Motion and twisting of magnetic particles ingested by alveolar macrophages in the human lung: effect of smoking and disease

BACKGROUND: Magnetic microparticles being ingested by alveolar macrophages can be used as a monitor for intracellular phagosome motions and cytoskeletal mechanical properties. These studies can be performed in the human lung after voluntary inhalation. The influence of cigarette smoking and lung diseases on cytoskeleton dependent functions was studied. METHODS: Spherical 1.3 μm diameter ferrimagnetic iron oxide particles were inhaled by 17 healthy volunteers (40 – 65 years), 15 patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis (IPF), and 18 patients with chronic obstructive bronchitis (COB). The retained particles were magnetized and aligned in an external 100 mT magnetic field. All magnetized particles induce a weak magnetic field of the lung, which was detected by a sensitive SQUID (superconducting quantum interference device) sensor. Cytoskeletal reorganizations within macrophages and intracellular transport cause stochastic magnetic dipole rotations, which are reflected in a decay of the magnetic lung field, called relaxation. Directed phagosome motion was induced in a weak magnetic twisting field. The resistance of the cytoplasm to particle twisting was characterized by the viscosity and the stiffness (ratio between stress to strain) of the cytoskeleton. RESULTS: One week after particle inhalation and later macrophage motility (relaxation) and cytoskeletal stiffness was not influenced by cigarette smoking, neither in healthy subjects, nor in the patients. Patients with IPF showed in tendency a faster relaxation (p = 0.06). Particle twisting revealed a non-Newtonian viscosity with a pure viscous and a viscoelastic compartment. The viscous shear was dominant, and only 27% of the shear recoiled and reflected viscoelastic properties. In patients with IPF, the stiffness was reduced by 60% (p < 0.02). An analysis of the shear rate and stress dependence of particle twisting allows correlating the rheological compartments to cytoskeletal subunits, in which microtubules mediate the pure viscous (non-recoverable) shear and microfilaments mediate the viscoelastic (recoverable) behavior. The missing correlation between relaxation and particle twisting shows that both stochastic and directed phagosome motion reflect different cytoskeletal mechanisms. CONCLUSION: Faster relaxation and a soft cytoskeleton in patients with IPF indicate alterations in cytoskeleton dependent functions of alveolar macrophages, which may cause dysfunction's in the alveolar defense, like a slower migration, a retarded phagocytosis, a disturbed phagosome lysosome fusion and an impaired clearance

Three-loop matching coefficients for hot QCD: Reduction and gauge independence

We perform an integral reduction for the 3-loop effective gauge coupling and screening mass of QCD at high temperatures, defined as matching coefficients appearing in the dimensionally reduced effective field theory (EQCD). Expressing both parameters in terms of a set master (sum-) integrals, we show explicit gauge parameter independence. The lack of suitable methods for solving the comparatively large number of master integrals forbids the complete evaluation at the moment. Taking one generic class of masters as an example, we highlight the calculational techniques involved. The full result would allow to improve on one of the classic probes for the convergence of the weak-coupling expansion at high temperatures, namely the comparison of full and effective theory determinations of the spatial string tension. Furthermore, the full result would also allow to determine one new contribution of order O(g**7) to the pressure of hot QCD.Comment: 19 pages, 2 figures. v2: new Section 6 discussing applications, to match journal versio

Rare isotope production in statistical multifragmentation

Producing rare isotopes through statistical multifragmentation is investigated using the Mekjian method for exact solutions of the canonical ensemble. Both the initial fragmentation and the the sequential decay are modeled in such a way as to avoid Monte Carlo and thus provide yields for arbitrarily scarce fragments. The importance of sequential decay, exact particle-number conservation and the sensitivities to parameters such as density and temperature are explored. Recent measurements of isotope ratios from the fragmentation of different Sn isotopes are interpreted within this picture.Comment: 10 eps figure

Intermediate distance correlators in hot Yang-Mills theory

Lattice measurements of spatial correlation functions of the operators FF and FF-dual in thermal SU(3) gauge theory have revealed a clear difference between the two channels at "intermediate" distances, x ~ 1/(pi T). This is at odds with the AdS/CFT limit which predicts the results to coincide. On the other hand, an OPE analysis at short distances (x << 1/(pi T)) as well as effective theory methods at long distances (x >> 1/(pi T)) suggest differences. Here we study the situation at intermediate distances by determining the time-averaged spatial correlators through a 2-loop computation. We do find unequal results, however the numerical disparity is small. Apart from theoretical issues, a future comparison of our results with time-averaged lattice measurements might also be of phenomenological interest in that understanding the convergence of the weak-coupling series at intermediate distances may bear on studies of the thermal broadening of heavy quarkonium resonances.Comment: 31 page

Mucociliary and long-term particle clearance in airways of patients with immotile cilia

Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients

Metacognitive Reflection and Insight Therapy (MERIT) with a Patient with Persistent Negative Symptoms

Metacognition comprises a spectrum of mental activities involving thinking about thinking. Metacognitive impairments may sustain and trigger negative symptoms in people with schizophrenia. Without complex ideas of the self and others, there may be less reason to pursue goal-directed activities and less ability to construct meaning in daily activities, leading to the experience of negative symptoms. As these symptoms tend to be nonresponsive to pharmacotherapy and other kinds of treatment metacognition might be a novel treatment target; improvement of metacognition might lead to improvements in negative symptoms. One therapy that seeks to promote metacognition is the Metacognitive Reflection and Insight Therapy (MERIT). In this study, a case is presented in which a first episode patient with severe negative symptoms is treated with MERIT. A case illustration and the eight core principles of MERIT are presented. Independent assessments of metacognition and negative symptoms before and after therapy show a significant increase of metacognition and decrease of negative symptoms over the course of 40 weeks

Changes in immunocompetent cells after interstitial laser thermotherapy of breast cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Local tumour destruction has been shown to give rise to changes in immunocompetent cells. The aim of this study was to describe the effect of interstitial laser thermotherapy (ILT) of breast carcinoma in the tumour and in regional lymph nodes. METHODS: Seventeen women that underwent radical surgical excision after non-radical ILT were studied. ILT was performed at a steady-state temperature of 48°C for 30 min. Surgical excision was performed 12 (6-23) days after ILT. Six patients with breast cancer not treated with ILT before surgery served as controls. Immunohistological reactions were performed on core needle biopsies prior to treatment and on the excised specimens. RESULTS: ILT resulted in more CD8 lymphocytes and CD68 macrophages within the tumour (P < 0.05 and P < 0.01, respectively) and higher counts of CD20 (P < 0.05), CD68 (P < 0.001) and CD83 (P < 0.01) at the tumour border, when compared to pre-treatment values. In the control patients not receiving ILT, CD8 cells increased within the tumour after resection (P < 0.05). With the probable exception of CD25 Foxp3 cells, the presence of cancer in a lymph node influenced the findings in lymph nodes (examined for CD1a, CD25, Foxp3 CD25, CD83 cells). Thus, comparisons between ILT and control patients were restricted to patients without lymph node metastases. In these patients, ILT and resection were followed by a decrease in CD25 Foxp3 lymphocytes (P < 0.05), when compared to surgical resection alone. CONCLUSIONS: ILT induced changes in immunocompetent cells in patients with breast cancer. The stimulation of the immune system is an added feature of ILT in treatment of patients with breast cancer

A fresh look on three-loop sum-integrals

In order to prepare the ground for evaluating classes of three-loop sum-integrals that are presently needed for thermodynamic observables, we take a fresh and systematic look on the few known cases, and review their evaluation in a unified way using coherent notation. We do this for three important cases of massless bosonic three-loop vacuum sum-integrals that have been frequently used in the literature, and aim for a streamlined exposition as compared to the original evaluations. In passing, we speculate on options for generalization of the computational techniques that have been employed.Comment: 19 page

IBP methods at finite temperature

We demonstrate the applicability of integration-by-parts (IBP) identities in finite-temperature field theory. As a concrete example, we perform 3-loop computations for the thermodynamic pressure of QCD in general covariant gauges, and confirm earlier Feynman-gauge results.Comment: 16 pages, 4 Axodraw figure

Efficacy and acceptability of selective serotonin reuptake inhibitors for the treatment of depression in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants for the treatment of depression in patients with Parkinson's Disease (PD) but data on their efficacy are controversial.</p> <p>Methods</p> <p>We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the efficacy and acceptability of SSRIs in the treatment of depression in PD.</p> <p>Results</p> <p>Ten studies were included. In the comparison between SSRIs and Placebo (n = 6 studies), the combined risk ratio (random effects) was 1.08 (95% confidence interval: 0.77 - 1.55, p = 0.67). In the comparison between SSRIs and Tricyclic Antidepressants (TCAs) (n = 3 studies) the combined risk ratio was 0.75 (0.39 - 1.42, p = 0.37). An acceptability analysis showed that SSRIs were generally well tolerated.</p> <p>Conclusions</p> <p>These results suggest that there is insufficient evidence to reject the null hypothesis of no differences in efficacy between SSRIs and placebo in the treatment of depression in PD. Due to the limited number of studies and the small sample sizes a type II error (false negative) cannot be excluded. The comparison between SSRIs and TCAs is based on only three studies and further trials with more pragmatic design are needed.</p