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Background:
Arising from the relevance of sensorimotor training in the therapy of nonspecific low back pain patients and from the value of individualized therapy, the present trial aims to test the feasibility and efficacy of individualized sensorimotor training interventions in patients suffering from nonspecific low back pain.
Methods and study design:
A multicentre, single-blind two-armed randomized controlled trial to evaluate the
effects of a 12-week (3 weeks supervised centre-based and 9 weeks home-based) individualized sensorimotor exercise program is performed. The control group stays inactive during this period. Outcomes are pain, and pain-associated function as well as motor function in adults with nonspecific low back pain. Each participant is scheduled to five measurement dates: baseline (M1), following centre-based training (M2), following home-based training (M3) and at two follow-up time points 6 months (M4) and 12 months (M5) after M1. All investigations and the assessment of the primary and secondary outcomes are performed in a standardized order: questionnaires – clinical examination – biomechanics (motor function). Subsequent statistical procedures are executed after the examination of underlying assumptions for parametric or rather non-parametric testing.
Discussion:
The results and practical relevance of the study will be of clinical and practical relevance not only for researchers and policy makers but also for the general population suffering from nonspecific low back pain.
Trial registration:
Identification number DRKS00010129. German Clinical Trial registered on 3 March 2016.
Background:
All living cells display a rapid molecular response to adverse environmental conditions, and
the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair
the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock
protein (
hsp
) genes in
Caenorhabditis elegans
would affect their vulnerability to Manganese (Mn) toxicity.
Methods:
We exposed wild type and selected
hsp
mutant worms to Mn (30 min) and next evaluated
further the most susceptible strains. We analyzed survi
val, protein carbonylation (as a marker of oxidative
stress) and Parkinson
’
s disease related gene expression immediately after Mn exposure. Lastly, we observed
dopaminergic neurons in wild type worms and in
hsp-70
mutants following Mn treatment. Analysis of the
data was performed by one-way or two way ANOVA, depending on the case, followed by post-hoc
Bonferroni test if the overall
p
value was less than 0.05.
Results:
We verified that the loss of
hsp-70, hsp-3 and chn-1
increased the vulnerability to Mn, as
exposed mutant worms showed lower survival rate and increased protein oxidation. The importance of
hsp-70
against Mn toxicity was then corroborated in dopaminergic neurons, where Mn neurotoxicity was
aggravated. The lack of
hsp-70
also blocked the transcriptional upregulation of
pink1
, a gene that has been
linked to Parkinson
’
sdisease.
Conclusions:
Taken together, our data suggest that Mn exposu
re modulates heat shock protein expression,
particularly HSP-70, in
C. elegans
.Furthermore,lossof
hsp-70
increases protein oxidation and dopaminergic
neuronal degeneration following manganese exposure, which is associated with the inhibition of
pink1
increased expression, thus pot
entially exacerbating the v
ulnerability to this metal.
Background:
Environmental stress puts organisms at risk and requires specific stress-tailored responses to maximize
survival. Long-term exposure to stress necessitates a global reprogramming of the cellular activities at different
levels of gene expression.
Results:
Here, we use ribosome profiling and RNA sequencing to globally profile the adaptive response of
Arabidopsis thaliana
to prolonged heat stress. To adapt to long heat exposure, the expression of many genes is
modulated in a coordinated manner at a transcriptional and translational level. However, a significant group of
genes opposes this trend and shows mainly translational regulation. Different secondary structure elements are
likely candidates to play a role in regulating translation of those genes.
Conclusions:
Our data also uncover on how the subunit stoichiometry of multimeric protein complexes in plastids
is maintained upon heat exposure.
Background:
First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might
be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack
of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk.
Methods:
Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids,
biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal
cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835
incident cancer cases.
Results:
The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of
cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related
to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher
levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity
in the observed associations by lag time between blood draw and cancer diagnosis.
Conclusion:
Changes in blood lipid composition precede the diagnosis of common malignancies by several years.
Considering the consistency of the present results across three cancer types the observed alterations point to a
global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.
Aim: We aimed to identify patient characteristics and comorbidities that correlate with the initial exercise capacity of
cardiac rehabilitation (CR) patients and to study the significance of patient characteristics, comorbidities and training
methods for training achievements and final fitness of CR patients.
Methods: We studied 557 consecutive patients (51.7 Æ 6.9 years; 87.9% men) admitted to a three-week in-patient CR.
Cardiopulmonary exercise testing (CPX) was performed at discharge. Exercise capacity (watts) at entry, gain in training
volume and final physical fitness (assessed by peak O 2 utilization (VO 2peak ) were analysed using analysis of covariance
(ANCOVA) models.
Results: Mean training intensity was 90.7 Æ 9.7% of maximum heart rate (81% continuous/19% interval training, 64%
additional strength training). A total of 12.2 Æ 2.6 bicycle exercise training sessions were performed. Increase of training
volume by an average of more than 100% was achieved (difference end/beginning of CR: 784 Æ 623 watts  min). In the
multivariate model the gain in training volume was significantly associated with smoking, age and exercise capacity at
entry of CR. The physical fitness level achieved at discharge from CR as assessed by VO 2peak was mainly dependent on
age, but also on various factors related to training, namely exercise capacity at entry, increase of training volume and
training method.
Conclusion: CR patients were trained in line with current guidelines with moderate-to-high intensity and reached a
considerable increase of their training volume. The physical fitness level achieved at discharge from CR depended on
various factors associated with training, which supports the recommendation that CR should be offered to all cardiac
patients.
Editorial
(2016)
Background
Antiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)).
Methods
Sixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (β2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-β2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human β2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human β2GPI or after CL-micelle absorption.
Results
Comparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM aß2GPI and aCL. Anti-CL and anti-ß2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and ß2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL) + samples than in patients with APS. HumoAb against domain 1 recognized β2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-β2GPI humoAbs.
Conclusions
The LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.
A model analysis of mechanisms for radial microtubular patterns at root hair initiation sites
(2016)
Plant cells have two main modes of growth generating anisotropic structures. Diffuse growth where whole cell walls extend in specific directions, guided by anisotropically positioned cellulose fibers, and tip growth, with inhomogeneous addition of new cell wall material at the tip of the structure. Cells are known to regulate these processes via molecular signals and the cytoskeleton. Mechanical stress has been proposed to provide an input to the positioning of the cellulose fibers via cortical microtubules in diffuse growth. In particular, a stress feedback model predicts a circumferential pattern of fibers surrounding apical tissues and growing primordia, guided by the anisotropic curvature in such tissues. In contrast, during the initiation of tip growing root hairs, a star-like radial pattern has recently been observed. Here, we use detailed finite element models to analyze how a change in mechanical properties at the root hair initiation site can lead to star-like stress patterns in order to understand whether a stress-based feedback model can also explain the microtubule patterns seen during root hair initiation. We show that two independent mechanisms, individually or combined, can be sufficient to generate radial patterns. In the first, new material is added locally at the position of the root hair. In the second, increased tension in the initiation area provides a mechanism. Finally, we describe how a molecular model of Rho-of-plant (ROP) GTPases activation driven by auxin can position a patch of activated ROP protein basally along a 2D root epidermal cell plasma membrane, paving the way for models where mechanical and molecular mechanisms cooperate in the initial placement and outgrowth of root hairs.
Infants start learning the prosodic properties of their native language before 12 months, as shown by the emergence of a trochaic bias in English-learning infants between 6 and 9 months (Jusczyk et al., 1993), and in German-learning infants between 4 and 6 months (Huhle et al., 2009, 2014), while French-learning infants do not show a bias at 6 months (Hohle et al., 2009). This language-specific emergence of a trochaic bias is supported by the fact that English and German are languages with trochaic predominance in their lexicons, while French is a language with phrase-final lengthening but lacking lexical stress. We explored the emergence of a trochaic bias in bilingual French/German infants, to study whether the developmental trajectory would be similar to monolingual infants and whether amount of relative exposure to the two languages has an impact on the emergence of the bias. Accordingly, we replicated Hohle et al. (2009) with 24 bilingual 6-month-olds learning French and German simultaneously. All infants had been exposed to both languages for 30 to 70% of the time from birth. Using the Head Preference Procedure, infants were presented with two lists of stimuli, one made up of several occurrences of the pseudoword /GAba/ with word-initial stress (trochaic pattern), the second one made up of several occurrences of the pseudoword /gaBA/ with word-final stress (iambic pattern). The stimuli were recorded by a native German female speaker. Results revealed that these French/German bilingual 6-month olds have a trochaic bias (as evidenced by a preference to listen to the trochaic pattern). Hence, their listening preference is comparable to that of monolingual German-learning 6-month-olds, but differs from that of monolingual French-learning 6-month-olds who did not show any preference (Noble et al., 2009). Moreover, the size of the trochaic bias in the bilingual infants was not correlated with their amount of exposure to German. The present results thus establish that the development of a trochaic bias in simultaneous bilinguals is not delayed compared to monolingual German-learning infants (Hohle et al., 2009) and is rather independent of the amount of exposure to German relative to French.
Liverwort Blasia pusilla L. recruits soil nitrogen-fixing cyanobacteria of genus Nostoc as symbiotic partners. In this work we compared Nostoc community composition inside the plants and in the soil around them from two distant locations in Northern Norway. STRR fingerprinting and 16S rDNA phylogeny reconstruction showed a remarkable local diversity among isolates assigned to several Nostoc clades. An extensive web of negative allelopathic interactions was recorded at an agricultural site, but not at the undisturbed natural site. The cell extracts of the cyanobacteria did not show antimicrobial activities, but four isolates were shown to be cytotoxic to human cells. The secondary metabolite profiles of the isolates were mapped by MALDI-TOF MS, and the most prominent ions were further analyzed by Q-TOF for MS/MS aided identification. Symbiotic isolates produced a great variety of small peptide-like substances, most of which lack any record in the databases. Among identified compounds we found microcystin and nodularin variants toxic to eukaryotic cells. Microcystin producing chemotypes were dominating as symbiotic recruits but not in the free-living community. In addition, we were able to identify several novel aeruginosins and banyaside-like compounds, as well as nostocyclopeptides and nosperin.
Drugs as instruments
(2016)
Neuroenhancement (NE) is the non-medical use of psychoactive substances to produce a subjective enhancement in psychological functioning and experience. So far empirical investigations of individuals' motivation for NE however have been hampered by the lack of theoretical foundation. This study aimed to apply drug instrumentalization theory to user motivation for NE. We argue that NE should be defined and analyzed from a behavioral perspective rather than in terms of the characteristics of substances used for NE. In the empirical study we explored user behavior by analyzing relationships between drug options (use over-the-counter products, prescription drugs, illicit drugs) and postulated drug instrumentalization goals (e.g., improved cognitive performance, counteracting fatigue, improved social interaction). Questionnaire data from 1438 university students were subjected to exploratory and confirmatory factor analysis to address the question of whether analysis of drug instrumentalization should be based on the assumption that users are aiming to achieve a certain goal and choose their drug accordingly or whether NE behavior is more strongly rooted in a decision to try or use a certain drug option. We used factor mixture modeling to explore whether users could be separated into qualitatively different groups defined by a shared "goal X drug option" configuration. Our results indicate, first, that individuals decisions about NE are eventually based on personal attitude to drug options (e.g., willingness to use an over-the-counter product but not to abuse prescription drugs) rather than motivated by desire to achieve a specific goal (e.g., fighting tiredness) for which different drug options might be tried. Second, data analyses suggested two qualitatively different classes of users. Both predominantly used over-the-counter products, but "neuroenhancers" might be characterized by a higher propensity to instrumentalize over-the-counter products for virtually all investigated goals whereas "fatigue-fighters" might be inclined to use over-the-counter products exclusively to fight fatigue. We believe that psychological investigations like these are essential, especially for designing programs to prevent risky behavior.
Calcularis is a computer-based training program which focuses on basic numerical skills, spatial representation of numbers and arithmetic operations. The program includes a user model allowing flexible adaptation to the child's individual knowledge and learning profile. The study design to evaluate the training comprises three conditions (Calcularis group, waiting control group, spelling training group). One hundred and thirty-eight children from second to fifth grade participated in the study. Training duration comprised a minimum of 24 training sessions of 20 min within a time period of 6-8 weeks. Compared to the group without training (waiting control group) and the group with an alternative training (spelling training group), the children of the Calcularis group demonstrated a higher benefit in subtraction and number line estimation with medium to large effect sizes. Therefore, Calcularis can be used effectively to support children in arithmetic performance and spatial number representation.
Effects of resistance training in youth athletes on muscular fitness and athletic performance
(2016)
During the stages of long-term athlete development (LTAD), resistance training (RT) is an important means for (i) stimulating athletic development, (ii) tolerating the demands of long-term training and competition, and (iii) inducing long-term health promoting effects that are robust over time and track into adulthood. However, there is a gap in the literature with regards to optimal RT methods during LTAD and how RT is linked to biological age. Thus, the aims of this scoping review were (i) to describe and discuss the effects of RT on muscular fitness and athletic performance in youth athletes, (ii) to introduce a conceptual model on how to appropriately implement different types of RT within LTAD stages, and (iii) to identify research gaps from the existing literature by deducing implications for future research. In general, RT produced small -to -moderate effects on muscular fitness and athletic performance in youth athletes with muscular strength showing the largest improvement. Free weight, complex, and plyometric training appear to be well -suited to improve muscular fitness and athletic performance. In addition, balance training appears to be an important preparatory (facilitating) training program during all stages of LTAD but particularly during the early stages. As youth athletes become more mature, specificity, and intensity of RT methods increase. This scoping review identified research gaps that are summarized in the following and that should be addressed in future studies: (i) to elucidate the influence of gender and biological age on the adaptive potential following RT in youth athletes (especially in females), (ii) to describe RT protocols in more detail (i.e., always report stress and strain based parameters), and (iii) to examine neuromuscular and tendomuscular adaptations following RT in youth athletes.
Previous research on the interplay between static manual postures and visual attention revealed enhanced visual selection near the hands (near-hand effect). During active movements there is also superior visual performance when moving toward compared to away from the stimulus (direction effect). The "modulated visual pathways" hypothesis argues that differential involvement of magno- and parvocellular visual processing streams causes the near-hand effect. The key finding supporting this hypothesis is an increase in temporal and a reduction in spatial processing in near-hand space (Gozli et al., 2012). Since this hypothesis has, so far, only been tested with static hand postures, we provide a conceptual replication of Gozli et al.'s (2012) result with moving hands, thus also probing the generality of the direction effect. Participants performed temporal or spatial gap discriminations while their right hand was moving below the display. In contrast to Gozli et al (2012), temporal gap discrimination was superior at intermediate and not near hand proximity. In spatial gap discrimination, a direction effect without hand proximity effect suggests that pragmatic attentional maps overshadowed temporal/spatial processing biases for far/near-hand space.
An exploration of rhythmic grouping of speech sequences by french- and german-learning infants
(2016)
Rhythm in music and speech can be characterized by a constellation of several acoustic cues. Individually, these cues have different effects on rhythmic perception: sequences of sounds alternating in duration are perceived as short-long pairs (weak-strong/iambicpattern), whereas sequences of sounds alternating in intensity or pitch are perceived as loud-soft, or high-low pairs (strong-weak/trochaic pattern). This perceptual bias-called the lambic-Trochaic Law (ITL) has been claimed to be an universal property of the auditory system applying in both the music and the language domains. Recent studies have shown that language experience can modulate the effects of the ITL on rhythmic perception of both speech and non-speech sequences in adults, and of non-speech sequences in 7.5-month-old infants. The goal of the present study was to explore whether language experience also modulates infants' grouping of speech. To do so, we presented sequences of syllables to monolingual French- and German-learning 7.5-month-olds. Using the Headturn Preference Procedure (HPP), we examined whether they were able to perceive a rhythmic structure in sequences of syllables that alternated in duration, pitch, or intensity. Our findings show that both French- and German-learning infants perceived a rhythmic structure when it was cued by duration or pitch but not intensity. Our findings also show differences in how these infants use duration and pitch cues to group syllable sequences, suggesting that pitch cues were the easier ones to use. Moreover, performance did not differ across languages, failing to reveal early language effects on rhythmic perception. These results contribute to our understanding of the origin of rhythmic perception and perceptual mechanisms shared across music and speech, which may bootstrap language acquisition.
Relatedness strongly influences social behaviors in a wide variety of species. For most species, the highest typical degree of relatedness is between full siblings with 50% shared genes. However, this is poorly understood in species with unusually high relatedness between individuals: clonal organisms. Although there has been some investigation into clonal invertebrates and yeast, nothing is known about kin selection in clonal vertebrates. We show that a clonal fish, the Amazon molly (Poecilia formosa), can distinguish between different clonal lineages, associating with genetically identical, sister clones, and use multiple sensory modalities. Also, they scale their aggressive behaviors according to the relatedness to other females: they are more aggressive to non-related clones. Our results demonstrate that even in species with very small genetic differences between individuals, kin recognition can be adaptive. Their discriminatory abilities and regulation of costly behaviors provides a powerful example of natural selection in species with limited genetic diversity.
Background:
Exercising at intensities where fat oxidation rates are high has been shown to induce metabolic benefits in recreational and health-oriented sportsmen. The exercise intensity (Fat peak ) eliciting peak fat oxidation rates is therefore of particular interest when aiming to prescribe exercise for the purpose of fat oxidation and related metabolic effects. Although running and walking are feasible and popular among the target population, no reliable protocols are available to assess Fat peak as well as its actual velocity (V PFO ) during treadmill ergometry. Our purpose was therefore, to assess the reliability and day-to-day variability of V PFO and Fat peak during treadmill ergometry running.
Methods:
Sixteen recreational athletes (f = 7, m = 9; 25 ± 3 y; 1.76 ± 0.09 m; 68.3 ± 13.7 kg; 23.1 ± 2.9 kg/m 2 ) performed 2 different running protocols on 3 different days with standardized nutrition the day before testing. At day 1, peak oxygen uptake (VO 2peak ) and the velocities at the aerobic threshold (V LT ) and respiratory exchange ratio (RER) of 1.00 (V RER ) were assessed. At days 2 and 3, subjects ran an identical submaximal incremental test (Fat-peak test) composed of a 10 min warm-up (70 % V LT ) followed by 5 stages of 6 min with equal increments (stage 1 = V LT , stage 5 = V RER ). Breath-by-breath gas exchange data was measured continuously and used to determine fat oxidation rates. A third order polynomial function was used to identify V PFO and subsequently Fat peak . The reproducibility and variability of variables was verified with an int raclass correlation coef ficient (ICC), Pearson ’ s correlation coefficient, coefficient of variation (CV) an d the mean differences (bias) ± 95 % limits of agreement (LoA).
Results:
ICC, Pearson ’ s correlation and CV for V PFO and Fat peak were 0.98, 0.97, 5.0 %; and 0.90, 0.81, 7.0 %, respectively. Bias ± 95 % LoA was − 0.3 ± 0.9 km/h for V PFO and − 2±8%ofVO 2peak for Fat peak.
Conclusion:
In summary, relative and absolute reliability indicators for V PFO and Fat peak were found to be excellent. The observed LoA may now serve as a basis for future training prescriptions, although fat oxidation rates at prolonged exercise bouts at this intensity still need to be investigated.
Background The prognostic effect of multi-component cardiac rehabilitation (CR) in the modern era of statins and acute revascularisation remains controversial. Focusing on actual clinical practice, the aim was to evaluate the effect of CR on total mortality and other clinical endpoints after an acute coronary event.
Design Structured review and meta-analysis.
Methods Randomised controlled trials (RCTs), retrospective controlled cohort studies (rCCSs) and prospective controlled cohort studies (pCCSs) evaluating patients after acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) or mixed populations with coronary artery disease (CAD) were included, provided the index event was in 1995 or later.
Results Out of n=18,534 abstracts, 25 studies were identified for final evaluation (RCT: n=1; pCCS: n=7; rCCS: n=17), including n=219,702 patients (after ACS: n=46,338; after CABG: n=14,583; mixed populations: n=158,781; mean follow-up: 40 months). Heterogeneity in design, biometrical assessment of results and potential confounders was evident. CCSs evaluating ACS patients showed a significantly reduced mortality for CR participants (pCCS: hazard ratio (HR) 0.37, 95% confidence interval (CI) 0.20-0.69; rCCS: HR 0.64, 95% CI 0.49-0.84; odds ratio 0.20, 95% CI 0.08-0.48), but the single RCT fulfilling Cardiac Rehabilitation Outcome Study (CROS) inclusion criteria showed neutral results. CR participation was also associated with reduced mortality after CABG (rCCS: HR 0.62, 95% CI 0.54-0.70) and in mixed CAD populations.
Conclusions CR participation after ACS and CABG is associated with reduced mortality even in the modern era of CAD treatment. However, the heterogeneity of study designs and CR programmes highlights the need for defining internationally accepted standards in CR delivery and scientific evaluation.
SOPARSE predicts so-called local coherence effects: locally plausible but globally impossible parses of substrings can exert a distracting influence during sentence processing. Additionally, it predicts digging-in effects: the longer the parser stays committed to a particular analysis, the harder it becomes to inhibit that analysis. We investigated the interaction of these two predictions using German sentences. Results from a self-paced reading study show that the processing difficulty caused by a local coherence can be reduced by first allowing the globally correct parse to become entrenched, which supports SOPARSE’s assumptions.