Are lice good proxies for host history? A comparative analysis of the Australian magpie, Gymnorhina tibicen, and two species of feather louse.
Parasites have been recently advocated as useful proxies for unravelling a complex evolutionary history of a host. In the present study, two species of feather lice, Brueelia semiannulata and Philopterus sp. were analysed for mitochondrial variation and compared to mitochondrial and nuclear variation in their host, the Australian magpie Gymnorhina tibicen. Phylogenies constructed using maximum likelihood methods revealed geographic structuring for both species of feather lice and host. Our genetic analysis shows concordance of east-west structure between host and Philopterus sp. indicating that it is an informative proxy for host history. Analysis of the Philopterus sp. phylogeny also suggested cryptic structuring within the eastern magpie population that had not been previously realized through genetic analysis of the host. B. semiannulata however, did not show congruent phylogeographic structuring with the host. Rather than showing an east-west split between lineages, the phylogeny of B. semiannulata showed north-south geographic structuring. It is postulated that this incongruence may be due to ecological habitat differences and/or the dispersal ability of B. semiannulata.


Equol promotes rat osteoblast proliferation and differentiation through activating estrogen receptor.
Phytoestrogens have been suggested as alternative treatment for postmenopausal osteoporosis. Equol, a metabolite of daidzein, has been shown to inhibit bone loss in ovariectomized mice and rats. However, whether or not equol influences the formation of bone has not yet been investigated. Therefore, we investigated the effect of equol on the proliferation and differentiation of rat primary osteoblasts and explored the involved mechanisms. Different equol concentrations significantly promoted the proliferation of osteoblasts after 48- and 72-h incubations. The alkaline phosphatase (ALP) activity also increased significantly in all of the equol and 17β-estradiol (E2) groups, except for the lowest (0.01 μM) equol group. Equol also significantly elevated the osteocalcin levels. The effects of equol on osteoblast proliferation, ALP activity, and osteocalcin levels were blocked by the estrogen receptor (ER) antagonist ICI182780. After a 24-h incubation, the expression of protein kinase C alpha (PKCα) in osteoblasts was significantly increased by equol. In conclusion, our study demonstrated that equol could promote the proliferation and differentiation of rat osteoblasts through activating the ER-PKCα-related signaling pathway, suggesting that equol could promote bone formation. These results suggest that equol could be a potential alternative agent for the management of postmenopausal osteoporosis.


Functional Characterization of Entamoeba histolytica Argonaute Proteins Reveals a Repetitive DR-Rich Motif Region That Controls Nuclear Localization.
The RNA interference (RNAi) pathway regulates gene expression in many eukaryotic organisms. Argonaute (Ago) proteins, together with bound small RNAs (sRNAs), are key effectors that mediate gene silencing function. However, there is limited knowledge of Ago proteins and their functions in nonmodel systems. In the protozoan parasite Entamoeba histolytica, RNAi is a robust means for stable gene silencing mediated via large populations of antisense sRNAs. Here, we report functional characterization of three Ago proteins in E. histolytica (EhAgo2-1, EhAgo2-2, and EhAgo2-3). Our data show that each EhAgo protein has a distinct subcellular localization and binds 27-nucleotide (nt) sRNAs and that the localization of EhAgo proteins is altered in response to stress conditions. Via mutagenesis analyses, we demonstrated that the Ago PAZ (Piwi/Argonaute/Zwille) domain in all three EhAgos is essential for sRNA binding. With mutation of the PAZ domain in EhAgo2-2, there was no effect on the nuclear localization of the protein but a strong phenotype and a growth defect. We further show that EhAgo2-2 contains an unusual repetitive DR-rich (aspartic acid, arginine-rich) motif region which functions as a nuclear localization signal (NLS) and is both necessary and sufficient to mediate nuclear localization. Overall, our data delineate the localization and sRNA binding features of the three E. histolytica Ago proteins and demonstrate that the PAZ domain is necessary for sRNA binding. The repetitive DR-rich motif region in EhAgo2-2 has not previously been defined in other systems, which adds to the novel observations that can be made when studies of the RNAi pathway are extended to nonmodel systems.IMPORTANCE The protozoan parasite Entamoeba histolytica, which causes amebiasis and affects over 50 million people worldwide, contains an important RNAi pathway for gene silencing. Gene silencing via the RNAi pathway is mediated by the Argonaute (Ago) proteins. However, we lack knowledge on Ago function(s) in this nonmodel system. In this paper, we discovered that three E. histolytica Ago proteins (EhAgo2-1, EhAgo2-2, and EhAgo2-3) all bind 27-nt small RNAs and have distinct subcellular localizations, which change in response to stress conditions. The EhAgos bind small RNA populations via their PAZ domains. An unusual repetitive DR-rich motif region is identified in EhAgo2-2 that functions as a nuclear localization signal. Our results show for the first time an active nuclear transport process of the EhAgo2-2 RNA-induced silencing complex (RISC) in this parasite. These data add to the novel observations that can be made when studies of the RNAi pathway are extended to nonmodel systems.


Fruit and vegetable consumption and body mass index: a quantile regression approach.
Empirical evidence on the relationship between consumption of fruits and vegetables and body weight is inconclusive. Previous studies mostly use linear regression methods to study the correlates of the conditional mean of body mass index (BMI). This approach may be less informative if the association between fruit and vegetable consumption and BMI significantly varies across the BMI distribution. The association between fruit and vegetable consumption and the BMI is examined using quantile regression. A nationally representative sample of 11,818 individuals from the Canadian Community Health Survey (2004) is used. A quantile regression model is estimated to account for the potential heterogeneous association between fruit and vegetable intake and BMI at different points of the conditional BMI distribution. The analyses are stratified by gender. The multivariate analyses reveal that the association between fruit and vegetable intake and BMI is negative and statistically significant for both males and females; however, this association varies across the conditional quantiles of the BMI distribution. In particular, the estimates are larger for individuals at the higher quantiles of the distribution. The ordinary least squares (OLS) model overstates (understates) the association between FV intake and BMI at the lower (higher) half of the conditional BMI distribution. Findings of the standard models that assume uniform response across different quantiles of BMI distribution may be misleading. The findings of this paper suggest that increasing the intake of fruits and vegetables may be an effective dietary strategy to control weight and mitigate the risk of obesity.


Hierarchical Bayesian Causality Network to Extract High-Level Semantic Information in Visual Cortex.
Functional MRI (fMRI) is a brain signal with high spatial resolution, and visual cognitive processes and semantic information in the brain can be represented and obtained through fMRI. In this paper, we design single-graphic and matched/unmatched double-graphic visual stimulus experiments and collect 12 subjects' fMRI data to explore the brain's visual perception processes. In the double-graphic stimulus experiment, we focus on the high-level semantic information as "matching", and remove tail-to-tail conjunction by designing a model to screen the matching-related voxels. Then, we perform Bayesian causal learning between fMRI voxels based on the transfer entropy, establish a hierarchical Bayesian causal network (HBcausalNet) of the visual cortex, and use the model for visual stimulus image reconstruction. HBcausalNet achieves an average accuracy of 70.57% and 53.70% in single- and double-graphic stimulus image reconstruction tasks, respectively, higher than HcorrNet and HcasaulNet. The results show that the matching-related voxel screening and causality analysis method in this paper can extract the "matching" information in fMRI, obtain a direct causal relationship between matching information and fMRI, and explore the causal inference process in the brain. It suggests that our model can effectively extract high-level semantic information in brain signals and model effective connections and visual perception processes in the visual cortex of the brain.


Whole genome sequencing identified a 16 kilobase deletion on ECA13 associated with distichiasis in Friesian horses.
Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait. A genome wide association study (GWAS) was performed using the Axiom 670 k Equine Genotyping array (MNEc670k) utilizing 14 cases and 38 controls phenotyped for distichiasis. An additive single locus mixed linear model (EMMAX) approach identified a 1.83 Mb locus on ECA5 and a 1.34 Mb locus on ECA13 that reached genome-wide significance (pcorrected = 0.016 and 0.032, respectively). Only the locus on ECA13 withstood replication testing (p = 1.6 × 10- 5, cases: n = 5 and controls: n = 37). A 371 kb run of homozygosity (ROH) on ECA13 was found in 13 of the 14 cases, providing evidence for a recessive mode of inheritance. Haplotype analysis (hapQTL) narrowed the region of association on ECA13 to 163 kb. Whole-genome sequencing data from 3 cases and 2 controls identified a 16 kb deletion within the ECA13 associated haplotype (ECA13:g.178714_195130del). Functional annotation data supports a tissue-specific regulatory role of this locus. This deletion was associated with distichiasis, as 18 of the 19 cases were homozygous (p = 4.8 × 10- 13). Genotyping the deletion in 955 horses from 54 different breeds identified the deletion in only 11 non-Friesians, all of which were carriers, suggesting that this could be causal for this Friesian disorder. This study identified a 16 kb deletion on ECA13 in an intergenic region that was associated with distichiasis in Friesian horses. Further functional analysis in relevant tissues from cases and controls will help to clarify the precise role of this deletion in normal and abnormal eyelash development and investigate the hypothesis of incomplete penetrance.


In vitro cytotoxicity evaluation of a self-adhesive, methacrylate resin-based root canal sealer.
This study compared the cytotoxicity of MetaSEAL (Parkell Inc, Farmington, NY), a methacrylate resin-based sealer with an epoxy resin-based (AH Plus Jet; Dentsply Caulk, Milford, DE) and a zinc oxide-eugenol-based sealer (Pulp Canal Sealer; SybronEndo, Orange, CA). Five-millimeter diameter disks prepared from the respective sealer and disks prepared from Teflon (negative control) and polymethyl methacrylate (positive control) were placed in direct contact with a rat osteosarcoma (ROS) 17/2.8 rat osteoblast-like cell line at six intervals after setting completely at 72 hours and for 5 succeeding weeks after the disks were immersed in simulated body fluid. Succinate dehydrogenase activity was evaluated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. All sealers exhibited severe toxicity at 72 hours, after which toxicity decreased gradually over the experimental period except for Pulp Canal Sealer, which remained severely toxic. MetaSEAL was more toxic than AH Plus Jet during the first week. Both were similar to the toxicity profile of the positive control after the first week, which was probably diffusion controlled.


A single center retrospective cohort study evaluating use of direct oral anticoagulants (DOACs) in morbidly obese veteran population.
Direct oral anticoagulants (DOACs) are preferred over warfarin for the treatment of venous thromboembolism (VTE) as well as atrial fibrillation (AF). The efficacy and safety of fixed dose regimen of DOACs remains unclear in morbidly obese patient population and are currently not recommended for use in patients with a body mass index (BMI) > 40 kg/m2 or a weight of >120 kg. The goal of this study is to evaluate the use of DOACs in morbidly obese veteran population as compared to warfarin. This retrospective single center cohort study included morbidly obese patients weighing >120 kg or BMI > 40 kg/m2 who were prescribed DOACs or warfarin for AF or VTE between January 1st, 2015 to May 31st, 2018. Data was extracted from the computerized patient record system (CPRS) and the Salem Veterans Affairs Medical Center (SVAMC) data warehouse. The primary outcome was combined incidence of stroke/transient ischemic attack (TIA) and VTE. Secondary outcomes included all-cause mortality, ISTH major bleed and clinically relevant non major bleed as well as primary outcome and ISTH major bleeding analyses in the subgroups of AF and VTE patients. The study included 190 patients in warfarin group and 214 in DOACs group. Baseline characteristics were mostly well matched except for the follow up duration which was significantly longer in the warfarin group as compared to DOAC (p > 0.001). The annual incidence rate of primary outcome was similar between warfarin and DOACs (3.91% vs.1.61%; RR:2.436; 95% CI 0.85-8.54; p = 0.1543). This hypothesis generating study suggests that DOAC use may be feasible in morbidly obese patients. Additional studies are necessary to confirm this finding and further guide clinical practice in this area.


Reliability and Agreement of Automated Head Measurements From 3-Dimensional Photogrammetry in Young Children.
This study aimed to assess the reliability and agreement of automated head measurements using 3-dimensional (3D) photogrammetry in young children. Specifically, the study evaluated the agreement between manual and automated occipitofrontal circumference (OFC) measurements (n = 264) obtained from 3D images of 188 patients diagnosed with sagittal synostosis using a novel automated method proposed in this study. In addition, the study aimed to determine the interrater and intrarater reliability of the automatically extracted OFC, cephalic index, and volume. The results of the study showed that the automated OFC measurements had an excellent agreement with manual measurements, with a very strong regression score ( R2 = 0.969) and a small mean difference of -0.1 cm (-0.2%). The limits of agreement ranged from -0.93 to 0.74 cm, falling within the reported limits of agreement for manual OFC measurements. High interrater and intrarater reliability of OFC, cephalic index, and volume measurements were also demonstrated. The proposed method for automated OFC measurements was found to be a reliable alternative to manual measurements, which may be particularly beneficial in young children who undergo 3D imaging in craniofacial centers as part of their treatment protocol and in research settings that require a reproducible and transparent pipeline for anthropometric measurements. The method has been incorporated into CraniumPy, an open-source tool for 3D image visualization, registration, and optimization, which is publicly available on GitHub ( https://github.com/T-AbdelAlim/CraniumPy ).


[Regulation of beta-galactosidase synthesis in Escherichia coli by exogenous cyclic 3',5'-adenosine monophosphate].
The effect of cyclic 3',5'-adenosine monophosphate (cAMP) on the rate of beta-galactosidase biosynthesis was studied in the cells of Escherichia coli M-17 growing in MPB and mineral media with glucose and maltose, i.e. under the conditions of various catabolite repression, as well as upon lac-operon induction by isopropyl-beta-D-galactopyranoside (IPGP). The stimulating action of exogenous cAMP was found only in a medium with salts and glucose. The induction by IPGP was highest during the growth in a medium with glucose and maltose. When the medium contained IPGP, cAMP accelerated the enzyme synthesis in all media, but only at the early growth phases, while cAMP eliminated the effect of IPGP at the stationary phase of growth. The regulation of beta-galactosidase biosynthesis by cAMP demonstrated for the first time that this effect depended on the physiological state of E. coli: the expression of catabolite-sensitive E. coli genes was subject to both positive and negative regulation in one and the same inducible system. The effect exerted by cAMP depended on the nature of a carbon source in the growth medium.


Phosphatidylserine index as a marker of the procoagulant phenotype of acute myelogenous leukemia cells.
Patients with acute myelogenous leukemia (AML) are at risk for thrombotic complications. Risk to develop thrombosis is closely tied to leukemia subtype, and studies have shown an association between leukocytosis and thrombosis in AML M3. We evaluated the relative roles of cell count and the surface expression of tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a purified system and promoted experimental thrombus formation. In contrast, the TF-negative AML cell line, HEL, exhibited only prothrombinase activity and did not affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14 shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin increased their extrinsic tenase activity and PS expression. Clot initiation time inversely correlated with logarithm of PS index, defined as the product of multiplying leukocyte count with cell surface PS exposure. We propose that leukemia cell PS index may serve as a biomarker for procoagulant activity.


The Stokes-Einstein relation at moderate Schmidt number.
The Stokes-Einstein relation for the self-diffusion coefficient of a spherical particle suspended in an incompressible fluid is an asymptotic result in the limit of large Schmidt number, that is, when momentum diffuses much faster than the particle. When the Schmidt number is moderate, which happens in most particle methods for hydrodynamics, deviations from the Stokes-Einstein prediction are expected. We study these corrections computationally using a recently developed minimally resolved method for coupling particles to an incompressible fluctuating fluid in both two and three dimensions. We find that for moderate Schmidt numbers the diffusion coefficient is reduced relative to the Stokes-Einstein prediction by an amount inversely proportional to the Schmidt number in both two and three dimensions. We find, however, that the Einstein formula is obeyed at all Schmidt numbers, consistent with linear response theory. The mismatch arises because thermal fluctuations affect the drag coefficient for a particle due to the nonlinear nature of the fluid-particle coupling. The numerical data are in good agreement with an approximate self-consistent theory, which can be used to estimate finite-Schmidt number corrections in a variety of methods. Our results indicate that the corrections to the Stokes-Einstein formula come primarily from the fact that the particle itself diffuses together with the momentum. Our study separates effects coming from corrections to no-slip hydrodynamics from those of finite separation of time scales, allowing for a better understanding of widely observed deviations from the Stokes-Einstein prediction in particle methods such as molecular dynamics.


Fluctuation spectroscopy of giant unilamellar vesicles using confocal and phase contrast microscopy.
A widely used method to measure the bending rigidity of bilayer membranes is fluctuation spectroscopy, which analyses the thermally-driven membrane undulations of giant unilamellar vesicles recorded with either phase-contrast or confocal microscopy. Here, we analyze the fluctuations of the same vesicle using both techniques and obtain consistent values for the bending modulus. We discuss the factors that may lead to discrepancies.


To drain or not to drain after thyroid surgery: a randomized controlled trial at a tertiary Hospital in East Africa.
In many facilities, drains are routinely inserted after thyroidectomy with the aim of preventing hematoma formation and accumulation of seroma. The continued use of drains may be based more on tradition rather than proven scientific evidence. To assess the benefit of drain use after thyroidectomy by determining; length of hospital stay, post operative pain and wound sepsis. This was a randomized controlled trial, carried out at a tertiary national referral hospital (Mulago, Kampala). Over a 6 month period in 2011, we recruited 68 patients. Socio-demographic information and clinical parameters were recorded. Outcomes measures were evaluated. Data were double entered into epidata version 3.1.1 and analyzed using STATA version 10.0. Ethical approval was secured. Mean age of participants was 46 and 43.7 years in drain and no drain arm respectively. Most participants were female. Mean duration of hospital stay after thyroidectomy was significantly higher among the drain arm as compared with the no drain arm [2.41 (± 0.89) vs 1.71 (± 0.76) days (p = 0.0008)]. One patient (drain arm) had wound infection. The pain score on the postoperative day was statistically higher among in the drain arm than the no drain arm [5.71 vs 2.53 (p = 0.001)]. Not inserting a drain post operatively after thyroid surgery was associated with short hospital stay and less operative pain. Results of this study do not support routine drainage after thyroid surgery.


Atypical radiographic features in Pneumocystis carinii pneumonia.
In a review of clinical, pathologic, and radiographic findings from 30 patients with confirmed pneumocystis pneumonia, the disease presented a typical radiographic picture of acute bilateral perihilar and basilar infiltrate progressing to diffuse alveolar consolidation within 3-5 days and unassociated with adenopathy or pleural changes in 13 patients. However, the incidence of atypical radiographic features was appreciable (17 of the 30 patients showed at least one atypical finding) and, in addition, few radiographic findings completely excluded the diagnosis of pneumocystis infection.


Antiangiogenic effects of melatonin in endothelial cell cultures.
Endothelial cells represent one of the critical cellular elements in tumor microenvironment playing a crucial role in the growth and progression of cancer through controlling angiogenesis. Vascular endothelial growth factor (VEGF) produced from tumor cells is essential for the expansion of breast cancer and may function in both paracrine and autocrine manners to promote proliferation, growth, survival and migration of endothelial cells. Since melatonin regulates tumor microenvironment by decreasing the secretion of VEGF by malignant epithelial cells and also regulates VEGF expression in human breast cancer cells, the aim of the present study was to investigate the anti-angiogenic activity of melatonin against the pro-angiogenic effects of breast cancer cells. In this work, we demonstrate that melatonin strongly inhibited the proliferation as well as invasion/migration of human umbilical vein endothelial cells (HUVECs). Melatonin disrupted tube formation and counteracted the VEGF-stimulated tubular network formation by HUVEC. In addition, conditioned media collected from human breast cancer cells were angiogenically active and stimulated tubule length formation and this effect was significantly counteracted by the addition of anti-VEGF or melatonin. Melatonin also disintegrated preformed capillary network. All these findings demonstrate that melatonin may play a role in the paracrine interactions that take place between malignant epithelial cells and proximal endothelial cells. Melatonin could be important in reducing endothelial cell proliferation, invasion, migration and tube formation, through a downregulatory action on VEGF. Taken together, our findings suggest that melatonin could potentially be beneficial as an antiangiogenic agent in breast cancer with possible future clinical applications.


A Quiet Firehouse: Reducing Environmental Stimuli Among Professional On-Duty Firefighters.
Firehouse alarms are so loud that they cause a systemic response, similar to the flight-or-flight response. The purpose of the study was to reduce firehouse environmental stimuli to improve sleep quality and, thus, reduce cardiac burden. The intervention included restricted unnecessary fire alarms, reduced light levels, and regulated temperature in the bunkroom. Among 24 firefighters, 11 completed the matched post-assessment. Six weeks after implementing the interventions, measures revealed the average lux level dropped from 0.75 to 0.19 lux, P < 0.05, and the presence of elevated blood pressure reduced from 86% to 15%, P < 0.05. Results support that reducing environmental stimuli in firehouses reduces blood pressure, which is much easier than targeting behavior change. On the basis of this pilot study, the practice of routinely activating unnecessary fire alarms in firehouse bunkrooms should be discouraged.


Sensory-motor control in the ipsilesional upper extremity after stroke.
There is substantial evidence to indicate that sensory-motor control of the ipsilesional upper extremity (UE) in adults after unilateral stroke is abnormal. Some of the sensory-motor deficits differ as a function of the side of the cerebral lesion. Rapid movements of the ipsilesional UE that require precise timing and sequencing are more affected in individuals with lesions in the left hemisphere. In contrast, ipsilesional movements that have constrained spatial requirements are more affected in those with lesions in the right hemisphere. Ipsilesional UE coordination of discrete tasks may be normal, but the coordination of continuous tasks is affected in adults with left stroke. Sensation in the ipsilesional UE appears to be unaffected, or minimally affected after stroke. Strength deficits have been demonstrated in the ipsilesional UE, but primarily in those with right sided lesions. Ipsilesional performance deficits are revealed in clinical tests of function that use time to completion as the measure of success. Ipsilesional performance deficits may reflect motor control deficits that are masked on the contralateral side by hemiplegia and hemisensory loss. Interventions that focus on specific motor control deficits, such as speed of sensory-motor processing, through practice with the ipsilesional UE, may result in functional improvements in both limbs.


Vulnerable young women and frontline service providers identify options to improve the HIV-sensitivity of social protection programmes in Botswana: A modified Policy Delphi approach.
Poverty, lack of education and gender inequality make unemployed and out-of-school young women extremely vulnerable to HIV infection. Promotive social protection programmes aim to increase livelihood and capabilities and could empower this priority population to act on HIV prevention choices. In Botswana, they rarely benefit from such programmes.A modified Policy Delphi engaged a panel of 22 unemployed and out-of-school young women and eight frontline service providers to consider alternative policy and practice options, and tailor available programmes to their own needs and social situation. The panel assessed the desirability and feasibility of improvement proposals and, in a second round, ranked them for relative importance.Nearly all 40 improvement proposals were considered very desirable and definitely, or possibly, feasible, and panellists prioritised a wide range of proposals. Frontline service providers stressed foundational skills, like life skills and second chance education. Young women preferred options with more immediate benefits. Overall, panellists perceived positive role models for programme delivery, access to land and water, job skills training, and stipends as most important to empower HIV-vulnerable young women. Results suggest ample policy space to make existing social protection programmes in Botswana more inclusive of unemployed and out-of-school young women, hence more HIV-sensitive.


[Internal validity and diagnostic utility of the Eating Disorder Inventory in Mexican women].
To assess the diagnostic utility and internal validity of the Eating Disorder Inventory (EDI-2) in Mexican women. An observational, cross-sectional study was conducted between October 2000 and January 2001. The sample population consisted of two groups of women: patients diagnosed with anorexia nervosa or bulimia, but no other psychiatric pathology, seen by psychiatrists at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (National Institute of Medical Sciences and Nutrition Salvador Zubirán), and a randomly selected sample of women from a school in Mexico City. A structured interview was conducted using SCID/DSM-IV as the gold standard. Finally the EDI-2 was administered. Statistical analysis was performed using Student's t test for independent samples, Cronbach's alpha test, and calculation of sensitivity, specificity, and positive and negative predictive values. No significant differences were found for weight, height, and body mass index. Women with no eating disorders were younger than those with eating disorders (16.7 +/- 2.8 vs. 19.9 +/- 4.3, p = 0.004). The EDI-2 total score was clearly different between the groups (53.8 +/- 32.4 vs. 146.3 +/- 45.6 respectively, p < 0.001). All Cronbach's alpha coefficients for all subscales were over 0.85. For the total score, a sensitive cutoff point of 80 (sensitivity 90.9, 95% confidence interval [CI] 69.4 to 98.4; specificity 80, 95% CI 58.7 to 92.4) and a specific cutoff point of 105 (sensitivity 81.8, 95% CI 59 to 94; specificity 89.3, 95% CI 70.6 to 97.2) are recommended. The EDI-2 has a high internal validity and should be a useful tool to assess eating disorders.


Calcium-Promoted Interaction between the C2-Domain Protein EHB1 and Metal Transporter IRT1 Inhibits Arabidopsis Iron Acquisition.
Iron is a key transition element in the biosphere and is crucial for living organisms, although its cellular excess can be deleterious. Maintaining the balance of optimal iron availability in the model plant Arabidopsis (Arabidopsis thaliana) requires the precise operation of iron import through the principal iron transporter IRON-REGULATED TRANSPORTER1 (IRT1). Targeted inhibition of IRT1 can prevent oxidative stress, thus promoting plant survival. Here, we report the identification of an IRT1 inhibitor, namely the C2 domain-containing peripheral membrane protein ENHANCED BENDING1 (EHB1). EHB1 interacts with the cytoplasmically exposed variable region of IRT1, and we demonstrate that this interaction is greatly promoted by the presence of calcium. We found that EHB1 binds lipids characteristic of the plasma membrane, and the interaction between EHB1 and plant membranes is calcium-dependent. Molecular simulations showed that EHB1 membrane binding is a two-step process that precedes the interaction between EHB1 and IRT1. Genetic and physiological analyses indicated that EHB1 acts as a negative regulator of iron acquisition. The presence of EHB1 prevented the IRT1-mediated complementation of iron-deficient fet3fet4 yeast (Saccharomyces cerevisiae). Our data suggest that EHB1 acts as a direct inhibitor of IRT1-mediated iron import into the cell. These findings represent a major step in understanding plant iron acquisition, a process that underlies the primary production of bioavailable iron for land ecosystems.


Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years.
The genes responsible for obesity are candidate genes for obesity-related diseases, such as hypertension. Functional polymorphisms in the beta2- and beta3-adrenergic receptors have been reported to be associated with hypertension and obesity. To longitudinally clarify the relevance to alterations in beta-adrenergic receptor polymorphisms related to weight gain, blood pressure (BP) elevation, and sympathetic nerve activity as measured by plasma norepinephrine level, we studied 160 young, nonobese, normotensive men. Changes in body weight, BP, plasma norepinephrine levels, and beta2-adrenergic (Arg16Gly, Gln27Glu) and beta3-adrenergic (Trp64Arg) receptor polymorphisms were measured periodically over a 5-year period. Weight gain and BP elevation were defined as > or =10% increases from entry levels over 5 years in body mass index or mean BP. The presence of the Gly16 allele of Arg16Gly was associated with a higher frequency of weight gain and BP elevation over the 5-year period. The subjects carrying the Glu27 allele of Gln27Glu and the Trp64 allele of Trp64Arg had a higher frequency of BP elevation. Significantly higher levels of plasma norepinephrine at entry and at year 5 were observed in the subjects with the Gly16 allele of Arg16Gly and the Glu27 allele of Gln27Glu compared with those without the Gly16 or the Glu27 alleles. These results demonstrate that the Gly16 allele is related to greater weight gain and BP elevation. Additionally, Glu27 and Trp64 alleles are linked to BP elevation. The subjects carrying the beta2-polymorphisms linked to weight gain and BP elevation also have higher plasma norepinephrine levels that are present at entry before weight gain and BP elevation. These findings suggest that beta2-adrenergic receptor polymorphisms in association with a heightened sympathetic nerve activity could predict the future onset of obesity and hypertension, as shown in the 5-year longitudinal study.


[Recent new information on epidemiology of headache].
We reviewed the epidemiology of headache disorders for the most frequent primary headache-syndromes: migraine, tension-type headache and trigemino-autonomic headache syndromes. In the last years scientific data about headache disorders have increased. New studies investigated not only the prevalence of headaches, but also economic costs of this disorder. Epidemiologic headache research also investigates the quality of life.


Potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime.
In this study we investigated the efficacy of hyperbaric oxygen (HBO) therapy, alone or combined with the pentavalent antimonial glucantime on Leishmania amazonensis infection. In parallel, the effect of Brazilian red propolis gel (propain) alone or combined with glucantime on L. amazonensis infection was evaluated. The inhibition of the infection in macrophages treated with glucantime in combination with HBO exposition was greater than that of macrophages treated with glucantime alone or HBO alone. The susceptible mouse strain BALB/c infected in the shaved rump with L. amazonensis treated with glucantime and exposed to HBO showed: time points in the course of the disease in which lesions were smaller than those of mice treated with glucantime alone and revascularization of the skin in the lesion site; interferon-gamma (IFN-g) levels were not elevated in lymph node cells from these animals. Propain alone was not efficient against lesions, although less exudative lesions were observed in animals treated with propain alone or combined with glucantime. These results reveal the potential value of HBO and red propolis in combination with glucantime for treating cutaneous leishmaniasis and encourage further studies on the effect of more aggressive HBO, propolis and glucantime therapies on different mouse models of leishmaniasis.


Potential for MERLIN-Expo, an advanced tool for higher tier exposure assessment, within the EU chemical legislative frameworks.
MERLIN-Expo merges and integrates advanced exposure assessment methodologies, allowing the building of complex scenarios involving several pollution sources and targets. The assessment of exposure and risks to human health from chemicals is of major concern for policy and ultimately benefits all citizens. The development and operational fusion of the advanced exposure assessment methodologies envisaged in the MERLIN-Expo tool will have a significant impact in the long term on several policies dealing with chemical safety management. There are more than 30 agencies in Europe related to exposure and risk evaluation of chemicals, which have an important role in implementing EU policies, having especially tasks of technical, scientific, operational and/or regulatory nature. The main purpose of the present paper is to introduce MERLIN-Expo and to highlight its potential for being effectively integrated within the group of tools available to assess the risk and exposure of chemicals for EU policy. The main results show that the tool is highly suitable for use in site-specific or local impact assessment, with minor modifications it can also be used for Plant Protection Products (PPPs), biocides and REACH, while major additions would be required for a comprehensive application in the field of consumer and worker exposure assessment.


MEMS and the microbe.
In recent years, relatively simple MEMS fabrications have helped accelerate our knowledge of the microbial cell. Current progress and challenges in the application of lab-on-a-chip devices to the viable microbe are reviewed. Furthermore, the degree to which microbiologists are becoming the engineers and are tailoring microbial cells and protocells as potential components for bioMEMS devices is highlighted. We conclude this is a highly productive time for microbiologists and microengineers to unite their shared interest in the micron scale world.


The stability of truncated epidermal growth factor receptor mRNA is higher than that of the full-length receptor mRNA in rat hepatoma cells.
Truncated and full-length epidermal growth factor (EGF) receptors are produced in rat liver cells. The truncated EGF receptor mRNA is almost identical to the full-length EGF receptor mRNA except for the lack of a 3' region of the full-length receptor mRNA. To understand the stability of rat EGF receptor mRNAs, we analyzed the expression of EGF receptor mRNAs in the hepatoma cell line, AH66 and liver cells. Ten, 7 and 5 kb full-length and 2.7 kb truncated EGF receptor mRNAs were detected in both of them. The half-lives of the 10 and 2.7 kb EGF receptor mRNAs were determined in AH66 cells using a transcriptional inhibitor, 5,6-dichlororibofuranosylbenzimidazole. The half-lives of the 10 and 2.7 kb mRNAs were 1.2 and 11 h, respectively. These results indicated that the truncated mRNA is 4 times more stable than the full-length mRNA in rat cells. As for the stability, the role of a sequence of 3'-untranslated region of the EGF receptor mRNA was discussed.


Effect of catalytic nanomedicine on amputation-stage chronic venous ulcers: four case studies.
Chronic ulcers represent a significant challenge for patients with compromised microcirculation. As a novel branch of research, catalytic nanomedicine has exhibited promising outcomes with the development of nanostructured composites designed to disinfect and improve the healing of chronic wounds through the incorporation of bionanocatalysts within gel matrices. This study aimed to assess the impact of bionanocatalysts on 4 patients suffering from chronic venous ulcers, which had previously been indicated for lower extremity amputation. Bionanocatalysts were synthesized and incorporated into a gel matrix. Monthly debridement was conducted with the objective of completely removing nonviable tissue. The bionanocatalyst-embedded gel was applied every other day, covering the entire wound surface and secured with a secondary dressing. Encouragingly, all cases exhibited complete wound closure, and patients reported no adverse side effects. These findings offer robust support for the utilization of this technology in wound healing and prompt a reevaluation of the hypothesis regarding the mechanism of action of bionanocatalysts in chronic wounds. Future research endeavors should aim to quantitatively assess the bionanocatalysts' influence on the trajectory of wound healing, as well as address the myriad challenges associated with managing chronic wounds.


A biotin-conjugated photo-activated CO-releasing molecule (biotinCORM): efficient CO-release from an avidin-biotinCORM protein adduct.
Biotinylated pharmaceuticals are of great interest due to the strong interactions between biotinyl-functionality and streptavidin/avidin, which opens up avenues for efficient targeting and localisation. Three new carbon monoxide-releasing molecules (CO-RMs) have been synthesised and characterised using chemical and biological analysis. An alkyne-containing CO-RM 2 was found to be toxic to RAW 264.7 murine macrophages; and thus therapeutically viable CO-RM 1 was employed as the alkyne precursor for [3 + 2] cycloaddition chemistry enabling a new acid-containing CO-RM 4 and biotin-bioconugate-CO-RM (BiotinCORM 5) to be prepared. CO-RM 4 showed significantly improved solubility and BiotinCORM 5 acts as a photo-CO-RM. We have found that an avidin-CORM adduct of 5 is a CO-releasing protein, releasing CO on irradiation with light (400 nm). The avidin-biotinCORM adduct of 5 was found to have a binding energy of 10 kcal mol-1.


Experimental cell for molecular beam deposition and magnetic resonance studies of matrix isolated radicals at temperatures below 1 K.
We present the design and performance of an experimental cell constructed for matrix isolation studies of H and D atoms in solid H2/D2 films, which are created by molecular beam deposition at temperatures below 1 K. The sample cell allows sensitive weighing of the films by a quartz microbalance (QM) and their studies by magnetic resonance techniques in a strong magnetic field of 4.6 T. We are able to regulate the deposition rate in the range from 0.01 to 10 molecular layers/s, and measure the thickness with ≈0.2 monolayer resolution. The upper QM electrode serves as a mirror for a 128 GHz Fabry-Perot resonator connected to an electron spin resonance (ESR) spectrometer. H and D atoms were created by RF discharge in situ in the sample cell, and characterized by ESR and electron-nuclear double resonance. From the magnetic resonance measurements we conclude that the films are smooth and provide homogeneous trapping conditions for embedded atoms. The current sample cell design also makes it possible to calibrate the ESR signal and estimate the average and local concentrations of H and D radicals in the film.


Deficient double-strand break repair in oral squamous cell carcinoma cell lines.
Approximately 20% of oral squamous cell carcinoma (OSCC) cases arise without any identifiable environmental cause, suggesting involvement of genetic influences in their aetiology. DNA double-strand breaks (DSBs) sever both strands of DNA and pose a potential threat to genomic integrity. A hastened accumulation of somatic mutations consequent to DSB repair is deemed to be a likely event in tumorigenesis of OSCC. Two discrete chemical approaches, namely hydrogen peroxide and camptothecin, were used to induce DSB in oral cell lines derived from normal through dysplastic to OSCC tissues. After optimization, gamma histone 2Ax (γH2Ax) foci were counted as an indirect measure of kinetics of DSB and confirmed with Western blot of γH2Ax, Nbs1 and ATM. Maximal number of γH2Ax foci was detected 1 and 2 hours post-exposure to camptothecin and hydrogen peroxide, respectively; when adjusted for the baseline number of γH2Ax, neoplastic cell lines showed the lowest number of maximal DSB and slowest rate of repair compared to other cell lines. γH2 Ax Western blot closely mirrored the trend observed in immunofluorescent staining for γH2 Ax foci. Changes in the expression level of ATM and Nbs1 were minimal; however, ATM expression showed a slight gradual increase in normal cells which reached its peak at 2 hours after exposure to camptothecin. There is a difference in efficiency of DSB repair pathways in cell lines derived from different stages of oral tumorigenesis with neoplastic cell lines having the most defective DSB repair system.


A new method for analyzing diagnostic delay in gynecological cancer.
The aim of this article is to present a new methodology to illustrate, understand, and measure delay in health care. The method is inspired by process mapping tools as analytical framework and demonstrates its usefulness for studying diagnostic delay in gynecological cancer. Six women with a diagnostic delay of 6 weeks or more before treatment of gynecological cancer at a specialized regional department (the Department of Gynecology and Obstetrics, Odense University Hospital, Denmark) were included in the study. Maps of existing processes were performed for each patient reflecting the patients' pathway through the course of the disease. We combined 2 process mapping tools, namely, value stream mapping and business process modeling notation. The first method identifies the flow in a process as timelines. The latter introduces a set of easily recognizable graphical elements. Detailed information concerning the cancer patients' pathway was obtained. The method visualized the complexities within the diagnostic pathway. The role of different participants (patient, general practitioner, and local hospitals) became clear by arranging activities according to responsibilities and was shown to recurrently influence and contribute to the delay in the diagnostic process. Some important contributors to diagnostic delay in gynecological cancer, such as lack of cancer suspicion, competing diseases, negative test results, inexpedient referral patterns, and referrals without cancer suspicion, were found. Our results point out process mapping tools as a potential analytical framework to illustrate, understand, and measure delay in health care. Furthermore, the method was able to identify important contributors to the diagnostic delay in gynecological cancer patients.


[Study about collection of urine for bacteriologic culture].
This study was made in the City of São Paulo, in 30 hospitals with the objective of to identify and classify the procedures of collecting urine for bacteriologic study. The data's collect has been realized based on a record prepared for a systematic observation directly connected to a system interpretative of categories ("Good", "Fair" and "Poor") applied to all procedures. The results obtained have been presented in the tables distributed in the absolute end relative frequencies, grouped and classified by categories. The conclusions where in accordance to the specific objectives initially proposed and has been classified under the interpretative systems of the categories previously defined and adressed to the research.


The Lille Apathy Rating Scale: validation of a caregiver-based version.
Apathy is reported in 16.5% to 70% of Parkinson's disease (PD) patients. Our recently developed Lille Apathy Rating Scale (LARS) has been specifically validated for patient-based assessment of apathy in PD. The aim of the present study was to validate a caregiver-based version of the LARS. Sixty consecutive PD patients and their respective caregivers participated in the study. An informant-based version of the LARS (LARS-i) was developed to rate apathy via a caregiver-based structured interview. Apathy was also assessed in a patient-based interview using the LARS and the informant- and clinician-rated versions of the Apathy Evaluation Scale (AES). Cronbach's alpha and standardized alpha coefficients were 0.872 and 0.877, respectively, and the split-half reliability was 0.901 (revealing good internal consistency). The test-retest and inter-rater reliability values were 0.960 and 0.996, respectively. Criterion-related validity (according to an independent, expert diagnosis) was good. Scores on the LARS and the LARS-i were highly correlated. However, apathy was rated significantly more severely by the caregiver than by the patient. This difference was significantly higher for demented than nondemented PD patients. The LARS-i was seen to have excellent psychometric properties and appears to be valid for use in PD with respect to the patient-based LARS and the informant- and clinician-rated versions of the AES.


Reducing the risk of bacterial contamination of cellular blood components.
Transfusion-associated septic reactions occurring during or following the transfusion of cellular blood components was one of the earliest recognised complications of allogeneic blood transfusions. The presence of bacteria in cellular blood products thus has been a problem for many decades and currently it is the most common microbiological cause of transfusion-associated morbidity and mortality. Transfusion-associated septic reactions due to contaminated platelet concentrates appear to be much more common than those due to red cell concentrates. The prevalence of contaminated cellular blood products (red cells and platelets) is approximately 1 in 2,000. However, the transfusion to a recipient of a contaminated blood product may not be associated with morbidity, because many contaminated blood product units contain only few bacteria and such transfusions may be innocuous to the recipient. In other instances, contaminated blood product units may contain large numbers of virulent bacteria and endotoxins, and their transfusion may be associated with significant morbidity and may even be lethal to the recipient. The prevalence of severe episodes of transfusion-associated sepsis has not been clearly established, but is probably of the order of 1 in 50,000 for platelet units and 1 in 500,000 for red blood cell units transfused. As a result of the increased recognition that such transfusion-associated septic episodes can occur, a variety of measures have been proposed to try to prevent and/or control the rate of contamination of blood products.


[Current state of medical rehabilitation in the Republic of Byelarus].
Problems in the modern status of medical rehabilitation (MR) service in the Republic of Belarus, prerequisites for its creation, and prospects for development are discussed. The service is set up on the basis of laws of the Republic and normative acts of the Ministry of Health. Main aspects of these laws and acts are presented and their significance for the formation of MR service is discussed. Main stages in organization support of the service are characterized: evaluation of the disease consequences before rehabilitation measures, evaluation of the rehabilitation potential, rehabilitative measures proper, and assessment of their efficacy. Approaches to practical rehabilitation in Belarus and in foreign countries are presented in accordance with published reports. Economic efficiency of MR is discussed. Trends of research of MR service are outlined.


Treatment of congenital generalized lymphangiectasia with propranolol in a preterm infant.
Generalized lymphangiectasia is a rare congenital disorder characterized by dilated lymphatic vessels with a fatal prognosis, especially in cases with thoracic involvement. We describe the use of propranolol in the therapy of generalized lymphangiectasia in a preterm infant with hydrops fetalis. Propranolol was well tolerated and effective within the first months. It remains to be shown whether propranolol is a treatment option for infants with generalized lymphangiectasia.


Host defense against oropharyngeal and vaginal candidiasis: Site-specific differences.
Mucosal candidiasis is extremely common in immunocompromised patients. However, the prevalence of site-specific infection (i.e., oropharyngeal, vaginal, and esophageal candidiasis) can be quite variable depending on the immune status of the host. While vulvovaginal candidiasis is common in normal healthy women, oropharyngeal and esophageal candidiasis are more frequently encountered under immunocompromised states. Candida albicans, the causative agent in most cases of candidiasis, is a commensal organism of the gastrointestinal and lower female reproductive tracts. Thus, most healthy individuals have demonstrable Candida-specific immunity in the peripheral circulation. The pathogenic state is often precipitated by a deficiency or dysfunction in this immunity. Studies from animal models, women with recurrent vulvovaginal candidiasis, and HIV-infected individuals, however, suggest that distinct host defense mechanisms may function against oropharyngeal and vulvovaginal candidiasis. While cell-mediated immunity (CMI) appears important for protection against oropharyngeal candidiasis (OPC), there is little evidence to indicate that T cell-mediated immunity is protective against vulvovaginal candidiasis (VVC). Furthermore, whereas both local and systemically derived immune defenses appear important for protection against OPC, host defenses that protect against VVC appear limited to the local tissue and possibly restricted to innate mechanisms. Thus, current evidence suggests that VVC, unlike OPC, may not represent a strict opportunistic infection.


Abnormal bleeding associated with reproductive tract infection.
Reproductive tract infection is an often unrecognized, but relatively common, cause of abnormal reproductive tract bleeding. Postcoital bleeding, menorrhagia, metrorrhagia, and oral contraceptive break-through bleeding are potentially infection-related complaints. The microorganisms most often associated with abnormal reproductive tract bleeding include: Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus type 2, and microorganisms associated with bacterial vaginosis. The clinical conditions cervicitis, endometritis, and pelvic inflammatory disease and the related microorganisms are discussed, as are strategies for clinical management and counseling.


Enhancing the viability of Lactobacillus rhamnosus GG after spray drying and during storage.
Increasing knowledge about the human microbiome has led to a growing awareness of the potential of applying probiotics to improve our health. The pharmaceutical industry shows an emerging interest in pharmaceutical formulations containing these beneficial microbes, the so-called pharmabiotics. An important manufacturing step is the drying of the probiotics, as this can increase the stability and shelf life of the finished pharmabiotic product. Unfortunately, drying also puts stress on microbial cells, thus causing a decrease in viability. We aimed to examine the effect of different drying media and protective excipients on the viability of the prototype probiotic strain Lactobacillus rhamnosus GG after spray drying and during subsequent storage for 28 weeks. The presence of phosphates in the drying medium showed to have a superior protective effect, especially during long-term storage at room temperature. Addition of lactose or trehalose resulted in significantly improved survival rates after drying as well as during long-term storage for the tested excipients. Both disaccharides are characterized by a high glass transition temperature. Maltodextrin showed less protective capacities compared to lactose and trehalose in all tested conditions. The usage of mannitol or dextran resulted in sticky powders and low yields, so further testing was not possible. In addition to optimizing the viability, future research will also explore the functionality of cellular probiotic components after spray drying in order to safeguard the probiotic activity of the formulated pharmabiotics.


Stress-induced JNK activation is independent of Gadd45 induction.
DNA damage and environmental stress activate signaling and induce genes involved in cell cycle and cell death. Expression of the Gadd45 protein is induced following DNA damage and other stress. Gadd45 is believed to play a role in growth arrest and possibly in cell death. The JNK signaling pathway is also activated by some DNA-damaging agents. This activation leads to phosphorylation and activation of transcription factors, such as c-Jun/AP-1 and ATF2, which mediate immediate early gene induction. Recently Gadd45 was suggested to be involved in JNK activation. However, as this suggestion relied on in vitro experiments and ectopic overexpression of Gadd45 protein, we examined whether physiological levels of Gadd45 that are induced following exposure to DNA damaging agents and stress can lead to JNK induction. We found that JNK activation by UV irradiation and anisomycin treatment precedes the induction of gadd45 mRNA by these agents. Gadd45 protein induction by methyl methanesulfonate also lagged behind JNK activation. The use of protein synthesis inhibitors suggested that newly synthesized proteins, including the stress-induced Gadd45, make only a marginal contribution to JNK activation. We also found that stresses such as gamma irradiation induce Gadd45 and do not activate JNK in mouse fibroblasts. Therefore, stress-induced JNK does not depend on Gadd45 induction.


A comparison of the risk of QT prolongation among SSRIs.
To report QT prolongation potential in selective serotonin reuptake inhibitors (SSRIs) in order to advise clinicians on safe use of SSRIs other than citalopram in light of citalopram warnings. Primary literature and case reports were identified through a systematic search. Data from drug manufacturers, package inserts, and the ArizonaCERT database were also utilized. English-language studies and case reports were included. Studies demonstrate possible dose-related clinically significant QT prolongation with escitalopram. Fluoxetine, fluvoxamine, and sertraline at traditional doses demonstrate a lack of clinically significant increases in QTc in the majority of studies. Further, paroxetine monotherapy shows a lack of clinically significant QTc prolongation in all studies. However, case reports or reporting tools still link these SSRIs with QTc prolongation. Fluoxetine, escitalopram, and sertraline used in post-acute coronary syndrome patients did not demonstrate risk of QTc prolongation. For clinicians who choose not to use citalopram due to recent Food and Drug Administration (FDA) recommendations, other antidepressants within this class may be considered. When citalopram is not utilized based on risk factors for TdP, use of escitalopram is not likely the safest alternative. Based on current literature, fluoxetine, fluvoxamine, and sertraline appear to have similar, low risk for QT prolongation, and paroxetine appears to have the lowest risk. However, there are significant limitations in interpreting the studies, including varying definitions of significant QT prolongation. Therefore, choice of an alternative SSRI should be based on individual risk factors for arrhythmias and other patient-specific factors.


Field studies with convalescent serum and infectious bursal disease vaccine to control turkey coryza.
Convalescent serum given to 1-day-old poults delayed clinical signs of turkey coryza by several days and reduced mortality on infected farms. Turkey breeders immunized with cell-culture-adapted infectious bursal disease virus (IBDV) or turkey infectious bursal disease virus (TIBDV) had a marked increase in virus-neutralization (VN) antibody titers. The VN antibody titer was significantly higher in progeny poults than in poults from unimmunized breeders. Clinical turkey coryza and mortality was considerably less in poults from IBD- or TIBD-vaccinated breeders than in control poults. They also responded more favorably to hemorrhagic enteritis and fowl cholera vaccination.


[Synthesis of p-nitrophenyl laminarioligosides via transglycosylation reaction catalyzed by endo-1,3-beta-D- glucanase from marine mollusk].
The transglycosylation reaction catalyzed by endo-1,3-beta-D-glucanase LIV from the marine mollusk Spisula sachalinensis was studied with the goal of preparing p-nitrophenyl (Np) 1,3- and 1,3; 1,6-D-glucooligosides. As donors we used the 1,3;1,6-beta-D-glucans with various content of beta-1, 6-glucoside bonds: laminarians [from Laminaria cichorioides (10%), L. gurjanovae (2%), and Fucus evanescens (35%)] and translam (25%); as acceptor we used the p-nitrophenyl beta-D-glucoside (GNp). The maximal yield of the transglycosylation products was found when using laminaran from Laminaria cichorioides; donors with a lower or higher content of beta-1,6-glucoside bonds were less efficient. The laminaran from F. evanescens and translam gave no Np-laminaribioside. At optimal conditions (10 mg/ml of laminaran from L. cichorioides and 5 mg/ml of GNp), maximal yields of Np-laminaribioside, Np-trioside, Np-tetraoside, and Np-pentaoside were 19, 8, 3, and 1%, respectively. The first two compounds were isolated by chromatography on silica gel, their physicochemical characteristics were obtained, and their structures were established by 13C NMR spectroscopy.


Direct transcriptional control of a p38 MAPK pathway by the circadian clock in Neurospora crassa.
MAPK signal transduction pathways are important regulators of stress responses, cellular growth, and differentiation. In Neurospora, the circadian clock controls rhythms in phosphorylation of the p38-like MAPK (OS-2); however, the mechanism for this regulation is not known. We show that the WCC, a transcription factor and clock component, binds to the os-4 MAPKKK promoter in response to light and rhythmically in constant darkness, peaking in the subjective morning. Deletion of the WCC binding sites in the os-4 promoter disrupts both os-4 mRNA and OS-2 phosphorylation rhythms. The clock also indirectly regulates rhythmic expression of the histidyl-phosphotransferase gene, hpt-1, which peaks in the evening. Anti-phase expression of positive (OS-4) and negative (HPT-1) MAPK pathway regulators likely coordinate to enhance rhythmic MAPK activation to prepare cells to respond to osmotic stress during the day in the natural environment. Consistent with this idea, we show that wild type cells have a clock-dependent morning kinetic advantage in glycerol accumulation after salt stress as compared to evening treatment. Thus, circadian transcriptional control of MAPK pathway components leads to striking time-of-day-specific effects on the signaling status and physiological response of the pathway.


Isolation and characterization of subcellular membranes from canine stomach smooth muscle.
Subcellular membrane fractions were isolated from the circular muscle of the corpus of canine stomach by differential and isopycnic sucrose density gradient centrifugation. Differential centrifugation gave a mitochondrial fraction enriched (fourfold) in cytochrome c oxidase and a microsomal fraction enriched (fourfold) in 5'-nucleotidase and NADPH-cytochrome c reductase over postnuclear supernatant. On the basis of a study using continuous gradient, a discontinuous sucrose density gradient was prepared to yield F1 to F5 fractions. The F3 fraction at the interface of 18-32% (w/w) sucrose was maximally enriched (13-fold) in 5'-nucleotidase. The fraction contained very low levels of cytochrome c oxidase but did contain NADPH-cytochrome c reductase (eightfold enrichment). The F4 fraction, at the interface of 32-40% (w/w) sucrose, was maximally enriched in NADPH-cytochrome c reductase (12-fold) and cytochrome c oxidase (6-fold). The distribution of the azide-insensitive. ATP-dependent Ca2+ uptake correlated very well with that of 5'-nucleotidase but less well with NADPH-cytochrome c reductase and not at all with cytochrome c oxidase. Sodium azide and ruthenium red inhibited the ATP-dependent Ca2+ uptake by the mitochondrial fraction and postnuclear supernatant, but not by the F3 fraction. ATP-dependent Ca2+ uptake by the F3 fraction was inhibited by calcium ionophores A23187 and ionomycin, but not by the sodium ionophore, monensin. These results are consistent with the hypothesis that the plasma membrane plays a major role ih regulating intracellular Ca2+ concentration in canine corpus circular muscle.


The role of current herbal extracts in bone regeneration through dental implants: in vitro/in vivo/clinical studies.
The quality and quantity of bone at the interface of an implant system are determining factors in the implant's stability. Alternative agents have been studied to augment implants and bone defects, including bone-conductive and bone-inducing agents. By modifying implant surface coatings on the nanoscale, one can enhance osseointegration by stimulating bone cell adhesion, bone matrix formation, and mineralization. Because alternative agents stimulate osteoblasts to mineralize and can control pectin structure, plant-derived silicone has been suggested as a potential candidate for surface nanocoatings on orthopedic and dental titanium implants. Inducing the differentiation of cells or accelerating bone regeneration is possible with the plant extract. Coating these extracts on implant devices can improve cell attachment, differentiation, and proliferation. This review article discusses the role of herbal materials in bone regeneration through dental implants.


Modulation of vasopressin action by reducing agents in Bufo marinus.
The effects of the reducing agent dithiothreitol (DTT) on vasopressin (AVP)-stimulated osmotic water flow and adenylate cyclase activity were studied in the urinary bladder of Bufo marinus. DTT produced concentration-dependent inhibition of the hydroosmotic water permeability response to 10 mU/ml AVP and 10 mM theophylline but did not inhibit the response to 10 mM adenosine 3',5'-cyclic monophosphate (cAMP). The inhibitory effects of DTT on AVP responsiveness were partially reversed by washing in DTT-free Ringer solution or by addition of oxidizing agents such as dehydroascorbic acid (DHA) or H2O2. The inhibitory effects of DTT were completely reversed by washing in DTT-free Ringer plus addition of DHA. In addition, the inhibitory effects of DTT on AVP-induced osmotic water flow were partially reversed by the GTP analogue 5'-guanylyl imidodiphosphate [Gpp(NH)p]. DTT also inhibited the adenylate cyclase response to AVP but did not alter the response to AVP plus Gpp(NH)p or the response to NaF. These observations suggest that the inhibitory effect of thiol compounds on AVP responsiveness may be modulated through alterations of a redox system distal to the hormone receptor but proximal to the catalytic subunit of adenylate cyclase. Inasmuch as Gpp(NH)p partially reversed the inhibitory effects of DTT on AVP-stimulated osmotic water permeability and prevented the inhibitory effect of DTT on AVP-stimulated adenylate cyclase, an effect on either GTPase or binding of GTP to the regulatory protein of adenylate cyclase is suggested by these observations.


The Gender-Specific Associations Between Religion/Spirituality and Suicide Risk in a Sample of Austrian Psychiatric Inpatients.
Most studies have found religion/spirituality to be protective against suicide risk, with a stronger effect among women. To understand this effect, theories of suicide and clinical samples are needed, but related studies are lacking. We applied two established suicide models in 753 psychiatric inpatients. Religion/spirituality correlated protectively with components of the suicide models, with stronger associations among women. The protective effect emerged especially for the capability aspect of suicide among men and for the motivational aspect among women, suggesting very different causal mechanisms, but this has to be replicated with longitudinal studies.


Changes in the transport of mitochondrial Ca2+ during the culture growth cycle of Tetrahymena pyriformis.
The properties of the Ca2+ transport system of mitochondria, isolated in various phases of growth of static cultures of Tetrahymena pyriformis, were studied. A large increase in the endogenous energy-dependent Ca2+ content of mitochondria was observed as cultures of T. pyriformis passed through the exponential and stationary phases of growth (approx. 0.25 and 50 nmol Ca2+ per mg mitochondrial protein, respectively). Simultaneously, the mitochondria dramatically lost their ability to withstand large concentrations of Ca2+ and ADP. However, in the latter case they were able to phosphorylate a large amount of ADP if the strong Ca2+ chelator, ethylene glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, was initially present in the incubation medium. Furthermore, all the changes observed in mitochondria from the stationary phase cells were completely reversed when cell proliferation was re-activated after the lag phase, either by reseeding the stationery cells in fresh growth medium or by oxygenation of the old medium. In aerobic conditions even a small addition of Ca2+ was able to induce rapid release of Ca2+ from mitochondria isolated during the stationary phase of growth. It is suggested that the redistribution of Ca2+ between the mitochondria and the cytoplasm at the onset of the lag phase may serve as the main trigger for the subsequent biochemical and morphological changes observed in T. pyriformis.


Incident Cardiovascular Diseases Among Survivors of High-Risk Stage II-III Colorectal Cancer: A Cluster-Wide Cohort Study.
The incidence and survival of colorectal cancer (CRC) are increasing. There is an increasing number of long-term survivors, many of whom are elderly and have comorbidities. We conducted a population-based study in Hong Kong to assess the long-term cardiovascular disease (CVD) incidence associated with adjuvant fluoropyrimidine-based chemotherapy among CRC survivors. Using the population-based electronic medical database of Hong Kong, we identified adults who were diagnosed with high-risk stage II-III CRC and treated with radical surgery followed by adjuvant fluoropyrimidine-based chemotherapy between 2010 and 2019. We evaluated the cause-specific cumulative incidence of CVD (including ischemic heart disease, heart failure, cardiomyopathy, and stroke) using the flexible parametric competing risk modeling framework. The control group without a history of CVD was selected from among a noncancer random sample from primary care clinics in the same geographic area. We analyzed 1,037 treated patients with CRC and 5,078 noncancer controls. The adjusted cause-specific hazard ratio (HR) for CVD in the cancer cohort compared with the control group was 2.11 (95% CI, 1.39-3.20). The 1-, 5-, and 10-year cause-specific cumulative incidences were 2.0%, 4.5%, and 5.4% in the cancer cohort versus 1.2%, 3.0%, and 3.8% in the control group, respectively. Age at cancer diagnosis (HR per 5-year increase, 1.16; 95% CI, 1.08-1.24), male sex (HR, 1.40; 95% CI, 1.06-1.86), comorbidity (HR, 1.88; 95% CI, 1.36-2.61 for 1 comorbidity vs none, and HR, 6.61; 95% CI, 4.55-9.60 for ≥2 comorbidities vs none), diabetes (HR, 1.38; 95% CI, 1.04-1.84), hypertension (HR, 3.27; 95% CI, 2.39-4.50), and dyslipidemia/hyperlipidemia (HR, 2.53; 95% CI, 1.68-3.81) were associated with incident CVD. Exposure to adjuvant fluoropyrimidine-based chemotherapy was associated with an increased risk of CVD among survivors of high-risk stage II-III CRC. Cardiovascular risk monitoring of this group throughout cancer survivorship is advisable.


The Gigli saw, a useful tool for cutting a metal ring causing penile strangulation.
Penile strangulation is a rare pediatric urology emergency. A 13-year-old boy with no psychiatric history was referred to the university hospital 2 h after a metallic ring was self-placed over his penis. Under general anesthesia, a Gigli saw cut the cockring in two places. The patient was discharged home on postoperative day 1. He neither attended a consultation at the one-month follow-up nor saw a psychiatrist. Thirteen similar cases have been reported in children since 1975. We were the first team to use a Gigli saw in a child in our department.


Double jeopardy: Minority stress and the influence of transgender identity and race/ethnicity.
Background: Prior research suggests transgender individuals with multiple minority statuses experience higher psychological stress compared to their singly disadvantaged counterparts, and both Black, Indigenous, People of Color (BIPOC), and transgender minorities experience more frequent and severe forms of discrimination than White and cisgender individuals. Aims: This study aims to examine racial/ethnic differences in gender-related discrimination and psychological distress within a sample of transgender individuals. Methods: Using data from a convenience sample of 99 self-identified transgender adults recruited through North American LGBTQ organizations, data were analyzed to determine the relationship between race/ethnicity, gender minority stress, and psychological distress. Results: When White and BIPOC participants are compared, no significant group differences were found in levels of gender discrimination or victimization. However, some individual racial/ethnic groups reported significantly higher or lower scores and results indicate that changes in reported gender minority stress are in fact positively correlated with reported psychological distress. Conclusion: This research highlights that BIPOC are a heterogeneous group; by solely examining race/ethnicity as a binary variable, studies mask potential important differences among different groups.


Pneumatosis of the intestines, colon and liver in a young cat.
To describe a case of naturally occurring pneumatosis intestinalis, pneumatosis coli and emphysematous hepatitis in a cat. A 9-month-old, indoors-only, female spayed, domestic medium hair cat presented for vomiting, open-mouth breathing and acute collapse. The initial physical examination identified moderate to severe hypothermia [35°C (95°F)], obtunded mentation, weak femoral pulses, tachycardia (heart rate 240 beats per min), pale pink mucous membranes and significant splenomegaly on abdominal palpation. Immediate diagnostics performed [packed cell volume and total solids (PCV, TS), venous blood gas and electrolytes] revealed severe anaemia (PCV 12%), hypoproteinaemia (TS = 2.2 g/dl), and severe metabolic acidosis (pH 6.956). Additional diagnostics performed included Feline Leukaemia Virus and Feline Immunodeficiency Virus testing (FeLV/FIV), complete blood count (CBC) with pathology review, serum biochemistry profile, prothrombin time (PT) and partial thromboplastin time (PTT), urinalysis, and abdominal radiographs. Abdominal radiographs were consistent with gas within hepatic and splenic veins and parenchyma, small intestinal walls and colonic wall. Due to the guarded prognosis, euthanasia was elected. Necropsy was performed and the most significant gross and histopathological findings included intra-luminal and intra-mural intestinal haemorrhage and vascular congestion with mild neutrophilic hepatitis, and marked hepatic periportal emphysema. Clostridium perfrigens and Escherichia coli were cultured from the bowel wall; no bacterial growth from the liver or spleen was identified. This case report describes idiopathic emphysematous hepatitis, with concurrent emphysema of the spleen and intestinal wall and intestinal haemorrhage. To the authors' knowledge, this type of pathology in a feline patient has not been previously described.


Detrimental effects of ethanol on murine frostbite.
Many references have been made concerning the adverse effects of ethanol in human frostbite. The lack of experimental evidence to support this belief prompted the authors to undertake this investigation. Nineteen Swiss-Webster mice (25 +/- 2 gm) were given intraperitoneal injections of 0.2 cm3 of 50 per cent ethanol (group A) or 0.2 cm3 saline (group B). Thirty minutes later, the animals were anesthetized with pentobarbital (group A 30 mg/kg; group B 50 mg/kg). Lower barbiturate dose was used in group A because of the synergistic central nervous system depressant effect when combined with alcohol. Tail lengths of all animals were measured. The tails were immersed in a 50 per cent ethylene glycol solution (-18 C) for 6 min and then thawed at room temperature (24 C). At 24 hrs, tail circulation was assessed by length of tail perfused with the vital dye alphazurine 2 gm given intraperitoneally. Mortality to 14 days was recorded. All animals survived the initial anesthetic and/or alcohol administration. Group A had a statistically significant (P less than 0.001 Students t test) decrease in length of tail perfused compared with group B at 24 hours (0.98 +/- 0.19 cm versus 2.58 +/- 0.23 cm). Fourteen day survival was 10 per cent in group A compared with 89 per cent in group B (P less than 0.001, chi-square test). We conclude that ethanol has significant adverse effects on tissue perfusion and mortality associated with severe murine frostbite.


Metabolic assessment of human liver transplants from biopsy samples at the donor and recipient stages using high-resolution magic angle spinning 1H NMR spectroscopy.
This work presents the first application of high-resolution magic angle spinning (HR-MAS) 1H NMR spectroscopy to human liver biopsy samples, allowing a determination of their metabolic profiles before removal from donors, during cold perfusion, and after implantation into recipients. The assignment of peaks observed in the 1H HR-MAS NMR spectra was aided by the use of two-dimensional J-resolved, TOCSY and 1H-13C HMQC spectra. The spectra were dominated by resonances from triglycerides, phospholipids, and glycogen and from a variety of small molecules including glycerophosphocholine (GPC), glucose, lactate, creatine, acetate, amino acids, and nucleoside-related compounds such as uridine and adenosine. In agreement with histological data obtained on the same biopsies, two of the six livers were found to contain high amounts of triglycerides by NMR spectroscopy, which also indicated that these tissues contained a higher degree of unsaturated lipids and a lower proportion of phospholipids and low molecular weight compounds. Additionally, proton T2 relaxation times indicated two populations of lipids, a higher mobility triglyceride fraction and a lower mobility phospholipid fraction, the proportions of which changed according to the degree of fat content. GPC was found to decrease from the pretransplant to the posttransplant biopsy of all livers except for one with a histologically confirmed high lipid content, and this might represent a biomarker of liver function posttransplantation. NMR signals produced by the liver preservation solution were clearly detected in the cold perfusion stage biopsies of all livers but remained in the posttransplant spectra of only the two livers with a high lipid content and were prominent mainly in the graft that later developed primary graft dysfunction. This study has shown biochemical differences between livers used for transplants that can be related to the degree and type of lipid composition. This technology might therefore provide a novel screening approach for donor organ quality and a means to assess function in the recipient after transplantation.


Synthetic aperture techniques with a virtual source element.
A new imaging technique has been proposed that combines conventional B-mode and synthetic aperture imaging techniques to overcome the limited depth of field for a highly focused transducer. The new technique improves lateral resolution beyond the focus of the transducer by considering the focus a virtual element and applying synthetic aperture focusing techniques. In this paper, the use of the focus as a virtual element is examined, considering the issues that are of concern when imaging with an array of actual elements: the tradeoff between lateral resolution and sidelobe level, the tradeoff between system complexity (channel count/amount of computation) and the appearance of grating lobes, and the issue of signal to noise ratio (SNR) of the processed image. To examine these issues, pulse-echo RF signals were collected for a tungsten wire in degassed water, monofilament nylon wires in a tissue-mimicking phantom, and cyst targets in the phantom. Results show apodization lowers the sidelobes, but only at the expense of lateral resolution, as is the case for classical synthetic aperture imaging. Grating lobes are not significant until spatial sampling is more than one wavelength, when the beam is not steered. Resolution comparable to the resolution at the transducer focus can be achieved beyond the focal region while obtaining an acceptable SNR. Specifically, for a 15-MHz focused transducer, the 6-dB beamwidth at the focus is 157 mum, and with synthetic aperture processing the 6-dB beamwidths at 3, 5, and 7 mm beyond the focus are 189 mum, 184 mum, and 215 mum, respectively. The image SNR is 38.6 dB when the wire is at the focus, and it is 32.8 dB, 35.3 dB, and 38.1 dB after synthetic aperture processing when the wire is 3, 5, and 7 mm beyond the focus, respectively. With these experiments, the virtual source has been shown to exhibit the same behavior as an actual transducer element in response to synthetic aperture processing techniques.


The biology of the cell - insights from mass cytometry.
In single-cell biology there is an ongoing push toward more and more comprehensive measurements made in individual cells. By combining measurements of proteins, mRNA, genetic, and epigenetic traits, in contexts of cell stimulation or drug treatment, novel single-cell analyses will help understand the determinants of cellular identity, differentiation decisions, and regulatory mechanisms governing cellular function in health and disease. Mass cytometry is a flexible methodology not only developed toward this aim, allowing analyses of cells in suspension such as blood but also extended for the analyses of tissue sections. Here, I will discuss the different measurements possible by mass cytometry and not only discuss its potential but also its limitations now and in the years to come.


Clinical and demographic predictors of survival for fibrolamellar carcinoma patients-A patient community, registry-based study.
Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer that affects primarily adolescents and young adults. It is associated with a poor overall prognosis. There is a need to better define risk factors, but small sample size has limited such studies. An FLC patient registry now provides data sufficient for statistically robust inferences. We leveraged a unique patient community-based FLC registry to analyze the prognostic impact of demographic and clinical characteristics evident at diagnosis. Variables were analyzed using Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariable models of 149 patients (88 females and 61 males), female gender was associated with statistically significant improved survival with HR of 0.52 (95% CI 0.29-0.93). Factors evident at diagnosis that are associated with worse survival included the presence of 10 or more tumors within the liver (HR 7.1; 95% CI 2.4-21.04), and metastases at diagnosis (HR 2.17; 95% CI 1.19-3.94). Positive lymph nodes at diagnosis, despite being found significantly associated with worse survival in a univariate analysis, did not remain significant when adjusted for covariates in a multivariable analysis. We found no statistically significant effect of age at diagnosis nor tumor size at diagnosis on survival. Female gender may confer a favorable prognosis in FLC. Established high-risk prognostic factors that we confirmed in this Registry included the diagnostic presence of numerous intrahepatic tumors, and metastases. This is the first study derived from a FLC patient community-based registry, and highlights how registries of rare tumors can empower patients to meaningfully advance clinical and scientific discoveries.


National Emphysema Treatment Trial state of the art: genetics of emphysema.
Although a hereditary contribution to emphysema has been long suspected, severe alpha1-antitrypsin deficiency remains the only conclusively proven genetic risk factor for chronic obstructive pulmonary disease (COPD). Recently, genome-wide linkage analysis has led to the identification of two promising candidate genes for COPD: TGFB1 and SERPINE2. Like multiple other COPD candidate gene associations, even these positionally identified genes have not been universally replicated across all studies. Differences in phenotype definition may contribute to nonreplication in genetic studies of heterogeneous disorders such as COPD. The use of precisely measured phenotypes, including emphysema quantification on high-resolution chest computed tomography scans, has aided in the discovery of additional genes for clinically relevant COPD-related traits. The use of computed tomography scans to assess emphysema and airway disease as well as newer genetic technologies, including gene expression microarrays and genome-wide association studies, has great potential to detect novel genes affecting COPD susceptibility, severity, and response to treatment.


A genome-wide association study on obesity and obesity-related traits.
Large-scale genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI), but few studies focused on obesity as a binary trait. Here we report the results of a GWAS and candidate SNP genotyping study of obesity, including extremely obese cases and never overweight controls as well as families segregating extreme obesity and thinness. We first performed a GWAS on 520 cases (BMI>35 kg/m(2)) and 540 control subjects (BMI<25 kg/m(2)), on measures of obesity and obesity-related traits. We subsequently followed up obesity-associated signals by genotyping the top ∼500 SNPs from GWAS in the combined sample of cases, controls and family members totaling 2,256 individuals. For the binary trait of obesity, we found 16 genome-wide significant signals within the FTO gene (strongest signal at rs17817449, P = 2.5 × 10(-12)). We next examined obesity-related quantitative traits (such as total body weight, waist circumference and waist to hip ratio), and detected genome-wide significant signals between waist to hip ratio and NRXN3 (rs11624704, P = 2.67 × 10(-9)), previously associated with body weight and fat distribution. Our study demonstrated how a relatively small sample ascertained through extreme phenotypes can detect genuine associations in a GWAS.


An Increasing Trend of Illicit Drug use among Romanian University Students from 1999 to 2011.
The present study investigates the evolution of illicit drug use among Romanian university students from 1999 to 2011. The study was performed in Cluj-Napoca, Romania, in three phases: in 1999 (T1), in 2003 (T2) and in 2011 (T3). The study was carried out by means of anonymous questionnaires among university students aged 19-24. The results show that among girls the lifetime illicit drugs use increased statistically significantly from 2.5% in 1999 to 7.5% in 2003 and to 15% in 2011. Among boys the trend was also increasing, the prevalence of illicit drug use was 14.2% at T1, 18.1% at T2, and it increased dramatically to 30.6% at T3. The percentage of students reporting cannabis use was almost identical with the total prevalence of illicit drug use. Ecstasy was the second most frequent drug used by the students; its consumption had also an increasing trend during the examined periods (from 0 to 5.6% among girls and from 0.8% to 11.2% among boys). The results of the bivariate correlation analyses show that lifetime illicit drug use was associated with having friends who experimented with illicit drugs both among boys and girls. Moreover, girls who declared stress management problems and depressive episodes were more likely to try illicit drugs, while among boys illicit drug use was associated with poorer academic performance. The data pointed out by our study call for comprehensive actions regarding the prevention of illicit drug use among Romanian young people.


Cues that signal the alcohol content of a beverage and their effectiveness at altering drinking rates in young social drinkers.
The aim of this study was to assess the impact of cues that signal the alcoholic strength of a beverage on drinking rate in young social drinkers. In Experiment 1, two groups of young social drinkers (n=20 per group) consumed a lager-based drink containing either 3% or 7% alcohol-by-volume. The pattern of drinking behaviour was observed, and drinking time was recorded. Self-reported mood was measured across the session, and participants also provided ratings of the drinks' sensory and hedonic properties. Experiment 2 replicated Experiment 1, but used a within-subjects design (n=12). In both experiments, participants took significantly longer to consume the 7% drink compared with the 3% drink, and the total inter-sip interval was longer for the 7% drink. These effects were most closely related to the participants' changing estimates of alcohol strength across the test session, alongside concomitant changes in various aspects of self-reported mood. Sensory and hedonic evaluations of the drinks did not affect drinking behaviour in either experiment. The findings suggest that the consumption rate of an alcoholic beverage can be modulated by its alcohol content, and that the perceived pharmacological effect of the alcohol serves as an effective signal to alter drinking behaviour.


Risk versus recovery: Care planning with individuals on community treatment orders.
Community treatment orders (CTOs) require individuals with a mental illness to accept treatment from mental health services. CTO legislation in South Australia states that treatment and care should be recovery-focused, although justification for use is predominantly risk-based, and care often coercive. Although CTOs are contested, individuals, families, and clinicians frequently engage in care planning within this context. This paper examines how the concepts of risk and risk management impact care planning from the perspectives of individuals on CTOs, their families, and clinicians. Ethnographic methods of observation and interview provided a detailed account of the perspectives of each group over an 18-month period from two community mental health teams in South Australia. Findings show that care planning occurred within a culture of practice dominated by risk. Risk, however, was understood differently by each participant group, with the dominant narrative informed by biogenetic understandings of mental illness. This dominance impacted on the positioning of participant groups in care planning, focus of care contacts, and care options available. To improve care experiences and outcomes for individuals on CTOs, narrow conceptualizations of risk and recovery need to broaden to include an understanding of personal and social adversities individuals face. A broader understanding should reposition participants in the care planning context and rebalance care discussions, from a focus on clinical recovery to recovering citizenship.


Should vascular surgeons perform endovascular procedures and how can they acquire the skills to do so?
Endovascular treatment techniques have already replaced some vascular operations. The likelihood is that new endovascular techniques involving stents and stented grafts will replace additional vascular operations. All of these treatments involve the use of catheter-guidewire, balloon, and imaging modalities, particularly digital fluoroscopy. These modalities have already and will increasingly help to improve and simplify standard vascular operations such as thromboembolectomy, infrainguinal bypasses, and management of aneurysms and arteriovenous fistulas. Accordingly, vascular surgeons must become familiar with and use these endovascular methods and techniques. This can be accomplished in a variety of ways, including working as part of a multidisciplinary vascular treatment group in which various specialists collaborate to provide the best, most cost-effective care to vascular disease patients.


Empagliflozin Induces White Adipocyte Browning and Modulates Mitochondrial Dynamics in KK Cg-Ay/J Mice and Mouse Adipocytes.
Background: White adipose tissue (WAT) browning is a promising target for obesity prevention and treatment. Empagliflozin has emerged as an agent with weight-loss potential in clinical and in vivo studies, but the mechanisms underlying its effect are not fully understood. Here, we investigated whether empagliflozin could induce WAT browning and mitochondrial alterations in KK Cg-Ay/J (KKAy) mice, and explored the mechanisms of its effects. Methods: Eight-week-old male KKAy mice were administered empagliflozin or saline for 8 weeks and compared with control C57BL/6J mice. Mature 3T3-L1 adipocytes were treated in the presence or absence of empagliflozin. Mitochondrial biosynthesis, dynamics, and function were evaluated by gene expression analyses, fluorescence microscopy, and enzymatic assays. The roles of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator-1-alpha (PGC-1α) were determined through AICAR (5-Aminoimidazole-4-carboxamide1-β-D-ribofuranoside)/Compound C and RNA interference, respectively. Results: Empagliflozin substantially reduced the bodyweight of KKAy mice. Mice treated with empagliflozin exhibited elevated cold-induced thermogenesis and higher expression levels of uncoupling protein 1 (UCP1) and other brown adipose tissue signature proteins in epididymal and perirenal WAT, which was an indication of browning in these WAT depots. At the same time, empagliflozin enhanced fusion protein mitofusin 2 (MFN2) expression, while decreasing the levels of the fission marker phosphorylated dynamin-related protein 1 (Ser616) [p-DRP1 (Ser616)] in epididymal and perirenal WAT. Empagliflozin also increased mitochondrial biogenesis and fusion, improved mitochondrial integrity and function, and promoted browning of 3T3-L1 adipocytes. Further, we found that AMPK signaling activity played an indispensable role in empagliflozin-induced browning and mitochondrial biogenesis, and that PGC-1α was required for empagliflozin-induced fusion. Whether empagliflozin activates AMPK by inhibition of SGLT2 or by independent mechanisms remains to be tested. Conclusion: Our results suggest that empagliflozin is a promising anti-obesity treatment, which can immediately induce WAT browning mitochondrial biogenesis, and regulate mitochondrial dynamics.


Congenital pseudoarthrosis of the tibia: treatment with pulsing electromagnetic fields.
Ninety-two patients with congenital pseudoarthrosis (infantile nonunion) were treated with pulsing electromagnetic fields (PEMF) in the United States and Europe in the past eight years. This represents the largest group of patients with infantile nonunions in which a common treatment modality has been used. Excluding the ten lesions (11%) which healed with refracture 48 lesions (59%) healed whereas 34 (41%) failed to heal. The success rate in 23 type I and 34 Type II lesions was 77% and 76%, respectively. Surgery in association with PEMF treatment did not improve the results of treatment. The most important variable was the radiographic morphology of the nonunion gap. Patients with spindled bone ends, a large gap and a grossly mobile lesion had a very poor prognosis relative to patients with a cystic or sclerotic transverse fracture line with a gap of less than 5 mm. The key to success in the treatment of infantile nonunions has been the combination of PEMF treatment with good orthopedic management, consisting of rigid immobilization, a nonweight-bearing status and rehabilitation with impact loading exercise. Infantile nonunion remains a major challenge to the orthopedic surgeon, but PEMFs appear to offer some important advantages for overcoming this pernicious condition. Dr. Harold Boyd's discussion of this paper follows. It was his final address to the AAOS.


Central catecholaminergic system stimulates secretion of CRH at different sites.
To explore a possible differential role of distinct catecholamine (CA) innervation sites in corticotropin-releasing hormone (CRH) secretion, especially under stress conditions, we compared the effects in adult female rats of selective CA denervation of either the whole hypothalamus, by a discrete pharmacological lesion of the ventral noradrenergic ascending bundle [VNAB; 3 micrograms of 6-hydroxydopamine (6-OHDA) in 0.2 microliter of vehicle, bilaterally] or of the paraventricular nuclei (PVN) alone (1 microgram of 6-OHDA in 0.2 microliter of vehicle, bilaterally). Although both procedures induced a similar dramatic fall in norepinephrine and epinephrine concentrations (-55 to -65%) measured by high-performance liquid chromatography in PVN punches, the VNAB lesion, unlike PVN denervation, depleted the median eminence (ME) of both amines (-80%). Concomitantly, the VNAB lesion led to a 97% reduction of the immunoreactive (ir) CRH-41 concentration in the hypophysial portal vessels, associated with a 64% fall in plasma adrenocorticotropic hormone (ACTH), and, in another group, with an 80% inhibition of ether stress-induced ACTH surge. The deletion of CA innervation of the PVN alone reduced irCRH-41 levels in the portal vessels by only 57% and plasma ACTH by 35%. This lesion did not significantly impair stress-induced ACTH release. These results suggest that the CA innervation of the hypothalamus exerts a stimulatory control on CRH-41-secreting neurons not only directly at the perikaryal level but also at other hypothalamic sites of VNAB innervation including peripheral contacts between the terminals of CA and CRH nerves in the external ME.


[Right heart failure due to pulmonary tumor microembolism -- a rare differential diagnosis].
A 69-year-old man presented with progressive dyspnea, hemoptysis and fatigue for the previous 4 weeks. Chest radiograph and CT-scan were suggestive of lung cancer. The patient's condition worsened and within in few days he developed respiratory failure and acute cor pulmonale. Despite intensive care measures directed at suspected lung thromboembolism, the patient died on day 12. Autopsy revealed disseminated obstruction of small pulmonary arteries by microscopic tumor emboli. No signs of venous thromboembolism were found. Pulmonary tumor microembolism should be considered whenever a patient with malignancy presents with unexplained progressive dyspnea or pulmonary hypertension.