Hedysari Extract Improves Regeneration after Peripheral Nerve Injury by Enhancing the Amplification Effect

Radix Hedysari is an herbal preparation frequently used in traditional Chinese medicine. It can promote regeneration after peripheral nerve injury, but its effect on the amplification ratio (the ratio of distal to proximal fibers) during peripheral nerve regeneration has not yet been examined. In this study, we explored the effect of Hedysari extract on the amplification ratio in the peripheral nerve. Male Sprague-Dawley rats were separated into three groups at random: normal group (without surgery), model group (given sleeve nerve bridging surgery, but without adjuvant treatment) and treatment group (given sleeve nerve bridging surgery and then given Hedysari extract as adjuvant treatment). Twelve weeks after surgery, general observations, electrophysiological examination, histological analysis, morphometric measurements, and amplification ratio calculations were made. The results showed that nerve conduction velocity, the fiber and axon diameter, the g-ratio, the number of regenerating nerve fibers and the amplification ratio were better in the treatment group than in the model group, suggesting that Hedysari extract can effectively promote the growth of lateral buds in the proximal nerve stump and substantially improve the amplification effect during peripheral nerve regeneration.     

Mitochondrial DNA and ancient population growth

In recent years, the study of mitochondrial DNA (mtDNA) variation has entered a new phase with an increasing emphasis on interpretations of demographic, rather than phylogenetic, history. Human mtDNA variation fits a “sudden expansion” model, where the human species expanded rapidly in size during the Late Pleistocene. This paper examines the sudden expansion model with the goal of partitioning total mtDNA diversity in contemporary populations into two components—diversity that existed prior to the population expansion and diversity that arose after the expansion. A method is developed for estimating these components. Analysis of mtDNA diversity within selected human populations shows that 64–80% of mtDNA diversity in contemporary populations arose after the expansion, a consequence of a high mutation rate relative to the number of generations since expansion. The basic model is extended to two components of excess diversity in sub-Saharan Africa—differences in population size before the expansion and differences in the timing of expansion. Results suggest that excess sub-Saharan African mtDNA diversity is due to the combined effects of the sub-Saharan African population being larger in size prior to the expansion and expanding earlier. Am J Phys Anthropol 105:1–7, 1998. © 1998 Wiley-Liss, Inc.     

The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones

Bariatric surgery for obesity has proved to be an extremely effective method of promoting long-term weight reduction with additional beneficial metabolic effects, such as improved glucose tolerance and remission of type 2 diabetes. A range of bariatric procedures are in common use, including gastric banding, sleeve gastrectomy and the Roux-en-Y gastric bypass. Although the mechanisms underlying the efficacy of bariatric surgery are unclear, gastrointestinal and pancreatic peptides are thought to play an important role. The aim of this review is to summarise the effects of different bariatric surgery procedures upon gastrointestinal and pancreatic peptides, including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic hormone (GIP), glucagon-like peptide 1 (GLP-1), peptide YY (PYY), oxyntomodulin, insulin, glucagon and somatostatin.     

Application of a new intraventricular injection technique in rat brain norepinephrine studies.

A new technique has been devised for injecting substances directly into the right lateral ventricle of the rat. Injections are made with the aid of a stainless steel band designed to conform to the rat's skull and equipped with a rigid sleeve. When properly aligned with the caudal edge of the optic orbit, the sleeve is positioned o over the right lateral ventricle. The sleeve prevents bending of the injection needle and controls its penetration to the desired depth. Histological examination and H³-norepinephrine disposition studies have demonstrated the validity and reproductibility of the method. In contrast to previous methods, an anesthetic is not required and surgical trauma is avoided. Furthermore, the efficiency of the new technique is such that one rat can be injected per minute.     

Model choice for phylogeographic inference using a large set of models

Model‐based analyses are common in phylogeographic inference because they parameterize processes such as population division, gene flow and expansion that are of interest to biologists. Approximate Bayesian computation is a model‐based approach that can be customized to any empirical system and used to calculate the relative posterior probability of several models, provided that suitable models can be identified for comparison. The question of how to identify suitable models is explored using data from Plethodon idahoensis, a salamander that inhabits the North American inland northwest temperate rainforest. First, we conduct an ABC analysis using five models suggested by previous research, calculate the relative posterior probabilities and find that a simple model of population isolation has the best fit to the data (PP = 0.70). In contrast to this subjective choice of models to include in the analysis, we also specify models in a more objective manner by simulating prior distributions for 143 models that included panmixia, population isolation, change in effective population size, migration and range expansion. We then identify a smaller subset of models for comparison by generating an expectation of the highest posterior probability that a false model is likely to achieve due to chance and calculate the relative posterior probabilities of only those models that exceed this expected level. A model that parameterized divergence with population expansion and gene flow in one direction offered the best fit to the P. idahoensis data (in contrast to an isolation‐only model from the first analysis). Our investigation demonstrates that the determination of which models to include in ABC model choice experiments is a vital component of model‐based phylogeographic analysis.     

Lumped Parameter and Feedback Control Models of the Auto-regulatory Response in the Circle of Willis

The Circle of Willis (CoW) is a ring-like structure of blood vessels found beneath the hypothalamus at the base of the brain. Its main function is to distribute oxygen-rich arterial blood to the cerebral mass. A 1-dimensional model of the CoW has been created to simulate a series of possible clinical scenarios such as occlusions in afferent arteries, absent or string-like circulus vessels, or arterial infarctions. The model captures cerebral haemodynamic auto-regulation by using a proportional-integral-derivative (PID) controller to modify efferent resistances and maintain optimal efferent flowrates for a given circle geometry and afferent blood pressure. Results match limited clinical data and results obtained in prior studies to within 6%. In addition, a set of boundary conditions and geometry is presented for which the auto-regulated system cannot provide the necessary efferent flowrates and perfusion, representing a condition with increased risk of stroke and highlighting the importance of modelling the haemodynamics of the CoW. The system model created is computationally simple so it can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures.     

Lumped parameter and feedback control models of the auto-regulatory response in the Circle of Willis

The Circle of Willis (CoW) is a ring-like structure of blood vessels found beneath the hypothalamus at the base of the brain. Its main function is to distribute oxygen-rich arterial blood to the cerebral mass. A 1-dimensional model of the CoW has been created to simulate a series of possible clinical scenarios such as occlusions in afferent arteries, absent or string-like circulus vessels, or arterial infarctions. The model captures cerebral haemodynamic auto-regulation by using a proportional-integral-derivative (PID) controller to modify efferent resistances and maintain optimal efferent flowrates for a given circle geometry and afferent blood pressure. Results match limited clinical data and results obtained in prior studies to within 6%. In addition, a set of boundary conditions and geometry is presented for which the auto-regulated system cannot provide the necessary efferent flowrates and perfusion, representing a condition with increased risk of stroke and highlighting the importance of modelling the haemodynamics of the CoW. The system model created is computationally simple so it can be used to identify at-risk cerebral arterial geometries and conditions prior to surgery or other clinical procedures.     

Understanding Host-Switching by Ecological Fitting

Despite the fact that parasites are highly specialized with respect to their hosts, empirical evidence demonstrates that host switching rather than co-speciation is the dominant factor influencing the diversification of host-parasite associations. Ecological fitting in sloppy fitness space has been proposed as a mechanism allowing ecological specialists to host-switch readily. That proposal is tested herein using an individual-based model of host switching. The model considers a parasite species exposed to multiple host resources. Through time host range expansion can occur readily without the prior evolution of novel genetic capacities. It also produces non-linear variation in the size of the fitness space. The capacity for host colonization is strongly influenced by propagule pressure early in the process and by the size of the fitness space later. The simulations suggest that co-adaptation may be initiated by the temporary loss of less fit phenotypes. Further, parasites can persist for extended periods in sub-optimal hosts, and thus may colonize distantly related hosts by a "stepping-stone" process.     

Surgical augmentation of skin blood flow and viability in a pig musculocutaneous flap model

A porcine rectus abdominis musculocutaneous (TRAM) flap model was designed and validated in nine pigs. This TRAM flap was based on the deep inferior epigastric (DIE) vessels with an 8 x 18 cm transverse skin paddle at the superior end of the rectus abdominis muscle. The model was subsequently used to test our hypothesis of surgical augmentation of flap viability by vascular territory expansion. Specifically, we observed that ligation of the superior epigastric (SE) vessels at 4, 7, 14, and 28 days (N = 6 to 8) prior to raising the TRAM flaps significantly increased (p less than 0.05) the length and area of the viable skin in the transverse skin paddles of the treatment flaps compared with the contralateral shammanipulated control flaps. This significant increase in skin viability was seen to be accompanied by a significant increase (p less than 0.05) in skin and muscle capillary blood flow in the treatment TRAM flaps compared with the controls (N = 9). The mechanism of vascular territory expansion is unclear. We postulate that hypoxia resulting from the ligation of the superior epigastric vessels prior to the flap surgery may play a role in the triggering of the deep inferior epigastric artery to take over some of the territory previously perfused by the superior epigastric artery. This would then increase the skin and muscle capillary blood flow in the transverse paddle when the TRAM flap was raised on the deep inferior epigastric vascular pedicle.     

Lower Fetuin-A,Retinol Binding Protein 4 and Several Metabolites after Gastric Bypass Compared to Sleeve Gastrectomy in Patients with Type 2 Diabetes

Background

Bypass of foregut secreted factors promoting insulin resistance is hypothesized to be one of the mechanisms by which resolution of type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery.

Aim

To identify insulin resistance-associated proteins and metabolites which decrease more after GBP than after sleeve gastrectomy (SG) prior to diabetes remission.

Methods

Fasting plasma from 15 subjects with T2D undergoing GBP or SG was analyzed by proteomic and metabolomic methods 3 days before and 3 days after surgery. Subjects were matched for age, BMI, metformin therapy and glycemic control. Insulin resistance was calculated using homeostasis model assessment (HOMA-IR). For proteomics, samples were depleted of abundant plasma proteins, digested with trypsin and labeled with iTRAQ isobaric tags prior to liquid chromatography-tandem mass spectrometry analysis. Metabolomic analysis was performed using gas chromatography-mass spectrometry. The effect of the respective bariatric surgery on identified proteins and metabolites was evaluated using two-way analysis of variance and appropriate post-hoc tests.

Results

HOMA-IR improved, albeit not significantly, in both groups after surgery. Proteomic analysis yielded seven proteins which decreased significantly after GBP only, including Fetuin-A and Retinol binding protein 4, both previously linked to insulin resistance. Significant decrease in Fetuin-A and Retinol binding protein 4 after GBP was confirmed using ELISA and immunoassay. Metabolomic analysis identified significant decrease of citrate, proline, histidine and decanoic acid specifically after GBP.

Conclusion

Greater early decrease was seen for Fetuin-A, Retinol binding protein 4, and several metabolites after GBP compared to SG, preceding significant weight loss. This may contribute to enhanced T2D remission observed following foregut bypass procedures.     

Modification of a freshwater sampler using evacuated tubes for microbial collections

The modification of a freshwater sampler utilizing three evacuated tubes for the collection of microbial samples is described. To avoid contamination sterile hypodermic needles covered with rubber sleeves are inserted into the evacuated tubes prior to lowering the sampler. At the requisite depth each sleeve is pushed down over the end of the needle so that the tubes fill with water.     

Finite element modeling of a progressively expanding shape memory stent

Cardiovascular stents are small cylindrical devices introduced in stenosed arteries to reopen the lumen and restore blood flow. However, this treatment presents complications, including restenosis, which is the reclosing of the artery's diameter after the insertion of a stent. The structure of the prosthesis penetrates into and injures the walls of the patient's artery. There then follows a proliferation of cells and the formation of scar tissue around the injury, similar to the scarring of other organic tissues. This reaction to the trauma subjects the artery to close. The proposed solution is to develop a Nitinol stent with a progressive expansion device made of polyethylene, allowing smooth and gradual contact between the stent and the artery's wall by creep effect. The purpose of this paper is to describe the technology and methodology for the numerical study of this kind of stent through the finite element method. ANSYS 8.0 software is used to perform the analysis. The Nitinol is modeled with a superelastic law and the polyethylene with a yield hardening law. A first simulation determines the final geometry of the stent laser cut from a small tube. A second simulation examines the behavior of the prosthesis during surgery and over the 4 weeks following the operation. The results demonstrate that a compromise can be reached between a limited expansion prior the inflation of the expandable balloon and a significant expansion by creep of the polymer rings.     

Validation of the antral mucosal/submucosal sleeve preparation: studies of gastrin and acetylcholine release in response to luminal stimulation.

In the present study we developed an experimental model for direct assessment of antral endocrine cell and cholinergic neural responses to luminal stimulation. A sleeve of antral mucosal/submucosal tissue was prepared from rat antrum, mounted in perfusion chamber, and perfused in both luminal and submucosal compartments. Morphological and functional integrity of the antral sleeve were confirmed by histological examination and measurement of protein synthesis. Antral gastrin release was assessed in response to luminal stimulation with acid, peptone and distension. Luminal acid (pH3) inhibited basal gastrin release by -70.4% and luminal peptone stimulated gastrin release to 210% above control (p < 0.02). Distention of the antral sleeve by hydrostatic pressure (3-25cm H2O) caused stepwise and significant increase in gastrin release that was reversible. 3H-acetylcholine was stimulated significantly by KCl (56mM) to values twice control. In summary, these results establish the integrity and responsiveness of the antral sleeve to pharmacological and luminal stimulation. The antral sleeve may be a useful model in assessing antral function in response to luminal stimulation.     

Molecular modelling of the mass density of single proteins

Using molecular dynamics (MD) simulations, the density of single proteins and its temperature dependence was modelled starting from the experimentally determined protein structure and a generic, transferable force field, without the need of prior parameterization. Although all proteins consist of the same 20 amino acids, their density in aqueous solution varies up to 10% and the thermal expansion coefficient up to twofold. To model the protein density, systematic MD simulations were carried out for 10 proteins with a broad range of densities (1.32-1.43 g/cm(3)) and molecular weights (7-97 kDa). The simulated densities deviated by less than 1.4% from their experimental values that were available for four proteins. Further analyses of protein density showed that it can be essentially described as a consequence of amino acid composition. For five proteins, the density was simulated at different temperatures. The simulated thermal expansion coefficients ranged between 4.3 and 7.1 × 10(-4) K(-1) and were similar to the experimentally determined values of ribonuclease-A and lysozyme (deviations of 2.4 and 14.6%, respectively). Further analyses indicated that the thermal expansion coefficient is linked to the temperature dependence of atomic fluctuations: proteins with a high thermal expansion coefficient show a low increase in flexibility at increasing temperature. A low increase in atomic fluctuations with temperature has been previously described as a possible mechanism of thermostability. Thus, a high thermal expansion coefficient might contribute to protein thermostability.     

Study of Pyrex and quartz insulators contamination effect on the X-ray intensity in a 4-kJ plasma focus device

The variation of the X-ray intensity has been investigated with the Pyrex and quartz insulators surface contamination in a 4-kJ plasma focus device with argon gas at 11.5-kV charging voltage. Elemental analysis (EDAX) showed that the Cu evaporated from the electrode material and was deposited on the sleeve surface improves the breakdown conditions. A small level of sleeve contamination by copper is found to be essential for good focusing action and high HXR intensity. The SEM imaging showed the grain-type structure of Cu formed on the surface and it changed the surface property. Resistance measurements of original and coated Pyrex surface proved that the copper deposition on the sleeve surface will reduce its resistance as compared to the almost infinitely large resistance of the uncontaminated sleeve. As the contamination is surpassed to some critical level, the HXR intensity from the device is deteriorated.     

Molecular modelling of the mass density of single proteins

Using molecular dynamics (MD) simulations, the density of single proteins and its temperature dependence was modelled starting from the experimentally determined protein structure and a generic, transferable force field, without the need of prior parameterization. Although all proteins consist of the same 20 amino acids, their density in aqueous solution varies up to 10% and the thermal expansion coefficient up to twofold. To model the protein density, systematic MD simulations were carried out for 10 proteins with a broad range of densities (1.32–1.43?g/cm³) and molecular weights (7–97?kDa). The simulated densities deviated by less than 1.4% from their experimental values that were available for four proteins. Further analyses of protein density showed that it can be essentially described as a consequence of amino acid composition. For five proteins, the density was simulated at different temperatures. The simulated thermal expansion coefficients ranged between 4.3 and 7.1?×?10^?4?K^?1 and were similar to the experimentally determined values of ribonuclease-A and lysozyme (deviations of 2.4 and 14.6%, respectively). Further analyses indicated that the thermal expansion coefficient is linked to the temperature dependence of atomic fluctuations: proteins with a high thermal expansion coefficient show a low increase in flexibility at increasing temperature. A low increase in atomic fluctuations with temperature has been previously described as a possible mechanism of thermostability. Thus, a high thermal expansion coefficient might contribute to protein thermostability.     

Quality assurance activities of the College of American Pathologists

Since its inception, the College of American Pathologists (CAP) has played a fundamental and pivotal role in the development and execution of quality assurance programs for laboratories. Within the realm of anatomic pathology, operational programs include those in surgical pathology, immunohistochemistry and cytopathology. The emphasis of prior cytopathology programs on cervical cytology has now been expanded to include body fluids and fine needle aspiration material. CAP's role in the expansion of quality assurance programs in cytology may be enhanced in the future by intersociety cooperation with established cytology organizations and will also be influenced by and closely linked to the expansion of its quality assurance programs in surgical pathology. As for the Papanicolaou smear, it can no longer be regarded as the "Cinderella of cytology"; it is in fact the present-day cynosure in the laboratory. In recognition of this, CAP has undertaken efforts to help heighten public awareness about the value of Papanicolaou smear testing and is encouraging women to become more informed about the process involved in the examination of their smears.     

Ex vivo expansion and lentiviral transduction of Macaca nemestrina CD4+ T cells

Background  Macaca nemestrina is a nonhuman primate used as a model in preclinical studies of hematopoietic stem cell transplantation and adoptive transfer of T cells. Adoptive T cell transfer studies typically require ex vivo expansion of substantial numbers of T cells prior to their reinfusion into the subject.
Methods  Pigtailed macaque peripheral blood CD4⁺ cells were expanded using CD3 and CD28 antibody-coated beads. These cells were transformed using Herpesvirus saimiri and were also transduced with HIV-1 based lentiviral vectors.
Results  We report an efficient method for the ex vivo expansion of CD4⁺ T cells from Macaca nemestrina peripheral blood. With this protocol, primary CD4⁺ T cells can be expanded between 300- to 6000-fold during 24-day period and can be efficiently transduced with lentiviral vectors. Furthermore, these T cells can be transformed by Herpesvirus saimiri and maintained in culture for several months. The transformed T cell lines can be productively infected with the simian immunodeficiency virus (SIV) strain SIV_mac239.
Conclusions  We have established methods for the expansion and transformation of primary M. nemestrina CD4⁺ T cells and demonstrated the utility of these methods for several applications.     

Inferences about human demography based on multilocus analyses of noncoding sequences

Data from 10 unlinked autosomal noncoding regions, resequenced in 15 individuals from each of three populations, were used in a multilocus analysis to test models of human demography. Each of the 10 regions consisted of approximately 2500 bp. The multilocus analysis, based on summary statistics (average and variance of Tajima's D and Fu and Li's D*), was used to test a family of models with recent population expansion. The African sample (Hausa of Cameroon) is compatible with a constant population size model and a range of models with recent expansion. For this population sample, we estimated confidence sets that showed the limited range of parameter values compatible with growth. For an exponential growth rate as low as 1 x 10(-3)/generation, population growth is unlikely to have started prior to 50,000 years ago. For higher growth rates, the onset of growth must be more recent. On the basis of the average value of Tajima's D, our sample from an Italian population was found to be incompatible with a constant population size model or any simple expansion model. In the Chinese sample, the variance of Tajima's D was too large to be compatible with the constant population size model or any simple expansion model.     

An Axisymmetric Computational Model of Skin Expansion and Growth

Skin expansion is the principal technique used in plastic surgery to repair large cutaneous defects, typically after tumour removal, burn care, craniofacial surgery and post-mastectomy breast reconstruction. It allows a gain of new tissue by means of gradual expansion of a prosthesis, surgically implanted beneath the patient’s skin. Nevertheless, wide clinical use is not supported by a deep quantitative knowledge of the phenomena occurring during the expansion. A finite element model of the skin expansion was developed to evaluate the stresses and the strains of the skin due to the expander inflation and validated by proper in vitro experiments; furthermore, a growth model based on the mechanical stimulus was implemented to estimate the skin area gain. The developed computational approach, composed of the skin expansion model interaction and the growth law, proved its validity to investigate skin expansion phenomena: its use suggests a new predictive tool to optimize clinical procedures and the expander devices’ design.