Co-Regulations of Spartina alterniflora Invasion and Exogenous Nitrogen Loading on Soil N2O Efflux in Subtropical Mangrove Mesocosms.
Both plant invasion and nitrogen (N) enrichment should have significant impact on mangrove ecosystems in coastal regions around the world. However, how N2O efflux in mangrove wetlands responds to these environmental changes has not been well studied. Here, we conducted a mesocosm experiment with native mangrove species Kandelia obovata, invasive salt marsh species Spartina alterniflora, and their mixture in a simulated tide rotation system with or without nitrogen addition. In the treatments without N addition, the N2O effluxes were relatively low and there were no significant variations among the three vegetation types. A pulse loading of exogenous ammonium nitrogen increased N2O effluxes from soils but the stimulatory effect gradually diminished over time, suggesting that frequent measurements are necessary to accurately understand the behavior of N-induced response of N2O emissions. With the N addition, the N2O effluxes from the invasive S. alterniflora were lower than that from native K. obovata mesocosms. This result may be attributed to higher growth of S. alterniflora consuming most of the available nitrogen in soils, and thus inhibiting N2O production. We concluded that N loading significantly increased N2O effluxes, while the invasion of S. alterniflora reduced N2O effluxes response to N loading in this simulated mangrove ecosystem. Thus, both plant invasion and excessive N loading can co-regulate soil N2O emissions from mangrove wetlands, which should be considered when projecting future N2O effluxes from this type of coastal wetland.


Participation with alcohol marketing and user-created promotion on social media, and the association with higher-risk alcohol consumption and brand identification among adolescents in the UK.
Aim: To explore participation with alcohol marketing (i.e. commenting on brand statuses) and user-created promotion on social media (i.e. photos of peers drinking) by young people in the United Kingdom (UK), and what association this has with higher-risk consumption and brand identification. Method: Online cross-sectional survey with 11-19-year olds in the UK (n = 3,399) (average age: 15 years old). Past-month participation was measured for five forms of alcohol marketing on social media and one form of user-created promotion (all Yes/No). Past-month awareness of nine wider alcohol marketing activities, social media apps used at least weekly, and ownership of branded merchandise were included as covariates. Outcomes included higher-risk consumption in current drinkers (≥5 AUDIT-C) and brand identification in all respondents (8 pictures with brand names removed). Results: Over one-in-ten respondents (13.2%) had participated with at least one form of marketing on social media or participated with user-created promotion (12.2%). For both, participation was greater in current drinkers and those of legal purchasing age. A logistic regression found that participation with two or more forms of marketing on social media (AOR = 1.96, p < .01) and participation with user-created promotion (AOR = 3.46, p < .001) were associated with higher-risk drinking. Respondents, on average, identified 2.58 (SD = 2.12) alcohol brands. A linear regression found participation with marketing on social media was not associated with brand identification (β = 0.01, p = .42) but participation with user-created promotion was (β = 0.05, p < .001). Conclusion: Social media provides opportunities for adolescents to participate with commercial marketing and user-created promotion and this is associated with higher-risk consumption and brand identification.


Studies on gastric mucoproteins. The production of radioactive mucoproteins by pig gastric mucosal scrapings in vitro.
1. Optimum conditions, including the effect of media of different pH values, were determined for the incorporation of radioactive precursors into mucoproteins by pig gastric mucosa in vitro. 2. Mucosal scrapings incorporated radioactivity from [U-(14)C]-glucose and from [G-(3)H]threonine or [G-(3)H]serine solely into the carbohydrate and protein portions respectively of the mucoprotein molecules. 3. Of the radioactive mucoprotein 22% was water-soluble and up to 80% of the remainder was soluble in other solvents. 4. Pronase was the most successful proteolytic enzyme tested for making the mucoprotein water-soluble, up to 94% dissolving after digestion. 5. The Pronase digestion products of the mucoproteins were separated from protein by equilibrium-density-gradient centrifugation in a CsCl gradient. 6. These Pronase-digested mucoproteins were further fractionated on Sepharose 4B and the isolated fractions analysed by chemical and sedimentation-velocity methods. 7. Pronase digestion and solvent extraction of mucosal scrapings labelled with (14)C in the carbohydrate and (3)H in the protein showed that one type of mucoprotein was the only non-diffusible biosynthetic product of the scrapings in vitro, and that this mucoprotein was the only mucoprotein constituent of the water-soluble and water-insoluble mucus.


Discovery radiomics via evolutionary deep radiomic sequencer discovery for pathologically proven lung cancer detection.
While lung cancer is the second most diagnosed form of cancer in men and women, a sufficiently early diagnosis can be pivotal in patient survival rates. Imaging-based, or radiomics-driven, detection methods have been developed to aid diagnosticians, but largely rely on hand-crafted features that may not fully encapsulate the differences between cancerous and healthy tissue. Recently, the concept of discovery radiomics was introduced, where custom abstract features are discovered from readily available imaging data. We propose an evolutionary deep radiomic sequencer discovery approach based on evolutionary deep intelligence. Motivated by patient privacy concerns and the idea of operational artificial intelligence, the evolutionary deep radiomic sequencer discovery approach organically evolves increasingly more efficient deep radiomic sequencers that produce significantly more compact yet similarly descriptive radiomic sequences over multiple generations. As a result, this framework improves operational efficiency and enables diagnosis to be run locally at the radiologist's computer while maintaining detection accuracy. We evaluated the evolved deep radiomic sequencer (EDRS) discovered via the proposed evolutionary deep radiomic sequencer discovery framework against state-of-the-art radiomics-driven and discovery radiomics methods using clinical lung CT data with pathologically proven diagnostic data from the LIDC-IDRI dataset. The EDRS shows improved sensitivity (93.42%), specificity (82.39%), and diagnostic accuracy (88.78%) relative to previous radiomics approaches.


Variations in the morphology, distribution, and arrangement of feathers in domesticated birds.
Domesticated birds exhibit a greater diversity in the morphology of their integument and its appendages than their wild ancestors. Many of these variations affect the appearance of a bird significantly and have been bred selectively by poultry and pigeon fanciers and aviculturists for the sake of visual appeal. Variations in feather distribution (e.g., feathering of legs and feet, featherless areas in normally feather-bearing skin) are widespread in chickens and pigeons. Variations in the number of feathers (e.g., increased number of tail feathers, lack of tail feathers) occur in certain pigeon and poultry breeds. Variations in feather length can affect certain body regions or the entire plumage. Variations in feather structure (e.g., silkiness, frilled feathering) can be found in exhibition poultry as well as in pet birds. Variations in feather arrangement (e.g., feather crests and vortices) occur in many domesticated bird species as a results of mutation and intense selective breeding. The causes of variations in the structure, distribution, length and arrangement of feathers is often unknown and opens a wide field for scientific research under various points of view (e.g., morphogenesis, pathogenesis, ethology, etc.). To that extent, variations in the morphology, distribution and arrangement of feathers in domesticated birds require also a concern for animal welfare because certain alleles responsible for integumentary variations in domesticated birds have pleiotropic effects, which often affect normal behaviour and viability.


Abnormal functional connectivity strength in age-related macular degeneration patients: a fMRI study.
Age-related macular degeneration (AMD) is a serious blinding eye disease. Previous neuroimaging studies reported that AMD were accompanied by abnormalities of the brain. However, whether AMD patients were associated with functional connectivity strength (FCS) or not remains unknown. In our study, the purpose of the study was to assess FCS changes in AMD patients. In our study, 20 AMD patients and 20 healthy controls (HCs), matched closely by sex, age, and educational level were underwent MRI scanning. FCS method and seed-based functional connectivity (FC) method were applied to investigate the functional network changes between two groups. Moreover, support vector machine (SVM) method was applied to assess the FCS maps as a feature to classification of AMD diseases. Our study reported that AMD patients showed decreased FCS values in the bilateral calcarine, left supplementary motor area, left superior parietal lobule and left paracentral lobule (ParaL) relative to the HC group. Meanwhile, our study found that the AMD patients showed abnormal FC within visual network, sensorimotor network and default mode network. Moreover, the SVM method showed that FCS maps as machine learning features shows good classification efficiency (area under curve = 0.82) in the study. Our study demonstrated that AMD patients showed abnormal FCS with the visual network, sensorimotor network and default mode network, which might reflect the impaired vision, cognition and motor function in AMD patients. In addition, FCS indicator can be used as an effective biological marker to assist the clinical diagnosis of AMD.


[Fecal microbiota transplantation regulates the cholinergic anti-inflammatory pathway in cerebral cortex of septic rats through intestinal microbiota].
To investigate the effects of fecal microbiota transplantation on septic gut flora and the cortex cholinergic anti-inflammatory pathway in rats. Sixty clean grade male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group, sepsis model group and fecal microbiota transplantation group by random number table, with 20 rats in each group. The rat model of sepsis was reproduced by injection of 10 mg/kg lipopolysaccharide (LPS) via tail vein, the rats in the NS control group was given the same amount of NS. The rats in the fecal microbiota transplantation group received nasogastric infusion of feces from healthy donor on the 1st day, 2 mL each time, for 3 times a day, the other two groups were given equal dose of NS by gavage. Fecal samples were collected on the 7th day after modeling, the levels of intestinal microbiota composition was determined using the 16SrDNA gene sequencing technology. The brain function was evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats, the brain tissues were harvested, the levels of protein expression of α7 nicotinic acetylcholine receptor (α7nAChR) were determined by Western Blot, and positive cells of Iba-1 in brain tissue were detected by immunohistochemistry method. The levels of interleukins (IL-6 and IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Seven days after the reproduction of the model, all rats in the NS control group survived, while 10 rats and 8 rats died in the sepsis model group and fecal microbiota transplantation group, respectively, with mortality rates of 50% and 40% respectively. Finally, there were 20 rats in the NS control group, 10 in the sepsis model group and 12 in the fecal microbiota transplantation group. Compared with the NS control group, the diversity and composition of intestinal flora were changed, the incidence of abnormal EEG increased significantly, the expression of α7nAchR in the cortex decreased significantly, and the levels of Iba-1, TNF-α, IL-6 and IL-1β were significantly increased in the model group, suggested that the intestinal flora was dysbiosis, and severe inflammatory reaction occurred in the cerebral cortex, and brain function was impaired. Compared with the model group, the diversity of intestinal flora in the fecal microbiota transplantation group was significantly increased (species index: 510.24±58.76 vs. 282.50±47.42, Chao1 index: 852.75±25.24 vs. 705.50±46.50, both P < 0.05), the dysbiosis of intestinal flora at phylum, family, genus level induced by LPS were also significantly reversed, and with the improvement of intestinal flora, the incidence of abnormal EEG waveforms was lower in the fecal microbiota transplantation group compared with that in the model group [25.0% (3/12) vs. 80.0% (8/10), P < 0.05], and the expression of α7nAChR protein in the cerebral cortex was significantly increased (α7nAChR/β-actin: 1.56±0.05 vs. 0.82±0.07, P < 0.05), immunohistochemistry analysis showed that Iba-1 positive expression of microglia decreased significantly, and cerebral cortex TNF-α, IL-6, IL-1β levels were significantly decreased [TNF-α (ng/L): 6.28±0.61 vs. 12.02±0.54, IL-6 (ng/L): 28.26±3.15 vs. 60.58±4.62, IL-1β (ng/L): 33.63±3.48 vs. 72.56±2.25, all P < 0.05]. The results reveal that fecal microbiota transplantation has remarkably modulated the dysbiosis of intestinal microbiota and activated cholinergic anti-inflammatory pathway, and ameliorate the brain dysfunction in septic rats.


Functional tests of enhancer conservation between distantly related species.
Expression patterns of orthologous genes are often conserved, even between distantly related organisms, suggesting that once established, developmental programs can be stably maintained over long periods of evolutionary time. Because many orthologous transcription factors are also functionally conserved, one possible model to account for homologous gene expression patterns, is conservation of specific binding sites within cis-regulatory elements of orthologous genes. If this model is correct, a cis-regulatory element from one organism would be expected to function in a distantly related organism. To test this hypothesis, we fused the green fluorescent protein gene to neuronal and muscular enhancer elements from a variety of Drosophila melanogaster genes, and tested whether these would activate expression in the homologous cell types in Caenorhabditis elegans. Regulatory elements from several genes directed appropriate expression in homologous tissue types, suggesting conservation of regulatory sites. However, enhancers of most Drosophila genes tested were not properly recognized in C. elegans, implying that over this evolutionary distance enough changes occurred in cis-regulatory sequences and/or transcription factors to prevent proper recognition of heterospecific enhancers. Comparisons of enhancer elements of orthologous genes between C. elegans and C. briggsae revealed extensive conservation, as well as specific instances of functional divergence. Our results indicate that functional changes in cis-regulatory sequences accumulate on timescales much shorter than the divergence of arthropods and nematodes, and that mechanisms other than conservation of individual binding sites within enhancer elements are responsible for the conservation of expression patterns of homologous genes between distantly related species.


Patient safety first... a California partnership for health.
In California in 2009, Anthem Blue Cross joined forces with three regional hospital associations (RHAs) and an independent evaluator in an initial three-year, $6-million effort to address patient safety. During Phase 1 of the Patient Safety First... a California Partnership for Health program (2010-2012), more than 180 of the 395 hospitals represented by the RHAs shared and implementated best practices in learning collaboratives. The three initial areas of focus were (1) health care-associated infections-ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLABSI), and catheter-associated urinary tract infection (CAUTI); (2) sepsis mortality; and (3) perinatal care-reduction of elective deliveries prior to 39 weeks of gestation. To measure progress, the difference in the average rates from 2009 (baseline) to 2012 was calculated using data from hospitals that reported for every quarter from 2009 through 2012. The rate decreases-57% for VAP cases per 1,000 ventilator-days, 43% for CLABSI cases per 1,000 central line-days, 24% reduction for CAUTI cases per 1,000 patient-days, 26% reduction for sepsis deaths per 100 sepsis cases, and 74% for elective deliveries < 39 gestational weeks-were statistically significant at the .05 level, except for CAUTI. A cost-avoidance analysis showed that these reductions were associated with a saving of 3,576 lives and an avoidance of $63.8 million in costs statewide (not limited to Anthem Blue Cross members). The Patient Safety First program provides a long-term opportunity for collaboration among different health care sectors to share best practices to improve health care for Californians. Phase 2 will continue to addresssepsis and elective deliveries and add other initiatives.


Influence of electroencephalography neurofeedback training on episodic memory: a randomized, sham-controlled, double-blind study.
The relationships between memory processes and oscillatory electroencephalography (EEG) are well established. Neurofeedback training (NFT) may cause participants to better regulate their brain EEG oscillations. The present study is a double-blind sham-controlled design investigating the effect of NFT on memory. NFT included up-training upper alpha (UA) band, up-training sensory-motor rhythm (SMR) band and sham protocol. Thirty healthy adult volunteers were randomly divided into three treatment groups. NFT sessions (30 min each) took place twice weekly for a total of 10 sessions while memory testing took place pre- and post-training. The results indicate dissociation between SMR and UA NFT and different memory processes. While the SMR protocol resulted in improving automatic, item-specific and familiarity-based processes in memory, the UA protocol resulted in improved strategic and controlled recollection. The implications of the results are discussed.


Pharmacokinetic considerations for use of artemisinin-based combination therapies against falciparum malaria in different ethnic populations.
Artemisinin-based combination therapy (ACT) is used extensively as first-line treatment for uncomplicated falciparum malaria. There has been no rigorous assessment of the potential for racial/ethnic differences in the pharmacokinetic properties of ACTs that might influence their efficacy. Areas covered: A comprehensive literature search was performed that identified 72 publications in which the geographical origin of the patients could be ascertained and the key pharmacokinetic parameters maximum drug concentration (Cmax), area under the plasma concentration-time curve (AUC) and elimination half-life (t½β) were available for one or more of the five WHO-recommended ACTs (artemether-lumefantrine, artesunate-amodiaquine, artesunate-mefloquine, dihydroartemisinin-piperaquine and artesunate-sulfadoxine-pyrimethamine). Comparisons of each of the three pharmacokinetic parameters of interest were made by drug (artemisinin derivative and long half-life partner), race/ethnicity (African, Asian, Caucasian, Melanesian, South American) and patient categories based on age and pregnancy status. Expert opinion: The review identified no evidence of a clinically significant influence of race/ethnicity on the pharmacokinetic properties of the nine component drugs in the five ACTs currently recommended by WHO for first-line treatment of uncomplicated falciparum malaria. This provides reassurance for health workers in malaria-endemic regions that ACTs can be given in recommended doses with the expectation of adequate blood concentrations regardless of race/ethnicity.


The effect of polyp location and patient gender on the presence of dysplasia in colonic polyps.
There is increasing evidence of significant clinical and biological differences between proximal and distal colorectal polyps, as well as possible differences based on patient gender. There is a need to optimize and individualize screening strategies. We studied the potential influence of gender and of polyp location on the presence of dysplasia in colon polyps. We used a prospective database on adenoma detection to identify patients. The primary outcome was the presence of dysplasia in colonic polyps. Covariates include age, gender, race, lesion size and site, and use of aspirin. Multivariate logistic regression analysis was used to analyze the relationship between the primary outcome and covariates. Results were reported as odds ratios (ORs), 95% confidence intervals (CIs), and P-values. A total of 2,400 patients (50.5% females and 49.5% males) completed colonoscopy for various indications. A total of 3,045 polyps were removed in 1,237 patients. Of those polyps, 54% (n=1,636) were on the right compared with 46% (n=1,409) in the left colon. The proportion of adenomas was significantly greater on the right colon when compared with the left: 69.4% vs. 39.3% (P=<0.0001). Multivariate logistic regression analysis showed that the right colon did have a significant association with dysplasia when controlling for age, gender, polyp size, and use of aspirin (OR=3.1 (95% CI: 2.3-4), P=<0.0001). Female gender was associated with decreased odds of finding dysplasia (OR=0.6 (95% CI: 0.46-0.78), P=0.03). Patient characteristics (male gender) as well procedure findings (increase polyp size and right-sided lesions) are associated with increased odds of dysplasia.


Beneficial effects of β-sitosterol on type 1 cholecystokinin receptor dysfunction induced by elevated membrane cholesterol.
The type 1 cholecystokinin receptor (CCK1R) mediates the actions of CCK to support nutritional homeostasis, including post-cibal satiety. However, elevated levels of membrane cholesterol, such as have been observed in metabolic syndrome, interfere with CCK stimulus-activity coupling at the CCK1R, thereby disrupting this important servomechanism. We hypothesize that reversal of the negative impact of cholesterol on this receptor could be useful in the management of obesity. We have studied the effects of β-sitosterol, a phytosterol structurally related to cholesterol, on CCK receptor function. This included CCK binding and biological activity at wild type CCK1R and CCK2R, as well as at CCK1R in a high cholesterol environment, and at a CCK1R mutant, Y140A, which mimics the behavior of wild type receptor in high cholesterol. β-sitosterol (100 μM and 10 μM) significantly improved the defective signaling of the CCK1R present in high cholesterol (p < 0.05), without affecting CCK binding affinity. This effect was absent at the CCK1R present in a normal cholesterol environment, as well as at the structurally-related CCK2R. Furthermore, the cholesterol-insensitive Y140A mutant of CCK1R was resistant to the effects of β-sitosterol. These data suggest that β-sitosterol affects CCK1R function in high cholesterol by competing with cholesterol at a receptor cholesterol-binding site and may shift its conformation toward normal. This phytosterol extends our understanding of the structure-activity relationships for developing a drug that can target the external surface of CCK1R. Since the concentrations of β-sitosterol shown to be effective in this study are similar to serum levels of this compound achievable during oral administration, it may be worthwhile to study possible beneficial effects of β-sitosterol in metabolic syndrome.


Application of optical coherence tomography enhances reproducibility of arthroscopic evaluation of equine joints.
Arthroscopy is widely used in various equine joints for diagnostic and surgical purposes. However, accuracy of defining the extent of cartilage lesions and reproducibility in grading of lesions are not optimal. Therefore, there is a need for new, more quantitative arthroscopic methods. Arthroscopic optical coherence tomography (OCT) imaging is a promising tool introduced for quantitative detection of cartilage degeneration and scoring of the severity of chondral lesions. The aim of this study was to evaluate the inter-investigator agreement and inter-method agreement in grading cartilage lesions by means of conventional arthroscopy and with OCT technique. For this aim, 41 cartilage lesions based on findings in conventional and OCT arthroscopy in 14 equine joints were imaged, blind coded and independently ICRS (International Cartilage Repair Society) scored by three surgeons and one PhD-student. The intra- and inter-investigator percentages of agreement by means of OCT (68.9% and 43.9%, respectively) were higher than those based on conventional arthroscopic imaging (56.7% and 31.7%, respectively). The intra-investigator Kappa coefficients were 0.709 and 0.565 for OCT and arthroscopy, respectively. Inter-investigator Kappa coefficients were 0.538 and 0.408 for OCT and arthroscopy, respectively. OCT can enhance reproducibility of arthroscopic evaluation of equine joints.


Antimicrobial properties of black grape (Vitis vinifera L.) peel extracts against antibiotic-resistant pathogenic bacteria and toxin producing molds.
Black grape peel possesses a substantial amount of polyphenolic antimicrobial compounds that can be used for controlling the growth of pathogenic microorganisms. The purpose of this study was to assess antibacterial and antifungal activity of black grape peel extracts against antibiotic-resistant pathogenic bacteria and toxin producing molds, respectively. Peel of grape was subjected to polyphenolic extraction using different solvents viz., water, ethanol, acetone, and methanol. Antibiotic-resistant strains of Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Salmonella typhimurium, and Escherichia coli were screened for the antibacterial activity of different grape extracts. Antibacterial activity was analyzed using agar well diffusion method. Penicillium chrysogenum, Penicillium expansum, Aspergillus niger and Aspergillus versicolor were screened for the antifungal activity. Antifungal activity was determined by counting nongerminated spores in the presence of peel extracts. As compared to other solvent extracts, methanol extracts possessed high antibacterial and antifungal activity. S. typhimurium and E. coli showed complete resistance against antibacterial action at screened concentrations of grape peel extracts. Maximum zone of inhibition was found in case of S. aureus, i.e., 22 mm followed by E. faecalis and E. aerogenes, i.e., 18 and 21 mm, respectively, at 1080 mg tannic acid equivalent (TAE)/ml. The maximum and minimum percent of growth inhibition was shown by P. expansum and A. niger as 73% and 15% at 1080 TAE/ml concentration of grape peel extract, respectively. Except S. typhimurium and E. coli, growth of all bacterial and mold species were found to be significantly (P < 0.05) inhibited by all the solvent extracts.


InferAMP, a python web app for copy number inference from discrete gene-level amplification signals noted in clinical tumor profiling reports.
As somatic next-generation sequencing gene panel analysis in advanced cancer patients is becoming more routine, oncologists are frequently presented with reports containing lists of genes with increased copy number. Distinguishing which of these amplified genes, if any, might be driving tumor growth and might thus be worth considering targeting can be challenging. One particular issue is the frequent absence of genomic contextual information in clinical reports, making it very challenging to determine which reported genes might be co-amplified and how large any such amplicons might be. We describe a straightforward Python web app, InferAMP, into which healthcare professionals may enter lists of amplified genes from clinical reports. The tool reports (1) the likely size of amplified genomic regions, (2) which reported genes are co-amplified and (3) which other cancer-relevant genes that were not evaluated in the assay may also be co-amplified in the specimen. The tool is accessible for web queries at http://inferamp.org.


Feline Pituitary Adenomas: Correlation of Histologic and Immunohistochemical Characteristics With Clinical Findings and Case Outcome.
Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.


Swelling behaviour of core-shell microgels in H2O, analysed by temperature-dependent FTIR spectroscopy.
Stimuli-responsive microgels are colloidal particles and promising candidates for applications such as targeted drug delivery, matrices for catalysts, nanoactuators and smart surface coatings. To tailor the response, the architecture of microgels is of paramount importance with respect to these applications. Statistical copolymer microgels based on N-isopropylmethacrylamide (NiPMAM) and N-n-propylacrylamide (NnPAM) show a cooperative phase transition leading to a collapse at a specific temperature. Interestingly, some core-shell microgel particles reveal a linear response of the hydrodynamic radius with temperature. Such observations were made by photon correlation spectroscopy (PCS), which is limited to the diffusion properties dominated by the particle shell. In this work we investigate the molecular hydration within the network of microgels in H2O by temperature-dependent FTIR spectroscopy. The phase transition temperature was determined by the shift in frequency of the NH bending vibration in homopolymer and statistical copolymer microgels and the results are in accordance with those from PCS. In contrast, experiments on core-shell particles show a broadening and shift of the respective phase transition temperatures of the core and shell indicating an interaction of the core and shell polymers on a molecular level that extends far into the core. In conclusion, temperature-dependent FTIR spectroscopy is a convenient approach to elucidate the internal architecture of complex microgel particles in H2O.


Comparison of N-epsilon-(Carboxymethyl)Lysine levels and percentage of eosinophils in induced sputum for assessment of small airway involvements in asthma.
N-epsilon-(Carboxymethyl)Lysine (CML), a major advanced glycation end product, is expressed in the lower respiratory tract. In this study, we compared the validity of measuring CML levels and percentage of eosinophils in induced sputum for assessment of airway functions, and evaluated the clinical implications of sputum CML levels in the asthmatic airways. We examined CML levels and percentage of eosinophils in induced sputum from 37 asthmatic patients and 15 normal controls, and evaluated the relationships between these parameters and clinical profiles of asthmatic patients. The percentage of eosinophils in induced sputum was significantly higher in asthmatic patients than in normal controls. Similarly, CML levels were also significantly higher in asthmatic patients than in normal controls (median (range): asthmatic patients 29.3 (18.4-64.7) microg/mL; normal controls 25.8 (14.0-47.0) microg/mL, p=0.02). However, there was no significant correlation between CML level and percentage of eosinophils. In asthmatic patients, percentage of eosinophils was significantly correlated with FEV1/FVC and degree of airway hyperreactivity to methacholine. However, CML level was correlated with FEV1/FVC, but not with methacholine reactivity. In contrast, CML level, but not percentage of eosinophils, was significantly correlated with degree of small airways dysfunction. Our novel, non-invasive technique of measurement of CML levels in induced sputum may prove to be important not only in the evaluation of small airway involvements, but also in helping us move toward a better understanding of the roles of the small airways in the pathogenesis of asthma.


Infodemiological data of Ironman Triathlon in the study period 2004-2013.
This article reports data concerning the Internet-related activities and interest for Ironman Triathlon competition. Google Trends (GT) was used and mined from 2004 onwards. The interest for Ironman Triathlon was found to be cyclic over time. The Triathlon-related Internet activities negatively correlated with the number of finishers per year (Pearson׳s correlation r=-0.690, p-value<0.05), while an increasing participation of female athletes who were less likely to surf the Internet could be noticed (r=-0.811, p-value<0.05). Further, younger athletes, who were more likely to access the web, were underrepresented in the Ironman Triathlon event. Moreover, there was a correlation between the biking time and the Internet query volumes (r=0.590, p-value<0.05), and, in particular, for the male athletes (r=0.664, p-value<0.05). Finally, the countries which most contributed to the Internet query volumes were those with the highest number of medals.


Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit?
The link between estrogen and the development and proliferation of breast cancer is well documented. Estrogen stimulates growth and inhibits apoptosis through estrogen receptor-mediated mechanisms in many cell types. Interestingly, there is strong evidence that estrogen induces apoptosis in breast cancer and other cell types. Forty years ago, before the development of tamoxifen, high-dose estrogen was used to induce tumor regression of hormone-dependent breast cancer in post-menopausal women. While the mechanisms by which estrogen induces apoptosis were not completely known, recent evidence from our laboratory and others demonstrates the involvement of the extrinsic (Fas/FasL) and the intrinsic (mitochondria) pathways in this process. We discuss the different apoptotic signaling pathways involved in E2 (17beta-estradiol)-induced apoptosis, including the intrinsic and extrinsic apoptosis pathways, the NF-kappaB (nuclear factor-kappa-B)-mediated survival pathway as well as the PI3K (phosphoinositide 3-kinase)/Akt signaling pathway. Breast cancer cells can also be sensitized to estrogen-induced apoptosis through suppression of glutathione by BSO (L-buthionine sulfoximine). This finding has implications for the control of breast cancer with low-dose estrogen and other targeted therapeutic drugs.


Elevated matrix metalloproteinase-8 in saliva and serum in polycystic ovary syndrome and association with gingival inflammation.
This study aimed to investigate the levels of matrix metalloproteinase-8 (MMP-8) and tissue inhibitors of MMP-1 (TIMP-1) in saliva and serum samples of women with polycystic ovary syndrome (PCOS; n = 80) and matched systemically healthy controls (n = 45), with varying degrees of gingival inflammation. Salivary levels of MMP-8 and the MMP-8/TIMP-1 ratio were significantly elevated in women with PCOS, who also exhibited more gingivitis than systemically healthy women. No major changes were observed in salivary TIMP-1 levels with regard to PCOS. Serum levels of MMP-8 and the MMP-8/TIMP-1 ratio were significantly higher in women with PCOS, irrespective of the presence of gingivitis, while there were no differences in TIMP-1 levels. A positive correlation was indicated between probing depth, bleeding on probing, plaque index and salivary or serum MMP-8 levels or MMP-8/TIMP-1 ratio in the case of PCOS, while a negative such correlation was revealed for TIMP-1 in systemically healthy women. Increased levels of MMP-8 in saliva and serum seem to be more pronounced in women with PCOS, and potentiated in the presence of gingival inflammation. Alterations in MMP/TIMP system triggered by local and systemic inflammation may be implicated in the pathogenesis of PCOS, or the deterioration of its clinical presentation.


Measuring finesse and gas absorption with Lorentzian recovery spectroscopy.
In this paper we present a method for obtaining accurate finesse by recovering the Lorentzian profile of cavity resonances with a laser continuously locked to the cavity and apply it to weak gas absorption measurements. The technique was implemented on our noise-immune cavity-enhanced optical heterodyne molecular spectroscopy (NICE-OHMS) experimental setup. The measurement is performed in the cavity-locked regime, leading to high repeatability and easy automation. The technique involves locking the carrier to a fundamental mode of the cavity and sweeping a second set of sidebands across adjacent cavity modes. The Lorentzian line shape can be reconstructed through a measurement of the transmitted optical power of the auxiliary sidebands. The cavity finesse and gas absorption can then be extracted from these power measurements. The accuracy of our measurements was verified by comparing our results to those obtained with the cavity ring down technique. We demonstrate the use of the technique in spectroscopy by measuring the absorption coefficient of the R(14) line of 12C16O that has been well characterized by others. The gas absorption results obtained were consistent with other experimental measurements and theoretical calculations.


Regulation of tubulin polypeptides and microtubule function: Luv1p [correction of Rki1p] interacts with the beta-tubulin binding protein Rbl2p.
Genetic analysis of microtubule functions in the yeast Saccharomyces cerevisiae suggests that cells manage the levels and activities of the tubulin polypeptides. These reactions may be involved in protein folding, formation of the heterodimer, and maintenance of the appropriate balance between alpha- and beta-tubulin. One protein involved in these functions is Rbl2p, which forms a complex with beta-tubulin. Here we describe the identification of a novel yeast gene, LUV1 [corrected], that interacts genetically with RBL2. Deletion of rki1 causes conditional defects in microtubule assembly and cell growth. Luv1p [corrected] can be isolated in a complex containing Rbl2p. The results support the existence of cellular mechanisms for regulating microtubule function through the tubulin polypeptides.


Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.
Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone.


Activation of Basolateral Amygdala to Nucleus Accumbens Projection Neurons Attenuates Chronic Corticosterone-Induced Behavioral Deficits in Male Mice.
The basolateral amygdala (BLA) is critical for reward behaviors via a projection to the nucleus accumbens (NAc). Specifically, BLA-NAc projections are involved in reinforcement learning, reward-seeking, sustained instrumental responding, and risk behaviors. However, it remains unclear whether chronic stress interacts with BLA-NAc projection neurons to result in maladaptive behaviors. Here we take a chemogenetic, projection-specific approach to clarify how NAc-projecting BLA neurons affect avoidance, reward, and feeding behaviors in male mice. Then, we examine whether chemogenetic activation of NAc-projecting BLA neurons attenuates the maladaptive effects of chronic corticosterone (CORT) administration on these behaviors. CORT mimics the behavioral and neural effects of chronic stress exposure. We found a nuanced role of BLA-NAc neurons in mediating reward behaviors. Surprisingly, activation of BLA-NAc projections rescues CORT-induced deficits in the novelty suppressed feeding, a behavior typically associated with avoidance. Activation of BLA-NAc neurons also increases instrumental reward-seeking without affecting free-feeding in chronic CORT mice. Taken together, these data suggest that NAc-projecting BLA neurons are involved in chronic CORT-induced maladaptive reward and motivation behaviors.


Biomarkers of the prothrombotic state in abdominal obesity.
Central obesity is specifically associated with cardiovascular disease. Nevertheless, the molecular events that promote these conditions remain incompletely defined and risk stratifying patients for cardiovascular disease continues a challenge. The aim of this study was to assess some cost-efficient haemostatic markers, and its association with central obesity and traditional cardiovascular risk factors, in a cohort of middle aged subjects, without clinical cardiovascular disease, as basis for an improved prevention and intervention. We studied 307 men, aged 45±7 years, which underwent medical history, physical examination, anthropometric measurements, plasmatic biochemical parameters, plasma concentrations of fibrinogen, prothrombin activity, activated partial thromboplastin time, platelet count and mean platelet volume. Prothrombin activity values were significantly higher in patients with central obesity (103 ± 16 % vs 111 ± 17 %, p<0.001). Across tertiles of fibrinogen (low and high), there was an increase in cholesterol, adjusted for age and body mass index (4.9±0.9 mmol/L vs 5.4±1.1 mmol/L, p< 0.01). High tertile of prothrombin activity showed higher levels of cholesterol (4.8±1.0 mmol/L vs 5.4±0.9 mmol/L , p< 0.05), triglycerides (1.07±0.6 mmol/L vs 1.32±0.9 mmol/L, p< 0.05), and waist circumference (92.8±8.3 cm vs 96.5±8.8 cm, p= ns) . Mean values of cholesterol were higher in low-activated partial thromboplastin time tertile (5.3±0.9 mmol/L vs 4.9±1.1 mmol/L, p<0.01). Participants in the high-mean platelet volume tertile showed higher levels of glycemia (5.7±0.6 mmol/L vs 5.99±0.7 mmol/L, p<0.05). Significant positive correlations were observed between fibrinogen and cholesterol (r=0.198, p<0.001) and triglycerides (r=0.116, p<0.05). Prothrombin activity was positively correlated with waist circumference (r=0.156, p<0.05), glucose (r=0.227, p<0.001), cholesterol (r=0.270, p=0.001), triglycerides (r=0.187, p=0.001) and mean platelet volume (r=0.130, p=0.05). Activated partial thromboplastin time was inversely related cholesterol (r=-0.172, p<0.01) concentrations. Mean platelet volume rose with increasing glucose concentrations (r=0.170, p<0.01). Haemostatic markers studied have shown association with abdominal adiposity and established cardiovascular risk factors. These markers are widely available, relatively inexpensive, and might allow risk stratifying patients for cardiovascular disease and the identification of hypercoagulable state in patients who might deserve preventive measures and are potential tools for assessing the impact of these measures.


Odorant response properties of convergent olfactory receptor neurons.
Information about odorant stimuli is thought to be represented in spatial and temporal patterns of activity across neurons in the olfactory epithelium and the olfactory bulb (OB). Previous studies suggest that olfactory receptor neurons (ORNs) distributed in the nasal cavity project to localized regions in the glomerular layer of the OB. However, the functional significance of this convergence is not yet known, and in no studies have the odorant response properties of individual ORNs projecting to defined OB regions been measured directly. We have retrogradely labeled mouse ORNs connecting to different glomeruli in the dorsal OB and tested single cells for responses to odorants using fura-2 calcium imaging. ORNs that project to clusters of dorsomedial (DM) glomeruli exhibit different odorant response profiles from those that project to dorsolateral (DL) glomeruli. DL-projecting ORNs showed responses to compounds with widely different structures, including carvone, eugenol, cinnamaldehyde, and acetophenone. In contrast, DM-projecting neurons exhibited responses to a more structurally restricted set of compounds and responded preferentially to organic acids. These data demonstrate that ORN afferents segregate by odorant responsiveness and that the homogeneity of ORN and glomerular input varies with different OB regions. The data also demonstrate that a subpopulation of ORNs projecting to DM glomeruli is functionally similar.


The coupling of direct analysis in real time ionization to Fourier transform ion cyclotron resonance mass spectrometry for ultrahigh-resolution mass analysis.
Direct Analysis in Real Time (DART) is an ambient ionization technique for mass spectrometry that provides rapid and sensitive analyses with little or no sample preparation. DART has been reported primarily for mass analyzers of low to moderate resolving power such as quadrupole ion traps and time-of-flight (TOF) mass spectrometers. In the current work, a custom-built DART source has been successfully coupled to two different Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers for the first time. Comparison of spectra of the isobaric compounds, diisopropyl methylphosphonate and theophylline, acquired by 4.7 T FT-ICR MS and TOF MS, demonstrates that the TOF resolving power can be insufficient for compositionally complex samples. 9.4 T FT-ICR MS yielded the highest mass resolving power yet reported with DART ionization for 1,2-benzanthracene and 9,10-diphenylanthracene. Polycyclic aromatic hydrocarbons exhibit a spatial dependence in ionization mechanisms between the DART source and the mass spectrometer. The feasibility of analyzing a variety of samples was established with the introduction and analysis of food products and crude oil samples. DART FT-ICR MS provides complex sample analysis that is rapid, highly selective and information-rich, but limited to relatively low-mass analytes.


A review of environmental enrichment for laying hens during rearing in relation to their behavioral and physiological development.
Globally, laying hen production systems are a focus of concern for animal welfare. Recently, the impacts of rearing environments have attracted attention, particularly with the trend toward more complex production systems including aviaries, furnished cages, barn, and free-range. Enriching the rearing environments with physical, sensory, and stimulatory additions can optimize the bird's development but commercial-scale research is limited. In this review, "enrichment" is defined as anything additional added to the bird's environment including structurally complex rearing systems. The impacts of enrichments on visual development, neurobehavioral development, auditory stimulation, skeletal development, immune function, behavioral development of fear and pecking, and specifically pullets destined for free-range systems are summarized and areas for future research identified. Visual enrichment and auditory stimulation may enhance neural development but specific mechanisms of impact and suitable commercial enrichments still need elucidating. Enrichments that target left/right brain hemispheres/behavioral traits may prepare birds for specific types of adult housing environments (caged, indoor, outdoor). Similarly, structural enrichments are needed to optimize skeletal development depending on the adult layer system, but specific physiological processes resulting from different types of exercise are poorly understood. Stimulating appropriate pecking behavior from hatch is critical but producers will need to adapt to different flock preferences to provide enrichments that are utilized by each rearing group. Enrichments have potential to enhance immune function through the application of mild stressors that promote adaptability, and this same principle applies to free-range pullets destined for variable outdoor environments. Complex rearing systems may have multiple benefits, including reducing fear, that improve the transition to the layer facility. Overall, there is a need to commercially validate positive impacts of cost-effective enrichments on bird behavior and physiology.


Treatment of contralateral hydrocele in neonatal testicular torsion: Is less more?
Treatment of neonatal testicular torsion has two objectives: salvage of the involved testicle (which is rarely achieved) and preservation of the contralateral gonad. The second goal universally involves contralateral testicular scrotal fixation to prevent the future occurrence of contralateral torsion. However, there is controversy with regards to management of a synchronous contralateral hydrocele. It has been our policy not to address the contralateral hydrocele through an inguinal incision to minimize potential injury to the spermatic cord. Our objective in this study was to determine whether the decision to manage a contralateral hydrocele in cases of neonatal testicular torsion solely through a scrotal approach is safe and effective. We reviewed all cases of neonatal testicular torsion occurring at our institution between the years 1999 and 2006. Age at presentation, physical examination, ultrasonographic and intraoperative findings were recorded. Patients were followed after initial surgical intervention to determine the likelihood of developing a subsequent hydrocele or hernia. Thirty-seven patients were identified as presenting with neonatal torsion. Age of presentation averaged 3.5 days (range 1-14 days). Left-sided pathology was seen more commonly than the right, with a 25:12 distribution. All torsed testicles were nonviable. Twenty-two patients were noted to have a contralateral hydrocele at presentation. All hydroceles were opened through a scrotal approach at the time of contralateral scrotal fixation. No patient underwent an inguinal exploration to examine for a patent process vaginalis. None of the patients who presented with a hydrocele have developed a clinical hydrocele or hernia after an average 7.5 years (range 4.3-11.2) follow-up. We have demonstrated that approaching a contralateral hydrocele in cases of neonatal testicular torsion solely through a scrotal incision is safe and effective. Inguinal exploration was not performed in our study and our long-term results demonstrate that such an approach would have brought no additional benefit. In avoiding an inguinal approach we did not subject our patients to unnecessary risk of testicular or vasal injury. Contralateral hydrocele is commonly seen in cases of neonatal testicular torsion. In our experience this is a condition of minimal clinical significance and does not warrant formal inguinal exploration for treatment. This conservative management strategy minimizes the potential of contralateral spermatic cord injury in the neonate. The aims of the study were met.


Rhabdomyolysis induced by Salmonella enterica serovar Typhi bacteraemia.
Rhabdomyolysis has been reported infrequently with salmonella infection. Since 1964, there have been at least 22 reports associated with gastroenteritis or bacteraemia. Twenty cases have been associated with non-typhoidal strains of Salmonella, with single reports of Salmonella enterica serovars Paratyphi and Typhi. A second case of typhoid fever associated with rhabdomyolysis was recently diagnosed in Ann Arbor, USA in a traveller returning from an endemic area. Prompt diagnosis and treatment resulted in a good outcome. Salmonella infection should be considered by clinicians as a possibility in the differential diagnosis of rhabdomyolysis.


A semantics-based approach to the "no negative evidence" problem.
Previous studies have shown that children retreat from argument-structure overgeneralization errors (e.g., *Don't giggle me) by inferring that frequently encountered verbs are unlikely to be grammatical in unattested constructions, and by making use of syntax-semantics correspondences (e.g., verbs denoting internally caused actions such as giggling cannot normally be used causatively). The present study tested a new account based on a unitary learning mechanism that combines both of these processes. Seventy-two participants (ages 5-6, 9-10, and adults) rated overgeneralization errors with higher (*The funny man's joke giggled Bart) and lower (*The funny man giggled Bart) degrees of direct external causation. The errors with more-direct causation were rated as less unacceptable than those with less-direct causation. This finding is consistent with the new account, under which children acquire-in an incremental and probabilistic fashion-the meaning of particular constructions (e.g., transitive causative = direct external causation) and particular verbs, rejecting generalizations where the incompatibility between the two is too great.


Towards practical lithium-metal anodes.
Lithium-ion batteries have had a tremendous impact on several sectors of our society; however, the intrinsic limitations of Li-ion chemistry limits their ability to meet the increasing demands of developing more advanced portable electronics, electric vehicles, and grid-scale energy storage systems. Therefore, battery chemistries beyond Li ions are being intensively investigated and need urgent breakthroughs toward commercial applications, wherein the use of metallic Li is one of the most intuitive choices. Despite several decades of oblivion due to safety concerns regarding the growth of Li dendrites, Li-metal anodes are now poised to be revived because of the advances in investigative tools and globally invested efforts. In this review, we first summarize the existing issues with regard to Li anodes and their underlying reasons and then highlight the recent progress made in the development of high-performance Li anodes. Finally, we propose the persisting challenges and opportunities toward the exploration of practical Li-metal anodes.


Temporary prostatic urethral stenting as a provocative tool to determine surgical eligibility in complex bladder outlet obstructed patients: our initial experience.
To evaluate the usefulness of a temporary prostatic urethral stent to determine which complex surgical patients would benefit from definitive surgical management of their benign prostatic hyperplasia. We retrospectively analyzed our benign prostatic hyperplasia database and identified all patients that received at least one temporary prostatic urethral stent between April 2008 and December 2010. Forty Spanner(TM) stents were placed in 20 patients. Mean age was 78.1 years and prostate size was 62.1 cm(3). Urinary retention was present in 60% (12/20) of patients. No statistically significant changes in mean maximal flow rate, average flow rate, and post void residual was noted. Seven patients (35%) did well with the stent and progressed to definitive surgical management whereas 10% of the cohort (2/20) leaked urine with the stent in place and subsequently went back to catheter management. Another 30% (6/20) were unable to tolerate the stent while 1 patient passed away unrelated to the stent. The use of the temporary prostatic urethral stent provided a good provocative test that enabled patients to experience what their voiding status would be if they were to undergo definitive surgical management.


Efficacy and safety of subconjunctival bevacizumab for recurrent pterygium.
To evaluate the clinical outcome(s) and complication(s) of subconjunctival bevacizumab treatment in patients with recurrent pterygium. This prospective case series included patients who had undergone pterygium surgery and were diagnosed with recurrent pterygium. All patients received one subconjunctival injection of 0.5 mL of bevacizumab (2.5 mg/0.1 mL). The main outcome was the change in size and clinical appearance. The clinical appearance of the pterygium was graded according to Tan and colleagues. The horizontal size of the pterygium (from limbus to apex) was recorded from baseline to 2 months after injection. Treatment-related complications and adverse events were reported. We included 36 eyes of 36 patients (18 males) with a mean age of 58.75 ± 10.98 years. Totally, 30.6% patients developed recurrent pterygium in both eyes (only the worst eye was treated), with 47.2% developing it in the left eye and 22.2% in the right eye. More than half the patients (58.3%) had a family history of pterygium. There was a significant difference in the size of pterygium at different intervals (P<0.05). Approximately two-thirds (66.7%) of patients presented with hyposphagma on the 2nd day after subconjunctival application; this value decreased to 30.6% by day 7 and to 0% at 1 month. Most patients (69.4%) exhibited amelioration of irritative symptoms within 2 days, 88.9% after 7 days, and 97.2% after 1 month. Subconjunctival bevacizumab injection is useful for the management of patients with recurrent pterygium, with no significant local or systemic adverse effects.


Regulation of renal Na+-K+-ATPase in the rat by adrenal steroids.
The effects of single and multiple injections of aldosterone and dexamethasone on renal Na+-K+-ATPase, in vitro renal gluconeogenesis, and urinary electrolyte excretion were examined in adrenalectomized rats in a dose-dependent manner. Single maximal and supramaximal doses of aldosterone (defined by the effect of electrolyte excretion) had no effect on Na+-K+-ATPase or gluconeogenesis. By contrast, a single administration of dexamethasone (in a dose range that increased fasting blood sugar, stimulated renal gluconeogenesis, and had no mineralocorticoid effects) yielded clear-cut activation of Na+-K+-ATPase. Multiple submaximal doses of dexamethasone produced quantitatively similar stimulation of Na+-K+-ATPase and gluconeogenesis. Multiple supramaximal doses of aldosterone stimulated Na+-K+-ATPase and gluconeogenesis, but maximal and submaximal doses of the hormone were without effect. Aldosterone had no effect on hepatic Na+-K+-ATPase or gluconeogenesis. These results suggest that activation of renal Na+-K+-ATPase can be considered a putative glucocorticoid (not mineralocorticoid) effect. Renal Na+-K+-ATPase activation by chronic aldosterone treatment may be mediated by glucocorticoid receptor sites and, hence, may not represent a genuine mineralocorticoid effect.


Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial.
Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative learning network. The digital platform contains a stepwise protocol to implement work-related stress-management interventions. It includes stress screeners, interventions and intervention providers to facilitate access to and the selection of matching work-related stress-management interventions. The collaborative learning network, including stakeholders from various organizations, plans meetings focussing on an exchange of experiences and good practices among organizations for the implementation of stress prevention measures. This paper describes the design of an integral stress-prevention strategy, Stress Prevention@Work, and the protocol for the evaluation of: 1) the effects of the strategy on perceived stress and work-related outcomes, and 2) the barriers and facilitators for implementation of the strategy. The effectiveness of Stress Prevention@Work will be evaluated in a cluster controlled trial, in a large healthcare organization in the Netherlands, at six and 12 months. An independent researcher will match teams on working conditions and size and allocate the teams to the intervention or control group. Teams in the intervention group will be offered Stress Prevention@Work. For each intervention team, one employee is responsible for applying the strategy within his/her team using the digital platform and visiting the collaborative learning network. Using a waiting list design, the control group will be given access to the strategy after 12 months. The primary outcome is the employees' perceived stress measured by the stress subscale of the Depression, Anxiety, and Stress Scale (DASS-21). Secondary outcome measures are job demands, job resources and the number of preventive stress measures implemented at the team level. Alongside the trial, a process evaluation, including barriers and facilitators of the implementation of Stress Prevention@Work, will be conducted in one healthcare organisation. If Stress Prevention@Work is found to be effective in one healthcare organisation, further implementation on a broader scale might lead to increased productivity and decreased stress and sick leave in other organizations. Results are expected in 2018. NTR5527 . Registered 7 Dec 2015.


Nuclear imaging to support anti-inflammatory drug discovery and development.
Nuclear medicine contributes important tools to support anti-inflammatory drug discovery and development. The support provided is manifold: new molecular entities (NME, either small molecules or biologics) labeled with radioisotopes can be applied in animal models and humans to measure biodistribution, target engagement, and pharmacokinetics. In addition, nuclear imaging techniques can be used to select or enrich the patient populations in clinical trials, to assess disease activity, target status and distribution and to quantify response to therapeutic interventions. In the first part of this review we will outline how nuclear imaging techniques can be applied to support informed decision making in drug development. In the second part, we will briefly high-light the use of nuclear imaging of inflammation in drug development in selected diseases, specifically rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), atherosclerosis and - as an emerging topic - cancer.


Metabolic syndrome and its correlated factors in an urban population in South West of Iran.
This study was designed to assess the prevalence of metabolic syndrome and its correlated factors in an urban population in Ahvaz. This descriptive analytical study performed with random cluster sampling method in 6 health centers in Ahvaz. In each selected center, 55 households were randomly selected. A questionnaire included: age, sex, marital status, ethnicity, education level, family history of diabetes (DM), Hypertension (HTN) and obesity, smoking and parity and previous history of gestational diabetes Mellitus in women were filled for each person.Blood pressure, weight, height, body mass index (BMI), abdominal and waist circumference were measured in each participant. Fasting blood glucose (FBS), serum total cholesterol, triglyceride and high density lipoprotein (HDL) level were measured in fasting blood sample. The mean age of all participants was 42.27 ± 14 years (44.2 ± 14.26 years in men and 40.5 ± 13.5 in women). From total 912 participant, 434(47.2%) were men and 478(52.8%) women. Prevalence of metabolic syndrome based on ATPIII criteria (update2005) was 22.8% (15.9% in men and 29.1% in women) that showed significant difference (P = 0.0001). Prevalence of each component of MS in studied population was: 29.4% for abdominal obesity, 40.7% for high TG level, 40.2% for low HDL, 15.4% for hypertension and 37.8% for abnormal FBS. Among these factor, age of patients, BMI, sex had significant differences between persons with or without Ms (P = 0.0001). Ethnicity (Arab or Persian), cigarette smoking and family history of diabetes mellitus, hypertension and obesity, marital statues, education level, parity and previous history of GDM in women showed no significant differences between persons with MS and without MS. Metabolic syndrome has high prevalence in our population and its prevalence increases with increasing age and BMI. Women are at higher risk for metabolic syndrome than men.


The Milieu Manager: A Nursing Staffing Strategy to Reduce Observer Use in the Acute Psychiatric Inpatient Setting.
Rising acuity levels in inpatient settings have led to growing reliance on observers and increased the cost of care. Minimizing use of observers, maintaining quality and safety of care, and improving bed access, without increasing cost. Nursing staff on two inpatient psychiatric units at an academic medical center pilot-tested the use of a "milieu manager" to address rising patient acuity and growing reliance on observers. Nursing cost, occupancy, discharge volume, unit closures, observer expense, and incremental nursing costs were tracked. Staff satisfaction and reported patient behavioral/safety events were assessed. The pilot initiatives ran for 8 months. Unit/bed closures fell to zero on both units. Occupancy, patient days, and discharges increased. Incremental nursing cost was offset by reduction in observer expense and by revenue from increases in occupancy and patient days. Staff work satisfaction improved and measures of patient safety were unchanged. The intervention was effective in reducing observation expense and improved occupancy and patient days while maintaining patient safety, representing a cost-effective and safe approach for management of acuity on inpatient psychiatric units.


Management of epithelial ingrowth and cysts.
In 12 consecutive cases of epithelial ingrowth operated on during the past 50 months, therapy included photocoagulation on the iris followed by excision of involved iris tissue and vitreous gel by means of instruments designed for vitreous surgery. Epithelium remaining on the posterior surface of the cornea, the ciliary body, and in the anterior chamber was destroyed by controlled transcorneal and transscleral cryotherapy. An intraocular air bubble was used to provide an insulating effect and a more effective, controllable freeze. All patients except two had improved vision postoperatively, and 3 of the 12 patients has postoperative visual acuity of 6/12 (20/40) or better. Similar closed-eye cryodestructive techniques have been used for treatment of enlarging epithelial cysts.


On enhancing the noise-reduction performance of the acoustic lined duct utilizing the phase-modulating metasurface.
This work proposes a noise-reduction structure that integrates phase-modulating metasurface (PMM) with acoustic liners (ALs) to enhance the narrow band absorption performance of a duct with relatively small length-diameter ratio. The PMM manipulates the wavefront by introducing different transmission phase shifts based on an array of Helmholtz resonators, so that the spinning wave within the duct can be generated. Compared with the plane wave, the generated spinning wave has a lower group velocity, which results in a greater traveling distance over the ALs in the duct. The optimization design is performed to determine the final structural parameters of the PMM, which is based on the predictions of the amplitude and phase shift of the acoustic wave at the outlet of the PMM using the theory of passive phased array. With the manipulation of the PMM, the incident plane wave is modulated into a spinning wave, and then enters into the acoustic liner duct (ALD), whose structural parameters are optimized by maximizing the transmission loss using the mode-matching technique. Finally, the noise-reduction performance of this combined structure is evaluated by numerical simulations in the presence of grazing flow. The results demonstrate that, compared with the traditional ALD, the proposed structure exhibits a significant increase in transmission loss within the considered frequency band, especially near the peak frequency of the narrow band noise.


Glucagon Like Peptide 1 and MicroRNA in Metabolic Diseases: Focusing on GLP1 Action on miRNAs.
Glucagon like peptide 1 (GLP1) is an incretin hormone released from the enteroendocrine L-type cells of the lower gastrointestinal tract. The active isoforms of GLP1 are rapidly degraded (<2 min) by protease dipeptidyl peptidase-4 (DPP-4) after their release. Among its functions, GLP1 exerts a pivotal role in regulating glucose and lipid metabolism. In particular, GLP1 increases glucose stimulated insulin secretion, functional pancreatic β-cell mass and decreases glucagon secretion from pancreatic α-cells. GLP1 can also be a regulator of lipid and lipoprotein metabolism ameliorating diabetic dyslipidemia, liver steatosis, and promoting satiety. Interestingly, it has been found that GLP1 and GLP1 agonists can modulate the expression of different microRNAs (miRNAs), a ~22 nucleotides small non-coding RNAs, key modulators of protein expression. In particular, in pancreas, GLP1 increases the expression levels of miRNA-212 and miRNA-132, stimulating insulin secretion. Similarly, GLP1 decreases miRNA-338 levels, leading to an increase of pancreatic β-cell function, followed by an improvement of diabetic conditions. Moreover, GLP1 modulation of miRNAs expression in the liver regulates hepatic lipid storage. Indeed, GLP1 down-regulates miRNA-34a and miRNA-21 and up-regulates miRNA-200b and miRNA-200c expression in liver, reducing intra hepatic lipid accumulation and liver steatosis. Clinical and pre-clinical studies, discussed in this review, suggest that modulation of GLP1/miRNAs pathway may be a useful and innovative therapeutic strategy for prevention and treatment of metabolic disorders, such as diabetes mellitus and liver steatosis.


Psychometric properties of the postpartum depression screening scale beyond the postpartum period.
Accurate postpartum depression screening measures are needed to identify mothers with depressive symptoms both in the postpartum period and beyond. Because it had not been tested beyond the immediate postpartum period, the reliability and validity of the Postpartum Depression Screening Scale (PDSS) and its sensitivity, specificity, and predictive value for diagnoses of major depressive disorder (MDD) were assessed in a diverse community sample of 238 mothers of 4- to 15-month-old infants. Mothers (N = 238; M age = 30.2, SD = 5.3) attended a lab session and completed the PDSS, the Beck Depression Inventory-II (BDI-II), and a structured clinical interview (SCID) to diagnose MDD. The reliability, validity, specificity, sensitivity, and predictive value of the PDSS to identify maternal depression were assessed. Confirmatory factor analysis supported the construct validity of five but not seven content subscales. The PDSS total and subscale scores demonstrated acceptable to high reliability (α = 0.68-0.95). Discriminant function analysis showed the scale correctly provided diagnostic classification at a rate higher than chance alone. Sensitivity and specificity for major depressive disorder (MDD) diagnosis were good and comparable to those of the BDI-II. Even in mothers who were somewhat more diverse and had older infants than those in the original normative study, the PDSS appears to be a psychometrically sound screener for identifying depressed mothers in the 15 months after childbirth.


Anesthesiologists, general surgeons, and tobacco interventions in the perioperative period.
Surgery presents an opportunity for interventions in cigarette smokers that will facilitate abstinence from tobacco. However, little attention has been paid to the role of anesthesiologists and surgeons in addressing tobacco use. To determine the practices and attitudes of these physicians regarding this issue, we sent a postal mail survey to a national random sampling of anesthesiologists and general surgeons engaged in active practice within the United States (1000 in each group). Response rates were 33% and 31% for anesthesiologists and surgeons, respectively. More than 90% of both groups almost always ask their patients about tobacco use, and almost all respondents believed that surgical patients should maintain abstinence after surgery. Most believed that it was their responsibility to advise their patients to quit smoking, but only 30% of anesthesiologists and 58% of surgeons routinely do so. Nonetheless, approximately 70% of both groups would be willing to spend an extra 5 min before surgery to help their patients quit. Barriers to intervention included a lack of training regarding intervention techniques, a perceived lack of effective interventions, and insufficient time to intervene. Intervention opportunities are not exploited consistently in the surgical population; educational efforts directed at physicians in surgical specialties are indicated.


Effect of AML serum on normal human myeloid differentiation and hexamethylene bisacetamide-induced granulocytic differentiation of the human HL-60 promyelocytic leukaemic cell line.
The effect of serum from 32 AML patients on the normal human myeloid differentiation and the hexamethylene-bisacetamide induced granulocytic differentiation of HL-60 promyelocytic leukaemic cell line was studied. Nonadherent normal mononuclear marrow cells were cultured in vitro at a concentration of 5 x 10(5) cells/ml for 6 days with each of the 32 AML sera. Ten normal human AB sera were used as control. The results showed an inhibitory activity on both morphological and functional differentiation of normal human myeloid immature marrow cells by 29 out of the 32 AML sera tested. These 29 AML sera were added to cultures of HL-60 (2.5 x 10(5)/ml) leukaemia cell line which incorporated 2 mM hexamethylene-bisacetamide for 6 days. The results showed no significant inhibition of hexamethylene-bisacetamide induced granulocytic differentiation by any of the 29 AML sera. The efficacy of hexamethylene-bisacetamide in inducing differentiation in the presence of inhibitory factors suggests a possible role in the treatment of AML patients.


Integrated Direct-to-Biology Platform for the Nanoscale Synthesis and Biological Evaluation of PROTACs.
Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that co-opt the cell's natural proteasomal degradation mechanisms to degrade undesired proteins. A challenge associated with PROTACs is the time and resource-intensive optimization; thus, the development of high-throughput platforms for their synthesis and biological evaluation is required. In this study, we establish an ultra-high-throughput experimentation (ultraHTE) platform for PROTAC synthesis, followed by direct addition of the crude reaction mixtures to cellular degradation assays without any purification. This 'direct-to-biology' (D2B) approach was validated and then exemplified in a medicinal chemistry campaign to identify novel BRD4 PROTACs. Using the D2B platform, the synthesis of 650 PROTACs was carried out in a 1536-well plate, and subsequent biological evaluation was performed by a single scientist in less than 1 month. Due to its ability to hugely accelerate the optimization of new degraders, we anticipate our platform will transform the synthesis and testing of PROTACs.


[Effect of different light regimens on the development of metabolic syndrome of aging rats].
During two years the influence of light regimens (standard lightning--LD, constant lightning--LL, natural lightning of the North-West of Russia--NL) and of melatonin on the development of metabolic syndrome of ageing LIO rats was studied. It was found out that during the process of ageing of rats kept in the conditions of the broken rhythm of day and night, different breaches of metabolism in the form of abdominal obesity, hyperinsulinemia, hypercholesterolemia, hyperglycemia, hyperbetalipoproteinemia and glycosuria occurred. These breaches can be considered to be metabolic syndrome or the syndrome of insulinoresistancy. The use of melatonin at night time starting from the rats' age of four months slowed down the age breaches of metabolism in rats. This fact proves indirectly the lack of this hormone in the conditions of natural lightning of the North-West of Russia.


Radiofrequency catheter ablation of idiopathic ventricular arrhythmias originating from intramural foci in the left ventricular outflow tract: efficacy of sequential versus simultaneous unipolar catheter ablation.
Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <-30 ms was recorded at those ablation sites. LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides.


Willingness to pay for mammography: item development and testing among five ethnic groups.
The goal of this study was to develop a willingness to pay (WTP) question for mammography that is appropriate for low income, ethnically-diverse women. Through qualitative research with 50 low income women of five ethnic groups we developed both a WTP question and a willingness to travel question (WTT). After being refined through interviews with 41 women, these questions were pilot tested on a random sample of 52 low income, ethnically-diverse women in the San Francisco area. Results show that the concepts underlying WTP and WTT were culturally appropriate to the five ethnicities in this study. Analyses generally confirm the validity of the WTP and WTT questions. As expected, WTP was associated with household income, perceived risk of cancer, and knowledge that one needs a mammogram even after a clinical breast examination. Despite the small samples, WTP varied among the ethnic groups. Additionally, WTT was moderately correlated with the natural log of WTP (r = 0.58, P < 0.001). These questions are now in use in a larger clinical trial and future analyses will explore willingness to pay and willingness to travel within and across the ethnic groups.


Activation of group III metabotropic glutamate receptors inhibits the production of RANTES in glial cell cultures.
The chemokine RANTES is critically involved in neuroinflammation and has been implicated in the pathophysiology of multiple sclerosis. We examined the possibility that activation of G-protein-coupled metabotropic glutamate (mGlu) receptors regulates the formation of RANTES in glial cells. A 15 hr exposure of cultured astrocytes to tumor necrosis factor-alpha and interferon-gamma induced a substantial increase in both RANTES mRNA and extracellular RANTES levels. These increases were markedly reduced when astrocytes were coincubated with l-2-amino-4-phosphonobutanoate (l-AP-4), 4-phosphonophenylglycine, or l-serine-O-phosphate, which selectively activate group III mGlu receptor subtypes (i.e., mGlu4, -6, -7, and -8 receptors). Agonists of mGlu1/5 or mGlu2/3 receptors were virtually inactive. Inhibition of RANTES release produced by l-AP-4 was attenuated by the selective group III mGlu receptor antagonist (R,S)-alpha-methylserine-O-phosphate or by pretreatment of the cultures with pertussis toxin. Cultured astrocytes expressed mGlu4 receptors, and the ability of l-AP-4 to inhibit RANTES release was markedly reduced in cultures prepared from mGlu4 knock-out mice. This suggests that activation of mGlu4 receptors negatively modulates the production of RANTES in glial cells. We also examined the effect of l-AP-4 on the development of experimental allergic encephalomyelitis (EAE) in Lewis rats. l-AP-4 was subcutaneously infused for 28 d by an osmotic minipump that released 250 nl/hr of a solution of 250 mm of the drug. Detectable levels of l-AP-4 ( approximately 100 nm) were found in the brain dialysate of EAE rats. Infusion of l-AP-4 did not affect the time at onset and the severity of neurological symptoms but significantly increased the rate of recovery from EAE. In addition, lower levels of RANTES mRNA were found in the cerebellum and spinal cord of EAE rats infused with l-AP-4. These results suggest that pharmacological activation of group III mGlu receptors may be useful in the experimental treatment of neuroinflammatory CNS disorders.


Immediate Effects of Clock-Turn Strategy on the Pattern and Performance of Narrow Turning in Persons With Parkinson Disease.
Turning difficulty is common in people with Parkinson disease (PD). The clock-turn strategy is a cognitive movement strategy to improve turning performance in people with PD despite its effects are unverified. Therefore, this study aimed to investigate the effects of the clock-turn strategy on the pattern of turning steps, turning performance, and freezing of gait during a narrow turning, and how these effects were influenced by concurrent performance of a cognitive task (dual task). Twenty-five people with PD were randomly assigned to the clock-turn or usual-turn group. Participants performed the Timed Up and Go test with and without concurrent cognitive task during the medication OFF period. The clock-turn group performed the Timed Up and Go test using the clock-turn strategy, whereas participants in the usual-turn group performed in their usual manner. Measurements were taken during the 180° turn of the Timed Up and Go test. The pattern of turning steps was evaluated by step time variability and step time asymmetry. Turning performance was evaluated by turning time and number of turning steps. The number and duration of freezing of gait were calculated by video review. The clock-turn group had lower step time variability and step time asymmetry than the usual-turn group. Furthermore, the clock-turn group turned faster with fewer freezing of gait episodes than the usual-turn group. Dual task increased the step time variability and step time asymmetry in both groups but did not affect turning performance and freezing severity. The clock-turn strategy reduces turning time and freezing of gait during turning, probably by lowering step time variability and asymmetry. Dual task compromises the effects of the clock-turn strategy, suggesting a competition for attentional resources.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A141).


The effect of intermittent local heat and cold on labor pain and child birth outcome.
Labor pain is one of the severest pains that cause many women request cesarean section for fear of pain. Thus, controlling labor pain is a major concern of maternity care. Nowadays, interest in non-pharmacological pain relief methods has been increased because of their lower side effects. The effects of discrete heat and cold on decreasing labor pain have been reported but there was no evaluation of the effects of simultaneous heat and cold. The aim of this study was to investigate the effect of intermittent heat and cold on pain severity and childbirth outcomes. This study was a randomized controlled trial. Sixty-four nulliparous women with term, One fetus, and low-risk pregnancy were divided into the intervention (32 participants) and the control group (32 participants) by random allocation. Excluding criteria were: administration of pain relief drugs, skin disease in the field of intervention, fetal distress, bleeding, fever, and disagreement with participation in the study. Warm and cold packs were used intermittently on low back and lower abdomen during the first phase and on perineum during the second phase of labor. Pain intensity was assessed with Visual Analogue Scale. Descriptive statistic, chi square, and t-test were used for data analysis. There were no significant differences in demographic and midwifery characteristics and the baseline pain between two groups. The pain was significantly lower in intervention group during the first and second phases of labor. Duration of the first and third phases of labor was shorter in the case group. There were no significant differences in type of delivery, perineal laceration, oxytocin uptake, fetal heart rate, and APGAR between two groups. Local warming with intermittent cold pack can reduce labor pain without adverse effects on maternal and fetal outcomes. It is an inexpensive and simple method. Intermittent local heat and cold therapy is a no pharmalogical, safe and effective method to relief labor pain.


Meta-Analysis of Alcohol and Serodiscordant Condomless Sex Among People Living with HIV.
While observational studies have found that alcohol consumption is associated with serodiscordant condomless sex among people living with HIV (PLHIV), no meta-analysis has yet examined this trend. We conducted a meta-analysis to synthesize empirical evidence on the association between alcohol and condomless sex with partners at risk of HIV acquisition. To meet inclusion criteria, studies: (1) specifically targeted PLHIV or provided stratified data for HIV-infected participants; (2) provided a quantitative measure of alcohol use; (3) provided a quantitative measure of condomless sex with serodiscordant partners; and (4) reported the results of statistical tests examining the relationship between alcohol use and serodiscordant condomless sex. Using random-effects models, weighted effect sizes were calculated. Three separate analyses were conducted to examine serodiscordant condomless sex in association with any alcohol consumption, binge/problematic drinking, and alcohol in a sexual context. A total of 36 independent effect sizes from 27 studies (including 25,065 HIV-infected participants) were pooled in the meta-analysis. Any alcohol consumption, binge/problematic drinking, and alcohol use in a sexual context were each associated with condomless sex with serodiscordant partners [OR 1.64 (95% CI 1.46-1.85); OR 1.65 (95% CI 1.14-2.39); OR 2.88 (95% CI 2.01-4.12), respectively]. Meta-analytic findings demonstrate a consistent positive relationship between alcohol use and serodiscordant condomless sex among PLHIV. Future public health programming for HIV-infected individuals needs to address the role of alcohol consumption in sexual risk-taking behavior.


Engineering and the law-employment obligations. I. Duties of an employee to his employer.
Problems that arise in connection with duties to the current employer(s) are discussed. Current employment law evolved from the feudal relationship between lords and peasants. An employee has a fiduciary duty toward his employer; this is a common law duty deriving its name from the duty of fides, or fidelity, between the master and the servant. In the case of a scientist or engineer employed to conduct research and/or development for a company or university, fiduciary duties obligate the employee to offer all benefits of the work he conducts for the employer to the employer. A scientist or engineer with interests that are adverse to a potential employer must disclose the existence and extent of such interests. An employee has a duty not to compete with his employer concerning the subject matter of the employment; this duty has been documented extensively in legal cases. An employee also has a duty not to act, or agree to act, for third parties whose interest conflict with those of his employer.


Psychological treatments for depression and anxiety in dementia and mild cognitive impairment.
Experiencing anxiety and depression is very common in people with dementia and mild cognitive impairment (MCI). Psychological interventions have been suggested as a potential treatment for these populations. Current research suggests that people with dementia and MCI have limited opportunities for psychological treatments aimed at improving their well-being. A systematic review of the evidence on their effectiveness is likely to be useful in terms of improving outcomes for patients and for future recommendations for practice. The main objective of this review was to assess the effectiveness of psychological interventions in reducing anxiety and depression in people with dementia or mild cognitive impairment (MCI). We searched the Cochrane Dementia and Cognitive Improvement Group Specialized Register and additional sources for both published and unpublished data. We included randomised controlled trials (RCTs) comparing a psychological intervention with usual care or a placebo intervention (social contact control) in people with dementia or MCI. Two review authors worked independently to select trials, extract data and assess studies for risk of bias, using a data extraction form. We contacted authors when further information was not available from the published articles. Six RCTs involving 439 participants with dementia were included in the review, but no studies of participants with MCI were identified. The studies included people with dementia living in the community or in nursing home care and were carried out in several countries. Only one of the studies was classified as low risk of bias. Five studies were at unclear or high risk of bias due to uncertainties around randomisation, blinding and selective reporting of results. The studies used the different psychological approaches of cognitive behavioural therapy (CBT), interpersonal therapy and counselling. Two studies were of multimodal interventions including a specific psychological therapy. The comparison groups received either usual care, attention-control educational programs, diagnostic feedback or services slightly above usual care.Meta-analysis showed a positive effect of psychological treatments on depression (6 trials, 439 participants, standardised mean difference (SMD) -0.22; 95% confidence interval (CI) -0.41 to -0.03, moderate quality evidence) and on clinician-rated anxiety (2 trials, 65 participants, mean difference (MD) -4.57; 95% CI -7.81 to -1.32, low quality evidence), but not on self-rated anxiety (2 trials, SMD 0.05; 95% CI -0.44 to 0.54) or carer-rated anxiety (1 trial, MD -2.40; 95% CI -4.96 to 0.16). Results were compatible with both benefit and harm on the secondary outcomes of patient quality of life, activities of daily living (ADLs), neuropsychiatric symptoms and cognition, or on carers' self-rated depressive symptoms, but most of the studies did not measure these outcomes. There were no reports of adverse events. We found evidence that psychological interventions added to usual care can reduce symptoms of depression and clinician-rated anxiety for people with dementia. We conclude that psychological interventions have the potential to improve patient well-being. Further high quality studies are needed to investigate which treatments are most effective and to evaluate the effect of psychological interventions in people with MCI.


Block copolymer-nanodiamond coassembly in solution: towards multifunctional hybrid materials.
Polymer-nanodiamond composites are excellent candidates for the fabrication of multifunctional hybrid materials. They integrate polymer flexibility and exceptional properties of nanodiamonds (NDs), such as biocompatibility, mechanical strength, color centers, and chemically-tailored surfaces. However, their development is hindered by the challenge of ensuring that NDs are homogeneously distributed in the composites. Here, we exploit colloidal coassembly between poly(isoprene-b-styrene-b-2-vinyl pyridine) (ISV) block copolymers (BCPs) and NDs to avoid ND self-agglomeration and direct ND spatial distribution. NDs were first air oxidized at 450 °C to obtain stable dispersions in dimethylacetamide (DMAc). By adding ISV into the dispersions, patchy hybrid micelles were formed due to H-bonds between NDs and ISV. The ISV-ND coassembly in DMAc was then used to fabricate nanocomposite films with a uniform sub-50 nm ND distribution, which has never been previously reported for an ND loading (φND) of more than 50 wt%. The films exhibit good transparency due to their well-defined nanostructures and smoothness and also exhibit an improved UV-absorption and hydrophilicity compared to neat ISV. More intriguingly, at a φND of 22 wt%, ISV and NDs coassemble into a network-like superstructure with well-aligned ND strings via a dialysis method. Transmission electron microscopy and dynamic light scattering measurements suggest a complex interplay between polymer-polymer, polymer-solvent, polymer-ND, ND-solvent, and ND-ND interactions during the formation of structures. Our work may provide an important foundation for the development of hierarchically ordered nanocomposites based on BCP-ND coassembly, which is beneficial for a wide spectrum of applications from biotechnology to quantum devices.


Fear of an unprecedented, invisible enemy: Difficulties experienced in establishing criteria for the release of COVID-19 patients from isolation in a Japanese University Hospital.
The novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, and the United States and European authorities established criteria for the release of COVID-19 patients from isolation in October 2020. However, a huge discrepancy exists between the hospital-discharge protocol for COVID-19 patients and the release of patients from in-hospital isolation. Our initially proposed criteria for in-hospital release from isolation was not adhered to by healthcare workers (HCWs) due to prevailing concerns regarding disease infectivity. Herein, we report difficulties encountered in attempting to establish a common understanding of the management of emerging infections. We performed a Google Form-based questionnaire survey targeting HCWs from Okayama University Hospital, Japan, via e-mail on January 21-28, 2021. The anonymous investigation required respondents to provide information regarding their background as well as perceptions regarding the requirement, level of understanding, and readiness for developing release criteria. We obtained 150 eligible responses, including 57 (38.0%) from medical doctors and 53 (35.3%) from nurses. Most HCWs managing COVID-19 patients advocated for the implementation of the criteria, whereas those not working in that capacity did not (p<0.001). Over half of the HCWs indicated discomfort at seeing COVID-19 patients transitioning to general management even after meeting the criteria. It was challenging to establish a common understanding regarding the ideal criteria for in-hospital release of COVID-19 patients from isolation in our hospital. The dissemination of our experiences and multifaceted discussions with HCWs would be of great value as a countermeasure against the emergent pandemic.