Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.
Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28<r(2)<0.56) with variants that have previously been reported to affect risk for nicotine dependence and smoking related diseases in adults. The data suggests that an age-associated relationship underlies the association of SNPs in CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults.


Predictors of annual pharmaceutical costs in Australia for community-based individuals with, or at risk of, cardiovascular disease: analysis of Australian data from the REACH registry.
Cardiovascular disease (CVD) remains a leading cause of death across the world and poses a significant economic burden. Research regarding per-person use and cost of cardiovascular pharmaceuticals in Australia, as well as potential predictors of pharmaceutical costs in populations using the 'bottom up' costing approach, is limited. Previous studies have adopted 'top down' costing approaches and have been based largely on hypothetical examples and considered only inpatient settings. To determine the distribution of pharmaceutical costs (from a governmental perspective) related to each cardiovascular risk factor for individuals with, or at high risk of, CVD by analysing data for Australian participants enrolled in the Reduction of Atherothrombosis for Continued Health (REACH) Registry. 2873 participants were recruited for the REACH Registry through 273 general (primary care) practices in Australia. Included among data collected at baseline was a cardiovascular medicines review. Average weighted costs per person were estimated using Government-reimbursed prices (2007). Annual costs were stratified by sex, age, disease group and other co-morbidities. A multivariate linear regression model was utilized to reveal the predictors of the pharmaceutical costs. The average annual median cost of cardiovascular pharmaceuticals per person was Australian dollars ($A)1310. Use of lipid-lowering agents, non-aspirin (acetylsalicylic acid) antiplatelet agents and thiazolidinediones (glitazones) added significantly to the average annual per-person costs. The multivariate regression model showed that the predictors of annual pharmaceutical costs were dyslipidemia (beta coefficient value [marginal annual cost associated with a condition] $A691; p < 0.001), hypertension ($A346; p < 0.001), vascular disease ($A340; p < 0.001), diabetes mellitus ($A298; p < 0.001), and obesity ($A52; p = 0.03). The same predictors, together with sex, were shown to have an impact on the number of medicines used. Among community-based Australians with, or at risk of, CVD, independent drivers of annual cardiovascular pharmaceutical costs are dyslipidemia (which accounts for half of per-person costs), followed by hypertension, established CVD, and diabetes. Obesity also independently adds to the cost of cardiovascular pharmaceuticals in community-based Australians with, or at risk of, CVD.


Dissecting human T cell responses against Bordetella species.
To identify the minimal structures that may be important for the creation of a synthetic and/or recombinant vaccine against whooping cough, human T cell clones were obtained against Bordetella antigens. Cloned peripheral blood T lymphocytes from an immune donor were grown in IL-2 and tested for proliferation in response to inactivated Bordetella species (B. pertussis, B. parapertussis, and B. bronchiseptica) and mutants deficient for the expression of virulence-associated antigens. All the T cell clones obtained were CD4+8- and recognized specifically the Bordetella antigens when presented by autologous B cells. On the basis of the responsiveness to the whole inactivated bacteria, it was possible to cluster the 12 clones obtained into four groups with the following specificity: (1) filamentous hemagglutinin (FHA); (2) B. pertussis-specific antigens; (3) virulence-associated Bordetella-specific antigens; and (4) nonvirulence-associated Bordetella-specific antigens. Using two new B. pertussis deletion mutants, clone 6 (representative of cluster 1) was found to recognize the COOH terminus of FHA. Furthermore, three out of four clones of cluster 3 were specifically stimulated by the soluble 69-kD protein from the outer membrane of B. pertussis. Surprisingly, none of the twelve clones obtained by stimulation in vitro with whole inactivated bacteria recognized pertussis toxin (PT), which is believed to be the most important protein to be included in an acellular vaccine. However, when a new generation of clones was obtained using soluble PT as the in vitro stimulus, it was observed that 11 clones of this group recognized this antigen. Thus, PT does not seem to be the most representative antigen on the whole inactivated bacteria, although T cell memory against PT exists in a donor who had the disease several years ago.


Myelin associated inhibitors: a link between injury-induced and experience-dependent plasticity.
In the adult, both neurologic recovery and anatomical growth after a CNS injury are limited. Two classes of growth inhibitors, myelin associated inhibitors (MAIs) and extracellular matrix associated inhibitors, limit both functional recovery and anatomical rearrangements in animal models of spinal cord injury. Here we focus on how MAIs limit a wide spectrum of growth that includes regeneration, sprouting, and plasticity in both the intact and lesioned CNS. Three classic myelin associated inhibitors, Nogo-A, MAG, and OMgp, signal through their common receptors, Nogo-66 Receptor-1 (NgR1) and Paired-Immunoglobulin-like-Receptor-B (PirB), to regulate cytoskeletal dynamics and inhibit growth. Initially described as inhibitors of axonal regeneration, subsequent work has demonstrated that MAIs also limit activity and experience-dependent plasticity in the intact, adult CNS. MAIs therefore represent a point of convergence for plasticity that limits anatomical rearrangements regardless of the inciting stimulus, blurring the distinction between injury studies and more "basic" plasticity studies.


Soy isoflavones improve plasma lipids in normocholesterolemic, premenopausal women.
Soy consumption is known to reduce plasma total cholesterol and LDL cholesterol in hypercholesterolemic subjects, but the responsible soy components and the effects in normocholesterolemic subjects remain unclear. The effects of soy isoflavone consumption on plasma total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerol, apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) concentrations and on LDL peak particle diameter were examined in normocholesterolemic, premenopausal women. Thirteen healthy, normocholesterolemic, free-living, premenopausal female volunteers took part in this randomized, crossover-controlled trial. Each subject acted as her own control. Three soy isoflavone intakes (control: 10.0 +/- 1.1; low: 64.7 +/- 9.4; and high: 128.7 +/- 15.7 mg/d), provided as soy protein isolate, were consumed for 3 menstrual cycles each. Total cholesterol, HDL cholesterol, LDL cholesterol, and triacylglycerol were measured over the menstrual cycle. Apolipoprotein A-I, apolipoprotein B, lipoprotein(a), and LDL peak particle diameter were evaluated in the midluteal phase. Total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations changed significantly across menstrual cycle phases (P < 0.005). During specific phases of the cycle, the high-isoflavone diet lowered LDL cholesterol by 7.6-10.0% (P < 0.05), the ratio of total cholesterol to HDL cholesterol by 10.2% (P < 0.005), and the ratio of LDL to HDL cholesterol by 13.8% (P < 0.002). Isoflavones significantly improved the lipid profile across the menstrual cycle in normocholesterolemic, premenopausal women. Although of small magnitude, these effects could contribute to a lower risk of developing coronary heart disease in healthy people who consume soy over many years.


Which factors increase risk of malalignment of the hip-knee-ankle axis in TKA?
Computer navigation has improved accuracy and reduced the percentage of alignment outliers in TKA. However, the characteristics of outliers and the risk factors for limb malalignment after TKA are still unclear. We therefore addressed the following questions: (1) What is the incidence and characteristics of outliers for postoperative limb mechanical axis (hip-knee-ankle [HKA] angle outside the conventional 180° ± 3° range) and component alignment in TKA? And (2) what are the preoperative clinical or radiographic risk factors for limb mechanical axis malalignment in TKA? We retrospectively reviewed the clinical and radiographic records of 1500 computer-assisted TKAs to identify outliers for postoperative HKA axis and component alignment and determined risk factors for malalignment. Full-length hip-to-ankle and knee radiographs were used to measure preoperative HKA angle, femoral coronal bowing, joint divergence angle, tibial subluxation, and tibial bone loss and postoperative HKA angle and femoral and tibial component angle. The incidence of outliers for postoperative limb mechanical axis, femoral component alignment, and tibial component alignment was 7% (112 of 1500 TKAs), 7%, and 8%, respectively, with 70% of limbs placed in excessive varus and 30% in excessive valgus. Preoperative varus deformity of more than 20° and femoral bowing of more than 5° were associated with increased risk of placing the limb mechanical axis outside the acceptable ± 3° range after computer-assisted TKA. The presence of preoperative radiographic risk factors should alert the surgeon to increased chance of malalignment and every measure should be undertaken in such at-risk knees to ensure proper limb and component alignment and soft tissue balance.


Transport of probe particles in a polymer network: effects of probe size, network rigidity and probe-polymer interaction.
Fundamental understanding of the effect of microscopic parameters on the dynamics of probe particles in different complex environments has wide implications. Examples include diffusion of proteins in biological hydrogels, porous media, polymer matrix, etc. Here, we use extensive molecular dynamics simulations to investigate the dynamics of the probe particle in a polymer network on a diamond lattice, which provides substantial crowding to mimic the cellular environment. Our simulations show that the dynamics of the probe increasingly becomes restricted, non-Gaussian and subdiffusive on increasing the network rigidity, binding affinity and probe size. In addition, the velocity autocorrelation functions show negative dips owing to the viscoelasticity and caging due to the surrounding network. These observations go with the general experimental findings. Importantly, for a probe particle of size comparable to the mesh size, unrestricted motion engulfing large length scales has been observed. This happens with a more flexible polymer network, which is easily pushed by the bigger probe. On increasing the rigidity of the network, the bigger probe can not efficiently push the network and as a result the long tail disappears. Our study gives a general qualitative picture of the transport of probes in a gel-like medium, as encountered in different contexts.


Differential gene responses 3 days following infarction in the fetal and adolescent sheep heart.
There are critical molecular mechanisms that can be activated to induce myocardial repair, and in humans this is most efficient during fetal development. The timing of heart development in relation to birth and the size/electrophysiology of the heart are similar in humans and sheep, providing a model to investigate the repair capacity of the mammalian heart and how this can be applied to adult heart repair. Myocardial infarction was induced by ligation of the left anterior descending coronary artery in fetal (105 days gestation when cardiomyocytes are proliferative) and adolescent sheep (6 mo of age when all cardiomyocytes have switched to an adult phenotype). An ovine gene microarray was used to compare gene expression in sham and infarcted (remote, border and infarct areas) cardiac tissue from fetal and adolescent hearts. The gene response to myocardial infarction was less pronounced in fetal compared with adolescent sheep hearts and there were unique gene responses at each age. There were also region-specific changes in gene expression between each age, in the infarct tissue, tissue bordering the infarct, and tissue remote from the infarction. In total, there were 880 genes that responded to MI uniquely in the adolescent samples compared with 170 genes in the fetal response, as well as 742 overlap genes that showed concordant direction of change responses to infarction at both ages. In response to myocardial infarction, there were specific changes in genes within pathways of mitochondrial oxidation, muscle contraction, and hematopoietic cell lineages, suggesting that the control of energy utilization and immune function are critical for effective heart repair. The more restricted gene response in the fetus may be an important factor in its enhanced capacity for cardiac repair.


Antitumor activity of water extract of a mushroom, Inonotus obliquus, against HT-29 human colon cancer cells.
In the current study, it was demonstrated that the hot water extract of I. obliquus (IOWE) exerts inhibitory activity against the proliferation of human colon cancer cells (HT-29). The inhibitory effect of IOWE on the growth of HT-29 cancer cells was evaluated by treating cells with IOWE at concentrations of 0.25, 0.5 and 1.0 mg/mL for 24 or 48 h. The IOWE inhibited cell growth in a dose-dependent manner, and this inhibition was accompanied by apoptotic cell death. The maximum inhibitory effect (56%) was observed when IOWE was treated at a concentration of 1.0 mg/mL for 48 h. The apoptotic effect of IOWE on HT-29 cells was also confirmed by flow cytometric analysis. In addition, the apoptotic cell percentage was closely associated with down-regulation of Bcl-2 and up-regulation of Bax and caspase-3. The results suggest that IOWE would be useful as an antitumor agent via the induction of apoptosis and inhibition of the growth of cancer cells through up-regulation of the expression of proapoptotic proteins and down-regulation of antiapoptotic proteins.


Schizotypal traits and forearm motor control against self-other produced action in a bimanual unloading task.
The present study investigated the relation between schizotypy and motor control against self- or other-produced action. We used an unloading task to focus on the timing component of anticipatory motor control. In the task, a weight was removed from a participants' hand by the participants themselves or by an experimenter (voluntary versus imposed unloading). Postural disturbance at the removal timing was measured as an index of predictive function in motor control. We hypothesized that the postural disturbance in the voluntary unloading would be positively related to schizotypal traits; however, the results did not support this theory. The results showed almost zero correlation between the schizotypy scores and the postural disturbance in the voluntary unloading condition. In contrast, the schizotypy scores positively correlated with the postural disturbance in the imposed unloading condition. These findings were replicated across two participant groups and two schizotypy scales. Further analyses on subscales of the schizotypy questionnaire found moderate levels of positive correlation between each subscale for Cognitive-Perceptual and Disorganization factors and the disturbance. Accordingly, the present study did not support the idea that non-pathological individuals with high schizotypal traits have deficits in prediction of self-produced actions, at least for a temporal domain. Instead, the results suggested that individuals with high schizotypal traits, particularly for the positive and disorganization symptoms, are not good at responding to others-produced actions. The schizophrenic symptoms were discussed in terms of the failure in the processes executed after calculating prediction of sensory consequences and dysfunction in internal models for "other people".


Glial glucose fuels the neuronal pentose phosphate pathway for long-term memory.
Brain function relies almost solely on glucose as an energy substrate. The main model of brain metabolism proposes that glucose is taken up and converted into lactate by astrocytes to fuel the energy-demanding neuronal activity underlying plasticity and memory. Whether direct neuronal glucose uptake is required for memory formation remains elusive. We uncover, in Drosophila, a mechanism of glucose shuttling to neurons from cortex glia, an exclusively perisomatic glial subtype, upon formation of olfactory long-term memory (LTM). In vivo imaging reveals that, downstream of cholinergic activation of cortex glia, autocrine insulin signaling increases glucose concentration in glia. Glucose is then transferred from glia to the neuronal somata in the olfactory memory center to fuel the pentose phosphate pathway and allow LTM formation. In contrast, our results indicate that the increase in neuronal glucose metabolism, although crucial for LTM formation, is not routed to glycolysis.


Endocytotic formation of vesicles and other membranous structures induced by Ca2+ and axolemmal injury.
Vesicles and/or other membranous structures that form after axolemmal damage have recently been shown to repair (seal) the axolemma of various nerve axons. To determine the origin of such membranous structures, (1) we internally dialyzed isolated intact squid giant axons (GAs) and showed that elevation of intracellular Ca2+ >100 microM produced membranous structures similar to those in axons transected in Ca2+-containing physiological saline; (2) we exposed GA axoplasm to Ca2+-containing salines and observed that membranous structures did not form after removing the axolemma and glial sheath but did form in severed GAs after >99% of their axoplasm was removed by internal perfusion; (3) we examined transected GAs and crayfish medial giant axons (MGAs) with time-lapse confocal fluorescence microscopy and showed that many injury-induced vesicles formed by endocytosis of the axolemma; (4) we examined the cut ends of GAs and MGAs with electron microscopy and showed that most membranous structures were single-walled at short (5-15 min) post-transection times, whereas more were double- and multi-walled and of probable glial origin after longer (30-150 min) post-transection times; and (5) we examined differential interference contrast and confocal images and showed that large and small lesions evoked similar injury responses in which barriers to dye diffusion formed amid an accumulation of vesicles and other membranous structures. These and other data suggest that Ca2+ inflow at large or small axolemmal lesions induces various membranous structures (including endocytotic vesicles) of glial or axonal origin to form, accumulate, and interact with each other, preformed vesicles, and/or the axolemma to repair the axolemmal damage.


Pioglitazone prevents the increase in plasma ketone concentration associated with dapagliflozin in insulin-treated T2DM patients: Results from the Qatar Study.
Because of the unique mechanism of action of sodium-glucose co-transport inhibitors (SGLT2i), which is independent of insulin secretion and insulin action, members of this class of drugs effectively lower plasma glucose concentration when used in combination with all other antidiabetic agents, including insulin. Increased plasma ketone concentration has been reported in association with SGLT2i initiation, which, under certain clinical conditions, has developed into diabetic ketoacidosis. The daily insulin dose often is reduced at the time of initiating SGLT2i therapy in insulin-treated patients to avoid hypoglycaemia. However, reduction of insulin dose can increase the risk of ketoacidosis. In the present study, we examined the effect of the addition of dapagliflozin plus pioglitazone on plasma ketone concentration in insulin-treated T2DM patients and compared the results to the effect of dapagliflozin alone. A total of 18 poorly controlled, insulin-treated T2DM participants in the Qatar Study received dapagliflozin (10 mg) plus pioglitazone (30 mg), and 10 poorly controlled non-insulin-treated T2DM patients received dapagliflozin (10 mg) alone for 4 months. Dapagliflozin plus pioglitazone produced a robust decrease in HbA1c (-1.4%) and resulted in a 50% reduction in daily insulin dose, from 133 to 66 units, while dapagliflozin alone caused a 0.8% reduction in HbA1c. Dapagliflozin caused a four-fold increase in fasting plasma ketone concentration, while the combination of pioglitazone plus dapagliflozin was not associated with a significant increase (0.13 vs 0.15 mM) in plasma ketone concentration or in risk of hypoglycaemia. These results demonstrate that the addition of pioglitazone to dapagliflozin prevents the increase in plasma ketone concentration associated with SGLT2i therapy.


Morphometry and acetylcholinesterase activity of the myenteric neurons of the mouse colon in the chronic phase of experimental Trypanosoma cruzi infection.
The myenteric plexus of the proximal colon, midcolon, and distal colon was studied in mice chronically infected with the Y strain of Trypanosoma cruzi by means of histochemical methods for NADH-diaphorase and acetylcholinesterase (AChE) on whole mount preparations. Ganglia of infected mice displayed an irregular distribution, with neurons severely altered in form and were found side by side with slightly degenerated or morphologically normal ones. Significant reductions of at least 36% in the numbers of neurons were recorded in all regions of the colons of infected animals, especially in the distal colon where the neuron number decreased by more than 44%. Measurements of neuron size suggest that the neuronal destruction caused by T. cruzi affected the medium and large neurons. The small neurons apparently were not affected by the infection. The histochemical demonstration of AChE by the direct coloring copper ferrocyanide method showed that in the control animals, most of the neurons of the plexus displayed AChE activity in the cytoplasm although the neurons showed different reaction intensities. The AChE activity was also present, but at a lower intensity, in the myenteric plexus of the colons of infected animals. These results suggest that the T. cruzi infection affects some categories of neurons and implies that some particular enteric neurotransmitter systems could be affected and the potency of their action upon intestinal function consequently reduced.


The relationship between IQ, memory, executive function, and processing speed in recent-onset psychosis: 1-year stability and clinical outcome.
Studies commonly report poor performance in psychotic patients compared with controls on tasks testing a range of cognitive functions, but, because current IQ is often not matched between these groups, it is difficult to determine whether this represents a generalized deficit or specific abnormalities. Fifty-three first-episode psychosis patients and 53 healthy controls, one-to-one matched for sex, age, and full-scale current IQ, were compared on Wechsler Adult Intelligence Scale (WAIS) subtests representing indices of perceptual organization, verbal comprehension, processing speed, and working memory as well as other tests of executive function and episodic memory. The groups showed an equivalent pattern of performance on all WAIS subtests except digit symbol processing speed, on which the patients were significantly worse. Patients were also worse on measures where performance correlated with digit symbol score, namely working and verbal memory tasks. Standardized residual scores for each subtest were calculated for each patient using the difference between their actual subtest score and a predicted subtest score based on their full-scale IQ and the performance of controls. Scaled scores and residual scores were examined for relationships with clinical measures. Digit symbol-scaled score was significantly correlated with concurrent negative syndrome score at baseline, and digit symbol residual score significantly predicted residual negative symptoms at 1-year follow-up. In summary, our comparison of patients and controls precisely matched for IQ revealed that processing speed was attenuated in recent-onset schizophrenia, contributed significantly to working and episodic memory deficits, and was a prognostic factor for poor outcome at 1 year.


Hospital Malnutrition, a Call for Political Action: A Public Health and NutritionDay Perspective.
Disease-related malnutrition (DRM) is prevalent in hospitals and is associated with increased care needs, prolonged hospital stay, delayed rehabilitation and death. Nutrition care process related activities such as screening, assessment and treatment has been advocated by scientific societies and patient organizations but implementation is variable. We analysed the cross-sectional nutritionDay database for prevalence of nutrition risk factors, care processes and outcome for medical, surgical, long-term care and other patients (n = 153,470). In 59,126 medical patients included between 2006 and 2015 the prevalence of recent weight loss (45%), history of decreased eating (48%) and low actual eating (53%) was more prevalent than low BMI (8%). Each of these risk factors was associated with a large increase in 30 days hospital mortality. A similar pattern is found in all four patient groups. Nutrition care processes increase slightly with the presence of risk factors but are never done in more than 50% of the patients. Only a third of patients not eating in hospital receive oral nutritional supplements or artificial nutrition. We suggest that political action should be taken to raise awareness and formal education on all aspects related to DRM for all stakeholders, to create and support responsibilities within hospitals, and to create adequate reimbursement schemes. Collection of routine and benchmarking data is crucial to tackle DRM.


Snapshots of the Signaling Complex DesK:DesR in Different Functional States Using Rational Mutagenesis and X-ray Crystallography.
We have developed protocols to generate site-specific variants of the histidine-kinase DesK and its cognate response regulator DesR, conducive to trapping different signaling states of the proteins. Co-expression of both partners in E. coli, ensuring an excess of the regulator, was essential for soluble production of the DesK:DesR complexes and further purification. The 3D structures of the complex trapped in the phosphotransferase and in the phosphatase reaction steps, were solved by X-ray crystallography using molecular replacement. The solution was not trivial, and we found that in silico-generated models used as search probes, were instrumental to succeeding in placing a large portion of the complex in the asymmetric unit. Electron density maps were then clear enough to allow for manual model building attaining complete atomic models. These methods contribute to tackling a major challenge in the bacterial signaling field, namely obtaining stable kinase:regulator complexes, in distinct conformational states, amenable for high-resolution crystallographic studies.


Computational reconstruction of Bole1a, a representative synthetic hepatitis C virus subtype 1a genome.
Hepatitis C virus (HCV) research is hampered by the use of arbitrary representative isolates in cell culture and immunology. The most replicative isolate in vitro is a subtype 2a virus (JFH-1); however, genotype 1 is more prevalent worldwide and represents about 70% of infections in the United States, and genotypes differ from one another by 31% to 33% at the nucleotide level. For phylogenetic and immunologic analyses, viruses H77 and HCV-1 (both subtype 1a) are commonly used based on their historic importance. In an effort to rationally design a representative subtype 1a virus (Bole1a), we used Bayesian phylogenetics, ancestral sequence reconstruction, and covariance analysis on a curated set of 390 full-length human HCV 1a sequences from GenBank. By design, Bole1a contains variations present in widely circulating strains and matches more epitope-sized peptides in a full-genome comparison to subtype 1a isolates than any other sequence studied. Parallel analyses confirm that selected epitopes from the Bole1a genome were able to elicit a robust T cell response. In a proof of concept for infectivity, the envelope genes (E1 and E2) of Bole1a were expressed in an HIV pseudoparticle system containing HCV envelope genes and HIV nonenvelope genes with luciferase expression. The resulting Bole1a pseudoparticle robustly infected Hep3B cells. In this study, we demonstrate that a rationally designed, fully synthetic HCV genome contains representative epitopes and envelope genes that assemble properly and mediate entry into target cells.


Proline metabolism increases katG expression and oxidative stress resistance in Escherichia coli.
The oxidation of l-proline to glutamate in Gram-negative bacteria is catalyzed by the proline utilization A (PutA) flavoenzyme, which contains proline dehydrogenase (PRODH) and Δ(1)-pyrroline-5-carboxylate (P5C) dehydrogenase domains in a single polypeptide. Previous studies have suggested that aside from providing energy, proline metabolism influences oxidative stress resistance in different organisms. To explore this potential role and the mechanism, we characterized the oxidative stress resistance of wild-type and putA mutant strains of Escherichia coli. Initial stress assays revealed that the putA mutant strain was significantly more sensitive to oxidative stress than the parental wild-type strain. Expression of PutA in the putA mutant strain restored oxidative stress resistance, confirming that depletion of PutA was responsible for the oxidative stress phenotype. Treatment of wild-type cells with proline significantly increased hydroperoxidase I (encoded by katG) expression and activity. Furthermore, the ΔkatG strain failed to respond to proline, indicating a critical role for hydroperoxidase I in the mechanism of proline protection. The global regulator OxyR activates the expression of katG along with several other genes involved in oxidative stress defense. In addition to katG, proline increased the expression of grxA (glutaredoxin 1) and trxC (thioredoxin 2) of the OxyR regulon, implicating OxyR in proline protection. Proline oxidative metabolism was shown to generate hydrogen peroxide, indicating that proline increases oxidative stress tolerance in E. coli via a preadaptive effect involving endogenous hydrogen peroxide production and enhanced catalase-peroxidase activity.


Effects of Selenium and Melatonin on Ocular Ischemic Syndrome.
To determine the effects of selenium, melatonin, and selenium + melatonin administered for one month on anterior chamber (AC) malondialdehyde (MDA) and AC glutathione (GSH) levels in patients with ocular ischemic syndrome. Thirty-five patients were included in the study. Study groups were formed as follows: (1) control group, (2) ischemia group, (3) selenium + ischemia group, (4) melatonin + ischemia group, and (5) selenium + melatonin + ischemia group. AC samples were obtained. MDA and GSH levels in AC samples were evaluated. MDA levels were significantly increased in ischemia groups. Selenium and melatonin supplementation resulted in reduction of MDA levels and significant increase in GSH values. Increased lipid peroxidation associated with ischemia of the anterior segment has been prevented by selenium and melatonin supplementation. This trial is registered with ClinicalTrials.gov NCT04005222.


An Integrated Multiomics Approach to Identify Candidate Antigens for Serodiagnosis of Human Onchocerciasis.
Improved diagnostic methods are needed to support ongoing efforts to eliminate onchocerciasis (river blindness). This study used an integrated approach to identify adult female Onchocerca volvulus antigens that can be explored for developing serodiagnostic tests. The first step was to develop a detailed multi-omics database of all O. volvulus proteins deduced from the genome, gene transcription data for different stages of the parasite including eight individual female worms (providing gene expression information for 94.8% of all protein coding genes), and the adult female worm proteome (detecting 2126 proteins). Next, female worm proteins were purified with IgG antibodies from onchocerciasis patients and identified using LC-MS with a high-resolution hybrid quadrupole-time-of-flight mass spectrometer. A total of 241 immunoreactive proteins were identified among those bound by IgG from infected individuals but not IgG from uninfected controls. These included most of the major diagnostic antigens described over the past 25 years plus many new candidates. Proteins of interest were prioritized for further study based on a lack of conservation with orthologs in the human host and other helminthes, their expression pattern across the life cycle, and their consistent expression among individual female worms. Based on these criteria, we selected 33 proteins that should be carried forward for testing as serodiagnostic antigens to supplement existing diagnostic tools. These candidates, together with the extensive pan-omics dataset generated in this study are available to the community (http://nematode.net) to facilitate basic and translational research on onchocerciasis.


The evaluation of hypoxia-inducible factor 1 in N-nitro-L-arginine methyl ester preeclampsia model of pregnant rats.
The objective of the study was to evaluate hypoxia-inducible factor 1 (HIF-1), which plays a major role in the stimulation of angiogenesis in placental tissues, by using immunohistochemical staining in preeclampsia model of rats, developed by N-nitro-L-arginine methyl ester (L-NAME) METHODS: Thirty pregnant rats were randomized into 2 groups (n = 15 in each group) on day 10 of gestation. L-NAME was given to rats in the study group by gavage. On days 0, 10, and 20 of gestation, rats were weighted, and urine protein values and blood pressures were measured. Hypoxia-inducible factor 1 expressions were assessed with immunohistochemical staining by using avidin-biotin peroxidase via selecting preparation. Systolic and diastolic blood pressures and urine protein value of L-NAME group on day 20 of gestation were found to be significantly higher than those obtained on days 0 and 10 of gestation in the same group and those obtained on day 20 of gestation in the sham group (P < 0.05). Maternal weight, number of fetuses, and mean fetal weight of rats in L-NAME group on day 20 of gestation were found to be significantly lower than those obtained from rats in the sham group (P < 0.05). Regarding HIF-1 expression of placental tissues, mild immunohistochemical staining was found in 2 rats (13.4%) and moderate in 13 rats (86.6%) in the L-NAME group. A significant difference was found in terms of HIF-1 positivity in the maternal placentas of both groups (P < 0.05). L-NAME preeclampsia model of pregnant rats is consistent with human preeclampsia in terms of hypertension, proteinuria, and intrauterine growth retardation; in addition, it also shows evidence of placental hypoxia findings.


The innovation catalysts.
A few years ago the software development company Intuit realized that it needed a new approach to galvanizing customers. The company's Net Promoter Score was faltering, and customer recommendations of new products were especially disappointing. Intuit decided to hold a two-day, off-site meeting for the company's top 300 managers with a focus on the role of design in innovation. One of the days was dedicated to a program called Design for Delight. The centerpiece of the day was a PowerPoint presentation by Intuit founder Scott Cook, who realized midway through that he was no Steve Jobs: The managers listened dutifully, but there was little energy in the room. By contrast, a subsequent exercise in which the participants worked through a design challenge by creating prototypes, getting feedback, iterating, and refining, had them mesmerized. The eventual result was the creation of a team of nine design-thinking coaches--"innovation catalysts"--from across Intuit who were made available to help any work group create prototypes, run experiments, and learn from customers. The process includes a "painstorm" (to determine the customer's greatest pain point), a "soljam" (to generate and then winnow possible solutions), and a "code-jam" (to write code "good enough" to take to customers within two weeks). Design for Delight has enabled employees throughout Intuit to move from satisfying customers to delighting them.


Job satisfaction and associated variables among nurse assistants working in residential care.
While the work situation for nurse assistants in residential care is strenuous, they themselves often state that they are satisfied with their job. More knowledge is clearly needed of the interrelationship of variables associated with job satisfaction. This study aims to investigate job satisfaction and explore associated variables among nurse assistants working in residential care. A total of 225 respondents completed a questionnaire measuring general job satisfaction, satisfaction with nursing-care provision and measures concerning person-centered care, work climate, leadership, and health complaints. Job satisfaction was the outcome measure and comparisons were made among those reporting low, moderate, and high levels of job satisfaction; multiple regression analyses were used to explore associated variables. The caring climate and personalized care provision were associated with general job satisfaction. High levels of satisfaction with nursing-care provision were also associated with the general work climate, organizational and environmental support, and leadership. Low job satisfaction was mainly associated with health complaints. Nurse assistants working in a positive work climate, caring climate, with a positive attitude to their leaders, who receive organizational and environmental support, provide person-centered care and experience a higher degree of job satisfaction. It seems essential, however, to include both general and context-specific measures when investigating job satisfaction in this field as they reveal different aspects of the nurse assistant's work situation.


Two-photon microperimetry: sensitivity of human photoreceptors to infrared light.
Microperimetry is a subjective ophthalmologic test used to assess retinal function at various specific and focal locations of the visual field. Historically, visible light has been described as ranging from 400 to 720 nm. However, we previously demonstrated that infra-red light can initiate visual transduction in rod photoreceptors by a mechanism of two-photon absorption by visual pigments. Here we introduce a newly designed and constructed two-photon microperimeter. We provide for the first time evidence of the presence of a nonlinear process occurring in the human retina based on psychophysical tests using newly developed instrumentation. Since infra-red light penetrates the aged front of the eye better than visible light, it has the potential for improved functional diagnostics in patients with age-related visual disorders.


Identification of larval and adult Simulium yahense and Simulium sanctipauli based on species-specific enzyme markers and their distribution at different breeding habitats in Central Liberia.
Human-biting adults and late instar larvae of the Simulium damnosum complex from four ecologically different simuliid breeding habitats in the Firestone Rubber Plantation at Harbel, Liberia, were identified morphologically and the monthly species composition of each site was recorded. Samples of the predominant species found at each site were assayed electrophoretically for species-specific variants of phosphoglucomutase (PGM) and trehalase (TRE). Enzyme identifications of flies and larvae were compared with morphological identifications to determine the accuracy of field identifications relying upon morphological characters. Enzyme identifications confirmed the accuracy of over 98% of the adult female identifications. S. yahense was found to be the predominant human-biting species at each site over the 10 months of sampling, with S. sanctipauli comprising a small percentage of the biting fly population. Species-specific larval enzymes confirmed the accuracy of more than 96% of the larval identifications. S. yahense was the predominant larval species found in smaller, more shaded, cooler breeding waters, while S. sanctipauli predominated in the single large watercourse that was sampled. Normally allopatric, mixed populations of these two larval species were found to exist at all sites, but sympatry occurred primarily during the wet season months of May-October. Biting activity of S. sanctipauli was found to be greatest during wet season months, and generally reflected the increase of S. sanctipauli in the larval populations of habitats dominated by S. yahense. The low human-biting activity of S. sanctipauli at all sites and during times which fostered large populations of S. sanctipauli larvae may be an indication of this specie's zoophilic tendency. Circumstantial evidence of hybridization, the expression of PGM and TRE species-specific variants for both species, was found in adults and larvae morphologically identified as S. yahense. The frequency of this "hybrid" condition, based upon PGM and TRE, was calculated to be comparable to the frequency of hybridization as determined by larval chromosome inversions.


Chlorella pyrenoidosa supplementation reduces the risk of anemia, proteinuria and edema in pregnant women.
Pregnancy anemia and pregnancy-induced hypertension (PIH) are common and potentially dangerous disorder in human pregnancy, and nutritional status of pregnant women is one of the leading causes. Chlorella contains large quantities of folate, vitamin B-12 and iron, and can help improve anemia and hypertensive disorder. Our objective was to investigate the preventive effects of Chlorella supplement on pregnancy anemia and PIH in Japanese pregnant women. A total of 70 pregnant women were placed into the control group (n = 38) or the Chlorella group (n = 32). The subjects in the Chlorella group were supplemented daily from 12th-18th wk of gestation until delivery with 6 g of Chlorella supplement. The proportion of anemic (hemoglobin level < 11 g/dL) subjects in the Chlorella group were significantly lower compared with the control group at the second and third trimesters. Additionally, in the Chlorella group, the incidences of proteinuria and edema, signs of PIH, were significantly lower during the third trimester. These results suggest that Chlorella supplementation significantly reduces the risk of pregnancy associated anemia, proteinuria and edema. Chlorella supplement may be useful as a resource of natural folate, vitamin B-12 and iron for pregnant women.


A SNP resource for human chromosome 22: extracting dense clusters of SNPs from the genomic sequence.
The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR-RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]


Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis.
Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulating CD14+ monocytes from healthy volunteers (n = 54) and intensive care unit (ICU) patients (n = 76), of which n = 36 had sepsis. RNA sequencing of selected samples revealed that monocytes from septic ICU patients display a peculiar activation pattern, which resembles characteristic functional stages of monocyte-derived macrophages and is distinct from controls or non-sepsis ICU patients. Focusing on 55 highly variable genes selected for further investigation, arachidonate 5-lipoxygenase-activating protein (ALOX5AP) was highly upregulated in monocytes of ICU patients and only normalized during 7 days in the ICU in non-sepsis patients. Strikingly, low monocytic guanine nucleotide exchange factor 10-like protein (ARHGEF10L) mRNA expression was associated with the disease severity and mortality of ICU patients. Collectively, our comprehensive analysis of circulating monocytes in critically ill patients revealed a distinct activation pattern, particularly in ICU patients with sepsis. The association with disease severity, the longitudinal recovery or lack thereof during the ICU stay, and the association with prognosis indicate the clinical relevance of monocytic gene expression profiles during sepsis.


Causal-based property generalization.
A central question in cognitive research concerns how new properties are generalized to categories. This article introduces a model of how generalizations involve a process of causal inference in which people estimate the likely presence of the new property in individual category exemplars and then the prevalence of the property among all category members. Evidence in favor of this causal-based generalization (CBG) view included effects of an existing feature's base rate (Experiment 1), the direction of the causal relations (Experiments 2 and 4), the number of those relations (Experiment 3), and the distribution of features among category members (Experiments 4 and 5). The results provided no support for an alternative view that generalizations are promoted by the centrality of the to-be-generalized feature. However, there was evidence that a minority of participants based their judgments on simpler associative reasoning processes.


Psychiatric aspects of AIDS.
AIDS represents a major health problem not only in this country but throughout the world. As a devastating viral infection, its physical symptoms are well recognized. It is now becoming clear that emotional and behavioral symptoms are also major components of the disease. It has been recognized for some time that some of these psychiatric symptoms develop as the patient's emotional response to having a fatal disease; but, it is now also recognized that psychiatric symptoms can be primary manifestations of the illness. What is more, it has been demonstrated that these psychiatric symptoms can be the very first sign of the disease. Accordingly, the role of mental health professionals and psychiatric hospitals in caring for AIDS patients is taking on new significance and is likely to expand greatly.


Motion and emotion: depression reduces psychomotor performance and alters affective movements in caregiving interactions.
Impaired social functioning is a well-established feature of depression. Evidence to date suggests that disrupted processing of emotional cues may constitute part of this impairment. Beyond processing of emotional cues, fluent social interactions require that people physically move in synchronized, contingent ways. Disruptions to physical movements are a diagnostic feature of depression (psychomotor disturbance) but have not previously been assessed in the context of social functioning. Here we investigated the impact of psychomotor disturbance in depression on physical responsive behavior in both an experimental and observational setting. In Experiment 1, we examined motor disturbance in depression in response to salient emotional sounds, using a laboratory-based effortful motor task. In Experiment 2, we explored whether psychomotor disturbance was apparent in real-life social interactions. Using mother-infant interactions as a model affective social situation, we compared physical behaviors of mothers with and without postnatal depression (PND). We found impairments in precise, controlled psychomotor performance in adults with depression relative to healthy adults (Experiment 1). Despite this disruption, all adults showed enhanced performance following exposure to highly salient emotional cues (infant cries). Examining real-life interactions, we found differences in physical movements, namely reduced affective touching, in mothers with PND responding to their infants, compared to healthy mothers (Experiment 2). Together, these findings suggest that psychomotor disturbance may be an important feature of depression that can impair social functioning. Future work investigating whether improvements in physical movement in depression could have a positive impact on social interactions would be of much interest.


The role of the parietal lobe in visual extinction studied with transcranial magnetic stimulation.
Interhemispheric competition between homologous areas in the human brain is believed to be involved in a wide variety of human behaviors from motor activity to visual perception and particularly attention. For example, patients with lesions in the posterior parietal cortex are unable to selectively track objects in the contralesional side of visual space when targets are simultaneously present in the ipsilesional visual field, a form of visual extinction. Visual extinction may arise due to an imbalance in the normal interhemispheric competition. To directly assess the issue of reciprocal inhibition, we used fMRI to localize those brain regions active during attention-based visual tracking and then applied low-frequency repetitive transcranial magnetic stimulation over identified areas in the left and right intraparietal sulcus to asses the behavioral effects on visual tracking. We induced a severe impairment in visual tracking that was selective for conditions of simultaneous tracking in both visual fields. Our data show that the parietal lobe is essential for visual tracking and that the two hemispheres compete for attentional resources during tracking. Our results provide a neuronal basis for visual extinction in patients with parietal lobe damage.


Effect of diet composition on the determination of ash and moisture content in solid cattle manure using visible and near-infrared spectroscopy.
Visible and near-infrared (Vis-NIR, 350-2500 nm) diffuse reflection spectroscopy (DRS) models built from "as-collected" samples of solid cattle manure accurately predict concentrations of moisture and crude ash. Because different organic molecules emit different spectral signatures, variations in livestock diet composition may affect the predictive accuracy of these models. This study investigates how differences in livestock diet composition affect Vis-NIR DRS prediction of moisture and crude ash. Spectral signatures of solid manure samples (n = 216) from eighteen groups of cattle on six different diets were used to calibrate and validate partial least squares (PLS) regression models. Seven groups of PLS models were created and validated. In the first group, two-thirds of all samples were randomly selected as the calibration set and the remaining one-third were used for the validation set. In the remaining six groups, samples were grouped by livestock diet (ration). Each ration in turn was held out of calibrations and then used as a validation set. When predicting crude ash, the fully random calibration model produced a root mean square deviation (RMSD) of 2.5% on a dry basis (db), ratio of standard error of prediction to the root mean squared deviation (RPD) of 3.1, bias of 0.14% (db), and correlation coefficient r(2) of 0.90., When predicting moisture, an RMSD of 1.5% on a wet basis (wb), RPD of 4.3, bias of -0.09% (wb), and r(2) of 0.95 was achieved. Model accuracy and precision were not impaired by exclusion of any single ration from model calibration.


Similarity thresholds used in DNA sequence assembly from short reads can reduce the comparability of population histories across species.
Comparing inferences among datasets generated using short read sequencing may provide insight into the concerted impacts of divergence, gene flow and selection across organisms, but comparisons are complicated by biases introduced during dataset assembly. Sequence similarity thresholds allow the de novo assembly of short reads into clusters of alleles representing different loci, but the resulting datasets are sensitive to both the similarity threshold used and to the variation naturally present in the organism under study. Thresholds that require high sequence similarity among reads for assembly (stringent thresholds) as well as highly variable species may result in datasets in which divergent alleles are lost or divided into separate loci ('over-splitting'), whereas liberal thresholds increase the risk of paralogous loci being combined into a single locus ('under-splitting'). Comparisons among datasets or species are therefore potentially biased if different similarity thresholds are applied or if the species differ in levels of within-lineage genetic variation. We examine the impact of a range of similarity thresholds on assembly of empirical short read datasets from populations of four different non-model bird lineages (species or species pairs) with different levels of genetic divergence. We find that, in all species, stringent similarity thresholds result in fewer alleles per locus than more liberal thresholds, which appears to be the result of high levels of over-splitting. The frequency of putative under-splitting, conversely, is low at all thresholds. Inferred genetic distances between individuals, gene tree depths, and estimates of the ancestral mutation-scaled effective population size (θ) differ depending upon the similarity threshold applied. Relative differences in inferences across species differ even when the same threshold is applied, but may be dramatically different when datasets assembled under different thresholds are compared. These differences not only complicate comparisons across species, but also preclude the application of standard mutation rates for parameter calibration. We suggest some best practices for assembling short read data to maximize comparability, such as using more liberal thresholds and examining the impact of different thresholds on each dataset.


Abnormal Biochemical Analytes Used for Aneuploidy Screening and Adverse Pregnancy Outcomes in Twin Gestations.
The objective of this study was to determine if first- and second-trimester biochemical markers for aneuploidy have an association with adverse pregnancy outcomes in twin gestations. A retrospective cohort study of patients who presented with dichorionic diamniotic twin gestations was performed. Patients with first-trimester low pregnancy-associated plasma protein A (PAPP-A) or low free β human chorionic gonadotropin (β-hCG), or second-trimester elevated α-fetoprotein (AFP), elevated inhibin A, elevated hCG, or low unconjugated estradiol were identified. The rates of adverse pregnancy outcomes were compared between patients with or without abnormal analytes with p < 0.05 used as significance. In this study, 340 pregnancies were included. Patients with a low PAPP-A had an increased risk for delivery < 37 weeks. Patients with an elevated second-trimester hCG had an increased risk for spontaneous delivery < 28 weeks and neonatal intensive care unit (NICU) admission. Patients with an elevated inhibin A had an increased risk of spontaneous delivery at < 37 and NICU admission. Patients with an elevated AFP had an increased risk of a NICU admission. Certain abnormal aneuploidy markers are associated with an increased risk of adverse pregnancy outcomes in twin gestations.


Stem anatomical characteristics of the climbing palm Desmoncus orthacanthos (Arecaceae) under two natural growth conditions in a tropical forest.
Desmoncus orthacanthos is a Neotropical climbing palm that resembles rattan and therefore has similar potential applications. The genus Desmoncus (subfamily Arecoideae, subtribe Bactridinae) is distributed throughout the Americas, from Veracruz, Mexico, to Brazil and Bolivia. The anatomical characteristics of its support tissue have not been thoroughly studied, although some observations from Central American artisans suggest that the stems collected from undisturbed sites possess better characteristics; these include a good capacity to withstand bending without breaking (i.e., higher fracture strength than plants from disturbed sites). Stem samples were collected from individuals from disturbed and undisturbed sites, at three points along the length of the stem (basal, medium and apical). Collections were made of one ramet from five individuals (n=5) at both sites. Each ramet was divided into three sections: basal, from soil surface to a height of 0.5 m; medium, from a height of 0.5 to 5.0 m; and apical, from a height 5.0 to 10.0 m. An anatomical analysis including vascular bundles, parenchyma elements and fibers was performed in the radial direction and also along the longitudinal direction of the stems. The amount of vascular bundles was greater for samples from undisturbed site stems; the amount of parenchyma cells differ between samples from both sites and the amount of fibers was greater for samples from disturbed site stems. The anatomical structural dimensions were smaller for samples from the undisturbed site stems. These findings partially confirm the artisans' belief and supports the conclusion that microclimatic conditions affect plant anatomical structure.


Chirp and self-phase modulation in induced-grating autocorrelation measurements of ultrashort pulses.
We show that induced-grating/four-wave-mixing ultrashort-pulse autocorrelation techniques that use slowly responding media offer the same phase information as interferometric second-harmonic generation. We also show that autocorrelation traces from nearly all possible induced-grating/four-wave-mixing beam geometries provide this information, with all yielding the same theoretical result, an integral of a fourth-order electric-field coherence function. Such traces clearly reveal chirp and self-phase-modulation effects without high-frequency fringes. Experiments using a two-beam-coupling arrangement in photorefractive media illustrate these effects.


Compressive and tensile strain sensing using a polymer planar Bragg grating.
A polymer planar Bragg grating sensor is used for measuring both mechanical compressive and tensile strain. The planar waveguide with integrated Bragg grating is fabricated in bulk Polymethylmethacrylate in a single writing step using combined amplitude and phase mask technique. After butt coupling of a single-mode optical fiber the planar structure can be applied for measuring both mechanical tensile and compressive strain alongside the integrated waveguide without the need of further modifications. In this respect, we particularly report for the first time compressive strain measurements using a polymer Bragg grating. Furthermore, the sensitivity of the sensor against tensile and compressive strain, its reproducibility and hysteresis are investigated and discussed.


Comparison of nasopharyngeal and oropharyngeal swabs for the diagnosis of eight respiratory viruses by real-time reverse transcription-PCR assays.
Many acute respiratory illness surveillance systems collect and test nasopharyngeal (NP) and/or oropharyngeal (OP) swab specimens, yet there are few studies assessing the relative measures of performance for NP versus OP specimens. We collected paired NP and OP swabs separately from pediatric and adult patients with influenza-like illness or severe acute respiratory illness at two respiratory surveillance sites in Kenya. The specimens were tested for eight respiratory viruses by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Positivity for a specific virus was defined as detection of viral nucleic acid in either swab. Of 2,331 paired NP/OP specimens, 1,402 (60.1%) were positive for at least one virus, and 393 (16.9%) were positive for more than one virus. Overall, OP swabs were significantly more sensitive than NP swabs for adenovirus (72.4% vs. 57.6%, p<0.01) and 2009 pandemic influenza A (H1N1) virus (91.2% vs. 70.4%, p<0.01). NP specimens were more sensitive for influenza B virus (83.3% vs. 61.5%, p = 0.02), parainfluenza virus 2 (85.7%, vs. 39.3%, p<0.01), and parainfluenza virus 3 (83.9% vs. 67.4%, p<0.01). The two methods did not differ significantly for human metapneumovirus, influenza A (H3N2) virus, parainfluenza virus 1, or respiratory syncytial virus. The sensitivities were variable among the eight viruses tested; neither specimen was consistently more effective than the other. For respiratory disease surveillance programs using qRT-PCR that aim to maximize sensitivity for a large number of viruses, collecting combined NP and OP specimens would be the most effective approach.


Accelerometer epoch setting is decisive for associations between physical activity and metabolic health in children.
When analysing physical activity (PA) levels using accelerometry, the epoch setting is critical to capture intensity-specific PA correctly. The aim of the present study was to investigate the PA intensity signatures related to metabolic health in children using different epoch settings. A sample of 841 Norwegian children (age 10.2 ± 0.3 years; BMI 18.0 ± 3.0; 50% boys) provided data on accelerometry (ActiGraph GT3X+) and several indices of metabolic health (aerobic fitness, abdominal fatness, insulin sensitivity, lipid metabolism, blood pressure) that were used to create a composite metabolic health score. We created intensity spectra from 0-99 to ≥ 10000 counts per minute (cpm) for files aggregated using 1, 10, and 60-second epoch periods and used multivariate pattern analysis to analyse the data. The association patterns with metabolic health differed substantially between epoch settings. The intensity intervals most strongly associated with metabolic health were 7000-8000 cpm for data analysed using 1-second epoch, 5500-6500 cpm for data analysed using 10-second epoch, and 4000-5000 cpm analysed using 60-second epoch. Aggregation of data over different epoch periods has a clear impact on how PA intensities in the moderate and vigorous range are associated with childhood metabolic health.


Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology.
The diagnosis of disseminated intravascular coagulation (DIC) should encompass both clinical and laboratory information. The International Society for Thrombosis and Haemostasis (ISTH) DIC scoring system provides objective measurement of DIC. Where DIC is present the scoring system correlates with key clinical observations and outcomes. It is important to repeat the tests to monitor the dynamically changing scenario based on laboratory results and clinical observations. The cornerstone of the treatment of DIC is treatment of the underlying condition. Transfusion of platelets or plasma (components) in patients with DIC should not primarily be based on laboratory results and should in general be reserved for patients who present with bleeding. In patients with DIC and bleeding or at high risk of bleeding (e.g. postoperative patients or patients due to undergo an invasive procedure) and a platelet count of <50 x 10(9)/l transfusion of platelets should be considered. In non-bleeding patients with DIC, prophylactic platelet transfusion is not given unless it is perceived that there is a high risk of bleeding. In bleeding patients with DIC and prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), administration of fresh frozen plasma (FFP) may be useful. It should not be instituted based on laboratory tests alone but should be considered in those with active bleeding and in those requiring an invasive procedure. There is no evidence that infusion of plasma stimulates the ongoing activation of coagulation. If transfusion of FFP is not possible in patients with bleeding because of fluid overload, consider using factor concentrates such as prothrombin complex concentrate, recognising that these will only partially correct the defect because they contain only selected factors, whereas in DIC there is a global deficiency of coagulation factors. Severe hypofibrinogenaemia (<1 g/l) that persists despite FFP replacement may be treated with fibrinogen concentrate or cryoprecipitate. In cases of DIC where thrombosis predominates, such as arterial or venous thromboembolism, severe purpura fulminans associated with acral ischemia or vascular skin infarction, therapeutic doses of heparin should be considered. In these patients where there is perceived to be a co-existing high risk of bleeding there may be benefits in using continuous infusion unfractionated heparin (UFH) due to its short half-life and reversibility. Weight adjusted doses (e.g. 10 mu/kg/h) may be used without the intention of prolonging the APTT ratio to 1.5-2.5 times the control. Monitoring the APTT in these cases may be complicated and clinical observation for signs of bleeding is important. In critically ill, non-bleeding patients with DIC, prophylaxis for venous thromboembolism with prophylactic doses of heparin or low molecular weight heparin is recommended. Consider treating patients with severe sepsis and DIC with recombinant human activated protein C (continuous infusion, 24 microg/kg/h for 4 d). Patients at high risk of bleeding should not be given recombinant human activated protein C. Current manufacturers guidance advises against using this product in patients with platelet counts of <30 x 10(9)/l. In the event of invasive procedures, administration of recombinant human activated protein C should be discontinued shortly before the intervention (elimination half-life approximately 20 min) and may be resumed a few hours later, dependent on the clinical situation. In the absence of further prospective evidence from randomised controlled trials confirming a beneficial effect of antithrombin concentrate on clinically relevant endpoints in patients with DIC and not receiving heparin, administration of antithrombin cannot be recommended. In general, patients with DIC should not be treated with antifibrinolytic agents. Patients with DIC that is characterised by a primary hyperfibrinolytic state and who present with severe bleeding could be treated with lysine analogues, such as tranexamic acid (e.g. 1 g every 8 h).


Health literacy practices and educational competencies for health professionals: a consensus study.
Health care professionals often lack adequate knowledge about health literacy and the skills needed to address low health literacy among patients and their caregivers. Many promising practices for mitigating the effects of low health literacy are not used consistently. Improving health literacy training for health care professionals has received increasing emphasis in recent years. The development and evaluation of curricula for health professionals has been limited by the lack of agreed-upon educational competencies in this area. This study aimed to identify a set of health literacy educational competencies and target behaviors, or practices, relevant to the training of all health care professionals. The authors conducted a thorough literature review to identify a comprehensive list of potential health literacy competencies and practices, which they categorized into 1 or more educational domains (i.e., knowledge, skills, attitudes) or a practice domain. The authors stated each item in operationalized language following Bloom's Taxonomy. The authors then used a modified Delphi method to identify consensus among a group of 23 health professions education experts representing 11 fields in the health professions. Participants rated their level of agreement as to whether a competency or practice was both appropriate and important for all health professions students. A predetermined threshold of 70% agreement was used to define consensus. After 4 rounds of ratings and modifications, consensus agreement was reached on 62 out of 64 potential educational competencies (24 knowledge items, 27 skill items, and 11 attitude items), and 32 out of 33 potential practices. This study is the first known attempt to develop consensus on a list of health literacy practices and to translate recommended health literacy practices into an agreed-upon set of measurable educational competencies for health professionals. Further work is needed to prioritize the competencies and practices in terms of relative importance.


Memory formation requires p38MAPK activity in the rat hippocampus.
Using the specific inhibitor of p38MAPK, SB203580, we show a direct involvement of this protein kinase in short- and long-term memory. When given into the CA1 region of the rat dorsal hippocampus immediately, but not 30 or 120 min after training in a one-trial inhibitory avoidance task, SB203580 blocked short- and long-term memory formation. The SB203580 inactive analog, SB202474, had no effect whatsoever. Learning of the avoidance task was accompanied by an immediate and transient increase in hippocampal p38MAPK phosphorylation. No change in p38MAPK phosphorylation was detected in control animals that only received the electric foot-shock associated with the learning paradigm. Therefore, formation of short and long-term memory for inhibitory avoidance requires p38MAPK activation in the rat hippocampus.


Tubulovascular cross-talk by vascular endothelial growth factor a maintains peritubular microvasculature in kidney.
Vascular endothelial growth factor A (VEGFA) production by podocytes is critical for glomerular endothelial health. VEGFA is also expressed in tubular epithelial cells in kidney; however, its physiologic role in the tubule has not been established. Using targeted transgenic mouse models, we found that Vegfa is expressed by specific epithelial cells along the nephron, whereas expression of its receptor (Kdr/Vegfr2) is largely restricted to adjacent peritubular capillaries. Embryonic deletion of tubular Vegfa did not affect systemic Vegfa levels, whereas renal Vegfa abundance was markedly decreased. Excision of Vegfa from renal tubules resulted in the formation of a smaller kidney, with a striking reduction in the density of peritubular capillaries. Consequently, elimination of tubular Vegfa caused pronounced polycythemia because of increased renal erythropoietin (Epo) production. Reducing hematocrit to normal levels in tubular Vegfa-deficient mice resulted in a markedly augmented renal Epo production, comparable with that observed in anemic wild-type mice. Here, we show that tubulovascular cross-talk by Vegfa is essential for maintenance of peritubular capillary networks in kidney. Disruption of this communication leads to increased renal Epo production and resulting polycythemia, presumably to counterbalance microvascular losses.


Conventional carotid endarterectomy versus stenting: comparison of restenosis rates in arteries with identical predisposing factors.
The aim of the study was to investigate the possible role of individual predisposition in the pathogenesis of carotid restenosis. Over 1700 patients have undergone carotid endarterectomy (CEA) in our institute over the past 15 years. We retrospectively reviewed the charts of those who also had contralateral carotid stenting (CAS) for primary atherosclerotic stenosis and recorded the rates of post-CEA and post-CAS restenosis ≥50%. In the 29 cases analyzed (21 men/8 women), CEA was performed with conventional technique and direct suturing in most cases. Mean ages at the time of CEA and CAS were 69.2±6.6 and 73±6.7 yrs, respectively, and risk profiles at the 2 time points were similar: hypertension (96.5%), dyslipidemia (55.2%), smoking (51.7%), diabetes (31%), coronary artery disease (48.3%), chronic obstructive pulmonary disease (37.9%), and chronic renal failure (13.8%). Antiplatelet therapy protocols were identical for the two procedures. During follow-up (mean: 67.25±51.6 months after CEA, 24.6±16.9 months after CAS), Duplex scans revealed restenosis in 12 patients (9 arteries treated with CEA, 6 managed with CAS). In three patients, restenosis was bilateral. Restenosis-free survival rates at five years were 85% after CEA and 66% after CAS (P=NS). In this selected group of patients, CEA and CAS were associated with a similar incidence of restenosis. Only 25% of the patients who developed restenosis did so after both procedures. These preliminary findings indicate that individual predisposition does not play a crucial role in the pathogenesis of restenosis. To confirm this conclusion, an analysis of a much larger, multicenter cohort is essential.


The effect of initial treatment on hearing prognosis in idiopathic sudden sensorineural hearing loss: a nationwide survey in Japan.
To investigate the hearing prognosis of idiopathic sudden sensorineural hearing loss (SSNHL) treated with different initial therapies. Subjects consisted of patients diagnosed with idiopathic SSNHL within 7 days from onset and showing severe hearing loss (≥60 dB), who were registered in a Japanese multicenter database between April 2014 and March 2016. Subjects were divided into four groups according to initial therapy: (1) steroids, (2) steroids + Prostaglandins (PGs), (3) intratympanic steroids (ITS), and (4) no steroids. Hearing outcomes were compared among the groups. In total, 1305 patients were enrolled. The final hearing level and hearing gain of patients treated with steroids + PGs were significantly higher than those of patients treated with steroids alone or no steroids. The ratio of good prognosis (complete recovery or marked improvement) in patients treated with steroids + PGs was higher than that in patients treated with steroids alone or no steroids. There was no difference in the prognosis of patients treated with steroids alone or no steroids. A large number of patients with idiopathic SSNHL were registered in a multicenter database. PG use in combination with steroid administration was associated with a good hearing prognosis in patients with severe hearing loss.


Contribution of organically grown crops to human health.
An increasing interest in organic agriculture for food production is seen throughout the world and one key reason for this interest is the assumption that organic food consumption is beneficial to public health. The present paper focuses on the background of organic agriculture, important public health related compounds from crop food and variations in the amount of health related compounds in crops. In addition, influence of organic farming on health related compounds, on pesticide residues and heavy metals in crops, and relations between organic food and health biomarkers as well as in vitro studies are also the focus of the present paper. Nutritionally beneficial compounds of highest relevance for public health were micronutrients, especially Fe and Zn, and bioactive compounds such as carotenoids (including pro-vitamin A compounds), tocopherols (including vitamin E) and phenolic compounds. Extremely large variations in the contents of these compounds were seen, depending on genotype, climate, environment, farming conditions, harvest time, and part of the crop. Highest amounts seen were related to the choice of genotype and were also increased by genetic modification of the crop. Organic cultivation did not influence the content of most of the nutritional beneficial compounds, except the phenolic compounds that were increased with the amounts of pathogens. However, higher amounts of pesticide residues and in many cases also of heavy metals were seen in the conventionally produced crops compared to the organic ones. Animal studies as well as in vitro studies showed a clear indication of a beneficial effect of organic food/extracts as compared to conventional ones. Thus, consumption of organic food seems to be positive from a public health point of view, although the reasons are unclear, and synergistic effects between various constituents within the food are likely.


Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL.
Although TP53, NOTCH1, and SF3B1 mutations may impair prognosis of patients with chronic lymphocytic leukemia (CLL) receiving frontline therapy, the impact of these mutations or any other, alone or in combination, remains unclear at relapse. The genome of 114 relapsed/refractory patients included in prospective trials was screened using targeted next-generation sequencing of the TP53, SF3B1, ATM, NOTCH1, XPO1, SAMHD1, MED12, BIRC3, and MYD88 genes. We performed clustering according to both number and combinations of recurrent gene mutations. The number of genes affected by mutation was ≥ 2, 1, and 0 in 43 (38%), 49 (43%), and 22 (19%) respectively. Recurrent combinations of ≥ 2 mutations of TP53, SF3B1, and ATM were found in 22 (19%) patients. This multiple-hit profile was associated with a median progression-free survival of 12 months compared with 22.5 months in the remaining patients (P = .003). Concurrent gene mutations are frequent in patients with relapsed/refractory CLL and are associated with worse outcome.


Logistic or linear? Estimating causal effects of experimental treatments on binary outcomes using regression analysis.
When the outcome is binary, psychologists often use nonlinear modeling strategies such as logit or probit. These strategies are often neither optimal nor justified when the objective is to estimate causal effects of experimental treatments. Researchers need to take extra steps to convert logit and probit coefficients into interpretable quantities, and when they do, these quantities often remain difficult to understand. Odds ratios, for instance, are described as obscure in many textbooks (e.g., Gelman & Hill, 2006, p. 83). I draw on econometric theory and established statistical findings to demonstrate that linear regression is generally the best strategy to estimate causal effects of treatments on binary outcomes. Linear regression coefficients are directly interpretable in terms of probabilities and, when interaction terms or fixed effects are included, linear regression is safer. I review the Neyman-Rubin causal model, which I use to prove analytically that linear regression yields unbiased estimates of treatment effects on binary outcomes. Then, I run simulations and analyze existing data on 24,191 students from 56 middle schools (Paluck, Shepherd, & Aronow, 2013) to illustrate the effectiveness of linear regression. Based on these grounds, I recommend that psychologists use linear regression to estimate treatment effects on binary outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913.
Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the BCR/ABL1-like predictor - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Ph-like were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies.


Immunomodulatory effects in mice of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose.
In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.


Prevalence of Congenital Malformations in Grenada.
To determine the prevalence of congenital malformations in Grenada for the period January 2000-December 2004. The study included neonates diagnosed with congenital malformations as well as those who were part of the Grenada Heart Foundation for the same time period. Patient delivery records from the three government hospitals were reviewed. Parents were contacted and a questionnaire administered to obtain demographic and maternal history related to the birth. The prevalence of birth defects was 0.78% (95%CI: 0.61, 0.98) for the five-year period among the 9004 live births. Cardiovascular malformations were the most prevalent (0.32%; 95% CI: 0.22, 0.45%), with abnormalities of the genitourinary system being the least prevalent (0.04%; 95% CI: 0.01, 0.11%). The prevalence of congenital malformations in Grenada is low in comparison to other developed and developing countries.


An erythrocyte vesicle protein exported by the malaria parasite promotes tubovesicular lipid import from the host cell surface.
Plasmodium falciparum is the protozoan parasite that causes the most virulent of human malarias. The blood stage parasites export several hundred proteins into their host erythrocyte that underlie modifications linked to major pathologies of the disease and parasite survival in the blood. Unfortunately, most are 'hypothetical' proteins of unknown function, and those that are essential for parasitization of the erythrocyte cannot be 'knocked out'. Here, we combined bioinformatics and genome-wide expression analyses with a new series of transgenic and cellular assays to show for the first time in malaria parasites that microarray read out from a chemical perturbation can have predictive value. We thereby identified and characterized an exported P. falciparum protein resident in a new vesicular compartment induced by the parasite in the erythrocyte. This protein, named Erythrocyte Vesicle Protein 1 (EVP1), shows novel dynamics of distribution in the parasite and intraerythrocytic membranes. Evidence is presented that its expression results in a change in TVN-mediated lipid import at the host membrane and that it is required for intracellular parasite growth, but not invasion. This exported protein appears to be needed for the maintenance of an essential tubovesicular nutrient import pathway induced by the pathogen in the host cell. Our approach may be generalized to the analysis of hundreds of 'hypothetical' P. falciparum proteins to understand their role in parasite entry and/or growth in erythrocytes as well as phenotypic contributions to either antigen export or tubovesicular import. By functionally validating these unknowns, one may identify new targets in host-microbial interactions for prophylaxis against this major human pathogen.


From the inside/out: Greene County jail inmates on restorative reentry.
The application of criminal justice sanctions is often misguided by a failure to recognize the need for a comprehensive approach in the transformation of offenders into law-abiding citizens. Restorative justice is a growing movement within criminal justice that recognizes the disconnect between offender rehabilitative measures and the social dynamics within which offender reentry takes place. By using restorative approaches to justice, what one hopes of these alternative processes is that the offenders become reconnected to the community and its values, something rarely seen in retributive models in which punishment is imposed and offenders can often experience further alienation from society. In this study, the authors wish to examine factors that contribute to failed prisoner reentry and reintegration and explore how restorative reintegration processes can address these factors as well as the needs, attitudes, and perceptions that help construct and maintain many of the obstacles and barriers returning inmates face when attempting to reintegrate into society.


A stochastic model study on the self-assembly process of a Pd2L4 cage consisting of rigid ditopic ligands.
The coordination self-assembly process of a Pd2L4 cage including rigid ditopic ligands, L, was studied numerically. A recently developed experimental approach (QASAP: quantitative analysis of self-assembly process) revealed that the rate-determining steps in the self-assembly of the Pd2L4 cage are intramolecular ligand exchanges at the late stages of the self-assembly. In this study, the self-assembly process before the rate-determining steps, which could not be investigated by experiment, was analyzed based on a minimal reaction network model. Only eight variable parameters of rate constants for ligand exchange reactions are sufficient enough to reproduce the time evolution of substrates and the products during the self-assembly of the cage. With these parameters, the major self-assembly pathway was determined. It was also found that a non-negligible amount of an incomplete cage (IC), Pd2L3X2 (X indicates the leaving ligand), which was not suggested by QASAP, should be transiently produced. Numerical tests also suggest that the small rate constant value of the intramolecular ligand exchanges due to a restricted geometry causes the final stage to seemingly become the rate-determining step.


Transactional sex among men and women in the south at high risk for HIV and other STIs.
Transactional sex refers to selling sex (exchanging sex for money, drugs, food, shelter, or other items) or purchasing sex (exchanging money, drugs, food, shelter, or other items for sex). These activities have been associated with a higher risk for HIV and other sexually transmitted infections in a variety of populations and settings. This paper examines correlates of purchasing and selling sex in a large sample of drug users, men who have sex with men, and sex partners of these groups. Using respondent-driven sampling, participants were recruited between 2005 and 2008 in two urban and two rural counties in North Carolina. We used multiple logistic regressions to examine separate models for selling and purchasing sex in men and women. In addition, we estimated direct and indirect associations among independent variables in the logistic regression models and transactional sex using structural equation models. The analysis shows that factors associated with women selling and buying sex include being homeless, use of stimulants, bisexual behavior, and neighborhood disorder. There was also a significant difference by race. For men, the factors associated with selling and buying sex include being homeless, bisexual behavior, and not being in a relationship. Although neighborhood violence and disorder show significance in bivariate associations with the outcome, these associations disappear in the structural equation models.


The role of substance P in myocardial dysfunction during ischemia and reperfusion.
Impairment of myocardial contraction ("myocardial stunning") occurs during reperfusion after short ischemic periods. Substance P (SP) is widely distributed in heart and can be released by various stimuli including myocardial hypoxia. Our previous study shows SP has a negative inotropic effect in guinea pig heart. The objective of this study was to investigate whether SP contributes to the myocardial stunning after brief global ischemia. Guinea pig hearts in a Langendorff preparation were subjected to 15 min of global ischemia followed by 60 min reperfusion. Experiments were performed without and with pretreatment with neurokinin-1 (NK1) receptor antagonists, spantide (10(-6)M) or CP-99,994-01 (10(-6)M) in order to study the role of SP. Experiments were also performed in hearts which were perfused with atropine, phentolamine, and nadolol (10(-6)M each) to examine the role of neurotransmitters and autonomic receptors. A group of hearts obtained from capsaicin-pretreated guinea pigs was also investigated. Left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), heart rate, and perfusion pressure were monitored. At the end of reperfusion, the LVDP of control hearts recovered to only 55 +/- 6% (+/- SEM) of preischemic baseline and the LVEDP increased significantly (P > 0.05). With pretreatment with spantide or CP-99,994-01, LVDP recovered to 88 +/- 2% or 78 +/- 2% of the preischemic baseline, respectively. The LVEDP of these hearts was not different from preischemic baseline and much smaller than in control hearts. There were no differences in heart rate and perfusion pressure compared to baseline among all groups. Similar results were obtained in hearts perfused with autonomic blockers. However, recoveries of LVDP and LVEDP were faster in hearts perfused with autonomic blockers during the first 10 min of reperfusion. Pretreatment with capsaicin also significantly improved recovery of LVDP and LVEDP. In conclusion, substance P is involved in postischemic myocardial dysfunction and neurokinin-1 receptors mediate this action. The NK1 receptor antagonists may be useful in prevention of "myocardial stunning".


A 7-day recall period for a clinical application of the oral health impact profile questionnaire.
Aims were to investigate and compare the validity and reliability of Oral Health Impact Profile (OHIP) scores referencing 7-day and 1-month recall periods in international prosthodontic patients. A sample of 267 patients (mean age = 54.0 years, SD = 17.2 years, 58 % women) with stable oral health-related quality of life was recruited from prosthodontic treatment centers in Croatia, Germany, Hungary, Japan, Slovenia, and Sweden. These patients completed the OHIP on two occasions using a new 7-day recall period and the traditional 1-month recall period. OHIP score validity and reliability were investigated with structural equation models (SEMs) that included OHIP(past 7 days) and OHIP(1 month) latent factors and single indicator measures of global oral health status. The SEMs assessed measurement invariance and the relative validities of the two OHIP latent factors (representing the two recall periods). The SEMs provided cogent evidence for recall period measurement invariance for the two OHIP forms and equal validities (r = .48) with external measures of global oral health status. When assessed in international prosthodontic patients, OHIP scores using the new 7-day recall period were as reliable and valid as the scores using the 1-month recall period. Conceptual advantages make a 7-day recall period a preferred frame of reference in clinical applications of the OHIP questionnaire.


Light-assisted templated self assembly using photonic crystal slabs.
We explore a technique which we term light-assisted templated self-assembly. We calculate the optical forces on colloidal particles over a photonic crystal slab. We show that exciting a guided resonance mode of the slab yields a resonantly-enhanced, attractive optical force. We calculate the lateral optical forces above the slab and predict that stably trapped periodic patterns of particles are dependent on wavelength and polarization. Tuning the wavelength or polarization of the light source may thus allow the formation and reconfiguration of patterns. We expect that this technique may be used to design all-optically reconfigurable photonic devices.


First Report of Zucchini yellow mosaic virus in Cucumber (Cucumis sativus) in India.
In August of 2002, cucumber (Cucumis sativus L. cv. Himangi) plants grown in commercial fields in Pune, western Maharashtra, India, exhibited chlorotic spots, veinal chlorosis, mosaic, blister formation and shoestring symptoms on leaves, stunted growth, and distortion of fruits. Incidence of virus infection in the fields varied from 25 to 38%. Crude sap extracted from infected cucumber leaf samples was inoculated mechanically onto cucumber and indicator host plants. The inoculated glasshouse-grown cucumber plants showed virus symptoms similar to those observed in the field. The virus produced chlorotic local lesions on Chenopodium amaranticolor and chlorotic spots followed by veinal chlorosis, mosaic, vein banding, and leaf distortion on Citrullus lanatus, C. melo, C. sativus, Cucurbita maxima, Cucurbita pepo, Luffa acutangula, and Trichosanthes anguina. The virus did not infect Nicotiana benthamiana, N. glutinosa, and N. tabacum cv. White Burley (1,2). Cucumber and indicator plants were tested using direct antigen coating enzyme-linked immunosorbent assays. A positive reaction was obtained with monoclonal antiserum to Zucchini yellow mosaic virus (ZYMV) but not with antisera to Papaya ringspot virus-P, Cucumber mosaic virus, and Watermelon mosaic virus (Agdia, Inc., Elkhart, IN). The disease was observed again in the field during July to September 2003. Natural infection of zucchini (Cucurbita pepo) by ZYMV has been reported previously from India (3). To our knowledge, this is the first report of ZYMV in cucumber in India. References: (1) H. Pospieszny et al. Plant Dis. 87:1399, 2003. (2) R. Provvidenti et al. Plant Dis. 68:443, 1984. (3) S. J. Singh et al. Indian Phytopathol. 56:174, 2003.


Identification of two mechanisms for current production in a biharmonic flashing electron ratchet.
Ratchets rectify the motion of randomly moving particles, which are driven by isotropic sources of energy such as thermal and chemical energy, without applying a net, time-averaged force between source and drain. This paper describes the behavior of a damped electron, modeled by a quantum Lindblad master equation, within a flashing ratchet (a one-dimensional potential that oscillates between a flat surface and a periodic asymmetric surface). By examining the complete space of all biharmonic potential shapes and a large range of oscillation frequencies, two modes of ratchet operation, differentiated by their oscillation frequencies (relative to the rate of electron relaxation), are identified. Slow-oscillating, strong friction ratchets operate by a classical, overdamped mechanism. In fast-oscillating, weak friction ratchets, current is primarily produced when the frequency of the oscillating potential is resonant with the beating of the electron wave function in the potential well. The shape of the ratchet potential determines the direction of the current (and, in some cases, straightforwardly accounts for current reversals), but the maximum achievable current at any shape is controlled by the degree of friction applied to the electron.