Variations in activation energy and nuclei size during nucleation explain chiral symmetry breaking.

We show that variations in enantiomer nuclei size and activation energy during the nucleation stage of crystallization are responsible for the chiral symmetry breaking resulting in excess of one of the possible enantiomers with respect to the other. By understanding the crystallisation process as a non-equilibrium self-assembly process, we quantify the enantiomeric excess through the probability distribution of the nuclei size and activation energy variations which are obtained from the free energy involved in the nucleation stage of crystallisation. We validate our theory by comparing it to Kondepudi et al. previous experimental work on sodium chlorate crystallisation. The results demonstrate that the self-assembly of enantiomeric crystals provides an explanation for chiral symmetry breaking. These findings could have practical applications for improving the production of enantiopure drugs in the pharmaceutical industry, as well as for enhancing our understanding of the origins of life since enantiomeric amino acids and monosaccharides are the building blocks of life.

Chiral symmetry breaking induced by energy dissipation.

Spontaneous chiral symmetry breaking is observed in a wide variety of systems on very different scales, from the subatomic to the cosmological. Despite its generality and importance for a large number of applications, its origin is still a matter of debate. It has been shown that the existence of a difference between the energies of the intermediate states of optical enantiomers leads to disparate production rates and thus to symmetry breaking. However, it is still unclear why this occurs. We measured for the first time the optical rotation angle of NaClO3 enantiomeric crystals in solution during their formation and found that the amount of energy needed to induce the enantiomeric excess is exactly the same as the energy dissipated per mole of solid salt calculated from the entropy production obtained from the proposed model. The irreversible nature of the process leading to entropy production thus explains the chiral symmetry breaking in the salt crystals studied. The proposed method could be used to explain the formation of self-organised structures generated by self-assembly of enantiomers arising from chiral symmetry breaking, such as those emerging in the production of advanced materials and synthetic biological tissues.

Enhancing particle transport in deformable micro-channels.

It is shown that the action of an oscillating force on particles moving through a deformable-walled channel causes them to travel greater distances than in the case of a rigid channel. This increase in the transport efficiency is due to an intensification of the stochastic resonance effect observed in corrugated rigid channels, for which the response to the force is maximal for an optimal value of the thermal noise. The distances traveled by the particles are even larger when the oscillation of the micro-channel is synchronized with that of an applied transverse force and also when a constant external force is considered. The phenomenon found could be observed in the transport of particles through elastic porous media, in drug delivery to cancerous tissues, and in the passage of substrates through transporters in biological membranes. Our results indicate that an appropriate channel design and a suitable choice of applied forces lead to optimal scenarios for particle transport.

Nonequilibrium thermodynamics of Janus particle self-assembly.

We compute the energetic cost of formation of Janus particle structures. Using an approach that couples particle dynamics to the evolution of fuel concentration in the medium, which we consider to be initially inhomogeneous, we show the different types of emerging structures. The energy dissipated in the formation of such structures is obtained from the entropy production rate, which is a non-monotonic function of the fraction of assembled particles and, thus, different in each self-assembly regime. An analysis of the free energy of these particles allows us to establish a thermodynamic criterion of structure formation based on the behavior of chemical potential as a function of the fraction of assembled particles.

Utility of the combination of hederagenin glucoside saponins and chromane hydrazone in the topical treatment of canine cutaneous leishmaniasis. An observational study.

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2-2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6-24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2-2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.

Role of Interfacial Entropy in the Particle-Size Dependence of Thermophoretic Mobility.

We show that changes in the surface tension of a particle due to the presence of nonionic surfactants and impurities, which alter the interfacial entropy, have an impact on the value of the thermophoretic mobility. We have found the existence of different behaviors of this quantity in terms of particle size which can be summarized through a power law. For particles that are small enough, the thermophoretic mobility is a constant, whereas for larger particles it is linear in the particle radius. These results show the important role of the interfacial entropic effects on the behavior of the thermophoretic mobility.

Entropic transport in a crowded medium.

To know how liquid matter moves through a crowded medium due to the action of a force constitutes currently a problem of great practical importance, present in cases as diverse as the transport of particles through a cell membrane and through a particulate porous medium. To calculate the mass flow through the system, we present an approach that emulates the texture of the medium by using entropic barriers that the particles must overcome in order to move. The model reproduces the scaling behavior of the velocity with the force found in many systems in order to show how the scaling exponent depends on the micro-structure of the medium. Our model offers a new perspective that is able to characterize the flow of matter through the medium and may be useful in studies of nano-fluids, oil recovery, soil drainage, tissue engineering, and drug delivery.

Self-assembling outside equilibrium: emergence of structures mediated by dissipation.

A set of disordered interacting building blocks may form ordered structures by means of a self-assembling process. An external intervention in the system by adding a chemical species or by applying forces leads to different self-assembly scenarios with the appearance of new structures. For instance, the formation of microtubules, gels, virus capsides, cells and living beings among others takes place by self-assembly under nonequilibrium conditions. A general evolution criterion able to account for why nature selects some structures outside equilibrium and not others is lacking. Nevertheless, progress in the understanding of nonequilibrium self-assembly (NESA) mechanisms has been made thanks to the formulation of models that take particular situations into consideration. We review recent efforts devoted to describing self-assembly out of equilibrium and we provide a reference linking several current concepts in order to help in the development of new models and experimental studies. We hope that the knowledge of the intimate mechanisms leading to the formation of structures will make the implementation of re-configurable and bio-inspired materials possible and give a simpler perspective on the understanding of the emergence of life.

Successful eradication of invasive Scopulariopsis brumptii in a liver transplant recipient.

Ten months after orthotopic liver transplant, a 53-year-old male patient developed cough and fever. Imaging revealed diffuse ground-glass opacities involving all lobes, and subsequent bronchoscopic washings revealed Scopulariopsis brumptii infection. The patient initially had significant clinical deterioration requiring intubation and extracorporeal membrane oxygenation. However, combination antifungal therapy, including posaconazole and terbinafine, eventually proved successful in eradicating the infection.

Quantitative 3D MRI reveals limited intra-lesional bony overgrowth at 1 year after microfracture-based cartilage repair.

OBJECTIVE: Intra-lesional bony overgrowth (BO) identified during or following cartilage repair treatment is being frequently described through subjective reports focusing primarily on incidence. Our objective was to quantify the exact volume of intra-lesional BO at 12 months post-cartilage repair treatment, to determine if a correlation exists between the extent of BO and clinical outcomes, and to visualize and characterize the BO. DESIGN: MRI scans were systematically obtained during a randomized clinical trial for cartilage repair (Stanish et al., 2013) that compared two microfracture-based treatments in 78 patients. Semi-automated morphological segmentation of pre-treatment, 1 and 12 months post-treatment scans utilizing a programmed anatomical atlas for all knee bone and cartilage structures permitted three-dimensional reconstruction, quantitative analysis, as well as qualitative characterization and artistic visualization of BO. RESULTS: Limited intra-lesional BO representing only 5.8 ± 5.7% of the original debrided cartilage lesion volume was found in 78 patients with available MRIs at 12 months. The majority (80%) of patients had very little BO (<10%). Most occurrences of BO carried either spotty (56.4%) or planar (6.4%) morphological features, and the remaining balance (37.2%) was qualitatively unobservable by eye. Pre-existing BO recurred at 12 months in the same intra-lesional location in 36% of patients. No statistical correlations were found between BO and clinical outcomes. CONCLUSIONS: Intra-lesional BO following microfracture-based treatments may not be as severe as previously believed, its incidence is partly explained by pre-existing conditions, and no relationship to clinical outcomes exists at 12 months. Morphologically, observable BO was categorized as comprising either spotty or planar bone.

Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

BACKGROUND: Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. METHODS: A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. RESULTS: Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. CONCLUSION: Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B19 disease.

Predicting cancer stages from tissue energy dissipation.

Understanding cancer staging in order to predict its progression is vital to determine its severity and to plan the most appropriate therapies. This task has attracted interest from different fields of science and engineering. We propose a computational model that predicts the evolution of cancer in terms of the intimate structure of the tissue, considering that this is a self-organised structure that undergoes transformations governed by non-equilibrium thermodynamics laws. Based on experimental data on the dependence of tissue configurations on their elasticity and porosity, we relate the cancerous tissue stages with the energy dissipated, showing quantitatively that tissues in more advanced stages dissipate more energy. The knowledge of this energy allows us to know the probability of observing the tissue in its different stages and the probability of transition from one stage to another. We validate our results with experimental data and statistics from the World Health Organisation. Our quantitative approach provides insights into the evolution of cancer through its different stages, important as a starting point for new and integrative research to defeat cancer.

Optimal transport of active particles induced by substrate concentration oscillations.

We show the existence of a stochastic resonant regime in the transport of active colloidal particles under confinement. The periodic addition of substrate to the system causes the spectral amplification to exhibit a maximum for an optimal noise level value. The consequence of this is that particles can travel longer distances with lower fuel consumption. The stochastic resonance phenomenon found allows the identification of optimal scenarios for the transport of active particles, enabling them to reach regions that are otherwise difficult to access, and may therefore find applications in transport in cell membranes and tissues for medical treatments and soil remediation.

[Comparison of self-reported anthropometric variables and real measurement data]. / Comparación entre variables antropométricas auto reportadas y mediciones reales.

The objectives of this study were to evaluate self-reporting of weight, height, and waist circumference, and to compare that perception with the real measurements in college students of the MESPYN cohort--Medellin, Salud Pública y Nutrición--from the University of Antioquia (UdeA), Colombia. A cross-sectional study was conducted starting with the first measurement of the MESPYN Cohort 2009-2010. The sample included volunteer students from different academic areas. Self-perception of weight, height, and waist circumference were recorded before the real measurements were performed. Intraclass correlation coefficients (ICC) were calculated for all the variables, and an alpha of 0.05 was used. The concordance between real measurements and self-referred values was evaluated with the Bland and Altman method. 424 volunteer students were included. The average real weight (kg) in males was 67.4 +/- 10.4 and self-reported: 67.0 +/- 11.0; in females the real value was 55.7 +/- 10.1 and self-reported: 55.0 +/- 9.0. The average real height (m) in males was 1.73 +/- 6.1 and self-reported: 1.73 +/- 6.0; in females the real value was 1.60 +/- 5.9 and self-reported: 1.61 +/- 6.0. In males, the average real waist circumference (cm) was 76.6 +/- 8.0 and self-reported: 75.0 +/- 14.0; in females the real value was 69.9 +/- 8.0 and self-reported: 70.0 +/- 9.0. Weight ICC: 0.956, 95% CI (0.95; 0.97), (p < 0.01); height ICC: 0.953, 95%IC (0.91; 0.97), (p < 0.01), and waist circumference ICC: 0.593, 95% IC (0.55; 0.65), (p < 0.01). In conclusion, anthropometric nutritional evaluation of UdeA students can be performed with self-reported data for weight and height, but the evaluation of abdominal obesity requires direct measurement of waist circumference.

Efficacy of cement restrictors: Experimental study and development of a classification. / Eficacia de los restrictores de cemento: estudio experimental y desarrollo de una clasificación.

INTRODUCTION: Cement restrictors (CRs) are devices that allow occlusion of the femoral canal in order to obtain greater interdigitation of the cement between the bone and a better pressurization, which generates an increase in the survival of cemented stems. The aim of this study was to evaluate the efficacy of the different CRs used and propose a classification of this device. MATERIALS AND METHODS: An experimental study was carried out, where 7 CR references of different designs and manufacturers were taken. Later, tests were carried out on 9 chlorinated polyvinyl chloride tubes for each reference, to achieve a total of 63 tests. RESULTS: In our study, 34.9% of the CRs in ultra high molecular weight polyethylene failed, presenting migration and allowing cement to leak while none of the gelatin RC failed. CONCLUSION: The RC with an umbrella design proved to be the less effective, presented a higher incidence of migration and cement leakage, while the gelatin CRs were the best performers. Based on the results of this study, an analysis of the CR design was carried out and a classification was proposed that divides these devices into 2 types.

Gene expression during activation of Paracoccidioides brasiliensis conidia.

This study focuses on gene expression during crucial biological phenomena of the dimorphic fungal human pathogen Paracoccidioides brasiliensis, the conidia-to-yeast (C-Y) transition and the conidia-to-mycelia (C-M) germination. We studied 10 genes involved in different cellular functions: oxidative stress response (alternative oxidase (AOX), superoxide dismutase (SOD), flavodoxin, conserved hypothetical protein (Y20)); cell metabolism (glyceraldehyde-3-phosphate dehydrogenase (GADPH), cholestenol Delta-isomerase (ChDI), glycine dehydrogenase (GDh)) and heat shock response (Heat shock protein 90 (HSP90)), and cell synthesis and wall structure (glucan synthase-1 (GS-1), α-1,3-glucan synthase (αGS), and mannosyltransferase (MT)). Gene expression was measured during the first 72 h and 96 h of C-Y and C-M, respectively, previously shown to be a fundamental time frame for the consolidation of these cellular processes. The gene expression of AOX, GAPDH, HSP90, MT, αGS, and GDh was significantly increased during the C-Y transition, while SOD, ChDI, GAPDH, MT, GDh, and GS-1 were increased during C-M germination. Additionally, some were highly expressed in each process: AOX, HSP90, and αGS during C-Y; SOD, ChDI, and GS-1 during C-M. Altogether, these data add new information regarding gene expression during the C-Y and C-M processes. Future research will be targeted to further characterize the true relevance of the studied genes during the morphological transition, either during adaptation to the environment or to the infected host.

Structural characteristics of the collagen network in human normal, degraded and repair articular cartilages observed in polarized light and scanning electron microscopies.

OBJECTIVE: This study characterizes collagen organization (CO) in human normal (n = 6), degraded (n = 6) and repair (n = 22) cartilages, using polarized light (PLM) and scanning electron (SEM) microscopies. DESIGN: CO was assessed using a recently developed PLM-CO score (Changoor et al. Osteoarthritis Cartilage 2011;19:126-35), and zonal proportions measured. SEM images were captured from locations matched to PLM. Fibre orientations were assessed in SEM and compared to those observed in PLM. CO was also assessed in individual SEM images and combined to generate a SEM-CO score for overall CO analogous to PLM-CO. Fibre diameters were measured in SEM. RESULTS: PLM-CO and SEM-CO scores were correlated, r = 0.786 (P < 0.00001, n = 32), after excluding two outliers. Orientation observed in PLM was validated by SEM since PLM/SEM correspondence occurred in 91.6% of samples. Proportions of the deep (DZ), transitional (TZ) and superficial (SZ) zones averaged 74.0 ± 9.1%, 18.6 ± 7.0%, and 7.3 ± 1.2% in normal, and 45.6 ± 10.7%, 47.2 ± 10.1% and 9.5 ± 3.4% in degraded cartilage, respectively. Fibre diameters in normal cartilage increased with depth from the articular surface [55.8 ± 9.4 nm (SZ), 87.5 ± 1.8 nm (TZ) and 108.2 ± 1.8 nm (DZ)]. Fibre diameters were smaller in repair biopsies [60.4 ± 0.7 nm (SZ), 63.2 ± 0.6 nm (TZ) and 67.2 ± 0.8 nm (DZ)]. Degraded cartilage had wider fibre diameter ranges and bimodal distributions, possibly reflecting new collagen synthesis and remodelling or collagen fibre unravelling. Repair tissues revealed the potential of microfracture-based repair procedures to produce zonal CO resembling native articular cartilage structure. Values are reported as mean ± 95% confidence interval. CONCLUSION: This detailed assessment of collagen architecture could benefit the development of cartilage repair strategies intended to recreate functional collagen architecture.

Presence and expression of the mating type locus in Paracoccidioides brasiliensis isolates.

Paracoccidioides brasiliensis has been classified in the phylum Ascomycota, order Onygenales, family Ajellomycetaceae, even in the absence of a known sexual cycle or mating system. The objective of this work was to determine the presence of the mating type locus in 71 P. brasiliensis isolates from various sources. A PCR assay using specific primers for the MAT 1 gene was developed and applied for the detection of such genes. Two heterothallic groups (MAT1-1 or MAT1-2) were recognized and, in some isolates, gene expression was confirmed indicating the existence of a basal gene expression. The distribution of two mating type loci in the studied population suggested that sexual reproduction might occur in P. brasiliensis. This finding points towards the possibility of applying a more precise definition of the concept of biological species to P. brasiliensis. Further studies should be conducted to confirm the sexual capacity of this fungus and its implications among phylogenetic species and geographical distribution.

The cannabinoid CP55,940 prolongs survival and improves locomotor activity in Drosophila melanogaster against paraquat: implications in Parkinson's disease.

Cannabinoids have been shown to function as protective agents via receptor-independent and/or receptor-dependent mechanisms against stressful conditions. However, the neuroprotective mechanism of cannabinoids is far from conclusive. Therefore, the genuine antioxidant impact of cannabinoids in vivo is still uncertain. In this study, we demonstrate for the first time that CP55,940, a nonselective CB(1)/CB(2) cannabinoid receptor agonist, significantly protects and rescues Drosophila melanogaster against paraquat (PQ) toxicity via a receptor-independent mechanism. Interestingly, CP55,940 restores the negative geotaxis activity (i.e., climbing capability) of the fly exposed to PQ. Moreover, Drosophila fed with (1-200 microM) SP600125, a specific inhibitor of the stress responsive Jun-N-terminal kinase (JNK) signaling, and 20 mM PQ increased survival percentage and movement function (i.e., climbing capability) when compared to flies only treated with PQ. Taken together our results suggest that exogenous antioxidant cannabinoids can protect against and rescue from locomotor dysfunction in wild type (Canton-S) Drosophila exposed to stress stimuli. Therefore, cannabinoids may offer promising avenues for the design of molecules to prevent, delay, or ameliorate the treatment of population at high risk of suffering Parkinson disease.

Clinical and Health Care Utilization Outcomes of Kidney Transplantation in HIV-Positive Recipients: A Nationwide Analysis From 2008-2013.

BACKGROUND: Kidney transplantation (KTxp) provides dialysis independence, improved quality of life, and prolonged life expectancy for patients with end-stage renal disease. Before and during the early antiretroviral therapy era, KTxp was not a consideration for patients with end-stage renal disease who were HIV-positive (HIV+ve) given their short life expectancy and prevailing organ procurement constraints. Recent advancements in antiretroviral therapy and HIV care have overhauled this paradigm and KTxp has now been performed for several years, however, pragmatic studies documenting outcomes are lacking. We herein document the effectiveness of KTxp in patients who are HIV+ve by reporting clinical and health care utilization outcomes in the United States. METHODS: Utilizing the Inpatient Databases of the Healthcare Cost & Utilization Project spanning 2008-2013, we identified all adult recipients of KTxp by procedural codes and recipients who are HIV+ve by ICD-9 codes. We extracted demographic, clinical, and resource utilization variables and compared recipients who are HIV+ve with those who are HIV-negative (HIV-ve). We then performed descriptive statistics and multivariate analysis using logistic regression to assess the effect of HIV on clinical and utilization outcomes. RESULTS: A total of 104,137 patients had kidney transplants during the study period. Of the total, 605 patients were HIV+ve. Infections rates were similar among patients who were HIV+ve and HIV-ve (odds ratio [OR] 1.18, confidence interval [CI] 0.58-2.40; P = .652). In-hospital mortality rates were also similar (OR 0.83, CI 0.18-3.69; P = .80). Hospital charges for patients who were HIV+ve were no different from patients who were HIV-ve ($195,099 ± 1074 vs $186,567 ± 9558; P = .38). CONCLUSION: Clinical and fiscal outcomes are comparable among patients who are HIV+ve and HIV-ve during transplant hospitalization.