Planning and Performance in Small Groups: Collective Implementation Intentions Enhance Group Goal Striving.
There are two key motivators to perform well in a group: making a contribution that (a) is crucial for the group (indispensability) and that (b) the other group members recognize (identifiability). We argue that indispensability promotes setting collective ("We") goals whereas identifiability induces individual ("I") goals. Although both goals may enhance performance, they should align with different strategies. Whereas pursuing collective goals should involve more cooperation, pursuing individual goals should involve less cooperation. Two experiments support this reasoning and show that planning out collective goals with collective implementation intentions (cIIs or "We-plans") relies on cooperation but planning out individual goals with individual implementation intentions (IIs or "I-plans") does not. In Experiment 1, three-member groups first formed a collective or an individual goal and then performed a first round of a physical persistence task. Groups then either formed a respective implementation intention (cII or II) or a control plan and then performed a second round of the task. Although groups with cIIs and IIs performed better on a physical persistence task than respective control groups, only cII groups interacted more cooperatively during task performance. To confirm the causal role of these interaction processes, Experiment 2 used the same persistence task and manipulated whether groups could communicate: When communication was hindered, groups with cIIs but not groups with IIs performed worse. Communication thus qualifies as a process making cIIs effective. The present research offers a psychology of action account to small group performance.


Couples' shared participation in novel and arousing activities and experienced relationship quality.
Using a newspaper questionnaire, a door-to-door survey, and 3 laboratory experiments, the authors examined a proposed effect of shared participation in novel and arousing activities on experienced relationship quality. The questionnaire and survey studies found predicted correlations of reported shared "exciting" activities and relationship satisfaction plus their predicted mediation by relationship boredom. In all 3 experiments, the authors found predicted greater increases in experienced relationship quality from before to after participating together in a 7-min novel and arousing (vs. a more mundane) task. Comparison with a no-activity control showed the effect was due to the novel-arousing task. The same effect was found on ratings of videotaped discussions before and after the experimental task. Finally, all results remained after controlling for relationship social desirability. Results bear on general issues of boredom and excitement in relationships and the role of such processes in understanding the typical early decline of relationship quality after the honeymoon period.


Population genomics of the inbred Scandinavian wolf.
The Scandinavian wolf population represents one of the genetically most well-characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a 'genetic rescue'. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long-term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non-neutral evolution on a finer scale than what has previously been possible.


Sex steroid hormones in relation to Barrett's esophagus: an analysis of the FINBAR Study.
Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol ORcontinuous per ½IQR = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone ORcontinuous per ½IQR = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis.


Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series.
Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-β (Aβ), tau, α-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77-87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, Aβ deposits were observed only in 160 (68.7 %). Further pathologies included α-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p < 0.001) and Alzheimer-related pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, Aβ parenchymal deposits, TDP-43 proteinopathy, α-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p < 0.0001). In addition to AD-neuropathologic change, tauopathies associated well with dementia, while TDP-43 pathology and α-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients.


Prevalence of older people with intellectual disability in Sweden: a spatial epidemiological analysis.
The expected increase in longevity of individuals with intellectual disabilities (ID) in many countries of the world is a direct result of medical and social advances, which have also extended the longevity of the general population. It is important to assess the need for social services for people with ID across different administrative levels to ensure sufficient resources are allocated to where they are most needed. This study estimates the annual prevalence of older people with ID from 2004 to 2012 and in different counties and municipalities in Sweden, by sex and age group; identifies proxy indicators related to the care of older people with ID in different counties in 2012 in Sweden and analyses the spatial distribution and clustering of municipalities with a high prevalence of older people with ID. Individuals with ID were identified through the national register based on the Swedish Act concerning Support and Service for Persons with Certain Functional Impairments (the LSS act) and the national death register. This study focuses on older individuals aged 55+ during the period of 2004-2012. The estimated prevalence was calculated at the county and municipality level and plotted on a municipality-level map. Moran's I statistics was used to identify any spatial clustering of municipalities with a large number of individuals with ID. The prevalence of ID among older individuals aged 55+ in Sweden increased from 2004 to 2012. The prevalence was consistently higher among men, and the gender gap increased slightly in recent years. Age-specific prevalence estimates showed ID to be higher in younger age groups, and the gender gap decreased in older age groups. The prevalence was higher in northern counties in Sweden (over 500 individuals per 100 000 population aged 55+). Higher prevalence areas were clustered in northern municipalities, whereas municipalities with high prevalence of older individuals with ID in the middle and southern regions of Sweden demonstrated a more widespread distribution. The existence of clusters of counties with a high prevalence of older individuals with ID necessitates further assessment of how resources have been allocated to different counties and municipalities in Sweden. Investigations of the quality of social services provided to individuals with ID across different counties in Sweden are warranted. It is important to ensure that high quality supports are being provided to older individuals with ID in order to grant them the same right to healthy ageing as their counterparts living without ID throughout their life course.


Characterization of Arabidopsis Tubby-like proteins and redundant function of AtTLP3 and AtTLP9 in plant response to ABA and osmotic stress.
Tubby and Tubby-like proteins (TLPs) play essential roles in the development and function of mammal neuronal cells. In addition to the conserved carboxyl (C)-terminal Tubby domain, which is required for their plasma membrane (PM) tethering, plant TLPs also possess an amino (N)-terminal F-box domain to interact with specific Arabidopsis Skp1-like (ASK) proteins as functional SCF-type E3 ligases. Here, we report the molecular characterization of Arabidopsis TLPs (AtTLPs). β-Glucuronidase staining showed overlapped but distinct expression patterns of AtTLPs in Arabidopsis. Yeast two-hybrid assays further revealed that AtTLP1, AtTLP3, AtTLP6, AtTLP7, AtTLP9, AtTLP10 and AtTLP11 all interacted with specific ASKs, but AtTLP2, AtTLP5 and AtTLP8 did not. Subcellular localization observations in both Arabidopsis protoplasts and tobacco pollen tubes indicated that all GFP-AtTLP fusion proteins, except GFP-AtTLP8 which lacks the conserved phosphatidylinositol 4,5-bisphosphate binding sites, were targeted to the PM. Detailed studies on AtTLP3 demonstrated that AtTLP3 is a PM-tethered PIP2 binding protein which functions redundantly with AtTLP9 in abscisic acid (ABA)- and osmotic stress-mediated seed germination. Our results suggest that AtTLPs possibly work in multiple physiological and developmental processes in Arabidopsis, and AtTLP3 is also involved in ABA signaling pathway like AtTLP9 during seed germination and early seedling growth.


Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects.
The aim of the present study was to determine the effect of purified high-dose anthocyanoside oligomer administration on nocturnal visual function and clinical symptoms in low-to-moderate myopia subjects. The study was a randomized, double-blind, placebo-controlled trial and involved sixty subjects with asthenopia and refractive errors between -1.00 and -8.00 diopters in both eyes. Thirty subjects were administered a purified high-dose anthocyanoside oligomer (100 mg tablet comprising 85 % anthocyanoside oligomer), and thirty were given a placebo in tablet form twice daily for 4 weeks. Prior to the treatment, the placebo and anthocyanoside groups were similar in terms of age and contrast sensitivity. Before and after treatment, subjects completed a questionnaire to determine their clinical symptoms and were also assessed for nocturnal visual function using contrast sensitivity testing. Questionnaire data analysis showed that, following treatment, twenty-two (73.3 %) anthocyanoside subjects showed improved symptoms, whereas only one placebo subject showed an improvement (Fisher's exact test, P<0.0001). Contrast sensitivity levels according to each cycle per degree significantly improved in the anthocyanoside group and remained stable in the placebo group. The mean contrast sensitivity change in the anthocyanoside group was 2.41 (SD) 1.91, compared with -0.66 (SD) 2.66 dB for the placebo group (unpaired Student's t test, P<0.0001). At all cycle per degree levels, contrast sensitivity changes in the anthocyanoside group were better than in the placebo group (unpaired Student's t test, P<0.05). The present data show that the administration of anthocyanoside oligomer appears to improve subjective symptoms and objective contrast sensitivity in myopia subjects with asthenopia.


Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines.
Uridine phosphorylase (UP) catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate and is a key enzyme in the pyrimidine-salvage pathway. Escherichia coli UP is structurally homologous to E. coli purine nucleoside phosphorylase and other members of the type I family of nucleoside phosphorylases. The structures of 5-benzylacyclouridine, 5-phenylthioacyclouridine, 5-phenylselenenylacyclouridine, 5-m-benzyloxybenzyl acyclouridine and 5-m-benzyloxybenzyl barbituric acid acyclonucleoside bound to the active site of E. coli UP have been determined, with resolutions ranging from 1.95 to 2.3 A. For all five complexes the acyclo sugar moiety binds to the active site in a conformation that mimics the ribose ring of the natural substrates. Surprisingly, the terminal hydroxyl group occupies the position of the nonessential 5'-hydroxyl substituent of the substrate rather than the 3'-hydroxyl group, which is normally required for catalytic activity. Until recently, inhibitors of UP were designed with limited structural knowledge of the active-site residues. These structures explain the basis of inhibition for this series of acyclouridine analogs and suggest possible additional avenues for future drug-design efforts. Furthermore, the studies can be extended to design inhibitors of human UP, for which no X-ray structure is available.


Distance determination by GIY-YIG intron endonucleases: discrimination between repression and cleavage functions.
GIY-YIG homing endonucleases are modular proteins, with conserved N-terminal catalytic domains connected by linkers to C-terminal DNA-binding domains. I-TevI, the T4 phage GIY-YIG intron endonuclease, functions both in promoting td intron homing, and in acting as a transcriptional autorepressor. Repression is achieved by binding to an operator, which is cleaved at 100-fold reduced efficiency relative to the intronless homing site. The linker includes a zinc finger, which functions in distance determination, to constrain the catalytic domain to cleave the homing site at a fixed position. Here we show that I-BmoI, a related GIY-YIG endonuclease lacking a zinc finger, also possesses some cleavage distance discrimination. Furthermore, hybrid endonucleases constructed by swapping the domains of I-BmoI and I-TevI are active, precise and demonstrate that features other than the zinc finger facilitate distance determination. Most importantly, I-TevI zinc finger mutants cleave the operator more efficiently than the homing site, the converse of wild-type protein. These results are consistent with the zinc finger acting as a measuring device, directing efficient cleavage of the homing site to promote intron mobility, while reducing cleavage at the operator to ensure transcriptional autorepression and phage viability.


Single-exposure phase-shifting digital holography using a random-phase reference wave.
We propose a single-exposure phase-shifting digital holography based on a wave-splitting method using a random-phase reference wave. A random-phase reference wave gives random-phase distribution on the digital hologram. Using the amplitude and the phase distributions of the reference wave, the fully complex amplitude of the object wave is obtained. The proposed method requires not devised optical systems but ordinary imaging devices, such as CCD cameras. A preliminary experimental result is given to confirm the proposed method.


Ultrastructural distribution of lectin-binding sites on gastric superficial mucus-secreting epithelial cells. The role of Golgi apparatus in the initial glycosylation.
Normal human gastric epithelial cells were examined by electron microscopy using each of five biotinylated lectins [Ulex europaeus agglutinin I (UEA-I), peanut agglutinin (PNA), wheat germ agglutinin (WGA), soybean agglutinin (SBA) and Dolichos biflorus agglutinin (DBA)] as a probe. We employed 35 gastric surgical specimens removed from complicated peptic disease. The lectin-binding sites were revealed with streptavidin-colloidal gold complex. All specimens were embedded in Spurr and LR White resins. In superficial foveolar epithelial cells, the lectins used were generally positive in all cell types (mainly UEA-1 and PNA) on the Golgi region and mucus cytoplasmic vacuoles, with many variations among cells in the same case. On the other hand, extracellular mucus was negative for WGA. Labelling with PNA revealed a biphasic pattern (peripheral positivity) on mucous droplets in surface and foveolar cells. The cis side of the Golgi apparatus was labelled with SBA and PNA and rough endoplasmic reticulum with SBA (only five cases). Lectin-binding variability could be related to heterogeneous composition of gastric mucus. Our results with SBA suggest initiation of O-glycosylation at the Golgi apparatus; however a role of the rough endoplasmic reticulum cannot be excluded (N-glycosylation). We propose the following sequence of sugar addition to the carbohydrate side-chains of gastric glycoproteins: (1) GaNAc (Golgi apparatus cis-side), (2) GlcNAc (Golgi apparatus intermediate face), (3) GalNac or Gal, alpha-L-fucose (Golgi apparatus trans-side).


Health and economic burden estimates of snakebite management upon health facilities in three regions of southern Burkina Faso.
Snakebite has become better recognized as a significant cause of death and disability in Sub-Saharan Africa, but the health economic consequences to victims and health infrastructures serving them remain poorly understood. This information gap is important as it provides an evidence-base guiding national and international health policy decision making on the most cost-effective interventions to better manage snakebite. Here, we assessed hospital-based data to estimate the health economic burden of snakebite in three regions of Burkina Faso (Centre-Ouest, Hauts Bassins and Sud-Ouest). Primary data of snakebite victims admitted to regional and district health facilities (eg, number of admissions, mortality, hospital bed days occupied) was collected in three regions over 17 months in 2013/14. The health burden of snakebite was assessed using Disability-Adjusted Life Years (DALYs) calculations based upon hospitalisation, mortality and disability data from admitted patients amongst other inputs from secondary sources (eg, populations, life-expectancy and age-weighting constants). An activity-based costing approach to determine the direct cost of snake envenoming included unit costs of clinical staff wages, antivenom, supportive care and equipment extracted from context-relevant literature. The 10,165 snakebite victims admitted to hospital occupied 28,164 hospital bed days over 17 months. The annual rate of hospitalisation and mortality of admitted snakebite victims was 173 and 1.39/100,000 population, respectively. The estimated annual (i) DALYs lost was 2,153 (0.52/1,000) and (ii) cost to hospitals was USD 506,413 (USD 49/hospitalisation) in these three regions of Burkina Faso. These costs appeared to be influenced by the number of patients receiving antivenom (10.90% in total) in each area (highest in Sud-Ouest) and the type of health facility. The economic burden of snake envenoming is primarily shouldered by the rural health centres closest to snakebite victims-facilities that are typically least well equipped or resourced to manage this burden. Our study highlights the need for more research in other regions/countries to demonstrate the burden of snakebite and the socioeconomic benefits of its management. This evidence can guide the most cost-effective intervention from government and development partners to meet the snakebite-management needs of rural communities and their health centres.


Polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues in the blood of harbor, Dall's and finless porpoises from the Japanese coastal waters.
This study investigated the accumulation of polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated analogues (OH-PBDEs and MeO-PBDEs) in the blood of harbor porpoises, Dall's porpoises, and finless porpoises stranded or bycaught in Japanese coastal waters and in the North Pacific Ocean. Moreover, we suggested the origins of these contaminants and the factors affecting their pattern of accumulation. Levels of PBDEs in Dall's porpoises were one order of magnitude greater than those in the other species. OH-PBDE and MeO-PBDE levels were comparable to those of PBDEs. However, no correlation was found between the levels of OH-PBDEs and PBDEs, whereas a strong correlation was found between that of OH-PBDEs and MeO-PBDEs (p < 0.001). 6OH-BDE47, reported compound biosynthesized by marine low-trophic level organisms, was the dominant congener. These results suggest that PBDEs found in these porpoise species derive from flame retardants, but OH-PBDEs and MeO-PBDEs are mainly of natural origins.


Structural and functional analyses reveal promiscuous and species specific use of ephrin receptors by Cedar virus.
Cedar virus (CedV) is a bat-borne henipavirus related to Nipah virus (NiV) and Hendra virus (HeV), zoonotic agents of fatal human disease. CedV receptor-binding protein (G) shares only ∼30% sequence identity with those of NiV and HeV, although they can all use ephrin-B2 as an entry receptor. We demonstrate that CedV also enters cells through additional B- and A-class ephrins (ephrin-B1, ephrin-A2, and ephrin-A5) and report the crystal structure of the CedV G ectodomain alone and in complex with ephrin-B1 or ephrin-B2. The CedV G receptor-binding site is structurally distinct from other henipaviruses, underlying its capability to accommodate additional ephrin receptors. We also show that CedV can enter cells through mouse ephrin-A1 but not human ephrin-A1, which differ by 1 residue in the key contact region. This is evidence of species specific ephrin receptor usage by a henipavirus, and implicates additional ephrin receptors in potential zoonotic transmission.


Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies.
The reactivities of a panel of 14 monoclonal antibodies (MAbs) with monomeric gp120 derived from 67 isolates of human immunodeficiency virus type 1 of clades A through F were assessed by using an antigen-capture enzyme-linked immunosorbent assay. The MAbs used were all raised against gp120 or gp120 peptides from clade B viruses and were directed at a range of epitopes relevant to human immunodeficiency virus type 1 neutralization: the V2 and V3 loops, discontinuous epitopes overlapping the CD4-binding site, and two other discontinuous epitopes. Four of the five V3 MAbs showed modest cross-reactivity within clade B but very limited reactivity with gp120s from other clades. These reactivity patterns are consistent with the known primary sequence requirements for the binding of these MAbs. One V3 human MAb (19b), however, was much more broadly reactive than the others, binding to 19 of 29 clade B and 10 of 12 clade E gp120s. The 19b epitope is confined to the flanks of the V3 loop, and these sequences are relatively conserved in clade B and E viruses. In contrast to the limited reactivity of V3 MAbs, CD4-binding site MAbs were much more broadly reactive across clades, two of these MAbs (205-46-9 and 21h) being virtually pan-reactive across clades A through F. Another human MAb (A-32) to a discontinuous epitope was also pan-reactive. The CD4-binding site is strongly conserved between clades; but when considering the epitopes near the CD4-binding site, clade D gp120 appears to be the most closely related to clade B and clade E appears to be the least related. A tentative rank order for these epitopes is B/D-A/C-E/F. V2 MAbs reacted sporadically within and between clades, and no clear pattern was observable. While results from binding assays do not predict neutralization serotypes, they suggest that there may be antigenic subtypes related, but not identical, to the genetic subtypes.


Subtypes of depression in a nationally representative sample.
Continued research efforts aim to elucidate the heterogeneity in depression. The identification of meaningful and valid subtypes has implications for research and clinical practice. Based on patterns of depressive symptomatology, this study identified a typology of depressive syndromes using data from a large, nationally representative survey. Analyses were based on a subsample of 12,180 respondents from the 2001-2002 Wave of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Latent class analysis was applied to the DSM-IV 'A' criteria for major depression to identify homogenous subtypes or classes of depressive syndromes. Associations between the emergent latent classes and demographic and clinical characteristics were assessed. Three clinically relevant subtypes were identified, in addition to a class who reported few depressive symptoms: severely depressed (40.9%), psychosomatic (30.6%), cognitive-emotional (10.2%) and non-depressed (18.3%). The odds of experiencing negative life events, psychiatric disorders, and having a family background of major depression were significantly higher for the severely depressed, psychosomatic and cognitive-emotional classes, compared to the non-depressed class. Several unique differences between the latent classes also emerged. Methodological shortcomings included: reliance on lay interviewer-administered structured interviews to determine diagnoses; basing sample selection on the endorsement of screener items; and, using measures of 'any anxiety disorder', 'any mood disorder', and 'any personality disorder' to determine psychiatric disorder prevalence rates. Significant heterogeneity in depressive symptomatology exists in this U.S. sample. Profiling symptom patterns is potentially useful as a first step in developing tailored intervention and treatment programmes.


Racial differences in health-related beliefs, attitudes, and experiences of VA cardiac patients: scale development and application.
To deternine whether there are racial differences in patients' health-related attitudes, beliefs, and experiences regarding invasive cardiac procedures, and to develop psychometrically and conceptually valid scales and single items to assess these dimensions. A survey was designed and administered to 854 white and black patients with ischemic heart disease at five VA medical centers. Patients were queried about the domains proposed to be important to treatment decision making by the Health Decision Model: sociodemographic characteristics, social interactions, health care experiences, patient preferences for care, knowledge about diseases and potential treatments, and health beliefs. Using multitrait analysis, the psychometric properties of scales assessing these domains were examined. It was then assessed whether there were racial differences in scale or individual item scores using chi2 and t test analyses. The analyses yielded eight psychometrically valid scales: disease severity, patient evaluation of physician's interpersonal style, patient evaluations of VA care, satisfaction with treatment decision making, perceived urgency of catheterization, vulnerability to catheterization, bodily impact of catheterization, and attitudes toward religion. There were only racial differences on mean scores for the latter scale. Individual item analyses indicated that black patients were less likely to have been encouraged by friends or family to have cardiac catheterization, and had less personal or familial experiences with this or other surgical procedures. In contrast to expectations, white patients were more likely to be skeptical of medical care. The multiple dimensions of white and black patients' health-related attitudes, beliefs, and experiences were examined, and few differences were found. These results suggest that racial differences in patients' attitudes, beliefs, and experiences are not a likely source of racial disparities in cardiac care. Future research will examine the association of beliefs, attitudes and experiences with actual use of invasive cardiac procedures.


Ultrasonography in the treatment of a pediatric midline neck mass.
To assess the effectiveness of ultrasonography for determining which pediatric midline neck masses should be treated surgically. Retrospective study. Tertiary care pediatric hospital. Pediatric patients with a midline neck mass who underwent ultrasonography from 2003 to 2011. Demographics, ultrasonography, and surgical and pathology reports were studied. The ultrasonography findings and pathological analyses were compared. One hundred twenty-two patients met the inclusion criteria. The most common diagnosis obtained by ultrasonography was thyroglossal duct cyst (48.4%), followed by reactive lymph node (27.9%). Ninety-five of 122 patients (77.9%) underwent surgery. Twenty-seven patients (22.1%) were treated nonsurgically. The diagnosis and characteristics obtained from ultrasonography were confirmed by surgical pathologic analysis in 84.2% of the surgical cases. Of the 95 patients who underwent surgery, 85 (89.5%) had a non-lymph node lesion diagnosed by ultrasonography and confirmed by pathologic analysis. Ultrasonography was only 66.1% accurate in specifically diagnosing thyroglossal duct cyst and 30.0% accurate in specifically diagnosing reactive lymph node when compared with surgical specimens. Ultrasonography is helpful in determining the pediatric midline neck masses that need to be removed surgically. It is less helpful in determining the exact pathologic characteristics of the lesion.


Hox Gene Loss during Dynamic Evolution of the Nematode Cluster.
HOX GENES ARE IMPORTANT: their central role in anterior-posterior patterning provides a framework for molecular comparison of animal body plan evolution. The nematode Caenorhabditis elegans stands out as having a greatly reduced Hox gene complement. To address this, orthologs of C. elegans Hox genes were identified in six species from across the Nematoda, and they show that rapid homeodomain sequence evolution is a general feature of nematode Hox genes. Some nematodes express additional Hox genes belonging to orthology groups that are absent from C. elegans but present in other bilaterian animals. Analysis of the genomic environment of a newly identified Brugia malayi Hox6-8 ortholog (Bm-ant-1) revealed that it lay downstream of the Bm-egl-5 Hox gene and that their homeodomain exons are alternately cis spliced to the same 5' exon. This organization may represent an intermediate state in Hox gene loss via redundancy. The Hox clusters of nematodes are the product of a dynamic mix of gene loss and rapid sequence evolution, with the most derived state observed in the model C. elegans.


Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model.
In earlier studies insects were proposed as suitable models for vertebrate blood-brain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain barrier of the desert locust (Schistocerca gregaria). In an in vivo study on the locust, we found an increased uptake of the two well-known Pgp substrates, rhodamine 123 and loperamide after co-administration with the Pgp inhibitors cyclosporine A or verapamil. Furthermore, ex vivo studies on isolated locust brains demonstrated differences in permeation of high and low permeability compounds. The vertebrate Pgp inhibitor verapamil did not affect the uptake of passively diffusing compounds but significantly increased the brain uptake of Pgp substrates in the ex vivo model. In addition, studies at 2°C and 30°C showed differences in brain uptake between Pgp-effluxed and passively diffusing compounds. The transcriptome data show a high degree of sequence identity of the locust Pgp transporter protein sequences to the human Pgp sequence (37%), as well as the presence of conserved domains. As in vertebrates, the locust brain-barrier function is morphologically confined to one specific cell layer and by using a whole-brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery.


[Effects of survival bias on the prevalence of malnutrition in six-year-old children in Brazil, based on the national survey on health and nutrition, 1989].
Child growth as measured by anthropometric indicators is an important tool for assessing children's nutritional status and society's developmental stage. This study uses the height-for-age indicator with the cutoff point at -2 Z to estimate prevalence of malnutrition in a population of six-year-old children included in the Brazilian National Survey on Health and Nutrition (PNSN). Prevalence variability was analyzed according to gender, trimestral age range, per capita family income, and region of residence. Based on estimates of mortality rates for children under five whose deaths could be ascribed to malnutrition, the survival bias correction was performed using the Boerma methodology. This correction, in turn, was more conspicuous within the low-income and less-developed segment of the population. There was an increase in the number of malnourished children in relation to those surviving at the time of investigation. When comparing less and more developed areas of the country (the Northeast and Southeast, respectively), we observed that malnutrition prevalence rates within the six-year-old group showed no change in the Southeast region, while in the Northeast they increased from 26% to 34%, thus representing a 31% increase in the malnutrition rate. Therefore, in absolute figures, these rates account for the addition of 90,100 children to the malnourished group.


Twin SVM for gesture classification using the surface electromyogram.
Surface electromyogram (sEMG) is a measure of the muscle activity from the skin surface, and is an excellent indicator of the strength of muscle contraction. It is an obvious choice for control of prostheses and identification of body gestures. Using sEMG to identify posture and actions that are a result of overlapping multiple active muscles is rendered difficult by interference between different muscle activities. In the literature, attempts have been made to apply independent component analysis to separate sEMG into components corresponding to the activities of different muscles, but this has not been very successful, because some muscles are larger and more active than the others. We address the problem of how to learn to separate each gesture or activity from all others. Multicategory classification problems are usually solved by solving many one-versus-rest binary classification tasks. These subtasks naturally involve unbalanced datasets. Therefore, we require a learning methodology that can take into account unbalanced datasets, as well as large variations in the distributions of patterns corresponding to different classes. This paper reports the use of twin support vector machine for gesture classification based on sEMG, and shows that this technique is eminently suited to such applications.


Sensitive determination of chlorogenic acid in pharmaceutical products based on the decoration of 3D macroporous carbon with Au nanoparticles via polyoxometalates.
A simple and sensitive electrochemical sensor is constructed for the detection of chlorogenic acid (CGA) based on Au nanoparticles (NPs)/polyoxometalates/3D macroporous carbon (Au-POMs-MPC). Serving as both a reducing and stabilizing agent, the Keggin-type POM, H3PW12O40, is used for the synthesis of stable colloidal Au NPs and then used to link them to MPC at a mild temperature. Because of the unique structural properties and synergetic catalytic effect, Au-POMs-MPC can be developed as an effective sensing platform for the detection of CGA, which showed high activity and excellent analytical performance towards CGA, such as a wide linear range of 2.28 nM-3.24 μM, a high sensitivity of 30 554.71 μA mM-1, and a low limit of detection of 2.15 nM. Importantly, the successfully fabricated Au-POMs-MPC device accurately measured the amount of CGA in pharmaceutical samples.


Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator.
The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was "non-MRI-conditional" (i.e., not approved by the Food and Drug Administration for MRI scanning). Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).


Dynamic complexities in host-parasitoid interaction
In the 1970s ecological research detected chaos and other forms of complex dynamics in simple population dynamics models, initiating a new research tradition in ecology. However, the investigations of complex population dynamics have mainly concentrated on single populations and not on higher dimensional ecological systems. Here we report a detailed study of the complicated dynamics occurring in a basic discrete-time model of host-parasitoid interaction. The complexities include (a) non-unique dynamics, meaning that several attractors coexist, (b) basins of attraction (defined as the set of the initial conditions leading to a certain type of an attractor) with fractal properties (pattern of self-similarity and fractal basin boundaries), (c) intermittency, (d) supertransients, (e) chaotic attractors, and (f) "transient chaos". Because of these complexities minor changes in parameter or initial values may strikingly change the dynamic behavior of the system. All the phenomena presented in this paper should be kept in mind when examining and interpreting the dynamics of ecological systems. Copyright 1999 Academic Press.


Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise.
Adaptive responses to exercise training (ET) are crucial in maintaining physiologic homeostasis and health span. Exercise-induced aerobic bioenergetic reactions in the mitochondria and cytosol increase production of reactive oxygen species, where excess of reactive oxygen species can be scavenged by enzymatic and nonenzymatic antioxidants (AO) to protect against deleterious oxidative stress. Free radicals, however, have recently been recognized as crucial signaling agents that promote adaptive mechanisms to ET, such as mitochondrial biogenesis, AO enzyme activity defense system upregulation, insulin sensitivity, and glucose uptake in the skeletal muscle. Commonly used nonenzymatic AO supplements, such as vitamins C and E, α-lipoic acid, and polyphenols, in combination with ET, have been proposed as ways to prevent exercise-induced oxidative stress and hence improve adaptation responses to endurance training. During the PubMed search, we selected studies that examined and compared ET effects with and without administration of commonly used AO supplements. Preclinical and clinical studies to date have shown inconsistent results indicating either positive or negative effects of endurance training combined with different blends of AO supplements (mostly vitamins C and E and α-lipoic acid) on redox status, mitochondrial biogenesis pathways, and insulin sensitivity. Preclinical reports on ET combined with resveratrol, however, have shown consistent positive effects on exercise performance, mitochondrial biogenesis, and insulin sensitivity, with clinical trials reporting mixed effects. Relevant clinical studies have been few and have used inconsistent results and methodology (types of compounds, combinations, and supplementation time). The future studies should investigate the effects of specific AO and other popular supplements, such as α-lipoic acid and resveratrol, on training effects in humans. Of particular importance are older adults who may be at higher risk of age-related increased oxidative stress, an impaired AO enzyme defense system, and comorbidities such as hypertension, insulin resistance, and diabetes.


Far-infrared observations of the night sky.
We have flown a telescope cooled to liquid-helium temperatures and made far-infrared observations of the night sky. A gallium-doped germanium detector, sensitive from 5.2 to 130 micrometers, detected a minimum signal of 10(-9) watt per square centimeter per steradian referred to 100 micrometers. The origin of this signal can be instrumental, atmospheric, interplanetary, or interstellar. We can place a firm upper limit on the color temperature of a dilute cosmic background flux.


Eukaryotic transcription factors can track and control their target genes using DNA antennas.
Eukaryotic transcription factors (TF) function by binding to short 6-10 bp DNA recognition sites located near their target genes, which are scattered through vast genomes. Such process surmounts enormous specificity, efficiency and celerity challenges using a molecular mechanism that remains poorly understood. Combining biophysical experiments, theory and bioinformatics, we dissect the interplay between the DNA-binding domain of Engrailed, a Drosophila TF, and the regulatory regions of its target genes. We find that Engrailed binding affinity is strongly amplified by the DNA regions flanking the recognition site, which contain long tracts of degenerate recognition-site repeats. Such DNA organization operates as an antenna that attracts TF molecules in a promiscuous exchange among myriads of intermediate affinity binding sites. The antenna ensures a local TF supply, enables gene tracking and fine control of the target site's basal occupancy. This mechanism illuminates puzzling gene expression data and suggests novel engineering strategies to control gene expression.


The enlightenment from Malaysian consumers' perspective toward cosmetic products.
Variety of cosmetic products was used in our daily life, yet the amount and types of the cosmetic products used by the consumers were varied, which may be due to the different perspectives held by each of the consumers. To explore consumers' perspectives toward cosmetic products. An interview guide was developed with a set of 12 semistructured questions. Participants in Kuantan, Pahang were recruited via the purposive sampling, and they undergo in-depth face-to-face interviews. All of the interviews were audio-recorded, transcribed verbatim, and were analyzed via thematic content analysis. For the awareness of cosmetic products, less aware about the cosmetic products in Malaysia were noted among the participants. In terms of perceptions about the cosmetic products, participants expressed positive perceptions toward natural cosmetic products, quality were seen as synonymous with branded products and halal certification. Next, for the attitude toward the use of cosmetic products, participants were influenced by ingredients, product brand, and halal certification. Based on personal experiences, they provide complaints and suggestions for the enhancement of cosmetic products' quality. Participants were found to have less awareness about the cosmetic products in Malaysia. Besides, they realized about the chemical ingredients and halal certification for the cosmetic products. Therefore, they held positive perceptions and practiced positive attitudes toward natural and halal cosmetic products. Finally, adverse reactions from the use of cosmetic products were commonly experienced by the participants, which contributed mainly by the ingredients. Thus, they hoped for serious approached to be enacted to solve this problem.


Bisdemethoxycurcumin-induced S phase arrest through the inhibition of cyclin A and E and induction of apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathways in human lung cancer NCI H460 cells.
Curcuminoids are the major natural phenolic compounds found in the rhizome of many Curcuma species. Curcuminoids consist of a mixture of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Although numerous studies have shown that curcumin induced cell apoptosis in many human cancer cells, however, mechanisms of BDMC-inhibited cell growth and -induced apoptosis in human lung cancer cells still remain unclear. Herein, we investigated the effect of BDMC on the cell death via the cell cycle arrest and induction of apoptosis in NCI H460 human lung cancer cells. Flow cytometry assay was used to measure viable cells, cell cycle distribution, the productions of reactive oxygen species (ROS) and Ca2+ , mitochondrial membrane potential (ΔΨm ) and caspase-3, -8 and -9 activity. DNA damage and condension were assayed by Comet assay and DAPI staining, respectively. Western blotting was used to measure the changes of cell cycle and apoptosis associated protein expressions. Results indicated that BDMC significantly induced cell death through induced S phase arrest and induced apoptosis. Moreover, DMC induced DNA damage and condension, increased ROS and Ca2+ productions and decreased the levels of ΔΨm and promoted activities caspase-3, -8, and -9. Western blotting results showed that BDMC inhibited Cdc25A, cyclin A and E for causing S phase arrest, furthermore, promoted the expression of AIF, Endo G and PARP and the levels of Fas ligand (Fas L) and Fas were also up-regulated. Results also indicated that BDMC increased ER stress associated protein expression such as GRP78, GADD153, IRE1α, IRE1β, ATF-6α, ATF-6β, and caspase-4. Taken together, we suggest that BDMC induced cell apoptosis through multiple signal pathways such as extrinsic, intrinsic and ES tress pathway. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1899-1908, 2016.


Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats.
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. In Parkinson's disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life. Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson's disease. The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats. Male Wistar rats received four injections of CBD (0.5 or 5 mg/kg) or vehicle (days 2-5). On days 3 and 5, animals received also one injection of 1 mg/kg reserpine or vehicle. Locomotor activity, vacuous chewing movements, and catalepsy were assessed from day 1 to day 7. On days 8 and 9, we evaluated animals' performance on the plus-maze discriminative avoidance task, for learning/memory assessment. CBD (0.5 and 5 mg/kg) attenuated the increase in catalepsy behavior and in oral movements - but not the decrease in locomotion - induced by reserpine. CBD (0.5 mg/kg) also ameliorated the reserpine-induced memory deficit in the discriminative avoidance task. Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson's disease and tardive dyskinesia.


Defects in mitochondrial fatty acid synthesis result in failure of multiple aspects of mitochondrial biogenesis in Saccharomyces cerevisiae.
Mitochondrial fatty acid synthesis (mtFAS) shares acetyl-CoA with the Krebs cycle as a common substrate and is required for the production of octanoic acid (C8) precursors of lipoic acid (LA) in mitochondria. MtFAS is a conserved pathway essential for respiration. In a genetic screen in Saccharomyces cerevisiae designed to further elucidate the physiological role of mtFAS, we isolated mutants with defects in mitochondrial post-translational gene expression processes, indicating a novel link to mitochondrial gene expression and respiratory chain biogenesis. In our ensuing analysis, we show that mtFAS, but not lipoylation per se, is required for respiratory competence. We demonstrate that mtFAS is required for mRNA splicing, mitochondrial translation and respiratory complex assembly, and provide evidence that not LA per se, but fatty acids longer than C8 play a role in these processes. We also show that mtFAS- and LA-deficient strains suffer from a mild haem deficiency that may contribute to the respiratory complex assembly defect. Based on our data and previously published information, we propose a model implicating mtFAS as a sensor for mitochondrial acetyl-CoA availability and a co-ordinator of nuclear and mitochondrial gene expression by adapting the mitochondrial compartment to changes in the metabolic status of the cell.


Resuscitation-induced gut edema and intestinal dysfunction.
Mesenteric venous hypertension and subsequent gut edema play a pivotal role in the development of intra-abdominal hypertension. Although gut edema is one cause of intra-abdominal hypertension, its impact on gut function is unknown. The purpose of this study was to create a model of acute hydrostatic gut edema and to evaluate its effect on gut motility and barrier function. The first study, group A, evaluated the effect of gut edema on transit over time using 20 mL/kg 0.9% saline. The second study, group B, focused on the 12-hour time period using 80 mL/kg 0.9% saline. Rats were randomized to superior mesenteric vein partial occlusion (venous hypertension) or sham surgery. At 6, 12, and 24 hours, group A underwent intestinal transit and tissue water weight measurements. At 12 hours, group B underwent tissue water, transit, ileal permeability and resistance, lactate and myeloperoxidase activity, and mucosal injury measurements. Venous hypertension with fluid resuscitation caused acute hydrostatic gut edema, delayed intestinal transit, increased mucosal permeability to macromolecules, and decreased tissue resistance over time. Mucosal injury was minimal in mesenteric venous hypertension. Acute mesenteric venous hypertension and resuscitation-induced gut edema, in the absence of ischemia/reperfusion injury, is associated with delayed intestinal transit and altered gut barrier function.


Transcriptome profiling of Zymomonas mobilis under ethanol stress.
High tolerance to ethanol is a desirable characteristics for ethanologenic strains used in industrial ethanol fermentation. A deeper understanding of the molecular mechanisms underlying ethanologenic strains tolerance of ethanol stress may guide the design of rational strategies to increase process performance in industrial alcoholic production. Many extensive studies have been performed in Saccharomyces cerevisiae and Escherichia coli. However, the physiological basis and genetic mechanisms involved in ethanol tolerance for Zymomonas mobilis are poorly understood on genomic level. To identify the genes required for tolerance to ethanol, microarray technology was used to investigate the transcriptome profiling of the ethanologenic Z. mobilis in response to ethanol stress. We successfully identified 127 genes which were differentially expressed in response to ethanol. Ethanol up- or down-regulated genes related to cell wall/membrane biogenesis, metabolism, and transcription. These genes were classified as being involved in a wide range of cellular processes including carbohydrate metabolism, cell wall/membrane biogenesis, respiratory chain, terpenoid biosynthesis, DNA replication, DNA recombination, DNA repair, transport, transcriptional regulation, some universal stress response, etc. In this study, genome-wide transcriptional responses to ethanol were investigated for the first time in Z. mobilis using microarray analysis.Our results revealed that ethanol had effects on multiple aspects of cellular metabolism at the transcriptional level and that membrane might play important roles in response to ethanol. Although the molecular mechanism involved in tolerance and adaptation of ethanologenic strains to ethanol is still unclear, this research has provided insights into molecular response to ethanol in Z. mobilis. These data will also be helpful to construct more ethanol resistant strains for cellulosic ethanol production in the future.


The International Cooperative Study on the Timing of Aneurysm Surgery. The North American experience.
The timing of aneurysm surgery after subarachnoid hemorrhage is a major neurosurgical controversy addressed by the International Cooperative Study on the Timing of Aneurysm Surgery (1980-1983). The present report examines the results of this trial in the subgroup of patients admitted to North American centers. The method of study was a large, multicenter, prospective, epidemiological survey. Neurosurgeons were required to indicate prospectively the interval to planned aneurysm surgery at the time of patient admission. Outcome at 6 months was determined by a blinded evaluator, and overall management results were analyzed by the planned surgical interval. Seven hundred seventy-two (21.9% of the total study population) patients admitted from days 0 to 3 after subarachnoid hemorrhage were accrued in North American centers. Overall outcome in patients planned for surgery in days 0-3 was equivalent in terms of mortality (after adjustment for prognostic variables) to patients planned for days 11-32, but the early patients had significantly improved rates of good recovery (70.9% versus 61.7%, p less than 0.01). Patients planned for surgery during the days 7-10 interval had nearly twice the mortality of patients in the other intervals. In contrast to the results from the overall trial, which found no difference between early and delayed surgery, results were best in North American centers when surgery was planned between days 0 and 3 after subarachnoid hemorrhage. These findings argue strongly for early diagnosis and referral for surgical intervention of North American patients suspected of having a ruptured cerebral aneurysm.


Epistatic analysis of the roles of the RAD27 and POL4 gene products in DNA base excision repair in S. cerevisiae.
The cellular role of the DNA polymerase encoded by the Saccharomyces cerevisiae POL4 gene is unclear. We have used an epistasis analysis to investigate whether the proteins encoded by the POL4 and RAD27 genes participate in alternative, non-redundant subpathways of DNA base excision repair (BER). We constructed strains in which the genes were deleted singly or in combination and have examined their sensitivity to DNA damaging agents as well as spontaneous mutation frequency. The double deletion strain is no more sensitive to damaging agents and has no higher spontaneous mutation frequency than the most sensitive single mutant. These data indicate that the protein encoded by the POL4 gene does not participate in a non-redundant subpathway of base excision repair under these conditions. We discuss the implications of these results in light of the recent classification of the POL4 gene product as a member of the DNA polymerase lambda family.


Digital pathology in the diagnostic setting: beyond technology into best practice and service management.
Digital pathology (DP) and whole-slide imaging (WSI) technology have matured substantially over the last few years and there is growing evidence from validation studies that WSI is comparable to glass slides for histopathology diagnosis, although with some limitations, which can be appropriately minimised. Whether the controlled environment of validation studies translates to the same level of robustness when WSI is used in the actual diagnostic setting depends on the technical quality of WSI acquisition and on factors that influence the pre-image acquisition variables including the quality of glass slide inputs, and postimage acquisition variables such as access and use of WSI. The concept of 'DP service management' is introduced to fulfil the holistic needs of a laboratory intending to use the DP solution incorporating WSI for diagnostic purposes. The DP service management team should be an integral part of the diagnostic laboratory as it plays a central role undertaking responsibility to address an extensive range of issues from technical and training to governance and accreditation, hence ensuring a viable and sustainable diagnostic DP integration and usage. The pathologist as a specialist in the field and key decision maker of histopathology diagnoses has the duty and responsibility to acquaint and familiarise with DP and WSI when using the technology, especially on their indications and limitations, so as to take full advantage of these tools to enhance diagnostic quality.


Efficacy of natural propolis extract in the control of American Foulbrood.
Paenibacillus larvae is the causative agent of American Foulbrood (AFB), a severe disease that affects larvae of the honeybees. Due to the serious effects associated with AFB and the problems related to the use of antibiotics, it is necessary to develop alternative strategies for the control of the disease. The aim of the present work was to evaluate the effect of a propolis ethanolic extract (PEE) against P. larvae and its potential for the control of AFB. In vitro activity of PEE against P. larvae isolates was evaluated by the disk diffusion method and the minimum inhibitory concentration (MIC) was determined. Toxicity for honeybees was evaluated by oral administration of PEE and its lethal concentration was assessed. Lastly, colonies from an apiary with episodes of AFB on previous years were divided into different groups and treated with sugar syrup supplemented with PEE by aspersion (group one), sugar syrup by aspersion (group two), fed with sugar syrup supplemented with PEE (group three) and fed with sugar syrup only (group four). All isolates were sensitive to PEE and the MIC median was 0.52% (range 0.32-0.64). PEE was not toxic for bees at least at 50%. Field assays showed that 21 and 42 days after the application of the treatments, the number of P. larvae spores/g of honey was significantly lower in colonies treated with PEE compared to the colonies that were not treated with PEE. To our knowledge, this is the first report about the use of propolis for the treatment of beehives affected with P. larvae spores.


Monoclonal antibodies protect from Staphylococcal Enterotoxin K (SEK) induced toxic shock and sepsis by USA300 Staphylococcus aureus.
Staphylococcus aureus is a leading infectious cause of life-threatening disease in humans, yet there is currently no vaccine to combat this bacterium. The pathogenesis of S. aureus is mediated by a diverse array of protein toxins including a large family of secreted pyrogenic superantigens. Neutralization of superantigens, including SEB and TSST-1, has proven to be protective in several animal models of toxic shock and sepsis. We demonstrate, for the first time, that a far more prevalent staphylococcal superantigen, SEK, can also induce lethal shock in mice. Additionally, we describe monoclonal antibodies (mAbs) that inhibit SEK-induced mitogenicity as well as protect against SEK-induced lethality, and enhance survival from S. aureus septicemia in murine models. MAb-4G3 (IgG2b), mAb-5G2 (IgG1), and mAb-9H2 (IgG1), all inhibit SEK-induced proliferation and cytokine production of human immune cells. We then demonstrate that passive immunization with a combination of mAb-4G3 and mAb-5G4, 2 mAbs that do not compete for epitope(s) on SEK, significantly enhance survival in a murine model of SEK-induced toxic shock (p = 0.006). In the setting of sepsis, passive immunization with this combination of mAbs also significantly enhances survival in mice after challenge with CA-MRSA strain USA300 (p = 0.03). Furthermore, septic mice that received mAb treatment in conjunction with vancomycin exhibit less morbidity than mice treated with vancomycin alone. Taken together, these findings suggest that the contribution of SEK to S. aureus pathogenesis may be greater than previously appreciated, and that adjunctive therapy with passive immunotherapy against SEs may be beneficial.


Design and optimization of NSAID loaded nanoparticles.
The objective of the study was to design and evaluate NSAID loaded Nanoparticles drug delivery system, where Flurbiprofen (model drug) Nanoparticles with suitable size range are envisaged to concentrate at inflammation sites due to increase fragility of blood vessels at those sites and increased aggregation and prostaglandin synthesis. Materials used were surfactant (pluronic F 68) and polymer (poly lactic co glycolic acid; PLGA). The flurbiprofen loaded nanoparticles were prepared by solvent diffusion nano-precipitation method. Experiment was carried out following 3(2) factorial designs, where drug-polymer ratio was varied to optimize the formulation. From I.R studies no drug-polymer interaction was found. Particles size analysis was done using Malvern Mastersizer. Two parameters, namely, drug-polymer ratio and solvent-nonsolvent ratio were chosen for optimization following the factorial design. Amount of drug loading and surfactant were kept constant, and only polymer load was varied. The in-vitro drug release profile from nanoparticles was found to follow Higuchi square root kinetics implying a diffusion dependent release as is expected of an insoluble, non-swellable nature of PLGA. It indicated that nanoparticles formed were matrix in nature, in which flurbiprofen dispersed uniformly. Suitable polynomial models were generated and statistically validated using ANOVA for the different responses, namely drug release (maximization) and particle size (minimization). Those models were solved numerically and simultaneously to optimize the required formulation. Optimized formulation were found to have a polymer-drug ratio of 18.89:1 and manufactured at a nonsolvent-solvent ratio of 4:1 to maximized release after 8 hrs and minimized particle size. The methodology avoids the use of organic solvent and thus provides a safe, reproducible and fast method of production of nanoparticles. The study collaborates on the feasibility and suitability of aqueous polymeric drug delivery system, employing statistical design to develop a clinically useful Nanoparticle system with targeting potential.


Induction by NGF of meiotic maturation of Xenopus oocytes expressing the trk proto-oncogene product.
The effect of nerve growth factor (NGF) was assessed in Xenopus oocytes expressing the human trk proto-oncogene product, p140prototrk. Oocytes injected with trk messenger RNA expressed polypeptides recognized by antibodies to the trk gene product. Exposure of these oocytes to nanomolar amounts of NGF resulted in specific surface binding of 125I-labeled NGF, tyrosine phosphorylation of p140prototrk, and meiotic maturation, as determined by germinal vesicle breakdown and maturation promoting factor (p34cdc2) kinase activation. Thus the trk proto-oncogene product can act as a receptor for NGF in a functionally productive manner.


The association between preoperative fatigue and instrumental activities in daily living with complications and length of hospital stay in patients undergoing colorectal surgery.
The incidence of colorectal cancer (CRC) is highest among the elderly. An important treatment modality is surgery. After surgery, due to poor functional recovery, some elderly have an increased risk for complications and prolonged length of hospital stay (LOS). Preoperative elevated levels of fatigue and impaired functioning in instrumental activities of daily living (iADL) might be associated with these outcomes, and may, therefore, be helpful to recognize patients with elevated risk for complications or prolonged LOS, who should undergo more thorough functional assessment. This exploratory study aims to assess whether physical fatigue, reduced activity and/or iADL, assessed preoperatively, are associated with postoperative complications and prolonged LOS, in elderly patients undergoing surgery for CRC. We performed an exploratory prospective study in older (≥ 65 years) patients (n = 57) who were scheduled to undergo elective surgery for colorectal cancer. Fatigue and iADL functioning were assessed with questionnaires. Multivariable regression analyses were used to examine the relationship of fatigue and iADL with complications and LOS. IADL was not associated with complications or LOS. Fatigue was not associated with complications. Patients with higher fatigue had increased LOS in the univariable analyses but not in the multivariable analyses after adjustment for nutritional status and neoadjuvant treatment. We found that fatigue was associated with increased LOS in the univariable analysis. The results from the multivariable analysis and path analysis indicate, however, that this is likely not a causal relationship; the observed relationship between physical fatigue and LOS appears to be confounded by nutritional status and by having received neoadjuvant treatment. Although fatigue is a predictor for increased LOS, assessment of fatigue and iADL has no additional value for identifying elderly at risk for poor functional outcome after CRC surgery.


BSDB: the biomolecule stretching database.
We describe the Biomolecule Stretching Data Base that has been recently set up at http://www.ifpan.edu.pl/BSDB/. It provides information about mechanostability of proteins. Its core is based on simulations of stretching of 17 134 proteins within a structure-based model. The primary information is about the heights of the maximal force peaks, the force-displacement patterns, and the sequencing of the contact-rupturing events. We also summarize the possible types of the mechanical clamps, i.e. the motifs which are responsible for a protein's resistance to stretching.


Valence and Conduction Band Densities of States of Metal Halide Perovskites: A Combined Experimental-Theoretical Study.
We report valence and conduction band densities of states measured via ultraviolet and inverse photoemission spectroscopies on three metal halide perovskites, specifically methylammonium lead iodide and bromide and cesium lead bromide (MAPbI3, MAPbBr3, CsPbBr3), grown at two different institutions on different substrates. These are compared with theoretical densities of states (DOS) calculated via density functional theory. The qualitative agreement achieved between experiment and theory leads to the identification of valence and conduction band spectral features, and allows a precise determination of the position of the band edges, ionization energy and electron affinity of the materials. The comparison reveals an unusually low DOS at the valence band maximum (VBM) of these compounds, which confirms and generalizes previous predictions of strong band dispersion and low DOS at the MAPbI3 VBM. This low DOS calls for special attention when using electron spectroscopy to determine the frontier electronic states of lead halide perovskites.


Cyclic AMP potentiates receptor-stimulated phosphoinositide hydrolysis in human neuroepithelioma cells.
A stimulatory role for cAMP in the regulation of receptor-activated phosphoinositide hydrolysis has been examined in human SK-N-MCIXC and SK-N-MCIIE neuroepithelioma cells. The addition of optimal concentrations of oxotremorine-M, norepinephrine, endothelin-1, and ATP enhanced the release of inositol phosphates by 2-9-fold after activation of muscarinic, alpha 1-adrenergic, endothelin, and P2 nucleotide receptors, respectively. All combinations of these agonists elicited a release of inositol phosphates that was at least additive. However, the combined presence of oxotremorine-M and norepinephrine resulted in a phosphoinositide hydrolysis that was 30% greater than additive. This potentiation of inositol lipid hydrolysis resulted from an increased activity of the muscarinic receptor after the addition or norepinephrine and persisted after alpha 1-adrenergic receptor blockade. The enhancement of muscarinic receptor-stimulated inositol phosphate release could be quantitatively mimicked by inclusion of the beta-adrenergic agonist isoproterenol (EC50 approximately 0.1 microM), but not by alpha 1- or alpha 2-adrenergic agonists. Potentiation of oxotremorine-M-stimulated inositol lipid hydrolysis observed in the presence of either norepinephrine or isoproterenol was reduced in the absence of added Ca2+. Addition of either norepinephrine or isoproterenol to SK-N-MCIXC cells also resulted in a 16-fold increase in cAMP concentration. Although the cell-permeant 8-chloro-4-phenylthio-cAMP had a small inhibitory effect on basal inositol phosphate release, its inclusion resulted in a 19-31% enhancement of muscarinic, endothelin, ATP, and alpha 1-adrenergic receptor-stimulated phosphoinositide hydrolysis. We conclude 1) that, in SK-N-MCIXC cells, the addition of beta-adrenergic agonists selectively enhances muscarinic receptor-stimulated phosphoinositide hydrolysis through a cAMP-dependent process and 2) that the ability of exogenously added cAMP to enhance the activation of all four inositol lipid-linked receptors indicates that the effects of cAMP on inositol lipid hydrolysis are compartmentalized in these cells.


Ensuring safe international trade: how are the roles and responsibilities evolving and what will the situation be in ten years' time?
The roles of the international standard-setting bodies that are mandated to facilitate safe trade, such as the World Organisation for Animal Health (OIE), the Codex Alimentarius Commission, the International Plant Protection Convention and the World Trade Organization, are well documented, as are the roles of the international organisations responsible for global health issues: the OIE, the World Health Organization and the Food and Agriculture Organization of the United Nations. However, developments in international trade, such as accelerating globalisation and the frequent emergence and re-emergence of diseases affecting both humans and animals, have brought new challenges and the need to reconsider the future roles of such organisations. New participants and new demands have also emerged to challenge these mandates, leading to potential areas of conflict. The need for countries to establish themselves as new trade partners, or to strengthen their positions while still maintaining safe trade, poses a challenge to standard-setting organisations, which must meet these demands while still remaining sensitive to the needs of developing countries. In this paper, the author describes and discusses some of these challenges and suggests how international organisations could evolve to confront such issues.


The quantity of food waste in the garbage stream of southern Ontario, Canada households.
There is little consensus on the amount of worldwide food waste generation because many current estimates are indirect and link back to the same limited primary datasets, with much of the data originating from fieldwork undertaken in the 1970s and 1980s. Direct measurement of waste streams, through waste composition studies, can be used to develop accurate estimates of food waste disposal. In Ontario, Canada, municipalities that undertake household waste composition studies all use a common direct measurement methodology that includes a broad range of waste categories, including food waste. The purpose of this research was to estimate the quantity of food waste disposed, in the garbage stream, by households in southern Ontario, Canada, and determine if this common methodology could be expanded and serve as the basis of a standardized and rigorous household food waste measurement methodology. Household waste composition study data (2012-2015), including a single "food waste" category, were gathered from 9 Ontario municipalities, aggregated and analyzed to develop estimates of food waste in the garbage stream. On average, households disposed 2.40 kg/week of food waste in the garbage, which comprised 35.4% of this waste stream. This does not include any food waste otherwise disposed (e.g., sink) or recycled (e.g., composted). Urban households disposed significantly greater amounts of food waste compared to rural households in the spring (p = 0.01) and summer (p = 0.02). Households with access to a green bin program disposed significantly less food waste than those with no access to a green bin program in the spring (p = 0.03) and summer (p<0.01). The common methodology used to develop these estimates shows promise as the basis of a household food waste measurement methodology. This future methodology would include dividing food waste into avoidable and unavoidable food waste categories, as well as adding subcategories (e.g., avoidable fruits and vegetables).


Electrographic seizures are associated with brain injury in newborns undergoing therapeutic hypothermia.
Seizures are common among newborns with hypoxic-ischaemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is associated with cerebral tissue injury independent of amplitude-integrated EEG (aEEG) background activity. Term neonates undergoing 72 h of TH at four centres were selected for study if they had continuous aEEG and MRI. The aEEG with corresponding 2-channel raw EEG (aEEG/EEG), was classified by severity of background and seizure burden; MR images were classified by the severity of tissue injury. Of 85 neonates, 52% had seizures on aEEG/EEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 h and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with severe injury on MRI were high seizure burden, poor aEEG background, 10 min Apgar and the need for more than one anticonvulsant. In multivariate logistic regression, high seizure burden was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to 17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant. Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.


Continuous decoding of grasping tasks for a prospective implantable cortical neuroprosthesis.
In the recent past several invasive cortical neuroprostheses have been developed. Signals recorded from the motor cortex (area MI) have been decoded and used to control computer cursors and robotic devices. Nevertheless, few attempts have been carried out to predict different grips.A Support Vector Machines (SVMs) classifier has been trained for a continuous decoding of four/six grip types using signals recorded in two monkeys from motor neurons of the ventral premotor cortex (area F5) during a reach-to-grasp task. The results showed that four/six grip types could be extracted with classification accuracy higher than 96% using window width of 75-150 ms. These results open new and promising possibilities for the development of invasive cortical neural prostheses for the control of reaching and grasping.


USP18 is an essential regulator of muscle cell differentiation and maturation.
The ubiquitin proteasomal system is a critical regulator of muscle physiology, and impaired UPS is key in many muscle pathologies. Yet, little is known about the function of deubiquitinating enzymes (DUBs) in the muscle cell context. We performed a genetic screen to identify DUBs as potential regulators of muscle cell differentiation. Surprisingly, we observed that the depletion of ubiquitin-specific protease 18 (USP18) affected the differentiation of muscle cells. USP18 depletion first stimulated differentiation initiation. Later, during differentiation, the absence of USP18 expression abrogated myotube maintenance. USP18 enzymatic function typically attenuates the immune response by removing interferon-stimulated gene 15 (ISG15) from protein substrates. However, in muscle cells, we found that USP18, predominantly nuclear, regulates differentiation independent of ISG15 and the ISG response. Exploring the pattern of RNA expression profiles and protein networks whose levels depend on USP18 expression, we found that differentiation initiation was concomitant with reduced expression of the cell-cycle gene network and altered expression of myogenic transcription (co) factors. We show that USP18 depletion altered the calcium channel gene network, resulting in reduced calcium flux in myotubes. Additionally, we show that reduced expression of sarcomeric proteins in the USP18 proteome was consistent with reduced contractile force in an engineered muscle model. Our results revealed nuclear USP18 as a critical regulator of differentiation initiation and maintenance, independent of ISG15 and its role in the ISG response.


Fusarium Wilt of African Daisy (Osteospermum sp.) Caused by Fusarium oxysporum in Italy.
During the fall of 2002, African daisy (Osteospermum sp.) plants showing symptoms of a wilt disease were observed in a commercial, nonheated glasshouse in Albenga in northern Italy. Wilted plants were first observed when outside temperatures were between 15 and 28°C. Symptoms were first observed on seedlings 40 days after they had been transplanted into pots. The vascular tissues of affected plants appeared brown. These plants were stunted and developed yellowed leaves with brown or black streaks in the vascular system. The vascular streaks in the yellow leaves extended from the crown and were continuous with a brown discoloration in the vascular system of the crown and upper taproot. Fusarium oxysporum was consistently and readily isolated from symptomatic vascular tissue onto a Fusarium-selective medium (1). Healthy, rooted, 40-day-old plants were inoculated by root-dip with a conidial suspension (1 × 107 CFU/ml) of three isolates of F. oxysporum obtained from infected plants and transplanted into pots filled with steam-sterilized soil. Noninoculated plants served as control treatments. Plants (10 per treatment) were grown in a glasshouse at an average temperature of 25°C (minimum of 12°C and maximum of 39°C). Wilt symptoms and vascular discoloration in the roots, crown, and veins developed within 20 days on each inoculated plant, while noninoculated plants remained healthy. F. oxysporum was consistently reisolated from infected plants. The pathogenicity test was conducted twice. To our knowledge, this is the first report of F. oxysporum on Osteospermum sp. in Italy or elsewhere in the world. Reference: (1) H. Komada. Rev. Plant Prot. Res. 8:114, 1975.


Ensuring health equity during the COVID-19 pandemic: the role of public health infrastructure.
The COVID-19 pandemic has significantly stressed public health systems around the world and exposed the gaps in health care for underserved and vulnerable populations. In the context of the social determinants of health, focusing on health system preparedness is paramount for protecting the health of all of society. Faced with old threats (e.g., re-emergence of measles), disruptive new technologies (e.g., electronic cigarettes), increased challenges (e.g. drug-resistant organisms), and new threats (e.g., the current pandemic, climate change, politicized misinformation), our health systems must be robust and resilient. The response must include those who now suffer disproportionately-the poor and the vulnerable. Current World Health Organization priorities call for infrastructures capable of detecting, monitoring, and responding to health emergencies, such as COVID-19, and the health impacts of climate change in the context of health for all. Health care infrastructure can be better prepared and more equitable if systems are strengthened by building on core competencies and following the recommendations made for leadership, stakeholder involvement, accreditation, data collection, and funding resources. Ensuring health equity in a pandemic requires robust and resilient public health infrastructure during normal times.


Non-line-of-sight ultraviolet single-scatter propagation model.
A universal non-line-of-sight (NLOS) ultraviolet single-scatter propagation model in noncoplanar geometry is proposed to generalize an existing restricted analytical model. This generalized model considers that the transmitter and the receiver cone axes lie in the same plane or different planes, where they can be pointed in arbitrary directions. The model is verified by extensive simulations, showing that the proposed model is consistent with the original NLOS single-scatter propagation model and the Monte Carlo model. The path loss performance is further investigated in terms of different noncoplanar geometric settings and path loss dependence is also analyzed for different factors, including scattering volume size, relative position between the scattering volume and the transceiver, and radiation intensity of the transmitter.


Phenotype and X inactivation in 45,X/46,X,r(X) cases.
We studied a new series of 21 individuals mosaic for a ring X chromosome [r(X)]. Of nine individuals with mental retardation, only one had a r(X) that lacked XIST (X-inactive-specific transcript) and was not subject to X inactivation, which would explain the abnormal phenotype; the remaining eight cases had XIST on their r(X). The majority of cases (five of seven) with mental retardation had an apparently early replicating r(X); but the androgen receptor gene (AR) was methylated on one allele in five of six informative cases, including two cases with an early replicating r(X). These conflicting results on two indicators of X inactivation suggest a potential dissociation between late replication and DNA methylation in these r(X) chromosomes, which may fail to become completely silenced. Of the twelve subjects who were not mentally retarded, all had XIST present on their r(X) and most (8/10) showed a late replicating r(X), together with AR methylation in all five informative cases, indicating r(X) inactivation. Thus, the unusual phenotypic features and mental retardation associated with the presence of a r(X) cannot be explained solely on the basis of presence or absence of XIST. The r(X) in cases with mental retardation were consistently smaller than those in individuals with normal intelligence, perhaps indicating inability for small rings to undergo structural changes associated with complete X inactivation or lethality in cases with a large non-inactivated r(X). Of the Turner syndrome features present in the r(X) cases, only edema was present in a lesser frequency than in 45,X individuals. Our cases generally had a less severe phenotype than those previously reported, suggesting that reported incidences of abnormalities may be influenced by ascertainment bias, with mental retardation potentially unrelated to the presence of the r(X) in some cases.


Rules of song development and their use in vocal interactions by birds with large repertoires.
Songbirds are well known for settling their disputes by vocal signals, and their singing plays a dominant role. Most studies on this issue have concentrated on bird species that develop and use small vocal repertoires. In this article we will go farther and focus on examples of how species with large song repertoires make use of their vocal competence. In particular, we will outline the study of interaction rules which have been elucidated by examining time- and pattern-specific relationships between signals exchanged by territorial neighbors. First we present an inquiry into the rules of song learning and development. In birds with large song repertoires, the ontogeny of such rules proceeds along a number of trajectories which help in understanding the often remarkable accomplishments of adult birds. In both approaches, our model species will be the Common Nightingale Luscinia megarhynchos that has been investigated intensively in the field and in the laboratory.


The signal recognition particle receptor is a complex that contains two distinct polypeptide chains.
Signal recognition particle (SRP) and SRP receptor are known to be essential components of the cellular machinery that targets nascent secretory proteins to the endoplasmic reticulum (ER) membrane. Here we report that the SRP receptor contains, in addition to the previously identified and sequenced 69-kD polypeptide (alpha-subunit, SR alpha), a 30-kD beta-subunit (SR beta). When SRP receptor was purified by SRP-Sepharose affinity chromatography, we observed the co-purification of two other ER membrane proteins. Both proteins are approximately 30 kD in size and are immunologically distinct from each other, as well as from SR alpha and SRP proteins. One of the 30-kD proteins (SR beta) forms a tight complex with SR alpha in detergent solution that is stable to high salt and can be immunoprecipitated with antibodies to either SR alpha or SR beta. Both subunits are present in the ER membrane in equimolar amounts and co-fractionate in constant stoichiometry when rough and smooth liver microsomes are separated on sucrose gradients. We therefore conclude that SR beta is an integral component of SRP receptor. The presence of SR beta was previously masked by proteolytic breakdown products of SR alpha observed by others and by the presence of another 30-kD ER membrane protein (mp30) which co-purifies with SR alpha. Mp30 binds to SRP-Sepharose directly and is present in the ER membrane in several-fold molar excess of SR alpha and SR beta. The affinity of mp30 for SRP suggests that it may serve a yet unknown function in protein translocation.


Nitric oxide induces osteoblast apoptosis through the de novo synthesis of Bax protein.
Nitric oxide (NO) plays a crucial role in the physiological and pathophysiological regulations of osteoblast functions. This study is designed to evaluate the toxic effects of NO released by sodium nitroprusside (SNP), an NO donor, on neonatal Wistar rat calvarial osteoblasts from the analyses of cell viability, alkaline phosphatase (ALP) activity, cell morphology, apoptotic cells, terminal deoxynucleotidyl transferase-mediated dUTP nick end-label (TUNEL) assay, DNA ladder, and immunocytochemistry and Western blot for proapoptotic Bax protein. SNP increased the levels of nitrite, an oxidative product of NO, in the culture medium of osteoblasts in concentration- and time-dependent manners, and altered cell morphologies to round and shrinkage shapes. Administration of osteoblasts with SNP resulted in concentration- and time-dependent decreases of cell viability and ALP activity. Analysis of apoptotic cells revealed that SNP increased the percentages of osteoblasts processing apoptosis. Analyses of TUNEL and DNA ladder showed that SNP caused DNA fragmentation. Pretreatment with cycloheximide, an inhibitor of protein synthesis, partially blocked SNP-induced osteoblast apoptosis. Imunocytochemical and immunoblotting analyses revealed that SNP increased Bax protein in osteoblasts. This study suggests that SNP could increase the levels of NO in osteoblasts, and cause osteoblast apoptosis possibly through the de novo synthesis of proapoptotic Bax protein.


Chronic retention of urine. The relationship between upper tract dilatation and bladder pressure.
Twenty-five men with chronic retention of urine were studied in order to investigate the relationship between upper tract dilatation and bladder pressure. Each underwent assessment of upper tract dilatation and urodynamic investigation before bladder drainage. Patients were reassessed 3 or more months after operation. Residual urine and detrusor contraction pressure decreased significantly after operation (P less than 0.0001:P less than 0.01). A significant increase in effective cystometric capacity and a significant decrease in pressure rise during filling led to an improvement in compliance. At pre-operative assessment, patients with upper tract dilatation had a significantly greater resting bladder pressure (P less than 0.05), end filling pressure (P less than 0.002) and pressure rise during filling (P less than 0.02) than those without upper tract dilatation. In addition, statistically significant correlations were found between serum creatinine and end filling pressure (P less than 0.05) and between upper tract dilatation and both high end filling pressure (greater than 25 cm H2O) and high pressure rise during filling (greater than 15 cm H2O: both P less than 0.05). Whilst high end filling pressure and high pressure rise during filling were found to be closely associated with upper tract dilatation (sensitivity 93 and 100%), there was a high false positive rate (specificity 64 and 45%). Furthermore, statistical analysis demonstrated that these data had a continuous though skewed distribution, suggesting that it is not possible to make a clear distinction between high and low pressure chronic retention.


Synthesis and structures of cadmium carboxylate and thiocarboxylate compounds with a sulfur-rich coordination environment: carboxylate exchange kinetics involving tris(2-mercapto-1-t-butylimidazolyl)hydroborato cadmium complexes, [Tm(Bu(t))]Cd(O2CR).
A series of cadmium carboxylate compounds in a sulfur-rich environment provided by the tris(2-tert-butylmercaptoimidazolyl)hydroborato ligand, namely, [Tm(Bu(t))]CdO2CR, has been synthesized via the reactions of the cadmium methyl derivative [Tm(Bu(t))]CdMe with RCO2H. Such compounds mimic aspects of cadmium-substituted zinc enzymes and also the surface atoms of cadmium chalcogenide crystals, and have therefore been employed to model relevant ligand exchange processes. Significantly, both (1)H and (19)F NMR spectroscopy demonstrate that the exchange of carboxylate groups between [Tm(Bu(t))]Cd(κ(2)-O2CR) and the carboxylic acid RCO2H is facile on the NMR time scale, even at low temperature. Analysis of the rate of exchange as a function of concentration of RCO2H indicates that reaction occurs via an associative rather than dissociative pathway. In addition to carboxylate compounds, the thiocarboxylate derivative [Tm(Bu(t))]Cd[κ(1)-SC(O)Ph] has also been synthesized via the reaction of [Tm(Bu(t))]CdMe with thiobenzoic acid. The molecular structure of [Tm(Bu(t))]Cd[κ(1)-SC(O)Ph] has been determined by X-ray diffraction, and an interesting feature is that, in contrast to the carboxylate derivatives [Tm(Bu(t))]Cd(κ(2)-O2CR), the thiocarboxylate ligand binds in a κ(1) manner via only the sulfur atom.


The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes.
Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.


Foreword: all things considered about probiotics, prebiotics and ıntestinal microbiota in children - from bench to bedside.
There are numerorus published and ongoing experimental/clinical studies about probiotics and prebiotics, intestinal microbiota and nutrition. Three years ago, at the first International Symposium of Probiotics Prebiotics in Paediatrics in Istanbul (2012) we highlighted the 'paediatric perspective' on these issues and brought together more than 40 global key opinion leaders and 400 attendants to have a chance to extensively discuss the past, present and the future. In 2014, the second state of art congress, held in Antalya, aimed to discuss the gut microbiota and microbiotics and their impact through lifespan. Selected papers of this conference are presented in this special issue 'prebiotics and probiotics in paediatrics' of Beneficial Microbes. A summary of the conference results is provided below.