Inbred SJL mice recapitulate human resistance to Cryptococcus infection due to differential immune activation.

IMPORTANCE: Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.

Foliar functional and genetic variation in a keystone Hawaiian tree species estimated through spectroscopy.

Imaging spectroscopy has the potential to map closely related plant taxa at landscape scales. Although spectral investigations at the leaf and canopy levels have revealed relationships between phylogeny and reflectance, understanding how spectra differ across, and are inherited from, genotypes of a single species has received less attention. We used a common-garden population of four varieties of the keystone canopy tree, Metrosideros polymorpha, from Hawaii Island and four F1-hybrid genotypes derived from controlled crosses to determine if reflectance spectra discriminate sympatric, conspecific varieties of this species and their hybrids. With a single exception, pairwise comparisons of leaf reflectance patterns successfully distinguished varieties of M. polymorpha on Hawaii Island as well as populations of the same variety from different islands. Further, spectral variability within a single variety from Hawaii Island and the older island of Oahu was greater than that observed among the four varieties on Hawaii Island. F1 hybrids most frequently displayed leaf spectral patterns intermediate to those of their parent taxa. Spectral reflectance patterns distinguished each of two of the hybrid genotypes from one of their parent varieties, indicating that classifying hybrids may be possible, particularly if sample sizes are increased. This work quantifies a baseline in spectral variability for an endemic Hawaiian tree species and advances the use of imaging spectroscopy in biodiversity studies at the genetic level.

HEMATOLOGICAL INDICES RELATED TO VITAMIN D DEFICIENCY IN OBESE CHILDREN.

Introduction: Vitamin D is involved in differentiation and induction of erythropoiesis in bone marrow cells. Aim: We compared the serum 25(OH) vitamin D level in obese children versus control and found correlations between vitamin D level and hematological indices in obese children. Materials and methods: 25 overweight and obese patients and 15 normal weight children were enrolled in an observational study . Results: In obese children, the serum level of 25(OH) vitamin D was significantly (p<0.04) lower (20.60 ng/mL) compared with the value from normal weight ones (25.63 ng/mL) and the body fat percentage BFP was higher. We found a positive correlation (r=0.44, p<0.05) between serum vitamin D and hemoglobin level and a negative one between serum vitamin D and the number of platelets (r= -0.43, p<0.05). Also, the serum iron was at the lower normal limit in the obese children and negatively correlated with the percent of the body fat (r= -0,62, p<0.05). Conclusion: Obese children have vitamin D deficiency. The hemoglobin level and the number of platelets are correlated with the serum level of 25(OH) vitamin D. Supplements with vitamin D may have pleiotropic effects, including those on bone marrow activity.

The Effects of Tooth Brushing on Whole Salivary Flow Rate in Older Adults.

OBJECTIVES: (1) To determine whether manual (MTB), or electric, tooth brushing (ETB) modulates whole salivary flow rate in older adults who are free of systemic disease. (2) To determine the duration of the brushing-related modulation of salivary flow rate. (3) To compare salivary flow rate modulation associated with MTB and ETB. METHOD: Twenty-one adults aged 60 years and older participated in two experimental sessions during which they used a manual, or electric, toothbrush to brush their teeth, tongue, and palate. Whole salivary flow rates were determined using the draining method before, during, and after brushing. Differences in salivary flow rates across time periods, and between conditions, were examined using paired samples t-tests applying a Holm-Bonferroni sequential procedure (pcorr < 0.0045). The relationship between tooth brushing and age with respect to maximum salivary flow rate increase was examined using Pearson's correlation coefficient (p < 0.05). RESULTS/CONCLUSION: Whole salivary flow rates increased during, and for up to 5 minutes following, tooth brushing in adults aged 60 years and older who were free of systemic disease. The salivary effects of MTB and ETB were not significantly different. A moderate, positive correlation was observed between tooth-brushing-related maximum salivary flow rate increase and age.

Decoupled dimensions of leaf economic and anti-herbivore defense strategies in a tropical canopy tree community.

Trade-offs among plant functional traits indicate diversity in plant strategies of growth and survival. The leaf economics spectrum (LES) reflects a trade-off between short-term carbon gain and long-term leaf persistence. A related trade-off, between foliar growth and anti-herbivore defense, occurs among plants growing in contrasting resource regimes, but it is unclear whether this trade-off is maintained within plant communities, where resource gradients are minimized. The LES and the growth-defense trade-off involve related traits, but the extent to which these trade-off dimensions are correlated is poorly understood. We assessed the relationship between leaf economic and anti-herbivore defense traits among sunlit foliage of 345 canopy trees in 83 species on Barro Colorado Island, Panama. We quantified ten traits related to resource allocation and defense, and identified patterns of trait co-variation using multivariate ordination. We tested whether traits and ordination axes were correlated with patterns of phylogenetic relatedness, juvenile demographic trade-offs, or topo-edaphic variation. Two independent axes described ~ 60% of the variation among canopy trees. Axis 1 revealed a trade-off between leaf nutritional and structural investment, consistent with the LES. Physical defense traits were largely oriented along this axis. Axis 2 revealed a trade-off between investments in phenolic defenses versus other foliar defenses, which we term the leaf defense spectrum. Phylogenetic relationships and topo-edaphic variation largely did not explain trait co-variation. Our results suggest that some trade-offs among the growth and defense traits of outer-canopy trees may be captured by the LES, while others may occur along additional resource allocation dimensions.

Airborne laser-guided imaging spectroscopy to map forest trait diversity and guide conservation.

Functional biogeography may bridge a gap between field-based biodiversity information and satellite-based Earth system studies, thereby supporting conservation plans to protect more species and their contributions to ecosystem functioning. We used airborne laser-guided imaging spectroscopy with environmental modeling to derive large-scale, multivariate forest canopy functional trait maps of the Peruvian Andes-to-Amazon biodiversity hotspot. Seven mapped canopy traits revealed functional variation in a geospatial pattern explained by geology, topography, hydrology, and climate. Clustering of canopy traits yielded a map of forest beta functional diversity for land-use analysis. Up to 53% of each mapped, functionally distinct forest presents an opportunity for new conservation action. Mapping functional diversity advances our understanding of the biosphere to conserve more biodiversity in the face of land use and climate change.

A Systematic Review Examining the Oral Health Status of Persons with Dementia.

While the oral health of persons with dementia has been shown to be poor, no systematic reviews have been published that examined the topic in depth, including participants with dementia representing the full spectrum of disease severity, and evaluating a broad scope of oral health assessments. The aim of this study was to conduct a current literature review to fill this gap in knowledge. A systematic search of 5 databases (CINAHL, PubMed, EMBASE, Scopus, and ISI Web of Science) was conducted to identify all relevant studies published up to May 2016. There were no exclusions related to study type, severity of dementia, dentate status, or living arrangements. Results were reported descriptively and summarized. Meta-analyses were performed where possible and reported as mean difference (MD) or standardized mean difference (SMD), with a 95% confidence interval (CI). Twenty-eight studies were identified. Assessments were conducted of tooth status, active dental caries, hygiene (plaque/calculus) of natural and artificial teeth, periodontal diseases, denture status (retention, stability, denture-related mucosal lesions), and oral health-related quality of life. Across all evaluations, persons with dementia generally had scores/results suggestive of poor oral health. In meta-analyses, compared with persons without dementia, those with dementia had a significantly fewer number of teeth (MD, -1.52; 95% CI, -0.2.52 to -0.52; P = 0.003; n = 13 studies), more carious teeth (SMD, 0.29; 95% CI, 0.03 to 0.48; P = 0.028; n = 9), significantly worse oral hygiene evaluated using a broad range of assessment tools (SMD, 0.88; 95% CI, 0.57 to 1.19, P < 0.0001; n = 7), and significantly poorer periodontal health (SMD, 0.38; 95% CI, 0.06 to 0.70; P = 0.02; n = 6 studies). The oral health status of persons with mild to severe forms of dementia, who were living in both the community and residential care facilities, was found to be poor across a broad range of dental assessments. Knowledge Transfer Statement: The results of this study define the scope of oral issues and quantify the degree of impairment in individuals with dementia, evaluated using a variety of oral health measures. The results revealed that poor oral health is associated with dementia.

Landscape-scale variation in plant community composition of an African savanna from airborne species mapping.

Information on landscape-scale patterns in species distributions and community types is vital for ecological science and effective conservation assessment and planning. However, detailed maps of plant community structure at landscape scales seldom exist due to the inability of field-based inventories to map a sufficient number of individuals over large areas. The Carnegie Airborne Observatory (CAO) collected hyperspectral and lidar data over Kruger National Park, South Africa, and these data were used to remotely identify > 500 000 tree and shrub crowns over a 144-km2 landscape using stacked support vector machines. Maps of community compositional variation were produced by ordination and clustering, and the importance of hillslope-scale topo-edaphic variation in shaping community structure was evaluated with redundancy analysis. This remote species identification approach revealed spatially complex patterns in woody plant communities throughout the landscape that could not be directly observed using field-based methods alone. We estimated that topo-edaphic variables representing catenal sequences explained 21% of species compositional variation, while we also uncovered important community patterns that were unrelated to catenas, indicating a large role for other soil-related factors in shaping the savanna community. Our results demonstrate the ability of airborne species identification techniques to map biodiversity for the evaluation of ecological controls on community composition over large landscapes.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

BACKGROUND: Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. METHODS: The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. RESULTS: A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. CONCLUSION: After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

Biocide-containing varnish for the protection of sandstone: comparison of formulations and laboratory test methods.

Two formulations of acrylic varnish, with and without either of two dry film biocides--one a mixture of isothiazolinones and benzimidazole derivatives, and the other a carbamate--were tested in vitro for their activity against mixtures of filamentous fungi and cyanobacteria found on sandstone buildings. Growth on filter-paper squares coated with the varnishes was assessed semi-quantitatively by naked eye, quantitatively by image analysis and chemically by measurement of ergosterol and chlorophyll a. The lower solvent content (higher resin) varnish was more inhibitory to cyanobacteria than the higher varnish content, whilst the opposite was true for the fungal inoculum. The carbamate biocide was effective against cyanobacteria, unlike the isothiazolinone mixture, but the latter produced more inhibition of fungal growth. The three assay methods produced generally similar results, although visual observation was obviously the most imprecise. There was an anomaly in the ergosterol measurements, which was considered to be caused by the varying ergosterol content and unequal inhibition of the three fungal genera used in the inoculum. Fusarium sp. was shown to contain higher levels of this membrane component than Cladosporium sp. and Penicillium sp. For this reason, the most appropriate method overall, giving reliable quantitative results, was deemed to be the image analysis.

Effect of dietary organic microminerals on starter pig performance, tissue mineral concentrations, and liver and plasma enzyme activities.

Weanling pigs (n = 160) were used to evaluate dietary essential microminerals (Cu, Fe, Mn, Se, and Zn) on performance, tissue minerals, and liver and plasma enzymatic activities during a 35-d postweaning period. A randomized complete block design with 5 treatments and 8 replicates was used in this study. Organic microminerals were added to complex nursery diets at 0 (basal), 50, 100, or 150% of the requirements of microminerals listed by the 1998 NRC. A fifth treatment contained inorganic microminerals at 100% NRC and served as the positive control. Pigs were bled at intervals with hemoglobin (Hb), hematocrit (Hct), glutathione peroxidase, and ceruloplasmin activities determined. Six pigs at weaning and 1 pig per pen at d 35 were killed, and the liver, heart, loin, kidney, pancreas, and the frontal lobe of the brain were collected for micromineral analysis. The liver was frozen in liquid N for determination of enzymatic activities. The analyzed innate microminerals in the basal diet met the NRC requirement for Cu and Mn but not Fe, Se, and Zn. Performance was not affected from 0 to 10 d postweaning, but when microminerals were added to diets, ADG, ADFI, and G:F improved (P < 0.01) from 10 to 35 d and for the overall 35-d period. Pigs fed the basal diet exhibited parakeratosis-like skin lesions, whereas those fed the supplemental microminerals did not. This skin condition was corrected after a diet with the added microminerals was fed. When the basal diet was fed, Hb and Hct declined, but supplemental microminerals increased Hb and Hct values. Liver catalase activity increased (P < 0.01) when microminerals were fed. The Mn superoxide dismutase activity tended to decline quadratically (P = 0.06) when supplemental microminerals were fed above that of the basal diet. Liver plasma glutathione peroxidase activities were greater (P < 0.01) when dietary organic and inorganic micromineral were fed. Liver concentrations of microminerals increased linearly (P < 0.01) as dietary microminerals increased, indicating that the liver was the primary storage organ. Micromineral tissue concentrations were least in pigs fed the basal diet and increased (quadratic, P < 0.01) to the 50% level of organic microminerals in the various tissues collected. The results indicated that innate microminerals, Cu and Mn, from a complex nursery diet may meet the micromineral needs of the weaned pig, but the need for Fe, Se, or Zn was not met by the basal diet.

Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties.

Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.

Functional MRI of oropharyngeal air-pulse stimulation.

Although the posterior oral cavity and oropharynx play a major role in swallowing, their central representation is poorly understood. High-field functional magnetic resonance imaging of the brain was used to study the central processing of brief air-pulses, delivered to the peritonsillar region of the lateral oropharynx, in six healthy adults. Bilateral air-pulse stimulation was associated with the activation of a bilateral network including the primary somatosensory cortex and the thalamus, classic motor areas (primary motor cortex, supplementary motor area, cingulate motor areas), and polymodal areas (including the insula and frontal cortex). These results suggest that oropharyngeal stimulation can activate a bilaterally distributed cortical network that overlaps cortical regions previously implicated in oral and pharyngeal sensorimotor functions such as tongue movement, mastication, and swallowing. The present study also demonstrates the utility of air-pulse stimulation in investigating oropharyngeal sensorimotor processing in functional brain imaging experiments.

Effect of x-ray irradiation on reducing the risk of listeriosis in ready-to-eat vacuum-packaged smoked mullet.

Listeria monocytogenes can pose a serious threat in several areas of the nation's food supply including ready-to-eat seafood products. Use of irradiation processing can potentially reduce the risk of listeriosis caused by consumption of ready-to-eat seafood products. This study measured the effect of X-ray irradiation on reducing the population of L. monocytogenes on ready-to-eat, vacuum-packaged smoked mullet. Smoked mullet were inoculated with a five-strain mixture of L. monocytogenes (10(4) CFU/g), vacuum packaged, and irradiated (0, 0.5, 1.0, 1.5, and 2.0 kGy). The packaged fish were then stored at 3 and 10 degrees C for 90 and 17 days, respectively. Radiation doses of 0.5, 1.0, and 1.5 kGy reduced the initial population of L. monocytogenes by 1.1, 1.6, and 2.1 log CFU/g, respectively. The 2.0-kGy dose reduced L. monocytogenes to undetectable levels with no recovery growth at either temperature. Compared to the control, irradiation at 1.5 kGy demonstrated 1.0 and 1.7 log CFU/g less growth at 3 degrees C after 60 days and 10 degrees C after 17 days, respectively. Sensory flavor analysis was conducted to determine if a difference existed between irradiated samples. Panelists indicated that there were no differences among treated and untreated samples. An X-ray dose of 2 kGy effectively eliminated 10(4) CFU/g L. monocytogenes on smoked mullet without changing sensory quality.

Plasmodium permeomics: membrane transport proteins in the malaria parasite.

Membrane transport proteins are integral membrane proteins that mediate the passage across the membrane bilayer of specific molecules and/or ions. Such proteins serve a diverse range of physiological roles, mediating the uptake of nutrients into cells, the removal of metabolic wastes and xenobiotics (including drugs), and the generation and maintenance of transmembrane electrochemical gradients. In this chapter we review the present state of knowledge of the membrane transport mechanisms underlying the cell physiology of the intraerythrocytic malaria parasite and its host cell, considering in particular physiological measurements on the parasite and parasitized erythrocyte, the annotation of transport proteins in the Plasmodium genome, and molecular methods used to analyze transport protein function.

Toxicología de las drogas de síntesis / Synthetic illicit drugs toxicology

Las drogas de síntesis o 'drogas de diseño' son sustancias psicoactivas de uso recreacional que se fabrican en laboratorios clandestinos. La producción, variedad y número de consumidores de estas drogas aumentan cada año en toda Europa, y con ellos los problemas sanitarios derivados de su uso. Estos problemas comprenden tanto sus efectos secundarios o la intoxicación aguda como sus aún no del todo conocidas repercusiones orgánicas a largo plazo, así como la toxicidad de las sustancias de corte, la de los productos residuales originados en la fabricación de la propia droga y su uso combinado con el de otras drogas. Dentro de la denominación de drogas de síntesis se diferencian principalmente cuatro grupos de sustancias muy diferentes: los derivados anfetamínicos, los opioides sintéticos, las arilhexilaminas y los derivados de la metacualona. Esta revisión aporta una descripción sistemática de dichos compuestos y de su efectos físicos y psíquicos. (AU)

Docosahexaenoic, arachidonic, palmitic, and oleic acids are differentially esterified into phospholipids of frog retina.

Docosahexaenoic acid (22:6n-3) is highly enriched in the retina. To determine if retinal cells take up and metabolize fatty acids in a specific manner, retinas from Rana pipiens were incubated for 3 h with an equimolar mixture of tritiated 22:6n-3, arachidonic acid (20:4n-6), palmitic acid, and oleic acid. The radiolabeling of retinal lipids was determined and compared to the endogenous fatty acid content of the lipids. The results showed that in most, but not all, cases, the relative labeling with the four precursor fatty acids was similar to their relative abundance in each glycerolipid. Thus, during retinal glycerolipid synthesis, either through de novo or acyl exchange reactions, fatty acids are incorporated in proportions reflecting their steady-state mass levels. Since other studies with labeled glycerol have shown greater differences between early labeling patterns and molecular species mass, the final incorporation we report may be due primarily to acyl exchange reactions.

Computer measurement of oral movement in swallowing.

This article describes a computer program that automatically detects and tracks small metal markers affixed to a subject's tongue and teeth in fluoroscopic image sequences of swallowing. The program, written in Microsoft Visual C++ using Windows NT 4.0 and the SAVANT imaging toolkit, involves marker detection and marker tracking. Marker detection is done by template matching. A generic marker template was designed by extracting the grayvalues of pixels within an imaged marker. Template matching with a weighted center-of-mass calculation determined marker location with subpixel accuracy. Marker tracking employed a nearest-neighbor algorithm since (a) the movement of each marker was less than the distance between any two markers and (b) marker trajectories did not overlap. Effects of head motion were attenuated by computing tongue trajectories with respect to a constant frame of reference given by reference markers on the maxillary teeth. Motions were converted from pixels/frame to millimeters/second using a calibration ring secured to the subject's neck. Results for several image sequences showed that our program performs very well in terms of marker detection and trajectory determination. Comparison of automatic and manual tracking of the same image sequences indicated a high degree of correspondence. Automatic tracking of oral movement by computer is a useful tool in kinematic studies of swallowing.

Oropharyngeal dysphagia in esophageal cancer before and after transhiatal esophagectomy.

Although dysphagia is the predominant symptom of esophageal cancer, the nature of the swallowing deficit remains unclear, particularly regarding an oropharyngeal motor component. The present study examined the oropharyngeal swallow in patients with esophageal cancer before and following transhiatal esophagectomy. Videofluoroscopic data were obtained from ten patients with esophageal cancer before and following transhiatal esophagectomy as they swallowed 2-, 5-, and 10-cc aliquots of liquid and puree, and 0.5 and 1 tsp of solid. Each swallow was rated on 36 parameters by three independent judges. Swallow-related hyoid bone movement, computed from digitized segments of the videofluoroscopic data, was compared pre- and postsurgically. All patients showed at least mild abnormality of the oropharyngeal swallow preoperatively. Abnormalities involved all stages of swallowing in nine of the ten patients; however, the oral preparatory/oral stage was relatively more impaired than the pharyngeal stage in the majority of patients. Postsurgically, all patients exhibited at least a mild oropharyngeal swallowing impairment. New or increased postoperative deficits involved the pharyngeal stage of swallowing, whereas oral stage abnormalities were generally improved or unchanged following surgery. Swallow-related hyoid kinematics were highly variable both before and following surgery. Anterior hyoid bone excursion was significantly reduced postoperatively in one patient and significantly increased in one patient. Patients with esophageal cancer exhibit oropharyngeal dysphagia, with different profiles of abnormality before and following esophagectomy.

Cerebral cortical representation of automatic and volitional swallowing in humans.

Although the cerebral cortex has been implicated in the control of swallowing, the functional organization of the human cortical swallowing representation has not been fully documented. Therefore, the present study determined the cortical representation of swallowing in fourteen healthy right-handed female subjects using single-event-related functional magnetic resonance imaging (fMRI). Subjects were scanned during three swallowing activation tasks: a naïve saliva swallow, a voluntary saliva swallow, and a water bolus swallow. Swallow-related laryngeal movement was recorded simultaneously from the output of a bellows positioned over the thyroid cartilage. Statistical maps were generated by computing the difference between the magnitude of the voxel time course during 1) a single swallowing trial and 2) the corresponding control period. Automatic and volitional swallowing produced activation within several common cortical regions, the most prominent and consistent being located within the lateral precentral gyrus, lateral postcentral gyrus, and right insula. Activation foci within the superior temporal gyrus, middle and inferior frontal gyri, and frontal operculum also were identified for all swallowing tasks. In contrast, activation of the caudal anterior cingulate cortex was significantly more likely in association with the voluntary saliva swallow and water bolus swallow than the naïve swallow. These findings support the view that, in addition to known brain stem areas, human swallowing is represented within a number of spatially and functionally distinct cortical loci which may participate differentially in the regulation of swallowing. Activation of the insula was significantly lateralized to the right hemisphere for the voluntary saliva swallow, suggesting a functional hemispheric dominance of the insula for the processing of swallowing.