Factors motivating the use of respiratory protection against volcanic ashfall: A comparative analysis of communities in Japan, Indonesia and Mexico.
Communities living near active volcanoes may be exposed to respiratory hazards from volcanic ash. Understanding their perception of the risks and the actions they take to mitigate against those risks is important for developing effective communication strategies. To investigate this issue, the first comparative study of risk perceptions and use of respiratory protection was conducted on 2003 residents affected by active volcanoes from three countries: Japan (Sakurajima volcano), Indonesia (Merapi and Kelud volcanoes) and Mexico (Popocatépetl volcano). The study was designed to test the explanatory value of a theoretical framework which hypothesized that use of respiratory protection (i.e., facemask) would be motivated by two cognitive constructs from protection motivation theory: threat appraisal (i.e., perceptions of harm/ worry about ash inhalation) and coping appraisal (i.e., beliefs about mask efficacy). Using structural equation modelling (SEM), important differences in the predictive ability of the constructs were found between countries. For example, perceptions of harm/ worry were stronger predictors of mask use in Japan and Indonesia than they were in Mexico where beliefs about mask efficacy were more important. The SEM also identified differences in the demographic variants of mask use in each country and how they were mediated by the cognitive constructs. Findings such as these highlight the importance of contextualising our understanding of protection motivation and, thus, the value of developing targeted approaches to promote precautionary behaviour.


The molecular basis of alpha-thalassemias: frequent occurrence of dysfunctional alpha loci among non-Asians with Hb H disease.
Study of Asians has previously indicated that deletion of alpha-globin structural genes is the predominant lesion in alpha-thalassemias and that Hb H disease occurs when three of four normal alpha loci per cell are deleted. To test the generality of this model, Hb H disease DNAs of both Asian and non-Asian origin were analyzed by restriction endonuclease mapping using the technique of Southern (1975). Whereas in normal DNA, alpha sequences are present in a single Eco Rl fragment of cellular DNA approximately 22.5 kb long, fragments of 22.5, 20 and 2.6 kb were found in various Hb H disease DNAs. The 20 kb Eco Rl fragment alone, in which a single alpha-globin structural locus resides, was found in Asian Hb H disease DNA. This finding is consistent with the deletion model of alpha-thalassemia. In contrast, seven of eight non-Asian Hb H disease DNAs displayed a more complex molecular composition. The fragment patterns observed were 22.5 kb alone, 22.5 plus 2.6 kb, 20 plus 2.6 kb and 20 kb alone. Non-Asian Hb H disease DNAs contained one, two or three alpha loci per cell in contrast to the one locus predicted by the simple deletion model of alpha-thalassemia. The data are best explained by the existence of defective alpha loci in certain individuals with alpha-thalassemia, particularly outside the Asian population. Restriction mapping of the 20 kb Eco Rl fragment found in Asian and some non-Asian Hb H disease DNAs demonstrated a striking similarity in the placement of restriction sites about the single alpha gene compared with sites about the two genes in the 22.5 kb Eco Rl fragment seen in normal DNA. These data are consistent with origin of the 20 kb fragment from the 22.5 kb normal Eco Rl fragment by either unequal crossing-over or a deletion event. The molecular heterogeneity and frequent occurrence of defective alpha loci in non-Asian Hb H disease DNAs described here may explain, in part, the clinical heterogeneity of alpha-thalassemias and the absence of the homozygous deletion state (hydrops fetalis) in non-Asians. Further study of cellular DNA fragments containing the defective alpha loci identified in this work may indicate the types of specific mutations responsible for abnormal globin gene expression and complement similar studies on abnormal beta genes in beta-thalassemias.


Neural representations of kinship.
While the fundamental relevance of kinship behavior for evolutionary and behavioral biology has long been recognized, the examination of kinship behavior from a neuroscience perspective is still in its infancy. Kinship is highly conserved from single-celled organisms to humans, where kin preferences are prevalent in behavior and vocal communication. Kin recognition mechanisms are varied, with evidence for both genetic and both prenatal as well as postnatal learning-based kin recognition. Learned kinship mechanisms are predominant in vertebrates and allow for flexibility regarding the concept of kin. We review new evidence for the lateral septum and its role in kinship behavior. We further discuss the discovery of nepotopy, a topographical representation of kin- and nonkin-responsive neurons in the lateral septum. Neural representations of self/other, familiar/unfamiliar, and nepotopy (kin/nonkin) may support a circuit-level framework for a social template through which the mammalian brain learns, categorizes, and selects behavior based on perceived identity.


Calibration and seasonal adjustment for matched case-control studies of vitamin D and cancer.
Vitamin D measurements are influenced by seasonal variation and specific assay used. Motivated by multicenter studies of associations of vitamin D with cancer, we formulated an analytic framework for matched case-control data that accounts for seasonal variation and calibrates to a reference assay. Calibration data were obtained from controls sampled within decile strata of the uncalibrated vitamin D values. Seasonal sine-cosine series were fit to control data. Practical findings included the following: (1) failure to adjust for season and calibrate increased variance, bias, and mean square error and (2) analysis of continuous vitamin D requires a variance adjustment for variation in the calibration estimate. An advantage of the continuous linear risk model is that results are independent of the reference date for seasonal adjustment. (3) For categorical risk models, procedures based on categorizing the seasonally adjusted and calibrated vitamin D have near nominal operating characteristics; estimates of log odds ratios are not robust to choice of seasonal reference date, however. Thus, public health recommendations based on categories of vitamin D should also define the time of year to which they refer. This work supports the use of simple methods for calibration and seasonal adjustment and is informing analytic approaches for the multicenter Vitamin D Pooling Project for Breast and Colorectal Cancer. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA.


Molecular basis of maternal inheritance.
The mechanism of preferential transmission (i.e., maternal inheritance) of cytoplasmic genes was investigated with chloroplast DNA of Chlamydomonas as a model system. The behavior of nuclear and chloroplast DNAs were compared in the sexual cycle; DNAs from male and female parents were distinguished by labeling with (14)N- or (15)NH(4)Cl and then by making the crosses: (14)N (female) x (15)N (male) and the reciprocal. Chloroplast DNAs from the two parents followed different paths in the zygote, but nuclear DNAs showed no differences. Chloroplast DNA from the female parent persists in the zygote, but undergoes a density shift of 0.003-0.005 g/cm(3) to a lighter buoyant density, whereas that from the male disappears soon after zygote formation. The possibility is discussed that a modification-restriction system may be involved.


Role of conformational heterogeneity in ligand recognition by viral RNA molecules.
Ribonucleic acid (RNA) molecules are known to undergo conformational changes in response to various environmental stimuli including temperature, pH, and ligands. In particular, viral RNA molecules are a key example of conformationally adapting molecules that have evolved to switch between many functional conformations. The transactivation response element (TAR) RNA from the type-1 human immunodeficiency virus (HIV-1) is a viral RNA molecule that is being increasingly explored as a potential therapeutic target due to its role in the viral replication process. In this work, we have studied the dynamics in TAR RNA in apo and liganded states by performing explicit-solvent molecular dynamics (MD) simulations initiated with 27 distinct structures. We determined that the TAR RNA structure is significantly stabilized on ligand binding with especially decreased fluctuations in its two helices. This rigidity is further coupled with the decreased flipping of bulge nucleotides, which were observed to flip more frequently in the absence of ligands. We found that initially-distinct structures of TAR RNA converged to similar conformations on removing ligands. We also report that conformational dynamics in unliganded TAR structures leads to the formation of binding pockets capable of accommodating ligands of various sizes.


Postpartum low-back pain.
To determine the prevalence of back pain and its development over the first postpartum period, 817 women who had been followed through pregnancy were studied a minimum of 12 months after delivery. More than 67% of the women experienced back pain directly after delivery, whereas 37% said they had back pain at the follow-up examination. Most of the women who had recovered became pain-free within 6 months. Factors that correlated to persistent postpartum back pain were the presence of back pain before pregnancy, the presence of back pain during pregnancy, physically heavy work, and multipregnancy. Of these four factors, physically heavy work was found to have the strongest association with persistent back pain at 12 months.


Description of clinical risk factor changes during naturopathic care for type 2 diabetes.
Survey findings report that 48% of people with type 2 diabetes use complementary and alternative medicine (CAM) practice. Publications suggest a high incidence of health promotion counseling in naturopathic practice, yet clinical data on risk factor changes are not available in the literature. The primary aim of this study was to describe clinical risk factor changes during the utilization of naturopathic CAM services in patients with type 2 diabetes. A retrospective, observational study design was used to describe naturopathic care. Abstracted medical charts were from patients of the Bastyr Center for Natural Health in Seattle, WA. The patients in this study had type 2 diabetes and received naturopathic care between 2001 and 2006. Abstracted data included patient demographics, duration of care, number of visits, laboratory values for hemoglobin A1c (HbA1c), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, triglycerides (TAG); and systolic/diastolic blood pressure (SPB, DBP). Thirty-seven (37) patient records met inclusion criteria and were abstracted in detail. Mean and median duration of care were 27 and 20 months, respectively. The mean number of visits was 11. Significant mean changes in clinical laboratory risk factors over the duration of care were: -0.65% for HbA1c (p = 0.046), -45 mg/dL for TAG (p = 0.037), -7 mm Hg in SBP (p = 0.02), and -5 mm Hg in DBP (p = 0.003). Mean changes for cholesterol did not reach statistical significance. The percentage of patients who reached new control, had clinically significant risk factor improvements, or had any improvement was: 26%, 42%, and 68% for HbA1c, 7%, 28%, and 62% for LDL, 0%, 25%, and 39% for HDL, 14%, 38%, and 52% for TAG, 16%, 51%, and 86% for SBP, and 27%, 54%, and 70% for DBP. COMMENTS/CONCLUSIONS: These preliminary outcomes suggest that risk factor improvements occur during naturopathic care for diabetes, although the contribution of naturopathic care to these changes cannot be determined. Effectiveness and generalizability of naturopathic approaches in treating type 2 diabetes should be evaluated in controlled prospective studies in representative populations or randomized trials.


A practical method of linking data from Medicare claims and a comprehensive electronic medical records system.
Linking administrative and clinical databases provides opportunities for richer studies to improve healthcare, but linkage may require sophisticated algorithms. Linking US Medicare data with large databases used for everyday clinical practice is seldom described in detail in medical literature. Test a deterministic method of linking data from a local electronic medical records system to Medicare data, and report specific details of the algorithm used as well as lessons learned from the linkage process. Medicare beneficiaries with medical encounters in selected Indiana counties in the 5-year period ending in 1999. For 6,388 beneficiaries with Medicare data indicating inpatient encounters in the system, 98% had links to the clinical database. Of 7,231 patients hospitalized and registered in the local clinical system, 86% contained a link to Medicare data, and 69% contained a link even without using Social security number (SSN) as an identifier. Medicare data that conflicted with local hospital records by indicating no local hospitalization occurred in 1.8%. More than 2,000 claims contained hospital identifiers that did not exist in the hospital codebook. Details of a practical, deterministic method of linking Medicare claims to a large electronic records system have been applied and described. Most records were linked without SSN. A variety of inconsistencies were found and these, along with missing or incomplete data, can influence linking. Integrity of specific variables must be assessed carefully.


The Role of p110δ in the Development and Activation of B Lymphocytes.
The phosphatidylinositol-3-kinase (PI3K) pathway has an essential role in signal transduction, where it is required for a number of different cellular processes including proliferation, differentiation, development, migration and growth. In the immune system, PI3K regulates inflammation by controlling the activation and recruitment of leukocytes. The generation of conditional knockout mice has allowed the study of PI3K isoforms specifically in B and T lymphocytes, and demonstrates the importance of intact signalling in their development and function. PI3K signalling must be tightly regulated in lymphocytes as excessive PI3K can lead to autoimmunity, immunodeficiency or cancer, whilst diminished signalling can result in developmental defects and immunodeficiency. Recent advances in the understanding of PI3K signalling have hastened the application of isoform-specific PI3K inhibitors, which are currently undergoing clinical trials. This review will focus on the p110δ catalytic subunit of the class 1A family of PI3K, and its role in the development and activation of B lymphocytes through various downstream effectors.


Effect of beam number on organ-at-risk sparing in dynamic multileaf collimator delivery of intensity modulated radiation therapy.
Due to practical limitations such as inter- and intraleaf transmission, nondivergent leaf end design, and leaf scatter, multileaf collimators (MLCs) are unable to accurately produce the ideal fluence patterns generated by inverse planning systems. Consequently, low dose regions receive substantially more radiation than they would with an ideal MLC that could generate the desired fluence pattern. Previous work by others has found that the discrepancy between desired and actual fluence patterns produced by an MLC increases rapidly with increasing complexity of the desired fluence map. In addition to the complexity of individual fluence maps, other parameters can contribute to the overall complexity of a treatment plan, most notably the number of beams. In this work, we investigate the effect of beam number on critical structure sparing for dynamic MLC delivered intensity modulated radiation therapy. Six cases from each of two challenging clinical sites, previously irradiated head and neck and paraspinal metastasis, were planned with the goal of minimizing the spinal cord dose. Plans were developed for five to 27 beams. All plans were renormalized such that the target volume receiving the prescription dose was the same for all plans of each site. For each case, we calculated the spinal cord D0.5 cm3 (the dose such that 0.5 cm3 of normal tissue receives greater than or equal to D0.5 cm3), normal tissue D1 cm3, the normal tissue mean dose, and the standard deviation of dose in the planning target volume (PTV). For the head and neck cases, the mean increase in spinal cord D0.5 cm3 between seven and 27 beam plans was 10% of the prescription dose, whereas for the paraspinal case, the increase was 2.6%. For the head and neck cases, the mean decrease in normal tissue D1 cm3 between seven and 11 beam plans was 2.6% and was constant for more than 11 beams. For the paraspinal cases, the mean decrease in normal tissue D1 cm3 between seven and 27 beam plans was 3.7%. The mean normal tissue dose was approximately independent of the number of beams for both sites. For the head and neck cases, the PTV standard deviation was independent of the number of beams, while for the paraspinal cases it decreased by an average of 1.8% from seven to 27 beams. Calculations for seven and 27 beams in which the MLC transmission was varied from 0% to 2% demonstrated that the increase in spinal cord D0.5 cm3 with increasing number of beams is largely due to MLC transmission, which is not included in the optimization. Increasing the number of beams increased the critical structure dose, although decreasing beam number results in increasing normal tissue D1 cm3 and target dose heterogeneity. The optimal tradeoff is dependent on the clinical situation, but seems to be seven to nine beams. Beam geometry optimization may reduce the number of beams required to provide adequate target coverage, thus limiting critical structure dose.


The metabolism of C1 inhibitor and C1q in patients with acquired C1-inhibitor deficiency.
The metabolism of 125I-labeled C1 inhibitor (C1INH) and C1q was studied in five patients with B cell lymphoproliferative disorders, C1INH deficiency, and angioedema. C1INH catabolism was markedly accelerated in these patients. The fractional catabolic rate (FCR) was 0.053 of the plasma pool per hour compared to that of normal subjects (0.025) or patients with hereditary angioneurotic edema (HANE) (0.035). The catabolism of two dysfunctional proteins Wel and Ta was studied. Protein Wel was catabolized at an accelerated rate (0.041) compared to that in patients with HANE (0.029) or in normal subjects (0.020). In contrast, the FCR of protein Ta was 0.012, which is similar to that in normal patients and in patients with HANE. The extravascular to plasma ratio (E/P) of the normal C1INH in patients was 1.55 compared to 0.60 in normal patients. This is consistent with the rapid extravascular sequestration of the C1INH. The synthesis rate of the C1INH was 0.29 mg/kg/hr in patients that is similar to that in control subjects. The metabolism of C1q was studied in two normal control subjects and three patients. The FCR of C1q was 0.051 in patients compared to 0.023 in control subjects. The E/P was increased in patients (2.8) compared to E/P in control subjects (0.6). The acquisition of C1INH deficiency results from increased consumption of C1INH in vivo.


Galactooligosaccharide improves the animal survival and alleviates motor neuron death in SOD1G93A mouse model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disease caused by selective degeneration and death of motor neurons. So far very limited therapeutic options have emerged to treat this fatal disease. Homocysteine (Hcy) lowering drugs have been suggested to be a palliative therapy of this disease. Folate, Vitamin B12 (VitB12) and Vitamin B6 (VitB6) are important elements involved in the Hcy metabolism and we proposed that medications which could promote the absorption of folate, VitB12 and VitB6 might have benefit for ALS. Galactooligosaccharides (GOS) is a prebiotic which could significantly improve the absorption and syntheses of B Vitamins. To investigate whether GOS could provide neuroprotective effect in ALS, we applied GOS and GOS-rich prebiotic yogurt in SOD1(G93A) mice and assessed their effects on the disease progression of ALS. Our results showed that GOS and prebiotics yogurt administration significantly delayed the disease onset and prolonged the lifespan in SOD1(G93A) mice. Also, these products increased the concentration of folate, VitB12 and reduced the level of Hcy. Moreover, we found that both GOS and prebiotics yogurt attenuated motor neurons loss, improved the atrophy and mitochondrial activity in myocyte. Furthermore, we demonstrated that GOS and GOS-rich prebiotic treatment suppressed the activation of astrocytes and microglia and regulated several inflammatory- and apoptosis-related factors. Our findings suggested that GOS might have therapeutic potential for ALS, and GOS-rich prebiotic yogurt might be considered as a nutritional therapy for this disease.


Interspecific competition of a new invasive mosquito, Culex coronator, and two container mosquitoes, Aedes albopictus and Cx. quinquefasciatus (Diptera: Culicidae), across different detritus environments.
The mosquito Culex coronator (Dyar and Knab) (Diptera: Culicidae) has undergone rapid range expansion in the United States since 2003, with its historical distribution in the southwest expanding eastward to the Atlantic coast. Although Cx. coronator nominally use small natural aquatic habitats for development, the use of containers (e.g., tires) makes it potentially important as container invasive. To determine the potential ecological effects of Cx. coronator on resident container species, we conducted a laboratory experiment to assess its competitive ability with two common tire-inhabiting species, Aedes albopictus (Skuse) and Culex quinquefasciatus (Say) (Diptera: Culicidae). Larvae were reared under a factorial design with each species alone and in combination (Cx. coronator + Ae. albopictus, Cx. coronator + Cx. quinquefasciatus) across three different resource environments (leaf detritus only, animal detritus only, animal + leaf). Mosquito performance (survival, adult male and female mass, and development time) was measured for each species across treatments. Female Cx. coronator developed slowest when grown with Ae. albopictus, or when grown with leaves only regardless of species combinations; similar patterns emerged for males although species effects were restricted to mass. Few differences were evident in performance for male and female Cx. coronator across detritus environments when grown with Cx. quinquefasciatus. Cx. quinquefasciatus did not vary in mass or development time in the presence of Cx. coronator compared with when grown alone. Ae. albopictus female mass was 15% lower in the presence of Cx. coronator. Survival of Cx. coronator was highest in animal and leaf detritus containers, although survival was generally lower when larvae were grown with Ae. albopictus. These findings suggest that the performance of Cx. coronator is similar to that of Cx. quinquefasciatus but it suffers in the presence of Ae. albopictus under some resource environments.


Effect of Tai Chi on depression symptoms and sleep quality among older adult women after exercise cessation.
This study investigated the effects of Tai Chi exercise on the psychological health and sleep quality of older adult women after exercise cessation. Nineteen Tai Chi practitioners and 20 controls completed the final tests. All participants completed the Profile of Mood States (POMS) and the Pittsburgh Sleep Quality Index (PSQI) at 0, 24 and 28 weeks (4 weeks after Tai Chi cessation). Compared with baseline, the fatigue, depression, total mood disturbance and PSQI scores in the Tai Chi group decreased at week 24 by 18.8%, 24.7%, 5.7% and 24.6%, and the vigour score increased by 18.3%. At week 28, depression and PSQI scores in the Tai Chi group decreased by 24.0% and 20.4%, respectively. Practicing Tai Chi for 24 weeks positively affected fatigue, depression, vigour and sleep quality among older adult women. The effect on reducing depression and improving sleep quality was sustained 4 weeks after Tai Chi was stopped.


Effects of oral erythromycin on fasting and postprandial antroduodenal motility in patients with type I diabetes, measured with an ambulatory manometric technique.
The aim of this double-blind crossover study was to evaluate the effects of oral erythromycin (250 mg t.i.d.) on fasting and postprandial gastrointestinal motility and gastrointestinal symptoms in patients with type I diabetes. Antroduodenal motility was recorded with an ambulatory manometric technique for a 20-h period, including a high-caloric high-fat dinner and a low-caloric low-fat breakfast and a long fasting period, after 2 weeks erythromycin and placebo treatment in 12 patients with type I diabetes. During the manometric study, plasma glucose concentrations were assessed by frequent self-testing. Gastrointestinal symptoms were scored daily to assess the severity of the symptoms (range 0-3). Oral erythromycin decreased the migrating motor complex cycle length from 118.9 +/- 46.0 to 86.2 +/- 25.3 min (P = 0.03) by shortening phase II from 68.7 +/- 23.5 to 48.5 +/- 19.4 min (P < 0.05). The total number of duodenal phase III increased from 48 to 62 (P = 0.075). However, the degree of antral participation to duodenal phase III did not increase. Erythromycin significantly decreased the duration of the postprandial period after dinner (from 417.0 +/- 137.9 to 348.8 +/- 93.8 min, P = 0.04). During this shorter postprandial period, the number of antral contractions (P < 0.01) and the antral motility index increased (P < 0.03), and early phase III activity at the level of the duodenum was abolished. In diabetic patients with antral hypomotility, after dinner, the mean symptom score improved significantly, from 2.07 +/- 0.86 to 1.52 +/- 0.63 (P = 0.018). This ambulatory antroduodenal manometric study showed that oral erythromycin (250 mg t.i.d.) improves both fasting and postprandial antroduodenal motor activity after a high-caloric meal in patients with type I diabetes. Furthermore, in diabetic subjects with postprandial antral hypomotility, erythromycin reduces dyspeptic symptoms.


Anisotropic odd viscosity via a time-modulated drive.
At equilibrium, the structure and response of ordered phases are typically determined by the spontaneous breaking of spatial symmetries. Out of equilibrium, spatial order itself can become a dynamically emergent concept. In this article, we show that spatially anisotropic viscous coefficients and stresses can be designed in a far-from-equilibrium fluid by applying to its constituents a time-modulated drive. If the drive induces a rotation whose rate is slowed down when the constituents point along specific directions, then anisotropic structures and mechanical responses arise at long timescales. We demonstrate that the viscous response of such two-dimensional anisotropic driven fluids can acquire a tensorial, dissipationless component called anisotropic odd (or Hall) viscosity. Classical fluids with internal torques can display additional components of the odd viscosity neglected in previous studies of quantum Hall fluids that assumed angular momentum conservation. We show that, unlike their isotropic counterparts, these anisotropic and angular momentum-violating odd-viscosity coefficients can change even the bulk flow of an incompressible fluid by acting as a source of vorticity. In addition, shear distortions in the shape of an inclusion result in torques. We derive how the odd-viscous coefficients depend on the nonlinear, dissipative response of a fluid of rotating rods, i.e., odd viscosity is not simply given by angular momentum density.


Effects of propofol on the expression of matric metalloproteinases in rat cardiac fibroblasts after hypoxia and reoxygenation.
Propofol is known to protect the myocardium against ischaemia/reperfusion (I/R) injury through its antioxidant and anti-inflammatory properties. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cell migration and invasion, and mediate tissue remodelling during I/R injury. They are regulated by various mechanisms including oxidative stress and AKT and ERK pathways. We investigated whether propofol affected the expression of MMPs and subsequent cell migration and invasion and the signalling pathways involved in primary rat cardiac fibroblasts undergoing hypoxia and reoxygenation. The phosphorylation of ERK and AKT signalling pathways was examined by western blot analysis in rat primary cardiac fibroblasts after hypoxia and reoxygenation. mRNA expression of MMP and TIMPS was analysed by real-time PCR, and proteolytic activities of MMP-2 and -9 were assessed. The effects of propofol on migration, invasion, wound healing, and cell proliferation activity were evaluated after reoxygenation. Propofol induced AKT and ERK1/2 activation. Subsequent activation of MMPs resulted in increased cell migration, invasion, and wound-healing activity under hypoxia-reoxygenation, which was decreased by LY294002 (AKT inhibitor) and U0126 (ERK inhibitor) in rat cardiac fibroblasts. However, propofol had no effect on proliferation or viability of cardiac fibroblasts after hypoxia-reoxygenation. Propofol affected the expression of MMPs and TIMPs and subsequently induced cell migration and invasive ability, through activation of the ERK and AKT signalling pathway in hypoxia-reoxygenated rat cardiac fibroblasts.


Coronary CT Angiography in Challenging Patients: High Heart Rate and Atrial Fibrillation. A Review.
Despite several strategies have been developed by different vendors to improve image quality and diagnostic accuracy of coronary CT angiography performed at high heart rate (HR) and HR variability, as in patients with atrial fibrillation (AF), some concerns and small clinical experience characterize these subsets of challenging patients. However, patients with AF have been reported to have higher risk of cardiovascular events and noninvasive evaluation of suspected coronary artery disease in this setting may be of extreme clinical interest. The goal of this review is to provide to the reader an overview on the use of cardiac CT in patients with AF and high HR and to outline the technological improvements recently introduced in the clinical field that may enable to definitively overcome the limitations of cardiac CT in this challenging scenario.


Ocriplasmin for pharmacologic vitreolysis.
The vitreous may play an important role in the pathogenesis of various retinal disorders. Pharmacologic vitreolysis uses intravitreal pharmacologic agents to provide liquefaction of the vitreous and complete vitreoretinal separation. Ocriplasmin, a genetically engineered version of plasmin, has been shown in clinical trials to be able to safely release vitreomacular adhesion and close Stage 2 macular holes in a significant number of patients. Advancements in the development of this safe and effective method of vitreolysis have provided an alternative, nonsurgical treatment option to physicians who manage these patients. A roundtable of clinical investigators convened to discuss and summarize recent progress in pharmacologic vitreolysis. Preclinical studies, and efficacy and safety data from controlled clinical trials of ocriplasmin were presented and discussed. Case studies were then presented to provide an opportunity for experts to reveal their specific thoughts regarding ocriplasmin for the treatment of vitreomacular adhesion and resulting vitreomacular traction and macular holes, based on their own interpretation of current clinical data and experience.


Expression of pro- and anti-angiogenic factors during the formation of the periocular vasculature and development of the avian cornea.
During embryonic development, endothelial precursor cells (angioblasts) migrate relatively long distances to form the primary vascular plexus. The migratory behavior of angioblasts and localization of the primitive blood vessels is tightly regulated by pro-angiogenic and anti-angiogenic factors encountered in the embryonic environment. Despite the importance of corneal avascularity to proper vision, it is not known when avascularity is established in the developing cornea and how pro- and anti-angiogenic factors regulate this process. Using Tg(tie1:H2B:eYFP) transgenic quail embryos to visualize fluorescently labeled angioblasts, we show that the presumptive cornea remains avascular despite the invasion of cells from the periocular region where migratory angioblasts reside and form the primary vasculature. Semiquantitative reverse transcriptase polymerase chain reaction analysis and spatiotemporal examination of gene expression revealed that pro- and anti-angiogenic factors were expressed in patterns indicating their potential roles in angioblast guidance. Our findings show for the first time that chick corneal avascularity is established and maintained during development as the periocular vasculature forms. We also identify potential candidate pro- and anti-angiogenic factors that may play crucial roles during vascular patterning in the anterior eye.


Preoperative dietary restriction reduces hepatic tumor load by reduced E-selectin-mediated adhesion in mice.
Inflammatory responses facilitate metastasis by increasing expression of adhesion molecules. Dietary restriction (30% reduction in daily calorie intake) reduces the expression of adhesion molecules and protects against surgically induced inflammation. DR might therefore beneficially interfere with surgery-induced inflammation and subsequent adhesion of circulating tumor cells. BALB/c mice were subjected to 2 weeks dietary restriction prior to inoculation with tumor cells. Intra-splenic injection of 5.0 x 10(4) C26-colon carcinoma cells was followed by splenectomy. Hepatic tumor load was scored after 10 days as a percentage (tumor surface/total liver surface) on H&E stained sections. Liver mRNA expression of adhesion molecules was determined and the effect of serum from dietary restriction mice on in vitro tumor growth and adhesion capacity was assessed. Preoperative dietary restriction significantly reduced mRNA expression levels of E-selectin (P = 0.0087) and hepatic tumor load (P = 0.036). Dietary restriction serum did not affect in vitro cell growth but reduced in vitro adhesion of C26 cells to endothelial cells (P = 0.0043). Preoperative dietary restriction reduces hepatic tumor load after injection with tumor cells. Reduced adhesion to endothelial cells and reduced mRNA expression of E-selectin suggest that dietary restriction reduces tumor load by lowering the adhesion of circulating tumor cells to hepatic vascular endothelium.


Dispensing Methadone at Hospital Discharge: One Hospital's Approach to Implementing the "72-hour Rule" Change.
Methadone for opioid use disorder treatment in ambulatory settings is restricted to federally licensed opioid treatment programs (OTPs) in the United States. However, these restrictions do not apply during hospitalization. A recent change to the rule governing methadone in non-OTP settings created an opportunity to dispense methadone at hospital discharge for up to 72 hours. Here, we describe one hospital's approach to dispensing methadone at discharge in alignment with the "72-hour rule," including implementation challenges and considerations for other hospitals planning on adopting this practice. Implementation included creating a workflow and detailed documents outlining dispensing procedure, educating interprofessional staff, and coordinating with local OTPs. Our experiences highlight the importance of pharmacy champions to support implementation and interdisciplinary staff education, the need to consider electronic health record capabilities, and the importance of having policies and practices that support appropriate interpretation of the "72-hour rule" renewal timeline. Exceptions to federal regulations allow greater flexibility in discharge planning for patients with opioid use disorder; however, dispensation workflow falls outside standard hospital care and may be challenging to implement.


Ear acupuncture and fMRI: a pilot study for assessing the specificity of auricular points.
In recent years research explored different acupuncture stimulation techniques but interest has focused primarily on somatic acupuncture and on a limited number of acupoints. As regards ear Acupuncture (EA) there is still some criticism about the clinical specificity of auricular points/areas representing organs or structures of the body. The aim of this study was to verify through (Functional magnetic resonance imaging) fMRI the hypothesis of EA point specificity using two auricular points having different topographical locations and clinical significance. Six healthy volunteers underwent two experimental fMRI sessions: the first was dedicated to the stimulation of Thumb Auricular Acupoint (TAA) and the second to the stimulation of Brain Stem Auricular Acupoint (BSAA). The stimulation of the needle placed in the TAA of the left ear produced an increase in activation bilaterally in the parietal operculum, region of the secondary somatosensory area SII. Stimulation of the needle placed in the BSAA of the left ear showed a pattern that largely overlapped regions belonging to the pain matrix, as shown to be involved in previous somatic acupuncture studies but with local differences in the left amygdala, anterior cingulate cortex, and cerebellum. The differences in activation patterns between TAA and BSAA stimulation support the specificity of the two acupoints. Moreover, the peculiarity of the regions involved in BSAA stimulation compared to those involved in the pain matrix, is in accordance with the therapeutic indications of this acupoint that include head pain, dizziness and vertigo. Our results provide preliminary evidence on the specificity of two auricular acupoints; further research is warranted by means of fMRI both in healthy volunteers and in patients carrying neurological/psychiatric syndromes.


A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology.
The ongoing pandemic spread of a new human coronavirus, SARS-CoV-2, which is associated with severe pneumonia/disease (COVID-19), has resulted in the generation of tens of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. Here, we present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and delabelling virus lineages that become unobserved and hence are probably inactive. By focusing on active virus lineages and those spreading to new locations, this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.


Pathogenesis of hepatitis C virus recurrence in the liver allograft.
1. Hepatitis C virus (HCV) infection in the allograft occurs in the setting of greater viral burden than in nontransplantation patients. 2. Infection of the allograft occurs early (within days and possibly during the intraoperative reperfusion phase). 3. Viral burden plateaus at 1 month posttransplantation and (in the absence of cholestatic HCV) peaks at the time of acute hepatitis (1 to 4 months). 4. Acute hepatitis is associated with immune cell infiltration and hepatocyte apoptosis. 5. Cholestatic HCV seems to be a disease of direct HCV cytopathic injury in the setting of extreme virus levels, an intrahepatic T helper subtype 2 cell (T(H)2)-like response, and lack of a specific HCV-directed response. 6. Chronic hepatitic HCV seems to behave at the molecular and/or cellular level in a similar fashion to the nontransplantation setting, with activation of T(H)1 inflammatory, profibrotic, and proapoptotic pathways. This process operates at a greater viral burden than pretransplantation and leads to more progressive disease. 7. More studies are required to examine and distinguish allograft rejection in the setting of HCV infection from HCV infection alone.


Semantic annotation for concept-based cross-language medical information retrieval.
We present a framework for concept-based cross-language information retrieval in the medical domain, which is under development in the MUCHMORE project. Our approach is based on using the Unified Medical Language System (UMLS) as the primary source of semantic data. Documents and queries are annotated with multiple layers of linguistic information. Linguistic processing includes part-of-speech tagging, morphological analysis, phrase recognition and the identification of medical terms and semantic relations between them. The paper describes experiments in monolingual and cross-language document retrieval, performed on a corpus of medical abstracts. Results show that linguistic processing, especially lemmatization and compound analysis for German, is a crucial step in achieving a good baseline performance. On the other hand, they show that semantic information, specifically the combined use of concepts and relations, increases the performance in monolingual and cross-language retrieval.


Immunoglobulin complex deposits in Plasmodium falciparum-infected placentas from Malawi and Papua New Guinea.
Term placentas from 35 patients infected with Plasmodium falciparum were obtained in Malawi in southeast Africa and six term placentas from patients infected with P. falciparum were obtained in Wewak, Papua New Guinea, Melanesia. The placental tissues were examined by light microscopy and by an immunohistologic method to compare the pathologic changes of placentas in the two malaria-endemic countries. Using the number of parasitized red blood cells (PRBC) in intervillous spaces, pregnant women from Malawi with placental parasitemia were categorized into three groups. In the high PRBC group (> 20%, group I), there was no deposition of IgE in fetal blood vessels. In contrast, IgE was observed in fetal blood vessels of the intermediate PRBC group (1-10%, group II) and low PRBC group (< 1%, group III). In all six placentas from Papua New Guinean women, deposition of immune complexes, including IgE, was observed in the fetal blood vessels. All placentas with deposition of IgE in fetal blood vessels showed no sequestration of malaria parasites in intervillous spaces. Our data indicate that the amount of deposition of IgE in the placenta from women infected with P. falciparum is inversely correlated with the degree of parasitemia at that site.


PKCδ is required for Jagged-1 induction of human mesenchymal stem cell osteogenic differentiation.
JAG1, the gene for the Jagged-1 ligand (Jag1) in the Notch signaling pathway, is variably mutated in Alagille Syndrome (ALGS). ALGS patients have skeletal defects, and additionally JAG1 has been shown to be associated with low bone mass through genome-wide association studies. Plating human osteoblast precursors (human mesenchymal stem cells-hMSCs) on Jag1 is sufficient to induce osteoblast differentiation; however, exposure of mouse MSC (mMSC) to Jag1 actually inhibits osteoblastogenesis. Overexpression of the notch-2 intracellular domain (NICD2) is sufficient to mimic the effect of Jag1 on hMSC osteoblastogenesis, while blocking Notch signaling with a γ-secretase inhibitor or with dominant-negative mastermind inhibits Jag1-induced hMSC osteoblastogenesis. In pursuit of interacting signaling pathways, we discovered that treatment with a protein kinase C δ (PKCδ) inhibitor abrogates Jag1-induced hMSC osteoblastogenesis. Jag1 results in rapid PKCδ nuclear translocation and kinase activation. Furthermore, Jag1 stimulates the physical interaction of PKCδ with NICD. Collectively, these results suggest that Jag1 induces hMSC osteoblast differentiation through canonical Notch signaling and requires concomitant PKCδ signaling. This research also demonstrates potential deficiencies in using mouse models to study ALGS bone abnormalities.


An Activatable Probe with Aggregation-Induced Emission for Detecting and Imaging Herbal Medicine Induced Liver Injury with Optoacoustic Imaging and NIR-II Fluorescence Imaging.
Whilte herbal medicines are widely used for health promotion and therapy for chronic conditions, inappropriate use of them may cause adverse effects like liver injury, and accurately evaluating their hepatotoxicity is of great significance for public health. Herein, an activatable probe QY-N for diagnosing herbal-medicine-induced liver injury by detecting hepatic NO with NIR-II fluorescence and multispectral optoacoustic tomography (MSOT) imaging is demonstrated. The probe includes a bismethoxyphenyl-amine-containing dihydroxanthene serving as electron donor, a quinolinium as electron acceptor, and a butylamine as recognition group and fluorescence quencher. The hepatic level of NO reacts with butylamine, thereby generating the activated probe QY-NO which exhibits a red-shifted absorption band (700-850 nm) for optoacoustic imaging and generates strong emission (910-1110 nm) for NIR-II fluorescence imaging. QY-NO is aggregation-induced-emission (AIE) active, which ensures strong emission in aggregated state. QY-N is utilized in the triptolide-induced liver injury mouse model, and experimental results demonstrate the QY-N can be activated by hepatic NO and thus be used in detecting herbal-medicine-induced liver injury. The temporal and spatial information provided by three-dimensional MSOT images well delineates the site and size of liver injury. Moreover, QY-N has also been employed to monitor rehabilitation of liver injury during treatment process.


Distinct and direct synergistic effects of IL-1 and IL-6 on proliferation and differentiation of primitive murine hematopoietic progenitor cells in vitro.
While interleukin-1 (IL-1) and IL-6 have been demonstrated to synergize with colony-stimulating factors (CSFs) and stem cell factor (SCF) to stimulate myeloid colony formation of primitive hematopoietic progenitor cells, it has not yet been established whether these effects are directly mediated. In the present study, direct effects of IL-1 and IL-6 were examined on primitive Lin-Sca-1+ murine bone-marrow progenitor cells that were cultured and plated individually. IL-1 and IL-6 showed not only overlapping, but also distinct, patterns of direct synergy. While IL-1 or IL-6 had no proliferative effects as single growth factors, IL-1, in combination with granulocyte-macrophage CSF (GM-CSF), IL-3, CSF-1, and SCF, but not granulocyte-CSF (G-CSF), enhanced the cloning frequency of Lin-Sca-1+ progenitors three- to five-fold, whereas IL-6 increased the cloning frequency in response to all four CSFs and SCF two- to seven-fold. In all cases, the size of the colonies observed were increased as well. Furthermore, the combined action of IL-1 and IL-6 resulted in additive or synergistic enhancement of CSF- and SCF-stimulated colony formation of Lin-Sca-1+ high proliferative potential colony-forming cells (HPP-CFCs). Finally, IL-6, but not IL-1, enhanced the number of immature blast cells observed in CSF- and SCF-stimulated cultures.


Molecular dynamics simulations of creatine kinase and adenine nucleotide translocase in mitochondrial membrane patch.
Interaction between mitochondrial creatine kinase (MtCK) and adenine nucleotide translocase (ANT) can play an important role in determining energy transfer pathways in the cell. Although the functional coupling between MtCK and ANT has been demonstrated, the precise mechanism of the coupling is not clear. To study the details of the coupling, we turned to molecular dynamics simulations. We introduce a new coarse-grained molecular dynamics model of a patch of the mitochondrial inner membrane containing a transmembrane ANT and an MtCK above the membrane. The membrane model consists of three major types of lipids (phosphatidylcholine, phosphatidylethanolamine, and cardiolipin) in a roughly 2:1:1 molar ratio. A thermodynamics-based coarse-grained force field, termed MARTINI, has been used together with the GROMACS molecular dynamics package for all simulated systems in this work. Several physical properties of the system are reproduced by the model and are in agreement with known data. This includes membrane thickness, dimension of the proteins, and diffusion constants. We have studied the binding of MtCK to the membrane and demonstrated the effect of cardiolipin on the stabilization of the binding. In addition, our simulations predict which part of the MtCK protein sequence interacts with the membrane. Taken together, the model has been verified by dynamical and structural data and can be used as the basis for further studies.


Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders.
An extensive literature stretching back decades has shown that prolonged stress or prolonged exposure to glucocorticoids-the adrenal steroids secreted during stress-can have adverse effects on the rodent hippocampus. More recent findings suggest a similar phenomenon in the human hippocampus associated with many neuropsychiatric disorders. This review examines the evidence for hippocampal atrophy in (1) Cushing syndrome, which is characterized by a pathologic oversecretion of glucocorticoids; (2) episodes of repeated and severe major depression, which is often associated with hypersecretion of glucocorticoids; and (3) posttraumatic stress disorder. Key questions that will be examined include whether the hippocampal atrophy arises from the neuropsychiatric disorder, or precedes and predisposes toward it; whether glucocorticoids really are plausible candidates for contributing to the atrophy; and what cellular mechanisms underlie the overall decreases in hippocampal volume. Explicit memory deficits have been demonstrated in Cushing syndrome, depression, and posttraumatic stress disorder; an extensive literature suggests that hippocampal atrophy of the magnitude found in these disorders can give rise to such cognitive deficits.


On the combustion mechanisms of ZrH2 in double-base propellant.
Metal hydrides are regarded as a series of promising hydrogen-supplying fuel for solid rocket propellants. Their effects on the energetic and combustion performances of propellants are closely related to their reaction mechanisms. Here we report a first attempt to determine the reaction mechanism of ZrH2, a high-density metal hydride, in the combustion of a double-base propellant to evaluate its potential as a fuel. ZrH2 is determined to possess good resistance to oxidation by nitrocellulose and nitroglycerine. Thus its combustion starts with dehydrogenation to generate H2 and metallic Zr. Subsequently, the newly formed Zr and H2 participate in the combustion and, especially, Zr melts and then combusts on the burning surface which favors the heat feedback to the propellant. This phenomenon is completely different from the combustion behavior of the traditional fuel Al, where the Al particles are ejected off the burning surface of the propellant to get into the luminous flame zone to burn. The findings in this work validate the potential of ZrH2 as a hydrogen-supplying fuel for double-base propellants.


Mesoporous titanium and niobium nitrides as conductive and stable electrocatalyst supports in acid environments.
The stability of carbon-based catalyst supports represents one of the biggest challenges for the commercialisation of proton-exchange membrane fuel cells (PEMFCs). Metal nitrides are an attractive alternative to carbon-based supports, owing to their high bulk conductivity and acid stability. We report the electrochemical stability evaluation of high-surface-area metal nitrides in acidic electrolytes. Three-dimensional mesoporous titanium (TiN) and niobium nitride (NbN) thin films were prepared using block copolymer self-assembly and were evaluated without using any conductive carbon additives or a carbon-based substrate. Both TiN and NbN are stable and maintain conductivity in acidic electrolytes up to at least 0.85 V (NbN) and 1.4 V (TiN) vs. reversible hydrogen electrode (RHE) after 2000 cycles. We also deposited platinum on the TiN films and demonstrate the expected cyclic voltammogram features, indicating the nitride's utility as a catalyst support.


Alpha-Tocopherol and Cyanocobalamin Combination Accelerates Peripheral Nerve Healing: An Experimental Animal Study.
To evaluate the functional and histopathological results of alpha-tocopherol (vitamin E) and vitamin B12 on an experimental rat model of peripheral nerve injury. This research included 32 Wistar Hannover rats. The sciatic nerves of the animals were crushed using an aneurysm clamp. The rats were divided into 4 groups, as group 0 (the controls; no treatment), and groups B12, E, and B12+E, respectively. The rats were analyzed functionally, using the sciatic functional index (SFI), and histopathologically. In the functional analysis, it was determined that vitamin E was as influential as B12. Concomitant use of these 2 vitamins was found to be more beneficial. The SFI was significantly higher in the B12+E group when compared with that of the B12 group, which indicated that vitamin E improved the healing effects of vitamin B12. In the histopathological evaluation, vitamin E was not effective in the treatment of axonal degeneration (AxD) or edema/inflammation (EI) by itself. Although vitamin B12 was effective in the treatment of EI, it was ineffective in the treatment of AxD. However, the combination of these vitamins decreased both AxD and EI, which showed that the additive effects of these vitamins could reverse neurological injury when used together. Vitamins B12 and E were effective in the functional recovery of peripheral nerve injury (PNI). Neither vitamin B12 nor E was effective in the treatment AxD; however, their combination was effective in the treatment of AxD. The results suggested that vitamin E was effective in the treatment of PNI, especially when combined with vitamin B12. It is our belief that the combination of these vitamins could be used in the treatment of PNI, especially after future studies have been conducted on humans.


Large-scale analysis of B-cell epitopes on influenza virus hemagglutinin - implications for cross-reactivity of neutralizing antibodies.
Influenza viruses continue to cause substantial morbidity and mortality worldwide. Fast gene mutation on surface proteins of influenza virus result in increasing resistance to current vaccines and available antiviral drugs. Broadly neutralizing antibodies (bnAbs) represent targets for prophylactic and therapeutic treatments of influenza. We performed a systematic bioinformatics study of cross-reactivity of neutralizing antibodies (nAbs) against influenza virus surface glycoprotein hemagglutinin (HA). This study utilized the available crystal structures of HA complexed with the antibodies for the analysis of tens of thousands of HA sequences. The detailed description of B-cell epitopes, measurement of epitope area similarity among different strains, and estimation of antibody neutralizing coverage provide insights into cross-reactivity status of existing nAbs against influenza virus. We have developed a method to assess the likely cross-reactivity potential of bnAbs for influenza strains, either newly emerged or existing. Our method catalogs influenza strains by a new concept named discontinuous peptide, and then provide assessment of cross-reactivity. Potentially cross-reactive strains are those that share 100% identity with experimentally verified neutralized strains. By cataloging influenza strains and their B-cell epitopes for known bnAbs, our method provides guidance for selection of representative strains for further experimental design. The knowledge of sequences, their B-cell epitopes, and differences between historical influenza strains, we enhance our preparedness and the ability to respond to the emerging pandemic threats.


Patterns of HIV prevalence among injecting drug users in the cross-border area of Lang Son Province, Vietnam, and Ning Ming County, Guangxi Province, China.
To assess patterns of injecting drug use and HIV prevalence among injecting drug users (IDUs) in an international border area along a major heroin trans-shipment route. Cross-sectional surveys of IDUs in 5 sites in Lang Son Province, Vietnam (n = 348) and 3 sites in Ning Ming County, Guangxi Province, China (n = 308). Respondents were recruited through peer referral ("snowball") methods in both countries, and also from officially recorded lists of IDUs in Vietnam. A risk behavior questionnaire was administered and HIV counseling and testing conducted. Participants in both countries were largely male, in their 20s, and unmarried. A majority of subjects in both countries were members of ethnic minority groups. There were strong geographic gradients for length of drug injecting and for HIV seroprevalence. Both mean years injecting and HIV seroprevalence declined from the Vietnamese site farthest from the border to the Chinese site farthest from the border. 10.6% of participants in China and 24.5% of participants in Vietnam reported crossing the international border in the 6 months prior to interview. Crossing the border by IDUs was associated with (1) distance from the border, (2) being a member of an ethnic minority group, and (3) being HIV seropositive among Chinese participants. Reducing the international spread of HIV among IDUs will require programs at the global, regional, national, and "local cross border" levels. At the local cross border level, the programs should be coordinated on both sides of the border and on a sufficient scale that IDUs will be able to readily obtain clean injection equipment on the other side of the border as well as in their country of residence.


Gospel Music: A Catalyst for Retention, Engagement, and Positive Health Outcomes for African Americans in a Cardiovascular Prevention and Treatment Program.
Mortality associated with cardiovascular disease is significantly higher in African Americans compared with people of other ethnicities, with hypertension being the single most significant risk factor in this population. Underdiagnosis and undertreatment of hypertension is common. Although cardiovascular lifestyle education and self-management programs are available for the general public, many African Americans prefer to learn about health-promoting activities through interactive programs led by church ministries. This study examined the influence of adding a faith-based protocol using creative musical expression as a catalyst for improving retention, engagement, and positive health outcomes for African Americans participating in a 1-y, lifestyle skills program for reducing cardiovascular risk factors. The study was a randomized, controlled trial. The study occurred at Rodman Street Missionary Baptist Church (Pittsburgh, PA, USA). Participants were African Americans with at least 2 of the following medical conditions: high blood pressure, elevated cholesterol and/or triglycerides, heart attack, angina, stroke, irregular heartbeats, palpitations, shortness of breath, dizziness or fainting, diabetes, and tobacco use. Intervention and control groups both participated every other week in one 45-min structured cardiovascular risk reduction educational session over the course of 1 year. During alternative weeks, sessions comprised blood pressure checks, coupled with individualized support discussions focused on challenges and identified obstacles to adherence. In addition to the aforementioned sessions, the intervention group participated in a novel gospel music program with weekly, 45-minute vocal and instrumental sessions. Outcome measures include retention, attendance, systolic and diastolic blood pressures, weight, body mass index, hip measurement, and waist measurement as well as the Short Form-12 (SH-12) Health Survey. Subjects in the intervention group demonstrated a statistically significant 83.3% retention rate in the course of 1 year compared with only 54.3% for the control group (cardiovascular lifestyle education sessions alone). Six dropouts were noted in the intervention group in sharp contrast to 16 dropouts in the control group. Participants in the intervention group were 4.21 times more likely to complete the program than the control group. A significant difference was also noted for attendance, which was higher for the intervention group (21.33 sessions for the intervention group vs 17.95 sessions for the control group). Statistically significant systolic blood pressure reductions noted in both groups were sustained 6 mo postprogram conclusion. In addition, a statistically significant pre-between post-between group improvement in SF-12 Physical Component Scores was noted for intervention subjects in sharp contrast with controls who actually demonstrated worsening scores. The addition of a gospel music program as a catalyst for increase engagement in a sustainable, healthy lifestyle program warrants further consideration and additional study in African American churches.


Color selection, color capture, and afterimage filling-in.
R. van Lier, M. Vergeer, and S. Anstis (2009) reported an afterimage that produced different percepts from an inducing stimulus depending on the shape of a subsequent contour. G. Francis (2010) explained this phenomenon with a model where the contour forms a boundary that traps the afterimage color as it spreads across a surface. We conducted a series of additional model simulations and experiments to test the explanation. We first tested the hypothesis that the contour traps the afterimage color by adding additional contours. Model simulations suggest that additional contours could block color from spreading to the middle of the surface. In two experiments, additional contours blocked color spreading when they were at the inducer edges but not when they were drawn away from the inducer edges. In a second set of experiments, we investigated the model prediction that the drawn contour defines the perceived shape of the afterimage. New model simulations predict that variations in the size of the drawn contour force the perceived afterimage to vary accordingly. However, an experimental study revealed that the perceived afterimage size remains the same as the inducing stimulus. The simulation and experimental results both highlight and challenge important characteristics of the model.


Mild hyperthermia accelerates doxorubicin clearance from tumour-extravasated temperature-sensitive liposomes.
Mild hyperthermia (HT) (40-43 °C) has been combined with temperature-sensitive liposomes (TSL), offering on-demand drug release for increased drug bioavailability and reduced systemic toxicity. Different HT regimens have been applied to trigger liposome drug release in the blood vessels (intravascular) of heated tumours or following tumour extravasation (interstitial). The present study systematically assessed the in vivo doxorubicin (Dox) release and therapeutic efficacy of Dox-loaded TSL with different release profiles. Low temperature-sensitive liposomes (LTSL-Dox), traditional-temperature-sensitive liposomes (TTSL-Dox), and non-temperature-sensitive liposomes (NTSL-Dox) were combined with a single or two HT in different tumour models (murine melanoma B16F10 tumour and human breast MDA-MB-435). The efficacy of each treatment was assessed by monitor tumour growth and mice survival. The level of Dox in tumour tissues was quantified using 14C-Dox and liquid scintillation while Dox release was assessed using live imaging and confocal laser scanning microscopy. Applying a second HT to release Dox from extravasated TTSL-Dox was not therapeutically superior to single HT application due to Dox clearance from the extravasated TTSL-Dox. Our findings revealed that enhanced blood perfusion in heated tumours during the second water bath HT could be seen as a hurdle for TTSL-Dox's anticancer efficacy, where the systemic toxicity of the redistributed Dox from the tumour tissues could be potentiated.


Interpreting change on ImPACT following sport concussion.
The purpose of this study was to examine the psychometric characteristics of Version 2.0 of ImPACT (Immediate Postconcussion Assessment and Cognitive Testing). The focus was on the stability of the test scores and the calculation of reliable change confidence intervals for the test-retest difference scores. A sample of 56 nonconcussed adolescents and young adults completed the test battery on two occasions. Test-retest coefficients, reliable change difference scores, and confidence intervals for measurement error are provided. These reliable change parameters were applied to a second sample of 41 concussed amateur athletes who were tested preseason and within 72 hr of injury. Applying these confidence intervals allows more precise determinations of deterioration, improvement, and recovery in the initial days following concussion.


The MiAge Calculator: a DNA methylation-based mitotic age calculator of human tissue types.
Cell division is important in human aging and cancer. The estimation of the number of cell divisions (mitotic age) of a given tissue type in individuals is of great interest as it allows not only the study of biological aging (using a new molecular aging target) but also the stratification of prospective cancer risk. Here, we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions. With the MiAge model, the MiAge Calculator was built using the training data of DNA methylation measures of 4,020 tumor and adjacent normal tissue samples from eight TCGA cancer types and was tested using the testing data of DNA methylation measures of 2,221 tumor and adjacent normal tissue samples of five other TCGA cancer types. We showed that within each of the thirteen cancer types studied, the estimated mitotic age is universally accelerated in tumor tissues compared to adjacent normal tissues. Across the thirteen cancer types, we showed that worse cancer survivals are associated with more accelerated mitotic age in tumor tissues. Importantly, we demonstrated the utility of mitotic age by showing that the integration of mitotic age and clinical information leads to improved survival prediction in six out of the thirteen cancer types studied. The MiAge Calculator is available at http://www.columbia.edu/∼sw2206/softwares.htm .


Environment and behavior of 2.5-million-year-old Bouri hominids.
The Hata Member of the Bouri Formation is defined for Pliocene sedimentary outcrops in the Middle Awash Valley, Ethiopia. The Hata Member is dated to 2.5 million years ago and has produced a new species of Australopithecus and hominid postcranial remains not currently assigned to species. Spatially associated zooarchaeological remains show that hominids acquired meat and marrow by 2.5 million years ago and that they are the near contemporary of Oldowan artifacts at nearby Gona. The combined evidence suggests that behavioral changes associated with lithic technology and enhanced carnivory may have been coincident with the emergence of the Homo clade from Australopithecus afarensis in eastern Africa.


4-Fluoro-N'-(2-hydroxy-3-methoxybenzylidene) benzohydrazide and its Oxidovanadium(V) Complex: Syntheses, Crystal Structures and Insulin-enhancing Activity.
A hydrated hydrazone compound, 4-fluoro-N'-(2-hydroxy-3-methoxybenzylidene)benzohydrazide monohydrate (H2L · H2O), was prepared and characterized by elemental analysis, HRMS, IR, UV-Vis and 1H NMR spectroscopy. Reaction of H2L, kojic acid (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one; Hka) and VO(acac)2 in methanol afforded a novel oxidovanadium(V) complex, [VO(ka)L]. The complex was characterized by elemental analysis, IR, UV-Vis and 1H NMR spectroscopy. Thermal analysis was also performed. Structures of H2L and the complex were further confirmed by single crystal structural X-ray diffraction. The vanadium complex is the first structurally characterized vanadium complex of kojic acid. Insulin-mimetic tests on C2C12 muscle cells indicate that the complex significantly stimulated cell glucose utilization with cytotoxicity at 0.11 g L-1.


Vascular calcifications in homozygote familial hypercholesterolemia.
Patients with homozygous familial hypercholesterolemia (hmzFH) attributable to LDL receptor gene mutations have shown a remarkable increase in survival over the last 20 years. Early onset coronary heart disease (CHD) and calcific aortic valve stenosis are the major complications of this disorder. We now report extensive premature calcification of the aorta in patients with hmzFH. We examined 25 hmzFH patients from Canada; mean age was 32 years (range 5 to 54), and mean baseline cholesterol before treatment was 19+/-5 mmol/L (737+/-206 mg/dL). Aortic calcification was quantified using computed tomography (CT). An elevated mean calcium score was found in patients by age 20 and correlated with age (r(2)=0.53, P=0.001). One quarter (24%) of patients underwent aortic valve surgery. We document premature severe aortic calcifications in all adult hmzFH patients studied. These presented considerable surgical management challenges. Strategies to identify and monitor aortic calcification in hmzFH by noninvasive techniques are required, as are clinical trials to determine whether additional or more intensive therapies will prevent the progression of such calcifications. Whether vascular calcifications in hmzFH subjects are related to sustained increases in LDL-C levels or to other mechanisms, such as abnormal osteoblast activity, remains to be determined.


The epidemiology of drug use disorders cross-nationally: Findings from the WHO's World Mental Health Surveys.
Illicit drug use and associated disease burden are estimated to have increased over the past few decades, but large gaps remain in our knowledge of the extent of use of these drugs, and especially the extent of problem or dependent use, hampering confident cross-national comparisons. The World Mental Health (WMH) Surveys Initiative involves a standardised method for assessing mental and substance use disorders via structured diagnostic interviews in representative community samples of adults. We conducted cross-national comparisons of the prevalence and correlates of drug use disorders (DUDs) in countries of varied economic, social and cultural nature. DSM-IV DUDs were assessed in 27 WMH surveys in 25 countries. Across surveys, the prevalence of lifetime DUD was 3.5%, 0.7% in the past year. Lifetime DUD prevalence increased with country income: 0.9% in low/lower-middle income countries, 2.5% in upper-middle income countries, 4.8% in high-income countries. Significant differences in 12-month prevalence of DUDs were found across country in income groups in the entire cohort, but not when limited to users. DUDs were more common among men than women and younger than older respondents. Among those with a DUD and at least one other mental disorder, onset of the DUD was usually preceded by the 'other' mental disorder. Substantial cross-national differences in DUD prevalence were found, reflecting myriad social, environmental, legal and other influences. Nonetheless, patterns of course and correlates of DUDs were strikingly consistent. These findings provide foundational data on country-level comparisons of DUDs.


Contrasted patterns of molecular evolution in dominant and recessive self-incompatibility haplotypes in Arabidopsis.
Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus) in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae.


Outcomes in off-pump vs. on-pump coronary artery bypass grafting stratified by pre-operative risk profile: an assessment using propensity score.
To assess the benefit of off-pump coronary surgery stratified by the pre-operative risk profile. Prospective and multicentric cohort study. All consecutive patients undergoing a first coronary bypass procedure between November 2001 and November 2003 were potentially eligible. Pre-operative EuroSCORE and in-hospital outcomes were prospectively collected using strictly standardized criteria. To ensure optimal adjustment, a propensity score was constructed using clinically relevant variables and incorporating individual centres. Of 1602 patients who underwent a first coronary bypass, EuroSCORE could be calculated in 1585: 787 were of moderate/high pre-operative risk profile (EuroSCORE > 3), of which 347 underwent off-pump procedures, and 798 were of low pre-operative risk profile (EuroSCORE < or = 3), of which 349 underwent off-pump procedures. After risk adjusting for propensity score, off-pump patients had less major events (post-operative death, myocardial infarction, and need for reoperation). This benefit was higher in the low-risk stratum (OR ranged between 0.27 and 0.4; P = 0.02-0.07) than in the high-risk stratum (OR between 0.4 and 0.7; P, not significant). In real-life conditions, off-pump coronary surgery may be more effective than on-pump surgery. In contrast with previous reports, our results suggest that this benefit may be higher in patients with low pre-operative risk.


Hantavirus (Bunyaviridae) infections in rodents from Orange and San Diego counties, California.
During a screening program to determine the extent of hantavirus activity in Orange and San Diego Counties, California, serum samples from 2,365 rodents representing nine genera and 15 species were tested for hantavirus antibodies. A reverse transcription-polymerase chain reaction on selected seropositive rodents was used to identify the specific hantavirus. Rodents positive for Sin Nombre virus (SNV) antibodies by Western blot included 86 (9.1%) of 948 deer mice (Peromyscus maniculatus), four (1.5%) of 275 California mice (Peromyscus californicus), one (0.5%) of 196 cactus mice (Peromyscus eremicus), 51 (12.2%) of 417 harvest mice (Reithrodontomys megalotis), and five (12.5%) of 40 California voles (Microtus californicus). All other specimens tested were negative for hantavirus antibodies. There was a correlation between age and sex of the reservoir host and prevalence of SNV antibody, especially among male deer mice and harvest mice. Few seasonal trends in antibody prevalence were observed and continued maintenance of SNV and El Moro Canyon virus was found at several foci over a 4-5-year period. Isla Vista virus was also found in voles and represents the first recorded in Orange County. Microhabitat selection on the part of these rodents based on plant density, plant height, and availability of food plants may explain, to some extent, all of the hantavirus-positive foci throughout the study area over a broad geographic range and the lack of antibody-positive rodents in dense chaparral, woodland, and riparian areas. The majority of rodents positive for SNV was identified from localities along coastal bluffs and the foothills of the Santa Ana Mountains, where trap success was high and P. maniculatus represented 43% of all rodents collected. Several residential, commercial, and industrial sites exist in these areas and the potential health risk should not be overlooked. This study represents an in-depth analysis of the prevalence, host distribution, and characteristics of rodent populations infected by three hantaviruses within a small, well-defined, geographic area.


The value of the 2011 ASAS classification criteria in patients with Spondyloarthritis and the prognosis of non-radiographic axial Spondyloarthritis: data from a large cohort of a tertiary referral hospital.
Spondyloarthritides (SpA) are a group of interrelated rheumatic disorders that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis related to inflammatory bowel disease and reactive arthritis. Since the latest classification criteria published from the ASAS (Assessment of SpondyloArthritis international Society), patients with these diagnoses can be classified either as having axial or peripheral SpA. In this study, these new criteria of ASAS will be applied to all patients with a clinical diagnosis of SpA that are followed in the Rheumatology Clinic of University Hospital of Heraklion. Furthermore, patients with non-radiographic axial SpA (nrAxSpA) will be monitored, both retrospectively and prospectively, for their long-term outcome in terms of imaging and clinical aspects (remission, disability, severe complications, eg, uveitis). This study is expected to give valuable information of the performance of these new criteria in daily clinical practice and of the prognosis of patients with non-radiographic axial SpA.


Changes in Sexual Activity and Function After Pelvic Organ Prolapse Surgery: A Systematic Review.
We aimed to systematically review the literature to describe sexual activity and function before and after prolapse surgery. We searched MEDLINE, EMBASE, and ClinicalTrials.gov databases from inception to April 2018. Prospective, comparative studies of reconstructive pelvic organ prolapse (POP) surgeries that reported sexual function outcomes were included. Studies were extracted for population characteristics, sexual function outcomes, and methodologic quality. Data collected included baseline and postoperative sexual activity, dyspareunia, and validated sexual function questionnaire scores. Change in validated scores were used to categorize overall sexual function as improved, unchanged, or worsened after surgery. The search revealed 3,124 abstracts and identified 74 articles representing 67 original studies. The overall quality of evidence was moderate to high. Studies reporting postoperative results found higher rates of sexual activity than studies reporting preoperative sexual activity in all POP surgeries except sacrospinous suspension, transvaginal mesh, and sacrocolpopexy. The prevalence of dyspareunia decreased after all prolapse surgery types. The risk of de novo dyspareunia ranged from 0% to 9% for all POP surgeries except posterior repair, which lacked sufficient data. Overall sexual function based on PISQ-12 (Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-12) scores improved for mixed native tissue repairs, anterior repairs, uterosacral suspensions, sacrospinous suspensions, and sacrocolpopexy; scores were similar for posterior repairs, transvaginal mesh, and biologic grafts. Sexual function did not worsen after any POP surgeries. Sexual function improves or remains unchanged after all types of reconstructive POP surgeries and does not worsen for any surgery type. Prevalence of total dyspareunia was lower after all POP surgery types, and de novo dyspareunia was low ranging 0-9%. This information can help surgeons counsel patients preoperatively. PROSPERO, CRD42019124308.


Generation of Helper Plasmids Encoding Mutant Adeno-associated Virus Type 2 Capsid Proteins with Increased Resistance against Proteasomal Degradation.
Adeno-associated virus type 2 (AAV2) vectors are widely used for both experimental and clinical gene therapy. A recent research has shown that the performance of these vectors can be greatly improved by substitution of specific surface-exposed tyrosine residues with phenylalanines. In this study, a fast and simple method is presented to generate AAV2 vector helper plasmids encoding capsid proteins with single, double or triple Y→F mutations. A one-step, high-fidelity polymerase chain reaction (PCR) cloning procedure involving the use of two partially overlapping primers to amplify a circular DNA template was applied to produce AAV2 cap genes encoding VP1 mutants with Y→F substitutions in residues 444, 500 or 730. The resulting constructs were used to make the different double and triple mutant by another round of PCR (Y444500F mutant), subcloning (Y444730F and Y500730F mutants) or a combination of both techniques (Y444500730F mutant). Nucleotide sequence analysis revealed successful introduction of the desired mutations in the AAV2 cap gene and showed the absence of any unintended mutations in the DNA fragments used to assemble the final set of AAV2 vector helper plasmids. The correctness of these plasmids was further confirmed by restriction mapping. PCR-based, single-step site-directed mutagenesis of circular DNA templates is a highly efficient and cost-effective method to generate AAV2 vector helper plasmids encoding mutant Cap proteins for the production of vector particles with increased gene transfer efficiency.


Multidimensional single cell based STAT phosphorylation profiling identifies a novel biosignature for evaluation of systemic lupus erythematosus activity.
Dysregulated cytokine action on immune cells plays an important role in the initiation and progress of systemic lupus erythematosus (SLE), a complex autoimmune disease. Comprehensively quantifying basal STATs phosphorylation and their signaling response to cytokines should help us to better understand the etiology of SLE. Phospho-specific flow cytometry was used to measure the basal STAT signaling activation in three immune cell types of peripheral-blood mononuclear cells from 20 lupus patients, 9 rheumatoid arthritis (RA) patients and 13 healthy donors (HDs). A panel of 27 cytokines, including inflammatory cytokines, was measured with Bio-Plex™ Human Cytokine Assays. Serum Prolactin levels were measured with an immunoradiometric assay. STAT signaling responses to inflammatory cytokines (interferon α [IFNα], IFNγ, interleukin 2 [IL2], IL6, and IL10) were also monitored. We observed the basal activation of STAT3 in SLE T cells and monocytes, and the basal activation of STAT5 in SLE T cells and B cells. The SLE samples clustered into two main groups, which were associated with the SLE Disease Activity Index 2000, their erythrocyte sedimentation rate, and their hydroxychloroquine use. The phosphorylation of STAT5 in B cells was associated with cytokines IL2, granulocyte colony-stimulating factor (G-CSF), and IFNγ, whereas serum prolactin affected STAT5 activation in T cells. The responses of STAT1, STAT3, and STAT5 to IFNα were greatly reduced in SLE T cells, B cells, and monocytes, except for the STAT1 response to IFNα in monocytes. The response of STAT3 to IL6 was reduced in SLE T cells. The basal activation of STATs signaling and reduced response to cytokines may be helpful us to identify the activity and severity of SLE.


Gene transfer into the medfly, Ceratitis capitata, with a Drosophila hydei transposable element.
Exogenous functional DNA was introduced into the germline chromosomes of the Mediterranean fruit fly (medfly) Ceratitis capitata with a germline transformation system based on the transposable element Minos from Drosophila hydei. Transformants were identified as phenotypic revertants of a white-eyed mutation carried by the recipient strain. Clusters of transformants were detected among the progeny of 390 individuals screened for germline transformation. Five independent and phenotypically active integration events were identified, in each of which a single copy of the transposon was inserted into a different site of the medfly genome. Molecular analysis indicates that they represent transposase-mediated insertions of the transposon into medfly chromosomes.


Shape control of III-V semiconductor nanocrystals: synthesis and properties of InAs quantum rods.
A novel approach for synthesis of soluble semiconductor quantum rods using metal nanoparticles to direct and catalyze one-dimensional growth is developed. The method is useful in particular for III-V semiconductors with cubic lattice, where the utilization of surfactant-controlled rod-growth is not easily realized. The growth takes place via the solution-liquid-solid (SLS) mechanism where proper precursors are injected into a coordinating solvent. Centrifugation is used for separation of rod-fractions with different lengths. The reaction is demonstrated for InAs, InP and GaAs. Focusing on InAs rods as a model system, we examined the effects of the type of metal catalyst, and the tuning of reaction conditions with respect to temperature, concentration, catalyst content and reaction time. Within the three types of metal catalysts used--Au, Ag and In, Au was found to provide the best control for achieving rod-growth even though the melting point of bulk gold is significantly higher then the reaction temperature. The structural properties of the rods were characterized by transmission electron microscopy, X-ray diffraction and energy dispersive X-ray spectroscopy. Rods have a cubic lattice and grow mainly along the [111] direction. The relative gold content decreases in shorter rods suggesting Au depletion as a cause for limiting the growth. Room and low temperature absorption and photoluminescence measurements show that the band-gap shifts to the red upon increasing rod length revealing strong quantum confinement along the long axis in InAs rods, providing spectral coverage of the near-IR range relevant for telecommunication applications. Emission intensity also decreases with increased rod-length. These length dependent properties manifest the transition from 0D to 1D quantum confined systems.


Herpesviruses and breast milk.
Breast milk has always been the best source of nourishment for newborns. However, breast milk can carry a risk of infection, as it can be contaminated with bacterial or viral pathogens. This paper reviews the risk of acquisition of varicella-zoster virus (VZV) and cytomegalovirus (CMV), herpesviruses frequently detected in breastfeeding mothers, via breast milk, focusing on the clinical consequences of this transmission and the possible strategies for preventing it. Maternal VZV infections are conditions during which breastfeeding may be temporarily contraindicated, but expressed breast milk should always be given to the infant. CMV infection acquired through breast milk rarely causes disease in healthy term newborns; an increased risk of CMV disease has been documented in preterm infants. However, the American Academy of Pediatrics (AAP) does not regard maternal CMV seropositivity as a contraindication to breastfeeding; according to the AAP, in newborns weighing less than 1500 g, the decision should be taken after weighing the benefits of breast milk against the risk of transmission of infection. The real efficacy of the different methods of inactivating CMV in breast milk should be compared in controlled clinical trials, rigorously examining the negative consequences that each of these methods can have on the immunological and nutritional properties of the milk itself, with a view to establish the best risk-benefit ratio of these strategies before they are recommended for use in clinical practice.


First identification of Rickettsia helvetica in questing ticks from a French Northern Brittany Forest.
Tick-borne rickettsiae are considered to be emerging, but data about their presence in western Europe are scarce. Ixodes ricinus ticks, the most abundant and widespread tick species in western Europe, were collected and tested for the presence of several tick-borne pathogens in western France, a region never previously explored in this context. There was a high tick abundance with a mean of 4 females, 4.5 males, and 23.3 nymphs collected per hour per collector. Out of 622 tested ticks, specific PCR amplification showed the presence of tick symbionts as well as low prevalence of Borrelia burgdorferi (0.8%), Bartonella spp. (0.17%), and Anaplasma phagocytophilum (0.09%). The most prevalent pathogen was Rickettsia helvetica (4.17%). This is the first time that this bacteria has been detected in ticks in this region, and this result raises the possibility that bacteria other than those classically implicated may be involved in rickettsial diseases in western France.


Strategies for skeletal muscle tissue engineering: seed vs. soil.
The most commonly used tissue engineering approach includes the ex vivo combination of site-appropriate cell(s) and scaffold material(s) to create three-dimensional constructs for tissue replacement or reconstruction. These three-dimensional combinations are typically subjected to a period of culture and conditioning (i.e., self-assembly and maturation) to promote the development of ex vivo constructs which closely mimic native target tissue. This cell-based approach is challenged by the host response to the engineered tissue construct following surgical implantation. As an alternative to the cell-based approach, acellular biologic scaffolds attract endogenous cells and remodel into partially functional mimics of native tissue upon implantation. The present review examines cell-types (i.e., seed), scaffold materials (i.e., soil), and challenges associated with functional tissue engineering. Skeletal muscle is used as the target tissue prototype but the discussed principles will largely apply to most body systems.


Trends in social inequalities for premature coronary heart disease mortality in Great Britain, 1994-2008: a time trend ecological study.
To compare trends in metrics of socioeconomic inequalities in premature coronary heart disease (CHD) mortality in Great Britain. Time trend ecological study with area-level deprivation as exposure. Great Britain, 1994-2008. Men and women aged younger than 75 years. No lower age limit. None. CHD mortality rates. There has been a decrease in socioeconomic inequalities in CHD mortality in absolute terms but an increase in relative terms. CHD mortality rates in men aged younger than 75 years fell by 69 per 100 000 (95% CIs 64 to 74) in the least deprived quintile and by 92 per 100 000 (95% CI 86 to 98) in the most deprived quintile (p for trend: <0.001). Mortality rate ratios comparing the most deprived quintile to the least deprived quintile increased in women aged younger than 75 years from 1.77 (95% CI 1.68 to 1.86) to 2.32 (95% CI 2.14 to 2.52). There was a weak negative association between the average decline of relative rates and area deprivation. It could either be said that inequalities in premature mortality from CHD between affluent and deprived areas have widened or narrowed between 1994 and 2008 depending on the measurement technique. In the context of falling CHD mortality rates, narrowing of absolute inequalities is to be expected, but increases in relative inequalities are a cause for concern.


Regulation of calcium in pancreatic α- and β-cells in health and disease.
The glucoregulatory hormones insulin and glucagon are released from the β- and α-cells of the pancreatic islets. In both cell types, secretion is secondary to firing of action potentials, Ca(2+)-influx via voltage-gated Ca(2+)-channels, elevation of [Ca(2+)](i) and initiation of Ca(2+)-dependent exocytosis. Here we discuss the mechanisms that underlie the reciprocal regulation of insulin and glucagon secretion by changes in plasma glucose, the roles played by different types of voltage-gated Ca(2+)-channel present in α- and β-cells and the modulation of hormone secretion by Ca(2+)-dependent and -independent processes. We also consider how subtle changes in Ca(2+)-signalling may have profound impact on β-cell performance and increase risk of developing type-2 diabetes.


Metabolic depression in land snails: in vitro analysis of protein kinase involvement in pyruvate kinase control in isolated Otala lactea tissues.
Isolated tissues from the land snail Otala lactea were used to examine the relationship between protein kinase activity and phosphorylation-induced changes associated with metabolic depression. Hepatopancreas and foot muscle were removed from active and estivating land snails and incubated in vitro under aerobic and anoxic conditions. Pyruvate kinase (PK), cAMP-dependent protein kinase (PKA), and protein kinase second messenger compounds (cyclic AMP and inositol 1,4,5-triphosphate) were measured after incubating the tissues for 4 hours. Pyruvate kinase from the hepatopancreas of active snails was phosphorylated during anoxic incubations as indicated by changes in the I50 value for L-alanine. However, measurements of PKA activity and of cellular cAMP concentrations suggested that PKA activity was lower in these incubated tissues. When foot muscle was used as the tissue source, incubation under anoxic conditions produced no changes in PK activity even though PKA activity was drastically reduced. Analysis of changes in inositol 1,4,5-triphosphate concentrations after tissue incubation showed that they were not consistent with changes in PK activity in either organ. These results suggest that PKA and Ca2+/phospholipid-dependent protein kinase C do not phosphorylate PK during anoxia in land snails. The differences between values measured in incubated tissues and those measured in vivo suggest that isolated O. lactea tissues are not a good in vitro model system for studying metabolic changes associated with depressed metabolism.


Is functional MR imaging assessment of hemispheric language dominance as good as the Wada test?: a meta-analysis.
To perform a systematic review and meta-analysis to quantitatively assess functional magnetic resonance (MR) imaging lateralization of language function in comparison with the Wada test. This study was determined to be exempt from review by the institutional review board. A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A structured Medline search was conducted to identify all studies that compared functional MR imaging with the Wada test for determining hemispheric language dominance prior to brain surgery. Studies meeting predetermined inclusion criteria were selected independently by two radiologists who also assessed their quality using the Quality Assessment of Diagnostic Accuracy Studies tool. Language dominance was classified as typical (left hemispheric language dominance) or atypical (right hemispheric language dominance or bilateral language representation) for each patient. A meta-analysis was then performed by using a bivariate random-effects model to derive estimates of sensitivity and specificity, with Wada as the standard of reference. Subgroup analyses were also performed to compare the different functional MR imaging techniques utilized by the studies. Twenty-three studies, comprising 442 patients, met inclusion criteria. The sensitivity and specificity of functional MR imaging for atypical language dominance (compared with the Wada test) were 83.5% (95% confidence interval: 80.2%, 86.7%) and 88.1% (95% confidence interval: 87.0%, 89.2%), respectively. Functional MR imaging provides an excellent, noninvasive alternative for language lateralization and should be considered for the initial preoperative assessment of hemispheric language dominance. Further research may help determine which functional MR methods are most accurate for specific patient populations.


Inertio-capillary cross-streamline drift of droplets in Poiseuille flow using dissipative particle dynamics simulations.
We find using dissipative particle dynamics (DPD) simulations that a deformable droplet sheared in a narrow microchannel migrates to steady-state position that depends upon the dimensionless particle capillary number , which controls the droplet deformability (with Vmax the centerline velocity, μf the fluid viscosity, Γ the surface tension, R the droplet radius, and H the gap), the droplet (particle) Reynolds number , which controls inertia, where ρ is the fluid density, as well as on the viscosity ratio of the droplet to the suspending fluid κ = μd/μf. We find that when the Ohnesorge number is around 0.06, so that inertia is stronger than capillarity, at small capillary number Cap < 0.1, the droplet migrates to a position close to that observed for hard spheres by Segre and Silberberg, around 60% of the distance from the centerline to the wall, while for increasing Cap the droplet steady-state position moves smoothly towards the centerline, reaching around 20% of the distance from centerline to the wall when Cap reaches 0.5 or so. For higher Oh, the droplet position is much less sensitive to Cap, and remains at around 30% of the distance from centerline to the wall over the whole accessible range of Cap. The results are insensitive to viscosity ratios from unity to the highest value studied here, around 13, and the drift towards the centerline for increasing Cap is observed for ratios of droplet diameter to gap size ranging from 0.1 to 0.3. We also find consistency between our predictions and existing perturbation theory for small droplet or particle size, as well as with experimental data. Additionally, we assess the accuracy of the DPD method and conclude that with current computer resources and methods DPD is not readily able to predict cross-stream-line drift for small particle Reynolds number (much less than unity), or for droplets that are less than one tenth the gap size, owing to excessive noise and inadequate numbers of DPD particles per droplet.