as sadness and loss of interest, persisted in treatment responders in a milder form than was initially present. Antidepressants may influence all symptoms of dPD, including those that share great overlap with the physical disease process. Additional research regarding adjunctive interventions is needed to help optimize the management of dPD.

Transient control for cascaded EDFAs by using a multi-objective optimization approach

NASA Astrophysics Data System (ADS)

Freitas, Marcio; Givigi, Sidney N., Jr.; Klein, Jackson; Calmon, Luiz C.; de Almeida, Ailson R.

2004-11-01

Erbium-doped fiber amplifiers (EDFA) have been used for some years now in building effective optical systems for the most diverse applications. For some applications, it is necessary to introduce some feedback control laws in order to avoid the generation of transients that could create impairments in the system. In this paper, we use a multi-objective optimization approach based on genetic algorithms, to study the introduction of proportional-derivative (PD) controllers into systems of cascaded EDFAs. We compare the use of individual controllers for each amplifier to the use of controllers to sets of amplifiers.

PD-1 or PD-L1 Blockade Restores Antitumor Efficacy Following SSX2 Epitope-Modified DNA Vaccine Immunization.

PubMed

Rekoske, Brian T; Smith, Heath A; Olson, Brian M; Maricque, Brett B; McNeel, Douglas G

2015-08-01

DNA vaccines have demonstrated antitumor efficacy in multiple preclinical models, but low immunogenicity has been observed in several human clinical trials. This has led to many approaches seeking to improve the immunogenicity of DNA vaccines. We previously reported that a DNA vaccine encoding the cancer-testis antigen SSX2, modified to encode altered epitopes with increased MHC class I affinity, elicited a greater frequency of cytolytic, multifunctional CD8(+) T cells in non-tumor-bearing mice. We sought to test whether this optimized vaccine resulted in increased antitumor activity in mice bearing an HLA-A2-expressing tumor engineered to express SSX2. We found that immunization of tumor-bearing mice with the optimized vaccine elicited a surprisingly inferior antitumor effect relative to the native vaccine. Both native and optimized vaccines led to increased expression of PD-L1 on tumor cells, but antigen-specific CD8(+) T cells from mice immunized with the optimized construct expressed higher PD-1. Splenocytes from immunized animals induced PD-L1 expression on tumor cells in vitro. Antitumor activity of the optimized vaccine could be increased when combined with antibodies blocking PD-1 or PD-L1, or by targeting a tumor line not expressing PD-L1. These findings suggest that vaccines aimed at eliciting effector CD8(+) T cells, and DNA vaccines in particular, might best be combined with PD-1 pathway inhibitors in clinical trials. This strategy may be particularly advantageous for vaccines targeting prostate cancer, a disease for which antitumor vaccines have demonstrated clinical benefit and yet PD-1 pathway inhibitors alone have shown little efficacy to date. ©2015 American Association for Cancer Research.

Useful field of view as a reliable screening measure of driving performance in people with Parkinson's disease: results of a pilot study.

PubMed

Classen, S; McCarthy, D P; Shechtman, O; Awadzi, K D; Lanford, D N; Okun, M S; Rodriguez, R L; Romrell, J; Bridges, S; Kluger, B; Fernandez, H H

2009-12-01

To determine the correlations of the Useful Field of View (UFOV), compared to other clinical tests of Parkinson's disease (PD); vision; and cognition with measures of on-road driving assessments and to quantify the UFOV's ability to indicate passing/failing an on-road test in people with PD. Nineteen randomly selected people with idiopathic PD, mean age = 74.8 (6.1), 14 (73.7%) men, 18 (94.7%) Caucasians, were age-matched to 104 controls without PD. The controls had a mean age of 75.4 (6.4), 59 (56.7%) men, 96 (92.3%) Caucasians. Both groups were referred for a driving evaluation after institutional review board approval. Compared to neuropsychological and clinical tests of vision and cognition, the UFOV showed the strongest correlations (r > .75, p < 0.05) with measures of failing a standardized road test and number of driving errors. Among PD patients, the UFOV Risk Index score of 3 (range 1-5) was established as the optimal cutoff value for passing the on-road test, with sensitivity 87 percent and specificity 82 percent, AUC = 92 percent (SE 0.61, p = .002). Similarly, the UFOV 2 (divided attention) optimum cutoff value is 223 ms (range 16-500 ms), sensitivity 87.5 percent, specificity 81.8 percent, AUC = 91 percent (SE 0.73, p = .003). The UFOV 3 (selected attention) optimal cutoff value is 273 ms (range 16-500 ms), sensitivity 75 percent, specificity 72.7 percent, AUC = 87 percent (SE 0.81, p = .007). In this pilot study among PD patients, the UFOV may be a superior screening measure (compared to other measures of disease, cognition, and vision) for predicting on-road driving performance but its rigor must be verified in a larger sample of people with PD.

Platinum-Based Nanocages with Subnanometer-Thick Walls and Well-Defined Facets

DOE PAGES

Zhang, Lei; Wang, Xue; Chi, Miaofang; ...

2015-07-24

A cost-effective catalyst should have a high dispersion of the active atoms, together with a controllable surface structure for the optimization of activity, selectivity, or both. We fabricated nanocages by depositing a few atomic layers of platinum (Pt) as conformal shells on palladium (Pd) nanocrystals with well-defined facets and then etching away the Pd templates. Density functional theory calculations suggest that the etching is initiated via a mechanism that involves the formation of vacancies through the removal of Pd atoms incorporated into the outermost layer during the deposition of Pt. With the use of Pd nanoscale cubes and octahedra asmore » templates, we obtained Pt cubic and octahedral nanocages enclosed by {100} and {111} facets, respectively, which exhibited distinctive catalytic activities toward oxygen reduction.« less

Engineering Defect-Free Nanoporous Pd from Optimized Pd-Ni Precursor Alloy by Understanding Palladium-Hydrogen Interactions During Dealloying

NASA Astrophysics Data System (ADS)

Schoop, Julius; Balk, T. John

2014-04-01

Thin films of nanoporous palladium (np-Pd) were produced from binary palladium-nickel (Pd-Ni) precursor alloys. A suitable precursor alloy and a method of dealloying to yield optimum nanoporosity (average pore/ligament size of 7 nm) were developed by studying the effects of various processing parameters on final microstructure. To obtain crack-free np-Pd, a 100 nm thin film of 20 at. pct Pd (80 at. pct Ni) can be dealloyed for ~5 hours in a 1 M solution of sulfuric acid, with oleic acid and oleylamine added as surfactants. Both shorter and longer dealloying times, as well as heating, inhibit the formation of crack-free np-Pd. Stress measurements at different stages of dealloying revealed that the necessary dealloying time is determined by the diffusion-controlled corrosion reaction occurring within the thin film during dealloying. Strong interaction between hydrogen and np-Pd was reflected in the stress evolution during dealloying. A mechanism is proposed for the formation of a Ni-rich dense top layer that results from H-induced swelling during initial dealloying and permits the development of defect-free np-Pd beneath, by limiting the speed of dealloying.

Pd-Pt and Fe-Ni nanoparticles formed by covalent molecular assembly in supercritical carbon dioxide.

PubMed

Puniredd, Sreenivasa Reddy; Weiyi, Seah; Srinivasan, M P

2008-04-01

We report the formation of Pd-Pt nanoparticles within a dendrimer-laden ultrathin film matrix immobilized on a solid support and constructed by covalent layer-by-layer (LbL) assembly using supercritical carbon dioxide (SCCO2) as the processing medium. Particle size distribution and composition were controlled by precursor composition. The precursor compositions are optimized for Pd-Pt nanoparticles and later extended to the formation of Fe-Ni nanoparticles. As an example of the application of nanoparticles in tribology, Fe-Ni nanoparticle-laden films were observed to exhibit better tribological properties than those containing the monometallic species, thereby suggesting that combination of nanoparticles can be used to derive greater benefits.

Analysis of automated quantification of motor activity in REM sleep behaviour disorder.

PubMed

Frandsen, Rune; Nikolic, Miki; Zoetmulder, Marielle; Kempfner, Lykke; Jennum, Poul

2015-10-01

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by dream enactment and REM sleep without atonia. Atonia is evaluated on the basis of visual criteria, but there is a need for more objective, quantitative measurements. We aimed to define and optimize a method for establishing baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. We analysed the electromyographic activity of the submental muscle in polysomnographs of 29 patients with idiopathic RBD (iRBD), 29 controls and 43 Parkinson's (PD) patients. Six adjustable parameters for motor activity were defined. Motor activity was detected and quantified automatically. The optimal parameters for separating RBD patients from controls were investigated by identifying the greatest area under the receiver operating curve from a total of 648 possible combinations. The optimal parameters were validated on PD patients. Automatic baseline estimation improved characterization of atonia during REM sleep, as it eliminates inter/intra-observer variability and can be standardized across diagnostic centres. We found an optimized method for quantifying motor activity during REM sleep. The method was stable and can be used to differentiate RBD from controls and to quantify motor activity during REM sleep in patients with neurodegeneration. No control had more than 30% of REM sleep with increased motor activity; patients with known RBD had as low activity as 4.5%. We developed and applied a sensitive, quantitative, automatic algorithm to evaluate loss of atonia in RBD patients. © 2015 European Sleep Research Society.

Optimization of Perovskite Gas Sensor Performance: Characterization, Measurement and Experimental Design.

PubMed

Bertocci, Francesco; Fort, Ada; Vignoli, Valerio; Mugnaini, Marco; Berni, Rossella

2017-06-10

Eight different types of nanostructured perovskites based on YCoO 3 with different chemical compositions are prepared as gas sensor materials, and they are studied with two target gases NO 2 and CO. Moreover, a statistical approach is adopted to optimize their performance. The innovative contribution is carried out through a split-plot design planning and modeling, also involving random effects, for studying Metal Oxide Semiconductors (MOX) sensors in a robust design context. The statistical results prove the validity of the proposed approach; in fact, for each material type, the variation of the electrical resistance achieves a satisfactory optimized value conditional to the working temperature and by controlling for the gas concentration variability. Just to mention some results, the sensing material YCo 0 . 9 Pd 0 . 1 O 3 (Mt1) achieved excellent solutions during the optimization procedure. In particular, Mt1 resulted in being useful and feasible for the detection of both gases, with optimal response equal to +10.23% and working temperature at 312 ∘ C for CO (284 ppm, from design) and response equal to -14.17% at 185 ∘ C for NO 2 (16 ppm, from design). Analogously, for NO 2 (16 ppm, from design), the material type YCo 0 . 9 O 2 . 85 + 1 % Pd (Mt8) allows for optimizing the response value at - 15 . 39 % with a working temperature at 181 . 0 ∘ C, whereas for YCo 0 . 95 Pd 0 . 05 O 3 (Mt3), the best response value is achieved at - 15 . 40 % with the temperature equal to 204 ∘ C.

Optimization of Perovskite Gas Sensor Performance: Characterization, Measurement and Experimental Design

PubMed Central

Bertocci, Francesco; Fort, Ada; Vignoli, Valerio; Mugnaini, Marco; Berni, Rossella

2017-01-01

Eight different types of nanostructured perovskites based on YCoO3 with different chemical compositions are prepared as gas sensor materials, and they are studied with two target gases NO2 and CO. Moreover, a statistical approach is adopted to optimize their performance. The innovative contribution is carried out through a split-plot design planning and modeling, also involving random effects, for studying Metal Oxide Semiconductors (MOX) sensors in a robust design context. The statistical results prove the validity of the proposed approach; in fact, for each material type, the variation of the electrical resistance achieves a satisfactory optimized value conditional to the working temperature and by controlling for the gas concentration variability. Just to mention some results, the sensing material YCo0.9Pd0.1O3 (Mt1) achieved excellent solutions during the optimization procedure. In particular, Mt1 resulted in being useful and feasible for the detection of both gases, with optimal response equal to +10.23% and working temperature at 312∘C for CO (284 ppm, from design) and response equal to −14.17% at 185∘C for NO2 (16 ppm, from design). Analogously, for NO2 (16 ppm, from design), the material type YCo0.9O2.85+1%Pd (Mt8) allows for optimizing the response value at −15.39% with a working temperature at 181.0∘C, whereas for YCo0.95Pd0.05O3 (Mt3), the best response value is achieved at −15.40% with the temperature equal to 204∘C. PMID:28604587

Effects of Metal Composition and Ratio on Peptide-Templated Multimetallic PdPt Nanomaterials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merrill, Nicholas A.; Nitka, Tadeusz T.; McKee, Erik M.

It can be difficult to simultaneously control the size, composition, and morphology of metal nanomaterials under benign aqueous conditions. For this, bio-inspired approaches have become increasing popular due to their ability to stabilize a wide array of metal catalysts under ambient conditions. In this regard, we used the R5 peptide as a 3D template for the formation of PdPt bimetallic nanomaterials. Monometallic Pd and Pt nanomaterials have been shown to be highly reactive towards a variety of catalytic processes, but by forming bimetallic species, increased catalytic activity may be realized. The optimal metal-to-metal ratio was determined by varying the Pd:Ptmore » ratio to obtain the largest increase in catalytic activity. To better understand the morphology and the local atomic structure of the materials, the bimetallic PdPt nanomaterials were extensively studied using transmission electron microscopy, extended X-ray absorption fine structure spectroscopy, X-ray photoelectron spectroscopy, and pair distribution function analysis. The resulting PdPt materials were determined to form multicomponent nanostructures where the Pt component demonstrated varying degrees of oxidation based upon the Pd:Pt ratio. To test the catalytic reactivity of the materials, olefin hydrogenation was conducted which indicated a slight catalytic enhancement for the multicomponent materials. These results suggest a strong correlation between the metal ratio and the stabilizing biotemplate in controlling the final materials morphology, composition, and the interactions between the two metal species.« less

Effects of metal composition and ratio on peptide-templated multimetallic PdPt nanomaterials

DOE PAGES

Merrill, Nicholas A.; Nitka, Tadeusz T.; McKee, Erik M.; ...

2017-02-03

It can be difficult to simultaneously control the size, composition, and morphology of metal nanomaterials under benign aqueous conditions. For this, bioinspired approaches have become increasingly popular due to their ability to stabilize a wide array of metal catalysts under ambient conditions. In this regard, we used the R5 peptide as a three-dimensional template for formation of PdPt bimetallic nanomaterials. Monometallic Pd and Pt nanomaterials have been shown to be highly reactive toward a variety of catalytic processes, but by forming bimetallic species, increased catalytic activity may be realized. The optimal metal-to-metal ratio was determined by varying the Pd:Pt ratiomore » to obtain the largest increase in catalytic activity. To better understand the morphology and the local atomic structure of the materials, the bimetallic PdPt nanomaterials were extensively studied by transmission electron microscopy, extended X-ray absorption fine structure spectroscopy, X-ray photoelectron spectroscopy, and pair distribution function analysis. The resulting PdPt materials were determined to form multicomponent nanostructures where the Pt component demonstrated varying degrees of oxidation based upon the Pd:Pt ratio. To test the catalytic reactivity of the materials, olefin hydrogenation was conducted, which indicated a slight catalytic enhancement for the multicomponent materials. Finally, these results suggest a strong correlation between the metal ratio and the stabilizing biotemplate in controlling the final materials morphology, composition, and the interactions between the two metal species.« less

Layer-by-Layer-Assembled AuNPs-Decorated First-Generation Poly(amidoamine) Dendrimer with Reduced Graphene Oxide Core as Highly Sensitive Biosensing Platform with Controllable 3D Nanoarchitecture for Rapid Voltammetric Analysis of Ultratrace DNA Hybridization.

PubMed

Jayakumar, Kumarasamy; Camarada, María Belén; Dharuman, Venkataraman; Rajesh, Rajendiran; Venkatesan, Rengarajan; Ju, Huangxian; Maniraj, Mahalingam; Rai, Abhishek; Barman, Sudipta Roy; Wen, Yangping

2018-06-27

The structure and electrochemical properties of layer-by-layer-assembled gold nanoparticles (AuNPs)-decorated first-generation (G1) poly(amidoamine) dendrimer (PD) with reduced graphene oxide (rGO) core as a highly sensitive and label-free biosensing platform with a controllable three-dimensional (3D) nanoarchitecture for the rapid voltammetric analysis of DNA hybridization at ultratrace levels were characterized. Mercaptopropinoic acid (MPA) was self-assembled onto Au substrate, then GG1PD formed by the covalent functionalization between the amino terminals of G1PD and carboxyl terminals of rGO was covalently linked onto MPA, and finally AuNPs were decorated onto GG1PD by strong physicochemical interaction between AuNPs and -OH of rGO in GG1PD, which was characterized through different techniques and confirmed by computational calculation. This 3D controllable thin-film electrode was optimized and evaluated using [Fe(CN) 6 ] 3-/4- as the redox probe and employed to covalently immobilize thiol-functionalized single-stranded DNA as biorecognition element to form the DNA nanobiosensor, which achieved fast, ultrasensitive, and high-selective differential pulse voltammetric analysis of DNA hybridization in a linear range from 1 × 10 -6 to 1 × 10 -13 g m -1 with a low detection limit of 9.07 × 10 -14 g m -1 . This work will open a new pathway for the controllable 3D nanoarchitecture of the layer-by-layer-assembled metal nanoparticles-functionalized lower-generation PD with two-dimensional layered nanomaterials as cores that can be employed as ultrasensitive and label-free nanobiodevices for the fast diagnosis of specific genome diseases in the field of biomedicine.

Artistic occupations are associated with a reduced risk of Parkinson's disease.

PubMed

Haaxma, Charlotte A; Borm, George F; van der Linden, Dimitri; Kappelle, Arnoud C; Bloem, Bastiaan R

2015-09-01

Parkinson's disease (PD) is preceded by a premotor phase of unknown duration. Dopaminergic degeneration during this phase may lead to subtle cognitive and behavioural changes, such as decreased novelty seeking. Consequently, premotor subjects might be most comfortable in jobs that do not require optimal dopamine levels, leading to an overrepresentation in structured and predictable occupations, or an underrepresentation in artistic occupations. In a case-control study, 750 men with PD (onset ≥40 years) and 1300 healthy men completed a validated questionnaire about their lifetime occupational status. Occupations were classified using the RIASEC model. Odds ratios (ORs) were calculated for the conventional and artistic categories, both for the most recent occupation before symptom onset, and for the very first occupation. Because farming has been associated with a PD risk, ORs were calculated separately for farming. A reduced risk of PD was found for men with an artistic occupation late in life (OR 0.14, 95% CI 0.04-0.53), while an artistic first occupation did not prevent PD (OR 0.72, CI 0.32-1.59). Conventional occupations showed no increased risk (recent: OR 1.07, CI 0.70-1.64; first: OR 1.14, CI 0.77-1.71). In support of previous reports, farming was associated with an increased risk of PD (recent: OR 2.6, CI 1.4-4.6; first: OR 2.7, CI 1.6-4.5). PD patients were older than controls, but various statistical corrections for age all lead to similar results. Artistic occupations late in life are associated with a reduced risk of subsequent PD, perhaps because this reflects a better preserved dopaminergic state. No initial occupation predicted PD, suggesting that the premotor phase starts later in life.

Fuzzy Controller Design Using Evolutionary Techniques for Twin Rotor MIMO System: A Comparative Study.

PubMed

Hashim, H A; Abido, M A

2015-01-01

This paper presents a comparative study of fuzzy controller design for the twin rotor multi-input multioutput (MIMO) system (TRMS) considering most promising evolutionary techniques. These are gravitational search algorithm (GSA), particle swarm optimization (PSO), artificial bee colony (ABC), and differential evolution (DE). In this study, the gains of four fuzzy proportional derivative (PD) controllers for TRMS have been optimized using the considered techniques. The optimization techniques are developed to identify the optimal control parameters for system stability enhancement, to cancel high nonlinearities in the model, to reduce the coupling effect, and to drive TRMS pitch and yaw angles into the desired tracking trajectory efficiently and accurately. The most effective technique in terms of system response due to different disturbances has been investigated. In this work, it is observed that GSA is the most effective technique in terms of solution quality and convergence speed.

Fuzzy Controller Design Using Evolutionary Techniques for Twin Rotor MIMO System: A Comparative Study

PubMed Central

Hashim, H. A.; Abido, M. A.

2015-01-01

This paper presents a comparative study of fuzzy controller design for the twin rotor multi-input multioutput (MIMO) system (TRMS) considering most promising evolutionary techniques. These are gravitational search algorithm (GSA), particle swarm optimization (PSO), artificial bee colony (ABC), and differential evolution (DE). In this study, the gains of four fuzzy proportional derivative (PD) controllers for TRMS have been optimized using the considered techniques. The optimization techniques are developed to identify the optimal control parameters for system stability enhancement, to cancel high nonlinearities in the model, to reduce the coupling effect, and to drive TRMS pitch and yaw angles into the desired tracking trajectory efficiently and accurately. The most effective technique in terms of system response due to different disturbances has been investigated. In this work, it is observed that GSA is the most effective technique in terms of solution quality and convergence speed. PMID:25960738

Parental bonds in children at high and low familial risk for panic disorder.

PubMed

Koszycki, Diana; Bilodeau, Cynthia; Zwanzger, Peter; Schneider, Barry H; Flament, Martine F; Bradwejn, Jacques

2013-04-01

A rejecting and overprotective parenting style is considered to be an important risk factor for the development of anxiety disorders. This study examined the role of perceived parental bonding as a potential environmental risk factor for panic disorder (PD) in unaffected offspring with parental PD. Children with a biological parent with PD (n = 71) and children of parents with no psychiatric history (n = 80) participated in the study. Results indicate that high risk children do not perceive their parents as being more protective and less caring than low risk controls. The optimal bonding type (high care, low protection) was the most frequently reported parenting style across groups. The constraining type of maternal bonding (high care, high protection) was less frequently reported by high risk children (p < 0.05). Overall, these data suggest that parental PD does not compromise the parent-child bonds in never-ill offspring.

Parkinson's disease-cognitive rating scale: psychometrics for mild cognitive impairment.

PubMed

Fernández de Bobadilla, Ramón; Pagonabarraga, Javier; Martínez-Horta, Saül; Pascual-Sedano, Berta; Campolongo, Antonia; Kulisevsky, Jaime

2013-09-01

Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and sensitivity to change in predementia stages of Parkinson's disease (PD) limit the utility of instruments measuring global cognition as screening and outcome measures in therapeutic trials. Investigators who were blinded to PD-Cognitive Rating Scale (PD-CRS) scores classified a cohort of prospectively recruited, nondemented patients into a PD with normal cognition (PD-NC) group and a PD with MCI (PD-MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia Rating Scale-2 (MDRS-2). The discriminative power of the PD-CRS for PD-MCI was examined in a representative sample of 234 patients (145 in the PD-NC group; 89 in the PD-MCI group) and in a control group of 98 healthy individuals. Sensitivity to change in the PD-CRS score (the minimal clinically important difference was examined with the Clinical Global Impression of Change scale and was calculated with a combination of distribution-based and anchor-based approaches) was explored in a 6-month observational multicenter trial involving a subset of 120 patients (PD-NC, 63; PD-MCI, 57). Regression analysis demonstrated that PD-CRS total scores (P < 0.001) and age (P = 0.01) independently differentiated PD-NC from PD-MCI. Area under the receiver operating characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80-0.90) indicated that a score ≤ 81 of 134 was the optimal cutoff point on the total score for the PD-CRS (sensitivity, 79%; specificity, 80%; positive predictive value, 59%; negative predictive value, 91%). A range of change from 10 to 13 points on the PD-CRS total score was indicative of clinically significant change. These findings suggest that the PD-CRS is a useful tool to identify PD-MCI and to track cognitive changes in nondemented patients with PD. © 2013 International Parkinson and Movement Disorder Society.

Efficacy of rasagiline and selegiline in Parkinson's disease: a head-to-head 3-year retrospective case-control study.

PubMed

Cereda, Emanuele; Cilia, Roberto; Canesi, Margherita; Tesei, Silvana; Mariani, Claudio Bruno; Zecchinelli, Anna Lena; Pezzoli, Gianni

2017-06-01

Monoamine oxidase type B (MAO-B) inhibitors, such as selegiline and rasagiline, can be used as monotherapy or adjuvant therapy to levodopa in Parkinson's disease (PD). Data on long-term efficacy of MAO-B inhibitors are limited with no head-to-head comparison available to date. The aim of this case-control retrospective study was to analyze data from patients with PD attending the Parkinson Institute (Milan, Italy) over a 6-year period (2009-2015) and compare the effects of selegiline and rasagiline on levodopa treatment outcomes. Patients with PD treated with either selegiline (n = 85) or rasagiline (n = 85) for 3 years as well as a control group of patients (N = 170) who have never received MAO-B inhibitors, were matched for gender, disease duration (±1 year) and age (±1 year) at baseline assessment (ratio 1:1:2). The Unified PD Rating Scale and the Hoehn-Yahr staging system were used for clinical comparisons. At baseline, mean PD duration was 6.5 years and clinical features were comparable across all three groups. After a mean follow-up of approximately 37 months, no differences in clinical progression of motor and non-motor symptoms were observed between the three groups. However, MAO-B inhibitor use was associated with ~2-fold lower change in daily dose of levodopa (p < 0.001) and lower dyskinesia scores (p = 0.028) than non-users. No intra-class differences were observed between selegiline and rasagiline. Long-term use of MAO-B inhibitors resulted in a significant reduction in levodopa requirements and a lower frequency of dyskinesias in patients with PD. Selegiline and rasagiline had equal efficacy in controlling motor symptoms in PD patients on optimized therapy.

Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

PubMed

Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn

2017-11-09

Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

The role of exergaming in Parkinson’s disease rehabilitation: a systematic review of the evidence

PubMed Central

2014-01-01

Evidence for exercise based computer games (exergaming) as a rehabilitation tool for people with Parkinson’s disease (PD) is only now emerging and is yet to be synthesised. To this end, we conducted a systematic review of the exergaming literature to establish what is known about the safety, feasibility and effectiveness of exergaming for rehabilitation of motor symptoms experienced by people with PD. Seven electronic databases were searched for key terms surrounding exergaming and PD. Data were extracted by two reviewers independently. From an initial yield of 1217 articles, seven were included in the review. Six studies used commercial games with the Nintendo Wii fit platform. The scientific quality of reporting was generally good, however the overall methodological design of studies was weak, with only one randomised controlled trial being reported. Safety: Participant safety was not measured in any of the studies. Feasibility: People with PD were able to play exergames, improve their performance of gameplay and enjoyed playing. However, one study observed that people with PD had difficulty with fast and complex games. Effectiveness: Six studies showed that exergaming elicited improvements in a range of clinical balance measures or reduction in the severity of motor symptoms. Results from the only randomised controlled trial showed that exergaming was as effective as traditional balance training for people with PD to improve the UPDRS II, standing balance and cognition, with improvements in both groups retained 60 days after the training ended. In conclusion, exergaming is an emerging tool to help rehabilitate motor skills in people with PD. Although we were able to establish that exergaming is feasible in people with PD, more research is needed to establish its safety and clinical effectiveness, particularly in the home. The use of commercial games may be too difficult for some people with PD and exergames tailored specifically to the rehabilitation needs and capabilities of people with PD are required for optimal efficacy, adherence and safety. PMID:24602325

The role of exergaming in Parkinson's disease rehabilitation: a systematic review of the evidence.

PubMed

Barry, Gillian; Galna, Brook; Rochester, Lynn

2014-03-07

Evidence for exercise based computer games (exergaming) as a rehabilitation tool for people with Parkinson's disease (PD) is only now emerging and is yet to be synthesised. To this end, we conducted a systematic review of the exergaming literature to establish what is known about the safety, feasibility and effectiveness of exergaming for rehabilitation of motor symptoms experienced by people with PD. Seven electronic databases were searched for key terms surrounding exergaming and PD. Data were extracted by two reviewers independently. From an initial yield of 1217 articles, seven were included in the review. Six studies used commercial games with the Nintendo Wii fit platform. The scientific quality of reporting was generally good, however the overall methodological design of studies was weak, with only one randomised controlled trial being reported. Participant safety was not measured in any of the studies. Feasibility: People with PD were able to play exergames, improve their performance of gameplay and enjoyed playing. However, one study observed that people with PD had difficulty with fast and complex games. Effectiveness: Six studies showed that exergaming elicited improvements in a range of clinical balance measures or reduction in the severity of motor symptoms. Results from the only randomised controlled trial showed that exergaming was as effective as traditional balance training for people with PD to improve the UPDRS II, standing balance and cognition, with improvements in both groups retained 60 days after the training ended. In conclusion, exergaming is an emerging tool to help rehabilitate motor skills in people with PD. Although we were able to establish that exergaming is feasible in people with PD, more research is needed to establish its safety and clinical effectiveness, particularly in the home. The use of commercial games may be too difficult for some people with PD and exergames tailored specifically to the rehabilitation needs and capabilities of people with PD are required for optimal efficacy, adherence and safety.

Design of the Park-in-Shape study: a phase II double blind randomized controlled trial evaluating the effects of exercise on motor and non-motor symptoms in Parkinson's disease.

PubMed

van der Kolk, Nicolien M; Overeem, Sebastiaan; de Vries, Nienke M; Kessels, Roy P C; Donders, Rogier; Brouwer, Marc; Berg, Daniela; Post, Bart; Bloem, Bas R

2015-04-16

Parkinson's disease (PD) is a neurodegenerative disorder with a wide range of motor and non-motor symptoms. Despite optimal medical management, PD still results in a high disability rate and secondary complications and many patients lead a sedentary lifestyle, which in turn is also associated with a higher co-morbidity and mortality. Exercise has been explored as a strategy to reduce secondary complications and results suggests that it not only provides general health benefits, but may also provide symptomatic relief. If this holds true exercise would be a very attractive addition to the therapeutic arsenal in PD. The supportive evidence remains incomplete. Here, we describe the design of the Park-in-Shape study, which primarily aims to evaluate whether aerobic exercise affords clinically relevant improvements in motor symptoms in sedentary PD patients. A specific new element is the introduction of gaming to optimize compliance to the exercise intervention. The Park-in-Shape study is a randomized controlled, assessor- and patient-blinded single center study. Two parallel groups will include a total of 130 patients, receiving either aerobic exercise on a home trainer equipped with gaming elements ("exergaming"), or a non-aerobic intervention (stretching, flexibility and relaxation exercises). Both groups are supported by a specifically designed motivational app that uses gaming elements to stimulate patients to exercise and rewards them after having completed the exercise. Both interventions are delivered at home at least 3 times a week for 30-45 minutes during 6 months. Eligible patients are community-dwelling, sedentary patients diagnosed with mild-moderate PD. The primary outcome is the MDS-UPDRS motor score (tested in the off state) after 6 months. Secondary outcomes include various motor and non-motor symptoms, quality of life, physical fitness, and adherence. This Park-in-Shape study is anticipated to answer the question whether high intensity aerobic exercise combined with gaming elements ("exergaming") provides symptomatic relief in PD. Strong elements include the double-blinded randomized controlled trial design, the MDS-UPDRS as valid primary outcome, the large sample size and unique combination of home-based pure aerobic exercise combined with gaming elements and motivational aspects. Dutch trial register NTR4743.

Low Pt-content ternary PdCuPt nanodendrites: an efficient electrocatalyst for oxygen reduction reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Shaofang; Zhu, Chengzhou; Song, Junhua

2017-01-01

Dendritic nanostructures are capturing increasing attentions in electrocatalysis owing to their unique structural features and low density. Herein, we report for the first time bromide ions mediated synthesis of low-Pt-content PdCuPt ternary nanodendrites via galvanic replacement reaction between Pt precursor and PdCu template in aqueous solution. The experimental results show that the ternary PdCuPt nanodendrites present enhanced electrocatalytic performance for oxygen reduction reaction in acid solution compared with commercial Pt/C as well as some state-of-the-art catalysts. In details, the mass activity of the PdCuPt catalyst with optimized composition is 1.73 A/mgPt at 0.85 V vs RHE, which is 14 timesmore » higher than that of commercial Pt/C catalyst. Moreover, the long-term stability test demonstrates its better durability in acid solution. After 5k cycles, there is still 70% electrochemical surface area maintained. This method provides an efficient way to synthesize trimetallic alloys with controllable composition and specific structure for oxygen reduction reaction.« less

Well-Coupled Nanohybrids Obtained by Component-Controlled Synthesis and in Situ Integration of Mn xPd y Nanocrystals on Vulcan Carbon for Electrocatalytic Oxygen Reduction.

PubMed

Lu, Yanan; Zhao, Shulin; Yang, Rui; Xu, Dongdong; Yang, Jing; Lin, Yue; Shi, Nai-En; Dai, Zhihui; Bao, Jianchun; Han, Min

2018-03-07

Development of cheap, highly active, and robust bimetallic nanocrystal (NC)-based nanohybrid (NH) electrocatalysts for oxygen reduction reaction (ORR) is helpful for advancing fuel cells or other renewable energy technologies. Here, four kinds of well-coupled Mn x Pd y (MnPd 3 , MnPd-Pd, Mn 2 Pd 3 , Mn 2 Pd 3 -Mn 11 Pd 21 )/C NHs have been synthesized by in situ integration of Mn x Pd y NCs with variable component ratios on pretreated Vulcan XC-72 C using the solvothermal method accompanied with annealing under Ar/H 2 atmosphere and used as electrocatalysts for ORR. Among them, the MnPd 3 /C NHs possess the unique "half-embedded and half-encapsulated" interfaces and exhibit the highest catalytic activity, which can compete with some currently reported non-Pt catalysts (e.g., Ag-Co nanoalloys, Pd 2 NiAg NCs, PdCo/N-doped porous C, G-Cu 3 Pd nanocomposites, etc.), and close to commercial Pt/C. Electrocatalytic dynamic measurements disclose that their ORR mechanism abides by the direct 4e - pathway. Moreover, their durability and methanol-tolerant capability are much higher than that of Pt/C. As revealed by spectroscopic and electrochemical analyses, the excellent catalytic performance of MnPd 3 /C NHs results from the proper component ratio of Mn and Pd and the strong interplay of their constituents, which not only facilitate to optimize the d-band center or the electronic structure of Pd but also induce the phase transformation of MnPd 3 active components and enhance their conductivity or interfacial electron transfer dynamics. This work demonstrates that MnPd 3 /C NHs are promising methanol-tolerant cathode electrocatalysts that may be employed in fuel cells or other renewable energy option.

Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants.

PubMed

McIntosh, Lindsey G; Mannava, Sishir; Camalier, Corrie R; Folley, Bradley S; Albritton, Aaron; Konrad, Peter E; Charles, David; Park, Sohee; Neimat, Joseph S

2014-01-01

Parkinson's disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

Palladium nanotubes formed by lipid tubule templating and their application in ethanol electrocatalysis.

PubMed

Wang, Yinan; Ma, Shenghua; Su, Yingchun; Han, Xiaojun

2015-04-13

Palladium nanotubes were fabricated by using lipid tubules as templates for the first time in a controlled manner. The positively charged lipid 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) was doped into lipid tubules to adsorb PdCl4 (2-) on the tubule surfaces for further reduction. The lipid tubule formation was optimized by studying the growing dynamics and ethanol/water ratio. The DOTAP-doped tubules showed pH stability from 0 to 14, which makes them ideal templates for metal plating. The Pd nanotubes are open-ended with a tunable wall thickness. They exhibited good electrocatalytic performance in ethanol. Their electrochemically active surface areas were 6.5, 10.6, and 83.2 m(2)  g(-1) for Pd nanotubes with 77, 101, and 150 nm wall thickness, respectively. These Pd nanotubes have great potential in fuel cells. The method demonstrated also opens up a way to synthesize hollow metal nanotubes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Charting the relationship between phase type-surface area-interactions between the constituent atoms and oxygen reduction activity of Pd–Cu nanocatalysts inside fuel cells by in operando high-energy X-ray diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maswadeh, Yazan; Shan, Shiyao; Prasai, Binay

The activity and stability of nanoalloy catalysts for chemical reactions driving devices for clean energy conversion, in particular the oxygen reduction reaction (ORR), depend critically on optimizing major structural characteristics of the nanoalloys, such as the phase composition, surface area and bonding interactions between the constituent atoms, for the harsh operating conditions inside the devices. The effort requires good knowledge of the potential effect of changes in these characteristics on the catalytic functionality of the nanoalloys and, hence, on the devices' performance. We present the results from an in operando high-energy X-ray diffraction (HE-XRD) study on the concurrent changes inmore » the structural characteristics and ORR activity of Pd–Cu nanoalloy catalysts as they function at the cathode of a proton exchange membrane fuel cell (PEMFC). We find that the as-prepared Pd–Cu nanoalloys with a chemical composition close to Pd1Cu1 are better ORR catalysts in comparison with Pd1Cu2, i.e. Pd-poor, and Pd3Cu1, i.e. Pd-rich, nanoalloys. Under operating conditions though, the former suffers a big loss in ORR activity appearing as a slow-mode oscillation in the current output of the PEMFC. Losses in ORR activity suffered by the latter also exhibit sudden drops and rises during the PEMFC operation. Through atomic pair distribution function (PDF) analysis of the in operando HE-XRD data, we identify the structural changes of Pd–Cu alloy NPs that are behind the peculiar decay of their ORR activity. The results uncover the instant link between the ever-adapting structural state of ORR nanocatalysts inside an operating PEMFC and the performance of the PEMFC. Besides, our results indicate that, among others, taking control over the intra-particle diffusion of metallic species in nanoalloy catalysts may improve the performance of PEMFCs significantly and, furthermore, in operando HE-XRD can be an effective tool to guide the effort. Finally, we argue that, though showing less optimal ORR activity in the as-prepared state, monophase Pd–Cu alloy catalysts with a composition ranging between Pd1Cu1 and Pd3Cu1 may deliver optimal performance inside operating PEMFCs.« less

Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

PubMed Central

Ahmad, Ijaz; Huang, Lingli; Hao, Haihong; Sanders, Pascal; Yuan, Zonghui

2016-01-01

Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model. PMID:26989688

Statistical Optimization of 1,3-Propanediol (1,3-PD) Production from Crude Glycerol by Considering Four Objectives: 1,3-PD Concentration, Yield, Selectivity, and Productivity.

PubMed

Supaporn, Pansuwan; Yeom, Sung Ho

2018-04-30

This study investigated the biological conversion of crude glycerol generated from a commercial biodiesel production plant as a by-product to 1,3-propanediol (1,3-PD). Statistical analysis was employed to derive a statistical model for the individual and interactive effects of glycerol, (NH 4 ) 2 SO 4 , trace elements, pH, and cultivation time on the four objectives: 1,3-PD concentration, yield, selectivity, and productivity. Optimum conditions for each objective with its maximum value were predicted by statistical optimization, and experiments under the optimum conditions verified the predictions. In addition, by systematic analysis of the values of four objectives, optimum conditions for 1,3-PD concentration (49.8 g/L initial glycerol, 4.0 g/L of (NH 4 ) 2 SO 4 , 2.0 mL/L of trace element, pH 7.5, and 11.2 h of cultivation time) were determined to be the global optimum culture conditions for 1,3-PD production. Under these conditions, we could achieve high 1,3-PD yield (47.4%), 1,3-PD selectivity (88.8%), and 1,3-PD productivity (2.1/g/L/h) as well as high 1,3-PD concentration (23.6 g/L).

Chemical fractionation and speciation modelling for optimization of ion-exchange processes to recover palladium from industrial wastewater.

PubMed

Folens, K; Van Hulle, S; Vanhaecke, F; Du Laing, G

2016-01-01

Palladium is used in several industrial applications and, given its high intrinsic value, intense efforts are made to recover the element. In this hydrometallurgic perspective, ion-exchange (IEX) technologies are principal means. Yet, without incorporating the chemical and physical properties of the Pd present in real, plant-specific conditions, the recovery cannot reach its technical nor economic optimum. This study characterized a relevant Pd-containing waste stream of a mirror manufacturer to provide input for a speciation model, predicting the Pd speciation as a function of pH and chloride concentration. Besides the administered neutral PdCl2 form, both positively and negatively charged [PdCln](2-n) species occur depending on the chloride concentration in solution. Purolite C100 and Relite 2AS IEX resins were selected and applied in combination with other treatment steps to optimize the Pd recovery. A combination of the cation and anion exchange resins was found successful to quantitatively recover Pd. Given the fact that Pd was also primarily associated with particles, laboratory-scale experiments focused on physical removal of the Pd-containing flow were conducted, which showed that particle-bound Pd can already be removed by physical pre-treatment prior to IEX, while the ionic fraction remains fully susceptible to the IEX mechanism.

Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease—A Computational Study

PubMed Central

Mandali, Alekhya; Chakravarthy, V. Srinivasa; Rajan, Roopa; Sarma, Sankara; Kishore, Asha

2016-01-01

Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients. PMID:27965590

An optimized proportional-derivative controller for the human upper extremity with gravity.

PubMed

Jagodnik, Kathleen M; Blana, Dimitra; van den Bogert, Antonie J; Kirsch, Robert F

2015-10-15

When Functional Electrical Stimulation (FES) is used to restore movement in subjects with spinal cord injury (SCI), muscle stimulation patterns should be selected to generate accurate and efficient movements. Ideally, the controller for such a neuroprosthesis will have the simplest architecture possible, to facilitate translation into a clinical setting. In this study, we used the simulated annealing algorithm to optimize two proportional-derivative (PD) feedback controller gain sets for a 3-dimensional arm model that includes musculoskeletal dynamics and has 5 degrees of freedom and 22 muscles, performing goal-oriented reaching movements. Controller gains were optimized by minimizing a weighted sum of position errors, orientation errors, and muscle activations. After optimization, gain performance was evaluated on the basis of accuracy and efficiency of reaching movements, along with three other benchmark gain sets not optimized for our system, on a large set of dynamic reaching movements for which the controllers had not been optimized, to test ability to generalize. Robustness in the presence of weakened muscles was also tested. The two optimized gain sets were found to have very similar performance to each other on all metrics, and to exhibit significantly better accuracy, compared with the three standard gain sets. All gain sets investigated used physiologically acceptable amounts of muscular activation. It was concluded that optimization can yield significant improvements in controller performance while still maintaining muscular efficiency, and that optimization should be considered as a strategy for future neuroprosthesis controller design. Published by Elsevier Ltd.

Dietary protein deficiency reduces lysosomal and nonlysosomal ATP-dependent proteolysis in muscle

NASA Technical Reports Server (NTRS)

Tawa, N. E. Jr; Kettelhut, I. C.; Goldberg, A. L.

1992-01-01

When rats are fed a protein deficient (PD) diet for 7 days, rates of proteolysis in skeletal muscle decrease by 40-50% (N. E. Tawa, Jr., and A. L. Goldberg. Am. J. Physiol. 263 (Endocrinol. Metab. 26): E317-325, 1992). To identify the underlying biochemical adaptations, we measured different proteolytic processes in incubated muscles. The capacity for intralysosomal proteolysis, as shown by sensitivity to methylamine or lysosomal protease inhibitors, fell 55-75% in muscles from PD rats. Furthermore, extracts of muscles of PD rats showed 30-70% lower activity of many lysosomal proteases, including cathepsins B, H, and C, and carboxypeptidases A and C, as well as other lysosomal hydrolases. The fall in cathepsin B and proteolysis was evident by 3 days on the PD diet, and both returned to control levels 3 days after refeeding of the normal diet. In muscles maintained under optimal conditions, 80-90% of protein breakdown occurs by nonlysosomal pathways. In muscles of PD rats, this ATP-dependent process was also 40-60% slower. Even though overall proteolysis decreased in muscles of PD rats, their capacity for Ca(2+)-dependent proteolysis increased (by 66%), as did the activity of the calpains (+150-250%). Thus the lysosomal and the ATP-dependent processes decrease coordinately and contribute to the fall in muscle proteolysis in PD animals.

The price of conserving avian phylogenetic diversity: a global prioritization approach

PubMed Central

Nunes, Laura A.; Turvey, Samuel T.; Rosindell, James

2015-01-01

The combination of rapid biodiversity loss and limited funds available for conservation represents a major global concern. While there are many approaches for conservation prioritization, few are framed as financial optimization problems. We use recently published avian data to conduct a global analysis of the financial resources required to conserve different quantities of phylogenetic diversity (PD). We introduce a new prioritization metric (ADEPD) that After Downlisting a species gives the Expected Phylogenetic Diversity at some future time. Unlike other metrics, ADEPD considers the benefits to future PD associated with downlisting a species (e.g. moving from Endangered to Vulnerable in the International Union for Conservation of Nature Red List). Combining ADEPD scores with data on the financial cost of downlisting different species provides a cost–benefit prioritization approach for conservation. We find that under worst-case spending $3915 can save 1 year of PD, while under optimal spending $1 can preserve over 16.7 years of PD. We find that current conservation spending patterns are only expected to preserve one quarter of the PD that optimal spending could achieve with the same total budget. Maximizing PD is only one approach within the wider goal of biodiversity conservation, but our analysis highlights more generally the danger involved in uninformed spending of limited resources. PMID:25561665

The price of conserving avian phylogenetic diversity: a global prioritization approach.

PubMed

Nunes, Laura A; Turvey, Samuel T; Rosindell, James

2015-02-19

The combination of rapid biodiversity loss and limited funds available for conservation represents a major global concern. While there are many approaches for conservation prioritization, few are framed as financial optimization problems. We use recently published avian data to conduct a global analysis of the financial resources required to conserve different quantities of phylogenetic diversity (PD). We introduce a new prioritization metric (ADEPD) that After Downlisting a species gives the Expected Phylogenetic Diversity at some future time. Unlike other metrics, ADEPD considers the benefits to future PD associated with downlisting a species (e.g. moving from Endangered to Vulnerable in the International Union for Conservation of Nature Red List). Combining ADEPD scores with data on the financial cost of downlisting different species provides a cost-benefit prioritization approach for conservation. We find that under worst-case spending $3915 can save 1 year of PD, while under optimal spending $1 can preserve over 16.7 years of PD. We find that current conservation spending patterns are only expected to preserve one quarter of the PD that optimal spending could achieve with the same total budget. Maximizing PD is only one approach within the wider goal of biodiversity conservation, but our analysis highlights more generally the danger involved in uninformed spending of limited resources.

Anticipatory and Compensatory Postural Adjustments in Response to External Lateral Shoulder Perturbations in Subjects with Parkinson's Disease.

PubMed

de Azevedo, Alexandre Kretzer E Castro; Claudino, Renato; Conceição, Josilene Souza; Swarowsky, Alessandra; Santos, Márcio José Dos

2016-01-01

The purpose of this study was to investigate the anticipatory (APA) and compensatory (CPA) postural adjustments in individuals with Parkinson's disease (PD) during lateral instability of posture. Twenty-six subjects (13 individuals with PD and 13 healthy matched controls) were exposed to predictable lateral postural perturbations. The electromyographic (EMG) activity of the lateral muscles and the displacement of the center of pressure (COP) were recorded during four time intervals that are typical for postural adjustments, i.e., immediately before (APA1, APA2) and after (CPA1 and CPA2) the postural disturbances. The magnitude of the activity of the lateral muscles in the group with PD was lower only during the CPA time intervals and not during the anticipatory adjustments (APAs). Despite this finding, subjects with PD exhibit smaller COP excursions before and after the disturbance, probably due to lack of flexibility and proprioceptive impairments. The results of this study suggest that postural instability in subjects with PD can be partially explained by decreased postural sway, before and after perturbations, and reduced muscular activity after body disturbances. Our findings can motivate new studies to investigate therapeutic interventions that optimize the use of postural adjustment strategies in subjects with PD.

Biomarkers for immunotherapy in bladder cancer: a moving target.

PubMed

Aggen, David H; Drake, Charles G

2017-11-21

Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U.S. Food and Drug Administration (FDA). The PD-1 antibody nivolumab also demonstrated an overall survival benefit, in this case in comparison to historical controls. Similarly, antibodies targeting PD-L1 including atezolizumab, durvalumab, and avelumab have now received accelerated approval from the FDA as second line treatments for mUC, with durable response lasting more than 1 year in some patients. Some of these agents are approved in the first line setting as well - based on single-arm phase II studies atezolizumab and pembrolizumab received accelerated approval for first-line treatment of cisplatin ineligible patients. Despite these multiple approvals, the development of clinically useful biomarkers to determine the optimal treatment for patients remains somewhat elusive. In this review, we examine key clinical trial results with anti-PD1/PD-L1 antibodies and discuss progress towards developing novel biomarkers beyond PD-L1 expression.

Optimal level of Au nanoparticles on Pd nanostructures providing remarkable electro-catalysis in direct ethanol fuel cell

NASA Astrophysics Data System (ADS)

Dutta, Abhijit; Mondal, Achintya; Broekmann, Peter; Datta, Jayati

2017-09-01

The designing and fabrication of economically viable electro-catalysts for ethanol oxidation reaction (EOR) in direct ethanol fuel cell (DEFC) has been one of the challenging issues over the decades. The present work deals with controlled synthesis of Pd coupled Au nano structure, as the non Pt group of catalysts for DEFC. The catalytic proficiency of bimetallic NPs (2-10 nm) are found to be strongly dependent on the Pd:Au ratio. The over voltage of EOR is considerably reduced by ∼260 mV with 33% of Au content in PdAu composition compared to Pd alone, demonstrating the beneficial role of Au and/or its surface oxides providing oxygen species at much lower potentials compared to Pd. The catalysts are further subjected to electrochemical analysis through voltammetry along with the temperature study on activation parameters. The quantitative determination of EOR products during the electrolysis is carried out by ion chromatographic analysis; vis-a-vis the coulombic efficiency of the product yield were derived from each of the compositions. Furthermore, a strong correlation among catalytic performances and bimetallic composition is established by screening the catalysts in an in-house fabricated direct ethanol anion exchange membrane fuel cell, DE(AEM)FC. The performance testing demonstrates outstanding increase of peak power density (∼40 mWcm-2, 93%) for the best accomplishment Au (33%) covered Pd (67%) catalyst in comparison with the monometallic Pd.

Immunotherapy for metastatic urothelial carcinoma: status quo and the future.

PubMed

Necchi, Andrea; Rink, Michael; Giannatempo, Patrizia; Raggi, Daniele; Xylinas, Evanguelos

2018-01-01

The treatment paradigm of urothelial carcinoma has been revolutionized by the advent of multiple anti-programmed-cell death-1/ligand-1 (PD-1/PD-L1) antibodies. Significant improvements have been obtained in the locally advanced or metastatic stage, which was lacking of therapeutic standards. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in this disease. Anti-PD-1/PD-L1 monoclonal antibodies have shown efficacy and safety in patients with urothelial carcinoma, regardless of their prognostic features. Efficacy was similar across different compounds, with objective responses that approximate 20%, with some differences favoring PD-L1-expressing patients. Typically, responding patients have good chances of achieving durable response, but biomarkers predictive of therapeutic effect are lacking. To date, evidences from randomized studies are limited to the second-line, postplatinum therapy. Despite the activity of PD-1/PD-L1 inhibitors is well established in metastatic urothelial carcinoma, multiple gray zones still exist regarding their optimal use in clinical practice. These uncertainties are related to patient and treatment-related criteria, to the optimal duration of treatment, including combination or sequence with standard chemotherapy. Special issues are represented by pseudoprogression or hyperprogression. Generally, enhanced predictive tools are needed and a myriad of further investigations are underway.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease.

PubMed

Conrad, Erin C; Mossner, James M; Chou, Kelvin L; Patil, Parag G

2018-05-23

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS. © 2018 S. Karger AG, Basel.

Human T cells engineered to express a programmed death 1/28 costimulatory retargeting molecule display enhanced antitumor activity.

PubMed

Ankri, Chen; Shamalov, Katerina; Horovitz-Fried, Miryam; Mauer, Shmuel; Cohen, Cyrille J

2013-10-15

Adoptive transfer of T cells genetically modified to express cancer-specific receptors can mediate impressive tumor regression in terminally ill patients. However, T cell function and persistence over time could be hampered by the activation of inhibitory costimulatory pathways, such as programmed death 1 (PD1)/programmed death ligand 1, leading to T cell exhaustion and providing tumor cells with an escape mechanism from immunosurveillance. In addition, the lack of positive costimulation at the tumor site can further dampen T cell response. Thus, as T cell genetic engineering has become clinically relevant, we aimed at enhancing T cell antitumor activity by genetically diverting T cell-negative costimulatory signals into positive ones using chimeric costimulatory retargeting molecules and which are composed of the PD1 extracellular domain fused to the signaling domains of positive costimulatory molecules such as CD28 and 4-1BB. After characterizing the optimal PD1 chimera, we designed and optimized a tripartite retroviral vector that enables the simultaneous expression of this chimeric molecule in conjunction with a cancer-specific TCR. Human T cells, transduced to express a PD1/28 chimeric molecule, exhibited enhanced cytokine secretion and upregulation of activation markers upon coculture with tumor cells. These engineered cells also proliferated better compared with control cells. Finally, we tested the function of these cells in two xenograft models of human melanoma tumors and show that PD1/28-engineered human T cells demonstrated superior antitumor function. Overall, we propose that engineering T cells with a costimulatory retargeting molecule can enhance their function, which bears important implications for the improvement of T cell immunotherapy.

Stability analysis via the concept of Lyapunov exponents: a case study in optimal controlled biped standing

NASA Astrophysics Data System (ADS)

Sun, Yuming; Wu, Christine Qiong

2012-12-01

Balancing control is important for biped standing. In spite of large efforts, it is very difficult to design balancing control strategies satisfying three requirements simultaneously: maintaining postural stability, improving energy efficiency and satisfying the constraints between the biped feet and the ground. In this article, a proportional-derivative (PD) controller is proposed for a standing biped, which is simplified as a two-link inverted pendulum with one additional rigid foot-link. The genetic algorithm (GA) is used to search for the control gain meeting all three requirements. The stability analysis of such a deterministic biped control system is carried out using the concept of Lyapunov exponents (LEs), based on which, the system stability, where the disturbance comes from the initial states, and the structural stability, where the disturbance comes from the PD gains, are examined quantitively in terms of stability region. This article contributes to the biped balancing control, more significantly, the method shown in the studied case of biped provides a general framework of systematic stability analysis for certain deterministic nonlinear dynamical systems.

PdCuPt Nanocrystals With Multi-branches for Enzyme-free Glucose Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Shaofang; Zhu, Chengzhou; Song, Junhua

By carefully controlling the synthesis condition, branched PtCu bimetallic templates were synthesized in aqueous solution. After the galvanic replacement reaction between PtCu templates and the Pt precursors, PdCuPt trimetallic nanocrystals with branched structures were obtained. Owing to the open structure and the optimized composition, the electrochemical experimental results reveal that the PdCuPt trimetallic nanocrystals exhibit high electrocatalytic activity, selectivity and stability for the oxidation of glucose in alkaline solution. In details, a sensitivity of 378 μA/mM/cm2 and a detection limit of 1.29 μM can be achieved. The good electrocatalytic performance should be attributed to the unique branched nanostructure as wellmore » as the synergistic effect among metals. The superior catalytic properties suggest that these nanocrystals are promising for enzyme-free detection of glucose.« less

A Randomized Controlled Trial to Determine the Appropriate Time to Initiate Peritoneal Dialysis after Insertion of Catheter (Timely PD Study).

PubMed

Ranganathan, Dwarakanathan; John, George T; Yeoh, Edward; Williams, Nicola; O'Loughlin, Barry; Han, Thin; Jeyaseelan, Lakshmanan; Ramanathan, Kavitha; Healy, Helen

2017-01-01

The optimal time for the commencement of peritoneal dialysis (PD) after PD catheter insertion is unclear. If dialysis is started too soon after insertion, dialysate leaks and infection could occur. However, by starting PD earlier, morbidity and costs can be reduced through lesser hemodialysis requirements. This is the first randomized controlled trial to determine the safest and shortest interval to commence PD after catheter insertion. All consecutive patients undergoing PD catheter insertion at the Royal Brisbane and Women's Hospital and Rockhampton Hospital from 1 March 2008 to 31 May 2013 who met the inclusion and exclusion criteria were invited to participate in the trial. Participants were randomized to 1 of 3 groups. Group 1 (G1) commenced PD at 1 week, group 2 (G2) at 2 weeks and group 3 (G3) at 4 weeks after PD catheter insertion. These groups were stratified by hospital and the presence of diabetes. Primary outcomes were the incidence of peritoneal fluid leaks or PD-related infection during the 4 weeks after commencement of PD. In total 122 participants were recruited, 39, 42, and 41 randomized to G1, G2, and G3, respectively. The primary outcome catheter leak was significantly higher in G1 (28.2%) compared with G3 (2.4%, p = 0.001) but not compared with G2 (9.5%, p = 0.044), based on intention to treat analysis. These differences were even more marked when analyzed with per protocol method: G1 had a significantly higher percentage (32.4 %) compared with G3 (3.3%, p = 0.003) but not compared with G2 (10.5%, p = 0.040). Event percentages of leak were statistically higher in G1 and occurred significantly earlier compared with other groups ( p = 0.002). Amongst diabetics, technique failure was significantly higher (28.6%) in G3 compared with 0% in G1 and 7.1% in G2 ( p = 0.036) and earlier in G3 at 163.2 days vs 176.8 and 175.8 ( p = 0.037) for G1 and G2, respectively. Leaks were higher in participants commencing PD at 1 week after catheter insertion compared with the other 2 groups, and technique failure was higher in diabetics starting PD at 4 weeks. Copyright © 2017 International Society for Peritoneal Dialysis.

Effects of annealing temperature on the H2-sensing properties of Pd-decorated WO3 nanorods

NASA Astrophysics Data System (ADS)

Lee, Sangmin; Lee, Woo Seok; Lee, Jae Kyung; Hyun, Soong Keun; Lee, Chongmu; Choi, Seungbok

2018-03-01

The temperature of the post-annealing treatment carried out after noble metal deposition onto semiconducting metal oxides (SMOs) must be carefully optimized to maximize the sensing performance of the metal-decorated SMO sensors. WO3 nanorods were synthesized by thermal evaporation of WO3 powders and decorated with Pd nanoparticles using a sol-gel method, followed by an annealing process. The effects of the annealing temperature on the hydrogen gas-sensing properties of the Pd-decorated WO3 nanorods were then examined; the optimal annealing temperature, leading to the highest response of the WO3 nanorod sensor to H2, was determined to be 600 °C. Post-annealing at 600 °C resulted in nanorods with the highest surface area-to-volume ratio, as well as in the optimal size and the largest number of deposited Pd nanoparticles, leading to the highest response and the shortest response/recovery times toward H2. The improved H2-sensing performance of the Pd-decorated WO3 nanorod sensor, compared to a sensor based on pristine WO3 nanorods, is attributed to the enhanced catalytic activity, increased surface area-to-volume ratio, and higher amounts of surface defects.

Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China.

PubMed

Liu, Si-Yang; Wu, Yi-Long

2017-07-05

Compared to chemotherapy, promising results have been obtained by blocking the PD-1 pathway using antibodies that inhibit programmed cell death protein 1 (PD-1) or programmed cell death protein ligand 1 (PD-L1). Furthermore, global researchers and doctors are exploring how to optimize this immunotherapy in 270 clinical studies. However, Chinese clinical trials of these agents remain in the early stages. We summarize the ongoing international and domestic clinical trials using PD-1 and PD-L1 inhibitors to treat lung cancer. This information can help researchers better understand the active and approved clinical trials in China, as well as the ongoing research regarding PD-1 and PD-L1 inhibitors.

A pilot study on the benefit of cognitive rehabilitation in Parkinson’s disease

PubMed Central

Adamski, Natalia; Adler, Matthias; Opwis, Klaus; Penner, Iris-Katharina

2016-01-01

Purpose: Patients with Parkinson’s disease (PD) show inefficiencies in cognitive performance including working memory functions. Since these problems impact on quality of life and overall well-being, the current study was aimed at improving patients’ situations by evaluating the computerized cognitive training tool, BrainStim. Method: A total of 19 healthy controls (HCs) and six patients with PD were included in the study. While all PD patients received cognitive training, the HC sample was subdivided into 12 subjects with training (HC-T) and 10 subjects without (HC-NT). Participants underwent a double baseline assessment, a post-training assessment, and a 3-month follow up on neuropsychological tests and self-report measures on fatigue and depression. Training was administered between the second baseline and postassessment. It comprised 16 supervised sessions according to a standardized training protocol over 4 weeks. Results: Significant improvements in verbal and visuospatial short-term and long-term memory were found in both training groups. In addition, the HC-T improved on mental speed, and verbal and visuospatial working memory. Both training groups showed stable results for all short-term visuospatial measures after 3 months. Further, the HC-T showed stable results for working memory, verbal, and visuospatial short-term and long-term memory. Conclusions: The efficacy of the applied computerized cognitive training tool BrainStim could be verified in patients with PD and healthy age-matched controls. The preliminary findings highlighted the suitability of a specific cognitive intervention to improve cognitive inefficiencies in patients with PD as well as in healthy older people. Further research on cognitive training in combination with PD drug therapy is needed to better understand the mutual interaction and to offer optimal therapeutic approaches to patients. PMID:27134671

A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study.

PubMed

2005-02-01

Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. Multicenter, randomized, placebo-controlled, double-blind, parallel-group study. Parkinson disease patients (N = 472) with at least 21/2 hours of daily "off" (poor motor function) time, despite optimized treatment with other anti-PD medications. Rasagiline, 1.0 or 0.5 mg/d, or matching placebo. Change from baseline in total daily off time measured by patients' home diaries during 26 weeks of treatment, percentage of patients completing 26 weeks of treatment, and adverse event frequency. During the treatment period, the mean adjusted total daily off time decreased from baseline by 1.85 hours (29%) in patients treated with 1.0 mg/d of rasagiline, 1.41 hours (23%) with 0.5 mg/d rasagiline, and 0.91 hour (15%) with placebo. Compared with placebo, patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day, and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day. Prespecified secondary end points also improved during rasagiline treatment, including scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (activities of daily living in the off state and motor performance in the "on" state). Rasagiline was well tolerated. Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients. In light of recently reported benefits in patients with early illness, rasagiline is a promising new treatment for PD.

Partial discharge localization in power transformers based on the sequential quadratic programming-genetic algorithm adopting acoustic emission techniques

NASA Astrophysics Data System (ADS)

Liu, Hua-Long; Liu, Hua-Dong

2014-10-01

Partial discharge (PD) in power transformers is one of the prime reasons resulting in insulation degradation and power faults. Hence, it is of great importance to study the techniques of the detection and localization of PD in theory and practice. The detection and localization of PD employing acoustic emission (AE) techniques, as a kind of non-destructive testing, plus due to the advantages of powerful capability of locating and high precision, have been paid more and more attention. The localization algorithm is the key factor to decide the localization accuracy in AE localization of PD. Many kinds of localization algorithms exist for the PD source localization adopting AE techniques including intelligent and non-intelligent algorithms. However, the existed algorithms possess some defects such as the premature convergence phenomenon, poor local optimization ability and unsuitability for the field applications. To overcome the poor local optimization ability and easily caused premature convergence phenomenon of the fundamental genetic algorithm (GA), a new kind of improved GA is proposed, namely the sequence quadratic programming-genetic algorithm (SQP-GA). For the hybrid optimization algorithm, SQP-GA, the sequence quadratic programming (SQP) algorithm which is used as a basic operator is integrated into the fundamental GA, so the local searching ability of the fundamental GA is improved effectively and the premature convergence phenomenon is overcome. Experimental results of the numerical simulations of benchmark functions show that the hybrid optimization algorithm, SQP-GA, is better than the fundamental GA in the convergence speed and optimization precision, and the proposed algorithm in this paper has outstanding optimization effect. At the same time, the presented SQP-GA in the paper is applied to solve the ultrasonic localization problem of PD in transformers, then the ultrasonic localization method of PD in transformers based on the SQP-GA is proposed. And localization results based on the SQP-GA are compared with some algorithms such as the GA, some other intelligent and non-intelligent algorithms. The results of calculating examples both stimulated and spot experiments demonstrate that the localization method based on the SQP-GA can effectively prevent the results from getting trapped into the local optimum values, and the localization method is of great feasibility and very suitable for the field applications, and the precision of localization is enhanced, and the effectiveness of localization is ideal and satisfactory.

Rotigotine transdermal system as add-on to oral dopamine agonist in advanced Parkinson's disease: an open-label study.

PubMed

Kim, Jong-Min; Chung, Sun Ju; Kim, Jae Woo; Jeon, Beom Seok; Singh, Pritibha; Thierfelder, Stephan; Ikeda, Junji; Bauer, Lars

2015-02-28

Achieving optimal symptom control with minimal side effects is a major goal in clinical practice. Dual-agent dopamine receptor agonist (DA) therapy in Parkinson's disease (PD) may represent a promising approach to treatment, as the combination of different pharmacokinetic/pharmacological profiles may result in a lesser need for high dosages and, accordingly, may be well tolerated. The objective of the current study was to investigate safety and efficacy of rotigotine transdermal system as add-on to oral DA in patients with advanced PD inadequately controlled with levodopa and low-dose oral DA. PD0015 was an open-label, multinational study in patients with advanced-PD and sleep disturbance or early-morning motor impairment. Patients were titrated to optimal dose rotigotine (≤8 mg/24 h) over 1-4 weeks and maintained for 4-7 weeks (8-week treatment). Dosage of levodopa and oral DA (pramipexole ≤1.5 mg/day, ropinirole ≤6.0 mg/day) was stable. Primary variable was Clinical Global Impressions (CGI) item 4: side effects, assessing safety. Other variables included adverse events (AEs), Patient Global Impressions of Change (PGIC), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, Parkinson's Disease Sleep Scale (PDSS-2), Pittsburgh Sleep Quality Index (PSQI), and "off" time. Of 90 patients who received rotigotine, 79 (88%) completed the study; 5 (6%) withdrew due to AEs. Most (83/89; 93%) had a CGI-4 score <3 indicating that rotigotine add-on therapy did not interfere with functioning; 6 (7%) experienced drug-related AEs that interfered with functioning (score ≥3). AEs occurring in ≥5% were application site pruritus (13%), dizziness (10%), orthostatic hypotension (10%), nausea (8%), dyskinesia (8%), and nasopharyngitis (6%). Numerical improvements in motor function (UPDRS III), activities of daily living (UPDRS II), sleep disturbances (PDSS-2, PSQI), and reduction in "off" time were observed. The majority (71/88; 81%) improved on PGIC. Addition of rotigotine transdermal system to low-dose oral DA in patients with advanced-PD was feasible and may be associated with clinical benefit. ClinicalTrials.gov identifier NCT01723904 . Trial registration date: November 6, 2012.

Palladium-zinc catalysts on mesoporous titania prepared by colloid synthesis. II. Synthesis and characterization of PdZn/TiO2 coating on inner surface of fused silica capillary

NASA Astrophysics Data System (ADS)

Okhlopkova, Lyudmila B.; Kerzhentsev, Michail A.; Tuzikov, Fedor V.; Larichev, Yurii V.; Ismagilov, Zinfer R.

2012-09-01

Nanoparticle-doped mesoporous titania coating was synthesized by incorporation of PdZn nanoparticles into TiO2 sol followed by dip coating of the sol on inner surface of fused silica capillary. Monodispersed PdZn bimetallic colloidal particles with average particle diameters of approximately 2 nm have been prepared by an ethylene glycol reduction of ZnCl2 and Pd(CH3COO)2 in the presence of polyvinylpyrrolidone. The textural properties, surface structure, chemical composition, and morphology of the samples were investigated by means of N2 sorption measurements, TEM, and X-ray diffraction. PdZn/TiO2 coating has been further analyzed by quantitative analysis of the SAXS data in combination with the density contrast method, providing direct structural-dispersion information about the active component and support. Calcination conditions suitable for surfactant removal have been optimized to obtain PdZn/TiO2 coatings with required metal particle size and composition. The high dispersion and chemical composition of the nanoparticles embedded in mesoporous titania coating have been retained with no modification after thermal treatment in vacuum at 300 °C. Results suggest how porous structure of the PdZn coating may be fine-tuned to improve the accessibility of the pores to reactants. The control of the pore size in the range of 4.9-6.8 nm of the mesoporous titania was achieved by adding co-surfactants, such as n-butanol.

A Randomized Controlled Exploratory Pilot Study to Evaluate the Effect of Rotigotine Transdermal Patch on Parkinson's Disease-Associated Chronic Pain.

PubMed

Rascol, Olivier; Zesiewicz, Theresa; Chaudhuri, K Ray; Asgharnejad, Mahnaz; Surmann, Erwin; Dohin, Elisabeth; Nilius, Sigrid; Bauer, Lars

2016-07-01

Pain is a troublesome nonmotor symptom of Parkinson's disease (PD). This double-blind exploratory pilot study (NCT01744496) was the first to specifically investigate the effect of a dopamine agonist on PD-associated pain as primary outcome. Patients with advanced PD (ie, receiving levodopa) and at least moderate PD-associated chronic pain (≥3 months, ≥4 points on 11-point Likert pain scale) were randomized to rotigotine (optimal/maximum dose ≤16 mg/24h) or placebo and maintained for 12 weeks. Primary efficacy variable was change in pain severity (Likert pain scale) from baseline to end of maintenance. Secondary variables included percentage of responders (≥2-point Likert pain scale reduction), King's PD Pain Scale (KPPS) domains, and PD Questionnaire (PDQ-8). Statistical analyses were exploratory. Of 68 randomized patients, 60 (rotigotine, 30; placebo, 30) were evaluable for efficacy. A numerical improvement in pain was observed in favor of rotigotine (Likert pain scale: least-squares mean [95%CI] treatment difference, -0.76 [-1.87 to 0.34]; P = .172), and proportion of responders was 18/30 (60%) rotigotine vs 14/30 (47%) placebo. An ∼2-fold numerical improvement in KPPS domain "fluctuation-related pain" was observed with rotigotine vs placebo. Rotigotine improved PDQ-8 vs placebo (-8.01 [-15.56 to -0.46]; P = .038). These results suggest rotigotine may improve PD-associated pain; a large-scale confirmatory study is needed. © 2015, The American College of Clinical Pharmacology.

Diagnosis of Parkinson’s disease on the basis of clinical–genetic classification: a population-based modelling study

PubMed Central

Nalls, Mike A.; McLean, Cory Y.; Rick, Jacqueline; Eberly, Shirley; Hutten, Samantha J.; Gwinn, Katrina; Sutherland, Margaret; Martinez, Maria; Heutink, Peter; Williams, Nigel; Hardy, John; Gasser, Thomas; Brice, Alexis; Price, T. Ryan; Nicolas, Aude; Keller, Margaux F.; Molony, Cliona; Gibbs, J. Raphael; Chen-Plotkin, Alice; Suh, Eunran; Letson, Christopher; Fiandaca, Massimo S.; Mapstone, Mark; Federoff, Howard J.; Noyce, Alastair J; Morris, Huw; Van Deerlin, Vivianna M.; Weintraub, Daniel; Zabetian, Cyrus; Hernandez, Dena G.; Lesage, Suzanne; Mullins, Meghan; Conley, Emily Drabant; Northover, Carrie; Frasier, Mark; Marek, Ken; Day-Williams, Aaron G.; Stone, David J.; Ioannidis, John P. A.; Singleton, Andrew B.

2015-01-01

Background Accurate diagnosis and early detection of complex disease has the potential to be of enormous benefit to clinical trialists, patients, and researchers alike. We sought to create a non-invasive, low-cost, and accurate classification model for diagnosing Parkinson’s disease risk to serve as a basis for future disease prediction studies in prospective longitudinal cohorts. Methods We developed a simple disease classifying model within 367 patients with Parkinson’s disease and phenotypically typical imaging data and 165 controls without neurological disease of the Parkinson’s Progression Marker Initiative (PPMI) study. Olfactory function, genetic risk, family history of PD, age and gender were algorithmically selected as significant contributors to our classifying model. This model was developed using the PPMI study then tested in 825 patients with Parkinson’s disease and 261 controls from five independent studies with varying recruitment strategies and designs including the Parkinson’s Disease Biomarkers Program (PDBP), Parkinson’s Associated Risk Study (PARS), 23andMe, Longitudinal and Biomarker Study in PD (LABS-PD), and Morris K. Udall Parkinson’s Disease Research Center of Excellence (Penn-Udall). Findings Our initial model correctly distinguished patients with Parkinson’s disease from controls at an area under the curve (AUC) of 0.923 (95% CI = 0.900 – 0.946) with high sensitivity (0.834, 95% CI = 0.711 – 0.883) and specificity (0.903, 95% CI = 0.824 – 0.946) in PPMI at its optimal AUC threshold (0.655). The model is also well-calibrated with all Hosmer-Lemeshow simulations suggesting that when parsed into random subgroups, the actual data mirrors that of the larger expected data, demonstrating that our model is robust and fits well. Likewise external validation shows excellent classification of PD with AUCs of 0.894 in PDBP, 0.998 in PARS, 0.955 in 23andMe, 0.929 in LABS-PD, and 0.939 in Penn-Udall. Additionally, when our model classifies SWEDD as PD, they convert within one year to typical PD more than would be expected by chance, with 4 out of 17 classified as PD converting to PD during brief follow-up; while SWEDD not classified as PD showed one conversion to PD out of 38 participants (test of proportions, p-value = 0.003). Interpretation This model may serve as a basis for future investigations into the classification, prediction and treatment of Parkinson’s disease, particularly those planning on attempting to identify prodromal or preclinical etiologically typical PD cases in prospective cohorts for efficient interventional and biomarker studies. Funding Please see the acknowledgements and funding section at the end of the manuscript. PMID:26271532

Effect of dopaminergic medication on speech dysfluency in Parkinson's disease: a longitudinal study.

PubMed

Tykalová, Tereza; Rusz, Jan; Čmejla, Roman; Klempíř, Jiří; Růžičková, Hana; Roth, Jan; Růžička, Evžen

2015-08-01

Although speech dysfluencies have been hypothesized to be associated with abnormal function of dopaminergic system, the effects of dopaminergic medication on speech fluency in Parkinson's disease (PD) have not been systematically studied. The aim of the present study was, therefore, to investigate the long-term effect of dopaminergic medication on speech fluency in PD. Fourteen de novo PD patients with no history of developmental stuttering and 14 age- and sex-matched healthy controls (HC) were recruited. PD subjects were examined three times; before the initiation of dopaminergic treatment and twice in following 6 years. The percentage of dysfluent words was calculated from reading passage and monolog. The amount of medication was expressed by cumulative doses of L-dopa equivalent. After 3-6 years of dopaminergic therapy, PD patients exhibited significantly more dysfluent events compared to healthy subjects as well as to their own speech performance before the introduction of dopaminergic therapy (p < 0.05). In addition, we found a strong positive correlation between the increased occurrence of dysfluent words and the total cumulative dose of L-dopa equivalent (r = 0.75, p = 0.002). Our findings indicate an adverse effect of prolonged dopaminergic therapy contributing to the development of stuttering-like dysfluencies in PD. These findings may have important implication in clinical practice, where speech fluency should be taken into account to optimize dopaminergic therapy.

Pharmacokinetic–pharmacodynamic relationships of central nervous system effects of scopolamine in healthy subjects

PubMed Central

Liem-Moolenaar, Marieke; de Boer, Peter; Timmers, Maarten; Schoemaker, Rik C; van Hasselt, J G Coen; Schmidt, Stephan; van Gerven, Joop M A

2011-01-01

AIM(S) Although scopolamine is a frequently used memory impairment model, the relationships between exposure and corresponding central nervous system (CNS) effects are mostly unknown. The aim of our study was to characterize these using pharmacokinetic–pharmacodynamic (PK–PD) modelling. METHODS In two double-blind, placebo-controlled, four-way crossover studies, 0.5-mg scopolamine was administered i.v. to 90 healthy male subjects. PK and PD/safety measures were monitored pre-dose and up to 8.5 h after administration. PK–PD relationships were modelled using non-linear mixed-effect modelling. RESULTS Most PD responses following scopolamine administration in 85 subjects differed significantly from placebo. As PD measures lagged behind the plasma PK profile, PK–PD relationships were modelled using an effect compartment and arbitrarily categorized according to their equilibration half-lives (t1/2keo; hysteresis measure). t1/2keo for heart rate was 17 min, saccadic eye movements and adaptive tracking 1–1.5 h, body sway, smooth pursuit, visual analogue scales alertness and psychedelic 2.5–3.5 h, pupil size, finger tapping and visual analogue scales feeling high more than 8 h. CONCLUSIONS Scopolamine affected different CNS functions in a concentration-dependent manner, which based on their distinct PK–PD characteristics seemed to reflect multiple distinct functional pathways of the cholinergic system. All PD effects showed considerable albeit variable delays compared with plasma concentrations. The t1/2keo of the central effects was longer than of the peripheral effects on heart rate, which at least partly reflects the long CNS retention of scopolamine, but possibly also the triggering of independent secondary mechanisms. PK–PD analysis can optimize scopolamine administration regimens for future research and give insight into the physiology and pharmacology of human cholinergic systems. PMID:21306419

Longitudinal decline of driving safety in Parkinson disease.

PubMed

Uc, Ergun Y; Rizzo, Matthew; O'Shea, Amy M J; Anderson, Steven W; Dawson, Jeffrey D

2017-11-07

To longitudinally assess and predict on-road driving safety in Parkinson disease (PD). Drivers with PD (n = 67) and healthy controls (n = 110) drove a standardized route in an instrumented vehicle and were invited to return 2 years later. A professional driving expert reviewed drive data and videos to score safety errors. At baseline, drivers with PD performed worse on visual, cognitive, and motor tests, and committed more road safety errors compared to controls (median PD 38.0 vs controls 30.5; p < 0.001). A smaller proportion of drivers with PD returned for repeat testing (42.8% vs 62.7%; p < 0.01). At baseline, returnees with PD made fewer errors than nonreturnees with PD (median 34.5 vs 40.0; p < 0.05) and performed similar to control returnees (median 33). Baseline global cognitive performance of returnees with PD was better than that of nonreturnees with PD, but worse than for control returnees ( p < 0.05). After 2 years, returnees with PD showed greater cognitive decline and larger increase in error counts than control returnees (median increase PD 13.5 vs controls 3.0; p < 0.001). Driving error count increase in the returnees with PD was predicted by greater error count and worse visual acuity at baseline, and by greater interval worsening of global cognition, Unified Parkinson's Disease Rating Scale activities of daily living score, executive functions, visual processing speed, and attention. Despite drop out of the more impaired drivers within the PD cohort, returning drivers with PD, who drove like controls without PD at baseline, showed many more driving safety errors than controls after 2 years. Driving decline in PD was predicted by baseline driving performance and deterioration of cognitive, visual, and functional abnormalities on follow-up. © 2017 American Academy of Neurology.

Sleep Duration and “on” Time during Different Periods of the Day and Night in Patients with Advanced Parkinson's Disease Receiving Adjunctive Ropinirole Prolonged Release

PubMed Central

Reichmann, Heinz; Cooper, James; Rolfe, Katie; Martinez-Martin, Pablo

2011-01-01

Patients undergoing long-term therapy for PD often experience motor fluctuations and nocturnal disturbances. In a post-hoc analysis, we explored effects of ropinirole prolonged release on sleep, night-time awakenings, and “on” time over 24 hours. Patients with advanced PD suboptimally controlled with L-dopa were randomized to adjunctive ropinirole prolonged release (2–24 mg/day) or placebo for 24 weeks. Awake/asleep and, if awake, “on”/“off” status was recorded via diary cards. At week 24 last observation carried forward, changes in nighttime or daytime sleep duration were not significantly different between treatments. Of patients with baseline awakenings, a significantly higher proportion in the ropinirole prolonged release group had a reduction in awakenings versus placebo. Patients receiving ropinirole prolonged release had a significantly greater increase in amount/percentage of awake time “on”/“on” without troublesome dyskinesia during all periods assessed (including night-time and early morning), versus placebo, and higher odds for being “on” on waking. Adjunctive once-daily ropinirole prolonged release may help provide 24-hour symptom control in patients with advanced PD not optimally controlled with L-dopa. PMID:21687750

Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients.

PubMed

Weintraub, Daniel; Koester, Juergen; Potenza, Marc N; Siderowf, Andrew D; Stacy, Mark; Voon, Valerie; Whetteckey, Jacqueline; Wunderlich, Glen R; Lang, Anthony E

2010-05-01

An association between dopamine-replacement therapies and impulse control disorders (ICDs) in Parkinson disease (PD) has been suggested in preliminary studies. To ascertain point prevalence estimates of 4 ICDs in PD and examine their associations with dopamine-replacement therapies and other clinical characteristics. Cross-sectional study using an a priori established sampling procedure for subject recruitment and raters blinded to PD medication status. Three thousand ninety patients with treated idiopathic PD receiving routine clinical care at 46 movement disorder centers in the United States and Canada. The Massachusetts Gambling Screen score for current problem/pathological gambling, the Minnesota Impulsive Disorders Interview score for compulsive sexual behavior and buying, and Diagnostic and Statistical Manual of Mental Disorders research criteria for binge-eating disorder. An ICD was identified in 13.6% of patients (gambling in 5.0%, compulsive sexual behavior in 3.5%, compulsive buying in 5.7%, and binge-eating disorder in 4.3%), and 3.9% had 2 or more ICDs. Impulse control disorders were more common in patients treated with a dopamine agonist than in patients not taking a dopamine agonist (17.1% vs 6.9%; odds ratio [OR], 2.72; 95% confidence interval [CI], 2.08-3.54; P < .001). Impulse control disorder frequency was similar for pramipexole and ropinirole (17.7% vs 15.5%; OR, 1.22; 95% CI, 0.94-1.57; P = .14). Additional variables independently associated with ICDs were levodopa use, living in the United States, younger age, being unmarried, current cigarette smoking, and a family history of gambling problems. Dopamine agonist treatment in PD is associated with 2- to 3.5-fold increased odds of having an ICD. This association represents a drug class relationship across ICDs. The association of other demographic and clinical variables with ICDs suggests a complex relationship that requires additional investigation to optimize prevention and treatment strategies. clinicaltrials.gov Identifier: NCT00617019.

Comparison of glycated albumin and hemoglobin A1c concentrations in diabetic subjects on peritoneal and hemodialysis.

PubMed

Freedman, Barry I; Shenoy, Rajeev N; Planer, Jonathan A; Clay, Kimberly D; Shihabi, Zak K; Burkart, John M; Cardona, Cesar Y; Andries, Lilian; Peacock, Todd P; Sabio, Hernan; Byers, Joyce R; Russell, Gregory B; Bleyer, Anthony J

2010-01-01

Relative to hemoglobin A(1c) (HbA(1c)), percentage of glycated albumin (GA%) more accurately reflects recent glycemic control in diabetic hemodialysis (HD) patients. To determine the accuracy of glycemic assays in a larger sample including patients on peritoneal dialysis (PD), HbA(1c) and GA% were measured in 519 diabetic subjects: 55 on PD, 415 on HD, and 49 non-nephropathy controls. Mean +/- SD serum glucose levels were higher in HD and PD patients relative to non-nephropathy controls (HD 169.7 +/- 62 mg/dL, PD 168.6 +/- 66 mg/dL, controls 146.1 +/- 66 mg/dL; p = 0.03 HD vs controls, p = 0.13 PD vs controls). GA% was also higher in HD and PD patients (HD 20.6% +/- 8.0%, PD 19.0% +/- 5.7%, controls 15.7% +/- 7.7%; p < 0.02 HD vs controls and PD vs controls). HbA(1c) was paradoxically lower in dialysis patients (HD 6.78% +/- 1.6%, PD 6.87% +/- 1.4%, controls 7.3% +/- 1.4%; p = 0.03 HD vs controls, p = 0.12 PD vs controls). The serum glucose/HbA(1c) ratio differed significantly between dialysis patients and controls (p < 0.0001 HD vs controls, p = 0.002 PD vs controls), while serum glucose/GA% ratio was similar across groups (p = 0.96 HD vs controls, p = 0.64 PD vs controls). In best-fit multivariate models with HbA(1c) or GA% as outcome variable, dialysis status was a significant predictor of HbA(1c) but not GA%. The relationship between HbA(1c) and GA% differs in diabetic patients with end-stage renal disease who perform either PD or HD compared to those without nephropathy. HbA(1c) significantly underestimates glycemic control in peritoneal and hemodialysis patients relative to GA%.

The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS): Unifying Efforts to Inform Practice and Improve Global Outcomes in Peritoneal Dialysis

PubMed Central

Perl, Jeffrey; Davies, Simon J.; Lambie, Mark; Pisoni, Ronald L.; McCullough, Keith; Johnson, David W.; Sloand, James A.; Prichard, Sarah; Kawanishi, Hideki; Tentori, Francesca; Robinson, Bruce M.

2016-01-01

♦ Background: Extending technique survival on peritoneal dialysis (PD) remains a major challenge in optimizing outcomes for PD patients while increasing PD utilization. The primary objective of the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) is to identify modifiable practices associated with improvements in PD technique and patient survival. In collaboration with the International Society for Peritoneal Dialysis (ISPD), PDOPPS seeks to standardize PD-related data definitions and provide a forum for effective international collaborative clinical research in PD. ♦ Methods: The PDOPPS is an international prospective cohort study in Australia, Canada, Japan, the United Kingdom (UK), and the United States (US). Each country is enrolling a random sample of incident and prevalent patients from national samples of 20 to 80 sites with at least 20 patients on PD. Enrolled patients will be followed over an initial 3-year study period. Demographic, comorbidity, and treatment-related variables, and patient-reported data, will be collected over the study course. The primary outcome will be all-cause PD technique failure or death; other outcomes will include cause-specific technique failure, hospitalizations, and patient-reported outcomes. ♦ Results: A high proportion of the targeted number of study sites has been recruited to date in each country. Several ancillary studies have been funded with high momentum toward expansion to new countries and additional participation. ♦ Conclusion: The PDOPPS is the first large, international study to follow PD patients longitudinally to capture clinical practice. With data collected, the study will serve as an invaluable resource and research platform for the international PD community, and provide a means to understand variation in PD practices and outcomes, to identify optimal practices, and to ultimately improve outcomes for PD patients. PMID:26526049

The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS): Unifying Efforts to Inform Practice and Improve Global Outcomes in Peritoneal Dialysis.

PubMed

Perl, Jeffrey; Davies, Simon J; Lambie, Mark; Pisoni, Ronald L; McCullough, Keith; Johnson, David W; Sloand, James A; Prichard, Sarah; Kawanishi, Hideki; Tentori, Francesca; Robinson, Bruce M

2016-01-01

♦ Extending technique survival on peritoneal dialysis (PD) remains a major challenge in optimizing outcomes for PD patients while increasing PD utilization. The primary objective of the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) is to identify modifiable practices associated with improvements in PD technique and patient survival. In collaboration with the International Society for Peritoneal Dialysis (ISPD), PDOPPS seeks to standardize PD-related data definitions and provide a forum for effective international collaborative clinical research in PD. ♦ The PDOPPS is an international prospective cohort study in Australia, Canada, Japan, the United Kingdom (UK), and the United States (US). Each country is enrolling a random sample of incident and prevalent patients from national samples of 20 to 80 sites with at least 20 patients on PD. Enrolled patients will be followed over an initial 3-year study period. Demographic, comorbidity, and treatment-related variables, and patient-reported data, will be collected over the study course. The primary outcome will be all-cause PD technique failure or death; other outcomes will include cause-specific technique failure, hospitalizations, and patient-reported outcomes. ♦ A high proportion of the targeted number of study sites has been recruited to date in each country. Several ancillary studies have been funded with high momentum toward expansion to new countries and additional participation. ♦ The PDOPPS is the first large, international study to follow PD patients longitudinally to capture clinical practice. With data collected, the study will serve as an invaluable resource and research platform for the international PD community, and provide a means to understand variation in PD practices and outcomes, to identify optimal practices, and to ultimately improve outcomes for PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

An expert opinion on safinamide in Parkinson's disease.

PubMed

Onofrj, Marco; Bonanni, Laura; Thomas, Astrid

2008-07-01

Dopamine replacement therapies (levodopa, dopamine receptor agonists, anticholinergics, monoamine oxidase B inhibitors, and catechol-O-methyltransferase inhibitors) remain the cornerstones of therapeutic interventions for Parkinson's disease (PD). Despite the treatment options for PD symptoms, a cure remains elusive. An optimal treatment would be one that combined relief in both motor and nonmotor symptoms with neuroprotective properties. Safinamide is an investigational drug for PD currently in development as add-on therapy to both dopamine agonists and levodopa. Safinamide is a unique molecule with a novel mode of action, targeting both dopaminergic and glutaminergic systems, and potentially provides motor symptom control. Preliminary results from experimental models suggest potential neuroprotective effects. Studies on the potential effects on nonmotor symptoms are ongoing. To review the mechanism of action and pharmacokinetics, and to evaluate the available clinical safety and efficacy results of safinamide. A search of the electronic database MEDLINE (PubMed, no time limits) was performed on 14 December 2007. The full text of all citations was obtained for review. Furthermore, two abstracts on safinamide published as proceedings of a European conference were reviewed. Safinamide is a promising investigational drug for PD with a novel mode of action. Early reports confirm the potential efficacy of safinamide in PD. Further studies on potential effects on cognition and neuroprotection are needed.

Pharyngeal Dystonia Mimicking Spasmodic Dysphonia.

PubMed

Shi, Lucy L; Simpson, C Blake; Hapner, Edie R; Jinnah, Hyder A; Johns, Michael M

2018-03-01

The aim of this study was to describe the presentation of pharyngeal dystonia (PD), which can occur as a focal or segmental dystonia with a primarily pharyngeal involvement for the discussion of treatment methods for controlling consequent symptoms. PD is specific to speech-related tasks. A retrospective medical record review of four patients with PD was performed. All patients were initially misdiagnosed with adductor spasmodic dysphonia and failed standard treatment with botulinum toxin type A (BTX). On laryngoscopy, the patients were discovered to have segmental or focal dystonia primarily affecting the pharyngeal musculature contributing to their vocal manifestations. A novel treatment regimen was designed, which involved directing BTX injections into the muscles involved in spasmodic valving at the oropharyngeal level. After titrating to an optimal dose, all patients showed improvement in their voice and speech with only mild dysphagia. These patients have maintained favorable results with repeat injections at 6- to 12-week intervals. PD, or dystonia with predominant pharyngeal involvement, is a rare entity with vocal manifestations that are not well described. It can be easily mistaken for spasmodic dysphonia. PD is specific to speech-related tasks. A novel method of BTX injections into the involved muscles results in a significant improvement in voice without significant dysphagia. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Reward Pays the Cost of Noise Reduction in Motor and Cognitive Control.

PubMed

Manohar, Sanjay G; Chong, Trevor T-J; Apps, Matthew A J; Batla, Amit; Stamelou, Maria; Jarman, Paul R; Bhatia, Kailash P; Husain, Masud

2015-06-29

Speed-accuracy trade-off is an intensively studied law governing almost all behavioral tasks across species. Here we show that motivation by reward breaks this law, by simultaneously invigorating movement and improving response precision. We devised a model to explain this paradoxical effect of reward by considering a new factor: the cost of control. Exerting control to improve response precision might itself come at a cost--a cost to attenuate a proportion of intrinsic neural noise. Applying a noise-reduction cost to optimal motor control predicted that reward can increase both velocity and accuracy. Similarly, application to decision-making predicted that reward reduces reaction times and errors in cognitive control. We used a novel saccadic distraction task to quantify the speed and accuracy of both movements and decisions under varying reward. Both faster speeds and smaller errors were observed with higher incentives, with the results best fitted by a model including a precision cost. Recent theories consider dopamine to be a key neuromodulator in mediating motivational effects of reward. We therefore examined how Parkinson's disease (PD), a condition associated with dopamine depletion, alters the effects of reward. Individuals with PD showed reduced reward sensitivity in their speed and accuracy, consistent in our model with higher noise-control costs. Including a cost of control over noise explains how reward may allow apparent performance limits to be surpassed. On this view, the pattern of reduced reward sensitivity in PD patients can specifically be accounted for by a higher cost for controlling noise. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi, China: determination of optimal cutoff value to identify heterozygous female neonates.

PubMed

Fu, Chunyun; Luo, Shiyu; Li, Qifei; Xie, Bobo; Yang, Qi; Geng, Guoxing; Lin, Caijuan; Su, Jiasun; Zhang, Yue; Wang, Jin; Qin, Zailong; Luo, Jingsi; Chen, Shaoke; Fan, Xin

2018-01-16

The aim of this study is to assess the disease incidence and mutation spectrum of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangxi, China, and to determine an optimal cutoff value to identify heterozygous female neonates. A total of 130, 635 neonates were screened from the year of 2013 to 2017. Neonates suspected for G6PD deficiency were further analyzed by quantitatively enzymatic assay and G6PD mutation analysis. The overall incidence of G6PD deficiency was 7.28%. A total of 14 G6PD mutations were identified, and different mutations lead to varying levels of G6PD enzymatic activities. The best cut-off value of G6PD activity in male subjects is 2.2 U/g Hb, same as conventional setting. In female population, however, the cut-off value is found to be 2.8 U/g Hb (sensitivity: 97.5%, specificity: 87.7%, AUC: 0.964) to best discriminate between normal and heterozygotes, and 1.6 U/g Hb (sensitivity: 82.2%, specificity: 85.9%, AUC: 0.871) between heterozygotes and deficient subjects. In conclusion, we have conducted a comprehensive newborn screening of G6PD deficiency in a large cohort of population from Guangxi, China, and first established a reliable cut-off value of G6PD activity to distinguish heterozygous females from either normal or deficient subjects.

Genomic, Proteomic and Morphological Characterization of Two Novel Broad Host Lytic Bacteriophages ΦPD10.3 and ΦPD23.1 Infecting Pectinolytic Pectobacterium spp. and Dickeya spp.

PubMed Central

Czajkowski, Robert; Ozymko, Zofia; de Jager, Victor; Siwinska, Joanna; Smolarska, Anna; Ossowicki, Adam; Narajczyk, Magdalena; Lojkowska, Ewa

2015-01-01

Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc), P. wasabiae (Pwa) and Dickeya solani (Dso) with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Pulsed-field gel electrophoresis (PFGE), genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed. PMID:25803051

Photocatalytic reductive dechlorination of 2-chlorodibenzo-p-dioxin by Pd modified g-C3N4 photocatalysts under UV-vis irradiation: Efficacy, kinetics and mechanism.

PubMed

Ding, Jiafeng; Long, Gaoyuan; Luo, Yang; Sun, Runze; Chen, Mengxia; Li, Yajun; Zhou, Yanfang; Xu, Xinhua; Zhao, Weirong

2018-05-09

Polychlorinated dibenzo-p-dioxins (PCDDs), as a group of notorious anthropogenic environmental toxicants, are arguably ubiquitous in nature. In this study, we investigated the photocatalytic reductive dechlorination of 2-chlorodibenzo-p-dioxin (2-CDD) over Pd/g-C 3 N 4 catalysts under UV-vis irradiation. The g-C 3 N 4 and a series of Pd/g-C 3 N 4 catalysts were prepared by thermal polymerization and mechanical mixing-illumination method and characterized by XRD, TEM, BET, SEM and UV-vis DRS analyses. Among all the samples, the Pd/g-C 3 N 4 (5 wt%) yielded the optimal dechlorination activity with a total 2-CDD conversion of 54% within 4 h, and 76% of those converted 2-CDD were evolved to dibenzo-p-dioxin (DD). The kinetics of dechlorination could be described as pseudo-first-order decay model (R 2  > 0.84). Corresponding rate constants (k) increased from 0.052 to 0.17 h -1 with Pd contents up to 5 wt% and decreased to 0.13 h -1 with a 10 wt% of Pd. The enhanced activities originated from the surface plasmonic resonance (SPR) effect of Pd nanoparticles and the formation of Schottky barrier between Pd and g-C 3 N 4 , which extend the spectrum responsive range and suppress the charge recombination of g-C 3 N 4 . This is the first report on the photocatalytic reductive removal of PCDDs and may provide a new approach for PCDDs pollution control. Copyright © 2018 Elsevier B.V. All rights reserved.

Study on the influence factors of camouflage target polarization detection

NASA Astrophysics Data System (ADS)

Huang, Yanhua; Chen, Lei; Li, Xia; Wu, Wenyuan

2016-10-01

The degree of linear polarization (DOLP) expressions at any polarizer direction (PD) was deduced based on the Stokes vector and Mueller matrix. The outdoors experiments were carried out to demonstrate the expressions. This paper mainly explored the DOLP-image-Contrast (DOLPC) between the target image and the background image, and the PD and RGB waveband that be considered two important influence factors were studied for camouflage target polarization detection. It was found that the DOLPC of target and background was obviously higher than intensity image. When setting the reference direction that polarizer was perpendicular to the incident face, the DOLP image of interval angle 60 degree between PD and reference direction had relatively high DOLPC, the interval angle 45 degree was the second, and the interval angle 35 degree was the third. The outdoors polarization detection experiment of controlling waveband showed that the DOLPC results was significantly different to use 650nm, 550nm and 450nm waveband, and the polarization detection performance by using 650nm band was an optimization method.

Determination of kinetic parameters of 1,3-propanediol fermentation by Clostridium diolis using statistically optimized medium.

PubMed

Kaur, Guneet; Srivastava, Ashok K; Chand, Subhash

2012-09-01

1,3-propanediol (1,3-PD) is a chemical compound of immense importance primarily used as a raw material for fiber and textile industry. It can be produced by the fermentation of glycerol available abundantly as a by-product from the biodiesel plant. The present study was aimed at determination of key kinetic parameters of 1,3-PD fermentation by Clostridium diolis. Initial experiments on microbial growth inhibition were followed by optimization of nutrient medium recipe by statistical means. Batch kinetic data from studies in bioreactor using optimum concentration of variables obtained from statistical medium design was used for estimation of kinetic parameters of 1,3-PD production. Direct use of raw glycerol from biodiesel plant without any pre-treatment for 1,3-PD production using this strain investigated for the first time in this work gave results comparable to commercial glycerol. The parameter values obtained in this study would be used to develop a mathematical model for 1,3-PD to be used as a guide for designing various reactor operating strategies for further improving 1,3-PD production. An outline of protocol for model development has been discussed in the present work.

Piezo-phototronic UV/visible photosensing with optical-fiber-nanowire hybridized structures.

PubMed

Wang, Zhaona; Yu, Ruomeng; Pan, Caofeng; Liu, Ying; Ding, Yong; Wang, Zhong Lin

2015-03-04

An optical-fiber-nanowire hybridized UV-visible photodetector (PD) is reported. The PD is designed to allow direct integration in optical communication systems without requiring the use of couplers via fiber-welding technology. The PD works in two modes: axial and off-axial illumination mode. By using the piezo-phototronic effect, the performance of the PD is enhanced/optimized by up to 718% in sensitivity and 2067% in photoresponsivity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bidirectional active control of structures with type-2 fuzzy PD and PID

NASA Astrophysics Data System (ADS)

Paul, Satyam; Yu, Wen; Li, Xiaoou

2018-03-01

Proportional-derivative and proportional-integral-derivative (PD/PID) controllers are popular algorithms in structure vibration control. In order to maintain minimum regulation error, the PD/PID control require big proportional and derivative gains. The control performances are not satisfied because of the big uncertainties in the buildings. In this paper, type-2 fuzzy system is applied to compensate the unknown uncertainties, and is combined with the PD/PID control. We prove the stability of these fuzzy PD and PID controllers. The sufficient conditions can be used for choosing the gains of PD/PID. The theory results are verified by a two-storey building prototype. The experimental results validate our analysis.

Neuropsychiatric Complications of Parkinson Disease Treatments: Importance of Multidisciplinary Care.

PubMed

Taylor, Jacob; Anderson, William S; Brandt, Jason; Mari, Zoltan; Pontone, Gregory M

2016-12-01

Although Parkinson disease (PD) is defined clinically by its motor symptoms, it is increasingly recognized that much of the disability and worsened quality of life experienced by patients with PD is attributable to psychiatric symptoms. The authors describe a model of multidisciplinary care that enables these symptoms to be effectively managed. They describe neuropsychiatric complications of PD itself and pharmacologic and neurostimulation treatments for parkinsonian motor symptoms and discuss the management of these complications. Specifically, they describe the clinical associations between motor fluctuations and anxiety and depressive symptoms, the compulsive overuse of dopaminergic medications prescribed for motor symptoms (the dopamine dysregulation syndrome), and neuropsychiatric complications of these medications, including impulse control disorders, psychosis, and manic syndromes. Optimal management of these problems requires close collaboration across disciplines because of the potential for interactions among the pathophysiologic process of PD, motor symptoms, dopaminergic drugs, and psychiatric symptoms. The authors emphasize how their model of multidisciplinary care facilitates close collaboration among psychiatrists, other mental health professionals, neurologists, and functional neurosurgeons and how this facilitates effective care for patients who develop the specific neuropsychiatric complications discussed. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Switching PD-based sliding mode control for hovering of a tilting-thruster underwater robot.

PubMed

Jin, Sangrok; Bak, Jeongae; Kim, Jongwon; Seo, TaeWon; Kim, Hwa Soo

2018-01-01

This paper presents a switching PD-based sliding mode control (PD-SMC) method for the 6-degree-of-freedom (DOF) hovering motion of the underwater robot with tilting thrusters. Four thrusters of robot can be tilted simultaneously in the horizontal and vertical directions, and the 6-DOF motion is achieved by switching between two thruster configurations. Therefore, the tilting speed of thruster becomes the most essential parameter to determine the stability of hovering motion. Even though the previous PD control ensures stable hovering motion within a certain ranges of tilting speed, a PD-SMC is suggested in this paper by combining PD control with sliding mode control in order to achieve acceptable hovering performance even at the much lower tilting speeds. Also, the sign function in the sliding mode control is replaced by a sigmoid function to reduce undesired chattering. Simulations show that while PD control is effective only for tilting duration of 600 ms, the PD-based sliding mode control can guarantee the stable hovering motion of underwater robot even for the tilting duration of up to 1500 ms. Extensive experimental results confirm the hovering performance of the proposed PD-SMC method is much superior to that of PD method for much larger tilting durations.

Theory and Applications of Weakly Interacting Markov Processes

DTIC Science & Technology

2018-02-03

Moderate deviation principles for stochastic dynamical systems. Boston University, Math Colloquium, March 27, 2015. • Moderate Deviation Principles for...Markov chain approximation method. Submitted. [8] E. Bayraktar and M. Ludkovski. Optimal trade execution in illiquid markets. Math . Finance, 21(4):681...701, 2011. [9] E. Bayraktar and M. Ludkovski. Liquidation in limit order books with controlled intensity. Math . Finance, 24(4):627–650, 2014. [10] P.D

Pharmacokinetic-Pharmacodynamic Modeling of the Anti-Tumor Effect of Sunitinib Combined with Dopamine in the Human Non-Small Cell Lung Cancer Xenograft.

PubMed

Hao, Fangran; Wang, Siyuan; Zhu, Xiao; Xue, Junsheng; Li, Jingyun; Wang, Lijie; Li, Jian; Lu, Wei; Zhou, Tianyan

2017-02-01

To investigate the anti-tumor effect of sunitinib in combination with dopamine in the treatment of nu/nu nude mice bearing non-small cell lung cancer (NSCLC) A549 cells and to develop the combination PK/PD model. Further, simulations were conducted to optimize the administration regimens. A PK/PD model was developed based on our preclinical experiment to explore the relationship between plasma concentration and drug effect quantitatively. Further, the model was evaluated and validated. By fixing the parameters obtained from the PK/PD model, simulations were built to predict the tumor suppression under various regimens. The synergistic effect was observed between sunitinib and dopamine in the study, which was confirmed by the effect constant (GAMA, estimated as 2.49). The enhanced potency of dopamine on sunitinib was exerted by on/off effect in the PK/PD model. The optimal dose regimen was selected as sunitinib (120 mg/kg, q3d) in combination with dopamine (2 mg/kg, q3d) based on the simulation study. The synergistic effect of sunitinib and dopamine was demonstrated by the preclinical experiment and confirmed by the developed PK/PD model. In addition, the regimens were optimized by means of modeling as well as simulation, which may be conducive to clinical study.

Mid-frontal theta activity is diminished during cognitive control in Parkinson's disease.

PubMed

Singh, Arun; Richardson, Sarah Pirio; Narayanan, Nandakumar; Cavanagh, James F

2018-05-23

Mid-frontal theta activity underlies cognitive control. These 4-8 Hz rhythms are modulated by cortical dopamine and can be abnormal in patients with Parkinson's disease (PD). Here, we investigated mid-frontal theta deficits in PD patients during a task explicitly involving cognitive control. We collected scalp EEG from high-performing PD patients and demographically matched controls during performance of a modified Simon reaction-time task. This task involves cognitive control to adjudicate response conflict and error-related adjustments. Task performance of PD patients was indistinguishable from controls, but PD patients had less mid-frontal theta modulations around cues and responses. Critically, PD patients had attenuated mid-frontal theta activity specifically associated with response conflict and post-error processing. These signals were unaffected by medication or motor scores. Post-error mid-frontal theta activity was correlated with disease duration. Classification of control vs. PD from these data resulted in a specificity of 69% and a sensitivity of 72%. These findings help define the scope of mid-frontal theta aberrations during cognitive control in PD, and may provide insight into the nature of PD-related cognitive dysfunction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Postural control and freezing of gait in Parkinson's disease.

PubMed

Schlenstedt, Christian; Muthuraman, Muthuraman; Witt, Karsten; Weisser, Burkhard; Fasano, Alfonso; Deuschl, Günther

2016-03-01

The relationship between freezing of gait (FOG) and postural instability in Parkinson's disease (PD) is unclear. We analyzed the impact of FOG on postural control. 31 PD patients with FOG (PD+FOG), 27 PD patients without FOG (PD-FOG) and 22 healthy control (HC) were assessed in the ON state. Postural control was measured with the Fullerton Advanced Balance (FAB) scale and with center of pressure (COP) analysis during quiet stance and maximal voluntary forward/backward leaning. The groups were balanced concerning age, disease duration and disease severity. PD+FOG performed significantly worse in the FAB scale (21.8 ± 5.8) compared to PD-FOG (25.6 ± 5.0) and HC (34.9 ± 2.4) (mean ± SD, p < 0.01). PD+FOG had impaired ability to voluntary lean forward, difficulties to stand on foam with eyes closed and reduced limits of stability compared to PD-FOG (p < 0.05). During quiet stance the average anterior-posterior COP position was significantly displaced towards posterior in PD+FOG in comparison to PD-FOG and HC (p < 0.05). The COP position correlated with severity of FOG (p < 0.01). PD+FOG and PD-FOG did not differ in average COP sway excursion, sway velocity, sway regularity and postural control asymmetry. PD+FOG have reduced postural control compared to PD-FOG and HC. Our results show a relationship between the anterior-posterior COP position during quiet stance and FOG. The COP shift towards posterior in PD+FOG leads to a restricted precondition to generate forward progression during gait initiation. This may contribute to the occurrence of FOG or might be a compensatory strategy to avoid forward falls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Periodontal disease and diabetes mellitus.

PubMed

Negrato, Carlos Antonio; Tarzia, Olinda; Jovanovič, Lois; Chinellato, Luiz Eduardo Montenegro

2013-01-01

Periodontal disease (PD) is one of the most commonly known human chronic disorders. The relationship between PD and several systemic diseases such as diabetes mellitus (DM) has been increasingly recognized over the past decades. The purpose of this review is to provide the reader with knowledge concerning the relationship between PD and DM. Many articles have been published in the English and Portuguese literature over the last 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of DM, PD and different clinical criteria were applied to determine the prevalence, extent and severity of PD, levels of glycemic control and diabetes-related complications. This paper provides a broad overview of the predominant findings from research conducted using the BBO (Bibliografia Brasileira de Odontologia), MEDLINE, LILACS and PubMed for Controlled Trials databases, in English and Portuguese languages published from 1960 to October 2012. Primary research reports on investigations of relationships between DM/DM control, PD/periodontal treatment and PD/DM/diabetes-related complications identified relevant papers and meta-analyses published in this period. This paper describes the relationship between PD and DM and answers the following questions: 1- The effect of DM on PD, 2- The effects of glycemic control on PD and 3- The effects of PD on glycemic control and on diabetes-related complications. The scientific evidence reviewed supports diabetes having an adverse effect on periodontal health and PD having an adverse effect on glycemic control and on diabetes-related complications. Further research is needed to clarify these relationships and larger, prospective, controlled trials with ethnically diverse populations are warranted to establish that treating PD can positively influence glycemic control and possibly reduce the burden of diabetes-related complications.

Periodontal disease and diabetes mellitus

PubMed Central

NEGRATO, Carlos Antonio; TARZIA, Olinda; JOVANOVIČ, Lois; CHINELLATO, Luiz Eduardo Montenegro

2013-01-01

Periodontal disease (PD) is one of the most commonly known human chronic disorders. The relationship between PD and several systemic diseases such as diabetes mellitus (DM) has been increasingly recognized over the past decades. Objective: The purpose of this review is to provide the reader with knowledge concerning the relationship between PD and DM. Many articles have been published in the english and Portuguese literature over the last 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of DM, PD and different clinical criteria were applied to determine the prevalence, extent and severity of PD, levels of glycemic control and diabetes-related complications. Methods: This paper provides a broad overview of the predominant findings from research conducted using the BBO (Bibliografia Brasileira de Odontologia), MEDLINE, LILACS and PubMed for Controlled Trials databases, in english and Portuguese languages published from 1960 to October 2012. Primary research reports on investigations of relationships between DM/DM control, PD/periodontal treatment and PD/DM/diabetes-related complications identified relevant papers and meta-analyses published in this period. Results: This paper describes the relationship between PD and DM and answers the following questions: 1- The effect of DM on PD, 2- The effects of glycemic control on PD and 3- The effects of PD on glycemic control and on diabetes-related complications. Conclusions: The scientific evidence reviewed supports diabetes having an adverse effect on periodontal health and PD having an adverse effect on glycemic control and on diabetes-related complications. Further research is needed to clarify these relationships and larger, prospective, controlled trials with ethnically diverse populations are warranted to establish that treating PD can positively influence glycemic control and possibly reduce the burden of diabetes-related complications. PMID:23559105

Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial.

PubMed

Devos, David; Moreau, Caroline; Maltête, David; Lefaucheur, Romain; Kreisler, Alexandre; Eusebio, Alexandre; Defer, Gilles; Ouk, Thavarak; Azulay, Jean-Philippe; Krystkowiak, Pierre; Witjas, Tatiana; Delliaux, Marie; Destée, Alain; Duhamel, Alain; Bordet, Régis; Defebvre, Luc; Dujardin, Kathy

2014-06-01

Even with optimal dopaminergic treatments, many patients with Parkinson's disease (PD) are frequently incapacitated by apathy prior to the development of dementia. We sought to establish whether rivastigmine's ability to inhibit acetyl- and butyrylcholinesterases could relieve the symptoms of apathy in dementia-free, non-depressed patients with advanced PD. We performed a multicentre, parallel, double-blind, placebo-controlled, randomised clinical trial (Protocol ID: 2008-002578-36; clinicaltrials.gov reference: NCT00767091) in patients with PD with moderate to severe apathy (despite optimised dopaminergic treatment) and without dementia. Patients from five French university hospitals were randomly assigned 1:1 to rivastigmine (transdermal patch of 9.5 mg/day) or placebo for 6 months. The primary efficacy criterion was the change over time in the Lille Apathy Rating Scale (LARS) score. 101 consecutive patients were screened, 31 were eligible and 16 and 14 participants were randomised into the rivastigmine and placebo groups, respectively. Compared with placebo, rivastigmine improved the LARS score (from -11.5 (-15/-7) at baseline to -20 (-25/-12) after treatment; F(1, 25)=5.2; p=0.031; adjusted size effect: -0.9). Rivastigmine also improved the caregiver burden and instrumental activities of daily living but failed to improve quality of life. No severe adverse events occurred in the rivastigmine group. Rivastigmine may represent a new therapeutic option for moderate to severe apathy in advanced PD patients with optimised dopaminergic treatment and without depression dementia. These findings require confirmation in a larger clinical trial. Our results also confirmed that the presence of apathy can herald a pre-dementia state in PD. Clinicaltrials.gov reference: NCT00767091.

Rotigotine transdermal patch in Chinese patients with advanced Parkinson's disease: A randomized, double-blind, placebo-controlled pivotal study.

PubMed

Zhang, Zhen-Xin; Liu, Chun-Feng; Tao, En-Xiang; Shao, Ming; Liu, Yi-Ming; Wang, Jian; Asgharnejad, Mahnaz; Xue, Hai-Bo; Surmann, Erwin; Bauer, Lars

2017-11-01

Rotigotine was demonstrated to be efficacious and well-tolerated in three placebo-controlled studies (CLEOPATRA-PD/PREFER/SP921) of patients with advanced-stage Parkinson's disease (PD), most of whom were Caucasian. This multicenter phase 3 study (SP1037; NCT01646255) was the first to investigate the efficacy and safety of rotigotine in Chinese patients with advanced-stage PD. Chinese patients with PD, inadequately controlled on levodopa (stable dose ≥200 mg/day), with ≥2.5 h/day "off" time, and Hoehn & Yahr stage 2-4, were randomized 1:1 to receive transdermal rotigotine or placebo, titrated over ≤7 weeks, maintained at optimal/maximum dose (4-16 mg/24 h) for 12 weeks. Primary efficacy variable: mean change in absolute "off" time (according to patient diaries) from baseline to end of maintenance. Safety variables included adverse events (AEs) and discontinuations due to AEs. 346 patients were randomized and 89.9% completed the study (87.8% placebo; 92.0% rotigotine). All were Chinese (58.7% male; mean ± SD age: 62.2 ± 8.9 years; mean ± SD time since PD diagnosis: 6.62 ± 3.70 years). Rotigotine significantly reduced "off" time vs placebo (LS mean [95% CI] treatment difference: -1.20 h/day [-1.83, -0.57]; p = 0.0002), and resulted in more responders (≥30% decrease in "off" time: 36.9% placebo; 48.8% rotigotine; p = 0.0269). AEs were reported for 86 (50.0%) placebo- and 103 (59.2%) rotigotine-treated patients; 15 discontinued due to AEs (placebo 7; rotigotine 8). The most common AEs (≥5%) were dizziness, nausea, pruritus, and dyskinesia. Rotigotine was efficacious in Chinese patients with advanced-stage PD as add-on therapy to levodopa, significantly reducing "off" time vs placebo; the treatment difference was similar to that observed in previous studies of mainly Caucasian patients. Rotigotine was generally well-tolerated and had a similar AE profile to those observed in previous studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Jinlei; Wu, Jinghe; Zhao, Xingju

Transitional metal nanoparticles or atoms deposited on appropriate substrates can lead to highly economical, efficient, and selective catalysis. One of the greatest challenges is to control the electronic metal–support interactions (EMSI) between the supported metal atoms and the substrate so as to optimize their catalytic performance. Here, from first-principles calculations, we show that an otherwise inactive Pd single adatom on TiO 2(110) can be tuned into a highly effective catalyst, e.g. for O 2 adsorption and CO oxidation, by purposefully selected metal–nonmetal co-dopant pairs in the substrate. Such an effect is proved here to result unambiguously from a significantly enhancedmore » EMSI. A nearly linear correlation is noted between the strength of the EMSI and the activation of the adsorbed O 2 molecule, as well as the energy barrier for CO oxidation. Particularly, the enhanced EMSI shifts the frontier orbital of the deposited Pd atom upward and largely enhances the hybridization and charge transfer between the O 2 molecule and the Pd atom. Upon co-doping, the activation barrier for CO oxidation on the Pd monomer is also reduced to a level comparable to that on the Pd dimer which was experimentally reported to be highly efficient for CO oxidation. The present findings provide new insights into the understanding of the EMSI in heterogeneous catalysis and can open new avenues to design and fabricate cost-effective single-atom-sized and/or nanometer-sized catalysts.« less

Temperature dependent selective detection of hydrogen and acetone using Pd doped WO3/reduced graphene oxide nanocomposite

NASA Astrophysics Data System (ADS)

Kaur, Jasmeet; Anand, Kanica; Kohli, Nipin; Kaur, Amanpreet; Singh, Ravi Chand

2018-06-01

Reduced graphene oxide (RGO) and Pd doped WO3 nanocomposites were fabricated by employing electrostatic interactions between poly (diallyldimethylammonium chloride) (PDDA) modified Pd doped WO3 nanostructures and graphite oxide (GO) and studied for their gas sensing application. XRD, Raman, FTIR, FESEM-EDX, TEM, TGA, XPS and Photoluminescence techniques were used for characterization of as-synthesized samples. Gas sensing studies revealed that the sensor with optimized doping of 1.5 mol% Pd and 1 wt% GO shows temperature dependent selectivity towards hydrogen and acetone. The role of WO3, Pd and RGO has been discussed in detail for enhanced sensing performance.

Imposed Faster and Slower Walking Speeds Influence Gait Stability Differently in Parkinson Fallers.

PubMed

Cole, Michael H; Sweeney, Matthew; Conway, Zachary J; Blackmore, Tim; Silburn, Peter A

2017-04-01

To evaluate the effect of imposed faster and slower walking speeds on postural stability in people with Parkinson disease (PD). Cross-sectional cohort study. General community. Patients with PD (n=84; 51 with a falls history; 33 without) and age-matched controls (n=82) were invited to participate via neurology clinics and preexisting databases. Of those contacted, 99 did not respond (PD=36; controls=63) and 27 were not interested (PD=18; controls=9). After screening, a further 10 patients were excluded; 5 had deep brain stimulation surgery and 5 could not accommodate to the treadmill. The remaining patients (N=30) completed all assessments and were subdivided into PD fallers (n=10), PD nonfallers (n=10), and age-matched controls (n=10) based on falls history. Not applicable. Three-dimensional accelerometers assessed head and trunk accelerations and allowed calculation of harmonic ratios and root mean square (RMS) accelerations to assess segment control and movement amplitude. Symptom severity, balance confidence, and medical history were established before participants walked on a treadmill at 70%, 100%, and 130% of their preferred speed. Head and trunk control was lower for PD fallers than PD nonfallers and older adults. Significant interactions indicated head and trunk control increased with speed for PD nonfallers and older adults, but did not improve at faster speeds for PD fallers. Vertical head and trunk accelerations increased with walking speed for PD nonfallers and older adults, while the PD fallers demonstrated greater anteroposterior RMS accelerations compared with both other groups. The results suggest that improved gait dynamics do not necessarily represent improved walking stability, and this must be respected when rehabilitating gait in patients with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Resonant tunnelling diode based high speed optoelectronic transmitters

NASA Astrophysics Data System (ADS)

Wang, Jue; Rodrigues, G. C.; Al-Khalidi, Abdullah; Figueiredo, José M. L.; Wasige, Edward

2017-08-01

Resonant tunneling diode (RTD) integration with photo detector (PD) from epi-layer design shows great potential for combining terahertz (THz) RTD electronic source with high speed optical modulation. With an optimized layer structure, the RTD-PD presented in the paper shows high stationary responsivity of 5 A/W at 1310 nm wavelength. High power microwave/mm-wave RTD-PD optoelectronic oscillators are proposed. The circuitry employs two RTD-PD devices in parallel. The oscillation frequencies range from 20-44 GHz with maximum attainable power about 1 mW at 34/37/44GHz.

The management of colonic trauma in the damage control era

PubMed Central

Shazi, B; Bruce, JL; Laing, GL; Sartorius, B

2017-01-01

INTRODUCTION The purpose of this study was to audit our current management of colonic trauma, and to review our experience of colonic trauma in patients who underwent initial damage control (DC) surgery. METHODS All patients treated for colonic trauma between January 2012 and December 2014 by the Pietermaritzburg Metropolitan Trauma Service were included in the study. Data reviewed included mechanism of injury, method of management (primary repair [PR], primary diversion [PD] or DC) and outcome (complications and mortality rate). Results A total of 128 patients sustained a colonic injury during the study period. Ninety-seven per cent of the injuries were due to penetrating trauma. Of these cases, 56% comprised stab wounds (SWs) and 44% were gunshot wounds (GSWs). Management was by PR in 99, PD in 20 and DC surgery in 9 cases. Among the 69 SW victims, 57 underwent PR, 9 had PD and 3 required a DC procedure. Of the 55 GSW cases, 40 were managed with PR, 9 with PD and 6 with DC surgery. In the PR group, there were 16 colonic complications (5 cases of breakdown and 11 of wound sepsis). Overall, nine patients (7%) died. CONCLUSIONS PR of colonic trauma is safe and should be used for the majority of such injuries. Persistent acidosis, however, should be considered a contraindication. In unstable patients with complex injuries, the optimal approach is to perform DC surgery. In this situation, formal diversion is contraindicated, and the injury should be controlled and dropped back into the abdomen at the primary operation. At the repeat operation, if the physiological insult has been reversed, then formal repair of the colonic injury is acceptable. PMID:27659359

The management of colonic trauma in the damage control era.

PubMed

Shazi, B; Bruce, J L; Laing, G L; Sartorius, B; Clarke, D L

2017-01-01

INTRODUCTION The purpose of this study was to audit our current management of colonic trauma, and to review our experience of colonic trauma in patients who underwent initial damage control (DC) surgery. METHODS All patients treated for colonic trauma between January 2012 and December 2014 by the Pietermaritzburg Metropolitan Trauma Service were included in the study. Data reviewed included mechanism of injury, method of management (primary repair [PR], primary diversion [PD] or DC) and outcome (complications and mortality rate). Results A total of 128 patients sustained a colonic injury during the study period. Ninety-seven per cent of the injuries were due to penetrating trauma. Of these cases, 56% comprised stab wounds (SWs) and 44% were gunshot wounds (GSWs). Management was by PR in 99, PD in 20 and DC surgery in 9 cases. Among the 69 SW victims, 57 underwent PR, 9 had PD and 3 required a DC procedure. Of the 55 GSW cases, 40 were managed with PR, 9 with PD and 6 with DC surgery. In the PR group, there were 16 colonic complications (5 cases of breakdown and 11 of wound sepsis). Overall, nine patients (7%) died. CONCLUSIONS PR of colonic trauma is safe and should be used for the majority of such injuries. Persistent acidosis, however, should be considered a contraindication. In unstable patients with complex injuries, the optimal approach is to perform DC surgery. In this situation, formal diversion is contraindicated, and the injury should be controlled and dropped back into the abdomen at the primary operation. At the repeat operation, if the physiological insult has been reversed, then formal repair of the colonic injury is acceptable.

Rotigotine and specific non-motor symptoms of Parkinson's disease: post hoc analysis of RECOVER.

PubMed

Ray Chaudhuri, K; Martinez-Martin, Pablo; Antonini, Angelo; Brown, Richard G; Friedman, Joseph H; Onofrj, Marco; Surmann, Erwin; Ghys, Liesbet; Trenkwalder, Claudia

2013-07-01

Non-motor symptoms of Parkinson's disease (PD) represent major causes of morbidity. RECOVER, a randomized controlled trial of rotigotine transdermal system, was the first prospective controlled trial to use the Non-Motor Symptoms Scale (NMSS) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD. Rotigotine improved NMSS total score compared with placebo, and the "Sleep/fatigue" and "Mood/apathy" domains. This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy. Patients with PD and unsatisfactory early-morning motor impairment were randomized to transdermal patches of rotigotine (2-16 mg/24 h) or placebo. Treatment was titrated to optimal dose over 1-8 weeks, maintained for 4 weeks. The NMSS was assessed at baseline and end of treatment. Post hoc analyses are presented for individual items of the "Sleep/fatigue" and "Mood/apathy" domains. The interpretation of p-values is considered exploratory in nature. Of 287 patients randomized, NMSS data were available for 267 patients (178 rotigotine, 89 placebo). Within the "Sleep/fatigue" domain there was a significant difference, in favor of rotigotine, in change from baseline score in 1 of 5 items: "fatigue (tiredness) or lack of energy" (ANCOVA, p < 0.0001). Within the "Mood/apathy" domain, there were significant differences in favor of rotigotine in 4 of 7 items: "lost interest in surroundings" (p < 0.0001), "lost interest in doing things" (p < 0.0001), "seems sad or depressed" (p < 0.01), and "difficulty experiencing pleasure" (p < 0.05). Rotigotine transdermal system may improve non-motor symptoms such as fatigue, symptoms of depression, anhedonia, and apathy in patients with PD; further prospective controlled studies are required to confirm this post hoc analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Global optimization of small bimetallic Pd-Co binary nanoalloy clusters: a genetic algorithm approach at the DFT level.

PubMed

Aslan, Mikail; Davis, Jack B A; Johnston, Roy L

2016-03-07

The global optimisation of small bimetallic PdCo binary nanoalloys are systematically investigated using the Birmingham Cluster Genetic Algorithm (BCGA). The effect of size and composition on the structures, stability, magnetic and electronic properties including the binding energies, second finite difference energies and mixing energies of Pd-Co binary nanoalloys are discussed. A detailed analysis of Pd-Co structural motifs and segregation effects is also presented. The maximal mixing energy corresponds to Pd atom compositions for which the number of mixed Pd-Co bonds is maximised. Global minimum clusters are distinguished from transition states by vibrational frequency analysis. HOMO-LUMO gap, electric dipole moment and vibrational frequency analyses are made to enable correlation with future experiments.

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

Interaction effect of psychological distress and asthma control on productivity loss?

PubMed

Moullec, Grégory; FitzGerald, J Mark; Rousseau, Roxanne; Chen, Wenjia; Sadatsafavi, Mohsen

2015-06-01

Little is known about the potential synergistic effect of comorbid psychological distress (PD) and uncontrolled asthma (UA) on productivity loss. We estimated the productivity loss associated with the combination of these two potentially preventable conditions in employed adults with asthma. A population-based random sample of 300 adults with asthma in British Columbia, Canada, was prospectively recruited between Dec 2010 and Aug 2012. PD and productivity loss due to absenteeism and presenteeism was measured using validated instruments, and asthma control was ascertained using 2010 Global Initiative for Asthma management strategy. We used two-part regression models to study the contribution of UA and PD to productivity loss. Compared with reference group (controlled asthma (CA)+noPD), those with UA+noPD had CAD$286 (95%CI $276-297) weekly productivity loss, and those with CA+PD had CAD$465 ($445-485). Those with UA+PD had CAD$449 (437-462) in productivity loss. There was no significant interaction effect of PD with asthma control levels on productivity loss (p=0.22). In patients without PD, uncontrolled asthma was associated with a higher productivity loss than controlled asthma, but this was not the case in patients with PD. This finding can be explained by the fact that the contribution of PD to productivity loss is so large that there is no room for synergy with asthma control. Future studies should assess the impact of interventions that modify PD in patients with asthma. Copyright ©ERS 2015.

Shape-dependent electrocatalysis: formic acid electrooxidation on cubic Pd nanoparticles.

PubMed

Vidal-Iglesias, Francisco J; Arán-Ais, Rosa M; Solla-Gullón, José; Garnier, Emmanuel; Herrero, Enrique; Aldaz, Antonio; Feliu, Juan M

2012-08-07

The electrocatalytic properties of palladium nanocubes towards the electrochemical oxidation of formic acid were studied in H(2)SO(4) and HClO(4) solutions and compared with those of spherical Pd nanoparticles. The spherical and cubic Pd nanoparticles were characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The intrinsic electrocatalytic properties of both nanoparticles were shown to be strongly dependent on the amount of metal deposited on the gold substrate. Thus, to properly compare the activity of both systems (spheres and nanocubes), the amount of sample has to be optimized to avoid problems due to a lower diffusion flux of reactants in the internal parts of the catalyst layer resulting in a lower apparent activity. Under the optimized conditions, the activity of the spheres and nanocubes was very similar between 0.1 and 0.35 V. From this potential value, the activity of the Pd nanocubes was remarkably higher. This enhanced electrocatalytic activity was attributed to the prevalence of Pd(100) facets in agreement with previous studies with Pd single crystal electrodes. The effect of HSO(4)(-)/SO(4)(2-) desorption-adsorption was also evaluated. The activity found in HClO(4) was significantly higher than that obtained in H(2)SO(4) in the whole potential range.

Musculoskeletal problems in Parkinson's disease: neglected issues.

PubMed

Kim, Young Eun; Lee, Woong-Woo; Yun, Ji Young; Yang, Hui June; Kim, Han-Joon; Jeon, Beom S

2013-07-01

To identify the prevalence and clinical features of musculoskeletal problems in patients with Parkinson disease (PD) compared to controls. 400 PD patients and 138 age- and sex-matched controls were interviewed by physicians about their musculoskeletal problems. The prevalence of musculoskeletal problems was significantly higher in the PD group than in the control group (66.3% vs. 45.7%, P < 0.001). Commonly involved body sites were the low back, knee, and shoulder in that order. The low back was more frequently involved in the PD group than in the control group (44.3% vs. 24.6%, P < 0.001), and the shoulder tended to be more involved in the PD group than in the control group (15.0% vs. 8.7%, P = 0.061). However, the knee was similarly involved in both group (12.3% vs. 18.0%, P = 0.121). Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in the PD group than in the control group (P < 0.05). Older age, female, and a higher score on the Unified Parkinson's Disease Rating Scale I & II were associated with musculoskeletal problems in the PD group. Only 26.8% of the PD patients and 52.5% of the controls with musculoskeletal problems answered that their musculoskeletal problems were recovering. Furthermore, musculoskeletal problems in the PD group tended to receive less treatment than that of the control group (P = 0.052). Musculoskeletal problems were more common in the PD group than in the controls. Furthermore, despite PD patients having a higher prevalence, they did not receive adequate treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Core–shell PdPb@Pd aerogels with multiply-twinned intermetallic nanostructures: facile synthesis with accelerated gelation kinetics and their enhanced electrocatalytic properties

DOE PAGES

Zhu, Chengzhou; Shi, Qiurong; Fu, Shaofang; ...

2018-04-04

Delicately engineering well-defined noble metal aerogels with favorable structural and compositional features is of vital importance for wide applications. Here, we reported a one-pot and facile method for synthesizing core–shell PdPb@Pd hydrogels/aerogels with multiply-twinned grains and an ordered intermetallic phase using sodium hypophosphite as a multifunctional reducing agent. Due to the accelerated gelation kinetics induced by increased reaction temperature and the specific function of sodium hypophosphite, the formation of hydrogels can be completed within 4 h. As a result, owing to their unique porous structure and favorable geometric and electronic effects, the optimized PdPb@Pd aerogels exhibit enhanced electrochemical performance towardsmore » ethylene glycol oxidation with a mass activity of 5.8 times higher than Pd black.« less

Core–shell PdPb@Pd aerogels with multiply-twinned intermetallic nanostructures: facile synthesis with accelerated gelation kinetics and their enhanced electrocatalytic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Chengzhou; Shi, Qiurong; Fu, Shaofang

Delicately engineering well-defined noble metal aerogels with favorable structural and compositional features is of vital importance for wide applications. Here, we reported a one-pot and facile method for synthesizing core–shell PdPb@Pd hydrogels/aerogels with multiply-twinned grains and an ordered intermetallic phase using sodium hypophosphite as a multifunctional reducing agent. Due to the accelerated gelation kinetics induced by increased reaction temperature and the specific function of sodium hypophosphite, the formation of hydrogels can be completed within 4 h. As a result, owing to their unique porous structure and favorable geometric and electronic effects, the optimized PdPb@Pd aerogels exhibit enhanced electrochemical performance towardsmore » ethylene glycol oxidation with a mass activity of 5.8 times higher than Pd black.« less

Evaluation of rotigotine transdermal patch for the treatment of apathy and motor symptoms in Parkinson's disease.

PubMed

Hauser, Robert A; Slawek, Jaroslaw; Barone, Paolo; Dohin, Elisabeth; Surmann, Erwin; Asgharnejad, Mahnaz; Bauer, Lars

2016-06-07

This multicenter, double-blind, placebo-controlled study assessed the efficacy of rotigotine transdermal patch on apathy and motor symptoms in patients with Parkinson's disease (PD). Patients with PD-associated apathy (Unified Parkinson's Disease Rating Scale [UPDRS] I item 4 [motivation] ≥2 and patient-rated Apathy Scale [AS] ≥14) were randomized 1:1:1 to "low-dose" rotigotine (≤6 mg/24 h for early PD [those not receiving levodopa] or ≤8 mg/24 h for advanced PD [those receiving levodopa]), "high-dose" rotigotine (≤8 mg/24 h for early PD or ≤16 mg/24 h for advanced PD), or placebo, and maintained at optimal/maximal dose for 12 weeks. Coprimary efficacy variables were: change from baseline to End of Maintenance in patient-rated AS and UPDRS II + III total score. Recruitment was stopped after an interim futility analysis; therefore, all p values are exploratory. Of 122 patients randomized, 81.1 % completed the study (placebo, n = 32/40 [80.0 %]; low-dose rotigotine, n = 30/41 [73.2 %]; high-dose rotigotine, n = 37/41 [90.2 %]). No treatment difference was observed in the change in patient-rated AS (least squares mean [95 % confidence interval (CI)] difference: low-dose, 0.04 [-2.42, 2.50], p =0.977; high-dose, -0.22 [-2.61, 2.18], p = 0.859). Rotigotine improved UPDRS II + III total scores versus placebo (least squares mean [95 % CI] treatment difference: low-dose, -7.29 [-12.30, -2.28], p = 0.005; high-dose, -6.06 [-10.90, -1.21], p = 0.015), and the "mood/apathy" domain of the Non-Motor Symptom Scale as rated by the investigator (secondary outcome). The most frequent adverse events in rotigotine-treated patients were application site reactions, somnolence, and nausea. Rotigotine did not improve PD-associated apathy as rated by the patient but provided clinically relevant improvement in motor control and activities of daily living. ClinicalTrials.gov identifier NCT01782222 . Trial registration date: January 30, 2013.

Enhancement in the catalytic activity of Pd/USY in the heck reaction induced by H2 bubbling.

PubMed

Okumura, Kazu; Tomiyama, Takuya; Moriyama, Sayaka; Nakamichi, Ayaka; Niwa, Miki

2010-12-24

Pd was loaded on ultra stable Y (USY) zeolites prepared by steaming NH(4)-Y zeolite under different conditions. Heck reactions were carried out over the prepared Pd/USY. We found that H₂ bubbling was effective in improving not only the catalytic activity of Pd/USY, but also that of other supported Pd catalysts and Pd(OAc)₂. Moreover, the catalytic activity of Pd/USY could be optimized by choosing appropriate steaming conditions for the preparation of the USY zeolites; Pd loaded on USY prepared at 873 K with 100% H₂O gave the highest activity (TOF = 61,000 h⁻¹), which was higher than that of Pd loaded on other kinds of supports. The prepared Pd/USY catalysts were applicable to the Heck reactions using various kinds of substrates including bromo- and chloro-substituted aromatic and heteroaromatic compounds. Characterization of the acid properties of the USY zeolites revealed that the strong acid site (OH(strong)) generated as a result of steaming had a profound effect on the catalytic activity of Pd.

Core–shell PdPb@Pd aerogels with multiply-twinned intermetallic nanostructures: facile synthesis with accelerated gelation kinetics and their enhanced electrocatalytic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Chengzhou; Shi, Qiurong; Fu, Shaofang

Delicately engineering the well-defined noble metal aerogels with favorable structural and compositional features is of vital importance for wide applications. Here, we reported one-pot and facile method for synthesizing core-shell PdPb@Pd hydrogels/aerogels with multiply-twinned grains and ordered intermetallic phase using sodium hypophosphite as a multifunctional reducing agent. Due to the accelerated gelation kinetics induced by increased reaction temperature and specific function of sodium hypophosphite, the formation of hydrogels can be completed within 4 hrs, far faster than the previous reports. Owe to their unique porous structure and favorable geometric and electronic effects, the optimized PdPb@Pd aerogels exhibit enhanced electrochemical performancemore » towards ethylene glycol oxidation with a mass activity of 5.8 times higher than Pd black.Core–shell PdPb@Pd aerogels with multiply-twinned grains and an ordered intermetallic phase was synthesized, which exhibited good electrocatalytic activity towards ethanol oxidation.« less

Lateral stepping for postural correction in Parkinson's disease.

PubMed

King, Laurie A; Horak, Fay B

2008-03-01

To characterize the lateral stepping strategies for postural correction in patients with Parkinson's disease (PD) and the effect of their anti-parkinson medication. Observational study. Outpatient neuroscience laboratory. Thirteen participants with idiopathic PD in their on (PD on) and off (PD off) levodopa state and 14 healthy elderly controls. Movable platform with lateral translations of 12 cm at 14.6 cm/s ramp velocity. The incidence and characteristics of 3 postural strategies were observed: lateral side-step, crossover step, or no step. Corrective stepping was characterized by latency to step after perturbation onset, step velocity, and step length and presence of an anticipatory postural adjustment (APA). Additionally, percentages of trials resulting in falls were identified for each group. Whereas elderly control participants never fell, PD participants fell in 24% and 35% of trials in the on and off medication states, respectively. Both PD and control participants most often used a lateral side-step strategy; 70% (control), 67% (PD off), and 73% (PD on) of all trials, respectively. PD participants fell most often when using a crossover strategy (75% of all crossover trials) or no-step strategy (100% of all no-step trials). In the off medication state, PD participants' lateral stepping strategies were initiated later than controls (370+/-37 ms vs 280+/-10 ms, P<.01), and steps were smaller (254+/-20 mm vs 357+/-17 mm, P<.01) and slower (0.99+/-0.08 m/s vs 1.20+/-0.07 m/s, P<.05). No differences were found between the PD off versus PD on state in the corrective stepping characteristics. Unlike control participants, PD participants often (56% of side-step strategy trials) failed to activate an APA before stepping, although their APAs, when present, were of similar latency and magnitude as for control participants. Levodopa on or off state did not significantly affect falls, APAs, or lateral step latency, velocity, or amplitude (P>.05). PD participants showed significantly more postural instability and falls than age-matched controls when stepping was required for postural correction in response to lateral disequilibrium. Although PD participants usually used a similar lateral stepping strategy as controls in response to lateral translations, lack of an anticipatory lateral weight shift, and bradykinetic characteristics of the stepping responses help explain the greater rate of falls in participants with PD. Differences were not found between the levodopa on and off states. The results suggest that rehabilitation aimed at improving lateral stability in PD should include facilitating APAs before a lateral side-stepping strategy with faster and larger steps to recover equilibrium.

Fabrication of Defined Polydopamine Nanostructures by DNA Origami-Templated Polymerization.

PubMed

Tokura, Yu; Harvey, Sean; Chen, Chaojian; Wu, Yuzhou; Ng, David Y W; Weil, Tanja

2018-02-05

A versatile, bottom-up approach allows the controlled fabrication of polydopamine (PD) nanostructures on DNA origami. PD is a biosynthetic polymer that has been investigated as an adhesive and promising surface coating material. However, the control of dopamine polymerization is challenged by the multistage-mediated reaction mechanism and diverse chemical structures in PD. DNA origami decorated with multiple horseradish peroxidase-mimicking DNAzyme motifs was used to control the shape and size of PD formation with nanometer resolution. These fabricated PD nanostructures can serve as "supramolecular glue" for controlling DNA origami conformations. Facile liberation of the PD nanostructures from the DNA origami templates has been achieved in acidic medium. This presented DNA origami-controlled polymerization of a highly crosslinked polymer provides a unique access towards anisotropic PD architectures with distinct shapes that were retained even in the absence of the DNA origami template. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Airway somatosensory deficits and dysphagia in Parkinson's disease.

PubMed

Hammer, Michael J; Murphy, Caitlin A; Abrams, Trisha M

2013-01-01

Individuals with Parkinson's disease (PD) often experience substantial impairment of swallow control, and are typically unaware of the presence or severity of their impairments suggesting that these individuals may also experience airway sensory deficits. However, the degree to which impaired swallow function in PD may relate to airway sensory deficits has yet to be formally tested. The purpose of this study was to examine whether airway sensory function is associated with swallow impairment in PD. Eighteen PD participants and 18 healthy controls participated in this study and underwent endoscopic assessment of airway somatosensory function, endoscopic assessment of swallow function, and clinical ratings of swallow and disease severity. PD participants exhibited abnormal airway somatosensory function and greater swallow impairment compared with healthy controls. Swallow and sensory deficits in PD were correlated with disease severity. Moreover, PD participants reported similar self-rated swallow function as healthy controls, and swallow deficits were correlated with sensory function suggesting an association between impaired sensory function and poor self-awareness of swallow deficits in PD. These results suggest that control of swallow is influenced by airway somatosensory function, that swallow-related deficits in PD are related to abnormal somatosensation, and that swallow and airway sensory function may degrade as a function of disease severity. Therefore, the basal ganglia and related neural networks may play an important role to integrate airway sensory input for swallow-related motor control. Furthermore, the airway deficits observed in PD suggest a disintegration of swallow-related sensory and motor control.

Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

PubMed

Hove, Michael J; Keller, Peter E

2015-03-01

Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. © 2014 New York Academy of Sciences.

Rehabilitation for Parkinson's disease: Current outlook and future challenges.

PubMed

Abbruzzese, Giovanni; Marchese, Roberta; Avanzino, Laura; Pelosin, Elisa

2016-01-01

Rehabilitation is considered as an adjuvant to pharmacological and surgical treatments for Parkinson's disease (PD) to maximize functional ability and minimize secondary complications. Originally, approaches were based on empirical experience, but growing evidence suggests that exercise-dependent plasticity constitutes the main mechanism underlying the effects of physiotherapy. Exercise increases synaptic strength and influences neurotransmission, thus potentiating functional circuitry in PD. In addition, exercise is a pivotal element of motor learning. PD patients retain a sufficient capacity of motor learning, though learning rates and performance are reduced in comparison to normal controls. Recent meta-analyses demonstrated that rehabilitation could induce short-lasting, but clinically important benefits, particularly for gait and balance. However, the interventions are largely heterogeneous (stretching, muscle strengthening, balance, postural exercises, occupational therapy, cueing, treadmill training), and there is still no consensus about the optimal approach. Innovative techniques have been recently proposed: virtual reality and exergaming, motor imagery and action observation, robot-assisted physiotherapy and non-conventional therapies (e.g.: dance, martial arts). The rehabilitative program for PD should be "goal-based" (targeted to practicing and learning specific activities in the core areas), but a number of practice variables (intensity, specificity, complexity) need to be identified and the program should tailored to the individual patients' characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Screening for impulse control symptoms in patients with de novo Parkinson disease: a case-control study.

PubMed

Weintraub, Daniel; Papay, Kimberly; Siderowf, Andrew

2013-01-08

To determine the frequency and correlates of impulse control and related behavior symptoms in patients with de novo, untreated Parkinson disease (PD) and healthy controls (HCs). The Parkinson's Progression Markers Initiative is an international, multisite, case-control clinical study conducted at 21 academic movement disorders centers. Participants were recently diagnosed, untreated PD patients (n = 168) and HCs (n = 143). The outcome measures were presence of current impulse control and related behavior symptoms based on recommended cutoff points for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP)-Short Form. There were 311 participants with complete QUIP data. Frequencies of impulse control and related behavior symptoms for patients with PD vs HCs were as follows: gambling (1.2% vs. 0.7%), buying (3.0% vs. 2.1%), sexual behavior (4.2% vs. 3.5%), eating (7.1% vs. 10.5%), punding (4.8% vs. 2.1%), hobbyism (5.4% vs. 11.9%), walkabout (0.6% vs. 0.7%), and any impulse control or related behavior (18.5% vs. 20.3%). In multivariable models, a diagnosis of PD was not associated with symptoms of any impulse control or related behavior (p ≥ 0.10 in all cases). PD itself does not seem to confer an increased risk for development of impulse control or related behavior symptoms, which further reinforces the reported association between PD medications and impulse control disorders in PD. Given that approximately 20% of patients with newly diagnosed PD report some impulse control or related behavior symptoms, long-term follow-up is needed to determine whether such patients are at increased risk for impulse control disorder development once PD medications are initiated.

Optimization of Materials and Interfaces for Spintronic Devices

NASA Astrophysics Data System (ADS)

Clark, Billy

In recent years' Spintronic devices have drawn a significant amount of research attention. This interest comes in large part from their ability to enable interesting and new technology such as Spin Torque Transfer Random Access Memory or improve existing technology such as High Signal Read Heads for Hard Disk Drives. For the former we worked on optimizing and improving magnetic tunnel junctions by optimizing their thermal stability by using Ta insertion layers in the free layer. We further tried to simplify the design of the MTJ stack by attempting to replace the Co/Pd multilayer with CoPd alloy. In this dissertation, we detail its development and examine the switching characteristics. Lastly we look at a highly spin polarized material, Fe2MnGe, for optimizing Hard Drive Disk read heads.

Colonic bacterial composition in Parkinson's disease.

PubMed

Keshavarzian, Ali; Green, Stefan J; Engen, Phillip A; Voigt, Robin M; Naqib, Ankur; Forsyth, Christopher B; Mutlu, Ece; Shannon, Kathleen M

2015-09-01

We showed that Parkinson's disease (PD) patients have alpha-synuclein (α-Syn) aggregation in their colon with evidence of colonic inflammation. If PD patients have altered colonic microbiota, dysbiosis might be the mechanism of neuroinflammation that leads to α-Syn misfolding and PD pathology. Sixty-six sigmoid mucosal biopsies and 65 fecal samples were collected from 38 PD patients and 34 healthy controls. Mucosal-associated and feces microbiota compositions were characterized using high-throughput ribosomal RNA gene amplicon sequencing. Data were correlated with clinical measures of PD, and a predictive assessment of microbial community functional potential was used to identify microbial functions. The mucosal and fecal microbial community of PD patients was significantly different than control subjects, with the fecal samples showing more marked differences than the sigmoid mucosa. At the taxonomic level of genus, putative, "anti-inflammatory" butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia were significantly more abundant in feces of controls than PD patients. Bacteria from the genus Faecalibacterium were significantly more abundant in the mucosa of controls than PD. Putative, "proinflammatory" Proteobacteria of the genus Ralstonia were significantly more abundant in mucosa of PD than controls. Predictive metagenomics indicated that a large number of genes involved in metabolism were significantly lower in the PD fecal microbiome, whereas genes involved in lipopolysaccharide biosynthesis and type III bacterial secretion systems were significantly higher in PD patients. This report provides evidence that proinflammatory dysbiosis is present in PD patients and could trigger inflammation-induced misfolding of α-Syn and development of PD pathology. © 2015 International Parkinson and Movement Disorder Society.

An equivalent method for optimization of particle tuned mass damper based on experimental parametric study

NASA Astrophysics Data System (ADS)

Lu, Zheng; Chen, Xiaoyi; Zhou, Ying

2018-04-01

A particle tuned mass damper (PTMD) is a creative combination of a widely used tuned mass damper (TMD) and an efficient particle damper (PD) in the vibration control area. The performance of a one-storey steel frame attached with a PTMD is investigated through free vibration and shaking table tests. The influence of some key parameters (filling ratio of particles, auxiliary mass ratio, and particle density) on the vibration control effects is investigated, and it is shown that the attenuation level significantly depends on the filling ratio of particles. According to the experimental parametric study, some guidelines for optimization of the PTMD that mainly consider the filling ratio are proposed. Furthermore, an approximate analytical solution based on the concept of an equivalent single-particle damper is proposed, and it shows satisfied agreement between the simulation and experimental results. This simplified method is then used for the preliminary optimal design of a PTMD system, and a case study of a PTMD system attached to a five-storey steel structure following this optimization process is presented.

Pd and polyaniline nanocomposite on carbon fiber paper as an efficient direct formic acid fuel cell anode

NASA Astrophysics Data System (ADS)

Pandey, Rakesh K.

2018-03-01

Direct formic acid fuel cells are advantageous as portable power generating devices. In the present work, an anode catalyst for direct formic acid fuel cell (DFAFC) is presented which has good catalytic activity for formic acid oxidation. The catalyst is composed of Pd and conducting polymer polyaniline (Pd-PANI) nanocomposite. The catalyst was prepared by using a single step galvanostatic electrochemical deposition method. The Pd-PANI catalyst was electrodeposited at different time durations and a comparison of the catalytic activity at each deposition time was carried out and optimized.

Study of Chemistry and Structure-Property Relationship on Tunable Plasmonic Nanostructures

NASA Astrophysics Data System (ADS)

Jing, Hao

In this dissertation, the rational design and controllable fabrication of an array of novel plasmonic nanostructures with geometrically tunable optical properties are demonstrated, including metal-semiconductor hybrid hetero-nanoparticles, bimetallic noble metal nanoparticles and hollow nanostructures (nanobox and nanocage). Firstly, I have developed a robust wet chemistry approach to the geometry control of Ag-Cu2O core-shell nanoparticles through epitaxial growth of Cu2O nanoshells on the surfaces of various Ag nanostructures, such as quasi-spherical nanoparticles, nanocubes, and nanocuboids. Precise control over the core and the shell geometries enables me to develop detailed, quantitative understanding of how the Cu2O nanoshells introduce interesting modifications to the resonance frequencies and the extinction spectral line shapes of multiple plasmon modes of the Ag cores. Secondly, I present a detailed and systematic study of the controlled overgrowth of Pd on Au nanorods. The overgrowth of Pd nanoshells with fine-controlled dimensions and architectures on single-crystalline Au nanorods through seed-mediated growth protocol in the presence of various surfactants is investigated. Thirdly, I have demonstrated that creation of high-index facets on subwavelength metallic nanoparticles provides a unique approach to the integration of desired plasmonic and catalytic properties on the same nanoparticle. Through site-selective surface etching of metallic nanocuboids whose surfaces are dominated by low-index facets, I have controllably fabricated nanorice and nanodumbbell particles, which exhibit drastically enhanced catalytic activities arising from the catalytically active high index facets abundant on the particle surfaces. And the nanorice and nanodumbbell particles also possess appealing tunable plasmonic properties that allow us to gain quantitative insights into nanoparticle-catalyzed reactions with unprecedented sensitivity and detail through time-resolved plasmon-enhanced spectroscopic measurements, such as surface-enhanced Raman scattering (SERS). Last but not least, I have demonstrated that the capability of geometry control over Ag-Pd bimetallic hollow nanostructures through nanoscale galvanic replacement can be greatly enhanced by the use of appropriate mild reducing agents, such as ascorbic acid and formaldehyde. With the aid of mild reducing agents, we have been able to fine-tailor the compositions, interior architectures, and surface morphologies of Ag-Pd bimetallic hollow nanoparticles with increased structural complexity through surface ligand-free galvanic replacement processes at room temperature. This reducing agent-mediated galvanic replacement provides a unique way of achieving both enhanced optical tunability and optimized catalytic activities through deliberate control over the geometries of complex Ag-Pd bimetallic nanoparticles.

Pulse duration settings in subthalamic stimulation for Parkinson's disease

PubMed Central

Steigerwald, Frank; Timmermann, Lars; Kühn, Andrea; Schnitzler, Alfons; Reich, Martin M.; Kirsch, Anna Dalal; Barbe, Michael Thomas; Visser‐Vandewalle, Veerle; Hübl, Julius; van Riesen, Christoph; Groiss, Stefan Jun; Moldovan, Alexia‐Sabine; Lin, Sherry; Carcieri, Stephen; Manola, Ljubomir

2017-01-01

ABSTRACT Background Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double‐blind conditions. Evidence‐based recommendations on optimal stimulator settings are needed. Results from the CUSTOM‐DBS study are reported, comparing 2 pulse durations. Methods A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side‐effect thresholds and unified PD rating scale (UPDRS) III were measured in meds‐off (primary outcome). The therapeutic window was the difference between patients’ efficacy and side effect thresholds. Results The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). Interpretation Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation‐related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:29165837

Core-Shell PdPb@Pd Aerogels with Multiply-Twinned Intermetallic Nanostructures: Facile Synthesis with Accelerated Gelation Kinetics and Their Enhanced Electrocatalytic Properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Chengzhou; Shi, Qiurong; Fu, Shaofang

2018-04-04

Delicately engineering the well-defined noble metal aerogels with favorable structural and compositional features is of vital importance for wide applications. Here, we reported one-pot and facile method for synthesizing core-shell PdPb@Pd hydrogels/aerogels with multiply-twinned grains and ordered intermetallic phase using sodium hypophosphite as a multifunctional reducing agent. Due to the accelerated gelation kinetics induced by increased reaction temperature and specific function of sodium hypophosphite, the formation of hydrogels can be completed within 4 hrs, far faster than the previous reports. Owe to their unique porous structure and favorable geometric and electronic effects, the optimized PdPb@Pd aerogels exhibit enhanced electrochemical performancemore » towards ethylene glycol oxidation with a mass activity of 5.8 times higher than Pd black.« less

Screening for impulse control symptoms in patients with de novo Parkinson disease

PubMed Central

Papay, Kimberly; Siderowf, Andrew

2013-01-01

Objective: To determine the frequency and correlates of impulse control and related behavior symptoms in patients with de novo, untreated Parkinson disease (PD) and healthy controls (HCs). Methods: The Parkinson's Progression Markers Initiative is an international, multisite, case-control clinical study conducted at 21 academic movement disorders centers. Participants were recently diagnosed, untreated PD patients (n = 168) and HCs (n = 143). The outcome measures were presence of current impulse control and related behavior symptoms based on recommended cutoff points for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP)-Short Form. Results: There were 311 participants with complete QUIP data. Frequencies of impulse control and related behavior symptoms for patients with PD vs HCs were as follows: gambling (1.2% vs 0.7%), buying (3.0% vs 2.1%), sexual behavior (4.2% vs 3.5%), eating (7.1% vs 10.5%), punding (4.8% vs 2.1%), hobbyism (5.4% vs 11.9%), walkabout (0.6% vs 0.7%), and any impulse control or related behavior (18.5% vs 20.3%). In multivariable models, a diagnosis of PD was not associated with symptoms of any impulse control or related behavior (p ≥ 0.10 in all cases). Conclusions: PD itself does not seem to confer an increased risk for development of impulse control or related behavior symptoms, which further reinforces the reported association between PD medications and impulse control disorders in PD. Given that approximately 20% of patients with newly diagnosed PD report some impulse control or related behavior symptoms, long-term follow-up is needed to determine whether such patients are at increased risk for impulse control disorder development once PD medications are initiated. PMID:23296128

Placebo Controlled Study of Repetitive Transcranial Magnetic Stimulation for the Treatment of Parkinson’s Disease

DTIC Science & Technology

2004-03-01

References Aarsland D., Larsen J.P., Waage 0., Langeveld J.H. Maintenance electroconvulsive therapy for Parkinson’s disease. Convuls Ther. 1997; 13: 274-277...following electroconvulsive therapy . 1: Psychopharmacology (Berl). 1982; 76: 371-376. Belmaker R.H., Grisaru N. Magnetic stimulation of the brain in...rTMS might have any long-lasting therapeutic effects (weeks or months) in persons with PD who are already receiving optimal available therapy

Haptoglobin Phenotype Modifies Serum Iron Levels and the Effect of Smoking on Parkinson Disease Risk

PubMed Central

Costa-Mallen, Paola; Zabetian, Cyrus P.; Agarwal, Pinky; Hu, Shu-Ching; Yearout, Dora; Samii, Ali; Leverenz, James B.; Roberts, John W.; Checkoway, Harvey

2015-01-01

Introduction Haptoglobin is a hemoglobin-binding protein that exists in three functionally different phenotypes, and haptoglobin phenotype 2-1 has previously been associated with Parkinson disease (PD) risk, with mechanisms not elucidated. Some evidence is emerging that low levels of serum iron may increase PD risk. In this study we investigated whether PD patients have lower serum iron and ferritin than controls, and whether this is dependent on haptoglobin phenotype. We also investigated the effect of Hp phenotype as a modifier of the effect of smoking on PD risk. Methods The study population consisted of 128 PD patients and 226 controls. Serum iron, ferritin, and haptoglobin phenotype were determined, and compared between PD cases and controls. Stratified analysis by haptoglobin phenotype was performed to determine effect of haptoglobin phenotype on serum iron parameter differences between PD cases and controls and to investigate its role in the protective effect of smoking on PD risk. Results PD cases had lower serum iron than controls (83.28 ug/100ml vs 94.00 ug/100 ml, p 0.006), and in particular among subjects with phenotype 2-1. The protective effect of smoking on PD risk resulted stronger in subjects with phenotype 1-1 and 2-2, and weakest among subjects with phenotype 2-1. Ferritin levels were higher in PD cases than controls among subjects of White ethnicity. Conclusions Our results report for the first time that the haptoglobin phenotype may be a contributor of iron levels abnormalities in PD patients. The mechanisms for these haptoglobin-phenotype specific effects will have to be further elucidated. PMID:26228081

Substrate co-doping modulates electronic metal–support interactions and significantly enhances single-atom catalysis

DOE PAGES

Shi, Jinlei; Wu, Jinghe; Zhao, Xingju; ...

2016-10-07

Transitional metal nanoparticles or atoms deposited on appropriate substrates can lead to highly economical, efficient, and selective catalysis. One of the greatest challenges is to control the electronic metal–support interactions (EMSI) between the supported metal atoms and the substrate so as to optimize their catalytic performance. Here, from first-principles calculations, we show that an otherwise inactive Pd single adatom on TiO 2(110) can be tuned into a highly effective catalyst, e.g. for O 2 adsorption and CO oxidation, by purposefully selected metal–nonmetal co-dopant pairs in the substrate. Such an effect is proved here to result unambiguously from a significantly enhancedmore » EMSI. A nearly linear correlation is noted between the strength of the EMSI and the activation of the adsorbed O 2 molecule, as well as the energy barrier for CO oxidation. Particularly, the enhanced EMSI shifts the frontier orbital of the deposited Pd atom upward and largely enhances the hybridization and charge transfer between the O 2 molecule and the Pd atom. Upon co-doping, the activation barrier for CO oxidation on the Pd monomer is also reduced to a level comparable to that on the Pd dimer which was experimentally reported to be highly efficient for CO oxidation. The present findings provide new insights into the understanding of the EMSI in heterogeneous catalysis and can open new avenues to design and fabricate cost-effective single-atom-sized and/or nanometer-sized catalysts.« less

Adaptive deep brain stimulation in advanced Parkinson disease.

PubMed

Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

2013-09-01

Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

Predictive display design for the vehicles with time delay in dynamic response

NASA Astrophysics Data System (ADS)

Efremov, A. V.; Tiaglik, M. S.; Irgaleev, I. H.; Efremov, E. V.

2018-02-01

The two ways for the improvement of flying qualities are considered: the predictive display (PD) and the predictive display integrated with the flight control system (FCS). The both ways allow to transforming the controlled element dynamics in the crossover frequency range, to improve the accuracy of tracking and to suppress the effect of time delay in the vehicle response too. The technique for optimization of the predictive law is applied to the landing task. The results of the mathematical modeling and experimental investigations carried out for this task are considered in the paper.

Can sensory attention focused exercise facilitate the utilization of proprioception for improved balance control in PD?

PubMed

Lefaivre, Shannon C; Almeida, Quincy J

2015-02-01

Impaired sensory processing in Parkinson's disease (PD) has been argued to contribute to balance deficits. Exercises aimed at improving sensory feedback and body awareness have the potential to ameliorate balance deficits in PD. Recently, PD SAFEx™, a sensory and attention focused rehabilitation program, has been shown to improve motor deficits in PD, although balance control has never been evaluated. The objective of this study was to measure the effects of PD SAFEx™ on balance control in PD. Twenty-one participants with mild to moderate idiopathic PD completed 12 weeks of PD SAFEx™ training (three times/week) in a group setting. Prior to training, participants completed a pre-assessment evaluating balance in accordance with an objective, computerized test of balance (modified clinical test of sensory integration and balance (m-CTSIB) and postural stability testing (PST)) protocols. The m-CTSIB was our primary outcome measure, which allowed assessment of balance in both eyes open and closed conditions, thus enabling evaluation of specific sensory contributions to balance improvement. At post-test, a significant interaction between time of assessment and vision condition (p=.014) demonstrated that all participants significantly improved balance control, specifically when eyes were closed. Balance control did not change from pre to post with eyes open. These results provide evidence that PD SAFEx™ is effective at improving the ability to utilize proprioceptive information, resulting in improved balance control in the absence of vision. Enhancing the ability to utilize proprioception for individuals with PD is an important intermediary to improving balance deficits. Copyright © 2015. Published by Elsevier B.V.

Grapevines undergo varying shifts in secondary metabolic profiles when infected with Xylella fastidiosa

USDA-ARS?s Scientific Manuscript database

Pierce’s disease (PD) is a devastating disease of grapevine caused by the bacterial pathogen Xylella fastidiosa (Xf). Key to the development and optimization of PD-tolerant grape cultivars is improved understanding about how grapevines defend themselves against Xf. This study complements histologica...

A facile self-assembly approach to prepare palladium/carbon nanotubes catalyst for the electro-oxidation of ethanol

NASA Astrophysics Data System (ADS)

Wen, Cuilian; Zhang, Xinyuan; Wei, Ying; Zhang, Teng; Chen, Changxin

2018-02-01

A facile self-assembly approach is reported to prepare palladium/carbon nanotubes (Pd/CNTs) catalyst for the electro-oxidation of ethanol. In this method, the Pd-oleate/CNTs was decomposed into the Pd/CNTs at an optimal temperature of 195 °C in air, in which no inert gas is needed for the thermal decomposition process due to the low temperature used and the decomposed products are also environmental friendly. The prepared Pd/CNTs catalyst has a high metallic Pd0 content and the Pd particles in the catalyst are disperse, uniform-sized with an average size of ˜2.1 nm, and evenly distributed on the CNTs. By employing our strategy, the problems including the exfoliation of the metal particles from the CNTs and the aggregation of the metal particles can be solved. Comparing with the commercial Pd/C one, the prepared Pd/CNTs catalyst exhibits a much higher electrochemical activity and stability for the electro-oxidation of ethanol in the direct ethanol fuel cells.

Weight Change Is a Characteristic Non-Motor Symptom in Drug-Naïve Parkinson's Disease Patients with Non-Tremor Dominant Subtype: A Nation-Wide Observational Study.

PubMed

Mun, Jun Kyu; Youn, Jinyoung; Cho, Jin Whan; Oh, Eung-Seok; Kim, Ji Sun; Park, Suyeon; Jang, Wooyoung; Park, Jin Se; Koh, Seong-Beom; Lee, Jae Hyeok; Park, Hee Kyung; Kim, Han-Joon; Jeon, Beom S; Shin, Hae-Won; Choi, Sun-Ah; Kim, Sang Jin; Choi, Seong-Min; Park, Ji-Yun; Kim, Ji Young; Chung, Sun Ju; Lee, Chong Sik; Ahn, Tae-Beom; Kim, Won Chan; Kim, Hyun Sook; Cheon, Sang Myung; Kim, Jae Woo; Kim, Hee-Tae; Lee, Jee-Young; Kim, Ji Sun; Kim, Eun-Joo; Kim, Jong-Min; Lee, Kwang Soo; Kim, Joong-Seok; Kim, Min-Jeong; Baik, Jong Sam; Park, Ki-Jong; Kim, Hee Jin; Park, Mee Young; Kang, Ji Hoon; Song, Sook Kun; Kim, Yong Duk; Yun, Ji Young; Lee, Ho-Won; Song, In-Uk; Sohn, Young H; Lee, Phil Hyu; Park, Jeong-Ho; Oh, Hyung Geun; Park, Kun Woo; Kwon, Do-Young

2016-01-01

Despite the clinical impact of non-motor symptoms (NMS) in Parkinson's disease (PD), the characteristic NMS in relation to the motor subtypes of PD is not well elucidated. In this study, we enrolled drug-naïve PD patients and compared NMS between PD subtypes. We enrolled 136 drug-naïve, early PD patients and 50 normal controls. All the enrolled PD patients were divided into tremor dominant (TD) and non-tremor dominant (NTD) subtypes. The Non-Motor Symptom Scale and scales for each NMS were completed. We compared NMS and the relationship of NMS with quality of life between normal controls and PD patients, and between the PD subtypes. Comparing with normal controls, PD patients complained of more NMS, especially mood/cognitive symptoms, gastrointestinal symptoms, unexplained pain, weight change, and change in taste or smell. Between the PD subtypes, the NTD subtype showed higher total NMS scale score and sub-score about weight change. Weight change was the characteristic NMS related to NTD subtype even after controlled other variables with logistic regression analysis. Even from the early stage, PD patients suffer from various NMS regardless of dopaminergic medication. Among the various NMS, weight change is the characteristic NMS associated with NTD subtype in PD patients.

Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study.

PubMed

Min Lee, Charles Kyung; Li, Shufeng; Tran, Duy Cong; Zhu, Gefei Alex; Kim, Jinah; Kwong, Bernice Y; Chang, Anne Lynn S

2018-05-29

Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized. (s): To assess the nature of dermatitis after PD-1/PD-L1 inhibitor exposure and oncologic outcomes associated with dermatitis. Retrospective, matched, case-control study conducted at a single academic center. The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). Overall tumor response rate was 65.0% for cases and 17.0% for controls (p=0.0007), odds ratio: 7.3 (95% CI 2.3-23.1). Progression Free Survival (PFS) and Overall Survival (OS) times were significantly longer for cases than controls by Kaplan-Meier analysis (p<0.0001 and 0.0203, respectively). Retrospective design and relatively small sample size precluded matching on all cancer types. Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The predictive value of PD-1/PD-L1 related dermatitis on cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types. Copyright © 2018. Published by Elsevier Inc.

A palladium-doped ceria@carbon core-sheath nanowire network: a promising catalyst support for alcohol electrooxidation reactions

NASA Astrophysics Data System (ADS)

Tan, Qiang; Du, Chunyu; Sun, Yongrong; Du, Lei; Yin, Geping; Gao, Yunzhi

2015-08-01

A novel palladium-doped ceria and carbon core-sheath nanowire network (Pd-CeO2@C CSNWN) is synthesized by a template-free and surfactant-free solvothermal process, followed by high temperature carbonization. This hierarchical network serves as a new class of catalyst support to enhance the activity and durability of noble metal catalysts for alcohol oxidation reactions. Its supported Pd nanoparticles, Pd/(Pd-CeO2@C CSNWN), exhibit >9 fold increase in activity toward the ethanol oxidation over the state-of-the-art Pd/C catalyst, which is the highest among the reported Pd systems. Moreover, stability tests show a virtually unchanged activity after 1000 cycles. The high activity is mainly attributed to the superior oxygen-species releasing capability of Pd-doped CeO2 nanowires by accelerating the removal of the poisoning intermediate. The unique interconnected one-dimensional core-sheath structure is revealed to facilitate immobilization of the metal catalysts, leading to the improved durability. This core-sheath nanowire network opens up a new strategy for catalyst performance optimization for next-generation fuel cells.A novel palladium-doped ceria and carbon core-sheath nanowire network (Pd-CeO2@C CSNWN) is synthesized by a template-free and surfactant-free solvothermal process, followed by high temperature carbonization. This hierarchical network serves as a new class of catalyst support to enhance the activity and durability of noble metal catalysts for alcohol oxidation reactions. Its supported Pd nanoparticles, Pd/(Pd-CeO2@C CSNWN), exhibit >9 fold increase in activity toward the ethanol oxidation over the state-of-the-art Pd/C catalyst, which is the highest among the reported Pd systems. Moreover, stability tests show a virtually unchanged activity after 1000 cycles. The high activity is mainly attributed to the superior oxygen-species releasing capability of Pd-doped CeO2 nanowires by accelerating the removal of the poisoning intermediate. The unique interconnected one-dimensional core-sheath structure is revealed to facilitate immobilization of the metal catalysts, leading to the improved durability. This core-sheath nanowire network opens up a new strategy for catalyst performance optimization for next-generation fuel cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03023d

A simple attitude control of quadrotor helicopter based on Ziegler-Nichols rules for tuning PD parameters.

PubMed

He, ZeFang; Zhao, Long

2014-01-01

An attitude control strategy based on Ziegler-Nichols rules for tuning PD (proportional-derivative) parameters of quadrotor helicopters is presented to solve the problem that quadrotor tends to be instable. This problem is caused by the narrow definition domain of attitude angles of quadrotor helicopters. The proposed controller is nonlinear and consists of a linear part and a nonlinear part. The linear part is a PD controller with PD parameters tuned by Ziegler-Nichols rules and acts on the quadrotor decoupled linear system after feedback linearization; the nonlinear part is a feedback linearization item which converts a nonlinear system into a linear system. It can be seen from the simulation results that the attitude controller proposed in this paper is highly robust, and its control effect is better than the other two nonlinear controllers. The nonlinear parts of the other two nonlinear controllers are the same as the attitude controller proposed in this paper. The linear part involves a PID (proportional-integral-derivative) controller with the PID controller parameters tuned by Ziegler-Nichols rules and a PD controller with the PD controller parameters tuned by GA (genetic algorithms). Moreover, this attitude controller is simple and easy to implement.

Voice Tremor in Parkinson's Disease: An Acoustic Study.

PubMed

Gillivan-Murphy, Patricia; Miller, Nick; Carding, Paul

2018-01-30

Voice tremor associated with Parkinson disease (PD) has not been characterized. Its relationship with voice disability and disease variables is unknown. This study aimed to evaluate voice tremor in people with PD (pwPD) and a matched control group using acoustic analysis, and to examine correlations with voice disability and disease variables. Acoustic voice tremor analysis was completed on 30 pwPD and 28 age-gender matched controls. Voice disability (Voice Handicap Index), and disease variables of disease duration, Activities of Daily Living (Unified Parkinson's Disease Rating Scale [UPDRS II]), and motor symptoms related to PD (UPDRS III) were examined for relationship with voice tremor measures. Voice tremor was detected acoustically in pwPD and controls with similar frequency. PwPD had a statistically significantly higher rate of amplitude tremor (Hz) than controls (P = 0.001). Rate of amplitude tremor was negatively and significantly correlated with UPDRS III total score (rho -0.509). For pwPD, the magnitude and periodicity of acoustic tremor was higher than for controls without statistical significance. The magnitude of frequency tremor (Mftr%) was positively and significantly correlated with disease duration (rho 0.463). PwPD had higher Voice Handicap Index total, functional, emotional, and physical subscale scores than matched controls (P < 0.001). Voice disability did not correlate significantly with acoustic voice tremor measures. Acoustic analysis enhances understanding of PD voice tremor characteristics, its pathophysiology, and its relationship with voice disability and disease symptomatology. Copyright © 2018 The Voice Foundation. All rights reserved.

Tuning fuzzy PD and PI controllers using reinforcement learning.

PubMed

Boubertakh, Hamid; Tadjine, Mohamed; Glorennec, Pierre-Yves; Labiod, Salim

2010-10-01

In this paper, we propose a new auto-tuning fuzzy PD and PI controllers using reinforcement Q-learning (QL) algorithm for SISO (single-input single-output) and TITO (two-input two-output) systems. We first, investigate the design parameters and settings of a typical class of Fuzzy PD (FPD) and Fuzzy PI (FPI) controllers: zero-order Takagi-Sugeno controllers with equidistant triangular membership functions for inputs, equidistant singleton membership functions for output, Larsen's implication method, and average sum defuzzification method. Secondly, the analytical structures of these typical fuzzy PD and PI controllers are compared to their classical counterpart PD and PI controllers. Finally, the effectiveness of the proposed method is proven through simulation examples. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Morphologic changes in the mesolimbic pathway in Parkinson's disease motor subtypes.

PubMed

Nyberg, Eric M; Tanabe, Jody; Honce, Justin M; Krmpotich, Theodore; Shelton, Erika; Hedeman, Jessica; Berman, Brian D

2015-05-01

Parkinson's disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. Cortical atrophy patterns may further help distinguish between PD motor subtypes. Comparable differences in subcortical volumes have not been found. Twenty-one cognitively intact and treated PD patients, including 12 tremor dominant (TD) subtype, Nine postural instability gait dominant (PIGD) subtype, and 20 matched healthy control subjects underwent 3.0 T high-resolution structural MRI scanning. Subcortical volumetric analysis was performed using FreeSurfer and shape analysis was performed with FIRST to assess for differences between PD patients and controls and between PD subtypes. No significant differences in subcortical volumes were found between motor PD subtypes, but comparing grouped PD patients with controls revealed a significant increase in hippocampal volume in PD patients (p = 0.03). A significant shape difference was detected in the right nucleus accumbens (NAcc) between PD and controls and between motor subtypes. Shape differences were driven by positive deviations in the TD subtype. Correlation analysis revealed a trend between hippocampal volume and decreasing MDS-UPDRS (p = 0.06). While no significant differences in subcortical volumes between PD motor subtypes were found, increased hippocampal volumes were observed in PD patients compared to controls. Right NAcc shape differences in PD patients were driven by changes in the TD subtype. These unexpected findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway. Further studies are needed to replicate and determine the clinical significance of such morphologic changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Acting without being in control: Exploring volition in Parkinson's disease with impulsive compulsive behaviours.

PubMed

Ricciardi, Lucia; Haggard, Patrick; de Boer, Lieke; Sorbera, Chiara; Stenner, Max-Philipp; Morgante, Francesca; Edwards, Mark J

2017-07-01

Several aspects of volitional control of action may be relevant in the pathophysiology of impulsive-compulsive behaviours (ICB) in Parkinson's disease (PD). We aimed to explore multiple aspects of action control, assessing reward-related behaviour, inhibition (externally and internally triggered) and sense of agency in PD patients, with and without ICB compared to healthy subjects. Nineteen PD patients with ICB (PD-ICB), 19 PD without ICB (PD-no-ICB) and 19 healthy controls (HC) underwent a battery of tests including: Intentional Binding task which measures sense of agency; Stop Signal Reaction Time (SSRT) measuring capacity for reactive inhibition; the Marble task, assessing intentional inhibition; Balloon Analog Risk Task for reward sensitivity. One-way ANOVA showed significant main effect of group for action binding (p = 0.004, F = 6.27). Post hoc analysis revealed that PD-ICB had significantly stronger action binding than HC (p = 0.004), and PD-no-ICB (p = 0.04). There was no difference between PD-no-ICB and HC. SSRT did not differ between PD groups, whereas a significant difference between PD-no-ICB and HC was detected (p = 0.01). No other differences were found among groups in the other tasks. PD patients with ICB have abnormal performance on a psychophysical task assessing sense of agency, which might be related to a deficit in action representation at cognitive/experiential level. Yet, they have no deficit on tasks evaluating externally and internally triggered inhibitory control, or in reward-based decision-making. We conclude that impaired sense of agency may be a factor contributing to ICB in PD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Gene promoter methylation in glucose-6-phosphate dehydrogenase deficiency].

PubMed

Xu, Dan-Dan; Wen, Fei-Qiu; Lv, Rong-Yu; Zhang, Min; Chen, Yun-Sheng; Chen, Xiao-Wen

2016-05-01

To investigate the features of methylation in the promoter region of glucose-6-phosphate dehydrogenase (G6PD) gene and the association between gene promoter methylation and G6PD deficiency. Fluorescent quantitative PCR was used to measure the mRNA expression of G6PD in 130 children with G6PD deficiency. Sixty-five children without G6PD deficiency served as the control group. The methylation-sensitive high-resolution melting curve analysis and bisulfite PCR sequencing were used to analyze gene promoter methylation in 22 children with G6PD deficiency and low G6PD mRNA expression. The G6PD gene promoter methylation was analyzed in 44 girls with normal G6PD mRNA expression (7 from G6PD deficiency group and 37 from control group). Twenty-two (16.9%) children with G6PD deficiency had relatively low mRNA expression of G6PD; among whom, 16 boys showed no methylation, and 6 girls showed partial methylation. Among the 44 girls with normal G6PD mRNA expression, 40 showed partial methylation, and 4 showed no methylation (1 case in the G6PD group and 3 cases in the control group). Gene promoter methylation is not associated with G6PD deficiency in boys. Girls have partial methylation or no methylation in the G6PD gene, suggesting that the methylation may be related to G6PD deficiency in girls.

Mesoporous silica nanoparticle supported PdIr bimetal catalyst for selective hydrogenation, and the significant promotional effect of Ir

NASA Astrophysics Data System (ADS)

Yang, Hui; Huang, Chao; Yang, Fan; Yang, Xu; Du, Li; Liao, Shijun

2015-12-01

A mesoporous silica nanoparticle (MSN) supported bimetal catalyst, PdIr/MSN, was prepared by a facile impregnation and hydrogen reduction method. The strong promotional effect of Ir was observed and thoroughly investigated. At the optimal molar ratio of Ir to Pd (NIr/NPd = 0.1), the activity of PdIr0.1/MSN was up to eight times and 28 times higher than that of monometallic Pd/MSN and Ir/MSN, respectively. The catalysts were characterized comprehensively by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and hydrogen temperature programmed reduction, which revealed that the promotional effect of Ir may be due to the enhanced dispersion of active components on the MSN, and to the intensified Pd-Ir electronic interaction caused by the addition of Ir.

Premorbid dietetic habits and risk for Parkinson's disease.

PubMed

Ayuso-Peralta, L; Jiménez-Jiménez, F J; Cabrera-Valdivia, F; Molina, J; Javier, M R; Almazán; De Pedro-Cuesta, J; Tabernero, C; Giménez-Roldán, S

1997-01-01

To evaluate the possible role of antioxidant (vitamins A, E, C, beta-carotene, zinc, selenium) or pro-oxidant (iron, copper, manganese) factors present in the diet, in the risk for Parkinson's disease (PD), we conducted a dietetic study (pre- and postmarriage) which included 91 foodstuffs. We interviewed separately 119 PD patients (64 males, 55 females, age 65.3 +/- 8.5 years, age at marriage 27.8 +/- 5.9 years) and their spouses (age 65.0 +/- 9.2 years, age at marriage 27.2 +/- 5.9 years) as the control group (C). Premarriage consumption for each foodstuff was classified into: (1) rarely of annually, (2) monthly, or (3) weekly; and postmarriage consumption (which included the period between age at marruage and age 40 years; only concordant answers were considered to be valid) into: (1) PD > Control, (2) Control > PD, and (3) PD = Control. The premarriage interview showed a trend towards a lower consumption of peas in PD patients as compared to controls. The postmarriage interview in PD patients showed a higher tendency for the consumption of rice, bluefish, liver paté and eggs, and a less consumption of tea than controls. We were unable to find any consistent trend towards a lower consumption of vitamins E and C during adulthood in PD patients, but they seemed to have eaten selenium-rich foodstuffs more frequently than controls. These results differ from those obtained by previous studies, and question the possible role of premorbid dietary habits on the risk for PD.

Cognition and connectomes in nondementia idiopathic Parkinson’s disease

PubMed Central

Tanner, Jared J.; Couret, Michelle; Goicochea, Shelby; Mareci, Thomas H.; Price, Catherine C.

2018-01-01

In this study, we investigate the organization of the structural connectome in cognitively well participants with Parkinson’s disease (PD-Well; n = 31) and a subgroup of participants with Parkinson’s disease who have amnestic disturbances (PD-MI; n = 9). We explore correlations between connectome topology and vulnerable cognitive domains in Parkinson’s disease relative to non-Parkinson’s disease peers (control, n = 40). Diffusion-weighted MRI data and deterministic tractography were used to generate connectomes. Connectome topological indices under study included weighted indices of node strength, path length, clustering coefficient, and small-worldness. Relative to controls, node strength was reduced 4.99% for PD-Well (p = 0.041) and 13.2% for PD-MI (p = 0.004). We found bilateral differences in the node strength between PD-MI and controls for inferior parietal, caudal middle frontal, posterior cingulate, precentral, and rostral middle frontal. Correlations between connectome and cognitive domains of interest showed that topological indices of global connectivity negatively associated with working memory and displayed more and larger negative correlations with neuropsychological indices of memory in PD-MI than in PD-Well and controls. These findings suggest that indices of network connectivity are reduced in PD-MI relative to PD-Well and control participants. PMID:29911667

Qualitative Characteristics of Depression in Parkinson's Patients and Controls.

PubMed

Kritzinger, Cleo; Vollstedt, Eva-Juliane; Hückelheim, Katja; Lorwin, Anne; Graf, Julia; Tunc, Sinem; Klein, Christine; Kasten, Meike

2015-01-01

Depression is common in Parkinson's disease (PD); in light of typical PD pathology it may differ phenomenologically from depression in the general population. To assess depressive symptoms in PD patients and control groups and compare symptom profiles. After postal screening of 10,000 citizens of Lübeck, 642 participants were examined and the Beck Depression Inventory (BDI) was sufficiently answered by 477 subjects. Based on motor examinations, we distinguished PD patients, Healthy Controls (HC, no motor impairment), and Disease Controls (DC, motor impairment other than PD). The sample comprised 331 men and 311 women, aged 65 ± 8 years. Out of the overall sample, 198 (41.5%) had a BDI score ≥9. BDI results above 9 points occurred in 34.5% of HC, 50.3% of DC, and 42.4% of PD patients. Compared to the control groups (HC, DC) the PD patients endorsed more "dissatisfaction" and "loss of appetite" but less "feelings of guilt," "self-hate," and "loss of libido." Depressive symptoms are more frequent in PD patients compared to HC but not DC. Interestingly, the distribution of individual symptoms of the BDI differs between groups with an emphasis on loss of pleasure/enjoyment in the PD group, a symptom typically considered to be dopaminergically transmitted.

Optimizing hippocampal segmentation in infants utilizing MRI post-acquisition processing.

PubMed

Thompson, Deanne K; Ahmadzai, Zohra M; Wood, Stephen J; Inder, Terrie E; Warfield, Simon K; Doyle, Lex W; Egan, Gary F

2012-04-01

This study aims to determine the most reliable method for infant hippocampal segmentation by comparing magnetic resonance (MR) imaging post-acquisition processing techniques: contrast to noise ratio (CNR) enhancement, or reformatting to standard orientation. MR scans were performed with a 1.5 T GE scanner to obtain dual echo T2 and proton density (PD) images at term equivalent (38-42 weeks' gestational age). 15 hippocampi were manually traced four times on ten infant images by 2 independent raters on the original T2 image, as well as images processed by: a) combining T2 and PD images (T2-PD) to enhance CNR; then b) reformatting T2-PD images perpendicular to the long axis of the left hippocampus. CNRs and intraclass correlation coefficients (ICC) were calculated. T2-PD images had 17% higher CNR (15.2) than T2 images (12.6). Original T2 volumes' ICC was 0.87 for rater 1 and 0.84 for rater 2, whereas T2-PD images' ICC was 0.95 for rater 1 and 0.87 for rater 2. Reliability of hippocampal segmentation on T2-PD images was not improved by reformatting images (rater 1 ICC = 0.88, rater 2 ICC = 0.66). Post-acquisition processing can improve CNR and hence reliability of hippocampal segmentation in neonate MR scans when tissue contrast is poor. These findings may be applied to enhance boundary definition in infant segmentation for various brain structures or in any volumetric study where image contrast is sub-optimal, enabling hippocampal structure-function relationships to be explored.

Hyperbranched polyglycerol is an efficacious and biocompatible novel osmotic agent in a rodent model of peritoneal dialysis.

PubMed

Mendelson, Asher A; Guan, Qiunong; Chafeeva, Irina; da Roza, Gerald A; Kizhakkedathu, Jayachandran N; Du, Caigan

2013-01-01

To enhance the effectiveness of peritoneal dialysis (PD), new biocompatible PD solutions may be needed. The present study was designed to test the efficacy and biocompatibility of hyperbranched polyglycerol (HPG)-a nontoxic, nonimmunogenic water-soluble polyether polymer-in PD. Adult Sprague-Dawley rats were instilled with 30 mL HPG solution (molecular weight 3 kDa; 2.5% - 15%) or control glucose PD solution (2.5% Dianeal: Baxter Healthcare Corporation, Deerfield, IL, USA), and intraperitoneal fluid was recovered after 4 hours. Peritoneal injury and cellular infiltration were determined by histologic and flow cytometric analysis. Human peritoneal mesothelial cells were assessed for viability in vitro after 3 hours of PD fluid exposure. The 15% HPG solution achieved a 4-hour dose-related ultrafiltration up to 43.33 ± 5.24 mL and a dose-related urea clearance up to 39.17 ± 5.21 mL, results that were superior to those with control PD solution (p < 0.05). The dialysate-to-plasma (D/P) ratios of urea with 7.5% and 15% HPG solution were not statistically different from those with control PD solution. Compared with fluid recovered from the control group, fluid recovered from the HPG group contained proportionally fewer neutrophils (3.63% ± 0.87% vs 9.31% ± 2.89%, p < 0.0001). Detachment of mesothelial cells positive for human bone marrow endothelial protein 1 did not increase in the HPG group compared with the stain control (p = 0.1832), but it was elevated in the control PD solution group (1.62% ± 0.68% vs 0.41% ± 0.31%, p = 0.0031). Peritoneal biopsies from animals in the HPG PD group, compared with those from control PD animals, demonstrated less neutrophilic infiltration and reduced thickness. Human peritoneal mesothelial cell survival after HPG exposure was superior in vitro (p < 0.0001, 7.5% HPG vs control; p < 0.01, 15% HPG vs control). Exposure to glucose PD solution induced cytoplasmic vacuolation and caspase 3-independent necrotic cell death that was not seen with HPG solution. Our novel HPG PD solution demonstrated effective ultrafiltration and waste removal with reduced peritoneal injury in a rodent model of PD.

Hyperbranched Polyglycerol Is an Efficacious and Biocompatible Novel Osmotic Agent in a Rodent Model of Peritoneal Dialysis

PubMed Central

Mendelson, Asher A.; Guan, Qiunong; Chafeeva, Irina; da Roza, Gerald A.; Kizhakkedathu, Jayachandran N.; Du, Caigan

2013-01-01

♦ Objectives: To enhance the effectiveness of peritoneal dialysis (PD), new biocompatible PD solutions may be needed. The present study was designed to test the efficacy and biocompatibility of hyperbranched polyglycerol (HPG)—a nontoxic, nonimmunogenic water-soluble polyether polymer—in PD. ♦ Methods: Adult Sprague-Dawley rats were instilled with 30 mL HPG solution (molecular weight 3 kDa; 2.5% - 15%) or control glucose PD solution (2.5% Dianeal: Baxter Healthcare Corporation, Deerfield, IL, USA), and intraperitoneal fluid was recovered after 4 hours. Peritoneal injury and cellular infiltration were determined by histologic and flow cytometric analysis. Human peritoneal mesothelial cells were assessed for viability in vitro after 3 hours of PD fluid exposure. ♦ Results: The 15% HPG solution achieved a 4-hour dose-related ultrafiltration up to 43.33 ± 5.24 mL and a dose-related urea clearance up to 39.17 ± 5.21 mL, results that were superior to those with control PD solution (p < 0.05). The dialysate-to-plasma (D/P) ratios of urea with 7.5% and 15% HPG solution were not statistically different from those with control PD solution. Compared with fluid recovered from the control group, fluid recovered from the HPG group contained proportionally fewer neutrophils (3.63% ± 0.87% vs 9.31% ± 2.89%, p < 0.0001). Detachment of mesothelial cells positive for human bone marrow endothelial protein 1 did not increase in the HPG group compared with the stain control (p = 0.1832), but it was elevated in the control PD solution group (1.62% ± 0.68% vs 0.41% ± 0.31%, p = 0.0031). Peritoneal biopsies from animals in the HPG PD group, compared with those from control PD animals, demonstrated less neutrophilic infiltration and reduced thickness. Human peritoneal mesothelial cell survival after HPG exposure was superior in vitro (p < 0.0001, 7.5% HPG vs control; p < 0.01, 15% HPG vs control). Exposure to glucose PD solution induced cytoplasmic vacuolation and caspase 3-independent necrotic cell death that was not seen with HPG solution. ♦ Conclusions: Our novel HPG PD solution demonstrated effective ultrafiltration and waste removal with reduced peritoneal injury in a rodent model of PD. PMID:23349194

Tunable Catalysis of Water to Peroxide with Anionic, Cationic, and Neutral Atomic Au, Ag, Pd, Rh, and Os

NASA Astrophysics Data System (ADS)

Suggs, K.; Kiros, F.; Tesfamichael, A.; Felfli, Z.; Msezane, A. Z.

2015-05-01

Fundamental anionic, cationic, and neutral atomic metal predictions utilizing density functional theory calculations validate the recent discovery identifying the interplay between Regge resonances and Ramsauer-Townsend minima obtained through complex angular momentum analysis as the fundamental atomic mechanism underlying nanoscale catalysis. Here we investigate the optimization of the catalytic behavior of Au, Ag, Pd, Rh, and Os atomic systems via polarization effects and conclude that anionic atomic systems are optimal and therefore ideal for catalyzing the oxidation of water to peroxide, with anionic Os being the best candidate. The discovery that cationic systems increase the transition energy barrier in the synthesis of peroxide could be important as inhibitors in controlling and regulating catalysis. These findings usher in a fundamental and comprehensive atomic theoretical framework for the generation of tunable catalytic systems. The ultimate aim is to design giant atomic catalysts and sensors, in the context of the recently synthesized tri-metal Ag@Au@Pt and bimetal Ag@Au nanoparticles for greatly enhanced plasmonic properties and improved chemical stability for chemical and biological sensing. Research was supported by U.S. DOE Office of Basic Energy Sciences.

What Information Theory Says About Best Response and About Binding Contracts

NASA Technical Reports Server (NTRS)

Wolpert, David H.

2004-01-01

Product Distribution (PD) theory is the information-theoretic extension of conventional full- rationality game theory to bounded rational games. Here PD theory is used to investigate games in which the players use bounded rational best-response strategies. This investigation illuminates how to determine the optimal organization chart for a corporation, or more generally how to order the sequence of moves of the players / employees so as to optimize an overall objective function. It is then shown that in the continuum-time limit, bounded rational best response games result in a variant of the replicator dynamics of evolutionary game theory. This variant is then investigated for team games, in which the players share the same utility function, by showing that such continuum- limit bounded rational best response is identical to Newton-Raphson iterative optimization of the shared utility function. Next PD theory is used to investigate changing the coordinate system of the game, i.e., changing the mapping from the joint move of the players to the arguments in the utility functions. Such a change couples those arguments, essentially by making each players move be an offered binding contract.

To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease.

PubMed

Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2015-04-01

Cognitive decline is a burdensome extra-motor symptom associated with Parkinson's disease (PD). This study aimed at investigating intrinsic functional connectivity (iFC) of the brain in cognitively unimpaired (PD-CU) and impaired PD patients (PD-CI) compared with age-matched healthy controls. "Resting-state" functional magnetic resonance imaging was acquired in 53 subjects, that is, 14 PD-CU patients, 17 PD-CI patients, and 22 control subjects. Cognition and cognitive status for patient classification were assessed using detailed neuropsychological testing. In PD-CU patients versus controls, we demonstrated significantly increased iFC (hyperconnectivity) presenting as network expansions in cortical, limbic, and basal ganglia-thalamic areas. Significantly, decreased iFC in PD-CI patients compared with control subjects was observed, predominantly between major nodes of the default mode network. In conclusion, the increased iFC might be the initial manifestation of altered brain function preceding cognitive deficits. Hyperconnectivity could be an adaptive (compensatory) mechanism by recruiting additional resources to maintain normal cognitive performance. As PD-related pathology progresses, functional disruptions within the default mode networks seem to be considerably associated with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

Using Gastrocnemius sEMG and Plasma α-Synuclein for the Prediction of Freezing of Gait in Parkinson's Disease Patients

PubMed Central

Yang, Qiong; Zhang, Lin-Yuan; Chen, Sheng-Di; Liu, Jun

2014-01-01

Freezing of gait (FOG) is a complicated gait disturbance in Parkinson's disease (PD) and a relevant subclinical predictor algorithm is lacking. The main purpose of this study is to explore the potential value of surface electromyograph (sEMG) and plasma α-synuclein levels as predictors of the FOG seen in PD. 21 PD patients and 15 normal controls were recruited. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Freezing of gait questionnaire (FOG-Q). Simultaneously, gait analysis was also performed using VICON capture system in PD patients and sEMG data was recorded as well. Total plasma α-synuclein was quantitatively assessed by Luminex assay in all participants. Recruited PD patients were classified into two groups: PD patients with FOG (PD+FOG) and without FOG (PD-FOG), based on clinical manifestation, the results of the FOG-Q and VICON capture system. PD+FOG patients displayed higher FOG-Q scores, decreased walking speed, smaller step length, smaller stride length and prolonged double support time compared to the PD-FOG in the gait trial. sEMG data indicated that gastrocnemius activity in PD+FOG patients was significantly reduced compared to PD-FOG patients. In addition, plasma α-synuclein levels were significantly decreased in the PD+FOG group compared to control group; however, no significant difference was found between the PD+FOG and PD-FOG groups. Our study revealed that gastrocnemius sEMG could be used to evaluate freezing gait in PD patients, while plasma α-synuclein might discriminate freezing of gait in PD patients from normal control, though no difference was found between the PD+FOG and PD-FOG groups. PMID:24586710

Large Marks-decahedral Pd nanoparticles synthesized by a modified hydrothermal method using a homogeneous reactor

NASA Astrophysics Data System (ADS)

Zhao, Haiqiang; Qi, Weihong; Ji, Wenhai; Wang, Tianran; Peng, Hongcheng; Wang, Qi; Jia, Yanlin; He, Jieting

2017-05-01

Fivefold symmetry appears only in small particles and quasicrystals because internal stress in the particles increases with the particle size. However, a typical Marks decahedron with five re-entrant grooves located at the ends of the twin boundaries can further reduce the strain energy. During hydrothermal synthesis, it is difficult to stir the reaction solution contained in a digestion high-pressure tank because of the relatively small size and high-temperature and high-pressure sealed environment. In this work, we optimized a hydrothermal reaction system by replacing the conventional drying oven with a homogeneous reactor to shift the original static reaction solution into a full mixing state. Large Marks-decahedral Pd nanoparticles ( 90 nm) have been successfully synthesized in the optimized hydrothermal synthesis system. Additionally, in the products, round Marks-decahedral Pd particles were also found for the first time. While it remains a challenge to understand the growth mechanism of the fivefold twinned structure, we proposed a plausible growth-mediated mechanism for Marks-decahedral Pd nanoparticles based on observations of the synthesis process.

Interrogating the catalytic mechanism of nanoparticle mediated Stille coupling reactions employing bio-inspired Pd nanocatalysts.

PubMed

Pacardo, Dennis B; Slocik, Joseph M; Kirk, Kyle C; Naik, Rajesh R; Knecht, Marc R

2011-05-01

To address issues concerning the global environmental and energy state, new catalytic technologies must be developed that translate ambient and efficient conditions to heavily used reactions. To achieve this, the structure/function relationship between model catalysts and individual reactions must be critically discerned to identify structural motifs responsible for the reactivity. This is especially true for nanoparticle-based systems where this level of information remains limited. Here we present evidence indicating that peptide-capped Pd nanoparticles drive Stille C-C coupling reactions via Pd atom leaching. Through a series of reaction studies, the materials are shown to be optimized for reactivity under ambient conditions where increases in temperature or catalyst concentration deactivate reactivity due to the leaching process. A quartz crystal microbalance analysis demonstrates that Pd leaching occurs during the initial oxidative addition step at the nanoparticle surface by aryl halides. Together, this suggests that peptide-based materials may be optimally suited for use as model systems to isolate structural motifs responsible for the generation of catalytically reactive materials under ambient synthetic conditions. © The Royal Society of Chemistry 2011

Interrogating the catalytic mechanism of nanoparticle mediated Stille coupling reactions employing bio-inspired Pd nanocatalysts

NASA Astrophysics Data System (ADS)

Pacardo, Dennis B.; Slocik, Joseph M.; Kirk, Kyle C.; Naik, Rajesh R.; Knecht, Marc R.

2011-05-01

To address issues concerning the global environmental and energy state, new catalytic technologies must be developed that translate ambient and efficient conditions to heavily used reactions. To achieve this, the structure/function relationship between model catalysts and individual reactions must be critically discerned to identify structural motifs responsible for the reactivity. This is especially true for nanoparticle-based systems where this level of information remains limited. Here we present evidence indicating that peptide-capped Pd nanoparticles drive Stille C-C coupling reactions via Pd atom leaching. Through a series of reaction studies, the materials are shown to be optimized for reactivity under ambient conditions where increases in temperature or catalyst concentration deactivate reactivity due to the leaching process. A quartz crystal microbalance analysis demonstrates that Pd leaching occurs during the initial oxidative addition step at the nanoparticle surface by aryl halides. Together, this suggests that peptide-based materials may be optimally suited for use as model systems to isolate structural motifs responsible for the generation of catalytically reactive materials under ambient synthetic conditions.

[PD-L1 expression: An emerging biomarker in non-small cell lung cancer].

PubMed

Adam, Julien; Planchard, David; Marabelle, Aurélien; Soria, Jean-Charles; Scoazec, Jean-Yves; Lantuéjoul, Sylvie

2016-01-01

Therapies targeting immune checkpoints, in particular programmed death 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1), are major new strategies for the treatment of several malignancies including mestatatic non-small cell lung cancer (NSCLC). The identification of predictive biomarkers of response is required, considering efficacy, cost and potential adverse events. Expression of PD-L1 by immunohistochemistry has been associated with higher response rate and overall survival in several clinical trials evaluating anti-PD-1 and anti-PD-L1 monoclonal antibodies. Thus, PD-L1 immunohistochemical companion assays could be required for treatment with some of these therapies in NSCLC. However, heterogeneity in methodologies of PD-L1 assays in terms of primary antibodies and scoring algorithms, and tumor heterogenity for PD-L1 expression are important issues to be considered. More studies are required to compare the different assays, ensure their harmonization and standardization and identify the optimal conditions for testing. PD-L1 expression is likely an imperfect predictive biomarker for patient selection and association with other markers of the tumor immune microenvironment will be probably necessary in the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Feasibility and effects of home-based smartphone-delivered automated feedback training for gait in people with Parkinson's disease: A pilot randomized controlled trial.

PubMed

Ginis, Pieter; Nieuwboer, Alice; Dorfman, Moran; Ferrari, Alberto; Gazit, Eran; Canning, Colleen G; Rocchi, Laura; Chiari, Lorenzo; Hausdorff, Jeffrey M; Mirelman, Anat

2016-01-01

Inertial measurement units combined with a smartphone application (CuPiD-system) were developed to provide people with Parkinson's disease (PD) real-time feedback on gait performance. This study investigated the CuPiD-system's feasibility and effectiveness compared with conventional gait training when applied in the home environment. Forty persons with PD undertook gait training for 30 min, three times per week for six weeks. Participants were randomly assigned to i) CuPiD, in which a smartphone application offered positive and corrective feedback on gait, or ii) an active control, in which personalized gait advice was provided. Gait, balance, endurance and quality of life were assessed before and after training and at four weeks follow-up using standardized tests. Both groups improved significantly on the primary outcomes (single and dual task gait speed) at post-test and follow-up. The CuPiD group improved significantly more on balance (MiniBESTest) at post-test (from 24.8 to 26.1, SD ∼ 5) and maintained quality of life (SF-36 physical health) at follow-up whereas the control group deteriorated (from 50.4 to 48.3, SD ∼ 16). No other statistically significant differences were found between the two groups. The CuPiD system was well-tolerated and participants found the tool user-friendly. CuPiD was feasible, well-accepted and seemed to be an effective approach to promote gait training, as participants improved equally to controls. This benefit may be ascribed to the real-time feedback, stimulating corrective actions and promoting self-efficacy to achieve optimal performance. Further optimization of the system and adequately-powered studies are warranted to corroborate these findings and determine cost-effectiveness.

Single session intermittent theta-burst stimulation on the left premotor cortex does not alleviate freezing of gait in Parkinson's disease.

PubMed

Tard, Céline; Devanne, Hervé; Defebvre, Luc; Delval, Arnaud

2016-08-15

To investigate the efficiency of intermittent theta-burst stimulation (iTBS) to alleviate the symptoms of freezing of gait (FoG) in Parkinson's disease (PD). We performed a cross-over, sham-controlled study of patients with severe PD, bilateral motor signs and debilitating, severe FoG, that was levodopa-sensitive but not controlled by optimal dopatherapy. We applied iTBS to the left premotor cortex and measured FoG, gait initiation and continuous gait, before and immediately after the iTBS session. All patients received sham and true iTBS with a one-week interval and in randomized order. 15 patients were included in the study. Recordings were performed under usual medication and all patients always showed unresponsive freezing. The pre- and post-stimulation gait trajectories did not differ in terms of the mean trajectory completion time or the percent time with FoG. The percent time with FoG was 6% greater after sham stimulation and 3% lower after iTBS (p>0.05). Visual cueing modified gait initiation and continuous gait but these latter were not influenced by rTMS. The present study provides Class I evidence that iTBS of the left premotor cortex does not alleviate FoG in PD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Switching from an oral dopamine receptor agonist to rotigotine transdermal patch: a review of clinical data with a focus on patient perspective.

PubMed

Chung, Sun Ju; Asgharnejad, Mahnaz; Bauer, Lars; Benitez, Arturo; Boroojerdi, Babak; Heidbrede, Tanja; Little, Allison; Kim, Han Joon

2017-07-01

Dopamine receptor agonists (DAs) are commonly used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In certain situations, switching from oral DAs to rotigotine transdermal patch may be beneficial for the patient (e.g., optimal symptom control/side effects/perioperative management, preference for once-daily/non-oral administration, RLS augmentation treatment). Areas covered: This narrative review summarizes available data on DA dose equivalency, dose conversions, switching schedules, safety, tolerability, efficacy and patient treatment preferences of switching from oral DAs to rotigotine (and vice versa) in patients with PD/RLS. The studies were identified in a PubMed search (up to 8 November 2016) using terms ('dopamine receptor agonist' OR 'rotigotine') AND 'switch'. Expert commentary: Randomized controlled studies often do not address the challenges clinicians face in practice, e.g., switching medications within the same class when dosing is not a one-to-one ratio. The authors describe three open-label studies in PD where oral DAs were successfully switched to rotigotine, and review three studies in RLS where oral DAs/levodopa were switched to rotigotine. Finally, the authors provide a suggested tool for switching from oral DAs to rotigotine, which includes dose conversion factors and switching schedules. The authors' view is that low-dose oral DAs (equivalent to ≤8 mg/24 h rotigotine) may be switched overnight.

Optimizing parameter of particle damping based on Leidenfrost effect of particle flows

NASA Astrophysics Data System (ADS)

Lei, Xiaofei; Wu, Chengjun; Chen, Peng

2018-05-01

Particle damping (PD) has strongly nonlinearity. With sufficiently vigorous vibration conditions, it always plays excellent damping performance and the particles which are filled into cavity are on Leidenfrost state considered in particle flow theory. For investigating the interesting phenomenon, the damping effect of PD on this state is discussed by the developed numerical model which is established based on principle of gas and solid. Furtherly, the numerical model is reformed and applied to study the relationship of Leidenfrost velocity with characteristic parameters of PD such as particle density, diameter, mass packing ratio and diameter-length ratio. The results indicate that particle density and mass packing ratio can drastically improve the damping performance as opposed as particle diameter and diameter-length ratio, mass packing ratio and diameter-length ratio can low the excited intensity for Leidenfrost state. For discussing the application of the phenomenon in engineering, bound optimization by quadratic approximation (BOBYQA) method is employed to optimize mass packing ratio of PD for minimize maximum amplitude (MMA) and minimize total vibration level (MTVL). It is noted that the particle damping can drastically reduce the vibrating amplitude for MMA as Leidenfrost velocity equal to the vibrating velocity relative to maximum vibration amplitude. For MTVL, larger mass packing ratio is best option because particles at relatively wide frequency range is adjacent to Leidenfrost state.

APPETITE PREDICTS INTAKE AND NUTRITIONAL STATUS IN PATIENTS RECEIVING PERITONEAL DIALYSIS.

PubMed

Young, Valerie; Balaam, Sarah; Orazio, Linda; Bates, Annerley; Badve, Sunil V; Johnson, David W; Campbell, Katrina L

2016-06-01

Sub-optimal nutrition status is common amongst patients receiving peritoneal dialysis (PD) and leads to poor clinical outcome. This population experiences multi-factorial challenges to achieving optimal nutritional status, particularly driven by inadequate intake. The aim of this investigation was to identify factors associated with inadequate protein intake and sub-optimal nutritional status in patients undergoing PD. This was a cross-sectional study of 67 adult patients receiving PD (mean age 59 ± 14 years; 57% male) within a single centre. Participants were consecutively recruited and interviewed by renal dietitians, collecting: Subjective Global Assessment (SGA); quality of life (using EQ-5D); dietary intake (via dietary interview); and appetite (using Appetite and Diet Assessment Tool). Participant demographics were obtained via survey or medical charts. Main outcome measures were inadequate dietary protein intake (<1.1 g/kg adjusted body weight/day) and malnutrition (as defined by SGA rating B or C). Overall, 15 (22%) patients were malnourished and 29 (43%) had inadequate protein intake. Poor appetite (anorexia) was reported in 62% (18/29) of participants with inadequate protein malnourished patients reported anorexia versus 12 (23%) of the well-nourished patients (p = 0.0001). Anorexia was a key risk factor for inadequate protein intake and malnutrition in patients undergoing PD. These findings highlight a need to closely monitor patients with appetite disturbances. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-ε-caprolactone nanoparticles.

PubMed

Ahmed, Iman S; El-Hosary, Rania; Shalaby, Samia; Abd-Rabo, Marwa M; Elkhateeb, Dalia G; Nour, Samia

2016-05-17

In this work lyophilized poly-ε-caprolactone nanoparticles (NPs) loaded with atorvastatin calcium (AC) were developed in an attempt to improve the in-vivo performance of AC following oral administration. The individual and combined effects of several formulation variables were previously investigated using step-wise full factorial designs in order to produce optimized AC-NPs with predetermined characteristics including particle size, drug loading capacity, drug release profile and physical stability. Four optimized formulations were further subjected in this work to lyophilization to promote their long-term physical stability and were fully characterized. The pharmacodynamics (PD)/pharmacokinetics (PK) properties of two optimized freeze-dried AC-NPs formulations showing acceptable long-term stability were determined and compared to a marketed AC immediate release tablet (Lipitor(®)) in albino rats. PD results revealed that the two tested formulations were equally effective in reducing low density lipoproteins (LDL) and triglycerides (TG) levels when given in reduced doses compared to Lipitor(®) and showed no adverse effects. PK results, on the other hand, revealed that the two freeze-dried AC-NPs formulations were of significantly lower bioavailability compared to Lipitor(®). Taken together the PD and PK results demonstrate that the improved efficacy obtained at reduced doses from the freeze-dried AC-NPs could be due to increased concentration of AC in the liver rather than in the plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrochemical transformation of trichloroethylene in aqueous solution by electrode polarity reversal.

PubMed

Rajic, Ljiljana; Fallahpour, Noushin; Yuan, Songhu; Alshawabkeh, Akram N

2014-12-15

Electrode polarity reversal is evaluated for electrochemical transformation of trichloroethylene (TCE) in aqueous solution using flow-through reactors with mixed metal oxide electrodes and Pd catalyst. The study tests the hypothesis that optimizing electrode polarity reversal will generate H2O2 in Pd presence in the system. The effect of polarity reversal frequency, duration of the polarity reversal intervals, current intensity and TCE concentration on TCE removal rate and removal mechanism were evaluated. TCE removal efficiencies under 6 cycles h(-1) were similar in the presence of Pd catalyst (50.3%) and without Pd catalyst (49.8%), indicating that Pd has limited impact on TCE degradation under these conditions. The overall removal efficacies after 60 min treatment under polarity reversal frequencies of 6, 10, 15, 30 and 90 cycles h(-1) were 50.3%, 56.3%, 69.3%, 34.7% and 23.4%, respectively. Increasing the frequency of polarity reversal increases TCE removal as long as sufficient charge is produced during each cycle for the reaction at the electrode. Electrode polarity reversal shifts oxidation/reduction and reduction/oxidation sequences in the system. The optimized polarity reversal frequency (15 cycles h(-1) at 60 mA) enables two reaction zones formation where reduction/oxidation occurs at each electrode surface. Published by Elsevier Ltd.

Electrochemical transformation of trichloroethylene in aqueous solution by electrode polarity reversal

PubMed Central

Rajic, Ljiljana; Fallahpour, Noushin; Yuan, Songhu; Alshawabkeh, Akram N.

2014-01-01

Electrode polarity reversal is evaluated for electrochemical transformation of trichloroethylene (TCE) in aqueous solution using flow-through reactors with mixed metal oxide electrodes and Pd catalyst. The study tests the hypothesis that optimizing electrode polarity reversal will generate H2O2 in Pd presence in the system. The effect of polarity reversal frequency, duration of the polarity reversal intervals, current intensity and TCE concentration on TCE removal rate and removal mechanism were evaluated. TCE removal efficiencies under 6 cycles h−1 were similar in the presence of Pd catalyst (50.3%) and without Pd catalyst (49.8%), indicating that Pd has limited impact on TCE degradation under these conditions. The overall removal efficacies after 60 min treatment under polarity reversal frequencies of 6, 10, 15, 30 and 90 cycles h−1 were 50.3%, 56.3%, 69.3%, 34.7% and 23.4%, respectively. Increasing the frequency of polarity reversal increases TCE removal as long as sufficient charge is produced during each cycle for the reaction at the electrode. Electrode polarity reversal shifts oxidation/reduction and reduction/oxidation sequences in the system. The optimized polarity reversal frequency (15 cycles h−1 at 60 mA) enables two reaction zones formation where reduction/oxidation occurs at each electrode surface. PMID:25282093

Enhancement of Sn-Bi-Ag Solder Joints with ENEPIG Surface Finish for Low-Temperature Interconnection

NASA Astrophysics Data System (ADS)

Pun, Kelvin P. L.; Islam, M. N.; Rotanson, Jason; Cheung, Chee-wah; Chan, Alan H. S.

2018-05-01

Low-temperature soldering constitutes a promising solution in interconnect technology with the increasing trend of heat-sensitive materials in integrated circuit packaging. Experimental work was carried out to investigate the effect of electroless Ni/electroless Pd/immersion gold (ENEPIG) layer thicknesses on Sn-Bi-Ag solder joint integrity during extended reflow at peak temperatures as low as 175°C. Optimizations are proposed to obtain reliable solder joints through analysis of interfacial microstructure with the resulting joint integrity under extended reflow time. A thin Ni(P) layer with thin Pd led to diffusion of Cu onto the interface resulting in Ni3Sn4 intermetallic compound (IMC) spalling with the formation of thin interfacial (Ni,Cu)3Sn4 IMCs which enhance the robustness of the solder after extended reflow, while thick Ni(P) with thin Pd resulted in weakened solder joints with reflow time due to thick interfacial Ni3Sn4 IMCs with the entrapped brittle Bi-phase. With a suitable thin Ni(P), the Pd thickness has to be optimized to prevent excessive Ni-P consumption and early Cu outward diffusion to enhance the solder joint during extended reflow. Based on these findings, suitable Ni(P) and Pd thicknesses of ENEPIG are recommended for the formation of robust low-temperature solder joints.

A Simple Attitude Control of Quadrotor Helicopter Based on Ziegler-Nichols Rules for Tuning PD Parameters

PubMed Central

He, ZeFang

2014-01-01

An attitude control strategy based on Ziegler-Nichols rules for tuning PD (proportional-derivative) parameters of quadrotor helicopters is presented to solve the problem that quadrotor tends to be instable. This problem is caused by the narrow definition domain of attitude angles of quadrotor helicopters. The proposed controller is nonlinear and consists of a linear part and a nonlinear part. The linear part is a PD controller with PD parameters tuned by Ziegler-Nichols rules and acts on the quadrotor decoupled linear system after feedback linearization; the nonlinear part is a feedback linearization item which converts a nonlinear system into a linear system. It can be seen from the simulation results that the attitude controller proposed in this paper is highly robust, and its control effect is better than the other two nonlinear controllers. The nonlinear parts of the other two nonlinear controllers are the same as the attitude controller proposed in this paper. The linear part involves a PID (proportional-integral-derivative) controller with the PID controller parameters tuned by Ziegler-Nichols rules and a PD controller with the PD controller parameters tuned by GA (genetic algorithms). Moreover, this attitude controller is simple and easy to implement. PMID:25614879

The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.

PubMed

Sato, Yasunori; Kinoshita, Masahiko; Takemura, Shigekazu; Tanaka, Shogo; Hamano, Genya; Nakamori, Shoji; Fujikawa, Masahiro; Sugawara, Yasuhiko; Yamamoto, Takatsugu; Arimoto, Akira; Yamamura, Minako; Sasaki, Motoko; Harada, Kenichi; Nakanuma, Yasuni; Kubo, Shoji

2017-03-01

An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Impulse control disorders in Parkinson's disease: crossroads between neurology, psychiatry and neuroscience.

PubMed

Bugalho, Paulo; Oliveira-Maia, Albino J

2013-01-01

Non-motor symptoms contribute significantly to Parkinson's disease (PD) related disability. Impulse control disorders (ICDs) have been recently added to the behavioural spectrum of PD-related non-motor symptoms. Such behaviours are characterized by an inappropriate drive to conduct repetitive behaviours that are usually socially inadequate or result in harmful consequences. Parkinson disease impulse control disorders (PD-ICDs) have raised significant interest in the scientific and medical community, not only because of their incapacitating nature, but also because they may represent a valid model of ICDs beyond PD and a means to study the physiology of drive, impulse control and compulsive actions in the normal brain. In this review, we discuss some unresolved issues regarding PD-ICDs, including the association with psychiatric co-morbidities such as obsessive-compulsive disorder and with dopamine related side effects, such as hallucinations and dyskinesias; the relationship with executive cognitive dysfunction; and the neural underpinnings of ICDs in PD. We also discuss the contribution of neuroscience studies based on animal-models towards a mechanistic explanation of the development of PD-ICDs, specifically regarding corticostriatal control of goal directed and habitual actions.

Interference from retrieval cues in Parkinson's disease.

PubMed

Crescentini, Cristiano; Marin, Dario; Del Missier, Fabio; Biasutti, Emanuele; Shallice, Tim

2011-11-01

Existing studies on memory interference in Parkinson's disease (PD) patients have provided mixed results and it is unknown whether PD patients have problems in overcoming interference from retrieval cues. We investigated this issue by using a part-list cuing paradigm. In this paradigm, after the study of a list of items, the presentation of some of these items as retrieval cues hinders the recall of the remaining ones. We tested PD patients' (n = 19) and control participants' (n = 16) episodic memory in the presence and absence of part-list cues, using initial-letter probes, and following either weak or strong serial associative encoding of list items. Both PD patients and control participants showed a comparable and significant part-list cuing effect after weak associative encoding (13% vs. 12% decrease in retrieval in part-list cuing vs. no part-list cuing -control- conditions in PD patients and control participants, respectively), denoting a similar effect of cue-driven interference in the two populations when a serial retrieval strategy is hard to develop. However, only PD patients showed a significant part-list cuing effect after strong associative encoding (20% vs. 5% decrease in retrieval in patients and controls, respectively). When encoding promotes the development of an effective serial retrieval strategy, the presentation of part-list cues has a specifically disruptive effect in PD patients. This indicates problems in strategic retrieval, probably related to PD patients' increased tendency to rely on external cues. Findings in control conditions suggest that less effective encoding may have contributed to PD patients' memory performance.

Brain iron concentrations in regions of interest and relation with serum iron levels in Parkinson disease.

PubMed

Costa-Mallen, Paola; Gatenby, Christopher; Friend, Sally; Maravilla, Kenneth R; Hu, Shu-Ching; Cain, Kevin C; Agarwal, Pinky; Anzai, Yoshimi

2017-07-15

Brain iron has been previously found elevated in the substantia nigra pars compacta (SNpc), but not in other brain regions, of Parkinson's disease (PD) patients. However, iron in circulation has been recently observed to be lower than normal in PD patients. The regional selectivity of iron deposition in brain as well as the relationship between SNpc brain iron and serum iron within PD patients has not been completely elucidated. In this pilot study we measured brain iron in six regions of interest (ROIs) as well as serum iron and serum ferritin, in 24 PD patients and 27 age- gender-matched controls. Brain iron was measured on magnetic resonance imaging (MRI) with a T2 prime (T2') method. Difference in brain iron deposition between PD cases and controls for the six ROIs were calculated. SNpc/white matter brain iron ratios and SNpc/serum iron ratios were calculated for each study participant, and differences between PD patients and controls were tested. PD patients overall had higher brain iron than controls in the SNpc. PD patients had significantly higher SNpc/white matter brain iron ratios than controls, and significantly higher brain SNpc iron/serum iron ratios than controls. These results indicate that PD patients' iron metabolism is disrupted toward a higher partitioning of iron to the brain SNpc at the expenses of iron in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding the cellular basis and pathophysiology of Peyronie’s disease to optimize treatment for erectile dysfunction

PubMed Central

Alzubaidi, Raidh

2017-01-01

Erectile dysfunction (ED) is a common condition that significantly impacts a man’s physical and psychological well-being. ED is often associated with Peyronie’s disease (PD), which is an abnormal curvature of the penis. Delayed treatment of or surgical invention for PD often results in ED and therefore unsatisfied patients. The pathophysiology of PD is incompletely understood, but has been studied extensively and based on our current understanding of PD physiology, many medical treatment options have been proposed. In this paper, we will review what is known about the pathophysiology of PD and the medical treatment options that have been trialed as a result. More investigations in regards to the basic science of PD need to be carried out in order to elucidate the exact mechanisms of the fibrosis, and propose new, more successful treatment options which should be implemented prior to the onset of ED. PMID:28217450

Recombinant human G6PD for quality control and quality assurance of novel point-of-care diagnostics for G6PD deficiency.

PubMed

Kahn, Maria; LaRue, Nicole; Zhu, Changcheng; Pal, Sampa; Mo, Jack S; Barrett, Lynn K; Hewitt, Steve N; Dumais, Mitchell; Hemmington, Sandra; Walker, Adrian; Joynson, Jeff; Leader, Brandon T; Van Voorhis, Wesley C; Domingo, Gonzalo J

2017-01-01

A large gap for the support of point-of-care testing is the availability of reagents to support quality control (QC) of diagnostic assays along the supply chain from the manufacturer to the end user. While reagents and systems exist to support QC of laboratory screening tests for glucose-6-phosphate dehydrogenase (G6PD) deficiency, they are not configured appropriately to support point-of-care testing. The feasibility of using lyophilized recombinant human G6PD as a QC reagent in novel point-of-care tests for G6PD deficiency is demonstrated. Human recombinant G6PD (r-G6PD) was expressed in Escherichia coli and purified. Aliquots were stored at -80°C. Prior to lyophilization, aliquots were thawed, and three concentrations of r-G6PD (representing normal, intermediate, and deficient clinical G6PD levels) were prepared and mixed with a protective formulation, which protects the enzyme activity against degradation from denaturation during the lyophilization process. Following lyophilization, individual single-use tubes of lyophilized r-G6PD were placed in individual packs with desiccants and stored at five temperatures for one year. An enzyme assay for G6PD activity was used to ascertain the stability of r-G6PD activity while stored at different temperatures. Lyophilized r-G6PD is stable and can be used as a control indicator. Results presented here show that G6PD activity is stable for at least 365 days when stored at -80°C, 4°C, 30°C, and 45°C. When stored at 55°C, enzyme activity was found to be stable only through day 28. Lyophilized r-G6PD enzyme is stable and can be used as a control for point-of-care tests for G6PD deficiency.

Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.

PubMed

Gong, Jun; Chehrazi-Raffle, Alexander; Reddi, Srikanth; Salgia, Ravi

2018-01-23

Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.

Differentiating Patients with Parkinson's Disease from Normal Controls Using Gray Matter in the Cerebellum.

PubMed

Zeng, Ling-Li; Xie, Liang; Shen, Hui; Luo, Zhiguo; Fang, Peng; Hou, Yanan; Tang, Beisha; Wu, Tao; Hu, Dewen

2017-02-01

Parkinson's disease (PD) is one of the most common neurodegenerative disorders in the world. Previous studies have focused on the basal ganglia and cerebral cortices. To date, the cerebellum has not been systematically investigated in patients with PD. In the current study, 45 probable PD patients and 40 age- and gender-matched healthy controls underwent structural magnetic resonance imaging, and we used support vector machines combining with voxel-based morphometry to explore the cerebellar structural changes in the probable PD patients relative to healthy controls. The results revealed that the gray matter alterations were primarily located within the cerebellar Crus I, implying a possible important role of this region in PD. Furthermore, the gray matter alterations in the cerebellum could differentiate the probable PD patients from healthy controls with accuracies of more than 95 % (p < 0.001, permutation test) via cross-validation, suggesting the potential of analyzing the cerebellum in the clinical diagnosis of PD.

Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab.

PubMed

Zhang, Fei; Qi, Xiaoqiang; Wang, Xiaoxiao; Wei, Diyang; Wu, Jiawei; Feng, Lingling; Cai, Haiyan; Wang, Yugang; Zeng, Naiyan; Xu, Ting; Zhou, Aiwu; Zheng, Ying

2017-10-27

Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain. The binding involves extensive hydrogen-bonding and hydrophobic interactions. Notably there are multiple aromatic residues from the CDR loops forming Pi-Pi stacking or cation-Pi interactions within the center of the binding interface and the buried surface area is more than 2000 Å 2 , which is the largest amongst all the known PD-L1/antibody structures. Mutagenesis study revealed that two hot-spot residues (E58, R113) of PD-L1 contribute significantly to the binding of atezolizumab. The structure also shows that atezolizumab binds PD-L1 with a distinct heavy and light chain orientation and it blocks PD-1/PD-L1 interaction through competing with PD-1 for the same PD-L1 surface area. Taken together, the complex structure of PD-L1/atezolizumab solved here revealed the molecular mechanism of atezolizumab in immunotherapy and provides basis for future monoclonal antibody optimization and rational design of small chemical compounds targeting PD-L1 surface.

Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab

PubMed Central

Wei, Diyang; Wu, Jiawei; Feng, Lingling; Cai, Haiyan; Wang, Yugang; Zeng, Naiyan; Xu, Ting; Zhou, Aiwu; Zheng, Ying

2017-01-01

Monoclonal antibodies targeting PD-1/PD-L1 signaling pathway have achieved unprecedented success in cancer treatment over the last few years. Atezolizumab is the first PD-L1 monoclonal antibody approved by US FDA for cancer therapy; however the molecular basis of atezolizumab in blocking PD-1/PD-L1 interaction is not fully understood. Here we have solved the crystal structure of PD-L1/atezolizumab complex at 2.9 angstrom resolution. The structure shows that atezolizumab binds the front beta-sheet of PD-L1 through three CDR loops from the heavy chain and one CDR loop from the light chain. The binding involves extensive hydrogen-bonding and hydrophobic interactions. Notably there are multiple aromatic residues from the CDR loops forming Pi-Pi stacking or cation-Pi interactions within the center of the binding interface and the buried surface area is more than 2000 Å2, which is the largest amongst all the known PD-L1/antibody structures. Mutagenesis study revealed that two hot-spot residues (E58, R113) of PD-L1 contribute significantly to the binding of atezolizumab. The structure also shows that atezolizumab binds PD-L1 with a distinct heavy and light chain orientation and it blocks PD-1/PD-L1 interaction through competing with PD-1 for the same PD-L1 surface area. Taken together, the complex structure of PD-L1/atezolizumab solved here revealed the molecular mechanism of atezolizumab in immunotherapy and provides basis for future monoclonal antibody optimization and rational design of small chemical compounds targeting PD-L1 surface. PMID:29163822

Effect of acoustic parameters on the cavitation behavior of SonoVue microbubbles induced by pulsed ultrasound.

PubMed

Lin, Yutong; Lin, Lizhou; Cheng, Mouwen; Jin, Lifang; Du, Lianfang; Han, Tao; Xu, Lin; Yu, Alfred C H; Qin, Peng

2017-03-01

SonoVue microbubbles could serve as artificial nuclei for ultrasound-triggered stable and inertial cavitation, resulting in beneficial biological effects for future therapeutic applications. To optimize and control the use of the cavitation of SonoVue bubbles in therapy while ensuring safety, it is important to comprehensively understand the relationship between the acoustic parameters and the cavitation behavior of the SonoVue bubbles. An agarose-gel tissue phantom was fabricated to hold the SonoVue bubble suspension. 1-MHz transmitting transducer calibrated by a hydrophone was used to trigger the cavitation of SonoVue bubbles under different ultrasonic parameters (i.e., peak rarefactional pressure (PRP), pulse repetition frequency (PRF), and pulse duration (PD)). Another 7.5-MHz focused transducer was employed to passively receive acoustic signals from the exposed bubbles. The ultraharmonics and broadband intensities in the acoustic emission spectra were measured to quantify the extent of stable and inertial cavitation of SonoVue bubbles, respectively. We found that the onset of both stable and inertial cavitation exhibited a strong dependence on the PRP and PD and a relatively weak dependence on the PRF. Approximate 0.25MPa PRP with more than 20μs PD was considered to be necessary for ultraharmonics emission of SonoVue bubbles, and obvious broadband signals started to appear when the PRP exceeded 0.40MPa. Moreover, the doses of stable and inertial cavitation varied with the PRP. The stable cavitation dose initially increased with increasing PRP, and then decreased rapidly after 0.5MPa. By contrast, the inertial cavitation dose continuously increased with increasing PRP. Finally, the doses of both stable and inertial cavitation were positively correlated with PRF and PD. These results could provide instructive information for optimizing future therapeutic applications of SonoVue bubbles. Copyright © 2016 Elsevier B.V. All rights reserved.

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index

PubMed Central

Hacker, Mallory L.; Turchan, Maxim; Molinari, Anna L.; Currie, Amanda D.

2017-01-01

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50–75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT (n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t-tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (p > 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = −0.89; DBS+ODT = −0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152). PMID:28676842

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

PubMed

Millan, Sarah H; Hacker, Mallory L; Turchan, Maxim; Molinari, Anna L; Currie, Amanda D; Charles, David

2017-01-01

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT ( n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t -tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group ( p > 0.05). BMI change over two years was not different between the groups ( p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

Chest ultrasound and hidden lung congestion in peritoneal dialysis patients.

PubMed

Panuccio, Vincenzo; Enia, Giuseppe; Tripepi, Rocco; Torino, Claudia; Garozzo, Maurizio; Battaglia, Giovanni Giorgio; Marcantoni, Carmelita; Infantone, Lorena; Giordano, Guido; De Giorgi, Maria Loreta; Lupia, Mario; Bruzzese, Vincenzo; Zoccali, Carmine

2012-09-01

Chest ultrasound (US) is a non-invasive well-validated technique for estimating extravascular lung water (LW) in patients with heart diseases and in end-stage renal disease. We systematically applied this technique to the whole peritoneal dialysis (PD) population of five dialysis units. We studied the cross-sectional association between LW, echocardiographic parameters, clinical [pedal oedema, New York Heart Association (NYHA) class] and bioelectrical impedance analysis (BIA) markers of volume status in 88 PD patients. Moderate to severe lung congestion was evident in 41 (46%) patients. Ejection fraction was the echocardiographic parameter with the strongest independent association with LW (r = -0.40 P = 0.002). Oedema did not associate with LW on univariate and multivariate analysis. NYHA class was slightly associated with LW (r = 0.21 P = 0.05). Among patients with severe lung congestion, only 27% had pedal oedema and the majority (57%) had no dyspnoea (NYHA Class I). Similarly, the prevalence of patients with BIA, evidence of volume excess was small (11%) and not significantly different (P = 0.79) from that observed in patients with mild or no congestion (9%). In PD patients, LW by chest US reveals moderate to severe lung congestion in a significant proportion of asymptomatic patients. Intervention studies are necessary to prove the usefulness of chest US for optimizing the control of fluid excess in PD patients.

The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

PubMed

Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

2015-08-01

Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

A driven active mass damper by using output of a neural oscillator (effects of position control system changes on vibration mitigation performance)

NASA Astrophysics Data System (ADS)

Hongu, J.; Iba, D.; Sasaki, T.; Nakamura, M.; Moriwaki, I.

2015-03-01

In this paper, a design method for a PD controller, which is a part of a new active mass damper system using a neural oscillator for high-rise buildings, is proposed. The new system mimicking the motion of bipedal mammals is a quite simple system, which has the neural oscillator synchronizing with the acceleration response of the structure. The travel distance and direction of the auxiliary mass of the active mass damper is decided by the output of the neural oscillator, and then, the auxiliary mass is transferred to the decided location by using the PD controller. Therefore, the performance of the PD controller must be evaluated by the vibration energy absorbing efficiency by the system. In order to bring the actual path driven by the PD controller in closer alignment with the ideal path, which is assumed to be a sinusoidal wave under resonance, firstly, the path of the auxiliary mass driven by the PD controller is analytically derived, and the inner product between the vector of ideal and analytical path is evaluated. And then, the PD gain is decided by the maximum value of the inner product. Finally, numerical simulations confirm the validity of the proposed design method of the PD controller.

Size-controlled synthesis of Pd nanocrystals using a specific multifunctional peptide

NASA Astrophysics Data System (ADS)

Chiu, Chin-Yi; Li, Yujing; Huang, Yu

2010-06-01

Here we report a peptide-mediated synthesis of Pd NCs in aqueous solution with controllable size in the sub-10 nanometre regime. The specific multifunctional peptide Q7 selected using the phage display technique can bind to the Pd NC surface and act as a stabilizer to mediate Pd crystal nucleation and growth. At the nucleation stage, Q7 bound to and helped stabilize the different-sized small Pd NC nuclei achieved using different concentrations of the external reducing agent, NaBH4. At the growth stage, Q7 played the dual role of binding to and reducing the precursor onto the existing nuclei, which led to the further controllable growth of the Pd NCs. By using the variable sizes of nuclei as seeds, and by introducing different amounts of precursors Pd NCs with tunable sizes from 2.6 to 6.6 nm were achieved with good size distribution.Here we report a peptide-mediated synthesis of Pd NCs in aqueous solution with controllable size in the sub-10 nanometre regime. The specific multifunctional peptide Q7 selected using the phage display technique can bind to the Pd NC surface and act as a stabilizer to mediate Pd crystal nucleation and growth. At the nucleation stage, Q7 bound to and helped stabilize the different-sized small Pd NC nuclei achieved using different concentrations of the external reducing agent, NaBH4. At the growth stage, Q7 played the dual role of binding to and reducing the precursor onto the existing nuclei, which led to the further controllable growth of the Pd NCs. By using the variable sizes of nuclei as seeds, and by introducing different amounts of precursors Pd NCs with tunable sizes from 2.6 to 6.6 nm were achieved with good size distribution. Electronic Supplementary Information (ESI) available. Experimental details for peptide selection, peptide synthesis and Pd NCs synthesis; Q7 peptide sequence molecular structure and characterization; TEM images of Pd NCs. See DOI: 10.1039/c0nr00194e/

New concepts for HgI2 scintillator gamma ray spectroscopy

NASA Technical Reports Server (NTRS)

Iwanczyk, Jan S.

1994-01-01

The primary goals of this project are development of the technology for HgI2 photodetectors (PD's), development of a HgI2/scintillator gamma detector, development of electronics, and development of a prototype gamma spectrometer. Work on the HgI2 PD's involved HgI2 purification and crystal growth, detector surface and electrical contact studies, PD structure optimization, encapsulation and packaging, and testing. Work on the HgI2/scintillator gamma detector involved a study of the optical - mechanical coupling for the optimization of CsI(Tl)/HgI2 gamma ray detectors and determination of the relationship between resolution versus scintillator type and size. The development of the electronics focused on low noise amplification circuits using different preamp input FET's and the use of a coincidence technique to maximize the signal, minimize the noise contribution in the gamma spectra, and improve the overall system resolution.

Peritoneal dialysis catheter implantation: avoiding problems and optimizing outcomes.

PubMed

Crabtree, John H

2015-01-01

The success of peritoneal dialysis (PD) as renal replacement therapy is dependent upon the patient having a functional long-term peritoneal access. There are a number of identified best practices that must be adhered to during PD catheter placement to achieve a durable and infection-resistant access. The clinical setting, available resources, and the employed catheter insertion method may not always permit complete adherence to these practices; however, an attempt should be made to comply with them as closely as possible. Although omission of any one of the practices can lead to catheter loss, departures from some are committed more frequently, manifesting as commonly occurring clinical problems, such as drain pain, catheter tip migration, omental entrapment, pericatheter leaks and hernias, and poor exit-site location. Understanding the technical pitfalls in PD catheter placement that lead to these problems, enable the provider to modify practice habits to avoid them and optimize outcomes. © 2014 Wiley Periodicals, Inc.

Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy

PubMed Central

Huurneman, Luc J.; Neely, Michael; Veringa, Anette; Docobo Pérez, Fernando; Ramos-Martin, Virginia; Tissing, Wim J.; Alffenaar, Jan-Willem C.

2016-01-01

Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC50) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC50)/15.4 predicted terminal galactomannan (P = 0.003), and a ratio of >6 suggested a lower terminal galactomannan level (P = 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival. PMID:26833158

Role of habenula and amygdala dysfunction in Parkinson disease patients with punding.

PubMed

Markovic, Vladana; Agosta, Federica; Canu, Elisa; Inuggi, Alberto; Petrovic, Igor; Stankovic, Iva; Imperiale, Francesca; Stojkovic, Tanja; Kostic, Vladimir S; Filippi, Massimo

2017-06-06

To assess whether a functional dysregulation of the habenula and amygdala, as modulators of the reward brain circuit, contributes to Parkinson disease (PD) punding. Structural and resting-state functional MRI were obtained from 22 patients with PD punding, 30 patients with PD without any impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor impairment, and cognitive status, and 30 healthy controls. Resting-state functional connectivity of the habenula and amygdala bilaterally was assessed using a seed-based approach. Habenula and amygdala volumes and cortical thickness measures were obtained. Compared to both healthy controls and PD cases without any ICB (PD-no ICB), PD-punding patients showed higher functional connectivity of habenula and amygdala with thalamus and striatum bilaterally, and lower connectivity between bilateral habenula and left frontal and precentral cortices. In PD-punding relative to PD-no ICB patients, a lower functional connectivity between right amygdala and hippocampus was also observed. Habenula and amygdala volumes were not different among groups. PD-punding patients showed a cortical thinning of the left superior frontal and precentral gyri and right middle temporal gyrus and isthmus cingulate compared to healthy controls, and of the right inferior frontal gyrus compared to both controls and PD-no ICB patients. A breakdown of the connectivity among the crucial nodes of the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex) might be a contributory factor to punding in PD. This study provides potential instruments to detect and monitor punding in patients with PD. © 2017 American Academy of Neurology.

Assessment of Oropharyngeal Dysphagia in Patients With Parkinson Disease: Use of Ultrasonography.

PubMed

Oh, Eun Hyun; Seo, Jin Seok; Kang, Hyo Jung

2016-04-01

To compare tongue thickness, the shortest hyoid-thyroid approximation (distance between the hyoid bone and thyroid cartilage), and the time interval between the initiation of tongue movement and the time of the shortest hyoid-thyroid approximation, by using ultrasonography in healthy controls and patients with Parkinson disease (PD). Healthy controls and PD patients with dysphagia were compared. Ultrasonography was performed 3 times for the evaluation of tongue thickness, the shortest hyoid-thyroid approximation, and the time between the initiation of tongue movement and the shortest hyoid-thyroid approximation. A total of 24 healthy controls and 24 PD patients with dysphagia were enrolled. No significant differences were demonstrated between the two groups for the shortest hyoid-thyroid approximation (controls, 1.19±0.34 cm; PD patients, 1.37±0.5 cm; p=0.15) and tongue thickness (controls, 4.42±0.46 cm; PD patients, 4.27±0.51 cm; p=0.3). In contrast, the time to the shortest hyoid-thyroid approximation was significantly different between the two groups (controls, 1.53±0.87 ms; PD patients, 2.4±1.4 ms, p=0.048). Ultrasonography can be useful in evaluating dysphagia in patients with PD by direct visualization and measurement of the hyoid bone. Moreover, ultrasonography might contribute to a greater understanding of the pathophysiology of dysphagia in PD.

Orthopedic Surgery and Post-Operative Cognitive Decline in Idiopathic Parkinson’s Disease: Considerations from a Pilot Study

PubMed Central

Price, Catherine C.; Levy, Shellie-Anne; Tanner, Jared; Garvan, Cyndi; Ward, Jade; Akbar, Farheen; Bowers, Dawn; Rice, Mark; Okun, Michael

2016-01-01

BACKGROUND Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in “healthy” adults. Although individuals with neurodegenerative disorders such as Parkinson’s disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. OBJECTIVE To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. METHODS A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD “healthy” controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), three-weeks, three-months, and one-year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers. RESULTS Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals. CONCLUSION This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. PMID:26683785

Effect of Dopamine Therapy on Nonverbal Affect Burst Recognition in Parkinson's Disease

PubMed Central

Péron, Julie; Grandjean, Didier; Drapier, Sophie; Vérin, Marc

2014-01-01

Background Parkinson's disease (PD) provides a model for investigating the involvement of the basal ganglia and mesolimbic dopaminergic system in the recognition of emotions from voices (i.e., emotional prosody). Although previous studies of emotional prosody recognition in PD have reported evidence of impairment, none of them compared PD patients at different stages of the disease, or ON and OFF dopamine replacement therapy, making it difficult to determine whether their impairment was due to general cognitive deterioration or to a more specific dopaminergic deficit. Methods We explored the involvement of the dopaminergic pathways in the recognition of nonverbal affect bursts (onomatopoeias) in 15 newly diagnosed PD patients in the early stages of the disease, 15 PD patients in the advanced stages of the disease and 15 healthy controls. The early PD group was studied in two conditions: ON and OFF dopaminergic therapy. Results Results showed that the early PD patients performed more poorly in the ON condition than in the OFF one, for overall emotion recognition, as well as for the recognition of anger, disgust and fear. Additionally, for anger, the early PD ON patients performed more poorly than controls. For overall emotion recognition, both advanced PD patients and early PD ON patients performed more poorly than controls. Analysis of continuous ratings on target and nontarget visual analog scales confirmed these patterns of results, showing a systematic emotional bias in both the advanced PD and early PD ON (but not OFF) patients compared with controls. Conclusions These results i) confirm the involvement of the dopaminergic pathways and basal ganglia in emotional prosody recognition, and ii) suggest a possibly deleterious effect of dopatherapy on affective abilities in the early stages of PD. PMID:24651759

Glucose-6-phosphate dehydrogenase deficiency and diabetes mellitus with severe retinal complications in a Sardinian population, Italy.

PubMed

Pinna, Antonio; Contini, Emma Luigia; Carru, Ciriaco; Solinas, Giuliana

2013-01-01

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is one of the most common human genetic abnormalities, with a high prevalence in Sardinia, Italy. Evidence indicates that G6PD-deficient patients are protected against vascular disease. Little is known about the relationship between G6PD deficiency and diabetes mellitus. The purpose of this study was to compare G6PD deficiency prevalence in Sardinian diabetic men with severe retinal vascular complications and in age-matched non-diabetic controls and ascertain whether G6PD deficiency may offer protection against this vascular disorder. Erythrocyte G6PD activity was determined using a quantitative assay in 390 diabetic men with proliferative diabetic retinopathy (PDR) and 390 male non-diabetic controls, both aged ≥50 years. Conditional logistic regression models were used to investigate the association between G6PD deficiency and diabetes with severe retinal complications. G6PD deficiency was found in 21 (5.4 %) diabetic patients and 33 (8.5 %) controls (P=0.09). In a univariate conditional logistic regression model, G6PD deficiency showed a trend for protection against diabetes with PDR, but the odds ratio (OR) fell short of statistical significance (OR=0.6, 95% confidence interval=0.35-1.08, P=0.09). In multivariate conditional logistic regression models, including as covariates G6PD deficiency, plasma glucose, and systemic hypertension or systolic or diastolic blood pressure, G6PD deficiency showed no statistically significant protection against diabetes with PDR. The prevalence of G6PD deficiency in diabetic men with PDR was lower than in age-matched non-diabetic controls. G6PD deficiency showed a trend for protection against diabetes with PDR, but results were not statistically significant.

Clinical characteristics of sleep disorders in patients with Parkinson's disease.

PubMed

Mao, Zhi-Juan; Liu, Chan-Chan; Ji, Su-Qiong; Yang, Qing-Mei; Ye, Hong-Xiang; Han, Hai-Yan; Xue, Zheng

2017-02-01

In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease (PD), 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). It was found that poor sleep quality (77.11%) and excessive daytime sleepiness (32.34%) were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency (SE) was significantly decreased (P<0.01), and sleep latency (SL) and the arousal index (AI) were increased (P<0.05) in the PD group as compared with those in the control group. SE and total sleep time (TST) were positively correlated with the Hoehn and Yahr (H&Y) stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group (P<0.05). Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

Rule-Based Categorization Deficits in Focal Basal Ganglia Lesion and Parkinson’s Disease Patients

PubMed Central

Ell, Shawn W.; Weinstein, Andrea; Ivry, Richard B.

2010-01-01

Patients with basal ganglia (BG) pathology are consistently found to be impaired on rule-based category learning tasks in which learning is thought to depend upon the use of an explicit, hypothesis-guided strategy. The factors that influence this impairment remain unclear. Moreover, it remains unknown if the impairments observed in patients with degenerative disorders such as Parkinson's disease (PD) are also observed in those with focal BG lesions. In the present study, we tested patients with either focal BG lesions or PD on two categorization tasks that varied in terms of their demands on selective attention and working memory. Individuals with focal BG lesions were impaired on the task in which working-memory demand was high and performed similarly to healthy controls on the task in which selective-attention demand was high. In contrast, individuals with PD were impaired on both tasks, and accuracy rates did not differ between on- and off-medication states for a subset of patients who were also tested after abstaining from dopaminergic medication. Quantitative, model-based analyses attributed the performance deficit for both groups in the task with high working-memory demand to the utilization of suboptimal strategies, whereas the PD-specific impairment on the task with high selective-attention demand was driven by the inconsistent use of an optimal strategy. These data suggest that the demands on selective attention and working memory affect the presence of impairment in patients with focal BG lesions and the nature of the impairment in patients with PD. PMID:20600196

Task-Rest Modulation of Basal Ganglia Connectivity in Mild to Moderate Parkinson’s Disease

PubMed Central

Müller-Oehring, Eva M.; Sullivan, Edith V.; Pfefferbaum, Adolf; Huang, Neng C.; Poston, Kathleen L.; Bronte-Stewart, Helen M.; Schulte, Tilman

2014-01-01

Parkinson’s disease (PD) is associated with abnormal synchronization in basal ganglia-thalamo-cortical loops. We tested whether early PD patients without demonstrable cognitive impairment exhibit abnormal modulation of functional connectivity at rest, while engaged in a task, or both. PD and healthy controls underwent two functional MRI scans: a resting-state scan and a Stroop Match-to-Sample task scan. Rest-task modulation of basal ganglia (BG) connectivity was tested using seed-to-voxel connectivity analysis with task and rest time series as conditions. Despite substantial overlap of BG–cortical connectivity patterns in both groups, connectivity differences between groups had clinical and behavioral correlates. During rest, stronger putamen–medial parietal and pallidum–occipital connectivity in PD than controls was associated with worse task performance and more severe PD symptoms suggesting that abnormalities in resting-state connectivity denote neural network dedifferentiation. During the executive task, PD patients showed weaker BG-cortical connectivity than controls, i.e., between caudate–supramarginal gyrus and pallidum–inferior prefrontal regions, that was related to more severe PD symptoms and worse task performance. Yet, task processing also evoked stronger striatal–cortical connectivity, specifically between caudate–prefrontal, caudate–precuneus, and putamen–motor/premotor regions in PD relative to controls, which was related to less severe PD symptoms and better performance on the Stroop task. Thus, stronger task-evoked striatal connectivity in PD demonstrated compensatory neural network enhancement to meet task demands and improve performance levels. fMRI-based network analysis revealed that despite resting-state BG network compromise in PD, BG connectivity to prefrontal, premotor, and precuneus regions can be adequately invoked during executive control demands enabling near normal task performance. PMID:25280970

Personality Traits in Panic Disorder Patients With and Without Comorbidities.

PubMed

Zugliani, Morena M; Martin-Santos, Rocio; Nardi, Antonio Egidio; Freire, Rafael Christophe

2017-11-01

Panic disorder (PD) is often correlated with high neuroticism and low extraversion. This study aims to ascertain whether PD patients differ from healthy controls in regard to personality traits and determine if these traits are correlated with comorbid disorders, anxiety, and depression symptoms. Personality traits of 69 PD patients and 42 controls were compared using the Maudsley Personality Inventory. In PD patients, comorbidities, anxiety, and depression symptoms were also evaluated. PD patients showed higher neuroticism and lower extraversion compared with healthy controls. Patients without comorbidities presented similar results to controls, whereas those with comorbidities presented higher neuroticism and lower extraversion scores. PD per se may be unrelated to deviant personality traits, although comorbidities with major depressive disorder and agoraphobia are probably associated with high neuroticism and low extraversion. These traits show a strong correlation with the accumulation and severity of these disorders.

Synthesis and antimicrobial activity of palladium nanoparticles from Prunus × yedoensis leaf extract

USDA-ARS?s Scientific Manuscript database

The eco-friendly production of palladium nanoparticles (PdNPs) by Prunus × yedoensis tree leaf extract was studied for the first time. Initial confirmation of PdNP production was confirmed by a color change from light yellow to dark brown. The optimization parameters show that pH 7, 8% leaf extract,...

Variation in nuclear size and PD-L2 positivity correlate with aggressive chromophobe renal cell carcinoma.

PubMed

Mostafa, Mohamed E; Abdelkader, Amrou; Kuroda, Naoto; Pérez-Montiel, Delia; Banerjee, Anjishnu; Hes, Ondrej; Iczkowski, Kenneth A

2018-06-01

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 "worst" high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ± 0.5 and 2.4 ± 0.4 respectively (P < .001), and 3.4 ± 0.4 for metastases (P < .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ± 3.0 for adverse group, 5.7 ± 2.7 for controls, and 4.1 ± 1.6 for metastases (P = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ 2 1.6, P = .2), but was higher in metastases (χ 2 6.9, P < .01), or metastases plus adverse primary tumors (χ 2 4.8, P = .03), compared to good-pathology primary tumors. In conclusion, VNS is an easily obtained measurement that can predict adverse behavior of chromophobe RCC, and may impart value for needle biopsy reporting and the choice of active surveillance. PD-L2 was elevated in metastases but was less useful for primary tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

PubMed

Luo, ChunYan; Song, Wei; Chen, Qin; Yang, Jing; Gong, QiYong; Shang, Hui-Fang

2017-07-01

Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

Optimized hydrogen sensing characteristic of Pd/ZnO nanoparticles based Schottky diode on glass substrate

NASA Astrophysics Data System (ADS)

Chandra, Lalit; Sahu, Praveen Kumar; Dwivedi, R.; Mishra, V. N.

2017-10-01

The present work deals with the development of the Pd/ZnO naoparticles based sensor for detection of hydrogen (H2) gas at relatively low temperature (75-110 °C). Pd/ZnO Schottky diode was fabricated by ZnO nanoparticles based thin film on glass substrate using sol-gel spin coating technique. These ZnO nanoparticles have been characterized by x-ray diffraction (XRD), atomic force microscopy (AFM), energy dispersive x-ray spectroscope (EDS), and field emission scanning electron microscope (FE-SEM) which reveals the ZnO film having particles size in the range of ~25 to ~110 nm with ~52.73 nm surface roughness. Gas dependent diode parameters such as barrier height and ideality factor have been evaluated upon exposure of H2 gas concentration in the range from 200-2000 ppm over the temperature range from 75 to 110 °C. The sensitivity of the Pd/ZnO sensor has been studied in terms of change in diode forward current upon exposure to H2 gas. Experimental result shows the optimized sensitivity ~246.22% for H2 concentration of 2000 ppm at temperature 90 °C. The hydrogen sensing mechanism has been explained by surface and subsurface adsorption of H2 molecules on Pd surface; subsequently, dissociation of H2 molecules into H  +  H atoms and diffusion to trap sites (oxygen ions) available on ZnO surface, resulting in formation of dipole moments at Pd/ZnO interface. The variation in the sensitivity, response and recovery time with temperature of Pd/ZnO sensor has also been studied.

[Relationship between the Fnu4HI site polymorphism of monoamine oxidase A gene and Parkinson's disease].

PubMed

Jiang, Xiao-hua; Yang, Hui; Yang, Jing-fang; Dong, Xiu-min; Xu, Qun-yuan; Chen, Biao

2003-06-01

To study the association between the polymorphism of human monoamine oxidase type A (MAO-A) gene and Parkinson's disease(PD). Fnu4HI restriction fragment length polymorphism(RFLP) and PCR-RFLP were used to detect the mutation of MAO-A gene. The frequencies of alleles and genotypes at the MAO-A Fnu4HI locus on the X chromosome in different PD group were compared with those of the control group. It was found that the frequencies of G allele in the patients with PD and controls were 0.613 and 0.527 respectively, P=0.039 "the frequencies of TT genotype were 0.303 and 0.415(P=0.014), and the frequencies of GG genotype were 0.564 and 0.451 respectively(P=0.021). When the patients were divided into two groups by age-onset, significant difference in the allelic and genotypic frequencies was observed only between early-onset PD group and control group. And when the PD patients were grouped by sex, significant difference was observed only between male PD group and male control group (the frequencies of G allele being 0.669 and 0.500 respectively, P=0.005). This study revealed significant differences between PD group and control group in allelic and genotypic frequencies. The findings supported the hypothesis about an association between MAO-A gene and PD, suggesting that age at onset of PD and gender predisposition might be related to the putative association, and Fnu4HI SNP be a risk factor for PD.

Ocular Motor and Sensory Function in Parkinson Disease

PubMed Central

Almer, Zina; Klein, Kathyrn S.; Marsh, Laura; Gerstenhaber, Melissa; Repka, Michael X.

2011-01-01

Purpose To evaluate the effect of dopaminergic medication and deep brain stimulation on ocular function in Parkinson disease (PD) and to measure vision-related quality of life in subjects with PD. Design Prospective comparative case series. Participants and Controls Twenty-seven PD and 16 control subjects were recruited. Methods We measured visual acuity, ocular motor function, convergence, and vision-related quality of life using the Visual Function Questionnaire–25 (VFQ-25). Visual sensory and motor measurements were made during the “on” and “off” states of PD dopaminergic treatment. Main Outcome Measures Convergence ability and vision related quality of life. Results The PD subjects had a mean age of 58.8 years; 30% were female. Their mean duration of PD was 10.9 ± 6.8 years. The control subjects had a mean age of 61.6 years; 56% were female. There was no difference in visual acuity, contrast sensitivity or color vision of the PD subjects in their “on” state compared with controls. Convergence amplitudes measured with base-out prism were significantly poorer in PD subjects compared with controls (24.1 ± 8 Δ vs 14.8 ±10.3 Δ; P=0.003). The mean composite VFQ-25 score was significantly worse in the PD subjects compared with the controls (87.1 ± 8.69 vs 96.6 ± 3.05; P=0.0001). Comparing the PD subjects in their “on” with their “off” states, there was no difference in distance exodeviation, near exodeviation or ocular ductions. Mean convergence amplitudes and near point of convergence were better in the “on” state compared with the “off” state, 14.8±10.3 Δ vs 10.7±9.0 Δ, (P=0.0006), and 13.1±9.1 cm vs 18.1±12.2, (P=0.002), respectively. Conclusions Convergence ability is significantly poorer in PD subjects in both their “on” and “off” states compared with controls, but significantly improves with systemic dopaminergic treatment. Ocular motor function in PD subjects fluctuates in response to treatment, which complicates ophthalmic management. PD subjects have a significant reduction in vision-related quality of life, especially near activities, that is not associated with visual acuity. PMID:21959370

Gut microbiota in patients with Parkinson's disease in southern China.

PubMed

Lin, Aiqun; Zheng, Wenxia; He, Yan; Tang, Wenli; Wei, Xiaobo; He, Rongni; Huang, Wei; Su, Yuying; Huang, Yaowei; Zhou, Hongwei; Xie, Huifang

2018-05-16

Accumulating evidence has revealed alterations in the communication between the gut and brain in patients with Parkinson's disease (PD), and previous studies have confirmed that alterations in the gut microbiome play an important role in the pathogenesis of numerous diseases, including PD. The aim of this study was to determine whether the faecal microbiome of PD patients in southern China differs from that of control subjects and whether the gut microbiome composition alters among different PD motor phenotypes. We compared the gut microbiota composition of 75 patients with PD and 45 age-matched controls using 16S rRNA next-generation-sequencing. We observed significant increases in the abundance of four bacterial families and significant decreases in the abundance of seventeen bacterial families in patients with PD compared to those of the controls. In particular, the abundance of Lachnospiraceae was reduced by 42.9% in patients with PD, whereas Bifidobacteriaceae was enriched in patients with PD. We did not identify a significant difference in the overall microbial composition among different PD motor phenotypes, but we identified the association between specific taxas and different PD motor phenotypes. PD is accompanied by alterations in the abundance of specific gut microbes. The abundance of certain gut microbes was altered depending on clinical motor phenotypes. Based on our findings, the gut microbiome may be a potential PD biomarker. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Effect of Agoraphobia on Oxidative Stress in Panic Disorder

PubMed Central

Karlidag, Rifat; Cumurcu, Birgul Elbozan; Turkoz, Yusuf; Kartalci, Sukru; Ozcan, A. Cemal; Erdemli, M. Erman

2013-01-01

We aimed to investigate whether agoraphobia (A) in panic disorder (PD) has any effects on oxidative and anti-oxidative parameters. We measured total antioxidant capacity (TAC), paraoxonase (PON), arylesterase (ARE) antioxidant and malondialdehyde (MDA) oxidant levels using blood samples from a total of 31 PD patients with A, 22 PD patients without A and 53 control group subjects. There was a significant difference between the TAC, PON, ARE and MDA levels of the three groups consisting of PD with A, PD without A and the control group. The two-way comparison to clarify the group creating the difference showed that the TAC, PON, and ARE antioxidants were significantly lower in the PD with A group compared to the control group while the MDA oxidant was significantly higher. There was no significant difference between the PD without A and control groups for TAC, PON, ARE and MDA levels. We clearly demonstrated that the oxidative stress and damage to the anti-oxidative mechanism are significantly higher in the PD group with A. These findings suggest that oxidative/anti-oxidative mechanisms may play a more important role on the pathogenesis of PB with A. PMID:24474979

Glycemic Control and Mortality in Diabetic Patients Undergoing Dialysis Focusing on the Effects of Age and Dialysis Type: A Prospective Cohort Study in Korea.

PubMed

Park, Ji In; Bae, Eunjin; Kim, Yong-Lim; Kang, Shin-Wook; Yang, Chul Woo; Kim, Nam-Ho; Lee, Jung Pyo; Kim, Dong Ki; Joo, Kwon Wook; Kim, Yon Su; Lee, Hajeong

2015-01-01

Active glycemic control has been proven to delay the onset and slow the progression of diabetic retinopathy, nephropathy, and neuropathy in diabetic patients, but the optimal level is obscure in end-stage renal disease. In this study, we evaluated the effect of hemoglobin A1c (HbA1c) on mortality of diabetic patients on dialysis, focusing on age and dialysis type. Of 3,302 patients enrolled in the prospective cohort for end-stage renal disease in Korea between August 2008 and October 2013, 1,239 diabetic patients who had been diagnosed with diabetes or having HbA1c≥6.5% at the time of enrollment were analyzed. Age was categorized as <55, 55-64 and ≥65 years old. Age, sex, modified Charlson comorbidity index, hemoglobin, primary renal disease, body mass index, and dialysis duration were adjusted. A total of 873 patients received hemodialysis (HD) and 366 underwent peritoneal dialysis (PD). During the mean follow-up of 19.1 months, 141 patients died. Patients with poor glucose control (HbA1c≥8%) showed worse survival than patients with HbA1c<8% (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.48-3.29; P<0.001). Subgroup analysis divided by age revealed that HbA1c≥8% was a predictor of mortality in age <55 (HR, 4.3; 95% CI, 1.78-10.41; P = 0.001) and age 55-64 groups (HR, 3.3; 95% CI, 1.56-7.05; P = 0.002), but not in age ≥65 group. Combining dialysis type and age, poor glucose control negatively affected survival only in age < 55 group among HD patients, but it was significant in age < 55 and age 55-64 groups in PD patients. Deaths from infection were more prevalent in the PD group, and poor glucose control tended to correlate with more deaths from infection in PD patients (P = 0.050). In this study, the effect of glycemic control differed according to age and dialysis type in diabetic patients. Thus, the target of glycemic control should be customized; further observational studies may strengthen the clinical relevance.

Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Piragliatin, a Glucokinase Activator, and Glyburide, a Sulfonylurea, in Type 2 Diabetic Patients.

PubMed

Zhai, S; Georgy, A; Liang, Z; Zhi, J

2016-11-01

A glucokinase activator and a sulfonylurea might be coprescribed to synergize treatment success for type 2 diabetes (T2D). This clinical pharmacology study was designed to investigate the potential glucose-lowering effect or pharmacodynamic (PD), pharmacokinetic (PK), and safety/tolerability interactions between piragliatin and glyburide in T2D patients already taking glyburide but not adequately controlled. This was an open-label, multiple-dose, 3-period, single-sequence crossover design: on days -1, 6, and 12, PD and PK samples were drawn with glyburide alone (period 0), piragliatin + glyburide (period 1), and piragliatin alone (period 2) treatments. The glucose-lowering effect, including fasting plasma glucose (FPG), of piragliatin was more pronounced when it was administered concomitantly with glyburide as compared to piragliatin or glyburide administered alone. However, this enhancement cannot be explained by a potential PK interaction between piragliatin and glyburide. Other than hypoglycemia, there were no clinically relevant safety findings. Thus, the enhanced PD effect warrants further investigation to define the optimal dose combination between glucokinase activators and sulfonylureas with regard to efficacy, safety, and tolerability. © 2016, The American College of Clinical Pharmacology.

Postural control deficit during sit-to-walk in patients with Parkinson's disease and freezing of gait.

PubMed

Mezzarobba, Susanna; Grassi, Michele; Valentini, Roberto; Bernardis, Paolo

2018-03-01

The intricate linkage between Freezing of Gait (FoG) and postural control in Parkinson's disease (PD) is unclear. We analyzed the impact of FoG on dynamic postural control. 24 PD patients, 12 with (PD + FoG), 12 without FoG (PD-FoG), and 12 healthy controls, were assessed in ON state. Mobility and postural control were measured with clinical scales (UPDRS III, BBS, MPAS) and with kinematic and kinetic analysis during three tasks, characterized by levels of increasing difficulty to plan sequential movement of postural control: walk (W), gait initiation (GI) and sit-to-walk (STW). The groups were balanced by age, disease duration, disease severity, mobility and balance. During STW, the spatial distribution of COP trajectories in PD + FoG patients are spread over medial-lateral space more than in the PD-FoG (p < .001). Moreover, the distribution of COP positions. in the transition between sit-to-stand and gait initiation, is not properly shifted toward the leading leg, as in PD-FoG and healthy controls, but it is more centrally dispersed (p < .01) with a delayed weight forward progression (p < .05). In GI task and walk task, COM and COP differences are less evident and even absent between PD patients. PD + FoG show postural control differences in STW, compared with PD-FoG and healthy. Different spatial distribution of COP trajectories, between two PD groups are probably due to a deficit to plan postural control during a more demanding motor pattern, such as STW. Copyright © 2018 Elsevier B.V. All rights reserved.

Impulse-Control Disorders in Parkinson's Disease: A Meta-Analysis and Review of Case-Control Studies.

PubMed

Molde, Helge; Moussavi, Yasaman; Kopperud, Stine Therese; Erga, Aleksander Hagen; Hansen, Anita Lill; Pallesen, Ståle

2018-01-01

Although several case-control studies on the prevalence of Impulse-Control Disorders (ICDs) in Parkinson's Disease (PD) have been conducted, no meta-analytic study on this topic has previously been published. Thus, knowledge about the overall prevalence rate of ICD in PD and factors that might moderate this relationship is lacking. Prevalence studies of ICDs in PD were identified by computer searches in the MEDLINE, PsycINFO, and Web of Science databases, covering the period from January 2000 to February 2017. Data for N  = 4,539, consisting of 2,371 PD patients and 2,168 healthy controls, representing 14 case-control studies were included. Estimation of the odds ratio ( OR ) of ICDs in PD compared to healthy controls was conducted using random-effects models. Mixed-effects models were applied in the moderator analysis of heterogeneity. Publication bias was estimated using a contour-enhanced funnel plot, the Rüker's test, and fail-safe N test for estimating the number of potential missing studies. Overall, the results showed significantly higher ratios for several ICDs in PD compared to healthy controls with the estimated overall OR s ranging between 2.07, 95% CI [1.26, 3.48], for having any ICDs, and 4.26, 95% CI [2.17, 8.36], for hypersexuality. However, the random-effects results for shopping were non-significant, though the fixed-effects model was significant ( OR  = 1.66, 95%CI [1.21, 2.27]). The testing of potential moderator variables of heterogeneity identified the following two variables that were both associated with increased risk: being medically treated for PD and disease duration. The results must be interpreted with some caution due to possible small-studies effect or publication bias. Individuals with PD seem to have a significantly greater risk of suffering from ICDs compared to healthy controls. Gambling, hypersexuality, eating, punding, and hobbying are all ICDs significantly associated with PDs being medically treated for PD.

Theoretical study of the structures and chemical ordering of CoPd nanoalloys supported on MgO(001)

NASA Astrophysics Data System (ADS)

Taran, Songul; Garip, Ali Kemal; Arslan, Haydar

2016-06-01

Metal nanoalloys on oxide surface are a widely studied topic in surface science and technology. In this study, the structures of CoPd nanoalloys adsorbed on MgO(001) have been searched by basin-hopping global optimization method within an atomistic model. Two different sizes (34 and 38 atom) have been considered for all compositions of CoPd/MgO(001) nanoalloys. Co and Pd atoms, for all the compositions, have cube-on-cube (001) epitaxy with substrate at interface. For both sizes, we have found that Pd rich composition nanoalloys have three layers, Co rich composition nanoalloys have four layers in morphology. Excess energy and second difference in energy analyzes have been performed to investigate the relative stability of nanoalloys with respect to their size and composition.

Changing Landscape for Peritoneal Dialysis: Optimizing Utilization.

PubMed

Schreiber, Martin J

2017-03-01

The future growth of peritoneal dialysis (PD) will be directly linked to the shift in US healthcare to a value-based payment model due to PD's lower yearly cost, early survival advantage over in-center hemodialysis, and improved quality of life for patients treating their kidney disease in the home. Under this model, nephrology practices will need an increased focus on managing the transition from chronic kidney disease to end-stage renal disease (ESRD), providing patient education with the aim of accomplishing modality selection and access placement ahead of dialysis initiation. Physicians must expand their knowledge base in home therapies and work toward increased technique survival through implementation of specific practice initiatives that highlight PD catheter placement success, preservation of residual renal function, consideration of incremental PD, and competence in urgent start PD. Avoidance of both early and late PD technique failures is also critical to PD program growth. Large dialysis organizations must continue to measure and improve quality metrics for PD, expand their focus beyond the sole provision of PD to holistic patient care, and initiate programs to reduce PD hospitalization rates and encourage physicians to consider the benefits of PD as an initial modality for appropriate patients. New and innovative strategies are needed to address the main reasons for PD technique failure, improve the connectivity of the patient in the home, leverage home biometric data to improve overall outcomes, and develop PD cycler devices that lower patient treatment burden and reduce both treatment fatigue and treatment-dependent complications. © 2017 Wiley Periodicals, Inc.

Swallowing in patients with Parkinson's disease: a surface electromyography study.

PubMed

Ws Coriolano, Maria das Graças; R Belo, Luciana; Carneiro, Danielle; G Asano, Amdore; Al Oliveira, Paulo José; da Silva, Douglas Monteiro; G Lins, Otávio

2012-12-01

Our goal was to study deglutition of Parkinson's disease (PD) patients and normal controls (NC) using surface electromyography (sEMG). The study included 15 patients with idiopathic PD and 15 age-matched normal controls. Surface electromyography was collected over the suprahyoid muscle group. Conditions were the following: swallow at once 10 and 20 ml of water and 5 and 10 ml of yogurt of firm consistency, and freely drink 100 ml of water. During swallowing, durations of sEMG were significantly longer in PD patients than in normal controls but no significant differences of amplitudes were found. Eighty percent of the PD patients and 20 % of the NC needed more than one swallow to consume 20 ml of water, while 70 % of the PD patients and none of the NC needed more than one swallow to consume 5 ml of yogurt. PD patients took significantly more time and needed significantly more swallows to drink 100 ml of water than normal controls. We conclude that sEMG might be a simple and useful tool to study and monitor deglutition in PD patients.

Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson's Disease.

PubMed

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B; Lipton, Richard B; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Pre-clinical markers of Parkinson's Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD.

Digitized Spiral Drawing: A Possible Biomarker for Early Parkinson’s Disease

PubMed Central

San Luciano, Marta; Wang, Cuiling; Ortega, Roberto A.; Yu, Qiping; Boschung, Sarah; Soto-Valencia, Jeannie; Bressman, Susan B.; Lipton, Richard B.; Pullman, Seth; Saunders-Pullman, Rachel

2016-01-01

Introduction Pre-clinical markers of Parkinson’s Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown. Methods 138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices. Results All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD. Conclusion Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD. PMID:27732597

A quantitative approach to developing Parkinsonian monkeys (Macaca fascicularis) with intracerebroventricular 1-methyl-4-phenylpyridinium injections.

PubMed

Li, Hao; Lei, Xiaoguang; Huang, Baihui; Rizak, Joshua D; Yang, Lichuan; Yang, Shangchuan; Wu, Jing; Lü, Longbao; Wang, Jianhong; Yan, Ting; Li, Hongwei; Wang, Zhengbo; Hu, Yingzhou; Le, Weidong; Deng, Xingli; Li, Jiali; Xu, Lin; Zhang, Baorong; Hu, Xintian

2015-08-15

Non-human primate Parkinson's disease (PD) models are essential for PD research. The most extensively used PD monkey models are induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the modeling processes of developing PD monkeys cannot be quantitatively controlled with MPTP. Therefore, a new approach to quantitatively develop chronic PD monkey models will help to advance the goals of "reduction, replacement and refinement" in animal experiments. A novel chronic PD monkey models was reported using the intracerebroventricular administration of 1-methyl-4-phenylpyridinium (MPP(+)) in Cynomolgus monkeys (Macaca fascicularis). This approach successfully produced stable and consistent PD monkeys with typical motor symptoms and pathological changes. More importantly, a sigmoidal relationship (Y=8.15801e(-0.245/x); R=0.73) was discovered between PD score (Y) and cumulative dose of MPP(+) (X). This relationship was then used to develop two additional PD monkeys under a specific time schedule (4 weeks), with planned PD scores (7) by controlling the dose and frequency of the MPP(+) administration as an independent validation of the formula. We developed Parkinsonian monkeys within controlled time frames by regulating the accumulated dose of MPP(+) intracerebroventricular administered, while limiting side effects often witnessed in models developed with the peripheral administration of MPTP, makes this model highly suitable for treatment development. This novel approach provides an edge in evaluating the mechanisms of PD pathology associated with environmental toxins and novel treatment approaches as the formula developed provides a "map" to control and predict the modeling processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantitative Analysis of Voice in Parkinson Disease Compared to Motor Performance: A Pilot Study.

PubMed

Silbergleit, Alice K; LeWitt, Peter A; Peterson, Edward L; Gardner, Glendon M

2015-01-01

Characteristic features of hypokinetic dysarthria develop in Parkinson disease (PD). We hypothesized that quantified acoustic changes of voice might provide a correlate of disease severity. To determine if there are significant differences in acoustic measures of voice between mild and moderate PD; 2) To evaluate correlations between acoustic parameters of voice and subtests of the UPDRS in mild and moderate PD. Twenty six participants with PD underwent vocal acoustic testing while off PD medication, for comparison to 22 healthy controls. Participants with PD were divided into two groups based upon UPDRS activities of daily living (ADL) ratings: summed scores were used to define mild and moderate PD. Participants voiced /i/ ("ee") at comfort, high, and low pitch (3 trials/pitch). The CSpeech Waveform Analysis Program was used to analyze cycle-to-cycle frequency ("jitter") and amplitude ("shimmer") irregularities of the vocal signal, signal-to-noise ratio, and maximum phonation frequency range converted to semitones. Sections of UPDRS scores were correlated to acoustic variables of voice. Key findings included a significant difference between the semitone range of the control subjects and the moderate PD group (p = 0.036). Further analyses revealed significant differences in semitone range for males between the controls vs. mild PD (p = 0.014), and controls vs. moderate PD (p = 0.005). Significant correlations were also found between acoustic findings and both the ADL and motor portions of the UPDRS. Acoustic analysis of voice, particularly frequency range, may provide a quantifiable correlate of disease progression in PD.

Disturbance of gut satiety peptide in purging disorder.

PubMed

Keel, Pamela K; Eckel, Lisa A; Hildebrandt, Britny A; Haedt-Matt, Alissa A; Appelbaum, Jonathan; Jimerson, David C

2018-01-01

Little is known about biological factors that contribute to purging after normal amounts of food-the central feature of purging disorder (PD). This study comes from a series of nested studies examining ingestive behaviors in bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp) (n = 26), and controls (n = 26). Based on distinct subjective responses to a fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether postprandial PYY response was significantly greater and ghrelin levels significantly lower in women with PD compared to controls and women with BNp. Participants completed structured clinical interviews, self-report questionnaires, and laboratory assessments of gut peptide and subjective responses to a fixed meal. Women with PD demonstrated a significantly greater postprandial PYY response compared to women with BNp and controls, who did not differ significantly. PD women also endorsed significantly greater gastrointestinal distress, and PYY predicted gastrointestinal intestinal distress. Ghrelin levels were significantly greater in PD and BNp compared to controls, but did not differ significantly between eating disorders. Women with BNp endorsed significantly greater postprandial hunger, and ghrelin predicted hunger. PD is associated with a unique disturbance in PYY response. Findings contribute to growing evidence of physiological distinctions between PD and BNp. Future research should examine whether these distinctions account for differences in clinical presentation as this could inform the development of specific interventions for patients with PD. © 2017 Wiley Periodicals, Inc.

[Gene copy number, mRNA transcription and protein expression of PD-1 gene in primary hepatocarcinoma patients].

PubMed

Fan, Hui-Min; Wu, Ling-Jie; Hu, Feng-Yu; Yang, Zhan

2012-08-01

To study the gene copy number, mRNA transcription and protien expression of programmed cell death 1 (PD-1) gene in primary hepatocellular carcinoma (PHC) patients and normal control individuals (NC) who are anti-HBs positive, and to investigate the variations in PD-1 gene copy numbers and its relationship with PHC. Real-time PCR was adopted to detect the PD-1 gene copy numbers and their mRNA expressions in peripheral blood mononuclear cells (PBMCs) from 24 samples of PHC patients and 26 of NC. Protein expression level of PD-1 on CD8+ T was analyzed by flow cytometry. In terms of number of PD-1 gene copy numbers, the percentage of cases of haploid (single) was 34.62% and 4.17% in PHC group and control group respectively while the percentage of cases of diploid (double) was 61.54% and 95.83% respectively. The difference between the two was statistically significant (chi2 = 7.639, P = 0.006). The rate of cases with double PD-1 gene copy numbers was found to be higher in patients with PHC than in control group. It was also found that the average expression of PD-1 mRNA was 2.35E-03 in control group and 1.23E-03 in PHC group. The expression level was significant lower in PHC group than that in control group when compared by using Mann-whitey technic (U = 153, P = 0.009). Furthermore, the frequency of PD-1 protein expression on CD8+ T cells was 3.72 +/- 0.32 in control group and 16.13 +/- 1.68 in PHC group. The level of PD-1 mRNA expression was higher in PHC and significant differences was shown between two groups (t = -7.073, P = 0.000). Our study suggests that the variation in PD-1 gene copy number may trigger primary hepatocellular carcinoma to HBV carriers. The relationship between the variation of PD-1 gene copy numbers and its association with primary hepatocellular carcinoma is worth further focus.

Neuromuscular Impairments Are Associated With Impaired Head and Trunk Stability During Gait in Parkinson Fallers.

PubMed

Cole, Michael H; Naughton, Geraldine A; Silburn, Peter A

2017-01-01

Background The trunk plays a critical role in attenuating movement-related forces that threaten to challenge the body's postural control system. For people with Parkinson's disease (PD), disease progression often leads to dopamine-resistant axial symptoms, which impair trunk control and increase falls risk. Objective This prospective study aimed to evaluate the relationship between impaired trunk muscle function, segmental coordination, and future falls in people with PD. Methods Seventy-nine PD patients and 82 age-matched controls completed clinical assessments and questionnaires to establish their medical history, symptom severity, balance confidence, and falls history. Gait characteristics and trunk muscle activity were assessed using 3-dimensional motion analysis and surface electromyography. The incidence, cause, and consequence of any falls experienced over the next 12 months were recorded and indicated that 48 PD and 29 control participants fell at least once during this time. Results PD fallers had greater peak and baseline lumbar multifidus (LMF) and thoracic erector spinae (TES) activations than control fallers and nonfallers. Analysis of covariance indicated that the higher LMF activity was attributable to the stooped posture adopted by PD fallers, but TES activity was independent of medication use, symptom severity, and trunk orientation. Furthermore, greater LMF and TES baseline activity contributed to increasing lateral head, trunk, and pelvis movements in PD fallers but not nonfallers or controls. Conclusions The results provide evidence of neuromuscular deficits for PD fallers that are independent of medications, symptom severity, and posture and contribute to impaired head, trunk, and pelvis control associated with falls in this population. © The Author(s) 2016.

The effect of speed-accuracy strategy on response interference control in Parkinson's disease.

PubMed

Wylie, S A; van den Wildenberg, W P M; Ridderinkhof, K R; Bashore, T R; Powell, V D; Manning, C A; Wooten, G F

2009-07-01

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinson's disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy. PD patients (n=28) and healthy controls (n=17) performed an arrow version of the flanker task under task instructions that either emphasized speed or accuracy of responses. Reaction time (RT) and accuracy rates decreased with speed compared to accuracy instructions, although to a lesser extent for the PD group. Differences in flanker interference effects among PD and healthy controls depended on speed-accuracy strategy. Compared to the healthy controls, PD patients showed larger flanker interference effects under speed stress. RT distribution analyses suggested that PD patients have greater difficulty suppressing incorrect response activation when pressing for speed. These initial findings point to an important interaction between strategic and computational aspects of interference control in accounting for cognitive impairments of PD. The results are also compatible with recent brain imaging studies that demonstrate basal ganglia activity to co-vary with speed-accuracy adjustments.

Graph theory network function in Parkinson's disease assessed with electroencephalography.

PubMed

Utianski, Rene L; Caviness, John N; van Straaten, Elisabeth C W; Beach, Thomas G; Dugger, Brittany N; Shill, Holly A; Driver-Dunckley, Erika D; Sabbagh, Marwan N; Mehta, Shyamal; Adler, Charles H; Hentz, Joseph G

2016-05-01

To determine what differences exist in graph theory network measures derived from electroencephalography (EEG), between Parkinson's disease (PD) patients who are cognitively normal (PD-CN) and matched healthy controls; and between PD-CN and PD dementia (PD-D). EEG recordings were analyzed via graph theory network analysis to quantify changes in global efficiency and local integration. This included minimal spanning tree analysis. T-tests and correlations were used to assess differences between groups and assess the relationship with cognitive performance. Network measures showed increased local integration across all frequency bands between control and PD-CN; in contrast, decreased local integration occurred in PD-D when compared to PD-CN in the alpha1 frequency band. Differences found in PD-MCI mirrored PD-D. Correlations were found between network measures and assessments of global cognitive performance in PD. Our results reveal distinct patterns of band and network measure type alteration and breakdown for PD, as well as with cognitive decline in PD. These patterns suggest specific ways that interaction between cortical areas becomes abnormal and contributes to PD symptoms at various stages. Graph theory analysis by EEG suggests that network alteration and breakdown are robust attributes of PD cortical dysfunction pathophysiology. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The importance of loss of control while eating in adolescents with purging disorder.

PubMed

Goldschmidt, Andrea B; Accurso, Erin C; O'Brien, Setareh; Kara Fitzpatrick, Kathleen; Lock, James D; Le Grange, Daniel

2016-08-01

Although many individuals with purging disorder (PD) report loss of control (LOC) eating, it is unclear whether they differ from those who do not, or from other eating disorders involving purging and/or LOC. We compared PD with LOC (PD-LOC), PD without LOC (PD-noLOC), bulimia nervosa (BN), and anorexia nervosa-binge/purge subtype (AN-B/P) on measures of eating-related and general psychopathology in treatment-seeking adolescents. PD-LOC comprised ∼30% of PD diagnoses. PD-LOC and PD-noLOC did not differ from one another, or from BN and AN-B/P, on most measures of psychopathology, with some exceptions. PD-noLOC was similar to AN-B/P (p = 0.99) and significantly different from BN on eating concerns (p < 0.001), while PD-LOC was similar to BN, AN-B/P, and PD-noLOC on this measure (ps ≥ 0.06). PD-LOC reported higher self-esteem than BN, AN-B/P, and PD-noLOC (ps < 0.001). PD was largely similar to other eating disorders characterized by purging, regardless of whether LOC eating was present. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:801-804). © 2016 Wiley Periodicals, Inc.

Al{sub x}Ga{sub 1-x}N-based back-illuminated solar-blind photodetectors with external quantum efficiency of 89%

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cicek, E.; McClintock, R.; Cho, C. Y.

2013-11-04

We report on high performance Al{sub x}Ga{sub 1−x}N-based solar-blind ultraviolet photodetector (PD) array grown on sapphire substrate. First, high quality, crack-free AlN template layer is grown via metalorganic chemical vapor deposition. Then, we systematically optimized the device design and material doping through the growth and processing of multiple devices. After optimization, uniform and solar-blind operation is observed throughout the array; at the peak detection wavelength of 275 nm, 729 μm{sup 2} area PD showed unbiased peak external quantum efficiency and responsivity of ∼80% and ∼176 mA/W, respectively, increasing to 89% under 5 V of reverse bias. Taking the reflection loses into consideration,more » the internal quantum efficiency of these optimized PD can be estimated to be as high as ∼98%. The visible rejection ratio measured to be more than six orders of magnitude. Electrical measurements yielded a low-dark current density: <2 × 10{sup −9} A/cm{sup 2}, at 10 V of reverse bias.« less

Correlation between decreased CSF α-synuclein and Aβ₁₋₄₂ in Parkinson disease.

PubMed

Buddhala, Chandana; Campbell, Meghan C; Perlmutter, Joel S; Kotzbauer, Paul T

2015-01-01

Accumulation of misfolded α-synuclein (α-syn) protein in Lewy bodies and neurites is the cardinal pathologic feature of Parkinson disease (PD), but abnormal deposition of other proteins may also play a role. Cerebrospinal fluid (CSF) levels of proteins known to accumulate in PD may provide insight into disease-associated changes in protein metabolism and their relationship to disease progression. We measured CSF α-syn, amyloid β₁₋₄₂ (Aβ₁₋₄₂), and tau from 77 nondemented PD and 30 control participants. CSF α-syn and Aβ₁₋₄₂ were significantly lower in PD compared with controls. In contrast with increased CSF tau in Alzheimer disease, CSF tau did not significantly differ between PD and controls. CSF protein levels did not significantly correlate with ratings of motor function or performance on neuropsychological testing. As expected, CSF Aβ₁₋₄₂ inversely correlated with [(11)C]-Pittsburgh compound B (PiB) mean cortical binding potential, with PiB(+) PD participants having lower CSF Aβ₁₋₄₂ compared with PiB(-) PD participants. Furthermore, CSF α-syn positively correlated with Aβ₁₋₄₂ in PD participants but not in controls, suggesting a pathophysiologic connection between the metabolisms of these proteins in PD. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiscale entropy analysis of electroencephalography during sleep in patients with Parkinson disease.

PubMed

Chung, Chen-Chih; Kang, Jiunn-Horng; Yuan, Rey-Yue; Wu, Dean; Chen, Chih-Chung; Chi, Nai-Fang; Chen, Po-Chih; Hu, Chaur-Jong

2013-07-01

Sleep disorders are frequently seen in patients with Parkinson disease (PD), including rapid eye movement (REM) behavior disorder and periodic limb movement disorder. However, knowledge about changes in non-REM sleep in patients with PD is limited. This study explored the characteristics of electroencephalography (EEG) during sleep in patients with PD and non-PD controls. We further conducted multiscale entropy (MSE) analysis to evaluate and compare the complexity of sleep EEG for the 2 groups. There were 9 patients with PD (Hoehn-Yahr stage 1 or 2) and 11 non-PD controls. All participants underwent standard whole-night polysomnography (PSG), which included 23 channels, 6 of which were for EEG. The raw data of the EEG were extracted and subjected to MSE analysis. Patients with PD had a longer sleep onset time and a higher spontaneous EEG arousal index. Sleep stage-specific increased MSE was observed in patients with PD during non-REM sleep. The difference was more marked and significant at higher time scale factors (TSFs). In conclusion, increased biosignal complexity, as revealed by MSE analysis, was found in patients with PD during non-REM sleep at high TSFs. This finding might reflect a compensatory mechanism for early defects in neuronal network control machinery in PD.

Controllable synthesis of palladium nanocubes/reduced graphene oxide composites and their enhanced electrocatalytic performance

NASA Astrophysics Data System (ADS)

Zhang, Yuting; Huang, Qiwei; Chang, Gang; Zhang, Zaoli; Xia, Tiantian; Shu, Honghui; He, Yunbin

2015-04-01

Homogeneous distribution of cube-shaped Pd nanocrystals on the surface of reduced graphene oxide is obtained via a facile one-step method by employing AA and KBr as the reductant and capping agent, respectively. The experimental factors affecting the morphology and structure of Pd nanoparticles have been systematically investigated to explore the formation mechanism of Pd nanocubes (PdNCs). It is revealed that PdNCs enclosed by active {100} facets with an average side length of 15 nm were successfully synthesized on the surface of reduced graphene oxide. KBr plays the role for facet selection by surface passivation and AA controls the reduction speed of Pd precursors, both of which govern the morphology changes of palladium nanoparticles. In the further electrochemical evaluations, the Pd nanocubes/reduced graphene oxide composites show better electrocatalytic activity and stability towards the electro-oxidation of ethanol than both reduced graphene oxide supported Pd nanoparticles and free-standing PdNCs. It could be attributed to the high electrocatalytic activity of the dominated active {100} crystal facets of Pd nanocubes and the enhanced electron transfer of graphene. The developed approach provide a versatile way for shape-controlled preparation of noble metal nanoparticles, which can work as novel electrocatalysts in the application of direct alcohols fuel cells.

Asymmetries in reactive and anticipatory balance control are of similar magnitude in Parkinson's disease patients.

PubMed

Boonstra, Tjitske A; van Kordelaar, Joost; Engelhart, Denise; van Vugt, Jeroen P P; van der Kooij, Herman

2016-01-01

Many Parkinson's disease (PD) patients show asymmetries in balance control during quiet stance and in response to perturbations (i.e., reactive balance control) in the sagittal plane. In addition, PD patients show a reduced ability to anticipate to self-induced disturbances, but it is not clear whether these anticipatory responses can be asymmetric too. Furthermore, it is not known how reactive balance control and anticipatory balance control are related in PD patients. Therefore, we investigated whether reactive and anticipatory balance control are asymmetric to the same extent in PD patients. 14 PD patients and 10 controls participated. Reactive balance control (RBC) was investigated by applying external platform and force perturbations and relating the response of the left and right ankle torque to the body sway angle at the excited frequencies. Anticipatory postural adjustments (APAs) were investigated by determining the increase in the left and right ankle torque just before the subjects released a force exerted with the hands against a force sensor. The symmetry ratio between the contribution of the left and right ankle was used to express the asymmetry in reactive and anticipatory balance control; the correlation between the two ratio's was investigated with Spearman's rank correlation coefficients. PD patients were more asymmetric in anticipatory (p=0.026) and reactive balance control (p=0.004) compared to controls and the symmetry ratios were significantly related (ρ=0.74; p=0.003) in PD patients. These findings suggest that asymmetric reactive balance control during bipedal stance may share a common pathophysiology with asymmetries in the anticipation of voluntary perturbations during, for instance, gait initiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Positive deviance as a novel tool in malaria control and elimination: methodology, qualitative assessment and future potential.

PubMed

Shafique, Muhammad; Edwards, Hannah M; De Beyl, Celine Zegers; Thavrin, Bou Kheng; Min, Myo; Roca-Feltrer, Arantxa

2016-02-16

Positive deviance (PD) is an asset-based, community-driven approach to behaviour change that has successfully been applied to address many health and social problems. It is yet to have been assessed for malaria control but may represent a promising tool for malaria elimination given its suitability in targeting small and remote population groups, apparent sustainability and ability to instil a high amount of community mobilisation. Here, the PD methodology as applied to malaria is explained, with focus upon and qualitative assessment of a proof of concept study in Cambodia. Three villages in Battambang, northwestern Cambodia were selected for the intervention, with an estimated population of 5036 including both residents and migrant workers. In August 2010, field teams conducted a 1 week PD process to sensitise and mobilise the community, establish normative behaviours in relation to malaria control and prevention, identify positive deviant behaviours from within the community, and identify PD volunteers. Until March 2011, PD volunteers were supported by field teams via monthly meetings to conduct activities in their respective communities to increase practice of PD behaviours. In February 2012, 1 year following the end of external support, evaluative interviews were conducted with community members to qualitatively assess community acceptance and interpretation of the PD intervention, perceived behaviour changes, and perceived positive outcomes. Qualitative data from focus group discussions and in-depth interviews showed that the PD approach was well-accepted into the communities and created a strong sense of community empowerment. Positive behaviour change was linked to the PD intervention, including greater usage of nets by forest goers, and use of public health facilities for malaria diagnosis and treatment. One year following the end of external assistance, PD volunteers were still conducting activities in their respective communities. PD offers a promising tool in malaria control and elimination settings. Work is ongoing to quantitatively measure impact of PD on behaviours and malaria transmission and once gathered, national malaria control programmes should be encouraged to look at including PD as part of their national strategies. Feasibility of scale-up, cost-effectiveness, and applicability to other settings and diseases is also currently being explored.

Emotion recognition in Parkinson's disease: Static and dynamic factors.

PubMed

Wasser, Cory I; Evans, Felicity; Kempnich, Clare; Glikmann-Johnston, Yifat; Andrews, Sophie C; Thyagarajan, Dominic; Stout, Julie C

2018-02-01

The authors tested the hypothesis that Parkinson's disease (PD) participants would perform better in an emotion recognition task with dynamic (video) stimuli compared to a task using only static (photograph) stimuli and compared performances on both tasks to healthy control participants. In a within-subjects study, 21 PD participants and 20 age-matched healthy controls performed both static and dynamic emotion recognition tasks. The authors used a 2-way analysis of variance (controlling for individual participant variance) to determine the effect of group (PD, control) on emotion recognition performance in static and dynamic facial recognition tasks. Groups did not significantly differ in their performances on the static and dynamic tasks; however, the trend was suggestive that PD participants performed worse than controls. PD participants may have subtle emotion recognition deficits that are not ameliorated by the addition of contextual cues, similar to those found in everyday scenarios. Consistent with previous literature, the results suggest that PD participants may have underlying emotion recognition deficits, which may impact their social functioning. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

On the Role of Mining Exposure in Epigenetic Effects in Parkinson's Disease.

PubMed

Castillo, Sebastian; Muñoz, Patricia; Behrens, Maria Isabel; Diaz-Grez, Fernando; Segura-Aguilar, Juan

2017-08-01

To explore the possible influence of heavy metal mining on incidence of Parkinson's disease (PD), global DNA methylation was assessed in blood samples from a population of PD patients (n = 45) and control subjects (n = 52) in Antofagasta neighborhood, a Chilean city built for exclusive use of mining companies. Comparisons were made with PD subjects (n = 52) and control subjects (n = 59) from Santiago Chile, a city having little association with mining. All subjects were assessed by two neurologists and PD diagnosis was based on UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria. From blood samples obtained from each individual, a decrease in global DNA methylation was observed in PD patients either exposed (49% of control, P < 0.001) or not exposed (47% of control, P < 0.001) to mining activity. Although there was no difference in levels of DNA methylation between PD patients from the two cities, there was a lower level of DNA methylation in control subjects from Santiago versus Antofagasta.

Dual-functional Pt-on-Pd supported on reduced graphene oxide hybrids: peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic.

PubMed

Zhang, Xiahong; Wu, Genghuang; Cai, Zhixiong; Chen, Xi

2015-03-01

In this study, a facile hydrothermal method was developed to synthesize Pt-on-Pd supported on reduced graphene oxide (Pt-on-Pd/RGO) hybrids. Because of the synergistic effect between Pt-on-Pd and RGO, the obtained Pt-on-Pd/RGO had superior peroxidase-mimic activities in H2O2 reduction and TMB oxidation. The reaction medium was optimized and a sensing approach for H2O2 was developed with a linear range from 0.98 to 130.7 μM of H2O2. In addition, the characteristic of electrocatalytic oxidation of methanol was investigated. The peak current density value, j(f), for the Pt-on-Pd/RGO hybrid (328 mA mg(Pt)(-1)) was about 1.85 fold higher than that of commercial Pt black (177 mA mg(Pt)(-1)) and, also, more durable electrocatalytic activity could be obtained. For the first time, the dual-functional Pt-on-Pd/RGO with peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic was reported. Copyright © 2014 Elsevier B.V. All rights reserved.

A palladium-doped ceria@carbon core-sheath nanowire network: a promising catalyst support for alcohol electrooxidation reactions.

PubMed

Tan, Qiang; Du, Chunyu; Sun, Yongrong; Du, Lei; Yin, Geping; Gao, Yunzhi

2015-08-28

A novel palladium-doped ceria and carbon core-sheath nanowire network (Pd-CeO2@C CSNWN) is synthesized by a template-free and surfactant-free solvothermal process, followed by high temperature carbonization. This hierarchical network serves as a new class of catalyst support to enhance the activity and durability of noble metal catalysts for alcohol oxidation reactions. Its supported Pd nanoparticles, Pd/(Pd-CeO2@C CSNWN), exhibit >9 fold increase in activity toward the ethanol oxidation over the state-of-the-art Pd/C catalyst, which is the highest among the reported Pd systems. Moreover, stability tests show a virtually unchanged activity after 1000 cycles. The high activity is mainly attributed to the superior oxygen-species releasing capability of Pd-doped CeO2 nanowires by accelerating the removal of the poisoning intermediate. The unique interconnected one-dimensional core-sheath structure is revealed to facilitate immobilization of the metal catalysts, leading to the improved durability. This core-sheath nanowire network opens up a new strategy for catalyst performance optimization for next-generation fuel cells.

Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab)

PubMed Central

Gill, Amanda L.; Green, Samantha A.; Abdullah, Shahed; Le Saout, Cecile; Pittaluga, Stefania; Chen, Hui; Turnier, Refika; Lifson, Jeffrey; Godin, Steven; Qin, Jing; Sneller, Michael C.; Cuillerot, Jean-Marie; Sabzevari, Helen; Lane, H. Clifford; Catalfamo, Marta

2016-01-01

Objective: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Methods: Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. Results: PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Conclusion: Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans. PMID:27490642

Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti-programed death-ligand 1 (Avelumab).

PubMed

Gill, Amanda L; Green, Samantha A; Abdullah, Shahed; Le Saout, Cecile; Pittaluga, Stefania; Chen, Hui; Turnier, Refika; Lifson, Jeffrey; Godin, Steven; Qin, Jing; Sneller, Michael C; Cuillerot, Jean-Marie; Sabzevari, Helen; Lane, H Clifford; Catalfamo, Marta

2016-10-23

The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans.

Silver and palladium alloy nanoparticle catalysts: reductive coupling of nitrobenzene through light irradiation.

PubMed

Peiris, Sunari; Sarina, Sarina; Han, Chenhui; Xiao, Qi; Zhu, Huai-Yong

2017-08-15

Silver-palladium (Ag-Pd) alloy nanoparticles strongly absorb visible light and exhibit significantly higher photocatalytic activity compared to both pure palladium (Pd) and silver (Ag) nanoparticles. Photocatalysts of Ag-Pd alloy nanoparticles on ZrO 2 and Al 2 O 3 supports are developed to catalyze the nitroaromatic coupling to the corresponding azo compounds under visible light irradiation. Ag-Pd alloy NP/ZrO 2 exhibited the highest photocatalytic activity for nitrobenzene coupling to azobenzene (yield of ∼80% in 3 hours). The photocatalytic efficiency could be optimized by altering the Ag : Pd ratio of the alloy nanoparticles, irradiation light intensity, temperature and wavelength. The rate of the reaction depends on the population and energy of the excited electrons, which can be improved by increasing the light intensity or by using a shorter wavelength. The knowledge developed in this study may inspire further studies on Ag alloy photocatalysts and organic syntheses using Ag-Pd nanoparticle catalysts driven under visible light Irradiation.

[Determination of ru, rh and Pd in 30% trialkyl phosphine oxide (TRPO)-kerosene by inductively coupled plasma-atomic emission spectrum (ICP-AES)].

PubMed

Wang, Jian-Chen; Zhang, Lin

2013-07-01

The determination method of Ru, Rh and Pd in 30% TRPO-kerosene ICP-AES was studied by using aqueous calibration reference solution and choosing ethanol as diluent. The effects of the contents of 30% TRPO-kerosene and aqueous solution and the concentration of HNO3 in 30% TRPO-kerosene on the intensities of Ru, Rh and Pd were described. The optimized condition for preparing samples and calibration solutions was chosen as follows: The contents of 30% TRPO-kerosene and aqueous phase were 10% (V/V) and 5% (V/V) respectively and the concentration of HNO3 30% TRPO-kerosene was 0.20 mol x L(-1). The determination method of Au, Ru and Pd was set up according to the above condition. The detection limit, precision and recovery ratio of Ru, Rh and Pd are well. The method is not only used in determination of Au, Ru and Pd in 30% TRPO-kerosene, but also used in other organic phases.

Basic science breaks through: New therapeutic advances in Parkinson's disease.

PubMed

Brundin, Patrik; Atkin, Graham; Lamberts, Jennifer T

2015-09-15

Parkinson's disease (PD) is the second most common neurodegenerative disease and is typically associated with progressive motor dysfunction, although PD patients also exhibit a variety of non-motor symptoms. The neuropathological hallmark of PD is intraneuronal inclusions containing primarily α-Synuclein (α-Syn), and several lines of evidence point to α-Syn as a key contributor to disease progression. Thus, basic research in the field of PD is largely focused on understanding the pathogenic properties of α-Syn. Over the past 2 y, these studies helped to identify several novel therapeutic strategies that have the potential to slow PD progression; such strategies include sequestration of extracellular α-Syn through immunotherapy, reduction of α-Syn multimerization or intracellular toxicity, and attenuation of the neuroinflammatory response. This review describes these and other putative therapeutic strategies, together with the basic science research that led to their identification. The current breadth of novel targets for the treatment of PD warrants cautious optimism in the fight against this devastating disease. © 2015 International Parkinson and Movement Disorder Society.

Impact of Parkinson's disease and levodopa on resting state functional connectivity related to speech prosody control.

PubMed

Elfmarková, Nela; Gajdoš, Martin; Mračková, Martina; Mekyska, Jiří; Mikl, Michal; Rektorová, Irena

2016-01-01

Impaired speech prosody is common in Parkinson's disease (PD). We assessed the impact of PD and levodopa on MRI resting-state functional connectivity (rs-FC) underlying speech prosody control. We studied 19 PD patients in the OFF and ON dopaminergic conditions and 15 age-matched healthy controls using functional MRI and seed partial least squares correlation (PLSC) analysis. In the PD group, we also correlated levodopa-induced rs-FC changes with the results of acoustic analysis. The PLCS analysis revealed a significant impact of PD but not of medication on the rs-FC strength of spatial correlation maps seeded by the anterior cingulate (p = 0.006), the right orofacial primary sensorimotor cortex (OF_SM1; p = 0.025) and the right caudate head (CN; p = 0.047). In the PD group, levodopa-induced changes in the CN and OF_SM1 connectivity strengths were related to changes in speech prosody. We demonstrated an impact of PD but not of levodopa on rs-FC within the brain networks related to speech prosody control. When only the PD patients were taken into account, the association between treatment-induced changes in speech prosody and changes in rs-FC within the associative striato-prefrontal and motor speech networks was found. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

PubMed

Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

2018-06-07

Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

Brazilian Samba Protocol for Individuals With Parkinson’s Disease: A Clinical Non-Randomized Study

PubMed Central

2017-01-01

Background In the 10 most populated countries in the world, Parkinson's disease (PD) affects more than 5 million individuals. Despite optimal treatment options already developed for the disease, concomitant involvement of other areas of health care plays an important role in complementing the treatment. From this perspective, dancing can be viewed as a non-drug alternative that can reduce falls by improving some motor skills, such as mobility, balance, gait, and posture, and can also improve the overall quality of life. Brazilian samba promotes improvement in motor and non-motor symptoms in individuals with PD, providing a new treatment option for this population. Objective The main objective of this quasi-experimental study is to provide a 12-week samba protocol (2x/week) for individuals with PD and to compare its effects with the group without intervention. The hypothesis is that the Brazilian samba protocol will promote improvement in primary (motor) and secondary (non-motor) outcomes in individuals with PD. Methods The sample will be selected at random from individuals diagnosed with PD in the city of Florianopolis (SC, Brazil). Sample size calculation was performed with the G*Power 3.1.9.2 software, with 0.447 effect size, at 5% significance level, power of 0.9, and test and sample loss of 20%. This yielded 60 individuals divided between the intervention and control groups. The questionnaires will be filled out before and after the dance intervention. The data collection for the control group will be held simultaneously to the intervention group. The classes will last for 1 hour, twice a week in the evening for 12 weeks, and all classes will be divided into warm-up, main part, and relaxation. Two-way analysis of variance with repeated measures and Sidak post-hoc comparison test will be used for a comparative analysis of the final results of the control group with the experimental group and of the within-group changes between pre- and postintervention period. Results We expect to complete follow-up in September 2017. Conclusions The major inspiration for this study was to encourage the creation of new rehabilitation programs that do not emphasize doctor involvement. This is a unique protocol for PD and we believe it can be an important tool to alleviate the motor and non-motor symptoms of individuals with PD. Dance is a simple activity depending on little equipment and few financial resources, facilitating its implementation and improving the cost-benefit relationship. In addition, activities that have a cultural aspect for the population in question, and which are pleasant, enable the participants to commit long term. This can enhance patient’s compliance with the therapy, which is often a problem for many rehabilitation programs. PMID:28676466

PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.

PubMed

Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying

2018-04-01

The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined. We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls. Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-γ-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Color Discrimination in Patients with Gaucher Disease and Parkinson Disease.

PubMed

Simon-Tov, Shlomi; Dinur, Tama; Giladi, Nir; Bar-Shira, Anat; Zelis, Mayaan; Zimran, Ari; Elstein, Deborah

2015-01-01

Poor color discrimination among patients with Parkinson disease (PD) has long been recognized. It has been shown that carrying one or two mutations in the β-glucocerebrosidase gene (GBA) for the autosomal disease Gaucher disease (GD), as based initially on clinical evidence, is a genetic risk factor for early-onset PD. The purpose of this study was to assess color discrimination in patients with one or two GBA mutations relative to healthy controls to ascertain whether this function is affected when persons with GD or even one GBA mutation develop PD. The Farnsworth-Munsell 100 hue test (FMHT) was evaluated among patients with GD+PD compared to patients with GD only, obligate GBA carriers with and without PD, patients with PD only, and healthy controls. FMHT outcome include computer-generated TES (Total Error Score) and values recommended by Vingrys & King-Smith. Six groups of 10 persons were tested. Significant differences were seen for male GD+PD and for age in PD. The highest mean TES was in the PD only group, the lowest in the GD only group. There was a significant difference because of PD in groups with GD and GBA carriers. GD+PD means were between GD only and PD only mean scores. These findings confirm that PD impacts color discrimination, more in males with GD+PD but nonetheless, GD+PD patients (but not GBA carriers) had better scores than PD only patients.

Impairment of work productivity in panic disorder patients.

PubMed

Lee Park, Yu; Kim, Won; Chae, Jeong-Ho; Seo Oh, Kang; Frick, Kevin D; Woo, Jong-Min

2014-03-01

Panic disorder (PD) has a critical impact on productivity at the workplace. This study aimed to identify the lost productivity time (LPT) for patients with PD. It also assessed change in LPT for patients with PD after 12 weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared with healthy controls. Working patients diagnosed with PD without other major medical or psychiatric illness were enrolled at outpatient psychiatric clinics (N=108). Age and sex-matched healthy controls were recruited through advertisement (N=108). Health and productivity, PD symptoms, and depressive symptoms were assessed using the Korean version of the World Health Organization's Health and Work Performance Questionnaire (HPQ), the Panic Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression (HAM-D), respectively at baseline, week 4, and week 12. At baseline, the PD group showed significantly higher LPT compared to the control group (103.02 vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group displayed significant clinical improvement as well as improved productivity with a marked reduction in LPT. Among the patients who completed the treatment, LPT due to PD was reduced from 104.38 to 55.15h in the past 4 weeks. There may be selection bias due to case-control study design. These data suggest that, after the treatment, there was significant improvement in clinical symptoms, and that productivity loss due to PD was almost entirely recovered to the level of healthy controls after 12 weeks of psychiatric outpatient treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Automatic Online Motor Control Is Intact in Parkinson's Disease With and Without Perceptual Awareness.

PubMed

Merritt, Kate E; Seergobin, Ken N; Mendonça, Daniel A; Jenkins, Mary E; Goodale, Melvyn A; MacDonald, Penny A

2017-01-01

In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson's disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients ( n = 14) and healthy controls ( n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls'. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses.

Study of telomere length and different markers of oxidative stress in patients with Parkinson's disease.

PubMed

Watfa, G; Dragonas, C; Brosche, T; Dittrich, R; Sieber, C C; Alecu, C; Benetos, A; Nzietchueng, R

2011-04-01

Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. There was a trend for lower TL in PD patients: 6.06 ± 0.81 kb in PD versus 6.45 ± 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.

Platinum and palladium incorporation into phosphate/viologen-phosphonates of zirconium and hafnium: synthesis and characterization

NASA Astrophysics Data System (ADS)

Dokoutchaev, Alexandre; Krishnan, Venkatesan V.; Thompson, Mark E.; Balasubramanian, Mahalingam

1998-10-01

We have continued previous efforts to synthesize and characterize a microporous metal phosphate/viologen-phosphonate compound, [(ZrF) 2(PO 4)(O 3PCH 2CH 2-4,4'-bipyridinium-CH 2CH 2PO 3)] ṡF·2H 2O, ZrPO PV. A derivative of this material has been shown to be an efficient catalyst for the production of hydrogen peroxide from hydrogen and oxygen. This paper has two objectives—one is to optimize the synthetic routes leading to the preparation of MPO PV (M=zirconium or hafnium) and the second is to characterize MPO PV and the derivatives formed by Pt or Pd incorporation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray powder diffraction (XRD), inductively coupled plasma-mass spectrometry (ICP-MS) and X-ray absorption fine structure analysis (XAFS). Powder XRD data have shown much higher crystallinity in MPO PV samples prepared by hydrothermal methods than those prepared by reflux methods. In the hydrothermal synthesis, the amount of mineralizer (HF) present controlled the crystallite size (as determined from TEM micrographs). The larger the quantity of HF in the bomb, the larger the size of the crystals but the lower the yield of the MPO PV material. Crystal sizes of about 2.5 μm in length and 0.15 μm in diameter have been made with very large quantities of HF as mineralizer (10 times the required stoichiometric amount). Ion exchange of the material by PdCl 42- has resulted in the incorporation of the PdCl 42- ions in place of X - in the material. This has been confirmed by XAFS studies that demonstrate the oxidation state of Pd is 2+ and show four Cl atoms bound to Pd. Upon reduction it has been confirmed (by XAFS) that the palladium exists as metal with oxidation state of zero. Ion exchange by PdCl 42- and PtCl 42- and subsequent reduction of the material suspension by hydrogen result in the formation of separate Pt and Pd colloids in the close vicinity of the crystallites. TEM micrographs show clearly that the Pt metal obtained after reduction forms much smaller particles in comparison to Pd. These exchanged and reduced materials have also been investigated as catalysts for production of hydrogen peroxide in mixed acetone/water medium. The production of hydrogen peroxide is enhanced by increasing amounts of Pd in the catalyst. Hydrogen peroxide yields are the highest for catalysts containing only Pd as opposed to a mixture of Pt and Pd.

Fibroblast growth factor 20 (FGF20) polymorphism is a risk factor for Parkinson's disease in Chinese population.

PubMed

Pan, Jing; Li, Hui; Wang, Ying; Ma, Jian-Fang; Zhang, Jin; Wang, Gang; Liu, Jun; Wang, Xi-Jin; Xiao, Qin; Chen, Sheng-Di

2012-06-01

The etiology of Parkinson's disease (PD) is not well established. Genetic variation in fibroblast growth factor 20 (FGF20) might influence the risk of PD occurrence and development. In this study, Two DNA polymorphisms at genetic variation in FGF20, rs2720208 (C/T) and rs1721100 (C/G), were genotyped by direct sequencing in Han Chinese population, including 394 PD patients and 383 healthy controls. Statistical analyses revealed that for rs1721100 (C/G) polymorphism, there were significant differences in genotype distribution between PD and healthy-matched controls. For rs12720208 (C/T) polymorphism, there was no significant difference in genotype distribution and gender and age-related differences between PD and control group. Results in this study revealed that the rs1721100(C/G) polymorphism is a risk factor for PD in Han Chinese population, while rs12720208(C/T) polymorphism is not significantly associated with PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of EPI distortion correction pipelines on the connectome in Parkinson's Disease

NASA Astrophysics Data System (ADS)

Galvis, Justin; Mezher, Adam F.; Ragothaman, Anjanibhargavi; Villalon-Reina, Julio E.; Fletcher, P. Thomas; Thompson, Paul M.; Prasad, Gautam

2016-03-01

Echo-planar imaging (EPI) is commonly used for diffusion-weighted imaging (DWI) but is susceptible to nonlinear geometric distortions arising from inhomogeneities in the static magnetic field. These inhomogeneities can be measured and corrected using a fieldmap image acquired during the scanning process. In studies where the fieldmap image is not collected, these distortions can be corrected, to some extent, by nonlinearly registering the diffusion image to a corresponding anatomical image, either a T1- or T2-weighted image. Here we compared two EPI distortion correction pipelines, both based on nonlinear registration, which were optimized for the particular weighting of the structural image registration target. The first pipeline used a 3D nonlinear registration to a T1-weighted target, while the second pipeline used a 1D nonlinear registration to a T2-weighted target. We assessed each pipeline in its ability to characterize high-level measures of brain connectivity in Parkinson's disease (PD) in 189 individuals (58 healthy controls, 131 people with PD) from the Parkinson's Progression Markers Initiative (PPMI) dataset. We computed a structural connectome (connectivity map) for each participant using regions of interest from a cortical parcellation combined with DWI-based whole-brain tractography. We evaluated test-retest reliability of the connectome for each EPI distortion correction pipeline using a second diffusion scan acquired directly after the participants' first. Finally, we used support vector machine (SVM) classification to assess how accurately each pipeline classified PD versus healthy controls using each participants' structural connectome.

Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease

PubMed Central

Evatt, Marian L.; DeLong, Mahlon R.; Khazai, Natasha; Rosen, Ami; Triche, Shirley; Tangpricha, Vin

2009-01-01

Background A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed. Objective To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD). Design Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine. Setting Referral center (PD and AD patients), primary care clinics, and community setting (controls). Participants Participants were recruited into the study between May 1992 and March 2007. Every fifth consecutively enrolled PD patient was selected from the clinical research database. Unrelated AD (n=97) and control (n=99) participants were randomly selected from the database after matching for age, sex, race, APOE genotype, and geographic location. Main Outcome Measures Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations. Results Significantly more patients with PD (55%) had insufficient vitamin D than did controls (36%) or patients with AD (41%; P=.02, χ2 test). The mean (SD) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts (31.9 [13.6] ng/mL vs 34.8 [15.4] ng/mL and 37.0 [14.5] ng/mL, respectively; P=.03). Conclusions This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of PD. PMID:18852350

Elementary science teachers' integration of engineering design into science instruction: results from a randomised controlled trial

NASA Astrophysics Data System (ADS)

Maeng, Jennifer L.; Whitworth, Brooke A.; Gonczi, Amanda L.; Navy, Shannon L.; Wheeler, Lindsay B.

2017-07-01

This randomised controlled trial used a mixed-methods approach to investigate the frequency and how elementary teachers integrated engineering design (ED) principles into their science instruction following professional development (PD). The ED components of the PD were aligned with Cunningham and Carlsen's [(2014). Teaching engineering practices. Journal of Science Teacher Education, 25, 197-210] guidelines for ED PD and promoted inclusion of ED within science teaching. The treatment group included 219 teachers from 83 schools. Participants in the control group included 145 teachers from 60 schools in a mid-Atlantic state. Data sources, including lesson overviews and videotaped classroom observations, were analysed quantitatively to determine the frequency of ED integration and qualitatively to describe how teachers incorporated ED into instruction after attending the PD. Results indicated more participants who attended the PD (55%) incorporated ED into instruction compared with the control participants (24%), χ2(1, n = 401) = 33.225, p < .001, ? = 0.308. Treatment and control teachers taught similar science content (p's > .05) through ED lessons. In ED lessons, students typically conducted research and created and tested initial designs. The results suggest the PD supported teachers in implementing ED into their science instruction and support the efficacy of using Cunningham and Carlsen's (2014) guidelines to inform ED PD design.

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients

PubMed Central

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H.; Caviness, John N.; Shill, Holly A.; Sabbagh, Marwan; Samanta, Johan E.; Sue, Lucia I.; Beach, Thomas G.

2015-01-01

Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia. PMID:26041249

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson's Disease Patients.

PubMed

Mu, Liancai; Chen, Jingming; Sobotka, Stanislaw; Nyirenda, Themba; Benson, Brian; Gupta, Fiona; Sanders, Ira; Adler, Charles H; Caviness, John N; Shill, Holly A; Sabbagh, Marwan; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G

2015-08-01

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Dopaminergic modulation of arm swing during gait among Parkinson’s disease patients

PubMed Central

Sterling, Nicholas W.; Cusumano, Joseph P.; Shaham, Noam; Piazza, Stephen J.; Liu, Guodong; Kong, Lan; Du, Guangwei; Lewis, Mechelle M.; Huang, Xuemei

2015-01-01

Background Reduced arm swing amplitude, symmetry, and coordination during gait have been reported in Parkinson’s disease (PD), but the relationship between dopaminergic depletion and these upper limb gait changes remains unclear. This study investigated the effects of dopaminergic drugs on arm swing velocity, symmetry, and coordination in PD. Methods Forearm angular velocity was recorded in 16 PD and 17 control subjects (Controls) during free walking trials. Angular velocity amplitude of each arm, arm swing asymmetry, and maximum cross-correlation were compared between control and PD groups, and between OFF- and ON-medication states among PD subjects. Results Compared to Controls, PD subjects in the OFF-medication state exhibited lower angular velocity amplitude of the slower- (p=0.0018), but not faster- (p=0.2801) swinging arm. In addition, PD subjects demonstrated increased arm swing asymmetry (p=0.0046) and lower maximum cross-correlation (p=0.0026). Following dopaminergic treatment, angular velocity amplitude increased in the slower- (p=0.0182), but not faster- (p=0.2312) swinging arm among PD subjects. Furthermore, arm swing asymmetry decreased (p=0.0386), whereas maximum cross-correlation showed no change (p=0.7436). Pre-drug angular velocity amplitude of the slower-swinging arm was correlated inversely with the change in arm swing asymmetry (R=−0.73824, p=0.0011). Conclusions This study provides quantitative evidence that reduced arm swing and symmetry in PD can be modulated by dopaminergic replacement. The lack of modulations of bilateral arm coordination suggests that additional neurotransmitters may also be involved in arm swing changes in PD. Further studies are warranted to investigate the longitudinal trajectory of arm swing dynamics throughout PD progression. PMID:25502948

Dopaminergic modulation of arm swing during gait among Parkinson's disease patients.

PubMed

Sterling, Nicholas W; Cusumano, Joseph P; Shaham, Noam; Piazza, Stephen J; Liu, Guodong; Kong, Lan; Du, Guangwei; Lewis, Mechelle M; Huang, Xuemei

2015-01-01

Reduced arm swing amplitude, symmetry, and coordination during gait have been reported in Parkinson's disease (PD), but the relationship between dopaminergic depletion and these upper limb gait changes remains unclear. We aimed to investigate the effects of dopaminergic drugs on arm swing velocity, symmetry, and coordination in PD. Forearm angular velocity was recorded in 16 PD and 17 control subjects (Controls) during free walking trials. Angular velocity amplitude of each arm, arm swing asymmetry, and maximum cross-correlation were compared between control and PD groups, and between OFF- and ON-medication states among PD subjects. Compared to Controls, PD subjects in the OFF-medication state exhibited lower angular velocity amplitude of the slower- (p = 0.0018), but not faster- (p = 0.2801) swinging arm. In addition, PD subjects demonstrated increased arm swing asymmetry (p = 0.0046) and lower maximum cross-correlation (p = 0.0026). Following dopaminergic treatment, angular velocity amplitude increased in the slower- (p = 0.0182), but not faster- (p = 0.2312) swinging arm among PD subjects. Furthermore, arm swing asymmetry decreased (p = 0.0386), whereas maximum cross-correlation showed no change (p = 0.7436). Pre-drug angular velocity amplitude of the slower-swinging arm was correlated inversely with the change in arm swing asymmetry (R = -0.73824, p = 0.0011). This study provides quantitative evidence that reduced arm swing and symmetry in PD can be modulated by dopaminergic replacement. The lack of modulations of bilateral arm coordination suggests that additional neurotransmitters may also be involved in arm swing changes in PD. Further studies are warranted to investigate the longitudinal trajectory of arm swing dynamics throughout PD progression.

Fuzzy fractional order sliding mode controller for nonlinear systems

NASA Astrophysics Data System (ADS)

Delavari, H.; Ghaderi, R.; Ranjbar, A.; Momani, S.

2010-04-01

In this paper, an intelligent robust fractional surface sliding mode control for a nonlinear system is studied. At first a sliding PD surface is designed and then, a fractional form of these networks PDα, is proposed. Fast reaching velocity into the switching hyperplane in the hitting phase and little chattering phenomena in the sliding phase is desired. To reduce the chattering phenomenon in sliding mode control (SMC), a fuzzy logic controller is used to replace the discontinuity in the signum function at the reaching phase in the sliding mode control. For the problem of determining and optimizing the parameters of fuzzy sliding mode controller (FSMC), genetic algorithm (GA) is used. Finally, the performance and the significance of the controlled system two case studies (robot manipulator and coupled tanks) are investigated under variation in system parameters and also in presence of an external disturbance. The simulation results signify performance of genetic-based fuzzy fractional sliding mode controller.

Highly Enhanced H2 Sensing Performance of Few-Layer MoS2/SiO2/Si Heterojunctions by Surface Decoration of Pd Nanoparticles.

PubMed

Hao, Lanzhong; Liu, Yunjie; Du, Yongjun; Chen, Zhaoyang; Han, Zhide; Xu, Zhijie; Zhu, Jun

2017-10-17

A novel few-layer MoS 2 /SiO 2 /Si heterojunction is fabricated via DC magnetron sputtering technique, and Pd nanoparticles are further synthesized on the device surface. The results demonstrate that the fabricated sensor exhibits highly enhanced responses to H 2 at room temperature due to the decoration of Pd nanoparticles. For example, the Pd-decorated MoS 2 /SiO 2 /Si heterojunction shows an excellent response of 9.2 × 10 3 % to H 2 , which is much higher than the values for the Pd/SiO 2 /Si and MoS 2 /SiO 2 /Si heterojunctions. In addition, the H 2 sensing properties of the fabricated heterojunction are dependent largely on the thickness of the Pd-nanoparticle layer and there is an optimized Pd thickness for the device to achieve the best sensing characteristics. Based on the microstructure characterization and electrical measurements, the sensing mechanisms of the Pd-decorated MoS 2 /SiO 2 /Si heterojunction are proposed. These results indicate that the Pd decoration of few-layer MoS 2 /SiO 2 /Si heterojunctions presents an effective strategy for the scalable fabrication of high-performance H 2 sensors.

Sex differences in Parkinson's disease.

PubMed

Gillies, Glenda E; Pienaar, Ilse S; Vohra, Shiv; Qamhawi, Zahi

2014-08-01

Parkinson's disease (PD) displays a greater prevalence and earlier age at onset in men. This review addresses the concept that sex differences in PD are determined, largely, by biological sex differences in the NSDA system which, in turn, arise from hormonal, genetic and environmental influences. Current therapies for PD rely on dopamine replacement strategies to treat symptoms, and there is an urgent, unmet need for disease modifying agents. As a significant degree of neuroprotection against the early stages of clinical or experimental PD is seen, respectively, in human and rodent females compared with males, a better understanding of brain sex dimorphisms in the intact and injured NSDA system will shed light on mechanisms which have the potential to delay, or even halt, the progression of PD. Available evidence suggests that sex-specific, hormone-based therapeutic agents hold particular promise for developing treatments with optimal efficacy in men and women. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Eyeblink conditioning in the developing rabbit

PubMed Central

Brown, Kevin L.; Woodruff-Pak, Diana S.

2011-01-01

Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17–21 or PD 24–28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17–24 in rats (Stanton, Freeman, & Skelton, 1992), another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24–28 showed greater conditioning relative to littermates trained from PD 17–21. Both age groups displayed poor retention of eyeblink conditioning at retraining one month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory. PMID:21953433

OLFACTORY DYSFUNCTION IN PARKINSON’S DISEASE: POSITIVE EFFECT OF CIGARETTE SMOKING

PubMed Central

Sharer, James D.; Leon-Sarmiento, Fidias E.; Morley, James F.; Weintraub, Daniel; Doty, Richard L.

2014-01-01

Background There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson’s disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal non-motor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population. Methods We evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 Parkinson’s patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, current). Results The patients exhibited much lower UPSIT scores than did the controls (P<0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never- and past-PD smokers (respective Ps=0.0005 & 0.0019). The female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 & 0.06). Age-related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack years, was evident. Conclusions PD patients who currently smoke do not exhibit the smoking-related decline in olfaction observed in non-PD control subjects who currently smoke. The physiologic basis of this phenomenon is yet to be defined. PMID:25545729

Risk factors of severe peritoneal sclerosis in chronic peritoneal dialysis patients.

PubMed

Alatab, Sudabeh; Najafi, Iraj; Pourmand, Gholamreza; Hosseini, Mostafa; Shekarchian, Soroosh

2017-11-01

Peritoneal dialysis (PD) offers the healthiest way for starting renal replacement therapy (RRT) in End Stage Renal Disease patients, however exposes long-term PD patients to a dangerous complication named encapsulating peritoneal sclerosis (EPS). In this study, we searched for possible risk factors of EPS. Data were collected from two PD centers covering period 1995-2012 and comprised 464 patients. Control group defined as PD patients stayed on PD >42 month (n = 122), and case group was 12 confirmed EPS patients. Associations were analyzed using linear regression analysis. Prevalence and incidence of EPS were 2.59% and 8.9% with an incidence of 0.7% patient-years, respectively. The age at start of PD in EPS patients (32.75 ± 10.8 year) was significantly lower compared with control group (49.61 ± 16.18 year, p = .0001). The mean duration of PD in EPS and control group were 2494.4 ± 940.9 and 1890.2 ± 598.8 days (p = .002). Control group had 145 episodes of peritonitis during total duration of 7686 patient months (peritonitis rate of 1/53). This was 1/26 with a total 38 episodes of peritonitis during the total duration of 997 patient months (p = .01) for EPS group. In regression analysis, PD duration, age at PD start and duration of Ultrafiltration failure (UFF) were associated with EPS. Longer time being on PD, younger age, and higher UFF duration were the risk factors for EPS development.

Decreased PD-1 expression on circulating CD4+T cell and PD-L1 expression on myeloid dendritic cell correlate with clinical manifestations in systemic juvenile idiopathic arthritis.

PubMed

Cai, Li; Zhang, Chenxing; Wu, Jing; Zhou, Wei; Chen, Tongxin

2018-03-30

Programmed cell death-1 (PD-1) and its ligand (PD-L1) mediate negative signal in autoimmune diseases. While little is known about its role in juvenile idiopathic arthritis (JIA). The study aimed to reveal the circulating cell profile and the relative PD-1/PD-L1 expression of JIA subsets, elucidating their underlying immunomodulatory mechanisms. We detected the circulating cells and the relative PD-1/PD-L1 signaling in 101 JIA patients and 50 controls by flow cytometry and analyzed their association with disease activity and clinical manifestations. Different from other JIA types, active systemic JIA (sJIA) patients had lower percentage and count of CD4 + T cells and lower PD-1 expression on them compared with healthy controls (P<0.05), active polyarthritis (P<0.05) and enthesitis-related arthritis (ERA) patients (P<0.05). Also, they had higher percentage and count of myeloid dendritic cell (mDC) and lower PD-L1 expression on mDC compared with healthy controls (P<0.05). Both PD-1 on CD4 + T cell and PD-L1 on mDC were negatively correlated with JADAS-27 in sJIA patients (P<0.05). In addition, PD-1 expression on CD4 + T cell was negatively associated with the number of involved joints (P<0.05) and PD-L1 on mDC was lower in patients with fever (P<0.01), which could further divide patients into two groups of different manifestations. Our finding displayed decreased CD4 + T cell, increased mDC and reduced PD-1/PD-L1 signal in sJIA PBMC comparing with other JIA subsets, which might be helpful in JIA differential diagnosis and responsible for distinct clinical manifestations via different mechanisms. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

The effects of anxiety and external attentional focus on postural control in patients with Parkinson's disease

PubMed Central

Jazaeri, Seyede Zohreh; Azad, Akram; Mehdizadeh, Hajar; Habibi, Seyed Amirhassan; Mandehgary Najafabadi, Mahbubeh; Saberi, Zakieh Sadat; Rahimzadegan, Hawre; Moradi, Saeed; Behzadipour, Saeed; Parnianpour, Mohamad; Khalaf, Kinda

2018-01-01

Background Although anxiety is a common non-motor outcome of Parkinson's disease (PD) affecting 40% of patients, little attention has been paid so far to its effects on balance impairment and postural control. Improvement of postural control through focusing on the environment (i.e. external focus) has been reported, but the role of anxiety, as a confounding variable, remains unclear. Objectives This study aimed to investigate the influence of anxiety and attentional focus instruction on the standing postural control of PD patients. Methods Thirty-four patients with PD (17 with high anxiety (HA-PD) and 17 with low anxiety (LA-PD)), as well as 17 gender- and age-matched healthy control subjects (HC) participated in the study. Postural control was evaluated using a combination of two levels of postural difficulty (standing on a rigid force plate surface with open eyes (RO) and standing on a foam surface with open eyes (FO)), as well as three attentional focus instructions (internal, external and no focus). Results Only the HA-PD group demonstrated significant postural control impairment as compared to the control, as indicated by significantly greater postural sway measures. Moreover, external focus significantly reduced postural sway in all participants especially during the FO condition. Conclusion The results of the current study provide evidence that anxiety influences balance control and postural stability in patients with PD, particularly those with high levels of anxiety. The results also confirmed that external focus is a potential strategy that significantly improves the postural control of these patients. Further investigation of clinical applicability is warranted towards developing effective therapeutic and rehabilitative treatment plans. PMID:29390029

Control of Pierce's Disease by Phage

PubMed Central

Das, Mayukh; Bhowmick, Tushar Suvra; Ahern, Stephen J.; Young, Ry; Gonzalez, Carlos F.

2015-01-01

Pierce’s Disease (PD) of grapevines, caused by Xylella fastidiosa subsp. fastidiosa (Xf), is a limiting factor in the cultivation of grapevines in the US. There are presently no effective control methods to prevent or treat PD. The therapeutic and prophylactic efficacy of a phage cocktail composed of four virulent (lytic) phages was evaluated for control of PD. Xf levels in grapevines were significantly reduced in therapeutically or prophylactically treated grapevines. PD symptoms ceased to progress one week post-therapeutic treatment and symptoms were not observed in prophylactically treated grapevines. Cocktail phage levels increased in grapevines in the presence of the host. No in planta phage-resistant Xf isolates were obtained. Moreover, Xf mutants selected for phage resistance in vitro did not cause PD symptoms. Our results indicate that phages have great potential for biocontrol of PD and other economically important diseases caused by Xylella. PMID:26107261

Risk and Prognosis of Bacteremia and Fungemia Among Peritoneal Dialysis Patients: A Population-Based Cohort Study.

PubMed

Dalgaard, Lars Skov; Nørgaard, Mette; Povlsen, Johan Vestergaard; Jespersen, Bente; Jensen-Fangel, Søren; Ellermann-Eriksen, Svend; Østergaard, Lars; Schønheyder, Henrik Carl; Søgaard, Ole Schmeltz

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study. Central and North Denmark regions. patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts. Copyright © 2016 International Society for Peritoneal Dialysis.

Perceived Treatment Status of Fluctuations in Parkinson Disease Impacts Suicidality.

PubMed

Hinkle, Jared T; Perepezko, Kate; Mari, Zoltan; Marsh, Laura; Pontone, Gregory M

2018-01-31

On/off motor fluctuations in Parkinson disease (PD) can be associated with extreme mood fluctuations and severe dysphoria. The impact of these affective symptoms may be overlooked in the treatment of motor fluctuations. Our goal was to examine the relationship between motor fluctuations, their treatment status, and suicidality in PD participants. We analyzed data from the Methods of Optimal Depression Detection in Parkinson's Disease (MOOD-PD) study of 223 individuals with PD. Suicidality was measured using items from four depression scales: Hamilton Depression Rating Scale (HAM-D-17); Montgomery-Åsberg Depression Rating Scale (MADRS); Inventory for Depressive Symptomatology (IDS-C); and the self-rated Beck Depression Inventory (BDI). Multivariable Poisson regression analyses tested whether self-reported motor fluctuations and their treatment status were associated with suicidality while controlling for recognized risk factors. Thirty-seven participants (16.6%) self-reported suicidality and 89 (39.5%) self-reported motor fluctuations, of whom 21 (23.6%) perceived their fluctuations as untreated. Participants reporting untreated motor fluctuations more frequently had a current depressive disorder (p < 0.001) and endorsed suicidality (p = 0.006) than participants with treated or no fluctuations. They also had significantly higher total scores on the HAM-D-17, MADRS, IDS-C, and BDI depression scales (p < 0.001 for each). Regression analyses showed significant associations between untreated motor fluctuations and higher scores on suicide questions extracted from the HAM-D-17, MADRS, and IDS-C (p < 0.01 for each). PD patients with untreated motor fluctuations are at increased risk for suicidal thoughts and should be monitored for mood changes as treatment is adapted. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Rotigotine Transdermal Patch Does Not Make Parkinson Disease Patients Sleepy During Daytime.

PubMed

Ohta, Kouichi; Osada, Takashi

2015-01-01

To assess quantitatively the influence of rotigotine transdermal patch on daytime sleepiness, the most common adverse event by non-ergot dopamine agonists (DAs), in Parkinson disease (PD) patients. An open-label study enrolled PD patients with unsatisfactory control of motor symptoms. Treatment with rotigotine transdermal patch was titrated to optimal dose (4-8 mg/24 hours) over 2 to 4 weeks. Primary outcome was Epworth Sleepiness Scale (ESS) for daytime sleepiness. Secondary outcomes included Hoehn&Yahr stage, time spent with dyskinesia, Clinical Global Impression of Improvement (CGI-I) of motor symptoms, adverse events, and compliance. The subjects were 31 PD patients (age 72 ± 8, Hoehn &Yahr stage 2.7 ± 0.9, mean ± SD). The ESS did not increase after rotigotine treatment (7.2 ± 4.9 before treatment, 6.2 ± 4.0 with 4 mg/24 hour, and 8.1 ± 6.4 with 8 mg/24 hour). The CGI-I score improved after treatment; responder rate reached 88.9% with 8 mg/24 hours. No patients showed worsening in other secondary outcomes. In 13 patients treated with equivalent doses of rotigotine switched from other DAs (pramipexole, ropinirole, and cabergoline), ESS did not increase after treatment (10.0 ± 4.6 before and 8.6 ± 4.5 after treatment) and decreased without worsening of CGI-I in 54% patients. Other secondary outcomes did not worsen after treatment. Twenty four-hour transdermal delivery of rotigotine at doses up to 8 mg/24 hours does not worsen the daytime sleepiness in PD patients and often improves it when switched from other non-ergot DAs. This is achieved together with satisfactory improvement in motor symptoms, demonstrating that this new modality of non-ergot DA is well tolerated and beneficial in PD patients.

Hyposalivation and xerostomia among Parkinson's disease patients and its impact on quality of life.

PubMed

Barbe, A G; Heinzler, A; Derman, Shm; Hellmich, M; Timmermann, L; Noack, M J

2017-05-01

Parkinson's disease (PD) adversely affects oral health (OH). However, the informative value of xerostomia compared to objective parameters and its impact on quality of life (QoL) are still unclear. This study aimed to explore whether xerostomia correlates with hyposalivation and to define its impact on OH-related QoL. Whole stimulated saliva (WSS) was collected from 30 patients with PD and 30 matched healthy controls. Objective parameters (community periodontal index of treatment needs, plaque/gingivitis index, mucosa situation and cheilitis angularis) and questionnaires (German Oral Health Impact Profile [OHIPG]-14, visual analogue scale [VAS], xerostomia [yes/no] and the Unified Parkinson's Disease Rating Scale-II) were assessed. Eighty-seven per cent of patients with PD showed hyposalivation vs 50% of controls (P = 0.001); 50% of patients with PD reported xerostomia, and none of controls (P < 0.001). The OHIPG-14 was impaired in patients with PD compared to controls (P < 0.001), PD patients with xerostomia reported mean VAS values of 4.1 (s.d.: 2.2). WSS did not correlate with VAS values. Half of the patients with PD reported xerostomia and underestimated their xerostomic status, with higher probability than healthy controls. WSS did not reflect the grade of xerostomia. Patients with PD suffered from impaired OH-related QoL. Dental teams should not overlook these oral health risks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-cell-density batch fermentation of Rhodococcus opacus PD630 using a high glucose concentration for triacylglycerol production.

PubMed

Kurosawa, Kazuhiko; Boccazzi, Paolo; de Almeida, Naomi M; Sinskey, Anthony J

2010-06-01

Biodiesel, monoalkyl esters of long-chain fatty acids with short-chain alcohols derived from triacylglycerols (TAGs), can be produced from renewable biomass sources. Recently, there has been interest in producing microbial oils from oleaginous microorganisms. Rhodococcus opacus PD630 is known to accumulate large amounts of TAGs. Following on these earlier works we demonstrate that R. opacus PD630 has the uncommon capacity to grow in defined media supplemented with glucose at a concentration of 300 g l(-1) during batch-culture fermentations. We found that we could significantly increase concentrations of both glucose and (NH4)2SO4 in the production medium resulting in a dramatic increase in fatty acid production when pH was controlled. We describe the experimental design protocol used to achieve the culture conditions necessary to obtain both high-cell-density and TAG accumulation; specifically, we describe the importance of the C/N ratio of the medium composition. Our bioprocess results demonstrate that R. opacus PD630 grown in batch-culture with an optimal production medium containing 240 g l(-1) glucose and 13.45 g l(-1) (NH4)2SO4 (C/N of 17.8) yields 77.6 g l(-1) of cell dry weight composed of approximately 38% TAGs indicating that this strain holds great potential as a future source of industrial biodiesel on starchy cellulosic feedstocks that are glucose polymers. 2010 Elsevier B.V. All rights reserved.

Effect of Systematic Control of Pd Thickness and Annealing Temperature on the Fabrication and Evolution of Palladium Nanostructures on Si (111) via the Solid State Dewetting.

PubMed

Kunwar, Sundar; Pandey, Puran; Sui, Mao; Zhang, Quanzhen; Li, Ming-Yu; Lee, Jihoon

2017-12-01

Si-based optoelectronic devices embedded with metallic nanoparticles (NPs) have demonstrated the NP shape, size, spacing, and crystallinity dependent on light absorption and emission induced by the localized surface plasmon resonance. In this work, we demonstrate various sizes and configurations of palladium (Pd) nanostructures on Si (111) by the systematic thermal annealing with the variation of Pd thickness and annealing temperature. The evolution of Pd nanostructures are systematically controlled by the dewetting of thin film by means of the surface diffusion in conjunction with the surface and interface energy minimization and Volmer-Weber growth model. Depending on the control of deposition amount ranging between 0.5 and 100 nm at various annealing temperatures, four distinctive regimes of Pd nanostructures are demonstrated: (i) small pits and grain formation, (ii) nucleation and growth of NPs, (iii) lateral evolution of NPs, and (iv) merged nanostructures. In addition, by the control of annealing between 300 and 800 °C, the Pd nanostructures show the evolution of small pits and grains, isolated NPs, and finally, Pd NP-assisted nanohole formation along with the Si decomposition and Pd-Si inter-diffusion. The Raman analysis showed the discrepancies on phonon modes of Si (111) such that the decreased peak intensity with left shift after the fabrication of Pd nanostructures. Furthermore, the UV-VIS-NIR reflectance spectra revealed the existence of surface morphology dependent on absorption, scattering, and reflectance properties.

Effect of Systematic Control of Pd Thickness and Annealing Temperature on the Fabrication and Evolution of Palladium Nanostructures on Si (111) via the Solid State Dewetting

NASA Astrophysics Data System (ADS)

Kunwar, Sundar; Pandey, Puran; Sui, Mao; Zhang, Quanzhen; Li, Ming-Yu; Lee, Jihoon

2017-05-01

Si-based optoelectronic devices embedded with metallic nanoparticles (NPs) have demonstrated the NP shape, size, spacing, and crystallinity dependent on light absorption and emission induced by the localized surface plasmon resonance. In this work, we demonstrate various sizes and configurations of palladium (Pd) nanostructures on Si (111) by the systematic thermal annealing with the variation of Pd thickness and annealing temperature. The evolution of Pd nanostructures are systematically controlled by the dewetting of thin film by means of the surface diffusion in conjunction with the surface and interface energy minimization and Volmer-Weber growth model. Depending on the control of deposition amount ranging between 0.5 and 100 nm at various annealing temperatures, four distinctive regimes of Pd nanostructures are demonstrated: (i) small pits and grain formation, (ii) nucleation and growth of NPs, (iii) lateral evolution of NPs, and (iv) merged nanostructures. In addition, by the control of annealing between 300 and 800 °C, the Pd nanostructures show the evolution of small pits and grains, isolated NPs, and finally, Pd NP-assisted nanohole formation along with the Si decomposition and Pd-Si inter-diffusion. The Raman analysis showed the discrepancies on phonon modes of Si (111) such that the decreased peak intensity with left shift after the fabrication of Pd nanostructures. Furthermore, the UV-VIS-NIR reflectance spectra revealed the existence of surface morphology dependent on absorption, scattering, and reflectance properties.

Pesticide exposure and risk of Parkinson's disease: A family-based case-control study

PubMed Central

Hancock, Dana B; Martin, Eden R; Mayhew, Gregory M; Stajich, Jeffrey M; Jewett, Rita; Stacy, Mark A; Scott, Burton L; Vance, Jeffery M; Scott, William K

2008-01-01

Background Pesticides and correlated lifestyle factors (e.g., exposure to well-water and farming) are repeatedly reported risk factors for Parkinson's disease (PD), but few family-based studies have examined these relationships. Methods Using 319 cases and 296 relative and other controls, associations of direct pesticide application, well-water consumption, and farming residences/occupations with PD were examined using generalized estimating equations while controlling for age-at-examination, sex, cigarette smoking, and caffeine consumption. Results Overall, individuals with PD were significantly more likely to report direct pesticide application than their unaffected relatives (odds ratio = 1.61; 95% confidence interval, 1.13–2.29). Frequency, duration, and cumulative exposure were also significantly associated with PD in a dose-response pattern (p ≤ 0.013). Associations of direct pesticide application did not vary by sex but were modified by family history of PD, as significant associations were restricted to individuals with no family history. When classifying pesticides by functional type, both insecticides and herbicides were found to significantly increase risk of PD. Two specific insecticide classes, organochlorines and organophosphorus compounds, were significantly associated with PD. Consuming well-water and living/working on a farm were not associated with PD. Conclusion These data corroborate positive associations of broadly defined pesticide exposure with PD in families, particularly for sporadic PD. These data also implicate a few specific classes of pesticides in PD and thus emphasize the need to consider a more narrow definition of pesticides in future studies. PMID:18373838

The Intonation-Syntax Interface in the Speech of Individuals with Parkinson’s Disease

PubMed Central

MacPherson, Megan K.; Huber, Jessica E.; Snow, David P.

2012-01-01

Purpose This study examined the effect of Parkinson’s disease (PD) on the intonational marking of final and nonfinal syntactic boundaries and investigated whether the effect of PD on intonation was sex-specific. Method Eight women and 8 men with PD and 16 age- and sex-matched control participants read a passage at comfortable pitch, rate, and loudness. Nuclear tones from final and nonfinal syntactic boundaries in clauses and lists were extracted. Measures of F0 were made on each tone contour. Results Individuals with PD demonstrated impaired differentiation of syntactic boundary finality/nonfinality with contour direction. They produced a lower proportion of falling contours in final boundaries and a higher proportion of falling contours in nonfinal boundaries than control participants. While not mediated by syntax, the effect of PD on F0 standard deviation (F0 SD) and pitch range (PRST) was sex-specific. Women with PD produced greater F0 SD and PRST than men with PD and women without PD. Men with PD produced lower PRST than men without PD. Conclusions Impaired intonational marking of syntactic boundaries likely contributes to dysprosody and reduced communicative effectiveness in PD. The effect of PD on intonation was sex-specific. The results were not fully explained by PD-related motor execution impairments. PMID:20699346

Parkinson disease and musculoskeletal pain: an 8-year population-based cohort study.

PubMed

Lien, Wei-Hung; Lien, Wei-Chih; Kuan, Ta-Shen; Wu, Shang-Te; Chen, Yi-Ting; Chiu, Ching-Ju

2017-07-01

The aim of this study was to evaluate the incidence and clinical features of musculoskeletal pain (MSP) in patients with Parkinson disease (PD) compared with a control group without the disease. The retrospective cohort study used a subset of the Taiwan National Health Insurance Research Database (NHIRD) comprising information on 1 million beneficiaries randomly sampled from the entire population of Taiwan. A total of 490 patients aged 50 and above with newly diagnosed Parkinson disease were identified during a period from 2000 to 2005. Among them, 199 developed MSP after PD. The control group consisted of 1960 participants without PD over the study period randomly selected by matching PD cases according to the date of PD incidence, age, and sex. The study groups were then followed to the end of 2007. Musculoskeletal pain was the end point. The incidence rate ratios of MSP were higher in the PD group than in the control group, representing an adjusted hazard ratio of 1.31 (95% confidence interval 1.09 to 1.58). PD was associated with a significantly elevated risk of MSP in all sex and age stratifications, with the highest hazard ratio noted for middle-aged male patients with PD, followed by older male patients with PD. This study showed that the PD may significantly increase the risk of developing MSP. The risk of developing MSP seems to be greatest for middle-aged male patients with PD. Clinicians should be more alert for MSP in patients with PD, and early intervention should be considered.

Association of Parkinson's Disease and Its Subtypes with Agricultural Pesticide Exposures in Men: A Case-Control Study in France.

PubMed

Moisan, Frédéric; Spinosi, Johan; Delabre, Laurène; Gourlet, Véronique; Mazurie, Jean-Louis; Bénatru, Isabelle; Goldberg, Marcel; Weisskopf, Marc G; Imbernon, Ellen; Tzourio, Christophe; Elbaz, Alexis

2015-11-01

Pesticides have been associated with Parkinson's disease (PD), but there are few data on important exposure characteristics such as dose-effect relations. It is unknown whether associations depend on clinical PD subtypes. We examined quantitative aspects of occupational pesticide exposure associated with PD and investigated whether associations were similar across PD subtypes. As part of a French population-based case-control study including men enrolled in the health insurance plan for farmers and agricultural workers, cases with clinically confirmed PD were identified through antiparkinsonian drug claims. Two controls were matched to each case. Using a comprehensive occupational questionnaire, we computed indicators for different dimensions of exposure (duration, cumulative exposure, intensity). We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) among exposed male farmers (133 cases, 298 controls). We examined the relation between pesticides and PD subtypes (tremor dominant/non-tremor dominant) using polytomous logistic regression. There appeared to be a stronger association with intensity than duration of pesticide exposure based on separate models, as well as a synergistic interaction between duration and intensity (p-interaction = 0.04). High-intensity exposure to insecticides was positively associated with PD among those with low-intensity exposure to fungicides and vice versa, suggesting independent effects. Pesticide exposure in farms that specialized in vineyards was associated with PD (OR = 2.56; 95% CI: 1.31, 4.98). The association with intensity of pesticide use was stronger, although not significantly (p-heterogeneity = 0.60), for tremor-dominant (p-trend < 0.01) than for non-tremor-dominant PD (p-trend = 0.24). This study helps to better characterize different aspects of pesticide exposure associated with PD, and shows a significant association of pesticides with tremor-dominant PD in men, the most typical PD presentation. Moisan F, Spinosi J, Delabre L, Gourlet V, Mazurie JL, Bénatru I, Goldberg M, Weisskopf MG, Imbernon E, Tzourio C, Elbaz A. 2015. Association of Parkinson's disease and its subtypes with agricultural pesticide exposures in men: a case-control study in France. Environ Health Perspect 123:1123-1129; http://dx.doi.org/10.1289/ehp.1307970.

Effect of Parkinson's disease on the production of structured and unstructured speaking tasks: Respiratory physiologic and linguistic considerations

PubMed Central

Huber, Jessica E.; Darling, Meghan

2012-01-01

Purpose The purpose of the present study was to examine the effects of cognitive-linguistic deficits and respiratory physiologic changes on respiratory support for speech in PD, using two speech tasks, reading and extemporaneous speech. Methods Five women with PD, 9 men with PD, and 14 age- and sex-matched control participants read a passage and spoke extemporaneously on a topic of their choice at comfortable loudness. Sound pressure level, syllables per breath group, speech rate, and lung volume parameters were measured. Number of formulation errors, disfluencies, and filled pauses were counted. Results Individuals with PD produced shorter utterances as compared to control participants. The relationships between utterance length and lung volume initiation and inspiratory duration were weaker in individuals with PD than for control participants, particularly for the extemporaneous speech task. These results suggest less consistent planning for utterance length by individuals with PD in extemporaneous speech. Individuals with PD produced more formulation errors in both tasks and significantly fewer filled pauses in extemporaneous speech. Conclusions Both respiratory physiologic and cognitive-linguistic issues affected speech production by individuals with PD. Overall, individuals with PD had difficulty planning or coordinating language formulation and respiratory support, in particular during extemporaneous speech. PMID:20844256

Corpus callosal atrophy and associations with cognitive impairment in Parkinson disease

PubMed Central

Bledsoe, Ian O.; Merkitch, Doug; Dinh, Vy; Bernard, Bryan; Stebbins, Glenn T.

2017-01-01

Objective: To investigate atrophy of the corpus callosum on MRI in Parkinson disease (PD) and its relationship to cognitive impairment. Methods: One hundred patients with PD and 24 healthy control participants underwent clinical and neuropsychological evaluations and structural MRI brain scans. Participants with PD were classified as cognitively normal (PD-NC; n = 28), having mild cognitive impairment (PD-MCI; n = 47), or having dementia (PDD; n = 25) by Movement Disorder Society criteria. Cognitive domain (attention/working memory, executive function, memory, language, visuospatial function) z scores were calculated. With the use of FreeSurfer image processing, volumes for total corpus callosum and its subsections (anterior, midanterior, central, midposterior, posterior) were computed and normalized by total intracranial volume. Callosal volumes were compared between participants with PD and controls and among PD cognitive groups, covarying for age, sex, and PD duration and with multiple comparison corrections. Regression analyses were performed to evaluate relationships between callosal volumes and performance in cognitive domains. Results: Participants with PD had reduced corpus callosum volumes in midanterior and central regions compared to healthy controls. Participants with PDD demonstrated decreased callosal volumes involving multiple subsections spanning anterior to posterior compared to participants with PD-MCI and PD-NC. Regional callosal atrophy predicted cognitive domain performance such that central volumes were associated with the attention/working memory domain; midposterior volumes with executive function, language, and memory domains; and posterior volumes with memory and visuospatial domains. Conclusions: Notable volume loss occurs in the corpus callosum in PD, with specific neuroanatomic distributions in PDD and relationships of regional atrophy to different cognitive domains. Callosal volume loss may contribute to clinical manifestations of PD cognitive impairment. PMID:28235816

Traditional neuropsychological correlates and reliability of the automated neuropsychological assessment metrics-4 battery for Parkinson's disease.

PubMed

Hawkins, Keith A; Jennings, Danna; Vincent, Andrea S; Gilliland, Kirby; West, Adrienne; Marek, Kenneth

2012-08-01

The automated neuropsychological assessment metrics battery-4 for PD offers the promise of a computerized approach to cognitive assessment. To assess its utility, the ANAM4-PD was administered to 72 PD patients and 24 controls along with a traditional battery. Reliability was assessed by retesting 26 patients. The cognitive efficiency score (CES; a global score) exhibited high reliability (r = 0.86). Constituent variables exhibited lower reliability. The CES correlated strongly with the traditional battery global score, but displayed weaker relationships to UPDRS scores than the traditional score. Multivariate analysis of variance revealed a significant difference between the patient and control groups in ANAM4-PD performance, with three ANAM4-PD tests, math, tower, and pursuit tracking, displaying sizeable differences. In discriminant analyses these variables were as effective as the total ANAM4-PD in classifying cases designated as impaired based on traditional variables. Principal components analyses uncovered fewer factors in the ANAM4-PD relative to the traditional battery. ANAM4-PD variables correlated at higher levels with traditional motor and processing speed variables than with untimed executive, intellectual or memory variables. The ANAM4-PD displays high global reliability, but variable subtest reliability. The battery assesses a narrower range of cognitive functions than traditional tests, and discriminates between patients and controls less effectively. Three ANAM4-PD tests, pursuit tracking, math, and tower performed as well as the total ANAM4-PD in classifying patients as cognitively impaired. These findings could guide the refinement of the ANAM4-PD as an efficient method of screening for mild to moderate cognitive deficits in PD patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

PubMed

Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates.

PubMed

Miao, Jing-Kun; Chen, Qi-Xiong; Bao, Li-Ming; Huang, Yi; Zhang, Juan; Wan, Ke-Xing; Yi, Jing; Wang, Shi-Yi; Zou, Lin; Li, Ting-Yu

2013-09-23

Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10 U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females. G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve. Our results demonstrated that using 2.10 U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55 U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10 U/g Hb. Our study found that high cutoffs, 2.35 and 2.55 U/g Hb, would increase assay's sensitivity to identify male and female G6PD deficiency neonates, respectively. We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Preclinical pharmacokinetic/pharmacodynamic modeling and simulation in the pharmaceutical industry: an IQ consortium survey examining the current landscape.

PubMed

Schuck, Edgar; Bohnert, Tonika; Chakravarty, Arijit; Damian-Iordache, Valeriu; Gibson, Christopher; Hsu, Cheng-Pang; Heimbach, Tycho; Krishnatry, Anu Shilpa; Liederer, Bianca M; Lin, Jing; Maurer, Tristan; Mettetal, Jerome T; Mudra, Daniel R; Nijsen, Marjoleen Jma; Raybon, Joseph; Schroeder, Patricia; Schuck, Virna; Suryawanshi, Satyendra; Su, Yaming; Trapa, Patrick; Tsai, Alice; Vakilynejad, Majid; Wang, Shining; Wong, Harvey

2015-03-01

The application of modeling and simulation techniques is increasingly common in preclinical stages of the drug discovery and development process. A survey focusing on preclinical pharmacokinetic/pharmacodynamics (PK/PD) analysis was conducted across pharmaceutical companies that are members of the International Consortium for Quality and Innovation in Pharmaceutical Development. Based on survey responses, ~68% of companies use preclinical PK/PD analysis in all therapeutic areas indicating its broad application. An important goal of preclinical PK/PD analysis in all pharmaceutical companies is for the selection/optimization of doses and/or dose regimens, including prediction of human efficacious doses. Oncology was the therapeutic area with the most PK/PD analysis support and where it showed the most impact. Consistent use of more complex systems pharmacology models and hybrid physiologically based pharmacokinetic models with PK/PD components was less common compared to traditional PK/PD models. Preclinical PK/PD analysis is increasingly being included in regulatory submissions with ~73% of companies including these data to some degree. Most companies (~86%) have seen impact of preclinical PK/PD analyses in drug development. Finally, ~59% of pharmaceutical companies have plans to expand their PK/PD modeling groups over the next 2 years indicating continued growth. The growth of preclinical PK/PD modeling groups in pharmaceutical industry is necessary to establish required resources and skills to further expand use of preclinical PK/PD modeling in a meaningful and impactful manner.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, B; Yu, H; Jara, H

Purpose: To compare enhanced Laws texture derived from parametric proton density (PD) maps to other MRI-based surrogate markers (T2, PD, ADC) in assessing degrees of liver fibrosis in a murine model of hepatic fibrosis using 11.7T scanner. Methods: This animal study was IACUC approved. Fourteen mice were divided into control (n=1) and experimental (n=13). The latter were fed a DDC-supplemented diet to induce hepatic fibrosis. Liver specimens were imaged using an 11.7T scanner; the parametric PD, T2, and ADC maps were generated from spin-echo pulsed field gradient and multi-echo spin-echo acquisitions. Enhanced Laws texture analysis was applied to the PDmore » maps: first, hepatic blood vessels and liver margins were segmented/removed using an automated dual-clustering algorithm; secondly, an optimal thresholding algorithm was applied to reduce the partial volume artifact; next, mean and stdev were corrected to minimize grayscale variation across images; finally, Laws texture was extracted. Degrees of fibrosis was assessed by an experienced pathologist and digital image analysis (%Area Fibrosis). Scatterplots comparing enhanced Laws texture, T2, PD, and ADC values to degrees of fibrosis were generated and correlation coefficients were calculated. Unenhanced Laws texture was also compared to assess the effectiveness of the proposed enhancements. Results: Hepatic fibrosis and the enhanced Laws texture were strongly correlated with higher %Area Fibrosis associated with higher Laws texture (r=0.89). Only a moderate correlation was detected between %Area Fibrosis and unenhanced Laws texture (r=0.70). Strong correlation also existed between ADC and %Area Fibrosis (r=0.86). Moderate correlations were seen between %Area Fibrosis and PD (r=0.65) and T2 (r=0.66). Conclusions: Higher degrees of hepatic fibrosis are associated with increased Laws texture. The proposed enhancements improve the accuracy of Laws texture. Enhanced Laws texture features are more accurate than PD and T2 in assessing fibrosis, and can potentially serve as an accurate surrogate marker for hepatic fibrosis.« less

The Impact of PD-L1 Expression in Patients with Metastatic GEP-NETs

PubMed Central

Kim, Seung Tae; Ha, Sang Yun; Lee, Sujin; Ahn, Soomin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Kim, Kyoung-Mee; Park, Young Suk

2016-01-01

Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET. The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed. Primary sites were 24 foregut-derived GEP-NETs, including stomach (n=1), duodenum (n=2), biliary tract (n=7), and pancreas (n=14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p=0.008) but not with gender, primary site, and number of metastatic sites (p>0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p=0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p=0.037). The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs. PMID:26958083

Imaging, biodistribution, and dosimetry of radionuclide-labeled PD-L1 antibody in an immunocompetent mouse model of breast cancer

PubMed Central

Josefsson, Anders; Nedrow, Jessie R.; Park, Sunju; Banerjee, Sangeeta Ray; Rittenbach, Andrew; Jammes, Fabien; Tsui, Benjamin; Sgouros, George

2015-01-01

The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radioactive isotope Indium-111 (111In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of 111In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Co-injection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of 111In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of 111In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy, and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy. PMID:26554829

Blood dendritic cell frequency declines in idiopathic Parkinson's disease and is associated with motor symptom severity.

PubMed

Ciaramella, Antonio; Salani, Francesca; Bizzoni, Federica; Pontieri, Francesco E; Stefani, Alessandro; Pierantozzi, Mariangela; Assogna, Francesca; Caltagirone, Carlo; Spalletta, Gianfranco; Bossù, Paola

2013-01-01

The role of inflammation in Parkinson's Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson's Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation.

DRUM-PD: The use of a drum circle to improve the symptoms and signs of Parkinson's disease (PD)

PubMed Central

Pantelyat, Alexander; Syres, Candace; Reichwein, Suzanne; Willis, Allison

2015-01-01

Background Physical therapy can improve motor function in patients with PD. Music performance may be used to improve motor skills by rhythmic entrainment. Drumming has long been a part of traditional healing rituals worldwide, and is increasingly being utilized as a therapeutic strategy. Methods This pilot controlled prospective cohort trial assessed feasibility and effects of twice-weekly group West African drum circle classes for 6 weeks on PD patients’ quality of life, symptoms, motor findings, cognition, and mood. Ten patients with PD were recruited into the drum circle group. Ten patients with PD were matched pairwise to each of the drum circle participants, and enrolled in a no-intervention control group. Both groups completed the PD-specific Parkinson Disease Questionnaire (PDQ)-39 quality of life assessment and the Geriatric Depression Scale (GDS), and underwent motor and cognitive assessments by a rater blinded to group at baseline, 6 weeks, and 12 weeks. Results Drummers had significantly improved PDQ-39 scores from baseline to 6 weeks (−5.8, p=0.042), whereas the control group's scores were unchanged. Walking performance was significantly faster at baseline for controls; after 6 weeks of drumming this difference was no longer significant, and remained non-significant at 12 weeks. The drummers trended (p=0.069) toward improvement in walking from baseline to 12 weeks. Other outcomes did not significantly change from baseline to 6 or 12 weeks. Conclusions Drum circle classes significantly and reversibly improved quality of life in patients with PD. This pilot trial's findings merit larger controlled investigations comparing drumming classes to established interventions in PD, such as physical therapy. PMID:27340683

The sensitivity of the sole of the foot in patients with Morbus Parkinson.

PubMed

Prätorius, B; Kimmeskamp, S; Milani, T L

2003-08-07

The sensory input of the foot has an important influence on balance. In patients with Morbus Parkinson (PD-patients) balance control is often impaired. Therefore, the aim of this study was to quantify the sensitivity of the plantar foot in PD-patients. Five sites of the plantar foot were examined in 24 PD-patients and in 20 controls using Semmes-Weinstein Monofilaments for touch pressure and a vibration-exciter (30 Hz) for vibration. The results show significantly higher thresholds in PD-patients. For each tested location (except the heel) the thresholds are at least twice as high as in controls. Moreover, this study proved the correlation between motor and somatosensory systems: the stronger the motor deficiencies in PD-patients (Unified Parkinson's Disease Rating System score) the higher the sensitivity thresholds for vibration. In conclusion, reduced sensitivity of the plantar foot may contribute to impaired balance control.

Lower urinary tract symptoms in Parkinson's disease: Prevalence, aetiology and management.

PubMed

McDonald, Claire; Winge, Kristian; Burn, David J

2017-02-01

Lower urinary tract symptoms (LUTS) are common in Parkinson's disease (PD), effecting 27-85% of patients with PD. Irritative symptoms predominate and urodynamic studies confirm high prevalence of detrusor overactivity in PD. LUTS are present early in PD and are more common in PD than in age matched controls. The assessment of LUTS in PD is complicated by coexisting bradykinesia and cognitive impairment. Although LUTS become more troublesome as PD progresses it remains unclear if LUTS severity correlates with motor symptoms and/or duration of PD. The underlying cause of LUTS in PD remains to be fully elucidated. Animal and human studies suggest the net effect of the basal ganglia is to supress micturition. Although LUTS are a common in PD, few studies have examined the assessment and management of LUTS specifically in patients with PD. Pilot studies have suggested that bladder training, antimuscarinic drugs and intravesical botulinum toxin maybe helpful but these trials have been small and frequently lacked a suitable control group making them vulnerable to the placebo effect. Furthermore the adverse effects of antimuscarinic drugs on cognitive and gastrointestinal function may limit the use of these drugs in PD. In this review we summarise the literature describing the prevalence of LUTS in PD, discuss the emerging data delineating the underlying pathophysiology of LUTS and examine interventions helpful in the management of LUTS in people with PD. Copyright © 2016. Published by Elsevier Ltd.

Rotenone, Paraquat, and Parkinson’s Disease

PubMed Central

Tanner, Caroline M.; Kamel, Freya; Ross, G. Webster; Hoppin, Jane A.; Goldman, Samuel M.; Korell, Monica; Marras, Connie; Bhudhikanok, Grace S.; Kasten, Meike; Chade, Anabel R.; Comyns, Kathleen; Richards, Marie Barber; Meng, Cheryl; Priestley, Benjamin; Fernandez, Hubert H.; Cambi, Franca; Umbach, David M.; Blair, Aaron; Sandler, Dale P.; Langston, J. William

2011-01-01

Background Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans. Objectives Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans. Methods We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case. Results In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7). Conclusions PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology. PMID:21269927

Obsessive compulsive personality disorder and Parkinson's disease.

PubMed

Nicoletti, Alessandra; Luca, Antonina; Raciti, Loredana; Contrafatto, Donatella; Bruno, Elisa; Dibilio, Valeria; Sciacca, Giorgia; Mostile, Giovanni; Petralia, Antonio; Zappia, Mario

2013-01-01

To evaluate the frequency of personality disorders in Parkinson's disease (PD) patients and in a group of healthy controls. Patients affected by PD diagnosed according to the United Kingdom Parkinson's disease Society Brain Bank diagnostic criteria and a group of healthy controls were enrolled in the study. PD patients with cognitive impairment were excluded from the study. Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders. Presence of personality disorders, diagnosed according to the DSM-IV, was confirmed by a psychiatric interview. Clinical and pharmacological data were also recorded using a standardized questionnaire. 100 PD patients (57 men; mean age 59.0 ± 10.2 years) and 100 healthy subjects (52 men; mean age 58.1 ± 11.4 years) were enrolled in the study. The most common personality disorder was the obsessive-compulsive personality disorder diagnosed in 40 PD patients and in 10 controls subjects (p-value<0.0001) followed by the depressive personality disorder recorded in 14 PD patients and 4 control subjects (p-value 0.02). Obsessive-compulsive personality disorder was also found in 8 out of 16 de novo PD patients with a short disease duration. PD patients presented a high frequency of obsessive-compulsive personality disorder that does not seem to be related with both disease duration and dopaminergic therapy.

Altered Pharyngeal Muscles in Parkinson Disease

PubMed Central

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Beach, Thomas G.

2012-01-01

Dysphagia (impaired swallowing) is common in Parkinson disease (PD) patients and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor (PC) and cricopharyngeal (CP) sphincter muscles in postmortem specimens from 8 PD and 4 age-matched control patients. Pharyngeal muscles in PD patients exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, the PD patients with dysphagia had a higher percentage of atrophic myofibers vs. with those without dysphagia and controls. The fast-to-slow fiber type transition is consistent with abnormalities in swallowing, slow movement of food and increased tone in the CP sphincter in PD patients. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in PD patients. PMID:22588389

Altered pharyngeal muscles in Parkinson disease.

PubMed

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

2012-06-01

Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

Effect of Pd Surface Roughness on the Bonding Process and High Temperature Reliability of Au Ball Bonds

NASA Astrophysics Data System (ADS)

Huang, Y.; Kim, H. J.; McCracken, M.; Viswanathan, G.; Pon, F.; Mayer, M.; Zhou, Y. N.

2011-06-01

A 0.3- μm-thick electrolytic Pd layer was plated on 1 μm of electroless Ni on 1 mm-thick polished and roughened Cu substrates with roughness values ( R a) of 0.08 μm and 0.5 μm, respectively. The rough substrates were produced with sand-blasting. Au wire bonding on the Ni/Pd surface was optimized, and the electrical reliability was investigated under a high temperature storage test (HTST) during 800 h at 250°C by measuring the ball bond contact resistance, R c. The average value of R c of optimized ball bonds on the rough substrate was 1.96 mΩ which was about 40.0% higher than that on the smooth substrate. The initial bondability increased for the rougher surface, so that only half of the original ultrasonic level was required, but the reliability was not affected by surface roughness. For both substrate types, HTST caused bond healing, reducing the average R c by about 21% and 27%, respectively. Au diffusion into the Pd layer was observed in scanning transmission electron microscopy/ energy dispersive spectroscopy (STEM-EDS) line-scan analysis after HTST. It is considered that diffusion of Au or interdiffusion between Au and Pd can provide chemically strong bonding during HTST. This is supported by the R c decrease measured as the aging time increased. Cu migration was indicated in the STEM-EDS analysis, but its effect on reliability can be ignored. Au and Pd tend to form a complete solid solution at the interface and can provide reliable interconnection for high temperature (250°C) applications.

Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders

PubMed Central

Ogaki, Kotaro; Koga, Shunsuke; Heckman, Michael G.; Fiesel, Fabienne C.; Ando, Maya; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Moussaud-Lamodière, Elisabeth L.; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Strongosky, Audrey J.; Uitti, Ryan J.; McCarthy, Allan; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Rudzinska, Monika; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Puschmann, Andreas; Nishioka, Kenya; Funayama, Manabu; Hattori, Nobutaka; Parisi, Joseph E.; Petersen, Ronald C.; Graff-Radford, Neill R.; Boeve, Bradley F.; Springer, Wolfdieter; Wszolek, Zbigniew K.; Dickson, Dennis W.

2015-01-01

Objective: To assess the role of CHCHD2 variants in patients with Parkinson disease (PD) and Lewy body disease (LBD) in Caucasian populations. Methods: All exons of the CHCHD2 gene were sequenced in a US Caucasian patient-control series (878 PD, 610 LBD, and 717 controls). Subsequently, exons 1 and 2 were sequenced in an Irish series (355 PD and 365 controls) and a Polish series (394 PD and 350 controls). Immunohistochemistry and immunofluorescence studies were performed on pathologic LBD cases with rare CHCHD2 variants. Results: We identified 9 rare exonic variants of unknown significance. These variants were more frequent in the combined group of PD and LBD patients compared to controls (0.6% vs 0.1%, p = 0.013). In addition, the presence of any rare variant was more common in patients with LBD (2.5% vs 1.0%, p = 0.050) compared to controls. Eight of these 9 variants were located within the gene's mitochondrial targeting sequence. Conclusions: Although the role of variants of the CHCHD2 gene in PD and LBD remains to be further elucidated, the rare variants in the mitochondrial targeting sequence may be a risk factor for Lewy body disorders, which may link CHCHD2 to other genetic forms of parkinsonism with mitochondrial dysfunction. PMID:26561290

Differential Effects of Tango Versus Dance for PD in Parkinson Disease

PubMed Central

McNeely, Marie E.; Mai, Marina M.; Duncan, Ryan P.; Earhart, Gammon M.

2015-01-01

Over half of the general population does not achieve recommended daily levels of physical activity, and activity levels in people with Parkinson disease (PD) are lower than in healthy older adults. Dance can serve as an adjunct to traditional treatments to improve gait, balance, and quality of life in people with PD. This study directly compares a tango dance intervention and a dance intervention based on the Dance for PD model, which integrates multiple dance styles. Eleven people with PD participated in a community-based mixed styles dance intervention called Dance for Parkinson’s (D4PD). Participants in the D4PD group were matched to participants in an ongoing community-based exercise study who participated in tango dance. The groups received 12 weeks of intervention, attending 1-h group classes twice a week. Participants were evaluated off anti-PD medication before and after intervention. Measures of balance, repeated sit-to-stand performance and endurance (mini-balance evaluation systems test, four square step test, five times sit to stand, 6-min walk time) improved from pre to post similarly in both groups. Motor sign severity (movement disorders society unified Parkinson disease rating scale motor subsection) and functional mobility (timed up and go) improved in the tango group and worsened in the D4PD group. Gait velocity was not affected by either intervention. Direct comparisons of different interventions are ­critical for developing optimal exercise interventions designed to specifically target motor impairments in PD. Tango dance interventions may preferentially improve mobility and motor signs in people with PD, compared to D4PD. PMID:26733865

Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jimenez-Jimenez, F.J.; Mateo, D.; Gimenez-Roldan, S.

1992-01-01

Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedatingmore » the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed.« less

Cyclooxygenase-2 polymorphisms in Parkinson's disease.

PubMed

Håkansson, Anna; Bergman, Olle; Chrapkowska, Cecilia; Westberg, Lars; Belin, Andrea Carmine; Sydow, Olof; Johnels, Bo; Olson, Lars; Holmberg, Björn; Nissbrandt, Hans

2007-04-05

Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of pathophysiological importance for the neurodegeneration in Parkinson's disease (PD). For example, in a large epidemiological study, use of NSAIDs was associated with a lower risk of PD. Genetic variants of the COX-2 gene might therefore influence the risk of developing the disease. The genotype distribution of four common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G, rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and control subjects in a Swedish population. No differences could be seen between the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the allele frequency of the C8473T SNP was found to differ when male patients were compared to controls (P = 0.007). In females no difference could be seen between PD-patients and controls. In conclusion, the results suggest a possible influence of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men. (c) 2006 Wiley-Liss, Inc.

Prefrontal Cortical GABA Levels in Panic Disorder Determined by Proton Magnetic Resonance Spectroscopy

PubMed Central

Hasler, Gregor; van der Veen, Jan Willem; Geraci, Marilla; Shen, Jun; Pine, Daniel; Drevets, Wayne C.

2009-01-01

Background Panic disorder (PD) is hypothesized to be associated with altered function of the major inhibitory neurotransmitter, gamma-amino butyric acid (GABA). Previous proton magnetic resonance spectroscopy (MRS) studies found lower GABA concentrations in the occipital cortex of subjects with PD relative to healthy controls. The current study is the first MRS study to compare GABA concentrations between unmedicated PD subjects and controls in the prefrontal cortex (PFC). Methods Unmedicated subjects with PD (n=17) and age- and sex-matched healthy controls (n=17) were scanned on a 3 Tesla scanner using a transmit-receive head coil that provided a sufficiently homogenous radiofrequency field to obtain spectroscopic measurements in the dorsomedial/dorsal anterolateral and ventromedial areas of the PFC. Results The prefrontal cortical GABA concentrations did not differ significantly between PD subjects and controls. There also was no statistically significant difference in Glx, choline or N-acetyl-aspartate concentrations. Conclusions The previously reported finding of reduced GABA concentrations in the occipital cortex of PD subjects does not appear to extend to the PFC. PMID:18692172

Vocal Responses to Perturbations in Voice Auditory Feedback in Individuals with Parkinson's Disease

PubMed Central

Liu, Hanjun; Wang, Emily Q.; Metman, Leo Verhagen; Larson, Charles R.

2012-01-01

Background One of the most common symptoms of speech deficits in individuals with Parkinson's disease (PD) is significantly reduced vocal loudness and pitch range. The present study investigated whether abnormal vocalizations in individuals with PD are related to sensory processing of voice auditory feedback. Perturbations in loudness or pitch of voice auditory feedback are known to elicit short latency, compensatory responses in voice amplitude or fundamental frequency. Methodology/Principal Findings Twelve individuals with Parkinson's disease and 13 age- and sex- matched healthy control subjects sustained a vowel sound (/α/) and received unexpected, brief (200 ms) perturbations in voice loudness (±3 or 6 dB) or pitch (±100 cents) auditory feedback. Results showed that, while all subjects produced compensatory responses in their voice amplitude or fundamental frequency, individuals with PD exhibited larger response magnitudes than the control subjects. Furthermore, for loudness-shifted feedback, upward stimuli resulted in shorter response latencies than downward stimuli in the control subjects but not in individuals with PD. Conclusions/Significance The larger response magnitudes in individuals with PD compared with the control subjects suggest that processing of voice auditory feedback is abnormal in PD. Although the precise mechanisms of the voice feedback processing are unknown, results of this study suggest that abnormal voice control in individuals with PD may be related to dysfunctional mechanisms of error detection or correction in sensory feedback processing. PMID:22448258

Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.

PubMed

Rocha, Natalia Pessoa; Assis, Frankcinéia; Scalzo, Paula Luciana; Vieira, Érica Leandro Marciano; Barbosa, Izabela Guimarães; de Souza, Mariana Soares; Christo, Paulo Pereira; Reis, Helton José; Teixeira, Antonio Lucio

2018-02-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

Mutations in the GIGYF2 (TNRC15) Gene at the PARK11 Locus in Familial Parkinson Disease

PubMed Central

Lautier, Corinne; Goldwurm, Stefano; Dürr, Alexandra; Giovannone, Barbara; Tsiaras, William G.; Pezzoli, Gianni; Brice, Alexis; Smith, Robert J.

2008-01-01

The genetic basis for association of the PARK11 region of chromosome 2 with familial Parkinson disease (PD) is unknown. This study examined the GIGYF2 (Grb10-Interacting GYF Protein-2) (TNRC15) gene, which contains the PARK11 microsatellite marker with the highest linkage score (D2S206, LOD 5.14). The 27 coding exons of the GIGYF2 gene were sequenced in 123 Italian and 126 French patients with familial PD, plus 131 Italian and 96 French controls. A total of seven different GIGYF2 missense mutations resulting in single amino acid substitutions were present in 12 unrelated PD index patients (4.8%) and not in controls. Three amino acid insertions or deletions were found in four other index patients and absent in controls. Specific exon sequencing showed that these ten sequence changes were absent from a further 91 controls. In four families with amino acid substitutions in which at least one other PD case was available, the GIGYF2 mutations (Asn56Ser, Thr112Ala, and Asp606Glu) segregated with PD. There were, however, two unaffected carriers in one family, suggesting age-dependent or incomplete penetrance. One index case (PD onset age 33) inherited a GIGYF2 mutation (Ile278Val) from her affected father (PD onset age 66) and a previously described PD-linked mutation in the LRRK2 gene (Ile1371Val) from her affected mother (PD onset age 61). The earlier onset and severe clinical course in the index patient suggest additive effects of the GIGYF2 and LRRK2 mutations. These data strongly support GIGYF2 as a PARK11 gene with a causal role in familial PD. PMID:18358451

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Adoptive transfer of murine T cells expressing a chimeric-PD1-Dap10 receptor as an immunotherapy for lymphoma.

PubMed

Lynch, Adam; Hawk, William; Nylen, Emily; Ober, Sean; Autin, Pierre; Barber, Amorette

2017-11-01

Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumour recognition and T-cell effector functions. The programmed death protein 1 (PD1) receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3ζ. Additionally, chimeric antigen receptor therapies use various co-stimulatory domains to enhance efficacy. Hence, the inclusion of a Dap10 or CD28 co-stimulatory domain in the chPD1 receptor was compared to determine which domain induced optimal anti-tumour immunity in a mouse model of lymphoma. The chPD1 T cells secreted pro-inflammatory cytokines and lysed RMA lymphoma cells. Adoptive transfer of chPD1 T cells significantly reduced established tumours and led to tumour-free survival in lymphoma-bearing mice. When comparing chPD1 receptors containing a Dap10 or CD28 domain, both receptors induced secretion of pro-inflammatory cytokines; however, chPD1-CD28 T cells also secreted anti-inflammatory cytokines whereas chPD1-Dap10 T cells did not. Additionally, chPD1-Dap10 induced a central memory T-cell phenotype compared with chPD1-CD28, which induced an effector memory phenotype. The chPD1-Dap10 T cells also had enhanced in vivo persistence and anti-tumour efficacy compared with chPD1-CD28 T cells. Therefore, adoptive transfer of chPD1 T cells could be a novel therapy for lymphoma and inclusion of the Dap10 co-stimulatory domain in chimeric antigen receptors may induce a preferential cytokine profile and T-cell differentiation phenotype for anti-tumour therapies. © 2017 John Wiley & Sons Ltd.

A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson's disease.

PubMed

Su, Lining; Wang, Chunjie; Zheng, Chenqing; Wei, Huiping; Song, Xiaoqing

2018-04-13

Parkinson's disease (PD) is a long-term degenerative disease that is caused by environmental and genetic factors. The networks of genes and their regulators that control the progression and development of PD require further elucidation. We examine common differentially expressed genes (DEGs) from several PD blood and substantia nigra (SN) microarray datasets by meta-analysis. Further we screen the PD-specific genes from common DEGs using GCBI. Next, we used a series of bioinformatics software to analyze the miRNAs, lncRNAs and SNPs associated with the common PD-specific genes, and then identify the mTF-miRNA-gene-gTF network. Our results identified 36 common DEGs in PD blood studies and 17 common DEGs in PD SN studies, and five of the genes were previously known to be associated with PD. Further study of the regulatory miRNAs associated with the common PD-specific genes revealed 14 PD-specific miRNAs in our study. Analysis of the mTF-miRNA-gene-gTF network about PD-specific genes revealed two feed-forward loops: one involving the SPRK2 gene, hsa-miR-19a-3p and SPI1, and the second involving the SPRK2 gene, hsa-miR-17-3p and SPI. The long non-coding RNA (lncRNA)-mediated regulatory network identified lncRNAs associated with PD-specific genes and PD-specific miRNAs. Moreover, single nucleotide polymorphism (SNP) analysis of the PD-specific genes identified two significant SNPs, and SNP analysis of the neurodegenerative disease-specific genes identified seven significant SNPs. Most of these SNPs are present in the 3'-untranslated region of genes and are controlled by several miRNAs. Our study identified a total of 53 common DEGs in PD patients compared with healthy controls in blood and brain datasets and five of these genes were previously linked with PD. Regulatory network analysis identified PD-specific miRNAs, associated long non-coding RNA and feed-forward loops, which contribute to our understanding of the mechanisms underlying PD. The SNPs identified in our study can determine whether a genetic variant is associated with PD. Overall, these findings will help guide our study of the complex molecular mechanism of PD.

Speed Pressure in Conflict Situations Impedes Inhibitory Action Control in Parkinson’s Disease

PubMed Central

Van Wouwe, N.C.; van den Wildenberg, W.P.M.; Claassen, D.O.; Kanoff, K.; Bashore, T.R.; Wylie, S.A.

2014-01-01

Parkinson’s disease (PD) is a neurodegenerative basal ganglia disease that disrupts cognitive control processes involved in response selection. The current study investigated the effects of PD on the ability to resolve conflicts during response selection when performance emphasized response speed versus response accuracy. Twenty-one (21) PD patients and 21 healthy controls (HC) completed a Simon conflict task, and a subset of 10 participants from each group provided simultaneous movement-related potential (MRP) data to track patterns of motor cortex activation and inhibition associated with the successful resolution of conflicting response tendencies. Both groups adjusted performance strategically to emphasize response speed or accuracy (i.e., speed-accuracy effect). For HC, interference from a conflicting response was reduced when response accuracy rather than speed was prioritized. For PD patients, however, there was a reduction in interference, but it was not statistically significant. The conceptual framework of the Dual-Process Activation-Suppression (DPAS) model revealed that the groups experienced similar susceptibility to making fast impulsive errors in conflict trials irrespective of speed-accuracy instructions, but PD patients were less proficient and delayed compared to HC at suppressing the interference from these incorrect response tendencies, especially under speed pressure. Analysis of MRPs on response conflict trials showed attenuated inhibition of the motor cortex controlling the conflicting impulsive response tendency in PD patients compared to HC. These results further confirm the detrimental effects of PD inhibitory control mechanisms and their exacerbation when patients perform under speed pressure. The results also suggest that a downstream effect of inhibitory dysfunction in PD is diminished inhibition of motor cortex controlling conflicting response tendencies. PMID:25017503

Deregulation of protein translation control, a potential game-changing hypothesis for Parkinson's disease pathogenesis.

PubMed

Taymans, Jean-Marc; Nkiliza, Aurore; Chartier-Harlin, Marie-Christine

2015-08-01

Protein translation is one of the most fundamental and exquisitely controlled processes in biology, and is energetically demanding. The deregulation of this process is deleterious to cells, as demonstrated by several diseases caused by mutations in protein translation machinery. Emerging evidence now points to a role for protein translation in the pathogenesis of Parkinson's disease (PD); a debilitating neurodegenerative movement disorder. In this paper, we propose a hypothesis that protein translation machinery, PD-associated proteins and PD pathology are connected in a functional network linking cell survival to protein translation control. This hypothesis is a potential game changer in the field of the molecular pathogenesis of PD, with implications for the development of PD diagnostics and disease-modifying therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of loss of control eating in purging disorder.

PubMed

Forney, K Jean; Haedt-Matt, Alissa A; Keel, Pamela K

2014-04-01

Purging Disorder (PD), an Other Specified Feeding or Eating Disorder (APA, 2013), is characterized by recurrent purging in the absence of binge eating. Though objectively large binge episodes are not present, individuals with PD may experience a loss of control (LOC) while eating a normal or small amounts of food. The present study sought to examine the role of LOC eating in PD using archival data from 101 women with PD. Participants completed diagnostic interviews and self-report questionnaires. Analyses examined the relationship between LOC eating and eating disorder features, psychopathology, personality traits, and impairment in bivariate models and then in multivariate models controlling for purging frequency, age, and body mass index. Across bivariate and multivariate models, LOC eating frequency was associated with greater disinhibition around food, hunger, depressive symptoms, negative urgency, distress, and impairment. LOC eating is a clinically significant feature of PD and should be considered in future definitions of PD. Future research should examine whether LOC eating better represents a dimension of severity in PD or a specifier that may impact treatment response or course. Copyright © 2013 Wiley Periodicals, Inc.

Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson's disease.

PubMed

Barbieri, Fabio A; Polastri, Paula F; Baptista, André M; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Beretta, Victor S; Gobbi, Lilian T B

2016-04-01

The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson's disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n=8) and bilateral group (n=11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups×medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups×medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior-posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior-posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks. Copyright © 2015 Elsevier B.V. All rights reserved.

The effects of dual tasking on handwriting in patients with Parkinson's disease.

PubMed

Broeder, S; Nackaerts, E; Nieuwboer, A; Smits-Engelsman, B C M; Swinnen, S P; Heremans, E

2014-03-28

Previous studies have shown that patients with Parkinson's disease (PD) experience extensive problems during dual tasking. Up to now, dual-task interference in PD has mainly been investigated in the context of gait research. However, the simultaneous performance of two different tasks is also a prerequisite to efficiently perform many other tasks in daily life, including upper limb tasks. To address this issue, this study investigated the effect of a secondary cognitive task on the performance of handwriting in patients with PD. Eighteen PD patients and 11 age-matched controls performed a writing task involving the production of repetitive loops under single- and dual-task conditions. The secondary task consisted of counting high and low tones during writing. The writing tests were performed with two amplitudes (0.6 and 1.0cm) using a writing tablet. Results showed that dual-task performance was affected in PD patients versus controls. Dual tasking reduced writing amplitude in PD patients, but not in healthy controls (p=0.046). Patients' writing size was mainly reduced during the small-amplitude condition (small amplitude p=0.017; large amplitude p=0.310). This suggests that the control of writing at small amplitudes requires more compensational brain-processing recourses in PD and is as such less automatic than writing at large amplitudes. In addition, there was a larger dual-task effect on the secondary task in PD patients than controls (p=0.025). The writing tests on the writing tablet proved highly correlated to daily life writing as measured by the 'Systematic Screening of Handwriting Difficulties' test (SOS-test) and other manual dexterity tasks, particularly during dual-task conditions. Taken together, these results provide additional insights into the motor control of handwriting and the effects of dual tasking during upper limb movements in patients with PD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway.

PubMed

Zhang, Song-An; Niyazi, Hu-Er-Xi-Dan; Hong, Wen; Tuluwengjiang, Gu-Li-Xian; Zhang, Lei; Zhang, Yang; Su, Wei-Peng; Bao, Yong-Xing

2017-03-01

This study aimed to investigate the effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 signaling pathway. A total of 43 adult female Wistar rats were selected and injected with HeLa cells in the caudal vein to construct a rat model of cervical cancer. All model rats were randomly divided into the radiotherapy group ( n = 31) and the control group ( n = 12). The immunophenotype of Treg cells was detected by the flow cytometry. The protein expressions of EBI3, PD-1, and PD-L1 in cervical cancer tissues were tested by the streptavidin-peroxidase method. HeLa cells in the logarithmic growth phase were divided into four groups: the blank, the negative control group, the EBI3 mimics group, and the EBI3 inhibitors group. Western blotting was used to detect PD-1 and PD-L1 protein expressions. MTT assay was performed to measure the proliferation of Treg cells. Flow cytometry was used to detect cell cycle and apoptosis, and CD4 + /CD8 + T cell ratio in each group. Compared with before and 1 week after radiotherapy, the percentages of CD4 + T cells and CD8 + T cells were significantly decreased in the radiotherapy group at 1 month after radiotherapy. Furthermore, down-regulation of EBI3 and up-regulation of PD-1 and PD-L1 were observed in cervical cancer tissues at 1 month after radiotherapy. In comparison to the blank and negative control groups, increased expression of EBI3 and decreased expressions of PD-1 and PD-L1 were found in the EBI3 mimics group. However, the EBI3 inhibitors group had a lower expression of EBI3 and higher expressions of PD-1 and PD-L1 than those in the blank and negative control groups. The EBI3 mimics group showed an increase in the optical density value (0.43 ± 0.05), while a decrease in the optical density value (0.31 ± 0.02) was found in the EBI3 inhibitors group. Moreover, compared with the blank and negative control groups, the apoptosis rates of Treg/CD4 + T/CD8 + T cells were decreased in the EBI3 mimics group, but the EBI3 inhibitors group exhibited an increase in apoptosis rate. In conclusion, over-expression of EBI3 could reduce the apoptosis of Treg/CD4 + T/CD8 + T cells and prevent radiation-induced immunosuppression of cervical cancer HeLa cells by inhibiting the activation of PD-1/PD-L1 signaling pathway.

Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

PubMed

Marques, Ana; Dutheil, Frédéric; Durand, Elodie; Rieu, Isabelle; Mulliez, Aurélien; Fantini, Maria Livia; Boirie, Yves; Durif, Franck

2018-05-31

To detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l -1 ; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p < 0.001), female gender (p < 0.033), longer duration of PD (p = 0.001), lower dose of dopaminergic treatment (p = 0.023), and higher score of dysautonomia (p = 0.017). Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

PubMed

Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-02-01

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

PubMed Central

Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-01-01

Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications. PMID:23899625

Enhanced performance of a novel anodic PdAu/VGCNF catalyst for electro-oxidation in a glycerol fuel cell.

PubMed

Yahya, N; Kamarudin, S K; Karim, N A; Masdar, M S; Loh, K S

2017-11-25

This study presents a novel anodic PdAu/VGCNF catalyst for electro-oxidation in a glycerol fuel cell. The reaction conditions are critical issues affecting the glycerol electro-oxidation performance. This study presents the effects of catalyst loading, temperature, and electrolyte concentration. The glycerol oxidation performance of the PdAu/VGCNF catalyst on the anode side is tested via cyclic voltammetry with a 3 mm 2 active area. The morphology and physical properties of the catalyst are examined using X-ray diffraction (XRD), field emission scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. Then, optimization is carried out using the response surface method with central composite experimental design. The current density is experimentally obtained as a response variable from a set of experimental laboratory tests. The catalyst loading, temperature, and NaOH concentration are taken as independent parameters, which were evaluated previously in the screening experiments. The highest current density of 158.34 mAcm -2 is obtained under the optimal conditions of 3.0 M NaOH concentration, 60 °C temperature and 12 wt.% catalyst loading. These results prove that PdAu-VGCNF is a potential anodic catalyst for glycerol fuel cells.

Asphyxia due to laryngeal spasm as a severe complication of awake deep brain stimulation for Parkinson's disease: a case report.

PubMed

von Eckardstein, Kajetan L; Sixel-Döring, Friederike; Kazmaier, Stephan; Trenkwalder, Claudia; Hoover, Jason M; Rohde, Veit

2016-11-08

In accordance with German neurosurgical and neurological consensus recommendations, lead placements for deep brain stimulation (DBS) in patients with Parkinson's disease (PD) are usually performed with the patient awake and in "medication off" state. This allows for optimal lead position adjustment according to the clinical response to intraoperative test stimulation. However, exacerbation of Parkinsonian symptoms after withdrawal of dopaminergic medication may endanger the patient by inducing severe "off" state motor phenomena. In particular, this can be a problem in awake craniotomies utilizing intraoperative airway management and resuscitation. We report the case of a PD patient with progressive orofacial and neck muscle dystonia resulting in laryngeal spasm during DBS lead placement. This led to upper airway compromise and asphyxia, requiring resuscitation. Laryngeal spasms may occur as a rare "off" state motor complication in patients with PD. Other potential causes of intraoperative difficulties breathing include bilateral vocal cord palsy, positional asphyxia, and silent aspiration. In our practice, we have adjusted our medication regimen and now allow patients to receive their standard dopaminergic medication until the morning of surgery. Neurologists and neurosurgeons performing lead placement procedures for PD should be aware of this rare but unsafe condition to most optimized treatment.

Study on the Application of an Ultra-High-Frequency Fractal Antenna to Partial Discharge Detection in Switchgears

PubMed Central

Yao, Chenguo; Chen, Pan; Huang, Congjian; Chen, Yu; Qiao, Panpan

2013-01-01

The ultra-high-frequency (UHF) method is used to analyze the insulation condition of electric equipment by detecting the UHF electromagnetic (EM) waves excited by partial discharge (PD). As part of the UHF detection system, the UHF sensor determines the detection system performance in signal extraction and recognition. In this paper, a UHF antenna sensor with the fractal structure for PD detection in switchgears was designed by means of modeling, simulation and optimization. This sensor, with a flat-plate structure, had two resonance frequencies of 583 MHz and 732 MHz. In the laboratory, four kinds of insulation defect models were positioned in the testing switchgear for typical PD tests. The results show that the sensor could reproduce the electromagnetic waves well. Furthermore, to optimize the installation position of the inner sensor for achieving best detection performance, the precise simulation model of switchgear was developed to study the propagation characteristics of UHF signals in switchgear by finite-difference time-domain (FDTD) method. According to the results of simulation and verification test, the sensor should be positioned at the right side of bottom plate in the front cabinet. This research established the foundation for the further study on the application of UHF technique in switchgear PD online detection. PMID:24351641

A novel high-performance self-powered ultraviolet photodetector: Concept, analytical modeling and analysis

NASA Astrophysics Data System (ADS)

Ferhati, H.; Djeffal, F.

2017-12-01

In this paper, a new MSM-UV-photodetector (PD) based on dual wide band-gap material (DM) engineering aspect is proposed to achieve high-performance self-powered device. Comprehensive analytical models for the proposed sensor photocurrent and the device properties are developed incorporating the impact of DM aspect on the device photoelectrical behavior. The obtained results are validated with the numerical data using commercial TCAD software. Our investigation demonstrates that the adopted design amendment modulates the electric field in the device, which provides the possibility to drive appropriate photo-generated carriers without an external applied voltage. This phenomenon suggests achieving the dual role of effective carriers' separation and an efficient reduce of the dark current. Moreover, a new hybrid approach based on analytical modeling and Particle Swarm Optimization (PSO) is proposed to achieve improved photoelectric behavior at zero bias that can ensure favorable self-powered MSM-based UV-PD. It is found that the proposed design methodology has succeeded in identifying the optimized design that offers a self-powered device with high-responsivity (98 mA/W) and superior ION/IOFF ratio (480 dB). These results make the optimized MSM-UV-DM-PD suitable for providing low cost self-powered devices for high-performance optical communication and monitoring applications.

Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention.

PubMed

Duchesne, C; Lungu, O; Nadeau, A; Robillard, M E; Boré, A; Bobeuf, F; Lafontaine, A L; Gheysen, F; Bherer, L; Doyon, J

2015-10-01

Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Current status in the treatment options for esophageal achalasia

PubMed Central

Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang

2013-01-01

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an “on-demand” strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further. PMID:24023484

Current status in the treatment options for esophageal achalasia.

PubMed

Chuah, Seng-Kee; Chiu, Chien-Hua; Tai, Wei-Chen; Lee, Jyong-Hong; Lu, Hung-I; Changchien, Chi-Sin; Tseng, Ping-Huei; Wu, Keng-Liang

2013-09-07

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD). Publications on the long-term success of laparoscopic surgery continue to emerge. In addition, laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication. The optimal treatment option is an ongoing matter of debate. In this review, we provide an update of the current progress in the treatment of esophageal achalasia. Unless new conclusive data prove otherwise, LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications. However, PD is the first choice for non-surgical treatment and is more cost-effective. Repeated PD according to an "on-demand" strategy based on symptom recurrence can achieve long-term remission. Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options. POEM has shown promise but its long-term efficacy and safety need to be assessed further.

Identifying the Atomic-Level Effects of Metal Composition on the Structure and Catalytic Activity of Peptide-Templated Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merrill, Nicholas A.; McKee, Erik M.; Merino, Kyle C.

2015-10-12

Bioinspired approaches for the formation of metallic nanomaterials have been extensively employed for a diverse range of applications including diagnostics and catalysis. These materials can often be used under sustainable conditions; however, it is challenging to control the material size, morphology, and composition simultaneously. Here we have employed the R5 peptide, which forms a 3D scaffold to direct the size and linear shape of bimetallic PdAu nanomaterials for catalysis. The materials were prepared at varying Pd:Au ratios to probe optimal compositions to achieve maximal catalytic efficiency. These materials were extensively characterized at the atomic level using transmission electron microscopy, extendedmore » X-ray absorption fine structure spectroscopy, and atomic pair distribution function analysis derived from high-energy X-ray diffraction patterns to provide highly resolved structural information. The results confirmed PdAu alloy formation, but also demonstrated that significant surface structural disorder was present. The catalytic activity of the materials was studied for olefin hydrogenation, which demonstrated enhanced reactivity from the bimetallic structures.These results present a pathway to the bioinspired production of multimetallic materials with enhanced properties, which can be assessed via a suite of characterization methods to fully ascertain structure/function relationships.« less

Management of postural sensory conflict and dynamic balance control in late-stage Parkinson's disease.

PubMed

Colnat-Coulbois, S; Gauchard, G C; Maillard, L; Barroche, G; Vespignani, H; Auque, J; Perrin, P P

2011-10-13

Parkinson's disease (PD) is known to affect postural control, especially in situations needing a change in balance strategy or when a concurrent task is simultaneously performed. However, few studies assessing postural control in patients with PD included homogeneous population in late stage of the disease. Thus, this study aimed to analyse postural control and strategies in a homogeneous population of patients with idiopathic advanced (late-stage) PD, and to determine the contribution of peripheral inputs in simple and more complex postural tasks, such as sensory conflicting and dynamic tasks. Twenty-four subjects with advanced PD (duration: median (M)=11.0 years, interquartile range (IQR)=4.3 years; Unified Parkinson's Disease Rating Scale (UPDRS): M "on-dopa"=13.5, IQR=7.8; UPDRS: M "off-dopa"=48.5, IQR=16.8; Hoehn and Yahr stage IV in all patients) and 48 age-matched healthy controls underwent static (SPT) and dynamic posturographic (DPT) tests and a sensory organization test (SOT). In SPT, patients with PD showed reduced postural control precision with increased oscillations in both anterior-posterior and medial-lateral planes. In SOT, patients with PD displayed reduced postural performances especially in situations in which visual and vestibular cues became predominant to organize balance control, as was the ability to manage balance in situations for which visual or proprioceptive inputs are disrupted. In DPT, postural restabilization strategies were often inefficient to maintain equilibrium resulting in falls. Postural strategies were often precarious, postural regulation involving more hip joint than ankle joint in patients with advanced PD than in controls. Difficulties in managing complex postural situations, such as sensory conflicting and dynamic situations might reflect an inadequate sensory organization suggesting impairment in central information processing. Copyright © 2011. Published by Elsevier Ltd.

Smoking, genes encoding dopamine pathway and risk for Parkinson's disease.

PubMed

Gu, Zhuqin; Feng, Xiuli; Dong, Xiumin; Chan, Piu

2010-09-20

Smoking has been reported to be inversely associated with Parkinson's disease (PD) in many studies, but a recent study in China found that smoking increased the risk of PD. Variants in genes associated with dopamine metabolism found to increase the risk for PD have also been associated with smoking behavior. To investigate the association between smoking and PD in a Chinese population and determine whether the genetic variants of genes involved in dopamine metabolism influence the relationship between smoking and risk for PD. Chinese PD patients were recruited from Xuanwu Hospital. Controls were sampled from community. Detailed information on life-long smoking behavior was collected by face-to-face interview. Genotypes were determined for SLC6A3 VNTR, COMT Val108/158Met and MAO-B intron13 A/G polymorphisms by PCR-RFLP, DHPLC and sequencing. Chi-square and logistic regression model were used in the analysis. 176 PD cases and 354 controls were enrolled in this study. 23.9% cases are smokers, compared to 48.0% in controls. Ever smoking is inversely associated with PD (odds ratio=0.14, 95% CI 0.08-0.26, adjusted for age and gender). None of the above-mentioned genetic polymorphisms was associated with PD risk or smoking. When each variant was included in the logistic regression model, the inverse association between smoking and PD remained the same, and the interactions between smoking and variants were not significant in the model. Our data support a reduction of PD risk associated with smoking in a Chinese population. These variants of genes associated with DA uptake and metabolism do not affect the inverse association between smoking and PD. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Automatic Online Motor Control Is Intact in Parkinson’s Disease With and Without Perceptual Awareness

PubMed Central

Seergobin, Ken N.; Mendonça, Daniel A.

2017-01-01

Abstract In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson’s disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients (n = 14) and healthy controls (n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls’. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses. PMID:29085900

Effect of Visual Cues on the Resolution of Perceptual Ambiguity in Parkinson’s Disease and Normal Aging

PubMed Central

Díaz-Santos, Mirella; Cao, Bo; Mauro, Samantha A.; Yazdanbakhsh, Arash; Neargarder, Sandy; Cronin-Golomb, Alice

2017-01-01

Parkinson’s disease (PD) and normal aging have been associated with changes in visual perception, including reliance on external cues to guide behavior. This raises the question of the extent to which these groups use visual cues when disambiguating information. Twenty-seven individuals with PD, 23 normal control adults (NC), and 20 younger adults (YA) were presented a Necker cube in which one face was highlighted by thickening the lines defining the face. The hypothesis was that the visual cues would help PD and NC to exert better control over bistable perception. There were three conditions, including passive viewing and two volitional-control conditions (hold one percept in front; and switch: speed up the alternation between the two). In the Hold condition, the cue was either consistent or inconsistent with task instructions. Mean dominance durations (time spent on each percept) under passive viewing were comparable in PD and NC, and shorter in YA. PD and YA increased dominance durations in the Hold cue-consistent condition relative to NC, meaning that appropriate cues helped PD but not NC hold one perceptual interpretation. By contrast, in the Switch condition, NC and YA decreased dominance durations relative to PD, meaning that the use of cues helped NC but not PD in expediting the switch between percepts. Provision of low-level cues has effects on volitional control in PD that are different from in normal aging, and only under task-specific conditions does the use of such cues facilitate the resolution of perceptual ambiguity. PMID:25765890

Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder.

PubMed

Kaplan, Johanna S; Erickson, Kristine; Luckenbaugh, David A; Weiland-Fiedler, Petra; Geraci, Marilla; Sahakian, Barbara J; Charney, Dennis; Drevets, Wayne C; Neumeister, Alexander

2006-10-01

Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. The sample size was limited, however, all patients were drug-free at the time of testing. The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.

Analysis of new lactotransferrin gene variants in a case-control study related to periodontal disease in dog.

PubMed

Morinha, Francisco; Albuquerque, Carlos; Requicha, João; Dias, Isabel; Leitão, José; Gut, Ivo; Guedes-Pinto, Henrique; Viegas, Carlos; Bastos, Estela

2012-04-01

The molecular and genetic research has contributed to a better understanding of the periodontal disease (PD) in humans and has shown that many genes play a role in the predisposition and progression of this complex disease. Variations in human lactotransferrin (LTF) gene appear to affect anti-microbial functions of this molecule, influencing the PD susceptibility. PD is also a major health problem in small animal practice, being the most common inflammatory disease found in dogs. Nevertheless, the research in genetic predisposition to PD is an unexplored subject in this species. This work aims to contribute to the characterization of the genetic basis of canine PD. In order to identify genetic variations and verify its association with PD, was performed a molecular analysis of LTF gene in a case-control approach, including 40 dogs in the PD cases group and 50 dogs in the control group. In this study were detected and characterized eight new single nucleotide variations in the dog LTF gene. Genotype and allele frequencies of these variations showed no statistically significant differences between the control and PD cases groups. Our data do not give evidence for the contribution of these LTF variations to the genetic background of canine PD. Nevertheless, the sequence variant L/15_g.411C > T leads to an aminoacid change (Proline to Leucine) and was predicted to be possibly damaging to the LTF protein. Further investigations would be of extreme value to clarify the biological importance of these new findings.

Diagnostic value of combined assessment of olfaction and sustantia nigra hyperechogenicity for Parkinson's disease.

PubMed

López Hernández, N; García Escrivá, A; Shalabi Benavent, M

2015-10-01

Hyposmia and substantia nigra hyperechogenicity (SN+) are characteristic markers of Parkinson's disease (PD), although their diagnostic value in isolation may be limited. We evaluated the combined prevalence of both disorders in patients diagnosed with PD and assessed their diagnostic yield compared to a sample with essential tremor (ET) and another group of healthy subjects. Patients diagnosed with PD and ET and treated in our outpatient clinic were enrolled. Olfaction was assessed using the "Sniffin' Sticks" odour identification test (SS-12) and hyperechogenicity of the substantia nigra (SN+) was assessed by transcranial duplex ultrasound. A total of 98 subjects were analysed, comprising 30 with PD, 21 with ET, and 47 controls. The respective prevalence rates of hyposmia (SS-12 < 8) and SN+ (area > .24cm(2)) were 70% and 83.3% in PD, 33.3% and 9.5% in ET, and 17% and 10.6% in controls. Both markers were present in 63% of patients with PD, none of the patients with ET, and only 2 of the controls. Combined use of substantia nigra sonography and olfactory testing with SS-12, two rapid, safe, and accessible tests, was more specific than each isolated marker for distinguishing patients with PD from patients with ET and control subjects. Since both markers have been described in very early phases of PD, combined use may be helpful in providing early diagnosis of PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Development of electrochemical sensor for the determination of palladium ions (Pd2+) using flexible screen printed un-modified carbon electrode.

PubMed

Velmurugan, Murugan; Thirumalraj, Balamurugan; Chen, Shen-Ming; Al-Hemaid, Fahad M A; Ajmal Ali, M; Elshikh, Mohamed S

2017-01-01

To date, the development of different modified electrodes have received much attention in electrochemistry. The modified electrodes have some drawbacks such as high cost, difficult to handle and not eco friendly. Hence, we report an electrochemical sensor for the determination of palladium ions (Pd 2+ ) using an un-modified screen printed carbon electrode has been developed for the first time, which are characterized and studied via scanning electron microscope and cyclic voltammetry. Prior to determination of Pd 2+ ions, the operational conditions of un-modified SPCE was optimized using cyclic voltammetry and showed excellent electro-analytical behavior towards the determination of Pd 2+ ions. Electrochemical determination of Pd 2+ ions reveal that the un-modified electrode showed lower detection limit of 1.32μM with a linear ranging from 3 to 133.35μM towards the Pd 2+ ions concentration via differential pulse voltammetry. The developed sensor also applied to the successfully determination of trace level Pd 2+ ions in spiked water samples. In addition, the advantage of this type of electrode is simple, disposable and cost effective in electrochemical sensors. Copyright © 2016 Elsevier Inc. All rights reserved.

Preparation of PdCu Alloy Nanocatalysts for Nitrate Hydrogenation and Carbon Monoxide Oxidation

DOE PAGES

Cai, Fan; Yang, Lefu; Shan, Shiyao; ...

2016-06-30

Alloying Pd with Cu is important for catalytic reactions such as denitrification reaction and CO oxidation reaction, but understanding of the catalyst preparation and its correlation with the catalyst’s activity and selectivity remains elusive. Herein, we report the results of investigations of the preparation of PdCu alloy nanocatalysts using different methods and the catalytic properties of the catalysts in catalytic denitrification reaction and CO oxidation reaction. PdCu alloy nanocatalysts were prepared by conventional dry impregnation method and ligand-capping based wet chemical synthesis method, and subsequent thermochemical activation as well. The alloying characteristics depend on the bimetallic composition. PdCu/Al 2O 3more » with a Pd/Cu ratio of 50:50 was shown to exhibit an optimized hydrogenation activity for the catalytic denitrification reaction. The catalytic activity of the PdCu catalysts was shown to be highly dependent on the support, as evidenced by the observation of an enhanced catalytic activity for CO oxidation reaction using TiO 2 and CeO 2 supports with high oxygen storage capacity. Lastly, we discussed the implications of the results to the refinement of the preparation of the alloy nanocatalysts.« less

The impact of personality disorder pathology on the effectiveness of Cognitive Therapy and Interpersonal Psychotherapy for Major Depressive Disorder.

PubMed

van Bronswijk, Suzanne C; Lemmens, Lotte H J M; Viechtbauer, Wolfgang; Huibers, Marcus J H; Arntz, Arnoud; Peeters, Frenk P M L

2018-01-01

Despite extensive research, there is no consensus how Personality Disorders (PD) and PD features affect outcome for Major Depressive Disorder (MDD). The present study evaluated the effects of PD (features) on treatment continuation and effectiveness in Cognitive Therapy (CT) and Interpersonal Psychotherapy (IPT) for MDD. Depressed outpatients were randomized to CT (n=72) and IPT (n=74). Primary outcome was depression severity measured repeatedly with the Beck Depression Inventory-II (BDI-II) at baseline, three months, at the start of each therapy session, at post-treatment and monthly during five months follow-up. Comorbid PD and PD features did not affect dropout. Multilevel and Cox regression models indicated no negative effect of PD on BDI-II change and remission rates during treatment and follow-up, irrespective of the treatment received. For both therapies, higher dependent PD features predicted overall lower BDI-II scores during treatment, however this effect did not sustain through follow-up. Cluster A PD features moderated treatment outcome during treatment and follow-up: individuals with high cluster A PD features had greater BDI-II reductions over time in CT as compared to IPT. Not all therapists and participants were blind to the assessment of PD (features), and assessments were performed by one rater. Further research must investigate the state and trait dependent changes of PD and MDD over time. We found no negative impact of PD on the effectiveness and treatment retention of CT and IPT for MDD during treatment and follow-up. If replicated, cluster A PD features can be used to optimize treatment selection. Copyright © 2017 Elsevier B.V. All rights reserved.

Iowa Gambling Task Performance in Parkinson Disease Patients with Impulse Control Disorders.

PubMed

Biars, Julia W; Johnson, Nicole L; Nespeca, Michelle; Busch, Robyn M; Kubu, Cynthia S; Floden, Darlene P

2018-04-27

A subgroup of patients with Parkinson disease (PD) develops impulse control disorders (ICD) associated with their dopamine replacement therapy. Patients and their families may be reluctant to report ICD symptoms or unaware these symptoms are related to PD medication, which can make detecting an ICD difficult for clinicians. Ideally, a behavioral measure that is sensitive to ICD could be employed to ensure that patients with these behaviors are identified and treated. The Iowa Gambling Task (IGT), a standardized decision-making task, has proven sensitive in other populations with impulse control problems. We hypothesized that the IGT would differentiate between PD patients with and without ICD. We compared IGT performance and disease variables in 24 PD patients with ICD and 24 PD patients without ICD. Patient groups were matched in terms of age, sex, and duration of PD. There were no significant differences in IGT scores between PD groups. IGT performance declined with increasing age, but the majority of patients performed within normal limits based on published age- and education-corrected normative data. The IGT did not distinguish between PD patients with and without ICD. Increasing age negatively impacted performance in both groups. Other studies have found that IGT performance may decline in normal aging. Our results suggest that the IGT lacks the sensitivity and specificity needed to differentiate between age-related deficits and disruption in frontal-subcortical circuits underlying ICD associated with PD medications. Therefore, the IGT is not an appropriate behavioral measure for ICD in PD patients.

HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers.

PubMed

Pai, Sara I; Jack Lee, J; Carey, Thomas E; Westra, William H; Ferrone, Soldano; Moore, Charles; Mosunjac, Marina B; Shin, Dong M; Ferris, Robert L

2018-02-01

Human immunodeficiency virus (HIV)-infected individuals are at increased risk for developing several non-AIDS related malignancies and are often excluded from cancer immunotherapy regimens. To evaluate the immune competence of this cancer patient population, we evaluated HLA class I antigen presenting machinery (APM) component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-) head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers in the United States were identified. HLA class I APM component, PD-1, and PD-L1 expression were analyzed by immunohistochemical staining with monoclonal antibodies (mAbs). Clinical data was abstracted from the medical records. There was no significant difference between the cases and controls in LMP2, TAP1, HLA-A and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p = .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In addition, HLA-A expression was significantly associated with PD-L1 expression in the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC do not have any detectable defects in HLA class I APM component expression and in PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit from the recently FDA-approved immune checkpoint blockade therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes

PubMed Central

Waling, Maria; Isaksson, Andreas; Tellström, Anna; Lundin-Olsson, Lillemor; Brage, Søren; Ryberg, Mats; Svensson, Michael; Olsson, Tommy

2017-01-01

Background Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed. Methods Thirty-two patients with type 2 diabetes (age 59±8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX). Results For the within group analyses, fat mass decreased by 5.7 kg (IQR: −6.6, −4.1; p<0.001) in the PD group and by 6.7 kg (−8.2, −5.3; p<0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p<0.001) and PD-EX (p<0.001) groups. HbA1c decreased by 0.9% (−1.2, −0.6; p<0.001) in the PD group and 1.1% (−1.7, −0.7; p<0.01) in the PD-EX group. Leptin decreased by 62 % (p<0.001) in the PD group and 42 % (p<0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p<0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (−3.6, −1.3) in the PD group and by 1.2 kg (−1.3, 1.0) in the PD-EX group (p<0.05 for the difference between intervention groups). Conclusions A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness. PMID:27235022

The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer

PubMed Central

Zhao, Lian; Yu, Haibo; Yi, Shuijing; Peng, Xiaowei; Su, Peng; Xiao, Zhiming; Liu, Rui; Tang, Anliu; Li, Xiayu; Liu, Fen; Shen, Shourong

2016-01-01

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3′ untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy. PMID:27248318

The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer.

PubMed

Zhao, Lian; Yu, Haibo; Yi, Shuijing; Peng, Xiaowei; Su, Peng; Xiao, Zhiming; Liu, Rui; Tang, Anliu; Li, Xiayu; Liu, Fen; Shen, Shourong

2016-07-19

microRNAs (miRNAs) play critical roles in cancer development and progression. This study investigated the effects of miR-138-5p in human colorectal cancer (CRC) development. miR-138-5p was frequently downregulated in CRC tissues and was associated with advanced clinical stage, lymph node metastasis and poor overall survival. We found that miR-138-5p decreased expression of programmed cell death ligand 1 (PD-L1) through interaction with its PD-L1 3' untranslated region. miR-138-5p also dramatically suppressed CRC cell growth in vitro and inhibited tumorigenesis in vivo. PD-L1 and miR-138-5p levels were inversely correlated in human CRC tumors, and miR-138-5p inhibited PD-L1 expression in tumor models. These results suggest that miR-138-5p is a tumor suppressor in CRC, and its effects are exerted at least partially through PD-L1 downregulation. Low miR-138-5p and high PD-L1 levels correlated with shorter overall CRC patient survival, indicating that miR-138-5p and PD-L1 may serve as CRC biomarkers for risk group assignment, optimal therapy selection and clinical outcome prediction. Targeting PD-L1, possibly by administering miR-138-5p mimics, might be a clinically effective anti-CRC therapeutic strategy.

Risk of Injurious Fall and Hip Fracture up to 26 y before the Diagnosis of Parkinson Disease: Nested Case-Control Studies in a Nationwide Cohort.

PubMed

Nyström, Helena; Nordström, Anna; Nordström, Peter

2016-02-01

Low muscle strength has been found in late adolescence in individuals diagnosed with Parkinson disease (PD) 30 y later. This study investigated whether this lower muscle strength also may translate into increased risks of falling and fracture before the diagnosis of PD. Among all Swedish citizens aged ≥50 y in 2005, two nested case-control cohorts were compiled. In cohort I, individuals diagnosed with PD during 1988-2012 (n = 24,412) were matched with up to ten controls (n = 243,363), and the risk of fall-related injuries before diagnosis of PD was evaluated. In cohort II, individuals with an injurious fall in need of emergency care during 1988-2012 (n = 622,333) were matched with one control (n = 622,333), and the risk of PD after the injurious fall was evaluated. In cohort I, 18.0% of cases and 11.5% of controls had at least one injurious fall (p < 0.001) prior to PD diagnosis in the case. Assessed by conditional logistic regression analysis adjusted for comorbid diagnoses and education level, PD was associated with increased risks of injurious fall up to 10 y before diagnosis (odds ratio [OR] 1.19, 95% CI 1.08-1.31; 7 to <10 y before diagnosis) and hip fracture ≥15 y before diagnosis (OR 1.36, 95% CI 1.10-1.69; 15-26 y before diagnosis). In cohort II, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with PD during follow-up (p < 0.001). The risk of PD was increased for up to 10 y after an injurious fall (OR 1.18, 95% CI 1.02-1.37; 7 to <10 y after diagnosis). An important limitation is that the diagnoses were obtained from registers and could not be clinically confirmed for the study. The increased risks of falling and hip fracture prior to the diagnosis of PD may suggest the presence of clinically relevant neurodegenerative impairment many years before the diagnosis of this disease.

Preparation of Palladium(II) Ion-Imprinted Polymeric Nanospheres and Its Removal of Palladium(II) from Aqueous Solution

NASA Astrophysics Data System (ADS)

Tao, Hu-Chun; Gu, Yi-Han; Liu, Wei; Huang, Shuai-Bin; Cheng, Ling; Zhang, Li-Juan; Zhu, Li-Li; Wang, Yong

2017-11-01

Three kinds of functional monomers, 4-vinylpridine(4-VP), 2-(allylthio)nicotinic acid(ANA), and 2-Acetamidoacrylic acid(AAA), were used to synthetize palladium(II) ion-imprinted polymeric nanospheres (Pd(II) IIPs) via precipitation-polymerization method in order to study the effects of different functional monomers on the adsorption properties of ion-imprinted materials. The results of UV spectra in order to study the interaction between template ion PdCl4 2- and functional monomers showed that there were great differences in structure after the template reacted with three functional monomers, 4-VP and ANA caused a large structural change, while AAA basically did not change. Further results on the adsorption performance of Pd(II) IIPs on Pd(II) confirmed 4-VP was the most promising candidate for the synthesis of Pd(II) IIPs with an adsorption capacity of 5.042 mg/g as compared with ANA and AAA. The influence of operating parameters on Pd(II) IIP's performance on Pd(II) adsorption was investigated. There was an increase in the adsorption capacity of Pd(II) IIPs at higher pH, temperature, and initial concentration of Pd(II). The results of multi-metal competitive adsorption experiments showed that Pd(II) IIPs had selectivity for Pd(II). An adsorption equilibrium could be reached at 180 min. Kinetic analysis showed that the adsorption test data fitted best to the pseudo-second order kinetic model, and the theoretical equilibrium adsorption capacity was about 5.085 mg/g. The adsorption isotherms of Pd(II) by Pd(II) IIPs agreed well with the Freundlich equation, suggesting a favorable adsorption reaction under optimal conditions. These results showed that Pd(II) IIPs have potential application in the removal of Pd(II) from aqueous solutions and may provide some information for the selection of functional monomers in the preparation of Pd(II) IIPs.

Walking economy in people with Parkinson's disease.

PubMed

Christiansen, Cory L; Schenkman, Margaret L; McFann, Kim; Wolfe, Pamela; Kohrt, Wendy M

2009-07-30

Gait dysfunction is an early problem identified by patients with Parkinson's disease (PD). Alterations in gait may result in an increase in the energy cost of walking (i.e., walking economy). The purpose of this study was to determine whether walking economy is atypical in patients with PD when compared with healthy controls. A secondary purpose was to evaluate the associations of age, sex, and level of disease severity with walking economy in patients with PD. The rate of oxygen consumption (VO(2)) and other responses to treadmill walking were compared in 90 patients (64.4 +/- 10.3 years) and 44 controls (64.6 +/- 7.3 years) at several walking speeds. Pearson correlation coefficients (r) were calculated to determine relationships of age, sex, and disease state with walking economy in PD patients. Walking economy was significantly worse in PD patients than in controls at all speeds above 1.0 mph. Across all speeds, VO(2) was 6 to 10% higher in PD patients. Heart rate, minute ventilation, respiratory exchange ratio, and rating of perceived exertion were correspondingly elevated. No significant relationship of age, sex, or UPDRS score with VO(2) was found for patients with PD. The findings suggest that the physiologic stress of daily physical activities is increased in patients with early to mid-stage PD, and this may contribute to the elevated level of fatigue that is characteristic of PD. Copyright 2009 Movement Disorder Society.

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.

PubMed

Tinaz, Sule; Lauro, Peter M; Ghosh, Pritha; Lungu, Codrin; Horovitz, Silvina G

2017-01-01

Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional "disconnection" in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.

Available Resources | Division of Cancer Prevention

Cancer.gov

Preclinical pharmacology and efficacy studies Identification and evaluation of intermediate biomarkers Formulation optimization for enhanced bioavailability and clinical usefulness Analytical method development for investigational agents in bulk form and in biological fluids and tissues PK and PK-PD modeling to optimize dosing regimen Scale-up non-cGMP and cGMP production of

Multiplex primer extension reaction screening and oxidative challenge of glucose-6-phosphate dehydrogenase mutants in hemizygous and heterozygous subjects.

PubMed

Ko, Chun Hay; Yung, Edmund; Li, Karen; Li, Chung Leung; Ng, Pak Cheung; Fung, Kwok Pui; Wong, Raymond Pui-On; Chui, Kit Man; Gu, Goldie Jia-Shi; Fok, Tai Fai

2006-01-01

The primary objective of our study was to provide a simple and reliable assay for identifying the majority of G6PD genetic variants in the Chinese population. We optimized the multiplex primer extension reaction (MPER) assay for simultaneous screening of 14-point mutations in 98 G6PD-deficient subjects. Our data demonstrated that this method is precise, cost-effective and has successfully identified mutations in 97 out of 98 subjects, including all heterozygous mutants. We also detected a relatively high incidence (12.3%) of c.871G > A, and all of them harbored the silent mutation c.1311C > T. Apart from the screening program, the pharmacogenetic relationship between G6PD level and residual reduced glutathione (GSH) level was studied upon oxidative challenge by alpha-naphthol. The GSH levels were correlated with their status of G6PD deficiency, but no significant difference was observed between individual G6PD-deficient groups. Our data demonstrated the potentials of the MPER assay for characterization of G6PD deficiency and other genetic diseases.

Application of HFCT and UHF Sensors in On-Line Partial Discharge Measurements for Insulation Diagnosis of High Voltage Equipment

PubMed Central

Álvarez, Fernando; Garnacho, Fernando; Ortego, Javier; Sánchez-Urán, Miguel Ángel

2015-01-01

Partial discharge (PD) measurements provide valuable information for assessing the condition of high voltage (HV) insulation systems, contributing to their quality assurance. Different PD measuring techniques have been developed in the last years specially designed to perform on-line measurements. Non-conventional PD methods operating in high frequency bands are usually used when this type of tests are carried out. In PD measurements the signal acquisition, the subsequent signal processing and the capability to obtain an accurate diagnosis are conditioned by the selection of a suitable detection technique and by the implementation of effective signal processing tools. This paper proposes an optimized electromagnetic detection method based on the combined use of wideband PD sensors for measurements performed in the HF and UHF frequency ranges, together with the implementation of powerful processing tools. The effectiveness of the measuring techniques proposed is demonstrated through an example, where several PD sources are measured simultaneously in a HV installation consisting of a cable system connected by a plug-in terminal to a gas insulated substation (GIS) compartment. PMID:25815452

Core/shell face-centered tetragonal FePd/Pd nanoparticles as an efficient non-Pt catalyst for the oxygen reduction reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Huiyuan; Jiang, Guangming; Zhang, Xu

We report the synthesis of core/shell face-centered tetragonal (fct)-FePd/Pd nanoparticles (NPs) via reductive annealing of core/shell Pd/Fe 3O 4 NPs followed by temperature-controlled Fe etching in acetic acid. Among three different kinds of core/shell FePd/Pd NPs studied (FePd core at similar to 8 nm and Pd shell at 0.27, 0.65, or 0.81 nm), the fct-FePd/Pd-0.65 NPs are the most efficient catalyst for the oxygen reduction reaction (ORR) in 0.1 M HClO 4 with Pt-like activity and durability. This enhanced ORR catalysis arises from the desired Pd lattice compression in the 0.65 nm Pd shell induced by the fct-FePd core. Lastly,more » our study offers a general approach to enhance Pd catalysis in acid for ORB.« less

Core/shell face-centered tetragonal FePd/Pd nanoparticles as an efficient non-Pt catalyst for the oxygen reduction reaction

DOE PAGES

Zhu, Huiyuan; Jiang, Guangming; Zhang, Xu; ...

2015-10-04

We report the synthesis of core/shell face-centered tetragonal (fct)-FePd/Pd nanoparticles (NPs) via reductive annealing of core/shell Pd/Fe 3O 4 NPs followed by temperature-controlled Fe etching in acetic acid. Among three different kinds of core/shell FePd/Pd NPs studied (FePd core at similar to 8 nm and Pd shell at 0.27, 0.65, or 0.81 nm), the fct-FePd/Pd-0.65 NPs are the most efficient catalyst for the oxygen reduction reaction (ORR) in 0.1 M HClO 4 with Pt-like activity and durability. This enhanced ORR catalysis arises from the desired Pd lattice compression in the 0.65 nm Pd shell induced by the fct-FePd core. Lastly,more » our study offers a general approach to enhance Pd catalysis in acid for ORB.« less

Translational PK/PD of Anti-Infective Therapeutics

PubMed Central

Rathi, Chetan; Lee, Richard E.; Meibohm, Bernd

2016-01-01

Translational PK/PD modeling has emerged as a critical technique for quantitative analysis of the relationship between dose, exposure and response of antibiotics. By combining model components for pharmacokinetics, bacterial growth kinetics and concentration-dependent drug effects, these models are able to quantitatively capture and simulate the complex interplay between antibiotic, bacterium and host organism. Fine-tuning of these basic model structures allows to further account for complicating factors such as resistance development, combination therapy, or host responses. With this tool set at hand, mechanism-based PK/PD modeling and simulation allows to develop optimal dosing regimens for novel and established antibiotics for maximum efficacy and minimal resistance development. PMID:27978987

Controlling the growth of palladium aerogels with high-performance toward bioelectrocatalytic oxidation of glucose.

PubMed

Wen, Dan; Herrmann, Anne-Kristin; Borchardt, Lars; Simon, Frank; Liu, Wei; Kaskel, Stefan; Eychmüller, Alexander

2014-02-19

We report the controllable synthesis of Pd aerogels with high surface area and porosity by destabilizing colloidal solutions of Pd nanoparticles with variable concentrations of calcium ions. Enzyme electrodes based on Pd aerogels co-immobilized with glucose oxidase show high activity toward glucose oxidation and are promising materials for applications in bioelectronics.

HLA-DRB1 Alleles Are Associated with the Susceptibility to Sporadic Parkinson’s Disease in Chinese Han Population

PubMed Central

Sun, Congcong; Wei, Lei; Luo, Feifei; Li, Yi; Li, Jiaobiao; Zhu, Feiqi; Kang, Ping; Xu, Rensi; Xiao, LuLu; Liu, Zhuolin; Xu, Pingyi

2012-01-01

Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The χ2 test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate. PMID:23139797

Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients

PubMed Central

Buhmann, Carsten; Forkmann, Katarina; Diedrich, Sabrina; Wesemann, Katharina; Bingel, Ulrike

2015-01-01

Background Pain is highly prevalent in patients with Parkinson’s disease (PD), but little is known about the underlying pathophysiological mechanisms. The susceptibility to pain is known to depend on ascending and descending pathways. Because parts of the descending pain inhibitory system involve dopaminergic pathways, dysregulations in dopaminergic transmission might contribute to altered pain processing in PD. Deficits in endogenous pain inhibition can be assessed using conditioned pain modulation (CPM) paradigms. Methods Applying such a paradigm, we investigated i) whether CPM responses differ between PD patients and healthy controls, ii) whether they are influenced by dopaminergic medication and iii) whether there are effects of disease-specific factors. 25 patients with idiopathic PD and 30 healthy age- and gender-matched controls underwent an established CPM paradigm combining heat pain test stimuli at the forearm and the cold pressor task on the contralateral foot as the conditioning stimulus. PD patients were tested under dopaminergic medication and after at least 12 hours of medication withdrawal. Results No significant differences between CPM responses of PD patients and healthy controls or between PD patients “on” and “off” medication were found. These findings suggest (i) that CPM is insensitive to dopaminergic modulations and (ii) that PD is not related to general deficits in descending pain inhibition beyond the known age-related decline. However, at a trend level, we found differences between PD subtypes (akinetic-rigid, tremor-dominant, mixed) with the strongest impairment of pain inhibition in the akinetic-rigid subtype. Conclusions There were no significant differences between CPM responses of patients compared to healthy controls or between patients “on” and “off” medication. Differences between PD subtypes at a trend level point towards different pathophysiological mechanisms underlying the three PD subtypes which warrant further investigation and potentially differential therapeutic strategies in the future. PMID:26270817

Development of an Agrobacterium-mediated transformation system for the cold-adapted fungi Pseudogymnoascus destructans and P. pannorum.

PubMed

Zhang, Tao; Ren, Ping; Chaturvedi, Vishnu; Chaturvedi, Sudha

2015-08-01

The mechanisms of cold adaptation by fungi remain unknown. This topic is of high interest due to the emergence of white-nose syndrome (WNS), a skin infection of hibernating bats caused by Pseudogymnoascus destructans (Pd). Recent studies indicated that apart from Pd, there is an abundance of other Pseudogymnoascus species in the hibernacula soil. We developed an Agrobacterium tumefaciens-mediated transformation (ATMT) system for Pd and a related fungus Pseudogymnoascus pannorum (Pp) to advance experimental studies. URE1 gene encoding the enzyme urease was used as an easy to screen marker to facilitate molecular genetic analyses. A Uracil-Specific Excision Reagent (USER) Friendly pRF-HU2 vector containing Pd or Pp ure1::hygromycin (HYG) disruption cassette was introduced into A. tumefaciens AGL-1 cells by electroporation and the resulting strains were co-cultivated with conidia of Pd or Pp for various durations and temperatures to optimize the ATMT system. Overall, 680 Pd (0.006%) and 1800 Pp (0.018%) transformants were obtained from plating of 10(7) conidia; their recoveries were strongly correlated with the length of the incubation period (96h for Pd; 72h for Pp) and with temperature (15-18°C for Pd; 25°C for Pp). The homologous recombination in transformants was 3.1% for Pd and 16.7% for Pp. The availability of a standardized ATMT system would allow future molecular genetic analyses of Pd and related cold-adapted fungi. Copyright © 2015. Published by Elsevier Inc.

Associations between serotonin-related gene polymorphisms and panic disorder.

PubMed

Maron, Eduard; Lang, Aavo; Tasa, Gunnar; Liivlaid, Liivi; Tõru, Innar; Must, Anne; Vasar, Veiko; Shlik, Jakov

2005-06-01

Studies suggest that vulnerability to panic attacks and panic disorder (PD) may be related to a deficient serotonin (5-HT) neurotransmission. In the present case-control study we investigated possible associations between PD phenotype and five candidate polymorphisms including 5-HT transporter (5-HTTLPR and VNTR), monoamine oxidase A (MAOA promoter region), tryptophan hydroxylase 1 (TPH1 218A/C) and 5-HT1B receptor (5-HT1BR 861G/C) genes. The study sample consisted of 158 patients with PD and 215 healthy control subjects. The analysis showed higher frequencies of LL genotype (p = 0.016) and L allele variant (p = 0.007) of 5-HTTLPR in the patients. No significant associations were observed between PD and other candidate gene polymorphisms. However, a higher frequency of longer allele genotypes of the MAOA promoter region was observed in female PD patients with agoraphobia than in female controls (p = 0.016). These findings indicate that genetic variants conceivably related to lower 5-HT neurotransmission may be involved in the development of PD.

Non-invasive 13C-glucose breath test using residual gas analyzer-mass spectrometry: a novel tool for screening individuals with pre-diabetes and type 2 diabetes.

PubMed

Ghosh, Chiranjit; Maity, Abhijit; Banik, Gourab D; Som, Suman; Chakraborty, Arpita; Selvan, Chitra; Ghosh, Shibendu; Ghosh, Barnali; Chowdhury, Subhankar; Pradhan, Manik

2014-09-01

We report, for the first time, the clinical feasibility of a novel residual gas analyzer mass spectrometry (RGA-MS) method for accurate evaluation of the (13)C-glucose breath test ((13)C-GBT) in the diagnosis of pre-diabetes (PD) and type 2 diabetes mellitus (T2D). In T2D or PD, glucose uptake is impaired and results in blunted isotope enriched (13)CO2 production in exhaled breath samples. Using the Receiver operating characteristics (ROC) curve analysis, an optimal diagnostic cut-off point of the (13)CO2/(12)CO2 isotope ratios expressed as the delta-over-baseline (DOB) value, was determined to be δDOB(13)C‰ = 28.81‰ for screening individuals with non-diabetes controls (NDC) and pre-diabetes (PD), corresponding to a sensitivity of 100% and specificity of 94.4%. We also determined another optimal diagnostic cut-off point of δDOB(13)C‰ = 19.88‰ between individuals with PD and T2D, which exhibited 100% sensitivity and 95.5% specificity. Our RGA-MS methodology for the (13)C-GBT also manifested a typical diagnostic positive and negative predictive value of 96% and 100%, respectively. The diagnostic accuracy, precision and validity of the results were also confirmed by high-resolution optical cavity enhanced integrated cavity output spectroscopy (ICOS) measurements. The δDOB(13)C‰ values measured with RGA-MS method, correlated favourably (R(2) = 0.979) with those determined by the laser based ICOS method. Moreover, we observed that the effects of endogenous CO2 production related to basal metabolic rates in individuals were statistically insignificant (p = 0.37 and 0.73) on the diagnostic accuracy. Our findings suggest that the RGA-MS is a valid and sufficiently robust method for the (13)C-GBT which may serve as an alternative non-invasive point-of-care diagnostic tool for routine clinical practices as well as for large-scale diabetes screening purposes in real-time.

An exploratory investigation of purging disorder.

PubMed

Smith, Kathryn E; Crowther, Janis H

2013-01-01

Purging Disorder (PD) is an understudied pattern of behaviors within the Eating Disorder Not Otherwise Specified (EDNOS) category. Such categorization may suggest that PD is not clinically significant as other eating disorders. However, evidence has suggested that PD is associated with significant impairments in psychosocial functioning and well-being. Despite the apparent clinical significance of PD, it remains to be determined if PD is distinct from other clinically significant eating disorders. The present study sought to assess the phenomenology, clinical significance, and distinctiveness of PD. Group scores on measures of eating pathology, body image disturbance, and psychological correlates were compared using MANOVA among a female undergraduate sample (N=94) meeting diagnostic criteria for PD (n=20), Bulimia Nervosa (BN; n=35), restrained eating (n=18), and healthy controls (n=21). Overall, results indicated the PD group reported less severe symptoms than BN but more severe symptoms than controls. The PD and restraint groups were similar on most variables (including subjective binge behavior), with the exception of perfectionism and hunger. Findings support the conceptualization of PD as existing along a spectrum of bulimic spectrum disorders rather than as a distinct diagnostic category. Copyright © 2012 Elsevier Ltd. All rights reserved.

Decreased NURR1 gene expression in patients with Parkinson’s disease

PubMed Central

Le, Weidong; Pan, Tianhong; Huang, Maosheng; Xu, Pingyi; Xie, Wenjie; Zhu, Wen; Zhang, Xiong; Deng, Hao; Jankovic, Joseph

2008-01-01

NURR1 is a transcription factor essential for the development, survival, and functional maintenance of midbrain dopaminergic (DAergic) neurons and NURR1 is a potential susceptibility gene for Parkinson’s disease (PD). To determine whether NURR1 gene expression is altered in patients with PD we measured its expression in human peripheral blood lymphocytes (PBL) in 278 patients with PD, 166 healthy controls (HC), and 256 neurological disease controls (NDC) by quantitative real-time PCR. NURR1 gene expression was significantly decreased in patients with PD (particularly those with family history of PD) as compared with HC (p < 0.01) and also as compared with NDC (p < 0.05). There was no significant difference in NURR1 gene expression among PD patients with or without anti-PD medications. When adjusted for gender, age, and ethnicity, lower levels of NURR1 gene expression were associated with significantly increased risk for PD in women, in patients 60 years old or older, and in patients of Caucasian origin. The observed reduction in PBL NURR1 gene expression indicates possible systemic involvement in PD, and the finding may help identify individuals with PD and other disorders associated with impaired central DAergic system. PMID:18684475

Developmental Risk Factors in Generalized Anxiety Disorder and Panic Disorder

PubMed Central

Newman, Michelle G.; Shin, Ki Eun; Zuellig, Andrea R.

2016-01-01

Background There is a lack of clarity regarding specific risk factors discriminating generalized anxiety disorder (GAD) from panic disorder (PD). Goal This study investigated whether GAD and PD could be discriminated through differences in developmental etiological factors including childhood parental loss/separation, psychological disorders, and maternal and paternal attachment. Method Twenty people with adult generalized anxiety disorder (GAD), 20 with adult panic disorder (PD), 11 with adult comorbid GAD and PD, and 21 adult non-anxious controls completed diagnostic interviews to assess symptoms of mental disorders in adulthood and childhood. Participants also reported on parental attachment, loss, and separation. Results Childhood diagnoses of GAD and PD differentiated clinical groups from controls as well as from each other, suggesting greater likelihood for homotypic over heterotypic continuity. Compared to controls, specific phobia was associated with all three clinical groups, and childhood depression, social phobia, and PTSD were uniquely associated with adult GAD. Both maternal and paternal attachment also differentiated clinical groups from controls. However, higher levels of subscales reflecting maternal insecure avoidant attachment (e.g., no memory of early childhood experiences and balancing/forgiving current state of mind) emerged as more predictive of GAD relative to PD. There were no group differences in parental loss or separation. Conclusions These results support differentiation of GAD and PD based on developmental risk factors. Recommendations for future research and implications of the findings for understanding the etiology and symptomatology of GAD and PD are discussed. PMID:27466747

α-Synuclein inclusions in the skin of Parkinson's disease and parkinsonism.

PubMed

Rodríguez-Leyva, Ildefonso; Calderón-Garcidueñas, Ana Laura; Jiménez-Capdeville, María E; Rentería-Palomo, Ana Arely; Hernandez-Rodriguez, Héctor Gerardo; Valdés-Rodríguez, Rodrigo; Fuentes-Ahumada, Cornelia; Torres-Álvarez, Bertha; Sepúlveda-Saavedra, Julio; Soto-Domínguez, Adolfo; Santoyo, Martha E; Rodriguez-Moreno, José Ildefonso; Castanedo-Cázares, Juan Pablo

2014-07-01

The presence in the brain of α-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of α-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of α-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP). Skin biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for α-synuclein, whereupon its presence was quantified as the percentage of positive cells. Patients were divided into those with PD and those with AP. AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP. Sixty-seven patients (34 with PD) and 20 controls were recruited. In the PD group, α-synuclein was detected in 58% of the cells in the spinous cell layer (SCL), 62% in the pilosebaceous unit (PSU), and 58% in the eccrine glands (EG). The AP-proteinopathies group showed 7%, 7%, and 0% expression of α-synuclein, respectively. No expression was found in the skin of the control group. The expression of α-synuclein in the skin was relatively high in the PD group, scarce in AP, and null for the individuals in the control group. While these findings require further confirmation, this minimally invasive technique may aid in the improvement of the accuracy of PD diagnoses.

Developmental risk factors in generalized anxiety disorder and panic disorder.

PubMed

Newman, Michelle G; Shin, Ki Eun; Zuellig, Andrea R

2016-12-01

There is a lack of clarity regarding specific risk factors discriminating generalized anxiety disorder (GAD) from panic disorder (PD). This study investigated whether GAD and PD could be discriminated through differences in developmental etiological factors including childhood parental loss/separation, psychological disorders, and maternal and paternal attachment. Twenty people with adult generalized anxiety disorder (GAD), 20 with adult panic disorder (PD), 11 with adult comorbid GAD and PD, and 21 adult non-anxious controls completed diagnostic interviews to assess symptoms of mental disorders in adulthood and childhood. Participants also reported on parental attachment, loss and separation. Childhood diagnoses of GAD and PD differentiated clinical groups from controls as well as from each other, suggesting greater likelihood for homotypic over heterotypic continuity. Compared to controls, specific phobia was associated with all three clinical groups, and childhood depression, social phobia, and PTSD were uniquely associated with adult GAD. Both maternal and paternal attachment also differentiated clinical groups from controls. However, higher levels of subscales reflecting maternal insecure avoidant attachment (e.g., no memory of early childhood experiences and balancing/forgiving current state of mind) emerged as more predictive of GAD relative to PD. There were no group differences in parental loss or separation. These results support differentiation of GAD and PD based on developmental risk factors. Recommendations for future research and implications of the findings for understanding the etiology and symptomatology of GAD and PD are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Mental object rotation in Parkinson's disease.

PubMed

Crucian, Gregory P; Barrett, Anna M; Burks, David W; Riestra, Alonso R; Roth, Heidi L; Schwartz, Ronald L; Triggs, William J; Bowers, Dawn; Friedman, William; Greer, Melvin; Heilman, Kenneth M

2003-11-01

Deficits in visual-spatial ability can be associated with Parkinson's disease (PD), and there are several possible reasons for these deficits. Dysfunction in frontal-striatal and/or frontal-parietal systems, associated with dopamine deficiency, might disrupt cognitive processes either supporting (e.g., working memory) or subserving visual-spatial computations. The goal of this study was to assess visual-spatial orientation ability in individuals with PD using the Mental Rotations Test (MRT), along with other measures of cognitive function. Non-demented men with PD were significantly less accurate on this test than matched control men. In contrast, women with PD performed similarly to matched control women, but both groups of women did not perform much better than chance. Further, mental rotation accuracy in men correlated with their executive skills involving mental processing and psychomotor speed. In women with PD, however, mental rotation accuracy correlated negatively with verbal memory, indicating that higher mental rotation performance was associated with lower ability in verbal memory. These results indicate that PD is associated with visual-spatial orientation deficits in men. Women with PD and control women both performed poorly on the MRT, possibly reflecting a floor effect. Although men and women with PD appear to engage different cognitive processes in this task, the reason for the sex difference remains to be elucidated.

Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1).

PubMed

Fuller, Michael J; Callendret, Benoit; Zhu, Baogong; Freeman, Gordon J; Hasselschwert, Dana L; Satterfield, William; Sharpe, Arlene H; Dustin, Lynn B; Rice, Charles M; Grakoui, Arash; Ahmed, Rafi; Walker, Christopher M

2013-09-10

Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but whether antiviral function can be restored in infected individuals is unknown. To address this question, chimpanzees with persistent HCV infection were treated with anti-PD-1 antibodies. A significant reduction in HCV viremia was observed in one of three treated animals without apparent hepatocellular injury. Viremia rebounded in the responder animal when antibody treatment was discontinued. Control of HCV replication was associated with restoration of intrahepatic CD4+ and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had a history of broader T-cell immunity to multiple HCV proteins than the two chimpanzees that did not respond to PD-1 therapy. The results suggest that successful PD-1 blockade likely requires a critical threshold of preexisting virus-specific T cells in liver and warrants consideration of therapeutic vaccination strategies in combination with PD-1 blockade to broaden narrow responses. Anti-PD-1 immunotherapy may also facilitate control of other persistent viruses, notably the hepatitis B virus where options for long-term control of virus replication are limited.

Walking economy during cued versus non-cued treadmill walking in persons with Parkinson's disease.

PubMed

Gallo, Paul M; McIsaac, Tara L; Garber, Carol Ewing

2013-01-01

Gait impairment is common in Parkinson's disease (PD) and may result in greater energy expenditure, poorer walking economy, and fatigue during activities of daily living. Auditory cueing is an effective technique to improve gait; but the effects on energy expenditure are unknown. To determine whether energy expenditure differs in individuals with PD compared with healthy controls and if auditory cueing improves walking economy in PD. Twenty participants (10 PD and 10 controls) came to the laboratory for three sessions. Participants performed two, 6-minute bouts of treadmill walking at two speeds (1.12 m·sec-1 and 0.67 m·sec-1). One session used cueing and the other without cueing. A metabolic cart measured energy expenditure and walking economy was calculated (energy expenditure/power). PD had worse walking economy and higher energy expenditure than control participants during cued and non-cued walking at the 0.67 m·sec-1 speed and during non-cued walking at the 1.12 m·sec-1. With auditory cueing, energy expenditure and walking economy worsened in both participant groups. People with PD use more energy and have worse walking economy than adults without PD. Walking economy declines further with auditory cuing in persons with PD.

Highly efficient photocatalytic degradation of methylene blue by PoPD/TiO2 nanocomposite

PubMed Central

Dong, Wenping; Cui, Guanwei; Ren, Zongming

2017-01-01

The poly-o-phenylenediamine (PoPD)/TiO2 nanocomposite was successfully synthesized via ‘in situ’ oxidative polymerization method. The modified photocatalysts were characterized by BET, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrarad spectra (FT-IR), thermogravimrtic analysis (TGA), X-ray photoelectron spectroscopy (XPS), Ultraviolet-visible diffuse reflectance spectrum (UV-Vis DRS) and Photocurrent Test. The results showed that the PoPD exists on the surface of TiO2, the presence of PoPD does not impact on the lattice structure and grain size of TiO2, and the presence of PoPD enhances the visible response and photoelectric property. The photocatalytic degradation of methylene blue (MB) was chosen as a model reaction to evaluate the photocatalytic activities of TiO2 and PoPD/TiO2. The optimal preparation condition was the molar ratio of oPD to TiO2 = 3:1, HCl concentration = 1.2 mol/L, the molar ratio of APS to oPD = 1:1. The apparent first-order rate constant kapp of PoPD/TiO2 nanocomposite was 0.0098 min-1, which is 6 times higher than TiO2 (0.0016 min-1). Meanwhile, the PoPD/TiO2 nanocomposites showed excellent photocatalytic stability, and the photocatalytic stability was depended on the stability of structure. At last, the photocatalytic mechanism of POPD/TiO2 nanocomposites was also proposed based on the synergetic effect between TiO2 and PoPD. PMID:28329007

An intelligent active force control algorithm to control an upper extremity exoskeleton for motor recovery

NASA Astrophysics Data System (ADS)

Hasbullah Mohd Isa, Wan; Taha, Zahari; Mohd Khairuddin, Ismail; Majeed, Anwar P. P. Abdul; Fikri Muhammad, Khairul; Abdo Hashem, Mohammed; Mahmud, Jamaluddin; Mohamed, Zulkifli

2016-02-01

This paper presents the modelling and control of a two degree of freedom upper extremity exoskeleton by means of an intelligent active force control (AFC) mechanism. The Newton-Euler formulation was used in deriving the dynamic modelling of both the anthropometry based human upper extremity as well as the exoskeleton that consists of the upper arm and the forearm. A proportional-derivative (PD) architecture is employed in this study to investigate its efficacy performing joint-space control objectives. An intelligent AFC algorithm is also incorporated into the PD to investigate the effectiveness of this hybrid system in compensating disturbances. The Mamdani Fuzzy based rule is employed to approximate the estimated inertial properties of the system to ensure the AFC loop responds efficiently. It is found that the IAFC-PD performed well against the disturbances introduced into the system as compared to the conventional PD control architecture in performing the desired trajectory tracking.

A hybrid joint based controller for an upper extremity exoskeleton

NASA Astrophysics Data System (ADS)

Mohd Khairuddin, Ismail; Taha, Zahari; Majeed, Anwar P. P. Abdul; Hakeem Deboucha, Abdel; Azraai Mohd Razman, Mohd; Aziz Jaafar, Abdul; Mohamed, Zulkifli

2016-02-01

This paper presents the modelling and control of a two degree of freedom upper extremity exoskeleton. The Euler-Lagrange formulation was used in deriving the dynamic modelling of both the human upper limb as well as the exoskeleton that consists of the upper arm and the forearm. The human model is based on anthropometrical measurements of the upper limb. The proportional-derivative (PD) computed torque control (CTC) architecture is employed in this study to investigate its efficacy performing joint-space control objectives specifically in rehabilitating the elbow and shoulder joints along the sagittal plane. An active force control (AFC) algorithm is also incorporated into the PD-CTC to investigate the effectiveness of this hybrid system in compensating disturbances. It was found that the AFC- PD-CTC performs well against the disturbances introduced into the system whilst achieving acceptable trajectory tracking as compared to the conventional PD-CTC control architecture.

Spatial emotional akinesia in Parkinson disease.

PubMed

Drago, Valeria; Foster, Paul S; Skidmore, Frank; Trifiletti, Daniel; Heilman, Kenneth M

2008-06-01

Patients with Parkinson disease (PD) exhibit motor and frontal-executive dysfunction and often seem to be emotionally apathetic. We investigated whether PD patients have alterations in their emotional reactivity and how this might impact their proximal (avoidance) versus distal (approach) allocation of attention-intention. Nine participants with PD and 9 normal controls were asked to judge the valence (pleasant-positive vs. unpleasant-negative) and arousal of 30 pictures from the International Affective Picture System. Participants were instructed to rate the pictures by marking 14-cm radial lines placed in front of them. On those lines where the subjects were going to rate emotional valence, the lines had a happy face at 1 end and a sad face at the other and when rating the arousal, they were presented with lines that had an "excited" and a "calm" face at opposite ends. For the emotional ratings, the dependent measures were the distances from the end of the line that had the "calm" or "sad" face to the participants' mark. For the approach-avoidance analysis, the dependent measure was the distance from the bottom of the line, regardless of the position of faces. The PD patients did not differ from controls when judging valence, but their judgments of arousal was lower than that of the controls. In addition, in contrast to the controls when judging neutral pictures and arousal, the PD patients, independent of the proximal or distal position of the sad/happy faces or excited/calm faces, demonstrated an overall proximal bias. When presented with emotional versus neutral stimuli, the control group reduced their extrapersonal spatial bias, whereas the subjects with PD did not change their spatial bias. The judgments of valence made by the subjects with PD were the same as that of the controls. These judgments might be based on cognitive decisions and as our PD subjects were not demented they could accurately determine valence. In contrast, judgments of arousal were reduced in the PD participants, and this result might reflect these patients impaired arousal-activation systems. Although emotional, versus neutral stimuli, induced a proximal deviation in the responses of the control subjects, the subjects with PD did not change their spatial bias. This Parkinsonian "emotional akinesia" might be related to either a reduced capacity to experience emotions or to an inability of emotional experiences to influence intentional and attentional systems.

Preterm delivery risk factors in singletons born after in vitro fertilization procedures.

PubMed

Ban Frangez, Helena; Korosec, Sara; Verdenik, Ivan; Kotar, Vanja; Kladnik, Urska; Vrtacnik Bokal, Eda

2014-05-01

Women delivering singletons after in vitro fertilization (IVF) procedures have a greater risk of preterm delivery (PD). The aim of our study was to analyze PD risk factors and to identify those that could possibly be prevented. In our matched controlled study we analyzed 1127 singleton deliveries after IVF and transfer of fresh embryos performed at the University Medical Center Ljubljana between 1 January 2002 and 31 December 2010. For every delivery included in the study group we chose three consecutive controls matched by maternal age, parity and maternity hospital. The main outcome measure was PD (<37 weeks). Investigated variables were: previous PD (PPD), conization, pregestational diabetes mellitus, uterine anomaly, operation on the uterus, chronic renal disease, maternal age and parity, and body mass index (BMI). Variables investigated within the IVF group were: stimulation protocol, laboratory procedure, number of retrieved oocytes and number and quality of transferred embryos. The PD rate after IVF was 1.5 times higher than after natural conception (11.5% in the IVF group and 7.7% in the control group, p<0.001). Conization and chronic renal disease were shown to be significant risk factors for PD in both the IVF group and the naturally conceiving controls. BMI>30 was an important risk factor only in the IVF group (OR 1.86 (1.06-3.27) vs. 1.10 (0.67-1.80)) and PPD only in the controls (OR 1.83 (0.78-4.28) vs. 3.22 (1.55-6.67)). Among the investigated PD risk factors, an IVF procedure was shown to be the fifth most important one. On analyzing parameters of the ovarian stimulation and IVF procedure, no PD risk factor was identified. IVF was shown to be a significant risk factor for PD. In the IVF population, BMI plays a far more important role in PD than in the fertile population. In our research PD reoccurrence in IVF group was less than expected, which could perhaps be explained by the surgical correction of gynecological pathology and, where necessary, its being combined with cerclage. The investigation of parameters related to the IVF procedure did not identify any risk factors for PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with gastric cancer.

PubMed

Savabkar, Sanaz; Azimzadeh, Pedram; Chaleshi, Vahid; Nazemalhosseini Mojarad, Ehsan; Aghdaei, Hamid Asadzadeh

2013-01-01

This study aimed to determine the association between PD-1.5C/T (rs2227981, +7785) and the risk of gastric cancer (GC) in an Iranian population. Gastric cancer is the fourth most common cancer in the world. The programmed death 1 (PD-1) is a member of the CD28 super family. PD-1 is a negative regulator of T-cell effector mechanisms which decrease immune responses against cancer. we conducted case- control study to investigate the association of PD-1.5 C/T polymorphism in 122 GC patients and 166 control individuals. DNA was extracted from blood specimens. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The frequency of CC, CT and TT genotypes was 53.6%, 42.2% and 4.2% in control group and 41%, 54.1% and 4.9% in gastric cancer patients respectively. CC genotype was more frequent in control individuals than in patients but we found no statically significant association. The frequencies of PD-1.5CT genotypes were significantly higher in GC patient compared with control individuals (OR= 1.77, 95% CI= 1.077-2.931; P=0.026). Allele distribution was similar in patients and healthy individuals (p = 0.061).Frequency of C and T alleles was 74.7%, 25.3% in control individuals and 68.03% and 31.97% in gastric cancer patients respectively. These results suggest that PD-1.5 C/T polymorphism may affect the GC risk and prognosis in an Iranian population.

Quantitative assessment of driving performance in Parkinson's disease

PubMed Central

Wood, J; Worringham, C; Kerr, G; Mallon, K; Silburn, P

2005-01-01

Objectives: The primary aim of this study was to determine how Parkinson's disease (PD) affects driving performance. It also examined whether changes in driver safety were related to specific clinical disease markers or an individual's self rating of driving ability. Methods: The driving performance of 25 patients with idiopathic PD and 21 age matched controls was assessed on a standardised open road route by an occupational therapist and driving instructor, to provide overall safety ratings and specific driving error scores. Results: The drivers with PD were rated as significantly less safe (p<0.05) than controls, and more than half of the drivers with PD would not have passed a state based driving test. The driver safety ratings were more strongly related to disease duration (r = –0.60) than to their on time Unified Parkinson's Disease Rating Scale (r = –0.24). Drivers with PD made significantly more errors than the control group during manoeuvres that involved changing lanes and lane keeping, monitoring their blind spot, reversing, car parking, and traffic light controlled intersections. The driving instructor also had to intervene to avoid an incident significantly more often for drivers with PD than for controls. Interestingly, driver safety ratings were unrelated to an individual's rating of their own driving performance, and this was the case for all participants. Conclusions: As a group, drivers with PD are less safe to drive than age matched controls. Standard clinical markers cannot reliably predict driver safety. Further studies are required to ascertain whether the identified driving difficulties can be ameliorated. PMID:15654027

A novel applicator design for intracavitary brachytherapy of the nasopharynx: Simulated reconstruction, image-guided adaptive brachytherapy planning, and dosimetry.

PubMed

Bacorro, Warren R; Agas, Ryan Anthony F; Cabrera, Stellar Marie R; Bojador, Maureen R; Sogono, Paolo G; Mejia, Michael Benedict A; Sy Ortin, Teresa T

2018-05-11

In nasopharyngeal cancer, brachytherapy is given as boost in primary treatment or as salvage for recurrent or persistent disease. The Rotterdam nasopharyngeal applicator (RNA) allows for suboptimal reduction of soft palate radiation dose, based on image-guided brachytherapy plans. Building on the RNA, we propose a novel design, the Benavides nasopharyngeal applicator (BNA). The virtual BNA was reconstructed on two cases (one T1, one T2) previously treated with intracavitary brachytherapy using the RNA. Dose was prescribed to the high-risk clinical target volumes (CTVs) and optimization was such that high-risk CTV D90 ≥ 100% of prescribed dose (PD), intermediate-risk-CTV D90 ≥ 75% PD, and soft palate D2cc ≤ 120% PD. The optimized RNA and BNA image-guided brachytherapy plans were compared in terms of CTV coverage and organs-at-risk sparing. Optimization objectives were more easily met with the BNA. For the T1 case, all three planning objectives were easily achieved in both the RNA and BNA, but with 18-19% lower soft palate doses with the BNA. For the T2 case, the CTV planning objectives were achieved in both the RNA and BNA, but the soft palate constraint was only achieved with the BNA, with 38-41% lower soft palate doses. Compared to the RNA, the BNA permits easier optimization and improves therapeutic ratio by a significant reduction of soft palate doses, based on simulation using a proposed system for CTV/organs-at-risk delineation, prescription, and optimization for image-guided adaptive brachytherapy. Clinical piloting using a prototype is necessary to evaluate its feasibility and utility. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.

PubMed

Goetz, Christopher G; Damier, Philippe; Hicking, Christine; Laska, Eugene; Müller, Thomas; Olanow, C Warren; Rascol, Olivier; Russ, Hermann

2007-01-15

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome. (c) 2006 Movement Disorder Society.

BEWARE: Body awareness training in the treatment of wearing-off related anxiety in patients with Parkinson's disease: study protocol for a randomized controlled trial.

PubMed

Ghielen, Ires; van den Heuvel, Odile A; de Goede, Cees J T; Houniet-de Gier, Marieke; Collette, Emma H; Burgers-Bots, Ingrid A L; Rutten, Sonja; Kwakkel, Gert; Vermunt, Kees; van Vliet, Bep; Berendse, Henk W; van Wegen, Erwin E H

2015-06-23

The wearing-off phenomenon in patients with Parkinson's disease (PD) is a complication of prolonged levodopa usage. During this phenomenon, motor symptoms such as rigidity and freezing re-emerge. This is often accompanied by non-motor symptoms, including anxiety, the so-called wearing-off related anxiety (WRA). Current treatment options are limited and typically focus on either the physical or mental aspects of wearing-off. An integrated approach seems warranted in order to optimally address the complex reciprocal interactions between these aspects. Also, because wearing-off is eventually inescapable, treatment needs to focus on coping, acceptance, and self-efficacy. We therefore developed an integrated body awareness intervention, combining principles from physical therapy with acceptance and commitment therapy to teach patients to deal with WRA. This study will investigate whether this new intervention, named BEWARE, is more effective than treatment as usual in increasing self-efficacy. This is a single-blinded randomized controlled trial in 36 PD patients who experience WRA. Subjects will be recruited from the outpatient clinic for movement disorders of the VU University Medical Center. After providing written informed consent, patients will be randomly assigned to an experimental (BEWARE) or treatment-as-usual (physical therapy) group. Clinical assessments will be performed prior to the intervention, directly after the 6-week intervention period, and at 3-month naturalistic follow-up by a blinded investigator not involved in the study. The primary outcome measure is self-efficacy, and secondary outcomes focus on mobility, daily functioning, anxiety, and quality of life. Because wearing-off is an inevitable consequence of levodopa therapy and current treatment options are insufficient, a multidisciplinary intervention that addresses both physical and mental aspects of wearing-off in PD may foster additional benefits for treating WRA in PD patients over mono-disciplinary care alone. ClinicalTrials.gov identifier: NCT02054845. Date of registration: 30 January 2014.

Quality of life related to swallowing in Parkinson's disease.

PubMed

Carneiro, Danielle; das Graças Wanderley de Sales Coriolano, Maria; Belo, Luciana Rodrigues; de Marcos Rabelo, Aneide Rocha; Asano, Amdore Guescel; Lins, Otávio Gomes

2014-10-01

Swallowing difficulties in Parkinson's disease can result in decreased quality of life. The swallowing quality of life questionnaire (SWAL-QOL) is an instrument for specifically assessing quality of life with respect to swallowing, which has been little explored in patients with Parkinson's disease (PD). The goal of this study was to evaluate the quality of life with respect to swallowing in persons with PD compared to controls and at several stages of the disease using the SWAL-QOL. The experimental group was composed of 62 persons with PD at stages 1-4. Forty-one age-matched healthy subjects constituted the control group. The SWAL-QOL scores were significantly lower for the patients with PD than for the controls in all SWAL-QOL domains. Eating duration had the largest difference in score between persons with PD and the controls and the lowest mean score, followed by communication, fatigue, fear, sleep, and food selection. The scores of most domains were lower at later stages of the disease. The scores for eating duration, symptom frequency, and sleep were significantly lower at stage 4 than stages 1 and 2. In conclusion, patients with PD have significantly lower scores in all domains of the SWAL-QOL than normal controls. This means swallowing difficulties occurring in patients with PD negatively affect their QOL. Progression of the disease worsens swallowing QOL, more specifically in the domains of eating duration, symptom frequency, and sleep. This occurs mostly at later stages of the disease.

Body mass index in Parkinson's disease: a meta-analysis.

PubMed

van der Marck, Marjolein A; Dicke, Heleen C; Uc, Ergun Y; Kentin, Zippora H A; Borm, George F; Bloem, Bastiaan R; Overeem, Sebastiaan; Munneke, Marten

2012-03-01

Prior work suggested that patients with Parkinson's disease (PD) have a lower Body Mass Index (BMI) than controls, but evidence is inconclusive. We therefore conducted a meta-analysis on BMI in PD. We searched MEDLINE, EMBASE, Cinahl and Scopus to identify cohort studies on BMI in PD, published before February 2011. Studies that reported mean BMI for PD patients and healthy controls were eligible. Twelve studies were included, with a total of 871 patients and 736 controls (in three studies controls consisted of subjects from other published studies). Our primary aim was to assess differences in BMI between patients and controls; this was analyzed with random effects meta-analysis. Our secondary aim was to evaluate the relation with disease severity (Hoehn and Yahr stage) and disease duration, using random effects meta-regression. PD patients had a significantly lower BMI than controls (overall effect 1.73, 95% CI 1.11-2.35, P<0.001). Pooled data of seven studies showed that patients with Hoehn and Yahr stage 3 had a lower BMI than patients with stage 2 (3.9, 95% CI 0.1-7.7, P<0.05). Disease duration was not associated with BMI. Because a low body weight is associated with negative health effects and a poorer prognosis, monitoring weight and nutritional status should be part of PD management. Copyright © 2011. Published by Elsevier Ltd.

Colloidal lithography nanostructured Pd/PdO x core-shell sensor for ppb level H2S detection.

PubMed

Benedict, Samatha; Lumdee, Chatdanai; Dmitriev, Alexandre; Anand, Srinivasan; Bhat, Navakanta

2018-06-22

In this work we report on plasma oxidation of palladium (Pd) to form reliable palladium/palladium oxide (Pd/PdO x ) core-shell sensor for ppb level H 2 S detection and its performance improvement through nanostructuring using hole-mask colloidal lithography (HCL). The plasma oxidation parameters and the sensor operating conditions are optimized to arrive at a sensor device with high sensitivity and repeatable response for H 2 S. The plasma oxidized palladium/palladium oxide sensor shows a response of 43.1% at 3 ppm H 2 S at the optimum operating temperature of 200 °C with response and recovery times of 24 s and 155 s, respectively. The limit of detection (LoD) of the plasma oxidised beam is 10 ppb. We further integrate HCL, a bottom-up and cost-effective process, to create nanodiscs of fixed diameter of 100 nm and varying heights (10, 15 and 20 nm) on 10 nm thin Pd beam which is subsequently plasma oxidized to improve the H 2 S sensing characteristics. The nanostructured Pd/PdO x sensor with nanodiscs of 100 nm diameter and 10 nm height shows an enhancement in sensing performance by 11.8% at same operating temperature and gas concentration. This nanostructured sensor also shows faster response and recovery times (15 s and 100 s, respectively) compared to the unstructured Pd/PdO x counterpart together with an experimental LoD of 10 ppb and the estimated limit going all the way down to 2 ppb. Material characterization of the fabricated Pd/PdO x sensors is done using UV-vis spectroscopy and x-ray photoemission spectroscopy.

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors.

PubMed

Abdin, Shifaa M; Zaher, Dana M; Arafa, El-Shaimaa A; Omar, Hany A

2018-01-25

Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors

PubMed Central

Abdin, Shifaa M.

2018-01-01

Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications. PMID:29370105

Colloidal lithography nanostructured Pd/PdO x core–shell sensor for ppb level H2S detection

NASA Astrophysics Data System (ADS)

Benedict, Samatha; Lumdee, Chatdanai; Dmitriev, Alexandre; Anand, Srinivasan; Bhat, Navakanta

2018-06-01

In this work we report on plasma oxidation of palladium (Pd) to form reliable palladium/palladium oxide (Pd/PdO x ) core–shell sensor for ppb level H2S detection and its performance improvement through nanostructuring using hole-mask colloidal lithography (HCL). The plasma oxidation parameters and the sensor operating conditions are optimized to arrive at a sensor device with high sensitivity and repeatable response for H2S. The plasma oxidized palladium/palladium oxide sensor shows a response of 43.1% at 3 ppm H2S at the optimum operating temperature of 200 °C with response and recovery times of 24 s and 155 s, respectively. The limit of detection (LoD) of the plasma oxidised beam is 10 ppb. We further integrate HCL, a bottom-up and cost-effective process, to create nanodiscs of fixed diameter of 100 nm and varying heights (10, 15 and 20 nm) on 10 nm thin Pd beam which is subsequently plasma oxidized to improve the H2S sensing characteristics. The nanostructured Pd/PdO x sensor with nanodiscs of 100 nm diameter and 10 nm height shows an enhancement in sensing performance by 11.8% at same operating temperature and gas concentration. This nanostructured sensor also shows faster response and recovery times (15 s and 100 s, respectively) compared to the unstructured Pd/PdO x counterpart together with an experimental LoD of 10 ppb and the estimated limit going all the way down to 2 ppb. Material characterization of the fabricated Pd/PdO x sensors is done using UV–vis spectroscopy and x-ray photoemission spectroscopy.

Fabrication of graphene-fullerene hybrid by self-assembly and its application as support material for methanol electrocatalytic oxidation reaction

NASA Astrophysics Data System (ADS)

Zhang, Xuan; Zhang, Jia-Wei; Xiang, Ping-Hua; Qiao, Jinli

2018-05-01

Graphene-fullerene hybrids were facilely fabricated by self-assembly of graphene oxide (GO) and multi-substituted fulleropyrrolidines (PyrC60). The hybrids (GO-PyrC60) were applied as support materials to deposit Pd nanoparticle catalyst by a simple hydrothermal co-reduction approach. The as-prepared electrocatalysts (Pd/RGO-PyrC60) were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), respectively. The RGO-PyrC60 hybrid supported Pd catalyst with the optimal ratio of RGO to PyrC60, exhibited much enhanced electrocatalytic activity and stability toward methanol oxidation reaction (MOR) compared to the RGO alone supported Pd as well as commercial Pd/C. The introduction of fulleropyrrolidine as spacer between graphene layers could increase the electrocatalytic activity and improve the long-term stability. This strategy may contribute to developing graphene-fullerene hydrids as effective support materials for advanced electrocatalysts.

In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB

PubMed Central

Vaddady, Pavan K; Lee, Richard E; Meibohm, Bernd

2011-01-01

For rapid anti-tuberculosis (TB) drug development in vitro pharmacokinetic/pharmacodynamic (PK/PD) models are useful in evaluating the direct interaction between the drug and the bacteria, thereby guiding the selection of candidate compounds and the optimization of their dosing regimens. Utilizing in vivo drug-clearance profiles from animal and/or human studies and simulating them in an in vitro PK/PD model allows the in-depth characterization of antibiotic activity of new and existing antibacterials by generating time–kill data. These data capture the dynamic interplay between mycobacterial growth and changing drug concentration as encountered during prolonged drug therapy. This review focuses on important PK/PD parameters relevant to anti-TB drug development, provides an overview of in vitro PK/PD models used to evaluate the efficacy of agents against mycobacteria and discusses the related mathematical modeling approaches of time–kill data. Overall, it provides an introduction to in vitro PK/PD models and their application as critical tools in evaluating anti-TB drugs. PMID:21359155

Highly Active and Selective Hydrogenation of CO2 to Ethanol by Ordered Pd-Cu Nanoparticles.

PubMed

Bai, Shuxing; Shao, Qi; Wang, Pengtang; Dai, Qiguang; Wang, Xingyi; Huang, Xiaoqing

2017-05-24

Carbon dioxide (CO 2 ) hydrogenation to ethanol (C 2 H 5 OH) is considered a promising way for CO 2 conversion and utilization, whereas desirable conversion efficiency remains a challenge. Herein, highly active, selective and stable CO 2 hydrogenation to C 2 H 5 OH was enabled by highly ordered Pd-Cu nanoparticles (NPs). By tuning the composition of the Pd-Cu NPs and catalyst supports, the efficiency of CO 2 hydrogenation to C 2 H 5 OH was well optimized with Pd 2 Cu NPs/P25 exhibiting high selectivity to C 2 H 5 OH of up to 92.0% and the highest turnover frequency of 359.0 h -1 . Diffuse reflectance infrared Fourier transform spectroscopy results revealed the high C 2 H 5 OH production and selectivity of Pd 2 Cu NPs/P25 can be ascribed to boosting *CO (adsorption CO) hydrogenation to *HCO, the rate-determining step for the CO 2 hydrogenation to C 2 H 5 OH.

Advances in the Treatment of Non-small Cell Lung Cancer: Focus on Nivolumab, Pembrolizumab, and Atezolizumab.

PubMed

Leventakos, Konstantinos; Mansfield, Aaron S

2016-10-01

Immunotherapy is revolutionizing the treatment of non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, including programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) monoclonal antibodies, are being introduced to routine clinical practice. This review summarizes clinical trials of nivolumab, pembrolizumab, and atezolizumab in patients with NSCLC. These agents have efficacy against NSCLC and a unique toxicity profile. The role of PD-L1 as a predictive biomarker is still unclear, partially because of the nuances of PD-L1 testing. These novel therapies also challenge our existing methodologies of radiologic assessment and efficacy analysis. This new era of immunotherapy has ushered in as much hope for patients as questions from physicians that need to be answered to clarify the optimal use of these agents.

Brazilian Samba Protocol for Individuals With Parkinson's Disease: A Clinical Non-Randomized Study.

PubMed

Tillmann, Ana Cristina; Andrade, Alexandro; Swarowsky, Alessandra; Guimarães, Adriana Coutinho De Azevedo

2017-07-04

In the 10 most populated countries in the world, Parkinson's disease (PD) affects more than 5 million individuals. Despite optimal treatment options already developed for the disease, concomitant involvement of other areas of health care plays an important role in complementing the treatment. From this perspective, dancing can be viewed as a non-drug alternative that can reduce falls by improving some motor skills, such as mobility, balance, gait, and posture, and can also improve the overall quality of life. Brazilian samba promotes improvement in motor and non-motor symptoms in individuals with PD, providing a new treatment option for this population. The main objective of this quasi-experimental study is to provide a 12-week samba protocol (2x/week) for individuals with PD and to compare its effects with the group without intervention. The hypothesis is that the Brazilian samba protocol will promote improvement in primary (motor) and secondary (non-motor) outcomes in individuals with PD. The sample will be selected at random from individuals diagnosed with PD in the city of Florianopolis (SC, Brazil). Sample size calculation was performed with the G*Power 3.1.9.2 software, with 0.447 effect size, at 5% significance level, power of 0.9, and test and sample loss of 20%. This yielded 60 individuals divided between the intervention and control groups. The questionnaires will be filled out before and after the dance intervention. The data collection for the control group will be held simultaneously to the intervention group. The classes will last for 1 hour, twice a week in the evening for 12 weeks, and all classes will be divided into warm-up, main part, and relaxation. Two-way analysis of variance with repeated measures and Sidak post-hoc comparison test will be used for a comparative analysis of the final results of the control group with the experimental group and of the within-group changes between pre- and postintervention period. We expect to complete follow-up in September 2017. The major inspiration for this study was to encourage the creation of new rehabilitation programs that do not emphasize doctor involvement. This is a unique protocol for PD and we believe it can be an important tool to alleviate the motor and non-motor symptoms of individuals with PD. Dance is a simple activity depending on little equipment and few financial resources, facilitating its implementation and improving the cost-benefit relationship. In addition, activities that have a cultural aspect for the population in question, and which are pleasant, enable the participants to commit long term. This can enhance patient's compliance with the therapy, which is often a problem for many rehabilitation programs. ©Ana Cristina Tillmann, Alexandro Andrade, Alessandra Swarowsky, Adriana Coutinho De Azevedo Guimarães. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 04.07.2017.

Moral decision-making and theory of mind in patients with idiopathic Parkinson's disease.

PubMed

Rosen, Jan B; Brand, Matthias; Polzer, Christin; Ebersbach, Georg; Kalbe, Elke

2013-09-01

Cognitive impairments in theory of mind (ToM), executive processing, and decision-making are frequent and highly relevant symptoms in patients with Parkinson's disease (PD). These functions have been related to moral decision-making. Their association to moral decision-making in PD, however, has not been studied yet. It was hypothesized that moral decisions in patients with PD differ from those in healthy control participants, and that more egoistic decisions are related to ToM as well as executive dysfunctions in patients with PD. Nineteen patients with PD and 20 healthy control participants were examined with an everyday moral decision-making task, comprised of 10 low and 10 high emotional forced-choice moral dilemma short stories with egoistic and altruistic options. All participants received an elaborate neuropsychological test battery. Electrodermal skin conductance responses were recorded to examine possible unconscious emotional reactions during moral decision-making. The groups performed comparably in total scores of moral decision-making. Although ToM did not differ between groups, it was inversely related to altruistic moral decisions in the healthy control group, but not in patients with PD. Executive functions were not related to moral decision-making. No differences were found for skin conductance responses, yet they differed from zero in both groups. Our findings indicate that moral decisions do not differ between patients with PD and healthy control participants. However, different underlying processes in both groups can be presumed. While healthy control participants seem to apply ToM to permit egoistic moral decisions in low emotional dilemmas, patients with PD seem to decide independently from ToM. These mechanisms as well as neuropsychological and neurophysiological correlates are discussed.

Prospective impact of panic disorder and panic-anxiety on asthma control, health service use, and quality of life in adult patients with asthma over a 4-year follow-up.

PubMed

Favreau, Helene; Bacon, Simon L; Labrecque, Manon; Lavoie, Kim L

2014-02-01

Background Panic disorder (PD) is a common anxiety disorder among asthmatic patients with overlapping symptoms (e.g., hyperventilation). However, the longitudinal impact of PD on asthma control remains poorly understood. This study assessed the impact of PD and panic-anxiety on asthma control over a 4.3-year follow-up in 643 adult asthmatic patients. Methods Consecutive patients presenting to a tertiary asthma clinic underwent a sociodemographic, medical history, and psychiatric (Primary Care Evaluation of Mental Disorders) interview and completed questionnaires including the Anxiety Sensitivity Index (ASI) to assess panic-anxiety. At follow-up, patients completed the Asthma Control (ACQ) and Asthma Quality of Life (AQLQ) questionnaires and reported emergency department visits and hospitalizations during the follow-up. Results Baseline frequency of PD was 10% (n = 65). In fully adjusted models, analyses revealed that PD and ASI scores predicted worse follow-up ACQ total scores (β = 0.292, p = .037; β = 0.012, p = .003) but not AQLQ total scores. ASI scores also predicted greater nocturnal and waking symptoms, activity limitations, and bronchodilator use on the ACQ (β = 0.012-0.018, p < .05) as well as lower symptom (β = -0.012, p = .006) and emotional distress (β = -0.014, p = .002) subscale scores on the AQLQ. Neither PD nor ASI scores were associated with hospitalizations, although ASI scores (but not PD) were associated with an increased risk of emergency department visits (relative risk = 1.023, 95% confidence interval = 1.001-1.044). Conclusions PD and anxiety sensitivity are prospectively associated with poorer asthma control and may be important targets for treatment.

Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancers

PubMed Central

Moore, Ellen C.; Cash, Harrison A.; Caruso, Andria M.; Uppaluri, Ravindra; Hodge, James W.; Van Waes, Carter; Allen, Clint T.

2016-01-01

Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. Syngeneic models of oral cancer were used to determine if blocking oncogenic signaling improved in vivo responses to PD-L1 monoclonal antibody (mAb). Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which was stable or increased by the addition of rapamycin, but suppressed when PD901 was added. Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. In vivo antibody depletion revealed a CD8 T cell, and not NK cell, -dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell–mediated antibody-dependent cellular cytotoxicity. Rapamycin also enhanced IFNγ or PD-L1 mAb treatment–associated induction of MHC class I expression on MOC1 tumor cells, an effect abrogated by depleting infiltrating CD8 T cells from the tumor microenvironment. This data conflicts with traditional views of rapamycin as a universal immunosuppressant, and when combined with evidence of enhanced antitumor activity with the combination of rapamycin and PD-L1 mAb, suggests that this treatment combination deserves careful evaluation in the clinical setting. PMID:27076449

Increased percentages of PD-1 on CD4+ T cells is associated with higher INF-γ production and altered IL-17 production in patients with systemic lupus erythematosus.

PubMed

Dolff, S; Quandt, D; Feldkamp, T; Jun, C; Mitchell, A; Hua, F; Specker, C; Kribben, A; Witzke, O; Wilde, B

2014-01-01

Programmed death (PD)-1 is a cell death receptor that, upon stimulation, leads to apoptosis. Previous studies have shown alteration of PD-1 expression on T cells and PD-1 genes in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the expression of this receptor on effector T cells in patients with SLE. In this study we enrolled 32 SLE patients and 31 healthy controls. T cells from peripheral blood were analysed by flow cytometry for the expression of PD-1. Interferon (IFN)-γ and interleukin (IL)-17-producing cells were investigated for the expression of this co-stimulatory marker. Percentages of CD4(+) T cells expressing PD-1 were significantly increased in patients with SLE compared to healthy controls. The percentage of PD-1 expression was correlated with the production of INF-γ (r = 0.83, p < 0.0001). We also investigated the production of IL-17 by PD-1(+) CD3(+) T cells. Inactive patients (3.2 ± 1.2% vs. 5.9 ± 3.5%, p = 0.002) and patients without lupus nephritis (LN) (3.2 ± 1.5% vs. 5.9 ± 3.5%, p = 0.005) showed lower levels of IL-17 compared to healthy controls. We have demonstrated increased expression of PD-1 on CD4(+) T cells in SLE patients and an association between PD-1 expression on CD4(+) T cells and IFN-γ expression on CD3(+) T cells. We have also shown that there is an altered subset of PD-1(+) T cells in inactive patients and patients without LN producing lower amounts of IL-17.

Association Between Helicobacter pylori Infection and Risk of Periodontal Diseases in Han Chinese: A Case-Control Study

PubMed Central

Yang, Jing; Zhang, Qiang; Chen, Ming; Wu, Wu-zhou; Wang, Rong; Liu, Chang-jun; Li, Bei; Shi, Xin-li; Du, Han-song; Tan, Hua-bing

2016-01-01

Background This study was performed to test the association between Helicobacter pylori (HP) and periodontal disease (PD). Material/Methods This was a case-control study in a comprehensive hospital, including all patients with newly diagnosed PD between 2012 and 2014 as cases and all patients without PD as controls, thorough periodontal examinations. Those who tested positive for HP were examined by means of polymerase chain reaction. Single and multivariate logistic regression was used to analyze the data using SPSS 19.0 software. Results This case-control study included 212 Han Chinese non-smoking adults. The results indicated that HP-positive status significantly increased the risk of PD (2.63 times higher (odds ratio [OR]=2.63; 95% confidence interval [CI]=1.48–4.67). After adjustment for age, sex, level of education, physical exercise, body mass index, and history of alcohol and diabetes mellitus, this association remained significantly (OR=2.82, 95% CI=1.55–5.13). Conclusions PD might be associated with HP infection in adults and HP infection may be a significant and independent risk factor for PD. PMID:26753766

Outlining a Population “at Risk” of Parkinson's Disease: Evidence from a Case-Control Study

PubMed Central

Schirinzi, Tommaso; Martella, Giuseppina; D'Elia, Alessio; Di Lazzaro, Giulia; Imbriani, Paola; Madeo, Graziella; Monaco, Leonardo; Maltese, Marta

2016-01-01

The multifactorial pathogenesis of Parkinson's Disease (PD) requires a careful identification of populations “at risk” of developing the disease. In this case-control study we analyzed a large Italian population, in an attempt to outline general criteria to define a population “at risk” of PD. We enrolled 300 PD patients and 300 controls, gender and age matched, from the same urban geographical area. All subjects were interviewed on demographics, family history of PD, occupational and environmental toxicants exposure, smoking status, and alcohol consumption. A sample of 65 patients and 65 controls also underwent serum dosing of iron, copper, mercury, and manganese by means of Inductively Coupled-Plasma-Mass-Spectrometry (ICP-MS). Positive family history, toxicants exposure, non-current-smoker, and alcohol nonconsumer status occurred as significant risk factors in our population. The number of concurring risk factors overlapping in the same subject impressively increased the overall risk. No significant differences were measured in the metal serum levels. Our findings indicate that combination of three to four concurrent PD-risk factors defines a condition “at risk” of PD. A simple stratification, based on these questionnaires, might be of help in identifying subjects suitable for neuroprotective strategies. PMID:27651975

Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

PubMed

Danti, S; Toschi, N; Diciotti, S; Tessa, C; Poletti, M; Del Dotto, P; Lucetti, C

2015-12-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. © 2015 EAN.

Altered moral decision-making in patients with idiopathic Parkinson's disease.

PubMed

Rosen, Jan B; Rott, Elisa; Ebersbach, Georg; Kalbe, Elke

2015-10-01

Moral decision-making essentially contributes to social conduct. Although patients with Parkinson's disease (PD) show deficits in (non-moral) decision making and related neuropsychological functions, i.e. executive functions, theory of mind (ToM), and empathy, moral decision-making has rarely been examined in PD patients. We examined possible alterations of moral decision-making and associated functions in PD. Twenty non-demented PD patients and 23 age- and education-matched healthy control participants were examined with tests that assess reasoning, executive functions (set-shifting and planning), ToM and empathy, decision-making under risk, and moral intuitions. Moral decision-making was assessed with a close-to-everyday moral dilemma paradigm that opposes socially oriented "altruistic" choices to self-beneficial "egoistic" choices in 20 moral dilemma short stories (10 high and 10 low emotional). Concurrently, electrodermal activity was recorded. PD patients made more egoistic moral decisions than healthy controls. Remarkably, while reasoning, planning and empathy correlated with moral decision-making in the control group, in the PD group neuropsychological functions and dopaminergic medication did not correlate with moral decisions. No evidence for reduced skin conductance responses in PD patients and no relationships between skin conductance responses and moral decisions were observed. This study provides evidence for moral decision-making dysfunctions in PD patients who made more egoistic moral decisions. As a possible underlying mechanism, reduced exercise of attentional control due to a dysfunctional interplay between the prefrontal cortex and the basal ganglia is discussed. Future research will have to determine the impact of PD patients' moral decision-making dysfunctions on everyday life and further determine correlates of the deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protein intake, nitrogen balance and nutritional status in patients with Parkinson's disease; time for a change?

PubMed

Zilli Canedo Silva, Maryanne; Carol Fritzen, Natali; de Oliveira, Marlon; Paes da Silva, Michel; Rasmussen Petterle, Ricardo; Teive, Hélio Afonso; de Mesquita Barros Almeida Leite, Christiane; Rabito, Estela Iraci; Madalozzo Schieferdecker, Maria Eliana; Carvalho, Mauricio

2015-06-01

To evaluate protein intake, nitrogen balance and nutritional status of clinically stable patients with Parkinson's disease (PD). A cross-sectional study of PD patients Hoehn-Yahr scale stage 1-3 and subjects with no neurologic disease (controls) matched for age and gender. All participants underwent a diet history interview, anthropometric measurements, bioelectrical impedance and food record over three non-consecutive days, including a weekend. A 24-hour urine collection and fasting venous blood sampling were collected from the participants for evaluation of creatinine clearance, creatinine height index and the nitrogen balance. The mean age of PD patients was 58.9 ± 12.8 year compared to 54.7 ± 12.6 year of the controls, P = 0.34. One third of PD group had symptoms of dysphagia and ingested less water and fibers when compared to controls. Calf circumference was small in PD group (35.5 ± 2.8 vs. 38.4 ± 3.5 cm, P = 0.012). Intake of nitrogen was significantly lower and nitrogen balance was negative in PD patients (-1.8 ± 3.9 vs. 1.1 ± 4.2 controls, P = 0.06). The antioxidants folate and vitamin E were consumed in small amounts in both groups, although significantly less in PD patients (P = 0.04 and 0.03, respectively). Daily intakes of protein of approximately 1.1 g/kg by clinically stable PD patients may not be enough to ensure a neutral calorie-nitrogen balance and muscle tissue conservation. Larger studies are necessary to provide a more comprehensive picture of PD patients' metabolic status. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Infections as a risk factor for Parkinson's disease: a case-control study.

PubMed

Vlajinac, Hristina; Dzoljic, Eleonora; Maksimovic, Jadranka; Marinkovic, Jelena; Sipetic, Sandra; Kostic, Vladimir

2013-05-01

The etiology of Parkinson's disease (PD) is unknown. The aim of the study was to test the hypothesis that some infectious diseases are related to the occurrence of PD. The case-control study, conducted in Belgrade during the period 2001-2005, comprised 110 subjects diagnosed for the first time as PD cases, and 220 controls chosen among patients with degenerative joint disease and some diseases of the digestive tract. According to logistic regression analysis, PD was significantly related to mumps [odds ratio adjusted on occupation and family history of PD (aOR) = 7.86, 95% confidence interval (CI) = 3.77-16.36], scarlet fever (aOR = 12.18, 95% CI = 1.97-75.19), influenza (aOR = 8.01, 95% CI = 4.61-13.92), whooping cough (aOR = 19.90, 95% CI = 2.07-190.66) and herpes simplex infections (aOR = 11.52, 95% CI = 2.25-58.89). Tuberculosis, measles and chicken pox were not associated with PD. Other infectious diseases we asked for were not reported (12 diseases), or were too rare (four diseases) to be analysed. The results obtained are in line with the suggestion that some infectious diseases may play a role in the development of PD.

Parkinson Patients' Initial Trust in Avatars: Theory and Evidence.

PubMed

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson's disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients' interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research.

The Role of Intrinsic Pathway in Apoptosis Activation and Progression in Peyronie's Disease

PubMed Central

Loreto, Carla; Caltabiano, Rosario; Vespasiani, Giuseppe; Castorina, Sergio; Ralph, David J.; Musumeci, Giuseppe; Djinovic, Rados; Sansalone, Salvatore

2014-01-01

Peyronie's disease (PD) is characterized with formation of fibrous plaques which result in penile deformity, pain, and erectile dysfunction. The aim of this study was to investigate the activation of the intrinsic apoptotic pathway in plaques from PD patients. Tunica albuginea from either PD or control patients was assessed for the expression of bax, bcl-2 and caspases 9 and 3 using immunohistochemistry and by measurement of apoptotic cells using TUNEL assay. Bax overexpression was observed in metaplastic bone tissue, in fibroblasts, and in myofibroblast of plaques from PD patients. Little or no bcl-2 immunostaining was detected in samples from either patients or controls. Caspase 3 immunostaining was very strong in fibrous tissue, in metaplasic bone osteocytes, and in primary ossification center osteoblasts. Moderate caspase 9 immunostaining was seen in fibrous cells plaques and in osteocytes and osteoblasts of primary ossification centers from PD patients. Control samples were negative for caspase 9 immunostaining. In PD patients the TUNEL immunoassay showed intense immunostaining of fibroblasts and myofibroblasts, the absence of apoptotic cells in metaplasic bone tissue and on the border between fibrous and metaplastic bone tissue. Apoptosis occurs in stabilized PD plaques and is partly induced by the intrinsic pathway. PMID:25197653

Parkinson Patients’ Initial Trust in Avatars: Theory and Evidence

PubMed Central

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson’s disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients’ interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research. PMID:27820864

Prevalence and treatment of depression in Parkinson's disease.

PubMed

Veazey, Connie; Aki, Sahinde Ozlem Erden; Cook, Karon F; Lai, Eugene C; Kunik, Mark E

2005-01-01

Parkinson's disease (PD) is a progressive neurological condition with debilitating symptoms, and depression is a common comorbid condition of this disease. The authors review existing literature on the prevalence and treatment of depression in PD. Prevalence estimates of depression vary widely, ranging from 7%-76%. This variation is due to inconsistent methodology. Treatment options for depression in PD include medication therapy, electroconvulsive therapy (ECT), and psychotherapy. There are few randomized controlled trials of these treatment options. The authors argue for more systematic and controlled research examining both the prevalence and treatment of depression in PD.

Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro

PubMed Central

2013-01-01

Programmed death-1 (PD-1) is a known immunoinhibitory receptor that contributes to immune evasion of various tumor cells and pathogens causing chronic infection, such as bovine leukemia virus (BLV) infection. First, in this study, to establish a method for the expression and functional analysis of bovine PD-1, hybridomas producing monoclonal antibodies (mAb) specific for bovine PD-1 were established. Treatment with these anti-PD-1 mAb enhanced interferon-gamma (IFN-γ) production of bovine peripheral blood mononuclear cells (PBMC). Next, to examine whether PD-1 blockade by anti-PD-1 mAb could upregulate the immune reaction during chronic infection, the expression and functional analysis of PD-1 in PBMC isolated from BLV-infected cattle with or without lymphoma were performed using anti-PD-1 mAb. The frequencies of both PD-1+ CD4+ T cells in blood and lymph node and PD-1+ CD8+ T cells in lymph node were higher in BLV-infected cattle with lymphoma than those without lymphoma or control uninfected cattle. PD-1 blockade enhanced IFN-γ production and proliferation and reduced BLV-gp51 expression and B-cell activation in PBMC from BLV-infected cattle in response to BLV-gp51 peptide mixture. These data show that anti-bovine PD-1 mAb could provide a new therapy to control BLV infection via upregulation of immune response. PMID:23876077

Inhibition of ongoing responses in patients with Parkinson's disease

PubMed Central

Gauggel, S; Rieger, M; Feghoff, T

2004-01-01

Objectives: We investigated the involvement of the basal ganglia in inhibiting ongoing responses in patients with Parkinson's disease (PD). Methods: Thirty two patients with PD and 31 orthopaedic controls performed the stop signal task, which allows an estimation of the time it takes to inhibit an ongoing reaction (stop signal reaction time, SSRT). Results: Patients with PD showed significantly longer SSRTs than the controls. This effect seemed to be independent of global cognitive impairment and severity of PD. Furthermore, in the PD patients, there was no significant relation between general slowing and inhibitory efficiency. Conclusions: Our results provide evidence for involvement of the basal ganglia in the inhibition of ongoing responses. PMID:15026491

In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a 'parallel progression approach to drug design' applied to β-blockers.

PubMed

Advani, Poonam; Joseph, Blessy; Ambre, Premlata; Pissurlenkar, Raghuvir; Khedkar, Vijay; Iyer, Krishna; Gabhe, Satish; Iyer, Radhakrishnan P; Coutinho, Evans

2016-01-01

The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development. We propose a theoretical approach, wherein 'parallel' information is generated to simultaneously optimize the pharmacokinetics (PK) and pharmacodynamics (PD) of lead candidates. β-blockers, though in use for many years, have suboptimal PKs; hence are an ideal test series for the 'parallel progression approach'. This approach utilizes molecular modeling tools viz. hologram quantitative structure activity relationships, homology modeling, docking, predictive metabolism, and toxicity models. Validated models have been developed for PK parameters such as volume of distribution (log Vd) and clearance (log Cl), which together influence the half-life (t1/2) of a drug. Simultaneously, models for PD in terms of inhibition constant pKi have been developed. Thus, PK and PD properties of β-blockers were concurrently analyzed and after iterative cycling, modifications were proposed that lead to compounds with optimized PK and PD. We report some of the resultant re-engineered β-blockers with improved half-lives and pKi values comparable with marketed β-blockers. These were further analyzed by the docking studies to evaluate their binding poses. Finally, metabolic and toxicological assessment of these molecules was done through in silico methods. The strategy proposed herein has potential universal applicability, and can be used in any drug discovery scenario; provided that the data used is consistent in terms of experimental conditions, endpoints, and methods employed. Thus the 'parallel progression approach' helps to simultaneously fine-tune various properties of the drug and would be an invaluable tool during the drug development process.

Crosslinked enzyme aggregates of hydroxynitrile lyase partially purified from Prunus dulcis seeds and its application for the synthesis of enantiopure cyanohydrins.

PubMed

Yildirim, Deniz; Tükel, S Seyhan; Alagöz, Dilek

2014-01-01

Hydroxynitrile lyases are powerful catalysts in the synthesis of enantiopure cyanohydrins which are key synthons in the preparations of a variety of important chemicals. The response surface methodology including three-factor and three-level Box-Behnken design was applied to optimize immobilization of hydroxynitrile lyase purified partially from Prunus dulcis seeds as crosslinked enzyme aggregates (PdHNL-CLEAs). The quadratic model was developed for predicting the response and its adequacy was validated with the analysis of variance test. The optimized immobilization parameters were initial glutaraldehyde concentration, ammonium sulfate saturation concentration, and crosslinking time, and the response was relative activity of PdHNL-CLEA. The optimal conditions were determined as initial glutaraldehyde concentration of 25% w/v, ammonium sulfate saturation concentration of 43% w/v, and crosslinking time of 18 h. The preparations of PdHNL-CLEA were examined for the synthesis of (R)-mandelonitrile, (R)-2-chloromandelonitrile, (R)-3,4-dihydroxymandelonitrile, (R)-2-hydroxy-4-phenyl butyronitrile, (R)-4-bromomandelonitrile, (R)-4-fluoromandelonitrile, and (R)-4-nitromandelonitrile from their corresponding aldehydes and hydrocyanic acid. After 96-h reaction time, the yield-enantiomeric excess values (%) were 100-99, 100-21, 100-99, 83-91, 100-99, 100-72, and 100-14%, respectively, for (R)-mandelonitrile, (R)-2-chloromandelonitrile, (R)-3,4-dihydroxymandelonitrile, (R)-2-hydroxy-4-phenyl butyronitrile, (R)-4-bromomandelonitrile, (R)-4-fluoromandelonitrile, and (R)-4-nitromandelonitrile. The results show that PdHNL-CLEA offers a promising potential for the preparation of enantiopure (R)-mandelonitrile, (R)-3,4-dihydroxymandelonitrile, (R)-2-hydroxy-4-phenyl butyronitrile, and (R)-4-bromomandelonitrile with a high yield and enantiopurity. © 2014 American Institute of Chemical Engineers.

Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance.

PubMed

Zhang, Jinfang; Bu, Xia; Wang, Haizhen; Zhu, Yasheng; Geng, Yan; Nihira, Naoe Taira; Tan, Yuyong; Ci, Yanpeng; Wu, Fei; Dai, Xiangpeng; Guo, Jianping; Huang, Yu-Han; Fan, Caoqi; Ren, Shancheng; Sun, Yinghao; Freeman, Gordon J; Sicinski, Piotr; Wei, Wenyi

2018-01-04

Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, and the underlying mechanism(s) is not well understood. Recent studies revealed that response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumour cells. Hence, it is important to understand the mechanistic pathways that control PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1-PD-L1 blockade in patients with cancer. Here we show that PD-L1 protein abundance is regulated by cyclin D-CDK4 and the cullin 3-SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of speckle-type POZ protein (SPOP) and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1. Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumour-infiltrating lymphocytes in mouse tumours and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD-1 immunotherapy enhances tumour regression and markedly improves overall survival rates in mouse tumour models. Our study uncovers a novel molecular mechanism for regulating PD-L1 protein stability by a cell cycle kinase and reveals the potential for using combination treatment with CDK4/6 inhibitors and PD-1-PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers.

Investigational agents in the treatment of Parkinson's disease: focus on safinamide.

PubMed

Malek, Naveed M; Grosset, Donald G

2012-01-01

The authors review management issues in Parkinson's disease (PD) and provide an overview of the current pharmacological management strategies, with a specific focus on safinamide. Current therapeutic management of PD largely involves strategies to optimize the replacement of deficient dopamine, using levodopa, dopamine agonists, and inhibitors of dopamine-metabolizing enzymes. Currently under investigation for use in the treatment of PD, safinamide has multiple modes of action including monoamine oxidase B inhibition. It is well absorbed orally, has a long plasma half-life, and does not have liver enzyme-inducing or liver enzyme-inhibiting activity. Peak plasma concentration occurs 2-4 hours after single oral doses. Safinamide as monotherapy and as an adjunct to dopamine agonists improves Unified Parkinson's Disease Rating Scale motor scores. One randomized, placebo-controlled trial involving 168 patients given a median safinamide dose of 70 mg/day (range 40-90 mg/day) significantly increased the proportion of responders - defined as patients improving their Unified Parkinson's Disease Rating Scale motor scores by 30% or more from baseline - after 3 months (37.5% for safinamide versus 21.4% for placebo; P < 0.05). Safinamide increased "on" time with no or minor dyskinesia compared with the placebo in another trial, but dyskinesia severity was not reduced. Safinamide was well tolerated, with an adverse effect profile similar to that of the placebo. Further Phase III trial data for safinamide efficacy is awaited, and will be of interest in a comparison with other developments in PD therapeutics: modified formulations of available compounds, new drug classes such as adenosine receptor antagonists, and gene-based therapies.

Determination of minimal clinically important change in early and advanced Parkinson's disease.

PubMed

Hauser, Robert A; Auinger, Peggy

2011-04-01

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

Influence of a removable prosthesis on oral health-related quality of life and mastication in elders with Parkinson disease.

PubMed

Ribeiro, Giselle R; Campos, Camila H; Rodrigues Garcia, Renata Cunha Matheus

2017-11-01

Parkinson disease (PD) symptoms, such as muscle rigidity, tremors in the lips and tongue, and involuntary mandibular movements, may cause oral health-related problems, mastication difficulties, and denture discomfort because of the difficulty in controlling a prosthesis with the oral musculature. The purpose of this observational clinical study was to evaluate the influence of oral rehabilitation with a removable prosthesis on oral health-related quality of life (OHRQoL) and masticatory efficiency (ME) in elders with PD. Thirty-four elders with PD (n=17, mean age 69.4 ±4.7 years) or without PD (n=17, mean age 70.7 ±4.7 years) were recruited. All participants first underwent OHRQoL and ME evaluations. Two months after the insertion of new removable prostheses, the participants were reassessed. The OHRQoL was measured with the Oral Health Impact Profile (OHIP-49). ME was evaluated by determining the percentage weight of the comminuted silicone-based artificial material that passed through a 2.8 mm sieve. For each group, data were compared between baseline and after insertion of new removable prostheses by paired t test or Wilcoxon sign test/signed-rank test. Group differences were assessed at each time point by t test (α=.05). After the insertion of removable prostheses, elders with PD showed improved OHRQoL and ME. Controls also showed improvements on both measures after insertion of removable prostheses. At baseline, elders with PD had lower OHRQoL and ME compared with the controls (P<.05). After removable prosthesis insertion, the elders with PD continued to show lower ME values than the controls, but their OHRQoL was similar. Oral rehabilitation with new removable dental prostheses improved the OHRQoL and ME in elders with and without PD, although ME did not reach control levels in elders with PD. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Pupillary Response to Cognitive Demand in Parkinson’s Disease: A Pilot Study

PubMed Central

Kahya, Melike; Moon, Sanghee; Lyons, Kelly E.; Pahwa, Rajesh; Akinwuntan, Abiodun E.; Devos, Hannes

2018-01-01

Previous studies have shown that pupillary response, a physiological measure of cognitive workload, reflects cognitive demand in healthy younger and older adults. However, the relationship between cognitive workload and cognitive demand in Parkinson’s disease (PD) remains unclear. The aim of this pilot study was to examine the pupillary response to cognitive demand in a letter-number sequencing (LNS) task between 16 non-demented individuals with PD (age, median (Q1–Q3): 68 (62–72); 10 males) and 10 control participants (age: 63 (59–67); 2 males), matched for age, education, and Montreal Cognitive Assessment (MOCA) scores. A mixed model analysis was employed to investigate cognitive workload changes as a result of incremental cognitive demand for both groups. As expected, no differences were found in cognitive scores on the LNS between groups. Cognitive workload, exemplified by greater pupil dilation, increased with incremental cognitive demand in both groups (p = 0.003). No significant between-group (p = 0.23) or interaction effects were found (p = 0.45). In addition, individuals who achieved to complete the task at higher letter-number (LN) load responded differently to increased cognitive demand compared with those who completed at lower LN load (p < 0.001), regardless of disease status. Overall, the findings indicated that pupillary response reflects incremental cognitive demand in non-demented people with PD and healthy controls. Further research is needed to investigate the pupillary response to incremental cognitive demand of PD patients with dementia compared to non-demented PD and healthy controls. Highlights -Pupillary response reflects cognitive demand in both non-demented people with PD and healthy controls-Although not significant due to insufficient power, non-demented individuals with PD had increased cognitive workload compared to the healthy controls throughout the testing-Pupillary response may be a valid measure of cognitive demand in non-demented individuals with PD-In future, pupillary response might be used to detect cognitive impairment in individuals with PD PMID:29692720

Aerodynamic Interactions of Propulsive Deceleration and Reaction Control System Jets on Mars-Entry Aeroshells

NASA Astrophysics Data System (ADS)

Alkandry, Hicham

Future missions to Mars, including sample-return and human-exploration missions, may require alternative entry, descent, and landing technologies in order to perform pinpoint landing of heavy vehicles. Two such alternatives are propulsive deceleration (PD) and reaction control systems (RCS). PD can slow the vehicle during Mars atmospheric descent by directing thrusters into the incoming freestream. RCS can provide vehicle control and steering by inducing moments using thrusters on the hack of the entry capsule. The use of these PD and RCS jets, however, involves complex flow interactions that are still not well understood. The fluid interactions induced by PD and RCS jets for Mars-entry vehicles in hypersonic freestream conditions are investigated using computational fluid dynamics (CFD). The effects of central and peripheral PD configurations using both sonic and supersonic jets at various thrust conditions are examined in this dissertation. The RCS jet is directed either parallel or transverse to the freestream flow at different thrust conditions in order to examine the effects of the thruster orientation with respect to the center of gravity of the aeroshell. The physical accuracy of the computational method is also assessed by comparing the numerical results with available experimental data. The central PD configuration decreases the drag force acting on the entry capsule due to a shielding effect that prevents mass and momentum in the hypersonic freestream from reaching the aeroshell. The peripheral PD configuration also decreases the drag force by obstructing the flow around the aeroshell and creating low surface pressure regions downstream of the PD nozzles. The Mach number of the PD jets, however, does not have a significant effect on the induced fluid interactions. The reaction control system also alters the flowfield, surface, and aerodynamic properties of the aeroshell, while the jet orientation can have a significant effect on the control effectiveness of the RCS.

PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis.

PubMed

Ishizaki, Yoshito; Yukaya, Naoko; Kusuhara, Koichi; Kira, Ryutaro; Torisu, Hiroyuki; Ihara, Kenji; Sakai, Yasunari; Sanefuji, Masafumi; Pipo-Deveza, Judy R; Silao, Catherine Lynn T; Sanchez, Benilda C; Lukban, Marissa B; Salonga, Aida M; Hara, Toshiro

2010-04-01

Although the exact pathogenesis of subacute sclerosing panencephalitis (SSPE) remains to be determined, our previous data suggested a genetic contribution to the host susceptibility to SSPE. During chronic viral infection, virus-specific cytotoxic T lymphocytes display poor effector functions. Since co-inhibitory molecules are involved in the suppression of T lymphocytes, we investigated whether single nucleotide polymorphisms (SNPs) of genes encoding co-inhibitory molecules contributed to a susceptibility to SSPE. Association studies on a total of 20 SNPs in 8 genes (CTLA4, CD80, CD86, PD1, PDL1, PDL2, BTLA and HVEM) and subsequent haplotype analysis of 4 SNPs in the PD1 genes were performed in Japanese and Filipino SSPE patients and controls. Then, we investigated a functional difference in promoter activity of two haplotypes and compared the expression levels of PD1 between SSPE and controls. The frequency of GCG(C) haplotype of PD1 containing -606G allele was significantly higher in SSPE patients than in controls both in Japanese and in Filipinos. The promoter activity was significantly higher in the construct with -606G allele than in that with -606A allele. The expression levels of PD1 were significantly higher in SSPE patients than in the controls. Our results suggested that the PD1 gene contributed to a genetic susceptibility to SSPE.

Alteration of the fecal microbiota in Chinese patients with Parkinson's disease.

PubMed

Qian, Yiwei; Yang, Xiaodong; Xu, Shaoqing; Wu, Chunyan; Song, Yanyan; Qin, Nan; Chen, Sheng-Di; Xiao, Qin

2018-05-01

Emerging evidences suggest that gut microbiota dysbiosis plays a role in Parkinson's disease (PD). However, the alterations in fecal microbiome in Chinese PD patients remains unknown. This case-control study was conducted to explore fecal microbiota compositions in Chinese PD patients. Microbiota communities in the feces of 45 patients and their healthy spouses were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S ribosomal RNA (rRNA) gene. The relationships between fecal microbiota and PD clinical characteristics were analyzed. The structure and richness of the fecal microbiota differed between PD patients and healthy controls. Genera Clostridium IV, Aquabacterium, Holdemania, Sphingomonas, Clostridium XVIII, Butyricicoccus and Anaerotruncus were enriched in the feces of PD patients after adjusting for age, gender, body mass index (BMI), and constipation. Furthermore, genera Escherichia/Shigella were negatively associated with disease duration. Genera Dorea and Phascolarctobacterium were negatively associated with levodopa equivalent doses (LED). Among the non-motor symptoms (NMSs), genera Butyricicoccus and Clostridium XlVb were associated with cognitive impairment. Overall, we confirmed that gut microbiota dysbiosis occurs in Chinese patients with PD. A well-controlled population involved was beneficial for the identification of microbiota associated with diseases. Additionally, the fecal microbiota was closely related to PD clinical characteristics. Elucidating these differences in the fecal microbiome will provide a foundation to improve our understanding the pathogenesis of PD and to support the potentially therapeutic options modifying the gut microbiota. Copyright © 2018 Elsevier Inc. All rights reserved.

Compulsive behaviors in patients with Parkinson's disease.

PubMed

Kenangil, Gülay; Ozekmekçi, Sibel; Sohtaoglu, Melis; Erginöz, Ethem

2010-05-01

Several impulse control disorders (ICDs) may develop in patients with Parkinson's disease (PD). We aimed to identify the frequency and phenomenology of ICDs in our PD population. Among 554 PD patients examined in a 3-year period, we identified 33 patients with ICDs. Disease duration, gender, and age-matched 65 PD patients without ICDs were selected as controls. We noted age-at-onset, duration, and severity of PD, dose and types of dopaminergic treatment, as well as presence of motor complications in both groups. Of 554 patients, 33 (5.9%) had ICDs, of whom, 27 were men (81%), mean age-at onset of PD was 48 and disease duration 8 years. While all patients with ICDs were on dopamine agonist drugs (+/- an adjuvant), all but 2 of controls were on dopamine agonists. Punding was the most frequent behavioral problem (57%), 42% exhibited aggressive hypersexuality, 27% compulsive eating, 24% pathologic shopping, and 21% compulsive medication. Severity of PD, presence of l-Dopa-induced motor complications, l-Dopa equivalent doses of dopamine agonists administered were not statistically different between 2 groups. In this study performed in a tertiary clinic for movement disorders in Turkey, several ICDs occurred in a small group of PD patients, mostly in men with young-onset disease, similar to the previous reported series. However, in contrast to the Western series, the number of gamblers was quite low because gambling is illegal in our country. We did not find any association between ICDs and severity of PD as well as doses of dopaminergic agents.

Lack of an association of programmed cell death-1 PD1.3 polymorphism with risk of hepatocellular carcinoma susceptibility in Turkish population: a case-control study.

PubMed

Bayram, Süleyman; Akkız, Hikmet; Ülger, Yakup; Bekar, Aynur; Akgöllü, Ersin; Yıldırım, Selçuk

2012-12-15

The programmed cell death-1 (PD-1) is a potent immunoregulatory molecule which is responsible for the negative regulation of T-cell activation and peripheral tolerance. Recently, overexpression of PD-1 has been reported to contribute to immune system evasion and poor survival of hepatocellular carcinoma (HCC). A common single nucleotide polymorphism in intron 4 of PD-1 gene called PD-1.3 has been reported to influence PD-1 expression, but its association with HCC has yet to be investigated. The aim of the present study was to investigate whether this polymorphism could be involved in the risk of HCC susceptibility. The genotype frequency of PD-1.3 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 236 subjects with HCC and 236 cancer-free control subjects matched on age, gender, smoking and alcohol status. No statistically significant differences were found in the genotype distributions of the PD-1.3 polymorphism among HCC and cancer-free control subjects (P=0.22). Our results demonstrate for the first time that the PD-1.3 polymorphism has not been in any major role in genetic susceptibility to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins. Copyright © 2012 Elsevier B.V. All rights reserved.

Principal component analysis of PiB distribution in Parkinson and Alzheimer diseases

PubMed Central

Markham, Joanne; Flores, Hubert; Hartlein, Johanna M.; Goate, Alison M.; Cairns, Nigel J.; Videen, Tom O.; Perlmutter, Joel S.

2013-01-01

Objective: To use principal component analyses (PCA) of Pittsburgh compound B (PiB) PET imaging to determine whether the pattern of in vivo β-amyloid (Aβ) in Parkinson disease (PD) with cognitive impairment is similar to the pattern found in symptomatic Alzheimer disease (AD). Methods: PiB PET scans were obtained from participants with PD with cognitive impairment (n = 53), participants with symptomatic AD (n = 35), and age-matched controls (n = 67). All were assessed using the Clinical Dementia Rating and APOE genotype was determined in 137 participants. PCA was used to 1) determine the PiB binding pattern in AD, 2) determine a possible unique PD pattern, and 3) directly compare the PiB binding patterns in PD and AD groups. Results: The first 2 principal components (PC1 and PC2) significantly separated the AD and control participants (p < 0.001). Participants with PD with cognitive impairment also were significantly different from participants with symptomatic AD on both components (p < 0.001). However, there was no difference between PD and controls on either component. Even those participants with PD with elevated mean cortical binding potentials were significantly different from participants with AD on both components. Conclusion: Using PCA, we demonstrated that participants with PD with cognitive impairment do not exhibit the same PiB binding pattern as participants with AD. These data suggest that Aβ deposition may play a different pathophysiologic role in the cognitive impairment of PD compared to that in AD. PMID:23825179

Frequency-velocity mismatch: a fundamental abnormality in parkinsonian gait.

PubMed

Cho, Catherine; Kunin, Mikhail; Kudo, Koji; Osaki, Yasuhiro; Olanow, C Warren; Cohen, Bernard; Raphan, Theodore

2010-03-01

Gait dysfunction and falling are major sources of disability for patients with advanced Parkinson's disease (PD). It is presently thought that the fundamental defect is an inability to generate normal stride length. Our data suggest, however, that the basic problem in PD gait is an impaired ability to match step frequency to walking velocity. In this study, foot movements of PD and normal subjects were monitored with an OPTOTRAK motion-detection system while they walked on a treadmill at different velocities. PD subjects were also paced with auditory stimuli at different frequencies. PD gait was characterized by step frequencies that were faster and stride lengths that were shorter than those of normal controls. At low walking velocities, PD stepping had a reduced or absent terminal toe lift, which truncated swing phases, producing shortened steps. Auditory pacing was not able to normalize step frequency at these lower velocities. Peak forward toe velocities increased with walking velocity and PD subjects could initiate appropriate foot dynamics during initial phases of the swing. They could not control the foot appropriately in terminal phases, however. Increased treadmill velocity, which matched the natural PD step frequency, generated a second toe lift, normalizing step size. Levodopa increased the bandwidth of step frequencies, but was not as effective as increases in walking velocity in normalizing gait. We postulate that the inability to control step frequency and adjust swing phase dynamics to slower walking velocities are major causes for the gait impairment in PD.

Frequency-Velocity Mismatch: A Fundamental Abnormality in Parkinsonian Gait

PubMed Central

Kunin, Mikhail; Kudo, Koji; Osaki, Yasuhiro; Olanow, C. Warren; Cohen, Bernard; Raphan, Theodore

2010-01-01

Gait dysfunction and falling are major sources of disability for patients with advanced Parkinson's disease (PD). It is presently thought that the fundamental defect is an inability to generate normal stride length. Our data suggest, however, that the basic problem in PD gait is an impaired ability to match step frequency to walking velocity. In this study, foot movements of PD and normal subjects were monitored with an OPTOTRAK motion-detection system while they walked on a treadmill at different velocities. PD subjects were also paced with auditory stimuli at different frequencies. PD gait was characterized by step frequencies that were faster and stride lengths that were shorter than those of normal controls. At low walking velocities, PD stepping had a reduced or absent terminal toe lift, which truncated swing phases, producing shortened steps. Auditory pacing was not able to normalize step frequency at these lower velocities. Peak forward toe velocities increased with walking velocity and PD subjects could initiate appropriate foot dynamics during initial phases of the swing. They could not control the foot appropriately in terminal phases, however. Increased treadmill velocity, which matched the natural PD step frequency, generated a second toe lift, normalizing step size. Levodopa increased the bandwidth of step frequencies, but was not as effective as increases in walking velocity in normalizing gait. We postulate that the inability to control step frequency and adjust swing phase dynamics to slower walking velocities are major causes for the gait impairment in PD. PMID:20042701

Propofol Requirement for Induction of Unconsciousness Is Reduced in Patients with Parkinson's Disease: A Case Control Study

PubMed Central

Xu, Xiao-ping; Yu, Xi-ya; Wu, Xi; Hu, Xiao-wu; Chen, Jian-chun; Li, Jin-bao; Deng, Xiao-ming

2015-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85–2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53–2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.) PMID:26495319

Digital PI-PD controller design for arbitrary order systems: Dominant pole placement approach.

PubMed

Dincel, Emre; Söylemez, Mehmet Turan

2018-05-02

In this paper, a digital PI-PD controller design method is proposed for arbitrary order systems with or without time-delay to achieve desired transient response in the closed-loop via dominant pole placement approach. The digital PI-PD controller design problem is solved by converting the original problem to the digital PID controller design problem. Firstly, parametrization of the digital PID controllers which assign dominant poles to desired location is done. After that the subset of digital PID controller parameters in which the remaining poles are located away from the dominant pole pair is found via Chebyshev polynomials. The obtained PID controller parameters are then transformed into the PI-PD controller parameters by considering the closed-loop controller zero and the design is completed. Success of the proposed design method is firstly demonstrated on an example transfer function and compared with the well-known PID controller methods from the literature through simulations. After that the design method is implemented on the fan and plate laboratory system in a real environment. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Detecting Motor Impairment in Early Parkinson’s Disease via Natural Typing Interaction With Keyboards: Validation of the neuroQWERTY Approach in an Uncontrolled At-Home Setting

PubMed Central

Ledesma-Carbayo, María J; Butterworth, Ian; Matarazzo, Michele; Montero-Escribano, Paloma; Puertas-Martín, Verónica; Gray, Martha L

2018-01-01

Background Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease and one of the most common forms of movement disorder. Although there is no known cure for PD, existing therapies can provide effective symptomatic relief. However, optimal titration is crucial to avoid adverse effects. Today, decision making for PD management is challenging because it relies on subjective clinical evaluations that require a visit to the clinic. This challenge has motivated recent research initiatives to develop tools that can be used by nonspecialists to assess psychomotor impairment. Among these emerging solutions, we recently reported the neuroQWERTY index, a new digital marker able to detect motor impairment in an early PD cohort through the analysis of the key press and release timing data collected during a controlled in-clinic typing task. Objective The aim of this study was to extend the in-clinic implementation to an at-home implementation by validating the applicability of the neuroQWERTY approach in an uncontrolled at-home setting, using the typing data from subjects’ natural interaction with their laptop to enable remote and unobtrusive assessment of PD signs. Methods We implemented the data-collection platform and software to enable access and storage of the typing data generated by users while using their computer at home. We recruited a total of 60 participants; of these participants 52 (25 people with Parkinson’s and 27 healthy controls) provided enough data to complete the analysis. Finally, to evaluate whether our in-clinic-built algorithm could be used in an uncontrolled at-home setting, we compared its performance on the data collected during the controlled typing task in the clinic and the results of our method using the data passively collected at home. Results Despite the randomness and sparsity introduced by the uncontrolled setting, our algorithm performed nearly as well in the at-home data (area under the receiver operating characteristic curve [AUC] of 0.76 and sensitivity/specificity of 0.73/0.69) as it did when used to evaluate the in-clinic data (AUC 0.83 and sensitivity/specificity of 0.77/0.72). Moreover, the keystroke metrics presented a strong correlation between the 2 typing settings, which suggests a minimal influence of the in-clinic typing task in users’ normal typing. Conclusions The finding that an algorithm trained on data from an in-clinic setting has comparable performance with that tested on data collected through naturalistic at-home computer use reinforces the hypothesis that subtle differences in motor function can be detected from typing behavior. This work represents another step toward an objective, user-convenient, and quasi-continuous monitoring tool for PD. PMID:29581092

Arrhythmokinesis is evident during unimanual not bimanual finger tapping in Parkinson's disease.

PubMed

Trager, Megan H; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren; Quinn, Emma; Bronte-Stewart, Helen

2015-01-01

Arrhythmokinesis, the variability in repetitive movements, is a fundamental feature of Parkinson's disease (PD). We hypothesized that unimanual repetitive alternating finger tapping (AFT) would reveal more arrhythmokinesis compared to bimanual single finger alternating hand tapping (SFT), in PD. The variability of inter-strike interval (CVISI) and of amplitude (CVAMP) during AFT and SFT were measured on an engineered, MRI-compatible keyboard in sixteen PD subjects off medication and in twenty-four age-matched controls. The CVISI and CVAMP of the more affected (MA) and less affected (LA) sides in PD subjects were greater during AFT than SFT (P < 0.05). However, there was no difference between AFT and SFT for controls. Both CVISI and CVAMP were greater in the MA and LA hands of PD subjects versus controls during AFT (P < 0.01). The CVISI and CVAMP of the MA, but not the LA hand, were greater in PDs versus controls during SFT (P < 0.05). Also, AFT, but not SFT, detected a difference between the MA and LA hands of PDs (P < 0.01). Unimanual, repetitive alternating finger tapping brings out more arrhythmokinesis compared to bimanual, single finger tapping in PDs but not in controls. Arrhythmokinesis during unimanual, alternating finger tapping captured a significant difference between both the MA and LA hands of PD subjects and controls, whereas that during a bimanual, single finger tapping task only distinguished between the MA hand and controls. Arrhythmokinesis underlies freezing of gait and may also underlie the freezing behavior documented in fine motor control if studied using a unimanual alternating finger tapping task.

BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer.

PubMed

Wieser, Verena; Gaugg, Inge; Fleischer, Martina; Shivalingaiah, Giridhar; Wenzel, Soeren; Sprung, Susanne; Lax, Sigurd F; Zeimet, Alain G; Fiegl, Heidelinde; Marth, Christian

2018-04-03

Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status. TP53 -mutated OC strongly expressed PD-L1 compared to TP53 wild-type OC ( p = 0.028) and BRCA1/2 -mutated OC increasingly expressed PD-1 ( p = 0.024) and PD-L1 ( p = 0.012) compared to BRCA1/2 wild-type OC. For the first time in human, we noted a strong correlation between tumoral IFNG and PD-1 or PD-L1 mRNA-expression, respectively ( p < 0.001). OC tissue increasingly expressed PD-1 compared to healthy controls (vs. ovaries: p < 0.001; vs. tubes: p = 0.018). PD-1 and PD-L1 mRNA-expression increased with higher tumor grade ( p = 0.008 and p = 0.027, respectively) and younger age (< median age, p = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high PD-1 and PD-L1 mRNA-expression was associated with reduced progression-free ( p = 0.024) and overall survival ( p = 0.049) but only in the univariate analysis. Our study suggests that in OC PD-1 / PD-L1 mRNA-expression is controlled by IFNγ and affected by TP53 and BRCA1/2 mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- PD1 / PD-L1 immunotherapy.

A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors

PubMed Central

Gabrielson, Matthew; Lisok, Ala; Wharram, Bryan; Sysa-Shah, Polina; Azad, Babak Behnam; Pomper, Martin G.; Nimmagadda, Sridhar

2016-01-01

Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIR-PD-L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings. PMID:26848870

Driving under low-contrast visibility conditions in Parkinson disease

PubMed Central

Uc, E Y.; Rizzo, M; Anderson, S W.; Dastrup, E; Sparks, J D.; Dawson, J D.

2009-01-01

Objective: To assess driving performance in Parkinson disease (PD) under low-contrast visibility conditions. Methods: Licensed, active drivers with mild to moderate PD (n = 67, aged 66.2 ± 9.0 years, median Hoehn–Yahr stage = 2) and controls (n = 51, aged 64.0 ± 7.2 years) drove in a driving simulator under high- (clear sky) and low-contrast visibility (fog) conditions, leading up to an intersection where an incurring vehicle posed a crash risk in fog. Results: Drivers with PD had higher SD of lateral position (SDLP) and lane violation counts (LVC) than controls during fog (p < 0.001). Transition from high- to low-contrast visibility condition increased SDLP and LVC more in PD than in controls (p < 0.01). A larger proportion of drivers with PD crashed at the intersection in fog (76.1% vs 37.3%, p < 0.0001). The time to first reaction in response to incursion was longer in drivers with PD compared with controls (median 2.5 vs 2.0 seconds, p < 0.0001). Within the PD group, the strongest predictors of poor driving outcomes under low-contrast visibility conditions were worse scores on measures of visual processing speed and attention, motion perception, contrast sensitivity, visuospatial construction, motor speed, and activities of daily living score. Conclusions: During driving simulation under low-contrast visibility conditions, drivers with Parkinson disease (PD) had poorer vehicle control and were at higher risk for crashes, which were primarily predicted by decreased visual perception and cognition; motor dysfunction also contributed. Our results suggest that drivers with PD may be at risk for unsafe driving in low-contrast visibility conditions such as during fog or twilight. GLOSSARY ADL = activities of daily living; CFT = Complex Figure Test; CS = contrast sensitivity; FOV = field of view; FR = functional reach; FVA = far visual acuity; JLO = judgment of line orientation; LVC = lane violation counts; PD = Parkinson disease; SDLP = SD of lateral position; SFM = structure from motion; SIREN = Simulator for Interdisciplinary Research in Ergonomics and Neuroscience; TFR = time to first reaction; UFOV = useful field of view; UPDRS = Unified Parkinson’s Disease Rating Scale. PMID:19805726

Impact of Cognitive Loading on Postural Control in Parkinson’s Disease With Freezing of Gait

PubMed Central

Buated, Wannipat; Lolekha, Praween; Hidaka, Shohei; Fujinami, Tsutomu

2016-01-01

Objective:To assess standing balance in Parkinson’s disease (PD) patients with and without freezing of gait (FOG) during cognitive loading. Method:A balance assessment with cognitive loading, reading (RE) and counting backward (CB), was performed by the Nintendo Wii Fit in 60 PD patients (Hoehn and Yahr stages 1-3) at Thammasat University Hospital, Thailand. The participants were grouped into FOG and non-FOG according to the Freezing of Gait–Questionnaire (FOG-Q) scores. The center of pressure (CoP) in terms of path length (PL), sway area (SA), root mean square (RMS), medio-lateral (ML), and antero-posterior (AP) were analyzed. Results:Significant increases of PL were observed in both groups of PD patients during cognitive loading (p < .001). Meanwhile, the increased differences of PL during cognitive loading in PD-FOG were larger than in PD-non-FOG. The ML displacement during counting backward was significantly increased in PD-FOG (p = .012). Conclusion:Cognitive loading influenced standing balance and postural sway of PD patients. The effects were more prominent in PD-FOG. These findings represent the interactions between cognitive function, postural control, and FOG in PD. PMID:28680941

Expression of PD-1 on peripheral blood Treg cells is related to the diagnosis, prognosis and treatment of T cell non-Hodgkin lymphoma.

PubMed

Zuo, Mengxuan; Shen, Haorui; Yin, Jingjing; Wang, Wei; Zhang, Yan; Zhou, Dao-Bin; Zhang, Wei

2018-05-24

The aim of study was to explore the PD-1 expression on Treg cells and its association with T-NHL. 137 patients newly diagnosed with T-NHL and 115 healthy controls were enrolled. The expression level of PD-1 was measured by flow cytometry at the time of diagnose and 3-8 course of treatment. Median fluorescence intensity (MFI) of PD-1 on Treg cells in T-NHL patients was significantly higher than that in healthy controls (P < 0.001). MFI of PD-1 in medium/high-risk T-NHL patients were higher than that in low-risk patients (P < 0.05). After treatment with Chidamide combined with chemotherapy, MFI of PD-1 significantly decreased (P < 0.05). In patients with high PD-1 expression (percentage>19.6% and MFI > 580), EFS was significantly lower than patients with low PD-1 expression (percentage<19.6% and MFI < 580). The PD-1expression on peripheral blood Treg cells of T-NHL patients is related to the diagnosis, prognosis and treatment of disease. Copyright © 2018. Published by Elsevier Ltd.

Controlled deposition of palladium nanodendrites on the tips of gold nanorods and their enhanced catalytic activity.

PubMed

Su, Gaoxing; Jiang, Huaqiao; Zhu, Hongyan; Lv, Jing-Jing; Yang, Guohai; Yan, Bing; Zhu, Jun-Jie

2017-08-31

Plasmonic Au-Pd nanostructures have drawn significant attention for use in heterogeneous catalysis. In this study, palladium nanodendrite-tipped gold nanorods (PdND-T-AuNRs) were subjected to a facile fabrication under mild reaction conditions. The palladium amounts on the two tips were tunable. In the preparation of PdND-T-AuNRs, dense capped AuNRs, a low reaction temperature, and suitable stabilizing agents were identified as critical reaction parameters for controlling palladium nanodendrites deposited on both ends of AuNRs. After overgrowth with palladium nanodendrites, the longitudinal surface plasmonic resonance peaks of PdND-T-AuNRs were red-shifted from 810 nm to 980 nm. The electrocatalytic activity of PdND-T-AuNRs for ethanol oxidation was examined, which was a bit weaker than that of cuboid core-shell Au-Pd nanodendrites; however, PdND-T-AuNRs were more stable in ethanol electrooxidation. Moreover, the photocatalytic activity of PdND-T-AuNRs for Suzuki cross-coupling reactions was investigated. At room temperature, nearly 100% yield was obtained under laser irradiation. The results can further enhance our capability of fine-tuning the optical, electronic, and catalytic properties of the bimetallic Au-Pd nanostructures.

Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease.

PubMed

Yang, Zi-Jiao; Wei, Jing; Mao, Cheng-Jie; Zhang, Jin-Ru; Chen, Jing; Ji, Xiao-Yan; Liu, Jun-Yi; Shen, Yun; Xiong, Kang-Ping; Huang, Jun-Ying; Yang, Ya-Ping; Liu, Chun-Feng

2016-12-01

Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.

Basal ganglia and beyond: The interplay between motor and cognitive aspects in Parkinson's disease rehabilitation.

PubMed

Ferrazzoli, Davide; Ortelli, Paola; Madeo, Graziella; Giladi, Nir; Petzinger, Giselle M; Frazzitta, Giuseppe

2018-07-01

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome.

PubMed

Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Lawrence, Andrew D; Woodhead, Zoe; Lees, Andrew J; Piccini, Paola; Politis, Marios

2015-11-01

Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) patients refers to the compulsive use of dopaminergic replacement therapy and has serious psycho-social consequences. Mechanisms underlying DDS are not clear although has been linked to dysfunctional brain reward networks. With fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS patients and 12 PD control patients in both the ON and OFF medication state. Behavioral measures of liking, wanting and subjectively 'feeling ON medication' were also collected. Behaviorally, PD DDS patients feel less ON and want their drugs more at baseline compared to PD controls. Following drug-cue exposure, PD DDS patients feel significantly more ON medication, which correlates with significant increases in reward related regions. The results demonstrate that exposure to drug-cues increases the subjective feeling of being 'ON' medication which corresponds to dysfunctional activation in reward related regions in PD DDS patients. These findings should be extended in future studies. Visual stimuli being sufficient to elicit behavioral response through neuroadaptations could have direct implications to the management of addictive behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuromelanin imaging and midbrain volumetry in progressive supranuclear palsy and Parkinson's disease.

PubMed

Taniguchi, Daisuke; Hatano, Taku; Kamagata, Koji; Okuzumi, Ayami; Oji, Yutaka; Mori, Akio; Hori, Masaaki; Aoki, Shigeki; Hattori, Nobutaka

2018-05-14

Background Nigral degeneration patterns differ between PSP and PD. However, the relationship between nigral degeneration and midbrain atrophy in PSP remains unclear. Objective We analyzed differences and relationships between nigral degeneration and midbrain atrophy in PSP and PD. Methods Neuromelanin-sensitive MRI and midbrain volumetry were performed in 11 PSP patients, 24 PD patients, and 10 controls to measure the neuromelanin-sensitive SNpc area and midbrain volume. Results The neuromelanin-sensitive SNpc area and midbrain volume were significantly smaller in PSP patients compared with PD patients and controls. Motor deficits were inversely correlated with neuromelanin-sensitive SNpc area in PD, but not PSP patients. There was no significant correlation between neuromelanin-sensitive SNpc area and midbrain volume in either disease group. Midbrain volumetry discriminated PSP from PD. Diagnostic accuracy was improved when neuromelanin-sensitive MRI analysis was added. Conclusions Neuromelanin-sensitive MRI and midbrain volumetry may reflect the clinical and pathological characteristics of PSP and PD. Combining neuromelanin-sensitive MRI and midbrain volumetry may be useful for differentiating PSP from PD. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Associations between Vitamin D Status, Supplementation, Outdoor Work and Risk of Parkinson's Disease: A Meta-Analysis Assessment.

PubMed

Shen, Liang; Ji, Hong-Fang

2015-06-15

The present study aimed to quantitatively assess the associations between vitamin D and Parkinson's Disease (PD) risks, which include: (i) risk of PD in subjects with deficient and insufficient vitamin D levels; (ii) association between vitamin D supplementation and risk of PD; and (iii) association between outdoor work and PD risk, through meta-analyzing available data. An electronic literature search supplemented by hand searching up to March 2015 identified seven eligible studies comprising 5690 PD patients and 21251 matched controls. Odds ratio (OR) and 95% confidence interval (CI) of PD risk were assessed through pooling the collected data from eligible studies using Stata software. Pooled data showed that subjects with deficient and insufficient vitamin D levels had increased PD risks compared with matched-controls according to the corresponding OR: 2.08, 95% CI: 1.63 to 2.65, and 1.29, 95% CI: 1.10 to 1.51. Vitamin D supplementation was associated with significantly reduced risk of PD (OR: 0.62, 95% CI: 0.35 to 0.90). Outdoor work was also related to reduced risk of PD (OR: 0.72, 95% CI: 0.63 to 0.81). The findings may stimulate larger, well-designed studies to further verify the associations between vitamin D and PD risk.

Biorefining of precious metals from wastes: an answer to manufacturing of cheap nanocatalysts for fuel cells and power generation via an integrated biorefinery?

PubMed

Yong, Ping; Mikheenko, Iryna P; Deplanche, Kevin; Redwood, Mark D; Macaskie, Lynne E

2010-12-01

Bio-manufacturing of nano-scale palladium was achieved via enzymatically-mediated deposition of Pd from solution using Desulfovibrio desulfuricans, Escherichia coli and Cupriavidus metallidurans. Dried 'Bio-Pd' materials were sintered, applied onto carbon papers and tested as anodes in a proton exchange membrane (PEM) fuel cell for power production. At a Pd(0) loading of 25% by mass the fuel cell power using Bio-Pd( D. desulfuricans ) (positive control) and Bio-Pd( E. coli ) (negative control) was ~140 and ~30 mW respectively. Bio-Pd( C. metallidurans ) was intermediate between these with a power output of ~60 mW. An engineered strain of E. coli (IC007) was previously reported to give a Bio-Pd that was >3-fold more active than Bio-Pd of the parent E. coli MC4100 (i.e. a power output of >110 mW). Using this strain, a mixed metallic catalyst was manufactured from an industrial processing waste. This 'Bio-precious metal' ('Bio-PM') gave ~68% of the power output as commercial Pd(0) and ~50% of that of Bio-Pd( D. desulfuricans ) when used as fuel cell anodic material. The results are discussed in relation to integrated bioprocessing for clean energy.

Haplotypes and gene expression implicate the MAPT region for Parkinson disease

PubMed Central

Tobin, J.E.; Latourelle, J.C.; Lew, M.F.; Klein, C.; Suchowersky, O.; Shill, H.A.; Golbe, L.I.; Mark, M.H.; Growdon, J.H.; Wooten, G.F.; Racette, B.A.; Perlmutter, J.S.; Watts, R.; Guttman, M.; Baker, K.B.; Goldwurm, S.; Pezzoli, G.; Singer, C.; Saint-Hilaire, M.H.; Hendricks, A.E.; Williamson, S.; Nagle, M.W.; Wilk, J.B.; Massood, T.; Laramie, J.M.; DeStefano, A.L.; Litvan, I.; Nicholson, G.; Corbett, A.; Isaacson, S.; Burn, D.J.; Chinnery, P.F.; Pramstaller, P.P.; Sherman, S.; Al-hinti, J.; Drasby, E.; Nance, M.; Moller, A.T.; Ostergaard, K.; Roxburgh, R.; Snow, B.; Slevin, J.T.; Cambi, F.; Gusella, J.F.; Myers, R.H.

2009-01-01

Background Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. Methods Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. Results After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. Conclusions This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk. PMID:18509094

Highly active carbon supported ternary PdSnPtx (x=0.1-0.7) catalysts for ethanol electro-oxidation in alkaline and acid media.

PubMed

Wang, Xiaoguang; Zhu, Fuchun; He, Yongwei; Wang, Mei; Zhang, Zhonghua; Ma, Zizai; Li, Ruixue

2016-04-15

A series of trimetallic PdSnPtx (x=0.1-0.7)/C catalysts with varied Pt content have been synthesized by co-reduction method using NaBH4 as a reducing agent. These catalysts were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and chronoamperometry (CA). The electrochemical results show that, after adding a minor amount of Pt dopant, the resultant PdSnPtx/C demonstrated more superior catalytic performance toward ethanol oxidation as compared with that of mono-/bi-metallic Pd/C or PdSn/C in alkaline solution and the PdSnPt0.2/C with optimal molar ratio reached the best. In acid solution, the PdSnPt0.2/C also depicted a superior catalytic activity relative to the commercial Pt/C catalyst. The possible enhanced synergistic effect between Pd, Sn/Sn(O) and Pt in an alloyed state should be responsible for the as-revealed superior ethanol electro-oxidation performance based upon the beneficial electronic effect and bi-functional mechanism. It implies the trimetallic PdSnPt0.2/C with a low Pt content has a promising prospect as anodic electrocatalyst in fields of alkali- and acid-type direct ethanol fuel cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of current evidence

PubMed Central

Rihawi, Karim; Gelsomino, Francesco; Sperandi, Francesca; Melotti, Barbara; Fiorentino, Michelangelo; Casolari, Laura; Ardizzoni, Andrea

2017-01-01

Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives. PMID:28818019

Direct and indirect effects of attention and visual function on gait impairment in Parkinson's disease: influence of task and turning.

PubMed

Stuart, Samuel; Galna, Brook; Delicato, Louise S; Lord, Sue; Rochester, Lynn

2017-07-01

Gait impairment is a core feature of Parkinson's disease (PD) which has been linked to cognitive and visual deficits, but interactions between these features are poorly understood. Monitoring saccades allows investigation of real-time cognitive and visual processes and their impact on gait when walking. This study explored: (i) saccade frequency when walking under different attentional manipulations of turning and dual-task; and (ii) direct and indirect relationships between saccades, gait impairment, vision and attention. Saccade frequency (number of fast eye movements per-second) was measured during gait in 60 PD and 40 age-matched control participants using a mobile eye-tracker. Saccade frequency was significantly reduced in PD compared to controls during all conditions. However, saccade frequency increased with a turn and decreased under dual-task for both groups. Poorer attention directly related to saccade frequency, visual function and gait impairment in PD, but not controls. Saccade frequency did not directly relate to gait in PD, but did in controls. Instead, saccade frequency and visual function deficit indirectly impacted gait impairment in PD, which was underpinned by their relationship with attention. In conclusion, our results suggest a vital role for attention with direct and indirect influences on gait impairment in PD. Attention directly impacted saccade frequency, visual function and gait impairment in PD, with connotations for falls. It also underpinned indirect impact of visual and saccadic impairment on gait. Attention therefore represents a key therapeutic target that should be considered in future research. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Microstructural changes in the substantia nigra of asymptomatic agricultural workers.

PubMed

Du, Guangwei; Lewis, Mechelle M; Sterling, Nicholas W; Kong, Lan; Chen, Honglei; Mailman, Richard B; Huang, Xuemei

2014-01-01

Parkinson's disease (PD) is marked by the loss of dopamine neurons in the substantia nigra (SN). Although the exact etiology is unknown, sporadic PD is hypothesized to be a result of genetic susceptibility interacting with environmental insult. Epidemiological studies suggest that pesticide exposure is linked to higher PD risk, but there are no studies demonstrating SN changes with chronic pesticide exposure in human subjects. Thus, high resolution T2-weighted magnetic resonance imaging (MRI) and diffusion tensor (DTI) images were obtained from 12 agricultural workers with chronic pesticide exposure, 12 controls, and 12 PD subjects. Neither controls nor pesticide-exposed subjects, had any parkinsonian symptoms. Exposure history to pesticides was assessed by a structured questionnaire. DTI measures in the SN, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were obtained for all subjects and compared among groups. Compared to controls, PD patients showed the expected significant changes in all DTI measurements in the SN. The pesticide-exposed subjects, compared to controls, had significantly lower FA values (p=0.022, after multiple comparisons correction), but no significant differences in RD, MD, or AD measures. The study is the first to demonstrate microstructural changes in the SN of human subjects with chronic pesticide exposure. The changes detected by MRI may mark "one of the hits" leading to PD, and underlie the increased risk of PD in pesticide users found in epidemiological studies. Further human studies assisted by these imaging markers may be useful in understanding the etiology of PD. Copyright © 2013 Elsevier Inc. All rights reserved.

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

PubMed

Dewey, D Campbell; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B

2014-10-15

To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. Copyright © 2014 Elsevier B.V. All rights reserved.

Automated Gait and Balance Parameters Diagnose and Correlate with Severity in Parkinson Disease

PubMed Central

Dewey, Daniel C.; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B.; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B.

2014-01-01

Objective To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Methods Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM® Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. Results 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R2 ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Interpretation Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. PMID:25082782

Objective Versus Subjective Measures of Executive Functions: Predictors of Participation and Quality of Life in Parkinson Disease?

PubMed

Vlagsma, Thialda T; Koerts, Janneke; Tucha, Oliver; Dijkstra, Hilde T; Duits, Annelien A; van Laar, Teus; Spikman, Jacoba M

2017-11-01

To determine whether objective (neuropsychological tests) and subjective measures (questionnaires) of executive functions (EFs) are associated in patients with Parkinson disease (PD), and to determine to what extent level of participation and quality of life (QoL) of patients with PD can be predicted by these measures of EFs. Correlational research design (case-control and prediction design). Departments of neuropsychology of 3 medical centers. A sample (N=136) of patients with PD (n=42) and their relatives, and controls without PD (n=94). Not applicable. A test battery measuring EFs. In addition, patients, their relatives, and controls completed the Dysexecutive Questionnaire, Brock Adaptive Functioning Questionnaire, and Barkley Deficits in Executive Functioning Scale - time management questionnaires measuring complaints about EFs. Participation and QoL were measured with the Impact on Participation and Autonomy scale and the Parkinson's Disease Questionnaire-39, respectively. Patients with PD showed impairments in EFs on objective tests and reported significantly more complaints about EFs than did controls without PD. No associations were found between patients' performances on objective and subjective measures of EFs. However, both objective and subjective measures predicted patients' level of participation. In addition, subjective measures of EFs predicted QoL in patients with PD. These findings show that objective and subjective measures of EFs are not interchangeable and that both approaches predict level of participation and QoL in patients with PD. However, within this context, sex needs to be taken into account. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Dulce Wireless Tijuana: A Randomized Control Trial Evaluating the Impact of Project Dulce and Short-Term Mobile Technology on Glycemic Control in a Family Medicine Clinic in Northern Mexico.

PubMed

Anzaldo-Campos, María Cecilia; Contreras, Sonia; Vargas-Ojeda, Adriana; Menchaca-Díaz, Rufino; Fortmann, Addie; Philis-Tsimikas, Athena

2016-04-01

The global epidemic of diabetes calls for innovative interventions. This study evaluated the effectiveness of the Project Dulce model, with and without wireless technology, on glycemic control and other clinical and self-reported outcomes in patients with poorly controlled type 2 diabetes in Mexico. Adults with type 2 diabetes and a glycated hemoglobin A1c (HbA1c) level of ≥8% were recruited from Family Medical Unit #27 of the Instituto Mexicano del Seguro Social (IMSS) in Tijuana, México, and randomly assigned to one of three groups: Project Dulce-only (PD); Project Dulce technology-enhanced with mobile tools (PD-TE); or IMSS standard of care/control group (CG). Clinical and self-reported outcomes were assessed at baseline, Month 4, and Month 10. Time-by-group interactions and within-group changes were analyzed. HbA1c reductions from baseline to Month 10 were significantly greater in PD-TE (-3.0% [-33 mmol/mol]) and PD (-2.6% [-28.7 mmol/mol]) compared with CG (-1.3% [-14.2 mmol/mol]) (P = 0.009 and 0.001, respectively). PD-TE and PD also exhibited significant improvement in diabetes knowledge when compared with CG (P < 0.05 for both). No statistically significant differences were detected between PD and PD-TE on these indicators (P = 0.54 and 0.86, respectively). Several within-group improvements were observed on other clinical and self-report indicators but did not vary significantly across groups. Project Dulce with and without wireless technology substantially improved glycemic control and diabetes knowledge in high-risk patients with type 2 diabetes in a Mexican family medical unit, suggesting that integrating peer-led education, nurse coordination, and 3G wireless technology is an effective approach for improving diabetes outcomes in high-risk populations.

Cerebrospinal Fluid Peptides as Potential Parkinson Disease Biomarkers: A Staged Pipeline for Discovery and Validation*

PubMed Central

Shi, Min; Movius, James; Dator, Romel; Aro, Patrick; Zhao, Yanchun; Pan, Catherine; Lin, Xiangmin; Bammler, Theo K.; Stewart, Tessandra; Zabetian, Cyrus P.; Peskind, Elaine R.; Hu, Shu-Ching; Quinn, Joseph F.; Galasko, Douglas R.; Zhang, Jing

2015-01-01

Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From ∼14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity = 76.7%, specificity = 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC = 0.853, sensitivity = 82.5%, specificity = 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC = 0.990, sensitivity = 95.0%, specificity = 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r = 0.381, p = 0.038)j and the validation (r = 0.339, p = 0.032) sets. The novel panel of CSF peptides, if validated in independent cohorts, could be used to assist in clinical diagnosis of PD and has the potential to help monitoring or predicting disease progression. PMID:25556233

The impact of phenotypic and genotypic G6PD deficiency on risk of plasmodium vivax infection: a case-control study amongst Afghan refugees in Pakistan.

PubMed

Leslie, Toby; Briceño, Marnie; Mayan, Ismail; Mohammed, Nasir; Klinkenberg, Eveline; Sibley, Carol Hopkins; Whitty, Christopher J M; Rowland, Mark

2010-05-25

The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A-) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection. A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06-0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02-0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15-0.94], p = 0.037). G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy.

Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease.

PubMed

Yadav, Santosh K; Kathiresan, Nagarajan; Mohan, Suyash; Vasileiou, Georgia; Singh, Anup; Kaura, Deepak; Melhem, Elias R; Gupta, Rakesh K; Wang, Ena; Marincola, Francesco M; Borthakur, Arijitt; Haris, Mohammad

2016-11-01

Parkinson's disease (PD) is a progressive neurological disorder and appears to have gender-specific symptoms. Studies have observed a higher frequency for development of PD in male than in female. In the current study, we evaluated the gender-based changes in cortical thickness and structural connectivity in PD patients. With informed consent, 64 PD (43 males and 21 females) patients, and 46 (12 males and 34 females) age-matched controls underwent clinical assessment including Mini-Mental State Examination (MMSE) and magnetic resonance imaging on a 1.5 Tesla clinical MR scanner. Whole brain high-resolution T1-weighted images were acquired from all subjects and used to measure cortical thickness and structural network connectivity. No significant difference in MMSE score was observed between male and female both in control and PD subjects. Male PD patients showed significantly reduced cortical thickness in multiple brain regions including frontal, parietal, temporal, and occipital lobes as compared with those in female PD patients. The graph theory-based network analysis depicted lower connection strengths, lower clustering coefficients, and altered network hubs in PD male than in PD female. Male-specific cortical thickness changes and altered connectivity in PD patients may derive from behavioral, physiological, environmental, and genetical differences between male and female, and may have significant implications in diagnosing and treating PD among genders.

Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

PubMed

Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

2018-04-01

To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

Examining the relationship between speech intensity and self-rated communicative effectiveness in individuals with Parkinson's disease and hypophonia.

PubMed

Dykstra, Allyson D; Adams, Scott G; Jog, Mandar

2015-01-01

To examine the relationship between speech intensity and self-ratings of communicative effectiveness in speakers with Parkinson's disease (PD) and hypophonia. An additional purpose was to evaluate if self-ratings of communicative effectiveness made by participants with PD differed from ratings made by primary communication partners. Thirty participants with PD and 15 healthy older adults completed the Communication Effectiveness Survey. Thirty primary communication partners rated the communicative effectiveness of his/her partner with PD. Speech intensity was calculated for participants with PD and control participants based on conversational utterances. Results revealed significant differences between groups in conversational speech intensity (p=.001). Participants with PD self-rated communicative effectiveness significantly lower than control participants (p=.000). Correlational analyses revealed a small but non-significant relationship between speech intensity and communicative effectiveness for participants with PD (r=0.298, p=.110) and control participants (r=0.327, p=.234). Self-ratings of communicative effectiveness made participants with PD was not significantly different than ratings made by primary communication partners (p=.20). Obtaining information on communicative effectiveness may help to broaden outcome measurement and may aid in the provision of educational strategies. Findings also suggest that communicative effectiveness may be a separate and a distinct construct that cannot necessarily be predicted from the severity of hypophonia. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic analysis of SCA2, 3 and 17 in idiopathic Parkinson's disease.

PubMed

Lim, S W; Zhao, Y; Chua, E; Law, H Y; Yuen, Y; Pavanni, R; Wong, M C; Ng, I S; Yoon, C S; Puong, K Y; Lim, S H; Tan, E K

2006-07-31

Recent reports of SCA2 and SCA3 patients who presented with levodopa responsive parkinsonism have generated considerable interest as they have implications for genetic testing. It is unclear whether ethnic race alone or founder effects within certain geographical region explain such an association. In this study, we conducted genetic analysis of SCA2, 3, 17 in an ethnic Chinese cohort with early onset and familial Parkinson's disease (PD) and healthy controls. A total of 191 subjects comprising of 91 PD and 100 healthy controls were examined. We identified one positive case of SCA2 in an early-onset sporadic PD patient who had CAG 36 repeats, yielding a prevalence of 2.2% in early-onset sporadic PD patients and less than 1.0% in our study PD population. The size of the repeats was lower than the expanded repeats (38-57) in SCA2 patients with ataxia in our population. All the children of the patient were physically normal even though some of them carried the repeat expansion of similar size. No cases and controls were positive for SCA3 and SCA17. We do not think routine screening of SCA2, SCA3 and SCA17 for all idiopathic PD patients is cost-effective in our ethnic Chinese population. However, SCA2 should be a differential diagnosis in young onset sporadic PD when genetic mutations of other known PD genes have been excluded.

String Vessel Formation is Increased in the Brain of Parkinson Disease.

PubMed

Yang, Panzao; Pavlovic, Darja; Waldvogel, Henry; Dragunow, Mike; Synek, Beth; Turner, Clinton; Faull, Richard; Guan, Jian

2015-01-01

String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.

History of smoking and olfaction in Parkinson's disease.

PubMed

Lucassen, Elisabeth B; Sterling, Nicholas W; Lee, Eun-Young; Chen, Honglei; Lewis, Mechelle M; Kong, Lan; Huang, Xuemei

2014-07-01

Olfactory dysfunction is the most common pre-motor symptom in Parkinson's disease (PD), and smoking is known to be associated with lower risk of PD. This study tested the hypothesis that smoking is associated with better olfaction in PD. Smoking history was obtained from 76 PD subjects (22 with a history of smoking [smokers], 54 who never smoked [nonsmokers]), and 70 controls (17 smokers, 53 nonsmokers). Olfaction was assessed using the 40-item University of Pennsylvania Smell Identification Test (UPSIT). The olfactory scores between groups and subgroups were compared using analysis of covariance with adjustment for age, gender, and monoamine oxidase B (MAO-B) inhibitor usage. Overall the olfactory score was lower in PD compared with controls (olfactory scores: 21.5 vs. 33.5, P < 0.0001). Among controls, there was no significant difference in olfaction between smokers and nonsmokers (olfactory scores, 33.2 vs. 34.2; P = 0.95). Among PD subjects, however, smokers scored significantly better regarding olfaction compared with nonsmokers (olfactory scores: 24.4 vs. 19.9, P = 0.02). These data suggest that a history of smoking is associated with better olfaction among PD patients. The finding may be related to why smoking may be protective against PD. Further studies are needed to confirm this finding and investigate the underlying mechanisms. © 2014 International Parkinson and Movement Disorder Society.

Crystal Structure of the Complex Between Programmed Death-1 (PD-1) and its Ligand PD-L2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazar-Molnar,E.; Yan, Q.; Cao, E.

2008-01-01

Programmed death-1 (PD-1) is a member of the CD28/B7 superfamily that delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The high-resolution crystal structure of the complex formed by the complete ectodomains of murine PD-1 and PD-L2 revealed a 1:1 receptor:ligand stoichiometry and displayed a binding interface and overall molecular organization distinct from that observed in the CTLA-4/B7 inhibitory complexes. Furthermore, our structure also provides insights into the association between PD-1 and PD-L1 and highlights differences in the interfaces formed by the two PD-1 ligands (PD-Ls) Mutagenesis studies confirmed the details of the proposed PD-1/PD-L binding interfacesmore » and allowed for the design of a mutant PD-1 receptor with enhanced affinity. These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy.« less

Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes.

PubMed

Otten, Julia; Stomby, Andreas; Waling, Maria; Isaksson, Andreas; Tellström, Anna; Lundin-Olsson, Lillemor; Brage, Søren; Ryberg, Mats; Svensson, Michael; Olsson, Tommy

2017-01-01

Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed. Thirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX). For the within group analyses, fat mass decreased by 5.7 kg (IQR: -6.6, -4.1; p < 0.001) in the PD group and by 6.7 kg (-8.2, -5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA 1c decreased by 0.9% (-1.2, -0.6; p < 0.001) in the PD group and 1.1% (-1.7, -0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (-3.6, -1.3) in the PD group and by 1.2 kg (-1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups). A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Yongsheng; Sun, Kewei; Tian, Yuan

We report a one-pot synthesis of urchin-like FePd-Fe3O4 nanocomposites, spherical clusters of FePd nanoparticles (NPs) with spikes of Fe3O4 nanorods (NRs), via controlled thermal decomposition of Fe(CO)5 and reduction of Pd(acac)2. The FePd NPs with sizes between 6 and 9 nm self-aggregate into 60 nm superparticles (SPs), and Fe3O4 NRs grow on the surface of these SPs. Reductive annealing at 500 °C converts the FePd-Fe3O4 into exchange-coupled nanocomposites L1(0)-FePd-Fe with their Hc tunable from 0.8 to 2.6 kOe and Ms controlled from 90 to 190 emu/g. The work provides a general approach to L1(0)-FePd-Fe nanocomposite magnets for understanding exchange couplingmore » at the nanoscale. The concept may be extended to other magnetic nanocomposite systems and may help to build superstrong magnets for magnetic applications.« less

Identification of Glutathione S-Transferase Pi as a Protein Involved in Parkinson Disease Progression

PubMed Central

Shi, Min; Bradner, Joshua; Bammler, Theo K.; Eaton, David L.; Zhang, JianPeng; Ye, ZuCheng; Wilson, Angela M.; Montine, Thomas J.; Pan, Catherine; Zhang, Jing

2009-01-01

Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique. Approximately 100 proteins displayed significant differences in their relative abundances between PD patients at various stages and controls; three of these proteins were validated using independent techniques. One of the confirmed proteins, glutathione S-transferase Pi, was further investigated in cellular models of PD, demonstrating that its level was intimately associated with several critical cellular processes that are directly related to neurodegeneration in PD. These results have, for the first time, suggested that the levels of glutathione S-transferase Pi may play an important role in modulating the progression of PD. PMID:19498008

A 25-Gbps high-sensitivity optical receiver with 10-Gbps photodiode using inductive input coupling for optical interconnects

NASA Astrophysics Data System (ADS)

Oku, Hideki; Narita, Kiyomi; Shiraishi, Takashi; Ide, Satoshi; Tanaka, Kazuhiro

2012-01-01

A 25-Gbps high-sensitivity optical receiver with a 10-Gbps photodiode (PD) using inductive input coupling has been demonstrated for optical interconnects. We introduced the inductive input coupling technique to achieve the 25-Gbps optical receiver using a 10-Gbps PD. We implemented an input inductor (Lin) between the PD and trans-impedance amplifier (TIA), and optimized inductance to enhance the bandwidth and reduce the input referred noise current through simulation with the RF PD-model. Near the resonance frequency of the tank circuit formed by PD capacitance, Lin, and TIA input capacitance, the PD photo-current through Lin into the TIA is enhanced. This resonance has the effects of enhancing the bandwidth at TIA input and reducing the input equivalent value of the noise current from TIA. We fabricated the 25-Gbps optical receiver with the 10-Gbps PD using an inductive input coupling technique. Due to the application of an inductor, the receiver bandwidth is enhanced from 10 GHz to 14.2 GHz. Thanks to this wide-band and low-noise performance, we were able to improve the sensitivity at an error rate of 1E-12 from non-error-free to -6.5 dBm. These results indicate that our technique is promising for cost-effective optical interconnects.

Implications of Parkinson's disease pathophysiology for the development of cell replacement strategies and drug discovery in neurodegenerative diseases.

PubMed

Pan-Montojo, Francisco; Funk, Richard H W

2012-11-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder traditionally characterized by the loss of dopaminergic neurons in the substantia nigra (SN) at the midbrain. The potential use of adult or embryonic stem cells, induced pluriputent stem (iPS) cells and endogenous neurogenesis in cell replacement strategies has lead to numerous studies and clinical trials in this direction. It is now possible to differentiate stem cells into dopaminergic neurons in vitro and clinical trials have shown an improvement in PD-related symptoms after intra-striatal embryonic transplants and acceptable cell survival rates on the mid term. However, clinical improvement is transitory and associated with a strong placebo effect. Interestingly, recent pathological studies in PD patients who received embryonic stem cells show that in PD patients, grafted neurons show PD-related pathology. In this manuscript we review the latest findings regarding PD pathophysiology and give an outlook on the implications of these findings in how cell replacement strategies for PD treatment should be tested. These include changes in the type of animal models used, the preparation/conditioning of the cells before intracerebral injection, specially regarding backbone chronic diseases in iPS cells and determining the optimal proliferation, survival, differentiation and migration capacity of the grafted cells.

Facile synthesis of PdSx/C porous nanospheres and their applications for ethanol oxidation reaction

NASA Astrophysics Data System (ADS)

Zhang, Qiang; Zhang, Fuhua; Ma, Xuemei; Zheng, Yiqun; Hou, Shifeng

2016-12-01

We report a facile approach for the synthesis of carbon-supported palladium polysulphide porous nanospheres (PdSx/C) and their applications for ethanol oxidation reaction. Typical synthesis started with generation of palladium/poly (3,4-ethylenedioxythiophene)(Pd/PEDOT) nanospheres, followed by a calcination process at an optimized temperature to form PdSx/C, with an average size of 2.47 ± 0.60 and 50 nm of PdSx nanoparticles and carbon porous nanospheres, respectively. Various techniques, such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and electrochemical techniques were performed to characterize their morphologies, compositions and structures. In contrary to most Pd-based electrochemical catalysts that could be easily poised with trace sulfur during the catalytic oxidation process, the as-prepared PdSx/C porous nanospheres exhibited high electrocatalytic activities and stabilities for the electrochemical catalytic oxidation of ethanol in alkaline medium. In particular, the forward peak current intensity achieved 162.1 mA mg-1 and still maintained at 46.7 mA mg-1 even after 1000 cycles. This current work not only offers a novel type of fuel-cell catalyst for ethanol oxidation reaction, but also provides a possible route for solving the sulfur-poisoning problem in catalysis.

Control of movement distance in Parkinson's disease.

PubMed

Pfann, K D; Buchman, A S; Comella, C L; Corcos, D M

2001-11-01

Studies of electromyographic (EMG) patterns during movements in Parkinson's disease (PD) have often yielded contradictory results, making it impossible to derive a set of rules to explain how muscles are activated to perform different movement tasks. We sought to clarify the changes in modulation of EMG parameters associated with control of movement distance during fast movements in patients with PD. Specifically, we studied surface EMG activity during rapid elbow flexion movements over a wide range of distances (5-72 degrees) in 14 patients with relatively mild symptoms of PD and 14 control subjects of similar age, sex, height, and weight. The PD group exhibited several changes in EMG modulation including impaired modulation of agonist burst duration; increased number of agonist bursts; reduced scaling of agonist EMG magnitude in the more severely impaired subjects; and increased temporal overlap of the antagonist and agonist signals in the most severely impaired subjects. These findings suggest that progressive motor dysfunction in PD is accompanied by increasing deficits in modulating muscle activation. These results help clarify previous disparate and sometimes contradictory results of EMG patterns in subjects with PD. Copyright 2001 Movement Disorder Society.

Assessment of postural asymmetry in mild to moderate Parkinson's disease.

PubMed

Geurts, A C H; Boonstra, T A; Voermans, N C; Diender, M G; Weerdesteyn, V; Bloem, B R

2011-01-01

Asymmetry of symptoms of Parkinson's disease is clinically most evident for appendicular impairments. For axial impairments such as freezing of gait, asymmetry is less obvious. To date, asymmetries in balance control in PD patients have seldom been studied. Therefore, in this study we investigated whether postural control can be asymmetrically affected in mild to moderate PD patients. Seventeen PD patients were instructed to stand as still and symmetrically as possible on a dual force-plate during two trials. Dynamic postural asymmetry was assessed by comparing the centre-of-pressure velocities between both legs. Results showed that four patients (24%) had dynamic postural asymmetry, even after correcting for weight-bearing asymmetry. Hence, this study suggests that postural control can be asymmetrical in early PD. However, future studies should investigate the prevalence of dynamic postural asymmetry, in a larger group of PD patients. It should also be further investigated whether this approach can be used as a tool to support the initial diagnosis or monitor disease progression, or as an outcome measure for interventions aimed at improving balance in PD. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of different high-palladium metal-ceramic alloys on the color of opaque and dentin porcelain.

PubMed

Stavridakis, Minos M; Papazoglou, Efstratios; Seghi, Robert R; Johnston, William M; Brantley, William A

2004-08-01

The color of dental porcelain depends on the type of metal substrate. Little research has been done to document the effects of different types of high-palladium alloys on the color of dental porcelain. The purpose of this in vitro study was to evaluate the effects of different high-palladium alloys on the resulting color of dentin porcelain, as well as on that of opaque porcelain after simulated dentin and glazing firing cycles. Three Pd-Cu-Ga alloys, Spartan Plus (S), Liberty (B), and Freedom Plus (F), and 5 Pd-Ga alloys, Legacy (L), IS 85 (I), Protocol (P), Legacy XT (X), and Jelenko No.1 (N), were examined. A Pd-Ag alloy, Super Star (T), was included for comparison to the high-palladium alloys, and the Au-Pd alloy, Olympia (O), served as the control. Six cast discs (16 x 1 mm) were prepared from each of the alloys. Shade B1 opaque porcelain (Vita-Omega) was applied at a final thickness of 0.1 mm. After 2 opaque porcelain firing cycles, the surfaces were airborne-particle abraded, and the specimens were divided into 2 groups. In the first group, 0.9 mm of B1 dentin porcelain was applied. The other group of specimens with only opaque porcelain underwent the same dentin porcelain and glazing firing cycles. Color differences (DeltaE) were determined with a colorimeter between the control and each experimental group, after the second opaque porcelain, second dentin porcelain, and glazing firing cycles. One-way analysis of variance and Dunnett's multiple range test were performed on the DeltaE data (alpha=.05). After the application of dentin porcelain, the 3 Pd-Cu-Ga alloys showed significantly different (P<.05) DeltaE values (S=2.3 +/- 0.5, B=1.4 +/- 0.3, and F=1.3 +/- 0.7) than the control group. After the glazing cycle of this group, the 3 Pd-Cu-Ga alloys and the Pd-Ag alloy exhibited significantly different (P<.05) DeltaE values (S=2.8 +/- 0.8, B=2.2 +/- 0.3, F=1.9 +/- 1.0, and T=1.4 +/- 0.5) than the control group. After the simulated dentin porcelain firing cycles, the specimens with only opaque porcelain exhibited significantly different (P<.05) DeltaE values (S=5.2 +/- 1.4, B=5.4 +/- 0.6, and F=3.9 +/- 0.2) than the control group. The color difference between the 3 Pd-Cu-Ga alloys with only opaque porcelain and the control group increased more after the simulated glazing cycle (S=6.6 +/- 1.5, B=6.3 +/- 0.5, and F=4.6 +/- 0.1). The observed color differences between the Pd-Ga alloys and the control group were not statistically significant at any point. The Pd-Cu-Ga alloys with only opaque porcelain, after the simulated dentin porcelain and glazing firing cycles, exhibited clinically unacceptable color differences. The application of dentin porcelain to the Pd-Cu-Ga alloys resulted in clinically acceptable color differences. The application of dentin porcelain to the Pd-Ag alloy, after the glazing firing cycle, resulted in clinically acceptable color differences (approximately 2.8 to 3.7 DeltaE CIELAB units). The Pd-Ag alloy specimens with only opaque porcelain did not exhibit significant color differences from the control group, whereas significant color differences from the control group after the dentin porcelain and glazing firing cycles were still clinically acceptable.

A Cane Improves Postural Recovery From an Unpracticed Slip During Walking in People With Parkinson Disease

PubMed Central

Saengsirisuwan, Vitoon; Carlson-Kuhta, Patricia; Horak, Fay B.

2012-01-01

Background Little is known about the effects of use of a cane on balance during perturbed gait or whether people with Parkinson disease (PD) benefit from using a cane. Objectives The purpose of this study was to evaluate the effects of cane use on postural recovery from a slip due to repeated surface perturbations in individuals with PD compared with age- and sex-matched individuals who were healthy. Design This was a prospective study with 2 groups of participants. Methods Fourteen individuals with PD (PD group) and 11 individuals without PD (control group) walked across a platform that translated 15 cm rightward at 30 cm/s during the single-limb support phase of the right foot. Data from 15 trials in 2 conditions (ie, with and without an instrumented cane in the right hand) were collected in random order. Outcome measures included lateral displacement of body center of mass (COM) due to the slip and compensatory step width and length after the perturbation. Results Cane use improved postural recovery from the first untrained slip, characterized by smaller lateral COM displacement, in the PD group but not in the control group. The beneficial effect of cane use, however, occurred only during the first perturbation, and those individuals in the PD group who demonstrated the largest COM displacement without a cane benefited the most from use of a cane. Both PD and control groups gradually decreased lateral COM displacement across slip exposures, but a slower learning rate was evident in the PD group participants, who required 6, rather than 3, trials for adapting balance recovery. Limitations Future studies are needed to examine the long-term effects of repeated slip training in people with PD. Conclusions Use of a cane improved postural recovery from an unpracticed slip in individuals with PD. Balance in people with PD can be improved by training with repeated exposures to perturbations. PMID:22628583

A cane improves postural recovery from an unpracticed slip during walking in people with Parkinson disease.

PubMed

Boonsinsukh, Rumpa; Saengsirisuwan, Vitoon; Carlson-Kuhta, Patricia; Horak, Fay B

2012-09-01

Little is known about the effects of use of a cane on balance during perturbed gait or whether people with Parkinson disease (PD) benefit from using a cane. The purpose of this study was to evaluate the effects of cane use on postural recovery from a slip due to repeated surface perturbations in individuals with PD compared with age- and sex-matched individuals who were healthy. This was a prospective study with 2 groups of participants. Fourteen individuals with PD (PD group) and 11 individuals without PD (control group) walked across a platform that translated 15 cm rightward at 30 cm/s during the single-limb support phase of the right foot. Data from 15 trials in 2 conditions (ie, with and without an instrumented cane in the right hand) were collected in random order. Outcome measures included lateral displacement of body center of mass (COM) due to the slip and compensatory step width and length after the perturbation. Cane use improved postural recovery from the first untrained slip, characterized by smaller lateral COM displacement, in the PD group but not in the control group. The beneficial effect of cane use, however, occurred only during the first perturbation, and those individuals in the PD group who demonstrated the largest COM displacement without a cane benefited the most from use of a cane. Both PD and control groups gradually decreased lateral COM displacement across slip exposures, but a slower learning rate was evident in the PD group participants, who required 6, rather than 3, trials for adapting balance recovery. Future studies are needed to examine the long-term effects of repeated slip training in people with PD. Use of a cane improved postural recovery from an unpracticed slip in individuals with PD. Balance in people with PD can be improved by training with repeated exposures to perturbations.

[Relationship between G6PD deficiency and hand-foot-mouth disease induced by enterovirus 71].

PubMed

Ou, Jun-Bin; Zhang, Cui-Mei; Fu, Si-Mao; Huang, Xiang; Huang, Lian-Hong

2013-09-01

To study the influence of glucose-6-phosphate dehydrogenase (G6PD) deficiency on hand-foot-mouth disease (HFMD) induced by enterovirus 71 (EV71) , and possible mechanisms. A total of 220 boys with HFMD induced by EV71 were classified into two groups based on disease severity: mild/moderate (n=145) and severe HFMD groups (n=75), and 132 healthy boys were selected as the control group. The activity of G6PD and levels of reduced glutathione (GSH) and malonaldehyde (MDA) in blood were measured using the automatic biochemical analyzer. The percentage of G6PD deficiency cases in the severe HFMD group was significantly higher than in the control group (P<0.0125). In the severe HFMD group, the durations of fever, mental abnormality, limb trembling and hospital stay were significantly longer in children with G6PD deficiency than in those with normal G6PD activity (P<0.05). In the acute and recovery stages, patients in the mild/moderate and severe HFMD groups had significantly lower GSH levels and G6PD activity and significantly higher MDA levels compared with those in the control group (P<0.05). In the acute stage, children in the mild/moderate and severe HFMD groups with G6PD deficiency had significantly lower GSH levels and significantly higher MDA levels compared with those with normal G6PD activity (P<0.01). In the acute and recovery stages, GSH level in children with HFMD was positively correlated with G6PD activity (r=0.61, P<0.01; r=0.58, P<0.01), and in the acute stage, MDA level was negatively correlated with G6PD activity (r=-0.29, P<0.01). G6PD deficiency is probably a predisposing factor for HFMD induced by EV71 and may aggravate the patient's condition. Its mechanism might be related to oxidative stress.

Association between PDCD1 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus in Three Main Ethnic Groups of the Malaysian Population.

PubMed

Chua, Kek Heng; Lian, Lay Hoong; Sim, Xiu Jia; Cheah, Tien Eang; Lau, Tze Pheng

2015-04-29

The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants.

Olfaction in Parkin carriers in Chinese patients with Parkinson disease.

PubMed

Wang, Ying; Wu, Jian-Jun; Liu, Feng-Tao; Chen, Kui; Chen, Chen; Luo, Su-Shan; Wang, Yi-Xuan; Li, Da-Ke; Guan, Rong-Yuan; Yang, Yu-Jie; An, Yu; Wang, Jian; Sun, Yi-Min

2017-05-01

Olfactory identification was reported to be better among PD (Parkinson disease) patients with Parkin mutations, but previous studies didn't eliminate the interference of other PD related genes on olfaction, and whether olfaction of Parkin mutations patients was better in Chinese population was still unknown. To assess olfaction function among PD patients with Parkin mutations in Chinese population. A total of 226 PD patients with a positive family history or an early-onset age (<50 years) were enrolled for genetic testing of PD related genes by target sequencing and multiple ligation-dependent probe amplification. The clinical data including olfactory function test were investigated. Linear regression was performed to adjust for the covariates between all groups. There were 68 patients found having a negative result in PD genetic testing and 43 patients carrying homozygous or compound heterozygous Parkin mutations. Among them, 49 PD panel negative patients and 33 PD- Parkin patients had results of olfactory assessment. PD -Parkin patients performed significantly better on the Sniffin' Sticks tests than panel negative patients (8.0 ± 1.7 vs. 5.7 ± 1.9, p  <   .001), but still worse compared to healthy controls (9.4 ± 1.5, p  =   .003). These differences persisted after adjusting for confounders. Among Chinese population, PD -Parkin patients had relatively preserved olfaction compared to PD panel negative patients after eliminating the interference of other PD related genes, but were still worse than healthy controls.

Use of an online portal to facilitate clinical trial recruitment: a preliminary analysis of Fox Trial Finder.

PubMed

Rocker, Charlotte; Cappelletti, Lily; Marshall, Claudia; Meunier, Claire C; Brooks, Deborah W; Sherer, Todd; Chowdhury, Sohini

2015-01-01

As in other therapeutic areas, clinical studies in Parkinson's disease (PD) face significant recruitment challenges. However, qualitative surveys suggest that individuals with PD are willing to participate in clinical research. The Michael J. Fox Foundation therefore established Fox Trial Finder in 2011 to facilitate connection between PD research teams and volunteers. Characterize the research volunteers (with and without PD) registered on Fox Trial Finder as of June 2014, and the published, recruiting studies to identify trends and highlight gaps between research requirements and available volunteers. Profiles of volunteers with and without PD were analyzed to explore trends in geography, demographics, family history and, for those volunteers with PD, disease progression and treatment history. Clinical study profiles were analyzed to determine study type, phase, sponsor, focus, location and eligibility criteria. The analysis focused on volunteers and studies based in the United States. The database contained 26,261 US-based volunteers, including 19,243 volunteers (73%) with PD and 7,018 (27%) controls without PD. The average time since diagnosis for PD volunteers was 5.7 years and the average age at diagnosis was 58 years. Control volunteers were more likely than volunteers with PD to be female (67% vs. 35%) and to have a family history of PD (49% vs. 12%). Fox Trial Finder's registration history to date demonstrates the high level of willingness among individuals affected by PD to participate in clinical research and provide a significant amount of personal health information to facilitate that participation.

Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset.

PubMed

Nichols, W C; Pankratz, N; Marek, D K; Pauciulo, M W; Elsaesser, V E; Halter, C A; Rudolph, A; Wojcieszek, J; Pfeiffer, R F; Foroud, T

2009-01-27

To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease. We performed a comprehensive study of all GBA exons in one patient with PD from each of 96 PD families, selected based on the family-specific lod scores at the GBA locus. Identified GBA variants were subsequently screened in all 1325 PD cases from 566 multiplex PD families and in 359 controls. Nine different GBA variants, five previously reported, were identified in 21 of the 96 PD cases sequenced. Screening for these variants in the full sample identified 161 variant carriers (12.2%) in 99 different PD families. An unbiased estimate of the frequency of the five previously reported GBA variants in the familial PD sample was 12.6% and in the control sample was 5.3% (odds ratio 2.6; 95% confidence interval 1.5-4.4). Presence of a GBA variant was associated with an earlier age at onset (p = 0.0001). On average, those patients carrying a GBA variant had onset with PD 6.04 years earlier than those without a GBA variant. This study suggests that GBA is a susceptibility gene for familial Parkinson disease (PD) and patients with GBA variants have an earlier age at onset than patients with PD without GBA variants.

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity.

PubMed

Nakayama, Masaaki; Zhu, Wan-Jun; Watanabe, Kimio; Gibo, Ayano; Sherif, Ali M; Kabayama, Shigeru; Ito, Sadayoshi

2017-10-31

Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H 2 ) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H 2 on the peritoneal membrane of experimental PD rats. Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8-11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H 2 PD group (PD solution with dissolved H 2 at 400 ppb). Furthermore, the influence of iron (FeCl 3 : 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H 2 PD groups). The H 2 PD solution was manufactured by bathing a PD bag in H 2 -oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis. In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H 2 PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H 2 PD group. H 2 -dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H 2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

Architecture of Pd-Au bimetallic nanoparticles in sodium bis(2-ethylhexyl)sulfosuccinate reverse micelles as investigated by X-ray absorption spectroscopy.

PubMed

Chen, Ching-Hsiang; Sarma, Loka Subramanyam; Chen, Jium-Ming; Shih, Shou-Chu; Wang, Guo-Rung; Liu, Din-Goa; Tang, Mau-Tsu; Lee, Jyh-Fu; Hwang, Bing-Joe

2007-09-01

In this study, we demonstrate the unique application of X-ray absorption spectroscopy (XAS) as a fundamental characterization tool to help in designing and controlling the architecture of Pd-Au bimetallic nanoparticles within a water-in-oil microemulsion system of water/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/n-heptane. Structural insights obtained from the in situ XAS measurements recorded at each step during the formation process revealed that Pd-Au bimetallic clusters with various Pd-Au atomic stackings are formed by properly performing hydrazine reduction and redox transmetalation reactions sequentially within water-in-oil microemulsions. A structural model is provided to explain reasonably each reaction step and to give detailed insight into the nucleation and growth mechanism of Pd-Au bimetallic clusters. The combination of in situ XAS analysis at both the Pd K-edge and the Au L(III)-edge and UV-vis absorption spectral features confirms that the formation of Pd-Au bimetallic clusters follows a (Pd(nuclei)-Au(stack))-Pd(surf) stacking. This result further implies that the thickness of Au(stack) and Pd(surf) layers may be modulated by varying the dosage of the Au precursor and hydrazine, respectively. In addition, a bimetallic (Pd-Au)(alloy) nanocluster with a (Pd(nuclei)-Au(stack))-(Pd-Au(alloy))(surf) stacking was also designed and synthesized in order to check the feasibility of Pd(surf) layer modification. The result reveals that the Pd(surf) layer of the stacked (Pd(nuclei)-Au)(stack) bimetallic clusters can be successfully modified to form a (Au-Pd alloy)(surf) layer by a co-reduction of Pd and Au ions by hydrazine. Further, we demonstrate the alloying extent or atomic distribution of Pd and Au in Pd-Au bimetallic nanoparticles from the derived XAS structural parameters. The complete XAS-based methodology, demonstrated here on the Pd-Au bimetallic system, can easily be extended to design and control the alloying extent or atomic distribution, atomic stacking, and electronic structure to construct many other types of bimetallic systems for interesting applications.

Can loss of the swallow tail sign help distinguish between Parkinson Disease and the Parkinson-Plus syndromes?

PubMed

Oustwani, Christopher Sami; Korutz, Alexander William; Lester, Malisa Siri; Kianirad, Yasaman; Simuni, Tanya; Hijaz, Tarek Aref

To determine if loss of the swallow tail sign (STS) can distinguish Parkinson Disease (PD) from the Parkinson-Plus syndromes. Twenty-five patients with PD, 21 with Parkinson-Plus syndromes, and 14 control patients were included. Presence of the STS was assessed. The STS was present in 79% of controls, statistically greater than the PD/Parkinson-Plus patients. There was no difference in the presence of the STS between the PD/Parkinson-Plus subgroups or when scanning at 1.5 T or 3 T. Loss of the STS could not distinguish between PD and Parkinson-Plus patients. The STS can be identified at both 1.5 T and 3 T. Copyright © 2017 Elsevier Inc. All rights reserved.

Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease

NASA Technical Reports Server (NTRS)

Hausdorff, J. M.; Cudkowicz, M. E.; Firtion, R.; Wei, J. Y.; Goldberger, A. L.

1998-01-01

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

Challenging Postural Tasks Increase Asymmetry in Patients with Parkinson’s Disease

PubMed Central

Beretta, Victor Spiandor; Gobbi, Lilian Teresa Bucken; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Barbieri, Fabio Augusto

2015-01-01

The unilateral predominance of Parkinson’s disease (PD) symptoms suggests that balance control could be asymmetrical during static tasks. Although studies have shown that balance control asymmetries exist in patients with PD, these analyses were performed using only simple bipedal standing tasks. Challenging postural tasks, such as unipedal or tandem standing, could exacerbate balance control asymmetries. To address this, we studied the impact of challenging standing tasks on postural control asymmetry in patients with PD. Twenty patients with PD and twenty neurologically healthy individuals (control group) participated in this study. Participants performed three 30s trials for each postural task: bipedal, tandem adapted and unipedal standing. The center of pressure parameter was calculated for both limbs in each of these conditions, and the asymmetry between limbs was assessed using the symmetric index. A significant effect of condition was observed, with unipedal standing and tandem standing showing greater asymmetry than bipedal standing for the mediolateral root mean square (RMS) and area of sway parameters, respectively. In addition, a group*condition interaction indicated that, only for patients with PD, the unipedal condition showed greater asymmetry in the mediolateral RMS and area of sway than the bipedal condition and the tandem condition showed greater asymmetry in the area of sway than the bipedal condition. Patients with PD exhibited greater asymmetry while performing tasks requiring postural control when compared to neurologically healthy individuals, especially for challenging tasks such as tandem and unipedal standing. PMID:26367032

Safety and efficacy of anti-PD-L1 therapy in the woodchuck model of HBV infection

PubMed Central

Balsitis, Scott; Gali, Volodymyr; Mason, Pamela J.; Chaniewski, Susan; Levine, Steven M.; Wichroski, Michael J.; Feulner, Michael; Song, Yunling; Granaldi, Karen; Loy, James K.; Thompson, Chris M.; Lesniak, Jacob A.; Brockus, Catherine; Kishnani, Narendra; Menne, Stephan; Cockett, Mark I.; Iyer, Renuka; Mason, Stephen W.

2018-01-01

Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters. We used woodchucks infected with WHV to assess the safety and efficacy of anti-PD-L1 monoclonal antibody therapy (αPD-L1) in a variety of WHV infection states. Experimentally-infected animals lacked PD-1 or PD-L1 upregulation compared to uninfected controls, and accordingly, αPD-L1 treatment in lab-infected animals had limited antiviral effects. In contrast, animals with naturally acquired WHV infections displayed elevated PD-1 and PD-L1. In these same animals, combination therapy with αPD-L1 and entecavir (ETV) improved control of viremia and antigenemia compared to ETV treatment alone, but with efficacy restricted to a minority of animals. Pre-treatment WHV surface antigen (sAg) level was identified as a statistically significant predictor of treatment response, while PD-1 expression on peripheral CD8+ T cells, T cell production of interferon gamma (IFN-γ) upon in vitro antigen stimulation (WHV ELISPOT), and circulating levels of liver enzymes were not. To further assess the safety of this strategy, αPD-L1 was tested in acute WHV infection to model the risk of liver damage when the extent of hepatic infection and antiviral immune responses were expected to be the greatest. No significant increase in serum markers of hepatic injury was observed over those in infected, untreated control animals. These data support a positive benefit/risk assessment for blockade of the PD-1:PD-L1 pathway in CHB patients and may help to identify patient groups most likely to benefit from treatment. Furthermore, the efficacy of αPD-L1 in only a minority of animals, as observed here, suggests that additional agents may be needed to achieve a more robust and consistent response leading to full sAg loss and durable responses through anti-sAg antibody seroconversion. PMID:29444087

The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis.

PubMed

Shen, Lei; Shi, Hong; Gao, Yan; Ou, Qinfang; Liu, Qianqian; Liu, Yuanyuan; Wu, Jing; Zhang, Wenhong; Fan, Lin; Shao, Lingyun

2016-12-01

PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased significantly in ATB patients than HD. ATB patients had a higher proportion of regulatory T cells (Treg, CD4 + CD25 + Foxp3+) than HD. The expressions of PD-1 and PD-L1 increased remarkably on CD4+T cell subsets, including Treg cells, Tresp (CD4 + CD25 - ) cells and Teff (CD4 + CD25 + Foxp3-) cells. Finally, clinical improvement following effective anti-TB therapy is correlated with significantly decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells. Thus, expression profiles of PD-1 in T cell subpopulations may be used as a candidate to predict the clinical efficacy of anti-tuberculosis therapy. Modulation of PD-1/PD-L1 pathway in CD4 subsets may offer an immunotherapy target for the control of tuberculosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

DNA hypermethylation and X chromosome inactivation are major determinants of phenotypic variation in women heterozygous for G6PD mutations.

PubMed

Wang, Jin; Xiao, Qi-Zhi; Chen, You-Ming; Yi, Sheng; Liu, Dun; Liu, Yan-Hui; Zhang, Cui-Mei; Wei, Xiao-Feng; Zhou, Yu-Qiu; Zhong, Xing-Ming; Zhao, Cun-You; Xiong, Fu; Wei, Xiang-Cai; Xu, Xiang-Min

2014-12-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked incompletely dominant enzyme deficiency that results from G6PD gene mutations. Women heterozygous for G6PD mutations exhibit variation in the loss of enzyme activity but the cause of this phenotypic variation is unclear. We determined DNA methylation and X-inactivation patterns in 71 G6PD-deficient female heterozygotes and 68 G6PD non-deficient controls with the same missense mutations (G6PD Canton c.1376G>T or Kaiping c.1388G>A) to correlate determinants with variable phenotypes. Specific CpG methylations within the G6PD promoter were significantly higher in G6PD-deficient heterozygotes than in controls. Preferential X-inactivation of the G6PD wild-type allele was determined in heterozygotes. The incidence of preferential X-inactivation was 86.2% in the deficient heterozygote group and 31.7% in the non-deficient heterozygote group. A significant negative correlation was observed between X-inactivation ratios of the wild-type allele and G6PD/6-phosphogluconate dehydrogenase (6PGD) ratios in heterozygous G6PD Canton (r=-0.657, p<0.001) or Kaiping (r=-0.668, p<0.001). Multivariate logistic regression indicated that heterozygotes with hypermethylation of specific CpG sites in the G6PD promoter and preferential X-inactivation of the wild-type allele were at risk of enzyme deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

[PD-L1 expression and PD-1/PD-L1 inhibitors in breast cancer].

PubMed

Monneur, Audrey; Gonçalves, Anthony; Bertucci, François

2018-03-01

The development of immune checkpoints inhibitors represents one of the major recent advances in oncology. Monoclonal antibodies directed against the programmed cell death protein 1 (PD-1) or its ligand (PD-L1) provides durable disease control, particularly in melanoma, lung, kidney, bladder and head and neck cancers. The purpose of this review is to synthesize current data on the expression of PD-L1 in breast cancer and on the preliminary clinical results of PD-1/PD-L1 inhibitors in breast cancer patients. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infiltrating lymphocytes as well as the presence of poor-prognosis factors, such as young age, high grade, ER-negativity, PR-negativity, and HER-2 overexpression, high proliferative index, and aggressive molecular subtypes (triple negative, basal-like, HER-2-overexpressing). Its prognostic value remains controversial when assessed with immunohistochemistry, whereas it seems favorable in triple-negative cancers when assessed at the mRNA level. Early clinical trials with PD-1/PD-L1 inhibitors in breast cancer have shown efficacy in terms of tumor response and/or disease control in refractory metastatic breast cancers, notably in the triple-negative subtype. Many trials are currently underway, both in the metastatic and neo-adjuvant setting. A crucial issue is identification of biomarkers predictive of response to PD-1/PD-L1 inhibitors. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson’s disease

PubMed Central

Furlong, Melissa; Tanner, Caroline M; Goldman, Samuel M; Bhudhikanok, Grace S.; Blair, Aaron; Chade, Anabel; Comyns, Kathleen; Hoppin, Jane A.; Kasten, Meike; Korell, Monica; Langston, J William; Marras, Connie; Meng, Cheryl; Richards, Marie; Ross, G Webster; Umbach, David M; Sandler, Dale P; Kamel, Freya

2014-01-01

Pesticides have been associated with Parkinson’s disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) Study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥ 5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥ 2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p=0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p=0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among people who used <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among people who used 2 or more practices (interaction p=0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides. PMID:25461423

Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson's Disease Susceptibility.

PubMed

Liu, Guiyou; Liu, Yongquan; Jiang, Qinghua; Jiang, Yongshuai; Feng, Rennan; Zhang, Liangcai; Chen, Zugen; Li, Keshen; Liu, Jiafeng

2016-09-01

A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk. A recent study indicated no evidence of the involvement of this variant in Parkinson's disease (PD). Here, we used the genetic and expression data to reinvestigate the potential association between TREM2 and PD susceptibility. In stage 1, using 10 independent studies (N = 89,157; 8787 cases and 80,370 controls), we conducted a subgroup meta-analysis. We identified a significant association between rs75932628 and PD (P = 3.10E-03, odds ratio (OR) = 3.88, 95 % confidence interval (CI) 1.58-9.54) in No-Northern Europe subgroup, and significantly increased PD risks (P = 0.01 for Mann-Whitney test) in No-Northern Europe subgroup than in Northern Europe subgroup. In stage 2, we used the summary results from a large-scale PD genome-wide association study (GWAS; N = 108,990; 13,708 cases and 95,282 controls) to search for other TREM2 variants contributing to PD susceptibility. We identified 14 single-nucleotide polymorphisms (SNPs) associated with PD within 50-kb upstream and downstream range of TREM2. In stage 3, using two brain expression GWAS datasets (N = 773), we identified 6 of the 14 SNPs regulating increased expression of TREM2. In stage 4, using the whole human genome microarray data (N = 50), we further identified significantly increased expression of TREM2 in PD cases compared with controls in human prefrontal cortex. In summary, convergent genetic and expression datasets demonstrate that TREM2 is a potent risk factor for PD and may be a therapeutic target in PD and other neurodegenerative diseases.

Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson's disease.

PubMed

Furlong, Melissa; Tanner, Caroline M; Goldman, Samuel M; Bhudhikanok, Grace S; Blair, Aaron; Chade, Anabel; Comyns, Kathleen; Hoppin, Jane A; Kasten, Meike; Korell, Monica; Langston, J William; Marras, Connie; Meng, Cheryl; Richards, Marie; Ross, G Webster; Umbach, David M; Sandler, Dale P; Kamel, Freya

2015-02-01

Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p=0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p=0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p=0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides. Published by Elsevier Ltd.

Increased suicide risk and clinical correlates of suicide among patients with Parkinson's disease.

PubMed

Lee, Taeyeop; Lee, Hochang Benjamin; Ahn, Myung Hee; Kim, Juyeon; Kim, Mi Sun; Chung, Sun Ju; Hong, Jin Pyo

2016-11-01

Parkinson's disease (PD) is a debilitating, neurodegenerative condition frequently complicated by psychiatric symptoms. Patients with PD may be at higher risk for suicide than the general population, but previous estimates are limited and conflicting. The aim of this study is to estimate the suicide rate based on the clinical case registry and to identify risk factors for suicide among patients diagnosed with PD. The target sample consisted of 4362 patients diagnosed with PD who were evaluated at a general hospital in Seoul, South Korea, from 1996 to 2012. The standardized mortality ratio for suicide among PD patients was estimated. In order to identify the clinical correlates of suicide, case-control study was conducted based on retrospective chart review. The 29 suicide cases (age: 62.3 ± 13.7 years; females: 34.5%) were matched with 116 non-suicide controls (age: 63.5 ± 9.2 years; females 56.9%) by the year of initial PD evaluation. The SMR for suicide in PD patients was 1.99 (95% CI 1.33-2.85). Mean duration from time of initial diagnosis to suicide among cases was 6.1 ± 3.5 years. Case-control analysis revealed that male, initial extremity of motor symptom onset, history of depressive disorder, delusion, any psychiatric disorder, and higher L-dopa dosage were significantly associated with suicide among PD patients. Other PD-related variables such as UPDRS motor score were not significantly associated with death by suicide. Suicide risk in PD patients is approximately 2 times higher than that in the general population. Psychiatric disorders, and also L-dopa medication need further attention with respect to suicide. Copyright © 2016 Elsevier Ltd. All rights reserved.

SNCA polymorphisms, smoking, and sporadic Parkinson's disease in Japanese.

PubMed

Miyake, Yoshihiro; Tanaka, Keiko; Fukushima, Wakaba; Kiyohara, Chikako; Sasaki, Satoshi; Tsuboi, Yoshio; Yamada, Tatsuo; Oeda, Tomoko; Shimada, Hiroyuki; Kawamura, Nobutoshi; Sakae, Nobutaka; Fukuyama, Hidenao; Hirota, Yoshio; Nagai, Masaki

2012-06-01

Several case-control studies and genome-wide association studies have examined the relationships between single nucleotide polymorphisms (SNPs) in the SNCA gene and Parkinson's disease (PD), and have provided inconsistent results. We investigated the relationships between SNPs rs356229, rs356219, rs356220, rs7684318, and rs2736990 and the risk of sporadic PD in Japan using data from a multicenter hospital-based case-control study. Included were 229 cases within 6 years of onset of PD as defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. Based on the recessive model, compared with subjects with the CC or CT genotype of SNP rs356220, those with the TT genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.42 (95% CI: 1.002-2.02). In the additive model, SNP rs2736990 was significantly related to the risk of sporadic PD: the adjusted OR was 1.30 (95% CI: 1.002-1.68). There were no significant relationships between SNP rs356229, rs356219, or rs7684318 and the risk of sporadic PD in any genetic model. The additive interactions between SNPs rs356219 and rs356220 and smoking with respect to sporadic PD were significant although the multiplicative interactions were not significant. This study suggests that SNCA SNPs rs356220 and rs2736990 are significantly associated with the risk of sporadic PD in Japanese. We also present new evidence for biological interactions between SNPs rs356219 and rs356220 and smoking that affect sporadic PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes.

PubMed

Choukem, S P; Sobngwi, E; Garnier, J P; Letellier, S; Mauvais-Jarvis, F; Calvo, F; Gautier, J-F

2015-09-01

Previously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels. In the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40 min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables. The maximum plasma glucose level after 200 min of glucose perfusion was 20.9±3.7 mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=-0.085, P=0.38). Neither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The Human Ortholog of Acid-Sensing Ion Channel Gene ASIC1a Is Associated With Panic Disorder And Amygdala Structure And Function

PubMed Central

Smoller, Jordan W.; Gallagher, Patience J.; Duncan, Laramie E.; McGrath, Lauren M.; Haddad, Stephen A.; Holmes, Avram.; Wolf, Aaron B.; Hilker, Sidney; Block, Stefanie R.; Weill, Sydney; Young, Sarah; Choi, Eun Young; Rosenbaum, Jerrold F.; Biederman, Joseph; Faraone, Stephen V.; Roffman, Joshua; Manfro, Gisele G.; Blaya, Carolina; Hirshfeld-Becker, Dina R.; Stein, Murray B.; Van Ameringen, Michael; Tolin, David F.; Otto, Michael W.; Pollack, Mark H.; Simon, Naomi M.; Buckner, Randy L.; Ongur, Dost; Cohen, Bruce M.

2014-01-01

Background Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide (CO2), possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that CO2-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods We conducted a case-control analysis (N=414 PD cases, 846 healthy controls) of ACCN2single nucleotide polymorphisms (SNPs) and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n=1,048) and/or task-evoked reactivity to emotional stimuli (n=103) in healthy individuals. Results Two SNPs at the ACCN2 locus showed evidence of association with PD: rs685012 (OR=1.32, gene-wise corrected p=0.011) and rs10875995 (OR=1.26, gene-wise corrected p=0.046). The association appeared to be stronger when early-onset (age ≤ 20) PD cases and when cases with prominent respiratory symptoms were compared to controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p=0.035), as well as task-evoked amygdala reactivity to fearful and angry faces (p=0.0048). Conclusions Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to anxiety proneness. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD. PMID:24529281

Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17 Imbalance from Asthmatic Children.

PubMed

Xi, Xia; Liu, Jing-Mei; Guo, Jun-Ying

2018-06-06

The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in asthma pathogenesis, but no therapeutic targets could modulate the Th17/Treg balance specifically for asthma. Since previous studies have shown the programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis in this disease, we hypothesized that the PD-1/PD-L1 pathway might be involved in the regulation of Treg/Th17 imbalance in asthmatic children. The percentage of Treg and Th17 cells and the expression of PD-1 and PD-L1 were detected by flow cytometry in children with asthma and healthy controls. CD4+ T cells were stimulated with Th17 and Treg differentiating factors, and treated with anti-PD-1. Then cells were harvested and measured for Th17 and Treg percentages and Foxp3 and RORγt levels using RT-PCR. We observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 in the two subsets also changed in the mild persistent and moderate to severe persistent groups compared with healthy controls. In vitro, administration of anti-PD-1 could decrease Th17 percentages and RORγt mRNA, and increase Treg percentages and Foxp3 mRNA in CD4+ T cells of children with asthma in the mild persistent and moderate to persistent groups. Additionally, the role played by anti-PD-1 in regulating Treg/Th17 balance was further confirmed in an asthmatic mouse model. Alteration of the PD-1/PD-L1 pathway can modulate Treg/Th17 balance in asthmatic children. Treatment with anti-PD-1 posed protective effects on asthma models, providing a novel theoretical target for asthma. © 2018 S. Karger AG, Basel.

Automatic sleep classification using a data-driven topic model reveals latent sleep states.

PubMed

Koch, Henriette; Christensen, Julie A E; Frandsen, Rune; Zoetmulder, Marielle; Arvastson, Lars; Christensen, Soren R; Jennum, Poul; Sorensen, Helge B D

2014-09-30

The golden standard for sleep classification uses manual scoring of polysomnography despite points of criticism such as oversimplification, low inter-rater reliability and the standard being designed on young and healthy subjects. To meet the criticism and reveal the latent sleep states, this study developed a general and automatic sleep classifier using a data-driven approach. Spectral EEG and EOG measures and eye correlation in 1s windows were calculated and each sleep epoch was expressed as a mixture of probabilities of latent sleep states by using the topic model Latent Dirichlet Allocation. Model application was tested on control subjects and patients with periodic leg movements (PLM) representing a non-neurodegenerative group, and patients with idiopathic REM sleep behavior disorder (iRBD) and Parkinson's Disease (PD) representing a neurodegenerative group. The model was optimized using 50 subjects and validated on 76 subjects. The optimized sleep model used six topics, and the topic probabilities changed smoothly during transitions. According to the manual scorings, the model scored an overall subject-specific accuracy of 68.3 ± 7.44 (% μ ± σ) and group specific accuracies of 69.0 ± 4.62 (control), 70.1 ± 5.10 (PLM), 67.2 ± 8.30 (iRBD) and 67.7 ± 9.07 (PD). Statistics of the latent sleep state content showed accordances to the sleep stages defined in the golden standard. However, this study indicates that sleep contains six diverse latent sleep states and that state transitions are continuous processes. The model is generally applicable and may contribute to the research in neurodegenerative diseases and sleep disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Integrated PK-PD and agent-based modeling in oncology.

PubMed

Wang, Zhihui; Butner, Joseph D; Cristini, Vittorio; Deisboeck, Thomas S

2015-04-01

Mathematical modeling has become a valuable tool that strives to complement conventional biomedical research modalities in order to predict experimental outcome, generate new medical hypotheses, and optimize clinical therapies. Two specific approaches, pharmacokinetic-pharmacodynamic (PK-PD) modeling, and agent-based modeling (ABM), have been widely applied in cancer research. While they have made important contributions on their own (e.g., PK-PD in examining chemotherapy drug efficacy and resistance, and ABM in describing and predicting tumor growth and metastasis), only a few groups have started to combine both approaches together in an effort to gain more insights into the details of drug dynamics and the resulting impact on tumor growth. In this review, we focus our discussion on some of the most recent modeling studies building on a combined PK-PD and ABM approach that have generated experimentally testable hypotheses. Some future directions are also discussed.

Integrated PK-PD and Agent-Based Modeling in Oncology

PubMed Central

Wang, Zhihui; Butner, Joseph D.; Cristini, Vittorio

2016-01-01

Mathematical modeling has become a valuable tool that strives to complement conventional biomedical research modalities in order to predict experimental outcome, generate new medical hypotheses, and optimize clinical therapies. Two specific approaches, pharmacokinetic-pharmacodynamic (PK-PD) modeling, and agent-based modeling (ABM), have been widely applied in cancer research. While they have made important contributions on their own (e.g., PK-PD in examining chemotherapy drug efficacy and resistance, and ABM in describing and predicting tumor growth and metastasis), only a few groups have started to combine both approaches together in an effort to gain more insights into the details of drug dynamics and the resulting impact on tumor growth. In this review, we focus our discussion on some of the most recent modeling studies building on a combined PK-PD and ABM approach that have generated experimentally testable hypotheses. Some future directions are also discussed. PMID:25588379

From portable dialysis to a bioengineered kidney.

PubMed

van Gelder, Maaike K; Mihaila, Silvia M; Jansen, Jitske; Wester, Maarten; Verhaar, Marianne C; Joles, Jaap A; Stamatialis, Dimitrios; Masereeuw, Roos; Gerritsen, Karin G F

2018-05-01

Since the advent of peritoneal dialysis (PD) in the 1970s, the principles of dialysis have changed little. In the coming decades, several major breakthroughs are expected. Areas covered: Novel wearable and portable dialysis devices for both hemodialysis (HD) and PD are expected first. The HD devices could facilitate more frequent and longer dialysis outside of the hospital, while improving patient's mobility and autonomy. The PD devices could enhance blood purification and increase technique survival of PD. Further away from clinical application is the bioartificial kidney, containing renal cells. Initially, the bioartificial kidney could be applied for extracorporeal treatment, to partly replace renal tubular endocrine, metabolic, immunoregulatory and secretory functions. Subsequently, intracorporeal treatment may become possible. Expert commentary: Key factors for successful implementation of miniature dialysis devices are patient attitudes and cost-effectiveness. A well-functioning and safe extracorporeal blood circuit is required for HD. For PD, a double lumen PD catheter would optimize performance. Future research should focus on further miniaturization of the urea removal strategy. For the bio-artificial kidney (BAK), cost effectiveness should be determined and a general set of functional requirements should be defined for future studies. For intracorporeal application, water reabsorption will become a major challenge.

[Dysphagia in Parkinson's Disease: Pathophysiology, Diagnosis and Therapy].

PubMed

Suttrup, I; Warnecke, T

2016-07-01

Oropharyngeal and esophageal dysphagia are a frequent, but seldom diagnosed symptom of Parkinson's disease (PD). More than 80 % of patients with PD develop dysphagia during the course of their disease leading to a reduced quality of life, complicated medication intake, malnutrition and aspiration pneumonia, which is a major cause of death in PD. The underlying pathophysiology is poorly understood. Impaired dopaminergic and non-dopaminergic mechanisms of the cortical swallowing network as well as peripheral neuromuscular involvement have been suggested to contribute to its multifactorial genesis. Diagnostic screening methods include PD-specific questionnaires and a modified water test. Fiber optic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS), which complement each other, are the gold standard for evaluation of PD-related dysphagia. For evaluation of esophageal dysphagia, the high-resolution manometry (HRM) may be a helpful tool. In addition to dysphagia-specific treatment by speech and language therapists (SLTs), optimized dopaminergic medication is a meaningful therapeutic option. A promising novel method is intensive training of expiratory muscle strength (EMST). Deep brain stimulation does not seem to have a clinically relevant effect on swallowing function in PD. © Georg Thieme Verlag KG Stuttgart · New York.