Reproducibility of MUAP properties in array surface EMG recordings of the upper trapezius and sternocleidomastoid muscle

The use of array surface EMG recordings for detailed assessment of motor control and muscle properties is increasing. Motor unit action potentials (MUAPs) and their properties can be extracted from these recordings. The objective of this study was to determine the reproducibility of variables obtained from array surface EMG recordings of the shoulder and neck muscles during different functional tasks.Eight-channel linear arrays were placed on the upper trapezius (UT) and sternocleidomastoid (SCM) muscles of 12 healthy subjects. Subjects performed 3 tasks: shoulder abduction (90°), ironing (repetitively touching two ends of a horizontal bar in front of the subject), and 90° head turning. The protocol was performed twice while electrodes remained on and repeated a third time a week later.Three global and six MUAP-related variables were calculated. Intra-class correlation coefficients (ICC) were calculated to assess reliability and smallest detectable changes (SDC) were calculated to assess agreement.In general, the EMG variables showed high levels of reliability which suggests they may be effective for differentiating between-subjects. SDC was found to be considerably lower for the frequency-related (5–23%) than for the amplitude-related variables (15–78%), indicating that the frequency-related variables may be more suitable for investigating interventions which aim to modify motor control. There was no difference in reproducibility between global and MUAP-related variables, which justifies their complementary use.     

No difference in between-country variability in use of newly approved orphan and non- orphan medicinal products - a pilot study

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, which rapidly leads to chronic respiratory failure requiring mechanical ventilation. Currently, forced vital capacity (FVC) < 50% is considered as physiologic marker for admitting patients to Noninvasive Positive Pressure Ventilation (NPPV) intervention, although it has been recently shown the median survival of patients with baseline FVC < 75% much shorter than median survival of patients with baseline FVC > 75%, independently by any treatment.

Aim

To assess the role of NPPV in improving outcome of ALS, a retrospective analysis was performed to investigate 1 year survival of ALS patients with FVC < 75% and nocturnal respiratory insufficiency, treated with NPPV, compared to a well-matched population of ALS patients, who refused or was intolerant to NPPV.

Methods

We investigated seventy-two consecutive ALS patients who underwent pulmonary function test. Forty-four presented a FVC > 75% and served as control group. Twenty-eight patients presented a FVC < 75% and showed, at polysomnography analysis, nocturnal respiratory insufficiency, requiring NPPV; sixteen were treated with NPPV, while twelve refused or were intolerant.

Results

Increased survival rate at 1 year in patients with FVC < 75% treated with NPPV, as compared to those who refused or could not tolerate NPPV (p = 0.02), was observed. The median rate of decline in FVC% was slower in NPPV patients than in patients who did not use NPPV (95% CI: 0.72 to 1.85; p < 0.0001).

Conclusion

This report demonstrates that early treatment with NPPV prolongs survival and reduces decline of FVC% in ALS.     

Effects of a defective ERAD pathway on growth and heterologous protein production in <Emphasis Type="Italic">Aspergillus niger</Emphasis>

Endoplasmic reticulum associated degradation (ERAD) is a conserved mechanism to remove misfolded proteins from the ER by targeting them to the proteasome for degradation. To assess the role of ERAD in filamentous fungi, we have examined the consequences of disrupting putative ERAD components in the filamentous fungus Aspergillus niger. Deletion of derA, doaA, hrdC, mifA, or mnsA in A. niger yields viable strains, and with the exception of doaA, no significant growth phenotype is observed when compared to the parental strain. The gene deletion mutants were also made in A. niger strains containing single- or multicopies of a glucoamylase–glucuronidase (GlaGus) gene fusion. The induction of the unfolded protein response (UPR) target genes (bipA and pdiA) was dependent on the copy number of the heterologous gene and the ERAD gene deleted. The highest induction of UPR target genes was observed in ERAD mutants containing multiple copies of the GlaGus gene. Western blot analysis revealed that deletion of the derA gene in the multicopy GlaGus overexpressing strain resulted in a 6-fold increase in the intracellular amount of GlaGus protein detected. Our results suggest that impairing some components of the ERAD pathway in combination with high expression levels of the heterologous protein results in higher intracellular protein levels, indicating a delay in protein degradation.     

Functional characteristics of the high affinity IgG receptor, FcγRI

IgG FcRs are important mediators of immunity and play a key role during Ab-based immunotherapy. Within the leukocyte IgG receptor family, only FcγRI is capable of IgG binding with high affinity. FcγRI exists as a complex of a ligand binding α-chain and an FcR γ-chain. The receptors' α-chain can, furthermore, elicit several functions independent of the ITAM-bearing FcR γ-chain. Functional implications of high-affinity IgG binding and mechanisms underlying FcR γ-chain-independent signaling remain unclear to this day. In this paper, we provide an overview of past literature on FcγRI and address the implications of recently described interactions between cytosolic proteins and the FcγRI α-chain, as well as cytokine-enhanced FcγRI immune complex binding. Furthermore, an analysis of potential polymorphisms within the FCGR1A gene is provided.     

An oral health care guideline for institutionalised older people

Institutionalized older people are prone to oral health problems and their negative impact due to frailty, disabilities, multi-morbidity, and multiple medication use. Until recently, no evidence-based oral health care guideline for institutionalized older people has been available. For that reason, the Dutch Association of Nursing Home Physicians developed the Oral health care Guideline for Older people in Long-term care Institutions (OGOLI), meeting the requirements of the AGREE instrument for assessing a guideline's quality. This short report presents the keynotes and the content of the Oral health care Guideline. Most recommendations are based on expert opinions. Only 4 recommendations (education, pneumonia, use of an electric toothbrush, and fluoride rinsing in case of a sudden increase of oral plaque amount) are based on evidence level A2 conclusions. This emphasizes the need for further research on oral health of institutionalized older people.     

WISECONDOR: detection of fetal aberrations from shallow sequencing maternal plasma based on a within-sample comparison scheme

Genetic disorders can be detected by prenatal diagnosis using Chorionic Villus Sampling, but the 1:100 chance to result in miscarriage restricts the use to fetuses that are suspected to have an aberration. Detection of trisomy 21 cases noninvasively is now possible owing to the upswing of next-generation sequencing (NGS) because a small percentage of fetal DNA is present in maternal plasma. However, detecting other trisomies and smaller aberrations can only be realized using high-coverage NGS, making it too expensive for routine practice. We present a method, WISECONDOR (WIthin-SamplE COpy Number aberration DetectOR), which detects small aberrations using low-coverage NGS. The increased detection resolution was achieved by comparing read counts within the tested sample of each genomic region with regions on other chromosomes that behave similarly in control samples. This within-sample comparison avoids the need to re-sequence control samples. WISECONDOR correctly identified all T13, T18 and T21 cases while coverages were as low as 0.15–1.66. No false positives were identified. Moreover, WISECONDOR also identified smaller aberrations, down to 20 Mb, such as del(13)(q12.3q14.3), +i(12)(p10) and i(18)(q10). This shows that prevalent fetal copy number aberrations can be detected accurately and affordably by shallow sequencing maternal plasma. WISECONDOR is available at bioinformatics.tudelft.nl/wisecondor.     

The complete mitochondrial genome of Taeniogonalos taihorina (Bischoff) (Hymenoptera: Trigonalyidae) reveals a novel gene rearrangement pattern in the Hymenoptera

The family Trigonalyidae is considered to be one of the most basal lineages in the suborder Apocrita of Hymenoptera. Here, we determine the first complete mitochondrial genome of the Trigonalyidae, from the species Taeniogonalos taihorina (Bischoff, 1914). This mitochondrial genome is 15,927 bp long, with a high A + T-content of 84.60%. It contains all of the 37 typical animal mitochondrial genes and an A + T-rich region. The orders and directions of all genes are different from those of previously reported hymenopteran mitochondrial genomes. Eight tRNA genes, three protein-coding genes and the A + T-rich region were rearranged, with the dominant gene rearrangement events being translocation and local inversion. The arrangements of three tRNA clusters, trnY–trnM–trnI–trnQ, trnW–trnL2–trnC, and trnH–trnA–trnR–trnN–trnS–trnE–trnF, and the position of the cox1 gene, are novel to the Hymenoptera, even the insects. Six long intergenic spacers are present in the genome. The secondary structures of the RNA genes are normal, except for trnS2, in which the D-stem pairing is absent.     

Computational and experimental investigation of local stress fiber orientation in uniaxially and biaxially constrained microtissues

The orientation of cells and associated F-actin stress fibers is essential for proper tissue functioning. We have previously developed a computational model that qualitatively describes stress fiber orientation in response to a range of mechanical stimuli. In this paper, the aim is to quantitatively validate the model in a static, heterogeneous environment. The stress fiber orientation in uniaxially and biaxially constrained microscale tissues was investigated using a recently developed experimental system. Computed and experimental stress fiber orientations were compared, while accounting for changes in orientation with location in the tissue. This allowed for validation of the model, and additionally, it showed how sensitive the stress fiber orientation in the experimental system is to the location where it is measured, i.e., the heterogeneity of the stress fiber orientation. Computed and experimental stress fiber orientations showed good quantitative agreement in most regions. A strong local alignment near the locations where boundary conditions were enforced was observed for both uniaxially and biaxially constrained tissues. Excepting these regions, in biaxially constrained tissues, no preferred orientation was found and the distribution was independent of location. The stress fiber orientation in uniaxially constrained tissues was more heterogeneous, and stress fibers mainly oriented in the constrained direction or along the free edge. These results indicate that the stress fiber orientation in these constrained microtissues is mainly determined by the local mechanical environment, as hypothesized in our model, and also that the model is a valid tool to predict stress fiber orientation in heterogeneously loaded tissues.     

Computational model predicts cell orientation in response to a range of mechanical stimuli

To build anisotropic, mechanically functioning tissue, it is essential to understand how cells orient in response to mechanical stimuli. Therefore, a computational model was developed which predicts cell orientation, based on the actin stress fiber distribution inside the cell. In the model, the stress fiber distribution evolves dynamically according to the following: (1) Stress fibers contain polymerized actin. The total amount of depolymerized plus polymerized actin is constant. (2) Stress fibers apply tension to their environment. This active tension is maximal when strain rate and absolute strain are zero and reduces with increasing shortening rate and absolute strain. (3) A high active fiber stress in a direction leads to a large amount of fibers in this direction. (4) The cell is attached to a substrate; all fiber stresses are homogenized into a total cell stress, which is in equilibrium with substrate stress. This model predicts that on a substrate of anisotropic stiffness, fibers align in the stiffest direction. Under cyclic strain when the cellular environment is so stiff that no compaction occurs (1 MPa), the model predicts strain avoidance, which is more pronounced with increasing strain frequency or amplitude. Under cyclic strain when the cellular environment is so soft that cells can compact it (10 kPa), the model predicts a preference for the cyclically strained compared to the compacting direction. These model predictions all agree with experimental evidence. For the first time, a computational model predicts cell orientation in response to this range of mechanical stimuli using a single set of parameters.