STRENGTH AND CONDITIONING PROGRAMMES FOR IMPROVING BACK MUSCLE FATIGABILITY IN FIREFIGHTERS

Back pain and back-related injuries are common in firefighters. The purpose of this study was to compare the effectiveness of two different types of strength and conditioning programmes in improving back muscle fatigability in firefighters. A total of 12 male firefighters completed 16 weeks on supervised exercise intervention programme. The Functional Group was prescribed unilateral movements that mimicked the asymmetrical nature of firefighting tasks. The Conventional Group performed more bilaterally loaded, symmetrical exercise training. The lumbar extensor muscles’ resistance to fatigue was assessed using the Modified Sorensen test with electromyography (EMG). The EMG median frequency slope was less steep (p = 0.023, η²p =0.420) after training, indicating improvement in fatigability. There was no difference between the groups (p = .605, η²p = 0.028) and no interaction effect (p = 0.245, η²p =0.132). In conclusion, a well-rounded strength and conditioning programme is promising in improving back muscle fatigability in firefighters

Measures to predict the individual variability of corticospinal responses following transcranial direct current stimulation

Individual responses to transcranial direct current stimulation (tDCS) are varied and therefore potentially limit its application. There is evidence that this variability is related to the contributions of Indirect waves (I-waves) recruited in the cortex. The latency of motor-evoked potentials (MEPs) can be measured through transcranial magnetic stimulation (TMS), allowing an individual\u27s responsiveness to tDCS to be determined. However, this single-pulse method requires several different orientations of the TMS coil, potentially affecting its reliability. Instead, we propose a paired-pulse TMS paradigm targeting I-waves as an alternative method. This method uses one orientation that reduces inter- and intra-trial variability. It was hypothesized that the paired-pulse method would correlate more highly to tDCS responses than the single-pulse method. In a randomized, double blinded, cross-over design, 30 healthy participants completed two sessions, receiving 20 min of either anodal (2 mA) or sham tDCS. TMS was used to quantify Short interval intracortical facilitation (SICF) at Inter stimulus intervals (ISIs) of 1.5, 3.5 and 4.5 ms. Latency was determined in the posterior-anterior (PA), anterior-posterior (AP) and latero-medial (LM) coil orientations. The relationship between latency, SICF measures and the change in suprathreshold MEP amplitude size following tDCS were determined with Pearson\u27s correlations. TMS measures, SICI and SICF were also used to determine responses to Anodal-tDCS (a-tDCS). Neither of the latency differences nor the SICF measures correlated to the change in MEP amplitude from pre-post tDCS (all P > 0.05). Overall, there was no significant response to tDCS in this cohort. This study highlights the need for testing the effects of various tDCS protocols on the different I-waves. Further research into SICF and whether it is a viable measure of I-wave facilitation is warranted

A porcine model of heart failure with preserved ejection fraction:magnetic resonance imaging and metabolic energetics

Aims A significant proportion of heart failure (HF) patients have HF preserved ejection fraction (HFpEF). The lack of effective treatments for HFpEF remains a critical unmet need. A key obstacle to therapeutic innovation in HFpEF is the paucity of pre-clinical models. Although several large animal models have been reported, few demonstrate progression to decompensated HF. We have established a model of HFpEF by enhancing a porcine model of progressive left ventricular (LV) pressure overload and characterized HF in this model including advanced cardiometabolic imaging using cardiac magnetic resonance imaging and hyperpolarized carbon-13 magnetic resonance spectroscopy. Methods and results Pigs underwent progressive LV pressure overload by means of an inflatable aortic cuff. Pigs developed LV hypertrophy (50% increase in wall thickness, P <0.001, and two-fold increase in mass compared to sham control, P <0.001) with no evidence of LV dilatation but a significant increase in left atrial volume (P = 0.013). Cardiac magnetic resonance imaging demonstrated T1 modified Look-Locker inversion recovery values increased in 16/17 segments compared to sham pigs (P <0.05-P <0.001) indicating global ventricular fibrosis. Mean LV end-diastolic (P = 0.047) and pulmonary capillary wedge pressures (P = 0.008) were elevated compared with sham control. One-third of the pigs demonstrated clinical signs of frank decompensated HF, and mean plasma BNP concentrations were raised compared with sham control (P = 0.008). Cardiometabolic imaging with hyperpolarized carbon-13 magnetic resonance spectroscopy agreed with known metabolic changes in the failing heart with a switch from fatty acid towards glucose substrate utilization. Conclusions Progressive aortic constriction in growing pigs induces significant LV hypertrophy with cardiac fibrosis associated with left atrial dilation, raised filling pressures, and an ability to transition to overt HF with raised BNP without reduction in LVEF. This model replicates many aspects of clinical HFpEF with a predominant background of hypertension and can be used to advance understanding of underlying pathology and for necessary pre-clinical testing of novel candidate therapies

Tedizolid Activity Against Clinical Mycobacterium abscessus Complex Isolates—An in vitro Characterization Study

Mycobacterium abscessus complex consist of three rapidly growing subspecies: M. abscessus, M. massiliense, and M. bolletii. They are clinically important human pathogens responsible for opportunistic pulmonary and skin and soft tissue infections. Treatment of M. abscessus infections is difficult due to in vitro resistance to most antimicrobial agents. Tedizolid (TZD) is a next-generation oxazolidinone antimicrobial with a wide spectrum of activity even against multidrug resistant Gram-positive bacteria. In this study, the in vitro activity of TZD against the M. abscessus complex (n = 130) was investigated. Susceptibility testing by broth microdilution showed lower TZD minimum inhibitory concentrations (MICs) when compared to linezolid. The MIC50 and MIC90 was 1 mg/L and 4 mg/L, respectively across all M. abscessus complex members, reflecting no difference in subspecies response to TZD. Pre-exposure of M. abscessus complex to subinhibitory concentrations of TZD did not trigger any inducible drug resistance. Single-drug time kill assays and bactericidal activity assays demonstrated bacteriostatic activity of TZD in all three M. abscessus subspecies, even at high drug concentrations of 4 to 8x MIC. Combination testing of TZD with clarithromycin, doxycycline and amikacin using the checkerboard approach showed no antagonistic interactions. TZD may be an effective therapeutic antimicrobial agent for the treatment of M. abscessus infections

Nasopharyngeal Carcinoma Metastatic to the Mandible

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck region, especially among those of Chinese origin. NPC has multifactorial aetiologies including genetic susceptibility, consumption of food with high salt content, and the Epstein–Barr virus. The primary tumour usually arises from the lateral walls of the nasopharynx and is characterized by a rich sub-mucosal lymphatic structure, often leading to cervical lymph node metastasis. Distant metastasis has been recognized to be a major cause of treatment failure in patients with nasopharyngeal carcinoma. Bone, liver and lung are the most frequent sites of NPC metastases

Fully gapped topological surface states in Bi2_2Se3_3 films induced by a d-wave high-temperature superconductor

Topological insulators are a new class of materials, that exhibit robust gapless surface states protected by time-reversal symmetry. The interplay between such symmetry-protected topological surface states and symmetry-broken states (e.g. superconductivity) provides a platform for exploring novel quantum phenomena and new functionalities, such as 1D chiral or helical gapless Majorana fermions, and Majorana zero modes which may find application in fault-tolerant quantum computation. Inducing superconductivity on topological surface states is a prerequisite for their experimental realization. Here by growing high quality topological insulator Bi$_2$Se$_3$ films on a d-wave superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ using molecular beam epitaxy, we are able to induce high temperature superconductivity on the surface states of Bi$_2$Se$_3$ films with a large pairing gap up to 15 meV. Interestingly, distinct from the d-wave pairing of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$, the proximity-induced gap on the surface states is nearly isotropic and consistent with predominant s-wave pairing as revealed by angle-resolved photoemission spectroscopy. Our work could provide a critical step toward the realization of the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274

Grain boundary effects on magnetotransport in bi-epitaxial films of La0.7_{0.7}Sr0.3_{0.3}MnO3_3

The low field magnetotransport of La$_{0.7}$Sr$_{0.3}$MnO$_3$ (LSMO) films grown on SrTiO$_3$ substrates has been investigated. A high qualtity LSMO film exhibits anisotropic magnetoresistance (AMR) and a peak in the magnetoresistance close to the Curie temperature of LSMO. Bi-epitaxial films prepared using a seed layer of MgO and a buffer layer of CeO$_2$ display a resistance dominated by grain boundaries. One film was prepared with seed and buffer layers intact, while a second sample was prepared as a 2D square array of grain boundaries. These films exhibit i) a low temperature tail in the low field magnetoresistance; ii) a magnetoconductance with a constant high field slope; and iii) a comparably large AMR effect. A model based on a two-step tunneling process, including spin-flip tunneling, is discussed and shown to be consistent with the experimental findings of the bi-epitaxial films.Comment: REVTeX style; 14 pages, 9 figures. Figure 1 included in jpeg format (zdf1.jpg); the eps was huge. Accepted to Phys. Rev.

Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS

Symmetry and Topology in Superconductors - Odd-frequency pairing and edge states -

Superconductivity is a phenomenon where the macroscopic quantum coherence appears due to the pairing of electrons. This offers a fascinating arena to study the physics of broken gauge symmetry. However, the important symmetries in superconductors are not only the gauge invariance. Especially, the symmetry properties of the pairing, i.e., the parity and spin-singlet/spin-triplet, determine the physical properties of the superconducting state. Recently it has been recognized that there is the important third symmetry of the pair amplitude, i.e., even or odd parity with respect to the frequency. The conventional uniform superconducting states correspond to the even-frequency pairing, but the recent finding is that the odd-frequency pair amplitude arises in the spatially non-uniform situation quite ubiquitously. Especially, this is the case in the Andreev bound state (ABS) appearing at the surface/interface of the sample. The other important recent development is on the nontrivial topological aspects of superconductors. As the band insulators are classified by topological indices into (i) conventional insulator, (ii) quantum Hall insulator, and (iii) topological insulator, also are the gapped superconductors. The influence of the nontrivial topology of the bulk states appears as the edge or surface of the sample. In the superconductors, this leads to the formation of zero energy ABS (ZEABS). Therefore, the ABSs of the superconductors are the place where the symmetry and topology meet each other which offer the stage of rich physics. In this review, we discuss the physics of ABS from the viewpoint of the odd-frequency pairing, the topological bulk-edge correspondence, and the interplay of these two issues. It is described how the symmetry of the pairing and topological indices determines the absence/presence of the ZEABS, its energy dispersion, and properties as the Majorana fermions.Comment: 91 pages, 38 figures, Review article, references adde