Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli.
Quorum sensing is a cell-to-cell signalling mechanism in which bacteria secrete hormone-like compounds called autoinducers. When these auto-inducers reach a certain threshold concentration, they interact with bacterial transcriptional regulators, thereby regulating gene expression. Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 as well as E. coli K-12 produces the autoinducer-2 (AI-2), which is synthesized by the product of the luxS gene, and previous work from our laboratory has shown that genes encoding the EHEC type III secretion system were activated by quorum sensing. Recently, by hybridizing an E. coli K-12 gene array with cDNA synthesized from RNA extracted from EHEC strain 86-24 and its isogenic luxS mutant, we observed that other potential virulence-associated factors, such as genes encoding the expression and assembly of flagella, motility and chemotaxis, were also activated by quorum sensing. The array data also indicated that several genes encoding putative E. coli regulators were controlled by quorum sensing. In this report, we describe a two-component system regulated by quorum sensing that shares homology with Salmonella typhimurium PmrAB, which we have named quorum sensing E. coli regulator B and C (QseBC). The qseBC genes, previously identified only as open reading frames b3025 and b3026, are organized in an operon in the E. coli chromosome, with qseB encoding the response regulator and qseC the sensor kinase. We confirmed the regulation of qseBC by quorum sensing using qseB::lacZ transcriptional fusions and characterized the phenotypes of an isogenic qseC mutation in EHEC. This mutant expressed less flagellin and had reduced motility compared with the wild-type and complemented strains. Transcription of flhD, fliA, motA and fliC::lacZ fusions was decreased in the qseC mutant, suggesting that qseBC is a transcriptional regulator of flagella genes. A qseC mutant was also generated in E. coli K-12 strain MC1000 that showed the same phenotypes as the EHEC mutant, indicating that qseBC regulates flagella and motility by quorum sensing in both EHEC and K-12. QseBC activates transcription of flhDC, which is the master regulator for the flagella and motility genes and, in the absence of flhD, QseBC failed to activate the transcription of fliA. Motility of a luxS, but not of a qseC, mutant can be restored by providing AI-2 exogenously as preconditioned media, suggesting that the qseC mutant is unable to respond to AI-2. However, QseC has no effect on the expression of other quorum sensing-controlled genes such as those encoding for the type III secretion system. These data indicate that QseBC is one component of the quorum-sensing regulatory cascade in both EHEC and K-12 that is involved in the regulation of flagella and motility genes, but that additional regulators in this cascade remain to be characterized.


Transcript level coordination of carbon pathways during silicon starvation-induced lipid accumulation in the diatom Thalassiosira pseudonana.
Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterized alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels.


Patient-centred care to improve dietetic practice: an integrative review.
Patient-centred care (PCC) is associated with significant improvements in patients' health outcomes and healthcare systems. There is an opportunity to better understand PCC in dietetics. Thus, the present integrative review aims to critically synthesise literature relating to PCC in dietetics. A systematic literature search was conducted between February and March 2016. Studies were included if they (i) involved dietitians and/or patients who had participated in an individual dietetic consultation; (ii) related to one or more components of PCC; and (iii) were empirical full-text studies in English, involving adult participants, published between 1997 and 2016. Following title and abstract screening, full texts were retrieved and independently assessed for inclusion by two of the investigators. Two independent investigators conducted data extraction and quality assessment using the Mixed Methods Appraisal Tool. Study findings were analysed thematically using meta-synthesis. Twenty-seven studies met the inclusion criteria. Six themes were discovered inductively: (i) establishing a positive dietitian-patient relationship; (ii) displaying humanistic behaviours; (iii) using effective communication skills; (iv) individualising and adapting care; (v) redistributing power to the patient; and (vi) lacking time for PCC practices. The first three themes were closely related. Studies used a broad range of methodological designs. Limitations of the studies included a lack of reflexivity and a lack of representativeness of the study population. It is apparent that dietitians require good communication skills and humanistic qualities to build positive relationships with patients. Patients strongly desire individualised nutrition care and greater involvement in care. Ensuring dietitians are able to incorporate patient-centred practises during care requires further research.


Structure of the amantadine binding site of influenza M2 proton channels in lipid bilayers.
The M2 protein of influenza A virus is a membrane-spanning tetrameric proton channel targeted by the antiviral drugs amantadine and rimantadine. Resistance to these drugs has compromised their effectiveness against many influenza strains, including pandemic H1N1. A recent crystal structure of M2(22-46) showed electron densities attributed to a single amantadine in the amino-terminal half of the pore, indicating a physical occlusion mechanism for inhibition. However, a solution NMR structure of M2(18-60) showed four rimantadines bound to the carboxy-terminal lipid-facing surface of the helices, suggesting an allosteric mechanism. Here we show by solid-state NMR spectroscopy that two amantadine-binding sites exist in M2 in phospholipid bilayers. The high-affinity site, occupied by a single amantadine, is located in the N-terminal channel lumen, surrounded by residues mutated in amantadine-resistant viruses. Quantification of the protein-amantadine distances resulted in a 0.3 A-resolution structure of the high-affinity binding site. The second, low-affinity, site was observed on the C-terminal protein surface, but only when the drug reaches high concentrations in the bilayer. The orientation and dynamics of the drug are distinct in the two sites, as shown by (2)H NMR. These results indicate that amantadine physically occludes the M2 channel, thus paving the way for developing new antiviral drugs against influenza viruses. The study demonstrates the ability of solid-state NMR to elucidate small-molecule interactions with membrane proteins and determine high-resolution structures of their complexes.


Microbiological Contamination of Drugs during Their Administration for Anesthesia in the Operating Room.
The aseptic techniques of anesthesiologists in the preparation and administration of injected medications have not been extensively investigated, but emerging data demonstrate that inadvertent lapses in aseptic technique may be an important contributor to surgical site and other postoperative infections. A prospective, open, microbiological audit of 303 cases in which anesthesiologists were asked to inject all bolus drugs, except propofol and antibiotics, through a 0.2-µm filter was performed. The authors cultured microorganisms, if present, from the 0.2-µm filter unit and from the residual contents of the syringes used for drawing up or administering drugs. Participating anesthesiologists rated ease of use of the filters after each case. Twenty-three anesthesiologists each anesthetized up to 25 adult patients. The authors isolated microorganisms from filter units in 19 (6.3%) of 300 cases (3 cases were excluded), including Staphylococcus capitis, Staphylococcus warneri, Staphylococcus epidermidis, Staphylococcus haemolyticus, Micrococcus luteus/lylae, Corynebacterium, and Bacillus species. The authors collected used syringes at the end of each case and grew microorganisms from residual drug in 55 of these 2,318 (2.4%) syringes including all the aforementioned microorganisms and also Kocuria kristinae, Staphylococcus aureus, and Staphylococcus hominus. Participants' average rating of ease of use of the filter units was 3.5 out of 10 (0 being very easy and 10 being very difficult). Microorganisms with the potential to cause infection are being injected (presumably inadvertently) into some patients during the administration of intravenous drugs by bolus during anesthesia. The relevance of this finding to postoperative infections warrants further investigation.


Legionnaires' disease after bone marrow transplantation.
Four patients developed legionnaires' disease after bone marrow transplantation. Two cases occurred early after transplant and were considered as part of a hospital epidemic due to contamination of water supply. The other two cases were considered to be sporadic because they occurred 3-4 weeks after hospital discharge. The outcome was good in two patients. In the third patient, recurrent disease was probably due to acquired resistance to macrolides, and complete cure was achieved after treatment with pefloxacin and rifampicin. The fourth patient died of overwhelming infection despite early treatment with erythromycin and pefloxacin. During the same period we treated 14 patients with pefloxacin for prevention of bacterial infection, of whom none developed Legionella pneumophila infection, while three of the patients reported here were in a group of 11 patients who received only oral non-absorbable antibiotics for gut decontamination. The fourth patient in this report was receiving no antibiotics. Thus pefloxacin seems to be effective as prophylaxis against L. pneumophila infection. When the hospital water supply was heated to 60 degrees C and chlorinated, the nosocomial cases in the hospital completely disappeared.


Pinocytic loading of cytochrome c into intact cells specifically induces caspase-dependent permeabilization of mitochondria: evidence for a cytochrome c feedback loop.
Previous studies introduced cytochrome c into intact cells via the disruptive techniques of microinjection or electroporation to provide support for the hypothesis that, in whole cells, cytochrome c release from mitochondria triggers caspase activation and other degradative changes. However, the types of measurements that could be undertaken with these techniques was limited. We used the simple and relatively gentle technique of pinocytic loading to demonstrate that, in intact cells, cytosolic cytochrome c specifically induced activation of caspase-3- and -9-like enzymes, and a loss of mitochondrial polarization coincident with an increase in mitochondrial permeability. Our results support the prediction from in vitro studies that activation of caspases-3 and -9 is downstream of cytochrome c release and provide the first direct evidence that, in whole cells, cytochrome c-dependent caspase-activation can exert a feedback effect to elicit mitochondrial permeabilization and collapse of the mitochondrial trans-membrane potential.


Proteome-wide evidence for enhanced positive Darwinian selection within intrinsically disordered regions in proteins.
Understanding the adaptive changes that alter the function of proteins during evolution is an important question for biology and medicine. The increasing number of completely sequenced genomes from closely related organisms, as well as individuals within species, facilitates systematic detection of recent selection events by means of comparative genomics. We have used genome-wide strain-specific single nucleotide polymorphism data from 64 strains of budding yeast (Saccharomyces cerevisiae or Saccharomyces paradoxus) to determine whether adaptive positive selection is correlated with protein regions showing propensity for different classes of structure conformation. Data from phylogenetic and population genetic analysis of 3,746 gene alignments consistently shows a significantly higher degree of positive Darwinian selection in intrinsically disordered regions of proteins compared to regions of alpha helix, beta sheet or tertiary structure. Evidence of positive selection is significantly enriched in classes of proteins whose functions and molecular mechanisms can be coupled to adaptive processes and these classes tend to have a higher average content of intrinsically unstructured protein regions. We suggest that intrinsically disordered protein regions may be important for the production and maintenance of genetic variation with adaptive potential and that they may thus be of central significance for the evolvability of the organism or cell in which they occur.


In vitro motility of immunoadsorbed brain myosin-V using a Limulus acrosomal process and optical tweezer-based assay.
To facilitate functional studies of novel myosins, we have developed a strategy for characterizing the mechanochemical properties of motors isolated by immunoadsorption directly from small amounts of crude tissue extracts. In this initial study, silica beads coated with an antibody that specifically recognizes the tail of myosin-V were used to immunoadsorb this motor protein from brain extracts. The myosin-containing beads were then positioned with optical tweezers onto actin filaments nucleated from Limulus sperm acrosomal processes and observed for motility using high resolution video DIC microscopy. The addition of brush border spectrin to the motility chamber enabled the growth of stable actin filament tracks that were approximately 4-fold longer than filaments grown in the absence of this actin crosslinking protein. The velocity of myosin-V immunoadsorbed from brain extracts was similar to that observed for purified myosin-V that was antibody-linked to beads or assessed using the sliding actin filament assay. Motile beads containing myosin-V immunoadsorbed from brain extracts bound poorly to nucleated actin filaments and were incapable of linear migrations following the addition of a different antibody that specifically recognizes the motor-containing head domain of myosin-V. Myosin-V motility was most robust in the absence of Ca2+. Interestingly, skeletal muscle tropomyosin and brush border spectrin had no detectable effect on myosin-V mechanochemistry. Myosin-V containing beads were also occasionally observed migrating directly on acrosomal processes in the absence of exogenously added actin.(ABSTRACT TRUNCATED AT 250 WORDS)


Brown Rot-Type Fungal Decomposition of Sorghum Bagasse: Variable Success and Mechanistic Implications.
Sweet sorghum is a promising crop for a warming, drying African climate, and basic information is lacking on conversion pathways for its lignocellulosic residues (bagasse). Brown rot wood-decomposer fungi use carbohydrate-selective pathways that, when assessed on sorghum, a grass substrate, can yield information relevant to both plant biomass conversion and fungal biology. In testing sorghum decomposition by brown rot fungi (Gloeophyllum trabeum, Serpula lacrymans), we found that G. trabeum readily degraded sorghum, removing xylan prior to removing glucan. Serpula lacrymans, conversely, caused little decomposition. Ergosterol (fungal biomarker) and protein levels were similar for both fungi, but S. lacrymans produced nearly 4x lower polysaccharide-degrading enzyme specific activity on sorghum than G. trabeum, perhaps a symptom of starvation. Linking this information to genome comparisons including other brown rot fungi known to have a similar issue regarding decomposing grasses (Postia placenta, Fomitopsis pinicola) suggested that a lack of CE 1 feruloyl esterases as well as low xylanase activity in S. lacrymans (3x lower than in G. trabeum) may hinder S. lacrymans, P. placenta, and F. pinicola when degrading grass substrates. These results indicate variability in brown rot mechanisms, which may stem from a differing ability to degrade certain lignin-carbohydrate complexes.


Overactive bladder: treatment options in primary care medicine.
Overactive bladder is a highly prevalent condition, affecting approximately 33 million adults in the United States. Despite the considerable impact this condition has on patients' quality of life, overactive bladder remains underrecognized and undertreated as a result of patient embarrassment and reluctance to seek medical help, as well as a lack of proactive questioning by physicians. The present article encourages physicians to initiate a dialogue with patients regarding urinary control and, specifically, overactive bladder. Treatment options for overactive bladder recommended in the current article include both nonpharmacologic and pharmacologic therapies. Properties of antimuscarinic agents, including three new drug therapies, are reviewed and provided for physicians to optimize therapy options, particularly among elderly patients.


Getting evidence-based pressure ulcer prevention into practice: a process evaluation of a multifaceted intervention in a hospital setting.
To describe registered nurses', assistant nurses' and first-line managers' experiences and perceptions of a multifaceted hospital setting intervention focused on implementing evidence-based pressure ulcer prevention. Pressure ulcer prevention is deficient. Different models exist to support implementation of evidence-based care. Little is known about implementation processes. A descriptive qualitative approach. Five focus-group nurse interviews and five individual first-line manager interviews were conducted at five Swedish hospital units. Qualitative content analysis was used. The findings support that the intervention and the implementation process changed the understanding and way of working with pressure ulcer prevention: from treating to preventing. This became possible as 'Changed understanding enables changed actions - through one's own performance and reflection on pressure ulcer prevention'. Having a common outlook on pressure ulcer prevention, easy access to pressure-reducing equipment, and external and internal facilitator support were described as important factors for changed practices. Bedside support, feedback and discussions on current results increased the awareness of needed improvements. The multifaceted intervention approach and the participants' positive attitudes seemed to be crucial for changing understanding and working more preventatively. The strategies used and the skills of the facilitators need to be tailored to the problems surrounding the context. Feedback discussions among the staff regarding the results of the care provided also appear to be vital. It is crucial that dedicated facilitators are involved to promote the implementation process. A preventative mindset should be strived for. Creating an implementation plan with an outcome and a process evaluation should be emphasised. It is important to give the staff regular feedback on the quality of care and on those occasions allocate time for discussion and reflection.


Changes in gene expression and cellular architecture in an ovarian cancer progression model.
Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. Mouse ovarian surface epithelial (MOSE) cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non-tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cytoskeletal regulatory proteins (focal adhesion kinase, α-actinin, and vinculin). The cytoskeletal disorganization was accompanied by altered patterns of serine and tyrosine phosphorylation as well as changed expression and subcellular localization of integral signaling intermediates APC and PKCβII. Our studies have identified genes that are aberrantly expressed during MOSE cell neoplastic progression. We show that early stage dysregulation of actin microfilaments is followed by progressive disorganization of microtubules and intermediate filaments at later stages. These stage-specific, step-wise changes provide further insights into the time and spatial sequence of events that lead to the fully transformed state since these changes are also observed in aggressive human ovarian cancer cell lines independent of their histological type. Moreover, our studies support a link between aberrant cytoskeleton organization and regulation of important downstream signaling events that may be involved in cancer progression. Thus, our MOSE-derived cell model represents a unique model for in depth mechanistic studies of ovarian cancer progression.


Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI): Protocol for a Cross-Over Trial.
People with vascular cognitive impairment (VCI) constitute a clinically heterogeneous group, but previous symptomatic drug trials in VCI did not take this clinical heterogeneity into account. Executive dysfunction and memory impairment are the cognitive domains that are most frequently impaired in VCI, and these impairments are likely to reflect vascular damage to specific neurotransmitter systems, which opens the possibility for targeted symptomatic treatment directed at specific neurotransmitters. Here we describe the design of the "Symptomatic Treatment of Vascular Cognitive Impairment" (STREAM-VCI) trial. In this proof-of-concept study, we investigate whether people with VCI with executive dysfunction due to vascular damage to the monoaminergic neurotransmitter system differentially respond to a monoaminergic challenge, whereas people with VCI with memory dysfunction associated with vascular damage to the cholinergic system will in turn respond to a cholinergic challenge. The STREAM-VCI is a single center, double blind, three-way cross-over trial among 30 people with VCI, in which subjects received a single dose of galantamine, methylphenidate, or placebo on separate occasions. The most important inclusion criteria were a diagnosis of VCI with a Mini-Mental State Examination score of ≥16 and a Clinical Dementia Rating of 0.5-1.0. For each person, the challenges consisted of a single 16 mg dose of galantamine, 10 mg of methylphenidate, and placebo, in random order on three separate visits. Change in performance in executive functioning and memory was assessed directly after the challenge using standardized neuropsychological tests. We will correlate a positive response to the cholinergic and monoaminergic treatment with differences in structural and functional connectivity at baseline using structural magnetic resonance imaging (MRI), diffusion tension MRI, and resting-state functional MRI. The protocol of this study is approved by the Medical Ethics Committee of VU University Medical Center and the competent authority. The first participant was enrolled in April 2014. In September 2017, enrolment for the study was completed. We expect to publish the results in 2018. STREAM-VCI is the first study to investigate the association of a response to a cholinergic and monoaminergic treatment with structural and functional connectivity of the monoaminergic and/or cholinergic systems on MRI. We aim to predict on an individual basis which individuals show a positive response to a cholinergic and/or monoaminergic challenge in people with VCI. This may be instrumental in moving in the direction of individually-tailored pharmacological interventions based on MRI measures in people with VCI. ClinicalTrials.gov NCT02098824; https://clinicaltrials.gov/ct2/show/NCT02098824 (Archived by WebCite at http://www.webcitation.org/6xhO7Ya1q).


Association between nailfold capillaroscopy findings and pulmonary function tests in patients with systemic sclerosis.
To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.


Differential roles of α6β2* and α4β2* neuronal nicotinic receptors in nicotine- and cocaine-conditioned reward in mice.
Mesolimbic α6* nicotinic acetylcholine receptors (nAChRs) are thought to have an important role in nicotine behavioral effects. However, little is known about the role of the various α6*-nAChRs subtypes in the rewarding effects of nicotine. In this report, we investigated and compared the role of α6*-nAChRs subtypes and their neuro-anatomical locus in nicotine and cocaine reward-like effects in the conditioned place preference (CPP) paradigm, using pharmacological antagonism of α6β2* nAChRs and genetic deletion of the α6 or α4 subunits in mice. We found that α6 KO mice exhibited a rightward shift in the nicotine dose-response curve compared with WT littermates but that α4 KO failed to show nicotine preference, suggesting that α6α4β2*-nAChRs are involved. Furthermore, α6β2* nAChRs in nucleus accumbens were found to have an important role in nicotine-conditioned reward as the intra-accumbal injection of the selective α6β2* α-conotoxin MII [H9A; L15A], blocked nicotine CPP. In contrast to nicotine, α6 KO failed to condition to cocaine, but cocaine CPP in the α4 KO was preserved. Intriguingly, α-conotoxin MII [H9A; L15A], blocked cocaine conditioning in α4 KO mice, implicating α6β2* nAChRs in cocaine reward. Importantly, these effects did not generalize as α6 KO showed both a conditioned place aversion to lithium chloride as well as CPP to palatable food. Finally, dopamine uptake was not different between the α6 KO or WT mice. These data illustrate that the subjective rewarding effects of both nicotine and cocaine may be mediated by mesolimbic α6β2* nAChRs and that antagonists of these receptor subtypes may exhibit therapeutic potential.


The importance of beta diversity in local gall-inducing arthropod distribution.
Many studies over the past twenty years have documented the richness of arthropod galling species around the world, and some have proposed hypotheses to explain local and global patterns of galling species richness. However, few studies have been directed toward understanding how the gall-inducing species are locally distributed. The aim of this study was to determine the distribution of gall-inducing arthropods species at Coiba National Park, a tropical habitat on the Pacific coast of Panama. Our results suggest that more gall-inducing species had an aggregated distribution, and gall-inducing arthropod diversity shows a strong beta diversity component. Geographic distance was not correlated with similarity in gall-inducing species composition between the studied sites. This fact has important implications when trying to estimate gall-inducing arthropod richness and general patterns, and could cause contradictory results for hypotheses that attempt to explain the local and global patterns of galling species richness.


International variations in the treatment and co-morbidity of left ventricular systolic dysfunction: data from the EuroHeart Failure Survey.
Treatment of heart failure (HF) due to left ventricular systolic dysfunction (LVSD) is effective, but many patients are not treated in accordance with guidelines. This may reflect a lack of adequate organisation of care or co-morbidity contra-indicating therapy. To evaluate the effect of co-morbidities on the prescription of neurohormonal antagonists for HF. The EuroHeart Failure Survey identified 10,701 patients with suspected or confirmed HF during 2000 and 2001, 64% of whom had an imaging test and 3658 had documented LVSD. This last group constitutes the focus of this report. Renal dysfunction was associated with lower prescription of ACE inhibitors at discharge (74% vs. 83%, p<0.001). Beta-blockers were less often used in patients with respiratory disease (32% vs. 53%, p<0.001). Co-morbidity did not appear to affect the use of spironolactone. There were few important international differences in uptake of key therapies amongst European countries with widely differing cultures and economic status. Guidelines appear successful in creating a relatively uniform approach to the treatment for HF due to LVSD in diverse medical cultures. Relevant co-morbidity seems to be responsible for a substantial reduction in the prescription of ACE inhibitors and beta-blockers. However, whilst co-morbidity indicates the need for greater caution, it is often not a valid contra-indication to life-saving therapy.


Online mutability of step direction during rapid stepping reactions evoked by postural perturbation.
Stepping reactions are often triggered rapidly in response to loss of balance. It has been unclear whether spatial step parameters are defined at time of step-initiation or whether they can be modulated online, during step execution, in response to sensory feedback about the evolving state of instability. This study explored the capacity to actively alter step direction subsequent to step initiation in six healthy young-adult subjects. To elicit forward-step reactions, subjects were released suddenly from a tethered forward lean. A second perturbation (medio-lateral support-surface translation) was applied at lags of 0-200 ms. Active reaction to the second perturbation was determined primarily through analysis of swing-leg hip-abductor activation. In addition, to gauge the biomechanical consequence of the changes in muscle activation, we compared the measured medio-lateral swing-foot displacement to that predicted by a simple passive mechanical model. Perturbations at 0-100 ms lag evoked active medio-lateral swing-foot deviation, allowing balance to be recovered with a single step. However, when the second perturbation occurred near foot-off (200-ms lag), there was no evidence of active alteration of step direction and subjects typically required additional steps to recover balance. The results suggest that step direction can be reparameterized during early stages of stepping reactions, but that step direction was not actively modulated in response to perturbation arising near start of swing phase.


Ultrasensitive detection of 1,4-Bis(4-vinylpyridyl)phenylene in a small volume of low refractive index liquid by surface-enhanced Raman scattering-active light waveguide.
This paper reports a novel surface-enhanced Raman scattering (SERS)-active light waveguide method for ultrasensitive detection of a sample dissolved in a small volume of low refractive index liquid. The SERS-active light waveguide demonstrated in this study was constructed via the light-guiding silica capillary. The surface of its inner wall was modified with SERS-active silver nanoparticles that can remarkably enhance Raman signals. The capillary with SERS-active modified layer was filled with the sample solution to form the SERS-active liquid core (LC) fiber. The incident laser beam travels through the waveguide in a totally reflective mode within the fiber wall and penetrates a small distance into the sample solution by the evanescent wave field. The Raman scattering of the analytes adsorbed onto the surface of the SERS-active modified layer can be excited by the laser beam and refracted into the fiber wall. Thus, a sample dissolved in low index liquid, e.g., methanol, can be quantitatively monitored by Raman spectroscopy and detection limit of its concentration is lower than 10(-9) mol/L.


Adenosine and its agonists cause retinal vasodilation and hemorrhages. Implications for ischemic retinopathies.
Animals were given a 0.1-mL intravitreous injection of various agents and followed up with frequent ophthalmoscopic examinations. Fundus photographs were performed before injection and at six and 24 hours after injection. Vascular caliber was assessed by a previously described technique of performing measurements on fundus photographs taken and projected in a standardized fashion. No significant vascular dilation was identified for vehicle alone, carbachol, histamine, isoproterenol hydrochloride, or bradykinin. Mild dilation within one hour, but not persisting for 24 hours, was noted for dibutyryl cyclic adenosine monophosphate. Prominent dilation within one hour, becoming maximal by five hours but not persisting for 24 hours, was noted for adenosine, dipyridamole, and sodium nitroprusside. The adenosine-induced vasodilation was effectively blocked by an adenosine receptor antagonist, BW-A1433U. N-ethylcarboxamidoadenosine (NECA), a nonspecific adenosine selective agonist, was a much more potent vasodilator than two relatively selective A1 adenosine agonists, N6-cyclopentyladenosine and N6-phenylisopropyladenosine, suggesting that A2 receptors are involved. The vascular dilation caused by adenosine, dipyridamole, and particularly NECA, but not nitroprusside or dibutyryl cyclic adenosine monophosphate, was accompanied by retinal hemorrhages, producing a picture reminiscent of some features of ischemic retinopathies. This study suggests that adenosine may be an important mediator of vasodilation, and therefore blood flow, in the retina.


Curvature Sensing by a Viral Scission Protein.
Membrane scission is the final step in all budding processes wherein a membrane neck is sufficiently constricted so as to allow for fission and the release of the budded particle. For influenza viruses, membrane scission is mediated by an amphipathic helix (AH) domain in the viral M2 protein. While it is known that the M2AH alters membrane curvature, it is not known how the protein is localized to the center neck of budding virions where it would be able to cause membrane scission. Here, we use molecular dynamics simulations on buckled lipid bilayers to show that the M2AH senses membrane curvature and preferentially localizes to regions of high membrane curvature, comparable to that seen at the center neck of budding influenza viruses. These results were then validated using in vitro binding assays to show that the M2AH senses membrane curvature by detecting lipid packing defects in the membrane. Our results show that the M2AH senses membrane curvature and suggest that the AH domain may localize the protein at the viral neck where it can then mediate membrane scission and the release of budding viruses.


Deletion of L-selectin increases atherosclerosis development in ApoE-/- mice.
Atherosclerosis is an inflammatory disease characterized by accumulation of leukocytes in the arterial intima. Members of the selectin family of adhesion molecules are important mediators of leukocyte extravasation. However, it is unclear whether L-selectin (L-sel) is involved in the pathogenesis of atherosclerosis. In the present study, mice deficient in L-selectin (L-sel(-/-)) animals were crossed with mice lacking Apolipoprotein E (ApoE(-/-)). The development of atherosclerosis was analyzed in double-knockout ApoE/L-sel (ApoE(-/-)L-sel(-/-)) mice and the corresponding ApoE(-/-) controls fed either a normal or a high cholesterol diet (HCD). After 6 weeks of HCD, aortic lesions were increased two-fold in ApoE(-/-)L-sel(-/-) mice as compared to ApoE(-/-) controls (2.46%±0.54% vs 1.28%±0.24% of total aortic area; p<0.05). Formation of atherosclerotic lesions was also enhanced in 6-month-old ApoE(-/-)L-sel(-/-) animals fed a normal diet (10.45%±2.58% vs 1.87%±0.37%; p<0.05). In contrast, after 12 weeks of HCD, there was no difference in atheroma formation between ApoE(-/-)L-sel(-/-) and ApoE(-/-) mice. Serum cholesterol levels remained unchanged by L-sel deletion. Atherosclerotic plaques did not exhibit any differences in cellular composition assessed by immunohistochemistry for CD68, CD3, CD4, and CD8 in ApoE(-/-)L-sel(-/-) as compared to ApoE(-/-) mice. Leukocyte rolling on lesions in the aorta was similar in ApoE(-/-)L-sel(-/-) and ApoE(-/-) animals. ApoE(-/-)L-sel(-/-) mice exhibited reduced size and cellularity of peripheral lymph nodes, increased size of spleen, and increased number of peripheral lymphocytes as compared to ApoE(-/-) controls. These data indicate that L-sel does not promote atherosclerotic lesion formation and suggest that it rather protects from early atherosclerosis.


Socio demographic profile and presentations of patients with ruptured gravid uterus in Calabar Nigeria.
To study the Socio-demographic profiles and mode of clinical presentations of with uterine rupture in pregnancy in Calabar, Nigeria. Medical records of 67 patients managed for ruptured gravid uterus over 10 years in Maternity section of the University of Calabar Teaching Hospital Calabar, Nigeria were reviewed. An incidence of 1 in 213 of all deliveries during the period was established. Majority (49.2%) were aged between 31 to 40 years and 43.3% had no formal education. Unemployed patients were 29.9%, 42.3% did not book for antenatal care while 32.8% were attended to by traditional birth attendants (TBA) and in the churches. The Commonest clinical presentations were fetal heart rate abnormalities (52.2%) and maternal collapse (46.3%). Majority (50.7%) resulted from neglected obstructed labour. Ruptured uterus is a problem of ignorance among women of low socioeconomic group with most of them having unskilled and substandard care during pregnancy and delivery. Improvement in Socio-economic conditions and modification of some harmful cultural practices against women generally will reduce the problem of rupture uterus in our society.


Multilateration with the wide-angle airborne laser ranging system: positioning precision and atmospheric effects.
Numerical simulations based on previously validated models for the wide-angle airborne laser ranging system are used here for assessing the precision in coordinate estimates of ground-based cube-corner retroreflectors (CCR's). It is shown that the precision can be optimized to first order as a function of instrument performance, number of laser shots (LS's), and network size. Laser beam divergence, aircraft altitude, and CCR density are only second-order parameters, provided that the number of echoes per LS is greater than 20. Thus precision in the vertical is approximately 1 mm, with a signal-to-noise ratio of 50 at nadir, a 10-km altitude, a 20 degrees beam divergence, and approximately 5 x 10(3) measurements. Scintillation and fair-weather cumulus clouds usually have negligible influence on the estimates. Laser biases and path delay are compensated for by adjustment of aircraft offsets. The predominant atmospheric effect is with mesoscale nonuniform horizontal temperature gradients, which might lead to biases near 0.5 mm.


Health at school: a hidden health care system emerges from the shadows.
A vast array of child health professionals-99,000 counselors; 56,000 nurses; 30,000 school psychologists; 15,000 social workers; and smaller numbers of dental hygienists, dentists, physicians, and substance abuse counselors-provide care to children and adolescents at school. However, most thought leaders in child health know little about this "hidden" system of care or are skeptical about its capacity to contribute to children's well-being. Increased interest in prevention and chronic disease management, powered by escalating concern about childhood overweight, might end the isolation of school health programs and link them more effectively to community-based prevention programs and health care services.


Describing perceived stigma against Alzheimer's disease in a general population in France: the STIG-MA survey.
Alzheimer's disease (AD) causes progressive loss of memory and disability, especially in older people. As worldwide population grows older, AD is responsible for an important social and economical burden in many nations. People suffering from AD may experience health-related stigma that influences their attitudes towards seeking assistance. The STIG-MA survey describes perceived stigma against AD in a French population. The STIG-MA questionnaire was completed anonymously by people attending an awareness campaign about AD in Creuse, France, in September 2010. Participants answered 10 questions about how they would feel or react if they had AD. Stigma scores were compared by age, activity, and interest in AD. Thirty-three percent of people attending the campaign filled out the survey. Most were women (85%) younger than 50 years (59%); 10% were older people (older than 75 years). Twenty-one percent worked in health or social fields. Interest in AD was professional (48%), related to family (41%), or personal (11%). Professionals in health fields expressed the highest levels of stigma (p = 0.02). Low stigma was most frequent in older people (p = 0.05). Type of interest did not influence stigma. Shame, loss of self-esteem, and fear of exclusion were expressed the most. The STIG-MA survey confirms that AD is a stigmatizing condition in France. The difference between perceived stigma of older people, those most exposed to AD, and that of health professionals may influence attitudes towards screening and care. Further studies of perceived stigma in these populations are necessary to adapt intervention strategies.


The clinical effectiveness of diabetes education models for Type 2 diabetes: a systematic review.
To examine the clinical effectiveness of patient education models for adults with Type 2 diabetes. Electronic databases were searched from 2002 to January 2007. A systematic review of the literature on educational interventions in diabetes was undertaken. This was an update of a previous systematic review. Including studies identified in the previous systematic review, there were 13 published studies. Eight studies of education on multiple aspects of diabetes self-management were identified that provided education that was focused on a particular aspect of self-management. The quality of reporting and methodology of the studies was variable. Studies of multi-component educational interventions yielded mixed results. Some trials reported significant improvements on measures of diabetic control but others did not. Positive effects may be attributable to longer-term interventions with a shorter duration between the end of the intervention and the follow-up evaluation point. There may also be an effect of having a multi-professional team delivering the educational programme. Studies of focused educational interventions did not yield consistent results. Some effects were shown on measures of diabetic control in studies that focused on diet or exercise alone. Although the effects shown were generally small, those that were present did appear to be relatively long-lasting. This update review does not substantially alter the conclusions of the previous systematic review; for each outcome, the proportion of studies that demonstrated significant effects of education was similar. Based on the evidence, it would seem that education delivered by a team of educators, with some degree of reinforcement of that education made at additional points of contact, may provide the best opportunity for improvements in patient outcomes. Educators need to have time and resources to fulfil the needs of any structured educational programme. There is also a need for education to have a clear programme at the outset. From the evidence reported it is unclear what resources would need to be directed at the educators themselves to ensure that they can deliver programmes successfully. Any future research should consider patient education within the context of overall diabetes care and as such follow guidelines for the development and evaluation of complex interventions. Good-quality, longer-term studies would be desirable, but these would require careful consideration around the nature of any control group. Information is needed to clarify the sensitivity of diabetes education programmes to the performance of the diabetes educators, in order to ensure success and cost-effectiveness of education programmes.


Scanning electron microscopy and calcification in amelogenesis imperfecta in anterior and posterior human teeth.
Teeth fragments from members of a family clinically and genetically diagnosed as having amelogenesis imperfecta were studied by scanning electron microscopy and X-ray microprobe analysis to establish the morphological patterns and the quantitative concentration of calcium in the enamel of anterior (canine, incisor) and posterior (premolar and molar) teeth. The prism patterns in the enamel of teeth from both regions were parallel or irregularly decussate, with occasional filamentous prisms accompanied by small, irregularly rounded formations. Prismless enamel showed the R- and P-type patterns. Calcium levels in enamel of amelogenesis imperfecta and control teeth differed significantly between anterior and posterior teeth, indicating that the factors that influence normal mineralization in different regions of the dental arch are not altered in the process of amelogenesis imperfecta.


Dynamical transition in a small helical peptide and its implication for vibrational energy transport.
The two-dimensional infrared spectrum of an octameric helical peptide in chloroform was measured as a function of temperature. Isotope labeling of the carbonyl group of one of the amino acids was used to obtain information for an isolated vibration. The antidiagonal width of the 2D-IR signal, which is a measure of the homogeneous dephasing time T(2), is constant from 220 to 260 K (within experimental error), and increases steeply above. The homogeneous dephasing time of the carbonyl vibration is attributed to the flexibility of the system and/or its immediate surrounding. The system undergoes a dynamical transition at about 270 K, with similarities to the protein dynamical transition. Furthermore, the temperature dependence of the antidiagonal width strongly resembles that of the efficiency of vibrational energy transport along the helix, which has been studied in a recent paper (J. Phys. Chem. B 2008, 112, 15487). The connection between the two processes, structural flexibility and energy transport mechanism, is discussed.


Generating New Space-Filling Test Instances for Continuous Black-Box Optimization.
This article presents a method to generate diverse and challenging new test instances for continuous black-box optimization. Each instance is represented as a feature vector of exploratory landscape analysis measures. By projecting the features into a two-dimensional instance space, the location of existing test instances can be visualized, and their similarities and differences revealed. New instances are generated through genetic programming which evolves functions with controllable characteristics. Convergence to selected target points in the instance space is used to drive the evolutionary process, such that the new instances span the entire space more comprehensively. We demonstrate the method by generating two-dimensional functions to visualize its success, and ten-dimensional functions to test its scalability. We show that the method can recreate existing test functions when target points are co-located with existing functions, and can generate new functions with entirely different characteristics when target points are located in empty regions of the instance space. Moreover, we test the effectiveness of three state-of-the-art algorithms on the new set of instances. The results demonstrate that the new set is not only more diverse than a well-known benchmark set, but also more challenging for the tested algorithms. Hence, the method opens up a new avenue for developing test instances with controllable characteristics, necessary to expose the strengths and weaknesses of algorithms, and drive algorithm development.


Predictors of faster decline of residual renal function in Taiwanese peritoneal dialysis patients.
Loss of residual renal function (RRF) in peritoneal dialysis (PD) patients is a powerful predictor of mortality. The present study was conducted to determine the predictors of faster decline of RRF in PD patients in Taiwan. The study enrolled 270 patients starting PD between January 1996 and December 2005 in a single hospital in Taiwan. We calculated RRF as the mean of the sum of 24-hour urea and creatinine clearance. The slope of the decline of residual glomerular filtration rate (GFR) was the main outcome measure. Data on demographic, clinical, laboratory, and treatment parameters; episodes of peritonitis; and hypotensive events were analyzed by Student t-test, Mann-Whitney U-test, and chi-square, as appropriate. All variables with statistical significance were included in a multivariate linear regression model to select the best predictors (p < 0.05) for faster decline of residual GFR. All patients commencing PD during the study period were followed for 39.4 +/- 24.0 months (median: 35.5 months). The average annual rate of decline of residual GFR was 1.377 +/- 1.47 mL/min/m(2). On multivariate analysis, presence of diabetes mellitus (p < 0.001), higher baseline residual GFR (p < 0.001), hypotensive events (p = 0.001), use of diuretics (p = 0.002), and episodes of peritonitis (p = 0.043) independently predicted faster decline of residual GFR. Male sex, old age, larger body mass index, and presence of coronary artery disease or congestive heart failure were also risk factors on univariate analysis. Our results suggested that diabetes mellitus, higher baseline residual GFR, hypotensive events, and use of diuretics are independently associated with faster decline of residual GFR in PD patients in Taiwan.


Domiciliary and out-patient treatment of self-poisoning patients by medical and non-medical staff.
In a study of domiciliary and out-patient treatment of self-poisoning patients, using a brief problem-orientated approach, it was found that domiciliary treatment resulted in much higher attendance rates but no difference in outcome. Patients who completed out-patient treatment had a better outcome than those who failed to attend treatment sessions. Completion of out-patient treatment was more frequent among higher social class patients. Domiciliary treatment may be more appropriate in some cases for married patients and for those of lower social class. Medical and non-medical staff proved to be equally effective therapists. Future research should be concerned with evaluation of alternative methods of provision of help and further identification of patients who are most likely to benefit from treatment.


Skin color independent assessment of aging using skin autofluorescence.
Skin autofluorescence (AF) for the non-invasive assessment of the amount of accumulated tissue Advanced Glycation Endproducts (AGEs) increases with aging. In subjects with darker skin colors, measurements typically result in lower AF values than in subjects with fair skin colors, e.g. due to selective absorption by skin compounds. Our aim was to provide a new method for calculating skin AF, yielding values that are independent of skin color. The deviation of skin AF of healthy subjects with various darker skin types (N = 99) compared to reference values from Caucasians showed to be a function of various parameters that were derived from reflectance and emission spectra in the UV and visible range (adjusted R(2) = 80%). Validation of the new algorithm, based on these findings, in a separate dataset (N = 141) showed that results of skin AF can now be obtained to assess skin AGEs independently of skin color.


Designing a mixed methods study in primary care.
Mixed methods or multimethod research holds potential for rigorous, methodologically sound investigations in primary care. The objective of this study was to use criteria from the literature to evaluate 5 mixed methods studies in primary care and to advance 3 models useful for designing such investigations. We first identified criteria from the social and behavioral sciences to analyze mixed methods studies in primary care research. We then used the criteria to evaluate 5 mixed methods investigations published in primary care research journals. Of the 5 studies analyzed, 3 included a rationale for mixing based on the need to develop a quantitative instrument from qualitative data or to converge information to best understand the research topic. Quantitative data collection involved structured interviews, observational checklists, and chart audits that were analyzed using descriptive and inferential statistical procedures. Qualitative data consisted of semistructured interviews and field observations that were analyzed using coding to develop themes and categories. The studies showed diverse forms of priority: equal priority, qualitative priority, and quantitative priority. Data collection involved quantitative and qualitative data gathered both concurrently and sequentially. The integration of the quantitative and qualitative data in these studies occurred between data analysis from one phase and data collection from a subsequent phase, while analyzing the data, and when reporting the results. We recommend instrument-building, triangulation, and data transformation models for mixed methods designs as useful frameworks to add rigor to investigations in primary care. We also discuss the limitations of our study and the need for future research.


A new look at proton transfer dynamics along the hydrogen bonds in amides and peptides.
Vibrational spectroscopy with inelastic neutron scattering can provide spectra that are more detailed and easier to interpret than optical spectra. The spectral intensity depends on energy transfer and kinetic momentum transfer, allowing determination of the potential function. Experiments reveal that the proton involved in intermolecular hydrogen bonding in N-methylacetamide and polyglycine I vibrates almost independently. An ionic representation (N(delta-)...H(+)...O(delta-)) of the hydrogen bond is more realistic than the normally accepted covalent model (NH...O). For polyglycine I, the proton experiences a local, symmetric double-minimum potential arising from dynamic exchange between the amide-like (CONH) and imidol-like (HOCN) forms of the peptide unit.


Medication monitoring and optimization: a targeted pharmacist program for effective and cost-effective improvement of chronic therapy adherence.
Community pharmacies provide a promising platform for monitoring and improving therapy adherence and providing pharmaceutical care. Structured methods and appropriate software are important tools to increase pharmacist effectiveness and improve health outcomes. In 2006, the Medication Monitoring and Optimization (MeMO) program was introduced in several community pharmacies in the Netherlands. MeMO facilitates targeted and continuous patient-centered pharmaceutical care around chronic medication, such as for osteoporosis, cardiovascular disease, and asthma/chronic obstructive pulmonary disease (COPD). To describe the MeMO program and summarize findings from publications on its effectiveness, patient satisfaction, and cost-effectiveness. In the first part of this article, the MeMO program is extensively described. In the second part, a review of the evidence of effectiveness, cost-effectiveness, and patient satisfaction of the MeMO program is provided. Evidence is based on 5 previously published articles. The MeMO program starts with structured counseling sessions with patients at the initiation and follow-up of chronic therapies. This process is followed by a continuous phase in which patients' therapy adherence is monitored on a monthly basis, using standardized search algorithms in the pharmacy database. When the algorithm detects a patient's discontinuation of therapy, tailored interventions are used to improve adherence and optimize pharmacotherapy. For osteoporosis patients, treatment discontinuation with bisphosphonates after 1 year dropped from 31.7% to 16.1% (P less than 0.001). This program was shown to be cost-effective in patients initiating osteoporotic therapy. Future scenarios with lower drug prices (e.g., from generic prescribing) result in cost savings for the MeMO program. For lipid-lowering drugs, the MeMO program has been shown to lower therapy discontinuation after 1 year from 25.9% to 13.6% (P less than 0.001). By extrapolating these results to patients' lifetimes, the intervention was estimated to be cost-effective, with gains for primary prevention of cardiovascular events, and even cost saving in secondary prevention. Results from the ongoing MeMO asthma/COPD program are promising, showing marked improvements in therapy control and quality of life for asthma and COPD patients. Almost all patients participating in MeMO programs are satisfied with the pharmacy team and have gained knowledge of the effectiveness and administration of their medications and the importance of therapy adherence. The MeMO program is an effective and structured method to improve patients' adherence to chronic medication in the field of osteoporosis, lipid-lowering drugs, and asthma/COPD and is well received by patients. By targeting the program toward nonadherent and high-risk patients, the program showed favorable cost-effectiveness.


Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p.
In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohydrate reserve when cells are deprived of nutrients. Yeast mutated in SNF1, a gene encoding a protein kinase required for glucose derepression, has diminished glycogen accumulation and concomitant inactivation of glycogen synthase. Restoration of synthesis in an snf1 strain results only in transient glycogen accumulation, implying the existence of other SNF1-dependent controls of glycogen storage. A genetic screen revealed that two genes involved in autophagy, APG1 and APG13, may be regulated by SNF1. Increased autophagic activity was observed in wild-type cells entering the stationary phase, but this induction was impaired in an snf1 strain. Mutants defective for autophagy were able to synthesize glycogen upon approaching the stationary phase, but were unable to maintain their glycogen stores, because subsequent synthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulation in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also protected glycogen stores, but only very late in the stationary phase. Gph1p and Sga1p may therefore degrade physically distinct pools of glycogen. Pho85p is a cyclin-dependent protein kinase that antagonizes SNF1 control of glycogen synthesis. Induction of autophagy in pho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants. We propose that Snf1p and Pho85p are, respectively, positive and negative regulators of autophagy, probably via Apg1 and/or Apg13. Defective glycogen storage in snf1 cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy.


Prevalence study of yaws in the Democratic Republic of Congo using the lot quality assurance sampling method.
Until the 1970s the prevalence of non-venereal trepanomatosis, including yaws, was greatly reduced after worldwide mass treatment. In 2005, cases were again reported in the Democratic Republic of the Congo. We carried out a survey to estimate the village-level prevalence of yaws in the region of Equator in the north of the country in order to define appropriate strategies to effectively treat the affected population. We designed a community-based survey using the Lot Quality Assurance Sampling method to classify the prevalence of active yaws in 14 groups of villages (lots). The classification into high, moderate, or low yaws prevalence corresponded to World Health Organization prevalence thresholds for identifying appropriate operational treatment strategies. Active yaws cases were defined by suggestive clinical signs and positive rapid plasma reagin and Treponema pallidum hemagglutination serological tests. The overall prevalence in the study area was 4.7% (95% confidence interval: 3.4-6.0). Two of 14 lots had high prevalence (>10%), three moderate prevalence (5-10%) and nine low prevalence (<5%.). Although yaws is no longer a World Health Organization priority disease, the presence of yaws in a region where it was supposed to be eradicated demonstrates the importance of continued surveillance and control efforts. Yaws should remain a public health priority in countries where previously it was known to be endemic. The integration of sensitive surveillance systems together with free access to effective treatment is recommended. As a consequence of our study results, more than 16,000 people received free treatment against yaws.


The epidemiological characteristics of the 2007 foot-and-mouth disease epidemic in Sarpang and Zhemgang districts of Bhutan.
This study was undertaken to compare the epidemiological characteristics of the 2007 foot-and-mouth disease outbreak in two districts of Sarpang and Zhemgang in Bhutan. Zhemgang district recorded a significantly higher cumulative incidence in all species (26.9%) as well as for cattle (29.3%) compared to Sarpang (6.5% and 7.4%, respectively). The case fatality for cattle in Zhemgang (14.1%) was significantly higher than in Sarpang (3.3%). A total of 404 cattle and 73 pigs died of FMD in Zhemgang, whereas only 21 cattle died in Sarpang. Although all four species were affected in Sarpang, no sheep or goats were affected in Zhemgang. Spatiotemporal analyses showed the existence of four significant clusters, a primary one in Sarpang and three secondary clusters in Zhemgang. The virus belonged to the PanAsia strain of the Middle-East South-Asia topotype (O serotype), and the strain was closely related to the PanAsia strain that circulated in Bhutan during the 2003/2004 outbreaks. The severity of FMD infection in Zhemgang district could be attributed to low vaccination coverage (36.5% in 2006 when compared to 87.6% in Sarpang), inadequate biosecurity, poor nursing care of the sick animals and delayed reporting to the livestock centre. This study highlights the ability of the PanAsia strain of the O serotype to cause unprecedented morbidity and mortality, especially in a naïve population. The study also highlights the benefits of maintaining good herd immunity in the susceptible population, through adequate vaccination coverage, to minimize the severity of infection and limit the spread of disease from infected to non-infected herds.


Systematic Review: Acupuncture vs Standard Pharmacological Therapy for Migraine Prevention.
Standard pharmacological treatment of migraine has many shortcomings. Acupuncture is becoming a more widely used therapy for the prevention and treatment of migraine, but its effectiveness is still in question when compared to the pharmacological treatments even though very few of these have Class A and B evidence for migraine prevention. This is a systematic review of data from existing randomized trials that compare the effectiveness of acupuncture treatment with conventional migraine preventative medications. Custom-designed strategy was used for searching Pubmed (includes MEDLINE), Scopus (includes EMBASE). The inclusion criteria were English language and randomized trials. No date restriction was utilized. We included randomized trials and randomized controlled trials in adult patients that compared the clinical effects of acupuncture with a standard migraine preventive medication in patients with a diagnosis of chronic or episodic migraine with or without aura. We excluded letters and studies on acupuncture for headaches other than migraine. Two reviewers checked eligibility; extracted information on patients, interventions, methods, and results; and assessed the quality of the acupuncture intervention based on the American Academy of Neurology Classification of evidence matrix for therapeutic trials. The present review was not registered. Out of the 706 search results, 7 clinical trials, with a total of 1430 participants, met inclusion criteria for trials comparing the effectiveness of acupuncture to standard pharmacologic treatment. Several of the studies showed acupuncture to be more effective than standard pharmacological treatments for migraine prevention; however, methodological heterogeneity precluded aggregation of these data. There is growing evidence that acupuncture is just as effective and has fewer side effects than many of the standard pharmaceutical agents that are currently used. However, the heterogeneity of the existing studies limits the effective comparison and analysis.


Bioinformatic principles underlying the information content of transcription factor binding sites.
Empirically, it has been observed in several cases that the information content of transcription factor binding site sequences (R(sequence)) approximately equals the information content of binding site positions (R(frequency)). A general framework for formal models of transcription factors and binding sites is developed to address this issue. Measures for information content in transcription factor binding sites are revisited and theoretic analyses are compared on this basis. These analyses do not lead to consistent results. A comparative review reveals that these inconsistent approaches do not include a transcription factor state space. Therefore, a state space for mathematically representing transcription factors with respect to their binding site recognition properties is introduced into the modelling framework. Analysis of the resulting comprehensive model shows that the structure of genome state space favours equality of R(sequence) and R(frequency) indeed, but the relation between the two information quantities also depends on the structure of the transcription factor state space. This might lead to significant deviations between R(sequence) and R(frequency). However, further investigation and biological arguments show that the effects of the structure of the transcription factor state space on the relation of R(sequence) and R(frequency) are strongly limited for systems which are autonomous in the sense that all DNA-binding proteins operating on the genome are encoded in the genome itself. This provides a theoretical explanation for the empirically observed equality.


The heart of the matter: an atypical presentation of Takayasu arteritis in the Pediatric Emergency Department.
Takayasu arteritis (TA) is a rare chronic large-vessel vasculitis of unknown etiology. Although commonly thought of as an adult disease, initial manifestations frequently appear during adolescence. This is a case discussion of an 11-year-old boy with a recent history of fever who presented with shortness of breath, sore throat, chest pain, hypertension, and a new murmur. He had a markedly elevated antistreptolysin O titer, had a prolonged PR interval, and was initially evaluated with acute rheumatic fever. After admission, he had persistent hypertension, proteinuria, and hemoptysis, which prompted a magnetic resonance angiography that revealed aortic enhancement and thickening, and he was evaluated with TA. To our knowledge, this is the first case report in the pediatric literature of TA presenting with heart block. This case highlights the recondite nature of the systemic vasculitides and emphasizes the importance of keeping a broad differential diagnosis when seeing patients who present with common complaints.


Transcriptional activities of estrogen and glucocorticoid receptors are functionally integrated at the AP-1 response element.
Estrogens and glucocorticoids often act in opposition to regulate physiological responses. We investigated whether this might reflect the opposing actions of hormone-bound receptors on target genes regulated by the AP-1 response element. We performed a series of transfection experiments in which transcriptional activation, mediated by the AP-1 response element, was reflected in reporter gene activity. As previously described, we found that estrogens stimulate, whereas the glucocorticoid dexamethasone (Dex) inhibits, transcription through a model promoter from the collagenase gene (-73 to +63). This promoter bears a consensus AP-1 response element. When HeLa cells were treated with both estradiol and Dex, the steroids counteracted each other's transcriptional effects. The amount of transfected estrogen and glucocorticoid receptors (ER and GR) determined the extent to which Dex blunted estrogen stimulation or estrogen prevented Dex inhibition. The ER/GR interaction was observed both in the presence of estradiol and tamoxifen, which has previously been shown to have estrogen-like action at an AP-1 response element. The AP-1 family member c-Jun enhanced Dex inhibition and estradiol stimulation of transcriptional activation. c-Fos potentiated the effect of cotransfected c-Jun on estradiol stimulation but not Dex inhibition. The pattern of steroid responses was retained in the presence of the c-Jun activator phorbol 12-myristate 13-acetate. However, estradiol stimulation was lost in the presence of the c-Jun activator tumor necrosis factor-alpha. The ER/GR/AP-1 response element interaction was present, not only in a cell line originally derived from a uterine cervical adenocarcinoma (HeLa), but also in a cell line derived from the hypothalamus (GT1-1). Lastly, both progesterone receptor types A and B also interacted with the ER at the AP-1 site. These data indicate that opposing steroid influences can be mediated at the level of transcription through the AP-1 site and suggest that the integration of hormone action at this response element may underlie some of the opposing actions of estrogens and glucocorticoids or progestins on physiological responses.


Biomedical ontologies in action: role in knowledge management, data integration and decision support.
To provide typical examples of biomedical ontologies in action, emphasizing the role played by biomedical ontologies in knowledge management, data integration and decision support. Biomedical ontologies selected for their practical impact are examined from a functional perspective. Examples of applications are taken from operational systems and the biomedical literature, with a bias towards recent journal articles. The ontologies under investigation in this survey include SNOMED CT, the Logical Observation Identifiers, Names, and Codes (LOINC), the Foundational Model of Anatomy, the Gene Ontology, RxNorm, the National Cancer Institute Thesaurus, the International Classification of Diseases, the Medical Subject Headings (MeSH) and the Unified Medical Language System (UMLS). The roles played by biomedical ontologies are classified into three major categories: knowledge management (indexing and retrieval of data and information, access to information, mapping among ontologies); data integration, exchange and semantic interoperability; and decision support and reasoning (data selection and aggregation, decision support, natural language processing applications, knowledge discovery). Ontologies play an important role in biomedical research through a variety of applications. While ontologies are used primarily as a source of vocabulary for standardization and integration purposes, many applications also use them as a source of computable knowledge. Barriers to the use of ontologies in biomedical applications are discussed.


Isolated lung liposome-mediated gene transfer produces organ-specific transgenic expression.
Gene therapy is a promising strategy for the treatment of inoperable pulmonary tumors and rejection after lung transplantation. However, unlike ex vivo administration, intravenous in vivo transfection lacks organ specificity and has a limited duration of expression. The objectives of this study were to limit transfection to a single lung and to increase the duration of gene expression in vivo. Sixteen male Fisher rats were anesthetized and divided into two groups. Animals in group I (n = 7) received an intrajugular administration of 1,320 microg of chloramphenicol acetyl transferase (CAT) complementary DNA complexed with cationic liposomes. Animals in group II (n = 9) received 660 microg of CAT complementary DNA complexed with cationic liposomes into the pulmonary artery of an isolated left lung over 10 minutes. After 40 minutes of incubation, the lung was flushed with 10 mL of normal saline solution, and the perfusate was suctioned through a left pulmonary venotomy. The circulation to the left lung was then restored. After 48 hours, the animals were divided into subgroups (a and b) and CAT activity was assessed in the lungs, hearts, livers, and kidneys of groups Ia (n = 3) and IIa (n = 5). After 21 days, CAT activity was assessed in the left lungs of groups Ib (n = 4) and IIb (n = 4). After 48 hours, animals that had received intravenous administration of CAT cDNA showed strong expression in the lungs and hearts and negligible expression in the livers and kidneys. In contrast, animals in group IIa, which had received isolated left lung perfusion of CAT cDNA showed expression only in the left lung. After 21 days, the left lungs of animals in group Ib, which had received intravenous administration of CAT complementary DNA, showed no CAT expression, but the left lungs of animals in group IIb, which had received isolated left lung perfusion of CAT complementary DNA, exhibited strong CAT expression. Compared with intravenous administration, isolated lung liposome-mediated gene transfer provides prolonged organ-specific gene expression. This provides a useful model to study the effects of gene therapy on pulmonary tumors, which may have further application when gene therapy is used in clinical practice.


The interaction of cocaine with serotonin dorsal raphe neurons. Single-unit extracellular recording studies.
Cocaine potently inhibits the spontaneous activity of dorsal raphe serotonin (5-hydroxytryptamine [5-HT] neurons which possess impulse-modulating receptors of the 5-HT1A subtype. In an investigation of the neuropharmacologic mechanisms underlying this electrophysiologic effect, we have compared cocaine with structurally and functionally similar compounds, attempted to reverse cocaine-induced suppression of 5-HT dorsal raphe nucleus (DRN) neuronal activity, and assessed the effects of 5-HT depletion on the response to cocaine. Extracellular recordings in chloral hydrate-anesthetized rats were obtained using single-unit recording techniques; drugs were infused intravenously IV) in a cumulative dose manner. The active isomer (-)-cocaine (ID50 = 0.5 +/- 0.15 mg/kg) and the phenyltropane analogue WIN 35428 (ID50 = 0.17 +/- 0.03 mg/kg) that share the ability of cocaine to block monoamine uptake also inhibit impulse activity in 5-HT neurons. In contrast, the inactive isomers (+)-cocaine, (+)-pseudococaine and the metabolite benzoylecgonine do not exhibit the same range of potency (maximal 20% to 30% inhibition at a cumulative dose of 8 to 16 mg/kg). A selective inhibitor of uptake for 5-HT (fluoxetine; ID50 = 1.8 +/- 0.5 mg/kg), but not norepinephrine (desipramine) or dopamine (GBR 12909), mimicked cocaine, as did the monoamine releaser amphetamine (ID50 = 2.86 +/- 0.46 mg/kg). The putative 5-HT1A autoreceptor antagonist spiperone reversed the cocaine-induced depression of firing rate in 64% of 5-HT neurons tested whereas receptor antagonists for dopamine D2 (haloperidol), 5-HT2 (ketanserin), gamma-aminobutyric acid (picrotoxin) and 5-HT1/beta-adrenergic (propranolol) were ineffective. Following treatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (100 mg/kg/day of the base for 3 days), impulse depression induced by cocaine was significantly attenuated as compared to control, which suggests that the effects of cocaine may be dependent on endogenous 5-HT stores. In summary, these findings support the hypothesis that the inhibitory effects of cocaine on 5-HT DRN neurons are mediated by increased 5-HT available for interaction with 5-HT1A impulse-regulating autoreceptors in the DRN, as a consequence of cocaine-induced blockade of 5-HT reuptake processes. Further studies are required to clarify the relative contribution of cocaine-5-HT interactions to the behavioral and physiologic effects of this psychostimulant.


Safety and usefulness of non-occlusion image acquisition technique for optical coherence tomography.
Because optical coherence tomography (OCT) requires balloon-occlusion to overcome image attenuation by blood, the present study investigated the safety and usefulness of a new non-occlusive technique. The 40 angina patients were assigned to the continuous-flushing method or the balloon-occlusion method group. The continuous-flushing method was superior for observing proximal lesions compared with the balloon-occlusion method (94% vs 55%, p=0.01). There were no differences between groups in the visible length and image quality. There were no major complications during OCT. The continuous-flushing method is safe and useful for OCT.


Implementation of an Educational Cartoon ("the Patchbook") and Other Compliance-Enhancing Measures by Orthoptists in Occlusion Treatment of Amblyopia.
This implementation study evaluated orthoptists' use of an educational cartoon ("the Patchbook") and other measures to improve compliance with occlusion therapy for amblyopia. Participating orthoptists provided standard orthoptic care for one year, adding the Patchbook in the second year. They attended courses on compliance and intercultural communication by communication skills training. Many other compliance-enhancing measures were initiated. Orthoptists' awareness, attitude, and activities regarding noncompliance were assessed through interviews, questionnaires, and observations. Their use of the Patchbook was measured. The study was performed in low socio-economic status (SES) areas and in other areas in the Netherlands. It was attempted to integrate education on compliance into basic and continuing orthoptic training. The Patchbook was used by all 9 orthoptists who participated in low-SES areas and 17 of 23 orthoptists in other areas. Courses changed awareness and attitude about compliance, but this was not sustained. Although orthoptists estimated compliance during patching at 70%, three-quarters never suspected noncompliance during a full day of observation in any of their patients. Explanations to parents who spoke Dutch poorly were short. In the second year, explanations to children were longer. Implementation of all 7 additional compliance-enhancing measures failed. Education on compliance was not integrated into orthoptists' training. Almost all orthoptists used the Patchbook and, as another study demonstrated, it proved to be very effective, especially in low-SES areas. Duration of explanation was inversely proportional to parents' fluency in Dutch. Noncompliance was rarely suspected by orthoptists. Although 7 additional compliance-enhancing measures had been conceived and planned with the best intentions, they were not realized. These required extra, unpaid time from the orthoptists, which is especially scarce in hospitals in low-SES areas where the educational cartoon is most needed.


Clinical Anatomy for the Innervated Pattern and Boundary of the Subdeltoid Bursa.
The aim of this study was to accurately identify the distribution of sensory nerve branches running to bursa with mesoscopic dissection and boundaries following the injection of gelatin into the bursa. Eighteen shoulders of 11 Korean soft cadavers (average age, 65 years; age range, 43 - 88 years) were dissected. The most prominent point of greater tubercle of the humerus (GT) was used as a reference point. The horizontal line passing through GT was used as the x-axis while the vertical line passing through the GT was used as the y-axis. Average distances of the anterior, posterior, superior, and inferior from the GT were 1.9±0.6, 2.4±1.3, 2.1±0.7, and 3.2±1.5 cm, respectively. In 15 cases of 18 shoulders, the anterior branch of the axillary nerve was distributed to the subdeltoid bursa that was running posteriorly. The muscular branch of the anterior and middle parts of the deltoid was distributed to the branch of nerve that was running into the subdeltoid bursa. A branch of the posterior cord of brachial plexus was distributed to the subdeltoid bursa that was running anteriorly in three cases. Most of the branches of the axillary nerve were distributed into the posterolateral area. The branches of the posterior cord of brachial plexus were distributed in the anterolateral area. These results might be useful for preventing residual pain on the anterior shoulder region following an injection for the relief of shoulder pain.


[Sleep, depression, and antidepressive treatments (1)].
Sleep research in depressive disorders has advanced considerably in the last two decades. In this review we highlight the different facets of this research, including neurophysiological descriptions of sleep disturbances in depression and data regarding the effects of antidepressant treatments on sleep. The available information is discussed taking into consideration a possible pathogenic role of certain sleep changes in depression, as assumed by several theoretical models. The scope of these models and their explanatory power are briefly analysed. Some comments are made on conceptual and methodological problems in the field of sleep research in psychiatric disorders.


A comparison of association statistics between pooled and individual genotypes.
Markers for individual genotyping can be selected using quantitative genotyping of pooled DNA. This strategy saves time and money. To determine the efficacy of this approach, we investigated the bivariate distribution of association test statistics from pooled and individual genotypes. We used a sample of approximately 1,000 samples with individual and pooled genotyping on 40,000 SNPs. We found that the distribution of the joint test statistics can be modelled as a mixture of two bivariate normal distributions. One distribution has a correlation of zero, and is probably due to SNPs whose pooled genotyping was unsuccessful. The other distribution has a correlation of approximately 0.65 in our data. This latter distribution is probably accounted for by SNPs whose pooled genotyping accurately predicts the underlying allele frequency. Approximately 87% of the data belongs to this distribution. We also derived a method to investigate the effect of both the correlation and selection cut-off on the relative power of pooling studies. We demonstrate that pooled genotyping has good power to detect SNPs that are truly associated with disease-causing variants for SNPs showing good correlation between pooled and individual genotyping. Therefore, this approach is a cost effective tool for association studies.


Neutralization of proteolytic and hemorrhagic activities of Costa Rican snake venoms by a polyvalent antivenom.
The polyvalent antivenom produced at the Instituto Clodomiro Picado, Costa Rica, was tested for its capacity to neutralize proteolytic and hemorrhagic activities of ten Costa Rican crotaline venoms. In experiments with preincubation of venom and antivenom, the latter efficiently neutralized proteolytic activities of nine venoms, with ED50 ranging from 50 to 300 microliters antivenom/mg venom. The venom of Bothrops nummifer was neutralized less efficiently (ED50 = 760 microliters/mg.) Antivenom was also very effective in neutralizing hemorrhagic activity, having its lowest neutralizing ability against the venom of B. picadoi (ED = 430 microliters/mg) and its highest towards the venom of B. asper (Pacific region) (ED50 = 47 microliters/mg). There was a significant correlation between the ability of antivenom to neutralize proteolytic and hemorrhagic effects. In spite of the ability of antivenom to neutralize hemorrhage when incubated with venom prior to injection, hemorrhage was only partially neutralized when antivenom was administered i.v. at different time periods after envenomation. This suggests that the rapid development of local hemorrhage, instead of the absence of antivenom antibodies, is the explanation for the poor neutralization observed in these types of experiments.


Removal of PCR error products and unincorporated primers by metal-chelate affinity chromatography.
Immobilized Metal Affinity Chromatography (IMAC) has been used for decades to purify proteins on the basis of amino acid content, especially surface-exposed histidines and "histidine tags" genetically added to recombinant proteins. We and others have extended the use of IMAC to purification of nucleic acids via interactions with the nucleotide bases, especially purines, of single-stranded RNA and DNA. We also have demonstrated the purification of plasmid DNA from contaminating genomic DNA by IMAC capture of selectively-denatured genomic DNA. Here we describe an efficient method of purifying PCR products by specifically removing error products, excess primers, and unincorporated dNTPs from PCR product mixtures using flow-through metal-chelate affinity adsorption. By flowing a PCR product mixture through a Cu(2+)-iminodiacetic acid (IDA) agarose spin column, 94-99% of the dNTPs and nearly all the primers can be removed. Many of the error products commonly formed by Taq polymerase also are removed. Sequencing of the IMAC-processed PCR product gave base-calling accuracy comparable to that obtained with a commercial PCR product purification method. The results show that IMAC matrices (specifically Cu(2+)-IDA agarose) can be used for the purification of PCR products. Due to the generality of the base-specific mechanism of adsorption, IMAC matrices may also be used in the purification of oligonucleotides, cDNA, mRNA and micro RNAs.


NKT cells in HIV-1 infection.
Natural killer T (NKT) cells are a unique T cell population that have important immunoregulatory functions and have been shown to be involved in host immunity against a range of microorganisms. It also emerges that they might play a role in HIV-1 infection, and therefore be selectively depleted during the early stages of infection. Recent studies are reviewed regarding the dynamics of NKT depletion during HIV-1 infection and their recovery under highly active antiretroviral treatment (HAART). Possible mechanisms for these changes are proposed based on the recent developments in HIV pathogenesis. Further discussions are focused on HIV's disruption of NKT activation by downregulating CD1d expression on antigen presentation cells (APC). HIV-1 protein Nef is found to play the major role by interrupting the intracellular trafficking of nascent and recycling CD1d molecules.


Soft XAS as an in situ technique for the study of heterogeneous catalysts.
Soft X-ray absorption in situ studies of heterogeneous catalysts have been applied to areas such as copper methanol oxidation catalysts and cobalt Fischer-Tropsch type catalysts over a period of around two decades. The technique has the potential to offer several advantages for studying heterogeneous catalysts against hard X-ray XAS in: the systems that can be studied (includes elements such as C, N, O), the potential for surface sensitivity (crucial for catalysts, where reactions occur at surfaces) and the information content of the resulting spectra. Nevertheless, it is technically challenging and the necessary hardware has only been developed and evolved in a few specific groups worldwide. This perspective will introduce the technique in the context of other competing spectroscopies, summarise the development of hardware and the challenges that have been overcome in experimental terms, along with the outcome and impact on different fields within catalysis. Additionally, anticipated future trends and directions will be discussed.


Subtyping genotype 2 hepatitis C viruses from Tunisia: identification of two putative new subtypes.
HCV variants were classified into six genotypes (1-6) subdivided into several subtypes with different geographic distribution worldwide. Previous studies conducted in Tunisia showed that genotype 1 counts for more than 80 % of circulating HCV genotypes and most of the isolates belong to subtype 1b. Genotype 2 comes in the second position, however, few sequences have been analyzed and published. In the present study, 89 isolates from Tunisian patients, typed as genotype 2 by the InnoLIPA commercial probe hybridization test, were sequenced in the NS5B and Core/E1 regions. All the isolates, clustered with the genotype 2 reference sequences, in the NS5B and in the Core/E1 region and the phylogenetic analyses in the two genomic regions were perfectly concordant: subtype 2c was the most frequent (58 out of 89, 65.1 %) and few isolates belonged to subtypes 2k(n = 10), 2i(n = 5), and 2b(n = 1). Fifteen isolates did not match with any of the reference sequences representing the genotype 2 subtypes, identified up-to-date. They divided into 2 separate clusters with high bootstrap values in both genomic regions. This study shows perfect concordance between the NS5B and the Core/E1 region suggesting that any of the two regions can be used for genotyping and that intergenotypic and intragenotypic recombinants are not very frequent, at least for HCV isolates from genotype 2. The present study also shows a predominance of subtype 2c among genotype 2 HCV isolates circulating in Tunisia, the co-circulation of minor subtypes (2k, 2i, and 2b) and proposes the possible existence of two other new subtypes.


Capability beliefs and the intention to adopt evidence-based practices in the future among nursing students: An international study.
Capability beliefs and the intention to adopt EBP in future nursing practice have been identified as strong antecedents of subsequent utilization of EBP. Despite this, a multicountry comparison may yield interesting findings that can be useful in designing empirically based and culturally tailored strategies to facilitate and enhance students' capability beliefs as well as their intentions to integrate evidence into nursing practice. This report sought to compare capability beliefs and intentions to adopt EBP in the future among student nurses from four countries-specifically, Oman, India, Nigeria, and Saudi Arabia-and to identify specific variables that predict the intention to adopt EBP. This study employed a descriptive, cross-sectional, comparative research design to gather data from a convenience sample of 1387 nursing students from four countries using self-report questionnaires that captured their EBP capability beliefs and their intention to adopt EBP in clinical practice upon graduation. This study adhered to STROBE guideline for cross-sectional studies. Overall, nursing students reported a high intent to adopt EBP in their future nursing practice; however, the exact rate varied according to the country of origin. Students' gender, student track, education, country of origin, access to the internet, and capability beliefs were seen as important in explaining the likelihood of future implementation of evidence in clinical nursing practice. Capability beliefs among students were moderate, with large differences observed between countries. Although the surveyed nursing students reported moderate capability beliefs, their intention to adopt and integrate EBP in their future nursing practice was relatively high. The findings of this study highlight the critical role of nurse educators and nurse administrators in fostering EBP capability beliefs and future intentions to adopt among students through curricular review, implementation of evidence-based strategies, and the promotion of EBP culture within the clinical learning sites.


Cognitive development in schizophrenia: follow-back from the first episode.
Despite consensus that schizophrenia is a neurodevelopmental disorder characterized by cognitive deficits, objective data documenting the course of cognitive development remain sparse. We conducted a follow-back study of patients ascertained at the time of their initial episode of schizophrenia or schizoaffective disorder, and a group of demographically matched healthy volunteers. We obtained school records containing standardized achievement test scores from the 1st through 12th grades, and scholastic aptitude test results from the 11th and 12th grades, and examined the developmental trajectories of cognitive performance with respect to prospective examinations conducted following participants' enrollment in our study. We found significant differences in academic achievement tests as early as the first grade, with scores from participants who would later develop schizophrenia lagging behind their peers by 0.8 to 1.1 grade equivalents. This gap widened resulting in a difference between groups of 1.5 to 1.8 grade equivalents by the 12th grade. In the subset of patients for whom SAT scores were available, we found that WAIS-R Full Scale IQ was 11.5 points lower than predicted from earlier SAT scores, suggesting a substantial decline in cognitive ability accompanying the initial episode of illness. These findings suggest that schizophrenia is marked by substantial cognitive deficits in the first grade, that there may be additional subtle decline preceding the overt onset of psychotic symptoms, and that the initial episode of illness is marked by additional decline. These observations may help advance concepts of premorbid cognitive ability in the schizophrenia syndrome and constrain models of pathophysiology.


Intra-household conflicts in migration decisionmaking: return and pendulum migration in Morocco.
By analyzing the migration behavior and transnational residential strategies of first-generation, aging migrants from a particular Moroccan sending region, this study contributes to a conceptual critique of migration theories that identify the household as the most relevant decisionmaking unit. It highlights the role of intra-household power inequalities and conflicts in migration decisionmaking as well as the effects of migration decisions for intra-household power relations. Many labor migrants who left Morocco to work in Europe in the 1960s and 1970s did not realize their wish to return but instead ended up reunifying their families at the destination. An increasing proportion adopts a pendulum migration strategy to reconcile their own wish to retain strong ties with Morocco with the reluctance of children and spouses to return. Migrants who unilaterally decided not to reunify their families usually return after their active working life. However, this unilateral decision also blocks legal entry into Europe for their children, which has generated considerable intergenerational tensions.


Sub-Clinical Effects of Chronic Noise Exposure on Vestibular System.
to investigate the effect of chronic noise exposure on vestibular function of subjects without clinical evidence of vestibular disorders and with documented cochlear damage from noise. 25 patients with chronic noise-induced hearing loss (NIHL) and without vestibular complaints (group A) and 25 matched controls with sensorineural hearing loss without noise exposure (group B), underwent audiological and vestibular test including caloric and cervical vestibular-evoked myogenic potentials tests (cVEMPs). In subjects chronically exposed to noise, similarly to that of the auditory threshold, an increase in the evocation threshold of VEMPs has been documented, statistically significant (p<0,05) and independent of the performance of the auditory threshold. p1-n1 amplitude values showed a significant difference between group A and group B. No significant difference for p1-n1 latencies between the two groups was found. We have documented the possibility of vestibular lesion, along with cochlear damage, related to chronic acoustic trauma.