[Diagnosis and therapy of aggressive fibromatosis (extra-abdominal desmoid) in the head and neck area].
Desmoid tumours (extraabdominal desmoids, aggressive fibromatosis) are rare connective tissue tumours, that grow infiltratively and destructively. The analysis of the course of disease in three patients suffering from desmoid tumours in the head and neck region (regio submandibularis, regio parotidea, parapharyngeal space) confirmed the data in literature that painless swelling and dysfunction are the first non-specific signs of the disease. Morphologically reactive fibromatosis and fibrosarcoma should be considered (amongst others) in differential diagnosis. CT and MR scans are useful in determining the extent of the tumours and help to distinguish the tumour from nerves, vessels and bone. Surgery is the therapy of choice in the head and neck region. Primary surgery was performed in our patients. Due to recurrences two of our patients have been operated on several times including major plastic reconstructive surgery. One patient died three and a half years after primary treatment due to sarcomatous degeneration. A large parapharyngeal recurrence was successfully reduced by percutaneous radiation therapy in our second patient. Follow-up of our third patient was NAD 15 months after resection of a large parapharyngeal/mediastinal process including blocking of two cervical vertebrae. Summing up, desmoid tumours are rare connective tissue tumours in the head and neck region with a destructive biological behaviour similar to malignant tumours and a high recurrence rate. Surgery is the treatment of choice. In recurrences or if the tumour is not properly resectable, radiation must be considered, whereas the chemotherapeutical approach is not yet well established.


High levels of variation despite genetic fragmentation in populations of the endangered mountain pygmy-possum, Burramys parvus, in alpine Australia.
In endangered mammals, levels of genetic variation are often low and this is accompanied by genetic divergence among populations. The mountain pygmy-possum (Burramys parvus) is an endangered marsupial restricted to the alpine region of Victoria and New South Wales, Australia. By scoring variation at eight microsatellite loci, we found that B. parvus populations exhibit high levels of genetic divergence and fall into three distinct groups from the northern, central and southern areas of the distribution of this species, consistent with previous assessments of mitochondrial DNA variation. F(ST) values between populations from these regions ranged from 0.19 to 0.54. Within the central area, there was further genetic fragmentation, and a linear association between genetic and geographical distance. This pattern is likely to reflect limited dispersal across barriers despite the fact that individual B. parvus can move several kilometres. Levels of genetic variation within populations were high with the exception of a southern population where there was evidence of inbreeding. From a conservation perspective, all three areas where B. parvus are found should be considered as separate gene pools; management of populations within these areas needs to take into account the low gene flow between populations, as well as threats posed by roads, resorts and other developments in the alpine region. The low genetic variability and inbreeding in the southern population is of particular concern given the high levels of variability in other B. parvus populations.


Economic preferences and obesity: Evidence from a clinical lab-in-field study.
Many studies which describe the relationship between obesity and economic preference rely on healthy, clinically-irrelevant populations. Instead, we study economic decision-making of a clinically-relevant population of 299 people with obesity who participated in a 6-months Randomized Controlled Trial in two Sydney-based hospitals to prevent diabetes onset. To elicit preferences, we use incentive-compatible experimental tasks that participants completed during their medical screening examination. In this population, we find that participants are risk averse, show no evidence of present bias, and have impatience levels comparable to healthy samples described in the international literature. Variations in present bias and impatience are not significantly associated with variations in markers of obesity. We find however a statistically significant negative association between risk tolerance and markers of obesity for women. Importantly, impatience moderates the link between risk tolerance and obesity, a finding which we are able to replicate in nationally-representative survey data. We discuss explanations for why our findings deviate markedly from the literature for this understudied but highly policy-relevant population. One explanation is that our specific population consists of forward-looking, well-educated individuals, who are willing to participate in an intensive health intervention. Hence, other factors may be at play for why these individuals live with obesity.


The blood flow in the periodontal ligament regulated by the sympathetic and sensory nerves in the cat.
This study was carried out to investigate the nervous control of the blood flow in the periodontal ligament measured by laser Doppler flowmeter. Ten adult cats were anesthetized with pentobarbital sodium (initial dose of 30 mg/kg, i.v. and maintenance dose of 5 mg/kg, i.v.). After enucleating the left eye ball, the superior alveolar nerve was exposed. The bone overlying the labial aspect of the left maxillary canine tooth root was pared away until a transparent layer of bone was left covering the periodontal ligament. A laser light from a probe of the flowmeter fixed at the tooth was beamed through the thinned bone. Three different patterns of responses were observed following the electrical stimulation of the distal end of the cut superior alveolar nerve: an increasing, a decreasing and a biphasic change of blood flow. The application of capsaicin onto the superior alveolar nerve reduced the response of blood flow increase but had no effect on the response of blood flow decrease. On the other hand, the response of blood flow decrease was completely inhibited by the pretreatment with phentolamine while the response of blood flow increase was not affected. The present results suggest that blood flow in the periodontal ligament of cats is controlled by sympathetic alpha-adrenergic fibers for vasoconstriction and by sensory fibers for vasodilation.


The asbestos industry and statutory control of its hazards.
The difficulties of balancing the possible hazards of asbestos against its useful properties, the cost of control measures and the availability of adequate substitutes are described. The history of the asbestos industry, of recognition of the association between asbestos and respiratory disease and of the develpment of control regulations in the UK are outlined. The present provisions for inspection of work places, for medical services to workers and for environmental control within and outside the workplace have been reviewed and a Health and Safety Commission set up to implement them; their work is described. Although the regulations are being implemented, however, public anxiety has increased. Justification for such anxiety comes from reports of still-existing hazards and from the fact that the current standard was established on faulty grounds. Three studies are described which indicate that a dose-response relationship may exist in relation to the carcinogenicity of asbestos; however, there is still not enough evidence to set standards. Further studies have shown that the different types of asbestos incur different degrees of risk. The UK Asbestos Standards are thus undergoing revision, this time in consultation not only with physicians and hygienists, but also with members of industry, trades union members, academics and local authorities.


The alkaloids of Corydalis meifolia.
Six tetrahydroprotoberberines, (+)-sinactine, apocavidine, stylopine, (+)-cavidine, cheilanthifoline, and dehydrocavidine; two spirobenzylisoquinolines, yenhusomine and yenhusomidine; one phthalideisoquinoline, corlumine; one benzophenanthridine, dihydrosanguinarine and protopine, have been isolated from the leaves and stems of Corydalis meifolia Wall. Of these alkaloids, dehydrocavidine was a new base. The remaining alkaloids, although known, were isolated for the first time for this plant. (+)-Cavidine, protopine, corlumine, yenhusomine, and dehydrocavidine exhibited spasmolytic activity.


Early IL-4 production by non-CD4+ cells at the site of antigen deposition predicts the development of a T helper 2 cell response to Schistosoma mansoni eggs.
Cytokines play a major role in promoting naive Th cells to differentiate into Th1 or Th2 cells. While IL-4 is recognized as the primary pro-Th2 inducing cytokine, the identity of its cellular sources during the development of a Th2 response remains unclear. We have used Schistosoma mansoni eggs, potent stimulators of Th2 responses both during the natural progression of murine schistosomiasis and when experimentally isolated and injected into normal mice, to examine IL-4 production early in the evolution of an Ag-driven Th2 response. Analysis of peritoneal exudate cells by IL-4 specific reverse transcriptase-PCR and ELISPOT, at times following i.p. egg injection in naive C57BL/6 mice, revealed a marked, transient elevation in IL-4 production at 2 to 12 h after Ag exposure. This response was temporally accompanied by eosinophil and neutrophil infiltration and mast cell disappearance. The pattern of early IL-4 production and peritoneal cell infiltration was observed in egg-injected CD4+ cell-depleted and nude C57BL/6 mice, strongly suggesting that a non-T cell is the source of early IL-4 and that the stimulus leading to the egg-induced changes in cellular composition are T cell independent. In addition to IL-4 transcripts, peritoneal exudate cells from egg-injected T cell replete or deficient mice contained IFN-gamma and IL-12 transcripts. Control i.p. PBS injections led to no or minimal cytokine gene transcription. Early IL-4 was predictive of subsequent Th2 response development since, in contrast to C57BL/6 mice, egg-injected BALB/c mice demonstrated no detectable IL-4 production at 12 h and mounted a comparatively weak egg Ag-specific Th2 response.


[Research on the state of the cell membrane and the mechanism of corneal autolysis in the conservation process (author's transl)].
In this work we have thrown light on the basis of our experiments on 530 rabbits', dogs' and human eyes preserved under various conditions on the influence of antioxidation substances on corneal preservation. The development of autolysis is highly dependent on the absence of antioxident - also important for the survival of the cornea. From our results we have drawn conclusions regarding the participation of antioxidant (-tocopherol, chondroitin sulphate) on the self-regulating oxidation of structural lipids in the cell membranes of the cornea, and its effects on preservation.


Glycans of myelin proteins.
Human P0 is the main myelin glycoprotein of the peripheral nervous system. It can bind six different glycans, all linked to Asn(93) , the unique glycosylation site. Other myelin glycoproteins, also with a single glycosylation site (PMP22 at Asn(36) , MOG at Asn(31) ), bind only one glycan. The MAG has 10 glycosylation sites; the glycoprotein OMgp has 11 glycosylation sites. Aside from P0, no comprehensive data are available on other myelin glycoproteins. Here we review and analyze all published data on the physicochemical structure of the glycans linked to P0, PMP22, MOG, and MAG. Most data concern bovine P0, whose glycan moieties have an MW ranging from 1,294.56 Da (GP3) to 2,279.94 Da (GP5). The pI of glycosylated P0 protein varies from pH 9.32 to 9.46. The most charged glycan is MS2 containing three sulfate groups and one glucuronic acid; whereas the least charged one is the BA2 residue. All glycans contain one fucose and one galactose. The most mannose rich are the glycans MS2 and GP4, each of them has four mannoses; OPPE1 contains five N-acetylglucosamines and one sulfated glucuronic acid; GP4 contains one sialic acid. Furthermore, human P0 variants causing both gain and loss of glycosylation have been described and cause peripheral neuropathies with variable clinical severity. In particular, the substitution T(95) →M is a very common in Europe and is associated with a late-onset axonal neuropathy. Although peripheral myelin is made up largely of glycoproteins, mutations altering glycosylation have been described only in P0. This attractive avenue of research requires further study.


NADP-malic enzyme and Hsp70: co-purification of both proteins and modification of NADP-malic enzyme properties by association with Hsp70.
Different preparations of antibodies against 62 kDa NADP-malic enzyme (NADP-ME) from purified maize leaves cross-react with a 72 kDa protein from diverse tissues in many species. A 72 kDa protein, suggested to be a non-photosynthetic NADP-ME, has been purified from several plant species. However, to date, a cDNA coding for this putative 72 kDa NADP-ME has not been isolated. The screening of maize and tobacco leaf expression libraries using antibodies against purified 62 kDa NADP-ME allowed the identification of a heat shock protein (Hsp70). In addition, tandem mass spectrometry (MS/MS) studies indicate that along with NADP-ME, a 72 kDa protein, identified as an Hsp70 and reacting with the antibodies, is also purified from maize roots. On the other hand, the screening of a maize root cDNA library revealed the existence of a cDNA that encodes a mature 66 kDa NADP-ME. These results suggest that the 72 kDa protein is not actually an NADP-ME but in fact an Hsp70, at least in maize and tobacco. Probably, NADP-ME-Hsp70 association, taking place at least when preparing crude extracts, can lead to a co-purification of the proteins and can thus explain the cross-reaction of the antibodies. In the present work, we analyse and discuss a probable interaction of NADP-ME with Hsp70.


Clinical impact of pre-treatment FDG-PET/CT staging of primary ovarian, fallopian tube, and peritoneal cancers in women.
To assess the clinical impact of preoperative fludeoxyglucose (FDG) with positron emission tomography (PET) and computed tomography (CT) in women with ovarian, fallopian tube, or peritoneal cancer with focus on consequences of added findings (AFs). FDG-PET/CT was implemented as a standard imaging modality for women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer at our institution in 2008. After full implementation, all preoperative scans were reviewed and AFs were evaluated from January 2011 to December 2012. Decisions regarding further examination made at the first multidisciplinary team conference were recorded. Subsequent procedures were tracked via medical records, and the impact of AFs on additional examinations, delay, and change in treatment plans was evaluated. Forty-four (21.1%) of 209 women presented with AFs. Further examination was performed in 35/44 (79.5%). Malignancy was identified in 15/35 (42.9%), revealing metastases from ovarian, fallopian tube, or peritoneal cancer in 11, a synchronous primary cancer in 3, and recurrence of a previous cancer in 1 woman. The ovarian, fallopian tube, or peritoneal cancer metastases were localized in the lungs, uterus, colon, vagina, and breasts. The remaining 20 AFs revealed 2 benign lesions and 1 pre-malignant lesion, whereas no abnormality was found in 17. Further examination of AFs resulted in a significant time delay until treatment start of median 4 days (range 1-83 days, P < 0.004). Further examinations of AFs by FDG-PET/CT delayed time to start of treatment by median 4 days in women with newly diagnosed ovarian, fallopian tube, or peritoneal cancer in a contemporary institution with fast-track access to additional diagnostics. The clinical implications of this must be balanced against the gain of detecting unrecognized malignancy in 15 of 209 women (7.2%).


Corrupt practices in chinese medical care: the root in public policies and a call for Confucian-market approach.
This paper argues that three salient corrupt practices that mark contemporary Chinese health care, namely the over-prescription of indicated drugs, the prescription of more expensive forms of medication and more expensive diagnostic work-ups than needed, and illegal cash payments to physicians-i.e., red packages-result not from the introduction of the market to China, but from two clusters of circumstances. First, there has been a loss of the Confucian appreciation of the proper role of financial reward for good health care. Second, misguided governmental policies have distorted the behavior of physicians and hospitals. The distorting policies include (1) setting very low salaries for physicians, (2) providing bonuses to physicians and profits to hospitals from the excessive prescription of drugs and the use of more expensive drugs and unnecessary expensive diagnostic procedures, and (3) prohibiting payments by patients to physicians for higher quality care. The latter problem is complicated by policies that do not allow the use of governmental insurance and funds from medical savings accounts in private hospitals as well as other policies that fail to create a level playing field for both private and government hospitals. The corrupt practices currently characterizing Chinese health care will require not only abolishing the distorting governmental policies but also drawing on Confucian moral resources to establish a rightly directed appreciation of the proper place of financial reward in the practice of medicine.


Ultrasound-Guided Transgluteal Percutaneous Nephrolithotomy for a Patient with Complex Urogenital Reconstruction and Ectopic Kidney.
Pediatric patients with urolithiasis and complex reconstructed genitourinary anatomy pose a significant surgical challenge. We describe a technique utilized to treat an obstructing calculus in the ectopic kidney of a patient with a history of cloacal exstrophy, bladder augmentation, Monti catheterizable channel, and reconstructed abdominal wall. Case and Technique: A 5-year-old female with a history of cloacal exstrophy, pelvic kidney, and reconstructed urologic and abdominal wall anatomy presented after prior shockwave lithotripsy with an obstructing ureteropelvic junction calculus with signs of sepsis. Because of the patient's previous abdominal wall reconstruction with polytetrafluoroethylene mesh and the location of her pelvic kidney, traditional methods of percutaneous nephrostomy tube placement could not be performed. Transgluteal percutaneous nephrostomy tube was placed by interventional radiology. Subsequently, a percutaneous nephrolithotomy (PCNL) was performed through this tract. Transgluteal PCNL is a feasible option in children with complex congenital genitourinary anomalies with a history of reconstructed anatomy.


Historical increases in land-derived nutrient inputs may alleviate effects of a changing physical climate on the oceanic carbon cycle.
The implications of climate change and other human perturbations on the oceanic carbon cycle are still associated with large uncertainties. Global-scale modelling studies are essential to investigate anthropogenic perturbations of oceanic carbon fluxes but, until now, they have not considered the impacts of temporal changes in riverine and atmospheric inputs of P and N on the marine net biological productivity (NPP) and air-sea CO2 exchange (FCO2 ). To address this, we perform a series of simulations using an enhanced version of the global ocean biogeochemistry model HAMOCC to isolate effects arising from (1) increasing atmospheric CO2 levels, (2) a changing physical climate and (3) alterations in inputs of terrigenous P and N on marine carbon cycling over the 1905-2010 period. Our simulations reveal that our first-order approximation of increased terrigenous nutrient inputs causes an enhancement of 2.15 Pg C year-1 of the global marine NPP, a relative increase of +5% over the simulation period. This increase completely compensates the simulated NPP decrease as a result of increased upper ocean stratification of -3% in relative terms. The coastal ocean undergoes a global relative increase of 14% in NPP arising largely from increased riverine inputs, with regional increases exceeding 100%, for instance on the shelves of the Bay of Bengal. The imprint of enhanced terrigenous nutrient inputs is also simulated further offshore, inducing a 1.75 Pg C year-1 (+4%) enhancement of the NPP in the open ocean. This finding implies that the perturbation of carbon fluxes through coastal eutrophication may extend further offshore than that was previously assumed. While increased nutrient inputs are the largest driver of change for the CO2 uptake at the regional scale and enhance the global coastal ocean CO2 uptake by 0.02 Pg C year-1 , they only marginally affect the FCO2 of the open ocean over our study's timeline.


ToxicoDB: an integrated database to mine and visualize large-scale toxicogenomic datasets.
In the past few decades, major initiatives have been launched around the world to address chemical safety testing. These efforts aim to innovate and improve the efficacy of existing methods with the long-term goal of developing new risk assessment paradigms. The transcriptomic and toxicological profiling of mammalian cells has resulted in the creation of multiple toxicogenomic datasets and corresponding tools for analysis. To enable easy access and analysis of these valuable toxicogenomic data, we have developed ToxicoDB (toxicodb.ca), a free and open cloud-based platform integrating data from large in vitro toxicogenomic studies, including gene expression profiles of primary human and rat hepatocytes treated with 231 potential toxicants. To efficiently mine these complex toxicogenomic data, ToxicoDB provides users with harmonized chemical annotations, time- and dose-dependent plots of compounds across datasets, as well as the toxicity-related pathway analysis. The data in ToxicoDB have been generated using our open-source R package, ToxicoGx (github.com/bhklab/ToxicoGx). Altogether, ToxicoDB provides a streamlined process for mining highly organized, curated, and accessible toxicogenomic data that can be ultimately applied to preclinical toxicity studies and further our understanding of adverse outcomes.


Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC).
This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m(-2) per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m(-2) day(-1) for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5-16% and 2-22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25-101 weeks) for GEM and 26 weeks (range 16-46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2-65 weeks) and 18 weeks (range 4-51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1-101 weeks) and 30 weeks (1-101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.


STUDIES ON THE TOXICITY OF INFLUENZA VIRUSES : I. THE EFFECT OF INTRACEREBRAL INJECTION OF INFLUENZA VIRUSES.
Intracerebral injection of preparations of influenza viruses into mice led to tonic and clonic convulsions and death in tetanus, usually within 24 to 72 hours. Histological examination revealed the destruction of the ependymal lining of the ventricles as the dominant finding. These reactions were obtained in four different strains of mice as well as in rats, guinea pigs, and hamsters. They were observed in mice after injection of mouse and egg-adapted virus, and all strains of virus tested gave these responses as long as sufficient quantities of the agents were injected. Control materials, such as normal allantoic fluids, particulate components of normal chorio-allantoic membranes, and suspensions of normal murine lungs, gave uniformly negative results. Activation of a latent virus as well as the inadvertent admixture of a neurotropic agent to the influenza cultures was excluded. Propagation of the influenza viruses in the central nervous system could not be demonstrated and, in fact, the agents were no longer demonstrable in 4 days. It was concluded that the observed neurological reactions were the result of toxic activities rather than of virus propagation. Comparison between the infectivity, hemagglutinating capacity, and the toxic activity showed that preparations with the higher titers of virus and hemagglutinin were also the more toxic ones. The toxic agents could not be separated from the infectious particles by the use of such technics as differential high speed centrifugation, adsorption onto and elution from chicken red cells, and precipitation by protamine. The toxic effect of influenza A virus preparations was specifically neutralized by anti-influenza A and not by anti-influenza B serum, and conversely. In addition, antigenic differences were noted between two strains of influenza A virus by this method of testing.


Cortical pQCT measures are associated with fractures in dialysis patients.
To determine if pQCT could identify HD patients with fractures, we conducted a cross-sectional study in 52 men and women on HD. We found that cortical, but not trabecular, pQCT measures were associated with fractures. Fractures are common in hemodialysis (HD) patients, yet DXA is inconsistently associated with fractures. One explanation for this lack of association may be that HD patients have a selective decrease in cortical density not identified by standard DXA. We used pQCT to examine cross-sectional associations between cortical and trabecular measures and fractures in 36 men and 16 women, > or = 50 years of age, on HD for at least 1 year. We confirmed low-trauma nonspine fractures since starting HD. Prevalent vertebral fractures were identified by morphometry of lateral spine X-rays. pQCT measurements of the nondominant radius included trabecular density, cortical density, total area, cortical area, and cortical thickness. We also obtained DXA measurements of the hip and lumbar spine. We used logistic regression models, adjusted for age, weight, and sex, to examine the association between fracture (vertebral and/or self-reported nonspine) and each pQCT measure. Results are reported as ORs per SD decrease in the independent variable. The mean age was 65.8 +/- 9.0 (SD) years, the mean weight was 72.3 +/- 15.6 kg, most (32 of 52) subjects were white, and there were 32 fractures in 27 subjects (prevalent vertebral fracture or low-trauma fracture) since starting dialysis. A decrease in cortical density was associated with fractures (OR = 16.67; 95% CI: 2.94-83.33), as was a decrease in cortical area (OR = 3.04; 95% CI: 1.28-7.25) and a decrease in cortical thickness (OR = 3.26; 95% CI: 1.36-7.87). Fractures were not associated with pQCT trabecular density (OR = 1.18; 95% CI: 0.6-2.33), total area (OR = 1.1; 95% CI: 0.59-1.7), or DXA measurements of the hip and spine. Cortical parameters of the radius were associated with fractures in HD patients. If confirmed in prospective studies, these findings may explain the lack of association between fracture and standard DXA measurements and raise the possibility that pQCT could be used to identify HD patients at high risk of fracture.


Some consequences of using the Horsfall-Barratt scale for hypothesis testing.
Comparing treatment effects by hypothesis testing is a common practice in plant pathology. Nearest percent estimates (NPEs) of disease severity were compared with Horsfall-Barratt (H-B) scale data to explore whether there was an effect of assessment method on hypothesis testing. A simulation model based on field-collected data using leaves with disease severity of 0 to 60% was used; the relationship between NPEs and actual severity was linear, a hyperbolic function described the relationship between the standard deviation of the rater mean NPE and actual disease, and a lognormal distribution was assumed to describe the frequency of NPEs of specific actual disease severities by raters. Results of the simulation showed standard deviations of mean NPEs were consistently similar to the original rater standard deviation from the field-collected data; however, the standard deviations of the H-B scale data deviated from that of the original rater standard deviation, particularly at 20 to 50% severity, over which H-B scale grade intervals are widest; thus, it is over this range that differences in hypothesis testing are most likely to occur. To explore this, two normally distributed, hypothetical severity populations were compared using a t test with NPEs and H-B midpoint data. NPE data had a higher probability to reject the null hypothesis (H0) when H0 was false but greater sample size increased the probability to reject H0 for both methods, with the H-B scale data requiring up to a 50% greater sample size to attain the same probability to reject the H0 as NPEs when H0 was false. The increase in sample size resolves the increased sample variance caused by inaccurate individual estimates due to H-B scale midpoint scaling. As expected, various population characteristics influenced the probability to reject H0, including the difference between the two severity distribution means, their variability, and the ability of the raters. Inaccurate raters showed a similar probability to reject H0 when H0 was false using either assessment method but average and accurate raters had a greater probability to reject H0 when H0 was false using NPEs compared with H-B scale data. Accurate raters had, on average, better resolving power for estimating disease compared with that offered by the H-B scale and, therefore, the resulting sample variability was more representative of the population when sample size was limiting. Thus, there are various circumstances under which H-B scale data has a greater risk of failing to reject H0 when H0 is false (a type II error) compared with NPEs.


Risk targeting in cervical screening: a new look at an old problem.
In the face of continuing debate about the level of effectiveness of the United Kingdom cervical cytology screening programme in preventing cervical cancer, more precise targeting of high risk groups might offer a means of enhancing its efficiency. Broad risk targeting is already practised by screening only sexually active women aged 20 to 65 years. This paper describes a risk scoring system constructed from the available literature and designed to be used by primary care health professionals and patients. The system involves four independent risk factors: educational level, current smoking habit, years of oral contraceptive use and number of sexual partners. Since the objective is simply to identify women at relatively high risk, inclusion of a factor neither requires nor implies causality. The next steps are to study the feasibility of putting the scale to practical use and to investigate its predictive value in a prospective evaluation.


Identification of a metabolic reaction network from time-series data of metabolite concentrations.
Recent development of high-throughput analytical techniques has made it possible to qualitatively identify a number of metabolites simultaneously. Correlation and multivariate analyses such as principal component analysis have been widely used to analyse those data and evaluate correlations among the metabolic profiles. However, these analyses cannot simultaneously carry out identification of metabolic reaction networks and prediction of dynamic behaviour of metabolites in the networks. The present study, therefore, proposes a new approach consisting of a combination of statistical technique and mathematical modelling approach to identify and predict a probable metabolic reaction network from time-series data of metabolite concentrations and simultaneously construct its mathematical model. Firstly, regression functions are fitted to experimental data by the locally estimated scatter plot smoothing method. Secondly, the fitted result is analysed by the bivariate Granger causality test to determine which metabolites cause the change in other metabolite concentrations and remove less related metabolites. Thirdly, S-system equations are formed by using the remaining metabolites within the framework of biochemical systems theory. Finally, parameters including rate constants and kinetic orders are estimated by the Levenberg-Marquardt algorithm. The estimation is iterated by setting insignificant kinetic orders at zero, i.e., removing insignificant metabolites. Consequently, a reaction network structure is identified and its mathematical model is obtained. Our approach is validated using a generic inhibition and activation model and its practical application is tested using a simplified model of the glycolysis of Lactococcus lactis MG1363, for which actual time-series data of metabolite concentrations are available. The results indicate the usefulness of our approach and suggest a probable pathway for the production of lactate and acetate. The results also indicate that the approach pinpoints a probable strong inhibition of lactate on the glycolysis pathway.


Attitudes towards and use of general practitioner services among homosexual men with HIV infection or AIDS.
In a study of 263 homosexual men positive for the human immunodeficiency virus (HIV), it was found that 87% were registered with a general practitioner and of these, 55% said that the general practitioner knew their HIV status. Of the 104 men who had experienced symptoms, 39% had consulted the general practitioner for HIV-related advice. A total of 49% of those who were not registered used a specialist outpatient clinic for all their medical needs. Of those who were registered and whose general practitioner was aware of their HIV status but who did not consult their doctor, 72% used a specialist outpatient clinic. Reasons for not consulting the general practitioner included fears of breach of confidentiality and lack of confidence in the general practitioner's understanding of HIV. Fifteen per cent of the sample continued to see a general practitioner who was unaware of their HIV status, for non-HIV related advice. The needs of patients must be taken into account when planning more integrated hospital and community care for those with HIV infection or the acquired immune deficiency syndrome (AIDS).


The Interaction Between Morphological Awareness and Word Detection Skills in Predicting Speeded Passage Reading in Primary and Secondary School Chinese Readers.
Previous studies suggest that morphological awareness (MA) and word detection skills have facilitating roles in reading fluency; however, it is unknown whether they can interplay with each other in such roles. The present study explored the relationships of MA, word detection, and passage reading fluency across ages. In total, 180 Chinese primary and secondary school students, aged from 8.52 to 15.67 years, completed tasks for these aforementioned capacities. After controlling gender, non-verbal intelligence, and reading ability at the word level, the results showed that the participants with higher scores for MA or word detection performed better in passage reading fluency. However, the predictive effect of word detection on reading fluency became weaker as the children became older. The interaction between MA and word detection was positive in younger children, whereas this interaction tended to be negative for older children. The results demonstrated a dynamic interplay between MA and word detection in contributing to passage reading fluency in Chinese children. While it has a positive interaction with word detection on reading fluency in younger children, MA may become a compensator in older children (e.g., over 14 years old) whose word detection skills are less effective in facilitating fluent reading.


Progressive inflammatory and structural changes in the pulmonary vasculature of monocrotaline-treated rats.
The progression of changes in the bronchus-associated and intraacinar pulmonary arteries of rats treated with a single dose of monocrotaline (60 mg/kg) was evaluated by quantitative light and electron microscopy. The relative volume of vessel wall components was normalized to the surface area of the adventitial sheath. An increased relative volume of media was evident in intraacinar pulmonary arteries by 4 hr post-treatment. This increase may represent vascular smooth muscle contraction. Significant increases in adventitial mononuclear inflammatory cells were evident by 8-16 hr post-treatment in intraacinar pulmonary arteries and veins but not until 14 days post-treatment in major, bronchus-associated pulmonary arteries. Inflammatory cell influxes were associated with increased relative volume of adventitia, largely due to increased extracellular space. By 22 days posttreatment, there was right ventricular hypertrophy and a marked mononuclear vasculitis in major and intraacinar pulmonary arteries as well as intraacinar veins (confirmed as such by vascular perfusion of carbon/gelatin). There was increased relative medial volume in both major and intraacinar pulmonary arteries associated with increased extracellular matrix composed largely of collagen. Intraacinar veins developed intimal plaques of smooth muscle in a collagenous matrix. We conclude that (1) adventitial inflammation precedes morphologic evidence of medial changes in monocrotaline-induced pulmonary hypertension, (2) involvement of intraacinar arteries precedes that of major bronchus associated arteries, and (3) both pulmonary arteries and veins are involved in monocrotaline-induced pulmonary vascular disease in the rat.


Characterization of CD34+ peripheral blood cells from healthy adults mobilized by recombinant human granulocyte colony-stimulating factor.
Primed peripheral blood hematopoietic stem cells (PBSC) generate and sustain lymphohematopoiesis in myeloablated animals, and recent reports indicate that allogeneic transplantation using PBSC grafts may be feasible in humans. A major concern with the use of PBSC transplants is that permanent engraftment may be limited because of lack of sufficient numbers of primitive progenitor cells in the graft. In the present study, in vitro colony formation and immunophenotype of CD34+ cells in PB of healthy adults during short-term granulocyte colony-stimulating factor (G-CSF) administration were compared with that of CD34+ cells in normal bone marrow (BM). The number of CD34+ cells mobilized to PB peaked at day 4 or 5 of G-CSF administration. The phenotypic profile of CD34+ PB cells showed a substantial increase in the percentage of CD34+CD13+ and CD34+CD33+ cells (myeloid progenitors) and a corresponding decrease in the percentage of CD34+CD10+ and CD34+CD19+ cells (B lymphoid progenitors) compared with CD34+ BM cells. The other subsets studied, including CD34+CD38- and CD34+HLA-DR- cells, were present in both compartments in similar proportions. Furthermore, primed CD34+ PB cells were enriched for colony-forming cells (CFC) and displayed an increased clonogenicity when compared with their counterparts in BM. A comparison between a postulated PBSC graft and an average BM graft is presented, showing that such PBSC grafts will be enriched for CD34+ cells as a whole, CD34+CD33+ cells, and colony-forming cells (CFC), factors which have been shown to correlate to acceleration of hematologic reconstitution and reduction in requirements for supportive care in autografting. Hence, we predict that allogeneic transplantation using G-CSF-primed PBSC grafts will result in a more rapid hematologic reconstitution after myeloablative conditioning than BM grafting. The question of whether PBSC allografting will result in permanent engraftment and clinical benefits as observed in autografting has to be determined in prospective clinical studies.


Genetic influences on response to mood stabilizers in bipolar disorder: current status of knowledge.
Mood stabilizers form a cornerstone in the long-term treatment of bipolar disorder. The first representative of their family was lithium, still considered a prototype drug for the prevention of manic and depressive recurrences in bipolar disorder. Along with carbamazepine and valproates, lithium belongs to the first generation of mood stabilizers, which appeared in psychiatric treatment in the 1960s. Atypical antipsychotics with mood-stabilizing properties and lamotrigine, which were introduced in the mid-1990 s, form the second generation of such drugs. The response of patients with bipolar disorder to mood stabilizers has different levels of magnitude. About one-third of lithium-treated patients are excellent responders, showing total prevention of the episodes, and these patients are clinically characterized by an episodic clinical course, complete remission, a bipolar family history, low psychiatric co-morbidity and a hyperthymic temperament. It has been suggested that responders to carbamazepine or lamotrigine may differ clinically from responders to lithium. The main phenotype of the response to mood stabilizers is a degree of prevention against recurrences of manic and depressive episodes during long-term treatment. The most specific scale in this respect is the so-called Alda scale, where retrospective assessment of lithium response is scored on a 0-10 scale. The vast majority of data on genetic influences on the response to mood stabilizers has been gathered in relation to lithium. The studies on the mechanisms of action of lithium and on the neurobiology of bipolar disorder have led to the identification of a number of candidate genes. The genes studied for their association with lithium response have been those connected with neurotransmitters (serotonin, dopamine and glutamate), second messengers (phosphatidyl inositol [PI], cyclic adenosine-monophosphate [cAMP] and protein kinase C [PKC] pathways), substances involved in neuroprotection (brain-derived neurotrophic factor [BDNF] and glycogen synthase kinase 3-β [GSK-3β]) and a number of other miscellaneous genes. There are no published pharmacogenomic studies of mood stabilizers other than lithium, except for one study of the X-box binding protein 1 (XBP1) gene in relation to the efficacy of valproate. In recent years, a number of genome-wide association studies (GWAS) in bipolar disorders have been performed and some of those have also focused on lithium response. They suggest roles for the glutamatergic receptor AMPA (GRIA2) gene and the amiloride-sensitive cation channel 1 neuronal (ACCN1) gene in long-term lithium response. A promise for better elucidating the genetics of lithium response has been created by the formation of the Consortium on Lithium Genetics (ConLiGen) to establish the largest sample, to date, for the GWAS of lithium response in bipolar disorder. The sample currently comprises more than 1,200 patients, characterized by their response to lithium treatment according to the Alda scale. Preliminary results from this international study suggest a possible involvement of the sodium bicarbonate transporter (SLC4A10) gene in lithium response. It is concluded that the pharmacogenetics of response to mood stabilizers has recently become a growing field of research, especially so far as the pharmacogenetics of the response to lithium is concerned. Clearly, the ConLiGen project is a highly significant step in this research. Although the results of pharmacogenetic studies are of significant scientific value, their possible practical implications are yet to be seen.


Population genetics of Manihot esculenta ssp. flabellifolia gives insight into past distribution of xeric vegetation in a postulated forest refugium area in northern Amazonia.
The Guianas have often been proposed as a forest refugium; however, this view has received little testing. Studies of population genetics of forest taxa suggest that the central part of French Guiana remained forested, while the southern part (currently forested) may have harboured more open vegetation. Insights into the population structure of species restricted to non-forested habitats can help test this hypothesis. Using six microsatellite loci, we investigated the population genetics of French Guianan accessions of Manihot esculenta ssp. flabellifolia, a taxon restricted to coastal savannas and to rocky outcrops in the densely forested inland. Coastal populations were highly differentiated from one another, and our data suggest a recent colonization of these savannas by M. esculenta ssp. flabellifolia in a west-to-east process. Coastal populations were strongly differentiated from inselberg populations, consistent with an ancient separation of these two groups, with no or low subsequent gene flow. This supports the hypothesis that the central part of the region may have remained forested since the Last Glacial Maximum, impeding the establishment of Manihot. Contrary to coastal populations, inselberg Manihot populations were strikingly homogeneous at a broad spatial scale. This suggests they were connected until recently, either by a large continuous savanna area or by smaller, temporary disturbed areas shifting in space.


Remediation of hemorrhagic shock-induced intestinal barrier dysfunction by treatment with diphenyldihaloketones EF24 and CLEFMA.
Gut is very sensitive to hypoperfusion and hypoxia, and deranged gastrointestinal barrier is implicated in systemic failure of various organs. We recently demonstrated that diphenyldihaloketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one] improves survival in a rat model of hemorrhagic shock. In this study, we tested EF24 and its other analog CLEFMA (4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid) for their effect on intestinal barrier dysfunction in hypovolemic shock. Hypovolemia was induced in rats by withdrawing 50% of blood. EF24 or CLEFMA (0.4 mg/kg i.p.) treatment was provided, without volume resuscitation, after 1 hour of hemorrhage. Ileum was collected 5 hours after the treatment to investigate the expression of tight junction proteins (zonula occludens, claudin, and occludin) and epithelial injury markers [myeloperoxidase, ileal lipid-binding protein (ILBP), CD163, and plasma citrulline]. The ileal permeability for dextran-fluoroisothiocyanate and Evan's blue dye was determined. EF24 and CLEFMA reduced the hypovolemia-induced plasma citrulline levels and the ileal expression of myeloperoxidase, ILBP, and CD163. The drugs also restored the basal expression levels of zonula occludens, claudin, and occludin, which were substantially deranged by hypovolemia. In ischemic ileum, the expression of phospho(tyrosine)-zonula occludens-1 was reduced, which was reinstated by EF24 and CLEFMA. In contrast, the drug treatments maintained the hypovolemia-induced expression of phospho(threonine)-occludin, but reduced that of phospho(tyrosine)-occludin. Both EF24 and CLEFMA treatments reduced the intestinal permeability enhanced by hypovolemia. EF24 and CLEFMA attenuate hypovolemic gut pathology and protect barrier function by restoring the status of tight junction proteins. These effects were observed in unresuscitated shock, implying the benefit of EF24 and CLEFMA in prehospital care of shock.


Method for antibiotic determination in animal tissue, as applied to lasalocid.
The development of a tissue residue method for an antibiotic is dependent on the history of the overall problem; the current requirements that must be met for regulatory approval; the chemistry of the compound; its physical/chemical parameters; and its microbiological spectrum for the best possible fit of all of these to ensure a procedure that will work reliably in the originator's laboratory and to the same degree of effectiveness in anyone's laboratory. A note is made of those factors that must be included as controls on the procedure and those experiments that must be included to differentiate matrix from method influences.


Neuropsychological Performance and Functional Capacity Following Mild Traumatic Brain Injury in Veterans.
To examine the relationship between neuropsychological functioning and performance-based functional capacity in veterans with a history of mild traumatic brain injury (mTBI), as well as the moderating effects of age and psychiatric symptoms on this relationship. Three Veterans Affairs medical centers. One hundred nineteen Iraq/Afghanistan veterans with a history of mTBI and self-reported cognitive difficulties. Cross-sectional, secondary data analysis of baseline measures in a randomized controlled trial. The main outcome measure, functional capacity, was assessed using the objective and performance-based University of California San Diego Performance-based Skills Assessment-Brief. A global deficit score (GDS) was created as a composite score for performance on a battery of neuropsychological measures assessing domains of attention, processing speed, executive functioning, and verbal memory performance. Posttraumatic stress disorder (PTSD) symptom severity was assessed using the PTSD Checklist-Military Version, and depressive symptom severity was assessed using the Beck Depression Inventory, Second Edition. Bivariate analyses indicated that worse neuropsychological performance (ie, higher GDS) and greater PTSD symptom severity were associated with worse communication abilities and worse overall functional capacity. Multiple linear regressions demonstrated that GDS and PTSD symptom severity explained 9% of the variance in communication and 10% of the variance in overall functional capacity; however, GDS emerged as the only significant predictor in both regressions. Age, PTSD, and depressive symptom severity did not moderate the relationship between GDS and overall functional capacity. Performance in the verbal learning and memory domain emerged as the strongest neuropsychological predictor of communication and overall functional capacity. Worse neuropsychological functioning was moderately associated with worse performance-based functional capacity, even when accounting for PTSD symptom severity. Verbal learning and memory was the primary neuropsychological domain driving the relationship with functional capacity; improvement in verbal learning and memory may translate into improved functional capacity.


High-resolution 3D radial bSSFP with IDEAL.
Radial trajectories facilitate high-resolution balanced steady state free precession (bSSFP) because the efficient gradients provide more time to extend the trajectory in k-space. A number of radial bSSFP methods that support fat-water separation have been developed; however, most of these methods require an environment with limited B0 inhomogeneity. In this work, high-resolution bSSFP with fat-water separation is achieved in more challenging B0 environments by combining a 3D radial trajectory with the IDEAL chemical species separation method. A method to maintain very high resolution within the timing constraints of bSSFP and IDEAL is described using a dual-pass pulse sequence. The sampling of a unique set of radial lines at each echo time is investigated as a means to circumvent the longer scan time that IDEAL incurs as a multiecho acquisition. The manifestation of undersampling artifacts in this trajectory and their effect on chemical species separation are investigated in comparison to the case in which each echo samples the same set of radial lines. This new bSSFP method achieves 0.63 mm isotropic resolution in a 5-min scan and is demonstrated in difficult in vivo imaging environments, including the breast and a knee with ACL reconstruction hardware at 1.5 T.


Circulating vitamin D metabolites and kidney disease in type 1 diabetes.
Impaired vitamin D metabolism may contribute to the development and progression of diabetic kidney disease. The aim of the study was to test associations of circulating vitamin D metabolites with risks of incident microalbuminuria, impaired glomerular filtration rate (GFR), and hypertension in type 1 diabetes. We performed a cohort study of 1193 participants in the Diabetes Control and Complications Trial (DCCT), a randomized clinical trial of intensive diabetes therapy, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT and tested associations with incident microalbuminuria, impaired GFR, and hypertension over up to 16 yr of EDIC follow-up. At the time metabolites were measured, mean age was 32.4 yr; mean duration of diabetes, 7.5 yr; mean iothalamate GFR, 132.9 ml/min/1.73 m(2); and geometric mean albumin excretion rate, 11.8 mg/24 h. Over follow-up, 166 cases of microalbuminuria, 54 cases of impaired GFR, and 541 cases of hypertension were observed. Compared with 25(OH)D of at least 30 ng/ml, 25(OH)D below 20 ng/ml was associated with a 65% higher risk of microalbuminuria (95% confidence interval, 7 to 154%) in adjusted analyses. Low concentrations of 24,25-dihydroxyvitamin D, but not 1,25-dihydroxyvitamin D, were also associated with increased risk of microalbuminuria. No circulating vitamin D metabolite was associated with risk of impaired GFR or hypertension. Low plasma concentrations of 25(OH)D and 24,25-dihydroxyvitamin D are associated with increased risk of microalbuminuria in type 1 diabetes. In contrast, we did not find evidence linking impaired vitamin D metabolism to early GFR loss or the development of hypertension.


Precapillary control of the splanchnic vascular bed.
The accessibility of the mesenteric vasculature of the rat permits it to be used for intravital microscopy. Venous-arteriolar response and autoregulation are localized in the precapillary and terminal arterioles. Responses to intravasal application of noradrenaline are not influenced by arteriolar tone, induced by a venous-arteriolar response. This indicates a strong regulatory influence on the precapillary vessels originating from the venous side. Arteriolar and venous-arteriolar autoregulations are differentially effective in the individual organ circulations. Noradrenaline dose-response curves and frequency-response curves in the saline-perfused mesenteric vascular bed were analyzed with respect to the reactivity of the different groups of precapillary vessels. The sensitivity to noradrenaline, quantified by the ED50, was significantly smaller in the arterioles than in small precapillary arterioles or in larger arteries. Autoregulatory escape was recognized as a typical mechanism of flow redistribution consisting partially of vascular adjustment. Escape from vasoconstrictor influences was more pronounced during electrical stimulation than during responses to noradrenaline. The data suggest that distribution of splanchnic blood flow to individual organs is governed by venous-arteriolar and arteriolar autoregulation, whereas the sympathetic nerves and autoregulatory escape are major factors in controlling the redistribution of blood flow within the tissue or tissue layers.


Critical Stenosis Because of Vocal Cord Synechiae in a Child.
Stridor is a clinical sign of an underlying disease and a common reason for pediatric emergency department (PED) consultation. Patients presenting with stridor must be evaluated to determine the origin of this abnormality. We present the case of a 7-year-old female patient who presented to our Pediatric Emergency Department with a history of recurrent episodes of stridor with increasing frequency over the previous 4 years, for this reason she was previously admitted to the pediatric intensive care unit. Findings from the otorhinolaryngologic assessment with flexible fiber-optic endoscopy led to a diagnosis of congenital synechia of the vocal cords. The cervical CT scan evidenced critical stenosis of the airway. An initial cordectomy and placement of a silicone device for fixation were performed. Subsequently, the patient required 6 additional interventions for progressive dilation of the glottic space at the level of the vocal cords and injections of mitomycin C injections (an antineoplastic that inhibits collagen proliferation). This case highlights the importance of additional studies (especially examination of the upper airway) when atypical or recurrent findings are revealed by the clinical history, physical examination, or disease course in patients with croup to prioritize cases severe enough to require pediatric intensive care unit admission.


[Contamination Characteristics and Potential Ecological Risks of Typical Perfluoroalkyl Substances in the Water and Sediment of Coastal Tourism Resorts in Shandong Province].
Coastal tourism resorts have been developing rapidly in recent years, and the quality of their waterbodies directly affects human health. Perfluoroalkyl substances (PFASs) are found in every environmental medium and have garnered widespread social concern because of their potential ecological harm. This study investigated the contamination characteristics and potential ecological risks of 12 PFASs in the water and sediment of 20 coastal tourism resorts in Shandong Peninsula. The results revealed that all targeted pollutants were observed in the water and most sediment samples collected from the coastal tourism resorts. The sum of the 12 PFASs ∑PFASs averaged 67.91 ng·L-1 and 5.89 ng·g-1 in the water and sediment, respectively. The predominant compounds were perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in both water and sediment. The ∑PFASs and its homologues concentration indicated the spatial variations in the water and sediment of different tourism resorts, and the values were higher in the tourism resorts near the city center and the industrial areas than in other areas. The partition coefficient (Kd) of all the target compounds in the water/sediment system of different tourism resorts showed obvious differences. In addition, the Kd of the compounds with longer carbon chains (C ≥ 7) generally had higher Kd values, which suggests that long-chain PFAAs are prone to adsorption by sediment. Therefore, the discharge of municipal industrial wastewater and domestic sewage is the main source of contamination. The salinity of water and the total carbon contents of sediment did not show any effect on the partition of PFASs in the water/sediment system. PFOS and PFOA might have great potential ecological risks in the water environment of all tourism resorts.


Technologies and Challenges in Proteomic Analysis of Protein S-acylation.
Protein S-acylation (also called palmitoylation) is a pervasive post-translational modification that plays critical roles in regulating protein trafficking, localization, stability, activity, and complex formation. The past decade has witnessed tremendous advances in the study of protein S-acylation, largely owing to the development of novel S-acylproteomics technologies. In this review, we summarize current S-acylproteomics approaches, critically review published S-acylproteomics studies, and envision future directions for the burgeoning S-acylproteomics field. Emerging S-acylproteomics technologies promise to shed new light on this distinct post-translational modification and facilitate the discovery of new disease mechanisms, biomarkers, and therapeutic targets.


Response of human rheumatoid arthritis osteoblasts and osteoclasts to adiponectin.
Adiponectin is an effector molecule in the pathophysiology of rheumatoid arthritis, e.g. by inducing cytokines and matrix degrading enzymes in synovial fibroblasts. There is growing evidence that adiponectin affects osteoblasts and osteoclasts although the contribution to the aberrant bone metabolism in rheumatoid arthritis is unclear. Therefore, the adiponectin effects on rheumatoid arthritis-derived osteoblasts and osteoclasts were evaluated. Adiponectin and its receptors were examined in bone tissue. Primary human osteoblasts and osteoclasts were stimulated with adiponectin and analysed using realtime polymerase chain-reaction and immunoassays. Effects on matrix-production by osteoblasts and differentiation and resorptive activity of osteoclasts were examined. Immunohistochemistry of rheumatoid arthritis bone tissue showed adiponectin expression in key cells of bone remodelling. Adiponectin altered gene expression and cytokine release in osteoblasts and increased IL-8 secretion by osteoclasts. Adiponectin inhibited osterix and induced osteoprotegerin mRNA in osteoblasts. In osteoclasts, MMP-9 and tartrate resistant acid phosphatase expression was increased. Accordingly, mineralisation capacity of osteoblasts decreased whereas resorptive activity of osteoclasts increased. The results confirm the proinflammatory potential of adiponectin and support the idea that adiponectin influences rheumatoid arthritis bone remodelling through alterations in osteoblast and osteoclast.


9-cis retinoic acid regulation of rat growth hormone gene expression: potential roles of multiple nuclear hormone receptors.
Rat GH (rGH) gene expression is increased by both thyroid hormone (T3) and all-trans retinoic acid (RA) via a composite hormone response element (HRE) containing three putative half-sites (rGH-HRE). However, it is not known whether 9-cis RA (9cRA) also can regulate rGH gene expression. In this study, we performed a Northern blot analysis that demonstrated that 9cRA, as well as T3 and RA, increased rGH messenger RNA expression in rat pituitary GH3 cells. Transient transfection studies in GH3 cells, using reporter plasmids containing the rGH-HRE and mutated half-sites, revealed that 9cRA-stimulation of rGH transcription was mediated by the rGH-HRE and that all three half-sites are necessary. Additionally, we performed cotransfection studies to elucidate the particular receptor complexes involved in 9cRA regulation of rGH gene expression using CV-1 cells, which contain little or no endogenous RA receptors, and thyroid hormone receptors. Interestingly, in the presence of either retinoid X receptor alone, RA receptors alone, or both receptors, 9cRA caused similar induction of transcriptional activity. However, cotransfection of thyroid hormone receptors with these receptors repressed basal and blocked 9cRA-induced transcriptional activity in the absence of T3. Our data suggest that 9cRA-stimulation of rGH transcription is likely mediated by 9cRA-bound retinoid X receptor- and/or RA receptor-containing complexes but not by thyroid hormone receptor-containing complexes. Our studies provide evidence that several different members of the nuclear hormone receptor family can interact on this composite DNA element, with transcription stimulated or blocked depending on the presence or absence of cognate ligands.


Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome.
The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems. The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.


The impact of alcohol-specific rules, parental norms about early drinking and parental alcohol use on adolescents' drinking behavior.
The present study explores the role of having rules about alcohol, parental norms about early alcohol use, and parental alcohol use in the development of adolescents' drinking behavior. It is assumed that parental norms and alcohol use affect the rules parents have about alcohol, which in turn prevents alcohol use by adolescent children. Longitudinal data collected from 416 families consisting of both parents and two adolescents (aged 13 to 16 years) were used for the analyses. Results of structural equation modeling show that having clear rules decreases the likelihood of drinking in adolescence. However, longitudinally alcohol-specific rules have only an indirect effect on adolescents' alcohol use, namely through earlier drinking. Analyses focusing on explaining the onset of drinking revealed that having strict rules was related to the postponement of drinking initiation of older and younger adolescents. Further, parental norms about adolescents' early drinking and parental alcohol use were associated with having alcohol-specific rules. Parental norms were also related to adolescents' alcohol use. The current study is one of the first using a full family design to provide insight into the role of alcohol-specific rules on adolescents' drinking. It was shown that having strict rules is related to postponement of drinking, and that having alcohol-specific rules depends on other factors, thus underlining the complexity of the influence of parenting on the development of adolescents' alcohol use.


Oral cleanliness and gingival health among Special Olympics athletes in Europe and Eurasia.
Special Olympics athletes, as well as the general population of people with intellectual disabilities, are expected to have poorer gingival health. The aim of the study is to explore the prevalence of gingival signs of inflammation and its relationship to oral cleanliness and age among Special Olympics athletes from Europe and Eurasia. A retrospective longitudinal study was performed with data collected through standardized oral from 15.941 athletes from annual Special Olympics events held in 49 countries, from Europe and Eurasia between 2007 and 2012. The data was analysed descriptively, with One-Way ANOVA test and Chi-Square test. The level of significance was predetermined at a p value < 0.05. A total of 7,754 athletes presented with gingival signs (48.64%). There were no significant differences (p= 0,095) in mean gingival signs between age groups, however the association between mouth cleaning and age, was statistically significant. The data suggests that there is a high prevalence of gingival signs among individuals with special needs; over 50% in more than 20 countries. Therefore, there is a serious need for education and preventive programs for the patients, their parents and caregivers.


Relaxation of canine airway smooth muscle.
Relaxation of airway smooth muscle is an inadequately understood yet critical process that, if impaired, may have significant implications for asthma. Here we explore why relaxation is an important process to consider, how it may determine airway hyperresponsiveness, and some of the factors that influence relaxation of the airway smooth muscle. These include mechanical and biochemical factors such as deep inspirations or large amplitude oscillation of the muscle, plastic properties of the muscle, the load the muscle experiences, calcium, phosphorylation of the myosin light chain, cytoskeletal proteins, and sensitization.


Role of motion signals in recognizing subtle facial expressions of emotion.
Three studies investigated the importance of movement for the recognition of subtle and intense expressions of emotion. In the first experiment, 36 facial emotion displays were duplicated in three conditions either upright or inverted in orientation. A dynamic condition addressed the perception of motion by using four still frames run together to encapsulate a moving sequence to show the expression emerging from neutral to the subtle emotion. The multi-static condition contained the same four still presented in succession, but with a visual noise mask (200 ms) between each frame to disrupt the apparent motion, whilst in the single-static condition, only the last still image (subtle expression) was presented. Results showed a significant advantage for the dynamic condition, over the single- and multi-static conditions, suggesting that motion signals provide a more accurate and robust mental representation of the expression. A second experiment demonstrated that the advantage of movement was reduced with expressions of a higher intensity, and the results of the third experiment showed that the advantage for the dynamic condition for recognizing subtle emotions was due to the motion signal rather than additional static information contained in the sequence. It is concluded that motion signals associated with the emergence of facial expressions can be a useful cue in the recognition process, especially when the expressions are subtle.


Developmental modulation of myosin expression by thyroid hormone in avian skeletal muscle.
It is well established that a rise in circulating thyroid hormone during the second half of chick embryo development significantly influences muscle weight gain and bone growth. We studied thyroid influence on differentiation in slow anterior latissimus dorsi (ALD) and fast posterior latissimus dorsi (PLD) muscles of embryos rendered hypothyroid by hypophysectomy or administration of an anti-thyroid drug. The expression of native myosins and myosin light chains (MLCs) was studied by electrophoretic analysis, and the myosin heavy chain (MHC) was characterized by immunohistochemistry. The first effects of hypothyroid status were observed at day 21 of embryonic development (stage 46 according to Hamburger and Hamilton). Analysis of myosin isoform expression in PLD muscles of hypothyroid embryos showed persistence of slow migrating native myosins and slow MLCs as well as inhibition of neonatal fast MHC expression, indicating retarded differentiation of this muscle. In ALD muscle, hypothyroidism maintained fast embryonic MHC and induced noticeable amounts of fast MLCs, thus delaying slow muscle differentiation. Our results suggest that thyroid hormones play a role in modulating the appearance of neonatal fast MHC and the disappearance of isomyosins transiently present during embryogenesis. However, T3 supplemental treatment would seem to compensate in part for the effects of hypothyroidism induced by hypophysectomy, suggesting that thyroid hormone might interfere with other factors also accounting for the observed effects.


Detecting Variation in Clinical Practice Patterns for Geriatric Trauma Care Using Social Network Analysis.
To characterize hospital-level professional networks of physicians caring for older trauma patients as a function of trauma patient age distribution. The causal factors associated with between-hospital variation in geriatric trauma outcomes are poorly understood. Variation in physician practice patterns reflected by differences in professional networks might contribute to hospital-level differences in outcomes for older trauma patients. This is a population-based, cross-sectional study of injured older adults (age ≥65) and their physicians from January 1, 2014-December 31, 2015, using Healthcare Cost and Utilization Project inpatient data and Medicare claims from 158 hospitals in Florida. We used social network analyses to characterize hospitals in terms of network density, cohesion, small-worldness, and heterogeneity, then used bivariate statistics to assess the relationship between network characteristics and hospital-level proportion of trauma patients who were age ≥65. We identified 107,713 older trauma patients and 169,282 patient-physician dyads. The hospital-level proportion of trauma patients who were age ≥65 ranged from 21.5% to 89.1%. Network density, cohesion, and small-worldness in physician networks were positively correlated with hospital geriatric trauma proportions (R=0.29, P<0.001; R =0.16, P=0.048; and R =0.19, P<0.001, respectively). Network heterogeneity was negatively correlated with geriatric trauma proportion (R=0.40, P<0.001). Characteristics of professional networks among physicians caring for injured older adults are associated with the hospital-level proportion of trauma patients who are older, indicating differences in practice patterns at hospitals with older trauma populations. Associations between inter-specialty collaboration and patient outcomes should be explored as an opportunity to improve treatment of injured older adults.


Spin transition in a ferrous chloride complex supported by a pentapyridine ligand.
Ferrous chloride complexes [FeIILxCl] commonly attain a high-spin state independently of the supporting ligand(s) and temperature. Herein, we present the first report of a complete spin crossover with T1/2 = 80 K in [FeII(Py5OH)Cl]+ (Py5OH = pyridine-2,6-diylbis[di(pyridin-2-yl)methanol]). Both spin forms of the complex are analyzed by X-ray spectroscopy and DFT calculations.


Does intracisternal thrombolysis prevent vasospasm after aneurysmal subarachnoid hemorrhage? A meta-analysis.
Despite existing strategies for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage, vasospasm remains a persistent contributor to death and disability. The intracisternal application of thrombolytic agents to dissolve subarachnoid clot has been advocated. The goal of this analysis was to assess the currently available evidence regarding the effectiveness of this treatment. We conducted a systematic review of the published literature; all controlled trials were included. The outcomes of interest were delayed ischemic neurological deficits, poor Glasgow Outcome Scale scores, and death. A formal meta-analysis was performed with a random-effects model. The search revealed nine trials or trial subgroups (only one of which was randomized), with a total enrollment of 652 patients. Pooled results demonstrated beneficial effects of treatment, with absolute risk reductions of 14.4% (95% confidence interval, 6.5-22.5%; P < 0.001) for delayed ischemic neurological deficits, 9.5% (95% confidence interval, 4.2-14.8%; P < 0.01) for poor Glasgow Outcome Scale scores, and 4.5% (95% confidence interval, 1.5-7.5%; P < 0.05) for death. Regression analysis revealed that treatment effects did not significantly differ among the studies on the basis of the type of thrombolytic agent used (tissue plasminogen activator versus urokinase) or the method of administration (intraoperative versus postoperative) (P > 0.10). Studies that enrolled only patients at high risk for vasospasm seemed to demonstrate greater treatment effects. The meta-analysis suggests a clinically relevant and statistically significant beneficial effect of intracisternal thrombolysis. However, the results of the analysis are limited by the predominance of nonrandomized studies. Further randomized, blinded, placebo-controlled trials of high-risk patients would be justified.


Dietary bioactives: establishing a scientific framework for recommended intakes.
In the United States, dietary reference intakes describe the relations between nutrient intakes and indicators of adequacy, prevention of disease, and avoidance of excessive intakes among healthy populations for essential nutrients but not dietary bioactive components (DBCs), whose absence from the diet is presumably not deleterious to health (i.e., does not cause a deficiency syndrome). An appropriate framework is needed for establishing recommended intakes for which public health messages and food labeling for DBCs can be derived, because their putative health benefits may not be readily defined in the context of nutritional essentiality. In addition, a myriad of factors make determining their intake and status and investigating their discrete contributions to health particularly challenging. Therefore, the ASN Dietary Bioactive Components Research Interest Section felt it worthwhile to convene a special "hot topic" session at the 2014 Experimental Biology meeting to discuss this issue and serve as a call for future scientific dialogue on establishing a framework for recommended intakes of DBCs. This session summary captures the discussions and presentations that transpired during this session.


Interactive Data Comics.
This paper investigates how to make data comics interactive. Data comics are an effective and versatile means for visual communication, leveraging the power of sequential narration and combined textual and visual content, while providing an overview of the storyline through panels assembled in expressive layouts. While a powerful static storytelling medium that works well on paper support, adding interactivity to data comics can enable non-linear storytelling, personalization, levels of details, explanations, and potentially enriched user experiences. This paper introduces a set of operations tailored to support data comics narrative goals that go beyond the traditional linear, immutable storyline curated by a story author. The goals and operations include adding and removing panels into pre-defined layouts to support branching, change of perspective, or access to detail-on-demand, as well as providing and modifying data, and interacting with data representation, to support personalization and reader-defined data focus. We propose a lightweight specification language, COMICSCRIPT, for designers to add such interactivity to static comics. To assess the viability of our authoring process, we recruited six professional illustrators, designers and data comics enthusiasts and asked them to craft an interactive comic, allowing us to understand authoring workflow and potential of our approach. We present examples of interactive comics in a gallery. This initial step towards understanding the design space of interactive comics can inform the design of creation tools and experiences for interactive storytelling.


Executive summary on the optimization of the multidisciplinary and integrated approach to Polymyalgia Rheumatica and Giant Cell Arteritis in Madrid region.
Polymyalgia rheumatica and giant cell arteritis can be a medical emergency in which a delay in correct diagnosis and therapeutic management can cause serious complications. With the aim of improving the care of patients with these pathologies in the Community of Madrid, a study was designed to identify the causes and possible solutions to address the problems related to the diagnosis of these pathologies. After the analysis, 11 areas of improvement related to four different aspects of the care process were identified: coordination and protocols, equipment, training and awareness of pathologies, and patient experience. Of all the areas identified, it was considered a priority to resolve those related to the generation of protocols for the comprehensive management of the pathologies, which include all the specialties and levels of care involved. Another crucial aspect is the increase in the degree of clinical suspicion of these pathologies.


Poststroke Seizures and the Risk of Dementia Among Young Stroke Survivors.
The impact of new onset seizures in young stroke survivors on the subsequent development of dementia is poorly understood. This study aimed to assess the association between new onset of seizure and dementia in a population-based study of stroke patients. The IBM Watson Health MarketScan® Commercial Claims and Encounters database, for the years 2005-2014 served as the data source for this study. Using the International Classification of Diseases, Ninth Revision (ICD-9), we identified patients aged 18-60 years with ischemic strokes, IS (433.x1, 434.x1, and 436) and hemorrhagic strokes, HS (430, 431, 432.0, 432.1, and 432.9) between January 1, 2006, and December 31, 2009, which constituted our baseline study cohort. At baseline, all included participants were free of claims for dementia, brain tumors, toxin exposure, traumatic brain injury, and neuro-infectious diseases, identified using ICD-9 codes. They had at least 1-year continuous enrollment before the index stroke diagnosis and 5 years after, with no seizure claims within 1 year after the index date. The exposure of interest was seizures: a time-dependent variable. The study outcome of interest was dementia (ICD-9: 290.0, 290.10-13, 290.20-21, 290.3, 290.40-43, 291.2, 292.82, 294.10-11, 294.20-21, 294.8, 331.0, 331.11, 331.19, and 331.82), which occurred during the follow-up period from January 1, 2010, to December 31, 2014. A Cox proportional hazards regression model was applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the independent association of seizures with the occurrence of dementia. At the end of the baseline period, we identified 23,680 stroke patients (IS: 20,642 and HS: 3,038). The cumulative incidence of seizure was 6.7%, 6.4%, and 8.3% for all strokes, IS, and HS, respectively. The cumulative incidence of dementia was 1.3%, 1.4%, and 0.9% for all strokes, IS, and HS, respectively. After multivariable adjustment, young patients with stroke who developed seizures had a greater risk of dementia compared with those without seizures (All strokes adjusted HR: 2.53, 95%CI 1.84-3.48; IS: 2.52, 1.79-3.53; HS: 2.80, 1.05-7.43). These findings suggest that the onset of seizures in young stroke survivors is associated with a 2.53 times increased risk of developing dementia. This study provides Class II evidence that post stroke seizures increase the probability of dementia in young stroke survivors.


RECTIFICATION AND INDUCTANCE IN THE SQUID GIANT AXON.
Previous measurements have shown that the electrical properties of the squid axon membrane are approximately equivalent to those of a circuit containing a capacity shunted by an inductance and a rectifier in series. Selective ion permeability of a membrane separating two electrolytes may be expected to give rise to the rectification. A quasi-crystalline piezoelectric structure of the membrane is a plausible explanation of the inductance. Some approximate calculations of behavior of an axon with these membrane characteristics have been made. Fair agreement is obtained with the observed constant current subthreshold potential and impedance during the foot of the action potential. In a simple case a formal analogy is found between the calculated membrane potential and the excitability defined by the two factor formulations of excitation. Several excitation phenomena may then be explained semi-quantitatively by further assuming the excitability proportional to the membrane potential. Some previous measurements and subthreshold potential and excitability observations are not consistent with the circuit considered and indicate that this circuit is only approximately equivalent to the membrane.


Induction of heme oxygenase-1 antagonizes PM2.5-induced pulmonary VEGFA expression through regulating HIF-1α.
Particulate matter (PM) 2.5 has long been regarded as a major risk factor of the respiratory system, which constitutes a threat to human health. Although the positive relationship between PM2.5 exposure and the development of respiratory diseases has been well established, limited studies investigate the intrinsic self-protection mechanisms against PM2.5-induced respiratory injuries. Excessive pulmonary inflammation served as a key pathogenic mechanism in PM2.5-induced airway dysfunction, and we have previously shown that PM2.5 induced the production of vascular endothelial growth factor A (VEGFA) in the bronchial epithelial cells, which subsequently led to pulmonary inflammatory responses. In the current study, we found that PM2.5 also concurrently induced the expression of the stress-responsive protein heme oxygenase-1 (HO-1) along with VEGFA in the bronchial epithelial cells both in vivo and in vitro. Importantly, knocking down of HO-1 expression significantly increased the synthesis and secretion of VEGFA; while overexpression of HO-1 showed the opposite effects, indicating that HO-1 induction can antagonize VEGFA production in the bronchial epithelial cells upon PM2.5 exposure. Mechanistically, HO-1 inhibited PM2.5-evoked VEGFA induction through modulating hypoxia-inducible factor 1 alpha (HIF-1α), which was the upstream transcriptional factor of VEGFA. More specifically, HO-1 could not only inhibit HIF-1α expression, but also suppress its transactivity. Taken together, our results suggested that HO-1 was an intrinsic protective factor against PM2.5-induced pulmonary VEGFA production with a mechanism relating to HIF-1α, thus providing a potential treatment strategy against PM2.5 triggered airway injuries.


Deafness and cochlear implants: a deaf scholar's perspective.
During the past 3 decades, cochlear implants have dramatically influenced Deaf education and the Deaf Community. They have also served as catalysts for discord between some members of the Deaf Community and advocates of the technology. In this article, I do not intend to support either side of the spoken English versus sign language debate. Instead, I will discuss ethical and practical issues related to cochlear implants. More specifically, I will address the nature and notion of deafness and the purpose of Deaf education. Although many authors have discussed these issues, they have mostly done so from the perspective of hearing scholars and the hearing parents of deaf children. It is important to recognize that understanding deafness and the experience of life from a Deaf individual's perspective has important implications for further educational policy and practice.


A simulation study investigating power estimates in phenome-wide association studies.
Phenome-wide association studies (PheWAS) are a high-throughput approach to evaluate comprehensive associations between genetic variants and a wide range of phenotypic measures. PheWAS has varying sample sizes for quantitative traits, and variable numbers of cases and controls for binary traits across the many phenotypes of interest, which can affect the statistical power to detect associations. The motivation of this study is to investigate the various parameters which affect the estimation of statistical power in PheWAS, including sample size, case-control ratio, minor allele frequency, and disease penetrance. We performed a PheWAS simulation study, where we investigated variations in statistical power based on different parameters, such as overall sample size, number of cases, case-control ratio, minor allele frequency, and disease penetrance. The simulation was performed on both binary and quantitative phenotypic measures. Our simulation on binary traits suggests that the number of cases has more impact on statistical power than the case to control ratio; also, we found that a sample size of 200 cases or more maintains the statistical power to identify associations for common variants. For quantitative traits, a sample size of 1000 or more individuals performed best in the power calculations. We focused on common genetic variants (MAF > 0.01) in this study; however, in future studies, we will be extending this effort to perform similar simulations on rare variants. This study provides a series of PheWAS simulation analyses that can be used to estimate statistical power for some potential scenarios. These results can be used to provide guidelines for appropriate study design for future PheWAS analyses.


Optic disc neovascularization associated with ocular involvement in acute lymphocytic leukemia.
A case of vitreous involvement in acute lymphoblastic leukemia associated with neovascularization of the optic nerve head is presented. The diagnosis was made from a vitreous biopsy specimen obtained by pars plana vitrectomy and prepared by a membrane filter and modified Papanicolaou stain technique. Fibrovascular membranes and leukemic cells were seen on microscopic examination of the vitreous biopsy specimen. Retinal neovascularization associated with acute lymphoblastic leukemia is discussed.


Genes downstream from pucB and pucA are essential for formation of the B800-850 complex of Rhodobacter capsulatus.
The formation of the light-harvesting complex B800-850 (LH-II) of Rhodobacter capsulatus requires, in addition to the synthesis of the polypeptides alpha and beta (the gene products of pucA and pucB), the synthesis of bacteriochlorophyll and carotenoids and the expression of at least one gene localized downstream from the pucBA operon. This was concluded from the observation that a Tn5 insertion downstream from pucBA inhibited the formation of the LH-II complex and the formation of the pucBA mRNA. The Tn5 insertion point was mapped and found to be over 500 base pairs (bp) downstream from the end of the pucA gene, suggesting the presence of additional puc genes. A region of about 3,000 bp including the pucB and pucA genes and DNA downstream from pucA was sequenced and found to contain three open reading frames (ORFs C, D, and E). The polypeptide deduced from the first ORF (C) contains 403 amino acids with strongly hydrophobic stretches and one large and three small hydrophilic domains carrying many charged residues. The other two ORFs contain 113 (D) and 118 (E) codons. The amino acid sequences of the N terminus and two tryptic peptides of an alkaline-soluble Mr-14,000 subunit of the isolated LH-II complex were identical with the deduced amino acid sequence of ORF E.


Electroplating of Multiple Materials in Parallel Using Patterned Gels with Applications in Electrochemical Sensing.
Electrodeposition is a versatile technique for the fabrication of electrodes in micro-electroanalytical devices. Conductive but low-cost materials, such as copper, can be coated with functional yet higher-cost materials such as gold or silver using electrodeposition to lower the overall cost while maintaining functionality. When the electrodeposition of multiple materials is required, current methods use a multistep process that deposits one material at a time, which requires a significant amount of time and a significant number of steps. Additionally, they use a large volume of electrolytes suitable for coating large objects, which is wasteful and unnecessary for the prototyping or coating of microelectrodes with a small area. In this paper, a new method of electroplating is introduced in which we used gels to immobilize and pattern electroplating electrolytes on a substrate surface. Agarose, as an immobilizing medium, enables the immersion of the substrate in a common working electrolyte without cross-mixing different electrolytes. We demonstrate the printing of jelly electrolytes by using spot-dispensing or microfluidic flow. Xurographically patterned films laminated on the substrate function as a mask and confine the printed gels to desired locations. After printing, the substrate is placed in a common working electrolyte container, and multimaterial patterns are produced through the application of an electrical current in a single step.


Neonatal haematology in Zimbabwe. I: The platelet parameters.
Platelet parameters were determined in 600 full term healthy Zimbabwean neonates using a Coulter Counter Model S Plus. The mean +/- s.d. values obtained with ranges were: Platelet count 235 +/- 67 (range 100-410) x 10(9) l-1; Mean Platelet Volume (MPV) 9.5 +/- 1.0 (range 7.1-13.9) fl; Plateletcrit (PCT) 0.269 +/- 0.058 (range 0.142-0.524) and Platelet Distribution Width (PDW) 16.8 +/- 1.0 (range 12.2-19.8). Although platelet counts in this study were comparable to those established by others in both Black and Caucasian infants, the female Zimbabwean neonates had significantly higher counts than the males (p < 0.001). An inverse relationship between the number of circulating platelets and their MPV was also observed. Further studies are needed to delineate the range of normality of these platelet measurements in the African neonate so that abnormal cases can be adequately screened, investigated and appropriately treated.


Stakeholders perceptions regarding implementing maternal and newborn health care programs in Rwanda.
While maternal and newborn deaths has been decreasing since 2008 in Rwanda, there is room for improvement to meet its sustainable development goals. The maternal and newborn health care program needs to be monitored to ensure its effective implementation. This study therefore aimed to explore stakeholder's perceptions of the Rwandan maternal and newborn health care program to identify areas for improvement. The convergent, parallel, mixed method study used quantitative and qualitative data in a single phase. The quantitative data was obtained from 79 health care workers, ranging from maternal community health care workers to program supervisors. The 10 areas of the Project Implementation Profile (PIP) instrument checklist with a five-point Likert scale were used to indicate their perceptions (strongly disagree to strongly agree). The qualitative interviews of five nurse managers used a manifest inductive content analysis, directed approach that entailed using existing theory and prior research to develop the initial coding scheme before starting data analyse. There was disagreement about the level of top management support, human resources was regarded as an area of concern, with 18.7% (n = 14/79) indicating that they did not agree that this was adequately provided for; urgent solutions for unexpected problems was regarded as an areas of concern by 46.8% (n = 36/79). Top management support weakness were inadequate support training, materials, money for home visits, supervision and leaderships, and training of newly recruited maternity health care workers. For human resources, there were insufficient trained staff to take care of mothers and newborns due to the shortages of health providers. The management of unexpected problems was also an area of concerns and related to getting patients to health facilities during pregnancy emergencies and the lack of qualified birth attendants at health facilities. The study identified three areas for improvement: top management support, human resources and urgent solutions for unexpected problems, as they may be affecting the provision of maternal and newborn health care program services. Using the PIP enable managers to improve the country's maternal and newborn health care program, and to provide ongoing monitoring and evaluation of with respect to the desired outcomes of reducing maternal and neonatal mortality.


Should factor V Leiden mutation and prothrombin gene polymorphism testing be done in women with recurrent miscarriage from North India?
Role of thrombophilic factor (FV) in the etiology of recurrent miscarriages is not confirmed till date. It has been hypothesized that thrombophilic G1691A factor V Leiden (FVL), if detected well ahead in time among recurrent miscarriages may be a treatable. The role of FVL mutation in the pathogenesis of sporadic and recurrent miscarriages among North Indian women was studied to construct the frequency data in this part of the country. Further, we have evaluated the cost-benefit factor. This is a case-control study, women with recurrent miscarriages (n = 1,000) as cases and healthy parous women (n = 500) as controls were enrolled in the study between January 2003 and January 2012. DNA was extracted from peripheral blood and analyzed for the presence of FVL mutation and prothrombin gene polymorphism (G20210A). We have carried out the meta-analysis taking into consideration 20 other world populations. In total, 50 (5.0 %) cases and 12 (2.4 %) controls were heterozygous for the FVL mutation. The incidence of FVL was higher in recurrent miscarriage cases as compared to the control group (OR 2.14; 95 % CI 1.12-4.05). Our results revealed the absence of FVL mutation in a homozygous state among patients and controls. Although the heterozygous mutation is almost double in cases as compared to controls, we still suggest that looking at the cost-benefit analysis this test may not be included in the battery of tests performed on recurrent miscarriages among North Indians from this part of the country.