Mitochondrial DNA differentiation between the antitropical blue whiting species Micromesistius poutassou and Micromesistius australis.

This study investigated the biogeography and genetic variation in the antitropically distributed Micromesistius genus. A 579 bp fragment of the mitochondrial coI gene was analysed in 279 individuals of Micromesistius poutassou and 163 of Micromesistius australis. The time since divergence was estimated to be c. 2 million years before present (Mb.p.) with an externally derived clock rate by Bayesian methods. Congruent estimates were obtained with an additional data set of cytochrome b sequences derived from GenBank utilizing a different clock rate. The divergence time of 2 Mb.p. was in disagreement with fossil findings in New Zealand and previous hypotheses which suggested the divergence to be much older. It, therefore, appears likely that Micromesistius has penetrated into the southern hemisphere at least two times. Paleoceanographic records indicate that conditions that would increase the likelihood for transequatorial dispersals were evident c. 2-1·6 Mb.p.. Haplotype frequency differences, along with pairwise F(ST) values, indicated that Mediterranean M. poutassou is a genetically isolated population.

Early regeneration of thymic progenitors in rhesus macaques infected with simian immunodeficiency virus.

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model of AIDS, we examined the early effects of SIV on the thymus. We found that thymic infection by SIV resulted in increased apoptosis 7-14 d after infection, followed by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte progenitors occurred by day 50 and was accompanied by increased levels of cell proliferation in the thymus. Our results demonstrate a marked increase in thymic progenitor activity very early in the course of SIV infection, long before marked declines in peripheral CD4(+) T cell counts.

Value choices and considerations when limiting intensive care treatment: a qualitative study.

BACKGROUND: To shed light on the values and considerations that affect the decision-making processes and the decisions to limit intensive care treatment. METHOD: Qualitative methodology with participant observation and in-depth interviews, with an emphasis on eliciting the underlying rationale of the clinicians' actions and choices when limiting treatment. RESULTS: Informants perceived over-treatment in intensive care medicine as a dilemma. One explanation was that the decision-making base was somewhat uncertain, complex and difficult. The informants claimed that those responsible for taking decisions from the admitting ward prolonged futile treatment because they may bear guilt or responsibility for something that had gone wrong during the course of treatment. The assessments of the patient's situation made by physicians from the admitting ward were often more organ-oriented and the expectations were less realistic than those of clinicians in the intensive care unit who frequently had a more balanced and overall perspective. Aspects such as the personality and the speciality of those involved, the culture of the unit and the degree of interdisciplinary cooperation were important issues in the decision-making processes. CONCLUSION: Under-communicated considerations jeopardise the principle of equal treatment. If intensive care patients are to be ensured equal treatment, strategies for interdisciplinary, transparent and appropriate decision-making processes must be developed in which open and hidden values are rendered visible, power structures disclosed, employees respected and the various perspectives of the treatment given their legitimate place.

The principle of justice in patient priorities in the intensive care unit: the role of significant others.

BACKGROUND: Theoretically, the principle of justice is strong in healthcare priorities both nationally and internationally. Research, however, has indicated that questions can be raised as to how this principle is dealt with in clinical intensive care. OBJECTIVE: The objective of this article is to examine how significant others may affect the principle of justice in the medical treatment and nursing care of intensive care patients. METHOD: Field observations and in-depth interviews with physicians and nurses in intensive care units (ICU). Emphasis was placed on eliciting the underlying rationale for prioritisations in clinical intensive care with particular focus on clinicians' considerations when limiting ICU treatment. RESULTS: Significant others could induce an unintentional discrimination of ICU patients. Family members who were demanding received more time and attention for both the patient and themselves. Patients' and families' status and position and/or an interesting medical diagnosis seemed to govern the clinicians' priorities of patients and families-consciously as well as unconsciously. The clinicians emphasised that patient information given through families was important. However, patients' preferences and values conveyed to clinicians through their families were not always taken seriously. This even applied in cases with very serious prognoses and an explicit patient wish to forego life-prolonging treatment. CONCLUSION: The principle of justice was violated when qualified attention was given to significant others, and through this also to patients. Attention given to significant others was influenced by the healthcare workers' professional and personal values, attitudes and interests.

Muscle activation and length changes during two lunge exercises: implications for rehabilitation.

Eccentric exercises are commonly used as a treatment for various muscle and tendon injuries. During complex motions such as the forward lunge, however, it is not always clear which muscles may be contracting eccentrically and at what time. Because this exercise is used during rehabilitation, the purpose of this investigation was to determine what type of contractions take place during two different types of forward lunge and assess the implications for rehabilitation. Five experienced athletes performed five cycles for each of the walking and jumping forward lunges. Motion analysis was used to calculate the shortening or elongation of each muscle based on the change of position of their origin and insertion points during the lunge. Electromyography of the lateral hamstrings, rectus femoris and lateral gastrocnemius was combined with the muscle length change data to determine when isometric, concentric and eccentric activations occur during the lunge. Eccentric contractions in both the quadriceps and gastrocnemius were observed during the lunge. No hamstring eccentric contractions were found; however, the hamstrings showed isometric contractions during the first part of the stance phase.

Priority dilemmas in dialysis: the impact of old age.

AIM: This study explores priority dilemmas in dialysis treatment and care offered elderly patients within the Norwegian public healthcare system. BACKGROUND: Inadequate healthcare due to advanced age is frequently reported in Norway. The Norwegian guidelines for healthcare priorities state that age alone is not a relevant criterion. However, chronological age, if it affects the risk or effect of medical treatment, can be a legitimate criterion. METHOD: A qualitative approach is used. Data were collected through semistructured interviews and analysed through hermeneutical content analysis. The informants were five physicians and four nurses from dialysis wards. FINDINGS: Pressing priority dilemmas centre around decision-making concerning withholding and withdrawal of dialysis treatment. Advanced age is rarely an absolute or sole priority criterion. It seems, however, that advanced age appears to be a more subtle criterion in relation with, for example, comorbidity, functional status and cognitive impairment. Nurses primarily prioritise specialised dialysis care and not comprehensive nursing care. The complex needs of elderly patients are therefore often not always met. CONCLUSIONS: Clinical priorities should be made more transparent in order to secure legitimate and fair resource allocation in dialysis treatment and care. Difficult decisions concerning withholding or withdrawal of dialysis ought to be openly discussed within the healthcare team as well as with patients and significant others. The biomedical focus and limitations on comprehensive care during dialysis should be debated.

Postural control measured as the center of pressure excursion in young female gymnasts with low back pain or lower extremity injury.

Gymnasts are known to practice and compete although suffering from injuries and pain. Pain may change strategies for postural control. The primary aim of the present study was to investigate how center of pressure (COP) measurements are influenced by low back pain and lower extremity injury in top-level female gymnasts. A secondary aim was to study the reliability of these measurements using a test-retest design, and how this depends on the duration of the test. Fifty-seven top-level gymnasts were included in four groups: non-injured (NI, n=18), low back pain (LBP, n=11), lower extremity injury (LEI, n=17) and a multiple injury group (MI, n=11). COP excursion during quiet stance was measured on a force platform, during 120s: (1) hard surface/eyes open, (2) hard surface/eyes closed, (3) foam surface/eyes open and (4) foam surface/eyes closed. The COP excursion increased, for all groups, during the foam surface/eyes closed measurement compared to the other three tests. Furthermore, the LBP group showed a 49% (p=0.01) larger COP area compared to the LEI group in the foam surface/eyes closed condition. Measurements on foam surface were in general more reliable than tests on hard surface and tests with eyes closed were more reliable than tests with eyes open. Tests during 120s were in most cases more reliable than tests during 60s. In conclusion the COP excursion is influenced by injury location. Quiet stance measurements on foam surface with eyes closed seems to be reliable and sensitive in young female gymnasts.

Patellar tendon load in different types of eccentric squats.

BACKGROUND: Differences in mechanical loading of the patellar tendon have been suggested as a reason for varying effects in rehabilitation of patellar tendinopathy using different eccentric squat exercises and devices. The aim was to characterize the magnitude and pattern of mechanical load at the knee and on the patellar tendon during four types of eccentric squat. METHODS: Subjects performed squats with a submaximal free weight and with maximal effort in a device for eccentric overloading (Bromsman), on a decline board and horizontal surface. Kinematics was recorded with a motion-capture system, reaction forces with force plates, and electromyography from three leg muscles with surface electrodes. Inverse dynamics was used to calculate knee joint kinetics. FINDINGS: Eccentric work, mean and peak patellar tendon force, and angle at peak force were greater (25-30%) for squats on decline board compared to horizontal surface with free weight, but not in Bromsman. Higher knee load forces (60-80%), but not work, were observed with Bromsman than free weight. Angular excursions at the knee and ankle were larger with decline board, particularly with free weight, and smaller in Bromsman than with free weight. Mean electromyography was greater on a decline board for gastrocnemius (13%) and vastus medialis (6%) with free weight, but in Bromsman only for gastrocnemius (7%). INTERPRETATION: The results demonstrated clear differences in the biomechanical loading on the knee during different squat exercises. Quantification of such differences provides information that could be used to explain differences in rehabilitation effects as well as in designing more optimal rehabilitation exercises for patellar tendinopathy.

Trunk Muscle Activation at the Initiation and Braking of Bilateral Shoulder Flexion Movements of Different Amplitudes.

The aim of this study was to investigate if trunk muscle activation patterns during rapid bilateral shoulder flexions are affected by movement amplitude. Eleven healthy males performed shoulder flexion movements starting from a position with arms along sides (0°) to either 45°, 90° or 180°. EMG was measured bilaterally from transversus abdominis (TrA), obliquus internus (OI) with intra-muscular electrodes, and from rectus abdominis (RA), erector spinae (ES) and deltoideus with surface electrodes. 3D kinematics was recorded and inverse dynamics was used to calculate the reactive linear forces and torque about the shoulders and the linear and angular impulses. The sequencing of trunk muscle onsets at the initiation of arm movements was the same across movement amplitudes with ES as the first muscle activated, followed by TrA, RA and OI. All arm movements induced a flexion angular impulse about the shoulders during acceleration that was reversed during deceleration. Increased movement amplitude led to shortened onset latencies of the abdominal muscles and increased level of activation in TrA and ES. The activation magnitude of TrA was similar in acceleration and deceleration where the other muscles were specific to acceleration or deceleration. The findings show that arm movements need to be standardized when used as a method to evaluate trunk muscle activation patterns and that inclusion of the deceleration of the arms in the analysis allow the study of the relationship between trunk muscle activation and direction of perturbing torque during one and the same arm movement.

MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways.

Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase that sanitizes oxidative damage in the nucleotide pool, is important for maintaining several KRAS-driven pro-malignant traits in a nonsmall cell lung carcinoma (NSCLC) model. MTH1 suppression in KRAS-mutant NSCLC cells impairs proliferation and xenograft tumor formation. Furthermore, MTH1 levels modulate KRAS-induced transformation of immortalized lung epithelial cells. MTH1 expression is upregulated by oncogenic KRAS and correlates positively with high KRAS levels in NSCLC human tumors. At a molecular level, in p53-competent KRAS-mutant cells, MTH1 loss provokes DNA damage and induction of oncogene-induced senescence. In p53-nonfunctional KRAS-mutant cells, MTH1 suppression does not produce DNA damage but reduces proliferation and leads to an adaptive decrease in KRAS expression levels. Thus, MTH1 not only enables evasion of oxidative DNA damage and its consequences, but can also function as a molecular rheostat for maintaining oncogene expression at optimal levels. Accordingly, our results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors.

Effects of the diarrhetic shellfish toxin, okadaic acid, on cytoskeletal elements, viability and functionality of rat liver and intestinal cells.

The diarrhetic shellfish toxin, okadaic acid, administered to rats by intragastric intubation, caused intestinal damage, diarrhea and death, but had no detectable effect on the liver. In contrast, okadaic acid administered intravenously had little effect on intestinal function, but caused a rapid dissolution of hepatic bile canalicular actin sheaths, congestion of blood in the liver, hypotension and death at high doses. In isolated rat hepatocytes, okadaic acid induced disruption of the canalicular sheaths as well as of the keratin intermediate filament network. Both of these cytoskeletal changes could be prevented by addition of a cytoprotective flavonoid, naringin, to the isolated hepatocytes, whereas intravenously or intragastrically administered naringin failed to protect against the effects of okadaic acid in vivo. Freshly isolated colonocytes already had fragmented keratin and tubulin cytoskeletons, died rapidly and were not further afflicted by okadaic acid. Naringin had no protective effect on isolated colonocytes or on intestinal function in vivo, but the nonspecific protein kinase inhibitor, K-252a, and the protein-tyrosine-phosphatase inhibitor, vanadate, significantly reduced the extent of colonocytic keratin fragmentation, and an inhibitor of apoptotic caspases, zVAD.fmk, was strongly protective. Further studies of hepatic and intestinal cytoprotectants should focus on conditions that limit their effectiveness in vivo.

The prognostic value of Laurén's histopathological classification system and ABO blood groups in patients with stomach carcinoma.

The prognostic value of Laurén's histopathological classification system and the ABO blood group system has been studied in 275 patients with cancer of the stomach. The study disclosed a higher rate of tumours of intestinal type in females aged 70 years or more compared with those under 70 years, but no such relation for males. We found no relation between histopathological classification and blood groups. For patients with blood group A the 5-year survival was 17.5%, compared to 8.4% for blood group O (P less than 0.05). Survival for patients with intestinal and diffuse tumours was 17.7% and 4.8% respectively (P less than 0.01). A multivariate analysis showed that the histopathological classification system, independently, was an important factor with respect to survival (all other factors constant). Blood group might also be of importance as a prognostic factor, but further studies are necessary to confirm this.

Uptake, penetration, and binding of monoclonal antibodies with increasing affinity in human osteosarcoma multicell spheroids.

BACKGROUND: Multicell spheroids from the human osteosarcoma cell line, OHS, were incubated with increasing concentrations of the monoclonal antibodies TP-1, TP-3 and 9.2.27 having different affinities (Ka = 8.5 x 10(8) M-1, 3.4 x 10(9) M-1 and 1.4 x 10(11) M-1, respectively). MATERIALS AND METHODS: Uptake and penetration of the fluorescein labelled antibodies were studied using confocal laser scanning fluorescence microscopy, and antibodies bound per cell were measured using flow cytometry. RESULTS: The antibody with highest affinity, 9.2.27, bound to all available binding sites in one cell-layer before reaching the next, whereas TP-3 and TP-1 gradually bound to an increasing number of epitopes of all cells throughout the spheroids. The penetration rate and antibody uptake increased with increasing antibody concentration up to saturating concentrations. 9.2.27 required saturation concentrations to reach the center of the spheroids, whereas TP-1 and TP-3 penetrated the centre when concentrations below saturation were applied. CONCLUSION: The antibodies might be useful in radioimmunotherapy of micrometastases.

A new method for estimating the axis of rotation and the center of rotation.

A new method is presented for estimating the parameters of two different models of a joint. The two models are: (1) A rotational joint with a fixed axis of rotation, also referred to as a hinge joint and (2) a ball and socket model, corresponding to a spherical joint. Given the motion of a set of markers, it is shown how the parameters can be estimated, utilizing the whole data set. The parameters are estimated from motion data by minimizing two objective functions. The method does not assume a rigid body motion, but only that each marker rotates around the same fixed axis of rotation or center of rotation. Simulation results indicate that in situations where the rigid body assumption is valid and when measurement noise is present, the proposed method is inferior to methods that utilize the rigid body assumption. However, when there are large skin movement artefacts, simulation results show the proposed method to be more robust.

An in vitro comparison of bone deformation measured with surface and staple mounted strain gauges.

Chicken tibiae were chosen as a model for human second metatarsals. Local surface bone deformation in a 4-point bending configuration was measured in vitro by both strain gauge instrumented staples and strain gauges bonded to the bone's cortical surface. A series of staple bridge dimensions (0.5, 0.6, 0.8 and 1.0 mm) was compared to test for staple influence on bone characteristics and greatest measurement validity and reliability. Thicker staple inhibition of bone deformation was the greatest but differences to thinner staples were not statistically significant (p > 0.05). All staples except 0.5 mm had maximum deviations from linearity less than 1%. The 1.0 mm staple had an R2 value of 0.992 +/- 0.006 plotted against the 4-point bending input force and 0.994 +/- 0.002 plotted against the surface strain gauge signal. The mean intraclass correlation coefficients (ICC) calculated with four input forces (30, 60, 90 and 120 N) and for loading and unloading conditions for the 0.5, 0.6, 0.8 and 1.0 mm staples were 0.75, 0.83, 0.87 and 0.92, respectively. Finally, the differences in slope of the staple strain gauge signal plotted against surface strain gauge signal between input force loading and unloading conditions (0.32), and between input compression and tension conditions (0.79) was least for the 1.0 mm staple which also resulted in the lowest standard deviations. These results suggested the appropriateness of the 1.0 mm staple for in vivo application.

Cellular localization of kallikreins in rat submandibular and sublingual salivary glands: immunofluorescence tracing related to histological characteristics.

Immunohistochemical localization of rat salivary gland kallikrein was related to glandular structures in tissue processed and stained by various methods. In the submandibular gland, most of the kallikrein was located to cytoplasmic granules of the granular tubules. Cells of the striated ducts showed a faint cytoplasmic staining with a bright luminal rim that occasionally was seen also in the excretory ducts. Minor amounts of kallikrein was found in the interstitial tissue. In the sublingual gland, kallikrein was found in the cytoplasm of the striated duct cells and as a luminal rim in the main ducts. Acini were negative in both glands. Fixation in Helly's fluid preserved cytoplasmic granules and was thus superior for intracellular localization of kallikrein, whereas ethanol fixation, due to absence of non-specific background staining, afforded the most sensitive method for detection of small amounts of antigen. In the submandibular gland, best identification of granular tubules and striated ducts was achieved with DMAB-nitrite staining for tryptophan and counterstaining with Mayer's haemalum on sections of tissue fixed in Helly's fluid. In the sublingual gland, the duct system was best demonstrated by haematoxylin-eosin staining.

Plasma exchange in patients with Guillain-Barré syndrome: clinical improvement in patients with serum IgG antibodies to peripheral nerve tissue.

The mixed hemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange (PE) were examined in 24 patients, 16 patients with acute form and 8 patients with the chronic form of the disease. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after the PE. Before PE antibodies were detected in sera from 15 of the patients. These patients showed clinical improvement during the treatment, however in one of the patients only after a time interval of 2 weeks. After PE, antibodies were detected in sera from only 3 of the patients. The 9 patients without detectable antibodies showed no clinical improvement.

Local bone deformation at two predominant sites for stress fractures of the tibia: an in vivo study.

Local bone deformation was registered at two predominant injury sites for tibial stress fractures in a healthy female volunteer. Two instrumented strain gauge staples were inserted under local anesthesia to the anterior middiaphysis (AM) and to the posteromedial part of the distal tibia (PD). Calibration and reliability of the instrumented staple system have previously been demonstrated in vitro. Concomitant ground reaction forces were registered with a Kistler force plate. Studying peak values, it was shown that during a voluntary 30-cm forward jump, PD deformation was greater during forefoot landing (2700-4200 microstrain) than during a heel strike landing (1200-1900 microstrain) and also compared with the concomitant AM deformation under both above testing conditions (1300-1900 microstrain). The stance phase during walking resulted in PD deformation of 950 microstrain, whereas the concomitant AM deformation was 334 microstrain. The greatest AM deformation (mean, 2128 microstrain) was registered during ground contact after a voluntary vertical drop from a height of 45 cm, concomitant with a PD deformation of 436 microstrain. These data are the first to show different local deformations at various sites of the tibia in vivo. The PD deformation was larger than previously noted from other parts of the tibia, whereas the middiaphysis data are consistent with other reports. The results may support the clinical assumption of different etiologies for stress fractures at these predominant sites.

Calculations of mechanisms for balance control during narrow and single-leg standing in fit older adults: A reliability study.

For older people balance control in standing is critical for performance of activities of daily living without falling. The aims were to investigate reliability of quantification of the usage of the two balance mechanisms M(1) 'moving the centre of pressure' and M(2) 'segment acceleration' and also to compare calculation methods based on a combination of kinetic (K) and kinematic (Km) data, (K-Km), or Km data only concerning M(2). For this purpose nine physically fit persons aged 70-78 years were tested in narrow and single-leg standing. Data were collected by a 7-camera motion capture system and two force plates. Repeated measure ANOVA and Tukey's post hoc tests were used to detect differences between the standing tasks. Reliability was estimated by ICCs, standard error of measurement including its 95% CI, and minimal detectable change, whereas Pearson's correlation coefficient was used to investigate agreement between the two calculation methods. The results indicated that for the tasks investigated, M(1) and M(2) can be measured with acceptable inter- and intrasession reliability, and that both Km and K-Km based calculations may be useful for M(2), although Km data may give slightly lower values. The proportional M(1):M(2) usage was approximately 9:1, in both anterio-posterior (AP) and medio-lateral (ML) directions for narrow standing, and about 2:1 in the AP and of 1:2 in the ML direction in single-leg standing, respectively. In conclusion, the tested measurements and calculations appear to constitute a reliable way of quantifying one important aspect of balance capacity in fit older people.