A canine model of irreversible urethral sphincter insufficiency

OBJECTIVE To develop a canine model of external urinary sphincter insufficiency by creating irreversible damage to the sphincter, because there is a need for a reliable and reproducible large animal model for the study of stress urinary incontinence (SUI) caused by deficient sphincter function. MATERIALS AND METHODS About a quarter of the total external sphincter muscle was removed microsurgically from seven female dogs; three age-matched dogs served as normal controls. The dogs had standard urodynamic and radiographic studies before and at 1, 2, 3, 4 and 7 months after surgery. Three dogs were killed at 4 months and four at 7 months after surgery for tissue analyses. RESULTS The interventions produced a consistent outcome. Urodynamic studies showed a significant and sustained decrease in sphincter function, which included a static urethral pressure profile, stress urethral profile and detrusor leak-point pressure. Furthermore, in vivo pudendal nerve stimulation and organ-bath studies of the retrieved tissue strips confirmed the loss of sphincter tissue function. Histologically, absence of functional sphincter muscle was evident in the damaged sphincter region. CONCLUSIONS These results show that a reliable and reproducible canine model of irreversible sphincter insufficiency can be created by microsurgical removal of sphincter muscle tissue. This model of external sphincter insufficiency could be used for evaluating methods (e.g. cell therapies) for treating SUI

Bioink properties before, during and after 3D bioprinting

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction

Experimental Measurement of the Berry Curvature from Anomalous Transport

Geometrical properties of energy bands underlie fascinating phenomena in a wide-range of systems, including solid-state materials, ultracold gases and photonics. Most famously, local geometrical characteristics like the Berry curvature can be related to global topological invariants such as those classifying quantum Hall states or topological insulators. Regardless of the band topology, however, any non-zero Berry curvature can have important consequences, such as in the semi-classical evolution of a wave packet. Here, we experimentally demonstrate for the first time that wave packet dynamics can be used to directly map out the Berry curvature. To this end, we use optical pulses in two coupled fibre loops to study the discrete time-evolution of a wave packet in a 1D geometrical "charge" pump, where the Berry curvature leads to an anomalous displacement of the wave packet under pumping. This is both the first direct observation of Berry curvature effects in an optical system, and, more generally, the proof-of-principle demonstration that semi-classical dynamics can serve as a high-resolution tool for mapping out geometrical properties

Observation of Bose-Einstein Condensation in a Strong Synthetic Magnetic Field

Extensions of Berry's phase and the quantum Hall effect have led to the discovery of new states of matter with topological properties. Traditionally, this has been achieved using gauge fields created by magnetic fields or spin orbit interactions which couple only to charged particles. For neutral ultracold atoms, synthetic magnetic fields have been created which are strong enough to realize the Harper-Hofstadter model. Despite many proposals and major experimental efforts, so far it has not been possible to prepare the ground state of this system. Here we report the observation of Bose-Einstein condensation for the Harper-Hofstadter Hamiltonian with one-half flux quantum per lattice unit cell. The diffraction pattern of the superfluid state directly shows the momentum distribution on the wavefuction, which is gauge-dependent. It reveals both the reduced symmetry of the vector potential and the twofold degeneracy of the ground state. We explore an adiabatic many-body state preparation protocol via the Mott insulating phase and observe the superfluid ground state in a three-dimensional lattice with strong interactions.Comment: 6 pages, 5 figures. Supplement: 6 pages, 4 figure

Quantum transport in ultracold atoms

Ultracold atoms confined by engineered magnetic or optical potentials are ideal systems for studying phenomena otherwise difficult to realize or probe in the solid state because their atomic interaction strength, number of species, density, and geometry can be independently controlled. This review focuses on quantum transport phenomena in atomic gases that mirror and oftentimes either better elucidate or show fundamental differences with those observed in mesoscopic and nanoscopic systems. We discuss significant progress in performing transport experiments in atomic gases, contrast similarities and differences between transport in cold atoms and in condensed matter systems, and survey inspiring theoretical predictions that are difficult to verify in conventional setups. These results further demonstrate the versatility offered by atomic systems in the study of nonequilibrium phenomena and their promise for novel applications.Comment: 24 pages, 7 figures. A revie

Heterogeneous behavior of lipids according to HbA1(c) levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey

Background: Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. the threshold of HbA1(c) above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1(c) values; 2) detect a threshold of HbA1(c) beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1(c) individuals with type 1 diabetes.Methods: Effects of HbA1(c) quintiles (1st: 11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls.Results: Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1(c) quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1(c), OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1(c) quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1(c) in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control.Conclusions: Correlation of serum lipids with HbA1(c) is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1(c) with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1(c), refuting a unified explanation for cardiovascular risk in type 1 diabetes.CEDEBA Ctr Endocrinol Estado Bahia, Salvador, BA, BrazilUniversidade Federal de São Paulo, Ctr Diabet, São Paulo, BrazilUniv Estado Rio de Janeiro, Rio de Janeiro, BrazilAssoc Diabet Bauru, Bauru, BrazilUniversidade Federal de São Paulo, Ctr Diabet, São Paulo, BrazilWeb of Scienc

The use of mesenchymal stromal cells in treatment of lung disorders

The therapeutic use of mesenchymal stromal cells (MSCs) represents a promising alternative clinical strategy for treating acute and chronic lung disorders. Several pre-clinical reports demonstrated that MSCs can secrete multiple paracrine factors and that their immunomodulatory properties can support endothelial and epithelial regeneration, modulate the inflammatory cascade, and protect lungs from damage. The effects of MSC transplantation into patients suffering from lung diseases should be fully evaluated through careful assessment of safety and associated risks, which is a prerequisite for translation of pre-clinical research into clinical practise. In this article we summarise the current status of pre-clinical research and review initial MSC-based clinical trials for treating lung injuries and lung disorders

Abelian gauge potentials on cubic lattices

The study of the properties of quantum particles in a periodic potential subject to a magnetic field is an active area of research both in physics and mathematics; it has been and it is still deeply investigated. In this review we discuss how to implement and describe tunable Abelian magnetic fields in a system of ultracold atoms in optical lattices. After discussing two of the main experimental schemes for the physical realization of synthetic gauge potentials in ultracold set-ups, we study cubic lattice tight-binding models with commensurate flux. We finally examine applications of gauge potentials in one-dimensional rings.Comment: To appear on: "Advances in Quantum Mechanics: Contemporary Trends and Open Problems", G. Dell'Antonio and A. Michelangeli eds., Springer-INdAM series 201

Functional Genomics: New Insights into the 'Function' of Low Levels of Gene Expression in Stem Cells

Understanding the global gene expression profile of stem cells and their multilineage differentiation will be essential for their ultimate therapeutic application. Efforts to characterize stem cells have relied on analyzing the genome-wide expression profiles that are biased towards the identification of genes that display the most pronounced differential expression. Rather than being viewed as a “blank” state, recent studies suggest that stem cells express low levels of multiple lineage specific genes prior to differentiation, a phenomenon known as “lineage priming.” It is not likely that low levels of lineage-specific genes produce sufficient amounts of differentiation factors, but rather to provide rapid transcription to a wide range of lineage programs prior to differentiation. Thus, stem cell differentiation may involve the elimination of other potential pathways and the activation of a specific lineage program