Interfacial properties of the hexane + carbon dioxide + water system in the presence of hydrophilic silica.
Molecular dynamics simulations were conducted to study the interfacial behavior of the CO2 + H2O and hexane + CO2 + H2O systems in the presence of hydrophilic silica at geological conditions. Simulation results for the CO2 + H2O and hexane + CO2 + H2O systems are in reasonable agreement with the theoretical predictions based on the density functional theory. In general, the interfacial tension (IFT) of the CO2 + H2O system exponentially (linearly) decreased with increasing pressure (temperature). The IFTs of the hexane + CO2 + H2O (two-phase) system decreased with the increasing mole fraction of CO2 in the hexane/CO2-rich phase xCO2 . Here, the negative surface excesses of hexane lead to a general increase in the IFTs with increasing pressure. The effect of pressure on these IFTs decreased with increasing xCO2 due to the positive surface excesses of carbon dioxide. The simulated water contact angles of the CO2 + H2O + silica system fall in the range from 43.8° to 76.0°, which is in reasonable agreement with the experimental results. These contact angles increased with pressure and decreased with temperature. Here, the adhesion tensions are influenced by the variations in fluid-fluid IFT and contact angle. The simulated water contact angles of the hexane + H2O + silica system fall in the range from 58.0° to 77.0° and are not much affected by the addition of CO2. These contact angles increased with pressure, and the pressure effect was less pronounced at lower temperatures. Here, the adhesion tensions are mostly influenced by variations in the fluid-fluid IFTs. In all studied cases, CO2 molecules could penetrate into the interfacial region between the water droplet and the silica surface.


The metabolism of primaquine to its active metabolite is dependent on CYP 2D6.
The efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for CYP 2D6 in the generation of redox active metabolites. In the present study, the specific CYP 2D6 inhibitor paroxetine was used to assess its effects on the production of specific phenolic metabolites thought to be involved in PQ efficacy. Further, PQ causal prophylactic (developing liver stage) efficacy against Plasmodium berghei in CYP 2D knockout mice was assessed in comparison with a normal C57 background and with humanized CYP 2D6 mice to determine the direct effects of CYP 2D6 metabolism on PQ activity. PQ exhibited no activity at 20 or 40 mg/kg in CYP 2D knockout mice, compared to 5/5 cures in normal mice at 20 mg/kg. The activity against developing liver stages was partially restored in humanized CYP 2D6 mice. These results unambiguously demonstrate that metabolism of PQ by CYP 2D6 is essential for anti-malarial causal prophylaxis efficacy.


Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1.
We recently found a novel cell-cell adhesion system at cadherin-based adherens junctions (AJs), consisting at least of nectin, a Ca(2+)-independent homophilic immunoglobulin-like adhesion molecule, and afadin, an actin filament-binding protein that connects nectin to the actin cytoskeleton. Nectin is associated with cadherin through afadin and alpha-catenin. The cadherin-catenin system increases the concentration of nectin at AJs in an afadin-dependent manner. Nectin constitutes a family consisting of three members: nectin-1, -2, and -3. Nectin-1 serves as an entry and cell-cell spread mediator of herpes simplex virus type 1 (HSV-1). We studied here a role of the interaction of nectin-1alpha with afadin in entry and/or cell-cell spread of HSV-1. By the use of cadherin-deficient L cells overexpressing the full length of nectin-1alpha capable of interacting with afadin and L cells overexpressing a truncated form of nectin-1alpha incapable of interacting with afadin, we found that the interaction of nectin-1alpha with afadin increased the efficiency of cell-cell spread, but not entry, of HSV-1. This interaction did not affect the binding to nectin-1alpha of glycoprotein D, a viral component mediating entry of HSV-1 into host cells. Furthermore, the cadherin-catenin system increased the efficiency of cell-cell spread of HSV-1, although it also increased the efficiency of entry of HSV-1. It is likely that efficient cell-cell spread of HSV-1 is caused by afadin-dependent concentrated localization of nectin-1alpha at cadherin-based AJs.


Acceptability and barriers of a GP-physiotherapist partnership in the diagnosis and management of COPD in primary care: A qualitative study.
Chronic obstructive pulmonary disease (COPD) is commonly diagnosed and managed in primary care but there is evidence that this has been suboptimal, with low confidence expressed in providing interventions requiring behaviour change. The aim of this study was to determine the acceptability of a general practitioner (GP)-physiotherapist partnership in the diagnosis and management of COPD in primary care and to explore the experiences of participants during the implementation of the model. Semi-structured interviews were conducted with physiotherapists (n = 3), GPs (n = 2), practice nurses (PNs) (n = 2) and patients (n = 12) who had participated in the InNovaTivE Gp-physiotheRapist pArTnErship for copD (INTEGRATED) trial. We sought to explore participants' views about their experiences and perceived benefits, barriers and facilitators to the implementation of this model of care. Interviews were transcribed, coded and thematically analysed. Synthesis of the data was guided by the Theoretical Domains Framework for clinician interviews and the health belief model for patient interviews. All clinicians felt that this integrated model helped to optimise care for patients with COPD by facilitating evidence-based practice. GPs and PNs valued the physiotherapist's knowledge and skills relating to diagnosis and management, which was reported to complement their own management and improve patient outcomes. Patients reported a sense of empowerment following their appointments and acknowledged improved self-management skills. However, physiotherapists reported many patients were already engaging in positive health behaviours. Responses were mixed on the effectiveness of the model in facilitating teamwork between clinicians with different perspectives concerning management, communication pathways and logistical issues, such as time and room availability, being cited as barriers. An experienced cardiorespiratory physiotherapist embedded into a small number of primary care practices to work in partnership with GPs for COPD diagnosis and management was acceptable and viewed as beneficial for patients. Barriers relating to logistics and resources remain, which must be addressed to optimise implementation. Patient input was obtained from qualitative feedback from a prior study conducted by two authors and was used to refine the model of care to determine the added value of a physiotherapist integrated into the primary care team. This feedback was also used to refine the interview guides utilised in this study determine the acceptability of this model of care. We had health service involvement from the rehabilitation service of the local health district who were directly involved in determining study aims and establishing the project around the priorities for their chronic disease integration service. For example, this project aimed to engage with a less severe patient population in primary care who would benefit from pulmonary rehabilitation. The findings from this study will be used to further tailor the model of care to the needs of the public and patients. ACTRN12619001127190.


Suitable in-situ derivatization of alcohols by reaction with basic amines in Direct Analysis in Real Time mass spectrometry.
This work highlights the discovered in-situ analytical reaction between primary/secondary alcohols and nitrogenous bases (pyridine, quinoline) that involves the substitution of hydroxyl groups for nitrogen-containing charged species and proceeds in an ionization region of Direct Analysis in Real Time mass spectrometry (DART-MS) instrument at gas stream temperature of 150-450 °C. Resulted cations provide strong signals in mass spectra and this ensures high sensitivity of the analysis. Collision induced dissociation of such precursor ions gives rise to characteristic and simple fragmentation mass spectra revealing mainly protonated nitrogenous bases and carbonium cations resulting from the elimination of neutral nitrogen-containing bases. The dependence of signal response on gas stream temperature was elucidated. It was also found that, independently of gas stream temperature, high volatility low-molecular weight alcohols did not demonstrate characteristic DART spectra owing to a high rate of desorption/evaporation which does not provide sufficient probability of the reaction. To the best of our knowledge, this type of specific reactions in a plasma-based source of DART mass spectrometer is reported for the first time. It represents a new and interesting derivatization approach providing a rapid and sensitive complement method for the detection and identification of individual monools of various origin, profiling plant sterols and other steroid alcohols in different matrices.


Phenotypic and genotypic characterization of Canadian clinical isolates of Vibrio parahaemolyticus collected from 2000 to 2009.
Vibrio parahaemolyticus is the leading bacterial cause of food-borne illness due to the consumption of contaminated seafood. The aim of the present study was to determine the population of its subtypes and establish a better understanding of the various types of V. parahaemolyticus strains that are causing human illness in Canada. The subtypes for 100 human clinical isolates of V. parahaemolyticus collected between 2000 and 2009 were determined by performing serotyping, ribotyping, pulsed-field gel electrophoresis, and multilocus sequence typing. Within this panel of strains, there was a high level of diversity (between 22 and 53 subtypes per method), but the presence of predominant clones with congruent subtypes between the various methods was also observed. For example, all 32 isolates belonging to sequence type 36 (ST36) were from serogroup O4, while 31 of them were ribotype EcoVib235-287, and 24 of the 32 were SfiI pulsed-field gel electrophoresis (PFGE) pattern VPSF1.0001. With regard to the presence of known virulence genes, 74 of the 100 isolates were PCR positive for the presence of the thermostable direct hemolysin (tdh); and 59 of these 74 strains also contained the second virulence marker, the tdh-related hemolysin (trh). The detection of trh was more predominant (81%) among the clinical isolates, and only four (4%) of the clinical isolates tested negative for the presence of both tdh and trh. This database, comprising 100 clinical isolates of V. parahaemolyticus strains from Canada, forms a baseline understanding of subtype diversity for future source attribution and other epidemiologic studies.


Novel meroditerpenes from the brown alga Cystoseira sp.
Five new meroditerpenes have been isolated from a brown alga of the genus Cystoseira collected around the Canary Islands. One, cystoseirone diacetate (3), possesses a new rearranged structure with an unusual ether linkage in the diterpene side chain. Its biogenetic origin was explained as derived from the oxidation of amentol chromane diacetate (2) and subsequent cyclization. Structures were determined through the interpretation of the spectral data and by means of chemical transformations. The relative stereochemistry was proposed on the basis of ROESY correlations.


Oxidation of combined ingestion of glucose and fructose during exercise.
The purpose of the present study was to examine whether combined ingestion of a large amount of fructose and glucose during cycling exercise would lead to exogenous carbohydrate oxidation rates >1 g/min. Eight trained cyclists (maximal O(2) consumption: 62 +/- 3 ml x kg(-1) x min(-1)) performed four exercise trials in random order. Each trial consisted of 120 min of cycling at 50% maximum power output (63 +/- 2% maximal O(2) consumption), while subjects received a solution providing either 1.2 g/min of glucose (Med-Glu), 1.8 g/min of glucose (High-Glu), 0.6 g/min of fructose + 1.2 g/min of glucose (Fruc+Glu), or water. The ingested fructose was labeled with [U-(13)C]fructose, and the ingested glucose was labeled with [U-(14)C]glucose. Peak exogenous carbohydrate oxidation rates were approximately 55% higher (P < 0.001) in Fruc+Glu (1.26 +/- 0.07 g/min) compared with Med-Glu and High-Glu (0.80 +/- 0.04 and 0.83 +/- 0.05 g/min, respectively). Furthermore, the average exogenous carbohydrate oxidation rates over the 60- to 120-min exercise period were higher (P < 0.001) in Fruc+Glu compared with Med-Glu and High-Glu (1.16 +/- 0.06, 0.75 +/- 0.04, and 0.75 +/- 0.04 g/min, respectively). There was a trend toward a lower endogenous carbohydrate oxidation in Fruc+Glu compared with the other two carbohydrate trials, but this failed to reach statistical significance (P = 0.075). The present results demonstrate that, when fructose and glucose are ingested simultaneously at high rates during cycling exercise, exogenous carbohydrate oxidation rates can reach peak values of approximately 1.3 g/min.


Infant food problems and analytical aspects of providing safe and wholesome infant foods.
The technology of milk and infant food production, storage, and handling has advanced to the point that infant foods have had an excellent record of being free of recognized health hazards. The Infant Formula Council has published methods specifically for these foods. Methods are included from Standard Methods for the Examination of Dairy Products, Official Methods of Analysis, Bacteriological Analytical Manual, the Manual of Clinical Microbiology, and the U.S. Pharmacopeia. Criteria for microbiological quality have been issued by the Codex Alimentarius Commission, the International Commission for Microbiological Specifications for Foods, and the Public Health Service. Surveys in the United States and Canada have shown that sanitary standards are met with ease.


pH stability of individual folates during critical sample preparation steps in prevision of the analysis of plant folates.
The stability and eventual interconversion of nine mono-glutamate folates (5-methyl-tetrahydrofolate, tetrahydrofolate, 5-formyltetrahydrofolate, 5,10-methenyltetrahydrofolate, 5,10-methylenetetrahydrofolate, dihydrofolate, 10-formylfolic acid, 10-formyltetrahydrofolate and folic acid) during the typical sample preparation steps (heat treatment for 10 min at 100 degrees C and incubation for 2 h at 37 degrees C) at different pH values have been investigated by LC-MS/MS. An LC-MS/MS method with isotopically labelled [(13)C(5)]5-methyltetrahydrofolate and [(13)C(5)] folic acid as internal standards has been developed with enhanced sensitivity using a Chromolith RP-18 column. 5-Methyltetrahydrofolate, folic acid and 10-formylfolic acid are relatively stable at different pHs (from 2 to 10) with and without heat treatment. Tetrahydrofolate shows instability at low pH. 5-Formyltetrahydrofolate and 5,10-methenyltetrahydrofolate can interconvert by changes in pH. Tetrahydrofolate and 5,10-methylenetetrahydrofolate can interconvert with formaldehyde or by changes in pH. Incubation at 37 degrees C for 2 h is much less aggressive for most folates as compared with heat treatment at 100 degrees C. At 37 degrees C most folates are stable at pH values between 4 and 8 except tetrahydrofolate and dihydrofolate, which are degraded at low pH. 10-Formyltetrahydrofolate and 5,10-methylenetetrahydrofolate cannot be quantified in the present method because these compounds are converted to 5,10-methenyltetrahydrofolate and tetrahydrofolate, respectively, in the acidic mobile phase. This study provides useful information for the analysis of folates in the future as well as for the interpretation of quantitative results from earlier work.


[Fabry's disease in Spain. Study of 24 cases].
Fabry's disease is a rare metabolic disorder inherited as an X-linked trait resulting from a decreased activity of the alpha-galactosidase A lysosomal enzyme. This defect leads to an accumulation of unmetabolized neutral glycosphingolipids in all cell types. This condition displays a high rate of early mortality and affects both hemizygous males and heterozygous females. We present data from Spanish patients admitted to the Fabry Outcome Survey (FOS), a multicenter European registry for patients suffering from Fabry's disease, at the time of their inclusion. The study presents baseline data from 24 Spanish patients upon inclusion in the registry, with an analysis of their overall clinical characteristics and relationship to gender. The median age of onset of symptoms was 13 years, while it was 25.5 years for diagnosis. In 7 patients, the manifestations of the disease had been attributed to other processes. Predominant manifestations in males were angiokeratomas (86%), pain (71%), cardiovascular involvement (71%), kidney involvement (50%), digestive symptoms (43%) and ophthalmologic complications (43%). Among females, ophthalmologic complications were present in 50%, followed by cardiovascular involvement (40%); 30% of females had a painful clinical condition which is characteristic of the process. We present the clinical characteristics of the largest Spanish cohort of Fabry's disease sufferers reported so far. Due to the wide spectrum of clinical manifestations, their awareness allows an early diagnosis as well as the possibility of starting the specific therapy currently available.


Towards sustainability: new approaches to nano-drug preparation.
The conversion of drugs into drug nanoparticles (nano-drugs) represents a feasible method to enhance bioavailability of otherwise sparingly soluble-drugs. Nano-drugs enhance bioavailability through the improvement of dissolution rate and saturation solubility of drugs, by virtue of their small sizes. Nano-drugs available in the market are usually produced by top-down methods, such as wet milling and high pressure homogenization. These conventional top-down methods, however, suffer from high energy and time requirement, as well as wide and inconsistent nano-drug size distribution. Furthermore, commercially available nano-drugs are predominantly crystalline while amorphous nano-drugs are largely neglected despite their propensity to generate high saturation solubility. In this review, nonconventional methods to prepare crystalline and amorphous nano-drugs are discussed, with the bioavailability enhancing characteristics highlighted. Both top-down and bottom-up methods are covered, finally, a sustainability-based perspective comparing amorphous and crystalline nano-drugs is presented.


Against the inalienable right to withdraw from research.
In this paper I argue, against the current consensus, that the right to withdraw from research is sometimes alienable. In other words, research subjects are sometimes morally permitted to waive their right to withdraw. The argument proceeds in three major steps. In the first step, I argue that rights typically should be presumed alienable, both because that is not illegitimately coercive and because the general paternalistic motivation for keeping them inalienable is untenable. In the second step of the argument, I consider three special characteristics of the right to withdraw, first that its waiver might be exploitative, second that research involves intimate bodily access, and third that it is irreversible. I argue that none of these characteristics justify an inalienable right to withdraw. In the third step, I examine four considerations often taken to justify various other allegedly inalienable rights: concerns about treating yourself merely as a means as might be the case in suicide, concerns about revoking all your future freedoms in slavery contracts, the resolution of coordination problems, and public interest. I argue that the motivations involved in these four types of situations do not apply to the right to withdraw from research.


Toward spreadable entertainment-education: leveraging social influence in online networks.
Entertainment-education (EE) is a communication strategy that uses popular media to engage with audiences on prosocial topics such as health, social tolerance and sustainability. The purpose of EE serials on radio, television or the internet is to introduce new ideas, norms and practices by means of storytelling, as well as to offer points of engagement for audiences to talk about the themes raised by the intervention. However, in today's media landscape, it has become increasingly difficult to captivate audiences as they have fragmented across channels and have started to create and circulate content themselves. The concept of spreadable media allows us to deal with fragmentation and user-generated content in productive ways, as it recognizes the role of autonomous audience members in shaping the flows of media content in the online networks that underlie today's media landscape. In this article, we introduce spreadable EE: an innovative approach that builds on transmedia storytelling strategies to reach and captivate target audiences for a longer period of time, and that entails collaboration with online platforms, communities and social influencers to stimulate meaningful conversations. We enhance EE's theoretical, empirical and practical traditions with insights about how today's audiences have come to engage with media and propose strategic approaches to create and evaluate spreadable EE.


Sildenafil citrate (VIAGRA) improves erectile function in elderly patients with erectile dysfunction: a subgroup analysis.
The prevalence of erectile dysfunction (ED) increases with advancing age, with a particularly high prevalence of ED in elderly patients with diabetes. In the United States it is estimated that approximately 45% of men aged 65 to 69 years have moderate or complete ED. The efficacy and safety of oral sildenafil (VIAGRA) for treating ED in elderly men (aged > or = 65 years or older) were assessed. We analyzed data obtained from five double-blind, placebo-controlled studies of the efficacy and tolerability of oral sildenafil taken as required (but not more than once daily) over a 12-week to 6-month period. Two subgroups were evaluated: (i) elderly patients with ED of broad-spectrum etiology (n = 411), and (ii) elderly patients with ED and diabetes (n = 71). Efficacy was assessed using a global efficacy question, questions 3 and 4 of the International Index of Erectile Function (IIEF). and the five sexual function domains of the IIEF. All efficacy assessments indicated that sildenafil significantly improved erectile function both in elderly patients with ED of broad-spectrum etiology and in elderly patients with ED and diabetes. The most common adverse events were mild-to-moderate headache, flushing, and dyspepsia. The rates of discontinuation due to adverse events were low and were comparable to the rates with placebo. Sildenafil is an efficacious and well-tolerated treatment for ED in elderly men.


Seasonal variation in mortality in The Netherlands.
The aim was to describe the pattern of seasonal variation in all cause mortality in The Netherlands, and to analyse the contribution of specific causes of death to the winter excess of all cause mortality. Daily numbers of deaths in The Netherlands, by cause, were obtained for the period 1979-1987. Patterns of variation were analysed using Poisson regression. The model related the observed number of deaths to (1) the number expected for that day on the basis of person-days at risk by age and sex, (2) secular trend, and (3) first and higher order cosine terms where appropriate. All cause mortality has a bimodal peak in the first months of the year. After that it declines to reach a plateau in late spring. Mortality is lowest at the end of August, after which it rises steeply again. The winter excess of all cause mortality is primarily due to cardiovascular diseases (66%) and respiratory conditions (13%). Cardiovascular mortality peaks before respiratory mortality, suggesting different lag times in the effects of winter. There was an episode of exceptionally high mortality (above the normal winter excess) in early 1986, which was primarily due to cardiovascular diseases (39%) and respiratory conditions (25%). This episode was probably caused by a severe influenza epidemic, and was not followed by a compensatory lowering of mortality. The pattern of variation of mortality within the year suggests that it is not based on a simple relationship with climatological circumstances, because the latter fluctuate according to a less complex pattern. Cause specific data suggest an instantaneous effect of "winter" on the cardiovascular system, and a delayed effect mediated by respiratory infections.


Projection of Ia and Ib afferents from forelimb muscles to the C3-C4 segments of the cat spinal cord.
Group Ia muscle spindle afferents were activated separately by small stretches applied to the tendons of antibrachial muscles in the forelimb in the cat. Group Ib tendon organ afferents were stimulated electrically after a selective increase of the threshold of the Ia afferents. Recordings of focal synaptic potentials were made in the C3-C4 segments in the medial part of the base of the dorsal horn. It has been found that both Ia and Ib afferents have monosynaptic connections with neurones in this medial region. Quantitatively, these two groups of afferents produced focal synaptic potentials of approximately the same size. The connections may be to inhibitory interneurones projecting to the C3-C4 propriospinal neurones, which are known to receive disynaptic IPSPs from group I muscle afferents.


Volar Locking Plate Fixation for Distal Radius Fractures Distal to the Watershed Line with an Intact Lunate Volar Rim.
Background: We treated distal radius fractures (DRFs) beyond the watershed line without fracture of the lunate volar rim using a volar locking plate (VLP) and report the radiological and clinical outcomes at least 3 years after surgery. Methods: In 41 consecutive patients between January 2012 and August 2017, the fragment was composed of the radial styloid process (distal to the watershed line) and the lunate volar rim was intact. We evaluated demographic factors, radiological features and radiological/clinical outcomes at the final follow-up. Results: Twenty-nine patients were followed and evaluated. The mean follow-up period was 5.7 years. The mean patient age was 52.7 years and 24 patients had intracapsular intra-articular fractures. The fracture line was present in the lunate fossa in all patients. Twenty patients were classified as Soong grade 2, and five and four patients were grades 1 and 0, respectively. No radiological parameter (volar tilt, radial inclination, step-off and ulnar variance) was significantly different between the affected and contralateral normal sides. The mean visual analogue scale pain score and Disabilities of the Arm, Shoulder and Hand score, as well as the range of movement of the wrist, were not different between the affected and contralateral normal wrists. Finally, the grip strength on the affected side was 92% of the contralateral value. Major complications, such as nonunion, malunion and tendon rupture, were absent. Conclusions: DRFs distal to the watershed line with an intact lunate volar rim are rare and easy to miss. Careful inspection of 3D-CT images is necessary to determine these injuries, and the optimal choice for proper fixation of the fragment amongst the commercial VLPs would result in satisfactory radiological and clinical outcomes. Level of Evidence: Level IV (Therapeutic).


Developing and validating the Community-Oriented Frailty Index (COM-FI).
Methods for measuring frailty over-emphasise physical health, and consensus for a more holistic approach is increasing. However, holistic tools have had mixed success in meeting the validation criteria required of a frailty index. We report on the further development and validation of a Frailty Tool designed for use in the community with a greater emphasis on psychological markers, Holland et al's Community-Oriented Frailty Index (COM-FI). A total of 351 participants aged 58-96 were recruited from Retirement Villages and local communities across the West Midlands of the UK. Participants completed a series of measures designed to assess frailty and outcomes associated with frailty over a 2-year period. All three candidate items ('polypharmacy', 'exercise frequency', and the Coronary Heart Disease and Diabetes 'joint effect') were incorporated into the tool, and one variable, 'falls' was removed from the index. The revised COM-FI was shown to be valid and met Rockwood's validation criteria (Rockwood et al., 2006), with the exception that in this specific sample there was no significant gender difference and the index did not predict mortality. Overall, the COM-FI is a valid and reliable tool, although the capacity for the COM-FI to predict mortality over a 2-year period remains inconclusive given the small numbers of people at the higher ends of the frailty range. Prediction of need for social care was good, showing the utility of this community based tool.


Case Report: Traumatic anterior cerebral artery aneurysm in a 4-year old child.
Traumatic intracranial aneurysm in the proximal part of the anterior cerebral artery in the pediatric population has not been documented so far. Here we report the case of a 4 year-old child who developed a pseudo-aneurysm after minor head trauma and was managed successfully with trapping of the aneurysm. A ventriculo-peritoneal shunt was placed as the child became dependent on extraventricular drain during the post-operative period. The patient made excellent recovery in neurological status within 1 month of post-operative clinical follow up.


Letter from America: UK and US state-funded dental provision.
Current UK and US economic conditions have re-focussed attention on the need to deliver dental care with limited finance and resources. This raises hard questions determining which services will be offered and what they should achieve to satisfy public demands and needs. We consider impending dental health reforms in the US and UK within the context of contemporary experiences to identify issues and delivery goals for the two nations. The paper provides a brief history and background of the development of social dental care models in the UK and US, highlighting some differences in state-funded delivery of dental care. SHIFTING DEMAND: From the 1950s, demand for dental treatment has increased and acquired a more complex composition growing from predominantly surgical and restorative treatment to encompass preventive care and cosmetic services. PRIORITISING CARE ACCORDING TO NEED: Despite improvements in general health and technology, inequalities in access and utilisation of dental care are still experienced, primarily by groups with low socio-economic status. DELIVERY: BALANCING RESOURCES, DEMAND AND NEED: In developing and delivering reform agendas, much can be learned from previous policy interventions. Pressures of cost, coverage, and capacity, besides demand versus need must be carefully considered and balanced to deliver quality service and value for users and taxpayers. Ethical and moral consideration should be given to making services needs-driven to address high treatment requirements rather than the high care demands of the worried well. This challenge brings the additional political pressure of convincing many of the voters (and subsequent complainers) that their demands may be less important than the needs of others.


Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis.
Trend data for causes of child death are crucial to inform priorities for improving child survival by and beyond 2015. We report child mortality by cause estimates in 2000-13, and cause-specific mortality scenarios to 2030 and 2035. We estimated the distributions of causes of child mortality separately for neonates and children aged 1-59 months. To generate cause-specific mortality fractions, we included new vital registration and verbal autopsy data. We used vital registration data in countries with adequate registration systems. We applied vital registration-based multicause models for countries with low under-5 mortality but inadequate vital registration, and updated verbal autopsy-based multicause models for high mortality countries. We used updated numbers of child deaths to derive numbers of deaths by causes. We applied two scenarios to derive cause-specific mortality in 2030 and 2035. Of the 6·3 million children who died before age 5 years in 2013, 51·8% (3·257 million) died of infectious causes and 44% (2·761 million) died in the neonatal period. The three leading causes are preterm birth complications (0·965 million [15·4%, uncertainty range (UR) 9·8-24·5]; UR 0·615-1·537 million), pneumonia (0·935 million [14·9%, 13·0-16·8]; 0·817-1·057 million), and intrapartum-related complications (0·662 million [10·5%, 6·7-16·8]; 0·421-1·054 million). Reductions in pneumonia, diarrhoea, and measles collectively were responsible for half of the 3·6 million fewer deaths recorded in 2013 versus 2000. Causes with the slowest progress were congenital, preterm, neonatal sepsis, injury, and other causes. If present trends continue, 4·4 million children younger than 5 years will still die in 2030. Furthermore, sub-Saharan Africa will have 33% of the births and 60% of the deaths in 2030, compared with 25% and 50% in 2013, respectively. Our projection results provide concrete examples of how the distribution of child causes of deaths could look in 15-20 years to inform priority setting in the post-2015 era. More evidence is needed about shifts in timing, causes, and places of under-5 deaths to inform child survival agendas by and beyond 2015, to end preventable child deaths in a generation, and to count and account for every newborn and every child. Bill & Melinda Gates Foundation.


Description of Total Population Hospital Admissions for Treacher Collins Syndrome in Australia.
To describe patterns and demographic characteristics of total-population hospital admissions with a diagnosis of Treacher Collins syndrome (TCS) in Australia. Population summary data for inpatient hospitals admissions (public and private) with a principal diagnosis of TCS (ICD10-AM-Q87.04) were obtained from the Australian Institute of Health and Welfare National Hospital Morbidity Database for a 11-year period (2002-2013). The primary outcome was hospital separation rate (HSR), calculated by dividing the number of hospital separations by estimated resident population per year. Trends in HSR s adjusted for age and sex were investigated by negative binomial regression presented as annual percent change and the association of rates with age and sex was expressed as incidence rate ratio. In 244 admissions identified, we observed an increase of 4.55% (95% confidence interval [CI] -1.78, 11.29) in HSR's over the 11-year period. Rates were higher during infancy (1.87 [95% CI 1.42, 2.42]), declining markedly with increasing age. The average length of hospital stay was 6.09 days (95% CI 5.78, 6.40) per episode, but longer for females and infants. Findings indicate an increase in hospitalization rates, especially among infants and females which potentially relates to early airway intervention procedures possibly influenced by sex specific-disease severity and phenotypic variability of TCS. Awareness of the TCS phenotype and improved access to genetic testing may support more personalized and efficient care. Total-population administrative data offers a potential to better understand the health burden of rare craniofacial diseases.


Human 76p: A new member of the gamma-tubulin-associated protein family.
The role of the centrosomes in microtubule nucleation remains largely unknown at the molecular level. gamma-Tubulin and the two associated proteins h103p (hGCP2) and h104p (hGCP3) are essential. These proteins are also present in soluble complexes containing additional polypeptides. Partial sequencing of a 76- kD polypeptide band from these complexes allowed the isolation of a cDNA encoding for a new protein (h76p = hGCP4) expressed ubiquitously in mammalian tissues. Orthologues of h76p have been characterized in Drosophila and in the higher plant Medicago. Several pieces of evidence indicate that h76p is involved in microtubule nucleation. (1) h76p is localized at the centrosome as demonstrated by immunofluorescence. (2) h76p and gamma-tubulin are associated in the gamma-tubulin complexes. (3) gamma-tubulin complexes containing h76p bind to microtubules. (4) h76p is recruited to the spindle poles and to Xenopus sperm basal bodies. (5) h76p is necessary for aster nucleation by sperm basal bodies and recombinant h76p partially replaces endogenous 76p in oocyte extracts. Surprisingly, h76p shares partial sequence identity with human centrosomal proteins h103p and h104p, suggesting a common protein core. Hence, human gamma-tubulin appears associated with at least three evolutionary related centrosomal proteins, raising new questions about their functions at the molecular level.


Getting access to the self: Effects of self-management therapy on the development of self-regulation and inhibitory control in obese adolescents.
This study investigated the role of self-regulation competencies in general and specifically in a food-related context for the control of body weight in a three-year weight loss program. The sample consisted of 30 male and female adolescents (age range: 11-18 years) who participated in a three-year therapy program for severe obesity (mean BMI at the beginning of the intervention was 33.6). Assessment of self-regulation competencies was conducted at three different stages (1(st)-3(rd) graduation/class year). Therefore, three independent groups of adolescents (N = 10) at these different stages were tested (initial-to final-stage of therapy). At the time of testing the BMI of these groups significantly differed from 38.8 to 28.7. Analyses of covariance were performed to determine whether the adolescents also differed in self-regulation skills like "resistance to temptation" and food-related Stroop interference along with ameliorating their energy-balance regulation. In addition to the main effects of age and body mass index, adolescents further displayed significant improvements of executive functions with respect to resistance to temptation and inhibition. Interventions aimed at enhancing energy-balance regulation in adolescents may further benefit from efforts to facilitate executive functions such as self-regulation and food-related cognitive inhibition.


Vanadium complexes of the N(CH2CH2S)3(3-) and O(CH2CH2S)2(2-) ligands with coligands relevant to nitrogen fixation processes.
Vanadium(III) and vanadium(V) complexes derived from the tris(2-thiolatoethyl)amine ligand [(NS3)3-] and the bis(2-thiolatoethyl)ether ligand [(OS2)2-] have been synthesized with the aim of investigating the potential of these vanadium sites to bind dinitrogen and activate its reduction. Evidence is presented for the transient existence of (V(NS3)(N2)V(NS3), and a series of mononuclear complexes containing hydrazine, hydrazide, imide, ammine, organic cyanide, and isocyanide ligands has been prepared and the chemistry of these complexes investigated. [V(NS3)O] (1) reacts with an excess of N2H4 to give, probably via the intermediates (V(NS3)(NNH2) (2a) and (V(NS3)(N2)V(NS3) (3), the V(III) adduct [V(NS3)(N2H4)] (4). If 1 is treated with 0.5 mol of N2H4, 0.5 mol of N2 is evolved and green, insoluble [(V(NS3))n] (5) results. Compound 4 is converted by disproportionation to [V(NS3)(NH3)] (6), but 4 does not act as a catalyst for disproportionation of N2H4 nor does it act as a catalyst for its reduction by Zn/HOC6H3Pri2-2,6. Compound 1 reacts with NR1(2)NR2(2) (R1 = H or SiMe3; R2(2) = Me2, MePh, or HPh) to give the hydrazide complexes [V(NS3)(NNR2(2)] (R2(2) = Me2, 2b; R2(2) = MePh, 2c; R2(2) = HPh, 2d), which are not protonated by anhydrous HBr nor are they reduced by Zn/HOC6H3Pri2-2,6. Compound 2b can also be prepared by reaction of [V(NNMe2)(dipp)3] (dipp = OC6H3Pri2-2,6) with NS3H3. N2H4 is displaced quantitatively from 4 by anions to give the salts [NR3(4)][V(NS3)X] (X = Cl, R3 = Et, 7a; X = Cl, R3 = Ph, 7b; X = Br, R3 = Et, 7c; X = N3, R3 = Bu(n), 7d; X = N3, R3 = Et, 7e; X = CN, R3 = Et, 7f). Compound 6 loses NH3 thermally to give 5, which can also be prepared from [VCl3(THF)3] and NS3H3/LiBun. Displacement of NH3 from 6 by ligands L gives the adducts [V(NS3)(L)] (L = MeCN, nu CN 2264 cm-1, 8a; L = ButNC, nu NC 2173 cm-1, 8b; L = C6H11NC, nu NC 2173 cm-1, 8c). Reaction of 4 with N3SiMe3 gives [V(NS3)(NSiMe3)] (9), which is converted to [V(NS3)(NH)] (10) by hydrolysis and to [V(NS3)(NCPh3)] (11) by reaction with ClCPh3. Compound 10 is converted into 1 by [NMe4]OH and to [V(NS3)NLi(THF)2] (12) by LiNPri in THF. A further range of imido complexes [V(NS3)(NR4)] (R4 = C6H4Y-4 where Y = H (13a), OMe (13b), Me (13c), Cl (13d), Br (13e), NO2 (13f); R4 = C6H4Y-3, where Y = OMe (13g); Cl (13h); R4 = C6H3Y2-3,4, where Y = Me (13i); Cl (13j); R4 = C6H11 (13k)) has been prepared by reaction of 1 with R4NCO. The precursor complex [V(OS2)O(dipp)] (14) [OS2(2-) = O(CH2CH2S)2(2-)] has been prepared from [VO(OPri)3], Hdipp, and OS2H2. It reacts with NH2NMe2 to give [V(OS2)(NNMe2)(dipp)] (15) and with N3SiMe3 to give [V(OS2)(NSiMe3)(dipp)] (16). A second oxide precursor, formulated as [V(OS2)1.5O] (17), has also been obtained, and it reacts with SiMe3NHNMe2 to give [V(OS2)(NNMe2)(OSiMe3)] (18). The X-ray crystal structures of the complexes 2b, 2c, 4, 6, 7a, 8a, 9, 10, 13d, 14, 15, 16, and 18 have been determined, and the 51V NMR and other spectroscopic parameters of the complexes are discussed in terms of electronic effects.


A case of lipoma of lateral anterior neck treated with surgical enucleation.
Lipoma arise in almost 50% of all soft tumours. The neck lipomas are rare tumours that may present as painless masses with slow growth, in the lateral portions of the neck. Some lipomas, such as the one studied in our case, grow deep in the subcutaneous tissue, in close contact with muscles. Here, we report a case of lipoma extending from pre-tragal region up to the ascending branch of the mandible in a 62 year old man, treated with enucleation. The inferior margin of lipoma involved the pharyngeal and the superior margin was achieved by the top of the skull base. The mass of lipoma caused breathing difficulties in the patient, preventing regular sleep. No complication was recorded in the post-operative period and no further surgery was performed. The complete resolution after one year's follow-up, together with the rarity of the anatomical site, makes this case worthy of description. A correct diagnosis facilitated removal of this lesion with a surgical method.


The High Expression of Adhering and Circulating Integrin Serves as a Diagnostic Marker in Venous Thromboembolism.
To investigate the diagnostic value of circulating integrins β1, 2, and 3 in venous thrombosis (VTE). A total of 474 VTE patients and 306 patients with nonhigh risk for VTE as the control group were studied. Levels of adhering integrins β1, 2, and 3 were detected by flow cytometry. Levels of circulating integrins β1, 2, and 3 in serum were measured by enzyme-linked immunosorbent assay. We found that integrins β1, 2, and 3 were expressed highly both in serum and on the surface of leukocytes and platelets in venous thromboembolism. The levels of circulating integrins β1, 2, and 3 are positively correlated with adhering integrins. It showed excellent clinical diagnostic performance of circulating integrins β1, 2, and 3 in venous thromboembolism. Integrin subunit β can be used as a diagnostic marker with high sensitivity and specificity for venous thromboembolism.


[Rationalities of knowledge production: on transformations of objects, technologies and information in biomedicine and the life sciences].
Since decades, scientific change has been interpreted in the light of paradigm shifts and scientific revolutions. The Kuhnian interpretation of scientific change however is now more and more confronted with non-disciplinary thinking in both, science and studies on science. This paper explores how research in biomedicine and the life sciences can be characterized by different rationalities, sometimes converging, sometimes contradictory, all present at the same time with varying ways of influence, impact, and visibility. In general, the rationality of objects is generated by fitting new objects and findings into a new experimental context. The rationality of hypotheses is a move towards the construction of novel explanatory tools and models. This is often inseparable meshing with the third, the technological rationality, in which a technology-driven, self-supporting and sometimes self-referential refinement of methods and technologies comes along with an extension into other fields. During the second and the third phase, the new and emerging fields tend to expand their explanatory reach not only across disciplinary boundaries but also into the social sphere, creating what has been characterized as "exceptionalism" (e.g. genetic exceptionalism or neuro-exceptionalism). Finally, recent biomedicine and life-sciences reach a level in which experimental work becomes more and more data-driven because the technologically constructed experimental systems generate a plethora of findings (data) which at some point start to blur the original hypotheses. For the rationality of information the materiality of research practices becomes secondary and research objects are more and more getting out of sight. Finally, the credibility of science as a practice becomes more and more dependent on consensus about the applicability and relevance of its results. The rationality of interest (and accountability) has become more and more characteristic for a research process which is no longer primarily determined by the desire for knowledge but by the desire for relevance. This paper explores in which ways object-driven and hypotheses-driven experimental life-sciences transformed into domains of experimental research evolving in a technologically constructed, data-driven environment in which they are subjected to constant morphing due to the forces of different rationalities.


Psychological factors and barriers to donating and receiving milk from human milk banks: A review.
Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child.


Exploring the interplay of dopaminergic genotype and parental behavior in relation to executive function in early childhood.
Child genotype is an important biologically based individual difference conferring differential sensitivity to the effect of parental behavior. This study explored dopaminergic polygenic composite × parental behavior interactions in relation to young children's executive function. Participants were 135 36-month-old children and their mothers drawn from a prospective cohort followed longitudinally from pregnancy. A polygenic composite was created based on the number of COMT, DAT1, DRD2, and DRD4 alleles associated with increased reward sensitivity children carried. Maternal negative reactivity and responsiveness were coded during a series of structured mother-child interactions. Executive function was operationalized as self-control and working memory/inhibitory control. Path analysis supported a polygenic composite by negative reactivity interaction for self-control. The nature of the interaction was one of diathesis-stress, such that higher negative reactivity was associated with poorer self-control for children with higher polygenic composite scores. This result suggests that children with a higher number of alleles may be more vulnerable to the negative effect of negative reactivity. Negative reactivity may increase the risk for developing behavior problems in this population via an association with poorer self-control. Due to the small sample size, these initial findings should be treated with caution until they are replicated in a larger independent sample.


Phenotypic switching in cells transformed with the herpes simplex virus thymidine kinase gene.
Biochemical transformation of Ltk- cells with the herpes simplex virus thymidine kinase (tk) gene resulted in numerous TK+ colonies that survived selection in hypoxanthine-aminopterin-thymidine medium. Many of these TK+ cell lines switched phenotypes and reverted to the TK- state. In this report, we describe the biological and biochemical characteristics of three TK- revertant lines. One (K1B5) transiently expressed TK in the presence of bromodeoxyuridine, which selects for the TK- phenotype. Another TK- sibling (K1B6n) expressed TK only after removal from bromodeoxyuridine-containing medium. The last variant (K1B6me) lost the ability to switch to the TK+ phenotype, although it maintained the herpes simplex virus sequences coding for TK. Loss of the ability of K1B6me cells to express TK was correlated with extensive methylation of the sequence recognized by the restriction endonuclease HpaII (pCpCpGpG). After these cells were treated with 5-azacytidine, they regained the ability to clone in hypoxanthine-aminopterin-thymidine medium and reexpressed virus tk mRNA and enzyme. In addition, the HpaII sites that were previously shown to be refractile to enzyme digestion were converted to a sensitive state, demonstrating that they were no longer methylated.


[Neuropsychiatric features in Dementia with Lewy bodies and Alzheimer's disease].
Dementia with Lewy bodies (DLB) is commonly accompanied by neuropsychiatric symptoms. Among them, visual hallucinations are reportedly distinguishing DLB from Alzheimer's disease (AD). However, studies that compared frequency of delusions or depression between in DLB and in AD demonstrated conflicting results. Other neuropsychiatric symptoms including aggression, anxiety, and disinhibition have been rarely explored in DLB. In the present study, in order to elucidate the distinctive neuropsychiatric features in DLB, we analyzed neuropsychiatric symptoms in patients with DLB and with AD using data-based materials. Subjects were 15 DLB patients extracted from the Dementia Data Bank in the Hyogo Institute for Aging Brain and Cognitive Disorders, where clinical information of patients with dementia were prospectively assembled with planed, standardized assessments. Both patients groups did not differ in age, education, and duration of illness. The male proportion was significantly greater in the DLB group compared with the AD group (DLB: Male 8, Female 7; AD: Male 27, Female 124, p = 0.008). Patients' neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory during an interview with a caregiver familiar to the patient's everyday behavior. The Mini-Mental State Examination (MMSE) was used for assessing severity of cognitive impairment. The DLB group had significantly lower MMSE scores compared with AD group (DLB: 16.2 +/- 5.6, AD: 19.3 +/- 4.4, p = 0.013). None of neuropsychiatric symptoms, however, showed a significant relationship with MMSE scores in the DLB group. Hallucination were present in eight (53.3%) of the DLB group. Visual hallucinations were present in seven patients, and both visual and auditory hallucinations in one patient. The frequency of hallucinations (p < 0.0001) and that of visual hallucinations (p < 0.0001) were significantly greater in the DLB group than in the AD group. There was no significant difference in the frequency of auditory hallucinations. Delusions were present in 11 (73.3%) of the DLB group. Misidentification delusions were present in 11 patients, and persecutory delusions were coexisted in 8 patients. The frequency of delusions and that of persecutory delusions in the DLB group did not significantly differ from the AD group. However, the frequency of misidentification delusions was significantly greater in the DLB group than in the AD group (p < 0.0001). No significant difference was noted in the frequency of other neuropsychiatric symptoms. Hallucinations, especially visual hallucinations, and misidentification delusions are helpful diagnostic features of DLB in differentiating from AD.


Lunasin induces apoptosis and modifies the expression of genes associated with extracellular matrix and cell adhesion in human metastatic colon cancer cells.
Lunasin is an arginine-glycine-aspartic acid (RGD) cancer preventive peptide. The objective was to evaluate the potential of lunasin to induce apoptosis in human colon cancer cells and their oxaliplatin-resistant (OxR) variants, and its effect on the expression of human extracellular matrix and adhesion genes. Various human colon cancer cell lines which underwent metastasis were evaluated in vitro using cell flow cytometry and fluorescence microscopy. Lunasin cytotoxicity to different colon cancer cells correlated with the expression of α(5) b(1) integrin, being most potent to KM12L4 cells (IC(50) = 13 μM). Lunasin arrested cell cycle at G2/M phase with concomitant increase in the expression of cyclin-dependent kinase inhibitors p21 and p27. Lunasin (5-25 μM) activated the apoptotic mitochondrial pathway as evidenced by changes in the expressions of Bcl-2, Bax, nuclear clusterin, cytochrome c and caspase-3 in KM12L4 and KM12L4-OxR. Lunasin increased the activity of initiator caspase-9 leading to the activation of caspase-3 and also modified the expression of human extracellular matrix and adhesion genes, downregulating integrin α(5), SELE, MMP10, integrin β(2) and COL6A1 by 5.01-, 6.53-, 7.71-, 8.19- and 10.10-fold, respectively, while upregulating COL12A1 by 11.61-fold. Lunasin can be used in cases where resistance to chemotherapy developed.


[Comparison of Phoenix™ Yeast ID Panel and API® ID 32C commercial systems for the identification of Candida species isolated from clinical samples].
Opportunistic fungal pathogens are one of the important causes of nosocomial infections, and several different types of yeasts, especially Candida species are increasingly recovered from immunocompromised patients. Since many of the yeasts are resistant to the commonly used antifungal agents, the introduction of appropriate therapy depends on rapid and accurate identification. The aims of this study were to compare the commercial identification systems namely API® ID 32C (bioMerieux, France) and Phoenix™ Yeast ID Panel (Becton Dickinson Diagnostics, USA) for the identification of Candida species and to evaluate the effect of morphological findings in the identification process. A total of 211 yeast strains isolated from different clinical samples (111 urine, 34 blood/vascular catheter, 27 upper/lower respiratory tract, 16 abscess/pus, 13 throat/vagina swabs and 10 sterile body fluids) of 137 patients hospitalized in Uludag University Health and Research Center between October 2013 to January 2014, were included in the study. Samples were cultured on blood agar, chromogenic agar (CHROMagar Candida, BD, USA) and Saboraud's dextrose agar (SDA), and isolated yeast colonies were evaluated with germ tube test and morphological examination by microscopy on cornmeal/Tween-80 agar. The isolates were identified as well by two commercial systems according to the manufacturers' recommendations. Discrepant results between the systems were tried to be resolved by using morphological characteristics of the yeasts. Of the isolates 159 were identified identical by both of the systems, and the concordance between those systems were estimated as 75.4%. According to the concordant identification, the most frequently isolated species was C.albicans (44.1%) followed by C.tropicalis (9.9%), C.glabrata (9.5%), C.parapsilosis (8.5%) and C.kefyr (8.1%). The concordance rate was 81.7% in identification of frequently isolated species (C.albicans, C.tropicalis, C.parapsilosis, C.glabrata, C.kefyr), however it was 38.7% for the rarely isolated ones (C.krusei, C.lusitaniae, C.inconspicua/C.norvagensis, C.catenulata), representing statistical significance (p= 0.034; x2 test). Although not significant (p= 0.31; x2 test), the rate of concordance was increased (88.1%), when adding the morphological findings to the identification process. Of 211 isolates 37 (17.5%), 50 (23.7%) and 124 (58.8%) were identified according to their growth characteristics on chromogenic agar, blood agar and SDA, respectively, indicating no statistically significant difference between the media (p> 0.05). Although genotypic identification is essential, phenotypic methods are more commonly used in routine laboratories for the identification of yeast species. However, since genotypic identification could not be performed in this study, none of the systems were accepted as the standard method and therefore the sensitivity and specificity of the systems were not calculated. On the other hand, our data indicated that the two identification systems were comparable and careful observation of yeast morphology could add confidence to the identification. In conclusion, since the Phoenix™ Yeast ID system was found more practical with easier interpretation, and the results were obtained earlier than those of the API® ID 32C system (16 hours versus 48 hours), it was thought that Phoenix™ Yeast ID system may be used reliably in the routine laboratories. However, as none of the methods evaluated was completely reliable as a stand-alone, careful evaluation is necessary for species identification.


No strong evidence for abnormal levels of dysfunctional attitudes, automatic thoughts, and emotional information-processing biases in remitted bipolar I affective disorder.
Beck extended his original cognitive theory of depression by suggesting that mania was a mirror image of depression characterized by extreme positive cognition about the self, the world, and the future. However, there were no suggestions what might be special regarding cognitive features in bipolar patients (Mansell & Scott, 2006). We therefore used different indicators to evaluate cognitive processes in bipolar patients and healthy controls. We compared 19 remitted bipolar I patients (BPs) without any Axis I comorbidity with 19 healthy individuals (CG). All participants completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Automatic Thoughts Questionnaire, the Emotional Stroop Test, and an incidental recall task. No significant group differences were found in automatic thinking and the information-processing styles (Emotional Stroop Test, incidental recall task). Regarding dysfunctional attitudes, we obtained ambiguous results. It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Beck's theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.


Spatial distribution of trace metals in sediments from urban streams of Semarang, Central Java, Indonesia.
Elevated environmental concentrations of metals are usually associated with the impact of urbanization. The present study is focused on metal contamination in urban sediments. A field survey was carried out to determine the distribution of four metals, i.e., cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn), in the coastal urban area of Semarang, Central Java, Indonesia. Sediment samples were collected from 101 grids of 2x2 km. To map the spatial distribution of these metals, concentrations of each metal were plotted against the corresponding grid coordinate. Cd was below the detection limit (<0.03 microg/g) in all samples, whereas concentrations of Pb, Zn, and Cu fell into a wide range. Frequency distributions of Pb, Zn, and Cu concentrations indicated a similar pattern, in which the major proportion of the sites had a low metal concentration. Some sites, however, had extremely high metal concentrations, Zn up to 1257 microg/g, Pb up to 2666 microg/g, and Cu up to 448 microg/g. The data were used to define background concentrations for sediments in coastal zones of Indonesia ("reference values"). The proposed reference values are 25.6 microg/g, 132.2 microg/g, and 40.7 microg/g, respectively, for Pb, Zn, and Cu. The degree of metal contamination of each individual site was classified according to the calculated value of a combined pollution index, W. Four categories of the degree of metal contamination were proposed, i.e., unpolluted, slightly polluted, polluted, and heavily polluted. Based on this classification, from 101 sites investigated in the greater Semarang area, 51 are unpolluted, 36 slightly polluted, 9 polluted, and 5 heavily polluted.


Crystallization and preliminary X-ray crystallographic analysis of L-arabinose isomerase from thermophilic Geobacillus kaustophilus.
L-arabinose isomerase (AI), which catalyzes the isomerization of L-arabinose to L-ribulose, can also convert D-galactose to D-tagatose, a natural sugar replacer, which is of commercial interest in the food and healthcare industries. Intriguingly, mesophilic and thermophilic AIs showed different substrate preferences and metal requirements in catalysis and different thermostabilities. However, the catalytic mechanism of thermophilic AIs still remains unclear. Therefore, thermophilic Geobacillus kaustophilus AI (GKAI) was overexpressed, purified and crystallized, and a preliminary X-ray diffraction data set was obtained. Diffraction data were collected from a GKAI crystal to 2.70 Å resolution. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 224.12, b = 152.95, c = 91.28 Å, β = 103.61°. The asymmetric unit contained six molecules, with a calculated Matthews coefficient of 2.25 Å(3) Da(-1) and a solvent content of 45.39%. The three-dimensional structure determination of GKAI is currently in progress by molecular replacement and model building.


Bcl-2 antisense therapy in B-cell malignant proliferative disorders.
Overexpression of Bcl-2 oncogene has been clinically associated with an aggressive clinical course, chemotherapy and radiotherapy resistance, and poor survival in patients with malignant B-cell disorders. Patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, or non-Hodgkin's lymphoma have limited therapeutic options. Preclinical and early clinical data have shown that Bcl-2 oncoprotein can be decreased by Bcl-2 antisense therapy. Also, downregulation of Bcl-2 protein can result in reversal of chemotherapy resistance and improved antitumor activity of biologic agents. Various clinical trials are evaluating the role of targeting Bcl-2 as a mechanism to enhance the antitumor potential of chemotherapy and immunotherapy. Early results from these clinical studies are encouraging and confirm the proof of principle for antisense therapy. As current data mature, these trials will hopefully validate preliminary results and establish Bcl-2 antisense as an important addition to the current armamentarium used in the treatment of patients with B-cell neoplasms.


Children's Hospital Characteristics and Readmission Metrics.
Like their adult counterparts, pediatric hospitals are increasingly at risk for financial penalties based on readmissions. Limited information is available on how the composition of a hospital's patient population affects performance on this metric and hence affects reimbursement for hospitals providing pediatric care. We sought to determine whether applying different readmission metrics differentially affects hospital performance based on the characteristics of patients a hospital serves. We performed a cross-sectional analysis of 64 children's hospitals from the Children's Hospital Association Case Mix Comparative Database 2012 and 2013. We calculated 30-day observed-to-expected readmission ratios by using both all-cause (AC) and Potentially Preventable Readmissions (PPR) metrics. We examined the association between observed-to-expected rates and hospital characteristics by using multivariable linear regression. We examined a total of 1 416 716 hospitalizations. The mean AC 30-day readmission rate was 11.3% (range 4.3%-19.6%); the mean PPR rate was 4.9% (range 2.9%-6.9%). The average 30-day AC observed-to-expected ratio was 0.96 (range 0.63-1.23), compared with 0.95 (range 0.65-1.23) for PPR; 59% of hospitals performed better than expected on both measures. Hospitals with higher volumes, lower percentages of infants, and higher percentage of patients with low income performed worse than expected on PPR. High-volume hospitals, those that serve fewer infants, and those with a high percentage of patients from low-income neighborhoods have higher than expected PPR rates and are at higher risk of reimbursement penalties.


Ferroelectricity in high-density H2O ice.
The origin of longstanding anomalies in experimental studies of the dense solid phases of H2O ices VII, VIII, and X is examined using a combination of first-principles theoretical methods. We find that a ferroelectric variant of ice VIII is energetically competitive with the established antiferroelectric form under pressure. The existence of domains of the ferroelectric form within anti-ferroelectric ice can explain previously observed splittings in x-ray diffraction data. The ferroelectric form is stabilized by density and is accompanied by the onset of spontaneous polarization. The presence of local electric fields triggers the preferential parallel orientation of the water molecules in the structure, which could be stabilized in bulk using new high-pressure techniques.


Regulation of eIF4E guides a unique translational program to control erythroid maturation.
Translation control is essential in balancing hematopoietic precursors and differentiation; however, the mechanisms underlying this program are poorly understood. We found that the activity of the major cap-binding protein eIF4E is unexpectedly regulated in a dynamic manner throughout erythropoiesis that is uncoupled from global protein synthesis rates. Moreover, eIF4E activity directs erythroid maturation, and increased eIF4E expression maintains cells in an early erythroid state associated with a translation program driving the expression of PTPN6 and Igf2bp1. A cytosine-enriched motif in the 5' untranslated region is important for eIF4E-mediated translation specificity. Therefore, selective translation of key target genes necessary for the maintenance of early erythroid states by eIF4E highlights a unique mechanism used by hematopoietic precursors to rapidly elicit erythropoietic maturation upon need.


[Echocardiography and other imaging modalities in pulmonary arterial hypertension].
It is essential to diagnose pulmonary arterial hypertension in early stages of the disease. However, most patients have late diagnosis due to the lack of disease-specific symptoms and prominent findings. Although cardiac catheterization is the gold standard in the diagnosis of pulmonary arterial hypertension, noninvasive diagnostic modalities do also have major roles in the diagnosis, risk assessment and follow-up of the patients with pulmonary arterial hypertension. The focus of the present review is the clinical role of echocardiography and other imaging modalities in pulmonary arterial hypertension.


A Clinical Experience of Ectopic Pregnancies with Initial Free Intraperitoneal Fluid.
Extra-uterine pregnancy or Ectopic Pregnancy (EP) is a major health problem for pregnant women, presenting as a potentially life-threatening emergency in the first trimester. There are three major options for the treatment of EP: expectant management, surgical treatment and medical management. The presence of free intraperitoneal fluid in EP-diagnosed patients is crucial for treatment planning and evaluation. To compare the outcomes of both the expectant man-agement and medical treatment with methotrexate (MTX) in ectopic pregnancies with free intraperitoneal fluid. This retrospective cohort study inclu-ded a total of 91 ectopic pregnancies with or without rupture in which the women had initial free intraperitoneal fluid and were haemodynamically stable. Serial β-HCG measurements were used to assess the outcome of expectant management and medical treatment with MTX. For the statistical analysis, the SPSS statistical software package, version 22.0 (Chicago, IL, USA), was used. For the quantitative variables that were not distributed normally, the Kruskal-Wallis test and the Mann-Whitney U test were performed for the evaluation of differences between the groups. It was observed that the success rate with expectant management was 81% (initial β HCG concentration 626±443 mIU/mL). With a single dose of MTX, it was 76% (initial β HCG concentration 2124±1647 mIU/mL) and with a total single or double dose of MTX, it was 88% (initial β HCG concentration 2252±78 mIU/mL) from among EP with or without rupture in women with initial free intraperitoneal fluid during diagnosis. There was no significant difference between the groups with regard to ultrasonography findings. Expectant management or medical treatment with methotrexate should be the first line treatment for ectopic pregnancies with initial free intraperitoneal fluid, albeit with rupture, in patients who are haemodynamically stable, along with β-HCG follow-up.