Access to Dental Visits and Correlates of Preventive Dental Care in Children with Autism Spectrum Disorder.
Dental care received by children in the Autism Speaks Autism Treatment Network (ATN) was compared to National Survey of Children's Health (NSCH) data for children without special healthcare needs and children with parent-reported ASD. Correlates of obtained preventive dental services were examined within the ATN sample. Participants included 375 families of children ages 4 to 17 enrolled in the ATN. ATN families reported levels of preventive dental care that were similar to, or exceeded, NSCH-reported care. However, disparities in obtained preventive dental services emerged within the ATN sample. Lower intellectual functioning was the most consistent correlate of reduced access to and completion of preventive dental care. Implications for developing system-wide supports and targeted interventions are discussed.


Effects of β-hydroxy β-methyl butyrate supplementation to sows in late gestation on absorption and hepatic metabolism of glucose and amino acids during transition.
A multicatheter sow model was established to study the effects of dietary β-hydroxy β-methyl butyrate (HMB) supplementation on net portal flux (NPF) and net hepatic flux (NHF) of HMB, glucose, and the AA Ala, Gly, Ile, Leu, Phe, Tyr, and Val. Eight second parity sows were fitted with permanent indwelling catheters in an artery and in the portal, hepatic, and mesenteric veins. Eight hourly sets of blood samples were taken starting 30 min before the morning meal on day -3 and day 3 relative to parturition. Four control (CON) sows were fed a standard lactation diet from day -15 and throughout the experiment, and 4 HMB sows were fed the control diet supplemented with 15 mg Ca(HMB)(2)/kg BW mixed in one third of the morning meal from day -10 until parturition. Net portal flux of HMB was affected by treatment (Trt; P < 0.01) and peaked in the HMB sows at 6.9 mmol/h 30 min after the morning meal and then decreased towards preprandial level (0.0 mmol/h) 3.5 h after the meal, revealing that dietary HMB was rapidly absorbed from the intestine. The NHF of HMB tended to be affected by Trt (P = 0.06) showing a small hepatic uptake of HMB (1.1 mmol/h) in HMB sows. Net portal flux of glucose and all measured AA, except for Gly and Tyr, were affected the Trt × time interaction (P < 0.01). The NPF was positive for all nutrients, indicating absorption from the intestine to the portal blood. Absorption rates appeared to be more stable for HMB than for CON sows. Net hepatic flux of glucose was not affected by Trt. It was negative from 1.5 to 2.5 h after the meal, indicating hepatic uptake, but positive before and after, indicating net hepatic release of glucose. Net hepatic fluxes of AA were negative and were not affected by Trt (P > 0.10), except for Phe (P < 0.05). In conclusion, HMB reduced the variation in net portal flux of glucose and AA during 8 h of blood sampling and suggest that the improved sow productivity observed by others may be due to a more uniform nutrient absorption pattern into portal blood.


An economic evaluation of valsartan for post-MI patients in the UK who are not suitable for treatment with ACE inhibitors.
The overall objective of this study was to estimate the costs and outcomes associated with treatment with valsartan for post-myocardial infarction (post-MI) patients with left ventricular systolic dysfunction, heart failure, or both, who are not suitable for treatment with angiotensin-converting enzyme (ACE) inhibitors, compared to placebo. A Markov model, using data drawn from the Valsartan in Acute Myocardial Infarction (VALIANT) trial and other trials, was developed to predict the future health pathways, resource use, and costs for patients who have recently experienced an MI. Patients received either valsartan (mean dose 247 mg) or placebo. Cost data were drawn from national databases and published literature, although health outcome utility weights were derived from existing studies. Patient outcomes were modeled for 10 years, and incremental cost-effective ratios were calculated for valsartan compared with placebo. Over a period of 10 years, a cohort of 1000 patients treated with valsartan experienced 147 fewer cardiovascular deaths, 37 fewer nonfatal MIs, and 95 fewer cases of heart failure than a cohort who received placebo. The incremental cost of valsartan, compared with placebo, was 2680 pound per patient, although the incremental effectiveness of valsartan was 0.5021 quality-adjusted life-years (QALYs) gained per patient. Therefore, the incremental cost per QALY for treatment with valsartan was 5338 pound. When analysis was undertaken using life-years rather than QALYs, the cost per life-year gained was 4672 pound. For patients who are not suitable for treatment with ACE inhibitors, valsartan is a viable and cost-effective treatment for their management after an MI.


Nano-optogenetic CAR-T Cell Immunotherapy.
Chimeric antigen receptor (CAR)-T cell immunotherapy emerges as an effective cancer treatment. However, significant safety concerns remain, such as cytokine release syndrome (CRS) and "on-target, off-tumor" cytotoxicity, due to a lack of precise control over conventional CAR-T cell activity. To address this issue, a nano-optogenetic approach has been developed to enable spatiotemporal control of CAR-T cell activity. This system is comprised of synthetic light-sensitive CAR-T cells and upconversion nanoparticles acting as an in situ nanotransducer, allowing near-infrared light to wirelessly control CAR-T cell immunotherapy.


Finite-temperature conductivity and magnetoconductivity of topological insulators.
The electronic transport experiments on topological insulators exhibit a dilemma. A negative cusp in magnetoconductivity is widely believed as a quantum transport signature of the topological surface states, which are immune from localization and exhibit the weak antilocalization. However, the measured conductivity drops logarithmically when lowering temperature, showing a typical feature of the weak localization as in ordinary disordered metals. Here, we present a conductivity formula for massless and massive Dirac fermions as a function of magnetic field and temperature, by taking into account the electron-electron interaction and quantum interference simultaneously. The formula reconciles the dilemma by explicitly clarifying that the temperature dependence of the conductivity is dominated by the interaction, while the magnetoconductivity is mainly contributed by the quantum interference. The theory paves the road to quantitatively study the transport in topological insulators, and can be extended to other two-dimensional Dirac-like systems, such as graphene, transition metal dichalcogenides, and silicene.


Comparison of functional variants in IFNL4 and IFNL3 for association with HCV clearance.
Genetic polymorphisms within the interferon lambda (IFN-λ) region are strongly associated with hepatitis C virus (HCV) clearance; the IFNL4-ΔG/TT (rs368234815) polymorphism, which controls the generation of IFN-λ4 protein, is more strongly associated with HCV clearance than rs12979860 (the 'IL28B variant'). An IFNL3 3' untranslated region polymorphism (rs4803217) has been proposed as a causal variant that may affect HCV clearance by altering IFNL3 mRNA stability. We compared IFNL4-ΔG/TT and rs4803217 for association with response to pegylated-IFN-α/ribavirin in the VIRAHEP-C and HALT-C trials, and spontaneous HCV clearance in the ALIVE, UHS and WIHS studies. Genotyping was performed with TaqMan assays. We compared differences in mean reduction in HCV RNA levels by genotype and haplotype. For HCV clearance, we calculated p-values comparing c-statistics for IFNL4-ΔG/TT and rs4803217 genotypes by a bootstrap approach. Among European Americans, linkage disequilibrium between IFNL4-ΔG/TT and rs4803217 was strong (r(2)=0.89-0.99) and there were no significant differences between the variants. In African American (AA) individuals enrolled in VIRAHEP-C, HCV RNA at treatment day 28 was more strongly associated with IFNL4-ΔG/TT than rs4803217 (p=0.003); the IFNL4-ΔG:rs4803217-G haplotype, which includes the putatively favorable IFNL3 allele, was actually associated with the poorest day 28 response (p=0.03, comparison to IFNL4-ΔG:rs4803217-T haplotype). Among AA participants, associations were stronger for IFNL4-ΔG/TT than rs4803217 for undetectable HCV RNA at week 24 in Virahep-C (p=0.03) and week 20 in HALT-C (p=0.03), as well as for spontaneous HCV clearance (p=0.048). IFNL4-ΔG/TT is the primary IFN-λ region polymorphism for impaired HCV clearance.


Naturally occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients.
A small percentage of hemodialysis patients maintain higher hemoglobin concentrations without transfusion or erythropoietic therapy. Because uncertainty exists regarding the effects of higher hemoglobin concentration on mortality and quality of life among hemodialysis patients, studying this group of patients with sufficient endogenous erythropoietin may provide additional insights. The prospective, observational Dialysis Outcomes and Practice Patterns Study provides an opportunity to investigate this group. Among 29,796 patients in 12 nations, 545 (1.8%) maintained hemoglobin concentrations >12 g/dl for 4 months without erythropoietic support. This subset tended to be male, to have a longer duration of end-stage renal disease, and to not dialyze via a catheter. Cystic disease as the underlying cause of renal failure was over-represented in this group but was present in only 25%. Lung disease, smoking, and cardiovascular disease were associated with increased likelihood of naturally higher hemoglobin concentration. Quality-of-life scores were not higher among this subset compared with the other patients. Unadjusted mortality risk for patients with hemoglobin >12 g/dl and no erythropoietic therapy was lower than for the other patients, but after thorough adjustment for case mix, there was no difference between groups (relative risk, 0.98; 95% CI 0.80 to 1.19). These data show that naturally occurring hemoglobin concentration >12 g/dl does not associate with increased mortality among hemodialysis patients.


Long-Term Outcomes in Patients with Acute Kidney Injury.
The long-term sequelae of AKI have received increasing attention so that its associations with a number of adverse outcomes, including higher mortality and development of CKD, are now widely appreciated. These associations take on particular importance when considering the high incidence of AKI, with a lack of proven interventions and uncertainties around optimal care provision meaning that the long-term sequelae of AKI present a major unmet clinical need. In this review, we examine the published data that inform our current understanding of long-term outcomes following AKI and discuss potential knowledge gaps, covering long-term mortality, CKD, progression to ESKD, proteinuria, cardiovascular events, recurrent AKI, and hospital readmission.


Role of SMPD3 during Bone Fracture Healing and Regulation of Its Expression.
Sphingomyelin phosphodiesterase 3 (SMPD3), a lipid-metabolizing enzyme present in bone and cartilage, has important roles in the developing skeleton. We previously showed that SMPD3 deficiency results in delayed extracellular matrix (ECM) mineralization and severe skeletal deformities in an inducible knockout mouse model, Smpd3flox/flox ; Osx-Cre mice, in which Smpd3 was ablated in Osx-expressing chondrocytes and osteoblasts during early skeletogenesis. However, as shown in the current study, ablation of Smpd3 postnatally in 3-month-old Smpd3flox/flox ; Osx-Cre mice resulted in only a mild bone mineralization defect. Interestingly, though, there was a marked increase of unmineralized osteoid in the fractured tibiae of 3-month-old Smpd3flox/flox ; Osx-Cre mice. As was the case in the embryonic bones, we also observed impaired chondrocyte apoptosis at the fracture sites of Smpd3flox/flox ; Osx-Cre mice. We further examined how Smpd3 expression is regulated in ATDC5 chondrogenic cells by two major regulators of chondrogenesis, bone morphogenetic protein 2 (BMP-2) and PTHrP. Our data show that BMP-2 positively regulates Smpd3 expression via p38 mitogen-activated protein kinase. Taken together, our findings show that SMPD3 plays a significant role in ECM mineralization and chondrocyte apoptosis during fracture healing. Furthermore, our gene expression analyses suggest that BMP-2 and PTHrP exert opposing effects on the regulation of Smpd3 expression in chondrocytes.


The Anorexia Nervosa Genetics Initiative: Study description and sample characteristics of the Australian and New Zealand arm.
Anorexia nervosa is a severe psychiatric disorder with high mortality rates. While its aetiology is poorly understood, there is evidence of a significant genetic component. The Anorexia Nervosa Genetics Initiative is an international collaboration which aims to understand the genetic basis of the disorder. This paper describes the recruitment and characteristics of the Australasian Anorexia Nervosa Genetics Initiative sample, the largest sample of individuals with anorexia nervosa ever assembled across Australia and New Zealand. Participants completed an online questionnaire based on the Structured Clinical Interview Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) eating disorders section. Participants who met specified case criteria for lifetime anorexia nervosa were requested to provide a DNA sample for genetic analysis. Overall, the study recruited 3414 Australians and 543 New Zealanders meeting the lifetime anorexia nervosa case criteria by using a variety of conventional and social media recruitment methods. At the time of questionnaire completion, 28% had a body mass index ⩽ 18.5 kg/m2. Fasting and exercise were the most commonly employed methods of weight control, and were associated with the youngest reported ages of onset. At the time of the study, 32% of participants meeting lifetime anorexia nervosa case criteria were under the care of a medical practitioner; those with current body mass index < 18.5 kg/m2 were more likely to be currently receiving medical care (56%) than those with current body mass index ⩾ 18.5 kg/m2 (23%). Professional treatment for eating disorders was most likely to have been received from general practitioners (45% of study participants), dietitians (42%) and outpatient programmes (42%). This study was effective in assembling the largest community sample of people with lifetime anorexia nervosa in Australia and New Zealand to date. The proportion of people with anorexia nervosa currently receiving medical care, and the most common sources of treatment accessed, indicates the importance of training for general practitioners and dietitians in treating anorexia nervosa.


Reconstruction of parental microsatellite genotypes reveals female polyandry and philopatry in the lemon shark, Negaprion brevirostris.
Because sharks possess an unusual suite of reproductive characteristics, including internal fertilization, sperm storage, relatively low fecundity, and reproductive modes that range from oviparity to viviparity, they can provide important insight into the evolution of mating systems and sexual selection. Yet, to date, few studies have characterized behavioral and genetic mating systems in natural populations of sharks or other elasmobranchs. In this study, highly polymorphic microsatellite loci were used to examine breeding biology of a large coastal shark, the lemon shark, Negaprion brevirostris, at a tropical lagoon nursery. Over six years, 910 lemon sharks were sampled and genotyped. Young were assigned into sibling groups that were then used to reconstruct genotypes of unsampled adults. We assigned 707 of 735 young sharks to one of 45 female genotypes (96.2%), and 485 (66.0%) were assigned to a male genotype. Adult female sharks consistently returned to Bimini on a biennial cycle to give birth. Over 86% of litters had multiple sires. Such high levels of polyandry raise the possibility that polyandry evolved in viviparous sharks to reduce genetic incompatibilities between mother and embryos. We did not find a relationship between relatedness of mates and the number of offspring produced, indicating that inbreeding avoidance was probably not driving pre- or postcopulatory mate choice. Adult male sharks rarely sired more than one litter at Bimini and may mate over a broader geographic area.


Identification of an RNA-binding-loop in the N-terminal region of signal-recognition-particle protein SRP19.
Protein SRP19 is a 144-amino-acid polypeptide that associates intimately with the signal-recognition particle RNA (SRP RNA) and serves as an important structural and functional component of the SRP. We investigated the structure and RNA-binding activity of the human SRP19 protein by the use of comparative sequence analysis, high-stringency structure prediction, proteolytic susceptibility, and site-directed mutagenesis. SRP19 was found to consist of two distinct regions (called N-terminal and C-terminal regions) that are separated by a boundary of approximately 12-15 amino acid residues. Both regions contain an alpha-helix and several beta-strands that are connected by loops or turns. In agreement with the hypothetical model, proteolytic susceptibility demonstrated the predominant accessibility of two sites: one in a surface loop of the N-terminal region (YLNNKKTIAEGR33), and another site in the C-terminal tail at residues L129 and E133. The RNA-binding activities of mutant polypeptides with changes of conserved lysines and arginines (mutants K27Q, R33Q and R34Q) demonstrated that the proteolytically accessible loop of the N-terminal region is in direct contact with the SRP RNA. In contrast, alteration of a certain basic amino acid residues in the C-terminal region (R83, K116 and R118), as well as a deletion of four amino acid residues located at the boundary between the two regions, had no effect on the RNA-binding ability. The structural model that emerges from our data is thematically similar to that of ribosomal protein S5, the N-domain of which contains a loop motif believed to interact with double-stranded RNA. The presence of a similar structural feature in protein SRP19 has significant implications for the structure and function of the SRP19-RNA complex.


Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia.
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and impaired platelet production. Antibody binding to megakaryocytes may occur in ITP, but in vivo evidence of this phenomenon is lacking. We determined the proportion of megakaryocytes bound with immunoglobulin G (IgG) in bone marrow samples from primary patients with ITP (n = 17), normal controls (n = 13) and thrombocytopenic patients with myelodysplastic syndrome (MDS; n = 10). Serial histological sections from archived bone marrow biopsies were stained for CD61 and IgG. IgG binding and the number of bone marrow megakaryocytes were determined morphologically by a hematopathologist with four assessors after a calibration exercise to ensure consistency. The proportion of ITP patients with high IgG binding (>50% of bone marrow megakaryocytes) was increased compared with normal controls [12/17 (71%) vs. 3/13 (23%), P = 0.03]. However, the proportion of ITP patients with high IgG binding was no different than thrombocytopenic patients with MDS [12/17 (71%) vs. 7/10 (70%), P = 1.00]. IgG binding was associated with increased megakaryocyte numbers. Like platelet-associated IgG, megakaryocyte-associated IgG is related to thrombocytopenia but may not be specific for ITP. Mechanistic studies in ITP should focus on antibody specificity and include thrombocytopenic control patients.


A new species of Cambeva (Siluriformes, Trichomycteridae) from the Rio Iguaçu basin, Paraná State, Brazil and redescription of Cambeva stawiarski (Miranda Ribeiro 1968).
This work aimed to describe Cambeva cauim, sp. nov., endemic to the Rio Iguaçu basin, Brazil and redescribe Cambeva stawiarski using external and internal morphological data through the revision of specimens deposited in fish collections, including the type material. In this process, we have also added comments on the possible type locality of C. stawiarski. C. cauim, sp. nov. and C. stawiarski are mainly diagnosed by the anatomy and number of procurrent caudal-fin rays in addition to colouration and several meristic and morphometric characters. Both species are compared with other possibly related species and their synapomorphic characters are discussed. C. cauim, sp. nov. and C. stawiarski along with eight other congeners are endemic to the Rio Iguaçu basin, a high impacted freshwater region which could be considered as a biodiversity hotspot to the genus.


Conserved functional organization of the human immunodeficiency virus type 1 and visna virus Rev proteins.
Visna virus encodes a posttranscriptional regulatory protein that is functionally analogous to the Rev trans activator of human immunodeficiency virus type 1. Here, we demonstrate that the known functional organization of the human immunodeficiency virus type 1 Rev trans activator is shared by the distantly related visna virus Rev protein. In particular, both Rev proteins contain an N-terminal domain marked by a highly basic core motif that determines RNA sequence specificity, as well as a second C-terminal domain containing an essential leucine-rich motif that functions as an activation domain. Chimeric proteins consisting of the binding domain of one Rev protein fused to the activation domain of the other were fully functional in the viral sequence context cognate for the binding domain. We also describe derivatives of visna virus Rev bearing a defective activation domain that displayed a trans-dominant negative phenotype in transfected cells. These visna virus Rev mutants may prove useful in the derivation of transgenic animals resistant to this agriculturally important retroviral pathogen.


A nuclear DNA perspective on delineating evolutionarily significant lineages in polyploids: the case of the endangered shortnose sturgeon (Acipenser brevirostrum).
The shortnose sturgeon, Acipenser brevirostrum, oft considered a phylogenetic relic, is listed as an "endangered species threatened with extinction" in the US and "Vulnerable" on the IUCN Red List. Effective conservation of A. brevirostrum depends on understanding its diversity and evolutionary processes, yet challenges associated with the polyploid nature of its nuclear genome have heretofore limited population genetic analysis to maternally inherited haploid characters. We developed a suite of polysomic microsatellite DNA markers and characterized a sample of 561 shortnose sturgeon collected from major extant populations along the North American Atlantic coast. The 181 alleles observed at 11 loci were scored as binary loci and the data were subjected to multivariate ordination, Bayesian clustering, hierarchical partitioning of variance, and among-population distance metric tests. The methods uncovered moderately high levels of gene diversity suggesting population structuring across and within three metapopulations (Northeast, Mid-Atlantic, and Southeast) that encompass seven demographically discrete and evolutionarily distinct lineages. The predicted groups are consistent with previously described behavioral patterns, especially dispersal and migration, supporting the interpretation that A. brevirostrum exhibit adaptive differences based on watershed. Combined with results of prior genetic (mitochondrial DNA) and behavioral studies, the current work suggests that dispersal is an important factor in maintaining genetic diversity in A. brevirostrum and that the basic unit for conservation management is arguably the local population.


Mountain biking injuries: an update.
This article reviews the available literature regarding injuries in off-road bicyclists. Recent progress in injury research has allowed the description of several patterns of injury in this sport. Mountain biking remains popular, particularly among young males, although sales and participation figures have decreased in the last several years. Competition in downhill racing has increased, while cross-country racing has decreased somewhat in popularity. Recreational riders comprise the largest segment of participants, but little is known about the demographics and injury epidemiology of noncompetitive mountain cyclists. Most mountain bikers participating in surveys reported a history of previous injuries, but prospective studies conducted at mountain bike races have found injury rates of <1%. The most common mechanism of injury involves a forward fall over the handlebars, usually while riding downhill, which can result in direct trauma to the head, torso and upper extremities. A variety of factors can be associated with this type of fall, including trail surface irregularities, mechanical failures and loss of control. In mountain bike racing the risk of injury may be higher for women than men. Minor injuries such as abrasions and contusions occur frequently, but are usually of little consequence. Fractures usually involve the torso or upper extremities, and shoulder injuries are common. Head and face injuries are not always prevented by current helmet designs. Fatal injuries are rare but have been reported. Improvements in safety equipment, rider training and racecourse design are suggested injury prevention measures. The authors encourage continued research in this sport.


First clinical results with a 30 degrees end-to-side coronary anastomosis coupler.
The purpose of this study is to evaluate the safety and efficacy of a novel 30 degrees end-to-side coronary anastomotic coupler (Converge Medical, Inc., Sunnyvale, CA) that facilitates a non-penetrating, sutureless vein graft to coronary artery anastomosis. The Coupler utilizes a set of concentric mating frames approximating adjacent vessel tissue allowing for biological healing of the anastomosis. The frames are manufactured from Nitinol, a nickel titanium super-elastic metal alloy. The Nitinol frames attach the bypass graft to the coronary artery in a 30 degrees end-to-side configuration. Between November 2002 and March 2003 a total of 46 patients (44 male) with a mean age of 63.6+/-7.5 years were admitted for coronary artery revascularization and included in the study. The mean LVEF was 60.6+/-12.4%. Thirty-three patients were successfully treated with the Coupler. Nine patients did not meet the intraoperative inclusion criteria, and were excluded from the study due to small (<or=2.0mm) or severely calcified coronary vessels, or small vein grafts. Hemostasis could not be achieved with the Coupler in 3 patients, and in one patient the graft flow measured intraoperative was low. In these instances the Coupler was removed and the anastomosis was sutured without complication. Average mean flow rate using transit time method through the Coupler attached bypasses was 54+/-26ml/min. In a control angiography 2 months after surgery, 29 (96.7%) of the 30 connector grafts were patent. One stenosis of 50% occurred on the site of a connector anastomosis. Angiographic patency assessments for 81 hand sewn grafts revealed 73 (90.1%) patent grafts. Initial results indicate that the Converge Coupler can be used to create a safe and effective 30 degrees vein graft to coronary artery anastomosis under suitable conditions.


Optimal heat stress metric for modelling heat-related mortality varies from country to country.
Combined heat and humidity is frequently described as the main driver of human heat-related mortality, more so than dry-bulb temperature alone. While based on physiological thinking, this assumption has not been robustly supported by epidemiological evidence. By performing the first systematic comparison of eight heat stress metrics (i.e., temperature combined with humidity and other climate variables) with warm-season mortality, in 604 locations over 39 countries, we find that the optimal metric for modelling mortality varies from country to country. Temperature metrics with no or little humidity modification associates best with mortality in ~40% of the studied countries. Apparent temperature (combined temperature, humidity and wind speed) dominates in another 40% of countries. There is no obvious climate grouping in these results. We recommend, where possible, that researchers use the optimal metric for each country. However, dry-bulb temperature performs similarly to humidity-based heat stress metrics in estimating heat-related mortality in present-day climate.


The Role of Non-Caloric Sweeteners in Sensory Characteristics of Pastry Products.
The purpose of this work was to evaluate the role of non-caloric sweeteners in pastry products considering the product made with sugar as a control sample. Sensory preference and acceptability with consumers were determined through ranking test and 9-point hedonic scale respectively. The satiation and satiety were determined by the visual analogue scale (VAS). In addition, caloric intake; macronutrients; physical parameters such as yield, specific volume, hardness, cohesiveness, and gum; stability in storage time by microbiological analysis; and moisture variation of the samples were calculated. The results showed that the preference and sensory acceptability is significantly (p < 0.05) higher in the control sample; the sweeteners decreased the sensory response, but not the satiation and satiety, although these are not related to the sensory response and did not present significant differences with the control sample, except in the satiation parameter of the sample sweetened with Stevia. The physical and texture parameters highlight the best quality of the control sample and are related to the sensory response. The shelf life is also greater in the control sample, which shows that sugar contributes sweetness and other technological characteristics related to texture, stability during storage, aroma, color, and flavor, thanks to the Maillard reaction.


Balancing acute and long-term care: the mathematics of throughput in departments of geriatric medicine.
The empirical distribution of length of stay of patients in departments of geriatric medicine is fit extremely well by a sum of two exponentials. Most of the patients in a geriatric department are rehabilitated and discharged or they die within a few weeks of admission, but the few who become long-stay patients remain for months or even years. A model is presented for the flow of patients through a geriatric department, which has analogies to models of drug flow in pharmacokinetics. The theoretical model explains why the empirical pattern of length of stay in the occupied beds fits a sum of two exponentials; conversely, the empirical distribution, obtained from the midnight bed state report, can be used to study the effect of various policy decisions on both immediate and future admission rates for the department, and shows the benefits of policies which reduce long-stay patient numbers by improving long-stay rehabilitation.


Circulating Endothelial Cells as a Marker of Endothelial Injury in Severe COVID -19.
Beside the commonly described pulmonary expression of the coronavirus disease 2019 (COVID-19), major vascular events have been reported. The objective of this study was to investigate whether increased levels of circulating endothelial cells (CECs) might be associated with severe forms of COVID-19. Ninety-nine patients with COVID-19 were enrolled in this retrospective study. Patients in the intensive care units (ICU) had significantly higher CEC counts than non-ICU patients and the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines. Together, these data provide in vivo evidence that endothelial injury is a key feature of COVID-19.


Action of preoptic injections of beta-endorphin on temperature regulation in rabbits.
Male New Zealand White rabbits, Oryctolagus cuniculus, were stereotaxically implanted with a guide tube above the preoptic/anterior hypothalamus area (PO/AH) for the injection of the opioid peptide, beta-endorphin (beta-E), naloxone, sodium salicylate, or physiological saline. PO/AH and ear temperature, oxygen consumption, and evaporative heat loss (EHL) were recorded in free-moving rabbits before and after injection of saline followed with beta-E, naloxone, or sodium salicylate at ambient temperatures (Ta) of 2-31 degrees C. A 5-micrograms injection of beta-E promoted a rapid reduction in ear temperature followed by a prolonged rise in PO/AH (body) temperature. Preinjection with an isovolumetric amount of the opiate antagonist, naloxone, inhibited the thermoregulatory effects of beta-E. The beta-E-induced rise in body temperature was directly correlated with Ta. beta-E had no effect on oxygen consumption at Ta's of 5 and 27 degrees C. When measured 30 min after injection, beta-E demonstrated a significant inhibition of EHL at Ta's of 27 and 31 but not 5 degrees C. The beta-E-induced rise in body temperature was not antagonized with preinjections of sodium salicylate in the PO/AH. These data indicate that beta-E promotes a regulated increase in body temperature. The mechanism of activation appears to be distinct from that of an infectious fever.


Stroke unit care, inpatient rehabilitation and early supported discharge.
Stroke units reduce death and disability through the provision of specialist multidisciplinary care for diagnosis, emergency treatments, normalisation of homeostasis, prevention of complications, rehabilitation and secondary prevention. All stroke patients can benefit from provision of high-quality basic medical care and some need high impact specific treatments, such as thrombolysis, that are often time dependent. A standard patient pathway should include assessment of neurological impairment, vascular risk factors, swallowing, fluid balance and nutrition, cognitive function, communication, mood disorders, continence, activities of daily living and rehabilitation goals. Good communication and shared decision making with patients and their families are key to high-quality stroke care. Patients with mild or moderate disability, who are medically stable, can continue rehabilitation at home with early supported discharge teams rather than needing a prolonged stay in hospital. National clinical guidelines and prospective audits are integral to monitoring and developing stroke services in the UK.


On assembling polychlorinated aromatic hydrocarbons from carbon tetrachloride via dichlorocarbene intermediary by a solvothermal reaction: a reaction pattern from carbene-ylide interconversion.
[reaction: see text] The forced one-electron reduction of carbon tetrachloride with sodium in a sealed steel vessel is shown to have a narrow window of conditions to arrest the reaction at the polychlorinated aromatic hydrocarbons (PCAHs), as well as to prevent the reaction from proceeding all the way to the final stage of graphite and other carbon solids. The intermediates are quenched with toluene or benzene to give electrophilic substitution products and with water to give a quinomethine as the major product. The product pattern leads us to propose the carbene, perchlorobenzo[c,d]pyren-6-ylidene, or its reversible dimer as the major intermediate among others, that survives the severe conditions until coming into contact with these nucleophiles. Mainly from aromatic resonance stabilization, the carbene is proposed to have a delocalized singlet state analogous to a ylide electronic structure and, thus, undergoes observed ionic reactions instead of typical carbene reactions. This work serves as a mechanistic link on the structural evolution of carbon networks between molecular chemistry and nanomaterial chemistry.


What reduction in BMI SDS is required in obese adolescents to improve body composition and cardiometabolic health?
To study the impact of body mass index (BMI) SD score (SDS) improvement through lifestyle modification on metabolic risk and body composition over 12 months. Prospective cohort study. Hospital outpatient weight management clinic in the UK. 88 adolescents (40 males, 86% Caucasian) of median age 12.4 years (range 9.1-17.4) and mean (SD) BMI SDS 3.23 (0.49). BMI at baseline and 12 months was adjusted for age and gender providing BMI SDS using British 1990 growth reference data. Body composition was measured by bioimpedance. A standard oral glucose tolerance test (OGTT) examined glucose metabolism. Fasting lipid profiles, high sensitivity C-reactive protein (HsCRP) and blood pressure (BP) were measured. Reducing BMI SDS by >or=0.5 achieved significant improvements in important measures of body composition with mean waist circumference SDS reducing by 0.74 units and body fat SDS by 0.60 units, while also leading to significant reductions in key metabolic risk factors (triglycerides (-30%), low-density lipoprotein-cholesterol (-15%), HsCRP (-45%)). A lesser reduction of >or=0.25 improved insulin sensitivity, total cholesterol/high-density lipoprotein ratio and BP. The greater the BMI SDS reduction, the better the improvement seen in insulin sensitivity. The most insulinsensitive individuals at baseline were most likely to achieve BMI SDS changes of >or=0.5 regardless of baseline BMI SDS. Improvement in body composition and cardiometabolic risk can be seen with BMI SDS reductions of >or=0.25 in obese adolescents, while greater benefits accrue from losing at least 0.5 BMI SDS. The most insulin-sensitive individuals seem best able to effect these changes.


The kinetics of quantal releases during end-plate currents at the frog neuromuscular junction.
1. The preceding paper (Van der Kloot, 1988) described a method for estimating the timing of quantal releases during an end-plate current. This period of elevated quantal release is called the early release period or ERP (Barrett & Stevens, 1972b). In the present paper, this deconvolution method is used to study the effects of varying quantal output by extracellular ions, stimulus patterns and drugs. 2. The data were obtained by voltage clamping end-plates in low-Ca2+ high-Mg2+ solutions, or in solutions containing tubocurarine (measuring the decay of the miniature end-plate currents (MEPCs) before curarization and assuming a value for MEPC amplitude after curarization). Data were also obtained by extracellular recording in Ca2+-free solution, using a recording pipette filled with CaCl2 and regulating Ca2+ release with a bias current. The three approaches led to similar conclusions. 3. Quantal release rose during the ERP along a sigmoid curve and reached a maximum after about 1.4 ms at 10 degrees C. This is called the time to peak. Quantal release then fell, following an exponential time course with a time constant of about 1.2 ms (10 degrees C). This is called the time constant for decline. 4. The ERP was followed by further, elevated quantal release, at a much lower rate, which declined over a longer time course. This is called late release. The magnitude of late release appears to be almost independent of the magnitude of release during the ERP, although the deconvolution method is a poor one for determining late release. The remainder of the results therefore focus on the ERP. 5. Increasing [Ca2+]o increased quantal output, and the rate of quantal output. It did not change the time to peak or the time constant of decline. Similarly, replacing Ca2+ with Sr2+ did not alter the time course of the ERP. 6. Two-pulse facilitation increased quantal output without changing the time to peak or the time constant of decline. 7. Quantal output was enhanced still more following a brief series of repetitive nerve stimulations. There was a lengthening of the time to peak; there was no change in the decline. The depression produced by longer series of repetitive stimulations did not change the time course of the ERP. 8. 4-Aminopyridine (4-AP) and dimethylsulphoxide (DMSO) increased quantal output and lengthened the time to peak, without altering the time constant for decline. 9. Adenosine decreased quantal output without altering the time course of the ERP.(ABSTRACT TRUNCATED AT 400 WORDS)


Multi-resistant Gram-negative bacilli: from epidemics to endemics.
Infections due to multi-drug resistant Gram-negative bacilli represent a worrying situation for the management of hospitalized patients. In addition, these bacteria are increasingly involved in epidemics throughout the world. This review focuses on recent data that may help to understand the emergence and dissemination of multi-drug resistant bacilli and the current trend from epidemic to endemic situations. Well-established clones enhance their resistance phenotype by the acquisition of new resistant genes, via gene capture genetic units (plasmids, transposons or integrons), thus facilitating the co-selective process under different antimicrobial selective pressures and therefore the long-term persistence of organisms in selective environments. Not only resistant bacterial clones are selected, but also their genetic structures carrying resistance genes. Therefore, current epidemiology of multi-drug resistant bacilli is not only focused on bacterial clones but also on any kind of resistance gene capture units. In this scenario a multiclonal population structure of bacterial organisms corresponds to a collection of different strains sharing resistance genes carried by horizontally transferred genetic structures. As different strains tend to prefer different environments, this concept helps understand why the epidemiology of multi-drug resistant Gram-negative bacilli is moving from epidemics to endemics. The emergence and spread of multi-drug resistant bacilli in the nosocomial setting should be understood in terms of a complex interplay of bacterial clonality, resistance genes and genetic structures promoting rapid dissemination of antimicrobial resistance. Intervention strategies in the forthcoming scenario should identify existing epidemic and/or endemic situations involving clonal organisms or resistance genes carried by epidemic gene capture units.


Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers.
In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the "guardian of the genome," the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. This review discusses the functional foods bioactive compounds derived from several cruciferous vegetables and their use in altering the tumor-suppressive effect of p53 proteins. The association between the mutation of p53 and the incidence of gastrointestinal malignancies (gastric, small intestine, colon, liver, and pancreatic cancers) is also discussed. This review contains crucial information about the use of cruciferous vegetables in the treatment of gastrointestinal tract malignancies.


desynaptic5 carries a spontaneous semi-dominant mutation affecting Disrupted Meiotic cDNA 1 in barley.
Despite conservation of the process of meiosis, recombination landscapes vary between species, with large genome grasses such as barley (Hordeum vulgare L.) exhibiting a pattern of recombination that is very heavily skewed to the ends of chromosomes. We have been using a collection of semi-sterile desynaptic meiotic mutant lines to help elucidate how recombination is controlled in barley and the role of the corresponding wild-type (WT) meiotic genes within this process. Here we applied a combination of genetic segregation analysis, cytogenetics, and immunocytology to genetically map and characterize the meiotic mutant desynaptic5 (des5). We identified an exonic insertion in the positional candidate ortholog of Disrupted Meiotic cDNA 1 (HvDMC1) on chromosome 5H of des5. des5 exhibits a severe meiotic phenotype with disturbed synapsis, reduced crossovers, and chromosome mis-segregation. The meiotic phenotype and reduced fertility of des5 is similarly observed in Hvdmc1RNAi transgenic plants and HvDMC1p:GusPlus reporter lines show DMC1 expression specifically in the developing inflorescence. The des5 mutation maintains the reading frame of the gene and exhibits semi-dominance with respect to recombination in the heterozygote indicating the value of non-knockout mutations for dissection of the control of recombination in the early stages of meiosis.


[Preliminary results of a focus-group-based research project on the problems of implementing evidence-based practice in Belgium (Flanders). Do psychiatrists differ from other health care practitioners?].
The impact of evidence-based practice (EBP) has increased substantially in recent years. However, health care practitioners are experiencing difficulties in implementing EBP. The specific task was to find out what problems are encountered by Flemish (Belgian, Dutch-speaking) health care practitioners. method In order to explore this problem, we adopted a qualitative research strategy and set up 25 focus groups, 5 of which consisted solely of psychiatrists. results Psychiatrists shared with other health care disciplines some concerns about the characteristics of 'evidence' and about the influential role played by their 'partners' in the health care system, namely by government, commercial firms and patients. Psychiatrists perceived their discipline to be much more complex than other disciplines, particularly in areas such as research design, patients' problems, psychiatric diagnosis and therapeutic psychiatrist-patient relationships. The literature and the preliminary results of ongoing research revealed that other disciplines too are confronted with similar complexities. There seems to be no justification for ruling out the possibility of implementing EBP on the basis of discipline-related barriers.


The age of surgical operative video big data - My bicycle or our park?
Surgery is a major component of health-care provision. Operative intervention often employs minimally invasive approaches incorporating digital cameras creating a 'digital twin' of both intracorporeal appearances and operative performance. Video recordings provide richer detail than the traditional operative note and can couple with advanced computer technology to unlock new analytic capabilities capable of driving surgical advancement via quality improvement initiatives and new technology design. Surgical video is however an under-utilized technology resource, in part, because ownership along with broader issues including purpose, privacy, confidentiality, copyright and inclusion in outputs have been poorly considered using outdated categorisation. A first principles perspective on operative video classification as a useful public interest resource enshrining fundamental stakeholder (patients, physicians, institutions, industry and society) rights, roles and responsibilities. A facility of noble purpose, understandable to all, for fair, accountable, safe and transparent access to large volumes of anonymised surgical videos of intracorporeal operations that enables advances through cross-disciplinary research is proposed. Technology can be exploited to protect all relevant parties respecting both citizen data-rights and the special status doctor-patient relationship. Through general consensus, the capability can be understood, established and iterated to perfection. Overall we argue that new and specific classification of surgical video enables responsible curation and serves the public good better than the current model. Rather than being thought of as a bicycle where discrete ownership is ascribed, such data are better viewed as being more like a park, a regulated amenity we should preserve for better human life.


Optic nerve ultrasound and cardiopulmonary bypass: A pilot study.
Despite advances in surgical, anesthetic, perfusion, and postoperative care, adverse neurological consequences may occur following cardiac surgery and cardiopulmonary bypass (CPB). Consequences of the physiologic effects of CPB may alter the blood-brain barrier, autoregulation, and intracranial pressure (ICP) in the immediate postoperative period. We evaluated the effects of cardiac surgery and CPB on the central nervous system by measuring the optic nerve sheath diameter (ONSD) by using ultrasound as a surrogate marker of ICP. ONSD was measured after anesthetic induction and endotracheal intubation (time 1), after separation from CPB (time 2), and at the completion of the surgical procedure prior to leaving the OR (time 3). The study cohort included 14 patients, ranging in age from newborn to 6 years. When comparing the Fontan group (n = 5) to the non-Fontan group (n = 9), four elevated ONSD observations were recorded for the Fontan patients during the study period, including one at time 1, one at time 2, and two at time 3. In Fontan versus non-Fontan patients, ONSD was greater at all three time points compared to non-Fontan. The change in the ONSD from time 1 to time 2 was greater (+0.2 mm vs. -0.1 mm), and the mean value at time 2 was significantly higher (4.2 vs. 3.5 mm, P = 0.048). Patients with Fontan physiology may be more prone to higher levels of baseline intracranial pressure due to elevated systemic venous pressure and decreased cardiac output. Alternatively, the chronically high central venous pressures may artificially elevate ONSD without clinical changes in ICP, necessitating the development of separate normative values based on the type of congenital heart disease.


High-resolution mass spectrometry of viral assemblies: molecular composition and stability of dimorphic hepatitis B virus capsids.
Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecular particles is fundamental. HBV capsids are unusual in that they exhibit two distinct icosahedral geometries, nominally composed of 90 and 120 dimers with masses of approximately 3 and approximately 4 MDa, respectively. Here, a mass spectrometric approach was used to determine the masses of both capsids to within 0.1%. It follows that both lattices are complete, consisting of exactly 180 and 240 subunits. Nanoindentation experiments by atomic-force microscopy indicate that both capsids have similar stabilities. The data yielded a Young's modulus of approximately 0.4 GPa. This experimental approach, anchored on very precise and accurate mass measurements, appears to hold considerable potential for elucidating the assembly of viruses and other macromolecular particles.


Cancer Vaccines: A Brief Overview.
Vaccine approaches for cancer differ from traditional vaccine approaches for infectious disease in tending to focus on clearing active disease rather than preventing disease. In this review, we provide a brief overview of different types of vaccines and adjuvants that have been investigated for the purpose of controlling cancer burdens in patients, some of which are approved for clinical use or in late-stage clinical trials, such as the personalized dendritic cell vaccine sipuleucel-T (Provenge) and the recombinant viral prostate cancer vaccine PSA-TRICOM (Prostvac-VF). Vaccines against human viruses implicated in the development and progression of certain cancers, such as human papillomavirus in cervical cancer, are not considered here. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Vaccine types considered include autologous patient-derived immune cell vaccines, tumor antigen-expressing recombinant virus vaccines, peptide vaccines, DNA vaccines, and heterologous whole-cell vaccines derived from established human tumor cell lines. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. In particular, targeted ablation of these barricades with novel agents, such as the immune checkpoint drug ipilimumab (anti-CTLA-4) approved recently for clinical use, may offer significant leverage to vaccinologists seeking to control and prevent malignancy.


Telmisartan inhibits vasoconstriction via PPARγ-dependent expression and activation of endothelial nitric oxide synthase.
Telmisartan activates peroxisome proliferator-activated receptor-γ (PPARγ) in addition to serving as an angiotensin II type 1 receptor (AT(1)R) blocker. The PPARγ activity of telmisartan on resistance arteries has remained largely unknown. The present study investigated the hypothesis that telmisartan inhibited vascular tension in mouse mesenteric resistance arteries, which was attributed to an increased nitric oxide (NO) production through the PPARγ-dependent augmentation of expression and activity of endothelial nitric oxide synthase (eNOS). Second-order mesenteric arteries were isolated from male C57BL/6J, eNOS knockout and PPARγ knockout mice and changes in vascular tension were determined by isometric force measurement with a myograph. Expression and activation of relevant proteins were analysed by Western blotting. Real-time NO production was measured by confocal microscopy using the dye DAF. Telmisartan inhibited 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F(2α) (U46619)- or endothelin-1-induced contractions. An NOS inhibitor, N(G)-nitro-L-arginine methyl ester (l-NAME), or an inhibitor of soluble guanylate cyclase, 1H-[1,2,4]-oxadizolo[4,3-a]quinoxalin-1-one (ODQ), prevented telmisartan-induced inhibition of U46619 contractions. A PPARγ antagonist, GW9662, abolished telmisartan-induced inhibition. Likewise, the PPARγ antagonist rosiglitazone attenuated U46619-induced contractions. The effects of telmisartan and rosiglitazone were prevented by actinomycin-D, a transcription inhibitor. In contrast, losartan, olmesartan, and irbesartan did not inhibit contractions. The inhibition was absent in mesenteric arteries from eNOS knockout or PPARγ knockout mice. Telmisartan augmented eNOS expression, phosphorylation, and NO production, which were reversed by the co-treatment with GW9662. The present results suggest that telmisartan-induced inhibition of vasoconstriction in resistance arteries is mediated through a PPARγ-dependent increase in eNOS expression and activity that is unrelated to AT₁R blockade.


Effect of body mass index on breast cancer during premenopausal and postmenopausal periods: a meta-analysis.
There is no universal consensus on the relationship between body mass index (BMI) and breast cancer. This meta-analysis was conducted to estimate the overall effect of overweight and obesity on breast cancer risk during pre- and post-menopausal period. All major electronic databases were searched until April 2012 including Web of Knowledge, Medline, Scopus, and ScienceDirect. Furthermore, the reference lists and related scientific conference databases were searched. All prospective cohort and case-control studies investigating the association between BMI and breast cancer were retrieved irrespective of publication date and language. Women were assessed irrespective of age, race and marital status. The exposure of interest was BMI. The primary outcome of interest was all kinds of breast cancers confirmed pathologically. Study quality was assessed using the checklist of STROBE. Study selection and data extraction were performed by two authors separately. The effect measure of choice was risk ratio (RR(i)) and rate ratio (RR(a)) for cohort studies and odds ratio (OR) in case-control studies. Of 9163 retrieved studies, 50 studies were included in meta-analysis including 15 cohort studies involving 2,104,203 subjects and 3,414,806 person-years and 35 case-control studies involving 71,216 subjects. There was an inverse but non-significant correlation between BMI and breast cancer risk during premenopausal period: OR = 0.93 (95% CI 0.86, 1.02); RR(i) = 0.97 (95% CI 0.82, 1.16); and RR(a) = 0.99 (95% CI 0.94, 1.05), but a direct and significant correlation during postmenopausal period: OR = 1.15 (95% CI 1.07, 1.24); RR(i) = 1.16 (95% CI 1.08, 1.25); and RR(a) = 0.98 (95% CI 0.88, 1.09). The results of this meta-analysis showed that body mass index has no significant effect on the incidence of breast cancer during premenopausal period. On the other hand, overweight and obesity may have a minimal effect on breast cancer, although significant, but really small and not clinically so important.


Effects of dietary cholesterol and fatty acids on plasma lipoproteins.
The effects of dietary cholesterol and fatty acids on low density and high density lipoproteins (LDL and HDL) were studied in 20 young men. After 2-3 wk of evaluations on ad lib. diets, basal diets, which consisted of 15% protein, 45% carbohydrates, 40% fat, and 300 mg/day of cholesterol, were given for 4-5 wk (Basal). The ratio of dietary polyunsaturated to saturated fatty acids (P/S) for different groups of subjects were 0.25, 0.4, 0.8, or 2.5. 750 and 1,500 mg/d of cholesterol were added to the basal diets as 3 and 6 eggs, respectively. Total cholesterol and LDL cholesterol were lower in all subjects on the basal diets than on the ad lib. diets. Addition of 750 mg cholesterol to the diet with P/S = 0.25-0.4 raised LDL cholesterol by 16 +/- 14 mg/dl to 115% of basal diet values (n = 11, P less than 0.01); 1,500 mg increased LDL cholesterol by 25 +/- 19 mg/dl to 125% (n = 9, P less than 0.01). On the diet with P/S = 0.8, 750 mg produced insignificant increases in LDL cholesterol, but 1,500 mg produced increases of 17 +/- 22 mg/dl to 115% of basal (n = 6, P less than 0.02). On the P/S = 2.5 diet, neither 750 nor 1,500 mg produced significant changes. Thus, both the cholesterol contents and P/S ratios of diets were important in determining LDL levels. The lipid and apoprotein compositions, flotation rates, molecular weights, and binding by cellular receptors of LDL were virtually unchanged by the addition of cholesterol to the diets high in saturated fat. These diets, therefore, caused an increase in the number of LDL particles of virtually unchanged physical and biological properties. On the diet with low P/S ratio, HDL2 rose, whereas this effect was absent on diets with high P/S ratios. The response of LDL to dietary manipulations is consonant with epidemiologic data relating diets high in cholesterol and saturated fat to atherogenesis. The response of HDL2, however, is opposite to that of its putative role as a negative risk factor. Further work is needed to clarify this interesting paradox.


Evaluation of knowledge of the United Arab Emirates population on measles and its control, following a nationwide campaign.
In 2015, a nationwide campaign to eradicate measles was launched by the health authorities in the United Arab Emirates (UAE). This study aimed to assess the UAE society's knowledge of measles and its control following this campaign. A cross-sectional study was conducted among UAE residents above the age of 18 years from March to May 2017. A self-administered anonymous questionnaire was distributed, and a convenience sampling method was used. The data collected were entered and analyzed using the Statistical Package for the Social Sciences, version 22 software. A total of 391 questionnaires were completed from the overall 410 distributed. Most of the population have heard of measles (94.6%). However, only 23.5% claimed they have high knowledge of the disease. Information on measles was mainly acquired from family and friends (50.3%). Individuals with higher educational status were more knowledgeable about several aspects of the disease. Married individuals and those with children were more likely to identify the symptoms and associated conditions of the disease correctly. However, married participants had more misconception about the relationship between autism and the measles vaccine. No significant differences were found between the different age groups, genders, or nationalities. Despite the nationwide campaign to eradicate measles, based on the results of our study, the majority of the UAE population did not have knowledge about the measles disease and its preventive measures. It is important that public health authorities and public health organizations seek to address these issues.


Modulation of autoimmune rheumatic diseases by oestrogen and progesterone.
Sexual dimorphism is evident in the risk and expression of several human autoimmune diseases. Differences in disease manifestations observed between sexes are likely to involve immunomodulation by sex steroids, nonhormonal factors encoded by genes on the X and Y chromosomes, and immunological phenomena unique to pregnancy. In systemic lupus erythematosus (SLE), and perhaps other autoantibody-mediated diseases, oestrogen seems to increase the risk of disease in genetically predisposed women by targeting key immune pathways, including the type 1 interferon (IFN) response, differentiation of CD4(+) T helper cells and survival of autoreactive B cells. By contrast, progesterone seems to reduce the risk of SLE by counteracting the effects of oestrogen on some of these same pathways, which suggests that the balance between oestrogen and progesterone can determine disease expression. In this Review we focus on the roles of the sex steroid hormones oestrogen and progesterone in modulating the risk and expression of SLE and rheumatoid arthritis. Intensive research in this area promises to identify novel therapeutic strategies and improve understanding of the immunological requirements and complications of pregnancy, and is expected to define the mechanisms behind sexual dimorphism in autoimmunity, immunity and other aspects of human health--a newly announced directive of the NIH.


[Relationship between tobacco consumption and physical exercise in adolescents. Differences between genders].
The objective of this study was to analyze the relationship between physical exercise and sport activities with respect to tobacco consumption in adolescents according to gender. A total of 845 adolescents (412 males and 433 females) between 14 and 17 years of age enrolled in compulsory secondary education in Murcia (Spain) participated in the study. The International Physical Activity questionnaire was administered to all of them to determine their physical activity patterns, also the Youth Risk Behavior Surveillance questionnaire was given to evaluate their smoking behaviors. The results show a significant relationship between physical exercise and sport activity and tobacco consumption. In addition, a clear gender difference was found on tobacco use. Among males, a positive and significant relation between practice of sports and physical activity and tobacco use was found; while no association between both variables was found among females. In conclusion, differences between men and women related to practice of physical exercise and sport and tobacco consumption are associated with the characteristics of the current models used to promote practice of sports as well as the different motivations among men and women to engage in physical exercise and sport activity.


[Features of Urine Biomineralization in Long-Livers].
The increasing number of long-livers in the developed countries indicates the demand for clarification of the body vital systems' functioningfeatures which allow the long-livers to prolong their active involvement in social life. Aim of our study/research was to define a functional condition of urinary system in long-livers using the new diagnostic technology which analyses the structures of biological liquid at its phase transition in a solid state. A case series study was held. All long-livers suffered from atherosclerosis and its complications as well as from associated diseases. An exclusion criterion was acute conditions. The creatinine level in blood serum, indicators of common urine analysis and features of urine facies (using cuneiform dehydration) were defined. Participants included 60 long-livers (mean age 87.34±4.17 years) who were passing clinical laboratory tests at in-patient department of gerontological hospital. In urine facies of 41 (68.3%) long-livers a phenomenon of salt crystals distribution was identified. It presents the concentration of anisotropic salt crystals in the form of a ring in a regional facies zone. The tenfold increase in concentration of calcium and double increase in concentration of phosphorus in comparison with the central zone was detected in long-livers with a higher percent sulphur in the regional zone of urinefacies. The urine facies of the majority of long-livers have signs of age structure formation associated with a specific distribution of anisotropic salt crystals which fix detritus in its inert form to block the autointoxication.


[Disability in the population of the elderly: results of a field study].
The concept of disability has gained importance in geriatric research and practice. There is now insight into the impairing function not only of illness but also of its consequences for an autonomous and satisfactory way of life. The aim of the study reported here was to elucidate the relationships of old age disabilities and other potentially important factors such as physical and psychiatric impairments as well as demographic characteristics. A representative sample of old people in an urban community (Mannheim, F.R.G.) was the target population of this study. The results demonstrate--above all--a significant correlation between reduction in motor skill capacity and disability in carrying out activities of daily living. Psychiatric impairment--in particular organic psychiatric disorders--play a role as well. Old people with both physical and psychiatric impairments are the most disabled of the sample and must be considered a high-risk group for the loss of independent living.


An electrophysiological study of the forebrain projection of nucleus commissuralis: preliminary identification of presumed A2 catecholaminergic neurons.
Using a double-labeling technique (HRP combined with catecholamine fluorescence), up to 80% of all CA-containing neurons visualized in the nucleus commissuralis were found to project to or through the median forebrain bundle area (MFB). In addition at least 90% of all nucleus commissuralis neurons projecting through the MFB were found to be catecholaminergic. In a series of chloral hydrate-anesthetized rats, nucleus commissuralis neurons projecting through the MFB were identified with single-unit recordings by antidromic (AD) activation. These cells had a conduction velocity of about 0.5 m/s and a firing rate of 0-14 spikes/s. The pattern of discharge of these neurons was not correlated with the heart rate; they were unaffected by single-unit stimulation applied to the sciatic nerve but were powerfully excited by vagus nerve stimulation. For comparative purposes, NE-containing neurons were also recorded in the locus coeruleus (A6) in the course of the same experiments; in contrast with MFB-activated commissuralis neurons, A6 neurons were excited by both visceral (vagus nerve) and somatic (sciatic nerve) stimulation. The spontaneous firing rate of MFB-activated commissuralis neurons was inhibited by the intravenous administration of a low dose of the centrally acting antihypertensive agent clonidine (ED50: 28 micrograms/kg).


Effect of news coverage on the prevalence of drunk-driving behavior: evidence from a longitudinal study.
To examine the proposition that antidrunk driving messages in the news media contributed indirectly to the decline in drunk driving over the past two decades through their impact on related policy making processes. Time series regression techniques are applied to longitudinal data to examine the causal association between drivers' involvement in drunk-driving behavior, the volume of news coverage devoted to the drunk driving issue, and related policy making. Results show a significant contribution of news coverage to drunk-driving-related policy actions, which in turn are associated with a reduction in drunk driving among young and high-risk drivers. There was no evidence of a direct causal association between news coverage and change in drunk-driving behavior. News coverage of alcohol-related risky behaviors seems to provide a cost-effective way of reducing the prevalence of these practices by attracting institutional attention and prompting related environmental changes. Future interventions may benefit from actively seeking to influence news coverage of risky behaviors.


Swimming bacteria power microspin cycles.
Dense suspensions of swimming bacteria are living fluids, an archetype of active matter. For example, Bacillus subtilis confined within a disc-shaped region forms a persistent stable vortex that counterrotates at the periphery. Here, we examined Escherichia coli under similar confinement and found that these bacteria, instead, form microspin cycles: a single vortex that periodically reverses direction on time scales of seconds. Using experimental perturbations of the confinement geometry, medium viscosity, bacterial length, density, and chemotaxis pathway, we show that morphological alterations of the bacteria transition a stable vortex into a periodically reversing one. We develop a mathematical model based on single-cell biophysics that quantitatively recreates the dynamics of these vortices and predicts that density gradients power the reversals. Our results define how microbial physics drives the active behavior of dense bacterial suspensions and may allow one to engineer novel micromixers for biomedical and other microfluidic applications.


Identification of staphylococcal and streptococcal causes of bovine mastitis using 16S-23S rRNA spacer regions.
Bovine mastitis is caused mainly by certain Staphylococcus and Streptococcus species. The sequences of the 16S-23S rRNA spacer regions were determined for the nine species which cause mastitis: Staphylococcus aureus, Staphylococcus chromogenes, Staphylococcus epidermidis, Staphylococcus hyicus, Staphylococcus simulans, Staphylococcus xylosus, Streptococcus agalactiae, Streptococcus dysgalactiae and Streptococcus uberis. Significant variation was found between the spacer sequences of different species with the lengths of the spacers varying from 240 to 461 bp. Between genera the spacers shared only short conserved regions (8-9 bp) and within genera the sequence identities varied from 53 to 85%. This variation made it possible to construct specific primer pairs for these species and genera. The specificities of these primers were tested with 25 bacterial species and 51 isolates from cattle with clinical mastitis. The DNA-based identification of the mastitis species was mostly successful.


A Rare Case with Pulmonary Embolism and Literature Review.
Pulmonary embolism is rare in children, and most of them have high-risk factors, such as antiphospholipid syndrome, intravenous catheterization, fracture bed rest, etc. For children with pulmonary embolism without clear inducement, hereditary thrombophilia should be considered. Genetic protein S deficiency (PSD) is a kind of thrombophilia, which is caused by the mutation of PROS 1 gene, resulting in an increased tendency to thrombosis. The diagnosis of the two cases was made after detecting based on Thrombophilia screening and Sanger sequencing in clinical laboratory. Sanger sequencing found that case 2 and case 1 genotypes were the same, case 1 sister and grandfather carried c.200a>c (p.e67a) mutation, and case 1 aunt and grandmother did not carry PROS1 gene mutation. Case 1 received anticoagulation therapy for 3 months, and case 2 also received anticoagulation therapy for 3 months. During the 1 year follow-up, no new thrombotic events and no adverse reactions such as bleeding were observed in both patients. For children with pulmonary embolism without clear risk factors, PSD should be considered, and protein S activity should be tested before receiving anticoagulant drugs.


Vulvovaginal Candida albicans infections: pathogenesis, immunity and vaccine prospects.
Although a number of fungal species belonging to the genus Candida can cause acute vulvovaginal infection (VVC), Candida albicans is by far the most prevalent etiological agent, particularly for the most severe chronic condition known as recurrent vulvovaginal candidiasis (RVVC). This review focuses on recent advances in pathogenic mechanisms and host immune responses to C. albicans and on the utilisation of this information in the development of a vaccine to prevent and/or treat vaginal candidiasis. Currently, two vaccines with main or sole RVVC as clinical indication have completed a phase 1 clinical trial, and one of them has entered a phase 2 trial.


Separation of the action potential into a Na-channel spike and a K-channel spike by tetrodotoxin and by tetraethylammonium ion in squid giant axons internally perfused with dilute Na-salt solutions.
Squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution, which are known to produce long lasting action potentials in response to pulses of outward current, were investigated. The effects of tetrodotoxin (TTX) and of tetraethylammonium ion (TEA+) on such action potentials were studied. The results are summarized as follows: (a) An addition of 1--3 microM TTX to the external solution altered but did not block the action potentials; it increased the height of the action potential by approximately 15 mV, and it decreased the membrane conductance as the peak of excitation by about two-thirds. (b) Voltage-clamp experiments performed with both NaCl and TTX in the external CaCl2 solution revealed that the TTX-insensitive action potential does not involve a rise in gNa, whereas the experiments performed without TTX showed that the action potential is accompanied by a large rise in gNa. (c) Internally applied TEA+ was shown to selectively block the TTX-insensitive action potential, but it did not block the other component of the action potential, which is accompanied by a rise in gNa, and which is selectively suppressed by TTX. (d) The addition of a small amount of KCl to the external CaCl2 solution containing TTX greatly increased both the maximum peak inward current under voltage clamp and the maximum slope conductance. Furthermore, it was shown that K+ applied on both sides of the axon plays a dominant role in producing the membrane potential in the active state in the presence of TTX, even though a large amount of Ca2+ is presented in the bathing medium. These observations have led me to conclude that the sodium channel is responsible for the production of the TTX-sensitive component of the action potential under the ionic conditions of these experiments, and the potassium channel for the TTX-insensitive component of the action potential.


CCR4-NOT differentially controls host versus virus poly(a)-tail length and regulates HCMV infection.
Unlike most RNA and DNA viruses that broadly stimulate mRNA decay and interfere with host gene expression, human cytomegalovirus (HCMV) extensively remodels the host translatome without producing an mRNA decay enzyme. By performing a targeted loss-of-function screen in primary human fibroblasts, we here identify the host CCR4-NOT deadenylase complex members CNOT1 and CNOT3 as unexpected pro-viral host factors that selectively regulate HCMV reproduction. We find that the scaffold subunit CNOT1 is specifically required for late viral gene expression and genome-wide host responses in CCR4-NOT-disrupted cells. By profiling poly(A)-tail lengths of individual HCMV and host mRNAs using nanopore direct RNA sequencing, we reveal poly(A)-tails of viral messages to be markedly longer than those of cellular mRNAs and significantly less sensitive to CCR4-NOT disruption. Our data establish that mRNA deadenylation by host CCR4-NOT is critical for productive HCMV replication and define a new mechanism whereby herpesvirus infection subverts cellular mRNA metabolism to remodel the gene expression landscape of the infected cell. Moreover, we expose an unanticipated host factor with potential to become a therapeutic anti-HCMV target.


[Favorable effects of breathing and relaxation instructions in heart rehabilitation: a randomized 5-year follow-up study].
To determine the effect of breathing and relaxation instruction of patients after a myocardial infarction on the occurrence of cardiac events during 5 years. Prospective randomised. Kennemer Gasthuis, Haarlem, the Netherlands. In the period 1981-1983, 156 myocardial infarction patients were randomly assigned to either rehabilitation plus relaxation therapy (six weekly sessions of breathing and relaxation instruction) (n = 76) or cardiac rehabilitation alone (n = 80). The occurrence of cardiac events and the amount of medical consumption on the two treatments was compared during 5 years. At five-year follow-up, 12 cardiac deaths had occurred, 5 in the relaxation group and 7 in the control group, reinfarction was observed in 10 and 12 patients, and cardiac surgery was performed in 2 and 11, respectively. In total 15 (20%) and 26 patients (33%), respectively, had at least one of these events (odds ratio (OR) for the relaxation group: 0.51; 95% confidence interval (CI): 0.25-1.06). Medical consumption (counted as cardiac events and cardiac hospitalisations) was 30 patients (39%) experiencing 52 cardiac events in the relaxation group, for which the patients were hospitalized for a total of 476 days, and 38 patients (48%) experiencing 78 cardiac events in the control group (OR: 0.72; 95% CI: 0.38-1.36) with a total of 719 hospitalisation days; the total number of hospitalisations was reduced by 31% by relaxation instruction. In the long run, the disease course after myocardial infarction is probably influenced favourably by adding relaxation instruction to cardiac rehabilitation. The extra costs are compensated for by a decrease in hospitalisation for cardiac problems.


RNA Modification Level Estimation with pulseR.
RNA modifications regulate the complex life of transcripts. An experimental approach called LAIC-seq was developed to characterize modification levels on a transcriptome-wide scale. In this method, the modified and unmodified molecules are separated using antibodies specific for a given RNA modification (e.g., m⁶A). In essence, the procedure of biochemical separation yields three fractions: Input, eluate, and supernatent, which are subjected to RNA-seq. In this work, we present a bioinformatics workflow, which starts from RNA-seq data to infer gene-specific modification levels by a statistical model on a transcriptome-wide scale. Our workflow centers around the pulseR package, which was originally developed for the analysis of metabolic labeling experiments. We demonstrate how to analyze data without external normalization (i.e., in the absence of spike-ins), given high efficiency of separation, and how, alternatively, scaling factors can be derived from unmodified spike-ins. Importantly, our workflow provides an estimate of uncertainty of modification levels in terms of confidence intervals for model parameters, such as gene expression and RNA modification levels. We also compare alternative model parametrizations, log-odds, or the proportion of the modified molecules and discuss the pros and cons of each representation. In summary, our workflow is a versatile approach to RNA modification level estimation, which is open to any read-count-based experimental approach.


A HALP score-based prediction model for survival of patients with the upper tract urothelial carcinoma undergoing radical nephroureterectomy.
The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.


A systematic review of the burden of pertussis in South Korea.
This review summarizes the published data on epidemiology and burden of pertussis in South Korea as these may be under-categorized. A systematic literature review of PubMed, SCOPUS, EMBASE and KMBASE was performed to identify published literature in South Korea since 2000. Pertussis detection rates among 19 eligible studies range from 0.7% to 100% across different age groups, detection methods and study settings. Highest rates are observed in infants, while adolescents and adults with pertussis infection may suffer from persistent coughing. Vaccination uptake of pertussis booster dose among adolescents and adults remains low while seropositivity (detection of anti-pertussis immunoglobulin G), is high among adults. This review reveals a high burden of vaccine-preventable pertussis in South Korea. Besides primary childhood vaccination, strategies like maternal immunization and decennial revaccination of adults should be considered. Active testing, reporting and better utilization of vaccine registries may provide insights for decision-makers nationwide.


The effects of alpha and beta adrenergic agonists and cyclic adenosine 3':5'-monophosphate on epidermal metabolism.
Continuously regenerating stratified squamous epithelia form an interesting model for examining mechanisms controlling the balance between rates of cell formation and cell maturation and death. In vitro assays of rates of glycolysis and amino acid incorporation of epidermal sheets free from dermal contamination were used to examine rates of metabolism in both normal and hyperplastic epidermis after treatment with various adrenergic agonists and cAMP. Epinephrine and isoproterenol over the concentration range of 1 x 10(-9) to 1 x 10(-5) M depressed the rates of glycolysis and amino acid incorporation in normal epidermis. Dibutyryl cyclic AMP produced a 73 to 78% depression in metabolic activity and its action was enhanced by the addition of theophylline. The alpha adrenergic agonist norepinephrine produced similar reductions. When epidermal samples were treated with hexadecane to induce a mild hyperplasia, depressant effects of isoproterenol and epinephrine were lost, but dibutyryl cyclic AMP and norepinephrine still reduced metabolic activity. The results suggest that adrenergic agents and their putative second messenger cAMP cause reductions in epidermal metabolic activity, an effect similar to their effects on cell proliferation, and that increased rates of proliferation are associated with loss of beta adrenergic responsiveness of the epidermis.


Dietary supplements: physician knowledge and adverse event reporting.
Dietary supplement (DS) use among US military personnel is widespread. Many consume several different DS with multiple ingredients one or more times each week, representing a potential public health concern. The overall purpose of the study was to assess the knowledge and behaviors of health professionals and physicians regarding patterns of DS use and possible adverse events (AE) associated with DS use. We also determined how providers address the issue of DS with patients and evaluated provider knowledge regarding reporting systems. Two prospective, cross-sectional, web-based questionnaires were administered. First, health care providers who accessed the Natural Medicines Comprehensive Database to gather evidenced-based information on DS and herbal products were queried. Second, physicians who had graduated from the Uniformed Services University were sent a web-based questionnaire regarding DS knowledge, AE knowledge and reporting, and communication with patients about DS. The frequencies of responses were evaluated. Although 60% of the military physicians who responded to the questionnaires believed they had observed AE in association with a DS, only 18% actually reported them. Three of four physician respondents (approximately 73%) did not know how or where to report AE associated with DS. The majority of physicians (66%) routinely asked most of their patients about DS use, and 65% did not have a reliable source of information for herbal and DS products. Information gaps in DS information and AE reporting were identified. A centralized AE reporting system could serve to identify potentially harmful DS for further evaluation. Health professionals need to remain vigilant for AE associated with DS use and better informed on how to report these events.


Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats.
1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that are formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal neuropathy associated with several missense mutations in SPT. Oral L-serine supplementation suppressed the formation of 1-deoxySLs in patients with HSAN1 and preserved nerve function in an HSAN1 mouse model. Because 1-deoxySLs also are elevated in patients with type 2 diabetes mellitus, L-serine supplementation could also be a therapeutic option for diabetic neuropathy (DN). This was tested in diabetic STZ rats in a preventive and therapeutic treatment scheme. Diabetic rats showed significantly increased plasma 1-deoxySL concentrations, and L-serine supplementation lowered 1-deoxySL concentrations in both treatment schemes (P < 0.0001). L-serine had no significant effect on hyperglycemia, body weight, or food intake. Mechanical sensitivity was significantly improved in the preventive (P < 0.01) and therapeutic schemes (P < 0.001). Nerve conduction velocity (NCV) significantly improved in only the preventive group (P < 0.05). Overall NCV showed a highly significant (P = 5.2E-12) inverse correlation with plasma 1-deoxySL concentrations. In summary, our data support the hypothesis that 1-deoxySLs are involved in the pathology of DN and that an oral L-serine supplementation could be a novel therapeutic option for treating DN.


Motor function of gastric antrum and pylorus for evacuation of low and high viscosity meals in dogs.
In five conscious dogs motility of the antrum, pyloric sphincter, and duodenum was recorded with strain gauge transducers and induction coils. Gastric evacuation of low, medium, and high viscosity meals was measured via a duodenal cannula and observed simultaneously by radiography. Computer analysis of the propagation of the gastric waves revealed increased velocity in the distal antrum but no simultaneous contractions of the terminal antrum and pyloric sphincter. Radiography showed, and measurements of the antral diameter confirmed, that the indentations of the gastric waves were significantly deeper with the low viscosity liquid meal compared with the medium and high viscosity meals. Thereby, retropulsion of the medium and high viscosity ingesta was produced. Results indicated that gastric evacuation was regulated predominantly by the depth of the peristaltic indentation, which depended on the viscosity of the gastric contents. Nothing indicated that the phasic contractions of the pyloric sphincter were of importance for the regulation of gastric emptying.


Comprehensive Quantitative Spatiotemporal Gait Analysis Identifies Gait Characteristics for Early Dementia Subtyping in Community Dwelling Older Adults.
Background: Recent studies associated gait patterns with cognitive impairment stages. The current study examined the relation between dementia type and spatiotemporal gait characteristics under different walking conditions in pre and mild neurocognitive disorder stage. Methods: Community-dwelling older adults (age 50+) with memory complaints consulting a memory clinic underwent, at baseline and during follow-up (every 4 months), a standard dementia assessment and a comprehensive spatiotemporal gait analysis [walking on an electronic walkway at usual pace (UP) with and without a counting-backwards (CW) or animal-reciting dual-task (AW), at fast (FP) and at slow (SP) pace]. At baseline the participants were categorized according to the Clinical Dementia Rating (CDR) scale. At the end of the study, the dementia diagnosis was used to stratify the categories in three outcome groups: developed "No-dementia," "AD+FTD" (grouping Alzheimer's or Fronto-temporal dementia) or "VascD+LBD" dementia (grouping Vascular dementia or Lewy body dementia). The gait characteristics were compared per category in paired groups. Sub-analyzing in the ≥70-years-old participants evaluated the age effect. Results: Five hundred and thirty-six participants, age 50-to-95-years old were followed for 31-to-41 months. In the CDR 0, no differences were seen between eventual dementia and no-dementia individuals. In the CDR 0.5, CW dual task cost (DTC) step width was larger in the imminent "AD+FTD" and AW (normalized) gait speed was slower in the future "VascD+LBD" group compared to the no-dementia participants. Slower UP (normalized) gait speed differed the future "VascD+LBD" from the "AD+FTD" individuals. In the CDR 1: Wider steps in UP, SP and CW differed the "VascD+LBD" from the "AD+FTD" group. In the ≥70-years old CDR 0 category, higher AW cycle time variability in the imminent "AD+FTD" dementia group, wider UP step width and higher AW cycle time variability in the "VascD+LBD" group differed them from the no-dementia group up to 3 years before dementia diagnosis. The distinctive gait characteristics between the no-dementia and the imminent dementia groups in CDR 0.5 and CDR 1 remained the same as in the overall group. However, no gait differences were found between "VascD+LBD" and "AD+FTD" groups in the pre-dementia stages. Conclusion: Distinctive spatiotemporal gait characteristics were associated with specific dementia types up to 3 years before diagnosis. The association is influenced by the cognitive stage and age.


Variation in labial shoulder geometry of metal ceramic crown preparations: a finite element analysis.
Recent studies have highlighted variations in the geometry of teeth prepared to receive metal ceramic crowns, particularly in the region of the labial shoulder, where shoulder designs have often involved less reduction than is recommended. Using two-dimensional finite element analysis, this study subjected crowns, superimposed upon preparations with clinically common labial margin designs, to loads of 200N in three different directions. The resultant stress distribution within the labial marginal porcelain was examined. Results imply that variations in the marginal preparation geometry of metal ceramic crowns influenced the stress response of the finished crown. Within the limits of this study, a crown constructed a 1.3mm chamfer preparation appeared to have the best response to a simulated load applied to the palatal/incisal surface, at 45 degrees to the long axis.


Protistan plankton communities in the Galápagos Archipelago respond to changes in deep water masses resulting from the 2015/16 El Niño.
The Galápagos Archipelago lies within the Eastern Equatorial Pacific Ocean at the convergence of major ocean currents that are subject to changes in circulation. The nutrient-rich Equatorial Undercurrent upwells from the west onto the Galápagos platform, stimulating primary production, but this source of deep water weakens during El Niño events. Based on measurements from repeat cruises, the 2015/16 El Niño was associated with declines in phytoplankton biomass at most sites throughout the archipelago and reduced utilization of nitrate, particularly in large-sized phytoplankton in the western region. Protistan assemblages were identified by sequencing the V4 region of the 18S rRNA gene. Dinoflagellates, chlorophytes and diatoms dominated most sites. Shifts in dinoflagellate communities were most apparent between the years; parasitic dinoflagellates, Syndiniales, were highly detected during the El Niño (2015) while the dinoflagellate genus, Gyrodinium, increased at many sites during the neutral period (2016). Variations in protistan communities were most strongly correlated with changes in subthermocline water density. These findings indicate that marine protistan communities in this region are regimented by deep water mass sources and thus could be profoundly affected by altered ocean circulation.


Preparing medical students for clerkships: a descriptive analysis of transition courses.
Students have reported several challenging aspects of the transition to clerkships, such as applying clinical knowledge, learning experientially, using clinical skills, adjusting to clinical settings, and understanding roles. In an effort to address some of these challenges, a number of medical schools have added transition courses to their curricula, but little information about these courses has been published. The authors draw on findings from a study of the design and content of 30 transition courses offered in U.S. medical schools, to examine various approaches and provide a framework to guide the design of transition courses. Most courses (83%) were between one day and one week long. The authors identified three primary course themes: presentation of new information and skills, review and application of content covered in the preclerkship curriculum, and student well-being. All courses presented new information and skills, and more than half of the courses (53%) addressed all three themes. The most common curricular topics were technical/procedural skills, safety precautions, orientation to clinical settings, review of clinical skills, and stress management. Hands-on experience was the most frequently used instructional approach. Few courses had explicit goals and objectives, and evaluation of students was rare. Transition courses can address some of the needs and challenges associated with early clerkship experiences. These courses should explicitly target areas of need that are described in the literature as well as those identified within one's own institution. They should include clear objectives, learning activities tailored to the areas of need and objectives, and student and course evaluations.


Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer.
The survival of stage II colorectal cancer (CRC) patients is approximately 70% at 5 years. Identification of the patient subgroup at high risk for tumour recurrence and death would allow more informed use of chemotherapy for this stage of disease. Several clinical and pathological factors have been reported to associate with worse survival. In the present study we investigated the prognostic significance of two major genetic alterations in CRC: microsatellite instability (MSI+) and the type of Ki-RAS mutation. PCR-based molecular techniques were used to screen for MSI+ and Ki-RAS mutation in 396 stage II CRC patients with an average follow-up time of 75 months. Clinicopathological information was obtained by retrospective review of pathology reports. Prominent vascular invasion was identified in 19% of cases and was found to be an independent prognostic factor for poor outcome (relative risk = 2.08, 95% confidence interval: 1.22-3.57, p = 0.008). The MSI+ phenotype was found in 23% of proximal tumours and Ki-RAS mutations in 38% of the overall series. Neither MSI+ nor the type of Ki-RAS mutation showed prognostic significance in this cohort of stage II CRC. MSI+ and Ki-RAS mutation type are not useful markers for the identification of high-risk stage II CRC patients. Further prospective and/or cohort studies are required to determine whether these molecular changes have predictive value for survival benefit from 5-fluorouracil-based adjuvant chemotherapy.


Exact solution for infinitely strongly interacting Fermi gases in tight waveguides.
We present an exact analytical solution of the fundamental systems of quasi-one-dimensional spin-1/2 fermions with infinite repulsion for an arbitrary confining potential. The eigenfunctions are constructed by the combination of Girardeau's hard-core contacting boundary condition and group theoretical method, which guarantees the obtained states to be simultaneously the eigenstates of S and S_{z} and satisfy antisymmetry under odd permutation. We show that the total ground-state density profile behaves like the polarized noninteracting fermions, whereas the spin-dependent densities display different properties for different spin configurations. We also discuss the splitting of the ground states for large but finite repulsion.