Treatment patterns among colorectal cancer patients in South Australia: a demonstration of the utility of population-based data linkage.
Population level data on colorectal cancer (CRC) management in Australia are lacking. This study assessed broad level patterns of care and concordance with guidelines for CRC management at the population level using linked administrative data from both the private and public health sectors across South Australia. Disparities in CRC treatment were also explored. Linking information from the South Australian Cancer Registry, hospital separations, radiotherapy services and hospital-based cancer registry systems provided data on the socio-demographic, clinical and treatment characteristics for 4641 CRC patients, aged 50-79 years, diagnosed from 2003 to 2008. Factors associated with receiving site/stage-specific treatments (surgery, chemotherapy and radiotherapy) and overall concordance with treatment guidelines were identified using Poisson regression analysis. About 83% of colon and 56% of rectal cancer patients received recommended treatment. Provision of neo-adjuvant/adjuvant therapies may be less than optimal. Radiotherapy was less likely among older patients (prevalence ratio 0.7, 95% confidence interval 0.5-0.8). Chemotherapy was less likely among older patients (0.7, 0.6-0.8), those with severe or multiple co-morbidities (0.8, 0.7-0.9), and those from rural areas (0.9, 0.8-1.0). Overall discordance with treatment guidelines was more likely among rectal cancer patients (3.0, 2.7-3.3), older patients (1.6, 1.4-1.8), those with multiple co-morbid conditions (1.3, 1.1-1.4), and those living in rural areas (1.2, 1.0-1.3). Greater emphasis should be given to ensure CRC patients who may benefit from neo-adjuvant/adjuvant therapies have access to these treatments.


[Effect of cultivation parameters of antarctic strains Enterobacter hormaechei and Brevibacterium antarcticumon resistant to copper(II) ions].
Enterobacter hormaechei and Brevibacterium antarcticum strains isolated from ornithogenic soils of Galindez Island (West Antarctica) were investigated for their resistance to Cu2+ cations and for their capacity to Cu2+ uptake from the environment. The studied strains are capable to grow in the concentration range of copper 100-1100 mg/l and to extract 11-75% of Cu2+ from the environment depending on cultivation parameters and copper output concentration in the culture medium.


Relative number of cells projecting from contralateral and ipsilateral nucleus isthmi to loci in the optic tectum is dependent on visuotopic location: horseradish peroxidase study in the leopard frog.
The leopard frog optic tectum is the principal target of the contralateral retina. The retinal terminals form a topographic map of the visual field. The tectum also receives bilateral topographic input from a midbrain structure called nucleus isthmi. In this study we determined the relative strength of n. isthmi projections to different loci in the tectum. Horseradish peroxidase (HRP) was applied at single superficial tectal locations in a series of leopard frogs. The application sites were distributed across the tectum. Retrogradely filled cells were counted in ipsilateral and contralateral nucleus isthmi. Although all regions of the tectum receive input from both n. isthmi, the relative number of labeled cells in the two n. isthmi is dependent on visuotopic location. Input to the rostromedial tectum representing the visual field ipsilateral to the labeled tectum comes primarily from the contralateral n. isthmi. Input to the caudolateral tectum representing the visual field contralateral to the labeled tectum originates mostly from the ipsilateral n. isthmi. Tectal application sites representing the visual midline had approximately equal numbers of labeled cells in the two n. isthmi. The results are similar at postapplication survival times ranging from 2 to 14 days. Using application of HRP to rostral tectum and application of nuclear yellow to caudal tectum, we show that the anisotropy in isthmi labeling is not due to take up of these labels by isthmotectal fibers passing through the application sites that terminate elsewhere.


Pd(II)-Catalyzed Three-Component Synthesis of Furo[2,3-d]pyrimidines from β-Ketodinitriles, Boronic Acids, and Aldehydes.
A Pd(II)-catalyzed three-component synthesis of 2,4,6-triarylfuro[2,3-d]pyrimidines from β-ketodinitriles, boronic acids, and aldehydes has been developed. The participation of both nitrile (-CN) groups led to the concurrent construction of furo-pyrimidine via the formation of C-C, C═C, C-O, C-N, and C═N bonds. The compounds show excellent photoluminescence properties with absorption maxima ranging from 348 to 387 nm and emission from 468 to 533 nm. The synthetic utility of the protocol was further demonstrated through a few postsynthetic manipulations.


Quantification of Daily Physical Activity and Sedentary Behavior of Claudicating Patients.
Claudication is the most common manifestation of peripheral artery disease (PAD), producing significant ambulatory compromise. Limited information exists on the routine physical activity of claudicating patients. Our objective was to record the intensity/time profiles of physical activity and the timing and duration of sedentary behavior of a sample of community-dwelling claudicating patients. Forty-four claudicating patients referred to our vascular clinic were recruited. Physical activity was recorded using the ActiGraph GT1M activity monitor. The Actigraph monitor is a lightweight instrument designed to measure human movement through changes in acceleration, measured as counts over 1-minute time periods. Data from 7 consecutive days were used for the calculations. We processed the data using the ActiLife software program. The average daily activity of the claudicating patients shows a steady increase beginning approximately 05:30 AM until a peak plateau from approximately 10:00 AM to 01:30 PM followed by a steady decrease until approximately 09:30 PM, when a sustained period of inactivity begins. The average claudicating patient takes 3586 steps per day at an average intensity of 1.77 metabolic equivalents of task (METs, a physiological measure expressing the energy cost of physical activities). Average physical activity intensity and peak intensity fluctuate very little during the day, and they rarely exceed the level of light activity (light = <3 METs maximum effort, such as casual walking or light housework). During awake time, approximately 7 hours are spent in sedentary behaviors (<1.5 METs), and sedentary time is spread throughout the day mostly in short intervals between periods of low-energy activity. Our study objectively demonstrates the reduced physical activity of claudicating patients and documents physical activity/duration profiles throughout the day. The intensity of the physical activity of the average claudicating patient fluctuates very little during the day and rarely exceeds a light intensity level. Claudicating patients spend approximately half of their awake time in sedentary behavior and when they walk they do it in short bursts followed by several minutes of rest. We anticipate that changes in routine physical activity/duration profiles of patients with PAD will provide relevant, sensitive, and direct measures of the effectiveness of therapeutic interventions.


The β1-integrin-p-FAK-p130Cas-DOCK180-RhoA-vinculin is a novel regulatory protein complex at the apical ectoplasmic specialization in adult rat testes.
During spermatogenesis, step 1 spermatids (round spermatids) derive from spermatocytes following meiosis I and II at stage XIV of the epithelial cycle begin a series of morphological transformation and differentiation via 19 steps in rats to form spermatozoa. This process is known as spermiogenesis, which is marked by condensation of the genetic material in the spermatid head, formation of the acrosome and elongation of the tail. Since developing spermatids are lacking the robust protein synthesis and transcriptional activity, the cellular, molecular and morphological changes associated with spermiogenesis rely on the Sertoli cell in the seminiferous epithelium via desmosome and gap junction between Sertoli cells and step 1-7 spermatids. Interestingly, a unique anchoring junction type arises at the interface of step 8 spermatid and Sertoli cell known as apical ectoplasmic specialization (apical ES). Once it appears, apical ES is the only anchoring device restricted to the interface of step 8-19 spermatids and Sertoli cells to confer spermatid polarity, adhesion, signal communication and structural support, and to provide nutritional support during spermiogenesis, replacing desmosome and gap junction. While the adhesion protein complexes that constitute the apical ES are known, the signaling protein complexes that regulate apical ES dynamics, however, remain largely unknown. Herein we report the presence of a FAK (focal adhesion kinase)-p130Cas (p130 Crk-associated substrate)-DOCK180 (Dedicator of cytokinesis 180)-RhoA (Ras homolog gene family, member A)-vinculin signaling protein complex at the apical ES, which is also an integrated component of the β1-integrin-based adhesion protein complex based on co-immunoprecipitation experiment. It was also shown that besides p-FAK-Tyr(397) and p-FAK-Tyr(576), β1-integrin, p130Cas, RhoA and vinculin displayed stage-specific expression in the seminiferous epithelium during the epithelial cycle with predominant localization at the apical ES as demonstrated by immunohistochemistry. Based on these findings, functional studies can now be performed to assess the role of this β1-integrin-p-FAK-p130Cas-DOCK180-RhoA-vinculin protein complex in apical ES dynamics during spermiogenesis.


Endothelial dysfunction in cerebral microcirculation during hypothermic cardiopulmonary bypass in newborn lambs.
Inflammatory stimuli or mechanical stresses associated with hypothermic cardiopulmonary bypass could potentially impair cerebrovascular function, resulting in inadequate cerebral perfusion. We hypothesize that hypothermic cardiopulmonary bypass is associated with endothelial or vascular smooth muscle dysfunction and associated cerebral hypoperfusion. Therefore we studied the cerebrovascular response to endothelium-dependent vasodilator, acetylcholine, endothelium-independent nitric oxide donor, sodium nitroprusside, and vasoactive amine, serotonin, in newborn lambs undergoing hypothermic cardiopulmonary bypass (nasopharygeal temperature = 18 degrees C). Studies were performed on 13 newborn lambs equipped with a closed cranial window, allowing for direct visualization of surface pial arterioles. Six animals were studied while undergoing hypothermic cardiopulmonary bypass, whereas seven served as nonbypass, warm (37 degrees C) controls. Pial arteriolar caliber (range = 111 to 316 microm diameter) was monitored using video microscopy. Topical application of acetylcholine caused a dose-dependent increase in arteriolar diameter in the control group that was absent in animals undergoing hypothermic cardiopulmonary bypass. Hypothermic cardiopulmonary bypass did not alter the vasodilation in response to sodium nitroprusside. Furthermore, the contractile response to serotonin was fully expressed during hypothermic cardiopulmonary bypass. The specific loss of acetylcholine-induced vasodilation suggests endothelial cell dysfunction rather than impaired ability of vascular smooth muscle to respond to nitric oxide. It is speculated that loss of endothelium-dependent regulatory factors in the cerebral microcirculation during hypothermic cardiopulmonary bypass may enhance vasoconstriction, and impaired cerebrovascular function may be a basis for associated neurologic injury during or after hypothermic cardiopulmonary bypass.


Neonatal hip instability: a prospective comparison of clinical examination and anterior dynamic ultrasound.
Ultrasound is increasingly being used to complement the clinical examination in assessing neonatal hip instability. The clinical examination, although highly sensitive in detecting hip instability, can lead to considerable overtreatment. To compare anterior dynamic ultrasound and clinical examination in the assessment of neonatal hip instability and regarding treatment rates. 536 newborn infants (out of a population of 18,031) were selected, on the basis of a combination of risk factors, clinical signs of hip instability or ambiguous clinical findings, to undergo an anterior dynamic ultrasound examination of the hip, by a method developed by our group. This examination, performed by one out of seven experienced examiners, was compared with the standard clinical hip examination conducted by one of four pediatric orthopedic surgeons. The clinical examination was carried out both prior to and within a few hours after the ultrasound examination. The clinical examination diagnosed 81.7% of the hips as normal, 14.5% as unstable, and 3.8% as dislocatable or dislocated. With the dynamic ultrasound method, the corresponding figures were 87.8%, 10.4%, and 1.8%, respectively. Use of the criteria of the clinical examination resulted in treatment of 147 infants. Using the dynamic ultrasound examination as a criterion meant that 87 infants would receive treatment. The calculated treatment rate was 0.85% when based on the clinical stress test and 0.49% when based on the dynamic ultrasound. The dynamic ultrasound results reduced the treatment rate by over 40% when used as a basis for the decision regarding treatment.


The complex pathophysiology of acquired aplastic anaemia.
Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8(+) cytotoxic T cells, CD4(+) T cells including T helper type 1 (Th1), Th2, regulatory T cells and Th17 cells, natural killer (NK) cells and NK T cells, along with the abnormal production of cytokines including interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-β, IFN-γ and TNF-α genes, as well as certain human leucocyte antigen (HLA) alleles, may account for the propensity to immune-mediated killing of HSPCs and/or ineffective haematopoiesis. Although the inciting autoantigens remain elusive, autoantibodies are often detected in the serum. In addition, recent studies provide genetic and molecular evidence that intrinsic and/or secondary deficits in HSPCs and bone marrow mesenchymal stem cells may underlie the development of bone marrow failure.


Computational polarimetric microwave imaging.
We propose a polarimetric microwave imaging technique that exploits recent advances in computational imaging. We utilize a frequency-diverse cavity-backed metasurface, allowing us to demonstrate high-resolution polarimetric imaging using a single transceiver and frequency sweep over the operational microwave bandwidth. The frequency-diverse metasurface imager greatly simplifies the system architecture compared with active arrays and other conventional microwave imaging approaches. We further develop the theoretical framework for computational polarimetric imaging and validate the approach experimentally using a multi-modal leaky cavity. The scalar approximation for the interaction between the radiated waves and the target- often applied in microwave computational imaging schemes-is thus extended to retrieve the susceptibility tensors, and hence provides additional information about the targets. Computational polarimetry has relevance for existing systems in the field that extract polarimetric imagery, and particular for ground observation. A growing number of short-range microwave imaging applications can also notably benefit from computational polarimetry, particularly for imaging objects that are difficult to reconstruct when assuming scalar estimations.


Pre-hospital management of febrile seizures in children seen at the university college hospital, ibadan, Nigeria.
Febrile seizures are commonly encountered in emergency paediatric practice. Initial pre-hospital intervention given by caregivers has been shown to impact outcome. To describe the spectrum of pre-hospital interventions given for the treatment of childhood febrile seizures in Ibadan, Nigeria. All consecutive cases of febrile seizures seen at the emergency room of University College Hospital, Ibadan over a period of 13 months were the subjects of the study. Details of history of illness including the interventions given before presentation were recorded. All the children had lumbar puncture and examination of their cerebrospinal fluid (CSF). All were followed up till discharge and the outcome was recorded. A total of 147 children, 83 males and 64 females with febrile seizures were studied. Harmful traditional practices were found to be common in the cohort studied. Fifty-nine (40.1%) of the children received at least one form of intervention believed to be capable of aborting the seizure during the attack at home. Herbal preparation was the most common form of pre-hospital treatment, given in 15 (10.2%) of the cases. Other forms of pre-hospital interventions given were application of substances to the eyes (6.1%), incisions on the body (2%) and burns inflicted on the feet and buttocks (1.4%). None of the children received rectal diazepam or buccal midazolam as home remedy for seizures. There was a statistically significant relationship between harmful cultural practices and the socio-economic class of the caregivers (P=0.008). Pre-hospital treatment of childhood seizures in Ibadan comprises mainly harmful traditional practices. There is a need for appropriate health education to reduce the morbidity and mortality associated with febrile seizures in the locality.


Medical support of the Sinai Multinational Force and Observers: an update, 1990.
The Multinational Force and Observers in an 11-nation peacekeeping force established to monitor the 1979 Egyptian-Israeli Treaty of Peace. Provision of medical support for this force was the first employment of the U.S. Army Medical Department in an effort of this kind. This article is an update to "Medical Support of the Sinai Multinational Force and Observers, 1982," published in Military Medicine in October 1983. We compare the execution of medical support in 1982 with that of 1990 and describe medical conditions and problems encountered during our tour.


[Protective effect and mechanism of Ecliptae Herba on cigarette smoke extract-induced cytotoxicity of NHBE cells].
To investigate the protective effect and mechanism of Ecliptae Herba extract on cigarette smoke extract-induced cytotoxicity. The effect of Ecliptae Herba extract on CSE-induced NHBE cell proliferation was detected by MTT assay. GSH content was determined by DTNB colorimetry. GST activity was measured by CDNB colorimetric assay. NQO1 activity was detected by NADPH and DCIP. The protein expression was determined by Western blot assay. Ecliptae Herba extract reduced CSE's inhibitory effect on NHBE cells, recover the decrease in intracellular GSH caused by CSE and reduce the CSE-induced activity of GST and NQO1 and NQO1 protein expression. Ecliptae Herba extract can reduce CSE-induced injury on NHBE cells, which may be related to phase II detoxification enzymes.


Transcriptional signature of prion-induced neurotoxicity in a Drosophila model of transmissible mammalian prion disease.
Prion diseases are fatal transmissible neurodegenerative conditions of humans and animals that arise through neurotoxicity induced by PrP misfolding. The cellular and molecular mechanisms of prion-induced neurotoxicity remain undefined. Understanding these processes will underpin therapeutic and control strategies for human and animal prion diseases, respectively. Prion diseases are difficult to study in their natural hosts and require the use of tractable animal models. Here we used RNA-Seq-based transcriptome analysis of prion-exposed Drosophila to probe the mechanism of prion-induced neurotoxicity. Adult Drosophila transgenic for pan neuronal expression of ovine PrP targeted to the plasma membrane exhibit a neurotoxic phenotype evidenced by decreased locomotor activity after exposure to ovine prions at the larval stage. Pathway analysis and quantitative PCR of genes differentially expressed in prion-infected Drosophila revealed up-regulation of cell cycle activity and DNA damage response, followed by down-regulation of eIF2 and mTOR signalling. Mitochondrial dysfunction was identified as the principal toxicity pathway in prion-exposed PrP transgenic Drosophila. The transcriptomic changes we observed were specific to PrP targeted to the plasma membrane since these prion-induced gene expression changes were not evident in similarly treated Drosophila transgenic for cytosolic pan neuronal PrP expression, or in non-transgenic control flies. Collectively, our data indicate that aberrant cell cycle activity, repression of protein synthesis and altered mitochondrial function are key events involved in prion-induced neurotoxicity, and correlate with those identified in mammalian hosts undergoing prion disease. These studies highlight the use of PrP transgenic Drosophila as a genetically well-defined tractable host to study mammalian prion biology.


Oxysterols and retinal degeneration.
Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol-producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol-producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol-associated pathophysiology will help in the development of effective retinal degeneration therapies. LINKED ARTICLES: This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.


Glycemic exposure, glycemic control, and metabolic karma in diabetic complications.
Diabetes continues to cast a long shadow over the lives of many people. It is now clear that even transient hyper- or hypoglycemia or increased glycemic variability around healthy mean glucose levels can have long-lasting and long-term effects on the development and progression of diabetic complications, including cardiovascular disease, kidney disease, retinopathy, and neuropathy. Even after glycemic control has been achieved and maintained for many years, it appears hard to undo the changes that are instilled, including epigenetic programming, compositional changes, post-translational modifications, or simply lead time toward an inevitable fate. This phenomenon has become known as "metabolic memory" or the "legacy effect," but it may be better characterized as "metabolic karma," in which the intent and actions of an individual (with respect to metabolic control) influence the future health of that individual. This "bad karma" has been used to explain many clinical observations surrounding diabetes and its management, including the lack of benefits in many short- and intermediate-term trials, and the potential utility of early intensive glycemic control. Further understanding the molecular basis of a metabolic legacy in diabetes will certainly provide new targets for intervention.


Cardiovascular benefits of exercise.
Regular physical activity during leisure time has been shown to be associated with better health outcomes. The American Heart Association, the Centers for Disease Control and Prevention and the American College of Sports Medicine all recommend regular physical activity of moderate intensity for the prevention and complementary treatment of several diseases. The therapeutic role of exercise in maintaining good health and treating diseases is not new. The benefits of physical activity date back to Susruta, a 600 BC physician in India, who prescribed exercise to patients. Hippocrates (460-377 BC) wrote "in order to remain healthy, the entire day should be devoted exclusively to ways and means of increasing one's strength and staying healthy, and the best way to do so is through physical exercise." Plato (427-347 BC) referred to medicine as a sister art to physical exercise while the noted ancient Greek physician Galen (129-217 AD) penned several essays on aerobic fitness and strengthening muscles. This article briefly reviews the beneficial effects of physical activity on cardiovascular diseases.


Parametric Study of Colloidal Particle Confinement near a Surface in the Presence of DLVO and Structural Interactions Using Brownian Dynamic Simulations.
Total internal reflection microscopy (TIRM) has become a crucial technique for understanding the surface interactions and dynamics of Brownian colloidal particles near a surface. However, for select colloidal systems, experimental limitations associated with TIRM can occlude exploration of nano- and submicrometer colloids dispersed in complex or structured fluids. It should be possible to use Brownian dynamic simulations to quantify, explore, or circumvent these limitations to extend the TIRM technique further. A Brownian dynamics algorithm based on the Langevin equation was utilized to identify favorable colloidal systems for conducting TIRM experiments in electrolyte and nonadsorbing polyelectrolyte solutions. In electrolyte solution, the motion of polystyrene and silica particles of nanometer- and micrometer-sized radii was simulated near a glass slide in the presence of retarded van der Waals and electric double-layer forces to develop potential energy profiles. In the case of nonadsorbing polyelectrolyte solutions, a structural force was also implemented into the simulation, and the influence of structural interactions on particle confinement was explored as a function of particle size, particle density, and polyelectrolyte concentration. In electrolyte solutions, our results were able to identify the minimum particle size required for TIRM experiments as well as insight into particle selection based on material density. For structural or oscillatory forces, our results show that prior to conducting TIRM experiments, Brownian dynamics simulation can be used to select the appropriate particle size, material, and polyelectrolyte concentration range where the colloidal particle can sample multiple structural energy wells without confinement. These results provide insight into the colloidal system suitable to experimentally study near-surface particle diffusion dynamics for a range of separations in the presence of structural interactions.


Hybridization of a phospholipid polymer hydrogel with a natural extracellular matrix using active cell immobilization.
Three-dimensional tissue organization is still an obstacle in the field of tissue engineering, which generally involves cell immobilization, proliferation, and organization. As an artificial extracellular matrix (ECM) for providing a suitable environment of cells to construct tissues, combination of cytocompatible polymer hydrogels and natural ECM produced by the immobilized cells was considered. In this research, we designed a spontaneously forming hydrogel system between two water-soluble polymers for the immobilization of cells. These polymers were poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid-co-N-succinimidyloxycarbonyl tetra(ethylene glycol)methacrylate) (PMBVS) and poly(vinyl alcohol) (PVA) to form a PMBVS/PVA hydrogel in a cell culture medium under mild conditions. Basic fibroblast growth factor (bFGF) was conjugated with PMBVS (PMBV-bFGF). To enhance the growth of the immobilized cells, mouse fibroblast L929 cells were immobilized in the PMBVS/PVA hydrogel and the PMBV-bFGF/PVA hydrogel, and their proliferation and secretion of the ECM under stimulation with bFGF was observed. The ECM infiltrated and replaced the hydrogel, resulting in the formation of a hybrid hydrogel with the ECM and laden cells.


A regularized multivariate regression approach for eQTL analysis.
Expression quantitative trait loci (eQTLs) are genomic loci that regulate expression levels of mRNAs or proteins. Understanding these regulatory provides important clues to biological pathways that underlie diseases. In this paper, we propose a new statistical method, GroupRemMap, for identifying eQTLs. We model the relationship between gene expression and single nucleotide variants (SNVs) through multivariate linear regression models, in which gene expression levels are responses and SNV genotypes are predictors. To handle the high-dimensionality as well as to incorporate the intrinsic group structure of SNVs, we introduce a new regularization scheme to (1) control the overall sparsity of the model; (2) encourage the group selection of SNVs from the same gene; and (3) facilitate the detection of trans-hub-eQTLs. We apply the proposed method to the colorectal and breast cancer data sets from The Cancer Genome Atlas (TCGA), and identify several biologically interesting eQTLs. These findings may provide insight into biological processes associated with cancers and generate hypotheses for future studies.


Effect of a culturally safe student placement on students' understanding of, and confidence with, providing culturally safe podiatry care.
For university-based podiatry education there are little data available documenting the delivery method and impact of Aboriginal and Torres Strait Islander health curricula or the use of, and outcomes from, immersive clinical placements generally or specific to podiatry practice. Therefore, the primary aim of this study was to evaluate the effect of undertaking clinical placement in a culturally safe podiatry service for Aboriginal and Torres Strait Islander Peoples on podiatry students' understanding of, and confidence with, providing culturally safe podiatry care. Final year University of Newcastle undergraduate podiatry students attending a culturally safe Aboriginal and Torres Strait Islander student clinic at a local hospital were purposively recruited to participate. Students completed a custom-made and pilot-tested cultural awareness and capability survey before and after placement. Survey domains were determined from a principle component analysis. The Wilcoxon Signed Rank test was used to compare pre-placement scores on each domain of the survey to the post-placements scores. Effect sizes were calculated and interpreted as small (0.1-0.29), medium (0.3-0.49), and large (≥0.5). This study recruited 58 final year University of Newcastle podiatry students to complete baseline and follow-up surveys. For survey domain 1 (level of understanding of power relationships), domain 2 (level of understanding of the interrelationship between culture and self-perceived health), domain 3 (level of understanding of the importance of culture in clinical practice and access to health care), and domain 4 (level of confidence with providing culturally safe care) a statistically significant (p < 0.05) increase in scores was recorded post-placement. The effect sizes were medium to large. This study demonstrated that an immersive student placement at a culturally safe podiatry clinic significantly improved students' understanding of, and confidence with, providing culturally appropriate care to Aboriginal and Torres Strait Islander Peoples. This study provides foundation evidence of the role that such placements have on developing students' cultural capability in a tertiary health care setting, and will help inform future curricula development at both educational institutions and health services, as well as form the basis for ongoing research.


[Laparoendoscopic single-site radical nephrectomy for kidney tumor. Surgical technique, cosmetic and postoperative pain control outcomes].
Over the last few years, many urological laparoscopic operations have been successfully performed by LESS. However, the actual role of LESS in the field of minimally invasive urologic surgery remains to be determined with controversial data about postoperative pain control and almost no results on cosmetic data. The aim of the present study is to describe the technique and report the surgical outcomes of LESS radically nephrectomy (RN) in the treatment of renal cell carcinoma with special emphasis for postoperative pain control and almost no results on cosmetic data. LESS-RN was performed in 33 patients with renal tumors. The indications to perform a LESS-RN were represented by renal tumors not greater than T2, and without evidence of lymphadenopathy or renal vein involvement. The Endocone (Karl Storz, Tuttlingen, Germany) was inserted through a transumbilical incision. A combination of standard laparoscopic instruments and bent grasper and scissors was used. The step sequence of LESS-RN was comparable to standard laparoscopic RN. Demographic data and perioperative and postoperative variables were recorded and analyzed. The mean operative time was 143.7 ± 24.3 min, with a mean estimated blood loss of 122.3 ± 34.1 mL and a mean hospital stay of 3.8 ± 0.8 d. The mean length of skin incision was 4.1 ± 0.6 cm; all patients were discharged from hospital with minimal discomfort, as demonstrated by their pain assessment scores (visual analogue scale: 1.9 ± 0.8). The definitive pathologic results revealed a renal cell carcinoma in all cases and a stage distribution of four T1a, 27 T1b, and 2 T2 tumors. All patients were very satisfied with the appearance of the scars, and at a median follow-up period of 13.2 ± 3.9 mo, all patients were alive without evidence of tumor recurrence or port-site metastasis. LESS is a safe and feasible surgical procedure for RN in the treatment of renal cell carcinoma and has excellent cosmetic results.


Attributable costs of surgical site infection and endometritis after low transverse cesarean delivery.
Accurate data on costs attributable to hospital-acquired infections are needed to determine their economic impact and the cost-benefit of potential preventive strategies. To determine the attributable costs of surgical site infection (SSI) and endometritis (EMM) after cesarean section by means of 2 different methods. Retrospective cohort. Barnes-Jewish Hospital, a 1,250-bed academic tertiary care hospital. There were 1,605 women who underwent low transverse cesarean section from July 1999 through June 2001. Attributable costs of SSI and EMM were determined by generalized least squares (GLS) and propensity score matched-pairs by means of administrative claims data to define underlying comorbidities and procedures. For the matched-pairs analyses, uninfected control patients were matched to patients with SSI or with EMM on the basis of their propensity to develop infection, and the median difference in costs was calculated. The attributable total hospital cost of SSI calculated by GLS was $3,529 and by propensity score matched-pairs was $2,852. The attributable total hospital cost of EMM calculated by GLS was $3,956 and by propensity score matched-pairs was $3,842. The majority of excess costs were associated with room and board and pharmacy costs. The costs of SSI and EMM were lower than SSI costs reported after more extensive operations. The attributable costs of EMM calculated by the 2 methods were very similar, whereas the costs of SSI calculated by propensity score matched-pairs were lower than the costs calculated by GLS. The difference in costs determined by the 2 methods needs to be considered by investigators who are performing cost analyses of hospital-acquired infections.


Amine end-functionalized poly(2-ethyl-2-oxazoline) as promising coating material for antifouling applications.
The antifouling behavior of different poly(2-ethyl-2-oxazoline) (PEtOx) coatings was investigated under "real live" conditions. Amine end-functionalized PEtOx of different molar masses have been prepared using a new and straightforward, two step synthesis method. Subsequently, the PEtOx were attached to glass surfaces via a tetraether lipid and a common silane, respectively. The polymers and coatings were characterized using techniques such as 1H NMR spectroscopy and MALDI-TOF-MS as well as XPS and contact angle measurements. In a next step, the coatings were exposed to the simultaneous attack of five different bacteria in synthetic river water. A clear reduction of the biofilm formation was observed. In addition, the stability of the coatings against thermal, mechanical, and chemical stress was studied.


Periosteal versus true cross-sectional geometry: a comparison along humeral, femoral, and tibial diaphyses.
Cross-sectional geometric (CSG) properties of human long bone diaphyses are typically calculated from both periosteal and endosteal contours. Though quantification of both is desirable, periosteal contours alone have provided accurate predictions of CSG properties at the midshaft in previous studies. The relationship between CSG properties calculated from external contours and "true" (endosteal and periosteal) CSG properties, however, has yet to be examined along the whole diaphysis. Cross-sectional computed tomography scans were taken from 21 locations along humeral, femoral, and tibial diaphyses in 20 adults from a late prehistoric central Illinois Valley cemetery. Mechanical properties calculated from images with (a) artificially filled medullary cavities ("solid") and (b) true unaltered cross-sections were compared at each section location using least squares regression. Results indicate that, in this sample, polar second moments of area (J), polar section moduli (Z(p) ), and cross-sectional shape (I(max) /I(min) ) calculated from periosteal contours correspond strongly with those calculated from cross-sections that include the medullary cavity. Correlations are high throughout most of the humeral diaphysis and throughout large portions of femoral and tibial diaphyses (R(2) = 0.855-0.998, all P < 0.001, %SEE ≤ 8.0, %PE ≤ 5.0), the major exception being the proximal quarter of the tibial diaphysis for J and Z(p). The main source of error was identified as variation in %CA. Results reveal that CSG properties quantified from periosteal contours provide comparable results to (and are likely to detect the same differences among individuals as) true CSG properties along large portions of long bone diaphyses.


Particle engineering: a strategy for establishing drug substance physical property specifications during small molecule development.
A strategy for physical property control of a drug substance has been developed that utilizes a science-based approach to define key drivers for particle control. These drivers are based on in vivo performance (or expected performance), content uniformity of the drug substance in drug product, and manufacturability of drug product. Quality by design principles have been used in developing the strategy. The strategy has been designed to provide expectations in terms of particle control at each state of development, translating to early-phase projects and carrying through until launch and beyond.


A technique for localizing LDL by immunofluorescence in formalin-fixed and paraffin-embedded atherosclerotic lesions.
A protocol has been developed by which apo beta, the protein component of plasma low density lipoproteins (LDL), can be localized in four micron-thick sections of formalin-fixed and paraffin-embedded arteries with atherosclerotic involvement from man or non-human primate. An immunofluorescence procedure was employed that utilized affinity column-purified antibody coupled to fluorescein isothiocyanate (FITC). Although fixation reduced the intensity of fluorescence relative to that in cryostat sections, sufficient sensitivity was usually achieved when microscopy was performed using incident-light fluorescence together with a filter system adjusted for maximum absorption of FITC and by using oil immersion objectives. Furthermore, the use of various counterstains altered the color of the autofluorescence, normally strongly yellow, thus greatly enhancing the contrast and visualization of the apple green specific fluorescence. Non-chelated eriochrome black reduced tissue autofluorescence to barely visible levels, a feature useful in black and white photographs to demonstrate the localization pattern of LDL in arteries. This stain also reduced non-specific fluorescence. Other counterstains that proved useful were emthyl green, flazo orange and chelated eriochrome black. The latter two were particularly valuable for cellular detection. At low magnification LDL localization in atherosclerotic lesions from both human aortas and coronary arteries from monkeys fed an atherogenic diet, gave a pattern similar to those reported in cryostat sections of human lesions. At higher magnification, the improved detail of LDL localization could presumably be discerned as a result of immobilization of the soluble antigen by fixation, and by the ability to cut thinner sections of embedded material. This immunofluorescence procedure to localize LDL in formalin-fixed and paraffin-embedded atherosclerotic lesions should prove useful in both prospective as well as retrospective studies on clinical or chemical-pathological correlative studies on human tissues or in studies on atherogenesis using animal models.


Movement and habitat selection of the western spadefoot (Spea hammondii) in southern California.
Agricultural activity, urban development and habitat alteration have caused the disappearance of the western spadefoot (Spea hammondii) from 80% of its geographic range in southern California. Despite the western spadefoot's continuing decline, little research has been conducted on its natural history. The home range of adult spadefoots is unknown, and their use of upland habitat is poorly understood. Both factors are important for the long-term conservation of the species because adult spadefoots spend the majority of their lives away from breeding pools in self-excavated burrows. Between January 2012 and January 2013, we surgically implanted radio transmitters in 15 spadefoots at two locations and recorded their movements and habitat use. The mean distance moved between burrow locations was 18 m (SD ± 24.1 m, range1-204 m). The mean distance of burrows from the breeding pools was 40 m (SD ± 37.42 m, range 1-262 m). Rain was a significant predictor of spadefoot movement, with more rain predicting higher probability of movement and larger distances moved. At remote sensing scale (1 m) spadefoots selected grassland habitat for their burrow locations. At the microsite scale (< 1 m) spadefoots strongly selected duff over grass or shrub cover. Spadefoots burrowed in friable, sandy/loam soil with significantly less clay than random pseudoabsence points. This research enhances our understanding of a little-studied species and will contribute to the development of effective management plans for the western spadefoot.


Serum Autotaxin/ENPP2 correlates with insulin resistance in older humans with obesity.
Autotaxin (ATX) is an adipocyte-derived lysophospholipase D that generates the lipid signaling molecule lysophosphatidic acid (LPA). The ATX/LPA pathway in adipose tissue has recently been implicated in obesity and insulin resistance in animal models, but the role of circulating ATX in humans remains unclear. The aim of the present study was to determine the relationship between serum ATX and insulin resistance. Older (60-75 years), nondiabetic human participants with overweight or obesity (BMI 25-37 kg m(-2) ) were characterized for metabolic phenotype including measures of energy, glucose, and lipid homeostasis. The relationship between serum ATX and metabolic parameters was then determined using correlative and predictive statistics. Serum ATX was higher in females than in males. After controlling for sex, serum ATX correlated with multiple measures of adiposity and glucose homeostasis/insulin action. Serum ATX and BMI also independently predicted glucose infusion rate during a hyperinsulinemic euglycemic clamp and homeostatic model assessment of insulin resistance after controlling for sex and medication use. Serum ATX correlates with and predicts measures of glucose homeostasis and insulin sensitivity in older humans, suggesting that it may be a potential pathogenic factor and/or diagnostic/therapeutic target for insulin resistance in this population.


Investigating intracellular persistence of Staphylococcus aureus within a murine alveolar macrophage cell line.
Staphylococcus aureus is a particularly difficult pathogen to eradicate from the respiratory tract. Previous studies have highlighted the intracellular capacity of S.aureus in several phagocytic and non-phagocytic cells. The aim of this study was to define S.aureus interaction within a murine alveolar macrophage cell line. Cell line MH-S was infected with Newman strain. Molecular mechanisms involved in phagocytosis were explored. To assess whether S.aureus survives intracellularly quantitative (gentamicin protection assays and bacterial plating) and qualitative analysis (immunofluorescence microscopy) were performed. Bacterial colocalization with different markers of the endocytic pathway was examined to characterize its intracellular trafficking. We found that S.aureus uptake requires host actin polymerization, microtubule assembly and activation of phosphatidylinositol 3-kinase signaling. Time course experiments showed that Newman strain was able to persist within macrophages at least until 28.5 h post infection. We observed that intracellular bacteria are located inside an acidic subcellular compartment, which co-localizes with the late endosome/lysosome markers Lamp-1, Rab7 and RILP. Colocalization counts with TMR-dextran might reflect a balance between bacterial killing and intracellular survival. This study indicates that S.aureus persists and replicates inside murine alveolar macrophages, representing a privileged niche that can potentially offer protection from antimicrobial activity and immunological host defense mechanisms.


Infection with the human immunodeficiency virus (HIV) is associated with an in vivo increase in B lymphocyte activation and immaturity.
The expression of phenotypic markers on B lymphocytes in patients with the acquired immune deficiency syndrome (AIDS), in human immunodeficiency virus (HIV) seropositive individuals, and in healthy seronegative donors was examined by two-color flow cytometry. Patients with AIDS and HIV-seropositive individuals showed an elevated percentage of B cells bearing an activation marker, the transferrin receptor, when compared with donors not infected with HIV. A decrease in the percentage of resting (Leu-8 positive) B cells was also seen in AIDS patients and HIV-seropositive individuals. An increased percentage of circulating, immature (CALLA-positive, CD10) B cells was seen in AIDS patients. These phenotypic changes were accompanied by an increased level of spontaneous IgG and IgM secretion, and increased cell size within the total B cell population and in some B cell subpopulations, in patients with AIDS and in HIV-seropositive people. These results demonstrate that phenotypic changes indicative of in vivo B cell activation and immaturity accompany the polyclonal production of Ig seen in HIV-infected individuals.


Stroke network performance during the first COVID-19 pandemic stage: A meta-analysis based on stroke network models.
The effect of the COVID pandemic on stroke network performance is unclear, particularly with consideration of drip&ship vs. mothership models. We systematically reviewed and meta-analyzed variations in stroke admissions, rate and timing of reperfusion treatments during the first wave COVID pandemic vs. the pre-pandemic timeframe depending on stroke network model adopted. The systematic review followed registered protocol (PROSPERO-CRD42020211535), PRISMA and MOOSE guidelines. We searched MEDLINE, EMBASE, and CENTRAL until 9 October 2020 for studies reporting variations in ischemic stroke admissions, treatment rates, and timing in COVID (first wave) vs. control-period. Primary outcome was the weekly admission incidence rate ratio (IRR = admissions during COVID-period/admissions during control-period). Secondary outcomes were (i) changes in rate of reperfusion treatments and (ii) time metrics for pre- and in-hospital phase. Data were pooled using random-effects models, comparing mothership vs. drip&ship model. Overall, 29 studies were included in quantitative synthesis (n = 212,960). COVID-period was associated with a significant reduction in stroke admission rates (IRR = 0.69, 95%CI = 0.61-0.79), with higher relative presentation of large vessel occlusion (risk ratio (RR) = 1.62, 95% confidence interval (CI) = 1.24-2.12). Proportions of patients treated with endovascular treatment increased (RR = 1.14, 95%CI = 1.02-1.28). Intravenous thrombolysis decreased overall (IRR = 0.72, 95%CI = 0.54-0.96) but not in the mothership model (IRR = 0.81, 95%CI = 0.43-1.52). Onset-to-door time was longer for the drip&ship in COVID-period compared to the control-period (+32 min, 95%CI = 0-64). Door-to-scan was longer in COVID-period (+5 min, 95%CI = 2-7). Door-to-needle and door-to-groin were similar in COVID-period and control-period. Despite a 35% drop in stroke admissions during the first pandemic wave, proportions of patients receiving reperfusion and time-metrics were not inferior to control-period. Mothership preserved the weekly rate of intravenous thrombolysis and the onset-to-door timing to pre-pandemic standards.


Closing remarks: novel approaches to complex societal change and sustainability.
This paper summarizes some personal impressions of the 7th conference of the International Complex Systems Society, co-organized with "Future Earth", held in Stockholm on August 24-26, 2017. The main point is that it is urgent and important to consider the sustainability conundrum as long-term, society-driven one, and to place societal dynamics at the core of how we, as a global society, came to this point, how ongoing dynamics are driving us towards a tipping point, and which role the Information and Communication Technology revolution plays in that process. A much wider involvement of the social sciences is essential. This also requires major changes in our thinking about sustainability-we need to develop an approach in which change is the natural state of affairs and societies attempt to impose stability on the dynamics involved. We need to focus on learning from the past, about the present, but above all for the future. And we need to shift from an entity-focused approach to a relational one, which pays more attention to contexts and networks. Other issues raised by such a shift in our thinking are about the role of science, the adoption of complex systems approaches and a few others that the paper points to.


Birth setting, transfer and maternal sense of control: results from the DELIVER study.
In the Netherlands, low risk women receive midwife-led care and can choose to give birth at home or in hospital. There is concern that transfer of care during labour from midwife-led care to an obstetrician-led unit leads to negative birth experiences, in particular among those with planned home birth. In this study we compared sense of control, which is a major attribute of the childbirth experience, for women planning home compared to women planning hospital birth under midwife-led care. In particular, we studied sense of control among women who were transferred to obstetric-led care during labour according to planned place of birth: home versus hospital. We used data from the prospective multicentre DELIVER (Data EersteLIjns VERloskunde) cohort-study, conducted in 2009 and 2010 in the Netherlands. Sense of control during labour was assessed 6 weeks after birth, using the short version of the Labour Agentry Scale (LAS-11). A higher LAS-11 score indicates a higher feeling of control. We considered a difference of a minimum of 5.5 points as clinically relevant. Nulliparous- and parous women who planned a home birth had a 2.6 (95% CI 1.0, 4.3) and a 3.0 (1.6, 4.4) higher LAS score during first stage of labour respectively and during second stage a higher score of 2.8 (0.9, 4.7) and 2.3 (0.6, 4.0), compared with women who planned a hospital birth. Overall, women who were transferred experienced a lower sense of control than women who were not transferred. Parous women who planned a home birth and who were transferred had a 4.3 (0.2, 8.4) higher LAS score in 2nd stage, compared to those who planned a hospital birth and who were transferred. We found no clinically relevant differences in feelings of control among women who planned a home or hospital birth. Transfer of care during labour lowered feelings of control, but feelings of control were similar for transferred women who planned a home or hospital birth.As far as their expected sense of control is concerned, low risk women should be encouraged to give birth at the location of their preference.


The role of vitamins in cancer: a review.
Vitamins are essential nutrients for human metabolism, playing an important role as coenzymes or enzymes in many vital processes for the normal functioning of the body. In recent years, it has become apparent that vitamins are crucial in health and human disease, due to several studies that studied this relationship. Currently, it is known that vitamins can have an important role in the prevention and treatment of cancer, but until now no conclusive results were obtained. In this review, we will present the work and more relevant conclusions obtained in recent years of investigation about the relationship between vitamins and cancer, namely vitamin A, vitamin B complex, vitamin C, vitamin D, vitamin E, and vitamin K.


[Effects of space-flight factors on cytochemical characteristics of the motor analyzer neurons].
The work was designed to study metabolism of motoneurons in anterior horns of the spinal cord and sensorimotor cortex of Wistar rats after flights on Earth's satellites for 22.5 days (Kosmos-605), 19.5 days (Kosmos-782), and 18.5 days (Kosmos-936). Control rats underwent simulated space-flight factors under laboratory conditions excepting weightlessness. Rats placed in Kosmos-936 were subjected to artificial gravity (AG). They showed complete recovery of motoneuronal metabolism 25 days after landing unlike animals that had experienced weightlessness in which enhanced functional activity of the genetic apparatus was manifest as increased RNA level, protein content, and nuclei size. These finding may reflect differences of neuronal metabolism in animals experiencing weightlessness and AG. We believe they may be due to reduced static load on the locomotor system during the space flight.


Effect of infection with bovine respiratory syncytial virus on pulmonary clearance of an inhaled antigen in calves.
To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves. Eleven 6- to 8-week-old Holstein bull calves. Aerosolized (99m)technetium ((99m)Tc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and (99m)Tc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined. Clearance of (99m)Tc-DTPA was significantly increased during BRSV infection; clearance of (99m)Tc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of (99m)Tc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of (99m)Tc-OA were detected at time points when pulmonary clearance of (99m)Tc-OA was most delayed. BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease. Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.


A yeast-like mRNA capping apparatus in Plasmodium falciparum.
Analysis of the mRNA capping apparatus of the malaria parasite Plasmodium falciparum illuminates an evolutionary connection to fungi rather than metazoans. We show that P. falciparum encodes separate RNA guanylyltransferase (Pgt1) and RNA triphosphatase (Prt1) enzymes and that the triphosphatase component is a member of the fungal/viral family of metal-dependent phosphohydrolases, which are structurally and mechanistically unrelated to the cysteine-phosphatase-type RNA triphosphatases found in metazoans and plants. These results highlight the potential for discovery of mechanism-based antimalarial drugs designed to specifically block the capping of Plasmodium mRNAs. A simple heuristic scheme of eukaryotic phylogeny is suggested based on the structure and physical linkage of the triphosphatase and guanylyltransferase enzymes that catalyze cap formation.


Involvement of IFN-gamma receptor-medicated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection.
IFN-gamma has been implicated in the pathogenesis of experimental cerebral malaria (ECM). We have used mice lacking the alpha chain of the IFN-gamma receptor (KO mice) to define its role in the pathogenesis of ECM. Infected KO mice did not develop ECM and showed no leukocyte or parasite sequestration in the brain, and no hemorrhages. The resistance of KO mice to ECM was associated with the absence of any increases of TNF-alpha and ICAM-1 proteins in the brain, which are both essential for ECM. Wild-type (WT) mice which do not develop ECM, despite increased local production of TNF-alpha protein, showed no leukocyte accumulation in the brain and this was correlated with the absence of ICAM-1 protein from brain microvessels. KO mice infected with 106 parasitized erythrocytes (PE) of Plasmodium berghei ANKA (PbA) did not develop ECM, but they had high parasitemia and died earlier than WT mice which did not develop ECM. However, KO mice did not develop higher parasitemia than WT mice when both groups were infected with a lower dose (5x10(5) PE) of PbA-infected red blood cells. This indicates that different doses of PE may trigger different IFN-gamma responses and that there may be a threshold concentration for protection against parasitemia.


Effects of changing gonadotropin-releasing hormone pulse frequency and estrogen treatment on levels of estradiol receptor-alpha and induction of Fos and phosphorylated cyclic adenosine monophosphate response element binding protein in pituitary gonadotropes: studies in hypothalamo-pituitary disconnected ewes.
Estrogen receptor-alpha (ER alpha) levels in gonadotropes are increased during the follicular phase of the ovine estrous cycle, a time of increased frequency of pulsatile secretion of GnRH and elevated plasma estrogen levels. In the present study, our first aim was to determine which of these factors causes the rise in the number of gonadotropes with ER alpha. Ovariectomized hypothalamo-pituitary disconnected ewes (n = 4-6) received the following treatments: 1) no treatment, 2) injection (im) of 50 microg estradiol benzoate (EB), 3) pulses (300 ng iv) of GnRH every 3 h, 4) GnRH treatment as in group 3 and EB treatment as in group 2, 5) increased frequency of GnRH pulses commencing 20 h before termination, and 6) GnRH treatment as in group 5 with EB treatment. These treatments had predictable effects on plasma LH levels. The number of gonadotropes in which ER alpha was present (by immunohistochemistry) was increased by either GnRH treatment or EB injection, but combined treatment had the greatest effect. Immunohistochemistry was also performed to detect phosphorylated cAMP response element binding protein (pCREB) and Fos protein in gonadotropes. The number of gonadotropes with Fos and with pCREB was increased only in group 6. We conclude that either estrogen or GnRH can up-regulate ER alpha in pituitary gonadotropes. On the other hand, during the period of positive feedback action of estrogen, the appearance of pCREB and Fos in gonadotropes requires the combined action of estrogen and increased frequency of GnRH input. This suggests convergence of signaling for GnRH and estrogen.


The challenge of acute rheumatic fever diagnosis in a high-incidence population: a prospective study and proposed guidelines for diagnosis in Australia's Northern Territory.
Accurate diagnosis of acute rheumatic fever (ARF) remains problematic in high-incidence settings and especially in the Aboriginal population of Australia's Northern Territory. Previous investigators have demonstrated that strict application of the 1992 Updated Jones Criteria results in under-diagnosis. This study's objectives were to review use of the Jones Criteria (1992 Update) in diagnosing ARF in Australian Aboriginal patients presenting with suspected rheumatic fever, and formulate a locally relevant algorithm to improve diagnosis. Patients presenting to Royal Darwin Hospital with suspected ARF were prospectively assessed during a 15-month period. Demographic information, clinical history, examination, laboratory and echocardiographic findings were documented in order to determine whether the Jones Criteria were fulfilled, and to identify alternative diagnoses. The hospital discharge diagnosis was recorded and patients were followed up 18-33 months later. Out of 35 patients with suspected ARF, all were Aboriginal Australians, 17 (49%) had a discharge diagnosis of definite ARF, 7 (20%) had definite non-rheumatic fever diagnoses (disseminated gonococcal infection, systemic lupus erythematosis, buttock abscess and other febrile illnesses in children with cardiac murmur due to previously undiagnosed RHD). The remaining 11 (31%) posed diagnostic difficulties because of mild symptoms that failed to fulfil Jones Criteria (attracting diagnoses such as 'unexplained arthralgia') or atypical features such as older age. Two patients whose illness initially failed to fulfil the Jones Criteria, who were neither diagnosed with ARF nor commenced on secondary benzathine penicillin prophylaxis, were found on follow-up to have definite and probable ARF, respectively. At least 29% (8/28) of patients without prior recognised ARF/RHD had echocardiographic evidence of established RHD, indicating that previous episodes were missed. Individual mild episodes of ARF may be overlooked, with patients missing out on the timely institution of secondary prophylaxis. The Jones Criteria should be supplemented by active exclusion of differential diagnoses and vigilant follow-up including echocardiography. 'Probable' and 'possible ARF' should be recognised as diagnostic categories applying to patients not fulfilling the Jones Criteria but who nevertheless should be offered prophylactic penicillin at least until further follow-up. A set of diagnostic guidelines is proposed.


Procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 are potential prognostic indicators in patients with clear cell renal cell carcinoma.
Intratumoral fibrosis is a frequent histologic finding in highly vascularized clear cell renal cell carcinoma (ccRCC). Here, we investigated the expression of a family of collagen-modifying enzymes, procollagen-lysine, 2-oxoglutarate 5-dioxygenases 1, 2, and 3 (PLOD1/2/3), in ccRCC tissues and assessed the prognostic value of wild-type and genetically mutated PLOD1/2/3 for ccRCC patients. Normal kidney and ccRCC mRNA and protein expression datasets were obtained from Oncomine, The Cancer Genome Atlas, and Human Protein Atlas databases. Associations between PLOD1/2/3 expression, clinicopathological variables, and patient survival were evaluated using Cox regression and Kaplan-Meier analyses. PLOD1/2/3 mRNA and protein expression levels were significantly elevated in ccRCC tissues compared with normal kidney. Increased PLOD1/2/3 mRNA expression was significantly associated with advanced tumor stage, high pathological grade, and shorter progression-free and overall survival (all p<0.01). Genetic mutation of PLOD1/2/3 was present in ~3% of ccRCC patients and was associated with significantly poorer prognosis compared with expression of wild-type PLOD1/2/3 (p<0.001). This study thus identifies tumor expression of wild-type or mutated PLOD1/2/3 mRNA as a potential predictive biomarker for ccRCC patients and sheds light on the underlying molecular pathogenesis of ccRCC.


Statin intolerance - a question of definition.
Statin therapy is the backbone of pharmacologic therapy for low-density lipoproteins cholesterol lowering and plays a pivotal role in cardiovascular disease prevention. Statin intolerance is understood as the inability to continue using a statin to reduce individual cardiovascular risk sufficiently, due to the development of symptoms or laboratory abnormalities attributable to the initiation or dose escalation of a statin. Muscle symptoms are the most common side effects observed. Areas covered: The main aim of this article is to present a review on published definitions of statin intolerance. In addition, a brief review on clinical aspects and risk factors of statin intolerance is provided and features for a common definition for statin intolerance are suggested. Expert opinion: A definition of statin intolerance by major drug regulatory agencies is not available. In clinical studies, different definitions are chosen and results are not comparable; different medical associations do not agree on one common definition. There is an unmet need to establish a common definition of statin intolerance to ensure an appropriate clinical use of this important drug class. Further work is required to develop a consensus definition on statin intolerance that could have significant positive impact on both research and clinical management.


Multimodality Intracoronary Imaging With Near-Infrared Spectroscopy and Intravascular Ultrasound in Asymptomatic Individuals With High Calcium Scores.
This study sought to determine the frequency of large lipid-rich plaques (LRP) in the coronary arteries of individuals with high coronary artery calcium scores (CACS) and to determine whether the CACS correlates with coronary lipid burden. Combined near-infrared spectroscopy and intravascular ultrasound was performed in 57 vessels in 20 asymptomatic individuals (90% on statins) with no prior history of coronary artery disease who had a screening CACS ≥300 Agatston units. Among 268 10-mm coronary segments, near-infrared spectroscopy images were analyzed for LRP, defined as a bright yellow block on the near-infrared spectroscopy block chemogram. Lipid burden was assessed as the lipid core burden index (LCBI), and large LRP were defined as a maximum LCBI in 4 mm ≥400. Vessel plaque volume was measured by quantitative intravascular ultrasound. Vessel-level CACS significantly correlated with plaque volume by intravascular ultrasound (r=0.69; P<0.0001) but not with LCBI by near-infrared spectroscopy (r=0.24; P=0.07). Despite a high CACS, no LRP was detected in 8 (40.0%) subjects. Large LRP having a maximum LCBI in 4 mm ≥400 were infrequent, found in only 5 (25.0%) of 20 subjects and in only 5 (1.9%) of 268 10-mm coronary segments analyzed. Among individuals with a CACS ≥300 Agatston units mostly on statins, CACS correlated with total plaque volume but not LCBI. This observation may have implications on coronary risk among individuals with a high CACS considering that it is coronary LRP, rather than calcification, that underlies the majority of acute coronary events.


Coordinate changes in histone modifications, mRNA levels, and metabolite profiles in clonal INS-1 832/13 β-cells accompany functional adaptations to lipotoxicity.
Lipotoxicity is a presumed pathogenetic process whereby elevated circulating and stored lipids in type 2 diabetes cause pancreatic β-cell failure. To resolve the underlying molecular mechanisms, we exposed clonal INS-1 832/13 β-cells to palmitate for 48 h. We observed elevated basal insulin secretion but impaired glucose-stimulated insulin secretion in palmitate-exposed cells. Glucose utilization was unchanged, palmitate oxidation was increased, and oxygen consumption was impaired. Halting exposure of the clonal INS-1 832/13 β-cells to palmitate largely recovered all of the lipid-induced functional changes. Metabolite profiling revealed profound but reversible increases in cellular lipids. Glucose-induced increases in tricarboxylic acid cycle intermediates were attenuated by exposure to palmitate. Analysis of gene expression by microarray showed increased expression of 982 genes and decreased expression of 1032 genes after exposure to palmitate. Increases were seen in pathways for steroid biosynthesis, cell cycle, fatty acid metabolism, DNA replication, and biosynthesis of unsaturated fatty acids; decreases occurred in the aminoacyl-tRNA synthesis pathway. The activity of histone-modifying enzymes and histone modifications of differentially expressed genes were reversibly altered upon exposure to palmitate. Thus, Insig1, Lss, Peci, Idi1, Hmgcs1, and Casr were subject to epigenetic regulation. Our analyses demonstrate that coordinate changes in histone modifications, mRNA levels, and metabolite profiles accompanied functional adaptations of clonal β-cells to lipotoxicity. It is highly likely that these changes are pathogenetic, accounting for loss of glucose responsiveness and perturbed insulin secretion.


Campus Service Use Among Students With Disabilities Who Have Experienced Sexual Violence: A Conceptual Model.
Students with disabilities are one student group with elevated risk of sexual violence. Although they would benefit from streamlined access to campus support, little is known about their patterns of campus service use. This qualitative analysis includes data from semi-structured interviews with 51 students with disabilities who experienced sexual violence focused on service use across campus. The resultant conceptual model shows that greater accessibility is associated with positive experiences, and lower accessibility is associated with negative experiences. Students with disabilities who experienced or expected negative reactions (e.g., judgment) were less likely to use services and were less satisfied. Advocacy and support in connecting students with disability or sexual violence services was associated with positive experiences and increased accessibility. These findings highlight key facilitators and barriers to campus service use for students with disabilities with sexual violence histories and suggest key intervention points for increasing accessibility, reducing stigma, and improving student experiences with campus providers, staff, and faculty.


Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against CCl4-induced liver injury in rats.
Curcumin and saikosaponin a, the bioactive phytochemicals of turmeric and Bupleurum, act as antioxidants. This study investigated the effects of supplementation with curcumin and/or saikosaponin a on hepatic lipids and antioxidant status in rats with CCl(4)-induced liver injury. Male Sprague-Dawley rats were randomly divided into control, CCl(4), CCl(4) + curcumin (0.005%; CU), CCl(4) + saikosaponin a (0.004%; SS), and CCl(4) + curcumin + saikosaponin a (0.005% + 0.004%; CU+SS) groups. CCl(4) (40% in olive oil) was injected intraperitoneally at a dose of 0.75 mL/kg once a week. Curcumin and/or saikosaponin a was administered orally 1 week before CCl(4) injection for 8 weeks. The pathological results showed that liver fibrosis was ameliorated in the SS and CU+SS groups. After 8 weeks, supplementation with curcumin and/or saikosaponin a significantly decreased plasma alanine aminotransferase and aspartate aminotransferase activities, as well as plasma and hepatic cholesterol and triglyceride levels. The CU+SS group showed reversal of the impaired hepatic superoxide dismutase activity and an increase in total glutathione level. Supplementation with curcumin and/or saikosaponin a significantly improved hepatic antioxidant status and suppressed malondialdehyde formation. Therefore, supplementation with curcumin and/or saikosaponin a protects against CCl(4)-induced liver injury by attenuating hepatic lipids and lipid peroxidation and enhancing antioxidant defense. Curcumin and saikosaponin a had no additive effects on hepatoprotection except for greater improvement in the total glutathione level and antioxidant status.


An efficient Bayesian inference framework for coalescent-based nonparametric phylodynamics.
The field of phylodynamics focuses on the problem of reconstructing population size dynamics over time using current genetic samples taken from the population of interest. This technique has been extensively used in many areas of biology but is particularly useful for studying the spread of quickly evolving infectious diseases agents, e.g. influenza virus. Phylodynamic inference uses a coalescent model that defines a probability density for the genealogy of randomly sampled individuals from the population. When we assume that such a genealogy is known, the coalescent model, equipped with a Gaussian process prior on population size trajectory, allows for nonparametric Bayesian estimation of population size dynamics. Although this approach is quite powerful, large datasets collected during infectious disease surveillance challenge the state-of-the-art of Bayesian phylodynamics and demand inferential methods with relatively low computational cost. To satisfy this demand, we provide a computationally efficient Bayesian inference framework based on Hamiltonian Monte Carlo for coalescent process models. Moreover, we show that by splitting the Hamiltonian function, we can further improve the efficiency of this approach. Using several simulated and real datasets, we show that our method provides accurate estimates of population size dynamics and is substantially faster than alternative methods based on elliptical slice sampler and Metropolis-adjusted Langevin algorithm. The R code for all simulation studies and real data analysis conducted in this article are publicly available at http://www.ics.uci.edu/∼slan/lanzi/CODES.html and in the R package phylodyn available at https://github.com/mdkarcher/phylodyn. firstname.lastname@example.com or firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


An Advanced Pharmacy Practice Framework for Australia.
The need to develop An Advanced Pharmacy Practice Framework for Australia (the "APPF") was identified during the 2010 review of the competency standards for Australian pharmacists. The Advanced Pharmacy Practice Framework Steering Committee, a collaborative profession-wide committee comprised of representatives of ten pharmacy organisations, examined and adapted existing advanced practice frameworks, all of which were found to have been based on the Competency Development and Evaluation Group (CoDEG) Advanced and Consultant Level Framework (the "CoDEG Framework") from the United Kingdom. Its competency standards were also found to align well with the Domains of the National Competency Standards Framework for Pharmacists in Australia (the "National Framework"). Adaptation of the CoDEG Framework created an APPF that is complementary to the National Framework, sufficiently flexible to customise for recognising advanced practice in any area of professional practice and has been approved by the boards/councils of all participating organisations. The primary purpose of the APPF is to assist the development of the profession to meet the changing health care needs of the community. However, it is also a valuable tool for assuring members of the public of the competence of an advanced practice pharmacist and the quality and safety of the services they deliver.


Bryo-FIGHTs: Emerging insights and principles acquired from non-vascular plant-pathogen interactions.
Since the dawn of land plant evolution, pathogenic microbes have impacted plant health and threatened their survival. Though much of our knowledge on plant-pathogen interactions is derived from flowering plants, emerging research leveraging evolutionarily divergent non-vascular/non-seed bryophytes is beginning to shed light on the history and diversity of plant immune and infection processes. Here, we highlight key bryophyte-microbe pathosystems used to address fundamental questions on plant health. To this end, we outline the idea that core molecular aspects impacting plant infection and immunity are likely conserved across land plants. We discuss recent advances in the emerging field of Evo-MPMI (evolutionary molecular plant-microbe interactions) and highlight future opportunities that will clarify our understanding of the evolutionary framework that underpins host-pathogen interactions across the full spectrum of plant evolution.


A developmental investigation of the first-letter advantage.
Skilled adult readers identify the first letter in a string of random consonants better than letters at any other position, and this advantage for the initial position is not seen with strings of symbols or familiar shapes. Here we examined the developmental trajectory of this first-letter advantage by testing children in Grades 1 to 5 of primary education in a target-in-string identification paradigm. Strings of five letters or five simple shapes were briefly presented, and children were asked to identify a target letter/shape at one of the five possible positions. Children responded by choosing between the target and an alternative that was a neighboring letter/shape (e.g., TPFMR-M vs. F at position 4). The serial position function linking accuracy to position-in-string was found to be affected by reading ability differently for letter stimuli compared with shape stimuli, and this was found to be almost entirely driven by differences in performance in identifying targets at the first position in strings. Here, accuracy increased more rapidly for letter stimuli than for shape stimuli as reading ability increased. This developmental pattern, plus the fact that letter strings were composed of random consonants and the task minimized the involvement of verbal recoding, allows us to exclude an explanation of the first-letter advantage in terms of serial reading strategies or phonological decoding. The findings suggest that the first-letter advantage is a function of, and a marker for, increasingly efficient orthographic processing.


[Health economic analysis of the effects of including complementary medicine in the benefit package of health insurance].
A randomized experiment was set up in which 7,500 policyholders of Switzerland's largest health insurance fund, Helvetia, were offered free supplementary insurance for complementary medicine for 3 years. This was meant to simulate a situation in which the experimental group had access to the full range of complementary medical treatments under their health insurance policies. The remaining policyholders in the scheme (670,000 people) formed the control group. A third group of policyholders who had taken out additional insurance for complementary medical services at their own expense is mentioned only in passing. The health insurer's cost and benefit data were analyzed to evaluate the effect of the offered free supplementary insurance for complementary medicine. In addition, a survey was carried out among random samples of subjects from the experimental group and from the control group using the 36-Item Short-Form Health Survey (SF-36) to examine the effects of including complementary medicine on people's subjective state of health. The analysis of the cost data showed that subjects in the experimental group used complementary medicine in addition to mainstream medical services. It became also clear that alternative medical treatments were given in combination with orthodox medicine; less than 1% of the experimental group used exclusively alternative medical services. However, as only a very small percentage of the experimental subjects (6.6%) took advantage of complementary medicine, no significant impact on overall health cost could be inferred. On the other hand, multiple regressions showed that the use of complementary medicine had a greater effect on the treatment costs than sex, age or language region. Neither at the beginning nor the end of the experiment were any significant differences noted in the scales of the SF-36 between the experimental and the control group; nor did multiple regressions reveal any effects on subjects' state of health due to the inclusion of complementary medicine in the basic insurance cover. This study was presented in the media and at a public hearing of the Swiss National Science Foundation. It triggered numerous valuable discussions. The study design and the conclusions were not left uncontested.


The power of an integrated informatic and molecular approach to type 1 diabetes research.
Recent years have witnessed an explosive growth in available biological data. This includes a tremendous quantity of sequence data (e.g., biological structures, genetic and physical maps, pathways) generated by genome and transcriptome projects focused on humans, mice, and a multitude of other species. Diabetes research stands to greatly benefit from this data, which is distributed across public and private databases and the scientific literature. The increasing quantity and complexity of this biological data necessitates use of novel bioinformatics strategies for its efficient retrieval, analysis, and interpretation. Bioinformatic capability is becoming increasingly indispensable for fast and comprehensive analysis of biological data by diabetes researchers. There is great potential for diabetes scientists and clinicians to take advantage of recent bioinformatics and knowledge discovery developments to radically transform and advance this field of research. This paper will review advances in the field of bioinformatics relevant to diabetes research and preview a new specialty diabetes database, Diabetaeta, that we are creating to serve as a central bioinformatic portal for type 1 diabetes research, as well as serving as a public repository for beta cell gene and protein expression data.


Bipolar radiofrequency ablation is useful for treating atrial fibrillation combined with heart valve diseases.
Atrial fibrillation (AF) is a common arrhymia, and it results in increased risk of thromboembolism and decreased cardiac function. In patients undergoing cardiac surgery, concomitant radiofrequency ablation to treat AF is effective in restoring sinus rhythm (SR). This study is an observational cohort study aimed to investigate the safety and efficacy of bipolar radiofrequency ablation (BRFA) for treating AF combined with heart valve diseases. Clinical data were analyzed retrospectively from 324 cases of rheumatic heart disease combined with persistent AF patients who underwent valve replacement concomitant BRFA. The modified left atrial and the simplified right atrial ablation were used for AF treatments. Of the 324 patients, 248 patients underwent mitral valve replacement and 76 patients underwent double valve replacement. Meanwhile, 54 patients underwent concomitant thrombectomy and 97 underwent tricuspid valvuloplasty. And all of them received temporary pacemaker implantation. The 24 hours holter electrocardiogram (ECG) monitoring and echocardiography was performed before the operation, on the first day after operation, on discharge day, and at 6 and 12 months after operation. There were 299 patients with SR on the first day after operation (92.30%), 12 patients with junctional rhythm (3.70%), 11 patients with AF (3.39%), and 2 patients with atrial flutter (0.62%). The temporary pacemaker was used in 213 patients (65.74%) with heart rates less than 70 beat/minute in the ICU. Two patients died early and the mortality rate was 0.62%. Two patients had left ventricular rupture and the occurrence rate was 0.62%. They both recovered. There was no degree III atrioventricular blockage and no permanent pacemaker implantation. Overall survival rate was 99.38% (322 cases) with SR conversion rate of 89.13% (287 cases) at discharge. The SR conversion rate was 87.54% and 87.01% at 6 and 12 months after operation. Sinus bradycardia occurred in 3.42% of patients at 6 months after operation and in 3.03% of patients at 12 months after operation. Echocardiography showed that the left atrial diameter was significantly decreased, and ejection fraction and fractional shortening were significantly improved. BRFA for treating AF in concomitant valve replacement is safe and with good efficacy.


Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for liver cancer.
Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Sorafenib is the only drug for patients with advanced-stage hepatocellular carcinoma (HCC) that has been shown to confer a survival benefit to patients with HCC; however, it has many side effects. Thus, alternate therapeutic strategies with improved safety and therapeutic efficacy for the management of HCC should be developed. We demonstrate that an extract of Graptopetalum paraguayense (GP) down-regulated the expression levels of several onco-proteins, including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active components in the GP extracts, we prepared extracts fractions and assessed their effects on the expression of onco-proteins in HCC cells. The fraction designated HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and suppressed the expression of the onco-proteins in HCC cells. The structure of the main active compound in HH-F3 was found to be similar to that of the proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in HCC cells by promoting the loss of mitochondrial membrane potential and the production of reactive oxygen species. HH-F3 also enhanced PTEN expression and decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically inhibits the proliferation of Huh7 cells. The treatment of a rat model with diethylnitrosamine (DEN)-induced liver cancer with extracts of GP and HH-F3 decreased hepatic collagen contents and inhibited tumor growth. These results indicate that GP extracts and HH-F3 can protect the liver by suppressing tumor growth; consequently, these compounds could be considered for the treatment of HCC.


[Behavior of ketoamine in animals].
A simple ketoamine 14C-fructosoglycine with all the fructose carbon atoms labelled was synthesized for studies of possible pathways of the ketoamines metabolism in animal body. The ketoamine bond in the fructosoglycine was not hydrolyzed during incubation with homogenates of rabbit liver, kidney, spleen and testicular tissues within 3 hrs at pH 4.8 and 7.3 as well as after hydrolysis with pancreatine (the enzymatic extract from bovine pancreas) at pH 8.4. 14C-fructosoglycine administered into rabbit circulation was mainly excreted with urine (about 70% of the label) within 8-14 days. The main part of the ketoamine was excreted as fructosoglycine and the lower amount--as glycated dipeptide; some amount of fructosoglycine was hydrolyzed liberating fructose or converted into aldimine which was hydrolyzed with formation of glucose. The ketoamine was metabolized also into non-reducing isosucrose-like glucofructoside, insensitive to acid and enzymatic hydrolysis.


Microfluidic fabrication of photo-responsive hydrogel capsules.
We report thermo- and photo-responsive hydrogel capsules, providing controlled encapsulation and triggered release of water-soluble encapsulants. Monodisperse O/W/O (oil-in-water-in-oil) double-emulsion drops are produced in a capillary microfluidic device as templates, which transform into hydrogel capsules upon polymerization of thermo-sensitive monomers in the water phase containing gold nanorods.


Ephrin B1-mediated repulsion and signaling control germinal center T cell territoriality and function.
Follicular T helper (TFH) cells orchestrate the germinal center (GC) reaction locally. Local mechanisms regulating their dynamics and helper functions are not well defined. Here we found that GC-expressed ephrin B1 (EFNB1) repulsively inhibited T cell to B cell adhesion and GC TFH retention by signaling through TFH-expressed EPHB6 receptor. At the same time, EFNB1 promoted interleukin-21 production from GC TFH cells by signaling predominantly through EPHB4. Consequently, EFNB1-null GCs were associated with defective production of plasma cells despite harboring excessive TFH cells. In a competitive GC reaction, EFNB1-deficient B cells more efficiently interacted with TFH cells and produced more bone-marrow plasma cells, likely as a result of gaining more contact-dependent help. Our results reveal a contact-dependent repulsive guidance system that controls GC TFH dynamics and effector functions locally.


Exploring the relationship between acculturation and smoking behavior within four Southeast Asian communities of Minnesota.
This study sought to measure the prevalence of smoking among the Hmong, Vietnamese, Lao, and Cambodian communities of Minnesota and explore the relationship between smoking and acculturation within these communities. A community-based participatory research framework was used through all phases of this study. Standard as well as community-developed measures of acculturation were used. Data were obtained by face-to-face and telephone interviews with 1,628 respondents from July 2006 to March 2007. Vietnamese and Cambodian men smoke at higher rates than men in the U.S. general population (35% and 58% compared with 20%, respectively). Most men across the Vietnamese, Cambodian, and Lao populations started smoking prior to immigration to the United States, although most former smokers quit smoking after immigration to the United States. Most male Hmong respondents started smoking after immigration. Education was predictive of smoking status across genders, with less education associated with greater odds of being a smoker. Logistic regression found some acculturation measures to be predictive of smoking status across both genders: Less acculturated male respondents and more acculturated female respondents are more likely to be smokers. Results of this study suggest that the role of acculturation in tobacco use may not be straightforward as has been presented previously. Other factors, such as social norms and cultural or linguistic isolation, may also be playing a role in tobacco use patterns and may play different roles for different subgroups. Further research is needed within each population and subgroups within those populations to understand these relationships and how they affect smoking behavior.


Toward jet injection by continuous-wave laser cavitation.
This is a study motivated by the need to develop a needle-free device for eliminating major global healthcare problems caused by needles. The generation of liquid jets by means of a continuous-wave laser, focused into a light absorbing solution, was studied with the aim of developing a portable and affordable jet injector. We designed and fabricated glass microfluidic devices, which consist of a chamber where thermocavitation is created and a tapered channel. The growth of a vapor bubble displaces and expels the liquid through the channel as a fast traveling jet. Different parameters were varied with the purpose of increasing the jet velocity. The velocity increases with smaller channel diameters and taper ratios, whereas larger chambers significantly reduce the jet speed. It was found that the initial position of the liquid-air meniscus interface and its dynamics contribute to increased jet velocities. A maximum velocity of 94±3 m/s for a channel diameter of D=120 μm, taper ratio n=0.25, and chamber length E=200 μm was achieved. Finally, agarose gel-based skin phantoms were used to demonstrate the potential of our devices to penetrate the skin. The maximum penetration depth achieved was ∼1 mm, which is sufficient to penetrate the stratum corneum and for most medical applications. A meta-analysis shows that larger injection volumes will be required as a next step to medical relevance for laser-induced jet injection techniques in general.


Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways.
Osteoblasts and adipocytes originate from a common progenitor, which arises from bone marrow mesenchymal stroma/stem cells (mMSC). Aging causes a decrease in the number of bone-forming osteoblasts and an increase in the number of marrow adipocytes. Here, we demonstrate that, during aging, the status of mMSC changes with respect to both their intrinsic differentiation potential and production of signaling molecules, which contributes to the formation of a specific marrow microenvironment necessary for maintenance of bone homeostasis. Aging causes a decrease in the commitment of mMSC to the osteoblast lineage and an increase in the commitment to the adipocyte lineage. This is reflected by changes in the expression of phenotype-specific gene markers. The expression of osteoblast-specific transcription factors, Runx2 and Dlx5, and osteoblast markers, collagen and osteocalcin, is decreased in aged mMSC. Conversely, the expression of adipocyte-specific transcription factor PPAR-gamma2, shown previously to regulate osteoblast development and bone formation negatively and to regulate marrow adipocyte differentiation positively, is increased, as is a gene marker of adipocyte phenotype, fatty acid binding protein aP2. Furthermore, production of an endogenous PPAR-gamma activator(s) that stimulates adipocyte differentiation and production of autocrine/paracrine factor(s) that suppresses the osteoblastic phenotype are also increased. In addition, expression of different components of TGF-beta and BMP2/4 signaling pathways is altered, suggesting that activities of these two cytokines essential for bone homeostasis change with aging.


Barriers and facilitators to caring for individuals with stroke in the community: the family's experience.
This project explored caregivers' perceptions regarding the barriers and facilitators to undertaking the post-stroke caregiving role, particularly as related to the health care system, with the ultimate goal of identifying potential strategies that would assist families in successfully undertaking the role. A qualitative study consisting of focus groups and individual interviews with caregivers of persons with stroke. Participants were asked about their needs in managing the care of their family member and the factors that facilitated and/or hindered the transition to the home and influenced them in maintaining their role. Information from 14 caregiver participants identified the following as primary barriers to undertaking and maintaining the caregiving role: lack of collaboration with the health care team, the intensity of the caregiving role, the negative impact on the caregiver, and the lack of community support for the caregiving role. Caregivers identified the following factors as facilitative: coordination of care, progress of the patient towards normalcy, mastery of the caregiving role, supportive social environment, and accessible community resources. The results indicate there are facilitators that caregivers perceive as important both to undertaking and to sustaining the caregiving role. Consideration of these results in the design of interventions may lead to more effective interventions to support caregivers in undertaking and continuing in the caregiver role.