Non-Motor Symptoms in Patients with Parkinson’s Disease – Correlations with Inflammatory Cytokines in Serum

Background

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder of the central nervous system. Motor symptoms are the focus of pharmacotherapy, yet non-motor features of the disease (e.g. fatigue, mood disturbances, sleep disturbances and symptoms of anxiety) are both common and disabling for the patient. The pathophysiological mechanisms behind the non-motor symptoms in PD are yet to be untangled. The main objective of this study was to investigate associations between pro-inflammatory substances and non-motor symptoms in patients with PD.

Methods and Materials

We measured C-reactive protein, interleukin (IL)-6, soluble IL-2 receptor (sIL-2R) and tumor necrosis factor-α (TNF-α) in blood samples from PD patients (n = 86) and healthy controls (n = 40). Symptoms of fatigue, depression, anxiety and sleeping difficulties were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT), the Hospital Anxiety and Depression Scale (HAD), and the Scales for Outcome in PD-Sleep Scale respectively.

Results

IL-6 was significantly higher in PD patients than in healthy controls. Compared to healthy controls, PD patients displayed significantly higher mean scores on HAD and lower scores on FACIT, thus indicating more severe symptoms as measured with these scales. Within the PD sample, high levels of both sIL-2R and TNF-α were significantly associated with more severe symptoms assessed by means of FACIT and HAD (depression and anxiety subscales). SIL-2-R levels were able to significantly predict FACIT and HAD scores after the effects of age, gender, anti-parkinsonian medications, and severity of motor symptoms were controlled for.

Discussion

We suggest that non-motor symptoms in PD patients, such as fatigue and depressive symptoms, might be generated via inflammatory mechanisms. This knowledge might contribute to the development of novel treatment options in PD, specifically targeting non-motor symptoms.     

TRIM5α associates with proteasomal subunits in cells while in complex with HIV-1 virions

Background

The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6.

Results

Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site.

Conclusions

Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions.     

Root growth in biopores—evaluation with in situ endoscopy

Background and aims

The significance of biopores for nutrient acquisition from the subsoil depends on root-soil contact, which in turn is influenced by root architecture. The aim of this study was to detect differences regarding the architecture and root-soil contact of homorhizous barley roots (Hordeum vulgare L.) and allorhizous oilseed rape roots (Brassica napus L.) growing in biopores.

Methods

In situ endoscopy was used as a technique that allows non-destructive display of pore wall characteristics and root morphology inside large biopores under field conditions.

Results

For both crops, about 85 % of all roots did establish contact to the pore wall. However, according to their different root architecture, the two crops varied in their strategy of resource acquisition: While barley was characterized by thin vertical or ingrowing roots, most of them in direct contact to the pore wall, oilseed rape established contact to the pore wall predominantly via lateral roots.

Conclusions

Root morphological and pore wall assessment with in situ endoscopy in combination with detailed studies of soil biochemical and soil physical parameters of the pore wall is considered an essential prerequisite for more precise future modelling of nutrient acquisition and uptake.     

Asymmetry in genitalia is in sync with lateralized mating behavior but not with the lateralization of other behaviors

Asymmetries in bilateral organisms attract a lot of curiosity given that they are conspicuous departures from the norm.They allow the investigation of the integration at different levels of biological organization.Here we study whether and how behavioral and asymmetrical anatomical traits coevolved and work together.We ask if asymmetry is determined locally for each trait or at a whole individual level in a species bearing conspicuous asymmetrical genitalia.Asymmetric genitalia evolved in many species;however,in most cases the direction of asymmetry is fixed.Therefore,it has been rarely determined if there is an association between the direction of asymmetry in genitalia and other traits.In onesided livebearer fish of the genus Jenynsia(Cyprinodontiformes,Anablepidae),the anal fin of males is modified into a gonopodium,an intromittent organ that serves to inseminate females.The gonopodium shows a conspicuous asymmetry,with its tip bending either to the left or the right.By surveying 13 natural populations of Jenynsia lineata,we found that both genital morphs are equally common in wild populations.In a series of experiments in a laboratory population,we discovered asymmetry and lateralization for multiple other traits;yet,the degree of integration varied highly among them.Lateralization in exploratory behavior in response to different stimuli was not associated with genital morphology.Interestingly,the direction of genital asymmetry was positively correlated with sidedness of mating preference and the number of neuromasts in the lateral line.This suggests integration of functionally linked asymmetric traits;however,there is no evidence that asymmetry is determined at the whole individual level in our study species.     

Does variation in morphology correspond with variation in habitat use in freshwater gastropods?

We tested if variations (i.e., breadth) in morphology and habitat use vary predictably among six aquatic gastropod species that were collected across Indiana and Illinois, USA. We predicted that interspecific morphological variation would positively covary with variation in habitat use among species. We used geometric morphometrics (Procrustes technique and relative warp analysis) to quantify morphology and multivariate analyses (PCA) to quantify habitat. Increased morphological breadth did not vary predictably with increased habitat breadth. However, we found that life history traits correspond with patterns in morphological and habitat breadth for these six aquatic gastropods. Pulmonate gastropods (use lungs for respiration) that lack an operculum cover exhibited decreased morphological breadth compared to coenogastropods (use gills for respiration). This pattern may ultimately be a function of behavioral adaptations in freshwater gastropods. Gastropods that are capable of breathing air or using other behavioral modifications such as burrowing to escape predators may not require high morphological breadth. Conversely, selection may favor higher morphological breadth in gastropods with gills that also do not move out of the water column to escape predators.     

Is Treatment with Trimetazidine Beneficial in Patients with Chronic Heart Failure?

Background

Whether additional benefit can be achieved with the use of trimetazidine (TMZ) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of TMZ treatment in CHF patients.

Methods

We searched PubMed, EMBASE, and Cochrane databases through October 2013 and included 19 RCTs involving 994 CHF patients who underwent TMZ or placebo treatment. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models.

Results

TMZ therapy was associated with considerable improvement in left ventricular ejection fraction (WMD: 7.29%, 95% CI: 6.49 to 8.09, p<0.01) and New York Heart Association classification (WMD: −0.55, 95% CI: −0.81 to −0.28, p<0.01). Moreover, treatment with TMZ also resulted in significant decrease in left ventricular end-systolic volume (WMD: −17.09 ml, 95% CI: −20.15 to −14.04, p<0.01), left ventricular end-diastolic volume (WMD: −11.24 ml, 95% CI: −14.06 to −8.42, p<0.01), hospitalization for cardiac causes (RR: 0.43, 95% CI: 0.21 to 0.91, p = 0.03), B-type natriuretic peptide (BNP; WMD: −157.08 pg/ml, 95% CI: −176.55 to −137.62, p<0.01) and C-reactive protein (CRP; WMD: −1.86 mg/l, 95% CI: −2.81 to −0.90, p<0.01). However, there were no significant differences in exercise duration and all-cause mortality between patients treated with TMZ and placebo.

Conclusions

TMZ treatment in CHF patients may improve clinical symptoms and cardiac function, reduce hospitalization for cardiac causes, and decrease serum levels of BNP and CRP.     

Ethics in Indigenous Research – Connecting with Community

The challenge for those responsible for funding, brokering and assessing the merit of proposed Indigenous research is to identify and then work co-operatively with appropriate representatives of Indigenous interests in order to increase the flow of benefits from research to Indigenous peoples. Experience in Australia has shown that this is not a straightforward process. In this paper we indicate some reasons why it is important for the research community to broker research with representative Indigenous organisations and to involve Indigenous peoples in the ethical assessment and conduct of research. We then identify some barriers to the achievement of these objectives and outline recently developed interventions from the field of health research that aim to promote a more effective working relationship between Indigenous peoples and members of the research community.

Socio-Demographic and Clinical Differences in Subjects with Tuberculosis with and without Diabetes Mellitus in Brazil – A Multivariate Analysis

Background

Several studies have evaluated the relationship between diabetes mellitus (DM) and tuberculosis (TB), but the nature of this relationship is not fully understood. TB incidence may be influenced by immunosuppression from DM, but this association may be confounded by other clinical and socioeconomic factors. We aimed to assess socio-demographic and clinical differences in TB patients with and without DM.

Methods

Using the Brazilian national surveillance system (SINAN), we compared 1,797 subjects with TB and DM with 29,275 subjects diagnosed with TB only in 2009. We performed multivariate analysis to identify factors associated with the presence of DM among TB patients.

Results

Subjects with TB – DM were older; have initial positive sputum smear test (OR = 1.42, 95% CI 1.26–1.60), and were more likely to die from TB (OR = 1.44, 95% CI 1.03–2.01). They were less likely to have been institutionalized [in prison, shelter, orphanage, psychiatric hospital (OR = 0.74, 95% CI 0.60–0.93)]; developed extra pulmonary TB (OR = 0.62, 95% CI 0.51–0.75) and to return to TB treatment after abandonment (OR = 0.66, 95% CI 0.51–0.86).

Conclusions

Prevalence of NCD continues to rise in developing countries, especially with the rise of elderly population, the prevention and treatment of infectious diseases will be urgent. DM and TB represent a critical intersection between communicable and non-communicable diseases in these countries and the effect of DM on TB incidence and outcomes provide numerous opportunities for collaboration and management of these complex diseases in the national public health programs.     

Monitoring in vivo changes in lung microstructure with ³He MRI in Sendai virus-infected mice

Recently, a Sendai virus (SeV) model of chronic obstructive lung disease has demonstrated an innate immune response in mouse airways that exhibits similarities to the chronic airway inflammation in human chronic obstructive pulmonary disease (COPD) and asthma, but the effect on distal lung parenchyma has not been investigated. The aim of our study is to image the time course and regional distribution of mouse lung microstructural changes in vivo after SeV infection. (1)H and (3)He diffusion magnetic resonance imaging (MRI) were successfully performed on five groups of C57BL/6J mice. (1)H MR images provided precise anatomical localization and lung volume measurements. (3)He lung morphometry was implemented to image and quantify mouse lung geometric microstructural parameters at different time points after SeV infection. (1)H MR images detected the SeV-induced pulmonary inflammation in vivo; spatially resolved maps of acinar airway radius R, alveolar depth h, and mean linear intercept Lm were generated from (3)He diffusion images. The morphometric parameters R and Lm in the infected group were indistinguishable from PBS-treated mice at day 21, increased slightly at day 49, and were increased with statistical significance at day 77 (p = 0.02). Increases in R and Lm of infected mice imply that there is a modest increase in alveolar duct radius distal to airway inflammation, particularly in the lung periphery, indicating airspace enlargement after virus infection. Our results indicate that (3)He lung morphometry has good sensitivity in quantifying small microstructural changes in the mouse lung and that the Sendai mouse model has the potential to be a valid murine model of COPD.     

Decreases in Plasma Aβ1-40 Levels with Aging in Non-Demented Elderly with ApoE-ε4 Allele

This report examines plasma amyloid proteins A40 and A42 and apolipoprotein E (apoE) levels and their relationships with age in non-demented older adults with (N = 32) or without the apoE-4 allele (N = 94). A levels did not differ between the groups whereas the 4 allele was associated with a significant reduction in plasma apoE. In subjects with the 4 allele, increasing age was associated with significant reduction in plasma A40. Subjects without the 4 allele showed a significant positive correlation between A40 and A42 levels. There was also a significant correlation between plasma A40 and apoE levels in all subjects.     

The marked decrease in cardiac MIBG-uptake correlates with the severity of sleep disturbance in patients with Parkinson’s disease

Sleep and Biological Rhythms - We investigated the relationship between sleep disturbances and 123I-meta-iodobenzylguanidine (MIBG)-uptake during myocardial scintigraphy in patients with...     

‘On-farm’ seed priming with zinc in chickpea and wheat in Pakistan

A series of on-station trials was implemented between 2002 and 2006 to assess the response of wheat (Triticum aestivum L.) and chickpea (Cicer arietinum) to zinc (Zn) added by soaking seeds (priming) in solutions of ZnSO₄ before sowing. Wheat seed was primed for 10 h in 0.3% Zn and chickpea for 6 h in 0.05% Zn. Seed treatments increased the seed concentration in wheat from 27 to 470 mg/kg and in chickpea from 49 to 780 mg/kg. Priming wheat seeds with 0.3% Zn significantly increased the mean shoot dry mass, Zn concentration and Zn uptake of 15-day-old seedlings relative to non-primed controls and seeds primed with water alone. Using 0.4% Zn further increased shoot Zn concentration but depressed shoot dry mass to the level of the non-primed control. In seven trials, mean grain yield of wheat was significantly increased from 2.28 to 2.42 t/ha (6%) by priming with water alone and to 2.61 t/ha (14%) by priming with 0.3% Zn. Mean grain yield of chickpea in seven trials was increased significantly from 1.39 to 1.65 t/ha (19%) by priming seeds with 0.05% Zn. The effect of priming chickpea seeds with water was intermediate (1.49 t/ha) and not statistically separable from the non-primed and zinc-primed treatments. Increased grain yield due to priming in both crops was associated with increases in total biomass but there was no significant effect of priming on harvest index. In addition to increasing yield, priming seeds with Zn also significantly increased grain zinc concentration, by 12% in wheat (mean of three trials) and by 29% in chickpea (one trial) and the total amount of Zn taken up by the grain (by 27% in wheat and by 130% in chickpea). Using ZnSO₄ to prime seeds was very cost-effective, with net benefit-to-cost ratios of 75 for wheat and 780 for chickpea. An erratum to this article can be found at     

Age-associated alterations in γδ T-cells are present predominantly in individuals infected with Cytomegalovirus

Background

Despite the common perception that latent Cytomegalovirus (CMV) infection is usually symptom-free, emerging epidemiological evidence suggests that it may in fact be associated with higher mortality over extended follow-up. Mechanisms responsible for this potentially important effect are unclear. CMV infection is known to have a large impact on the distribution of T cell phenotypes, especially the accumulation of late-stage differentiated CD8⁺, as well as Vδ2^- γδ T-cells, which are the main subset of γδ T-cells involved in anti-CMV immunity. Its impact on γδ T-cells in the aging context is less well-defined.

Results

Here, we investigated a group of healthy individuals aged between 21 and 89 years, in order to correlate the frequency and differentiation status of γδ T-cells with age. We found that these parameters were only marginally influenced by age, but were marked in people with a latent CMV infection. Thus, we observed a significant age-associated accumulation of late-differentiated T-cells within the Vδ2^- population, but only in CMV-seropositive donors. There was also a strong trend towards reduced frequency of early-differentiated cells within the Vδ2^- phenotype. Older people had significantly higher anti-CMV IgG titers, which in turn correlated significantly with a lower Vδ2⁺/Vδ2^- ratio and a shift from early- to a late-differentiated Vδ2^- T-cell phenotype.

Conclusions

Our findings demonstrate a strong influence of CMV on γδ T-cells during human ageing, similar to that observed for αβ T-cells. Differences between donors of different ages are more marked in CMV-infected individuals. The biological implications of this potent age-associated CMV-mediated immune-modulation require clarification.

     

Changes with age in the absorption spectrum of chlorophyll α in a diatom

Summary Absorption spectra of a young and an old culture of the diatom Pheodactylum tricornutum were measured in thin layers between two opal glass sheets. The spectra at 24° and at -196°C were replotted to give equal areas from 730–625 m to allow direct comparison. At 24°C the spectrum for the difference between the two cultures had a negative component of 18 m half width centered at 675 m and a positive region of W_0.5=26 m near 700 m.The spectra at -196°C may be somewhat distorted by clumping of the cells during freezing but nevertheless the 16 day culture clearly showed a smaller proportion of Ca 670 to Ca 680. This older culture has a shoulder due to a 707 m component. The difference curve at -196°C shows the decrease of an unsymmetrical band peaking at 669 m and an increase at 695 m in addition to the 707 m component. Due to the possibility of distortion, the presence of an actual component at 695 is doubtful in these particular cultures.The room temperature spectrum in the chloropyhll a region for the 5 day culture can be closely fitted by a single probability curve at 675 m having a half-width of 31 m. The sum of two components, with widths more reasonable for chlorophylls, also matched the data well enough. These two probability curves, of 22 m half width, centered on 669 and 683.2 m and had a height ratio, h₆₆₉/h₆₈₃ of 1.18. In the 16 day culture the ratio for these bands changed to 1.11 and there was extra absorption around 700 m.Dedicated to Professor C. B. van Niel on the occasion of his 70th birthday     

Apoptotic effects of ε-viniferin in combination with cis-platin in C6 cells

Glioblastoma (GBM) is one of the most common and lethal forms of primary brain tumors in human adults. Treatment options are limited, and in most cases ineffective. Natural products are sources of novel compounds endowed with therapeutic properties in many human diseases like cancer. ε-viniferin is a resveratrol dimer and well known for having antiproliferative and apoptotic effects on cancer cells. Cisplatin is a platinum containing anti-cancer drug. In this study, we aimed to investigate antiproliferative and apoptotic effects of using cis-platin and ε-viniferin alone or in combined treatment of C6 cells. Cell proliferation was detected by WST-1. Mitochondrial membrane potential changes in the cells (ΔΨm) were evaluated using cationic dye JC1. Apoptotic index which is a hallmark of late apoptosis was detected by using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method and apoptotic alterations were observed by transmission electron microscope (TEM). Activation of caspase-8, -9, -3 in C6 cells at various incubation periods was measured by flow cytometer. Apoptotic index increased at highest level in only combined treatment cells (91.6%) after 48 h incubation. These results were supported by TEM images. Caspase-8 activation in C6 cells increased to a maximum (12.5%) after 6 h by using combined cis-platin/ε-viniferin treatment (13.25/95 μM). Caspase-9 was activated at 44.5% after combined treatment for 24 h. This rate is higher than using cis-platin (14.2%) or ε-viniferin (43.3%) alone. The combined 13.25 μM/cisplatin and 95 μM ε-viniferin treatment caused maximum caspase-3 activation in C6 cells (15.5%) at the end of the 72 h incubation. In conclusion, it was observed that caspase-8, -9, -3 activation which was determined in vitro, trigerred apoptotic mechanism in C6 cells by using low concentrations of combined cis-platin and ε-viniferin.     

Is Participation in Organized Leisure-Time Activities Associated with School Performance in Adolescence?

BackgroundOrganized leisure-time activities (OLTA) have been identified as a context suitable for improvement of school performance. This study aimed to assess the associations between participation in OLTA and school engagement, school-related stress, academic achievement and whether these associations differ by specific pattern of OLTA participation, gender and age. Furthermore, it assessed whether OLTA participants are more likely to acquire support for schoolwork from outside the family.MethodsThe sample concerned 10,483 adolescents (49.2% boys) aged 11, 13 and 15 from the Health Behaviour in School-aged Children data collection in 2014 in the Czech Republic. Logistic regressions adjusted for gender and age were used to analyse the associations between participation in OLTA and four education-related outcomes.ResultsParticipation in OLTA was associated with higher school engagement, lower levels of school-related stress and better academic achievement regardless of gender and age. The strongest associations were observed for adolescents involved in various types of OLTA concurrently, with odds ratios ranging from 1.34 (95% confidence interval (CI) 1.17–1.54) for lower school-related stress to 1.97 (95% CI 1.73–2.25) for above-average academic achievement. OLTA participants were also more likely to have a non-familial person to help them with schoolwork, though this association was weaker in 15-year-olds.ConclusionYouth involvement in OLTA is linked to general better school performance and attachment to school. Adolescents participating in more activities at the same time have the best school performance.     

Intraindividual Variability in Inhibitory Function in Adults with ADHD – An Ex-Gaussian Approach

Objective

Attention deficit disorder (ADHD) is commonly associated with inhibitory dysfunction contributing to typical behavioral symptoms like impulsivity or hyperactivity. However, some studies analyzing intraindividual variability (IIV) of reaction times in children with ADHD (cADHD) question a predominance of inhibitory deficits. IIV is a measure of the stability of information processing and provides evidence that longer reaction times (RT) in inhibitory tasks in cADHD are due to only a few prolonged responses which may indicate deficits in sustained attention rather than inhibitory dysfunction. We wanted to find out, whether a slowing in inhibitory functioning in adults with ADHD (aADHD) is due to isolated slow responses.

Methods

Computing classical RT measures (mean RT, SD), ex-Gaussian parameters of IIV (which allow a better separation of reaction time (mu), variability (sigma) and abnormally slow responses (tau) than classical measures) as well as errors of omission and commission, we examined response inhibition in a well-established GoNogo task in a sample of aADHD subjects without medication and healthy controls matched for age, gender and education.

Results

We did not find higher numbers of commission errors in aADHD, while the number of omissions was significantly increased compared with controls. In contrast to increased mean RT, the distributional parameter mu did not document a significant slowing in aADHD. However, subjects with aADHD were characterized by increased IIV throughout the entire RT distribution as indicated by the parameters sigma and tau as well as the SD of reaction time. Moreover, we found a significant correlation between tau and the number of omission errors.

Conclusions

Our findings question a primacy of inhibitory deficits in aADHD and provide evidence for attentional dysfunction. The present findings may have theoretical implications for etiological models of ADHD as well as more practical implications for neuropsychological testing in aADHD.     

Chloroquine–astemizole hybrids with potent in vitro and in vivo antiplasmodial activity

A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds 5–8 possessed improved in vitro activity against a CQ-resistant strain of Plasmodium falciparum, and examples 7 and 8 were active in vivo in mouse models of malaria.