Changes in the flexion relaxation response induced by lumbar muscle fatigue

<p>Abstract</p> <p>Background</p> <p>The flexion relaxation phenomenon (FRP) is an interesting model to study the modulation of lumbar stability. Previous investigations have explored the effect of load, angular velocity and posture on this particular response. However, the influence of muscular fatigue on FRP parameters has not been thoroughly examined. The objective of the study is to identify the effect of erector spinae (ES) muscle fatigue and spine loading on myoelectric silence onset and cessation in healthy individuals during a flexion-extension task.</p> <p>Methods</p> <p>Twenty healthy subjects participated in this study and performed blocks of 3 complete trunk flexions under 4 different experimental conditions: no fatigue/no load (1), no fatigue/load (2), fatigue/no load(3), and fatigue/load (4). Fatigue was induced according to the Sorenson protocol, and electromyographic (EMG) power spectral analysis confirmed that muscular fatigue was adequate in each subject. Trunk and pelvis angles and surface EMG of the ES L2 and L5 were recorded during a flexion-extension task. Trunk flexion angle corresponding to the onset and cessation of myoelectric silence was then compared across the different experimental conditions using 2 × 2 repeated-measures ANOVA.</p> <p>Results</p> <p>Onset of myoelectric silence during the flexion motion appeared earlier after the fatigue task. Additionally, the cessation of myoelectric silence was observed later during the extension after the fatigue task. Statistical analysis also yielded a main effect of load, indicating a persistence of ES myoelectric activity in flexion during the load condition.</p> <p>Conclusion</p> <p>The results of this study suggest that the presence of fatigue of the ES muscles modifies the FRP. Superficial back muscle fatigue seems to induce a shift in load-sharing towards passive stabilizing structures. The loss of muscle contribution together with or without laxity in the viscoelastic tissues may have a substantial impact on post fatigue stability.</p

Statistical Analysis of Molecular Signal Recording

A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a “molecular ticker tape”, in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1) the polymerase biochemical parameters, and (2) the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales.United States. Defense Advanced Research Projects Agency. Living Foundries ProgramGoogle (Firm)New York Stem Cell Foundation. Robertson Neuroscience Investigator AwardNational Institutes of Health (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Transformative R01 1R01GM104948)National Institutes of Health (U.S.) (Single Cell Grant 1 R01 EY023173)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (CAREER Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS1042134)Paul G. Allen Family Foundation (Distinguished Investigator in Neuroscience Award

Concentration-Dependent Activity of Hydromethylthionine on Cognitive Decline and Brain Atrophy in Mild to Moderate Alzheimer’s Disease

ACKNOWLEDGMENTS We gratefully acknowledge study investigators and the generosity of study participants. We gratefully acknowledge Professor Gordon Wilcock for critical review and commentary on drafts of the manuscript. Author’s disclosures available online (https://www.j-alz.com/manuscript-disclosures/19-0772r1). SUPPLEMENTARY MATERIAL The supplementary material is available in the electronic version of this article: http://dx.doi.org/10.3233/JAD-190772. Availability of data and materials The datasets and analyses used during the current study are available from the corresponding author on reasonable request.Peer reviewedPublisher PD

Detection of microRNA Expression in Human Peripheral Blood Microvesicles

MicroRNAs (miRNA) are small non-coding RNAs that regulate translation of mRNA and protein. Loss or enhanced expression of miRNAs is associated with several diseases, including cancer. However, the identification of circulating miRNA in healthy donors is not well characterized. Microvesicles, also known as exosomes or microparticles, circulate in the peripheral blood and can stimulate cellular signaling. In this study, we hypothesized that under normal healthy conditions, microvesicles contain miRNAs, contributing to biological homeostasis.Microvesicles were isolated from the plasma of normal healthy individuals. RNA was isolated from both the microvesicles and matched mononuclear cells and profiled for 420 known mature miRNAs by real-time PCR. Hierarchical clustering of the data sets indicated significant differences in miRNA expression between peripheral blood mononuclear cells (PBMC) and plasma microvesicles. We observed 71 miRNAs co-expressed between microvesicles and PBMC. Notably, we found 33 and 4 significantly differentially expressed miRNAs in the plasma microvesicles and mononuclear cells, respectively. Prediction of the gene targets and associated biological pathways regulated by the detected miRNAs was performed. The majority of the miRNAs expressed in the microvesicles from the blood were predicted to regulate cellular differentiation of blood cells and metabolic pathways. Interestingly, a select few miRNAs were also predicted to be important modulators of immune function.This study is the first to identify and define miRNA expression in circulating plasma microvesicles of normal subjects. The data generated from this study provides a basis for future studies to determine the predictive role of peripheral blood miRNA signatures in human disease and will enable the definition of the biological processes regulated by these miRNA

Research capacity building integrated into PHIT projects: leveraging research and research funding to build national capacity

Background: Inadequate research capacity impedes the development of evidence-based health programming in sub-Saharan Africa. However, funding for research capacity building (RCB) is often insufficient and restricted, limiting institutions’ ability to address current RCB needs. The Doris Duke Charitable Foundation’s African Health Initiative (AHI) funded Population Health Implementation and Training (PHIT) partnership projects in five African countries (Ghana, Mozambique, Rwanda, Tanzania and Zambia) to implement health systems strengthening initiatives inclusive of RCB. Methods: Using Cooke’s framework for RCB, RCB activity leaders from each country reported on RCB priorities, activities, program metrics, ongoing challenges and solutions. These were synthesized by the authorship team, identifying common challenges and lessons learned. Results: For most countries, each of the RCB domains from Cooke’s framework was a high priority. In about half of the countries, domain specific activities happened prior to PHIT. During PHIT, specific RCB activities varied across countries. However, all five countries used AHI funding to improve research administrative support and infrastructure, implement research trainings and support mentorship activities and research dissemination. While outcomes data were not systematically collected, countries reported holding 54 research trainings, forming 56 mentor-mentee relationships, training 201 individuals and awarding 22 PhD and Masters-level scholarships. Over the 5 years, 116 manuscripts were developed. Of the 59 manuscripts published in peer-reviewed journals, 29 had national first authors and 18 had national senior authors. Trainees participated in 99 conferences and projects held 37 forums with policy makers to facilitate research translation into policy. Conclusion: All five PHIT projects strongly reported an increase in RCB activities and commended the Doris Duke Charitable Foundation for prioritizing RCB, funding RCB at adequate levels and time frames and for allowing flexibility in funding so that each project could implement activities according to their trainees’ needs. As a result, many common challenges for RCB, such as adequate resources and local and international institutional support, were not identified as major challenges for these projects. Overall recommendations are for funders to provide adequate and flexible funding for RCB activities and for institutions to offer a spectrum of RCB activities to enable continued growth, provide adequate mentorship for trainees and systematically monitor RCB activities. Electronic supplementary material The online version of this article (10.1186/s12913-017-2657-6) contains supplementary material, which is available to authorized users

Data-driven quality improvement in low-and middle-income country health systems: lessons from seven years of implementation experience across Mozambique, Rwanda, and Zambia

Well-functioning health systems need to utilize data at all levels, from the provider, to local and national-level decision makers, in order to make evidence-based and needed adjustments to improve the quality of care provided. Over the last 7 years, the Doris Duke Charitable Foundation’s African Health Initiative funded health systems strengthening projects at the facility, district, and/or provincial level to improve population health. Increasing data-driven decision making was a common strategy in Mozambique, Rwanda and Zambia. This paper describes the similar and divergent approaches to increase data-driven quality of care improvements (QI) and implementation challenge and opportunities encountered in these three countries

A Nomenclature for Vertebral Fossae in Sauropods and Other Saurischian Dinosaurs

The axial skeleton of extinct saurischian dinosaurs (i.e., theropods, sauropodomorphs), like living birds, was pneumatized by epithelial outpocketings of the respiratory system. Pneumatic signatures in the vertebral column of fossil saurischians include complex branching chambers within the bone (internal pneumaticity) and large chambers visible externally that are bounded by neural arch laminae (external pneumaticity). Although general aspects of internal pneumaticity are synapomorphic for saurischian subgroups, the individual internal pneumatic spaces cannot be homologized across species or even along the vertebral column, due to their variability and absence of topographical landmarks. External pneumatic structures, in contrast, are defined by ready topological landmarks (vertebral laminae), but no consistent nomenclatural system exists. This deficiency has fostered confusion and limited their use as character data in phylogenetic analysis.We present a simple system for naming external neural arch fossae that parallels the one developed for the vertebral laminae that bound them. The nomenclatural system identifies fossae by pointing to reference landmarks (e.g., neural spine, centrum, costal articulations, zygapophyses). We standardize the naming process by creating tripartite names from “primary landmarks,” which form the zygodiapophyseal table, “secondary landmarks,” which orient with respect to that table, and “tertiary landmarks,” which further delineate a given fossa.The proposed nomenclatural system for lamina-bounded fossae adds clarity to descriptions of complex vertebrae and allows these structures to be sourced as character data for phylogenetic analyses. These anatomical terms denote potentially homologous pneumatic structures within Saurischia, but they could be applied to any vertebrate with vertebral laminae that enclose spaces, regardless of their developmental origin or phylogenetic distribution

Efflux in Fungi: La Pièce de Résistance

Pathogens must be able to overcome both host defenses and antimicrobial treatment in order to successfully infect and maintain colonization of the host. One way fungi accomplish this feat and overcome intercellular toxin accumulation is efflux pumps, in particular ATP-binding cassette transporters and transporters of the major facilitator superfamily. Members of these two superfamilies remove many toxic compounds by coupling transport with ATP hydrolysis or a proton gradient, respectively. Fungal genomes encode a plethora of members of these families of transporters compared to other organisms. In this review we discuss the role these two fungal superfamilies of transporters play in virulence and resistance to antifungal agents. These efflux transporters are responsible not only for export of compounds involved in pathogenesis such as secondary metabolites, but also export of host-derived antimicrobial compounds. In addition, we examine the current knowledge of these transporters in resistance of pathogens to clinically relevant antifungal agents