Hypoxic acclimation negatively impacts the contractility of steelhead trout (Oncorhynchus mykiss) spongy myocardium.

Cardiac stroke volume (SV) is compromised in Atlantic cod and rainbow trout following acclimation to hypoxia (i.e., 40% air saturation; ~8 kPa O2) at 10-12°C, and this is not due to changes in heart morphometrics or maximum achievable in vitro end-diastolic volume. To examine if this diminished SV may be related to compromised myocardial contractility, we used the work-loop method to measure work and power in spongy myocardial strips from normoxic- and hypoxic-acclimated steelhead trout when exposed to decreasing Po2 levels (21 to 1.5 kPa) at several frequencies (30-90 contractions/min) at 14°C (their acclimation temperature). Work required to lengthen the muscle, as during filling of the heart, was strongly frequency dependent (i.e., increased with contraction rate) but was not affected by hypoxic acclimation or test Po2. In contrast, although shortening work was less frequency dependent, this parameter and network (and power) 1) were consistently lower (by ~30-50 and ~15%, respectively) in strips from hypoxic-acclimated fish and 2) fell by ~40-50% in both groups from 20 to 1.5 kPa Po2, despite the already-reduced myocardial performance in the hypoxic-acclimated group. In addition, strips from hypoxic-acclimated trout showed a poorer recovery of net power (by ~15%) when returned to normoxia. These results strongly suggest that hypoxic acclimation reduces myocardial contractility, and in turn, may limit SV (possibly by increasing end-systolic volume), but that this diminished performance does not improve the capacity to maintain myocardial performance under oxygen limiting conditions.

Neutron emission spectroscopy of D plasmas at JET with a compact liquid scintillating neutron spectrometer.

Neutron emission spectroscopy is a diagnostic technique that allows for energy measurements of neutrons born in nuclear reactions. The JET tokamak fusion experiment (Culham, UK) has a special role in this respect as advanced spectrometers for 2.5 MeV and 14 MeV neutrons have been developed here for the first time for measurements of the neutron emission spectrum from D and DT plasmas with unprecedented accuracy. Twin liquid scintillating neutron spectrometers were built and calibrated at the Physikalisch-Technische Bundesanstalt (PTB) (Braunschweig, Germany) and installed on JET in the recent years with tangential-equatorial (KM12) and vertical-radial (KM13) view lines, with the latter only recently operational. This article reports on the performance of KM12 and on the development of the data analysis methods in order to extract physics information upon D ions kinematics in JET auxiliary-heated D plasmas from 2.5 MeV neutron measurements. The comparison of these results with the correspondents from other JET neutron spectrometers is also presented: their agreement allows for JET unique capability of multi-lines of sight neutron spectroscopy and for benchmarking other 14 MeV neutron spectrometers installed on the same lines of sight in preparation for the DT experimental campaign at JET.

Tomographic analysis of neutron and gamma pulse shape distributions from liquid scintillation detectors at Joint European Torus.

The Joint European Torus (JET, Culham, UK) is the largest tokamak in the world devoted to nuclear fusion experiments of magnetic confined Deuterium (D)/Deuterium-Tritium (DT) plasmas. Neutrons produced in these plasmas are measured using various types of neutron detectors and spectrometers. Two of these instruments on JET make use of organic liquid scintillator detectors. The neutron emission profile monitor implements 19 liquid scintillation counters to detect the 2.45 MeV neutron emission from D plasmas. A new compact neutron spectrometer is operational at JET since 2010 to measure the neutron energy spectra from both D and DT plasmas. Liquid scintillation detectors are sensitive to both neutron and gamma radiation but give light responses of different decay time such that pulse shape discrimination techniques can be applied to identify the neutron contribution of interest from the data. The most common technique consists of integrating the radiation pulse shapes within different ranges of their rising and/or trailing edges. In this article, a step forward in this type of analysis is presented. The method applies a tomographic analysis of the 3-dimensional neutron and gamma pulse shape and pulse height distribution data obtained from liquid scintillation detectors such that n/γ discrimination can be improved to lower energies and additional information can be gained on neutron contributions to the gamma events and vice versa.

Muscle-only intra-oral mucosal defect reconstruction.

Reconstructive requirements of medium to large sized oral mucosal defects following oncological resection include restoration of mucosal continuity with prevention of salivary leak and fistula formation, predictable soft tissue healing, and ensuring optimal oral function and cosmetic restoration. Such defects frequently mandate the use of microvascular free tissue transfer of fasciocutaneous flaps such as the radial forearm or anterolateral thigh flaps, or, for larger defects incorporating significant dead-space, muscle flaps such as rectus abdominis or latissimus dorsi. Commonly described techniques for re-establishing continuity of the epithelial component include using native mucosa, split skin graft, or a myocutaneous flap skin paddle. Few case series reports exist of non-epithelial reconstructive approaches. Here, the authors report a large series of muscle only flaps for oral defect reconstruction following oncologic resection. The current study demonstrates that mucosalised muscle is an effective additional method for intra-oral mucosal defect reconstruction.

Radical surgical treatment of bisphosphonate related osteonecrosis of the jaw.

We describe a case of a 64-year-old female diagnosed with multiple myeloma in 2001. She was treated with pamidronate and subsequently zolodronic acid before developing spontaneous bisphosphonate related osteonecrosis (BRONJ) of the left maxilla in December 2008. Over the next two years the BRONJ was treated conservatively but gradually became more symptomatic. About three years after her last dose of zolodronic acid with her symptoms increasing, she underwent radical surgical excision of all diseased bone and flap reconstruction. The patient is now six months postoperative and symptom free.

The IMAP flap for pharygoesophageal reconstruction following stricture release.

Small-medium pharyngo-oesophageal or peri-tracheostoma defects represent a difficult reconstructive problem. Previous solutions included locoregional options such as the deltopectoral flap, or microvascular free tissue transfer. The authors present a novel application of the internal mammary artery perforator (IMAP) flap for reconstructing such defects. The IMAP flap may be mapped using pre-operative Doppler or CTA, and is raised on a single perforator. The relatively quick and simple flap raise provides robust fasciocutaneous tissue, may be tunneled subcutaneously to reach the neck and yields an inconspicuous donor site. The authors provide several cases demonstrating applications of the IMAP flap for reconstructing small-medium sized defects following release of annular pharyngoesophageal stricture, and studies documenting post-operative swallow. Overall, the pedicled IMAP fasciocutaneous flap is a useful technique to provide excellent composite tissue to reconstruct defects resulting from release of annular pharyngeal strictures. It is technically simple, and yields an inconspicuous anterior chest donor site.

Skeletal and cardiac muscle defects in a murine model of Emery-Dreifuss muscular dystrophy.

Previous histological findings, physiological data, and behavioral observations on the A-type lamin knockout mouse (Lmna(-/-)) suggest that important aspects of this model resemble the human Emery-Dreifuss muscular dystrophy (EDMD) phenotype. The main goal of our experiments was to study skeletal and cardiac muscle function in this murine model to obtain the semiquantitative data needed for more detailed comparisons with human EDMD defects. Measurements of the mechanical properties of preparations from two different skeletal muscle groups, the soleus and the diaphragm, were made in vitro. In addition, records of the electrocardiogram, and measurements of heart rate variability were obtained; and phasic contractions (unloaded shortening) of enzymatically isolated ventricular myocytes were monitored. Soleus muscles from Lmna(-/-) mice produced less force and work than control preparations. In contrast, force and work production in strips of diaphragm were not changed significantly. Lead II electrocardiograms from conscious, restrained Lmna(-/-) mice revealed slightly decreased heart rates, with significant prolongations of PQ, QRS, and 'QT' intervals compared with those from control recordings. These ECG changes resemble some aspects of the ECG records from humans with EDMD; however, the cardiac phenotype in this Lmna(-/-) mouse model appears to be less well-defined/developed. Ventricular myocytes isolated from Lmna(-/-) mice exhibited impaired contractile responses, particularly when superfused with the beta-adrenergic agonist, isoproterenol (1 microM). This deficit was more pronounced in myocytes isolated from the left ventricle(s) than in myocytes from the right ventricle(s). In summary, tissues from the Lmna(-/-) mouse exhibit a number of skeletal and cardiac muscle deficiencies, some of which are similar to those which have been reported in studies of human EDMD.

Trading force for speed: why superfast crossbridge kinetics leads to superlow forces.

Superfast muscles power high-frequency motions such as sound production and visual tracking. As a class, these muscles also generate low forces. Using the toadfish swimbladder muscle, the fastest known vertebrate muscle, we examined the crossbridge kinetic rates responsible for high contraction rates and how these might affect force generation. Swimbladder fibers have evolved a 10-fold faster crossbridge detachment rate than fast-twitch locomotory fibers, but surprisingly the crossbridge attachment rate has remained unchanged. These kinetics result in very few crossbridges being attached during contraction of superfast fibers (only approximately 1/6 of that in locomotory fibers) and thus low force. This imbalance between attachment and detachment rates is likely to be a general mechanism that imposes a tradeoff of force for speed in all superfast fibers.

The whistle and the rattle: the design of sound producing muscles.

Vertebrate sound producing muscles often operate at frequencies exceeding 100 Hz, making them the fastest vertebrate muscles. Like other vertebrate muscle, these sonic muscles are "synchronous," necessitating that calcium be released and resequestered by the sarcoplasmic reticulum during each contraction cycle. Thus to operate at such high frequencies, vertebrate sonic muscles require extreme adaptations. We have found that to generate the "boatwhistle" mating call (approximately 200 Hz), the swimbladder muscle fibers of toadfish have evolved (i) a large and very fast calcium transient, (ii) a fast crossbridge detachment rate, and (iii) probably a fast kinetic off-rate of Ca2+ from troponin. The fibers of the shaker muscle of rattlesnakes have independently evolved similar traits, permitting tail rattling at approximately 90 Hz.

Influence of muscle length on work from trabecular muscle of frog atrium and ventricle.

The work capacity of segments of atrial and ventricular muscle from the frog Rana pipiens was measured as a function of muscle length using the work loop technique. Both the work done during shortening and the work required to re-lengthen the muscle after shortening increased with muscle length. Net work increased with length up to a maximum, beyond which work declined. The optimum sarcomere length for work output was 2.5-2.6 microns for both atrial and ventricular muscle. Isometric force increased with muscle length to lengths well beyond the optimum for work output. Thus, the decline in work at long lengths is not simply a consequence of a reduction in the capacity of heart muscle to generate force. It is proposed that it is the non-linear increase in work required to re-lengthen muscle with increasing muscle length which limits net work output and leads to a maximum in the relationship between net work and muscle length. Extension of the results from muscle strips to intact hearts suggests that the work required to fill the ventricle exceeds that available from atrial muscle at all but rather short ventricular muscle lengths.

Influence of muscle length on work from trabecular muscle of frog atrium and ventricle

The work capacity of segments of atrial and ventricular muscle from the frog Rana pipiens was measured as a function of muscle length using the work loop technique. Both the work done during shortening and the work required to re-lengthen the muscle after shortening increased with muscle length. Net work increased with length up to a maximum, beyond which work declined. The optimum sarcomere length for work output was 2.5­2.6 µm for both atrial and ventricular muscle. Isometric force increased with muscle length to lengths well beyond the optimum for work output. Thus, the decline in work at long lengths is not simply a consequence of a reduction in the capacity of heart muscle to generate force. It is proposed that it is the non-linear increase in work required to re-lengthen muscle with increasing muscle length which limits net work output and leads to a maximum in the relationship between net work and muscle length. Extension of the results from muscle strips to intact hearts suggests that the work required to fill the ventricle exceeds that available from atrial muscle at all but rather short ventricular muscle lengths.