Combined Analysis of Extant Rhynchonellida (Brachiopoda) using Morphological and Molecular Data.
Independent molecular and morphological phylogenetic analyses have often produced discordant results for certain groups which, for fossil-rich groups, raises the possibility that morphological data might mislead in those groups for which we depend upon morphology the most. Rhynchonellide brachiopods, with more than 500 extinct genera but only 19 extant genera represented today, provide an opportunity to explore the factors that produce contentious phylogenetic signal across datasets, as previous phylogenetic hypotheses generated from molecular sequence data bear little agreement with those constructed using morphological characters. Using a revised matrix of 66 morphological characters, and published ribosomal DNA sequences, we performed a series of combined phylogenetic analyses to identify conflicting phylogenetic signals. We completed a series of parsimony-based and Bayesian analyses, varying the data used, the taxa included, and the models used in the Bayesian analyses. We also performed simulation-based sensitivity analyses to assess whether the small size of the morphological data partition relative to the molecular data influenced the results of the combined analyses. In order to compare and contrast a large number of phylogenetic analyses and their resulting summary trees, we developed a measure for the incongruence between two topologies and simultaneously ignore any differences in phylogenetic resolution. Phylogenetic hypotheses generated using only morphological characters differed among each other, and with previous analyses, whereas molecular-only and combined Bayesian analyses produced extremely similar topologies. Characters historically associated with traditional classification in the Rhynchonellida have very low consistency indices on the topology preferred by the combined Bayesian analyses. Overall, this casts doubt on the use of morphological systematics to resolve relationships among the crown rhynchonellide brachiopods. However, expanding our dataset to a larger number of extinct taxa with intermediate morphologies is necessary to exclude the possibility that the morphology of extant taxa is not dominated by convergence along long branches.


Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology-Like Setting.
Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time-point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. When diurnal variation is larger than the inter-individual variation, time of day should be taken into account. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food). The aim of the present study was to determine whether a set of often used biomarkers shows diurnal variation in a setting resembling large molecular epidemiology studies, i.e., non-fasted and limited control possibilities for other environmental influences. We show that markers for which diurnal variation is not an issue are adrenocorticotropic hormone, follicle stimulating hormone, estradiol and high-density lipoprotein. For all other tested markers diurnal variation was observed in at least one gender (cholesterol, cortisol, dehydroepiandrosterone sulfate, free fatty acids, low-density lipoprotein, luteinizing hormone, prolactin, progesterone, testosterone, triglycerides, total triiodothyronine and thyroid-stimulating hormone) or could not reliably be detected (human growth hormone). Thus, studies investigating these markers should take diurnal variation into account, for which we provide some options. Furthermore, our study indicates the need for investigating diurnal variation (in literature or experimentally) before setting up studies measuring markers in routine and controlled settings, especially since time-of-day likely matters for many more markers than the ones investigated in the present study.


The Post-illumination Pupil Response (PIPR) Is Associated With Cognitive Function in an Epidemiologic Cohort Study.
We conducted a cross-sectional study on 403 participants in the 10-year follow-up examination of the Beaver Dam Offspring Study. The participants included 172 male and 231 female, with age ranging from 33 to 81 years (mean ± SD, 60.7 ± 9.3). The post-illumination pupil response (PIPR) was recorded using binocular infrared pupillometer (Neur-Optics, Inc., Irvine, CA). Cognitive testing consisted of Trail Making Test (TMT) Parts A and B, Rey Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Verbal Fluency Test (VFT) (F, A, and S). Principal component analysis (PCA) was used to calculate an overall cognitive function score. There was a significant reduction in the mean baseline pupil diameter by 0.21 mm for every 5-year increase in age (95% CI: -0.25, -0.17). There was also a significant increase in the PCA cognitive score by 0.20 (linear regression, 95% CI: 0.08, 0.32) for every 0.1 unit increase in the PIPR. The association remained significant after adjusting for age, sex, education, medications, systemic and ocular disease, and short form-12 physical and mental component score. The results of this study demonstrated a modest association between the PIPR and cognitive function, warranting longitudinal studies to evaluate the role of the PIPR in predicting cognitive function in the middle-aged and older adults.


Effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation.
Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides -0.14 mmol/l, p=0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio -0.25, p=0.001), LDL particle size increased (median difference +0.45 nm, p=0.048) and hsCRP decreased (median difference -0.18 mg/l, p=0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. ClinicalTrials.gov NCT01130948.


Are Health Facility Management Committees in Kenya ready to implement financial management tasks: findings from a nationally representative survey.
Community participation in peripheral public health facilities has in many countries focused on including community representatives in Health Facility Management Committees (HFMCs). In Kenya, HFMC roles are being expanded with the phased implementation of the Health Sector Services Fund (HSSF). Under HSSF, HFMCs manage facility funds which are dispersed directly from central level into facility bank accounts. We assessed how prepared HFMCs were to undertake this new role in advance of HSSF roll out, and considered the implications for Kenya and other similar settings. Data were collected through a nationally representative sample of 248 public health centres and dispensaries in 24 districts in 2010. Data collection included surveys with in-charges (n = 248), HFMC members (n = 464) and facility users (n = 698), and record reviews. These data were supplemented by semi-structured interviews with district health managers in each district. Some findings supported preparedness of HFMCs to take on their new roles. Most facilities had bank accounts and HFMCs which met regularly. HFMC members and in-charges generally reported positive relationships, and HFMC members expressed high levels of motivation and job satisfaction. Challenges included users' low awareness of HFMCs, lack of training and clarity in roles among HFMCs, and some indications of strained relations with in-charges. Such challenges are likely to be common to many similar settings, and are therefore important considerations for any health facility based initiatives involving HFMCs. Most HFMCs have the basic requirements to operate. However to manage their own budgets effectively and meet their allocated roles in HSSF implementation, greater emphasis is needed on financial management training, targeted supportive supervision, and greater community awareness and participation. Once new budget management roles are fully established, qualitative and quantitative research on how HFMCs are adapting to their expanded roles, especially in financial management, would be valuable in informing similar financing mechanisms in Kenya and beyond.


Why do captive tufted capuchins (Cebus apella) urine wash?
Urine washing (UW) has been observed in numerous species of prosimians and New World monkeys. The functional significance of UW in Cebidae, specifically, Cebus apella, has not been determined. The objective of our study was to test two major hypotheses related to the function of UW: (1) UW functions as a thermoregulatory mechanism, and (2) UW functions as a means of social communication related to (a) territoriality, (b) sexual encounters, or (c) intragroup aggression/agitation. We collected focal data on a captive group of 28 tufted capuchins (C. apella; July-October 2004 and February-July 2005). We found no significant correlation between UW rates and temperature, at a constant, moderate humidity level. Rates of UW were significantly greater outdoors (no conspecific neighbors) vs. indoors (conspecific neighbors). Qualitative evidence suggests a relationship between UW by the alpha male and sexual solicitations from females. UW rates associated with aggression received were significantly higher than UW rates associated with aggression given and UW rates associated with potential fear/stress. There was also a significant negative correlation between cortisol measures and UW frequencies. Our results suggest that UW does not function in thermoregulation or in territorial communication. Alternatively, our results suggest that UW may be associated with sexual encounters and receiving aggression. Additionally, further investigation is warranted to determine whether UW is used as an appeasement mechanism or as a stress reliever or as both.


Eighth International Chorea-Acanthocytosis Symposium: Summary of Workshop Discussion and Action Points.
Chorea-Acanthocytosis (ChAc) is a rare hereditary neurological disorder characterized by abnormal movements, red blood cell pathology, and progressive neurodegeneration. Little is understood of the pathogenesis of ChAc and related disorders (collectively Neuroacanthocytosis). The Eighth International Chorea-Acanthocytosis Symposium was held in May 2016 in Ann Arbor, MI, USA, and focused on molecular mechanisms driving ChAc pathophysiology. Accompanying the meeting, members of the neuroacanthocytosis research community and other invited scientists met in a workshop to discuss the current understanding and next steps needed to better understand ChAc pathogenesis. These discussions identified several broad and critical needs for advancing ChAc research and patient care, and led to the definition of 18 specific action points related to functional and molecular studies, animal models, and clinical research. These action points, described below, represent tractable research goals to pursue for the next several years.


De novo transcriptome analysis of Perna viridis highlights tissue-specific patterns for environmental studies.
The tropical green-lipped mussel Perna viridis is a common biomonitor throughout the Indo-Pacific region that is used for environmental monitoring and ecotoxicological investigations. However, there is limited molecular data available regarding this species. We sought to establish a global transcriptome database from the tissues of adductor muscle, gills and the hepatopancreas of P. viridis in an effort to advance our understanding of the molecular aspects involved during specific toxicity responses in this sentinel species. Illumina sequencing results yielded 544,272,542 high-quality filtered reads. After de novo assembly using Trinity, 233,257 contigs were generated with an average length of 1,264 bp and an N50 length of 2,868 bp; 192,879 assembled transcripts and 150,111 assembled unigenes were obtained after clustering. A total of 93,668 assembled transcripts (66,692 assembled genes) with putative functions for protein domains were predicted based on InterProScan analysis. Based on similarity searches, 44,713 assembled transcripts and 25,319 assembled unigenes were annotated with at least one BLAST hit. A total of 21,262 assembled transcripts (11,947 assembled genes) were annotated with at least one well-defined Gene Ontology (GO) and 5,131 assembled transcripts (3,181 assembled unigenes) were assigned to 329 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The quantity of assembled unigenes and transcripts obtained from male and female mussels were similar but varied among the three studied tissues, with the highest numbers recorded in the gills, followed by the hepatopancreas, and then the adductor muscle. Multivariate analyses revealed strong tissue-specific patterns among the three different tissues, but not between sexes in terms of expression profiles for annotated genes in various GO terms, and genes associated with stress responses and degradation of xenobiotics. The expression profiles of certain selected genes in each tissue type were further validated using real-time quantitative polymerase chain reaction assays and a similar tissue-specific trend was seen. The extensive sequence data generated from this study will provide a valuable molecular resource for facilitating environmental studies with P. viridis, and highlight the importance of tissue-specific approaches in the future.


Population structure and intraspecific aggression in the invasive ant species Anoplolepis gracilipes in Malaysian Borneo.
Invasive species are one of the main sources of the ongoing global loss of biodiversity. Invasive ants are known as particularly damaging invaders and their introductions are often accompanied by population-level behavioural and genetic changes that may contribute to their success. Anoplolepis gracilipes is an invasive ant that has just recently received increased attention due to its negative impact on native ecosystems. We examined the behaviour and population structure of A. gracilipes in Sabah, Malaysia. A total of 475 individuals from 24 colonies were genotyped with eight microsatellite markers. Intracolonial relatedness was high, ranging from 0.37 to 1 (mean +/- SD: 0.82 +/- 0.04), while intercolonial relatedness was low (0.0 +/- 0.02, range -0.5-0.76). We compared five distinct sampling regions in Sabah and Brunei. A three-level hierarchical F-analysis revealed high genetic differentiation among colonies within the same region, but low genetic differentiation within colonies or across regions. Overall levels of heterozygosity were unusually high (mean H(O) = 0.95, mean H(E) = 0.71) with two loci being entirely heterozygous, indicating an unusual reproductive system in this species. Bioassays revealed a negative correlation between relatedness and aggression, suggesting kinship as one factor facilitating supercolony formation in this species. Furthermore, we genotyped one individual per nest from Sabah (22 nests), Sarawak (one nest), Brunei (three nests) and the Philippines (two nests) using two mitochondrial DNA markers. We found six haplotypes, two of which included 82.1% of all sequences. Our study shows that the sampled area in Sabah consists of a mosaic of differently interrelated nests in different stages of colony establishment. While some of the sampled colonies may belong to large supercolonies, others are more likely to represent recently introduced or dispersed propagules that are just beginning to expand.


A Structural Study of CESA1 Catalytic Domain of Arabidopsis Cellulose Synthesis Complex: Evidence for CESA Trimers.
A cellulose synthesis complex with a "rosette" shape is responsible for synthesis of cellulose chains and their assembly into microfibrils within the cell walls of land plants and their charophyte algal progenitors. The number of cellulose synthase proteins in this large multisubunit transmembrane protein complex and the number of cellulose chains in a microfibril have been debated for many years. This work reports a low resolution structure of the catalytic domain of CESA1 from Arabidopsis (Arabidopsis thaliana; AtCESA1CatD) determined by small-angle scattering techniques and provides the first experimental evidence for the self-assembly of CESA into a stable trimer in solution. The catalytic domain was overexpressed in Escherichia coli, and using a two-step procedure, it was possible to isolate monomeric and trimeric forms of AtCESA1CatD. The conformation of monomeric and trimeric AtCESA1CatD proteins were studied using small-angle neutron scattering and small-angle x-ray scattering. A series of AtCESA1CatD trimer computational models were compared with the small-angle x-ray scattering trimer profile to explore the possible arrangement of the monomers in the trimers. Several candidate trimers were identified with monomers oriented such that the newly synthesized cellulose chains project toward the cell membrane. In these models, the class-specific region is found at the periphery of the complex, and the plant-conserved region forms the base of the trimer. This study strongly supports the "hexamer of trimers" model for the rosette cellulose synthesis complex that synthesizes an 18-chain cellulose microfibril as its fundamental product.


Systematic review of primary osseointegrated dental implants in head and neck oncology.
The aim of this paper is to provide a systematic review of articles concerning primary osseointegrated dental implants in the head and neck oncology setting. We searched MEDLINE (1950 to March 2009) and Embase (1980 to March 2009) using the terms head and neck, oral, maxillofacial, craniofacial, jaws, mandible, maxilla, zygoma, dental implants, osseointegrated implants, implants, tumour, cancer, oncology, immediate, simultaneous, and primary. Two authors independently reviewed the abstracts, and all those written in the English language that referred to the placement of primary dental implants in patients with cancer of the head neck were included. Articles that referred to craniofacial or extraoral implants were excluded. Of 892 abstracts 83 were eligible for further consideration; the full articles were evaluated, and 41 that complied fully with the inclusion criteria are presented as a tabulated summary. There are three case reports, 13 reviews, and 25 clinical studies. Eight of the clinical studies refer solely to the insertion of dental implants at the time of primary oncological resection, and only two were of a prospective design. We have concisely summarised publications concerning primary dental implants, and our findings will help to inform head and neck cancer teams, particularly oncological surgeons, restorative dentists, and maxillofacial prosthodontists of the evidence base surrounding this approach to oral rehabilitation.


Association between 5-HTTLPR and Borderline Personality Disorder Traits among Youth.
This study provides the first genetic association examination of borderline personality disorder (BPD) traits in children and adolescents (ages 9-15) using two independent samples of youth recruited from the general community. We tested the a priori hypothesis that the serotonin transporter promoter gene (5-HTTLPR) would relate specifically to BPD traits in youth. This association was hypothesized based on prior genetic association research with BPD adults and theory positing that emotion dysregulation may be a core risk process contributing to BPD. Youth provided DNA via buccal cells. Both youth and a parent completed self-report measures assessing youth's BPD traits and depressive symptoms. Results from both Study 1 (N = 242) and an independent replication sample of Study 2 (N = 144) showed that carriers of the short allele of 5-HTTLPR exhibited the highest levels of BPD traits. This relation was observed even after controlling for the substantial co-occurrence between BPD traits and depressive symptoms. This specific association between 5-HTTLPR and BPD traits among youth supports previous genetic associations with adults diagnosed with BPD and provides preliminary support for a developmental extension of etiological risk for BPD among youth.


Linear Methods for Efficient and Fast Separation of Two Sources Recorded with a Single Microphone.
This letter addresses the problem of separating two speakers from a single microphone recording. Three linear methods are tested for source separation, all of which operate directly on sound spectrograms: (1) eigenmode analysis of covariance difference to identify spectro-temporal features associated with large variance for one source and small variance for the other source; (2) maximum likelihood demixing in which the mixture is modeled as the sum of two gaussian signals and maximum likelihood is used to identify the most likely sources; and (3) suppression-regression, in which autoregressive models are trained to reproduce one source and suppress the other. These linear approaches are tested on the problem of separating a known male from a known female speaker. The performance of these algorithms is assessed in terms of the residual error of estimated source spectrograms, waveform signal-to-noise ratio, and perceptual evaluation of speech quality scores. This work shows that the algorithms compare favorably to nonlinear approaches such as nonnegative sparse coding in terms of simplicity, performance, and suitability for real-time implementations, and they provide benchmark solutions for monaural source separation tasks.


Efficacy and side effects of 'swinging eyelid' orbital decompression in Graves' orbitopathy: a proposal for standardized evaluation of diplopia.
To evaluate the efficacy and side effects of 'swinging eyelid' orbital decompression in patients with Graves' orbitopathy (GO). To calculate the incidence of postoperative new-onset diplopia (NOD) using a newly proposed scoring system for diplopia. We reviewed the clinical data on proptosis, visual acuity, and diplopia in 104 consecutive patients (198 orbits) with GO, who underwent orbital decompression. A combined lateral canthal and inferior fornix incision ('swinging eyelid' approach) was used for removal of the medial wall, the orbital floor and, if indicated, the lateral wall. Indications for surgery were disfiguring/congestive GO (DGO) in 79 patients (149 orbits) and compressive optic neuropathy (CON) in 25 patients (49 orbits). Diplopia was scored according to four grades. In both groups, the incidence of new-onset (continuous) diplopia (NOD), deterioration of diplopia (DOD), and improvement of diplopia (IOD) were calculated, using strictly defined criteria. Our data on NOD were compared to those from other series, after recalculation according to our criteria. The mean proptosis reduction was 4.6 mm (range 0-9.5 mm) after three-wall decompression (95 patients, 180 orbits) vs 3.1 mm (range 0-7 mm) after two-wall decompression (nine patients, 18 orbits). The visual acuity improved in 98% of the patients with CON. In patients with DGO, NOD occurred in 14%. In patients with CON, NOD was not observed, but DOD occurred in 41%. Our data compare favourably to the reported incidence of NOD after either transantral or transnasal decompression. "Swinging eyelid' orbital decompression is efficacious for proptosis reduction as well as for optic nerve decompression. A scoring system for standardized evaluation of diplopia is proposed.


Nonexercise activity thermogenesis--liberating the life-force.
Obesity occurs when energy intake exceeds energy expenditure over a protracted period of time. The energy expenditure associated with everyday activity is called NEAT (Nonexercise activity thermogenesis). NEAT varies between two people of similar size by 2000 kcal day(-1) because of people's different occupations and leisure-time activities. Data support the central hypothesis that NEAT is pivotal in the regulation of human energy expenditure and body weight regulation and that NEAT is important for understanding the cause and effective treatment for obesity.


Human amniotic epithelial cells as novel feeder layers for promoting ex vivo expansion of limbal epithelial progenitor cells.
Human amniotic epithelial cells (HAECs) are a unique embryonic cell source that potentially can be used as feeder layers for expanding different types of stem cells. In vivo, HAECs uniformly expressed pan-cytokeratins (pan-CK) and heterogeneously expressed vimentin (Vim). The two phenotypes expressing either pan-CK(+)/Vim(+) or pan-CK(+)/Vim(-) were maintained in serum-free media with high calcium. In contrast, all HAECs became pan-CK(+)/Vim(+) in serum-containing media, which also promoted HAEC proliferation for at least eight passages, especially supplemented with epidermal growth factor and insulin. Mitomycin C-arrested HAEC feeder layers were more effective in promoting clonal growth of human limbal epithelial progenitors than conventional 3T3 murine feeder layers. Cells in HAEC-supported clones were uniformly smaller, sustained more proliferation, and expressed less CK12 and connexin 43 but higher levels of stem cell-associated markers such as p63, Musashi-1, and ATP-binding cassette subfamily G2 than those of 3T3-supported clones. Subculturing of clonally expanded limbal progenitors from HAEC feeder layers, but not from 3T3 feeder layers, gave rise to uniformly p63-positive epithelial progenitor cells as well as nestin-positive neuronal-like progenitors. Collectively, these results indicated that HAECs can be used as a human feeder layer equivalent for more effective ex vivo expansion of adult epithelial stem cells from the human limbus. Disclosure of potential conflicts of interest is found at the end of this article.


Cardiovascular events in chronic myeloid leukemia clinical trials. Is it time to reassess and report the events according to cardiology guidelines?
Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML). Although these treatments have changed the natural course of CML and many other cancers, they may cause cardiovascular and/or metabolic complications. In this review, we discuss how overlooking the main drivers of cardiovascular events (CVEs) and lack of standard definitions for cardiovascular adverse events might have affected these event rates in CML trials. Methodological limitations that affect the available data are discussed, with an emphasis on the future direction of cardiovascular safety research in trials of investigational drugs in cancer treatment.


The epidemiology of tuberculosis in health care workers in South Africa: a systematic review.
In South Africa, workplace acquired tuberculosis (TB) is a significant occupational problem among health care workers. In order to manage the problem effectively it is important to know the burden of TB in health care workers. This systematic review describes the epidemiology of TB in South African health care workers. A comprehensive search of electronic databases [MEDLINE, EMBASE, Web of Science (Social Sciences Citation Index/Science Citation Index), Cochrane Library (including CENTRAL register of Controlled Trials), CINAHL and WHO International Clinical Trials Registry Platform (ICTRP)] was conducted up to April 2015 for studies reporting on any aspect of TB epidemiology in health care workers in South Africa. Of the 16 studies included in the review, ten studies reported on incidence of active TB disease in health care workers, two report on the prevalence of active TB disease, two report on the incidence of latent TB infection, three report on the prevalence of latent TB infection and four studies report on the number of TB cases in health care workers in various health care facilities in South Africa. Five studies provide information on risk factors for TB in health care workers. All of the included studies were conducted in publicly funded health care facilities; predominately located in KwaZulu-Natal and Western Cape provinces. The majority of the studies reflect a higher incidence and prevalence of active TB disease in health care workers, including drug-resistant TB, compared to the surrounding community or general population. There is relatively little research on the epidemiology of TB in health care workers in South Africa, despite the importance of the issue. To determine the true extent of the TB epidemic in health care workers, regular screening for TB disease should be conducted on all health care workers in all health care facilities, but future research is required to investigate the optimal approach to TB screening in health care workers in South Africa. The evidence base shows a high burden of both active and latent TB in health care workers in South Africa necessitating an urgent need to improve existing TB infection, prevention and control measures in South African health care facilities.


Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines.
The F11 Receptor (F11R; aka JAM-A, JAM-1) is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs). Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the de-novo transcription and translation of F11R molecules, induced in ECs by exposure to inflammatory cytokines. The experimental approach utilized isolated, washed human platelet suspensions and cultured human venous endothelial cells (HUVEC) and human arterial endothelial cells (HAEC) exposed to the proinflammatory cytokines TNF-alpha and/or IFN-gamma, for examination of the ability of human platelets to adhere to the inflamed ECs thru the F11R. Our strategy was based on testing the effects of the following inhibitors on this activity: general mRNA synthesis inhibitors, inhibitors of the NF-kappaB and JAK/STAT pathways, and small interfering F11R-mRNA (siRNAs) to specifically silence the F11R gene. Treatment of inflamed ECs with the inhibitors actinomycin, parthenolide or with AG-480 resulted in complete blockade of F11R- mRNA expression, indicating the involvement of NF-kappaB and JAK/STAT pathways in this induction. Transfection of ECs with F11R siRNAs caused complete inhibition of the cytokine-induced upregulation of F11R mRNA and inhibition of detection of the newly- translated F11R molecules in cytokine-inflamed ECs. The functional consequence of the inhibition of F11R transcription and translation was the significant blockade of the adhesion of human platelets to inflamed ECs. These results prove that de novo synthesis of F11R in ECs is required for the adhesion of platelets to inflamed ECs. Because platelet adhesion to an inflamed endothelium is crucial for plaque formation in non-denuded blood vessels, we conclude that the de-novo translation of F11R is a crucial early step in the initiation of atherogenesis, leading to atherosclerosis, heart attacks and stroke.


Analysis of the treadmilling model during metaphase of mitosis using fluorescence redistribution after photobleaching.
One recent hypothesis for the mechanism of chromosome movement during mitosis predicts that a continual, uniform, poleward flow or "treadmilling" of microtubules occurs within the half-spindle between the chromosomes and the poles during mitosis (Margolis, R. L., and L. Wilson, 1981, Nature (Lond.), 293:705-711). We have tested this treadmilling hypothesis using fluorescent analog cytochemistry and measurements of fluorescence redistribution after photobleaching to examine microtubule behavior during metaphase of mitosis. Mitotic BSC 1 mammalian tissue culture cells or newt lung epithelial cells were microinjected with brain tubulin labeled with 5-(4,6-dichlorotriazin-2-yl) amino fluorescein (DTAF) to provide a fluorescent tracer of the endogenous tubulin pool. Using a laser microbeam, fluorescence in the half-spindle was photobleached in either a narrow 1.6 micron wide bar pattern across the half-spingle or in a circular area of 2.8 or 4.5 micron diameter. Fluorescence recovery in the spindle fibers, measured using video microscopy or photometric techniques, occurs as bleached DTAF-tubulin subunits within the microtubules are exchanged for unbleached DTAF-tubulin in the cytosol by steady-state microtubule assembly-disassembly pathways. Recovery of 75% of the bleached fluorescence follows first-order kinetics and has an average half-time of 37 sec, at 31-33 degrees C. No translocation of the bleached bar region could be detected during fluorescence recovery, and the rate of recovery was independent of the size of the bleached spot. These results reveal that, for 75% of the half-spindle microtubules, FRAP does not occur by a synchronous treadmilling mechanism.


Conjugative transposition of Tn916 requires the excisive and integrative activities of the transposon-encoded integrase.
Transposon Tn916 is a 16.4-kb broad-host-range conjugative transposon originally detected in the chromosome of Enterococcus faecalis DS16. Transposition of Tn916 and related transposons involves excision of a free, nonreplicative, covalently closed circular intermediate that is substrate for integration. Excisive recombination requires two transposon-encoded proteins, Xis-Tn and Int-Tn, whereas the latter protein alone is sufficient for integration. Here we report that conjugative transposition of Tn916 requires the presence of a functional integrase in both donor and recipient strains. We have constructed a mutant, designated Tn916-int1, by replacing the gene directing synthesis of Int-Tn by an allele inactivated in vitro. In mating experiments, transfer of Tn916-int1 from Bacillus subtilis to E. faecalis was detected only when the transposon-encoded integrase was supplied by trans-complementation in both the donor and the recipient. These results suggest that conjugative transposition of Tn916 requires circularization of the element in the donor followed by transfer and integration of the nonreplicative intermediate in the recipient.


Perceptions of local health care quality in 7 rural communities with telemedicine.
Rural health services are difficult to maintain because of low patient volumes, limited numbers of providers, and unfavorable economies of scale. Rural patients may perceive poor quality in local health care, directly impacting the sustainability of local health care services. This study examines perceptions of local health care quality in 7 rural, underserved communities where telemedicine was implemented. This study also assesses factors associated with travel outside of local communities for health care services. Community-based pretelemedicine and posttelemedicine random telephone surveys were conducted in 7 northern California rural communities assessing local residents' perceptions of health care quality and the frequency of travel outside their community for health care services. Five-hundred rural residents were interviewed in each of the pretelemedicine and posttelemedicine surveys. Between surveys, telemedicine services were made available in each of the communities. Residents aware of telemedicine services in their community had a significantly higher opinion of local health care quality (P =.002). Satisfaction with telemedicine was rated high by both rural providers and patients. Residents with lower opinions of local health care quality were more likely to have traveled out of their community for medical care services (P =.014). The introduction of telemedicine into rural communities is associated with increases in the local communities' perception of local health care quality. Therefore, is it possible that telemedicine may result in a decrease in the desire and need for local patients to travel outside of their community for health care services.


Cognitive and Neuroanatomical Correlates in Early Versus Late Onset Parkinson's Disease Dementia.
Aging is the most important risk factor of development of dementia in Parkinson's disease (PD), but there are no data on clinical and radiological heterogeneity of PD dementia (PDD) depending on age at onset. The goal of this study was to examine whether patients with PDD are clinically and radiologically heterogeneous depending on age at onset. A total of 116 patients with PD dementia and 121 age- and sex-matched normal controls were enrolled. The subjects were divided into early-onset (EOPDD; n = 39) and late-onset (LOPDD; n = 77) PDD with the respective age-matched control group based on a cutoff value of 70 years. The effects of diagnosis, age, and their interaction on neuropsychological tests, cortical thickness, and substantia innominata volume were assessed using analysis of covariance. EOPDD patients had a poorer cognitive performance on digit backward, forward span test (p = 0.011 and 0.05), and visual recognition memory function (p = 0.012) compared with LOPDD patients. Additionally, EOPDD patients exhibited cortical thinning in the left anterior cingulate gyrus and the right inferior temporal gyrus, with significantly decreased normalized substantia innominata volume (p = 0.044). Our data demonstrated that EOPDD patients exhibit poorer cognitive performance and more severe atrophy in the cortex and substantia innominata, implying that EOPDD may be a distinct phenotype different from LOPDD.


Association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity.
Various methods have been proposed to evaluate a patient's developmental status. However, most of them lacked precision and failed to give a reliable estimate of skeletal maturity. The aims of this study were to evaluate the association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity and to determine its validity in assessing the different stages of the adolescent growth spurt. A cross-sectional study was performed on the pretreatment lateral cephalograms of 252 subjects aged 8 to 21 years. The sample was divided into 6 groups based on the cervical vertebral maturation stages. The frontal sinus index was calculated by dividing the frontal sinus height and width, and the cervical stages were evaluated on the same radiograph. The Kruskal-Wallis test was applied to compare frontal sinus index values at different cervical stages, and the post hoc Dunnett T3 test was applied to compare frontal sinus index values between adjacent cervical stages for each sex. The Kendall tau-b values were computed to assess the correlation between the cervical stages and the sinus index. A P value of ≤0.05 was considered statistically significant. The height and width of the frontal sinus were significantly larger in the male subjects than in the females. A significant association was found between the frontal sinus height and width and cervical stages (P ≤0.001) in both sexes. However, the changes in the frontal sinus index across the different cervical stages were found to be significant (P ≤0.001) in male subjects only. Similarly, a weak negative correlation was found between the sinus index and the cervical stages in male subjects (tau-b = -0.271; P <0.001), whereas no correlation was found in female subjects (tau-b = -0.006; P <0.928). However, the post hoc analysis showed that the values of the sinus index were comparable between any 2 adjacent cervical stages. The frontal sinus index cannot be used to identify the prepubertal, pubertal, and postpubertal stages of the adolescent growth spurt. Therefore, it cannot be used as a reliable maturity indicator.


The potential of synthetic indolylquinoline derivatives for Aβ aggregation reduction by chemical chaperone activity.
Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular β-amyloid (Aβ) is a major constituent of senile plaques, one of the pathological hallmarks of AD. Aβ deposition causes neuronal death via a number of possible mechanisms such as increasing oxidative stress. Therefore therapeutic approaches to identify novel Aβ aggregate reducers could be effective for AD treatment. Using a Trx-His-Aβ biochemical assay, we screened 11 synthetic indolylquinoline compounds, and found NC009-1, -2, -6 and -7 displaying potential to reduce Aβ aggregation. Treating Tet-On Aβ-GFP 293 cells with these compounds reduced Aβ aggregation and reactive oxygen species. These compounds also promoted neurite outgrowth in Tet-On Aβ-GFP SH-SY5Y cells. Furthermore, treatment with above compounds improved neuronal cell viability, neurite outgrowth, and synaptophysin expression level in mouse hippocampal primary culture under oligomeric Aβ-induced cytotoxicity. Moreover, the tested NC009-1 significantly ameliorated Aβ-induced inhibition of hippocampal long-term potentiation in mouse hippocampal slices. Our results demonstrate how synthetic indolylquinoline compounds are likely to work as chemical chaperones in Aβ-aggregation reduction and neuroprotection, providing insight into the possible applications of indolylquinoline compounds in AD treatment.


Epidemiologic features of asymptomatic cerebral infarction in patients with nonvalvular atrial fibrillation.
We performed unenhanced computed tomographic scans on 141 asymptomatic patients with nonvalvular atrial fibrillation. Thirty-six patients (26%) had hypodense areas consistent with cerebral infarction. The majority of these were small deep infarcts, seen in 29 patients (21%), but 13 patients (9%) had cortical or large deep infarctions. Twelve patients had more than one infarct on computed tomographic scan. Increasing age and increased left atrial diameter were the only clinical features associated with asymptomatic infarction. Patients older than 65 years with a left atrial diameter greater than 5.0 cm (n = 23) had a 52% prevalence of asymptomatic infarction. Patients younger than 65 years with a left atrial diameter less than 5.0 cm (n = 38) had an 11% prevalence of silent infarction. Patients with only one of these risk factors (n = 72) had a 24% prevalence of silent infarction. Infarction was more common in those with chronic (34%) as opposed to intermittent (22%) nonvalvular atrial fibrillation, but this difference was not significant. Hypertension, diabetes, duration of atrial fibrillation, congestive heart failure, history of myocardial infarction, and echocardiographic evidence of left ventricular dysfunction were not associated with asymptomatic infarction. A history of hypertension was present in only 35% of our patients with small-deep asymptomatic infarction, similar to the percentage in patients without stroke. Asymptomatic cerebral infarction is common in nonvalvular atrial fibrillation. The association with enlarged left atria and the lack of correlation with major cerebrovascular risk factors suggests a cardioembolic mechanism. Further study is needed to determine the functional and prognostic significance of these strokes.


First Report of Brown Root Rot of Alfalfa Caused by Phoma sclerotioides in Wisconsin.
Brown root rot (BRR) has been associated with winterkill of alfalfa (Medicago sativa L.) in the temperate regions of North America where winters are severe (1). Although suspected, BRR has not been associated with winterkill of alfalfa in the upper Midwestern United States. Alfalfa plants exhibiting symptoms resembling those induced by the causal agent Phoma sclerotioides G. Preuss ex Sacc. were collected from fields in Marinette, Pierce, and Marathon counties in Wisconsin during the spring and early summer of 2003. Symptoms included stunting and decline in 1- to 3-year-old plants that were slow to break dormancy in the early spring. Roots frequently exhibited dark brown lesions or were entirely decayed. Advanced lesions often formed dark bands around the circumference of tap and secondary roots. Beaked pycnidial structures typical of P. sclerotioides were also observed on many samples with advanced lesions. Plants with symptoms of BRR were also observed in Clark, Langlade, Lincoln, Oconto, Shawno, Taylor, and Wood counties. Several lesion areas of tissue on the tap and lateral roots of each sample were excised with a sterile scalpel. Total DNA was extracted using the Fast DNA kit (Bio 101, Carlsbad, CA). In addition, soil samples were collected in the root rhizosphere of symptomatic plants from four fields in two counties. Soil DNA was extracted with the Ultra-Clean DNA soil extraction kit (Mo Bio, Solana Beach, CA). DNA extractions were diluted 1:10 or 1:50, and samples were evaluated for the presence of P. sclerotioides using polymerase chain reaction (PCR)-based sequence-characterized amplified region (SCAR) markers according to the method described previously (4). Amplicons of the expected size (499 bp) were detected from alfalfa roots sampled from Marathon (4 of 4), Marinette (4 of 5), and Pierce (4 of 4) counties but not in roots from healthy controls produced in the greenhouse at Prosser, WA. PCR amplicons were also produced from all field soil samples in Marathon and Marinette counties. Proof of pathogenicity via Koch's postulates for this host-pathogen system was not attempted because of the extensive time period required (1). However, characteristic beaked pycnidia were present, and the pathogen was identified using PCR on DNA from roots symptomatic of BRR. Detection of BRR has been limited in the United States to Wyoming (2), but has been thought to occur in other states with severe winters (3). To our knowledge, this is the first report of P. sclerotioides in Wisconsin. References: (1) J. G. N. Davidson. Brown root rot. Pages 29-31 in: Compendium of Alfalfa Diseases. 2nd ed. D. L. Stuteville and D. C. Erwin, eds. The American Phytopathological Society, St. Paul, MN, 1990. (2) F. A. Gray et al. Pages 27-28 in: Proc. 10th Western Alfalfa Improv. Conf., 1997. (3) C. R. Hollingsworth et al. Can. J Plant Pathol. 25:215, 2003. (4) R. C. Larsen et al. Plant Dis. 86:928, 2002.


A murine model to characterize the antithrombotic effect of molecules targeting human von Willebrand factor.
von Willebrand factor (VWF) is a promising target for developing antithrombotic drugs. The absence of accessible animal models impedes the study of specific human VWF (huVWF) targeting molecules in thrombosis. huVWF is not functional in the mouse because of a lack of interaction between huVWF and murine glycoprotein Ib. Using site-directed mutagenesis, we have replaced single or multiple amino acids in huVWF with their murine counterparts to eliminate species incompatibility. Using hydrodynamic injection, we have expressed the different chimeric VWF constructs into VWF(-/-) mice. Only huVWF with a complete murine A1 domain insertion was able to correct bleeding in vivo and form occlusive thrombi in mesenteric vessels after FeCl(3) treatment. Using this model, we tested the antithrombotic effect of monoclonal antibodies against huVWF, blocking its interaction with collagens (mAbs 203 and 505) or with glycoprotein IIbIIIa (mAb 9). The 3 mAbs inhibited the thrombotic process in arterioles of VWF(-/-) mice expressing huVWFmuA1. Inhibiting VWF-interaction with collagens was more potent, emphasizing the potential of such a target as an antithrombotic tool. Our results validate our murine model as a simple in vivo tool to evaluate anti-huVWF agents.


Expression of mammalian paralogues of HRAD9 and Mrad9 checkpoint control genes in normal and cancerous testicular tissue.
Human and mouse paralogues of the evolutionarily conserved mammalian HRAD9 and Mrad9 cell cycle checkpoint control genes have been isolated and called HRAD9B and Mrad9B, respectively. HRAD9B encodes a protein that is 414 amino acids long and is 55% similar and 35% identical to the HRAD9 gene product. The Mrad9B protein is 398 amino acids long and is 50% similar and 35% identical to its paralogue. We demonstrate that the encoded human protein is nuclear and can physically interact with checkpoint proteins HRAD1, HRAD9, HHUS1, and HHUS1B, much like HRAD9. Northern blot analysis to detect tissue specificity indicates that the human and mouse genes are expressed predominantly in the testis. The abundance of HRAD9B RNA, as judged by quantitative reverse transcription-PCR, is very low in most testicular tumors, particularly those of germ cell origin, i.e., seminomas, relative to normal testis control, nonseminomas, or Leydig tumor cells. RNA levels corresponding to HRAD17, another checkpoint control gene, demonstrated a similar pattern, but in general, higher quantities of this message were detected in samples. Furthermore, normal/tumor tissue differences were not as dramatic or consistent from sample to sample, especially for the seminomas. Our results demonstrate for the first time that HRAD9 and Mrad9 are part of a gene family and reveal a new genetic element encoding a product that interacts with multiple, known cell cycle checkpoint control proteins. The findings also indicate that HRAD9B can serve as a biomarker in particular for testicular seminomas and might be causally related to the disease.


The Theory of Industrial Society and Cultural Schemata: Does the "Cultural Myth of Stigma" Underlie the WHO Schizophrenia Paradox?
The WHO's International Studies of Schizophrenia conclude that schizophrenia may have a more benign course in "developing" societies than in the West. The authors focus on this finding's most common corollary: cultural schemata are shaped by the transition from agrarian to industrial society. Developing societies are viewed as traditional, gemeinschaft cultures lacking the stigmatizing beliefs about persons with mental illness held in modern, gesellschaft cultures of developed societies. The Stigma in Global Context-Mental Health Study formalized the cultural myth of public stigma (CMPS) with propositions linking level of development to intolerant, exclusionary, and individualistic attitudes. In 17 countries, the authors find no support for the corollary; where support is found, the findings are opposite expectations, with developed societies reporting lower stigma levels. Reconceptualizing of the cultural landscape on more specific dimensions also produces null or contrary findings. This correction to nostalgic myths of cultural context in developing societies thwarts misguided treatment, policy, and stigma-reduction efforts.


Anti-TNF-α treatment for pelvic pain associated with endometriosis.
Endometriosis is a chronic, recurring condition that can develop during the reproductive years. It is characterised by the development of endometrial tissue outside the uterine cavity. It is the most common cause of pelvic pain in women. This endometrial tissue development is dependent on oestrogen produced primarily by the ovaries and, therefore, traditional management has focused on suppression of ovarian function. Mounting evidence shows that altered immune function plays a crucial role in the genesis and development of endometriosis. In this review we considered modulation of the inflammation as an alternative approach. To determine the effectiveness and safety of anti-tumour necrosis factor-α (anti-TNF-α) treatment in the management of endometriosis in premenopausal women. For the first publication of this review, we searched for trials in the following databases (from their inception to August 2009): Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and PsycINFO. In addition, we searched all reference lists of included trials and contacted experts in the field in an attempt to locate trials. We reran this search to 3 September 2012 for this update. Randomised controlled trials (RCTs) comparing anti-TNF-α drugs with placebo, no treatment, medical treatment, or surgery for pelvic pain associated with endometriosis were included. Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data using data extraction forms. The domains assessed for risk of bias were sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting. We used risk ratios (RR) for reporting dichotomous data with 95% confidence intervals (CI), whilst we expressed continuous data as mean differences (MD). We assessed statistical heterogeneity using the I(2) statistic. Only one trial involving 21 participants was included. The results showed no evidence of an effect of infliximab, one of the known anti-TNF-α drugs, on pelvic pain reduction using the Biberoglu-Behrman (BB) score (0 to 3 scale) for participants (MD -0.14, 95% CI -0.43 to 0.15), the BB score for clinicians (MD -0.14, 95% CI -0.39 to 0.11), or a visual analogue pain score (VAS, 100 mm scale) (MD -5.60, 95% CI -16.10 to 4.90), or on the use of pain killers (ibuprofen, g/day) (MD -0.10, 95% CI -0.30 to 0.10). There was no evidence of an increase in adverse events in the infliximab group compared with placebo (RR 3.73, 95% CI 0.22 to 63.66). We found no evidence of clinical benefits of infliximab for endometriotic lesions, dysmenorrhoea, dyspareunia, or pelvic tenderness. To date, there is no trial that has reported a cost-effectiveness analysis of anti-TNF-α drugs, or the odds of recurrence. This review was updated in 2012. The results of the original review published in 2010 remain unchanged. There is still not enough evidence to support the use of anti-TNF-α drugs in the management of women with endometriosis for the relief of pelvic pain.


Risk of infection and estimated incidence of tuberculosis in northern Uganda.
The main goals of our study were to evaluate: 1) the annual risk of tuberculosis infection (ARTI) and its annual decrease in Uganda; 2) the expected incidence of new tuberculosis cases and the notification rate; and 3) the role of incentives given to children tested in increasing compliance with the survey procedures. The methodology is based on performing the standard World Health Organization (WHO) tuberculin test on children of the same age groups at intervals of 10-15 yrs, identifying infected persons by induration distribution analysis, and converting the prevalence rates detected into risk rates according to the ARTI model. Two thousand six hundred and twenty one school children aged 10 yrs old and bacilli Calmette-Guérin (BCG) nonvaccinated, in six study areas, were injected with two tuberculin units (TU) of purified protein derivative (PPD) RT 23 Copenhagen. The detected prevalence was 14 +/- 1.4% (prevalence +/- 95% confidence interval (95% CI)) and the ARTI value 1.2 +/- 0.9%, with an estimated annual decrease of 0.83% from 1958 to 1970 and 2.9% in the 1970-1987 period. The estimated expected incidence of new cases in Uganda was 59 smear positive and 75 smear negative/extrapulmonary cases per 100,000 population in 1987, and 53 and 65, respectively, in 1990, with an overall 68% notification coverage. No significant improvement in children returning for reading was observed in the group receiving incentives. We conclude that the average decrease (2.9%) probably represents the natural decline of tuberculosis in Uganda. The coverage appears encouraging, although the ARTI detected could be underestimated, since the existing ARTI model was developed and validated before the human immunodeficiency virus (HIV) era.(ABSTRACT TRUNCATED AT 250 WORDS)


Gender differences in the relation between comorbidity and mortality of patients with Alzheimer's disease. Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) Study Group.
To investigate whether differences in the number and type of comorbid conditions may help explain the gender gap in mortality among patients with AD. The prevalence and incidence of AD are higher among women, who also have more severe cognitive impairment and accelerated decline. However, men have an exceedingly higher mortality. The authors conducted a retrospective cohort study on 5,831 men and 17,918 women with a diagnosis of AD. Data were from the Systematic Assessment of Geriatric drug use via Epidemiology (SAGE) database, which includes information on residents of 1,492 nursing homes in five US states (1992-1995). Men and women were compared with respect to demographic characteristics, dementia severity, psychiatric and behavioral symptoms, indicators of physical disability, and general health status. Also compared were age- and race-adjusted prevalence of all comorbid conditions at each level of cognitive impairment. In survival analyses, the risk of death and of hospitalization were determined by gender and level of cognitive impairment. Finally, gender-related differences in the intensity of pharmacologic treatment were examined. Women were older than men (83+/-7 versus 81+/-7 years) and were more likely to exhibit severe cognitive deterioration (27% versus 19% among men). Overall, there were no significant gender-related differences on several measures of physical disability (activities of daily living performance, gait and history of falls, incontinence, pressure sores), but significantly more women were underweight (45% versus 37% among men). However, the age- and race-adjusted 1-year mortality rate was 17% for women and 31% for men. The mortality rate of women at the highest degree of dementia severity was lower than the rate for men with minimal cognitive impairment. At any level of cognitive impairment, the prevalence of arrhythmia, chronic obstructive pulmonary disease, PD, and cancer was higher among men. Women were also less likely to be hospitalized, and they received fewer medications for each given disease. The survival advantage of women with AD relative to men may occur as a result of fewer comorbid clinical conditions associated with the diagnosis of dementia.


The Role of Maternal Nutrition on Oocyte Size and Quality, with Respect to Early Larval Development in The Coral-Eating Starfish, Acanthaster planci.
Variation in local environmental conditions can have pronounced effects on the population structure and dynamics of marine organisms. Previous studies on crown-of-thorns starfish, Acanthaster planci, have primarily focused on effects of water quality and nutrient availability on larval growth and survival, while the role of maternal nutrition on reproduction and larval development has been overlooked. To examine the effects of maternal nutrition on oocyte size and early larval development in A. planci, we pre-conditioned females for 60 days on alternative diets of preferred coral prey (Acropora abrotanoides) versus non-preferred coral prey (Porites rus) and compared resulting gametes and progeny to those produced by females that were starved over the same period. Females fed ad libitum with Acropora increased in weight, produced heavier gonads and produced larger oocytes compared to Porites-fed and starved females. Fed starfish (regardless of whether it was Acropora or Porites) produced bigger larvae with larger stomachs and had a higher frequency of normal larvae that reached the late bipinnaria / early brachiolaria stage compared to starved starfish. Females on Acropora diet also produced a higher proportion of larvae that progressed to more advanced stages faster compared to Porites-fed starfish, which progressed faster than starved starfish. These results suggest that maternal provisioning can have important consequences for the quality and quantity of progeny. Because food quality (coral community structure) and quantity (coral abundance) varies widely among reef locations and habitats, local variation in maternal nutrition of A. planci is likely to moderate reproductive success and may explain temporal and spatial fluctuations in abundance of this species.


Androgen-Regulated SPARCL1 in the Tumor Microenvironment Inhibits Metastatic Progression.
Prostate cancer is a leading cause of cancer death in men due to the subset of cancers that progress to metastasis. Prostate cancers are thought to be hardwired to androgen receptor (AR) signaling, but AR-regulated changes in the prostate that facilitate metastasis remain poorly understood. We previously noted a marked reduction in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) expression during invasive phases of androgen-induced prostate growth, suggesting that this may be a novel invasive program governed by AR. Herein, we show that SPARCL1 loss occurs concurrently with AR amplification or overexpression in patient-based data. Mechanistically, we demonstrate that SPARCL1 expression is directly suppressed by androgen-induced AR activation and binding at the SPARCL1 locus via an epigenetic mechanism, and these events can be pharmacologically attenuated with either AR antagonists or HDAC inhibitors. We establish using the Hi-Myc model of prostate cancer that in Hi-Myc/Sparcl1(-/-) mice, SPARCL1 functions to suppress cancer formation. Moreover, metastatic progression of Myc-CaP orthotopic allografts is restricted by SPARCL1 in the tumor microenvironment. Specifically, we show that SPARCL1 both tethers to collagen in the extracellular matrix (ECM) and binds to the cell's cytoskeleton. SPARCL1 directly inhibits the assembly of focal adhesions, thereby constraining the transmission of cell traction forces. Our findings establish a new insight into AR-regulated prostate epithelial movement and provide a novel framework whereby SPARCL1 in the ECM microenvironment restricts tumor progression by regulating the initiation of the network of physical forces that may be required for metastatic invasion of prostate cancer.


The mitochondrial sulfur dioxygenase ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 is required for amino acid catabolism during carbohydrate starvation and embryo development in Arabidopsis.
The sulfur dioxygenase ETHYLMALONIC ENCEPHALOPATHY PROTEIN1 (ETHE1) catalyzes the oxidation of persulfides in the mitochondrial matrix and is essential for early embryo development in Arabidopsis (Arabidopsis thaliana). We investigated the biochemical and physiological functions of ETHE1 in plant metabolism using recombinant Arabidopsis ETHE1 and three transfer DNA insertion lines with 50% to 99% decreased sulfur dioxygenase activity. Our results identified a new mitochondrial pathway catalyzing the detoxification of reduced sulfur species derived from cysteine catabolism by oxidation to thiosulfate. Knockdown of the sulfur dioxygenase impaired embryo development and produced phenotypes of starvation-induced chlorosis during short-day growth conditions and extended darkness, indicating that ETHE1 has a key function in situations of high protein turnover, such as seed production and the use of amino acids as alternative respiratory substrates during carbohydrate starvation. The amino acid profile of mutant plants was similar to that caused by defects in the electron-transfer flavoprotein/electron-transfer flavoprotein:ubiquinone oxidoreductase complex and associated dehydrogenases. Thus, in addition to sulfur amino acid catabolism, ETHE1 also affects the oxidation of branched-chain amino acids and lysine.


PERSPECTIVE ON OPPORTUNITIES FOR RESEARCH AND INTERVENTIONS PROVIDED BY COMMUNITY BASED HEALTH INFORMATION SYSTEM ILLUSTRATED BY THE POTENTIAL USE OF MOTIVATIONAL INTERVIEWING INTERVENTION.
With the growth of Community-Based Health Information (CBHIS) for decision making and service provision in the low income settings, innovative models of addressing Maternal and Newborn Health (MNH) morbidity and mortality are necessary. World Health Organization (WHO) estimates that five hundred thousand mothers and about three million newborns die each year in middle and low income countries. To stimulate interest in utilisation CBHIS for research and interventions, with an illustration of potential using on Motivational Interviewing intervention. Literature searched electronically, discussion with behavioural experts, health system researchers, and maternal and Newborn Health (MNH) experts, and book reviews. Broad selection criteria including all current literature relevantsubjects including CBHIS, behaviour change methods and Community MNH. A checklist for relevance was used to identify the relevant behaviour change intervention to use in the illustration. A method that met the criteria was identified, and based on a discussion with behavioural experts, the decision to use it the illustration was reached. Motivational Interviewing Intervention (MII) should be considered for implementation and study on near-term Pregnant women in a setting where these mothers can be identified and a targeted intervention instituted.


Effects of protein kinase and phosphatase inhibitors on slow shortening of guinea pig cochlear outer hair cells.
The intracellular mechanisms of slow shortening in isolated guinea pig cochlear outer hair cells were investigated using inhibitors and/or an activator of protein kinases and protein phosphatases. The slow shortening was induced by tetanic electrical field stimulation, and changes in the cell length, volume and intracellular Cl- concentration were microscopically monitored using a chloride-sensitive fluorescent dye. The slow shortening was inhibited by a calmodulin inhibitor, W-7, and a calcium calmodulin-dependent protein kinase II (CaMKII) inhibitor, KN-62. The inhibition by W-7 or KN-62, was abolished by the supplemented conductance of K+ with valinomycin. Among the protein phosphatase inhibitors tested, a type 1 and 2A protein phosphatase inhibitor, calyculin A, inhibited the slow shortening. The inhibition by calyculin A was abolished by the increased Cl- permeability, but neither by the increased K+ conductance with valinomycin nor by the increased Ca2+ conductance with A23187. A protein serine/threonine phosphatase activator, N-acetylsphingosine, inhibited the shortening, which was abolished by either valinomycin or a type 2A protein phosphatase inhibitor, okadaic acid, but not by calyculin A. These findings suggest the following signaling mechanisms in the slow shortening of outer hair cells; the K+ channel opening is facilitated through protein phosphorylation by CaMKII and suppressed via okadaic acid-sensitive dephosphorylation, and the Cl- channel opening depends on calyculin A-sensitive protein phosphatase activity.


Recent advances in banana (musa spp.) biofortification to alleviate vitamin A deficiency.
Vitamin A deficiency (VAD) is one of the most prevalent micronutrient deficiencies that disproportionately affects low income populations in developing countries. Traditional breeding and modern biotechnology have significant potential to enhance micronutrient bioavailability in crops through biofortification. Bananas (Musa spp.) are economically important fruit crops grown throughout tropical and sub-tropical regions of the world where VAD is most prevalent. Some banana genotypes are rich in provitamin A carotenoids (pVACs), providing an opportunity to use bananas as a readily available vehicle for provitamin A delivery. This review summarizes the progress made in carotenoid research in bananas relative to banana diversity and the use of conventional breeding and transgenic approaches aimed at banana biofortification to address vitamin A deficiency. Existing reports on sampling strategies, pVAC retention and bioavailability are also evaluated as essential components for a successful banana biofortification effort. The wide variability of pVACs reported in banana cultivars coupled with recent advances in unraveling the diversity and genetic improvement of this globally important but often-neglected staple fruit crop underscores their importance in biofortification schemes.


Fe(II) complexes that mimic the active site structure of acetylacetone dioxygenase: O2 and NO reactivity.
Acetylacetone dioxygenase (Dke1) is a bacterial enzyme that catalyzes the dioxygen-dependent degradation of β-dicarbonyl compounds. The Dke1 active site contains a nonheme monoiron(II) center facially ligated by three histidine residues (the 3His triad); coordination of the substrate in a bidentate manner provides a five-coordinate site for O(2) binding. Recently, we published the synthesis and characterization of a series of ferrous β-diketonato complexes that faithfully mimic the enzyme-substrate intermediate of Dke1 (Park, H.; Baus, J.S.; Lindeman, S.V.; Fiedler, A.T. Inorg. Chem.2011, 50, 11978-11989). The 3His triad was modeled with three different facially coordinating N3 supporting ligands, and substituted β-diketonates (acac(X)) with varying steric and electronic properties were employed. Here, we describe the reactivity of our Dke1 models toward O(2) and its surrogate nitric oxide (NO), and report the synthesis of three new Fe(II) complexes featuring the anions of dialkyl malonates. Exposure of [Fe((Me2)Tp)(acac(X))] complexes (where (R2)Tp = hydrotris(pyrazol-1-yl)borate with R-groups at the 3- and 5-positions of the pyrazole rings) to O(2) at -70 °C in toluene results in irreversible formation of green chromophores (λ(max) ∼750 nm) that decay at temperatures above -60 °C. Spectroscopic and computational analyses suggest that these intermediates contain a diiron(III) unit bridged by a trans μ-1,2-peroxo ligand. The green chromophore is not observed with analogous complexes featuring (Ph2)Tp and (Ph)TIP ligands (where (Ph)TIP = tris(2-phenylimidazoly-4-yl)phosphine), since the steric bulk of the phenyl substituents prevents formation of dinuclear species. While these complexes are largely inert toward O(2), (Ph2)Tp-based complexes with dialkyl malonate anions exhibit dioxygenase activity and thus serve as functional Dke1 models. The Fe/acac(X) complexes all react readily with NO to yield high-spin (S = 3/2) {FeNO}(7) adducts that were characterized with crystallographic, spectroscopic, and computational methods. Collectively, the results presented here enhance our understanding of the chemical factors involved in the oxidation of aliphatic substrates by nonheme iron dioxygenases.


Getting on with your computer is associated with job satisfaction in primary care: entrants to primary care should be assessed for their competency with electronic patient record systems.
Job satisfaction in primary care is associated with getting on with your computer. Many primary care professionals spend longer interacting with their computer than anything else in their day. However, the computer often makes demands rather than be an aid or supporter that has learned its user's preferences. The use of electronic patient record (EPR) systems is underrepresented in the assessment of entrants to primary care, and in definitions of the core competencies of a family physician/general practitioner. We call for this to be put right: for the use of the EPR to support direct patient care and clinical governance to be given greater prominence in training and assessment. In parallel, policy makers should ensure that the EPR system use is orientated to ensuring patients receive evidence-based care, and EPR system suppliers should explore how their systems might better support their clinician users, in particular learning their preferences.


Association of Bedtime with both Suicidal Ideation and Suicide Planning among Korean Adolescents.
In comparison to other countries, the South Korean population has a short average sleep duration, and studies have suggested that insufficient sleep is a risk factor for suicidal behavior. This study aimed to examine the association of bedtime with suicidal ideation and with suicide planning, respectively, among Korean adolescents. This study included 48,218 participants from the 2017 Korea Youth Risk Behavior Web-based Survey. Participants were divided into three categories: pre-23:00 bedtime, 23:00-01:30 bedtime, and post-01:30 bedtime. Suicidal ideation and suicide planning were the main dependent variables, and multiple logistic regression analysis was performed to examine the target association. For both male and female respondents, compared to those who had a pre-23:00 bedtime, those whose bedtime was after 01:30 were more likely to have suicidal ideation (post-01:30 bedtime for men: OR = 1.29, 95% CI = 1.16-1.45; for women: OR = 1.32, 95% CI = 1.20-1.44). For suicide planning, the results were also significant for both genders (post-01:30 bedtime for men: OR = 1.41, 95% CI = 1.16-1.70; for women: OR = 1.21, 95% CI = 1.03-1.43). Odds of suicidal ideation were higher for those who had a post-01:30 bedtime on weekdays but not weekends. We found that, among adolescents, going to bed after 01:30 is significantly associated with suicidal ideation and suicide planning, after adjusting for demographic, socioeconomic, and health-related characteristics. Therefore, late bedtime should be the timepoint of a suicide intervention for adolescents, in order to prevent developing suicidal ideations and suicide planning.


Is the promise of methadone Kenya's solution to managing HIV and addiction? A mixed-method mathematical modelling and qualitative study.
Promoted globally as an evidence-based intervention in the prevention of HIV and treatment of heroin addiction among people who inject drugs (PWID), opioid substitution treatment (OST) can help control emerging HIV epidemics among PWID. With implementation in December 2014, Kenya is the third Sub-Saharan African country to have introduced OST. We combine dynamic mathematical modelling with qualitative sociological research to examine the 'promise of methadone' to Kenya. We model the HIV prevention impact of OST in Nairobi, Kenya, at different levels of intervention coverage. We draw on thematic analyses of 109 qualitative interviews with PWID, and 43 with stakeholders, to chart their narratives of expectation in relation to the promise of methadone. The modelled impact of OST shows relatively slight reductions in HIV incidence (5-10%) and prevalence (2-4%) over 5 years at coverage levels (around 10%) anticipated in the planned roll-out of OST. However, there is a higher impact with increased coverage, with 40% coverage producing a 20% reduction in HIV incidence, even when accounting for relatively high sexual transmissions. Qualitative findings emphasise a culture of 'rationed expectation' in relation to access to care and a 'poverty of drug treatment opportunity'. In this context, the promise of methadone may be narrated as a symbol of hope-both for individuals and community-in relation to addiction recovery. Methadone offers HIV prevention potential, but there is a need to better model the effects of sexual HIV transmission in mediating the impact of OST among PWID in settings characterised by a combination of generalised and concentrated epidemics. We find that individual and community narratives of methadone as hope for recovery coexist with policy narratives positioning methadone primarily in relation to HIV prevention. Our analyses show the value of mixed methods approaches to investigating newly-introduced interventions.


Ambulatory impedance cardiography: a systematic review.
Standard noninvasive impedance cardiography has been used to examine the cardiovascular responses of individuals to a wide range of stimuli in critical care and laboratory settings. It has been shown to be a reliable alternative to invasive thermodilution techniques and an acceptable alternative to the use of a pulmonary artery catheter. Ambulatory impedance cardiography provides a similar assessment of cardiac function to standard noninvasive impedance cardiography, but it does so while individuals engage in activities of daily living. It offers portability and the option of managing complex patients in outpatient settings. To critically examine through a literature analysis the validity, reliability, and sensitivity of ambulatory impedance cardiography for the assessment of cardiac performance during activities of daily living. The Cochrane Database of Systematic Reviews (CDSR), The Cochrane Database of Methodology Reviews (CDMR), The Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), National Health Service Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA), and The Cochrane Methodology Register (CMR; 1966-2005); MEDLINE (1950-2005); and CINAHL (1982-2005) were searched using the following terms: ambulatory cardiac performance, impedance cardiac performance, AIM cardiac performance monitor, thoracic electrical bio-impedance, impedance cardiography, ambulatory impedance monitor, bio-impedance technology, ambulatory impedance cardiography, bio-electric impedance; also included were reference lists of retrieved articles. Studies were selected if they used an ambulatory impedance monitor to examine one or more of the following cardiovascular responses: pre-ejection period (PEP), left ventricular ejection time (LVET), stroke volume (SV), or a combination of these. Studies have been predominantly descriptive and have been focused on a young, male population with a normal body mass index (BMI; 25-29 kg/m). Inconsistencies in determining specific markers of cardiac function (e.g., PEP and SV) across studies necessitated that results be reported by outcome for each study separately. Ambulatory impedance monitors are valid and reliable instruments used for the physiologic measurement of cardiac performance. Sensitivity is established utilizing within-individual measurements of relative change. This is especially important in light of an aging population and technical advances in healthcare. Further research is warranted using nursing interventions that focus on an older, female population who have a BMI greater than 30 kg/m. Availability of noninvasive ambulatory measures of cardiac function has the potential to improve care for a variety of patient populations, including those with hypertension, heart failure, pain, anxiety, and depressive symptoms.


Nicotinic receptor subtype-selective circuit patterns in the subthalamic nucleus.
The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neurons but exerted strong inhibition in 58% of α7 neurons, indicating an additional diversity of STN neurons: responses to electrical stimulation. Chronic exposure to nicotine selectively affects α4β2 nAChRs in STN: this treatment increased the number of α4β2 neurons, upregulated α4-containing nAChR number and sensitivity, and enhanced the basal firing rate of α4β2 neurons both ex vivo and in vivo. Thus, chronic nicotine enhances the function of the microcircuit involving α4β2 nAChRs. This indicates chronic exposure to nicotinic agonist as a potential pharmacological intervention to alter selectively the balance between these two microcircuits, and may provide a means to inhibit substantia nigra dopaminergic neurons.


Longitudinal dietary change from adolescence to adulthood: perceptions, attributions and evidence.
Dietary patterns and change in eating habits are influenced by multiple factors from an individual's internal and external environment. A longitudinal dietary survey study provided quantitative evidence of dietary change and investigated factors influencing dietary change from adolescence to adulthood, using sociodemographic data and participants' own perceptions of, and attributions for, their dietary change. Longitudinal dietary data were obtained in 1980 and 2000 (average age 11.6 and 32.5 years, respectively). Two questionnaires (2000) and 2 x 3-day food diaries (1980 and 2000) were collected from 198 participants. Foods consumed were assigned to one of the five food groups from The Balance of Good Health (a UK food guide). Questionnaire responses were used to examine how subjects perceived their own dietary change and the factors to which they attributed such change. Six key factors were identified from the questionnaire: parents, partners, children, nutritional awareness, employment and lack of time. Demographic and key factors were associated with degree of change in intake. The complex process of change in food consumption can be linked with an individual's attributions for change.


A signal sequence suppressor mutant that stabilizes an assembled state of the twin arginine translocase.
The twin-arginine protein translocation (Tat) system mediates transport of folded proteins across the cytoplasmic membrane of bacteria and the thylakoid membrane of chloroplasts. The Tat system of Escherichia coli is made up of TatA, TatB, and TatC components. TatBC comprise the substrate receptor complex, and active Tat translocases are formed by the substrate-induced association of TatA oligomers with this receptor. Proteins are targeted to TatBC by signal peptides containing an essential pair of arginine residues. We isolated substitutions, locating to the transmembrane helix of TatB that restored transport activity to Tat signal peptides with inactivating twin arginine substitutions. A subset of these variants also suppressed inactivating substitutions in the signal peptide binding site on TatC. The suppressors did not function by restoring detectable signal peptide binding to the TatBC complex. Instead, site-specific cross-linking experiments indicate that the suppressor substitutions induce conformational change in the complex and movement of the TatB subunit. The TatB F13Y substitution was associated with the strongest suppressing activity, even allowing transport of a Tat substrate lacking a signal peptide. In vivo analysis using a TatA-YFP fusion showed that the TatB F13Y substitution resulted in signal peptide-independent assembly of the Tat translocase. We conclude that Tat signal peptides play roles in substrate targeting and in triggering assembly of the active translocase.


Intersectional Escape: Older Women Elude Agentic Prescriptions More Than Older Men.
Both older individuals and women are proscribed from engaging in power-related behaviors, with women proscribed from behaving agentically and older individuals expected to cede desirable resources through "Succession." However, little is known about whether these overlapping agency prescriptions equally target men and women across the lifespan. In seven studies, we find that older men face the strongest prescriptions to behave less agentically and cede resources, whereas older women are comparatively spared. We show that agency prescriptions more strongly target older men, compared to older women (Studies 1a, 1b, 2) and their younger counterparts (Studies 3 and 4) and examine social and economic consequences for agentic behavior in political, economic, and academic domains. We also find that older men garner more extreme (i.e., polarized) reactions due to their greater perceived resource threat (Studies 4-6). We conclude by discussing theoretical implications for diversity research and practical considerations for accommodating the fast-aging population.


Relationship between crown-like structures and sex-steroid hormones in breast adipose tissue and serum among postmenopausal breast cancer patients.
Postmenopausal obesity is associated with increased circulating levels of androgens and estrogens and elevated breast cancer risk. Crown-like structures (CLS; microscopic foci of dying adipocytes surrounded by macrophages) are proposed to represent sites of increased aromatization of androgens to estrogens. Accordingly, we examined relationships between CLS and sex-steroid hormones in breast adipose tissue and serum from postmenopausal breast cancer patients. Formalin-fixed paraffin embedded benign breast tissues collected for research from postmenopausal women (n = 83) diagnosed with invasive breast cancer in the Polish Breast Cancer Study (PBCS) were evaluated. Tissues were immunohistochemically stained for CD68 to determine the presence of CLS per unit area of adipose tissue. Relationships were assessed between CD68 density and CLS and previously reported sex-steroid hormones quantified using radioimmunoassays in serum taken at the time of diagnosis and in fresh frozen adipose tissue taken at the time of surgery. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relationships between hormones (in tertiles) and CLS. CLS were observed in 36% of benign breast tissues, with a higher frequency among obese versus lean women (54% versus 17%, p = 0.03). Detection of CLS was not related to individual hormone levels or breast tumor pathology characteristics. However, detection of CLS was associated with hormone ratios. Compared with women in the highest tertile of estrone:androstenedione ratio in fat, those in the lowest tertile were less likely to have CLS (OR 0.12, 95% CI 0.03-0.59). A similar pattern was observed with estradiol:testosterone ratio in serum and CLS (lowest versus highest tertile, OR 0.18, 95% CI 0.04-0.72). CLS were more frequently identified in the breast fat of obese women and were associated with increased ratios of select estrogens:androgens in the blood and tissues, but not with individual hormones. Additional studies on CLS, tissue and blood hormone levels, and breast cancer risk are needed to understand and confirm these findings.


Optimal sterile insect release for area-wide integrated pest management in a density regulated pest population.
To determine optimal sterile insect release policies in area-wide integrated pest management is a challenge that users of this pest control method inevitably confront. In this note we provide approximations to best policies of release through the use of simulated annealing. The discrete time model for the population dynamics includes the effects of sterile insect release and density dependence in the pest population. Spatial movement is introduced through integrodifference equations, which allow the use of the stochastic search in cases where movement is described through arbitrary dispersal kernels. As a byproduct of the computations, an assessment of appropriate control zone sizes is possible.


Diet quality of adults using intuitive eating for weight loss - pilot study.
As the incidence of obesity and related disease steadily increases, researchers and medical practitioners are continuously examining new approaches to prevent and manage the epidemic. Intuitive eating (IE) is a new and innovative approach that uses an individual's response to internal cues of hunger, satiety, and appetite, and replaces calorie restriction (CR). CR is the standard approach for weight reduction. This study was a randomized controlled trial with two groups in which we accessed records of the dietary intake of obese adults using CR and IE to achieve weight loss. The participants were sedentary obese individuals with no history of chronic diseases. They engaged in physical activity three times per week for 30 min and recorded their daily food intake in a food diary. Instructions were given for CR and IE at the start and midpoint of the study. The duration of the study was six weeks. Weight and waist circumference were measured, and body mass index (BMI) calculated. The CR group's total weight loss was significantly (p = 0.03) lower than that of the IE group. The CR group had consistent weight loss throughout the study, while the IE group's weight loss was significantly less at the endpoint compared to the midpoint. CR is a superior approach to weight management than IE.


Antecedents and Consequences of Student-Athletes' Identity Profiles in Upper Secondary School.
This study examined the identity profiles that upper secondary school Finnish student-athletes show and the extent to which these profiles were associated with their athletic and academic achievements and withdrawal from sports and school. A total of 391 adolescent athletes (51% female) completed assessments of student and athletic identity four times during their time in upper secondary school. Using growth mixture modeling, three groups were identified: dual identity (77%), changing identity (5%), and athletic identity (18%). The higher the academic achievement was at Time 1, the more likely the athletes were to show a dual identity than an athletic identity profile. Similarly, athletes with dual identity showed higher subsequent academic achievement at Time 4 than those with an athletic identity profile. Finally, athletes with dual identity were more likely and athletes with athletic identity less likely to withdraw from sport activities during upper secondary school than would be expected by chance.


Cucurbits Plants: A Key Emphasis to Its Pharmacological Potential.
Cucurbita genus has received a renowned interest in the last years. This plant species, native to the Americas, has served worldwide folk medicine for treating gastrointestinal diseases and intestinal parasites, among other clinical conditions. These pharmacological effects have been increasingly correlated with their nutritional and phytochemical composition. Among those chemical constituents, carotenoids, tocopherols, phenols, terpenoids, saponins, sterols, fatty acids, and functional carbohydrates and polysaccharides are those occurring in higher abundance. However, more recently, a huge interest in a class of triterpenoids, cucurbitacins, has been stated, given its renowned biological attributes. In this sense, the present review aims to provide a detailed overview to the folk medicinal uses of Cucurbita plants, and even an in-depth insight on the latest advances with regards to its antimicrobial, antioxidant and anticancer effects. A special emphasis was also given to its clinical effectiveness in humans, specifically in blood glucose levels control in diabetic patients and pharmacotherapeutic effects in low urinary tract diseases.


Inhibition of mTOR-dependent autophagy sensitizes leukemic cells to cytarabine-induced apoptotic death.
The present study investigated the role of autophagy, a cellular self-digestion process, in the cytotoxicity of antileukemic drug cytarabine towards human leukemic cell lines (REH, HL-60, MOLT-4) and peripheral blood mononuclear cells from leukemic patients. The induction of autophagy was confirmed by acridine orange staining of intracellular acidic vesicles, electron microscopy visualization of autophagic vacuoles, as well as by the increase in autophagic proteolysis and autophagic flux, demonstrated by immunoblot analysis of p62 downregulation and LC3-I conversion to autophagosome-associated LC3-II in the presence of proteolysis inhibitors, respectively. Moreover, the expression of autophagy-related genes Atg4, Atg5 and Atg7 was stimulated by cytarabine in REH cells. Cytarabine reduced the phosphorylation of the major negative regulator of autophagy, mammalian target of rapamycin (mTOR), and its downstream target p70S6 kinase in REH cells, which was associated with downregulation of mTOR activator Akt and activation of extracellular signal- regulated kinase. Cytarabine had no effect on the activation of mTOR inhibitor AMP-activated protein kinase. Leucine, an mTOR activator, reduced both cytarabine-induced autophagy and cytotoxicity. Accordingly, pharmacological downregulation of autophagy with bafilomycin A1 and chloroquine, or RNA interference-mediated knockdown of LC3β or p62, markedly increased oxidative stress, mitochondrial depolarization, caspase activation and subsequent DNA fragmentation and apoptotic death in cytarabine-treated REH cells. Cytarabine also induced mTOR-dependent cytoprotective autophagy in HL-60 and MOLT-4 leukemic cell lines, as well as primary leukemic cells, but not normal leukocytes. These data suggest that the therapeutic efficiency of cytarabine in leukemic patients could be increased by the inhibition of the mTOR-dependent autophagic response.


Malignant pleural mesothelioma patients' experience by gender: findings from a cross-sectional UK-national questionnaire.
Malignant mesothelioma is an aggressive malignancy of mesothelial surfaces, most commonly those of the pleura. The aim of this study was to understand, using a national questionnaire, the gendered care experiences of patients with malignant pleural mesothelioma (MPM).Patients were asked about their experience of the diagnostic process, about information clarity, health care professionals' knowledge, general practitioner support and overall satisfaction with care received. Recruitment of patients was carried out in three UK countries (England, Wales and Scotland) via mesothelioma clinical nurse specialists. In total, 503 patients completed the questionnaire. 460 had MPM, the remainder had other types of mesothelioma. In accord with the study protocol, only the MPM patients were included in this study.Primary and secondary measures were: (1) time from symptom to diagnosis, (2) satisfaction with the diagnosis and treatment, and (3) quality of life and well-being. There were gender differences in time from symptom to diagnosis. The time from symptom to diagnosis was significantly longer for women than men (median=152 days vs men=92 days, p=0.01). Lack of a verified source of exposure to asbestos was a hindrance to private treatment access for women (95% of those that access private treatment are men). Patients were five times more likely to be satisfied if they thought that the doctors knew enough about their condition (OR=4.4, p=0.001) and nearly three times more likely to be satisfied if information was presented in a sensitive way (OR=2.8,p=0.01). This study has several implications for clinical practice. Our findings suggest that the diagnostic time in women might be reduced by reviewing diagnostic processes including occupational history taking, and by revising the occupational risk of mesothelioma categorisation.


Balloon sinuplasty versus surgical management of chronic rhinosinusitis.
The first US Food and Drug Administration-approved dilating balloon catheter system for obstructed paranasal sinus drainage pathways was introduced in September 2005. It was discussed as an alternative treatment option for traditional endoscopic sinus surgery for those suffering from chronic rhinosinusitis. Widespread patient interest has ensued, although controversy regarding application of this device continues. Many otolaryngologists have been trained to use the device, and more than 88,000 patients have had surgery using this device. Like similar dilating catheters used in other specialties to relieve obstruction, it is a minimally invasive tool for mucosal-sparing dilation of sinus ostia or sinus outflow tracts. Although studies have been completed that demonstrate feasibility, safety, and long-term patency of dilated sinuses, the evolving indications for its use remain controversial. Referring physicians and patients can expect a range of opinions on the role of these devices in the treatment of rhinosinusitis for the foreseeable future.