Orthosis reduces breast pain and mechanical forces through natural and augmented breast tissue in women lying prone

BACKGROUND: Breast implant displacement or rupture can cause aesthetic problems and serious medical complications. Activities with prone positioning and loading of the anterior chest wall, such as massage, chiropractic or osteopathic therapies may increase the risk of implant failure and can also cause discomfort in women with natural breast tissue. Here we test the effectiveness of a newly developed orthosis on pain, mechanical pressure and displacement of breast tissue in women with cosmetic augmentation, post-mastectomy reconstruction, lactating or natural breast tissue. METHODS: Thirty-two females volunteers, aged 25–56 years with augmented, reconstructed, natural or lactating breast tissue and cup sizes B-F, participated in this open-label clinical trial. We measured pain perception, peak pressure, maximum force, and breast tissue displacement using different sizes of the orthosis compared to no orthosis. Different densities of the orthosis were also tested in a subgroup of women (n = 7). Pain perception was rated using a validated 11-point visual-analogue scale. Peak pressure and maximum force were assessed using a bilateral set of capacitance-pliance® sensor strips whilst participants were load bearing in a prone position, and breast displacement was measured by magnetic-resonance-imaging. RESULTS: The orthosis significantly reduced pain, breast displacement and mechanical pressures in women with natural and augmented breast tissue in prone position. Greater relief of pain and greater reduction in mechanical forces were found with increased size and density of the orthosis. Use of the orthosis improved overall comfort by 64-100%, lowered peak pressure by up to 85% and maximum force by up to 96%. Medio-lateral displacement of breast tissue was reduced by 16%, resulting in a 51% desirable increase of breast tissue height. CONCLUSION: Our study demonstrated that the newly developed orthosis significantly reduced pain, mechanical pressure and breast tissue displacement in women with augmented and natural breast tissue when lying prone. Our findings are of clinical significance, potentially reducing the risk of complication from prone activities in women with breast augmentation or reconstruction, as well as improving comfort whilst undergoing prone procedures. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register, ACTRN12613000541707

Protein design in a lattice model of hydrophobic and polar amino acids

A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on three-dimensional lattice structures. Previous studies employing a sequence-space Monte-Carlo technique resulted in the successful design of one sequence in ten attempts. The present work also entails the exploration of conformations that compete significantly with the target structure for being its ground state. The design procedure is successful in all the ten cases.Comment: RevTeX, 12 pages, 1 figur

Modeling study on the validity of a possibly simplified representation of proteins

The folding characteristics of sequences reduced with a possibly simplified representation of five types of residues are shown to be similar to their original ones with the natural set of residues (20 types or 20 letters). The reduced sequences have a good foldability and fold to the same native structure of their optimized original ones. A large ground state gap for the native structure shows the thermodynamic stability of the reduced sequences. The general validity of such a five-letter reduction is further studied via the correlation between the reduced sequences and the original ones. As a comparison, a reduction with two letters is found not to reproduce the native structure of the original sequences due to its homopolymeric features.Comment: 6 pages with 4 figure

The PDZ domain of the SpoIVB serine peptidase facilitates multiple functions

During spore formation in Bacillus subtilis, the SpoIVB protein is a critical component of the sigma (K) regulatory checkpoint. SpoIVB has been shown to be a serine peptidase that is synthesized in the spore chamber and which self-cleaves, releasing active forms. These forms can signal proteolytic processing of the transcription factor sigma (K) in the outer mother cell chamber of the sporulating cell. This forms the basis of the sigma (K) checkpoint and ensures accurate sigma (K)-controlled gene expression. SpoIVB has also been shown to activate a second distinct process, termed the second function, which is essential for the formation of heat-resistant spores. In addition to the serine peptidase domain, SpoIVB contains a PDZ domain. We have altered a number of conserved residues in the PDZ domain by site-directed mutagenesis and assayed the sporulation phenotype and signaling properties of mutant SpoIVB proteins. Our work has revealed that the SpoIVB PDZ domain could be used for up to four distinct processes, (i) targeting of itself for trans proteolysis, (11) binding to the protease inhibitor BofC, (iii) signaling of pro-sigma (K) processing, and (iv) signaling of the second function of SpoIVB

Statics, metastable states and barriers in protein folding: A replica variational approach

Protein folding is analyzed using a replica variational formalism to investigate some free energy landscape characteristics relevant for dynamics. A random contact interaction model that satisfies the minimum frustration principle is used to describe the coil-globule transition (characterized by T_CG), glass transitions (by T_A and T_K) and folding transition (by T_F). Trapping on the free energy landscape is characterized by two characteristic temperatures, one dynamic, T_A the other static, T_K (T_A> T_K), which are similar to those found in mean field theories of the Potts glass. 1)Above T_A, the free energy landscape is monotonous and polymer is melted both dynamically and statically. 2)Between T_A and T_K, the melted phase is still dominant thermodynamically, but frozen metastable states, exponentially large in number, appear. 3)A few lowest minima become thermodynamically dominant below T_K, where the polymer is totally frozen. In the temperature range between T_A and T_K, barriers between metastable states are shown to grow with decreasing temperature suggesting super-Arrhenius behavior in a sufficiently large system. Due to evolutionary constraints on fast folding, the folding temperature T_F is expected to be higher than T_K, but may or may not be higher than T_A. Diverse scenarios of the folding kinetics are discussed based on phase diagrams that take into account the dynamical transition, as well as the static ones.Comment: 41 pages, LaTeX, 9 EPS figure

An Analytical Approach to the Protein Designability Problem

We present an analytical method for determining the designability of protein structures. We apply our method to the case of two-dimensional lattice structures, and give a systematic solution for the spectrum of any structure. Using this spectrum, the designability of a structure can be estimated. We outline a heirarchy of structures, from most to least designable, and show that this heirarchy depends on the potential that is used.Comment: 16 pages 4 figure

Coarse grained description of the protein folding

We consider two- and three-dimensional lattice models of proteins which were characterized previously. We coarse grain their folding dynamics by reducing it to transitions between effective states. We consider two methods of selection of the effective states. The first method is based on the steepest descent mapping of states to underlying local energy minima and the other involves an additional projection to maximally compact conformations. Both methods generate connectivity patterns that allow to distinguish between the good and bad folders. Connectivity graphs corresponding to the folding funnel have few loops and are thus tree-like. The Arrhenius law for the median folding time of a 16-monomer sequence is established and the corresponding barrier is related to easily identifiable kinetic trap states.Comment: REVTeX, 9 pages, 15 EPS figures, to appear in Phys. Rev.

Steric constraints in model proteins

A simple lattice model for proteins that allows for distinct sizes of the amino acids is presented. The model is found to lead to a significant number of conformations that are the unique ground state of one or more sequences or encodable. Furthermore, several of the encodable structures are highly designable and are the non-degenerate ground state of several sequences. Even though the native state conformations are typically compact, not all compact conformations are encodable. The incorporation of the hydrophobic and polar nature of amino acids further enhances the attractive features of the model.Comment: RevTex, 5 pages, 3 postscript figure

Scaling of folding properties in simple models of proteins

Scaling of folding properties of proteins is studied in a toy system -- the lattice Go model with various two- and three- dimensional geometries of the maximally compact native states. Characteristic folding times grow as power laws with the system size. The corresponding exponents are not universal. Scaling of the thermodynamic stability also indicates size-related deterioration of the folding properties.Comment: REVTeX, 4 pages, 4 EPS figures, PRL (in press

Reply to Comment on "Criterion that Determines the Foldability of Proteins"

We point out that the correlation between folding times and $\sigma = (T_{\theta } - T_{f})/T_{\theta }$ in protein-like heteropolymer models where $T_{\theta }$ and $T_{f}$ are the collapse and folding transition temperatures was already established in 1993 before the other presumed equivalent criterion (folding times correlating with $T_{f}$ alone) was suggested. We argue that the folding times for these models show no useful correlation with the energy gap even if restricted to the ensemble of compact structures as suggested by Karplus and Shakhnovich (cond-mat/9606037).Comment: 6 pages, Latex, 2 Postscript figures. Plots explicitly showing the lack of correlation between folding time and energy gap are adde