Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease.

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

A importância de Moisés: ponto de encontro da cultura do judaísmo e da psicanálise / Moses: bridging the fields of culture judaism and psychoanalysis

O artigo discute o papel de Moisés no Judaísmo à luz da reconstrução histórica de Freud (1939/2004) e de suas análises da força e permanência desta cultura e de sua tradição. Com esse personagem articulador, Freud elabora sua teoria da tradição e da transmissão, afirmando e forjando seu edifício conceitual, sobre os fenômenos sociais, em analogia com suas observações das psicanálises (individuais) que conduziu. Cotejando a versão freudiana, a versão exegética (Sellin, 1922, citado em Freud, 1939/2004), e a versão da Torá desse legislador, e tomando contradições e inconsistências pululantes na jornada do grande profeta, o artigo procura mostrar como desse personagem e de seu acontecer-histórico (die Geschichte) se derivam importantes consequências para a história primordial (die Urgeschichte) da cultura, dos monoteísmos e da própria clínica da subjetividade(AU)

Stretched arc discharge in produced water.

The objective of the present study was to investigate the feasibility of stretching an arc discharge in produced water to increase the volume of produced water treated by plasma. Produced water is the wastewater generated by hydraulic fracturing of shale during the production phase in shale-oil or shale-gas exploration. The electric conductivity of produced water is in the range of 50-200 mS/cm, which provides both a challenge and opportunity for the application of plasmas. Stretching of an arc discharge in produced water was accomplished using a ground electrode and two high-voltage electrodes: one positioned close to the ground electrode and the other positioned farther away from the ground. The benefit of stretching the arc is that the contact between the arc and water is significantly increased, resulting in more efficient plasma treatment in both performance and energy cost.

Note: an underwater multi-channel plasma array for water sterilization.

A simple yet effective method to generate multi-channel plasma array in water is presented in this paper. Thin circular metal disks sandwiched between dielectric layers were used, allowing the production of large-volume underwater plasma array with higher stability. The system can be further scaled up by stacking multiple metal disks, making it suitable for large-scale industrial water treatment. Generation of UV and reactive species was identified by optical emission spectroscopy. Sterilization experiments were performed. Results show that the device was effective in deactivating E. coli in water over a wide range of initial concentrations ranging from 10(4) to 10(8) CFU/ml.

Generation and characterization of antibodies specific for caspase-cleaved neo-epitopes: a novel approach.

Apoptosis research has been significantly aided by the generation of antibodies against caspase-cleaved peptide neo-epitopes. However, most of these antibodies recognize the N-terminal fragment and are specific for the protein in question. The aim of this project was to create antibodies, which could identify caspase-cleaved proteins without a priori knowledge of the cleavage sites or even the proteins themselves. We hypothesized that many caspase-cleavage products might have a common antigenic shape, given that they must all fit into the same active site of caspases. Rabbits were immunized with the eight most prevalent exposed C-terminal tetrapeptide sequences following caspase cleavage. After purification of the antibodies we demonstrated (1) their specificity for exposed C-terminal (but not internal) peptides, (2) their ability to detect known caspase-cleaved proteins from apoptotic cell lysates or supernatants from apoptotic cell culture and (3) their ability to detect a caspase-cleaved protein whose tetrapeptide sequence differs from the eight tetrapeptides used to generate the antibodies. These antibodies have the potential to identify novel neo-epitopes produced by caspase cleavage and so can be used to identify pathway-specific caspase cleavage events in a specific cell type. Additionally this methodology may be applied to generate antibodies against products of other proteases, which have a well-defined and non-promiscuous cleavage activity.

Biological responses of Bacillus stratosphericus to floating electrode-dielectric barrier discharge plasma treatment.

AIMS: Dielectric barrier discharge (DBD) plasma is used for sterilization of contaminated inanimate surfaces but seldomly optimized and depends upon the type of organisms and the plasma treatment duration, (net energy deposited) this efficacy varies. The proposed study was designed to see biological responses of one of the robust organism, Bacillus stratosphericus. METHODS AND RESULTS: DBD plasma was applied over various durations to B. stratosphericus either surface-dried or suspension in de-ionized water, and viability, culturability, and viable but nonculturability (VBNC) were assayed using standard techniques. Depending upon the exposure of B. stratosphericus to DBD plasma resulted in three viability states, viable and culturable at low plasma doses and VBNC or disintegrated bacteria at higher plasma doses. Although organism's respiration levels at relatively low levels, immediately after plasma treatment, over the course of 24-h respiratory activity was increased c. eight times (and found still nonculturable during colony assays). CONCLUSIONS: The loss of culturability is hypothesized to be induced as one of the responses to oxidative stress and it remains to be unclear if the response is temporary or indefinite. Appropriate plasma powers should be used to avoid VBNC-like status. 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay is a good alternative method to detect VBNC state. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus stratosphericus has the potential to turn into VBNC upon plasma application, and XTT assay can be an alternative method to detect VBNC state.

Critical pathways in cellular senescence and immortalization revealed by gene expression profiling.

Bypassing cellular senescence and becoming immortal is a prerequisite step in the tumorigenic transformation of a cell. It has long been known that loss of a key tumor suppressor gene, such as p53, is necessary, but not sufficient, for spontaneous cellular immortalization. Therefore, there must be additional mutations and/or epigenetic alterations required for immortalization to occur. Early work on these processes included somatic cell genetic studies to estimate the number of senescence genes, and microcell-mediated transfer of chromosomes into immortalized cells to identify putative senescence-inducing genetic loci. These principal studies laid the foundation for the field of senescence/immortalization, but were labor intensive and the results were somewhat limited. The advent of gene expression profiling and bioinformatics analysis greatly facilitated the identification of genes and pathways that regulate cellular senescence/immortalization. In this review, we present the findings of several gene expression profiling studies and supporting functional data, where available. We identified universal genes regulating senescence/immortalization and found that the key regulator genes represented six pathways: the cell cycle pRB/p53, cytoskeletal, interferon-related, insulin growth factor-related, MAP kinase and oxidative stress pathway. The identification of the genes and pathways regulating senescence/immortalization could provide novel molecular targets for the treatment and/or prevention of cancer.

The influence of prosthetic foot alignment on trans-tibial amputee gait.

An optimally aligned prosthesis, as accomplished by the subjective judgment of the prosthetist, guarantees the best quality of gait. Yet, amputees can adapt to a large variety of geometrical configurations of the prosthetic components. Different external rotation angles of the foot in trans-tibial (TT) prostheses were investigated. The study tried to identify (a) the relationship between foot angle and other gait parameters and (b) the compensating pattern of the amputees to excessive external rotation of the foot. Eight (8) TT amputees, fitted with an identical type of prosthesis, were investigated during ambulation. The prosthetic foot was externally rotated as follows: optimal angle (10.94 x degrees +/- 5.21 degrees), optimal angle plus another 18 degrees, and optimal angle plus another 36 degrees. Analysis of gait was performed with the aid of an electronic walkway. Speed of gait, stance and swing time, and foot angle were monitored in 4 runs for each of the three foot angles. Speed of gait remained almost constant in the three tests. Stance and swing time, as well as step length, significantly changed when 36 degrees were added to the optimal foot angle. This foot position significantly influenced inter-legs time difference and symmetry between the legs. During ambulation, prosthetic foot external rotation was decreased by internal rotation of the limb at the hip joint level. It is concluded that TT amputees can maintain an efficient speed of gait even when the prosthetic foot is malpositioned in excessive external rotation. Although such a malalignment significantly influences other gait parameters during walking, amputees are able to adapt themselves by internal rotation of the hip joint in the amputated leg.

Role of small loops in DNA melting.

Short melted regions less than 100 base pairs (bp) in length are rarely found in the differential melting curves (DMC) of natural DNAs. Therefore, it is supposed that their characteristics do not affect DNA melting behavior. However, in our previous study, a strong influence of the form of the entropy factor of small loops on melting of cross-linked DNAs was established (D. Y. Lando, A. S. Fridman et al., Journal of Biomolecular Structure and Dynamics, 1997, Vol. 15, pp. 141-150; Journal of Biomolecular Structure and Dynamics, 1998, Vol. 16, pp. 59-67). Quite different dependencies of the melting temperature on the relative concentration of interstrand cross-links were obtained for the loop entropy factors given by the Fixman-Freire (Jacobson-Stockmayer) and Wartell-Benight relations. In the present study, the influence of the entropy factor of small loops on the melting of natural DNAs, cross-linked DNAs and periodical double-stranded polynucleotides is compared using computer simulation. A fast combined computational method for calculating DNA melting curves was developed for this investigation. It allows us to assign an arbitrary dependence of the loop entropy factor on the length of melted regions for the terms corresponding to small loops (less than tau bp in length). These terms are calculated using Poland's approach. The Fixman-Freire approach is used for long loops. Our calculations have shown that the temperature dependence of the average length of interior melted regions (loops) has a maximum at T approximately T(m) (T(m) is the DNA melting temperature) in contrast to the dependence of the total average length of melted regions, which increases almost monotonously. Computer modeling demonstrates that prohibition of formation of loops less than tau base pairs in length does not markedly change the DMC for tau < 150 bp. However, the same prohibition strongly affects the average length of internal melted regions for much smaller tau's. The effect is already noticeable for tau = 1 bp and increases with tau. A tenfold increase in the entropy factor of all loops with length less than tau bp causes a noticeable alteration of the DMC for tau > or = 30 bp. It is shown that DMCs are identical for the Wartell-Benight and for the Fixman-Freire (Jacobson-Stockmayer) form of the loop entropy factor. However, for low degree of denaturation, the average length of internal melted regions is 40% lower for the Wartell-Benight form due to the fluctuational opening of short AT-rich regions less than 10 bp in length. The same calculations carried out for periodical polynucleotides demonstrate a much stronger difference in melting behavior for different forms of entropy factors of short loops. The strongest difference occurs if the length of stable GC-rich and unstable AT-rich stretches is equal to 30 bp. However, the comparison carried out in this work demonstrates that the entropy factor of short loops influences melting behavior of cross-linked DNA much stronger than of unmodified DNA with random or periodical sequences.

Melting of cross-linked DNA IV. Methods for computer modeling of total influence on DNA melting of monofunctional adducts, intrastrand and interstrand cross-links formed by molecules of an antitumor drug.

A theoretical method is developed for calculation of melting curves of covalent complexes of DNA with antitumor drugs. The method takes into account all the types of chemical modifications of the double helix caused by platinum compounds and DNA alkylating agents: 1) monofunctional adducts bound to one nucleotide; 2) intrastrand cross-links which appear due to bidentate binding of a drug molecule to two nucleotides that are included into the same DNA strand; 3) interstrand cross-links caused by bidentate binding of a molecule to two nucleotides of different strands. The developed calculation method takes into account the following double helix alterations at sites of chemical modifications: 1) a change in stability of chemically modified base pairs and neighboring ones, that is caused by all the types of chemical modifications; 2) a change in the energy of boundaries between helical and melted regions at sites of chemical modification (local alteration of the factor of cooperativity of DNA melting), that is caused by all the types of chemical modifications, too; 3) a change in the loop entropy factor of melted regions that include interstrand cross-links; 4) the prohibition of divergence of DNA strands in completely melted DNA molecules, which is caused by interstrand cross-links only. General equations are derived, and three calculation methods are proposed to calculate DNA melting curves and the parameters that characterize the helix-coil transition.

Melting of cross-linked DNA. III. Calculation of differential melting curves.

In our previous papers I and II (D. Y. Lando et al, J. Biomol. Struct. Dynam. (1997) v. 15, N1, p. 129-140, p. 141-150), two methods were developed for calculation of melting curves of cross-linked DNA. One of them is based on Poland's and another on the Fixman-Freire approach. In the present communication, III, a new theoretical method is developed for computation of differential melting curves of DNAs cross-linked by anticancer drugs and their inactive analogs. As Poland's approach, the method allows study of the influence of the loop entropy factor, delta(n), on melting behavior (n is the length of a loop in base pairs). However the method is much faster and requires computer time that inherent for the most rapid Fixman-Freire calculation approach. In contrast to the computation procedures described before in communications I and II, the method is suitable for computation of differential melting curves in the case of long DNA chains, arbitrary loop entropy factors of melted regions and arbitrary degree of cross-linking including very low values that occur in vivo after administration of antitumor drugs. The method is also appropriate for DNAs without cross-links. The results of calculation demonstrate that even very low degree of cross-linking alters the DNA differential melting curve. Cross-linking also markedly strengthens the influence of particular function delta(n) upon melting behavior.

[Granulomatous pleurisy after mammaplasty, induced by polyacrylamide gel]. / Granulematoznyi plevrit posle mammoplastiki, vyzvannyi poliakrilamidnym gelem.

A case of iatrogenic granulomatous pleurisy in a 36-year-old female developed after cosmetic correction of the mammary gland shape with polyacrylamide gel (an interfall injection). Symptoms of spontaneous left-side pneumothorax developed one month after the manipulation. Histological examination of the parietal and visceral pleura biopsy revealed multiple non-immune corpuscular mature macrophagal granulomas around gel particles resulting in the pleura damage and pneumothorax. A complete recovery. This is the first publication of pneumothorax of such genesis.

On nonlinear dynamics of three-dimensional astrophysical disks.

Nonlinear processes concerned with different aspects of nonlinear dynamics of astrophysical disks--structures, flows, turbulence--are reviewed. Special attention is paid to the influence of the three dimentionality of disks on their nonlinear behavior.

Melting of cross-linked DNA: II. Influence of interstrand linking on DNA stability.

In the previous paper (D.Y. Lando, J. Biomol. Struct. Dynam, 15, 129-140 (1997)) the melting of cross-linked DNA with N base pairs and omega interstrand cross-links has been considered theoretically. In the present study on the basis of these results, two simple schemes are developed for the computation of melting curves of cross-linked DNA. The investigation of influence of interstrand linking on DNA stability has been carried out by computer simulation. It is shown that the relative concentration of cross-links, CCT = omega/N, their distribution along a DNA molecule, and particular values of the entropy factors of small loops formed by cross-links in melted regions strongly affect the DNA melting temperature, Tm. On the contrary, for DNA without cross-links, a ten-fold increase or decrease in the entropy factors of small loops does not cause the Tm variation. The comparison of the results of calculation with experimental data suggests that the majority of types of cross-link neither maintain ordered parallel orientation of bases in melted regions nor increase considerably the thermostability of cross-linked base pairs. Four different ways of influence of interstrand cross-linking on the DNA double helix stability are considered. It is shown that cross-linking significantly enhances the influence of single strand stiffness in melted regions on DNA melting behavior.

[Immediate posterior stabilization of pelvic fractures using threaded compression rods].

Operative management of pelvic ring disruptions remains a challenge for the orthopedist. Surgical stabilization of an unstable pelvic ring not only involves urgent control of shock, but also protects soft tissues and enables the patient to ambulate earlier and to be comfortable when resting. Appropriate management of pelvic ring injuries requires understanding the anatomy and biomechanics of the pelvis and the mechanism of injury. The choice of posterior stabilization depends on the type of fracture. In this study we evaluated posterior tansiliac fixation using threaded compression rods (sacral bars), 1 of the techniques for treating pelvic instability with disruption of the posterior osseous - ligamentous complex. We used this method during 1987 - 1991 on 17 multitrauma patients with unstable pelvic injuries. We also conducted a long-term follow-up of more than 2 years. The 2 type C3 patients required revision of the posterior fixation, due to loss of stability and recurrence of dislocation of the sacroiliac joint. This seems to support the view that posterior sacral bar fixation is not suitable for bilateral rotational and vertical instability, and that it should be limited to certain posterior injury patterns, including lateral compression injuries and unilateral vertical instability when the contralateral hemipelvis is stable. It is important therefore, that the trauma surgeon be familiar with more than 1 technique of stabilization. Our study indicated that fixation with sacral bars is still an easy, safe and useful method for treating posterior pelvic instability, even though anatomical reduction of the sacroiliac joint is difficult. It should be one of the techniques with which the orthopedic trauma surgeon is acquainted and is ready to use when necessary.

Drift mechanism caused by a nonlinear wave and the Cassini Division and Uranian rings formation.

The mechanism leading to the observed coexistence of gaps and narrow ringlets in the planetary rings is found. It is based upon the quasi-stationary radial drift of the matter under action of two forces in the disk plane: the Coriolis force and the Reynolds stresses. To an accuracy of the factor of 2 the first force coincides with the Lorentz force, therefore the radial drift in rings is similar to the gradient drift of plasma in the magnetic field. The second force is produced by the wave generated by the nearby satellite in the resonance position. In inertial systems, the second force alone causes a matter flow in its direction, called acoustic streaming. Since the radial drift is caused by nonlinear time-averaged force of high-frequency harmonic interactions in the wave, it exists in the wave propagation zone: from the birth place of the wave-the resonance position, up to the reflection point of the wave, where its group velocity vanishes. Our estimations show that the size of the density wave propagation zone corresponding to the density wave which had been formerly generated the 2:1 orbital resonance with Mimas is consistent with the width of the Cassini Division. In our case the nature of the radial drift is such that first of all it clears out the farthest from the resonance position; later, the closer areas also get affected by the drift. The zone closest to the resonance position itself is the last to be involved in the process. The matter carried away by the drift is partially accumulated near the resonance position forming a narrow dense ringlet. (c) 1996 American Institute of Physics.