The impact of predation by marine mammals on patagonian toothfish longline fisheries.
Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of "depredation hot spots" can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources.


Optimization of pegylated iron oxide nanoplatforms for antibody coupling and bio-targeting.
PEGylation has been established as a valuable strategy to minimize nanoparticle clearance by the reticulo-endothelial system due to hydrophilicity and steric repulsion of PEG chains. In this study we functionalized superparamagnetic iron oxide nanoparticle surface with two PEG differing in their length (n = 23 and 44) and terminal functionality, COOH and CH3. By varying the ratio of the two different PEG, we optimized the molecular architecture of the nanoplatform to obtain maximum stability and low toxicity under physiological conditions. The best nanoplatform was evaluated as MRI contrast for mouse brain vascularization imaging at 7 T. The carboxylic acid functions of the nanoplatform were used to covalently bind an antibody, Ab. This antibody, labeled with a fluorophore, targets the ETA receptor, a G-protein-coupled receptor involved in the endothelin axis and overexpressed in various solid tumours, including ovarian, prostate, colon, breast, bladder and lung cancers. In vitro studies, performed by flow cytometry and magnetic quantification, showed the targeting efficiency of the Ab-nanoplatforms. Clearly, an imaging tracer for cancer diagnosis from a bimodal contrast agent (fluorescence and MRI) was thus obtained.


Fluorescence-assisted cytological testing (FACT): Ex Vivo viral method for enhancing detection of rare cancer cells in body fluids.
Cytological analysis of body fluids is currently used for detecting cancer. The objective of this study was to determine if the herpes virus carrying an enhanced green fluorescent protein (EGFP) could detect rare cancer cells in body fluids against millions of normal cells. Human cancer cells suspended with normal murine cells were infected with NV1066 at a multiplicity of infection (MOI) of 0.5 and 1.0 for 18 h. Fluorescent microscopy and flow cytometry were used for EGFP detection of cancer cells. EGFP-expressing cells were confirmed as cancer cells with specific markers by immunohistochemistry staining. Limits of detection of cancer cells in body fluid were measured by serial dilutions. Applicability of technique was confirmed with samples from patients with malignant pleural effusions. NV1066 expressed EGFP in 111 human cancer cell lines detected by fluorescent microscopy at an MOI of 0.5. NV1066 selectively infected cancer cells and spared normal cells as confirmed by immunohistochemistry. Sensitivity of detecting fluorescent green cells was 92% (confidence interval [CI] 83% to 97%) at a ratio of 1 cancer cell to 1 million normal cells. EGFP-positive cells were detected by fluorescent microscopy in patients' malignant pleural effusion samples. Our data show proof of the concept that NV1066-induced EGFP expression allows detection of a single cancer cell against a background of 1 million normal cells. This method was demonstrated to be a reliable screening tool for human cancer cells in a suspension of normal murine cells as well as clinical specimens of malignant pleural effusions.


Potentiation of the contractile effects of norepinephrine by hypoxia.
Hypoxia has been found to depress the concentration response curve of norepinephrine (NE) in isoalted cat papillary muscles. To investigate the effects of hypoxia in intact hearts, a heart-lung preparation was developed and maximum left ventricular dp/dt (max dp/dt) was measured at constant heart rate, preload, and after load. Left main coronary arterial flow (Q(e)) was measured with an electromagnetic flow probe. As arterial P(O2) decreased from 90 mm Hg (96% saturation) to 20-25 mm Hg (40% saturation) at constant P(CO2) and pH, no change in max dp/dt occurred and Q(e) increased 298%. In contrast to cat papillary muscles, the contractile responses to NE were augmented in hypoxia. The NE dose-response curves shifted to the left. No deterioration of contractility occurred after exposure to NE. In contrast, the chronotropic response was unaltered in hypoxia. Dose-response curves to isoproterenol also were shifted to the left in hypoxia, but responses to paired pacing were unchanged. The responses to NE under oxygenated conditions were unaltered by mechanically increased coronary flow or by increased coronary flow with nitroglycerin. Although the mechanisms responsible for these effects are unknown, the results suggest that hypoxia may open previously nonfunctioning vascular channels and thereby allow more extensive exposure of beta adrenergic receptors to circulating catecholamines.


PREPARE: guidelines for planning animal research and testing.
There is widespread concern about the quality, reproducibility and translatability of studies involving research animals. Although there are a number of reporting guidelines available, there is very little overarching guidance on how to plan animal experiments, despite the fact that this is the logical place to start ensuring quality. In this paper we present the PREPARE guidelines: Planning Research and Experimental Procedures on Animals: Recommendations for Excellence. PREPARE covers the three broad areas which determine the quality of the preparation for animal studies: formulation, dialogue between scientists and the animal facility, and quality control of the various components in the study. Some topics overlap and the PREPARE checklist should be adapted to suit specific needs, for example in field research. Advice on use of the checklist is available on the Norecopa website, with links to guidelines for animal research and testing, at https://norecopa.no/PREPARE .


Cognitive and neural architecture of decision making competence.
Although cognitive neuroscience has made remarkable progress in understanding the neural foundations of goal-directed behavior and decision making, neuroscience research on decision making competence, the capacity to resist biases in human judgment and decision making, remain to be established. Here, we investigated the cognitive and neural mechanisms of decision making competence in 283 healthy young adults. We administered the Adult Decision Making Competence battery to assess the respondent's capacity to resist standard biases in decision making, including: (1) resistance to framing, (2) recognizing social norms, (3) over/under confidence, (4) applying decision rules, (5) consistency in risk perception, and (6) resistance to sunk costs. Decision making competence was assessed in relation to core facets of intelligence, including measures of crystallized intelligence (Shipley Vocabulary), fluid intelligence (Figure Series), and logical reasoning (LSAT). Structural equation modeling was applied to examine the relationship(s) between each cognitive domain, followed by an investigation of their association with individual differences in cortical thickness, cortical surface area, and cortical gray matter volume as measured by high-resolution structural MRI. The results suggest that: (i) decision making competence is associated with cognitive operations for logical reasoning, and (ii) these convergent processes are associated with individual differences within cortical regions that are widely implicated in cognitive control (left dACC) and social decision making (right superior temporal sulcus; STS). Our findings motivate an integrative framework for understanding the neural mechanisms of decision making competence, suggesting that individual differences in the cortical surface area of left dACC and right STS are associated with the capacity to overcome decision biases and exhibit competence in decision making.


Screening for enteropathogenic Escherichia coli in infants with diarrhea by the fluorescent-actin staining test.
The attaching effacing (AE) adherence property is now recognized as an important virulence characteristic of enteropathogenic Escherichia coli (EPEC). The fluorescent-actin staining (FAS) test (S. Knutton, T. Baldwin, P. H. Williams, and A. S. McNeish, Infect. Immun. 57:1290-1298, 1989), which is diagnostic for the AE lesions produced by EPEC (and Vero cytotoxin-producing E. coli), has provided an additional tool with which to investigate this important class of enteric pathogens. In this study, we screened for the AE adherence property in two groups of E. coli isolated from infants with diarrhea by using the FAS test and compared the results with those from O:H serotyping, localized adhesion to HEp-2 cells (LA), and the EPEC adherence factor (EAF) probe. Only 16 of 41 (39%) E. coli strains previously diagnosed as EPEC by O antigen serogrouping were FAS test positive, and of these only 12 belonged to recognized EPEC O:H serotypes; 9 strains which did belong to EPEC O:H serotypes were FAS test negative. Of a second group of 297 untyped E. coli, 7 (2.3%) were FAS test positive, and of these only 2 belonged to EPEC serogroups; 5 belonged to serogroups not regarded as EPEC serogroups or were nontypeable. Of the 23 FAS-test-positive strains identified, 10 were EAF probe positive and showed good LA; 13 were EAF probe negative and showed a quantitatively distinctly poor LA. EAF-positive and EAF-negative strains, however, showed equally good adhesion to human small intestinal mucosa. None of the FAS-test-positive E. coli hybridized with probes for Vero toxins 1 or 2. We conclude that the FAS test is diagnostic not only for classical EPEC and Vero cytotoxin-producing E. coli but also for EPEC strains which are not currently being diagnosed because they belong to serotypes not generally regarded as EPEC serotypes.


Subacute Thyroiditis: An Unusual Presentation of Fever of Unknown Origin Following Upper Respiratory Tract Infection.
BACKGROUND Fever of unknown origin (FUO) is a diagnosis that requires a demanding workup from physicians before confirming a diagnosis. Thyroid diseases are a rare cause of FUO. Subacute thyroiditis is an inflammatory disease that can lead to a wide spectrum of presentations. CASE REPORT We report a case of a previously healthy male who presented with persistent fever of 4 weeks following an upper respiratory tract infection associated with constitutional symptoms. His laboratory workup included complete blood counts (CBC), complete metabolic panel (blood urea and creatinine, liver function tests, and serum electrolytes), blood cultures, abdominal and pelvic ultrasound, and computed tomography abdomen and pelvis that were inconclusive. His thyroid function tests showed a hyperthyroid state and a thyroid scan confirmed a picture of thyroiditis. The patient was treated with Ibuprofen and then with prednisolone; he showed significant improvement over a few days and was discharged with treatment of tapering doses of prednisolone over 6 weeks. Two weeks after discharge the patient had a follow-up at an outpatient clinic and was found to be in good health with resolution of his symptoms. CONCLUSIONS Thyroid disorders are not a common cause of FUO, and even if the clinical assessment of the patient is not suggestive of thyroid disease, we should consider it a possible cause. and thyroid function test should be performed to exclude thyroid problems.


Synthesis and antibacterial evaluation of 3-Farnesyl-2-hydroxybenzoic acid from Piper multiplinervium.
3-Farnesyl-2-hydroxybenzoic acid is an antibacterial agent isolated from the leaves of Piper multiplinervium. This compound has activity against both Gram positive and Gram negative bacteria including Escherichia coli, Staphylococcus aureus and Helicobacter pylori. This research aimed to synthesize a natural antibacterial compound and its analogs. The synthesis of 3-Farnesyl-2-hydroxybenzoic acid consists of three steps: straightforward synthesis involving protection of phenolic hydroxyl group, coupling of suitable isoprenyl chain to the protected aromatic ring at ortho position followed by carboxylation with concomitant deprotection to give the derivatives of the salicylic acid. All the three prenylated compounds synthesized were found to exhibit spectrum of activity against S. aureus (ATCC) having MIC: 5.84×10(-3), 41.46×10(-2) and 6.19×10(-1) μmol/ml respectively. The compounds also displayed activity against resistance strain of S. aureus (SA1119B) having MIC: 5.84×10(-3), 7.29×10(-3) and 3.09×10(-1) μmol/ml respectively. This synthesis has been achieved and accomplished with the confirmation of it structure to that of the original natural product, thus producing the first synthesis of the natural product and providing the first synthesis of its analogs with 3-Farnesyl-2-hydroxybenzoic acid having biological activity higher than that of the original natural product.


Reconstructing accurate ToF-SIMS depth profiles for organic materials with differential sputter rates.
To properly process and reconstruct 3D ToF-SIMS data from systems such as multi-component polymers, drug delivery scaffolds, cells and tissues, it is important to understand the sputtering behavior of the sample. Modern cluster sources enable efficient and stable sputtering of many organics materials. However, not all materials sputter at the same rate and few studies have explored how different sputter rates may distort reconstructed depth profiles of multicomponent materials. In this study spun-cast bilayer polymer films of polystyrene and PMMA are used as model systems to optimize methods for the reconstruction of depth profiles in systems exhibiting different sputter rates between components. Transforming the bilayer depth profile from sputter time to depth using a single sputter rate fails to account for sputter rate variations during the profile. This leads to inaccurate apparent layer thicknesses and interfacial positions, as well as the appearance of continued sputtering into the substrate. Applying measured single component sputter rates to the bilayer films with a step change in sputter rate at the interfaces yields more accurate film thickness and interface positions. The transformation can be further improved by applying a linear sputter rate transition across the interface, thus modeling the sputter rate changes seen in polymer blends. This more closely reflects the expected sputtering behavior. This study highlights the need for both accurate evaluation of component sputter rates and the careful conversion of sputter time to depth, if accurate 3D reconstructions of complex multi-component organic and biological samples are to be achieved. The effects of errors in sputter rate determination are also explored.


Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects.
This study presents two novel theoretical models to elucidate frequency sensitive nuclear mechanisms in low-intensity ultrasound enhanced bioeffects. In contrast to the typical 1.5 MHz pulsed ultrasound regime, our group previously experimentally confirmed that ultrasound stimulation of anchored chondrocytes at resonant frequency maximized gene expression of load inducible genes which are regulatory markers for cellular response to external stimuli. However, ERK phosphorylation displayed no frequency dependency, suggesting that the biochemical mechanisms involved in enhanced gene expression is downstream of ERK phosphorylation. To elucidate such underlying mechanisms, this study presents a theoretical model of an anchored cell, representing an in vitro chondrocyte, in an ultrasound field. The model results showed that the mechanical energy storage is maximized at the chondrocyte's resonant frequency and the energy density in the nucleus is almost twice as high as in the cytoplasm. Next, a mechanochemical model was developed to link the mechanical stimulation of ultrasound and the increased mechanical energy density in the nucleus to the downstream targets of the ERK pathway. This study showed for the first time that ultrasound stimulation induces frequency dependent gene expression as a result of altered rates of transcription factors binding to chromatin.


[Programs for the detection of gynecologic cancer].
The author reviews the problem of the early detection of breast cancer in women. He tells about the etiopathogenic complex, and the risk factors in relation to breast cancer, and indicates the protocol followed for breast cancer early detection. The usefulness of the employed method is supported by the obtained results after studying 69,635 women, and makes an economical evaluation of the cancer detection campaigns.


Lycopene alleviates hepatic ischemia reperfusion injury via the Nrf2/HO-1 pathway mediated NLRP3 inflammasome inhibition in Kupffer cells.
Lycopene is a naturally occurring carotenoid found in many fruits and vegetables, which has antioxidant effects. Although lycopene's protective effect has been observed on ischemia reperfusion (IR) injury in different organs, the effect of lycopene on Kupffer cells (KCs) has not been clearly elucidated in IR-induced acute hepatic inflammatory injury. Mice were administered with either olive oil (10 mL/kg body weight) as the control or lycopene (20 mg/kg body weight) by gavage for 2 weeks before undergoing hepatic IR injury. In this study, we observed that the levels of aspartate aminotransferases (AST), alanine aminotransferase (ALT), and the percentages of hepatocellular apoptosis in mice pretreated with lycopene were significantly lower than control mice. Lycopene inhibited F4/80+ macrophage and Ly6G+ neutrophil accumulation, which further decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin 6 (IL-6). Interestingly, lycopene induced increased autophagy in KCs, which was evidenced by elevated autophagosomes and the increased protein level of LC3B. In these KCs, lycopene-induced upregulation of autophagy inhibited NOD-like receptor family pyrin domain-containing 3 protein (NLRP3) inflammasome activation, which was demonstrated by the reduced mRNA and protein levels of NLRP3, cleaved caspase-1, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and IL-1β. Furthermore, 3-methyladenine, an autophagy inhibitor, abolished lycopene's inhibitory effect on the NLRP3 inflammasome in KCs, which led to increased hepatic IR injury. Intriguingly, we identified that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were elevated in KCs isolated from IR-stressed mice pretreated with lycopene. Nrf2-siRNA or HO-1-siRNA could block the autophagy activation enhanced by lycopene in KCs, resulting in the activation of the NLRP3 inflammasome and aggravated hepatic IR injury. Our findings demonstrated that lycopene promoted Nrf2/HO-1 pathway activation and further suppressed the NLRP3 inflammasome via enhancing KC autophagy, which alleviated hepatic IR injury.


Development and validation of a lifetime exposure questionnaire for use among Chinese populations.
The sunlight exposure questionnaire for use in the Chinese population was constructed based on extensive literature review and item suitability for measuring life-time exposure. The content validity index (CVI) was derived from ratings by, an expert panel to assess the item content and relevance. 650 population-based Chinese women completed the sunlight exposure questionnaire through telephone interview. To assess the questionnaire reliability, 94 women were re-interviewed after 2 weeks. 98.4% of the sunlight exposure questionnaire items were found to have valid CVI (>0.83). The Scree plot and the Principal Components Factor Analysis showed a two-factor construct was appropriate and no questionnaire item needed to be excluded. The questionnaire also had a good test-retest reliability (ICC: 0.59-0.93; k: 0.51-100). This sunlight exposure questionnaire was found to be adequate for measurement of life-time sunlight exposure among Hong Kong Chinese women.


Leaky waveguide modes along the edge of a dielectric wedge.
It is shown experimentally that a Gaussian beam focused from within a finite wedge onto its edge at an angle of total reflection excites a leaky waveguide mode propagating along the edge. This newly described phenomenon is interpreted in terms of waveguide modes of a tapered dielectric slab of a mode index, which is known to decrease with slab thickness. This decrease in the refractive index leads to a gradual refraction of the incident beam parallel to the edge. A numerical simulation of a focused Gaussian beam incident on a finite dielectric wedge gives a full account of this phenomenon.


Modeling of Biomechanics and Biorheology of Red Blood Cells in Type 2 Diabetes Mellitus.
Erythrocytes in patients with type-2 diabetes mellitus (T2DM) are associated with reduced cell deformability and elevated blood viscosity, which contribute to impaired blood flow and other pathophysiological aspects of diabetes-related vascular complications. In this study, by using a two-component red blood cell (RBC) model and systematic parameter variation, we perform detailed computational simulations to probe the alteration of the biomechanical, rheological, and dynamic behavior of T2DM RBCs in response to morphological change and membrane stiffening. First, we examine the elastic response of T2DM RBCs subject to static tensile forcing and their viscoelastic relaxation response upon release of the stretching force. Second, we investigate the membrane fluctuations of T2DM RBCs and explore the effect of cell shape on the fluctuation amplitudes. Third, we subject the T2DM RBCs to shear flow and probe the effects of cell shape and effective membrane viscosity on their tank-treading movement. In addition, we model the cell dynamic behavior in a microfluidic channel with constriction and quantify the biorheological properties of individual T2DM RBCs. Finally, we simulate T2DM RBC suspensions under shear and compare the predicted viscosity with experimental measurements. Taken together, these simulation results and their comparison with currently available experimental data are helpful in identifying a specific parametric model-the first of its kind, to our knowledge-that best describes the main hallmarks of T2DM RBCs, which can be used in future simulation studies of hematologic complications of T2DM patients.


Spatiotemporal prediction of fine particulate matter during the 2008 northern California wildfires using machine learning.
Estimating population exposure to particulate matter during wildfires can be difficult because of insufficient monitoring data to capture the spatiotemporal variability of smoke plumes. Chemical transport models (CTMs) and satellite retrievals provide spatiotemporal data that may be useful in predicting PM2.5 during wildfires. We estimated PM2.5 concentrations during the 2008 northern California wildfires using 10-fold cross-validation (CV) to select an optimal prediction model from a set of 11 statistical algorithms and 29 predictor variables. The variables included CTM output, three measures of satellite aerosol optical depth, distance to the nearest fires, meteorological data, and land use, traffic, spatial location, and temporal characteristics. The generalized boosting model (GBM) with 29 predictor variables had the lowest CV root mean squared error and a CV-R2 of 0.803. The most important predictor variable was the Geostationary Operational Environmental Satellite Aerosol/Smoke Product (GASP) Aerosol Optical Depth (AOD), followed by the CTM output and distance to the nearest fire cluster. Parsimonious models with various combinations of fewer variables also predicted PM2.5 well. Using machine learning algorithms to combine spatiotemporal data from satellites and CTMs can reliably predict PM2.5 concentrations during a major wildfire event.


Granulomatous infections complicating hairy cell leukemia.
Of 14 patients with hairy cell leukemia (HCL), four developed opportunistic granulomatous infections: blastomycosis, coccidioidomycosis and two Mycobacterium kansasii. The former two pathogens have not been reported with HCL, while M. kansasii infections appear to be common. While most reviews stress susceptibility to pyogenic bacteria and the predisposing role of iatrogenic factors, three of our patients were infected prior to any therapy. Thus, disease-related factors predispose to these granulomatous infections. Granulocytopenia and monocytopenia were present; the latter was not often corrected by splenectomy. There was impaired granuloma formation, with all infectious lesions appearing histologically as focal microabscesses containing few macrophages. Awareness of the frequency of opportunistic intracellular infections with early consideration of invasive diagnostic procedures to establish specific etiologic diagnosis may greatly prolong survival for many HCL patients.


Expression of the avirulence gene avrBs3 from Xanthomonas campestris pv. vesicatoria is not under the control of hrp genes and is independent of plant factors.
The avirulence gene avrBs3 from Xanthomonas campestris pv. vesicatoria pepper race 1 is responsible for the induction of a race-specific hypersensitive reaction in resistant pepper cultivars. A DNA region of 3.7 kb, containing several open reading frames and an internal repetitive region, was shown previously to be necessary for avirulence activity (U. Bonas, R. E. Stall, and B. Staskawicz, Mol. Gen. Genet. 218:127-136, 1989). The promoter of avrBs3 was identified by using gene fusions to beta-glucuronidase. Also, we mapped the transcription start site and showed that the avrBs3 gene is expressed constitutively in cells grown in minimal or complex medium and in planta. Polyclonal antibodies raised against a fusion protein produced in Escherichia coli allowed the identification of a 122-kDa protein in X. campestris pv. vesicatoria cells expressing the avrBs3 gene. The antibody is specific for AvrBs3 in X. campestris pv. vesicatoria cells but also recognizes homologous proteins in other pathovars of X. campestris. We found that AvrBs3 is localized intracellularly in X. campestris pv. vesicatoria and is mainly in the soluble fraction. The effect of mutations in the hrp gene cluster on the function of AvrBs3 was examined. Expression of AvrBs3 in X. campestris pv. vesicatoria grown in minimal or complex medium is independent of the hrp gene cluster that determines pathogenicity and hypersensitivity to X. campestris pv. vesicatoria. In the plant, however, the hrp genes are required for elicitation of a race-specific resistance response.


Media Exposure and Health in Europe: Mediators and Moderators of Media Systems.
This study examined media exposure as an explanatory factor for individual and cross-national differences in self-assessed general health. In studying media exposure, traditional media (television, radio, and newspapers) and contemporary media (internet) were separately considered. Aside from hypotheses about the relation between media exposure and general health, we also tested hypotheses regarding the mediating role of social isolation and mean world syndrome as well as the moderating role of different media systems across countries. Therefore, we used European Social Survey 2010, covering 25 European countries (n = 36,692). The results of our multilevel regression analyses indicated that exposure to television was negatively related to general health, whereas exposure to radio and newspapers were positively related to health. For contemporary media, findings indicated consistent positive relations between internet exposure and health across. Furthermore, limited support was found for the mediating role of social isolation and the mean world syndrome in the link between media exposure and health. Across media systems, findings for the relations between exposure to the various types of media and health proved to be robust.


Neurogenesis enhances response specificity to spatial pattern stimulation in hippocampal cultures.
Adult neurogenesis in the hippocampus facilitates cognitive functions such as pattern separation in mammals. However, it remains unclear how newborn neurons mediate changes in neural networks to enhance pattern separation ability. Here, we developed an in vitro model of adult neurogenesis using rat hippocampal cultures in order to investigate whether newborn neurons can be directly incorporated into neural networks related to pattern separation to produce functional improvements. We optimized at schedule of basic fibroblast growth factor (bFGF) administration to enhance neurogenesis, and then used a microelectrode array system to evaluate the responses of neural cultures to two different spatial pattern stimuli (L and inverted L shapes) before and after training. We found that early synaptic response times to a given pattern were shortened after training, and that this effect was more pronounced in cultures treated with bFGF. Furthermore, bFGF-treated cultures showed improved response specificity after training as indicated by calculated Kullback-Leibler divergence values, suggesting that pattern separation was better achieved in cultures with enhanced neurogenesis. Neural networks containing greater numbers of immature neurons exhibited higher response specificity to spatial pattern stimulation, suggesting the improvement of the pattern separation by neurogenesis enhancement. These results are the first in vitro demonstration that neurogenesis improves pattern separation. Our novel in vitro system will be a useful tool for investigating the contribution of adult neurogenesis to cognitive functions.


Frailty is associated with the clinical expression of neuropsychological deficits in older adults.
The aim was to determine whether frailty is associated with the relationship between neuropsychological markers and global cognition in older adults. Cross-sectional analyzes were conducted of baseline data from three large cohort studies: National Alzheimer's Coordinating Center (NACC), Rush Memory and Aging Project (MAP) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Studies recruited North American participants along the spectrum of cognitive functioning (44% no cognitive impairment at baseline). A frailty index was computed in each dataset. Frailty indices, neuropsychological tests (including measures of processing speed, episodic, semantic and working memory) and Mini-Mental State Examination (MMSE) scores were the variables of interest, with age, sex, education and apolipoprotein E ε4 evaluated as confounders. Across all studies, 23,819 participants aged 55-104 (57% female) were included in analyzes. Frailty index scores were significantly and inversely associated with MMSE scores and significantly moderated relationships between neuropsychological test scores and MMSE scores. In participants with higher frailty index scores, lower neuropsychological test scores were more strongly associated with lower MMSE scores (standardized interaction coefficients ranged from -0.19 to -1.17 in NACC, -0.03 to -2.27 in MAP and -0.04 to -0.38 in ADNI, depending on the neuropsychological test). These associations were consistent across the different databases and were mostly independent of the composition of frailty indices (i.e., after excluding possible symptoms of dementia). Amongst older Americans, frailty is associated with the cognitive expression of neuropsychological deficits. Implementation of frailty assessment in routine neurological and neuropsychological practice should be considered to optimize care outcomes for older adults.


Evidence on anti-malarial and diagnostic markets in Cambodia to guide malaria elimination strategies and policies.
Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities. From August 17th to October 1st, 2015, a cross sectional, nationally-representative malaria outlet survey was conducted in Cambodia. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was conducted among 180 communes. An audit was completed for all anti-malarials, malaria rapid diagnostic tests (RDT) and microscopy. A total of 26,664 outlets were screened, and 1303 outlets were eligible and interviewed. Among all screened outlets in the public sector, 75.9% of public health facilities and 67.7% of community health workers stocked both malaria diagnostic testing and a first-line artemisinin-based combination therapy (ACT). Among anti-malarial-stocking private sector outlets, 64.7% had malaria blood testing available, and 70.9% were stocking a first-line ACT. Market share data illustrate that most of the anti-malarials were sold or distributed through the private sector (58.4%), including itinerant drug vendors (23.4%). First-line ACT accounted for the majority of the market share across the public and private sectors (90.3%). Among private sector outlets stocking any anti-malarial, the proportion of outlets with a first-line ACT or RDT was higher among outlets that had reportedly received one or more forms of 'support' (e.g. reportedly received training in the previous year on malaria diagnosis [RDT and/or microscopy] and/or the national treatment guidelines for malaria) compared to outlets that did not report receiving any support (ACT: 82.1 and 60.6%, respectively; RDT: 78.2 and 64.0%, respectively). The results point to high availability and distribution of first-line ACT and widespread availability of malaria diagnosis, especially in the public sector. This suggests that there is a strong foundation for achieving elimination goals in Cambodia. However, key gaps in terms of availability of malaria commodities for case management must be addressed, particularly in the private sector where most people seek treatment. Continued engagement with the private sector will be important to ensure accelerated progress towards malaria elimination.


Toll-like receptor 9 polymorphisms influence mother-to-child transmission of human immunodeficiency virus type 1.
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and play a crucial role in the host's innate immune response. Genetic variations in TLR genes may influence host-viral interactions and might impact upon the risk of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus type 1 (HIV-1). The aim of this study was to investigate the influence of genetic variants of TLR 9 gene on MTCT. Three hundred children (118 HIV-1-infected and 182 HIV-1-uninfected) born to HIV-1-infected mothers were studied. Single nucleotide polymorphisms (SNPs) NM_017442.2: c.4-44G > A (rs352139) and c.1635A > G (rs352140) of the TLR9 gene were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using SNPStats program. When considered separately, neither of the two SNPs was significantly associated with risk of HIV-1 infection. However, the [A;A] and [G;G] haplotypes were associated with a higher risk of HIV-1 infection compared to the prevalent [G;A] haplotype [odds ratio (OR) = 3.16, 95% confidence interval (CI) 1.24-8.03, p = 0.016, and OR = 5.54, 95% CI 1.76-17.50, p = 0.004, respectively]. Overall, results demonstrate a significant correlation between specific genetic variants of the TLR9 gene and risk of MTCT of HIV-1, thus confirming a critical role of innate immunity in perinatal HIV-1 infection. Strategies aimed at modulating innate immunity might be useful for future treatment of pediatric HIV-1 infection and AIDS.


Waste effects on the behavior of 17beta-estradiol, estrone, and 17alpha-ethinylestradiol in agricultural soils in long- and short-term setups.
Natural and synthetic estrogens can reach agricultural soils with manures, biosolids, or wastewater. This study evaluates (i) the effects of long-term field application of such organic soil amendments and (ii) the short-term effects of 14 different organic amendments in one agricultural soil on mineralization and sorption of (14)C-labeled 17beta-estradiol, estrone, and 17alpha-ethinylestradiol. Long-term organic waste applications resulted in increasing soil organic carbon (SOC) contents, causing increased estrogen sorption. The mineralization of the estrogens was enhanced by up to 147% or depressed by up to 50%, depending on site and organic waste, but not related to changes in sorption parameters. Short-term organic waste amendments directly increased estradiol mineralization to up to 70% in the treated soil compared with 5% in the untreated control. Estradiol sorption increased with the amount of incorporated organic waste, but the log K(oc) values of 3.1-3.2 L kg(-1) for organic wastes showed a lower sorption potential for estrogens compared with 3.5 L kg(-1) in the untreated soil. The effects of organic waste amendments on estrogen behavior depend on amendment type and aging. Short-term organic waste applications to soil resulted in enhanced microbial estrogen mineralization likely due to cometabolic processes. In soils with a long history of organic waste amendments, the controlling factor for estrogen sorption is an increased SOC content. The observed positive or negative effects on estrogen mineralization in these soils are not well understood. Surprisingly, the increase in estrogen sorption to the soil solid phase either through short-term or long-term organic waste application does not control estrogen mineralization.


Concurrent Examination of Bobcats and Ticks Reveals High Prevalence of Cytauxzoon felis in Southern Illinois.
Cytauxzoon felis is an intraerythrocytic apicomplexan of felids enzootic in the southeastern United States. In domestic cats (Felis catus), this parasite can result in the highly fatal disease cytauxzoonosis or bobcat fever. Bobcats (Lynx rufus) are the wild animal reservoir host. To date, the characterization of prevalence of C. felis in bobcats is mostly based on broad-scale surveys from hunter-harvested specimens collected across large geographic areas, usually consisting of multiple states. Detailed studies on the development, transmission, distribution, effects, and prevalence of C. felis in the tick vectors are scarce. To fill some of these gaps in the literature, such as prevalence in ticks and bobcats in a discrete region, we examined bobcats and ticks in an 8,000-km2 portion of southern Illinois. We screened for C. felis using a nested polymerase chain reaction that amplifies a fragment of the nuclear small subunit (SSU) 18S rRNA. We screened 125 individual bobcats collected in southern Illinois from 2003 to 2015; of these, 70.6% were positive for C. felis. In addition, we screened 214 ticks of both vector species (Amblyomma americanum and Dermacentor variabilis) and detected C. felis in 15.6% of them; this prevalence is higher than reported by previous surveys. Our study reports the prevalence of C. felis in ticks and bobcats from south Illinois. We found that 70.6% of bobcats and 15.6% of ticks were infected with C. felis, which suggests risk of transmission to domestic cats.


[Endovascular aneurysm treatment: Radiological and macropathological findings of the endoluminal surface of modular stent grafts].
Characterization of the endoluminal surface of a modular stent graft and correlation of macropathological findings with results of radiological methods. Aneurysms of the infrarenal aorta were created in 36 mongrel FBI dogs using autologous material. Endovascular treatment was performed with modular stent grafts using two polyester-covered nitinol stents connected with overlap within the aneurysm. Follow-up was 1 and 6 weeks, and 6 months for 12 animals, respectively. Results were documented using sonography, intravascular ultrasound (IVUS), spiral CT, MRI, and digital subtraction angiography (DSA). After fixation, the aorta was prepared and incised lengthwise. Before histopathological work-up, the different segments were macropathologically characterized and correlated with the respective findings of the radiological methods. 4 cases showed high grade stenosis within the stent grafts and graft occlusion occurred in two cases. The connection sites of these modular stent grafts showed steps and partial separation of the graft components was causative in 5 of these cases. Migration of graft components occurred in three cases, one of them with complete disconnection of the modular device. Irregulartities and deposits on the endoluminal surface were systematically underestimated with all radiological techniques used. IVUS showed moderate concordance concerning deployment and unfolding of the stent graft, however, irregularities of the endoluminal surface were systematically underestimated. Concordance of MRI, sonography, and CT was worse. Contrast-enhanced T1-w MRI detected endoluminal deposits with moderate concordance. However, the thickness of deposits was underestimated. DSA, IVUS, and CT showed only poor concordance with macropathological findings. The connection site of modular stent grafts predisposes to stenosis, occlusion, and disconnection of the modular device. Stent deployment and unfolding of the membrane might be examined with IVUS. MRI is useful for detecting endoluminal deposits and stenosis. However, radiological methods will underrate irregularities and deposits of the endoluminal surface.


Analysis of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in human urine.
A new method was developed for the analysis of metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human urine. The metabolites are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-O-Gluc and NNAL-N-Gluc). The sum of these metabolites, total NNAL, was measured with this method. Urine was treated with beta-glucuronidase, which converts NNAL-O-Gluc and NNAL-N-Gluc to NNAL. After solvent partitioning and further purification on a liquid-liquid extraction cartridge and by high-performance liquid chromatography, total NNAL was quantified by gas chromatography with nitrosamine selective detection. The new method is accurate and precise, and the results are in good agreement with those obtained using the traditional method, which quantifies NNAL and its glucuronides separately. Levels of total NNAL +/- SD (pmol/mg creatinine) were 2.60 +/- 1.30 (n = 41) in smokers, 3.25 +/- 1.77 (n = 55) in snuff-dippers, and 0.042 +/- 0.020 (n = 18) in nonsmokers exposed to environmental tobacco smoke. The new method is faster and more sensitive than the traditional method and should greatly facilitate studies on human uptake of NNK.


From classical models of morphogenesis to agent-based models of pattern formation.
An extremely large body of theoretical work exists on pattern formation, but very few experimental results have confirmed the relevance of theoretical models. It is argued in this article that the notion of agent-based pattern formation, which is introduced and exemplified, can serve as a basis to study pattern formation in nature, especially because pattern-forming systems based on agents are (relatively) more easily amenable to experimental observations. Moreover, understanding agent-based pattern formation is a necessary step if one wishes to design distributed artificial pattern-forming systems. But, to achieve this goal, a theory of agent-based pattern formation is needed. This article suggests that it can certainly be derived from existing theories of pattern formation.


The use of non-pharmacological interventions for dementia behaviours in care homes: findings from four in-depth, ethnographic case studies.
antipsychotic medications have been used to manage behavioural and psychological symptoms of dementia (BPSD). Due to the potential risks associated with these medications for people with dementia, non-pharmacological interventions (NPIs) have been recommended as safer alternatives. However, it is unknown if, or how, these interventions are used in care homes to help people experiencing BPSD. to explore the use of NPIs in care homes to manage BPSD. In-depth, ethnographic case studies were conducted in four care homes; in total, they included interviews with 40 care-home staff and 384 hours of participant observations. NPIs, some of which are the focus of efficacy research, were used in care homes but predominantly as activities to improve the quality of life of all residents and not identified by staff as meeting individual needs in order to prevent or manage specific behaviours. Socially relevant activities such as offering a cup of tea were used to address behaviours in the moment. Residents with high levels of need experienced barriers to inclusion in the activities. there is a gap between rhetoric and practice with most NPIs in care homes used as social activities rather than as targeted interventions. If NPIs are to become viable alternatives to antipsychotic medications in care homes, further work is needed to embed them into usual care practices and routines. Training for care-home staff could also enable residents with high needs to gain better access to suitable activities.


[Eimeria of cattle in the Republic of Dagestan].
Data on Eimeria (Sporozoa: Coccidia) parasitizing cattle in different regions of the Republic of Dagestan are given. Eight species of the genus were found. Eimeria zuernii, E. subspherica, and E. bovis appeared to be the dominate species. Total infestation rate in the republic is 67.7%, while in mountain regions of Dagestan in is 83%.


The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis.
Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis. In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2). The risk estimate was expressed as odds ratio (OR) and 95% confidence interval (95% CI). Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005) and rs1126643 (2.37; 1.44-3.89; 0.001) with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03). Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034) and averaged platelet numbers (P = 0.012) between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively. Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.


The reaction of SLE antibodies with native, single stranded RNA: radioassay and binding specificities.
Escherichia coli 3H-tRNA and MS2 phage 125I-RNA were prepared and used in a sensitive nitrocellulose filter assay. Antibodies that bound these RNA ligands occurred in the sera of several patients with SLE, but not in sera of patients with other connective tissue diseases. The antibody populations that bound polyribonucleotides (largely IgG) were distinct from antibody populations that bound polydeoxyribonucleotides. Competition experiments showed that the anti-RNA antibodies preferentially bound native ssRNA as compared with synthetic single and double stranded polyribonucleotides. There was increasing affinity with increasing m.w. of the ssRNA. The anti-tRNA population was of restricted heterogeneity (Sips index 0.83) and bound tRNA with an average association constant (Ko) of 9 x 10(6) l/mole at 4 degrees C. The anti-MS2 RNA population was much more heterogeneous (Sips index 0.67) and bound MS2 RNA with a Ko of about 3 x 10(9) l/mole at 4 degrees C. Whereas NZB/NZW mice spontaneously produce RNA reactive antibodies with conformation specificity for native tRNA, human SLE anti-RNA antibodies appear to have very little of this type of conformation specificity.


Formation of new bioactive organic nitrites and their identification with gas chromatography-mass spectrometry and liquid chromatography coupled to nitrite reduction.
Nitric oxide (NO) donors, notably organic nitrates and nitrites are used therapeutically but tolerance develops rapidly, making the use of e.g. nitroglycerin difficult. NO donation in the pulmonary vascular bed might be useful in critically ill patients. Organic nitrites are not associated with tachyphylaxis but may induce methaemoglobinemia and systemic hypotension which might hamper their use. We hypothesised that new lung-selective NO donors can be identified by utilizing exhaled NO as measure for pulmonary NO donation and systemic arterial pressure to monitor hypotension and tolerance development. Solutions of alcohols and carbohydrates were reacted with NO gas and administered to ventilated rabbits for evaluation of in vivo NO donation. Chemical characterization was made by liquid chromatography with on-line nitrite reduction (LC-NO) and by gas chromatography-mass spectrometry (GC-MS). In vivo experiments showed that the hydroxyl-containing compounds treated with NO gas yielded potent NO donors, via nitrosylation to organic nitrites. Analyses by LC-NO showed that the reaction products were able to release NO in vitro. In GC-MS the reaction products were determined to be the organic nitrites, where some are new chemical entities. Non-polar donors preferentially increased exhaled NO with less effect on systemic blood pressure whereas more polar molecules had larger effects on systemic blood pressure and less on exhaled NO. We conclude that new organic nitrites suitable for intravenous administration are produced by reacting NO gas and certain hydroxyl-containing compounds in aqueous solutions. Selectivity of different organic nitrites towards the pulmonary and systemic circulation, respectively, may be determined by molecular polarity.


Interpreting Outcomes in DCDD Liver Transplantation: First Report of the Multicenter IDOL Consortium.
In the United States, 5% of adult liver transplant recipients receive a graft donation after circulatory determination of death (DCDD). Concerns for ischemic cholangiopathy (IC), a disease of diffuse intrahepatic stricturing limits broader DCDD use. Single-center reports demonstrate large variation in outcomes. Retrospective deidentified data collected between 2005 and 2013 were entered electronically by 10 centers via a Research Electronic Data Capture database. Our primary outcome was development of intrahepatic biliary strictures consistent with IC. Within 6 months post-DCDD transplant, 162 (21.8%) patients developed a biliary stricture, of which 88 (11.8%) exhibited intrahepatic structuring consistent with IC. Unadjusted 6-month IC rate among the 10 centers varied significantly (P = 0.006) from 6.3% to 25.9%. The only factor associated with increased risk of IC within 6 months was Roux-en-Y hepaticojejunostomy (vs duct-to-duct) (odds ratio, 3.06; 95% confidence interval, 1.52-6.16; P = 0.002). Graft failure by 6 months was more than 3 times higher for DCDD recipients with IC (odds ratio for IC, 3.36; 95% confidence interval, 1.95-5.79). This first report of the large combined experience with DCDD from the Improving DCDD Outcomes in Liver Transplant consortium demonstrates significant differences in IC among centers, the importance of biliary strictures as a risk factor for graft failure, and does not validate other risk factors for IC found in smaller studies.


The influence of adenine nucleotides and oxidizable substrates on triethyltin-mediated chloride uptake by rat liver mitochondria in potassium chloride media.
In a 100 mM-KCl medium, pH 6.8, containing ATP increasing concentrations of triethyltin cause an uptake of Cl- into mitochondria with a maximum at 1 muM. This can be inhibited by atractylate or oligomycin, but is virtually unaffected by the presence of rotenone. When the medium contains substrate (pyruvate, beta-hydroxybutyrate or succinate), both in the presence and absence of adenine nucleotides, Cl- uptake is greater with a maximum at 1-10 muM-triethyltin. If substrate oxidation is blocked by respiratory-chain inhibitors the Cl- uptake mediated by triethyltin is inhibited except in the media containing ATP, when the characteristics of Cl- uptake similar to that found in the medium containing ATP alone are observed. Under all conditions tested Cl- uptake is decreased by the presence of 2,4-dinitrophenol. It is concluded that energy from either the oxidation of substrate or the hydrolysis of ATP is associated with the generation of sufficient OH- to enable the triethyltin-mediated Cl-/OH- exchange to occur under the metabolic conditions relevant to this action of triethyltin.


Two alpha-adrenergic contractions with different Ca2+ activation mechanisms in response to field nerve stimulation in the circular smooth muscle of guinea-pig vas deferens.
1. Two noradrenergic components of contraction were induced by field nerve stimulation of the circular smooth muscle of guinea-pig vas deferens. One component occurred during the stimulation (former-response) and the other component occurred after stimulation had ceased (after-response), with a distinct tension fall between these two responses. 2. The effects of stimulation frequency and duration upon these components were examined. 3. Prazosin (0.05-0.5 microM) suppressed both responses, whereas nifedipine (0.02 microM) suppressed only the after-response. 4. It is suggested that in this tissue there are two neurogenic alpha-adrenergic contractions which possess different Ca2+ activation mechanisms. The former-response is due to an increase in cytoplasmic Ca2+ concentration through a pathway independent of action potentials, while the after-response is attributed to action potentials arising as a secondary response to the released noradrenaline.


Comparing exercise prescribed with exercise completed: effects of gender and mode of exercise.
The purpose of this study was to compare the amount of exercise prescribed with the amount completed between two different modes of training intervention and between the sexes. Thirty-two men (mean age = 39.1 years, body mass index = 32.9 kg x m(-2)) and women (mean age = 39.6 years, body mass index = 32.1 kg x m(-2)) were prescribed traditional resistance training or light-resistance circuit training for 16 weeks. Lean mass and fat mass were determined by dual-energy X-ray absorptiometry at weeks 1 and 16. A completion index was calculated to provide a measure of the extent to which participants completed exercise training relative to the amount of exercise prescribed. The absolute amount of exercise completed by the circuit training group was significantly greater than the amount prescribed (P < 0.0001). The resistance training group consistently under-completed relative to the amount prescribed, but the difference was not significant. The completion index for the circuit training group (26 +/- 21.7%) was significantly different from that of the resistance training group (-7.4 +/- 3.0%). The completion index was not significantly different between men and women in either group. These data suggest that overweight and obese individuals participating in light-resistance circuit training complete more exercise than is prescribed. Men and women do not differ in the extent to which they over- or under-complete prescribed exercise.


The impact of chronic physical illness, maternal depressive symptoms, family functioning, and self-esteem on symptoms of anxiety and depression in children.
The present study extends earlier research identifying an increased risk of anxiety among children with chronic physical illness (CwCPI) by examining a more complete model that explains how physical illness leads to increased symptoms of anxiety and depression. We tested a stress-generation model linking chronic physical illness to symptoms of anxiety and depression in a population-based sample of children aged 10 to 15 years. We hypothesized that having a chronic physical illness would be associated with more symptoms of anxiety and depression, increased levels of maternal depressive symptoms, more family dysfunction, and lower self-esteem; and, that maternal depressive symptoms, family dysfunction, and child self-esteem would mediate the influence of chronic physical illness on symptoms of anxiety and depression. Data came from the National Longitudinal Survey of Children and Youth (N = 10,646). Mediating processes were analyzed using latent growth curve modeling. Childhood chronic physical illness was associated with increases in symptoms of anxiety and depression, β = 0.20, p < 0.001. Mediating effects were also observed such that chronic physical illness resulted in increases in symptoms of maternal depression and family dysfunction, leading to declines in child self-esteem, and in turn, increases in symptoms of anxiety and depression. CwCPI are at-risk for symptoms of anxiety and depression. Some of this elevated risk appears to work through family processes and child self-esteem. This study supports the use of family-centered care approaches among CwCPI to minimize burden on families and promote healthy psychological development for children.


Monoethanolamine-induced glucose deprivation promotes apoptosis through metabolic rewiring in prostate cancer.
Rationale: Cancer cells rely on glucose metabolism for fulfilling their high energy demands. We previously reported that monoethanolamine (Etn), an orally deliverable lipid formulation, reduced intracellular glucose and glutamine levels in prostate cancer (PCa). Glucose deprivation upon Etn treatment exacerbated metabolic stress in PCa, thereby enhancing cell death. Moreover, Etn was potent in inhibiting tumor growth in a PCa xenograft model. However, the precise mechanisms underlying Etn-induced metabolic stress in PCa remain elusive. The purpose of the present study was to elucidate the mechanisms contributing to Etn-mediated metabolic rewiring in PCa. Methods: Glucose transporters (GLUTs) facilitate glucose transport across the plasma membrane. Thus, we assessed the expression of GLUTs and the internalization of GLUT1 in PCa. We also evaluated the effects of Etn on membrane dynamics, mitochondrial structure and function, lipid droplet density, autophagy, and apoptosis in PCa cells. Results: Compared to other GLUTs, GLUT1 was highly upregulated in PCa. We observed enhanced GLUT1 internalization, altered membrane dynamics, and perturbed mitochondrial structure and function upon Etn treatment. Etn-induced bioenergetic stress enhanced lipolysis, decreased lipid droplet density, promoted accumulation of autophagosomes, and increased apoptosis. Conclusion: We provide the first evidence that Etn alters GLUT1 trafficking leading to metabolic stress in PCa. By upregulating phosphatidylethanolamine (PE), Etn modulates membrane fluidity and affects mitochondrial structure and function. Etn also induces autophagy in PCa cells, thereby promoting apoptosis. These data strongly suggest that Etn rewires cellular bioenergetics and could serve as a promising anticancer agent for PCa.


Dynamics of anti-Toxoplasma gondii antibodies and seroconversion during pregnancy and lactation in naturally infected goats.
The objective of this work was to evaluate the dynamics of anti-T. gondii antibodies and seroconversion in naturally infected goats from the last third of pregnancy to 100 days of lactation and relate it to hematological and dehydration parameters. Blood samples were obtained from 56 goats in the different physiological states (pregnancy, kidding and lactation) as in different years (2019, 2021 and 2022). A total of 266 serum samples were obtained and evaluated by indirect fluorescent antibody test (IFAT) to end titer. The overall T. gondii seropositivity was 80.4% (45/56), with titers ranging from 100 to 25.600. The goats older than 3 years (4967 ± 1329) had significantly higher IFAT titers than the younger goats (2705 ± 681). The highest rate of positive seroconversion 31.1% (14/45) was found between kidding and 70 days of lactation; and of negative seroconversion 28.9% (13/45) between late pregnancy and kidding. The highest proportion of slightly dehydrated animals was found in the last third of pregnancy (14/25) and kidding (9/28). The correlation between seroconversion and T. gondii antibody titers was negative to the established dehydration index. These data suggest that in all physiological states and at different ages of goats, there is seroconversion which is not related to hydration status. Pregnancy, kidding and peak of lactation are stressful physiological periods, facilitating the reactivation of chronic T. gondii infections which are expressed by higher antibodies titers.


Long-term cost-effectiveness analysis of nebivolol compared with standard care in elderly patients with heart failure: an individual patient-based simulation model.
The SENIORS trial demonstrated that nebivolol is effective in the treatment of heart failure in elderly patients (e.g. > or = 70 years). This analysis evaluates the cost effectiveness of nebivolol compared with standard treatment. An individual patient-simulation model based on a Markov modelling framework was developed to compare costs and outcomes for nebivolol and standard care in patients with heart failure starting treatment at the age of 70 years. Health states were defined by New York Heart Association (NYHA) class and death. At a given NYHA class and a given cycle, patients could die, be hospitalized for cardiovascular disease or remain stable. Risks for these events were derived from individual patient data from the SENIORS trial. The risk of each event in a given cycle was based on the subject's baseline characteristics and time in the current health state. The economic analysis was conducted from the UK NHS perspective with a lifetime horizon. The costs (euro; year 2006 values) considered were drug costs for nebivolol and other cardiac drugs, costs of GP visits, outpatient specialist visits and cardiovascular-related hospitalizations. Univariate and probabilistic sensitivity analysis was conducted. In the baseline analysis, the total cost per patient was euro6740 and euro9288, and QALYs were 5.194 and 5.843 for patients aged 70 years at the start of treatment for the standard treatment and nebivolol groups, respectively. The probabilistic sensitivity analysis provided an incremental cost-effectiveness ratio of euro3926 (95% CI 3731, 4159) per QALY. This analysis indicates that nebivolol appears to be a cost-effective treatment for elderly patients with heart failure compared with standard care.


Multi-scale strategy to eradicate Pseudomonas aeruginosa on surfaces using solid lipid nanoparticles loaded with free fatty acids.
Infections are both frequent and costly in hospitals around the world, leading to longer hospital stays, overuse of antibiotics, and excessive costs to the healthcare system. Moreover, antibiotic resistant organisms, such as Pseudomonas aeruginosa are increasing in frequency, leading to 1.7 million infections per year in USA hospitals, and 99,000 deaths, both due to the evolution of antibiotic resistance and the formation of biofilms on medical devices. In particular, respiratory infections are costly, deadly to 4.5 million persons per year worldwide, and can spread to the lungs through the placement of endotracheal tubing. In this study, towards a reduction in infections, solid lipid nanoparticles were formulated from free fatty acids, or natural lipophilic constituents found in tissues of the body. A strategy was developed to target infections by producing coatings made of non-toxic chemistries lauric acid and oleic acid delivered by core-shell solid lipid nanoparticles that act against bacteria by multiple mechanisms at the nanoscale, including disruption of bacteria leading to DNA release, and reducing the adhesion of dead bacteria to ~1%. This is the first such study to explore an anti-infection surface relying on these multi-tier strategies at the nanoscale.


Differential distribution of hyperpolarization-activated and cyclic nucleotide-gated channels in cone bipolar cells of the rat retina.
The hyperpolarization-activated and cyclic nucleotide-gated (HCN) channel isoforms HCN1, HCN2, and HCN4 were localized by immunofluorescence in the rat retina. Double labeling with the vesicular glutamate transporter (VGLUT1) was used to identify bipolar cell axon terminals in the inner retina. The HCN1 channel was localized to two cell types with differing intracellular distributions, insofar as staining was seen in the dendrites of a putative OFF-type cone bipolar cell and in the axon terminals of an ON-type bipolar that ramifies in stratum 3 (s3) of the inner plexiform layer (IPL). Staining for HCN4 was seen in two sets of bipolar axon terminals located in s2 and s3 and positioned between the two bands of choline acetyltransferase (ChAT) staining. The cells that ramify in s2 were identified as type 3 cone bipolar cells and the cells that ramify in s3 cells as a subclass of type 5 cone bipolars. The latter group, designated here as type 5b, exhibit diffuse axon terminals and can be distinguished from the narrowly stratifying type 5a cells. Double labeling showed that type 5b cone bipolar cells express both HCN1 and HCN4 as well as HCN2. Superposition of HCN channel labeling with VGLUT1 staining confirmed the presence of a cone bipolar cell whose terminals ramify in the same stratum of the IPL as type 5b cells but that do not express these HCN channels.


The three-dimensional micro- and nanostructure of the aortic medial lamellar unit measured using 3D confocal and electron microscopy imaging.
Changes in arterial wall composition and function underlie all forms of vascular disease. The fundamental structural and functional unit of the aortic wall is the medial lamellar unit (MLU). While the basic composition and organization of the MLU is known, three-dimensional (3D) microstructural details are tenuous, due (in part) to lack of three-dimensional data at micro- and nano-scales. We applied novel electron and confocal microscopy techniques to obtain 3D volumetric information of aortic medial microstructure at micro- and nano-scales with all constituents present. For the rat abdominal aorta, we show that medial elastin has three primary forms: with approximately 71% of total elastin as thick, continuous lamellar sheets, 27% as thin, protruding interlamellar elastin fibers (IEFs), and 2% as thick radial struts. Elastin pores are not simply holes in lamellar sheets, but are indented and gusseted openings in lamellae. Smooth muscle cells (SMCs) weave throughout the interlamellar elastin framework, with cytoplasmic extensions abutting IEFs, resulting in approximately 20 degrees radial tilt (relative to the lumen surface) of elliptical SMC nuclei. Collagen fibers are organized as large, parallel bundles tightly enveloping SMC nuclei. Quantification of the orientation of collagen bundles, SMC nuclei, and IEFs reveal that all three primary medial constituents have predominantly circumferential orientation, correlating with reported circumferentially dominant values of physiological stress, collagen fiber recruitment, and tissue stiffness. This high resolution three-dimensional view of the aortic media reveals MLU microstructure details that suggest a highly complex and integrated mural organization that correlates with aortic mechanical properties.


Angiopoietin-2 plasma dosage predicts time to first treatment and overall survival in chronic lymphocytic leukemia.
The clinical relevance of angiopoietin-2 (Ang2) in chronic lymphocytic leukemia (CLL) was previously suggested by the association between high Ang2, and shorter progression-free survival reported in small series of patients. Here, we evaluated Ang2 glycoprotein levels in plasma samples collected from a multicentric cohort of CLL patients (n = 316) using an enzyme-linked immunosorbent assay method, and we investigated its prognostic role in relation to time to first treatment (TTFT) and overall survival. Based on a cutoff equal to 2459 pg/mL, we divided our cohort in 2 subsets (high and low Ang2) composing 100 (31.6%) and 216 (68.4%) patients, respectively. High Ang2 was predictive of reduced TTFT (P < .001) and overall survival (P = .002). Multivariate analysis confirmed that high Ang2 was an independent prognosticator for TTFT (hazard ratio = 1.739; 95% confidence interval, 1.059-2.857; P = .029). Significant associations were found between high Ang2 and advanced Binet stages (P < .001), high beta(2)-microglobulin (P < .001), unmutated variable region of immunoglobulin heavy chain gene status (P < .001), high CD38 and zeta-chain-associated protein kinase 70 expression (P < .001 and P = .003), and intermediate/high cytogenetic risk (P = .005). Moreover, Ang2 added prognostic power to other conventional prognosticators and helped to refine prognosis among CLL subsets with both high and low vascular endothelial growth factor plasma levels. Ang2 plasma level may be a useful independent prognosticator for CLL.


Proton dosimetry in a magnetic field: Measurement and calculation of magnetic field correction factors for a plane-parallel ionization chamber.
The combination of magnetic resonance imaging and proton therapy offers the potential to improve cancer treatment. The magnetic field (MF)-dependent change in the dosage of ionization chambers in magnetic resonance imaging-integrated proton therapy (MRiPT) is considered by the correction factor k B ⃗ , M , Q $k_{\vec{B},M,Q}$ , which needs to be determined experimentally or computed via Monte Carlo (MC) simulations. In this study, k B ⃗ , M , Q $k_{\vec{B},M,Q}$ was both measured and simulated with high accuracy for a plane-parallel ionization chamber at different clinical relevant proton energies and MF strengths. The dose-response of the Advanced Markus chamber (TM34045, PTW, Freiburg, Germany) irradiated with homogeneous 10× 10 cm2 quasi mono-energetic fields, using 103.3, 128.4, 153.1, 223.1, and 252.7 MeV proton beams was measured in a water phantom placed in the MF of an electromagnet with MF strengths of 0.32, 0.5, and 1 T. The detector was positioned at a depth of 2 g/cm2 in water, with chamber electrodes parallel to the MF lines and perpendicular to the proton beam incidence direction. The measurements were compared with TOPAS MC simulations utilizing COMSOL-calculated 0.32, 0.5, and 1 T MF maps of the electromagnet. k B ⃗ , M , Q $k_{\vec{B},M,Q}$ was calculated for the measurements for all energies and MF strengths based on the equation: k B ⃗ , M , Q = M Q M Q B ⃗ $k_{\vec{B},M,Q}=\frac{M_\mathrm{Q}}{M_\mathrm{Q}^{\vec{B}}}$ , where M Q B ⃗ $M_\mathrm{Q}^{\vec{B}}$ and MQ were the temperature and air-pressure corrected detector readings with and without the MF, respectively. MC-based correction factors were determined as k B ⃗ , M , Q = D det D det B ⃗ $k_{\vec{B},M,Q}=\frac{D_\mathrm{det}}{D_\mathrm{det}^{\vec{B}}}$ , where D det B ⃗ $D_\mathrm{det}^{\vec{B}}$ and Ddet were the doses deposited in the air cavity of the ionization chamber model with and without the MF, respectively. Furthermore, MF effects on the chamber dosimetry are studied using MC simulations, examining the impact on the absorbed dose-to-water ( D W $D_{W}$ ) and the shift in depth of the Bragg peak. The detector showed a reduced dose-response for all measured energies and MF strengths, resulting in experimentally determined k B ⃗ , M , Q $k_{\vec{B},M,Q}$ values larger than unity. For all energies and MF strengths examined, k B ⃗ , M , Q $k_{\vec{B},M,Q}$ ranged between 1.0065 and 1.0205. The dependence on the energy and the MF strength was found to be non-linear with a maximum at 1 T and 252.7 MeV. The MC simulated k B ⃗ , M , Q $k_{\vec{B},M,Q}$ values agreed with the experimentally determined correction factors within their standard deviations with a maximum difference of 0.6%. The MC calculated impact on D W $D_{W}$ was smaller 0.2 %. For the first time, measurements and simulations were compared for proton dosimetry within MFs using an Advanced Markus chamber. Good agreement of k B ⃗ , M , Q $k_{\vec{B},M,Q}$ was found between experimentally determined and MC calculated values. The performed benchmarking of the MC code allows for calculating k B ⃗ , M , Q $k_{\vec{B},M,Q}$ for various ionization chamber models, MF strengths and proton energies to generate the data needed for a proton dosimetry protocol within MFs and is, therefore, a step towards MRiPT.


Infection of primary canine duodenal epithelial cell cultures with Neospora caninum.
According to current knowledge, sexual development of the apicomplexan parasite Neospora caninum takes place in the canine intestine. However, to date there is no information on the interaction between the parasite and the canine intestinal epithelium, and, next to the clinical and in vivo research tools, an in vitro model comprised of canine intestinal cells infected with N. caninum would be very helpful for investigations at the cellular level. Following the isolation of cells of neonatal canine duodenum and growth of cell cultures to monolayers for 5-6 days, canine intestinal epithelial cells were exposed to cell culture-derived N. caninum tachyzoites and bradyzoites. The host cells remained viable during in vitro culture for an average of 2 wk. During this time span, N. caninum was found to readily adhere to any surface area of these cells, but infection took mostly place at sites where microvilli-like structures were missing, e.g., at the cell periphery, with tachyzoites exhibiting at least 3-4 times increased invasive capacities compared to bradyzoites. Once intracellular, parasites resided within a parasitophorous vacuole, moved toward the vicinity of the nucleus and the more distal portion of the epithelial cells, and proliferated to form vacuoles of not more than 2-4 parasites, which were surrounded by numerous mitochondria. Immunofluorescence staining and TEM of infected cells showed that the expression of cytokeratins and the structural integrity of desmosomes and tight junctions were not notably altered during infection. Furthermore, no changes could be detected in the alkaline phosphatase activities in cell culture supernatants of infected and noninfected cells. Canine duodenal epithelial cell cultures represent a useful tool for future studies on the characteristics of the intestinal phases of N. caninum infection.


Avian influenza overview May - August 2020.
Between 16 May and 15 August 2020, seven highly pathogenic avian influenza (HPAI) A(H5N8) virus outbreaks were reported in Europe in poultry, with one outbreak reported in Bulgaria(n=1) andsix in Hungary (n=6) and one low pathogenic avian influenza (LPAI) A(H5N3) virus outbreak was reported in poultry in Italy. All six outbreaks detected in Hungary were secondary outbreaks and seem to be the tail end of the HPAI A(H5N8) epidemic that wasobserved in poultry over the winter and spring in central Europe from December 2019 (n=334).Genetic analysis of the HPAI A(H5N8) viruses isolated during this reporting period from Bulgaria and Hungary did not identify any major changes compared tothe viruses collected in the respective countries during the first months of 2020. This suggests a persistence of the virus in the two countries rather than new introductions via infectedwild birds. HPAI A(H5N8) virus has been detected in poultry and wild birds in western Russia within the reporting period, and as of the middle of September also in Kazakhstan. The presence of HPAI virus in western Russiaand in north Kazakhstan,spatially associated with autumnmigration routes of wild waterbirds, is of concern due to the possible spread of the virus via wild birds migrating to the EU.It is highly recommended thatMember States take appropriate measures to promptly detect suspected cases of HPAI, including increasing biosecurity measures. According to past experiences (2005-2006 and 2016-2017 epidemic waves), the northern and eastern European areas might be at higher risk of virus introduction in the coming autumn-winter seasonand should be the key regions where prompt response measures to early detect the virusshould be set up. One human case due to A(H9N2) avian influenza virus infection was reported during the reporting period.


Malaria Parasitaemia among Blood Donors in Ilorin, Nigeria.
The prevalence of malaria parasitaemia among blood donors in Ilorin has not been documented. In this study, we determined the prevalence of malaria parasitaemia among blood donors in Ilorin, as well as, the sociodemographic and other factors associated with it. This was a hospital-based cross sectional study involving 308 consenting blood donors. The sociodemographic characteristics of participants as well as blood donation history were obtained using structured questionnaires specifically designed for this purpose. Giemsastained thick and thin blood films to identify malaria parasites were performed using standard method. ABO blood grouping and haemoglobin electrophoresis tests were also done using standard methods. The prevalence of malaria parasitaemia among blood donors in Ilorin was 27.3%. The parasite species found were more of Plasmodium falciparum(85.7%) than Plasmodium malariae(14.3%) . There was no age or sex difference in malaria parasitaemia. (p-value of 0.8 and 0.32 respectively). A greater proportion of blood group O individuals had malaria parasitaemia than groups A and B but this difference was not significant (p-value = 0.13). There was also no significant difference among haemoglobin genotypes. The prevalence of malaria parasites among blood donors in Ilorin is considerably high and lack of routine screening of blood puts recipients at risk. We recommend that routine screening for malaria parasites be commenced in our blood banks. Treatment of donor blood with riboflavin and UV light to inactivate malaria parasites and other infectious pathogens before they are transfused to patients may also be considered in our blood banks.


Antibiotic-resistant Escherichia coli in women with acute cystitis in Canada.
Trimethoprim-sulfamethoxazole (TMP-SMX) has been a traditional first-line antibiotic treatment for acute cystitis; however, guidelines do not recommend TMP-SMX in regions where Escherichia coli resistance exceeds 20%. While resistance is increasing, there are no recent Canadian estimates from a primary care setting to guide prescribing decisions. A total of 330 family physicians assessed 752 women with suspected acute cystitis between 2009 and 2011. Physicians documented clinical features and collected urine for cultures for 430 (57.2%) women. The proportion of resistant isolates of E coli and exact binomial 95% CIs were estimated nationally, and compared regionally and demographically. These estimates were compared with those from a 2002 national study. The proportion of TMP-SMX-resistant E coli was 16.0% nationally (95% CI 11.3% to 21.8%). This was not statistically higher than 2002 (10.9% [P=0.14]). TMP-SMX resistance was increased in women ≤50 years of age (21.4%) compared with older women (10.7% [P=0.037]). In women with no antibiotic exposure in the previous three months, TMP-SMX-resistant E coli remained more prevalent in younger women (21.8%) compared with older women (4.4% [P=0.003]). The proportion of ciprofloxacin-resistant E coli was 5.5% nationally (95% CI 2.7% to 9.9%), and was increased compared with 2002 (1.1% [P=0.036]). Ciprofloxacin resistance was highest in British Columbia (17.7%) compared with other regions (2.7% [P=0.003]), and was increased compared with 2002 levels in this province (0.0% [P=0.025]). Nitrofurantoin-resistant E coli levels were low (0.5% [95% CI 0.01% to 2.7%). The proportion of TMP-SMX-resistant E coli causing acute cystitis in women in Canada remains below 20% nationally, but may exceed this level in premenopausal women. Ciprofloxacin resistance has increased, notably in British Columbia. Nitrofurantoin resistance levels are low across the country. These observations indicate that TMP-SMX and nitrofurantoin remain appropriate empirical antibiotic agents for treating cystitis in primary care settings in Canada.


Association behaviour of glucitol amine gemini surfactants : Self-consistent-field theory and molecular-dynamics simulations.
The association behaviour of a number of glucitol amine gemini surfactants has been investigated by means of molecular dynamics and self-consistent-field calculations. We have shown that the titratable head group of the surfactant is responsible for a micelle-to-membrane transition when changing the pH. Furthermore, the association structure of this group of surfactants is shown to be very sensitive to ionic strength. The combination of a charged head group, a spacer, and the hydrophilic glucitol side chains is responsible for the possible structural transitions in the associates as a function of ionic strength and pH.


Influencing Factors on Radiotherapy Outcome in Stage I-II Glottic Larynx Cancer-A Multicenter Study.
Background and Purpose: Larynx cancer represents one of the most frequently diagnosed head and neck malignancies, which is most often confined to the glottic area. The aim of this study was to report the oncological outcome and identify prognostic factors in early-stage glottic squamous cell carcinoma treated with radiotherapy. Material and Methods: Patients (n = 761) diagnosed and treated in 10 centers between 1990 and 2015 were retrospectively analyzed. Probabilities of loco-regional control (LRC) and overall survival (OS) were calculated and possible prognostic factors were analyzed using Cox proportional hazards models. Results: The median follow-up was 63 months (range: 2-243). Three hundred and sixty-four, 148 and 249 patients had cT1a, cT1b, and cT2 stage I-II disease, respectively. Five and 10-years LRC/OS rates in the whole cohort were 83/82% and 80/68%, respectively. Three patients developed distant recurrences. In univariate analysis, male sex (HR: 3.49; 95% CI: 1.47-11.37; p < 0.01), T2 vs. T1a (HR: 1.62; 95% CI: 1.08-2.43; p = 0.02) and anterior commissure involvement (ACI) (HR: 1.66; 95% CI: 1.38-2.45; p < 0.01) were associated with impaired LRC. In multivariate analysis, male sex (HR: 3.42; 95% CI: 1.44-11.17; p < 0.01) and ACI (HR: 1.51; 95% CI: 1.01-2.28; p = 0.047) remained poor prognostic factors. No relation of treatment technique and biologically equivalent dose (BED) to oncological outcome was identified except for higher BED10(L = 25; T = 1) yielding better LRC in T1a tumors (p = 0.04) in univariate analyses. Conclusion: Our results highlight the negative impact of ACI on tumor control. A less-expected finding was the impact of sex on tumor control. Further research is needed to validate its prognostic value and investigate any related biologic or behavioral factors, which may be modified to improve oncologic outcome.


Studies on the formation of phycocyanin, porphyrins, and a blue phycobilin by wild-type and mutant strains of Cyanidium caldarium.
The synthesis of chlorophyll a and the bile-pigment and protein moieties of phycocyanin were arrested in illuminated cells of Cyanidium caldarium, strain III-D-2, incubated with chloramphenicol, ethionine, p-fluorophenylalanine, and p-chloromercuribenzoate. Pigment synthesis was similarly retarded in illuminated cells provided with nutrient medium lacking nitrogen.Porphobilinogen, porphyrins, and a blue phycobilin were excreted into the nutrient medium by illuminated and unilluminated cells of wild-type and mutant C. caldarium strains incubated with delta-aminolevulinic acid in darkness. Pigment production from delta-aminolevulinic acid was sensitive to treatment with chloramphenicol and ethionine. Cells of C. caldarium excreted 7 red-fluorescing porphyrins into the suspending medium during incubation with delta-aminolevulinic acid. Three of these porphyrins were identified as uroporphyrin III, coproporphyrin III, and protoporphyrin on the basis of their spectral properties and by paper chromatogaphy with standards. The blue phycobilin was characterized spectrally and compared with biliverdin. The algal phycobilin displayed properties of a pigment with a violin-type structure. The phycobilin may be an immediate precursor of phycocyanobilin, the phycocyanin chromophore, or identical to it.


Correlates of risky sexual behaviors in recently traditionally circumcised men from initiation lodges in the Eastern Cape, South Africa.
This exploratory quantitative study examines past risky sexual behaviors among young men who were circumcised as part of a rite of passage to adulthood embedded within a cultural and traditional belief system in the Eastern Cape Province in South Africa. Following permission from the Eastern Cape House of Traditional Leaders (ECHOTL), individual face-to-face interviews using a structured questionnaire were conducted among 114 initiates. The mean age of the participants was 18.9 years, ranging from 15 to 32 years old. About 79.8% reported already having had sex with a woman prior to initiation. Of those, 89% reported that they ever used condoms when having sex, and 61% reported consistent use. Logistic regression analysis showed that consistent condom use increased with higher educational levels. Those involved in other risky health behaviors (specifically, smoking) were also more likely to report inconsistent condom use. Most participants had positive beliefs about male circumcision and STI/HIV transmission. This study provides a first look at the sexual behaviors of young men at the time of their initiation in adulthood, a process that is intended to make it socially acceptable to initiate sexual relations and highlights a major public health challenge in integrating the protective health benefits of circumcision with indigenous cultural practices.


Dopamine-mediated gene regulation in models of Parkinson's disease.
The normal functioning of the basal ganglia is dependent on dopamine maintaining a balance between the two major output pathways of the striatum, through the D1 and D2 dopamine receptors, which have opposing effects on these pathways. Lesions of the dopamine system, such as occur in Parkinson's disease (PD), disrupt this balance. Gene regulation studies provide a measure of the cellular and molecular effects of dopamine on striatal neurons in animal models of PD. Dopamine agonists, involving selective or mixed D1 and D2 agonists, such as levodopa, are able to reverse many of the homeostatic changes induced by striatal dopamine depletion. However, following dopamine depletion, a supersensitive responsiveness of D1 striatal neurons to dopamine agonists develops, indicated by the induction of immediate early genes. The molecular and cellular mechanisms underlying the irreversibility of this supersensitive response with long-term dopamine agonist treatments may provide insights into dyskinesias that develop with long-term levodopa therapy in the treatment of PD.


Microfluidic technologies for vasculature biomimicry.
Microfluidic technology has been extensively employed in biology and medicine since the field emerged in the 1990s. By utilizing microfluidic approaches, a variety of vascular system-related structures and functions have been mimicked on in vitro platforms. Herein, we begin by introducing microfluidic circulatory devices for the study of two-dimensional (2D) endothelial cells culture. Next, we focus on recent progress on on-chip mimicry of native vasculature, specifically generation of complex three-dimensional (3D) structures within cell-laden hydrogels using microfluidics and self-assembly-based methods. The utilization of microfluidic technology will facilitate the construction of progressively biomimetic in vitro models that have great potential in complementing existing animal models. We envision such platforms to be utilized in a wide range of applications involving vascular systems, including microphysiological studies, drug screening, and disease modeling.


Preventing sports injuries: opportunities for intervention in youth athletics.
Participation in youth sports has steadily grown over the past 30 years and continues to rise. During the 1998-1999 school year over 360,000 collegiate athletes and almost 6.5 million high school athletes participated in sports. This expansion has been accompanied by an increased awareness of the injury problem associated with participation in youth sports. Estimates are that one-third of high school athletes will sustain an injury during a sports season serious enough to result in time lost from participation. While there may always be some risk associated with sports participation, health professionals can actively encourage injury prevention. In this paper, we describe the benefits of sport participation, the injury problem associated with sports, injury prevention frameworks, and conclude by discussing the changing role of the team physician in youth sports.


Synthetic Biology and the Gut Microbiome.
The gut microbiome plays a crucial role in maintaining human health. Functions performed by gastrointestinal microbes range from regulating metabolism to modulating immune and nervous system development. Scientists have attempted to exploit this importance through the development of engineered probiotics that are capable of producing and delivering small molecule therapeutics within the gut. However, existing synthetic probiotics are simplistic and fail to replicate the complexity and adaptability of native homeostatic mechanisms. In this review, the ways in which the tools and approaches of synthetic biology have been applied to improve the efficacy of therapeutic probiotics, and the ways in which they might be applied in the future is discussed. Simple devices, such as a bistable switches and integrase memory arrays, have been successfully implemented in the mammalian gut, and models for targeted delivery in this environment have also been developed. In the future, it will be necessary to introduce concepts such as logic-gating and biocontainment mechanisms into synthetic probiotics, as well as to expand the collection of relevant biosensors. Ideally, this will bring us closer to a reality in which engineered therapeutic microbes will be able to accurately diagnose and effectively respond to a variety of disease states.


Effects of the (Pro)renin Receptor on Cardiac Remodeling and Function in a Rat Alcoholic Cardiomyopathy Model via the PRR-ERK1/2-NOX4 Pathway.
Alcoholic cardiomyopathy (ACM) caused by alcohol consumption manifests mainly as by maladaptive myocardial function, which eventually leads to heart failure and causes serious public health problems. The (pro)renin receptor (PRR) is an important member of the local tissue renin-angiotensin system and plays a vital role in many cardiovascular diseases. However, the mechanism responsible for the effects of PRR on ACM remains unclear. The purpose of this study was to determine the role of PRR in myocardial fibrosis and the deterioration of cardiac function in alcoholic cardiomyopathy. Wistar rats were fed a liquid diet containing 9% v/v alcohol to establish an alcoholic cardiomyopathy model. Eight weeks later, rats were injected with 1 × 109v.g./100 μl of recombinant adenovirus containing EGFP (scramble-shRNA), PRR, and PRR-shRNA via the tail vein. Cardiac function was assessed by echocardiography. Cardiac histopathology was measured by Masson's trichrome staining, immunohistochemical staining, and dihydroethidium staining. In addition, cardiac fibroblasts (CFs) were cultured to evaluate the effects of alcohol stimulation on the production of the extracellular matrix and their underlying mechanisms. Our results indicated that overexpression of PRR in rats with alcoholic cardiomyopathy exacerbates myocardial oxidative stress and myocardial fibrosis. Silencing of PRR expression with short hairpin RNA (shRNA) technology reversed the myocardial damage mediated by PRR. Additionally, PRR activated phosphorylation of ERK1/2 and increased NOX4-derived reactive oxygen species and collagen expression in CFs with alcohol stimulation. Administration of the ERK kinase inhibitor (PD98059) significantly reduced NOX4 protein expression and collagen production, which indicated that PRR increases collagen production primarily through the PRR-ERK1/2-NOX4 pathway in CFs. In conclusion, our study demonstrated that PRR induces myocardial fibrosis and deteriorates cardiac function through ROS from the PRR-ERK1/2-NOX4 pathway during ACM development.


Emodin, a toxic metabolite of Aspergillus wentii isolated from weevil-damaged chestnuts.
A diarrheagenic toxin from culture extracts of Aspergillus wentii Wehmer isolated from weevil-damaged Chinese chestnuts was identified as emodin (2-methyl-4,5,7-trihydroxyanthraquinone). The orange-red, crystalline toxin (mp 255 to 257 C) showed ultraviolet absorption maxima in ethyl alcohol at 223, 250, 267, 290, and 442 nm, and infrared absorption maxima at 3,400 cm-1 (OH), 1,635, and 1,625 CM-1. Chemical shifts and coupling constants of the proton magnetic resonance spectra of the A. wentii toxin and of authentic emodin agreed. Mean lethal dose of emodin orally administered to 1-day-old DeKalb cockerels was 3.7 mg/kg.


Cell entry and antimicrobial properties of eukaryotic cell-penetrating peptides.
Antimicrobial drug action is limited by both microbial and host cell membranes. Microbes stringently exclude the entry of most drugs, and mammalian membranes limit drug distribution and access to intracellular pathogens. Recently, cell-penetrating peptides (CPPs) have been developed as carriers to improve mammalian cell uptake. Given that CPPs are cationic and often amphipathic, similar to membrane active antimicrobial peptides, it may be possible to use CPP activity to improve drug delivery to microbes. Here, two CPPs, TP10 and pVEC, were found to enter a range of bacteria and fungi. The uptake route involves rapid surface accumulation within minutes followed by cell entry. TP10 inhibited Candida albicans and Staphylococcus aureus growth, and pVEC inhibited Mycobacterium smegmatis growth at low micromolar doses, below the levels that harmed human HeLa cells. Therefore, although TP10 and pVEC entered all cell types tested, they preferentially damage microbes, and this effect was sufficient to clear HeLa cell cultures from noninvasive S. aureus infection. Also, conversion of the cytotoxicity indicator dye SYTOX Green showed that TP10 causes rapid and lethal permeabilization of S. aureus and pVEC permeabilizes M. smegmatis, but not HeLa cells. Therefore, TP10 and pVEC can enter both mammalian and microbial cells and preferentially permeabilize and kill microbes.


Multidisciplinary approach of complicated crown fractures of both superior central incisors: a case report.
Anterior crown fractures are a common form of traumatic dental injuries that mainly affect the maxillary central incisors, in children and teenagers. Since the development of the adhesive dentistry, many case reports of crown fractures restored using adhesive reattachment techniques were published. Complex cases, in which more than one tooth are involved, with fractures differing from each other, require specific treatment of each fracture, taking different advantages of the different remaining tooth structures. This case report describes a patient with dissimilar crown fractures of both superior central incisors. After the endodontic treatment, the patient was treated using the combination of several techniques: periodontal surgery (crown lengthening with apically repositioned flap and osseous resective surgery), adhesive technique and cast restoration plus esthetic crown. The periodontal procedure re-created the biologic width and proved to be a reliable adjunctive procedure to the adhesive and the prosthetic techniques used.