Commentary: the role of the toxicologic pathologist in academia.

Veterinary pathologists working as toxicologic pathologists in academic settings fill many vital roles, such as diagnosticians, educators, and/or researchers. These individuals have spent years investigating pathology problems that mainly or exclusively focus on the reactions of cells, organs, or systems to toxic materials. Thus, academic toxicologic pathologists are uniquely suited both to help trainees understand toxicity as a cause of pathology responses and also to provide expert consultation on toxicologic pathology. Most toxicologic pathologists in academia are employed at colleges of medicine or veterinary medicine, even though specific toxicologic pathology faculty appointments are uncommon in Europe and North America. Academic toxicologic pathologists typically receive lower financial compensation than do toxicologic pathologists in industry, but academic positions generally provide alternative rewards, such as higher workplace autonomy and scheduling flexibility, professional enrichment through student interactions, and enhanced opportunities for collaborative research and advanced diagnostic investigations. Regular participation by academic toxicologic pathologists in professional training opportunities (eg, as pathology and toxicology instructors in medical and veterinary medical courses, graduate programs, and residencies) offers an important means of engendering interest and inspiring veterinarians to select toxicologic pathology and toxicology as their own areas of future expertise.

Variation in the determinants of power of chemically skinned human muscle fibres.

We have explored the extent to which the maximal velocity of unloaded shortening (V(max)), the force generated per unit cross-sectional area (P(0)) and the curvature of the force-velocity relationship (a/P(0) in the Hill equation) contribute to differences in peak power of chemically skinned single fibres from the quadriceps muscle of healthy young male subjects. The analysis was restricted to type I and IIA fibres that contained a single type of myosin heavy chain on electrophoretic separation. Force-velocity relationships were determined from isotonic contractions of maximally activated fibres at 15 degrees C. Mean (+/- s.d.) peak powers were 1.99 +/- 0.72 watts per litre (W L(-1)) for type I fibres and 6.92 +/- 2.41 W L(-1), for type IIA fibres. The most notable feature, however, was the very large, sevenfold, range of power outputs within a single fibre type. This wide range was a consequence of variations in each of the three components determining power: P(0), V(max) and a/P(0). Within a single fibre type, P(0) varied threefold, and V(max) and a/P(0) two- to threefold. There were no obvious relationships between P(0) and V(max) or between P(0) and a/P(0). However, there was a suggestion of an inverse relationship between a/P(0) and V(max), the effect being to reduce, somewhat, the impact of differences in V(max) on peak power. In searching for the causes of variation in peak power of fibres of the same type, it appears likely that there are two factors, one that affects P(0) and another that leads to variation in both V(max) and a/P(0).

Barriers to achieving care at home at the end of life: transferring patients between care settings using patient transport services.

Enabling patients to be cared for in their preferred location often involves journeys between care settings. The challenge of ensuring journeys are timely and safe emerged as an important issue in an evaluation of palliative care services, which informed a service redesign programme in three areas of the United Kingdom by the Marie Curie Cancer Care 'Delivering Choice Programme'. This article explores perceptions of service users and key stakeholders of palliative care services about problems encountered in journeys between care settings during end-of-life care. This article draws on data from interviews with stakeholders (n = 44), patients (n = 16), carers (n = 19) and bereaved carers (n = 20); and focus groups (n = 9) with specialist nurses. Data were gathered in three areas of the United Kingdom. Data were analysed using a framework approach. Transport problems between care settings emerged as a key theme. Four particular problems were identified: (1) urgent need for transport due to patients' rapidly changing condition; (2) limited time to organise transfers; (3) the management of specialist equipment and (4) the need to clarify the resuscitation status of patients. Partnership working between Ambulance Services and secondary care is required to develop joint protocols of care to ensure timely and safe transportation between care settings of patients, who are near their end of life. Commissioning of services should be responsive to the complexities of patients' needs and those of their families.

Age-dependency in bone mass and geometry: a pQCT study on male and female master sprinters, middle and long distance runners, race-walkers and sedentary people.

OBJECTIVE: To investigate whether athletic participation allows master athletes to preserve their good bone health into old age. METHODS: Bone strength indicators of the tibia and the radius were obtained of master runners and race-walkers (n=300) competing at World and European Master Championships and of 75 sedentary controls, all aged 33-94 yrs. RESULTS: In the tibia, diaphyseal cortical area (Ar.Ct), polar moment of resistance (RPol) and trabecular bone mineral density (vBMD) were generally greater in athletes than controls at all ages. In the athletes, but not the controls, Ar.Ct, RPol (females) and trabecular vBMD were negatively correlated with age (p<0.01). Radius measures were comparable between athlete and control groups at all ages. The amalgamated data revealed negative correlations of age with Ar.Ct, RPol (females), cortical vBMD and trabecular vBMD (males; p<0.005) and positive correlations with endocortical circumference (p<0.001). CONCLUSION: This cross-sectional study found age-related differences in tibial bone strength indicators of master athletes, but not sedentary controls, thus, groups becoming more similar with advancing age. Age-related differences were noticeable in the radius too, without any obvious group difference. Results are compatible with the notion that bones adapt to exercise-specific forces throughout the human lifespan.

'A Friend in the Corner': supporting people at home in the last year of life via telephone and video consultation-an evaluation.

OBJECTIVE: To evaluate 'Gold Line', a 24/7, nurse-led telephone and video-consultation support service for patients thought to be in the last year of life in Bradford, Airedale, Wharfedale and Craven. METHOD: Data on the time and nature of all calls between 1 April 2014 and 30 March 2015 were obtained from the patient Electronic Records. Interviews with 13 participants captured patients and carers perspectives. RESULTS: To date, 3291 patients have been referred to the Gold Line. During the study period, 42% of registered patients had a non-cancer diagnosis and 45.2% of service users were not known to Specialist Palliative Care services. The median time on the caseload was 49 days (range 1-504 days). 4533 telephone calls and 573 video consultations were made involving 1813 individuals. 39% of the 5106 contacts were resolved by the Gold Line team without referral to other services. 69% of calls were made outside normal working hours. Interviews with patients and carers reported experiences of support and reassurance from the Gold Line and the importance of practical advice was emphasised. Current data (year to October 2015) show that 98.5% of calls (4500/4568) resulted in patients remaining in their place of residence. CONCLUSIONS: A nurse led, 24/7 telephone and video consultation service can provide valuable support for patients identified to be in the last year of life and for their carers. The line enabled them to feel supported and remain in their place of residence, hence reducing the pressure for avoidable hospital admissions and use of other services. Providing this service may encourage healthcare professionals to identify more patients approaching the last year of life, widening support offered to this group of patients beyond those known to specialist palliative care services.

Early Detection of Infection Chains & Outbreaks: Use Case Infection Control.

Within the HiGHmed Project there are three medical use cases. The use cases include the scopes cardiology, oncology and infection. They serve to specify the requirements for the development and implementation of a local and federated platform, with the result that data from medical care and research should be retrievable, reusable and interchangeable. The Use Case Infection Control aims to establish an early detection of transmission events as well as clusters and outbreaks of various pathogens. Therefore the use case wants to establish the smart infection control system (SmICS).

Intranuclear paracrystals observed in striated muscle specific LIM protein-deficient mouse cardiomyocytes.

A paracrystalline structure was observed within left ventricular cardiomyocyte nuclei of MLP(-/-) mice. The paracrystal possessed cross lines, approximately 8.0 micro m long and 0.3 micro m wide, with a slender spindle shape and a periodicity of 13 nm. Paracrystals were best observed along the longitudinal orientation of myofibrils and were detected in less than 10% of the nuclei observed. One dimension of the protein unit forming the paracrystal was 8.5 nm long. The electron density of the paracrystal appeared to be slightly higher than that of heterochromatin, suggesting that RNA-associated proteins are constituents of the paracrystal. This is the first report of intranuclear paracrystals in cardiomyocytes, which appear to be unique to MLP(-/-) mice.

Recruitment of single muscle fibers during submaximal cycling exercise.

In literature, an inconsistency exists in the submaximal exercise intensity at which type II fibers are activated. In the present study, the recruitment of type I and II fibers was investigated from the very beginning and throughout a 45-min cycle exercise at 75% of the maximal oxygen uptake, which corresponded to 38% of the maximal dynamic muscle force. Biopsies of the vastus lateralis muscle were taken from six subjects at rest and during the exercise, two at each time point. From the first biopsy single fibers were isolated and characterized as type I and II, and phosphocreatine-to-creatine (PCr/Cr) ratios and periodic acid-Schiff (PAS) stain intensities were measured. Cross sections were cut from the second biopsy, individual fibers were characterized as type I and II, and PAS stain intensities were measured. A decline in PCr/Cr ratio and in PAS stain intensity was used as indication of fiber recruitment. Within 1 min of exercise both type I and, although to a lesser extent, type II fibers were recruited. Furthermore, the PCr/Cr ratio revealed that the same proportion of fibers was recruited during the whole 45 min of exercise, indicating a rather constant recruitment. The PAS staining, however, proved inadequate to fully demonstrate fiber recruitment even after 45 min of exercise. We conclude that during cycling exercise a greater proportion of type II fibers is recruited than previously reported for isometric contractions, probably because of the dynamic character of the exercise. Furthermore, the PCr/Cr ratio method is more sensitive in determining fiber activation than the PAS stain intensity method.

Symmetry-breaking study with deformed ensembles.

A random matrix model to describe the coupling of m -fold symmetry is constructed. The particular threefold case is used to analyze data on eigenfrequencies of elastomechanical vibration of an anisotropic quartz block. It is suggested that such an experimental and theoretical study may supply a powerful means to discern the intrinsic symmetry of physical systems.

Level density for deformations of the Gaussian orthogonal ensemble.

Formulas are derived for the average level density of deformed, or transition, Gaussian orthogonal random matrix ensembles. After some general considerations about Gaussian ensembles, we derive formulas for the average level density for (i) the transition from the Gaussian orthogonal ensemble (GOE) to the Poisson ensemble and (ii) the transition from the GOE to m GOEs.

RNA content differs in slow and fast muscle fibers: implications for interpretation of changes in muscle gene expression.

Quantification of a specific muscle mRNA per total RNA (e.g., by Northern blot analysis) plays a crucial role in assessment of developmental, experimental, or pathological changes in gene expression. However, total RNA content per gram of a particular fiber type may differ as well. We have tested this possibility in the distinct fiber types of adult rat skeletal muscle. Sections of single fibers were hybridized against 28S rRNA as a marker for RNA content. Quantification of the hybridization showed that the 28S rRNA content decreases in the order I>IIA>IIX>IIB, where Type I fibers show a five- to sixfold higher expression level compared to Type IIB fibers. Results were verified with an independent biochemical determination of total RNA content performed on pools of histochemically defined freeze-dried single fibers. In addition, the proportion of myosin heavy chain (MHC) mRNA per microgram of total RNA was similar in slow and fast fibers, as demonstrated by Northern blot analysis. Consequently, Type I fibers contain five- to sixfold more MHC mRNA per microgram of tissue than IIB fibers. These differences are not reflected in the total fiber protein content. This study implies that proper assessment of mRNA levels in skeletal muscle requires evaluation of total RNA levels according to fiber type composition.

Effect of prior exercise on maximal short-term power output in humans.

The effect of prior exercise (PE) on subsequent maximal short-term power output (STPO) was examined during cycling exercise on an isokinetic ergometer. In the first series of experiments the duration of PE at a power output equivalent to 98% maximum O2 uptake (VO2max) was varied between 0.5 and 6 min before measurement of maximal STPO. As PE duration increased subsequent STPO fell to approximately 70% of control values after 3-6 min. In series ii the effect of varying the intensity of PE of fixed 6-min duration was studied in five subjects. After PE less than 60% VO2max there was an increase of 12% in STPO, but after greater than 60% VO2max there was a progressive fall in STPO as PE intensity increased, indicating a reduction of approximately 35% at 100% VO2max compared with control values. In series iii we examined the effect on STPO of allowing a recovery period after a fixed intensity (mean = 87% VO2max) of 6 min PE before measurement of STPO. This indicated a rapid recovery of dynamic function with a half time of approximately 32 s, which is similar to the kinetics of PC resynthesis and taken with the other findings suggests the dominant role that PC exerts on the STPO under these conditions.

Effect of fatigue on maximal power output at different contraction velocities in humans.

The effect of fatigue as a result of a standard submaximal dynamic exercise on maximal short-term power output generated at different contraction velocities was studied in humans. Six subjects performed 25-s maximal efforts on an isokinetic cycle ergometer at five different pedaling rates (60, 75, 90, 105, and 120 rpm). Measurements of maximal power output were made under control conditions [after 6 min of cycling at 30% maximal O2 uptake (VO2max)] and after fatiguing exercise that consisted of 6 min of cycling at 90% VO2max with a pedaling rate of 90 rpm. Compared with control values, maximal peak power measured after fatiguing exercise was significantly reduced by 23 +/- 19, 28 +/- 11, and 25 +/- 11% at pedaling rates of 90, 105, and 120 rpm, respectively. Reductions in maximum peak power of 11 +/- 8 and 14 +/- 8% at 60 and 75 rpm, respectively, were not significant. The rate of decline in peak power during the 25-s control measurement was least at 60 rpm (5.1 +/- 2.3 W/s) and greatest at 120 rpm (26.3 +/- 13.9 W/s). After fatiguing exercise, the rate of decline in peak power at pedaling rates of 105 and 120 rpm decreased significantly from 21.5 +/- 9.0 and 26.3 +/- 13.9 W/s to 10.0 +/- 7.3 and 13.3 +/- 6.9 W/s, respectively. These experiments indicate that fatigue induced by submaximal dynamic exercise results in a velocity-dependent effect on muscle power. It is suggested that the reduced maximal power at the higher velocities was due to a selective effect of fatigue on the faster fatigue-sensitive fibers of the active muscle mass.

Effects of high-frequency initial pulses and posttetanic potentiation on power output of skeletal muscle.

The effects of high-frequency initial pulses (HFIP) and posttetanic potentiation on mechanical power output during concentric contractions were examined in the in situ medial gastrocnemius of the rat with an intact origin on the femur and blood supply. Stimulation of the muscle was performed via the severed sciatic nerve. In the experiments, HFIP or the potentiating tetanus was followed by a stimulation of 80, 120, or 200 Hz. The results showed that both HFIP and the tetanus increased power output at high contraction velocities (>75 mm/s) when followed by a train of 80 or 120 Hz (200 Hz resulted in no effects). Mechanical power output was increased maximally by HFIP to 120 and 168% by the tetanus. Furthermore, when HFIP or the tetanus were followed by a train of 80 Hz, the peak power in the power-velocity curve tended to be shifted to a higher velocity.

In vivo specific tension of human skeletal muscle.

In this study, we estimated the specific tensions of soleus (Sol) and tibialis anterior (TA) muscles in six men. Joint moments were measured during maximum voluntary contraction (MVC) and during electrical stimulation. Moment arm lengths and muscle volumes were measured using magnetic resonance imaging, and pennation angles and fascicular lengths were measured using ultrasonography. Tendon and muscle forces were modeled. Two approaches were followed to estimate specific tension. First, muscle moments during electrical stimulation and moment arm lengths, fascicular lengths, and pennation angles during MVC were used (data set A). Then, MVC moments, moment arm lengths at rest, and cadaveric fascicular lengths and pennation angles were used (data set B). The use of data set B yielded the unrealistic specific tension estimates of 104 kN/m(2) in Sol and 658 kN/m(2) in TA. The use of data set A, however, yielded values of 150 and 155 kN/m(2) in Sol and TA, respectively, which agree with in vitro results from fiber type I-predominant muscles. In fact, both Sol and TA are such muscles. Our study demonstrates the feasibility of accurate in vivo estimates of human muscle intrinsic strength.

Repeated force production and metabolites in two medial gastrocnemius muscle compartments of the rat.

The most proximal and distal motor nerve branches in the rat medial gastrocnemius innervate discrete muscle compartments dominated by fast-twitch oxidative and fast-twitch glycolytic fibers, respectively. The functional consequences of the difference in oxidative capacity between these compartments were investigated. Wistar rats were anesthetized with pentobarbital sodium (90 mg/kg ip). Changes in force of both compartments during 21 isometric contractions (train duration 200 ms, stimulation frequency 120 Hz, 3 s between contractions) were studied in situ with and without blood flow. Without blood flow, force and phosphocreatine declined to a greater extent in the proximal than the distal compartment compared with the run with intact flow. After the protocol without blood flow, when flow was restored, the time constants for force recovery (which were closely associated to the recovery of phosphocreatine) were 37 +/- 7 (SD) (proximal compartment) and 148 +/- 20 s (distal compartment). It was concluded that the proximal compartment had a four times higher oxidative capacity and, therefore, a superior ability for repeated force production.

Relationships between energy expenditure and positive and negative mechanical work in repetitive lifting and lowering.

Determining the separate energy costs of the positive and negative mechanical work in repetitive lifting or lowering is quite complex, as a mixture of both work components will always be involved in the up- and downward motion of the lifter's body mass. In the current study, a new method was tested in which coefficients specifically related to the positive and negative work were estimated by multiple regression on a data set of weight-lifting and weight-lowering tasks. The energy cost was obtained from oxygen uptake measurements. The slopes of the regression lines for energy cost and mechanical work were steeper for positive than for negative work. The cost related to the negative work was approximately 0.3-0.5 times the cost of the positive work. This finding is well in line with data obtained directly from other isolated activities of either positive or negative work (e.g., ladder climbing vs. descending). However, the intercept values of the regression lines were not significantly different from zero or were even negative. This was most likely due to the metabolic energy not related to processes that yield mechanical work (e.g., isometric muscle actions) that was not constant among trials.

In vivo IIX and IIB fiber recruitment in gastrocnemius muscle of the rat is compartment related.

The purpose of the present study was to investigate to what extent fast-twitch IIX and IIB fiber recruitment was related to the natural existing muscle compartments (subvolumes of muscle innervated by different primary nerve branches) in rat medial gastrocnemius. Three groups (n = 6) of rats trotted on a motor-driven treadmill (20 degrees incline) at different speeds. A fourth group served as controls, and a fifth group received in situ electrical stimulation of all medial gastrocnemius muscle fibers. Postexercise glycogen levels (periodic acid-Schiff staining intensities) were made. Running caused more and in situ stimulation caused less glycogen breakdown in the proximal IIX and IIB fibers compared with the fibers of the same type in the most distal compartment. Furthermore, the boundaries of the most distal compartment could often be recognized in the periodic acid-Schiff-stained cross sections. It was concluded that during running the proximal IIX and IIB fibers were recruited to a greater extent (and at lower treadmill speeds) compared with the distal IIX and IIB fibers, respectively.

In situ rat fast skeletal muscle is more efficient at submaximal than at maximal activation levels.

The influence of stimulation frequency on efficiency (= total work output/high-energy phosphate consumption) was studied using in situ medial gastrocnemius muscle tendon complexes of the rat. The muscles performed 20 repeated concentric contractions (2/s) at 34 degrees C. During these repeated contractions, the muscle was stimulated via the severed sciatic nerve with either 60, 90, or 150 Hz. The muscle was freeze-clamped immediately after these contractions, and high-energy phosphate consumption was determined by measuring intramuscular chemical change relative to control muscles. The average values (+/-SD) of efficiency calculated for 60, 90, and 150 Hz were 18.5 +/- 1.5 (n = 7), 18.6 +/- 1.5 (n = 9), and 14.7 +/- 1.3 mJ/micromol phosphate (n = 9). The results indicate that the efficiency of the muscles that were submaximally activated (60 or 90 Hz) was higher (+26%, P < 0.05) than that of those maximally activated (150 Hz). Additional experiments showed that the low efficiency at maximal activation levels is unlikely to be the result of a higher energy turnover by the Ca2+ -ATPase relative to the total energy turnover. Therefore, alternative explanations are discussed.

Voluntary activation level and muscle fiber recruitment of human quadriceps during lengthening contractions.

Voluntary activation levels during lengthening, isometric, and shortening contractions (angular velocity 60 degrees/s) were investigated by using electrical stimulation of the femoral nerve (triplet, 300 Hz) superimposed on maximal efforts. Recruitment of fiber populations was investigated by using the phosphocreatine-to-creatine ratio (PCr/Cr) of single characterized muscle fibers obtained from needle biopsies at rest and immediately after a series of 10 lengthening, isometric, and shortening contractions (1 s on/1 s off). Maximal voluntary torque was significantly higher during lengthening (270 +/- 55 N.m) compared with shortening contractions (199 +/- 47 N.m, P < 0.05) but was not different from isometric contractions (252 +/- 47 N.m). Isometric torque was higher than torque during shortening (P < 0.05). Voluntary activation level during maximal attempted lengthening contractions (79 +/- 8%) was significantly lower compared with isometric (93 +/- 5%) and shortening contractions (92 +/- 3%, P < 0.05). Mean PCr/Cr values of all fibers from all subjects at rest were 2.5 +/- 0.6, 2.0 +/- 0.7, and 2.0 +/- 0.7, respectively, for type I, IIa, and IIax fibers. After 10 contractions, the mean PCr/Cr values for grouped fiber populations (regardless of fiber type) were all significantly different from rest (1.3 +/- 0.2, 0.7 +/- 0.3, and 0.8 +/- 0.6 for lengthening, isometric, and shortening contractions, respectively; P < 0.05). The cumulative distributions of individual fiber populations after either contraction mode were significantly different from rest (P < 0.05). Curves after lengthening contractions were less shifted compared with curves from isometric and shortening contractions (P < 0.05), with a smaller shift for the type IIax compared with type I fibers in the lengthening contractions. The results indicate a reduced voluntary drive during lengthening contractions. PCr/Cr values of single fibers indicated a hierarchical order of recruitment of all fiber populations during maximal attempted lengthening contractions.