380 research outputs found
Gastrocnemius vs. soleus strain: how to differentiate and deal with calf muscle injuries
Calf strains are common injuries seen in primary care and sports medicine clinics. Differentiating strains of the gastrocnemius or soleus is important for treatment and prognosis. Simple clinical testing can assist in diagnosis and is aided by knowledge of the anatomy and common clinical presentation
Initial intramuscular perfusion pressure predicts early skeletal muscle function following isolated tibial fractures
<p>Abstract</p> <p>Background</p> <p>The severity of associated soft tissue trauma in complex injuries of the extremities guides fracture treatment and decisively determines patient's prognosis. Trauma-induced microvascular dysfunction and increased tissue pressure is known to trigger secondary soft tissue damage and seems to adversely affect skeletal muscle function.</p> <p>Methods</p> <p>20 patients with isolated tibial fractures were included. Blood pressure and compartment pressure (anterior and deep posterior compartment) were measured continuously up to 24 hours. Corresponding perfusion pressure was calculated. After 4 and 12 weeks isokinetic muscle peak torque and mean power of the ankle joint in dorsal and plantar flexion were measured using a Biodex dynamometer.</p> <p>Results</p> <p>A significant inverse correlation between the anterior perfusion pressure at 24 hours and deficit in dorsiflexion at 4 weeks was found for both, the peak torque (R = -0.83; p < 0.01) and the mean power (R = -0.84; p < 0.01). The posterior perfusion pressure at 24 h and the plantar flexion after 4 weeks in both, peak torque (R = -0.73, p =< 0.05) and mean power (R = -0.7, p =< 0.05) displayed a significant correlation.</p> <p>Conclusion</p> <p>The functional relationship between the decrease in intramuscular perfusion pressures and muscle performance in the early rehabilitation period indicate a causative and prognostic role of early posttraumatic microcirculatory derangements and skeletal muscle function. Therapeutic concepts aimed at effective muscle recovery, early rehabilitation, and decreased secondary tissue damage, should consider the maintenance of an adequate intramuscular perfusion pressure.</p
High frequency of TTK mutations in microsatellite-unstable colorectal cancer and evaluation of their effect on spindle assembly checkpoint
Frameshift mutations frequently accumulate in microsatellite-unstable colorectal cancers (MSI CRCs) typically leading to downregulation of the target genes due to nonsense-mediated messenger RNA decay. However, frameshift mutations that occur in the 3' end of the coding regions can escape decay, which has largely been ignored in previous works. In this study, we characterized nonsense-mediated decay-escaping frameshift mutations in MSI CRC in an unbiased, genome wide manner. Combining bioinformatic search with expression profiling, we identified genes that were predicted to escape decay after a deletion in a microsatellite repeat. These repeats, located in 258 genes, were initially sequenced in 30 MSI CRC samples. The mitotic checkpoint kinase TTK was found to harbor decay-escaping heterozygous mutations in exon 22 in 59% (105/179) of MSI CRCs, which is notably more than previously reported. Additional novel deletions were found in exon 5, raising the mutation frequency to 66%. The exon 22 of TTK contains an A(9)-G(4)-A(7) locus, in which the most common mutation was a mononucleotide deletion in the A(9) (c.2560delA). When compared with identical non-coding repeats, TTK was found to be mutated significantly more often than expected without selective advantage. Since TTK inhibition is known to induce override of the mitotic spindle assembly checkpoint (SAC), we challenged mutated cancer cells with the microtubule-stabilizing drug paclitaxel. No evidence of checkpoint weakening was observed. As a conclusion, heterozygous TTK mutations occur at a high frequency in MSI CRCs. Unexpectedly, the plausible selective advantage in tumourigenesis does not appear to be related to SAC
Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts
<p>Abstract</p> <p>Background</p> <p>Amplification of the <it>ERBB2 </it>(<it>Her-2/neu</it>) oncogene, which occurs in approximately 25% of breast carcinomas, is a known negative prognostic factor. Available data indicate that a variable number of nearby genes on chromosome 17q may be co-amplified or deleted, forming a continuous amplicon of variable size. In approximately 25% of these patients, the amplicon extends to the gene for <it>topoisomerase II alpha </it>(<it>TOP2A</it>), a target for anthracyclines. We sought to understand the significance of these associated genomic changes for breast cancer prognosis and predicting response to therapy.</p> <p>Methods and patients</p> <p>Archival tissue samples from 63 breast cancer patients with <it>ERBB2 </it>amplification, stages 0–IV, were previously analyzed with FISH probes for genes located near <it>ERBB2</it>. In the present study, the clinical outcome data were determined for all patients presenting at stages I–III for whom adequate clinical follow up was available.</p> <p>Results</p> <p>Four amplicon patterns (Classes) were identified. These were significantly associated with the clinical outcome, specifically, recurrence of breast cancer. The Amplicon class IV with deleted <it>TOP2A </it>had 67% (6/9) cases with recurrence, whereas the other three classes combined had only 12% (3/25) cases (p-value = 0.004) at the time of last follow-up. <it>TOP2A </it>deletion was also significantly associated with time to recurrence (p-value = 0.0002). After adjusting for age in Cox regression analysis, the association between <it>TOP2A </it>deletion and time to recurrence remains strongly significant (p-value = 0.002) whereas the association with survival is marginally significant (p-value = 0.06).</p> <p>Conclusion</p> <p><it>TOP2A </it>deletion is associated with poor prognosis in <it>ERBB2</it>-amplified breast carcinomas. Clarification of the mechanism of this association will require additional study.</p
Cost-effectiveness of initiating extrafine- or standard size-particle inhaled corticosteroid for asthma in two health-care systems: a retrospective matched cohort study
Data acquisition and analyses were funded by Teva Pharmaceuticals
Lorentz violation, Gravity, Dissipation and Holography
We reconsider Lorentz Violation (LV) at the fundamental level. We show that
Lorentz Violation is intimately connected with gravity and that LV couplings in
QFT must always be fields in a gravitational sector. Diffeomorphism invariance
must be intact and the LV couplings transform as tensors under coordinate/frame
changes. Therefore searching for LV is one of the most sensitive ways of
looking for new physics, either new interactions or modifications of known
ones. Energy dissipation/Cerenkov radiation is shown to be a generic feature of
LV in QFT. A general computation is done in strongly coupled theories with
gravity duals. It is shown that in scale invariant regimes, the energy
dissipation rate depends non-triviallly on two characteristic exponents, the
Lifshitz exponent and the hyperscaling violation exponent.Comment: LateX, 51 pages, 9 figures. (v2) References and comments added.
Misprints correcte
Holographic studies of quasi-topological gravity
Quasi-topological gravity is a new gravitational theory including
curvature-cubed interactions and for which exact black hole solutions were
constructed. In a holographic framework, classical quasi-topological gravity
can be thought to be dual to the large limit of some non-supersymmetric
but conformal gauge theory. We establish various elements of the AdS/CFT
dictionary for this duality. This allows us to infer physical constraints on
the couplings in the gravitational theory. Further we use holography to
investigate hydrodynamic aspects of the dual gauge theory. In particular, we
find that the minimum value of the shear-viscosity-to-entropy-density ratio for
this model is .Comment: 45 pages, 6 figures. v2: References adde
Pulpal sequelae after trauma to anterior teeth among adult Nigerian dental patients
<p>Abstract</p> <p>Background</p> <p>Epidemiological studies show that about 11.6% to 33.0% of all boys and about 3.6% to 19.3% of all girls suffer dental trauma of varying severity before the age of 12 years. Moderate injuries to the periodontium such as concussion and subluxation are usually associated with relatively minor symptoms and hence may go unnoticed by the patient or the dentist, if consulted. Patients with these kinds of injuries present years after a traumatic accident most of the time with a single discoloured tooth. This study sets out to document the incidence of various posttraumatic sequelae of discoloured anterior teeth among adult Nigerian dental patients.</p> <p>Methods</p> <p>One hundred and sixty eight (168) traumatized discoloured anterior teeth in 165 patients were studied. Teeth with root canal treatment were excluded from the study. Partial obliteration was recorded when the pulp chamber or root canal was not discernible or reduced in size on radiographs, total obliteration was recorded when pulp chamber and root canal were not discernible. A retrospective diagnosis of concussion was made from patient's history of trauma to the tooth without abnormal loosening, while subluxation was made from patient's history of trauma to the tooth with abnormal loosening.</p> <p>Results</p> <p>Of the 168 traumatized discoloured anterior teeth, 47.6% and 31.6% had partial and total obliteration of the pulp canal spaces respectively, 20.8% had pulpal necrosis. Concussion and subluxation injuries resulted more in obliteration of the pulp canal space, while fracture of the teeth resulted in more pulpal necrosis (p < 0.001). Injuries sustained during the 1<sup>st </sup>and 2<sup>nd </sup>decade of life resulted more in obliteration of the pulp canal space, while injuries sustained in the 3<sup>rd </sup>decade resulted in more pulpal necrosis.</p> <p>Conclusion</p> <p>Calcific metamorphosis developed more in teeth with concussion and subluxation injuries. Pulpal necrosis occurred more often in traumatized teeth including fractures.</p
Non-Invasive Quantification of White and Brown Adipose Tissues and Liver Fat Content by Computed Tomography in Mice
OBJECTIVES: Obesity and its distribution pattern are important factors for the prediction of the onset of diabetes in humans. Since several mouse models are suitable to study the pathophysiology of type 2 diabetes the aim was to validate a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification of visceral, subcutaneous, brown and intrahepatic fat depots in mice. METHODS: Different lean and obese mouse models (C57BL/6, B6.V-Lep(ob), NZO) were used to determine the most adequate scanning parameters for the detection of the different fat depots. The data were compared with those obtained after preparation and weighing the fat depots. Liver fat content was determined by biochemical analysis. RESULTS: The correlations between weights of fat tissues on scale and weights determined by CT were significant for subcutaneous (r(2) = 0.995), visceral (r(2) = 0.990) and total white adipose tissue (r(2) = 0.992). Moreover, scans in the abdominal region, between lumbar vertebrae L4 to L5 correlated with whole-body fat distribution allowing experimenters to reduce scanning time and animal exposure to radiation and anesthesia. Test-retest reliability and measurements conducted by different experimenters showed a high reproducibility in the obtained results. Intrahepatic fat content estimated by CT was linearly related to biochemical analysis (r(2) = 0.915). Furthermore, brown fat mass correlated well with weighted brown fat depots (r(2) = 0.952). In addition, short-term cold-expose (4 °C, 4 hours) led to alterations in brown adipose tissue attributed to a reduction in triglyceride content that can be visualized as an increase in Hounsfield units by CT imaging. CONCLUSION: The 3D imaging of fat by CT provides reliable results in the quantification of total, visceral, subcutaneous, brown and intrahepatic fat in mice. This non-invasive method allows the conduction of longitudinal studies of obesity in mice and therefore enables experimenters to investigate the onset of complex diseases such as diabetes and obesity
Molecular subtypes of breast cancer and amplification of topoisomerase IIα: predictive role in dose intensive adjuvant chemotherapy
Benefit from chemotherapy treatment in breast cancer patients is determined by the molecular make-up of the tumour. In a retrospective analysis, we determined the molecular subtypes of breast cancer originally defined by expression microarrays by immunohistochemistry in tumours of patients who took part in a randomised study of adjuvant high-dose chemotherapy in breast cancer. In addition, the topoisomerase IIα (TOP2A) amplification status was determined by fluorescence in situ hybridisation and chromogenic in situ hybridisation. 411 of the 753 tumours (55%) were classified as luminal-like, 137 (18%) as basal-like and 205 (27%) as human epithelial receptor type 2 (HER2) amplified. The basal-like tumours were defined as having no expression of ER and HER2; 98 of them did express epidermal growth factor receptor and/or cytokeratin 5/6. The luminal-like tumours had a significantly better recurrence free and overall survival than the other two groups. From the 194 HER2-positive tumours, 47 (24%) were shown to harbour an amplification of TOP2A. Patients with an HER2-amplified tumour randomised to the high-dose therapy arm did worse than those in the conventional treatment arm, possibly caused by the lower cumulative anthracycline dose in the high-dose arm. The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose–response curve for anthracyclines in breast cancer. Possibly, the difference of the cumulative dose of only 25% between the treatment arms was insufficient to yield a survival difference
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