Effects Of Changes In Function Research Articles

EFFECT OF FEMORAL ROTATION ON DISLOCATION AFTER REVISION TOTAL HIP ARTHROPLASTY

Dislocation is a serious complication to be avoided in total hip arthroplasty (THA) and its incidence risk increases in revision surgery. Combined anteversion (CA) of the cup and stem is a concept for appropriate implant positioning; however, the effect of functional changes in femoral rotation has not been well investigated. The aim of this study was to investigate whether functional CA, considering femoral rotation, is associated with dislocation in patients undergoing revision THA.Seventy-three patients who underwent revision THA and had at least one year of follow-up with pre- and postoperative supine CT imaging were included. Cup and stem were placed with a target combined angle of 37.3° using Widmer's formula. Anatomical and functional CA was calculated postoperatively using the following formula: Anatomical CA: cup anteversion + 0.7 × anatomical stem anteversion; Functional CA: cup anteversion + 0.7 × (anatomical stem anteversion + femoral rotation). Patient demographics, cup and stem angles, CA and their relationship to dislocation were statistically evaluated.Dislocation was observed in 12 patients. In these dislocated cases, there were no significant differences in cup angle, stem angle and anatomical CA compared to non-dislocated cases. However, dislocated cases showed significantly higher values of functional CA [52.7 ± 17.5° (range, 5.9–69.3) vs. 36.0 ± 12.5° (range, 8.6–68.8), p=0.009] and significant deviation from identical CA [17.3 ± 9.6° (range, 2.8–32) vs. 7.5 ± 7.1° (range, 0.1–28.7), p=0.010].Functional CA considering femoral rotation was associated with dislocation in revision THA patients. This finding suggests that consideration of femoral rotation may be necessary for implant positioning in revision THA.

Structural disconnection and functional reorganization in Fabry disease: a multimodal MRI study.

Central nervous system involvement in Fabry disease, a rare systemic X-linked lysosomal storage disorder, is characterized by the presence of heterogeneous but consistent functional and microstructural changes. Nevertheless, knowledge about the degree and extension of macro-scale brain connectivity modifications is to date missing. In this work, we performed connectomic analyses of diffusion and resting-state functional MRI to investigate changes of both structural and functional brain organization in Fabry disease, as well as to explore the relationship between the two and their clinical correlates. In this retrospective cross-sectional study, 46 patients with Fabry disease (28F, 42.2 ± 13.2years) and 49 healthy controls (21F, 42.3 ± 16.3years) were included. All subjects underwent an MRI examination including anatomical, diffusion and resting-state functional sequences. Images were processed to obtain quantitative structural and functional connectomes, where the connections between regions of interest were weighted by the total intra-axonal signal contribution of the corresponding bundle and by the correlation between blood-oxygen level–dependent time series, respectively. We explored between-group differences in terms of both global network properties, expressed with graph measures and specific connected subnetworks, identified using a network-based statistics approach. As exploratory analyses, we also investigated the possible association between cognitive performance and structural and functional connectome modifications at both global and subnetwork level in a subgroup of patients (n = 11). Compared with healthy controls, patients with Fabry disease showed a significantly reduced global efficiency (P = 0.005) and mean strength (P < 0.001) in structural connectomes, together with an increased modularity (P = 0.005) in functional networks. As for the network-based statistics analysis, a subnetwork with decreased structural connectivity in patients with Fabry disease compared with healthy controls emerged, with eight nodes mainly located at the level of frontal or deep grey-matter areas. When probing the relation between altered global network metrics and neuropsychological tests, correlations emerged between the structural and functional disruption with results at verbal and working memory tests, respectively. Furthermore, structural disruption at subnetwork level was associated with worse executive functioning, with a significant moderation effect of functional changes suggesting a compensation mechanism. Taken together, these results further expand the current knowledge about brain involvement in Fabry disease, showing widespread structural disconnection and functional reorganization, primarily sustained by loss in axonal integrity and correlating with cognitive performance.

Metabolic changes in human brain evolution.

Because the human brain is considerably larger than those of other primates, it is not surprising that its energy requirements would far exceed that of any of the species within the order. Recently, the development of stem cell technologies and single-cell transcriptomics provides novel ways to address the question of what specific genomic changes underlie the human brain's unique phenotype. In this review, we consider what is currently known about human brain metabolism using a variety of methods from brain imaging and stereology to transcriptomics. Next, we examine novel opportunities that stem cell technologies and single-cell transcriptomics provide to further our knowledge of human brain energetics. These new experimental approaches provide the ability to elucidate the functional effects of changes in genetic sequence and expression levels that potentially had a profound impact on the evolution of the human brain.

Role of Astrocytes in Post-traumatic Epilepsy.

Traumatic brain injury, a common cause of acquired epilepsy, is typical to find necrotic cell death within the injury core. The dynamic changes in astrocytes surrounding the injury core contribute to epileptic seizures associated with intense neuronal firing. However, little is known about the molecular mechanisms that activate astrocytes during traumatic brain injury or the effect of functional changes of astrocytes on seizures. In this comprehensive review, we present our cumulated understanding of the complex neurological affection in astrocytes after traumatic brain injury. We approached the problem through describing the changes of cell morphology, neurotransmitters, biochemistry, and cytokines in astrocytes during post-traumatic epilepsy. In addition, we also discussed the relationship between dynamic changes in astrocytes and seizures and the current pharmacologic agents used for treatment. Hopefully, this review will provide a more detailed knowledge from which better therapeutic strategies can be developed to treat post-traumatic epilepsy.

Decreased neutrophil–associated miRNA and increased B-cell associated miRNA expression during tuberculosis

MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB. We utilised real-time PCR to evaluate the levels of microRNA transcripts in the peripheral blood of TB cases and healthy controls. We found that neutrophil-associated miR-197-3p, miR-99b-5p and miR-191-5p transcript levels were significantly lower in TB cases. Additionally, B-cell-associated miR-320a, miR-204-5p, miR331-3p and other transcript levels were higher in TB cases.The miRNAs differentially expressed in neutrophils are predominantly implicated in signalling pathways leading to cytokine productions. Here, the decreased expression in TB cases may imply a lack of suppression on signalling pathways, which may lead to increased production of pro-inflammatory cytokines such as interferon-gamma. Furthermore, the miRNAs differentially expressed in B-cells are mostly involved in the induction/suppression of apoptosis. Further functional studies are however required to elucidate the significance and functional effects of changes in the expression of these microRNAs.

Abstract 3243: Neutrophil elastase regulates PD-L1 expression in breast cancer

Abstract Introduction: We have previously reported that breast cancer cells take up the inflammatory mediator neutrophil elastase (NE) from tumor-associated neutrophils (TANs). NE uptake leads to: 1) increased cleavage of cyclin E (CCNE) to its low molecular weight isoforms and generation of the CCNE-derived immunogenic epitope CCNE144-152, 2) cross-presentation of the NE-derived epitope PR1, and 3) increased human leukocyte antigen (HLA) class I expression. NE is therefore a link between innate and adaptive immune responses in breast cancer. The current study was undertaken to investigate the effects of NE uptake on PD-L1 expression as another mechanism impacting adaptive immune responses in breast cancer. Methods: The breast cancer cell line MDA-MB-231 was maintained in standard media or media supplemented with NE. The effect of NE on cell surface expression of PD-L1 was determined using flow cytometry. Total PD-L1 protein expression was determined using western blot analysis performed on whole cell lysates. NE was inhibited with either elafin or alpha-1-antitrypsin to assess the requirement of enzymatic activity for the observed effects. Transcriptional regulation of PD-L1 expression by NE was assessed by qPCR. To evaluate specific transcription factors (TFs) involved in PD-L1 regulation, nuclear protein was isolated and analyzed for the activity of 16 TFs using a commercial plate array. The impact of NE uptake on TFs identified on the array was confirmed by western blot analysis. The functional effects of changes in PD-L1 expression were evaluated using an annexin V assay to assess T-cell apoptosis. Results: Addition of NE to breast cancer cells resulted in a reduction in PD-L1 surface expression as determined by flow cytometry and in total PD-L1 expression as shown by western blot analysis. The effect was reversed after removal of the cells from NE-supplemented media. The addition of elafin to inhibit NE enzymatic activity led to increased NE uptake by MDA-MB-231 cells with no change in PD-L1 cell surface expression. Treatment with alpha-1-antitrypsin prevented NE uptake and also abrogated its effect on PD-L1 expression. Together, these results suggest that uptake of enzymatically active NE is required to decrease PD-L1 expression. qPCR showed a decrease in the PD-L1 transcript suggesting that the effect of NE on PD-L1 is transcriptionally regulated. NE treatment resulted in decreased expression of TFs known to be involved in PD-L1 regulation, including STAT1, STAT3, and JUN. NE-treated breast cancer cells induced less apoptosis of T-cells compared with untreated breast cancer cells. Conclusions: Uptake of enzymatically active NE by breast cancer results in decreased cell surface and total PD-L1 expression, an effect that is in part transcriptionally regulated. These findings suggest another mechanism whereby the innate inflammatory mediator NE may impact adaptive immune responses in breast cancer. Citation Format: Victor Gall, Anne V. Philips, Akhil Chawla, Na Qiao, Lisa S. St. John, Pariya Sukhumalchandra, Mao Zhang, Jeffrey J. Molldrem, Gheath Alatrash, Elizabeth A. Mittendorf. Neutrophil elastase regulates PD-L1 expression in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3243.

The neural correlates of bilateral upper limb training after stroke: a systematic review

Background:Recovery of upper limb (UL) function after stroke is poor with only a third of stroke survivors regaining some functional use. Bilateral training (BT) of the ULs is a promising intervention but its underlying mechanisms are unclear. BT involves practicing identical movements with both UL (e.g. carrying a box, lifting two cups) and is not to be confused with bimanual training where both limbs perform different movements (e.g. tying shoelaces). It is important to understand how BT affects both UL motor recovery and neuroplasticity in order to assess its potential as a therapeutic intervention. This is the first review of the effects of BT on motor recovery and neuroplasticity together. Purpose: This systematic review aimed to elucidate the mechanisms underlying BT by determining (i) the effects of functional changes by BT on neuroplasticity and (ii) the relationships between changes in UL function and changes in neuroplasticity as a result of BT. Methods: The complete holdings of 11 databases were searched up until December 2014.Trial registers and reference lists of included studies and reviews were checked. Quantitative studies of any design employing BT with both UL motor and neurophysiological outcomes involving adult stroke survivors were included. Studies not available in English or in full text were excluded. Two independent reviewers selected studies, extracted data and reviewed methodological quality using the Effective Public Health Practice Project (EPHPP) tool. The EPHPP tool was selected from four reviews. Where a decision could not be made between the two reviewers, a third reviewer was sought and consensus reached through discussion. Results: From 41,438 records, eight studies comprising 164 participantswere included. The global rating formethodological quality was ‘strong’ for two studies, ‘moderate’ for two studies and ‘weak’ for the remaining four. Considerable heterogeneity of participants, modes of BT, comparators and measures meant pooled outcome analysis was not possible. The variation in modes of BT included: in-phase and anti-phasemovements, functional tasks involving objects and movements only, mechanically coupled and free movement, auditory cued and self-paced movements. The most common outcomemeasure usedwas theUL section of the Fugl–Meyer whichwas used in six studies; however some studies used different subsections. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) were used in three and five studies respectively, employing a wide range of measures. Only five studies reported neural correlates of BT, but findings were inconsistent. No clear pattern of neuroplasticity associated with BT was apparent from this review. Conclusion(s): Current evidence from this systematic review indicates that the neural correlates of BT after stroke are currently unknown and need to be examined systematically to understand the therapeutic potential of different modes ofBT. Future research needs to identify effective training modes of BT, match the optimal mode to people with specific stroke lesions anduse appropriate outcomemeasures. Implications: Physiotherapists should use their clinical reasoning when using BT, considering various modes of delivery in conjunction with patients’ UL impairments and functional goals.

Interpreting genetic effects through models of cardiac electromechanics

Multiscale models of cardiac electromechanics are being increasingly focused on understanding how genetic variation and environment underpin multiple disease states. In this paper we review the current state of the art in both the development of specific models and the physiological insights they have produced. This growing research body includes the development of models for capturing the effects of changes in function in both single and multiple proteins in both specific expression systems and in vivo contexts. Finally, the potential for using this approach for ultimately predicting phenotypes from genetic sequence information is discussed.

O‐GlcNAc signaling attenuates mitochondrial permeability transition

We have shown that glycosylation of proteins with O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) preserves mitochondrial membrane potential, attenuates post‐hypoxic injury, and reduces myocardial infarct size in vivo. Based on our recent identification of voltage dependent anion channel (VDAC) as an O‐GlcNAc modified protein, we hypothesized that O‐GlcNAc signaling mediates cardioprotection by attenuating sensitivity to mPTP formation. Here, isolated cardiac mitochondria from Vehicle‐ (normal O‐GlcNAc), PUGNAc‐ (high O‐GlcNAc; 50mg/kg, 18hours), or TT04‐treated (low O‐GlcNAc; 10mg/kg, 18hours) C57BL/6J mice showed no difference in total VDAC levels (n&gt;/=3/group). for O‐GlcNAc and immunoblot for VDAC (n&gt;/=3/group), and vice versa, revealed a significant increase in O‐ GlcNAc modified VDAC for cardiac mitochondria from high O‐GlcNAc mice with Vehicle, while a significant reduction of O‐GlcNAc‐modified VDAC was observed with cardiac mitochondria from low O‐GlcNAc mice compared to Vehicle. To assess functional effects of changes in O‐GlcNAc modification of VDAC on mPTP formation, cardiac mitochondria from high, normal, and low O‐GlcNAc mice were challenged with 100μM CaCl2 and the decrease in spectrohotometric absorbance recorded as an index of mitochondrial swelling. Mitochondria from high O‐GlcNAc mice were significantly less sensitive to calcium‐induced swelling, those from low O‐GlcNAc mice were more sensitive to calcium‐induced swelling compared with Vehicle. We that prevention of mPTP formation, potentially via O‐GlcNAc modification of VDAC, represents a novel mechanism of cardioprotection. NIH (HL0833220), AHA (0535270N) and AHA (0715493B).

Changes in the properties of mouse tongue muscle fibres before and after weaning

The purpose of this study was to clarify any changes in muscle fibre properties in different regions of murine tongue during development, and to assess the effects of functional changes including weaning on these muscle fibres. The tongue was divided into upper and lower regions at the lateral margin, and the expression of myosin heavy chain (MHC) isoforms at different ages was investigated. Expression of genes encoding MHC proteins was quantified at the transcription level by quantitative reverse transcriptase polymerase chain reaction, and the protein expression of MHC isoforms was assessed by immunostaining. No difference was found in isoform expression between the upper and lower regions of the tongue before weaning. However, the expression of MHC-2b increased markedly in both regions after weaning, while that of MHC-2a decreased. At the age of 16 weeks, the expression of MHC-2b in the lower region was greater than that in the upper region. These findings show that during weaning, when there is a shift from sucking behaviour to mastication, the expression of MHC-2b increases along with an increase in the speed and strength of muscle contraction. Also, contraction force becomes stronger in the lower region of the tongue than the upper region at the age of 16 weeks.

Human factors research needs for an aging population : Czaja, S.J. (Ed) National Academy Press, Washington, DC, 1990, 85pp, 156 refs

This book describes the demographic, sociological, and ecological background of the aging society, identifies human factors problems associated with aging, summarizes currently relevant information, and recommends directions for research. It suggests a program of research and technology development for the purpose of ameliorating the effects of functional changes that accompany the aging process and provides a basis for additional research and application of human factors engineering data to the design of environments in which aging people must function.

Defining features of natural kinds and artifacts

Two experiments investigated the role of three types of features (physical characteristics, functions, and chromosomal/molecular structure) in determining membership in natural kind and artifact categories. In the first, subjects decided if an object “X” would still be an “X” if it were different in one type of feature. A significant interaction was found between word type and change type, with the effects of chromosomal/molecular changes significantly greater for natural kinds than for artifacts, and the effects of functional changes significantly greater for artifacts than natural kinds. In the second experiment, subjects judged whether something would be an “X” if it were unlike instances of “X” in two of the above types of features, but like instances of “X” in one. There was again a significant interaction, with the effects of chromosomal/molecular features significantly greater for natural kinds than for artifacts, and the effects of functional changes significantly greater for artifacts than for natural kinds. These results suggest that chromosomal/molecular features define membership in natural kind categories and functional features define membership in artifact categories. The implications of these findings for the meaning of “defining features” are also discussed.

A 31P nuclear-magnetic-resonance study of the metabolic and functional effects of changes in extracellular Ca2+ on the isolated perfused rat heart

A 31P nuclear-magnetic-resonance study of the metabolic and functional effects of changes in extracellular Ca2+ on the isolated perfused rat heart

The Effect of Functional Changes upon the Variability of Lizard and Snake Body Scale Numbers

moderate lognormal effects (Simpson et al., 1960:90) because the absolute dispersion of the measurements increases in direct proportion to the mean, while the distributions of the measurements appear to conform closely to the normal distribution. The most easily visualized examples of logarithmic effects involve ontogenetic weight or length studies, where the dispersion of the measurement is proportional to the mean length or weight of the population at the time of sampling. Less obvious is the variation of body scale counts in squamates (lizards and snakes), where the numbers of scales are fixed throughout life. In the latter case, lognormal relationships were suspected when large samples consistently showed slight positive skews (Klauber, 1941; Kerfoot, 1969), and when probits of log-transformed values more closely approximated straight lines (Wright, 1968:267). Given certain restrictions (origin intercept, direct proportionality; Kerfoot, 1969), the variability of lognormally distributed variables is conveniently expressed by the coefficient of variation,