Hepatitis C virus core protein potentiates c-Jun N-terminal kinase activation through a signaling complex involving TRADD and TRAF2.
The hepatitis C virus (HCV) core protein is a multifunctional viral nucleocapsid protein. Previously, it has been demonstrated that the HCV core protein interacts with the cytoplasmic domain of tumor necrosis factor receptor 1 (TNFR1). Since the TNFR1 is engaged in stimulation of transcriptional factor NF-kappaB and AP-1 through activation of IkappaB kinase and c-Jun N-terminal kinase (JNK, or stress-activated protein kinase), respectively, we have examined whether the interaction between core protein and TNFR1 can modulate JNK. In this study, we demonstrate that the HCV core protein synergistically activates TNFalpha-induced JNK at a core concentration dependent manner in human embryonic kidney (HEK) 293 cells. HCV core-mediated synergism of JNK activation was also detected in stable cells expressing HCV core protein. Furthermore, we demonstrate that HCV core protein does not compete with TNF receptor-associated death domain (TRADD) for its interaction with the death domain of TNFR1. Our in vivo data show that HCV core and TRADD form a ternary complex with TNFR1. These findings suggest that the HCV core protein modulates TNFR1 signaling and may, thus, play a role in chronic infection of HCV patients.


Acid-base status of diabetic mothers and their infants following spinal anesthesia for cesarean section.
Acid-base status and Apgar scores were evaluated in 10 rigidly controlled insulin-dependent diabetic mothers and 10 healthy nondiabetic control women having spinal anesthesia for cesarean section. Dextrose-free intravenous solutions were used for volume expansion before induction of anesthesia, and hypotension was prevented in all cases by prompt treatment with ephedrine. There were no significant differences in the acid-base values between the diabetic and nondiabetic mothers and the infants of the diabetic and control group. Apgar scores were also similar in the two groups. If maternal diabetes is well controlled, if dextrose-containing solutions are not used for maternal intravascular volume expansion before delivery, and if maternal hypotension is avoided, spinal anesthesia can be used safely for diabetic mothers having cesarean section.


Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes.
Estrogen biosynthesis from C(19) steroids is catalyzed by aromatase cytochrome P450. Aromatase is expressed in breast adipose tissue through the use of a distal, cytokine-responsive promoter (promoter I.4). Breast tumors, however, secrete soluble factors that stimulate aromatase expression through an alternative proximal promoter, promoter II. In other estrogenic tissues such as ovaries, transcription from promoter II requires the presence of the Ftz-F1 homologue steroidogenic factor-1 (SF-1); adipose tissue, however, does not express SF-1. We have explored the hypothesis that in adipose tissue, an alternative Ftz-F1 family member, liver receptor homologue-1 (LRH-1), substitutes for SF-1 in driving transcription from promoter II. In transient transfection assays using 3T3-L1 preadipocytes, promoter II reporter constructs were modestly (2-3-fold) stimulated by either treatment with activators of protein kinases A or C (PKA/C) or by cotransfection with LRH-1. In combination, these treatments synergistically activated promoter II (>30-fold). Induction by LRH-1 (but not by PKA/C) required an AGGTCA motif at -130 base pairs, to which LRH-1 bound in gel shift assays. Activity of GAL4-LRH-1 fusion proteins was not altered by activators of PKA or PKC. Quantitative real-time PCR revealed that LRH-1 (but not SF-1) is expressed in the preadipocyte fraction of human adipose tissue at levels comparable with that of liver. Differentiation of cultured human preadipocytes into mature adipocytes was associated with a time-dependent induction of peroxisome proliferator-activated receptor-gamma (PPARgamma), and rapid loss of LRH-1 and aromatase expression. We conclude that LRH-1 is a preadipocyte-specific nuclear receptor that regulates expression of aromatase in adipose tissue. Alterations in LRH-1 expression and/or activity in adipose tissue could therefore have considerable effects on local estrogen production and breast cancer development.


Treatment of childhood spasticity of cerebral origin with intrathecal baclofen: a series of 52 cases.
Continuous intrathecal baclofen infusion (CIBI) for spasticity of spinal and cerebral origin has been practised for over two decades. More recently, it has been used for severe spasticity of cerebral origin in children. Intrathecal baclofen (ITB) appears most beneficial in severe spastic tetraparetics or tetraplegics, but the evaluation of the outcome of ITB and the benefit of the treatment are largely subjective. The evidence base for this treatment has been questioned, in particular for ambulant children, mainly because of the lack of objective outcome measures. Fifty-two spastic tetraparetic children have been treated by this method in Nottingham, from 1998 to 2003. This represents a large homogeneous series of CIBI in children with severe spasticity of cerebral origin. We carried out a prospective audit of our experience, morbidity and observations during that period. We identified that the lack of a suitable scoring system for the evaluation of effectiveness and benefit is a drawback. As a result of these observations a multicentre randomized controlled trial on ITB in tetraplegia-paresis and ambulant children is advocated.


Field-level bird abundances are enhanced by landscape-scale agri-environment scheme uptake.
Despite two decades of agri-environment schemes (AESs) aimed at mitigating farmland biodiversity losses, the evidence that such programmes actually benefit biodiversity remains limited. Using field-level surveys, we assess the effectiveness of AESs in enhancing bird abundances in an upland area of England, where schemes have been operating for over 20 years. In such a region, the effects of AESs should be readily apparent, and we predict that bird abundances will co-vary with both field- and landscape-scale measures of implementation. Using an information theoretic approach, we found that, for abundances of species of conservation concern and upland specialists, measures of AES implementation and habitat type at both scales appear in the most parsimonious models. Field-level bird abundances are higher where more of the surrounding landscape is included in an AES. While habitat remains a more influential predictor, we suggest that landscape-scale implementation results in enhanced bird abundances. Hence, measures of the success of AESs should consider landscape-wide benefits as well as localized impacts.


IL-15 drives the specific migration of CD94+ and TCR-gammadelta+ intraepithelial lymphocytes in organ cultures of treated celiac patients.
Celiac disease (CD) is an under-diagnosed but extremely frequent disease, triggered by the ingestion of gliadin. The pathogenic mechanisms of CD are still poorly understood, but intraepithelial lymphocytes are considered to have a key role. We intended to define the subsets of T lymphocytes migrating upon gliadin challenge in organ cultures of treated celiac patients and establish the type of factor(s) driving such an infiltration. Duodenum biopsies from 10 treated celiacs and 7 controls were cultured in vitro with/without gliadin digest (1 mg/ml) or interleukin (IL)-15 (10 ng/ml). In 7 treated celiacs IL-7, IL-4, and IL-2 were similarly tested. Intraepithelial CD3, CD8, TCR-gammadelta, and CD94 were detected by immunohistochemistry and numbered per mm epithelium. IL-15 but not IL-7, IL-4, or IL-2 induced intraepithelial increase of CD3+ and CD8+ cells in celiac and control intestine (p < 0.001 vs cultures with medium). IL-15 induced increases in the number of intraepithelial TCR- gammadelta+ and CD94+ cells only in celiacs (p < 0.001). IL-7 was also effective in increasing intraepithelial TCR-gammadelta+ (but not CD94+) cells in celiac biopsies (p < 0.001). Gliadin induced intraepithelial migration of CD3+, CD8+ (p < 0.001), and CD94+ (p < 0.05) cells in celiacs, but not in controls. The results we describe in this report indicate that IL-15 might have a key role in modulating and driving intraepithelial infiltration and ultimately in the pathogenesis of CD.


Pulmonary airways: 3-D reconstruction from multislice CT and clinical investigation.
In the framework of computer-aided diagnosis, this paper proposes a novel functionality for the computerized tomography (CT)-based investigation of the pulmonary airways. It relies on an energy-based three-dimensional (3-D) reconstruction of the bronchial tree from multislice CT acquisitions, up to the sixth- to seventh-order subdivisions. Global and local analysis of the reconstructed airways is possible by means of specific visualization modalities, respectively, the CT bronchography and the virtual bronchoscopy. The originality of the 3-D reconstruction approach consists in combining axial and radial propagation potentials to control the growth of a subset of low-order airways extracted from the CT volume by means of a robust mathematical morphology operator-the selective marking and depth constrained (SMDC) connection cost. The proposed approach proved to be robust with respect to a large spectrum of airway pathologies, including even severe stenosis (bronchial lumen obstruction/collapse). Validated by expert radiologists, examples of airway 3-D reconstructions are presented and discussed for both normal and pathological cases. They highlight the interest in considering CT bronchography and virtual bronchoscopy as complementary tools for clinical diagnosis and follow-up of airway diseases.


The role of protective behavioral strategies and anxiety in problematic drinking among college students.
The use of protective behavioral strategies (PBS) has been shown to reduce heavy alcohol consumption and alcohol-related problems among college students. Limited research has examined how mental health is related to PBS use in the prediction of alcohol outcomes. Consequently, the aims of the present study were to (a) examine the relationship between anxiety symptoms and the use of PBS, (b) examine PBS as a mediator of the association between anxiety and alcohol-related problems, and (c) test anxiety as a moderator of the relationship between the use of PBS and alcohol-related problems. Participants were college students (N = 199, 67% women) who completed self-report measures of typical anxiety symptoms, use of PBS, and alcohol-related problems. Results indicated that anxiety was significantly negatively related to PBS use. Additionally, the association between anxiety and alcohol-related consequences was mediated by the use of PBS. The association between PBS use and alcohol-related problems was also contingent on one's level of anxiety. That is, although the relationship between the use of PBS and problems was negative regardless of anxiety level, those with higher anxiety exhibited a stronger, negative relationship between PBS and problems. These findings suggest that PBS is both a mediator in the anxiety and alcohol-related problems association as well as an important factor in reducing negative consequences for college students higher in anxiety. Results indicate that college students with anxiety would be ideal candidates for harm-reduction interventions that emphasize the use of PBS in drinking contexts.


DNA hybridization on microparticles: determining capture-probe density and equilibrium dissociation constants.
Many DNA-probe assays utilize oligonucleotide-coated microparticles for capture of complementary nucleic acids from solution. During development of these assays, as well as in other particle-based nucleic acid applications, it is useful to know both the amount of duplex formation expected under various experimental conditions and the coating density of the capture oligonucleotide on the particle surface. We examined the simplest form of a DNA-probe microparticle assay: hybridization of a particle-bound capture oligonucleotide to its solution-phase complement. Fluorescein-labeled solution-phase oligonucleotide was hybridized to varying amounts of particles, and the amount of labeled oligonucleotide remaining in solution at equilibrium was measured. We present a simple two-state, all-or-none model for bimolecular hybridization of non-self-complementary sequences that can be used to calculate the equilibrium dissociation constant ( Kd ) from hybridization data. With experimental conditions where both the Kd value and the concentration of capture probe in the reaction are small relative to the concentration of labeled complementary oligonucleotide in the reaction, density of the capture probe on the particle's surface can also be determined. Kd values for particle-based hybridization were different from those obtained from solution-phase thermodynamic parameters. At higher temperatures, hybridization on particles was more efficient than hybridization in solution.


Histological and ultrastructural studies of nephroblastoma in rats induced transplacentally by ethylnitrosourea.
Histologic and ultrastructural features of nephroblastomas in Sprague-Dawley rats induced by a single transplacental injection of ethylnitrosourea (ENU) on the 15-16th day of gestation are described and their significance is discussed with respect to the histogenesis of the tumors. Many renal tumors were observed, in addition to predominant occurrence of tumors of the nervous system. Forty-two of 142 offsprings survived over 100 days developed renal tumors, of which 37 rats had nephroblastomas, three rats had cortical adenomas, and one rat had a cystadenoma. The nephroblastomas were found in 35 rats unilaterally and in two rats bilaterally. Most of these tumors had various amounts of hyalinized stroma. In the kidneys with nephroblastomas, isolated, small foci of renal blastema were also occasionally noted. Electron microscopy revealed that nephroblastomas consisted of two types of cells, namely, epithelial and mesenchymal cells. The epithelial cells showed cellular differentiation of varying degree; they are freely lying in the stroma, forming well differentiated tubules or immature tubule-like structures and solid cell nests. Most of the undifferentiated cells observed around the tubular structures and cell nests are demonstrated to have epithelial features. These observations seem to support the concept that nephroblastoma is originated from metanephric blastema.


Unveiling the structural and functional consequences of the p.D109G pathogenic mutation in human αB-Crystallin responsible for restrictive cardiomyopathy and skeletal myopathy.
αB-Crystallin (αB-Cry) is expressed in many tissues, and mutations in this protein are linked to various diseases, including cataracts, Alzheimer's disease, Parkinson's disease, and several types of myopathies and cardiomyopathies. The p.D109G mutation, which substitutes a conserved aspartate residue involved in the interchain salt bridges, with glycine leads to the development of both restrictive cardiomyopathy (RCM) and skeletal myopathy. In this study, we generated this mutation in the α-Cry domain (ACD) which is crucial for forming the active chaperone dimeric state, using site-directed mutagenesis. After inducing expression in the bacterial host, we purified the mutant and wild-type recombinant proteins using anion exchange chromatography. Various spectroscopic evaluations revealed significant changes in the secondary, tertiary, and quaternary structures of human αB-Cry caused by this mutation. Furthermore, this pathogenic mutation led to the formation of protein oligomers with larger sizes than those of the wild-type protein counterpart. The mutant protein also exhibited increased chaperone activity and decreased chemical, thermal, and proteolytic stability. Atomic force microscopy (AFM), transmission electron microscopy (TEM), and fluorescence microscopy (FM) demonstrated that p.D109G mutant protein is more prone to forming amyloid aggregates. The misfolding associated with the p.D109G mutation may result in abnormal interactions of human αB-Cry with its natural partners (e.g., desmin), leading to the formation of protein aggregates. These aggregates can interfere with normal cellular processes and may contribute to muscle cell dysfunction and damage, resulting in the pathogenic involvement of the p.D109G mutant protein in restrictive cardiomyopathy and skeletal myopathy.


Formalization of the classification pattern: survey of classification modeling in information systems engineering.
Formalization is becoming more common in all stages of the development of information systems, as a better understanding of its benefits emerges. Classification systems are ubiquitous, no more so than in domain modeling. The classification pattern that underlies these systems provides a good case study of the move toward formalization in part because it illustrates some of the barriers to formalization, including the formal complexity of the pattern and the ontological issues surrounding the "one and the many." Powersets are a way of characterizing the (complex) formal structure of the classification pattern, and their formalization has been extensively studied in mathematics since Cantor's work in the late nineteenth century. One can use this formalization to develop a useful benchmark. There are various communities within information systems engineering (ISE) that are gradually working toward a formalization of the classification pattern. However, for most of these communities, this work is incomplete, in that they have not yet arrived at a solution with the expressiveness of the powerset benchmark. This contrasts with the early smooth adoption of powerset by other information systems communities to, for example, formalize relations. One way of understanding the varying rates of adoption is recognizing that the different communities have different historical baggage. Many conceptual modeling communities emerged from work done on database design, and this creates hurdles to the adoption of the high level of expressiveness of powersets. Another relevant factor is that these communities also often feel, particularly in the case of domain modeling, a responsibility to explain the semantics of whatever formal structures they adopt. This paper aims to make sense of the formalization of the classification pattern in ISE and surveys its history through the literature, starting from the relevant theoretical works of the mathematical literature and gradually shifting focus to the ISE literature. The literature survey follows the evolution of ISE's understanding of how to formalize the classification pattern. The various proposals are assessed using the classical example of classification; the Linnaean taxonomy formalized using powersets as a benchmark for formal expressiveness. The broad conclusion of the survey is that (1) the ISE community is currently in the early stages of the process of understanding how to formalize the classification pattern, particularly in the requirements for expressiveness exemplified by powersets, and (2) that there is an opportunity to intervene and speed up the process of adoption by clarifying this expressiveness. Given the central place that the classification pattern has in domain modeling, this intervention has the potential to lead to significant improvements.


Peripheral blood leucocyte subpopulations in patients splenectomized for trauma.
Monoclonal antibodies were used to type leucocyte subpopulations in peripheral blood mononuclear leucocytes (MNL) from patients who had had spleens removed following trauma. The proportion of OKT3+ (T) cell and OKT4+ ('T helper/inducer') cell was significantly decreased in splenectomized subjects. While a decrease was also observed for the OKT8+ ('T suppressor/cytotoxic') cells, this was not significant. The ratio of OKT4+/OKT8+ cells was significantly decreased in the splenectomized group. Interestingly, the absolute numbers of OKT3+, OKT4+ and OKT8+ cells were increased. The % of B lymphocytes (identified as Ig+ and FMC1+ cells) was significantly increased in patients. The proportion of MHC Class II+ cells (FMC4+) was also increased although not significantly. A marked increase in % of monocytes (FMC33+) was observed in patients. The changes in proportion of regulatory T cells and monocytes may in part explain the depressed mitogen responses of MNL from splenectomized subjects.


Developing Methods to Evaluate Content Quality of Dementia Websites.
With the popularity of the Internet, consumers are likely to resort to websites for dementia information. However, they may not have the knowledge or experience in distinguishing quality information from opinion pieces. This study investigated the developing methods, instruments and parameters for evaluating the content quality of dementia websites. By reviewing 18 existing instruments from the relevant literature, we identified four developing methods - questionnaire survey, automatic evaluation, Delphi method and focus group discussion. These instruments include six parameters - reliability, currency, readability, disclosure, objectivity and relevance - to evaluate the content quality. With the significant social and economic impact of dementia, developing specific instruments to measure the content quality of dementia websites is necessary.


Loneliness across phylogeny and a call for comparative studies and animal models.
Loneliness typically refers to the feelings of distress and dysphoria resulting from a discrepancy between a person's desired and achieved levels of social relations, and there is now considerable evidence that loneliness is a risk factor for poor psychological and physical health. Loneliness has traditionally been conceptualized as a uniquely human phenomenon. However, over millions of years of evolution, efficient and manifold neural, hormonal, and molecular mechanisms have evolved for promoting companionship and mutual protection/assistance and for organizing adaptive responses when there is a significant discrepancy between the preferred and realized levels of social connection. We review evidence suggesting that loneliness is not a uniquely human phenomenon, but, instead, as a scientific construct, it represents a generally adaptive predisposition that can be found across phylogeny. Central to this argument is the premise that the brain is the key organ of social connections and processes. Comparative studies and animal models, particularly when integrated with human studies, have much to contribute to the understanding of loneliness and its underlying principles, mechanisms, consequences, and potential treatments.


Additional evidence for an association between the dopamine D4 receptor (D4DR) exon III seven-repeat allele and substance abuse in opioid dependent subjects: relationship of treatment retention to genotype and personality.
The long form of the dopamine D4 receptor (D4DR) exon III repeat polymorphism has been linked in some but not all studies to impulsive, extravagant and novelty-seeking personality traits that are prominent in affiliated behaviours such as attention deficit disorder and substance abuse. In particular, we have reported previously an increased frequency of the long seven-repeat D4DR exon III allele in a group of 141 opioiddependent subjects compared to 110 control subjects. In order to further substantiate the role of D4DR in contributing to heroin addiction we have genotyped an additional, smaller cohort of opioid-dependent subjects. In this new group of 57 opioid-dependent subjects compared to an expanded group of 143 control subjects a significant difference was observed in overall genotype frequency (p=0.04). An excess of the seven-repeat allele of the D4DR receptor gene was also observed compared to control subjects (p=0.06). The frequency of the seven-repeat allele is 15.8% in the heroin addict population vs. 8.1% in the control group, conferring a relative risk of 2.07 (95% CI: 0.98-4.38). An association between two polymorphisms considered together (D4DR and dopamine D3 receptor) and treatment retention was observed (p=0.02). In a subgroup of 38 opioid-dependent subjects, who were successfully administered the TPQ, higher Harm Avoidance (p< 0.001) and Novelty Seeking (NS3; extravagant vs. reserved, p< 0.001) scores were found. In contrast to some previous reports, no relationship was apparent between TPQ scores and treatment retention in this small group of opioid-dependent subjects.


Development of Volumetric Independent Dose Calculation System for Verification of the Treatment Plan in Image-Guided Adaptive Brachytherapy.
Purpose: This study aimed to develop a volumetric independent dose calculation (vIDC) system for verification of the treatment plan in image-guided adaptive brachytherapy (IGABT) and to evaluate the feasibility of the vIDC in clinical practice with simulated cases. Methods: The vIDC is based on the formalism of TG-43. Four simulated cases of cervical cancer were selected to retrospectively evaluate the dose distributions in IGABT. Some reference point doses, such as points A and B and rectal points, were calculated by vIDC using absolute coordinate. The 3D dose volume was also calculated to acquire dose-volume histograms (DVHs) with grid resolutions of 1.0 × 1.0 (G1.0), 2.5 × 2.5 (G2.5), and 0.5 × 0.5 mm2 (G0.5). Dosimetric parameters such as D90% and D2cc doses covering 90% of the high-risk critical target volume (HR-CTV) and 2 cc of the organs at risk (OARs) were obtained from DVHs. D90% also converted to equivalent dose in 2-Gy fractions (EQD2) to produce the same radiobiological effect as external beam radiotherapy. In addition, D90% was obtained in two types with or without the applicator volume to confirm the effect of the applicator itself. Validation of the vIDC was also performed using gamma evaluation by comparison with Monte Carlo simulation. Results: The average percentage difference of point doses was <2.28%. The DVHs for the HR-CTV and OARs showed no significant differences between the vIDC and the treatment planning system (TPS). Without considering the applicator volume, the D90% of the HR-CTV calculated by the vIDC decreases with a decreasing calculated dose-grid size (32.4, 5.65, and -2.20 cGy in G2.5, G1.0, and G0.5, respectively). The overall D90% is higher when considering the applicator volume. The converted D90% by EQD2 ranged from -1.29 to 1.00%. The D2cc of the OARs showed that the averaged dose deviation is <10 cGy regardless of the dose-grid size. Based on gamma analysis, the passing rate was 98.81% for 3%/3-mm criteria. Conclusion: The vIDC was developed as an independent dose verification system for verification of the treatment plan in IGABT. We confirmed that the vIDC is suitable for second-check dose validation of the TPS under various conditions.


Streptomycin accumulation by Bacillus subtilis requires both a membrane potential and cytochrome aa3.
Cytochrome aa3 concentrations in the cytoplasmic membrane of Bacillus subtilis were altered by growth conditions, and the effects on the membrane potential (delta psi) in whole cells were measured. When cytochrome aa3 was absent, the magnitude of delta psi was not diminished by comparison with the delta psi measured in cells containing normal cytochrome aa3 concentrations. In addition, the energy-dependent uptake of proline and glutamate was comparable at both cytochrome aa3 concentrations. However, in the cytochrome aa3-deficient cell preparation, accumulation of the aminoglycoside antibiotic streptomycin was much lower than that of the cytochrome aa3-sufficient cells. When cells were cultured under conditions that stimulated higher than normal concentrations of cytochrome aa3, delta psi was also increased, and enhanced streptomycin accumulation was observed. Phenazine methosulfate-ascorbate was used both in delta psi measurements and in uptake studies to provide high rates of electron transport and maximal delta psi values. These results, taken together with those previously published (A. S. McEnroe and H. W. Taber, Antimicrob. Agents Chemother. 26:507-512, 1984) suggest that the uptake of streptomycin by B. subtilis requires adequate levels both of delta psi and cytochrome aa3.


Health, social, and dental professionals' experiences of working within an extended home-visit program in the child healthcare: a qualitative interview study in Sweden.
The goal of the Swedish child healthcare system is to reach all children with health-promotive actions and to create equal health opportunities for all children. In that context, an extended home-visit program - called Grow Safely - for first-time parents, with an interprofessional collaboration between child healthcare nurses, midwives, social workers, and dental assistants, was initiated. The current study aims at illuminating and evaluating the health, social, and dental professionals' experiences of working within this program and how such collaboration could benefit the professions. A qualitative method was chosen, and 13 interviews were carried out with professionals working within child healthcare centers that participated in an extended home-visit program in the southernmost part of Sweden. The interviews were analyzed via Burnard's approach to content analysis. The results showed that it was satisfying for the health, social, and dental professionals to work with the home-visit program and that they encountered positive feelings among the parents receiving it. The creation of deep conversations and parents opening up about feelings that could otherwise be shameful to express, was a positive aspect of the home visits. A negative aspect was the difficulty of handling the (sometimes necessary) interpretation over the phone during the visits, and another one was the fact that the visits were time-consuming and required logistical planning. Overall, the professionals were positive about the home-visit program in that they felt that they were able to give the families what they needed and to have discussions on sensitive issues. They also appreciated the fact that different professions collaborated in order to reach the same goal. This study showed that the health, social, and dental professionals enjoyed working with the home-visit program and that they encountered positive feelings among the parents regarding the collaborative visits being conducted within the home, where the families felt safe and relaxed. The professionals expressed that the home visits, despite the extended time they required and the logistical challenges involved, created a deeper collaboration between the professionals.


[Significance of percutaneous nephrostomy in calculous anuria in children. Apropos of 3 cases].
Percutaneous nephrostomy is a new and very efficient technique of the drainage of the obstructed kidney. It is better indicated to treat obstructive anuria in the child especially if the obstructive agent is a bilateral stone. Having performed such method successively in 3 patients suffering of calculus anuria, the author tries to point out its advantages and review literature data. Thus, this technique allows prompt drainage of urine and removes emergency in case of infected intra-renal retention. It takes an important part in diagnosis by permitting dye injection in the drained upper urinary system. It could also inform about residual value of the desobstructed kidney and predict changes of its potential recovery. It represents lastly, a first step for in-situ treatment of the stone.


Oncologists' and Patients' Perceptions of Initial, Intermediate, and Final Goals of Care Conversations.
Although recommendations are for goals of care (GoC) conversations to happen early and often, their timing and content over the disease course remain unclear. To describe perceptions of the timing and content of GoC conversations among oncologists and patients with advanced cancer. Semi-structured interviews with oncologists and patients at four hospitals in New York and Connecticut. We analyzed data using interpretive description. Oncologists (n = 21) were 67% male, averaged 46 years old (range 34-68 years), and had a mean 20 years (range 8-42 years) in practice. Advanced cancer patients (n = 39) were 59% female with a mean age of 58 years (range 26-88 years). Oncologists and patients viewed GoC conversations along an initial, intermediate, and final continuum. Oncologists reported having initial GoC conversations to build rapport, provide disease information, and clarify and consider treatment intent and options. Intermediate conversations focused on changes in treatment and side effects. Final conversations occurred when patients were hospice-eligible and covered the shift to comfort care, a treatment summary, and advance directives. Timing and content were influenced by cancer type, disease status, and emotional state. Patients supported beginning GoC conversations early, but had different preferences for content of initial conversations. Some wanted complete information; others found this overwhelming. Patients felt intermediate GoC conversations should occur at decision points with time for processing. Content of intermediate and final conversations was dependent on patients' prognosis, questions, and treatment decisions. Although GoC conversations should follow individual patient preferences, our findings offer structure for their timing and content.


The assessment and forecasting of carbon emission for Gansu-Qinghai-Shaanxi of China.
For regional development, the assessment of regional low-carbon development level can fully reflect the current situation of low-carbon development, and the carbon emission forecasting can reveal the future trend of carbon emission and the pressure of emission reduction. It is significant to assess the low-carbon development level and forecast carbon emission. Therefore, this research constructs an index system to objectively reflect the low-carbon development level, and proposes IE-TOPSIS comprehensive assessment method to assess the regional low-carbon development level. For promoting the low-carbon development of the less developed areas in China, Gansu, Qinghai, and Shaanxi provinces are selected as the research objects. The results of comprehensive assessment show that low-carbon development level of the three provinces over past decade had an increasing trend. Furthermore, this research establishes a GM-GRA-DPC-PSOSVR combined forecasting model for carbon emission forecasting and it has higher forecasting accuracy than individual models. From 2021 to 2025, the forecasting results show that carbon emission of Shaanxi will continue to increase under the current development pattern, Gansu will increase slowly, while Qinghai will decrease.


Interaction of verapamil with human platelet alpha-adrenergic receptors.
Platelet aggregation induced by epinephrine is an alpha-adrenergic event and is inhibited in vitro by the calcium-channel blocker, verapamil. We wondered whether this inhibition might be mediated by an interaction of verapamil with platelet alpha-adrenergic receptors. Verapamil inhibited the specific binding of [3H]dihydroergocryptine ([3H]DHE), a nonselective alpha-adrenergic antagonist, to intact platelets in a concentration-dependent and competitive manner. At 10 microM verapamil caused a fivefold decrease in the affinity of binding of [3H]DHE to platelet alpha-adrenergic receptors (P less than 0.001) with no change in the number of receptors per platelet. The inhibition of binding was not reversed by excess calcium. Verapamil also inhibited the binding of a selective alpha 2-adrenergic antagonist, [3H]yohimbine, to intact platelets, and inhibited the binding of an alpha 2-partial agonist, [3H]clonidine, to platelet membranes. Moreover there was a strong correlation between verapamil's effect on [3H]DHE binding and its effect on epinephrine-induced aggregation (r = 0.98). Although verapamil is commonly used as an inhibitor of calcium flux across cell membranes, the present studies demonstrate that verapamil also inhibits epinephrine-induced aggregation at the level of the platelet alpha-adrenergic receptor.


Role of RpoS and MutS in phase variation of Pseudomonas sp. PCL1171.
Pseudomonas sp. strain PCL1171 undergoes reversible colony phase variation between opaque phase I and translucent phase II colonies, which is dependent on spontaneous mutations in the regulatory genes gacA and gacS. Mutation of the mutS gene and constitutive expression of rpoS increases the frequency at which gac mutants appear 1000- and 10-fold, respectively. Experiments were designed to study the relationship between gacS, rpoS and mutS. These studies showed that (i) a functional gac system is required for the expression of rpoS, (ii) RpoS suppresses the expression of mutS and therefore increases the frequency of gac mutants, and (iii) upon mutation of rpoS and gacS, the expression of mutS is increased. Mutation of gacS abolishes suppression of mutS expression in stationary growth, suggesting that additional gac-dependent factors are involved in this suppression. In conclusion, inefficient mutation repair via MutS, of which the expression is influenced by gacA/S itself and by rpoS in combination with other factors, contributes to the high frequency of mutations accumulating in gacA/S. The role of RpoS in the growth advantage of a gac mutant was analysed, and mutation of rpoS only reduced the length of the lag phase, but did not affect the growth rate, suggesting a role for both RpoS and a reduction of metabolic load in the growth advantage of a gac mutant.


A Family-Focused Delirium Educational Initiative With Practice and Research Implications.
Delirium is burdensome and psychologically distressing for formal and informal caregivers, yet family caregivers often have very little understanding or knowledge about delirium. As part of a large multisite intervention study, the Early Nurse Detection of Delirium Superimposed on Dementia (END-DSD), the authors identified a need for family educational materials. This educational initiative's purpose was to develop a delirium admission brochure for family members to aid in the prevention and earlier identification of delirium during hospitalization. A brochure was developed using an iterative approach with an expert panel. Following three iterations, a final brochure was approved. The authors found that an iterative expert consensus approach can be used to develop a brochure for families. Major content areas were helping families understand the difference between delirium and dementia, signs and symptoms of delirium, causes of delirium, and strategies family members can use to prevent delirium. A caregiver-focused educational brochure is one intervention to use in targeting older adults hospitalized with delirium.


Isotropically etched radial micropore for cell concentration, immobilization, and picodroplet generation.
To enable several on-chip cell handling operations in a fused-silica substrate, small shallow micropores are radially embedded in larger deeper microchannels using an adaptation of single-level isotropic wet etching. By varying the distance between features on the photolithographic mask (mask distance), we can precisely control the overlap between two etch fronts and create a zero-thickness semi-elliptical micropore (e.g. 20 microm wide, 6 microm deep). Geometrical models derived from a hemispherical etch front show that micropore width and depth can be expressed as a function of mask distance and etch depth. These models are experimentally validated at different etch depths (25.03 and 29.78 microm) and for different configurations (point-to-point and point-to-edge). Good reproducibility confirms the validity of this approach to fabricate micropores with a desired size. To illustrate the wide range of cell handling operations enabled by micropores, we present three on-chip functionalities: continuous-flow particle concentration, immobilization of single cells, and picoliter droplet generation. (1) Using pressure differentials, particles are concentrated by removing the carrier fluid successively through a series of 44 shunts terminated by 31 microm wide, 5 microm deep micropores. Theoretical values for the concentration factor determined by a flow circuit model in conjunction with finite volume modeling are experimentally validated. (2) Flowing macrophages are individually trapped in 20 microm wide, 6 microm deep micropores by hydrodynamic confinement. The translocation of transcription factor NF-kappaB into the nucleus upon lipopolysaccharide stimulation is imaged by fluorescence microscopy. (3) Picoliter-sized droplets are generated at a 20 microm wide, 7 microm deep micropore T-junction in an oil stream for the encapsulation of individual E. coli bacteria cells.


Major histocompatibility complex class I evolution in songbirds: universal primers, rapid evolution and base compositional shifts in exon 3.
Genes of the Major Histocompatibility Complex (MHC) have become an important marker for the investigation of adaptive genetic variation in vertebrates because of their critical role in pathogen resistance. However, despite significant advances in the last few years the characterization of MHC variation in non-model species still remains a challenging task due to the redundancy and high variation of this gene complex. Here we report the utility of a single pair of primers for the cross-amplification of the third exon of MHC class I genes, which encodes the more polymorphic half of the peptide-binding region (PBR), in oscine passerines (songbirds; Aves: Passeriformes), a group especially challenging for MHC characterization due to the presence of large and complex MHC multigene families. In our survey, although the primers failed to amplify exon 3 from two suboscine passerine birds, they amplified exon 3 of multiple MHC class I genes in all 16 species of oscine songbirds tested, yielding a total of 120 sequences. The 16 songbird species belong to 14 different families, primarily within the Passerida, but also in the Corvida. Using a conservative approach based on the analysis of cloned amplicons (n = 16) from each species, we found between 3 and 10 MHC sequences per individual. Each allele repertoire was highly divergent, with the overall number of polymorphic sites per species ranging from 33 to 108 (out of 264 sites) and the average number of nucleotide differences between alleles ranging from 14.67 to 43.67. Our survey in songbirds allowed us to compare macroevolutionary dynamics of exon 3 between songbirds and non-passerine birds. We found compelling evidence of positive selection acting specifically upon peptide-binding codons across birds, and we estimate the strength of diversifying selection in songbirds to be about twice that in non-passerines. Analysis using comparative methods suggest weaker evidence for a higher GC content in the 3rd codon position of exon 3 in non-passerine birds, a pattern that contrasts with among-clade GC patterns found in other avian studies and may suggests different mutational mechanisms. Our primers represent a useful tool for the characterization of functional and evolutionarily relevant MHC variation across the hyperdiverse songbirds.


Preventing college women's sexual victimization through parent based intervention: a randomized controlled trial.
A randomized controlled trial, using parent-based intervention (PBI) was designed to reduce the incidence of alcohol-involved sexual victimization among first-year college students. The PBI, adapted from Turrisi et al. (2001), was designed to increase alcohol-specific and general communication between mother and daughter. Female graduating high school seniors and their mothers were recruited from the community and randomly assigned to one of four conditions: Alcohol PBI (n = 305), Enhanced Alcohol + Sex PBI (n = 218), Control (n = 288) or Unmeasured Control (n = 167). Mothers in the intervention conditions were provided an informational handbook and encouraged to discuss its contents with their daughters prior to college matriculation. Consistent with hypotheses, PBI, either standard or enhanced, was associated with lower incidence of incapacitated rape in the first year of college relative to controls. Path analysis revealed support for a hypothesized indirect effects model, by which intervention increased mother-daughter communication, which predicted lower frequency of first semester heavy episodic drinking, resulting in lower rates of alcohol-involved sexual victimization in the first year of college.


Efficacy and safety of selamectin against fleas and heartworms in dogs and cats presented as veterinary patients in North America.
A series of randomized, controlled, masked field studies was conducted to assess the efficacy and safety of selamectin in the treatment of flea infestations on dogs and cats, and in the prevention of heartworm infection in dogs. In addition, observations were made on the beneficial effect of selamectin treatment on dogs and cats showing signs of flea allergy dermatitis (FAD). In all studies selamectin was applied topically, once per month, in unit doses providing a minimum dosage of 6mgkg(-1). Dogs and cats with naturally occurring flea infestations, some of which also had signs associated with FAD, were assigned randomly to receive three months of topical treatment with selamectin (220 dogs, 189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins, n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as the day that the animal first received treatment. Flea burdens were assessed by flea comb counts and clinical evaluations of FAD were performed before treatment, and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%, respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%, respectively, compared with day 0 counts. Selamectin also was beneficial in alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397 dogs free of adult heartworm infection from four heartworm-endemic areas of the USA were allocated randomly to six months of treatment with selamectin (n=298) or ivermectin (n=99). Selamectin achieved a heartworm prevention rate of 100%, with all dogs testing negative for microfilariae and adult heartworm antigen on days 180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats having an age range of 6 weeks to 19 years (3954 doses). The animals included 19 purebred or crossbred Collies (Bearded, Border, and unspecified). There were no serious adverse events. Results of these studies indicated that selamectin was highly effective in the control of flea infestations in dogs and cats without the need for simultaneous treatment of the environment or of in-contact animals and also was beneficial in alleviating signs associated with FAD. Selamectin also was 100% effective in preventing the development of canine heartworms and was safe for topical use in dogs and cats.


A source of bias in the analysis of single channel data: assessing the apparent interaction between channel proteins.
A recent study of single sodium channel currents in neuroblastoma cells suggested interaction between ion channels in close proximity to one another (T. Kiss and K. Nagy, Eur. Biophys. J. 12, 13, 1985). The opening of one channel appeared to affect the likelihood that neighboring channels might open. Some of the conclusions were based on the analysis of observed channel openings that were segregated depending on whether one channel or more than one channel was open at the same time. We hypothesized that the longer one channel remained open, the more likely another channel operating independently, would open, thereby creating the impression of an apparent coupling of channel behavior. We performed simulations and measurements of single sodium channel currents to determine whether the technique of event segregation could account for apparent channel interactions. The simulations showed that the segregation of overlapping (more than one channel open at the same time) and nonoverlapping events led to a bias in the estimated open time and the derived closing rate. To avoid the bias, we found that random pairing of opening and closing events provided an unbiased estimate of the mean closing rate. Using this random assignment approach, we showed that the mean closing rate of single sodium channels in neonatal rat myocytes decreased with depolarization over a limited range of membrane potential. This suggested that the underlying closure mechanism(s) was voltage dependent. From the analysis of open times, we found no evidence for channel interaction in the time scale of tens of milliseconds. Depolarizing steps without events occurred in runs suggesting the existence of long-lived shut state(s). Double pulse experiments with the prepulse and test pulse above threshold showed significant inactivation of channels that did not open. The rate of inactivation of shut channels was substantially slower than the closure rate of open channels. The rate of inactivation of cardiac sodium channels appeared to be strongly dependent on the initial channel state.


Control of ribonucleic acid synthesis in eukaryotes. 2. The effect of protein synthesis on the activities of nuclear and total DNA-dependent RNA polymerase in yeast.
A thermosensitive conditional yeast mutant (ts-187) which suppresses protein synthesis at the nonpermissive temperature (36 degrees C) also suppresses RNA synthesis. The effect of temperature on the mutant is similar to the addition of cycloheximide--it inhibits the incorporation of labeled precursors into RNA in both whole cells and isolated nuclei. The effect of temperature is selective for the RNA polymerases bound to the nuclear template but not for the total RNA polymerases. Thus, the specific activities and total amounts of RNA polymerase species extracted and assayed with exogenous DNA template are similar in the ts-187 cultured at 23 degrees C and at 36 degrees C. On the contrary, the nuclear polymerases, i.e., RNA synthesis in isolated nuclei, are dramatically inhibited in cells cultured at 36 degrees C. When amino acid starved ts-187 cells are transferred to 36 degrees C, release from the inhibtion of RNA synthesis is observed. As with the addition of cycloheximide, this relaxation is observed in cells but not in isolated nuclei. The parental strain, A364A, which responds by stimulating instead of inhibiting protein synthesis when the temperature is increased to 36 degrees C, also exhibits an inhibition in the incorporation of labeled precursor into RNA as well as reducing RNA synthesis in isolated nuclei. However, these are transitory inhibitions and afterward there is reinitiation of both processes. Reinitiation of RNA synthesis in isolated nuclei is similar to the relaxed phenomenon and it is called "nuclear relaxation". This relaxation can only be obtained if protein synthesis is not inhibited; however, cellular relaxation occurs in the absence of protein synthesis. The repression of the nuclear RNA polymerase activities which starvation and inhibition of protein synthesis produce appears to be due to a restriction in the nuclear DNA template. This notion is supported by the fact that a net diminution of these nuclear enzyme activities is observed in spheroplasts cultured under starving conditions. Studies of the four main ribonucleotide pools indicate that stringency and inhibition of protein synthesis (ts-187 cultured at 36 degrees C) produce an increase in UTP and CTP pools. This is consistent with the concept that stringency and inhibition of protein synthesis affect the rate of utilization rather than the synthesis of these ribonucleotide residues. In the A364A and ts-187 yeast strains, the conversion of uracil but not of uridine into the UTP and CTP is inhibited when there is inhibition of the nuclear RNA polymerases. This indicates that the uracil phosphoribosyltransferase but not the uridine-cytidine kinase is allosterically inhibited by UTP and CTP in yeast. The feedback inhibition in the metabolic pathway of the base explains why relaxation cannot be detected when uracil instead of uridine is used as the labeled RNA precursor.


Ecological connectivity in the three-dimensional urban green volume using waveform airborne lidar.
The movements of organisms and the resultant flows of ecosystem services are strongly shaped by landscape connectivity. Studies of urban ecosystems have relied on two-dimensional (2D) measures of greenspace structure to calculate connectivity. It is now possible to explore three-dimensional (3D) connectivity in urban vegetation using waveform lidar technology that measures the full 3D structure of the canopy. Making use of this technology, here we evaluate urban greenspace 3D connectivity, taking into account the full vertical stratification of the vegetation. Using three towns in southern England, UK, all with varying greenspace structures, we describe and compare the structural and functional connectivity using both traditional 2D greenspace models and waveform lidar-generated vegetation strata (namely, grass, shrubs and trees). Measures of connectivity derived from 3D greenspace are lower than those derived from 2D models, as the latter assumes that all vertical vegetation strata are connected, which is rarely true. Fragmented landscapes that have more complex 3D vegetation showed greater functional connectivity and we found highest 2D to 3D functional connectivity biases for short dispersal capacities of organisms (6 m to 16 m). These findings are particularly pertinent in urban systems where the distribution of greenspace is critical for delivery of ecosystem services.


[Clinical and epidemiological characteristics of patients with eye tuberculosis].
The study has analyzed 514 new cases of eye tuberculosis registered in the dispensaries of 23 regions. Eye tuberculosis more frequently affects young and middle-aged women, urban citizens, persons who have adequate living and domestic conditions, moderate income, who are clerks or skilled workers, who have no bad habits, who suffer one or two concurrent diseases, who have no opportunity of receiving adequate treatment in a hospital or sanatorium due to familial or professional circumstances and more commonly those whose posterior eyeball is involved (chorioretinitis). Of great concern is eye tuberculosis detected in 87.4% of referrals, which determines the high proportion of advanced and far-advanced cases.


Evaluation of cognitive behavioral therapy/motivational enhancement therapy (CBT/MET) in a treatment trial of comorbid MDD/AUD adolescents.
Behavioral therapies developed specifically for co-occurring disorders remain sparse, and such therapies for comorbid adolescents are particularly rare. This was an evaluation of the long-term (2-year) efficacy of an acute phase trial of manualized cognitive behavioral therapy/motivation enhancement therapy (CBT/MET) vs. naturalistic treatment among adolescents who had signed consent for a treatment study involving the SSRI antidepressant medication fluoxetine and CBT/MET therapy for comorbid major depressive disorder (MDD) and an alcohol use disorder (AUD). We hypothesized that improvements in depressive symptoms and alcohol-related symptoms noted among the subjects who had received CBT/MET would exceed that of those in the naturalistic comparison group that had not received CBT/MET therapy. We evaluated levels of depressive symptoms and alcohol-related symptoms at a two-year follow-up evaluation among comorbid MDD/AUD adolescents who had received an acute phase trial of manual-based CBT/MET (in addition to the SSRI medication fluoxetine or placebo) compared to those who had received naturalistic care. In repeated measures ANOVA, a significant time by enrollment status difference was noted for both depressive symptoms and alcohol-related symptoms across the two-year time period of this study, with those receiving CBT/MET demonstrating superior outcomes compared to those who had not received protocol CBT/MET therapy. No significant difference was noted between those receiving fluoxetine vs. those receiving placebo on any outcome at any time point. These findings suggest long-term efficacy for an acute phase trial of manualized CBT/MET for treating comorbid MDD/AUD adolescents. Large multi-site studies are warranted to further clarify the efficacy of CBT/MET therapy among various adolescent and young adult comorbid populations.


Clinical, pathological and mineralogical features in two autopsy cases of workers exposed to agalmatolite dust.
An agalmatolite miner and processor showed large shadows at the bilateral hila accompanied by surrounding emphysematous changes and irregular shadows on chest X-ray films. Chest CT scans were characterized by a mixture of tiny irregular structures and small round opacities. Histopathological examination revealed massive fibrosis, which corresponded to large shadows, but only a small number of typical silicotic nodules, indicating mixed dust pneumoconiosis. Mineralogical examination of the autopsy lungs showed quartz, pyrophyllite, mica, and kaolinite. Quartz accounted for 70% of the amount of all mineral dust in both patients, but pyrophyllite accounted for 10.8% and 14.4%. The pulmonary mineral dust composition in the two patients was well consistent with the mineral composition of the raw clays in the agalmatolite mine. In the two patients, chest X-ray findings and histopathological findings of the lungs also suggested agalmatolite pneumoconiosis, which was confirmed by mineral analysis of the lungs.


The search for a sustainable alternative to slash-and-burn agriculture in the World's rain forests: the Guama Model and its implementation.
This account describes the context, history and outcomes of a series of studies into the ecology of slash-and-burn (S-B) agriculture in the world's humid tropics. These studies, which began in the mid-1980s, identified promising lines of research and continued to field trials, in Central America, of candidate agricultural systems as possible sustainable alternatives to the practice. The only system to emerge from 7 years' comparative trial with any promise of sustainability, in this context, was the agroforestry technique known as alley-cropping; but only with trees of the genus Inga. Inga alley-cropping then underwent field trials with subsistence farming families in northern Honduras. The system was aimed at the twin objectives of achieving food security in basic grains, on minimal inputs, and of providing the means of eliminating further S-B in the region. Since then, Inga alley-cropping has become the heart of a sustainable and integrated rural livelihood model (the Guama Model) which is being implemented successfully in northern Honduras with some 300 families. These families had been attempting to subsist on a few hectares of land degraded by decades or centuries of S-B. The development of Inga alley-cropping, supplemented by rock phosphate and other mineral supplements, as a sustainable subsistence and cash crop alternative means that land previously being held in reserve for subsequent S-B operations can now be planted to permanent forms of agroforestry. Entire landscapes can be re-greened by productive agroforest vegetation. Achieving this at scale will require the investment of huge extension effort and funds. However, the environmental, social and economic returns are also huge; and they are sustainable. In this programme,we are seeing the vitality and goodwill of hundreds of families focussed on the raising, planting and management of trees in ways that feed the living organisms of the soil and, hence, feed themselves. In so cheerfully planting out their own futures, they plant and reshape the future of their own country. Replicating this at scale, as Rattan Lal outlines below, could reshape the future of this planet. In the mid-1980s, progress on sustainable alternatives to S-B, especially in rain forests, was frustrated by a lack of conclusiveness in the literature as to why soil fertility fails so rapidly post-burn; but also by a degree of contradiction on the impacts of the burn on certain plant nutrients. Hands (Hands 1988 The ecology of shifting cultivation. MSc thesis, University of Cambridge) concentrated on the role of soil phosphorus and attempted to resolve these contradictions. The Cambridge Alley-cropping Projects (1988-2002) continued this theme and threw light on the question of sustainable food production in rain forest environments.


LETTER TO THE EDITOR
An isocyanurate silane coupling agent effectively attaches to E-glass fibers both from aqueous or CCl4 solution. SEM revealed remarkably different glass surface topographies that were solvent dependent. Application of the coupling agent from CCl4 solution gave rise to unprecendented polymeric bridges between adjacent parallel fibers. The existence of such large bridging structures has only recently been postulated, and it was not thought that such theoretical projections would ever be observed, as polymeric bridging structures typically should collapse in the absence of solvent. Copyright 1997 Academic Press. Copyright 1997Academic Press


Echocardiography in emergency.
The use of echocardiography is still far from optimal. It is difficult or impossible to ensure the 24-hour presence at a hospital of a cardiologist with experience in echocardiography. As a result other specialties are becoming familiar with this technique. Echocardiography has been recognized as of paramount importance in diagnosis, prognosis and therapeutic decisions in several diseases and therefore echocardiographic training with different levels of experience should be supported and coordinated by a reference group in such matters. The authors review some aspects of echocardiography in emergency. They emphasize the importance of continuous training and accreditation as required conditions to perform echocardiography.


Large-scale directional relationship extraction and resolution.
Relationships between entities such as genes, chemicals, metabolites, phenotypes and diseases in MEDLINE are often directional. That is, one may affect the other in a positive or negative manner. Detection of causality and direction is key in piecing pathways together and in examining possible implications of experimental results. Because of the size and growth of biomedical literature, it is increasingly important to be able to automate this process as much as possible. Here we present a method of relation extraction using dependency graph parsing with SVM classification. We tested the SVM classifier first on gold standard corpora from GENIA and find it achieved 82% precision and 94.8% recall (F-measure of 87.9) on these standardized test sets. We then applied the entire system to all available MEDLINE abstracts for two target interactions with known effects. We find that while some directional relations are extracted with low ambiguity, others are apparently contradictory, at least when considered in an isolated context. When examined, it is apparent some are dependent upon the surrounding context (e.g. whether the relationship referred to short-term or long-term effects, or whether the focus was extracellular versus intracellular). Thesaurus-based directional relation extraction can be done with reasonable accuracy, but is prone to false-positives on larger corpora due to noun modifiers. Furthermore, methods of resolving or disambiguating relationship context and contingencies are important for large-scale corpora.


Who invented the dichotomous key? Richard Waller's watercolors of the herbs of Britain.
On 27 March 1689, Richard Waller, Fellow and Secretary of the Royal Society presented his "Tables of the English Herbs reduced to such an order, as to find the name of them by their external figures and shapes" to his assembled colleagues at a meeting of the Royal Society. These tables were developed for the novice by being color images, composed in pencil and watercolor, of selected plants and their distinguishing characteristics. The botanical watercolors for the tables are now a Turning-the-Pages document online on the website of the Royal Society. However, for the past 320 years, the scientific context for the creation of these outstanding botanical watercolors has remained obscure. These tables were developed by Waller as an image-based dichotomous key, pre-dating by almost 100 years the text-based dichotomous keys in the first edition of Flora Française (1778) by Jean Baptiste Lamarck, who is generally given priority for the development of the dichotomous key. How these large folio images were arranged to illustrate a dichotomous key is unknown, but an arrangement based on Waller's description is illustrated here as leaf-ordering for the separate hierarchical clusters (tables). Although only 24 species of watercolored dicot herbs out of a total of 65 in the set of watercolors (the others being monocots) are used in these tables, they are a "proof of concept", serving as models upon which a method is based, that of using a key composed of dichotomous choices for aiding identification.


Carrying a rucksack on either shoulder or the back, does it matter? Load induced functional scoliosis in "normal" young subjects.
Approximately 40 million students in the United States and a similar number in Europe carry school rucksacks. The average student carries a rucksack weighing almost one fourth of his or her body weight. This has led to more than 7,000 A&E, referrals each year related to carrying school bags in the US. The purpose of this study was to investigate the effects of carrying a rucksack (on each shoulder or on both), on 3D spinal curvature in healthy young students. A convenience sample of 30 healthy young adults participated in this study. A Microscribe 3DX digitiser recorded the three dimensional coordinates of thirteen key anatomical landmarks along the spine in four different loading conditions; no rucksack (reference) carrying a rucksack (17% body weight) simultaneously on both shoulders and solely on the right or the left shoulder. The data obtained was analyzed using standard statistical methods. Carrying the load on both shoulders resulted in no difference in the frontal plane angle but significantly decreased the thoracic kyphosis in the sagittal plane. However, carrying the load on the right shoulder significantly increased the thoracic lateral curvature in the frontal plane and decreased the thoracic kyphosis in the sagittal plane. This study confirms that even carrying a 17% load causes significant changes in spinal alignment. It is essential that Health and Safety professionals promote the awareness and effects of diverse rucksack carriage modes and excessive rucksack weight to avoid the early onset of low back pain.


Successful recruitment methods in the community for a two-site clinical trial.
Effective screening and recruitment are essential to the success of randomized clinical trials. This report is to describe key screening and recruitment strategies in a two site randomized clinical trial (RCT) conducted in community settings with a vulnerable chronically ill population and to suggest valuable approaches when planning trials. Differences between sites in a complex study with two considerably different environments (academic versus home care) and their participant pools presented challenges which required different screening and recruitment methods. A high level of communication between sites, creative problem solving and the ability to be flexible when problems were encountered were needed for successful screening and recruitment.


Transitional sublethal and lethal effects of insecticides after dermal exposures to five economic species of wireworms (Coleoptera: Elateridae).
During an insecticide toxicity study involving field-collected dusky wireworm, Agriotes obscurus (L.) (Coleoptera: Elateridae), wireworms exposed dermally to six classes of insecticides exhibited characteristic transitional symptoms of toxicity. These symptoms, collectively termed "morbidity," were categorized as "writhing," "leg and mouthpart movements," or "mouthpart-only body movements." These symptoms could persist for long periods, depending on insecticide and dose, with morbid wireworms ultimately recovering or dying. Additional LC50 and LD50 toxicity studies showed that these stages of morbidity also occurred in four other wireworm species, notably Agriotes sputator (L.), Limonius canus LeConte, Ctenicera pruinina (Horn), and Ctenicera destructor (Brown). In addition, all species exposed dermally to clothianidin moved in significant numbers to the surface of soil in posttreatment holding cups. This movement was not observed when these species were exposed to chlorpyrifos or the control solvent. These findings suggest that toxicity trials involving wireworms should include observations on morbidity, and the duration of trials should continue until symptoms of morbidity cease. The long-term morbidity and potential recovery or death of wireworms exposed to certain insecticides has implications for how laboratory and field studies can be better designed and interpreted in the future.


Personal Exposure to PM2.5 Oxidative Potential in Association with Pulmonary Pathophysiologic Outcomes in Children with Asthma.
Fine particulate matter (PM2.5) with a higher oxidative potential has been thought to be more detrimental to pulmonary health. We aim to investigate the associations between personal exposure to PM2.5 oxidative potential and pulmonary outcomes in asthmatic children. We measured each of the 43 asthmatic children 4 times for airway mechanics, lung function, airway inflammation, and asthma symptom scores. Coupling measured indoor and outdoor concentrations of PM2.5 mass, constituents, and oxidative potential with individual time-activity data, we calculated 24 h average personal exposures 0-3 days prior to a health outcome measurement. We found that increases in daily personal exposure to PM2.5 oxidative potential were significantly associated with increased small, large, and total airway resistance, increased airway impedance, decreased lung function, and worsened scores of individual asthma symptoms and the total symptom score. Among the PM2.5 constituents, organic matters largely of indoor origin contributed the greatest to PM2.5 oxidative potential. Given that the variability in PM2.5 oxidative potential was a stronger driver than PM2.5 mass for the variability in the respiratory health outcomes, it is suggested to reduce PM2.5 oxidative potential, particularly by reducing the organic matter constituent of indoor PM2.5, as a targeted source control strategy in asthma management.


A multimodal perioperative plan for radical cystectomy and urinary intestinal diversion: effects, limits and complications of early artificial nutrition.
We evaluated the effects of early parenteral and enteral postoperative nutritional support on the restoration of normal bowel function, on the protein depletion that follows cystectomy and on observed complications. Immediate parenteral nutrition was initiated after surgery. It was progressively shifted to the enteral route through a needle catheter jejunostomy inserted at surgery. A total of 28 patients with a mean age of 74.2 years (range 55 to 82) were enrolled into the study. Disease was pathologically confined to the bladder in 22 patients, locally advanced in 3 and extravesical in 3. Urinary diversions included an ileocolonic pouch in 15 patients and an orthotopic ileal reservoir in 13. Of the 28 patients 15 (53.6%) completed the protocol, whereas 13 (46.4%) did not. Median time to peristalsis and spontaneous passage of flatus was postoperative day 2 (range 2 to 5) and median time to normal diet resumption was postoperative day 4 (range 3 to 8). No significant differences were observed between patients who completed the protocol and those who did not with regard to the restoration of normal bowel function, and total protein, serum albumin and lymphocyte count. Minor complications were observed in 9 patients and major complications developed in 4. Early postoperative artificial nutrition did not affect the return of bowel function or postoperative protein depletion. Different strategies for more effective nutritional support will be explored in further studies.


Long-term oral kinetin does not protect against α-synuclein-induced neurodegeneration in rodent models of Parkinson's disease.
Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity. Although the mechanism(s) underlying how this loss of activity causes degeneration remains unclear, increasing PINK1 activity may therapeutically benefit some forms of PD. However, we must first learn whether restoring PINK1 function prevents degeneration in patients harboring PINK1 mutations, or whether boosting PINK1 function can offer protection in more common causes of PD. To test these hypotheses in preclinical rodent models of PD, we used kinetin triphosphate, a small-molecule that activates both wild-type and mutant forms of PINK1, which affects mitochondrial function and protects neural cells in culture. We chronically fed kinetin, the precursor of kinetin triphosphate, to PINK1-null rats in which PINK1 was reintroduced into their midbrain, and also to rodent models overexpressing α-synuclein. The highest tolerated dose of oral kinetin increased brain levels of kinetin for up to 6 months, without adversely affecting the survival of nigrostriatal dopamine neurons. However, there was no degeneration of midbrain dopamine neurons lacking PINK1, which precluded an assessment of neuroprotection and raised questions about the robustness of the PINK1 KO rat model of PD. In two rodent models of α-synuclein-induced toxicity, boosting PINK1 activity with oral kinetin provided no protective effects. Our results suggest that oral kinetin is unlikely to protect against α-synuclein toxicity, and thus fail to provide evidence that kinetin will protect in sporadic models of PD. Kinetin may protect in cases of PINK1 deficiency, but this possibility requires a more robust PINK1 KO model that can be validated by proof-of-principle genetic correction in adult animals.


Cancer of the female breast. Improving the public's health through early detection.
Decision makers who represent the public need to understand the extent of the breast cancer problem, the potential for improvement, and the actions needed to achieve this potential. Informed, dedicated physicians, individually and collectively, are instrumental and can be most effective leaders in this process. There are several evidences of the fine tradition of the medical profession to advocate practices and policies in the interest of the best health of our patients. The North Carolina Medical Society recently adopted a position statement encouraging the provision of screening mammograms and pap smears by both private and self-insured third party payors; the North Carolina Academy of Family Practice recently adopted a position statement urging priority be placed on allocating resources for efficacious preventive services; the multiple specialty organizations developed the widely recognized national guidelines for early breast cancer detection; and the ACR continues its efforts to assure quality mammography services. To the end that this paper has informed and stimulated further sharing, discussion or debate about the extent of the breast cancer problem, the potential for improvement, and the actions needed to achieve this potential, it has accomplished its purpose. To the end that the physician community acts to improve early breast cancer detection, we will have fulfilled the common purpose that binds us as physicians to one another and to the people we are privileged and bound to serve.


Predicting survival after out-of-hospital cardiac arrest: role of the Utstein data elements.
Survival after out-of-hospital cardiac arrest depends on the links in the chain of survival. The Utstein elements are designed to assess these links and provide the basis for comparing outcomes within and across communities. We assess whether these measures sufficiently predict survival and explain outcome differences. We used an observational, prospective data collection, case-series of adult persons with nontraumatic out-of-hospital cardiac arrest from December 1, 2005, through March 1, 2007, from the multisite, population-based Resuscitation Outcomes Consortium Epistry-Cardiac Arrest. We used logistic regression, receiver operating curves, and measures of variance to estimate the extent to which the Utstein elements predicted survival to hospital discharge and explained outcome variability overall and between 7 Resuscitation Outcomes Consortium sites. Analyses were conducted for all emergency medical services-treated cardiac arrests and for the subset of bystander-witnessed patient arrests because of presumed cardiac cause presenting with ventricular fibrillation or ventricular tachycardia. Survival was 7.8% overall (n=833/10,681) and varied from 4.6% to 14.7% across Resuscitation Outcomes Consortium sites. Among bystander-witnessed ventricular fibrillation or ventricular tachycardia, survival was 22.1% overall (n=323/1459) and varied from 12.5% to 41.0% across sites. The Utstein elements collectively predicted 72% of survival variability among all arrests and 40% of survival variability among bystander-witnessed ventricular fibrillation. The Utstein elements accounted for 43.6% of the between-site survival difference among all arrests and 22.3% of the between-site difference among the bystander-witnessed ventricular fibrillation subset. The Utstein elements predict survival but account for only a modest portion of outcome variability overall and between Resuscitation Outcomes Consortium sites. The results underscore the need for ongoing investigation to better understand characteristics that influence cardiac arrest survival.


Definition of the consensus motif recognized by gamma-adaptin ear domains.
The heterotetrameric adaptor complex 1 (AP-1) and the monomeric Golgi-localized, gamma ear-containing, Arf-binding (GGA) proteins are components of clathrin coats associated with the trans-Golgi network and endosomes. The carboxyl-terminal ear domains (or gamma-adaptin ear (GAE) domains) of two gamma-adaptin subunit isoforms of AP-1 and of the GGAs are structurally similar and bind to a common set of accessory proteins. In this study, we have systematically defined a core tetrapeptide motif PsiG(P/D/E)(Psi/L/M) (where Psi is an aromatic residue), which is responsible for the interactions of accessory proteins with GAE domains. The definition of this motif has allowed us to identify novel GAE-binding partners named NECAP and aftiphilin, which also contain clathrin-binding motifs. These findings shed light on the mechanism of accessory protein recruitment to trans-Golgi network and endosomal clathrin coats.


Drones and global navigation satellite systems: current evidence from polar scientists.
Aerial unmanned vehicles, so-called drones, present a paradigm shift away from the long-term use by scientists of manned aeroplanes and helicopters. This is evident from the number of research articles that focus on data obtained with drones. This article examines the use of aerial drones for scientific research in cryospheric regions, especially Antarctica and the Arctic. Specifically, it aims to provide insights into the choices and performance of global navigation satellite systems (GNSS) use for drones, including augmentation systems. Data on drone GNSS navigation and positioning in the context of scientific polar research have been scarce. Drone survey data obtained from polar scientists in April 2019 is the first representative sample from this close-knit global community across the specialisms of climatology, ecology, geology, geomorphology, geophysics and oceanography. The survey results derived from 16 countries revealed that 14.71% of scientists used GALILEO, 27.94% used GLONASS and 45.59% used GPS. Many used a combination of two or more GNSS. Multiple regression analysis showed that there is no strong relationship between a specific pattern of GNSS augmentation and greater positioning accuracy. Further polar drone studies should assess the effects of phase scintillation on all GNSS, therefore BEIDOU, GALILEO, GLONASS and GPS.


[Staphylococcus cohnii spp urealyticus: case report on an uncommon pathogen].
Coagulase-negative Staphylococcus has emerged as an important agent in nosocomial infections. In this study, we report a case of bacteremia associated with a central venous catheter, caused by Staphylococcus cohnii spp urealyticus that was isolated in blood cultures from a 53-year-old male patient who was admitted to a general hospital in the city of São Paulo. We discuss in this report the difficulty in routinely identifying this microorganism in the clinical microbiology laboratory. Staphylococcus cohnii spp urealyticus is a microorganism found in human skin as part of the normal microbiota, and it can cause serious infections in humans, in some situations.


A T cell-specific knockout reveals an important role for protease-activated receptor 2 in lymphocyte development.
Activation of protease-activated receptor-2 (PAR2) expressed by T cells has been linked to the bone loss associated with periodontitis. We generated PAR2 conditional-null mice and crossed these with mice expressing Cre recombinase under control of the Lck proximal promoter, to produce T cell-specific PAR2-null mice in order to further study the cellular mechanism involved in periodontitis. Here we report that efficient deletion of PAR2 in thymocytes isolated from T cell-specific PAR2-null mice resulted in thymic and splenic hypoplasia and a reduction in the cells of the cortex and a loss of distinction between the cortex and the medulla of the thymus. FACS analysis confirmed significant reductions in CD4 and CD8 double negative (DN3 and DN4) sub-populations, as well as double positive and single positive T cells, in T cell-specific PAR2-null mice compared to Cre expressing PAR2 wild-type mice. The proportion of annexin V positive and propidium iodide negative cells was increased in CD4 and CD8 double negative, double positive and single positive T cells from T cell-specific PAR2-null mice. No change in the proportion of Ki67 positive cells was observed in sections of thymus from T cell-specific PAR2-null mice, suggesting that the depletion of T cell sub-populations in T cell-specific PAR2-null mice resulted from increased apoptosis rather than reduced proliferation. Together, these results demonstrate that PAR2 plays an important and previously unrecognised anti-apoptotic role in T cell development and suggest that the PAR2 conditional-null mouse will be an important resource for determining tissue and cell specific effects of PAR2.


Betulinic Acid Inhibits Cell Proliferation in Human Oral Squamous Cell Carcinoma via Modulating ROS-Regulated p53 Signaling.
Oral squamous cell carcinoma (OSCC) is a common cancer of the head and neck. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid. The present study was designed to explore the effects of BA on OSCC KB cell proliferation in vitro and on implanted tumor growth in vivo and to examine the possible molecular mechanisms. The results showed that BA dose-dependently inhibited KB cell proliferation and decreased implanted tumor volume. In addition, BA significantly promoted mitochondrial apoptosis, as reflected by an increase in TUNEL+ cells and the activities of caspases 3 and 9, an increase in Bax expression, and a decrease in Bcl-2 expression and the mitochondrial oxygen consumption rate. BA significantly increased cell population in the G0/G1 phase and decreases the S phase cell number, indicating the occurrence of G0/G1 cell cycle arrest. ROS generation was significantly increased by BA, and antioxidant NAC treatment markedly inhibited the effect of BA on apoptosis, cell cycle arrest, and proliferation. BA dose-dependently increased p53 expression in KB cells and implanted tumors. p53 reporter gene activity and p53 binding in the promoters of Bax were significantly increased by BA. Knockdown of p53 blocked BA-induced increase in apoptosis, cell cycle arrest, and inhibition of cell proliferation. NAC treatment suppressed BA-induced increase in p53 expression. Furthermore, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was increased by BA. Taken together, the data demonstrated that ROS-p53 signaling was crucial for BA-exhibited antitumor effect in OSCC. BA may serve as a potential drug for the treatment of oral cancer.


The Work of ASBH's Clinical Ethics Consultation Affairs Committee: Development Processes Behind Our Educational Materials.
The authors of this article are previous or current members of the Clinical Ethics Consultation Affairs (CECA) Committee, a standing committee of the American Society for Bioethics and Humanities (ASBH). The committee is composed of seasoned healthcare ethics consultants (HCECs), and it is charged with developing and disseminating education materials for HCECs and ethics committees. The purpose of this article is to describe the educational research and development processes behind our teaching materials, which culminated in a case studies book called A Case-Based Study Guide for Addressing Patient-Centered Ethical Issues in Health Care (hereafter, the Study Guide). In this article, we also enumerate how the Study Guide could be used in teaching and learning, and we identify areas that are ripe for future work.


The family child care home environment and children's diet quality.
Developing healthy eating behaviors and food preferences in early childhood may help establish future healthy diets. Large numbers of children spend time in child care, but little research has assessed the nutritional quality of meals and snacks in family child care homes. Therefore, it is important to assess foods and beverages provided, policies related to nutrition and feeding children, and interactions between providers and children during mealtimes. We examined associations between the nutrition environments of family child care homes and children's diet quality. We assessed the nutrition environments of 166 family child care homes using the Environment and Policy Assessment and Observation (EPAO) (scores range: 0-21). We also recorded foods and beverages consumed by 496 children in care and calculated healthy eating index (HEI) (scores range: 0-100). We used a mixed effects linear regression model to examine the association between the EPAO nutrition environment (and EPAO sub-scales) and child HEI, controlling for potential confounders. Family child care homes had a mean (standard deviation, SD) of 7.2 (3.6) children in care, 74.1% of providers were black or African American, and children had a mean (SD) age of 35.7 (11.4) months. In adjusted multivariable models, higher EPAO nutrition score was associated with increased child HEI score (1.16; 95% CI: 0.34, 1.98; p = 0.006). Higher scores on EPAO sub-scales for foods provided (8.98; 95% CI: 3.94, 14.01; p = 0.0006), nutrition education (5.37; 95% CI: 0.80, 9.94; p = 0.02), and nutrition policy (2.36; 95% CI: 0.23, 4.49; p = 0.03) were all associated with greater child HEI score. Foods and beverages served, in addition to nutrition education and nutrition policies in family child care homes, may be promising intervention targets for improving child diet quality.


Immunohistochemical location of the p75 neurotrophin receptor (p75NTR) in oral leukoplakia and oral squamous cell carcinoma.
Recent studies have demonstrated that the p75 neurotrophin receptor (p75NTR) is a useful marker of keratinocyte stem cells. Although the stem cell markers of original normal tissue have been used to identify cancer stem cells in a variety of cancers, the expression and function of p75NTR have been poorly understood in oral squamous cell carcinoma (OSCC). The objective of this study is, thus, to examine p75NTR expression immunohistochemically in oral leukoplakia (OL), the most frequent precancerous lesion, and OSCC, and to reveal the usefulness of p75NTR as a marker for undifferentiated cancer cells and a novel prognostic factor for OSCC patients. In this study immunohistochemical expression of p75NTR, Ki-67, cytokeratin (CK) 5, and CK14 was examined in 112 cases of OL and 81 of OSCC. The labeling indices (LIs) of p75NTR and Ki-67 were calculated, and the association of these LIs with histopathologic characteristics was then evaluated. In the normal oral epithelium and OL, p75NTR was expressed only in the basal layer, and its LI was invariant, irrespective of the extent of epithelial dysplasia. In OSCC, however, p75NTR-LI was significantly increased in association with upgrading of histologic grade and mode of tumor invasion. Furthermore, the prognosis of the high p75NTR-LI group (LI ≥ 53.1%) was poorer than that of the low p75NTR-LI group (LI < 53.1%). These results suggest that p75NTR is expressed in undifferentiated cell populations in OL and OSCC. Furthermore, p75NTR is possibly involved in invasion and poor prognosis in OSCC.


The calcium ionophore A23187 is a potent stimulator of the vitamin D3-25 hydroxylase in hepatocytes isolated from normocalcaemic vitamin D-depleted rats.
The role played by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and/or by calcium on the C-25 hydroxylation of vitamin D3 (D3) was studied in hepatocytes isolated from D-depleted rats which were divided into four treatment groups: Group 1 served as controls, Group 2 received calcium gluconate, Groups 3 and 4 were infused with 1,25(OH)2D3 at 7 and 65 pmol/24 h x 7 days respectively. The treatments normalized serum calcium in all but the controls which remained hypocalcaemic, while serum 1,25(OH)2D3 remained low in Groups 1 and 2 but increased to physiologic and supraphysiologic levels in Groups 3 and 4. The data show that basal D3-25 hydroxylase activities were not significantly affected by any of the treatments. Addition of CaCl2, EGTA, or Quin-2 in vitro revealed that relative to basal values, EGTA strongly inhibited the enzyme activity in all groups (P less than 0.0001), except in G 1; Quin-2 and CaCl2 had no significant effect on the activity of the enzyme in any of the groups. Addition of 1,25(OH)2D3 or A23187 in vitro in the presence of CaCl2 revealed that 1,25(OH)2D3 did not significantly affect enzyme activity, while A23187 was found to stimulate its activity in vitamin D-depleted animals, but most specifically in Group 2 (P less than 0.001); low serum calcium (Group 1) dampened (P less than 0.01), and 1,25(OH)2D3 treatment in vivo totally blunted (P less than 0.001) the response to A23187. The data suggest that 1,25(OH)2D3 supplementation in vivo has per se little or no effect on the basal D3-25 hydroxylase activity. The data show, however, that the magnitude of the response to various challenges in vitro is greatly influenced by the conditioning in vivo of the animals. They also show that A23187 can be a potent stimulator of the enzyme activity, which allowed us to demonstrate a significant reserve for the C-25 hydroxylation of D3 which is well expressed in hepatocytes obtained from D-depleted calcium-supplemented rats.


Development of subacute cutaneous lupus erythematosus associated with the use of imiquimod to treat actinic keratoses.
The immunomodulating drug imiquimod is approved by the U.S. Food and Drug Administration (FDA) to treat actinic keratoses, non-facial superficial basal cell carcinomas and genital warts. This drug elicits its immunological response by binding to toll-like receptor 7 (TLR-7) on dendritic cells inducing the production of interferon alpha (IFN-alpha) and other inflammatory cytokines. The authors report the case of a 56-year-old female who developed subacute cutaneous lupus erythematosus (SCLE), as well as severe autoimmune retinitis following a vigorous response to imiquimod 5% cream that was prescribed to treat actinic keratoses. Given the important role of IFN-alpha in the pathogenesis of cutaneous lupus, it is likely that imiquimod either induced or unmasked an autoimmune tendency in this patient.


Public health and health promotion capacity at national and regional level: a review of conceptual frameworks.
The concept of capacity building for public health has gained much attention during the last decade. National as well as international organizations increasingly focus their efforts on capacity building to improve performance in the health sector. During the past two decades, a variety of conceptual frameworks have been developed which describe relevant dimensions for public health capacity. Notably, these frameworks differ in design and conceptualization. This paper therefore reviews the existing conceptual frameworks and integrates them into one framework, which contains the most relevant dimensions for public health capacity at the country- or regional level. A comprehensive literature search was performed to identify frameworks addressing public health capacity building at the national or regional level. We content-analysed these frameworks to identify the core dimensions of public health capacity. The dimensions were subsequently synthesized into a set of thematic areas to construct a conceptual framework which describes the most relevant dimensions for capacities at the national- or regional level. The systematic review resulted in the identification of seven core domains for public health capacity: resources, organizational structures, workforce, partnerships, leadership and governance, knowledge development and country specific context. Accordingly, these dimensions were used to construct a framework, which describes these core domains more in detail. Our research shows that although there is no generally agreedupon model of public health capacity, a number of key domains for public health and health promotion capacity are consistently recurring in existing frameworks, regardless of their geographical location or thematic area. As only little work on the core concepts of public health capacities has yet taken place, this study adds value to the discourse by identifying these consistencies across existing frameworks and by synthesising them into a new framework. The framework proposed in this paper can act as a theoretical guide for academic researchers and institutions to set up their own public health capacity assessment. Significance for public healthAs the concept of public health capacities is increasingly debated across countries and national/ international organizations, there is no consensus on the main dimensions of public health capacity. This paper therefore provides a rigorous review of currently existing frameworks, which describe public health capacities at the national or regional level. The main objective is to highlight commonalities among these frameworks, and propose a country-level framework which integrates all reoccurring dimensions. Such a comparison can yield vital information on those dimensions for public health capacities, which are common across all frameworks, and hence could be considered indispensable, irrespective of their context or geographic origin. As such, this review and the subsequent presentation of a conceptual framework is targeted at academic researchers and policy makers, who are interested in setting up a capacity mapping process and who are looking for concepts and frameworks on which they can base their work.


Ammonia selectively stimulates neutral amino acid transport across blood-brain barrier.
The response to increased blood NH4+ of three blood-brain barrier transport systems, which are altered after portacaval anastomosis, was studied. NH4+ acetate was infused for 4 or 22 h to raise blood and brain NH4+, and brain glutamine, to levels similar to those observed after portacaval anastomosis. While brain glutamine content was much higher (16-20 mumol/g) than normal (6 mumol/g) at both times, the permeability of the blood-brain barrier to the neutral amino acid [14C]tryptophan was greater only after 22 h of infusion. After discontinuing the infusion for 5 h, tryptophan transport returned to normal, whereas brain glutamine remained elevated (13 mumol/g). Thus there seemed to be no relationship between the rate of transport and glutamine content. The permeability to [14C]sucrose was unaltered, showing that the integrity of the blood-brain barrier was maintained. Other changes that are characteristic of portacaval shunting, such as decreased basic amino acid ([14C]lysine) and monocarboxylic acid (3-[14C]hydroxybutyrate) transport, were not reproduced by 22 h of infusion. The results demonstrated that the continued presence of NH4+ could be responsible for the change in at least one of the transport systems that are affected by portacaval shunting.


Evaluation of the Heart and Stroke Foundation of Canada Research Scholarship Program: research productivity and impact.
To compare the research productivity, and its impact, of individuals awarded research scholarships from the Heart and Stroke Foundation of Canada (HSFC) with that of a parallel group of unsuccessful applicants during the funding years 1980/81 to 1989/90 inclusive. Research productivity was defined as the number of peer reviewed publications, and impact was evaluated from the number of publications cited; the number of citations per publication; the number of citations per individual; and the impact score. Data were collected on 192 individuals. Cohorts were defined as successful and unsuccessful individuals entering the system in the same year. The study comprised 10 separate cohorts. Data were collected on yearly publications and citation counts for each individual. These data, along with journal impact factors, were obtained from the Institute for Scientific Information. During the 10 years of the study, individuals funded by the HSFC published more papers, more of their papers were cited, and they received more citations per individual than the unfunded comparison group. This consistency in multiple indicators provides strong evidence that funded individuals are more productive and that their work has a greater impact on the body of knowledge in this area. Although this study cannot unequivocally show a direct causal relation between funding and research success, the trend as shown by the indicators studied suggests a beneficial effect.