Phenotypic analysis of EcR-A mutants suggests that EcR isoforms have unique functions during Drosophila development.
The steroid hormone ecdysone triggers transitions between developmental stages in Drosophila by acting through a heterodimer consisting of the EcR and USP nuclear receptors. The EcR gene encodes three protein isoforms (EcR-A, EcR-B1, and EcR-B2) that have unique amino termini but that contain a common carboxy-terminal region including DNA-binding and ligand-binding domains. EcR-A and EcR-B1 are expressed in a spatially complementary pattern at the onset of metamorphosis, suggesting that specific responses to ecdysone involve distinct EcR isoforms. Here, we describe phenotypes of EcR-A specific deletion mutants isolated using transposon mutagenesis. Western blot analysis shows that each of these mutants completely lacks EcR-A protein, while the EcR-B1 protein is still present. The EcR(112) strain has a deletion of EcR-A specific non-coding and regulatory sequences but retains the coding exons, while the EcR(139) strain has a deletion of EcR-A specific protein coding exons but retains the regulatory region. In these mutants, the developmental progression of most internal tissues that normally express EcR-B1 is unaffected by the lack of EcR-A. Surprisingly, however, we found that one larval tissue, the salivary gland, fails to degenerate even though EcR-B1 is the predominant isoform. This result may indicate that the low levels of EcR-A in this tissue are in fact required. We identified yet another type of mutation, the EcR(94) deletion, that removes the EcR-A specific protein coding exons as well as the introns between the EcR-A and EcR-B transcription start sites. This deletion places the EcR-A regulatory region adjacent to the EcR-B transcription start site. While EcR(112) and EcR(139) mutant animals die during mid and late pupal development, respectively, EcR(94) mutants arrest prior to pupariation. EcR-A mutant phenotypes and lethal phases differ from those of EcR-B mutants, suggesting that the EcR isoforms have distinct developmental functions.


Phytoextraction of metals and rhizoremediation of PAHs in co-contaminated soil by co-planting of Sedum alfredii with ryegrass (Lolium perenne) or castor (Ricinus communis).
A pot experiment was conducted to investigate the potential for phytoextraction of heavy metals and rhizoremediation of polycyclic aromatic hydrocarbons (PAHs) in co-contaminated soil by co-planting a cadmium/zinc (Cd/Zn) hyperaccumulator and lead (Pb) accumulator Sedum alfredii with ryegrass (Lolium perenne) or castor (Ricinus communis). Co-planting with castor decreased the shoot biomass of S. alfredii as compared to that in monoculture. Cadmium concentration in S. alfredii shoot significantly decreased when grown with ryegrass or castor as compared to that in monoculture. However, no reduction of Zn or Pb concentration in S. alfredii shoot was detected in co-planting treatments. Total removal of either Cd, Zn, or Pb by plants was similar across S. alfredii monoculture or co-planting with ryegrass or castor, except enhanced Pb removal in S. alfredii and ryegrass co-planting treatment. Co-planting of S. alfredii with ryegrass or castor significantly enhanced the pyrene and anthracene dissipation as compared to that in the bare soil or S. alfredii monoculture. This appears to be due to the increased soil microbial population and activities in both co-planting treatments. Co-planting of S. alfredii with ryegrass or castor provides a promising strategy to mitigate both metal and PAH contaminants from co-contaminated soils.


Impact of Cognitive Impairment on Adherence to Treatment and Self-Care in Patients with Type 2 Diabetes Mellitus.
Elderly patients with diabetes have a significantly increased prevalence of mild cognitive impairment compared with people of similar age without diabetes. Tasks related to diabetes self-management involve multiple cognitive skills and processes, such as memory, attention, planning, and calculating. Impaired cognitive function can threaten the patient's ability to perform self-monitoring. The objectives of the study were: to assess cognitive deficits and the level of self-care in elderly patients with diabetes, to identify correlations between cognitive deficits and self-care, and to determine which variables influence self-care behaviors and cognitive deficits. The study involved 169 patients with type 2 DM. Standardized tools were used: Mini-mental State Examination (MMSE) to assess cognitive function and the Self-Care of Diabetes Inventory (SCODI) to assess the level of self-care. Socioclinical data were taken from the hospital records. 56.8% of patients had cognitive impairment (MMSE≤26). In the comparative analysis, patients with cognitive impairment had significantly lower results in all domains of the SCODI: self-care maintenance (72.9 vs 75), self-care monitoring (53.1 vs 56.3), self-care management (71.9 vs 84.4), self-care confidence (79.5 vs 86.4). Correlation analysis showed that the MMSE score correlates significantly and positively (p˂0.05; r˃0) with all SCODI subscales, and the higher the MMSE score the higher the level of self-care (A: r=0.252, B: r=0.244, C: r=0.019, D: r=0.28). In this elderly type 2 diabetes population, and using only one test to verify the cognitive function, self-care management was worse in terms of self-care management (blood glucose control). Cognitive function components are independent determinants of self-care in patients with type 2 diabetes. Recall is an independent predictor of self-care maintenance, and writing a predictor of self-care monitoring.


An assessment of Norplant removal in Indonesia.
From 1987 to 1997, approximately four million Indonesian women had a Norplant insertion. Concerns have been raised about the timely removal of the implant within a few days of the user's request or at the end of the recommended five years of use and about the possibility of a large and rapidly increasing backlog of removal cases developing. This study of 2,979 Indonesian women in 14 provinces, all of whom had had Norplant inserted five or more years before they were interviewed, reveals that 66 percent had obtained removal by the end of the fifth year of use and 90 percent had done so by the end of the sixth year of use. The data from this study strongly suggest that no large backlog of removal cases exists, particularly after the sixth year of use. The major reason for the underreporting of removals is probably clients' use of nurse/midwives, of caregivers in the private sector, and of mass safari camps, because records from each of these sources are poor or nonexistent.


[Effect of Arnica montana on the state of lipid peroxidation and protective glutathione system of rat liver in experimental toxic hepatitis].
Effects of Tinctura Arnica on lipids peroxidation and on the protective glutathions system of liver in rats in case of experimental toxic hepatitis have been studied. Toxic hepatitis is accompanied by deep alterations of the oxidant-antioxidant status of the body. Intoxication of the body by CCl4 results in intensification of the free radicals formation particularly in liver: accumulation of lipids peroxidation molecular products, glutathione system enzyme activity inhibition in early terms and its partial restoration in remote terms has been seen. Our studies revealed that Arnica montana infusion inhibits the rate of lipids perioxidation products formation, affects the glutathione system enzymes activity.


Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study.
The environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets. Bayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD. Our analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9). Within plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD.


Impact of a long-term high-glucose environment on pro-inflammatory responses in macrophages stimulated with lipopolysaccharide.
Cumulative evidence has established that macrophages orchestrate inflammatory responses that crucially contribute to the pathogenesis of insulin-resistant obesity and type 2 diabetes. In the present study, we examined the impact of hyperglycemia on macrophage pro-inflammatory responses under an inflammatory stimulus. To conduct this study, RAW264.7 macrophages were cultured under normal- (5.5 mM) or high-glucose (22 or 40 mM) conditions for 7 days and stimulated with lipopolysaccharide (LPS). Long-term exposure to high glucose significantly enhanced the increase in the production of pro-inflammatory cytokines, including tumor necrosis-α, interleukin (IL)-1β, and IL-6, when macrophages were stimulated with LPS. The LPS-induced increases in inducible nitric oxide (NO) synthase (iNOS) expression and NO production were also significantly enhanced by long-term exposure of macrophages to high glucose. Treatment with N-acetyl-L-cysteine, a widely used thiol-containing antioxidant, blunted the enhancement of the LPS-induced upregulation of pro-inflammatory cytokine production, iNOS expression, and NO production in macrophages. When intracellular reactive oxygen species (ROS) were visualized using the fluorescence dye 5-(and-6)-chloromethyl-2',7'-dichlorofluorescein diacetate, acetyl ester, a significant increase in ROS generation was found after stimulation of macrophages with LPS, and this increased ROS generation was exacerbated under long-term high-glucose conditions. LPS-induced translocation of phosphorylated nuclear factor-κB (NF-κB), a transcription factor regulating many pro-inflammatory genes, into the nucleus was promoted under long-term high-glucose conditions. Altogether, the present results indicate that a long-term high-glucose environment can enhance activation of NF-κB in LPS-stimulated macrophages possibly due to excessive ROS production, thereby leading to increased macrophage pro-inflammatory responses.


Remyelination: what are the prospects for regenerative therapies in multiple sclerosis?
Multiple sclerosis (MS) involves the immune system attacking the myelin sheaths surrounding axons and is a major cause of disability in working-age adults. Various approved therapies now provide reasonably good control over MS neuroinflammation, but none have a pronounced impact on the neurodegeneration associated with the disease. One prominent approach to fulfilling the unmet need for neuroprotective therapies, is the search for agents that promote 'remyelination', namely the generation of new oligodendrocytes that can form replacement myelin sheaths around denuded axons. In this article, I discuss some emerging targets for remyelinating therapies, mainly being pursued by recently formed small companies translating academic findings.


Molecular diversity at the major cluster of disease resistance genes in cultivated and wild Lactuca spp.
Diversity was analyzed in wild and cultivated Lactuca germplasm using molecular markers derived from resistance genes of the NBS-LRR type. Three molecular markers, one microsatellite marker and two SCAR markers that amplified LRR-encoding regions, were developed from sequences of resistance gene homologs at the main resistance gene cluster in lettuce. Variation for these markers were assessed in germplasm including accessions of cultivated lettuce, Lactuca sativa L. and three wild Lactuca spp., L. serriola L., L. saligna and L. virosa L. Diversity was also studied within and between natural populations of L. serriola from Israel and California; the former is close to the center of diversity for Lactuca spp. while the latter is an area of more recent colonization. Large numbers of haplotypes were detected indicating the presence of numerous resistance genes in wild species. The diversity in haplotypes provided evidence for gene duplication and unequal crossing-over during the evolution of this cluster of resistance genes. However, there was no evidence for duplications and deletions within the LRR-encoding regions studied. The three markers were highly correlated with resistance phenotypes in L. sativa. They were able to discriminate between accessions that had previously been shown to be resistant to all known isolates of Bremia lactucae. Therefore, these markers will be highly informative for the establishment of core collections and marker-aided selection. A hierarchical analysis of the population structure of L. serriola showed that countries, as well as locations, were significantly differentiated. These differences may reflect local founder effects and/or divergent selection.


Equilibrium and kinetic study of sodium- and potassium-induced conformational changes of apo-alpha-lactalbumin.
Equilibrium and kinetics of Na+-and K+-induced conformational changes of apo-alpha-lactalbumin were studied by means of circular dichroism. While apo-alpha-lactalbumin was considerably unfolded in the absence of Na+ or K+ in 20 mM Tris at pH 8.0 and 25 degrees, both the monovalent cations restored the tertiary structure of the protein. Apparent binding constants of Na+ and K+ to the apoprotein were estimated from the equilibria of the Na+- and K+-induced conformational changes. Based on kinetic data of the conformational changes induced by the monovalent cations, binding mechanism of the ions to the apo-protein was examined. Bound alkali-metal ions stabilize the native-like state and an activated state in the unfolding-refolding reaction of the apoprotein.


[Advance on pharmacokinetics study of traditional Chinese medicine injections in recent ten years].
Traditional Chinese medicine(TCM) injections boast a definite efficacy and have been widely used in clinic. However, the problems in medication safety have been attracted increasing attention. Pharmacokinetics is of significance to guiding TCM injection administration regimen design and improving safety and effectiveness in clinical use. In recent years, with the improvement of ideas, technology and methods of TCM studies, the pharmacokinetic studies of TCM injections have been broadly performed, with a notable progress. This paper reviewed the advance in pharmacokinetics studies of TCM injections in recent ten years, which mainly focused on pre-clinical concentration-time course, distribution, metabolism and excretion in vivo based on analysis techniques, pharmacokinetic interactions of constitutes, impact of pathological state, pharmacokinetic interactions between TCM injection and chemical drugs, and clinical pharmacokinetics studies of TCM injections, in the expectation of providing reference for studies on quality control, product development and rational clinical use of TCM injections.


Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting).
Temporary interruption of cerebral blood flow during carotid endarterectomy can be avoided by using a shunt across the clamped section of the carotid artery. This may improve outcome. The objective of this review was to assess the effect of routine versus selective, or never, shunting during carotid endarterectomy, and to assess the best method for selecting patients for shunting. For the original review the authors searched the Cochrane Stroke Group trials register, Medline (1966 to 1994), Embase (1980 to 1995) and Index to Scientific and Technical Proceedings (1980 to 1994). They also hand searched Annals of Surgery (1981 to 1995), British Journal of Surgery (1985 to 1995), European Journal of Vascular Surgery (1988 to 1995) and World Journal of Surgery (1978 to 1995). For the updated review, for the dates January 1994 - December 2000 we: 1. Repeated all these searches performed for the original review and developed more comprehensive search strategies for Medline and Embase. The Cochrane Stroke Group Trials Register was last searched in May 2001. 2. Hand searched the Journal of Vascular Surgery, Stroke, Annals of Vascular Surgery, American Journal of Surgery and Cardiovascular Surgery. 3. Hand searched the abstracts from the International Stroke Conference, AGM of the Vascular Surgical Society (UK), AGM of the Association of Surgeons of Great Britain and Ireland and the Annual Meeting of the Society for Vascular Surgery (USA). 4. Searched reference lists from all relevant trials All the authors of studies included in the initial review, and other authors known to have published relevant work, were contacted requesting information about further published or unpublished data. Randomised and quasi-randomised trials of routine shunting compared with no shunting or selective shunting, and trials that compared different shunting policies in patients undergoing carotid endarterectomy. For the original review two reviewers independently performed the searches and applied the inclusion criteria. The data were extracted by one reviewer and double-checked. Trial quality was assessed. During the update, two reviewers independently performed the searches and applied the inclusion criteria. No new relevant randomised controlled trials were found. Despite recommendation from the original review that further studies were required, no new trials of adequate quality and fitting the inclusion criteria were found. The initial review included three trials. Two trials involving 590 patients compared routine shunting with no shunting. The other trial involving 131 patients compared shunting with a combination of electroencephalographic and carotid pressure measurement, with shunting by carotid pressure measurement alone. Allocation was adequately concealed in one trial, and one trial was quasi-randomised. Analysis was by intention-to-treat where possible. For routine versus no shunting, there was no significant difference in the rate of all stroke, ipsilateral stroke or death up to 30 days after surgery, although data were limited. There was no significant difference between the risk of ipsilateral stroke in patients selected for shunting with the combination of electroencephalographic and carotid pressure assessment compared to pressure assessment alone, although again the data were limited. When first published in 1995, this review concluded that the data available were too limited to either support or refute the use of routine or selective shunting in carotid endarterectomy. It was suggested that large scale randomised trials using no shunting as the control group were required. No one method of monitoring in selective shunting has been shown to produce better outcomes. No further prospective randomised or quasi-randomised trials have been performed since then and the conclusions therefore remain unchanged.


Validity and reliability of 6-minute pegboard and ring test in patients with asthma.
The 6-minute pegboard and ring test (6PBRT) is a test of upper-extremity functional capacity designed for and validated in chronic obstructive pulmonary disease. The aim of this study was to evaluate the validity and reliability of the 6PBRT in asthma patients. Thirty-four adults (30 women, 4 men) with well-controlled asthma were included. Unsupported upper-extremity exercise capacity was assessed using 6PBRT, maximal arm exercise capacity using an arm ergometer, handgrip strength using a hand dynamometer, activities of daily living with the London Chest Activities of Daily Living Scale (LCADL), Milliken ADL scale (MAS) and health-related quality of life using the Asthma Quality of Life Questionnaire (AQLQ) and Health Assessment Questionnaire Disability Index (HAQ-DI). The 6PBRT showed moderate to excellent test-retest reliability with an intraclass correlation coefficient (ICC) value of 0.872 [95% confidence interval (CI) 0.702-0.941]. The 6PBRT was reproducible according to Bland-Altman analysis, with upper and lower limits of agreement of 53.51 and -25.08 rings moved, respectively. The 6PBRT score was significantly correlated with maximum workload (r = 0.514, p = 0.002) achieved in the arm ergometer test, change in dyspnea during 6PBRT (r = -0.402, p = 0.020), LCADL-self-care (r = -0.364, p = 0.037), MAS total (r = 0.483, p = 0.005), AQLQ-symptom domain (r = 0.420, p = 0.026) and HAQ-DI total scores (r = -0.390, p = 0.025). The 6PBRT can be used as a valid and reliable test to evaluate functional arm exercise capacity in patients with well-controlled asthma.


Fungal and Bacterial Communities in Indoor Dust Follow Different Environmental Determinants.
People spend most of their time inside buildings and the indoor microbiome is a major part of our everyday environment. It affects humans' wellbeing and therefore its composition is important for use in inferring human health impacts. It is still not well understood how environmental conditions affect indoor microbial communities. Existing studies have mostly focussed on the local (e.g., building units) or continental scale and rarely on the regional scale, e.g. a specific metropolitan area. Therefore, we wanted to identify key environmental determinants for the house dust microbiome from an existing collection of spatially (area of Munich, Germany) and temporally (301 days) distributed samples and to determine changes in the community as a function of time. To that end, dust samples that had been collected once from the living room floors of 286 individual households, were profiled for fungal and bacterial community variation and diversity using microbial fingerprinting techniques. The profiles were tested for their association with occupant behaviour, building characteristics, outdoor pollution, vegetation, and urbanization. Our results showed that more environmental and particularly outdoor factors (vegetation, urbanization, airborne particulate matter) affected the community composition of indoor fungi than of bacteria. The passage of time affected fungi and, surprisingly, also strongly affected bacteria. We inferred that fungal communities in indoor dust changed semi-annually, whereas bacterial communities paralleled outdoor plant phenological periods. These differences in temporal dynamics cannot be fully explained and should be further investigated in future studies on indoor microbiomes.


[Prevention of heart contractile disorders in experimental infarct by using preliminary adaptation to stress exposure and opioid peptides].
Preliminary adaptation to brief immobilization stresses was shown to reduce impairments of the contractile function of the left ventricle in an experimental myocardial infarction both under conditions of physiological rest and following the short blocking of the aorta. This protective effect is occasioned, along with other factors, by the prevention of the stressory damage to the non-ischemic portions of the heart. The same adaptation increased the levels of enkephalins and beta-endorphin in the cerebral and adrenal structures. The preliminary administration of beta-endorphin prior to the stimulation of an experimental infarction considerably prevented stressory disorders of the contractile function of the right atrium.


Solid-state optical properties of self-assembling amyloid-like peptides with different charged states at the terminal ends.
The self-assembling of small peptides not only leads to the formation of intriguing nanoarchitectures, but also generates materials with unexpected functional properties. Oligopeptides can form amyloid-like cross-β assemblies that are able to emit intrinsic photoluminescence (PL), over the whole near-UV/visible range, whose origin is still largely debated. As proton transfer between the peptide chain termini within the assembly is one of the invoked interpretations of this phenomenon, we here evaluated the solid state PL properties of a series of self-assembled hexaphenylalanine peptides characterized by a different terminal charge state. Overall, our data indicate that the charge state of these peptides has a marginal role in the PL emission as all systems exhibit very similar multicolour PL associated with a violation of the Kasha's rule. On the other hand, charged/uncharged ends occasionally produce differences in the quantum yields. The generality of these observations has been proven by extending these analyses to the Aβ16-21 peptide. Collectively, the present findings provide useful information for deciphering the code that links the spectroscopic properties of these assemblies to their structural/electronic features.


Regional anesthesia in anesthetized or heavily sedated patients.
The American Society of Regional Anesthesia and Pain Medicine (ASRA) Practice Advisory on Neurologic Complications in Regional Anesthesia and Pain Medicine includes an evidence- and expert opinion-based section on performing procedures on anesthetized or heavily sedated patients. This practice advisory is based on existing scientific literature, pathophysiological principles, and expert opinion. The advisory panel examined the ability of anesthetized or heavily sedated patients to recognize and report intravascular injection of local anesthetic or impending neurologic injury. The advisory panel also considered whether or not the ability to recognize and report symptoms could actually affect the occurrence of nerve injury or local anesthetic systemic toxicity. The advisory contains recommendations pertaining to both adult and pediatric patients.


ANCA-negative EGPA: only eosinophils without vasculitis? Insights from anti-T2 biologics.
The pathogenic role of p-ANCA in eosinophilic granulomatosis with polyangiitis (EGPA) is a long-standing matter of debate. In this work, we report our real-life experience with EGPA patients, treated with biologics targeting type 2 (T2)-eosinophilic inflammation (Mepolizumab, Benralizumab, Dupilumab). Interestingly, we observed EGPA extrarespiratory relapses only in p-ANCA-positive patients (2/5 cutaneous vasculitis, 3/5 constitutional symptoms), with new rise of p-ANCA and normal eosinophil blood count. Notably, revising our cohort with the new ACR 2022 criteria, these five patients were the only ones to satisfy the entry criterion of vasculitis' defined diagnosis at disease onset. These observations may suggest that biologics, selectively turning off T2 inflammation, may have unmasked p-ANCA exclusive role in the pathogenesis of vasculitis in EGPA. Therefore, we raise the question whether EGPA vasculitis exists only in p-ANCA-positive patients, and whether p-ANCA-negative disease is "only eosinophils without vasculitis".


To think or not to think, that is the question: individual differences in suppression and rebound effects in autobiographical memory.
Two studies explored the effects of forget instructions on autobiographical memory at immediate test and following delays of either 12-13 months, or 3-4 months. Using the Autobiographical Think/No-Think procedure (cf., Noreen & MacLeod, 2013), 24 never-depressed participants (Study 1) first generated 12 positive and 12 negative autobiographical memories and associated cues. Participants were then asked to recall the memory associated with some of the cues (i.e., 'think' condition), or to avoid saying or thinking about the memory associated with other cues (i.e., 'no-think' condition). Participants were then asked to recall the memories associated with all the cues at immediate test and following a delay of 12-13 months. Participants were found to be successful at forgetting both positive and negative autobiographical memories following 'no-think' instructions at immediate test but this forgetting effect did not persist following a 12-13 month delay. This pattern of remembering and forgetting was replicated in a second study (using 27 never-depressed participants) following a 3-4 month delay. Participants who had been less successful at forgetting 'no-think' memories at immediate test, were more likely to show rebound effects for those memories following a delay compared to memories which received neither 'think' nor 'no-think' instructions. Individual differences in inhibitory control and the efficacy of potential therapeutic interventions of 'no-think' instructions are considered.


In situ study on surface roughening in radiation-resistant Ag nanowires.
Metallic materials subjected to heavy ion irradiation experience significant radiation damage. Free surface is a type of effective defect sinks to improve the radiation resistance in metallic materials. However, the radiation resistance of metallic nanowires (NWs) is largely unknown. Here we show, via in situ Kr ion irradiations in a transmission electron microscope, Ag NWs exhibited much better radiation resistance than coarse-grained Ag. Irradiation-induced prominent surface roughening in Ag NWs provides direct evidence for interaction between defect clusters and free surface. Diameter dependent variation of the surface roughness in irradiated Ag NWs has also been observed. This study provides insight on mechanisms of enhanced radiation resistance via free surfaces in metallic NWs.


In or out? Barriers and facilitators to refugee-background young people accessing mental health services.
Refugee young people have been identified as a group with high risk for mental health problems, due to their experience of trauma, forced migration, and stressors associated with settlement. A high prevalence of mental health problems is reported in this group, however some research suggests refugee young people have low rates of mental health service access. There is little information available on barriers and facilitators to mental service delivery for this group. Using data from 15 focus groups and five key informant interviews with a total of 115 service providers from 12 agencies in Melbourne, Australia, this paper explores barriers and facilitators to engaging young people from refugee backgrounds with mental health services. Eight key themes emerged: cultural concepts of mental health, illness, and treatment; service accessibility; trust; working with interpreters; engaging family and community; the style and approach of mental health providers; advocacy; and continuity of care.


Restricted diet rescues rat enteric motor neurones from age related cell death.
Alone among autonomic neurones, enteric neurones are known to be vulnerable to age related cell death; over 50% may be lost in aging rodents. A previous study demonstrated unexpectedly that neurones of the myenteric plexus from rats fed a restricted diet appeared not to suffer from extensive cell death in contrast with previous studies of ad libitum fed animals. To compare myenteric neurone numbers in the ileum of young and aging male Sprague-Dawley rats fed either ad libitum or a restricted diet. Neurones were counted in whole mount preparations of rat ileum stained immunohistochemically for the pan-neuronal marker PGP9.5, for choline acetyltransferase, or for nitric oxide synthase, or with NADH or NADPH histochemistry. Neurone numbers in the rat myenteric plexus were substantially affected by the dietary regimen: ad libitum feeding (50-60 g per day of standard rat chow) resulted in the death of about 50% of myenteric neurones in 24 month Sprague-Dawley rats, while numbers were unchanged when the daily dietary intake was halved between the ages of six and 24 months. Animals fed a double restricted diet (15 g per day) showed no cell loss at 30 months, as well as the predicted increase in longevity. Neurone loss was largely complete by 16 months in ad libitum fed animals. Numbers of cholinergic (possibly motor) neurones, as demonstrated by choline acetyltransferase immunohistochemistry, were substantially reduced in ad libitum fed aging rats but not in animals fed a restricted diet. Loss of cholinergic neurones after ad libitum feeding was confirmed by reduced numbers of neurones of a size range matching that of cholinergic neurones. Ad libitum feeding of adult rats has adverse effects on the survival of myenteric neurones, neurone loss commencing before 16 months of age. Cholinergic neurones appear to be particularly vulnerable to the effects of diet. Restricting dietary intake from six months of age prevents neurone loss almost entirely up to 30 months of age in these rats.


Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors.
Numerous medications, including drugs prescribed for noncardiac indications, can lead to QT prolongation and trigger torsade de pointes. Although this complication occurs only rarely, it may have lethal consequences. It is therefore important to know if patients with torsade de pointes associated with noncardiac drugs have risk factors that are easy to identify. We reviewed reports of drug-induced torsade de pointes and analyzed each case of torsade de pointes associated with a noncardiac drug for the presence of risk factors for the long QT syndrome that can be easily identified from the medical history or clinical evaluation (female gender, heart disease, electrolyte disturbances, excessive dosing, drug interactions, and history of familial long QT syndrome). We identified 249 patients with torsade de pointes caused by noncardiac drugs. The most commonly identified risk factor was female gender (71%). Other risk factors were frequently present (18%-41%). Virtually all patients had at least 1 of these risk factors, and 71% of patients had 2 or more risk factors. Our study suggests that almost all patients with torsade de pointes secondary to noncardiac drugs have risk factors that can be easily identified from the medical history before the initiation of therapy with the culprit drug.


Children's reasoning with peers and parents about moral dilemmas.
Children encounter moral norms in several different social contexts. Often it is in hierarchically structured interactions with parents or other adults, but sometimes it is in more symmetrically structured interactions with peers. Our question was whether children's discussions of moral norms differ in these two contexts. Consequently, we had 4- and 6-year-old children (N = 72) reason about moral dilemmas with their mothers or peers. Both age groups opposed their partner's views and explicitly justified their own views more often with peers than with mothers. Mothers adapted their discussions to the cognitive levels of their children (e.g., focused more on the abstract moral norms with 6-year-old children than with 4-year-old children), but almost always with a pedagogical intent. Our results suggest that with mothers, moral judgments are experienced mostly as non-negotiable dictums, but with coequal peers they are experienced more as personal beliefs that can be actively negotiated. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Can genetic variability in α-tocopherol bioavailability explain the heterogeneous response to α-tocopherol supplements?
Both vitamin E (VE) consumption and blood VE status have been negatively associated with the incidence of degenerative diseases and some cancers. However, the response to VE supplementation is very variable among individuals. This could be due to interindividual variability in VE bioavailability, due, at least partly, to genetic variations in genes involved in VE metabolism. Thus, the main objective was to identify single nucleotide polymorphisms (SNPs) that may be involved in the interindividual variability in α-tocopherol (TOL) bioavailability. The postprandial chylomicron (CM) TOL response (area under the curve of the postprandial CM TOL concentration) to a TOL-rich meal was highly variable (coefficient of variation=81%; n=38). This response was positively correlated with the fasting plasma TOL concentration (r=0.5, p=0.004). A significant (p=1.8×10(-8)) partial least-squares regression model, which included 28 SNPs in 11 genes, explained 82% of this response. First evidence that the interindividual variability in TOL bioavailability is, at least partly, modulated by a combination of SNPs. TOL bioavailability is, at least partly, modulated by genetic variations that can affect long-term TOL status. This allows us to propose a new hypothesis that links the biological response to VE supplementation with one's individual genetic characteristics.


Efficient and robust reforming catalyst in severe reaction conditions by nanoprecursor reduction in confined space.
The in situ autocombustion synthesis route is shown to be an easy and efficient way to produce nanoscaled nickel oxide containing lanthanum-doped mesoporous silica composite. Through this approach, ~3 nm NiO particles homogeneously dispersed in the pores of silica are obtained, while lanthanum is observed to cover the surface of the silica pore wall. Subsequent reduction of such composite precursors under hydrogen generates Ni(0) nanoparticles of a comparable size. Control over the size and size distribution of metallic nanoparticles clearly improved catalytic activity in the methane dry reforming reaction. In addition, these composite materials exhibit excellent stability under severe reaction conditions. This was achieved through the presence of LaOx species, which reduced active-site carbon poisoning, and the confinement effect of the mesoporous support, which reduced metallic particle sintering.


Knee injury patterns in young irish dancers.
To characterize knee injury patterns in Irish dancers. A retrospective chart review was performed for Irish dancers under age 19 who presented with knee injuries to the sports medicine or orthopedic clinic from January 1, 2000 to December 31, 2010. Data were collected on all knee injuries partially or directly related to Irish dance. Injury was defined as dance-related pain or damage to the structures in the knee that resulted in evaluation in the clinic. Survey data were collected to determine the number of different schools/studios represented by the dancers in the study. Sixty-seven Irish dancers with 86 knee injuries were evaluated. Half (50.7%) of these patients received more than one diagnosis during these visits. Overuse injuries accounted for 90.7% of knee injuries. Time to presentation ranged from less than 1 week to over 1 year. There was a significant difference in time to presentation, with traumatic injuries being evaluated sooner than overuse injuries. The most common diagnoses, accounting for 53.5% of injuries, were patellar tracking disorders, including patellofemoral syndrome, hypermobile patella, and patellar subluxation. In Irish dance overuse injuries represent the great majority of knee injuries, and patellofemoral tracking disorders are the most common diagnosis. For many dancers, there is often a delay of weeks to months between the onset of symptoms and evaluation in clinic. Prevention programs could potentially eliminate a large portion of knee pain experienced by young Irish dancers.


Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.
Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day). A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100). In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P < 0.001), but with negligible differences between these 2 treatments. The mean between-treatment difference was -0.1 for general fatigue (the primary outcome measure), 0.0 for physical fatigue, 0.0 for mental fatigue, 0.0 for reduced motivation, 0.3 for reduced activity, and 2.2 for the fatigue VAS. None of these differences was statistically significant. Similar to earlier results using pharmacologic doses, substitution treatment with 50 mg of DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.


Case-Based Understanding of the Role of the Scapula in Common Shoulder Pathologies.
Scapular dyskinesis is an extremely common component of shoulder pathology, especially in the overhead athlete; despite its prevalence, proper diagnosis and management of scapular disorders remains an enigma for many clinicians. An understanding of the contribution of the scapula to pathomechanics and clinical symptoms is necessary to optimize both surgical and nonsurgical treatment of shoulder disorders. Without correction of scapular dysfunction, even effective management of the pathoanatomy is unlikely to produce optimal results. It is important to examine the role of the scapula in common shoulder pathologies and elucidate a case-based treatment strategy for both surgical and nonsurgical shoulder disorders.


Understanding improved electrochemical properties of NiO-doped NiF2-C composite conversion materials by X-ray absorption spectroscopy and pair distribution function analysis.
The conversion reactions of pure NiF2 and the NiO-doped NiF2-C composite (NiO-NiF2-C) were investigated using X-ray absorption spectroscopy (XAS) and pair distribution function (PDF) analysis. The enhanced electronic conductivity of NiO-NiF2-C is associated with a significant improvement in the reversibility of the conversion reaction compared to pure NiF2. Different evolutions of the size distributions of the Ni nanoparticles formed during discharge were observed. While a bimodal nanoparticle size distribution was maintained for NiO-NiF2-C following the 1st and 2nd discharge, for pure NiF2 only smaller nanoparticles (∼14 Å) remained following the 2nd discharge. We postulate that the solid electrolyte interphase formed upon the 1st discharge at large overpotential retards the growth of metallic Ni leading to formation of smaller Ni particles during the 2nd discharge. In contrast, the NiO doping and the carbon layer covering the NiO-NiF2-C possibly facilitate the conversion process on the surface preserving the reaction kinetics upon the 2nd discharge. Based on the electronic conductivity and surface properties, the resulting size of the Ni nanoparticles is associated with the conversion kinetics and consequently the cyclability.


Protection against adverse biological effects induced by space radiation by the Bowman-Birk inhibitor and antioxidants.
This study was undertaken to evaluate the protective effects of the soybean-derived Bowman-Birk inhibitor (BBI), BBI concentrate (BBIC) and/or antioxidants against the adverse biological effects induced by space radiation in cultured human epithelial cells. The effects of BBI, BBIC and a combination of ascorbic acid, co-enzyme Q10, L-selenomethionine (SeM) and vitamin E succinate on proton and HZE-particle [high-energy (high E) nuclei of heavier (high atomic number, Z) elements] radiation-induced cytotoxicity in MCF10 human breast epithelial cells and a phenotypic change associated with transformation in HTori-3 human thyroid epithelial cells were assessed with a clonogenic survival assay and a soft agar colony formation assay. The results demonstrate that BBIC and antioxidants are effective in protecting against space radiation-induced cytotoxicity in MCF10 cells and BBI, BBIC and antioxidants are effective in protecting against a space radiation-induced phenotypic change associated with transformation of HTori-3 cells.


Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice.
Degenerative joint diseases such as osteoarthritis are characterised by aberrant region-specific bone formation and abnormal bone mineral content. A recent study suggested a role for the complement membrane attack complex in experimental models of osteoarthritis. Since CD59a is the principal regulator of the membrane attack complex in mice, we evaluated the impact of CD59a gene deletion upon maintenance of bone architecture. In vivo bone morphology analysis revealed that male CD59a-deficient mice have increased femur length and cortical bone volume, albeit with reduced bone mineral density. However, this phenomenon was not observed in female mice. Histomorphometric analysis of the trabecular bone showed increased rates of bone homeostasis, with both increased bone resorption and mineral apposition rate in CD59a-deficient male mice. When bone cells were studied in isolation, in vitro osteoclastogenesis was significantly increased in male CD59a-deficient mice, although osteoblast formation was not altered. Our data reveal, for the first time, that CD59a is a regulator of bone growth and homeostasis. CD59a ablation in male mice results in longer and wider bones, but with less density, which is likely a major contributing factor for their susceptibility to osteoarthritis. These findings increase our understanding of the role of complement regulation in degenerative arthritis.


Granularity of SERPINA1 alleles by DNA sequencing in CanCOLD.
DNA sequencing of the SERPINA1 gene to detect α1-antitrypsin (AAT) deficiency (AATD) may provide a better appreciation of the individual and cumulative impact of genetic variants on AAT serum levels and COPD phenotypes.AAT serum level and DNA sequencing of the coding regions of SERPINA1 were performed in 1359 participants of the Canadian Cohort Obstructive Lung Disease (CanCOLD) study. Clinical assessment for COPD included questionnaires, pulmonary function testing and computed tomography (CT) imaging. Phenotypes were tested for association with SERPINA1 genotypes collated into four groups: normal (MM), mild (MS and MI), intermediate (heterozygote MZ, non-S/non-Z/non-I, compound IS, and homozygote SS) and severe (ZZ and SZ) deficiency. Smoking strata and MZ-only analyses were also performed.34 genetic variants were identified including 25 missense mutations. Overall, 8.1% of alleles in this Canadian cohort were deficient and 15.5% of 1359 individuals were carriers of at least one deficient allele. Four AATD subjects were identified and had statistically lower diffusion capacity and greater CT-based emphysema. No COPD phenotypes were associated with mild and intermediate AATD in the overall cohort or stratified by smoking status. MZ heterozygotes had similar CT-based emphysema, but lowered diffusion capacity compared with normal and mild deficiency.In this Canadian population-based cohort, comprehensive genetic testing for AATD reveals a variety of deficient alleles affecting 15.5% of subjects. COPD phenotype was demonstrated in severe deficiency and MZ heterozygotes. This study shows the feasibility of implementing a diagnostic test for AATD using DNA sequencing in a large cohort.


Using Purely Sinusoidal Voltammetry for Rapid Inference of Surface-Confined Electrochemical Reaction Parameters.
Alternating current (AC) voltammetric techniques are experimentally powerful as they enable Faradaic current to be isolated from non-Faradaic contributions. Finding the best global fit between experimental voltammetric data and simulations based on reaction models requires searching a substantial parameter space at high resolution. In this paper, we estimate parameters from purely sinusoidal voltammetry (PSV) experiments, investigating the redox reactions of a surface-confined ferrocene derivative. The advantage of PSV is that a complete experiment can be simulated relatively rapidly, compared to other AC voltammetric techniques. In one example involving thermodynamic dispersion, a PSV parameter inference effort requiring 7,500,000 simulations was completed in 7 h, whereas the same process for our previously used technique, ramped Fourier transform AC voltammetry (ramped FTACV), would have taken 4 days. Using both synthetic and experimental data with a surface confined diazonium substituted ferrocene derivative, it is shown that the PSV technique can be used to recover the key chemical and physical parameters. By applying techniques from Bayesian inference and Markov chain Monte Carlo methods, the confidence, distribution, and degree of correlation of the recovered parameters was visualized and quantified.


A system for ultrasonic beacon-guidance of catheters and other minimally-invasive medical devices.
Catheters and other interventional medical devices are presently guided by X-ray imaging, despite the advantages of ultrasound imaging over X-ray imaging in cost, safety, and availability. X-ray imaging is used because ultrasound reflects specularly from catheters and similar devices; their visibility is highly angle-dependent. With an omni-directional receiver mounted on a device, the receiver's location in the ultrasound image can be deduced from knowing which acoustic ray struck the receiver and the time from transmission of the imaging pulse to its reception by the receiver. This information is independent of specular reflection. The location of the device can then be indicated in the ultrasound image by an arrow pointing to the sensor, making possible ultrasound guidance of these devices. This paper describes the technical and practical considerations in the design and construction of the device-mounted receiver and associated electronics, and describes some clinical uses.


Late recanalization of basilar artery occlusion in a previously healthy 17-month-old child.
Endovascular treatment of acute ischemic stroke in children is increasingly being reported, although the time window for intervention is unclear. We describe a previously healthy 17-month-old child who presented with vertebral artery thrombosis and cerebellar stroke requiring posterior fossa decompression. She later progressed to basilar artery thrombosis treated with mechanical thrombectomy 50 hours after clinical decline. At 3 month follow-up, the patient had a modified Rankin Scale score of 0.


Rac1 recruits the adapter protein CMS/CD2AP to cell-cell contacts.
Rac1 is a member of the Rho family of small GTPases, which regulate cell adhesion and migration through their control of the actin cytoskeleton. Rho-GTPases are structurally very similar, with the exception of a hypervariable domain in the C terminus. Using peptide-based pulldown assays in combination with mass spectrometry, we previously showed that the hypervariable domain in Rac1 mediates specific protein-protein interactions. Most recently, we found that the Rac1 C terminus associates to the ubiquitously expressed adapter protein CMS/CD2AP. CD2AP is critical for the formation and maintenance of a specialized cell-cell contact between kidney podocyte foot processes, the slit diaphragm. Here, CD2AP links the cell adhesion protein nephrin to the actin cytoskeleton. In addition, CMS/CD2AP binds actin-regulating proteins, such as CAPZ and cortactin, and has been implicated in the internalization of growth factor receptors. We found that CD2AP specifically interacts with the C-terminal domain of Rac1 but not with that of other Rho family members. Efficient interaction between Rac1 and CD2AP requires both the proline-rich domain and the poly-basic region in the Rac1 C terminus, and at least two of the three N-terminal SH3 domains of CD2AP. CD2AP co-localizes with Rac1 to membrane ruffles, and small interfering RNA-based experiments showed that CD2AP links Rac1 to CAPZ and cortactin. Finally, expression of constitutive active Rac1 recruits CD2AP to cell-cell contacts in epithelial cells, where we found CD2AP to participate in the control of the epithelial barrier function. These data identify CD2AP as a novel Rac1-associated adapter protein that participates in the regulation of epithelial cell-cell contact.


Assessment of homology-based predictions in CASP5.
This report describes the assessment of the homology-based predictions submitted to the fifth edition of the Critical Assessment of Methods for Protein Structure Prediction (CASP5) experiment. We assessed the ability of the methods to predict the overall fold, the portions of the structure that differ substantially between the target protein and its closest structural homologue and the conformation of the side-chains. We also compared the results with those obtained in previous editions of the experiment and derived some general conclusions about the state of the art of comparative modeling methods and their usefulness for experimentalists.


The use of traditional medicine in maternity care among African women in Africa and the diaspora: a systematic review.
There is a paucity of literature describing traditional health practices and beliefs of African women. The purpose of this study was to undertake a systematic review of the use of traditional medicine (TM) to address maternal and reproductive health complaints and wellbeing by African women in Africa and the diaspora. A literature search of published articles, grey literature and unpublished studies was conducted using eight medical and social science databases (CINAHL, EMBASE, Infomit, Ovid Medline, ProQuest, PsychINFO, PubMed and SCOPUS) from the inception of each database until 31 December 2016. Critical appraisal was conducted using a quality assessment tool (QAT). A total of 20 studies conducted in 12 African countries representing 11,858 women were included. No literature was found on African women in the diaspora related to maternal use of TM or complementary and alternative medicine (CAM). The prevalence of TM use among the African women was as high as 80%. The most common TM used was herbal medicine for reasons related to treatment of pregnancy related symptoms. Frequent TM users were pregnant women with no formal education, low income, and living far from public health facilities. Lack of access to the mainstream maternity care was the major determining factor for use of TM. TM is widely used by African women for maternal and reproductive health issues due to lack of access to the mainstream maternity care. Further research is required to examine the various types of traditional and cultural health practices (other than herbal medicine), the beliefs towards TM, and the health seeking behaviors of African women in Africa and the diaspora.


Body Weight Satisfaction, Comments, Nutrition and Injury Risk in 489 Adolescent Elite Athletes.
Exposure to critical body weight comments in youth athletes could lead to decreased self-esteem, affect body image, and increase the risk of eating disorders and cause depressive symptoms. The aim was to explore differences between sex, body mass index, sports type, with regards to body weight satisfaction, exposure to critical body weight comments from their coach and nutrition status in adolescent elite athletes. A questionnaire about body weight, critical body weight comments and nutrition was distributed to 489 adolescent elite athletes and injury prevalence was monitored across 20 weeks. The results showed that almost one in four athletes (n=116, 24%) was not satisfied with their weight and 12% (n=59) had received critical body weight comments from their coach. Of the athletes who were unsatisfied with their body weight (n=116), 47% wanted to lose weight (n=55). A significant (p<0.05) higher proportion of ice hockey players and swimmers used nutritional supplements, were unsatisfied with their body weight, and were more exposed to critical body weight comments compared to athletes from other sports. Adolescent elite athletes as young as 15-16 years old are exposed to critical body weight comments from their coach and experience challenges with body weight satisfaction that is partly dependent on the sport-specific context.


[Protective effects of puerarin on lens epithelial cells in rat diabetic cataract].
The therapeutic effects of general and local applications of puerarin in the treatment of streptozotocin (STZ)-induced rat diabetic model were compared. Experimental research. We equally divided normal Sprague-Dawley (SD) rats into a STZ group, a peritoneal injection group, a peribulbar injection group and a control group. STZ, peritoneal injection and peribulbar injection groups were first treated with STZ. Subsequently, the STZ group was injected with normal saline intraperitoneally, while in the later two groups puerarin was injected through peritoneal and peribular routes, respectively. Control group only received peritoneal injection of saline. The morphology of lens epithelial cells (LEC) and their subcellular structure were examined by bright-field microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) 20, 40 and 60 days after the injection. Nitrogen oxide (NO) and nitric oxide synthase (NOS) were measured by biochemistry methods. Finally, inducible nitric oxide synthase (iNOS) protein and mRNA levels were monitored by Western blot and RT-PCR, respectively. Data was processed with two factorial experiment analysis of variance. Twenty to sixty days after the injection, marked or complete lens opacities appeared in the STZ group, whereas only slight opacities appeared in the lens in peritoneal and peribulbar puerarin groups and the lens in the control group remained clear. At the 20th, 40th and 60th day after the injection, optical microscope detected pathological changes of LEC in the STZ group. The cell volume was decreased with a dense nucleus and many bubbles appeared around the equator area. Under TEM, enlargement of cell gap, vacuoles in the cytoplasm, swelling of mitochondria and unclear structure of rough endoplasmic reticulum appeared in the LEC of the STZ group. Part of the nucleus was in karyopyknosis and peripheral nucleus gap was enlargement. Under SEM, normal fiber conjunction structure of the lens disappeared, fibers were swelling, part of fiber membranes were discontinuous, detached, and accumulated in certain areas. Mild lens opacities detected by bright-field microscope were developed in peritoneal and peribulbar puerarin injection groups. Nucleus and fibers in the lens cells of both groups appeared to be normal, with minor swelling of mitochondria, minor enlargement of endoplasmic reticulum and slight increase of intracellular space. NO, NOS and iNOS protein and mRNA of the lens were increased and up-regulated in STZ group. In the other two groups only minor changes were present and the changes were significantly less than that of the STZ group but greater than that in the control group. Peritoneal and peribulbar injection of puerarin have similar therapeutic effects in the treatment of rat diabetic cataract.


Nucleotide sequence and transcriptional activity of the caprine arthritis-encephalitis virus long terminal repeat.
Caprine arthritis-encephalitis virus (CAEV) and visna virus are pathogenic lentiviruses of goats and sheep which share morphologic features and sequence homology with human T-cell lymphotropic virus type III (HTLV-III), the etiologic agent of the acquired immune deficiency syndrome. The nucleotide sequence of the CAEV long terminal repeat (LTR) was determined, and it was found to be 450 base pairs long, with U3, R, and U5 regions of 287, 85, and 78 base pairs, respectively. Portions of the CAEV LTR are closely homologous to analogous regions of visna virus. The CAEV LTR is not significantly homologous with the HTLV-III LTR; however, like HTLV-III, visna virus, and equine infectious anemia virus, CAEV uses tRNA lysine as a primer for reverse transcription. The transcriptional activity of the CAEV and visna virus LTRs was measured by a chloramphenicol acetyltransferase assay, and the activity of the visna virus LTR was generally higher in a variety of uninfected cell types. Infection of cells with visna virus markedly increased gene expression directed by either the CAEV or visna virus LTR, but in contrast, infection of cells with CAEV had little effect on the activity of either LTR. The lack of trans-activation by CAEV, a virus which causes debilitating arthritis and encephalitis in goats, suggests that trans-activation may not be a general property of pathogenic lentiviruses.


Functional replacement of ferredoxin by a cyanobacterial flavodoxin in tobacco confers broad-range stress tolerance.
Chloroplast ferredoxin (Fd) plays a pivotal role in plant cell metabolism by delivering reducing equivalents to various essential oxidoreductive pathways. Fd levels decrease under adverse environmental conditions in many microorganisms, including cyanobacteria, which share a common ancestor with chloroplasts. Conversely, stress situations induce the synthesis of flavodoxin (Fld), an electron carrier flavoprotein not found in plants, which can efficiently replace Fd in most electron transfer processes. We report here that chloroplast Fd also declined in plants exposed to oxidants or stress conditions. A purified cyanobacterial Fld was able to mediate plant Fd-dependent reactions in vitro, including NADP+ and thioredoxin reduction. Tobacco (Nicotiana tabacum) plants expressing Fld in chloroplasts displayed increased tolerance to multiple sources of stress, including redox-cycling herbicides, extreme temperatures, high irradiation, water deficit, and UV radiation. Oxidant buildup and oxidative inactivation of thioredoxin-dependent plastidic enzymes were decreased in stressed plants expressing plastid-targeted Fld, suggesting that development of the tolerant phenotype relied on productive interaction of this flavoprotein with Fd-dependent oxidoreductive pathways of the host, most remarkably, thioredoxin reduction. The use of Fld provides new tools to investigate the requirements of photosynthesis in planta and to increase plant stress tolerance based on the introduction of a cyanobacterial product that is free from endogenous regulation in higher plants.


Infantile acne: a retrospective study of 16 cases.
Infantile acne is a rare and poorly understood disorder. The objective of this study was to improve our knowledge about the epidemiology and clinical course of infantile acne, and evaluate approaches to treatment. This two-center retrospective study covered the period between 1985 and 2007. Inclusion criteria were: (i) age less than 24 months when lesions appeared; (ii) presence of both inflammatory and noninflammatory lesions; (iii) persistence of lesions for at least 2 months. The data were drawn from clinical and photographic records, followed by administration of a telephone questionnaire to parents. It was proposed that each case be reviewed on the basis of the child's appearance and score on an acne scar clinical grading scale. Sixteen children were included. Nine had a family history of severe adolescent acne. The average duration of disease was 22 months. Two patients had been effectively treated with oral isotretinoin. More than half of the patients exhibited scars. We re-examined five children (average acne scar clinical grading scale score = 12/540). On the basis of the frequency of scarring, and the severity and average duration of lesions, the use of oral retinoids in severe infantile acne warrants evaluation.


Salmonella typhimurium LT2 catabolizes propionate via the 2-methylcitric acid cycle.
We previously identified the prpBCDE operon, which encodes catabolic functions required for propionate catabolism in Salmonella typhimurium. Results from (13)C-labeling experiments have identified the route of propionate breakdown and determined the biochemical role of each Prp enzyme in this pathway. The identification of catabolites accumulating in wild-type and mutant strains was consistent with propionate breakdown through the 2-methylcitric acid cycle. Our experiments demonstrate that the alpha-carbon of propionate is oxidized to yield pyruvate. The reactions are catalyzed by propionyl coenzyme A (propionyl-CoA) synthetase (PrpE), 2-methylcitrate synthase (PrpC), 2-methylcitrate dehydratase (probably PrpD), 2-methylisocitrate hydratase (probably PrpD), and 2-methylisocitrate lyase (PrpB). In support of this conclusion, the PrpC enzyme was purified to homogeneity and shown to have 2-methylcitrate synthase activity in vitro. (1)H nuclear magnetic resonance spectroscopy and negative-ion electrospray ionization mass spectrometry identified 2-methylcitrate as the product of the PrpC reaction. Although PrpC could use acetyl-CoA as a substrate to synthesize citrate, kinetic analysis demonstrated that propionyl-CoA is the preferred substrate.


Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome.
Barth syndrome (BTHS) is a life-threatening genetic disorder with unknown pathogenicity caused by mutations in TAFAZZIN (TAZ) that affect remodeling of mitochondrial cardiolipin (CL). TAZ deficiency leads to accumulation of mono-lyso-CL (MLCL), which forms a peroxidase complex with cytochrome c (cyt c) capable of oxidizing polyunsaturated fatty acid-containing lipids. We hypothesized that accumulation of MLCL facilitates formation of anomalous MLCL-cyt c peroxidase complexes and peroxidation of polyunsaturated fatty acid phospholipids as the primary BTHS pathogenic mechanism. Using genetic, biochemical/biophysical, redox lipidomic and computational approaches, we reveal mechanisms of peroxidase-competent MLCL-cyt c complexation and increased phospholipid peroxidation in different TAZ-deficient cells and animal models and in pre-transplant biopsies from hearts of patients with BTHS. A specific mitochondria-targeted anti-peroxidase agent inhibited MLCL-cyt c peroxidase activity, prevented phospholipid peroxidation, improved mitochondrial respiration of TAZ-deficient C2C12 myoblasts and restored exercise endurance in a BTHS Drosophila model. Targeting MLCL-cyt c peroxidase offers therapeutic approaches to BTHS treatment.


Patterns of condom use among men who have sex with men in China: a systematic review and meta-analysis.
HIV is rapidly spreading among men who have sex with men (MSM) in China. We estimate and compare rates of condom use among MSM in different regions of China through a systematic literature review. Meta-analyses were conducted over a final set of 66 studies to estimate national and regional condom use rates among MSM with different types of male sex partners. Country-wide, there has been a modest increase in reported condom use at last sex among MSM, from 56.1% (95% CI: 53.4-58.7%) in 2003-2005 to 61.6% (95% CI: 58.4-64.8%) in 2006-2008. Consistent condom use has also increased, from 32.5% (95% CI: 28.6-36.7%) in 2003-2005 to 36.3% (95% CI: 33.7-38.9%) in 2006-2008. Condom use was greatest and increasing among commercial sex partners, from 49.8 to 75.2% at last anal sex. Further condom promotion is still required to reduce the incidence of HIV infection among MSM in China.


PFS Clustering Method.
This paper presents a method of cluster analysis based on a pseudo F-statistic (PFS) criterion function. It is designed to subdivide an ensemble into an optimal set of groups, where the number of groups is not specified and no ad hoc parameters are employed. Univariate and multivariate F-statistic and pseudo F-statistic consistency is displayed. Algorithms for feasible application of PFS are given. Results from simulations are utilized to demonstrate the capabilities of the PFS clustering method and to provide a comparative guide for other users.


The use of fibrin and poly(lactic-co-glycolic acid) hybrid scaffold for articular cartilage tissue engineering: an in vivo analysis.
Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid) (PLGA) hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2) solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG) analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG) in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.


Reconstructive Science in Orthopedic Oncology.
Limb salvage is widely practiced as standard of care in most cases of extremity bone sarcoma. Allograft and endoprosthesis reconstructions are the most widely utilized modalities for the reconstruction of large segment defects, however complication rates remain high. Aseptic loosening and infection remain the most common modes of failure. Implant integration, soft-tissue function, and infection prevention are crucial for implant longevity and function. Macro and micro alterations in implant design are reviewed in this manuscript. Tissue engineering principles using nanoparticles, cell-based, and biological augments have been utilized to develop implant coatings that improve osseointegration and decrease infection. Similar techniques have been used to improve the interaction between soft tissues and implants. Tissue engineered constructs (TEC) used in combination with, or in place of, traditional reconstructive techniques may represent the next major advancement in orthopaedic oncology reconstructive science, although preclinical results have yet to achieve durable translation to the bedside.


Mental Health Service Use and Psychopharmacological Treatment Following Psychotic Experiences in Preadolescence.
Psychotic experiences affect more than 10% of children and often co-occur with nonpsychotic mental disorders. However, longitudinal studies of the outcome of psychotic experiences based on unbiased information on mental health service use and psychotropic medications are scarce. The authors investigated whether psychotic experiences at ages 11-12 predicted a psychiatric diagnosis or treatment with psychotropic medications by ages 16-17. In a longitudinal register-based follow-up study of the Copenhagen Child Cohort 2000, a total of 1,632 children ages 11-12 were assessed for psychotic experiences in face-to-face interviews. The children were also assessed for mental disorders and IQ. National registries provided information on perinatal and sociodemographic characteristics, on psychiatric disorders diagnosed at child and adolescent mental health services, and on prescribed psychotropic medications through ages 16-17. Among children who had not been previously diagnosed, and after adjustment for sociodemographic and perinatal adversities and IQ, psychotic experiences at ages 11-12 predicted receiving a psychiatric diagnosis in child and adolescent mental health services before ages 16-17 (adjusted hazard ratio=3.13, 95% CI=1.93, 5.07). The risk was increased if the child met criteria for a co-occurring mental disorder (not diagnosed in mental health settings) at baseline compared with no psychotic experiences or diagnosis at baseline (adjusted hazard ratio=7.85, 95% CI=3.94, 15.63), but having psychotic experiences alone still marked a significantly increased risk of later psychiatric diagnoses (adjusted hazard ratio=2.76, 95% CI=1.48, 5.13). Similar patterns were found for treatment with psychotropic medications. Psychotic experiences in childhood predict mental health service use and use of psychotropic medications during adolescence. The study findings provide strong evidence that psychotic experiences in preadolescence index a transdiagnostic vulnerability for diagnosed psychopathology in adolescence.


Is the association of hypertension and panic disorder explained by clustering of autonomic panic symptoms in hypertensive patients?
Autonomic nervous system dysfunction may be implicated in the association of hypertension with panic attacks and panic disorder. We hypothesised that panic symptoms of autonomic origin are more common in attacks experienced by hypertensive than normotensive patients, that autonomic panic symptoms cluster together as a distinct factor, and that this factor is more prevalent in hypertensive patients with panic than in normotensives. We analysed all 346 structured questionnaires completed by primary care and hospital clinic patients who had reported experiencing full (n=287) or limited symptom panic attacks (n=59) (268 with hypertension, and 78 never having had hypertension). Frequency of sweating, flushes, and racing heart, symptoms selected prospectively as being most likely of autonomic origin, were compared between hypertensive and normotensive patients. Principal component analysis was performed with varimax orthogonal rotation. Using logistic regression, odds ratios were calculated for association of factor scores with hypertension. Sweating and flushes were significantly more common among hypertensive patients than normotensives (sweating; 65% v 46%, p=0.003, flushes; 55% v 40%, p=0.019). There was no significant difference between groups for frequency of racing heart nor any of the remaining panic symptoms analysed as secondary endpoints. Principal component analysis yielded four factors with eigenvalues >1.0. Factor 1 was dominated by autonomic symptoms, notably sweating and flushes, which had loadings of 0.68 and 0.61. On regression only this autonomic factor showed a significant association with hypertension, the odds ratio being 1.37 (95% C.I. 1.05 to 1.77, p=0.018). These findings support the possibility that autonomic dysfunction contributes to the association of hypertension with panic.


Sirtuin 1 and 7 mediate resveratrol-induced recovery from hyper-anxiety in high-fructose-fed prediabetic rats.
Hyperglycaemia in diabetes is either caused by reduced availability of insulin (type 1 diabetes, T1D) or insulin resistance to the cells (type 2 diabetes, T2D). In recent years, the prevalence of T2D has increased to an alarming proportion, encompassing 95 percent of the total diabetic burden, probably due to economy-driven changes in lifestyle. Recent epidemiological studies show comorbid depression, anxiety and related mental illness. To explore the molecular mechanisms underlying this comorbid conditions, we used Sprague-Dawley rats on high-fructose diet for 8 weeks to induce prediabetic condition. Rats with this metabolic syndrome also showed hyper-anxiety when they were subjected to anxiety-related behavioural assays. Rats were administered with resveratrol, an activator of sirtuins, and metformin, a standard antidiabetic drug, simultaneously with fructose. We observed that resveratrol was more effective in protecting from both the metabolic (prediabetic) and affective (anxiety) disorders than metformin. Molecular studies showed that recovery was associated with the upregulation of few nuclear sirtuins that act epigenetically - Sirt 1 and 7, which were significantly attenuated in the striatum of prediabetic rats. In conclusion, our study showed that hyper-anxiety associated with prediabetic condition is ameliorated by resveratrol through modulation of sirtuins, which is more or less similar to metformin.


The impact of temperature on insecticide toxicity against the malaria vectors Anopheles arabiensis and Anopheles funestus.
It is anticipated that malaria elimination efforts in Africa will be hampered by increasing resistance to the limited arsenal of insecticides approved for use in public health. However, insecticide susceptibility status of vector populations evaluated under standard insectary test conditions can give a false picture of the threat, as the thermal environment in which the insect and insecticide interact plays a significant role in insecticide toxicity. The effect of temperature on the expression of the standard WHO insecticide resistance phenotype was examined using Anopheles arabiensis and Anopheles funestus strains: a susceptible strain and the derived resistant strain, selected in the laboratory for resistance to DDT or pyrethroids. The susceptibility of mosquitoes to the pyrethroid deltamethrin or the carbamate bendiocarb was assessed at 18, 25 or 30 °C. The ability of the pyrethroid synergist piperonyl-butoxide (PBO) to restore pyrethroid susceptibility was also assessed at these temperatures. Temperature impacted the toxicity of deltamethrin and bendiocarb. Although the resistant An. funestus strain was uniformly resistant to deltamethrin across temperatures, increasing temperature increased the resistance of the susceptible An. arabiensis strain. Against susceptible An. funestus and resistant An. arabiensis females, deltamethrin exposure at temperatures both lower and higher than standard insectary conditions increased mortality. PBO exposure completely restored deltamethrin susceptibility at all temperatures. Bendiocarb displayed a consistently positive temperature coefficient against both susceptible and resistant An. funestus strains, with survival increasing as temperature increased. Environmental temperature has a marked effect on the efficacy of insecticides used in public health against important African malaria vectors. Caution must be exercised when drawing conclusions about a chemical's efficacy from laboratory assays performed at only one temperature, as phenotypic resistance can vary significantly even over a temperature range that could be experienced by mosquitoes in the field during a single day. Similarly, it might be inappropriate to assume equal efficacy of a control tool over a geographic area where local conditions vary drastically. Additional studies into the effects of temperature on the efficacy of insecticide-based interventions under field conditions are warranted.


Reusable Floating Spherical Hydrogel Evaporator for Solar Desalination with Salt Mitigation and Contaminant Elimination.
The generation of clean and drinkable fresh water from seawater and contaminated water holds great potential to mitigate water scarcity. Herein, a floating spherical hydrogel evaporator (SHE) is designed to achieve sunlight-driven desalination, self-salt cleaning, and removal of environmental contaminants. The spherical lightweight polystyrene is coated with a porous carbon-embedded sodium alginate/PVA/CMC photothermal hydrogel to generate a spherical hydrogel evaporator (SHE) that floats naturally. The SHE is very sensitive to the weight imbalance (500 mg) and can respond quickly to the accumulation of salt by rotation to the fresh evaporation surface, realizing excellent antisalt fouling performance. Remarkably, with energy localization by porous carbon, the spherical floating evaporator achieved a high evaporation rate of 2.65 kg m-2 h-1 with an evaporation efficiency of 98%. At the same time, SHE is also capable of adsorbing both organic contaminants and heavy metal ions through functional groups of the hydrogel, attaining 99% removal efficiency. Overall, this low-cost spherical floating evaporator may offer solution for eco-friendly and sustainable production of fresh water on a large scale.


The Nicotiana attenuata GLA1 lipase controls the accumulation of Phytophthora parasitica-induced oxylipins and defensive secondary metabolites.
Nicotiana attenuata plants silenced in the expression of GLYCEROLIPASE A1 (ir-gla1 plants) are compromised in the herbivore- and wound-induced accumulation of jasmonic acid (JA). However, these plants accumulate wild-type (WT) levels of JA and divinyl-ethers during Phytophthora parasitica infection. By profiling oxylipin-enriched fractions with targeted and untargeted liquid chromatography-tandem time-of-flight mass spectrometry approaches, we demonstrate that the accumulation of 9-hydroxy-10E,12Z-octadecadienoic acid (9-OH-18:2) and additional C18 and C19 oxylipins is reduced by ca. 20-fold in P. parasitica-infected ir-gla1 leaves compared with WT. This reduced accumulation of oxylipins was accompanied by a reduced accumulation of unsaturated free fatty acids and specific lysolipid species. Untargeted metabolic profiling of total leaf extracts showed that 87 metabolites accumulated differentially in leaves of P. parasitica-infected ir-gla1 plants with glycerolipids, hydroxylated-diterpene glycosides and phenylpropanoid derivatives accounting together for ca. 20% of these 87 metabolites. Thus, P. parasitica-induced oxylipins may participate in the regulation of metabolic changes during infection. Together, the results demonstrate that GLA1 plays a distinct role in the production of oxylipins during biotic stress responses, supplying substrates for 9-OH-18:2 and additional C18 and C19 oxylipin formation during P. parasitica infection, whereas supplying substrates for the biogenesis of JA during herbivory and mechanical wounding.


Top 10 research questions related to physical activity and cancer survivorship.
In the United States, there are more than 14 million cancer survivors. Many of these survivors have been treated with multimodal therapy including surgery, radiation therapy, chemotherapy, and targeted therapies. These therapies improve survival; however, they also cause acute and chronic side effects that can undermine health and quality of life. Physical activity (PA) and cancer survivorship is a rapidly growing field of inquiry that studies the role of PA in people diagnosed with cancer. In this article, we propose the following top 10 research questions for the field of PA and cancer survivorship: (1) Does PA reduce the risk for cancer recurrence and/or improve survival? (2) Does PA influence cancer treatment decisions, completion rates, and/or response? (3) What is the optimal PA prescription for cancer survivors? (4) What is the role of sedentary behavior in cancer survivorship? (5) What are the most effective PA behavior change interventions for cancer survivors? (6) Which cancer variables modify the PA response? (7) What are the safety issues concerning PA in cancer survivors? (8) Which specific cancer symptoms can be managed by PA? (9) Is there a role for PA in advanced cancer? And (10) How do we translate PA research into clinical and community oncology practice? The answers to these questions are critical not only for advancing the field of PA and cancer survivorship, but for improving the lives of the millions of cancer survivors every year who are diagnosed with cancer, going through treatments, recovering after treatments, or coping with advanced disease.


FIBTEM PLUS provides an improved thromboelastometry test for measurement of fibrin-based clot quality in cardiac surgery patients.
The viscoelastic functional fibrinogen (FF) and FIBTEM assays measure the contribution of fibrin to clot strength. Inhibition of platelet function is a necessary precondition for these tests to work. We investigated a novel test for measuring fibrin-based clotting, FIBTEM PLUS, in cardiac surgery and compared it with FF and FIBTEM. A prospective, observational study was performed which included 30 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Blood samples were drawn at the beginning of surgery (pre-CPB), approximately 20 minutes before weaning from CPB and 5 minutes after heparin neutralization. FF, FIBTEM, and FIBTEM PLUS tests were performed in duplicate for all blood samples. Additional coagulation parameters, including platelet count, plasma fibrinogen levels, factor XIII activity, and heparin concentration, were also recorded for each sample. At all time points, the lowest mean maximum clot firmness (MCF) was observed with FIBTEM PLUS, although a statistically significant difference between FIBTEM and FIBTEM PLUS was observed only at baseline (mean values 22 vs 19 mm, P = 0.01; FF value for comparison: 27.7 mm). FF maximum amplitude (MA) values were significantly higher than FIBTEM MCF and FIBTEM PLUS MCF pre-CPB, during CPB and after heparin neutralization (P ≤ 0.001 for FF MA versus FIBTEM MCF and for FF MA versus FIBTEM PLUS MCF at all time points). The difference between FIBTEM MCF and FIBTEM PLUS MCF correlated with platelet count (r = 0.46;P < 0.001), whereas differences between FF MA and FIBTEM MCF, or FF MA and FIBTEM PLUS MCF did not (r = -0.07, P = 0.51; r = 0.16, P = 0.12, respectively). Differences between the assays were unrelated to heparin levels, which decreased considerably after protamine administration compared with heparin levels recorded before weaning from CPB (decrease from 2.1 to 0.1 U/mL and from 2.8 to 0.2 U/mL for anti-factor IIa and anti-factor Xa, respectively). Agreement between duplicate measurements was similar with FIBTEM and FIBTEM PLUS assays and lower with FF. Significant positive correlations were found between MCF or MA and fibrinogen concentration (all P < 0.001); the highest correlation was with FIBTEM PLUS MCF (r = 0.70). The FIBTEM PLUS assay produces precise results. At baseline, it provides greater inhibition of platelets than FIBTEM, but there is no meaningful difference between FIBTEM PLUS and FIBTEM in patients with low platelet counts.


Interactions between vitamin D and IGF-I: from physiology to clinical practice.
The interplay between vitamin D and IGF-I is complex and occurs at both endocrine and paracrine/autocrine levels. Vitamin D has been shown to increase circulating IGF-I and IGFBP-3, with the consistent finding of a positive correlation between vitamin D and IGF-I serum values in population-based cohorts of healthy subjects. The modulation of IGF-I and IGFBP-3 concentrations by vitamin D may impact recombinant human (rh) GH dosing for the treatment of GHD. It might also underlie some of the extra-skeletal beneficial effects ascribed to vitamin D. On the other hand, IGF-I stimulates renal production of 1,25-dihydroxyvitamin D, which increases calcium and phosphate availability in the body and suppresses PTH secretion. This effect is responsible for an altered calcium-phosphate balance in uncontrolled acromegaly and might also account for the improvement in bone metabolism associated with rhGH treatment in patients with GHD. Data on the paracrine/autocrine vitamin D-IGF-I interactions are abundant, but mostly not linked to one another. As a result, it is not possible to draw a comprehensive picture of the physiological and/or pathological interrelations between vitamin D, IGF-I and IGF-binding proteins (IGFBP) in different tissues. A potential role of vitamin D action is related to its association with carcinogenesis, a paradigm being breast cancer. Current evidence indicates that, in breast tumours, vitamin D modulates the IGF-I/IGFBP ratio to decrease proliferation and increase apoptosis.


Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico.
Exposure to arsenic (As) concentrations in drinking water > 150 μg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk. We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008-2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine. After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 μg/L) and concentrations of total speciated urinary As (< 55.8 μg/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine. Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol. Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104-111; http://dx.doi.org/10.1289/ehp.1408742.


Effectiveness of a Critical Care Ultrasonography Course.
Widespread use of critical care ultrasonography (CCUS) for the management of patients in the ICU requires an effective training program. The effectiveness of national and regional CCUS training courses is not known. This study describes a national-level, simulation-based, 3-day CCUS training program and evaluates its effectiveness. Five consecutive CCUS courses, with a total of 363 people, were studied. The 3-day CCUS training program consisted of didactic lectures, ultrasonography interpretation sessions, and hands-on modules with live models. Thoracic, vascular, and abdominal ultrasonography were taught in addition to goal-directed echocardiography. Learners rotated between hands-on training and interpretation sessions. The teacher-to-learner ratio was 1:3 during hands-on training. Interpretation sessions were composed of interactive small groups that reviewed normal and abnormal ultrasonography images. Learners completed a video-based examination before and after completion of the courses. Hands-on image acquisition skills were tested at the completion of the course. Average scores on the pretest and posttest were 57% and 90%, respectively (P < .001). The average score on the hands-on test was 86%. Learners aged 20 to 39 years compared with learners ≥ 40 years old scored better on the pretest (64% vs 51%; P < 0.001), posttest (91% vs 88%; P < .010), and hands-on test (90% vs 82%; P < .001). Learners demonstrated a significant improvement in written test scores that assessed cognitive and image interpretation abilities. In addition, they demonstrated acquisition of practical skills as evidenced by high scores during hands-on testing. Further studies are needed to determine if a simulation-based CCUS course will translate into effective clinical practice and to measure the durability of training. This 3-day course is an effective method to train large groups of critical care clinicians in the skills requisite for CCUS (image acquisition and image interpretation).


Characterization of the Pinus massoniana transcriptional response to Bursaphelenchus xylophilus infection using suppression subtractive hybridization.
Pine wilt disease (PWD) caused by pine wood nematode (PWN), Bursaphelenchus xylophilus, is the most destructive diseases of pine and poses a threat of serious economic losses worldwide. Although several of the mechanisms involved in disease progression have been discovered, the molecular response of Pinus massoniana to PWN infection has not been explored. We constructed four subtractive suppression hybridization cDNA libraries by taking time-course samples from PWN-inoculated Masson pine trees. One-hundred forty-four significantly differentially expressed sequence tags (ESTs) were identified, and 124 high-quality sequences with transcriptional features were selected for gene ontology (GO) and individual gene analyses. There were marked differences in the types of transcripts, as well as in the timing and levels of transcript expression in the pine trees following PWN inoculation. Genes involved in signal transduction, transcription and translation and secondary metabolism were highly expressed after 24 h and 72 h, while stress response genes were highly expressed only after 72 h. Certain transcripts responding to PWN infection were discriminative; pathogenesis and cell wall-related genes were more abundant, while detoxification or redox process-related genes were less abundant. This study provides new insights into the molecular mechanisms that control the biochemical and physiological responses of pine trees to PWN infection, particularly during the initial stage of infection.


Growth of macrophages obtained from various sources.
Techniques to obtain macrophages from various sources of the mouse were reported. The following sources were included: peritoneal exudate, alveolar lavage, blood leucocytes, bone marrow, spleen, liver, lungs, lymph nodes, thymus, thyroid, heart muscle, kidney, and subcutaneous cover glass implants. Human blood macrophages were also included. Long-term cinemicrographic studies revealed sustained good growth of these macrophages. Cell multiplication was detected in all of these cultures except those obtained from the peritoneal exudate. Pure cultures of macrophages were obtained from blood of the mouse and human. Macrophages obtained from other sources were accompanied by some growth of fibroblasts. Methods to eliminate the fibroblasts in cultures were discussed.


Latent inhibition in the developing rat: an examination of context-specific effects.
Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.


A general method for fluorescent labeling of the N-termini of lanthipeptides and its application to visualize their cellular localization.
Labeling of natural products with biophysical probes has greatly contributed to investigations of their modes of action and has provided tools for visualization of their targets. A general challenge is the availability of a suitable functional group for chemoselective modification. We demonstrate here that an N-terminal ketone is readily introduced into various lanthipeptides by the generation of a cryptic N-terminal dehydro amino acid by the cognate biosynthetic enzymes. Spontaneous hydrolysis of the N-terminal enamines results in α-ketoamides that site-specifically react with an aminooxy-derivatized alkyne or fluorophore. The methodology was successfully applied to prochlorosins 1.7 and 2.8, as well as the lantibiotics lacticin 481, haloduracin α, and haloduracin β. The fluorescently modified lantibiotics were added to bacteria, and their cellular localization was visualized by confocal fluorescence microscopy. Lacticin 481 and haloduracin α localized predominantly at sites of new and old cell division as well as in punctate patterns along the long axis of rod-shaped bacilli, similar to the localization of lipid II. On the other hand, haloduracin β was localized nonspecifically in the absence of haloduracin α, but formed specific patterns when coadministered with haloduracin α. Using two-color labeling, colocalization of both components of the two-component lantibiotic haloduracin was demonstrated. These data with living cells supports a model in which the α component recognizes lipid II and then recruits the β-component.