Human renal adipose tissue from normal and tumor kidney: its influence on renal cell carcinoma.
Tumor cells can interact with neighboring adipose tissue. We evaluated components present in human adipose explants from normal (hRAN) and kidney cancer (hRAT) tissue, and we evaluated the effects of conditioned media (CMs) from hRAN and hRAT on proliferation, adhesion and migration of tumor and non-tumor human renal epithelial cell lines. In addition, we evaluated the expression of AdipoR1, ObR, CD44, vimentin, pERK and pPI3K on cell lines incubated with CMs. hRAN were obtained from healthy operated donors, and hRAT from patients who underwent a nephrectomy. hRAT showed increased levels of versican, leptin and ObR; and decreased levels of perilipin, adiponectin and AdipoR1, compared to hRAN. Cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRAT-CMs vs. hRAN- or control-CMs. Surprisingly, HK-2, 786-O and ACHN cells showed a significant decrease in cell migration after incubation with hRAN-CMs vs. control-CMs. No difference in proliferation of cell lines was found after 24 or 48 h of treatment with CMs. AdipoR1 in ACHN and Caki-1 cells decreased significantly after incubation with hRAT-CMs vs. hRAN-CMs and control-CMs. ObR and CD44 increased in tumor line cells, and vimentin increased in non-tumor cells, after incubation with hRAT-CMs vs. hRAN-CMs and control-CMs. We observed an increase in the expression of pERK and pPI3K in HK-2, 786-O and ACHN, incubated with hRAT-CMs. In conclusion, results showed that adipose microenvironment can regulate the behavior of tumor and non tumor human renal epithelial cells.


Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration.
To evaluate a new procedure for displacement of large, thick submacular hemorrhage in patients with age-related macular degeneration. Retrospective review of 11 eyes of 11 patients with age-related macular degeneration and thick submacular hemorrhage (defined as causing retinal elevation detectable on stereo fundus photographs) treated with vitrectomy, subretinal injection of tissue plasminogen activator (25 or 50 microg), and fluid-gas exchange with postoperative prone positioning. Outcome measures included displacement of hemorrhage from the fovea, best postoperative visual acuity, and final postoperative visual acuity. In the 11 affected eyes of 11 patients (seven men and four women; mean age, 76 years), preoperative visual acuity ranged from 20/200 to hand motions. With surgery, subretinal hemorrhage was displaced from the fovea in all 11 cases. Mean postoperative follow-up was 6.5 months (range, 1 to 15 months). Best postoperative visual acuity varied from 20/30 to 5/200, with improvement in nine (82%) cases and no change in two cases. Eight eyes (73%) measured 20/200 or better, with four of these eyes (36%) 20/80 or better. Final postoperative visual acuity ranged from 20/70 to light perception, with improvement in eight (73%) cases, no change in one case, and worsening in two cases. A statistically significant difference was found between preoperative and best postoperative visual acuity (P =.004) but not between preoperative and final visual acuity (P =.16). Hemorrhage recurred in three (27%) eyes, causing severe visual loss in one eye. This technique displaces submacular hemorrhage from the fovea and can improve vision in patients with age-related macular degeneration. However, recurrence of hemorrhage occurred in 27% of eyes and caused severe visual loss in one eye. A randomized, prospective clinical trial is necessary to determine the efficacy of this technique in comparison with other proposed treatments.


Breaking the Glass Ceiling: Increasing the Meaningful Involvement of Women Living With HIV/AIDS (MIWA) in the Design and Delivery of HIV/AIDS Services.
The meaningful involvement of women living with HIV/AIDS (MIWA) is a key feature of women-centred HIV care, yet little is known about transforming MIWA from principle to practice. Drawing on focus group data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), we explored HIV-positive women's meaningful involvement in the design and delivery of HIV/AIDS services in British Columbia, Canada. In this article, we highlight the benefits and tensions that emerge as women traverse multiple roles as service users and service providers within their care communities, and the impact this has on their access to care and overall health.


The impact of the AIDS pandemic on health services in Africa: evidence from demographic and health surveys.
We document the impact of the AIDS crisis on non-AIDS-related health services in 14 sub-Saharan African countries. Using multiple waves of Demographic and Health Surveys (DHS) for each country, we examine antenatal care, birth deliveries, and rates of immunization for children born between 1988 and 2005. We find deterioration in nearly all these dimensions of health care over this period. The most recent DHS survey for each country collected data on HIV prevalence, which allows us to examine the association between HIV burden and health care. We find that erosion of health services is the largest in regions that have developed the highest rates of HIV. Regions of countries that have light AIDS burdens have witnessed small or no declines in health care, using the measures noted above, while those regions shouldering the heaviest burdens have seen the largest erosion in non-HIV-related health services for pregnant women and children. Using semiparametric techniques, we can date the beginning of the divergence in the use of antenatal care and in children's immunizations between high- and low-HIV regions to the mid-1990s.


Normal growth and development of the trachea.
A quantitative study of the trachea has been made in 452 children with apparently normal tracheas ranging from 28 weeks' gestation to 14 years. In the neonatal period the trachea is funnel shaped with the upper end wider than the lower end. It becomes cylindrical with increasing age. The ratio of cartilage to muscle remains constant throughout childhood. The trachea appears to grow at a greater rate, in relation to crown-rump length, during the age of 1 month to 4 years than in utero or around puberty. Normal measurements for formalin-fixed tracheas related to crown-rump length are presented.


Vertebral artery fusiform aneurysm geometry in predicting rupture risk.
Cerebral aneurysms affect a significant portion of the adult population worldwide. Despite significant progress, the development of robust techniques to evaluate the risk of aneurysm rupture remains a critical challenge. We hypothesize that vertebral artery fusiform aneurysm (VAFA) morphology may be predictive of rupture risk and can serve as a deciding factor in clinical management. To investigate the VAFA morphology, we use a combination of image analysis and machine learning techniques to study a geometric feature set computed from a depository of 37 (12 ruptured and 25 un-ruptured) aneurysm images. Of the 571 unique features we compute, we distinguish five features for use by our machine learning classification algorithm by an analysis of statistical significance. These machine learning methods achieve state-of-the-art classification performance (81.43 ± 13.08%) for the VAFA morphology, and identify five features (cross-sectional area change of aneurysm, maximum diameter of nearby distal vessel, solidity of aneurysm, maximum curvature of nearby distal vessel, and ratio of curvature between aneurysm and its nearby proximal vessel) as effective predictors of VAFA rupture risk. These results suggest that the geometric features of VAFA morphology may serve as useful non-invasive indicators for the prediction of aneurysm rupture risk in surgical settings.


Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats.
Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic effects on cultured Vero cells. Real-time quantitative PCR analysis revealed that six of eight hit compounds significantly inhibited PRV replication. Among them, micafungin used clinically as an antifungal drug, displayed a prominent antiviral effect on PRV. Secondly, the antiviral effects of micafungin on PRV infected human cell lines (HEK293T and A549), and their transcriptome changes by PRV infection were investigated, compared to four different bat-derived cell lines (FBKT1 (Ryukyu flying fox), DEMKT1 (Leschenault's rousette), BKT1 (Greater horseshoe bat), YUBFKT1 (Eastern bent-wing bats)). In two human cell lines, unlike bat cells that induce an IFN-γ response pathway, an endoplasmic reticulum stress response pathway was commonly activated. Additionally, micafungin inhibits viral release rather than suppressing PRV genome replication in human cells, although it was disturbed in Vero cells. The target of micafungin's action may vary depending on the animal species, but it must be useful for human purposes as a first choice of medical care.


Propensity Score-Matched Comparison of Partial to Whole-Gland Cryotherapy for Intermediate-Risk Prostate Cancer: An Analysis of the Cryo On-Line Data Registry Data.
To compare the oncologic and functional outcomes of partial vs whole-gland cryotherapy for men with intermediate-risk prostate cancer. Men with intermediate-risk prostate cancer treated with primary prostate cryotherapy from 1993 to 2013 were selected from the Cryo On-Line Data Registry for a 1:1 matched comparison between those undergoing whole-gland and partial prostate cryotherapy (targeted ablation, unilateral/bilateral nerve-sparing ablations). A propensity score was developed based on age, prebiopsy serum prostate-specific antigen, biopsy Gleason score, clinical stage, prostate volume, neoadjuvant androgen deprivation status, year of surgery, and pretreatment potency. Outcomes were biochemical progression-free survival (BPFS) using the American Society for Therapeutic Radiation Oncology (ASTRO) and Phoenix criteria, 12-month continence (strictly pad free), and sexual function (potency sufficient for sexual intercourse). After propensity score matching, BPFS was compared using Kaplan-Meier analysis and functional outcomes using chi-square tests. In all, 897 men were identified (731 whole gland and 166 partial). Postmatching, 166 pairs of men were analyzed (mean follow-up 31 months). The 2/5-year BPFS rate was 87.2%/76.4% for whole-gland vs 80.7%/70.0% for partial ablation using Phoenix (p = 0.26) and 72.3%/69.6% for whole-gland vs 82.1%/75.0% for partial ablation using ASTRO criteria (p = 0.10). Of 164 pairs, the 12-month continence rate was similar, 94.1% vs 95.1% (p = 0.803). Of 139 pairs, the 12-month rate of effective intercourse was 29.5% for whole-gland and 46.8% for partial ablation (odds ratio 2.1, p = 0.003). The incidence of post-treatment urinary retention was 6.0% and 6.6% (p = 0.88) following whole-gland and partial ablation, respectively, and that of rectourethral fistula was 1.2% and 0% (p = 0.50). Partial ablation results in better post-treatment sexual function compared with whole-gland ablation in men with intermediate-risk prostate cancer. We did not observe a difference in early BPFS between the two groups.


Cumulative exposure to ionizing radiation from diagnostic and therapeutic cardiac imaging procedures: a population-based analysis.
The purpose of this study was to describe radiation exposure from cardiac imaging procedures over time in a general population. Cardiac imaging procedures frequently expose patients to ionizing radiation, but their contribution to effective doses of radiation in the general population is unknown. We used administrative claims to identify cardiac imaging procedures performed from 2005 to 2007 in 952,420 nonelderly insured adults in 5 U.S. health care markets. We estimated 3-year cumulative effective doses of radiation in millisieverts from these procedures We then calculated population-based annual rates of radiation exposure to effective doses < or =3 mSv/year (background level of radiation from natural sources), >3 to 20 mSv/year, or >20 mSv/year (upper annual limit for occupational exposure averaged over 5 years). A total of 90,121 (9.5%) individuals underwent at least 1 cardiac imaging procedure using radiation. Among patients who underwent > or =1 cardiac imaging procedures, the mean cumulative effective dose over 3 years was 23.1 mSv (range 1.5 to 543.7 mSv). Myocardial perfusion imaging accounted for 74% of the cumulative effective dose. Overall, 47.8% of cardiac imaging procedures were performed in physician offices; this proportion was higher for myocardial perfusion imaging (74.8%) and cardiac computed tomography studies (76.5%). The annual population-based rate of receiving an effective dose of >3 to 20 mSv/year was 89.0 per 1,000; and 3.3 per 1,000 for cumulative doses >20 mSv/year. Annual effective doses increased with age and were generally higher among men. Cardiac imaging procedures lead to substantial radiation exposure and effective doses for many patients in the U.S.


Elasto-morphology of P3HT:PCBM bulk heterojunction organic solar cells.
Predicting the mechanical properties of organic semiconductors is important when using these materials in flexible electronics applications. For instance, knowledge of the mechanical and thermal stability of thin film organic solar cells (OSCs) is critical for the roll-to-roll production of photovoltaic devices and their use under various operating conditions. Here, we examine the thermal and elasto-mechanical properties of the conjugated donor polymer poly-(3-hexylthiophene) (P3HT) and the interpenetrating mixtures of P3HT and phenyl-C61-butyric acid methyl (PCBM) ester bulk heterojunction (BHJ) active layers under the application of unidirectional tensile deformation using coarse-grained molecular dynamics (CGMD) simulations. The predictions are validated against previous experimental reports as well as with earlier modeling results derived using different intermolecular force fields. Our results reveal that PCBM molecules behave as anti-plasticizers when mixed with P3HT and tend to increase the tensile modulus and glass transition temperature, while decreasing the crack-onset strain relative to pure P3HT. The variations in the mechanical properties with the composition of the BHJ active layer suggest that, in the presence of small oligomers as additives in the BHJ, the P3HT:PCBM mixture resists the anti-plasticizing effect of PCBM molecules due to the low tensile modulus of the short polymer chains.


Pick a plan.
Lots of ideas on how to replace certain aspects of the Affordable Care Act have been tossed around in the seven or so years since more right-leaning lawmakers, economists and policy experts began to gripe about the healthcare reform law. Here are some of the suggestions that might come in handy as GOP leaders draft a plan to be presented in the next few weeks. The goal is to introduce a bill before Congress takes a spring break in April.


Parent-offspring conflict theory: an evolutionary framework for understanding conflict within human families.
Decades of research demonstrate that conflict shapes and permeates a broad range of family processes. In the current article, we argue that greater insight, integration of knowledge, and empirical achievement in the study of family conflict can be realized by utilizing a powerful theory from evolutionary biology that is barely known within psychology: parent-offspring conflict theory (POCT). In the current article, we articulate POCT for psychological scientists, extend its scope by connecting it to the broader framework of life history theory, and draw out its implications for understanding conflict within human families. We specifically apply POCT to 2 instances of early mother-offspring interaction (prenatal conflict and weaning conflict); discuss the effects of genetic relatedness on behavioral conflict between parents, children, and their siblings; review the emerging literature on parent-offspring conflict over the choice of mates and spouses; and examine parent-offspring conflict from the perspective of imprinted genes. This review demonstrates the utility of POCT, not only for explaining what is known about conflict within families but also for generating novel hypotheses, suggesting new lines of research, and moving us toward the "big picture" by integrating across biological and psychological domains of knowledge.


Effect of hormonal contraceptives on lipid profile and the risk indices for cardiovascular disease in a Ghanaian community.
Hormonal contraceptives (HCs) have been shown to alter lipid profile among various population groups with different patterns of dyslipidemia and cardiovascular (CV) risk. The study aimed at determining the lipid profile pattern and CV risk in a Ghanaian cohort. Purposive random sampling was done. Forty-seven and 19 cases were on oral contraceptives (OCs) and injectable contraceptives (ICs), respectively; five were on subdermal implant. Twenty-four non-users served as controls. Biodemographic and lipid profiles were determined. Total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and very-low-density lipid lipoprotein cholesterol (VLDLC), were determined. Castelli index I and II were calculated. The mean age difference between the HC and control groups was insignificant. However, diastolic blood pressure (BP) differences were significant (P=0.006). The body mass index (BMI) of the OC and IC groups were significantly different from the control group (P=0.003 and P=0.008, respectively). TC levels for the control and case groups were 3.35±0.62 mmol/L and 4.07±0.91 mmol/L, respectively (P=0.002). LDLC levels for the control and case groups were 1.74±0.57 mmol/L and 2.38±0.84 mmol/L, respectively (P=0.003). Castelli index I (TC/HDLC) and II (LDLC/HDLC) were significantly different between the control and OC groups (P=0.026 and P=0.014, respectively). Spearman's rho correlation showed significant influence of HC use on TG (P=0.026), TC (P=0.000), LDLC (P=0.004), and VLDLC (P=0.026) over time. HC use is associated with significant increases in BMI, diastolic BP, TC, LDLC, and Castelli index I and II. These changes carry a potential risk in the development of CV disease.


Are graduating residents sufficiently competent? Results of a national gap analysis survey of program directors and graduating residents in Japan.
To evaluate the self-assessed competency of graduating residents (GRs) in Japan upon completion of their residency and to identify the gap between their competency and the competency expected by their program directors (PDs). A list of 31 essential surgical procedures was compiled according to the consensus of surgical educators from around the country. A survey with this list was sent to all 909 GRs and their 611 PDs in 2016. The GRs rated their competency to perform these procedures and the PDs were asked to evaluate the expected competency of their GRs using the Zwisch Scale. The response rate was 56.3% for the GRs and 76.8% for the PDs. Fewer than half of the GRs who responded felt confident performing ten (32%) of the surgical procedures evaluated. For most procedures, the GRs' self-reported competency was lower than the expectation reported by their PDs. This gap was more than 10% for 13 of the procedures. More than half of the GRs in Japan lacked the confidence in their skill to perform one-third of the surgical procedures selected for evaluation in this study. These findings should be used to update the surgical education curriculum in Japan.


Environmentally Friendly Valorization of Solieria filiformis (Gigartinales, Rhodophyta) from IMTA Using a Biorefinery Concept.
Marine macroalgae (seaweed) are an excellent source of novel bioactive metabolites. The biorefinery concept applied to seaweed facilitates the extraction of many chemical constituents from the same biomass ensuring that the resource is used fully, generating few residues through a succession of extraction steps. In the present study, the biomass of the carragenophyte Solieria filiformis (Rhodophyta, Gigartinales) cultured in an integrated multi-trophic aquaculture (IMTA) system was evaluated to obtain valuable products by a biorefinery approach. Enzymatic-assisted extraction (EAE) and microwave-assisted extraction (MAE) were the eco-friendly technologies used to ensure an environmentally friendly valorization of the biomass. Three valuable products were successfully recovered: a water-soluble extract rich in proteins and sulfated polysaccharides suitable as a food supplement; a lipid fraction rich in polyunsaturated fatty acids (PUFAs) with potential to be used in the nutraceutical industry; and a pure ι-carrageenan with a powerful antiviral activity against Herpes simplex virus (EC50 = 6.3 µg mL-1) comparable to the commercial antiviral acyclovir (EC50 = 3.2⁻5.4 µg mL-1).


Cooking losses of thiamin in food and its nutritional significance.
To clarify the discrepancy between values of thiamin intake reported in national nutrition survey in Japan and judgment which was concluded by medical and biochemical examination in our field survey, thiamin of various daily foods were analyzed pre and post cooking in the various cooking methods, the following results were obtained. (1) The thiamin contents in cooked daily meals were 50-60 percent of the calculated values on an average. (2) The cooking losses of thiamin were particularly large in rice and green vegetables. (3) The loss of thiamin largest in boiling, followed by baking, parching and frying. (4) High temperature, pH, and chlorine on the public water accelerated thiamin losses. (5) The decrease of thiamin in cooked foods is caused by both of getting away of thiamin from foods and cleavage of thiamin of foods.


Omnidirectional Deformable Energy Textile for Human Joint Movement Compatible Energy Storage.
Omnidirectional deformability is an unavoidable basic requirement for wearable devices to accommodate human daily motion particularly at human joints. We demonstrate omnidirectionally bendable and stretchable textile-based electrochemical capacitor that retains high power performance under complex mechanical deformation. Judicious synergistic hybrid structure of woven elastic polymer yarns with carbon nanotubes and conductive polymers offers reliable electrical and electrochemical activity even under repeated cycles of severe complex deformation modes. The textile-based electrochemical capacitors exhibit omnidirectional stretchability with 93% of capacitance retention under repeated 50% omnidirectional stretching condition while demonstrating excellent specific capacitance (412 mF cm-2) and cycle stability (>2000 stretch). The wearable power source stably powers red LED under omnidirectional stretching that accompanies human elbow joint motion.


Kaiso Protein in the Regulation of Brain and Behavior.
Kaiso is a bimodal transcriptional repressor. It binds methylated CpG islands or the sequence- specific consensus in the DNA molecule with the Kaiso zinc-finger domain and recruits repressive protein complexes to these DNA fragments by the interaction of the BTB/POZ domain with the complex of NCoR1 corepressor and histone deacetylase, thereby performing transcription repression. Kaiso is involved in epigenetic regulation of transcription. Moreover, the complex Kaiso and catenin p120ctn modulates the transcription of the Wnt-target genes. The review discusses the role of Kaiso in the central nervous system. Kaiso molecules are abundant in the brain. MRI study did not show any alterations in the whole brain, hippocampus and striatum in Kaiso null mice. However, in Kaiso deficient mice the lateral ventricles were three-fold smaller compared with wild-type control. Kaiso deficiency increased the locomotor and exploratory activities as well as the prepuls inhibition of acoustic startle reflex without any adverse effect on anxiety-related behavior, learning and memory. At the same time, Kaiso deficiency produces a marked antidepressant-like effect. Thus, Kaiso involved in the mechanism of locomotion and depressive-like behavior. Kaiso inhibitors are expected to be promising atypical antidepressant drugs.


Addition of P3HT-grafted Silica nanoparticles improves bulk-heterojunction morphology in P3HT-PCBM blends.
We present molecular dynamics simulations of a ternary blend of P3HT, PCBM and P3HT-grafted silica nanoparticles (SiNP) for applications in polymer-based solar cells. Using coarse-grained models, we study the effect of SiNP on the spatial arrangement of PCBM in P3HT. Our results suggest that addition of SiNP not only alters the morphology of PCBM clusters but also improves the crystallinity of P3HT. We exploit the property of grafted SiNP to self-assemble into a variety of anisotropic structures and the tendency of PCBM to preferentially adhere to SiNP surface, due to favorable interactions, to achieve morphologies with desirable characteristics for the active layer, including domain size, crystallinity of P3HT, and elimination of isolated islands of PCBM. As the concentration of SiNP increases, the number of isolated PCBM molecules decreases, which in turn improves the crystallinity of P3HT domains. We also observe that by tuning the grafting parameters of SiNP, it is possible to achieve structures ranging from cylindrical to sheets to highly interconnected network of strings. The changes brought about by addition of SiNP shows a promising potential to improve the performance of these materials when used as active layers in organic photovoltaics.


Advances in the Management of Neuroblastoma.
Neuroblastoma is a malignant tumor of neuroblasts, immature nerve cells found in several areas of the body. It usually affects children under age of 5. As usual, the tumor has ability to grow rapidly and to expand vastly which ultimately leads to death. Mostly, management decisions can be drawn by the prediction of the stage of the disease as well as age at the time of its diagnosis. There are four main stages of neuroblastoma, and treatment is according to the low and high risk of the disease. Several cytotoxic agents along with other therapies (antibody therapy, gene therapy, and even immunological therapies, antiangiogenic therapy, etc.) are used. Immunotherapy also has an important treatment option used nowadays for neuroblastoma. The discovery of major neuroblastoma-predisposition gene anaplastic lymphoma kinase cause somatic transformation or gene strengthening in diagnosed neuroblastoma. Promising new antiangiogenic strategies have also been introduced for the treatment of neuroblastoma with multiple mylomas. To manage numerous myelomas and cancers, including neuroblastoma, bone marrow transplantation and peripheral blood stem cell transplantation may be used.


Multiple and Independent Phases of Transposable Element Amplification in the Genomes of Piciformes (Woodpeckers and Allies).
The small and conserved genomes of birds are likely a result of flight-related metabolic constraints. Recombination-driven deletions and minimal transposable element (TE) expansions have led to continually shrinking genomes during evolution of many lineages of volant birds. Despite constraints of genome size in birds, we identified multiple waves of amplification of TEs in Piciformes (woodpeckers, honeyguides, toucans, and barbets). Relative to other bird species' genomic TE abundance (< 10% of genome), we found ∼17-30% TE content in multiple clades within Piciformes. Several families of the retrotransposon superfamily chicken repeat 1 (CR1) expanded in at least three different waves of activity. The most recent CR1 expansions (∼4-7% of genome) preceded bursts of diversification in the woodpecker clade and in the American barbets + toucans clade. Additionally, we identified several thousand polymorphic CR1 insertions (hundreds per individual) in three closely related woodpecker species. Woodpecker CR1 insertion polymorphisms are maintained at lower frequencies than single nucleotide polymorphisms indicating that purifying selection is acting against additional CR1 copies and that these elements impose a fitness cost on their host. These findings provide evidence of large scale and ongoing TE activity in avian genomes despite continual constraint on genome size.


Effect of pruning on dendritic tree topology.
The variability in topological shapes of observed neuronal branching patterns can accurately be described by a simple model for random sequential growth. This finding is remarkable in view of the fact that the actual neuritic growth process can vary, and includes phases of regression and removal of branches which were not considered in the model. The aim of the present study is to investigate the influence of removal of branches on the topological structure of branching patterns as well as the effect of variable growth rules. A tree asymmetry index is used for the characterization of the topological structure of a tree. The mean value of the asymmetry index for a set of dendritic trees is sensitive to the mode of growth. The effect of removal of branches ("pruning") on the topological structure of dendritic trees has been studied for several random pruning schemes, namely (i) removal of uniform randomly chosen subtrees, (ii) removal of uniform randomly chosen terminal segments, (iii) uniform random pruning during the growth process itself, and (iv) non-uniform random pruning schemes. It was found that the effect of pruning depends on both the mode of pruning and the mode of growth. Uniform random (terminal) pruning had no effect on the mean and standard deviation of the asymmetry index of trees grown with an order-independent mode of branching. Changes in the mean of the asymmetry index could occur either with non-uniform random pruning or when trees are grown according to an order-dependent mode of branching. The effect of variable growth rules was studied for several specific schemes, and it could be shown that they all result in a substantial increase in the variation in the asymmetry index of the trees.


Trabecular bone histomorphometric measurements and contrast-to-noise ratio in CBCT.
The aim of this study was to evaluate how imaging parameters at clinical dental CBCT affect the accuracy in quantifying trabecular bone structures, contrast-to-noise ratio (CNR) and radiation dose. 15 radius samples were examined using CBCT (Accuitomo FPD; J. Morita Mfg., Kyoto, Japan). Nine imaging protocols were used, differing in current, voltage, rotation degree, voxel size, imaging area and rotation time. Radiation doses were measured using a kerma area product-meter. After segmentation, six bone structure parameters and CNRs were quantified. Micro-CT (μCT) images with an isotropic resolution of 20 μm were used as a gold standard. Structure parameters obtained by CBCT were strongly correlated to those by μCT, with correlation coefficients >0.90 for all studied parameters. Bone volume and trabecular thickness were not affected by changes in imaging parameters. Increased tube current from 5 to 8 mA, decreased isotropic voxel size from 125 to 80 μm and decreased rotation angle from 360° to 180° affected correlations for trabecular termini negatively. Decreasing rotation degree also weakened correlations for trabecular separation and trabecular number at 80 μm voxel size. Changes in the rotation degree and tube current affected CNR significantly. The radiation dose varied between 269 and 1153 mGy cm(2). Trabecular bone structure can be accurately quantified by clinical dental CBCT in vitro, and the obtained structure parameters are strongly related to those obtained by μCT. A fair CNR and strong correlations can be obtained with a low radiation dose, indicating the possibility for monitoring trabecular bone structure also in vivo.


[How to choose a radiological examination for a gastroenterological patient in 2016?]
During the two last decades, medical imaging showed considerable changes in technology and in knowledge of abdominal diseases. This review illustrates the consequences of this evolution on the prescription of a radiological examination for a gastroenterological patient, in 15 selected and illustrative topics.


The activity of glycogen synthase phosphatase limits hepatic glycogen deposition in the adrenalectomized starved rat.
Hepatocytes from adrenalectomized 48 h-starved rats responded to increasing glucose concentrations with a progressively more complete inactivation of phosphorylase. Yet no activation of glycogen synthase occurred, even in a K+-rich medium. Protein phosphatase activities in crude liver preparations were assayed with purified substrates. Adrenalectomy plus starvation decreased synthase phosphatase activity by about 90%, but hardly affected phosphorylase phosphatase activity. Synthase b present in liver extracts from adrenalectomized starved rats was rapidly and completely converted into the a form on addition of liver extract from a normal fed rat. Glycogen synthesis can be slowly re-induced by administration of either glucose or cortisol to the deficient rats. In these conditions there was a close correspondence between the initial recovery of synthase phosphatase activity and the amount of synthase a present in the liver. The latter parameter was strictly correlated with the measured rate of glycogen synthesis in vivo. The decreased activity of synthase phosphatase emerges thus as the single factor that limits hepatic glycogen deposition in the adrenalectomized starved rat.


Intervertebral Foramen Injection of Ozone Relieves Mechanical Allodynia and Enhances Analgesic Effect of Gabapentin in Animal Model of Neuropathic Pain.
In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain. Experimental trial in rats. Institute for Biomedical Sciences of Pain. By IVF injection, a volume of 50 µl containing 30 µg/mL ozone-oxygen mixture or 50 µl air was carried out on male Sprague-Dawley rats of naïve, inflammatory pain states produced by injections of either bee venom or complete Freud's adjuvant, and neuropathic pain state produced by spared nerve injury, respectively. The effects of IVF ozone on pain-related behaviors were evaluated for 2 weeks or one month. Then combined use of gabapentin (100 mg/1 kg body weight) with IVF ozone was evaluated in rats with neuropathic pain by intraperitoneal administration 5 days after the ozone treatment. Finally, the analgesic effects of another 4 drugs, AMD3100 (a CXCR4 antagonist), A-803467 (a selective Nav1.8 blocker), rapamycin (the mTOR inhibitor), and MGCD0103 (a selective histone deacetylase inhibitor) were evaluated for long term through IVF injection, respectively. (1) IVF injection of ozone at L4-5 was only effective in suppression of mechanical allodynia in rats with neuropathic pain but not with inflammatory pain; (2) the analgesic effects of IVF ozone lasted much longer (> 14 days) than other selective molecular target drugs (< 48 hours) inhibiting or antagonizing at Nav1.8 (A-803467), CXCR4 (AMD3100), mTOR (rapamycin), and histone deacetylase (MGCD0103); (3) combined use of systemic gabapentin and IVF ozone produced a synergistic analgesic effect in rats with neuropathic pain. Evaluation of the possible analgesic effects of the intraplantar injection of ozone was not performed. In the present study, we provided a line of evidence for the first time that IVF injection of ozone selectively relieved neuropathic pain but not inflammatory pain, and enhanced the analgesic effect of gabapentin. Chronic pain, neuropathic pain, inflammatory pain, ozone therapy, interventional therapy, gabapentin, spared nerve injury, bee venom, complete Freud's adjuvant.


[Problem of tuberculosis in Kirgizstan].
The socioeconomic factors have exerted a decisive impact on tuberculosis morbidity and mortality in the Kirghiz Republic. The National Tuberculosis Programme which defines the priorities of antituberculous measures adjusted to local conditions has been adopted up to 2000 to stabilize the endemia, by taking into account some recommendations.


Clinical outcomes following interval laparoscopic transabdominal cervico-isthmic cerclage placement: case series.
The purpose of this report is to describe outcomes following laparoscopic transabdominal cervico-isthmic cerclage placement in cases of cervical incompetence not amenable to a conventional transvaginal procedure. We reviewed records of the first 11 patients at an academic teaching hospital who underwent laparoscopic transabdominal cerclage placement as an interval procedure, using a technique we previously first described. For all patients, the clinical course, including surgical complications and outcome of all subsequent pregnancies, is briefly described. One case was complicated by a small bowel injury secondary to concomitant extensive enterolysis. Otherwise there were no complications. Mean estimated blood loss was <40 ml. To date, 10 patients have conceived a total of 12 pregnancies following the procedure. Two pregnancies resulted in spontaneous losses at 8 weeks gestation, two in deliveries by Caesarean section at 34.5 weeks, and eight in deliveries by elective Caesarean section at 38 weeks or more. Each delivery resulted in the birth of a healthy infant. In conclusion, patients who require a transabdominal cerclage may undergo a laparoscopic interval procedure and achieve outcomes similar to those following placement via laparotomy during pregnancy.


Prognostic value of myocardial ischemic electrocardiographic response in patients with normal stress echocardiographic study.
The prognostic value of ST-segment depression on exercise electrocardiogram (eECG) in the setting of a normal wall motion response in a stress echocardiographic study is not well defined. The aim of the study was to compare outcomes among patients with normal wall motion during stress echocardiography with and without ischemic exercise electrocardiographic changes. A total of 4,233 patients underwent stress echocardiography from 2007 to 2010. The primary outcomes were a composite of all-cause mortality and myocardial infarction. Coronary revascularization was a secondary outcome. A Cox regression model was used for the primary analysis. Ischemic exercise electrocardiographic changes were defined as ST-segment depression of at least 1 mm, on at least 3 consecutive beats, and in at least 2 contiguous leads. A normal stress echocardiogram was present in 2,975 patients; of them, 2,228 (74%) had a normal eECG and 747 (26%) had ischemic changes on eECG. Patients with and without ischemic changes during exercise electrocardiography were similar in age and gender. At 4-years follow-up, 36 patients (2.8%) with a normal eECG experienced a primary end point versus 12 patients (1.9%) in the group with an ischemic exercise electrocardiographic response (p = 0.56). The rate of coronary revascularization was similar between the groups (7.0% and 5.7%, respectively, p = 0.2). There were no differences in the primary outcomes of patients with and without exercise electrocardiographic changes and normal stress echocardiogram (hazard ratio 1.33, 95% confidence interval 0.69 to 2.58). In conclusion, a normal wall motion response even in the setting of an ischemic exercise electrocardiographic response portends a benign prognosis in patients undergoing stress echocardiography.


Bioavailability trials of beta-carotene from fresh and dehydrated drumstick leaves (Moringa oleifera) in a rat model.
Male albino rats (Charles Foster, n = 40) were fed a synthetic diet deficient in vitamin A for 4 weeks. Six rats died during the depletion period. Of the 34 surviving, 5 rats were continued on the vitamin A deficient diet for 4 more weeks and 24 were repleted with vitamin A (4000 IU/kg diet) in the form of vitamin A acetate (group A, n = 8), fresh drumstick leaves (group B, n = 8) or dehydrated drumstick leaves (group C, n = 8) for 4 weeks. The remaining 10 rats were continued on the vitamin A adequate diet for 4 (n = 5) and 8 weeks, respectively (n = 5). A marked reduction in food intake, body weight, accompanied by clinical signs of vitamin A deficiency and a decline in serum vitamin A (29.2 to 19.1 microg/dL) and liver vitamin A (3.7 to 2.0 microg/dL) were seen at the end of 4 weeks of feeding a vitamin A deficient diet. On repletion significant improvements in clinical signs, food intake and body weights were noted in the three groups compared to the baseline (n = 5) and at the end of 4 weeks of depletion. The gain in body weight was highest for the group repleted with dehydrated drumstick leaves. Among the repleted groups, the serum vitamin A was highest for group A (34.7 microg/dL) given synthetic vitamin A, compared to group B (25.8 microg/dL) and group C (28.2 microg/dL) given drumstick leaves. All these were significantly higher than the serum vitamin A values seen at the end of 4 weeks of depletion (19.1 microg/dL). A significant improvement was also observed in the liver retinol levels on repletion for 4 weeks in the three groups, compared to the vitamin A depleted rats. These results imply that beta-carotene from drumstick leaves was effective in overcoming vitamin A deficiency although serum vitamin A levels remained somewhat lower compared to the group repleted with vitamin A acetate. In terms of growth parameters, the fresh and dehydrated drumstick leaves were better than the synthetic vitamin A. It is therefore concluded that in the developing countries like India, sources of vitamin A such as drumstick leaves are valuable in overcoming the problem of vitamin A deficiency.


Sutures and suturing--current concepts.
Currently available suture materials can be classified as nonabsorbable and absorbable types. Too often the surgeon selects the material on the basis of handling properties alone. The "perfect" suture material does not exist. Physical properties such as tensile strength, reactivity, size, and absorbability must be considered in light of current knowledge of wound healing. Placement of sutures is obviously as important as selection of material.


Thermoelectric Transport in Nanocomposites.
Thermoelectric materials which can convert energies directly between heat and electricity are used for solid state cooling and power generation. There is a big challenge to improve the efficiency of energy conversion which can be characterized by the figure of merit (ZT). In the past two decades, the introduction of nanostructures into bulk materials was believed to possibly enhance ZT. Nanocomposites is one kind of nanostructured material system which includes nanoconstituents in a matrix material or is a mixture of different nanoconstituents. Recently, nanocomposites have been theoretically proposed and experimentally synthesized to be high efficiency thermoelectric materials by reducing the lattice thermal conductivity due to phonon-interface scattering and enhancing the electronic performance due to manipulation of electron scattering and band structures. In this review, we summarize the latest progress in both theoretical and experimental works in the field of nanocomposite thermoelectric materials. In particular, we present various models of both phonon transport and electron transport in various nanocomposites established in the last few years. The phonon-interface scattering, low-energy electrical carrier filtering effect, and miniband formation, etc., in nanocomposites are discussed.


Predicting metal-binding sites from protein sequence.
Prediction of binding sites from sequence can significantly help toward determining the function of uncharacterized proteins on a genomic scale. The task is highly challenging due to the enormous amount of alternative candidate configurations. Previous research has only considered this prediction problem starting from 3D information. When starting from sequence alone, only methods that predict the bonding state of selected residues are available. The sole exception consists of pattern-based approaches, which rely on very specific motifs and cannot be applied to discover truly novel sites. We develop new algorithmic ideas based on structured-output learning for determining transition-metal-binding sites coordinated by cysteines and histidines. The inference step (retrieving the best scoring output) is intractable for general output types (i.e., general graphs). However, under the assumption that no residue can coordinate more than one metal ion, we prove that metal binding has the algebraic structure of a matroid, allowing us to employ a very efficient greedy algorithm. We test our predictor in a highly stringent setting where the training set consists of protein chains belonging to SCOP folds different from the ones used for accuracy estimation. In this setting, our predictor achieves 56 percent precision and 60 percent recall in the identification of ligand-ion bonds.


Early onset first-episode psychosis during treatment with thalidomide for refractory ulcerative colitis: a case report.
Inflammatory bowel disease and schizophrenia spectrum disorders are complex and multifactorial conditions characterized by great variability of age at onset, clinical presentation, and longitudinal course. Several lines of evidence suggested different connections among immunological dysregulation, gastrointestinal inflammation, and psychosis, but to date many controversial issues still exist in this field. We present the case of a 14-year-old Caucasian boy with refractory ulcerative colitis, admitted to the Child Neuropsychiatry Unit of the Polyclinic Hospital of Bari in the course of his first-episode psychosis. He showed an acute onset of psychotic symptomatology during treatment with thalidomide, an immunomodulatory drug used in the experimental therapy of refractory inflammatory bowel disease. Thalidomide was discontinued and orally administered mesalazine was restarted. In addition, treatment with antipsychotics and mood stabilizers was introduced with gradual improvement of psychotic symptoms. According to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, a diagnosis of partial remission of a first episode of schizoaffective disorder was formulated after a 6-month follow-up. Throughout this period, both psychopharmacological and mesalazine-based gastrointestinal treatments were maintained with partial remission of psychiatric and gastrointestinal symptoms. We propose that refractory ulcerative colitis and psychosis might represent different manifestations of a common pathological pathway. However, it is also conceivable that thalidomide may have played a role in promoting the manifestation of psychotic symptoms in an individual with a specific vulnerability to schizoaffective disorders. Further investigations are needed to improve our knowledge regarding the complexity of brain-gut interactions, thus improving the management of co-existing inflammatory bowel and schizophrenia spectrum disorders.


The evaluation of new classification of Allergic Rhinitis in patients referred to a clinic in the city of Shiraz.
Allergic rhinitis is the most common cause of allergic diseases. The recent guidelines of Allergic Rhinitis and its Impact on Asthma (ARIA) group, classified it to intermittent (less than 4 days per week and for less than 4 weeks) and persistent (more than 4 days per week or lasting more than 4 weeks regardless of the number of days per week). The present study evaluates the patients with ARIA classification. The patients referred to Motahhari Clinic (Shiraz, Iran) were evaluated. Age, sex, seasonal or perennial, intermittent or persistent type, duration, sneezer or blocker, diurnal change and presence of allergic conjunctivitis were recorded. The patients who had one or more symptoms of; impairment of sleep, daily activity or work in school or troublesome symptoms had moderate to severe disease and those who did not have these problems have mild disease. The information of 96 patients (46 male and 50 female) were analysed (mean age+/-SD: 24.45+/-10.37 years). The mean duration of disease was 4.26+/-4.12 years, was more in female (P<0.05). Seasonal allergic rhinitis was present in 49 (52%) patients; 30 male, 19 female (P=0.007), perennial in 15 (16%), 1 male, 14 female and mixed type in 29 (30%); 11 male, 18 female. Mild intermittent rhinitis was diagnosed in only 2 (2%) patients, 1 male and 1 female, mild persistent rhinitis in 23 (24%); male 11, female 12; moderate/severe intermittent rhinitis in 4 (4%); 3 male, 1 female; and moderate/severe persistent rhinitis in 56 (58%); 22 male, 34 female (P<0.05). Fifty-seven percent were more sneezer and 36% were more blocker type, sneezers suffered more in days and others more at nights. Others were both sneezer and blocker. Sixty percent had allergic conjunctivitis too, 76% of them were moderate/severe persistent, and 85% were in seasonal or mixed groups. Eleven patients (12%), in persistent group, had history of asthma. Family history of allergic rhinitis and asthma was found in 53% and in 25% of patients, respectively. According to new guidelines for classification of allergic rhinitis, most of the patients are moderate to severe types. The classification of allergic rhinitis to seasonal and perennial disease is not proportional to intermittent and persistent types of classification. .


Initial Characterization of Osteoblast Differentiation and Loss of RUNX2 Stability in the Newly Established SK11 Human Embryonic Stem Cell-Derived Cell Line.
We describe a novel model for investigation of genetically normal human osteoblasts in culture. SK11 is a clonal progenitor cell line derived from human embryonic stem cells. Initially selected based on the expression of chondrogenic markers when differentiated in micromass culture, SK11 cells display typical mRNA expression patterns of bone phenotypic genes under osteogenic conditions. These include osterix, α1(I) collagen, alkaline phosphatase, osteonectin, osteopontin, and osteocalcin. Similar to well-characterized murine osteoblast cultures, the osteoblast master regulator RUNX2 was present during the first few days after plating, but the protein disappeared during the first week of culture. Loss of RUNX2 expression is considered an important regulatory feature for osteoblast maturation. Indeed, following ∼2 weeks of differentiation, SK11 cultures exhibited robust calcium deposition, evidenced by alizarin red staining. We also introduced a lentiviral vector encoding doxycycline (dox)-inducible FLAG-tagged RUNX2 into SK11 cells. Dox-mediated enhancement of RUNX2 expression resulted in accelerated mineralization, which was further increased by co-treatment with BMP-2. Like the endogenous RUNX2, expression of the virally coded FLAG-RUNX2 was lost during the first week of culture despite persistent dox treatment. By following RUNX2 decay after dox withdrawal from day-5 versus day-3 cultures, we demonstrated a developmentally regulated decrease in RUNX2 stability. Availability of culture models for molecular investigation of genetically normal human osteoblasts is important because differences between murine and human osteoblasts, demonstrated here by the regulation of matrix Gla Protein, may have significant biomedical implications.


Impact of interprofessional education on noninvasive ventilation in a tertiary neonatal intensive care unit.
To evaluate the impact and effectiveness of an experiential interprofessional education workshop on noninvasive ventilation (NIV) in the setting of a neonatal intensive care unit. In the present cross-sectional study, a full-day workshop, consisting of didactic and hands-on components, was developed to assess knowledge and perceptions, and to disseminate the latest evidence and practical aspects of NIV use. All health care professionals (HCPs) were asked to participate. Pre- and post-participation questionnaires and knowledge tests were used to assess the effectiveness of knowledge transfer, and to seek participants' reflections on the utility of the workshop. Among 214 participants, 206 (96%) and 195 (91%) completed the pre- and post-participation questionnaires, respectively. The majority agreed (14%) or strongly agreed (75%) that NIV education was important for their role. Participants scored their perceived comfort with NIV following the workshop highly (median 5 [interquartile range (IQR) 1]) on a five-point Likert scale and 96% would recommend it to a colleague. Median knowledge scores on NIV, assessed as percent correct responses, increased from 74% (IQR 16) to 86% (IQR 11) (P<0.05). A focused, context-specific workshop helped improve understanding and comfort among HCPs while reducing misconceptions about NIV. Further research to assess optimal delivery of NIV education and impact on patient outcomes is required.


High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial.
Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. NCT00128180.


Eccrine syringofibroadenoma: a report of 2 cases.
Eccrine syringofibroadenoma is a rare benign tumor of the skin arising from the acrosyringeal portion of the eccrine duct. The tumor was first described by Mascaro in 1963, and since then only 8 case reports in 6 publications have been documented. This lesion is likely to be misdiagnosed both clinically and histologically due both to its rarity and its similarity to other more aggressive skin tumors. This report of 2 cases is presented to highlight the salient pathologic and clinical features of the tumor and to describe the long term follow up of 2 patients in whom the lesions have been electively reviewed rather than excised.


[Parasitism in Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae) in Citrus orchards in Montenegro, RS, Brazil].
Phyllocnistis citrella Stainton, the citrus-leafminer, is an important pest of citrus worldwide. Knowledge of natural parasitism levels is fundamental to the establishment of tactics of management and control of this species. This work aimed to evaluate the parasitism in two citrus orchards, one of 'Montenegrina' (Citrus deliciosa Ten.) and the other of 'Murcott' (C. sinensis (L.) Osbeck x C. reticulata Blanco), located in Montenegro, RS. In fortnightly samplings, from July/2001 to June/2003, all leaves containing P. citrella pupae from randomly selected plants were collected and maintained individually until emergence of the parasitoids or the citrus-leafminer. Parasitism was calculated considering the number of emerged parasitoids relative to the total number of emerged individuals. Correlation and linear regression tests were done to evaluate the relationship and the influence of biotic and abiotic factors upon the parasitism index. In both orchards the greatest parasitism percentage was registered on autumn in both years. The total percentage was 36.2% in 'Murcott' and 26.4% in 'Montenegrina' in the first year, and 30.2% and 37.6%, respectively, in the second year. In 'Murcott', this index did not differed between the years (chi2 = 2.06; df = 1; P > 0.05), in 'Montenegrina' the parasitism was significantly higher in the second year (chi2 = 7.36; df = 1; P < 0.05). The correlation and linear regression tests indicated a strong influence, in the parasitism index, of the host populational density registered in the previous 45 and 135 days.


Fungal dermatitis, glossitis and disseminated visceral mycosis caused by different Metarhizium granulomatis genotypes in veiled chameleons (Chamaeleo calyptratus) and first isolation in healthy lizards.
Metarhizium (M.) granulomatis (formerly Chamaeleomyces granulomatis) invariably causes fatal fungal glossitis and systemic mycosis in veiled chameleons (Chamaeleo calyptratus). Isolation of M. granulomatis in other lizards thus far has not been described. The aim of this study therefore was to obtain information on the presence of M. granulomatis in reptiles kept as pets, and to examine whether there was an association between specific genotypes and clinical/pathological outcomes. Besides 18S ribosomal (r) DNA (SSU) and internal transcribed spacer1-5.8S (ITS1-5.8S) rDNA, a fragment of the large subunit of the 28S rDNA (LSU), including the domains 1 (D1) and D2, were sequenced for identification of the fungus and phylogenetic analysis. Metarhizium granulomatis was isolated from 23 veiled chameleons, two panther chameleons (Furcifer pardalis) and one central bearded dragon (Pogona vitticeps). Only the veiled chameleons revealed corresponding pathological findings in the form of glossal hemorrhage, granulomatous glossitis, pharyngitis, dermatitis and/or visceral mycosis. The infection site correlated to survival times of infected veiled chameleons. Combined long-term treatment with terbinafine and nystatin based on susceptibility testing may be helpful for prevention of disease and visceral spreading of the fungus, but elimination of the fungal pathogen or successful treatment of diseased veiled chameleons have not been achieved yet. Sequencing of the ribosomal genes yielded five different genotypes, with genotype A being strongly correlated with dermatitis, and remaining genotypes with pharyngitis and glossitis. However, disseminated visceral mycosis developed irrespective of the genotypes.


Breast metastasis as the initial presentation of malignant pleural mesothelioma.
Metastatic involvement of the breast is far less common than primary breast carcinoma, comprising 0.5%-6.6% of all breast malignancies. Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with higher incidence among men, particularly smokers, strongly associated with asbestos exposure. The epithelioid type of MPM can represent a diagnostic pitfall in this setting, as it shows similar histologic features to primary breast carcinoma as well as other metastatic epithelioid malignancies. We report a rare case of breast metastasis of malignant pleural mesothelioma in a 61-year-old female.


Metal-on-metal hip resurfacing: a skeptic's view.
Contemporary metal-on-metal hip resurfacing is the third attempt by its proponents to eliminate a diaphyseal femoral component. I have multiple objections with the resurfacing concept and believe even the premises for the use of resurfacing invalid. There is a high rate of success with circumferential bead or mesh-coated uncemented stemmed femoral components at 10 to 20 years and there have been no long-term adverse consequences of femoral stress shielding with a diaphyseal component. More acetabular bone may be removed with resurfacing, negating its "conservative" premise. One computer simulation suggested the range of hip motion might be considerably less with resurfacing compared with conventional hip arthroplasty. There are a very limited number of patients for whom hip resurfacing is truly indicated, and the femoral head may be unsuitable for resurfacing in 40% of selected patients. Resurfacing is technically more difficult than conventional hip arthroplasty. Early complications and revision for femoral neck fractures are more likely with resurfacing. Blood and urine metal ion levels, capsular lymphocytic aggregation, and hypersensitivity are concerns with metal-on-metal articulation. Metal-on-metal hip resurfacing should only be used by a limited number of hip surgeons. The risks and complications of metal-on-metal hip resurfacing outweigh any possible advantages.


Comparative Chromosome Map and Heterochromatin Features of the Gray Whale Karyotype (Cetacea).
Cetacean karyotypes possess exceptionally stable diploid numbers and highly conserved chromosomes. To date, only toothed whales (Odontoceti) have been analyzed by comparative chromosome painting. Here, we studied the karyotype of a representative of baleen whales, the gray whale (Eschrichtius robustus, Mysticeti), by Zoo-FISH with dromedary camel and human chromosome-specific probes. We confirmed a high degree of karyotype conservation and found an identical order of syntenic segments in both branches of cetaceans. Yet, whale chromosomes harbor variable heterochromatic regions constituting up to a third of the genome due to the presence of several types of repeats. To investigate the cause of this variability, several classes of repeated DNA sequences were mapped onto chromosomes of whale species from both Mysticeti and Odontoceti. We uncovered extensive intrapopulation variability in the size of heterochromatic blocks present in homologous chromosomes among 3 individuals of the gray whale by 2-step differential chromosome staining. We show that some of the heteromorphisms observed in the gray whale karyotype are due to distinct amplification of a complex of common cetacean repeat and heavy satellite repeat on homologous autosomes. Furthermore, we demonstrate localization of the telomeric repeat in the heterochromatin of both gray and pilot whale (Globicephala melas, Odontoceti). Heterochromatic blocks in the pilot whale represent a composite of telomeric and common repeats, while heavy satellite repeat is lacking in the toothed whale consistent with previous studies.


Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis.
The presence of five structural proteins of measles virus in brain material obtained at autopsy from four patients with subacute sclerosing panencephalitis (SSPE) was examined by immunofluorescence employing monoclonal antibodies. In addition, the humoral immune response against measles virus antigens in serum and cerebrospinal fluid was analysed by immunoprecipitation in combination with gel electrophoresis, revealing a reduced response mainly to the matrix (M) protein. In none of the brain material were all five structural proteins simultaneously detected. Nucleocapsid protein and phosphoprotein were found in every diseased brain area, whereas haemagglutinin (H) protein was detected in two, fusion (F) protein in three and M protein only in one SSPE case. In two cases, variations in the occurrence of H and F proteins could be observed between regions displaying different degrees of neuropathological changes. No correlation was observed between the humoral immune response and the immunohistological findings. These data support the hypothesis of a restricted synthesis of measles virus proteins, in particular the envelope and M proteins, in SSPE.


Convergent syntheses of oral THF 1beta-methylcarbapenems.
Convergent syntheses of oral THF 1beta-methylcarbapenems 4 (OCA-983) and 5 starting from M2-phosphate 1 were developed. Reaction of the M2-phosphate 1 with THF thiols containing a requisite prodrug side chain, 9 and 10, gave the desired oral THF 1beta-methylcarbapenems 4 and 5, respectively, in 46% and 42% overall yields.


Pseudoasymmetry: a final twist?
The original definition of "pseudoasymmetry" conveyed the apparent paradox that a tetrahedral center with four different groups did not result in overall chirality. However, there are problems in applying the concept to cyclic systems that do not contain chirotopic centers. Pseudoasymmetry appears most appropriate to acyclic systems with chirotopic carbon centers, e.g. the meso trihydroxyglutaric acids. Analogous cyclic cases, e.g. the isomeric 1,4-dimethylcyclobutanes, are best treated as diastereomers, and may indeed be described by an interesting extension of the like-unlike notation. Remarkably, in several tri- and tetramethylcyclohexanes, CIP descriptors cannot be applied even to chirotopic centers, which can only be described by the modified l-u notation.


The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells.
Pyocyanin, produced by Pseudomonas aeruginosa, has many deleterious effects on human cells that relate to its ability to generate reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Human cells possess several mechanisms to protect themselves from ROS, including manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and catalase. Given the link between pyocyanin-mediated epithelial cell injury and oxidative stress, we assessed pyocyanin's effect on MnSOD, CuZnSOD, and catalase levels in the A549 human alveolar epithelial cell line and in normal human bronchial epithelial cells. In both cell types, CuZnSOD and MnSOD were unaltered, but over 24 h pyocyanin significantly decreased cellular catalase activity and protein content. Pyocyanin also decreased catalase mRNA. Overexpression of MnSOD in A549 cells prevented pyocyanin-mediated loss of catalase protein, but catalase activity still declined. Furthermore, pyocyanin decreased catalase activity, but not protein, in A549 cells overexpressing human catalase. These data suggest a direct effect of pyocyanin on catalase activity. Addition of pyocyanin to catalase in a cell-free system also decreased catalase activity. Mammalian catalase binds four NADPH molecules, helping maintain enzyme activity. Spin-trapping data suggest that pyocyanin directly oxidizes this NADPH, producing superoxide. We conclude that pyocyanin may decrease cellular catalase activity via both transcriptional regulation and direct inactivation of the enzyme. Decreased cellular catalase activity and failure to augment MnSOD could contribute to pyocyanin-dependent cytotoxicity.


Sarcoidosis: a primary care review.
Sarcoidosis is a multisystemic disorder of unknown etiology that most commonly affects adults between 20 and 40 years of age. Patients with sarcoidosis frequently present with bilateral hilar lymphadenopathy and pulmonary infiltration, and often with ocular and skin lesions. The diagnosis is established when clinical and radiographic findings are supported by histologic evidence of non-caseating epithelioid cell granulomas found on tissue biopsy. Diagnosis of sarcoidosis requires exclusion of other causes of granuloma formation. Sarcoidosis is also characterized by distinctive laboratory abnormalities, including hyperglobulinemia, an elevated serum angiotensin converting enzyme level, evidence of depressed cellular immunity manifested by cutaneous anergy and, occasionally, hypercalcemia and hypercalciuria. Glucocorticoids remain the mainstay of therapy when treatment is required, although other anti-inflammatory agents are being used increasingly often.


Multiple geographic origins of commensalism and complex dispersal history of Black Rats.
The Black Rat (Rattus rattus) spread out of Asia to become one of the world's worst agricultural and urban pests, and a reservoir or vector of numerous zoonotic diseases, including the devastating plague. Despite the global scale and inestimable cost of their impacts on both human livelihoods and natural ecosystems, little is known of the global genetic diversity of Black Rats, the timing and directions of their historical dispersals, and the risks associated with contemporary movements. We surveyed mitochondrial DNA of Black Rats collected across their global range as a first step towards obtaining an historical genetic perspective on this socioeconomically important group of rodents. We found a strong phylogeographic pattern with well-differentiated lineages of Black Rats native to South Asia, the Himalayan region, southern Indochina, and northern Indochina to East Asia, and a diversification that probably commenced in the early Middle Pleistocene. We also identified two other currently recognised species of Rattus as potential derivatives of a paraphyletic R. rattus. Three of the four phylogenetic lineage units within R. rattus show clear genetic signatures of major population expansion in prehistoric times, and the distribution of particular haplogroups mirrors archaeologically and historically documented patterns of human dispersal and trade. Commensalism clearly arose multiple times in R. rattus and in widely separated geographic regions, and this may account for apparent regionalism in their associated pathogens. Our findings represent an important step towards deeper understanding the complex and influential relationship that has developed between Black Rats and humans, and invite a thorough re-examination of host-pathogen associations among Black Rats.


INSULIN ACTION IN ALLOXAN DIABETES MODIFIED BY ACTINOMYCIN D.
Insulin corrects the disturbances in lipid and carbohydrate metabolism in rats made diabetic with alloxan. However, the concomitant administration of actinomycin D with insulin prevents the repair of enzymatic defects in the syntheses of total fatty acids by adipose tissue, of monounsaturated fatty acids by liver microsomes, and of hepatic glycogen. The hypoglycemic action of insulin in diabetes is not modified by actinomycin injections. These findings indicate that a fundamental mechanism of action of insulin is the induction of enzyme synthesis through stimulating the renewal of cellular RNA.


An endogenously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct ligands for TCR with different kinetic stability.
Immunization with self peptides often elicits activation of CD4+ T cells in vivo. Although such peptides have been suggested to be derived from minor self determinants or self antigens sequestered from the immune system, we found that immunization with Ealpha peptide (Ealpha52-68), a major self determinant bound to I-Ab molecules, elicits an immune response in Ealpha-transgenic C57BL/6 (Ealpha-B6) mice where Ealpha52-68 is endogenously processed and presented by I-Ab molecules in the thymus and periphery. To better understand this response, a panel of T cell hybridomas raised against exogenous Ealpha52-68 were analyzed for their reactivity to spleen cells from Ealpha-B6 mice. Some hybridomas were stimulated with Ealpha-B6 spleen cells in the absence of exogenous Ealpha52-68, whereas others were not stimulated with them. The Ealpha52-68/I-Ab complex recognized by the TCR that is expressed on the hybridoma with reactivity to Ealpha-B6 spleen cells was found to be quite stable, whereas the complex recognized by the TCR on the hybridoma specific for the exogenous Ealpha52-68 lost the stimulation activity by incubation the complex at 37 degrees C for 10 min. Stimulation experiments using extensively substituted Ealpha analogue peptides suggested that amino acid residues at positions 57, 58, 60 and 62 of Ealpha52-68 are involved in the interaction with TCR recognizing the Ealpha52-68/I-Ab complex expressed on Ealpha-B6 spleen cells. While amino acid substitutions at positions 60 and 62 also affected the recognition of TCR specific for exogenous Ealpha52-68, all or many amino acid substitutions were allowed at position 58 or 57, respectively, without impairing the TCR recognition. Taken together, these results suggest that endogenously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct TCR ligands with different kinetic stability and probably with different configuration.


Mitochondrial oxidative stress plays a critical role in the cardiotoxicity of sunitinib: Running title: Sunitinib and oxidative stress in hearts.
Sunitinib is cardiotoxic, but the mechanisms are not entirely clear. We aimed to enlarge our knowledge about the role of mitochondria in cardiac toxicity of sunitinib in vitro and in vivo. For this reason, we studied the toxicity of sunitinib on cardiac H9c2 cells exposed for 24 h, permeabilized rat cardiac fibers exposed for 15 min and in mice treated orally with sunitinib for 2 weeks (7.5 mg/kg/day). In H9c2 cells exposed for 24 h, sunitinib was more cytotoxic under galactose (favoring mitochondrial metabolism) compared to glucose conditions (favoring glycolysis). Sunitinib dissipated the mitochondrial membrane potential starting at 10 μM under glucose and at 5 μM under galactose conditions. Sunitinib reduced activities of mitochondrial enzyme complexes of the electron transport chain (ETC), increased mitochondrial ROS accumulation and decreased the cellular GSH pool. Electron microscopy revealed swollen mitochondria with loss of cristae. Accordingly, sunitinib caused caspase 3 activation and DNA fragmentation in H9c2 cells. Co-exposure with mito-TEMPO (mitochondrial-specific ROS scavenger) for 24 h prevented ATP and GSH depletion, as well as the increases in H2O2 and caspase 3/7 activity observed with sunitinib. In mice, treatment with sunitinib for two weeks increased plasma concentrations of troponin I and creatine kinase MB, indicating cardiomyocyte damage. The activity of enzyme complexes of the ETCwas decreased, mitochondrial ROS were increased and cleavage of caspase 3 was increased, suggesting cardiomyocyte apoptosis. In conclusion, mitochondrial damage with ROS accumulation appears to be an important mechanism of cardiotoxicity associated with sunitinib, eventually leading to apoptotic cell death.


Innovative behaviour: the effect of structural and psychological empowerment on nurses.
This paper is a report of a study to investigate the relationship between structural empowerment/psychological empowerment and innovative behaviour. Innovative behaviour is essential for nurses in today's dynamic healthcare systems. Empowerment has become an increasingly important factor in predicting innovative behaviour. Structural empowerment refers to power based on the employee's position in the organization, while psychological empowerment consists of the fundamental personal convictions that employees have about their role in the organization. A cross-sectional correlational survey was conducted in The Netherlands in 2007 with 519 Registered Nurses. The instruments used were the Conditions of Work Effectiveness Questionnaire II, the Psychological Empowerment Instrument and the Questionnaire Innovative Behaviour. Four hypotheses were tested using descriptive statistics, bivariate and multiple regression and one-way analysis of variance. Structural and psychological empowerment were statistically significant predictors of innovative behaviour. Informal power and impact were the most relevant determinants of innovative behaviour, the latter the strongest. Psychological empowerment functioned as a mediator between structural empowerment and innovative behaviour. The expected moderating effect of structural empowerment was not proven. Organizations need to create the right conditions to be able to strengthen nurses' empowerment. Networking is an important skill which should be incorporated in the nursing education. Future research should take into consideration nursing culture and personality traits as determining factors. Replication of this study in another setting and a study examining causality are recommended so that additional empirical evidence may be obtained.


Mind-mindedness in parents of looked-after children.
The studies reported here aimed to test the proposal that mind-mindedness is a quality of personal relationships by assessing mind-mindedness in caregiver-child dyads in which the relationship has not spanned the child's life or in which the relationship has been judged dysfunctional. Studies 1 and 2 investigated differences in mind-mindedness between adoptive parents (ns = 89, 36) and biological parents from the general population (ns = 54, 114). Both studies found lower mind-mindedness in adoptive compared with biological parents. The results of Study 2 showed that this group difference was independent of parental mental health and could not fully be explained in terms of children's behavioral difficulties. Study 3 investigated differences in mind-mindedness in foster carers (n = 122), parents whose children had been the subject of a child protection plan (n = 172), and a community sample of biological parents (n = 128). The level of mind-mindedness in foster carers and parents who were involved with child protection services was identical and lower than that in the community sample; children's behavioral difficulties could not account for the difference between the 2 groups of biological parents. In all 3 studies, nonbiological carers' tendency to describe their children with reference to preadoption or placement experiences was negatively related to mind-mindedness. These findings are in line with mind-mindedness being a relational construct. (PsycINFO Database Record


Effects of sling exercise therapy on trunk muscle activation and balance in chronic hemiplegic patients.
Weakening of trunk muscles in stroke patients hinders functional ability, safety and balance. To confirm whether strengthening trunk muscles could facilitate rehabilitation of stroke patients, we investigated the effectiveness of sling exercise therapy (SET) using closed kinetic chain exercises to activate trunk muscles and improve balance in stroke patients. [Subjects and Methods] Twenty stroke patients with chronic hemiplegia were equally divided into 2 groups, a SET group and a control group that performed regular exercises on a mat with the assistance of a table. Patients in both groups exercised for 30 min, three times per week for 4 weeks. Trunk muscle activity was measured using surface electromyography, whereas balance was measured using the Berg Balance Scale, Frailty and Injuries Cooperative Studies of Intervention Technique, Timed Up & Go test, and BioRescue before and after the 4-week experimental period. [Results] Trunk muscle activity and balance before and after intervention in both groups were significantly different. However, no significant differences were observed between the 2 groups. [Conclusion] Although SET was not more effective than regular exercise, significant improvement was observed before and after SET. Therefore, SET can be considered effective in strengthening trunk muscles in stroke patients with chronic hemiplegia.


Geometric morphometrics of nested symmetries unravels hierarchical inter- and intra-individual variation in biological shapes.
Symmetry is a pervasive feature of organismal shape and the focus of a large body of research in Biology. Here, we consider complex patterns of symmetry where a phenotype exhibits a hierarchically structured combination of symmetries. We extend the Procrustes ANOVA for the analysis of nested symmetries and the decomposition of the overall morphological variation into components of symmetry (among-individual variation) and asymmetry (directional and fluctuating asymmetry). We illustrate its use with the Aristotle's lantern, the masticatory apparatus of 'regular' sea urchins, a complex organ displaying bilateral symmetry nested within five-fold rotational symmetry. Our results highlight the importance of characterising the full symmetry of a structure with nested symmetries. Higher order rotational symmetry appears strongly constrained and developmentally stable compared to lower level bilateral symmetry. This contrast between higher and lower levels of asymmetry is discussed in relation to the spatial pattern of the lantern morphogenesis. This extended framework is applicable to any biological object exhibiting nested symmetries, regardless of their type (e.g., bilateral, rotational, translational). Such cases are extremely widespread in animals and plants, from arthropod segmentation to angiosperm inflorescence and corolla shape. The method therefore widens the research scope on developmental instability, canalization, developmental modularity and morphological integration.


Actions versus Words: Exploring the contributions of working memory and motoric coding in children's instruction following using a dual-task paradigm.
Previous research in adults has showed that physical performance (i.e., enactment) of instructions at recall leads to better memory compared to verbal recall and that this effect does not rely solely on Working Memory resources. The current study aimed to replicate this finding in children. A group of 32 children encoded simple instructions verbally while engaging in a series of distractor tasks (articulatory suppression, backwards counting and a motor suppression task). Participants recalled information verbally or physically through enactment. The findings showed that although distractors impaired performance compared to a control condition (no distractor task), the enactment advantage remained intact in all conditions. These findings show that children's memory is superior when they perform, rather than when they verbally repeat instructions and crucially it is suggested that this effect does not rely solely on Working Memory resources.


[Morphological basics of scientific research in ophthalmology].
The article summarizes the results of a complex study on lacrimal gland secretion (crystallography), meibomian gland secretion (evaluation of the lipid layer in the intermarginal space of the eyelids) and nasolacrimal contents in dacryostenosis (cytology), and ocular surface condition in conjunctival pathology (impressional cytology). Samples of subretinal tissue (removed during endoscopic surgery in patients with age-related macular degeneration) and corneas (obtained in penetrating mini-keratoplasty performed after previous photorefractive or phototherapeutic keratoplasty) were studied by means of light and electronic microscopy. Engraftment potential of different implants used in orbital plastic surgery was studied experimentally. Data on prenatal development of retinal vascular system and structures responsible for proper ocular hydrodynamics is provided.


Artificial reservoirs complement natural ponds to improve pondscape resilience in conservation corridors in a biodiversity hotspot.
Natural ponds are rich in biodiversity, contributing greatly to regional aquatic biodiversity. Artificial reservoirs used for irrigation can be significant additional features of the landscape. They infill the local natural pondscape, and are attractors for aquatic insects. Here, we determine the extent to which artificial reservoirs represent the local natural pond biota, and how they contribute to the pondscape in conservation corridors used to mitigate the impact of plantation forestry in a global biodiversity hotspot. We did this by: 1) identifying the environmental factors, including plants, that drive dragonfly, water beetle, and water bug species richness, diversity and composition, and 2) determining the value of natural ponds vs. artificial reservoirs for maintaining the population size and expanding the area of occupancy for dragonflies, beetles and bugs in conservation corridors. While vegetation cover was central for maintaining species richness and composition of the assemblages in general, many other environmental variables are necessary to encourage the full suite of local diversity. Artificial reservoirs are attractive habitats to many species, overall increasing area of occupancy for 75% of them (ranging from 62-84% for different taxa). These reservoirs provide complementary alternative habitats to natural ponds, leading to improved ecological resilience across the pondscape. We conclude that maintaining a diverse and heterogeneous pondscape is important for conserving local aquatic insect diversity, and that artificial reservoirs increase the local area of occupancy for a range of pond insects in conservation corridors, and improve the biodiversity value of these pondscapes.


Precise Molecular Design Toward Organic-Inorganic Zinc Chloride ABX3 Ferroelectrics.
Organic-inorganic ABX3 (A, B = cations, X = anion) hybrids with perovskite structure have recently attracted tremendous interest due to their structural tunability and rich functional properties, such as ferroelectricity. However, ABX3 hybrid ferroelectrics with other structures have rarely been reported. Here, we successfully designed an ABX3 hybrid ferroelectric [(CH3)3NCH2F]ZnCl3 with a spontaneous polarization of 4.8 μC/cm2 by the molecular modification of [(CH3)4N]ZnCl3 through hydrogen/halogen substitution. It is the first zinc halide ABX3 ferroelectric, which contains one-dimensional [ZnCl3]-n chains of corner-sharing ZnCl4 tetrahedra, distinct from the anionic framework of corner-sharing or face-sharing BX6 octahedra in the ABX3 perovskites. From zero dimension to one dimension, the high symmetry of ZnCl4 tetrahedra is broken, and all of them align along one direction to form a polar [ZnCl3]-n chain, beneficial to the generation of ferroelectricity. This finding provides an efficient polar anionic framework for enriching the family of hybrid ferroelectrics by assembling with various cations and should inspire further exploration of new classes of organic-inorganic ABX3 ferroelectrics.


Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle.
Mitochondria-mediated apoptosis represents a central process driving age-related muscle loss. However, the temporal relation between mitochondrial apoptotic signaling and sarcopenia as well as the regulation of release of pro-apoptotic factors from the mitochondria has not been elucidated. In this study, we investigated mitochondrial apoptotic signaling in skeletal muscle of rats across a wide age range. We also investigated whether mitochondrial-driven apoptosis was accompanied by changes in the expression of Bcl-2 proteins and components of the mitochondrial permeability transition pore (mPTP). Analyses were performed on gastrocnemius muscle of 8-, 18-, 29- and 37-month-old male Fischer344 x Brown Norway rats (9 per group). Muscle weight declined progressively with advancing age, concomitant with increased apoptotic DNA fragmentation. Cytosolic and nuclear levels of apoptosis inducing factor (AIF) and endonuclease G (EndoG) increased in old and senescent animals. In contrast, cytosolic levels of cytochrome c were unchanged with age. Mitochondrial Bcl-2, Bax and Bid increased dramatically in 37-month-old rats, with no changes in the Bax/Bcl-2 ratio in any of the age groups. Finally, expression of cyclophilin D (CyPD) was enhanced at very old age. Our findings indicate that the mitochondrial caspase-independent apoptotic pathway may play a more prominent role in skeletal muscle loss than caspase-mediated apoptosis.


Mindfulness training attenuates the increase in salivary cortisol concentration associated with competition in highly trained wheelchair-basketball players.
This study determined the effect of 8 wk of mindfulness training (MT) on salivary cortisol (sCort) and rate of salivary Immunoglobulin-A (sIgA) secretion in wheelchair-basketball players during a competition period. The mindful group completed 8 weeks of MT in addition to training and competition. sCort and rate of sIgA secretion were measured at baseline, at 2-week intervals, the end and 2 weeks following the intervention. A significant time and group interaction was observed for sCort (F = 3.297, P = 0.040, ES = 0.191); sCort increased in the control group from MT-BL to MT-2wk (P = 0.001) and remained significantly elevated at MT-4wk (P = 0.013) and MT-6wk (P = 0.002). sCort decreased from MT-6wk to MT-8wk (P < 0.001) and concentrations were not different at MT-8wk and Post-2wk to MT-BL (P > 0.05). Mindful group sCort increased from MT-BL to MT-2wk (P = 0.042) but decreased to concentrations no different to MT-BL for the rest of the intervention period (P > 0.05). There were no group differences in rate of sIgA secretion during the intervention (P = 0.810). It was concluded that 8 weeks of MT attenuated the increase in sCort associated with the competition period.


Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice.
Butylated hydroxytoluene, a common food additive, is known to produce proliferative pulmonary changes characterized by increased DNA, RNA, and lung weight. In the present study, reactive hyperplasia and fibrosis were produced within 9 days after a single intraperitoneal injection of 400 mg. per kg. of butylated hydroxytoluene was given to mice. Initial perivascular edema with cell infiltrates was followed by necrosis of type 1 alveolar epithelial cells and by division of type 2 cells which repopulated the alveolar wall with unusually large epithelial cells containing abundant cytoplasm. DNA synthesis, as indexed by thymidine and uridine kinase levels and by 3H-thymidine uptake, increased at 2 days, peaked at 4 days, and dropped gradually to near normal by day 9. Differential counts of labeled cells revealed that the early rise was due to epithelial cell proliferation; in turn, interstitial and endothelial cells entered the proliferative phase. Endothelial labeling peaked at day 6 immediately following ultrastructural evidence of endothelial injury. It is concluded that the proliferative pulmonary changes that occur after the administration of butylated hydroxytoluene are a consequence of cell injury and necrosis. The reparative processes occur predominantly at the alveolar epithelium and interstitium with the production of fibrosis. The cellular hypertrophy and hyperplasia observed in this study account for the biochemical changes in pulmonary RNA and DNA that have been described previously.


Biases in Illumina transcriptome sequencing caused by random hexamer priming.
Generation of cDNA using random hexamer priming induces biases in the nucleotide composition at the beginning of transcriptome sequencing reads from the Illumina Genome Analyzer. The bias is independent of organism and laboratory and impacts the uniformity of the reads along the transcriptome. We provide a read count reweighting scheme, based on the nucleotide frequencies of the reads, that mitigates the impact of the bias.


An exploration of goal-setting practices in Queensland rehabilitation services.
Goals are vital in rehabilitation; however, how goal-setting occurs varies widely in clinical practice. This study aims to review goal-setting practices across the rehabilitation continuum within varied case mix services in Queensland, Australia. A descriptive multisite qualitative case study with medical record audits and interviews of adult rehabilitation clients was used to evaluate four propositions across three inpatient and two community rehabilitation services. The propositions evaluated the process in which goal-setting occurs, action planning and review of goals, as well as the type, specificity and client-centeredness of goals set. Goals (n = 1120) were often poorly defined, focussed on short term physical functioning and were predominantly set by individual disciplines with the client rather than using an interdisciplinary approach. Clients were not consistently given action plans to pursue goals (n = 59, 18%) and the review of goal progress (n = 60, 18%) was limited. Few clients reported receiving copies of their rehabilitation goals (n = 16, 25%). Goal-setting in rehabilitation should be specific, meaningful and include the client in action planning, feedback and review. However, goal-setting in rehabilitation is often multidisciplinary and unstructured.Implications for rehabilitationBest-practice rehabilitation team goal-negotiation and goal-setting should include a common goal focus and incorporate components of staff and client action planning, coping planning, feedback and review.Rehabilitation clients prefer shared-decision making approaches to setting meaningful and personalised goals, however, require time and support to engage in the goal-setting and negotiation process.Rehabilitation clinicians need training and support to improve their goal negotiation and goal writing skills to create specific, understandable and meaningful goals with rehabilitation clients.


Response of lactating dairy cows to diets containing wet corn gluten feed or a raw soybean hull-corn steep liquor pellet.
We evaluated effects of wet corn gluten feed (WCGF) and a novel product (SHSL) containing raw soybean hulls and corn steep liquor on performance and digestion in lactating dairy cows. In Experiment 1, 46 multiparous Holstein cows were assigned to control (C), WCGF (20% of diet DM), or SHSL (20% of diet DM). Diets were fed as a total mixed ration beginning after calving. The C diet contained (dry matter [DM] basis) 30% alfalfa hay, 15% corn silage, 32% corn, 9.3% whole cottonseed, 4.4% solvent soybean meal (SBM), and 3.3% expeller SBM. The WCGF replaced 10% alfalfa hay, 5% corn silage, and 5% corn grain, while expeller SBM replaced solvent SBM to maintain diet rumen undegradable protein. The SHSL replaced 10% alfalfa hay, 5% corn silage, 3% solvent SBM, and 2% corn. Dietary crude protein averaged 18.4%. Milk, energy-corrected milk (ECM), DM intake (DMI), and ECM/DMI were similar among diets during the first 13 wk of lactation. During wk 14 through 30 postpartum, WCGF and SHSL improved milk, ECM, milk component yield, and ECM/DMI. In Experiment 2, 6 cows were used to evaluate digestibility and rumen traits. Dry matter intake and total tract digestibilities of DM, fiber, and crude protein were not different among diets. Diets did not affect ruminal liquid dilution rate, pH, or concentrations of total volatile fatty acids or ammonia, but acetate:propionate was higher for C (3.38) than for WCGF (2.79) or SHSL (2.89). The WCGF and SHSL products can serve as alternative feedstuffs in diets fed to lactating dairy cattle.


Proof of Concept Study for the Design, Manufacturing, and Testing of a Patient-Specific Shape Memory Device for Treatment of Unicoronal Craniosynostosis.
Treatment of unicoronal craniosynostosis is a surgically challenging problem, due to the involvement of coronal suture and cranial base, with complex asymmetries of the calvarium and orbit. Several techniques for correction have been described, including surgical bony remodeling, early strip craniotomy with orthotic helmet remodeling and distraction. Current distraction devices provide unidirectional forces and have had very limited success. Nitinol is a shape memory alloy that can be programmed to the shape of a patient-specific anatomy by means of thermal treatment.In this work, a methodology to produce a nitinol patient-specific distractor is presented: computer tomography images of a 16-month-old patient with unicoronal craniosynostosis were processed to create a 3-dimensional model of his skull and define the ideal shape postsurgery. A mesh was produced from a nitinol sheet, formed to the ideal skull shape and heat treated to be malleable at room temperature. The mesh was afterward deformed to be attached to a rapid prototyped plastic skull, replica of the patient initial anatomy. The mesh/skull construct was placed in hot water to activate the mesh shape memory property: the deformed plastic skull was computed tomography scanned for comparison of its shape with the initial anatomy and with the desired shape, showing that the nitinol mesh had been able to distract the plastic skull to a shape close to the desired one.The shape-memory properties of nitinol allow for the design and production of patient-specific devices able to deliver complex, preprogrammable shape changes.