Reactivity to visual signals in neurofibromatosis type 1: is everything ok?
Deficits in multiple aspects of attention are a hallmark of the cognitive impairments found with neurofibromatosis type I (NF1). Given, however, that some attention components are hierarchically organized, it is possible that sustained attention, flexibility, and resistance to interference deficits observed in NF1 may be because of weakened lower order attention components. This study investigated the state of these low-level components in NF1. Twenty participants with NF1 (ages 7-13) and 20 matched controls participated in a visual task. They were required to locate a target as quickly and as accurately as possible and to ignore a potential distractor that could appear either before, at the same time, or after the target. Response times (RTs) were collected, and indices of alerting (i.e., reactivity to warning signals), distraction, and interruption (i.e., reactivity to signals appearing during attentive processing) were computed. The amplitude of the indices differed between the groups, F(2, 76) = 3.1, p < .05. No difference was found with alerting (p > .85) or distraction (p > .84), but the interruption index was higher in the NF1 group than the controls (p < .043). Elementary components on which more complex attention processes are based are not all ok in NF1. It is suggested that overreactivity to and longer inspection of visual signals occurring outside the current focus of attention characterizes NF1 and that this might be partially responsible for focus of attention instability and lower interference resistance in NF1.


Regulation and function of DNA methylation in vertebrates.
In vertebrates, genomic DNA is often methylated at the 5th position of cytosine in the sequence of CpG, and this is the only chemical modification that genomic DNA of vertebrates allows under physiological conditions. During evolution, vertebrates acquired CpG methylation as a new tool for controlling gene expression in addition to the varieties of transcription factors. In mammals, the methylation pattern of genomic DNA is erased and reset in germ line and at the early stage of embryogenesis. Maintenance-type methylation activity ensures clonal transmission of the lineage-specific methylation pattern in somatic cells. The methylation pattern is dynamic and changes during cell differentiation. Prior to the expression of tissue-specific genes, specific sites of the promoters are demethylated. In general, the methylation of a gene suppresses its expression. However, not much is known about the mechanisms that regulate the methylation state and the gene expression by DNA methylation.


[Significance of technical parameters in color-coded duplex ultrasound for vascular studies].
Reliable colour-coded ultrasound duplex investigations of the vascular system require sufficient knowledge of its technical features. The most important parameters are the emitted ultrasound frequency, the axial and lateral resolution, the relationship between the colour-coded and B-mode gain, the Doppler insonation angle of the vessels, the upper (aliasing threshold) and lower (wall filter) cut-off frequencies, the frame rate as well as the influence of digital image processing. The practical relevance of these features for assessing the velocity, direction, pulsatility, localisation and disturbance of flow in blood vessels is discussed in comparison to conventional Doppler and duplex techniques.


Impact of statin therapy on plasma levels of plasminogen activator inhibitor-1. A systematic review and meta-analysis of randomised controlled trials.
Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I² test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and "trim and fill" tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: -15.72 ng/ml, 95 % confidence interval [CI]: -25.01, -6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: -21.32 ng/ml, 95 % CI: -32.73, -9.91, I²=99 %) and particularly atorvastatin (WMD: -20.88 ng/mL, 95 % CI: -28.79, -12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.


Vitamin D therapy to reduce blood pressure and left ventricular hypertrophy in resistant hypertension: randomized, controlled trial.
Low 25-hydroxyvitamin D levels are associated with higher prevalent blood pressure. We tested whether high-dose intermittent oral vitamin D therapy could reduce blood pressure and left ventricular mass in patients with hypertension resistant to conventional treatment. We conducted a parallel-group, double-blind, randomized placebo-controlled trial. Patients with supine office blood pressure >140/90 mm Hg on ≥3 antihypertensive agents received 100 000 U oral vitamin D3 or matching placebo every 2 months. Office and 24-hour ambulatory blood pressure, glucose, and cholesterol were measured at baseline, 2, 4, and 6 months; left ventricular mass index was measured by cardiac MRI on a subgroup at baseline and 6 months. The primary outcome was mean 24-hour ambulatory blood pressure at 6 months. A total of 68 participants were randomized, 34 in each group. Mean age was 63 (SD 11) years, mean baseline office blood pressure was 154/84 (13/10) mm Hg, and mean baseline 25-hydroxyvitamin D level was 42 (16) nmol/L. Treatment with vitamin D did not reduce 24-hour ambulatory blood pressure (adjusted treatment effects: systolic, +3 mm Hg; 95% confidence interval, -4 to +11; P=0.33; diastolic, -2 mm Hg; 95% confidence interval, -6 to +2; P=0.29); similar results were seen for office blood pressure. Left ventricular mass index was measured in a subgroup (n=25); no reduction was seen with vitamin D treatment (adjusted treatment effect, +4 g/m(2); 95% confidence interval, 0 to +7; P=0.04). There was no significant change in cholesterol or glucose levels. Thus, 6 months of intermittent, high-dose oral vitamin D3 did not reduce blood pressure or left ventricular mass in patients with resistant hypertension.


Characterization of a yeast mitochondrial promoter by deletion mutagenesis.
We have generated collections of mutants of the promoter for the small rRNA gene from the mitochondria of yeast deleted from either the 3' or 5' end. Plasmids containing the partially deleted promoter were assayed for their ability to direct correct transcriptional initiation in a homologous in vitro system. We find that the region required for high-efficiency promoter function lies between positions -10 and +2. Our methods detected no effect of flanking sequences on the strength of this promoter.


Efficacy, pharmacokinetics, and biodistribution of thermosensitive chitosan/β-glycerophosphate hydrogel loaded with docetaxel.
Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.


Serum antibody levels to glycosylphosphatidylinositols in specimens derived from matched Malian children with severe or uncomplicated Plasmodium falciparum malaria and healthy controls.
Neutralizing antibodies to glycosylphosphatidylinositols (GPIs), which are Plasmodium falciparum surface protein anchor molecules implicated in malaria pathogenesis, are thought to protect against symptomatic malaria. Index cases of severe malaria in Malian children 3 months to 14 years of age were matched by age and residence to uncomplicated malaria and healthy controls. Serum antibodies to GPI (IgM and IgG) were measured at the time of severe malaria and after the malaria transmission season. The mean optical density values for IgM and IgG antibodies were higher in children with severe or uncomplicated malaria compared with healthy controls. Similarly, higher percentages of children with IgM and IgG antibodies to GPI were observed in the severe malaria group compared with matched healthy controls. IgG antibody levels to GPI were highest among children with cerebral malaria and children who died. The IgG antibody levels to GPI peaked during periods of malaria transmission and decreased after malaria transmission ended. A direct correlation between age and parasitemia and IgG antibodies to GPI was observed. In summary, higher levels of IgM and IgG antibodies to GPI in young children were associated with disease severity and were short-lived.


Intussusception: agonal phenomenon or cause of death?
This paper describes two cases of small intestinal intussusception, one in a child and one in an adult, where the findings at autopsy were atypical. The significance of intussusception in this situation is discussed and the literature related to deaths accompanied by acute small intestinal intussusception in the adult and paediatric population is reviewed. It is concluded that the findings represent a true pathological entity and not an 'agonal' event.


Lung crackles in bronchiectasis.
The inspiratory timing of lung crackles in patients with bronchiectasis was compared with the inspiratory timing of the lung crackles in chronic bronchitis and alveolitis. In severe obstructive chronic bronchitis the lung crackles are typically confined to early inspiration while in alveolitis the lung crackles continue to the end of inspiration but may begin in the early or the mid phase of inspiration. In uncomplicated bronchiectasis on the other hand, the lung crackles typically occur in the early and mid phase of inspiration, are more profuse, and usually fade by the end of inspiration. In addition in bronchiectasis, crackles are also usually present in expiration, they are gravity independent and become less profuse after coughing.


Soft-tissue defects after spinal instrumentation in 5 children: risk factors, management strategies, and outcomes.
Wound-related complications following complex posterior spine procedures in children may result in the need for serial debridements and may place spinal instrumentation at risk. In this study, the authors review their experience with the management of soft-tissue defects from spinal instrumentation in 5 high-risk pediatric patients. The use of various rotational and transpositional flaps in the management of these complicated cases is discussed, as well as their outcomes. The authors retrospectively reviewed the medical records of 5 patients who returned to the Neuro-Spine service at Texas Children's Hospital for erosion of spinal instrumentation through the skin between September 1, 2007, and October 31, 2012. Patient demographics and clinical and operative data were recorded. Risk factors such as young age (1 case), poor nutritional status (1 case), multiple previous surgeries (3 cases), severe neurological deficits (2 cases), and history of radiation therapy for malignancy (2 cases) were noted in the 5 patients. The paraspinous flap (4 cases) was the mainstay of the treatment. Follow-up ranged from 7.5 to 17.5 months (mean 11 ± 4.2 months). One of the patients required more than 1 procedure for revision of the wound. Cultures were positive in 2 of the 5 cases. Spinal instrumentation was removed in 3 of the 5 cases; however, in all 3 of the cases there was evidence of delayed instability that developed after the removal of spinal instrumentation. The use of local tissue flaps is safe and efficacious for treatment of posterior wound complications due to spinal instrumentation in children. Removal of spinal instrumentation should be avoided due to the development of delayed instability. Highly vascularized tissue is used to speed healing, clear bacteria, and eliminate dead space, obviating the need to remove contaminated spinal instrumentation.


Does spending time outdoors reduce stress? A review of real-time stress response to outdoor environments.
Everyday environmental conditions impact human health. One mechanism underlying this relationship is the experience of stress. Through systematic review of published literature, we explore how stress has been measured in real-time non-laboratory studies of stress responses to deliberate exposure to outdoor environments. The types of exposures evaluated in this review include: nature viewing, outdoor walks, outdoor exercise and gardening. We characterize study design, modalities of stress measurements, and statistical estimates of effect and significance. Heart rate, blood pressure, and self-report measures provide the most convincing evidence that spending time in outdoor environments, particularly those with green space, may reduce the experience of stress, and ultimately improve health. More work is needed to understand effects of in situ modifications to outdoor environments on residents' stress response.


Resection-inspired histopathological diagnosis of cerebral cavernous malformations using quantitative multiphoton microscopy.
Rationale: Cerebral cavernous malformation (CCM) is prone to recurring microhemorrhage, which can lead to drug-resistant epilepsy. Surgical resection is the first choice to control seizures for CCM-associated epilepsy. At present, removal of resection-related tissue only depends on cautious visual identification of CCM lesions and perilesional yellowish hemosiderin rim by the neurosurgeon. Inspired by the resection requirements, we proposed quantitative multiphoton microscopy (qMPM) for a histopathology-level diagnostic paradigm to assist clinicians in precisely complete resection. Methods: A total of 35 sections specimens collected from 12 patients with the CCM-related epilepsy were included in this study. First, qMPM utilized a label-free multi-channel selective detection to image the histopathological features based on the spectral characteristics of CCM tissues. Then, qMPM developed three customized algorithms to provide quantitative information, a vascular patterns classifier based on linear support vector machine, visualization of microhemorrhage regions based on hemosiderin-related parameters, and the CCM-oriented virtual staining generative adversarial network (CCM-stainGAN) was constructed to generate two types of virtual staining. Results: Focused on CCM lesion and perilesional regions, qMPM imaged malformed vascular patterns and micron-scale hemosiderin-related products. Four vascular patterns were automatically identified by the classifier with an area under the receiver operating characteristic curve of 0.97. Moreover, qMPM mapped different degrees of hemorrhage regions onto fresh tissue while providing three quantitative hemosiderin-related indicators. Besides, qMPM realized virtual staining by the CCM-stainGAN with 98.8% diagnostic accuracy of CCM histopathological features in blind analysis. Finally, we provided pathologists and surgeons with the qMPM-based CCM histopathological diagnostic guidelines for a more definitive intraoperative or postoperative diagnosis. Conclusions: qMPM can provide decision-making supports for histopathological diagnosis, and resection guidance of CCM from the perspectives of high-resolution precision detection and automated quantitative assessment. Our work will promote the development of MPM diagnostic instruments and enable more optical diagnostic applications for epilepsy.


Diabetes and pregnancy: perspectives from Asia.
There has been a marked increase in the prevalence of diabetes in Asia over recent years. Diabetes complicating pregnancy, in particular gestational diabetes, has also increased markedly in the region. Multi-ethnic studies have highlighted the increased risk of gestational diabetes mellitus among the different Asian populations. Prevalence of gestational diabetes in Asian countries varies substantially according to the screening strategy and diagnostic criteria applied, and ranges from 1% to 20%, with evidence of an increasing trend over recent years. The International Association for Diabetes in Pregnancy Study group criteria have been adopted by some Asian countries, although they present significant challenges in implementation, especially in low-resource settings. Studies on offspring of mothers with gestational diabetes have reported adverse cardiometabolic profiles and increased risk of diabetes and obesity. Gestational diabetes is likely to be a significant factor contributing to the epidemic of diabetes and other non-communicable diseases in the Asian region. In recognition of this, several large-scale prevention and intervention programmes are currently being implemented in different Asian countries in order to improve glucose control during pregnancy, as well as overall maternal health. Lessons emerging from gestational diabetes studies in Asia may help inform and provide insights on the overall burden and treatment strategies to target gestational diabetes, with the ultimate aim to reduce its adverse short- and long-term consequences.


Inhibition of retrograde transport modulates misfolded protein accumulation and clearance in motoneuron diseases.
Motoneuron diseases, like spinal bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS), are associated with proteins that because of gene mutation or peculiar structures, acquire aberrant (misfolded) conformations toxic to cells. To prevent misfolded protein toxicity, cells activate a protein quality control (PQC) system composed of chaperones and degradative pathways (proteasome and autophagy). Inefficient activation of the PQC system results in misfolded protein accumulation that ultimately leads to neuronal cell death, while efficient macroautophagy/autophagy-mediated degradation of aggregating proteins is beneficial. The latter relies on an active retrograde transport, mediated by dynein and specific chaperones, such as the HSPB8-BAG3-HSPA8 complex. Here, using cellular models expressing aggregate-prone proteins involved in SBMA and ALS, we demonstrate that inhibition of dynein-mediated retrograde transport, which impairs the targeting to autophagy of misfolded species, does not increase their aggregation. Rather, dynein inhibition correlates with a reduced accumulation and an increased clearance of mutant ARpolyQ, SOD1, truncated TARDBP/TDP-43 and expanded polyGP C9ORF72 products. The enhanced misfolded protein clearance is mediated by the proteasome, rather than by autophagy and correlates with the upregulation of the HSPA8 cochaperone BAG1. In line, overexpression of BAG1 increases the proteasome-mediated clearance of these misfolded proteins. Our data suggest that when the misfolded proteins cannot be efficiently transported toward the perinuclear region of the cells, where they are either degraded by autophagy or stored into the aggresome, the cells activate a compensatory mechanism that relies on the induction of BAG1 to target the HSPA8-bound cargo to the proteasome in a dynein-independent manner.


Biochemical study of cardiac valvular tissue. Biosynthesis in vitro of hexosamine-containing substances in bovine heart valve.
1. Two distinct hexosamine-containing substances have been obtained from bovine cardiac valvular tissue which was incubated with labelled glucosamine. These were identified as mucopolysaccharides and glycopeptides respectively, both by the elution pattern from a Sephadex G-50 column and by chemical analysis. 2. In the mucopolysaccharide fraction about 80% of both the total hexosamine and total radioactivity were present; the galactosamine/glucosamine ratio of the amounts was about 1.36. 3. The glycopeptide fractions had about 20% of both total hexosamine and total radioactivity; the galactosamine/glucosamine ratio of amounts was about 0.44. In this fraction, over 15% of radioactivity was present in sialic acid. 4. In contrast with the concentrations of the several chemical components, there were remarkable differences in the biosynthetic activities among the four valves; the tricuspid valve had highest specific radioactivity in all components of both substances, followed then in turn by mitral, aortic and pulmonary valves. 5. Glucosamine in mucopolysaccharides had a rapid rate of turnover, followed then in turn by turnover rates of both glucosamine and galactosamine in glycopeptides, and of galactosamine in mucopolysaccharides. The possible significance of these findings is discussed.


A cyamella causing popliteal tendonitis.
A 64-year-old man presented with intermittent but progressive lateral-sided knee pain. Symptoms mimicked those of a lateral meniscal tear. Magnetic resonance imaging revealed a cyamella associated with popliteal tendonitis and an intact lateral meniscus.


[Skvyrs'ka Etel Berkivna--a gifted researcher and pedagogue (to the 100th anniversary of birthday)].
E. B. Skvyrska was born in the town of Chigirin. In 1928 she graduated from the Agricultural-Pedagogical Division of the Kyiv Institute of People's Education (Taras Shevchenko Kyiv National University, now) in speciality pedagogue-biologist. In 1937 she finished the post-graduate course at the Institute of Biochemistry of the Academy of Sciences of the Ukrainian SSR, in 1940 she defended the thesis for the Candidate's degree in biology and the title of the senior researcher was conferred on her in 1941. Beginning from 1936, E. B. Skvyrska had been working at the Institute of Biochemistry. She was working at the Department of Structure and Biochemistry of Nervous System (till 1963), and then at the Department of Structure and Biochemistry of Nuclear Acids (till 1973). In 1958 she defended the thesis for the Doctor's degree. From 1938 to 1941 E. B. Skvyrska worked as the assistant, and from 1945 to 1950 as the docent of the Department of Biochemistry at the Taras Shevchenko Kyiv (State) National University. Up to 1941 her scientific work was dedicated to the investigation of peculiarities of carbohydrate metabolism of the central and peripheral nervous system depending on the animal age. Since 1951 E. B. Skvyrska was investigating the metabolism of high-molecular phosphorus-including compounds (nucleic acids, phosphoproteins and phospholipids) in the central nervous system during the excitation and inhibition, in ontogenesis, in functionally and morphologically different parts of the nervous system, in different structure elements of the nerve cell. The results of investigations allowed finding the biochemical peculiarities connected with the difference of structure and function of morphologically different divisions of the nervous system. Peculiarities and functioning of t-RNA and aminoacyl-t-RNA synthetases of rats in norm and during starvation were studied at the Department of Nucleic Acids. More than 50 scientific works have been published.


Plasma adiponectin levels in relation to prognosis in patients with angiographic coronary artery disease.
The objective was to study the associations between adiponectin levels and cardiovascular adverse clinical outcomes in patients with angiographic coronary artery disease (CAD) within the Han Chinese population in Beijing. A total of 449 hospitalized patients with angiographic CAD who were Han Chinese in Beijing participated in the study. Plasma adiponectin levels were examined from blood samples using a type of unique enzyme-linked immunosorbent assay that was developed by our laboratory. All of the patients' clinical data, including previously identified cardiovascular risk factors, creatinine clearance and left ventricle ejection fraction, were recorded after admission, and patients were followed up for 19±8 months. The primary end-point was marked by the occurrence of major adverse cardiovascular events (MACE), which included death, targeted vascular revascularization, acute coronary syndrome, heart failure, and transient ischemic attack (TIA) / stroke. A total of 109 cases of MACE occurred: 15 cases of death, 66 cases of acute coronary syndrome, 4 cases of TIA/stroke, 6 cases of targeted vessel revascularization, and 18 cases of heart failure. Among all the patients, 173 were assigned to the high adiponectin group and 276 were assigned to the low adiponectin group according to their baseline plasma adiponectin levels. The incidence of MACE was significantly higher in the low adiponectin group (P=.037). In a multivariate Cox regression analysis for adiponectin levels, previously documented risk factors, coronary artery stenosis scores, and low adiponectin levels were indicated as independent predictors of MACE in patients with CAD (RR 1.75; 95% CI, 1.066-2.865; P=.027). Further adjustment for hsCRP, Ccr, LVEF, fasting glucose and lipid profile did not attenuate this association (RR=2.36; 95% CI 1.338-4.167; P=.003). The relative risk for low adiponectin levels after additional adjustment for the coronary score was 2.42 (95% CI 1.367-4.279; P=.002). The Kaplan-Meier survival analysis curve suggested that patients with lower adiponectin concentrations had a decreased event-free survival ratio (log-rank χ(2) =4.592, P=.032). The results indicate a potential association between plasma adiponectin levels and cardiovascular prognosis in patients with CAD.


Current trends in vena cava reconstructive techniques with major liver resection: a systematic review.
Historically, invasion of the inferior vena cava (IVC) represented advanced and often unresectable hepatic disease. With surgical and anesthetic innovations, IVC resection and reconstruction have become feasible in selected patients. This review assesses technical variations in reconstructive techniques and post-operative management. A comprehensive literature search was performed according to PRISMA. Inclusion criteria were (i) peer-reviewed articles in English; (ii) at least three cases; (iii) hepatic IVC resection and reconstruction (January 2015-March 2020). Primary outcomes were reconstructive technique, anti-thrombotic regimen, post-operative IVC patency, and infection. Secondary outcomes included post-operative complications and malignant disease survival. Fourteen articles were included allowing for investigation of 351 individual patients. Analysis demonstrated significant heterogeneity in surgical reconstructive technique, anti-thrombotic management, and post-operative monitoring of patency. There was increased utilization of ex vivo approaches and decreased use of venovenous bypass compared with previously published reviews. This review of literature published between 2015 and 2020 reveals persistent heterogeneity of hepatic IVC reconstructive techniques and peri-operative management. Increased utilization of ex vivo approaches and decreased use of venovenous bypass point towards improved operative techniques, peri-operative management, and anesthesia. In order to gain evidence for consensus on management, a registry would be beneficial.


Savings and wealth in the United States: trends and implications.
As the debate over the future of Social Security in the United States begins to gather momentum, data suggest that many individuals are not heeding advice to increase personal savings. By its traditional measure, personal saving virtually disappeared in 1998. While there is some controversy over the measure, the dramatic decline points to changes in spending habits in recent years. There is little doubt that the robust economy and sharp rise in equity prices have played a major role in boosting consumption and the willingness of consumers to take on more debt. However, with individuals living longer, the data point to difficulties for many households in sustaining long retirements. This has implications for public policy, and the concept of forced saving should be part of any debate.


Sugarcane genome sequencing by methylation filtration provides tools for genomic research in the genus Saccharum.
Many economically important crops have large and complex genomes that hamper their sequencing by standard methods such as whole genome shotgun (WGS). Large tracts of methylated repeats occur in plant genomes that are interspersed by hypomethylated gene-rich regions. Gene-enrichment strategies based on methylation profiles offer an alternative to sequencing repetitive genomes. Here, we have applied methyl filtration with McrBC endonuclease digestion to enrich for euchromatic regions in the sugarcane genome. To verify the efficiency of methylation filtration and the assembly quality of sequences submitted to gene-enrichment strategy, we have compared assemblies using methyl-filtered (MF) and unfiltered (UF) libraries. The use of methy filtration allowed a better assembly by filtering out 35% of the sugarcane genome and by producing 1.5× more scaffolds and 1.7× more assembled Mb in length compared with unfiltered dataset. The coverage of sorghum coding sequences (CDS) by MF scaffolds was at least 36% higher than by the use of UF scaffolds. Using MF technology, we increased by 134× the coverage of gene regions of the monoploid sugarcane genome. The MF reads assembled into scaffolds that covered all genes of the sugarcane bacterial artificial chromosomes (BACs), 97.2% of sugarcane expressed sequence tags (ESTs), 92.7% of sugarcane RNA-seq reads and 98.4% of sorghum protein sequences. Analysis of MF scaffolds from encoded enzymes of the sucrose/starch pathway discovered 291 single-nucleotide polymorphisms (SNPs) in the wild sugarcane species, S. spontaneum and S. officinarum. A large number of microRNA genes was also identified in the MF scaffolds. The information achieved by the MF dataset provides a valuable tool for genomic research in the genus Saccharum and for improvement of sugarcane as a biofuel crop.


[Urodynamic abnormalities in the kidneys of pancreonecrosis].
This paper presents experience in monitoring renal ultrasound data in patients with pancreatonecrosis from 20 to 60 years. It is also present two clinical cases of renal urodynamics in destructive forms of acute pancreatitis. Edematous form of acute pancreatitis and pancreatic cause violations not only secretion but also excretory function of the nephros. In patients with pancreatic necrosis accompanied by the formation of zones of limited fluid in the retroperitoneal space including retroperitoneal phlegmon may occur ureteral compression which is accompanied by appearance of urodynamic disorders in the nephros of varying severity. Ultrasound monitoring of renal care for patients with edematous form of acute pancreatitis, pancreatic necrosis helps to diagnose renal urodynamic disorders which allows timely corrected in the early stages of treatment activities in these patients and improve outcomes.


Effects of in vitro exposure to arachidonic acid on TNF-alpha production by murine peritoneal macrophages.
Modifying the fatty acid composition of macrophages through diet can significantly alter some of their functions, such as tumoricidal capacity and tumor necrosis factor alpha (TNF-alpha) production. The mechanism of that modification, however, is unknown. In this report, we provide evidence that fatty acids added to macrophages in culture can significantly alter macrophage TNF-alpha production. For example when inflammatory macrophages were incubated with various doses of arachidonic acid [20:4(n-6)] during activation with lipopolysaccharide (LPS), we observed a dose-dependent decrease in the level of bioactive TNF-alpha with complete inhibition at 2-5 microM. This inhibition was specific for 20:4(n-6) because in vitro treatment with other fatty acids, such as eicosapentaenoic [20:5(n-3)] or docosahexaenoic [22:6(n-3)] acids, had differential effects. The inhibitory action of 20:4(n-6) did not involve toxicity because cell viability was not affected and in vitro interferon-gamma and lipopolysaccharide (LPS) activation of macrophages for killing of P815 tumor targets was not altered. Inhibition by 20:4(n-6) occurred posttranscriptionally, and could be reversed when macrophages were treated with indomethacin during activation. Arachidonic acid treatment also significantly increased the production of immunoreactive prostaglandin E2 (PGE2) by LPS-treated and untreated macrophages. These results suggest that in vitro treatment of macrophages with 20:4(n-6) may inhibit TNF-alpha production through an alteration in the levels of PGE2 at a posttranscriptional level. These results provide evidence that some dietary fats may affect macrophage activity through modification of eicosanoid synthesis.


Molecular classification of myeloproliferative neoplasms-pros and cons.
Dameshek first postulated a common myeloproliferative heritage for the myeloproliferative disorders, now termed neoplasms. This prescient observation was validated by the description of a common mutation in exon 14 of JAK2 for patients with essential thrombocythemia, polycythemia vera and primary myelofibrosis. In recent years, our knowledge of the molecular abnormalities underpinning these disorders has expanded significantly. At the same time, we have continued to use a classification based largely upon the first clinical descriptions of these entities, which sometimes proves problematic in differentiating between these conditions and normal reactive processes, myelodysplasia and between the myeloproliferative neoplasm entities themselves. Here, we discuss the pros and cons of a molecular classification and its potential utility in diagnosis, prognosis, and therapeutics.


gcPathogen: a comprehensive genomic resource of human pathogens for public health.
Here, we present the manually curated Global Catalogue of Pathogens (gcPathogen), an extensive genomic resource designed to facilitate rapid and accurate pathogen analysis, epidemiological exploration and monitoring of antibiotic resistance features and virulence factors. The catalogue seamlessly integrates and analyzes genomic data and associated metadata for human pathogens isolated from infected patients, animal hosts, food and the environment. The pathogen list is supported by evidence from medical or government pathogenic lists and publications. The current version of gcPathogen boasts an impressive collection of 1 164 974 assemblies comprising 986 044 strains from 497 bacterial taxa, 4794 assemblies encompassing 4319 strains from 265 fungal taxa, 89 965 assemblies featuring 13 687 strains from 222 viral taxa, and 646 assemblies including 387 strains from 159 parasitic taxa. Through this database, researchers gain access to a comprehensive 'one-stop shop' that facilitates global, long-term public health surveillance while enabling in-depth analysis of genomes, sequence types, antibiotic resistance genes, virulence factors and mobile genetic elements across different countries, diseases and hosts. To access and explore the data and statistics, an interactive web interface has been developed, which can be accessed at https://nmdc.cn/gcpathogen/. This user-friendly platform allows seamless querying and exploration of the extensive information housed within the gcPathogen database.


Informing a PCOS Lifestyle Program: Mapping Behavior Change Techniques to Barriers and Enablers to Behavior Change Using the Theoretical Domains Framework.
This article aimed to identify the behavior change techniques (BCTs) based on facilitators and barriers to lifestyle management in women with polycystic ovary syndrome (PCOS) according to the behavior change wheel (BCW). This qualitative study design using inductive thematic analysis following semistructured interviews (n = 20) identified barriers and enablers to lifestyle management. These were then mapped to Capability, Opportunity, Motivation-Behavioral Model (COM-B) constructs and the corresponding Theoretical Domains Framework (TDF) domains. This study included women with PCOS residing in Australia. Main outcome measures include intervention functions, policy categories, and BCTs described in the BCW. Twenty-three BCTs were recognized to influence behavior change in women with PCOS. Factors were categorized into the subcomponents of the COM-B: psychological capability (e.g., lack of credible information), physical capability (e.g., managing multiple health conditions), physical opportunity (e.g., limited access to resources), social opportunity (e.g., adequate social support), reflective motivation (e.g., positive health expectancies following behavior change), and automatic motivation (e.g., emotional eating). Future research should use this work to guide PCOS lifestyle intervention development and then test intervention effectiveness through an experimental phase to provide empirical evidence for wider use and implementation of tailored, theory-informed PCOS lifestyle programs as part of evidence-based PCOS management.


Loss of hydroxyl groups from the ceramide moiety can modify the lateral diffusion of membrane proteins in S. cerevisiae.
In the yeast Saccharomyces cerevisiae, structural diversities of complex sphingolipids [inositol phosphorylceramide (IPC), mannosylinositol phosphorylceramide, and mannosyldiinositol phosphorylceramide] are often observed in the presence or absence of hydroxyl groups on the C-4 position of long-chain base (C4-OH) and the C-2 position of very long-chain fatty acids (C2-OH), but the biological significance of these groups remains unclear. Here, we evaluated cellular membrane fluidity in hydroxyl group-defective yeast mutants by fluorescence recovery after photobleaching. The lateral diffusion of enhanced green fluorescent protein-tagged hexose transporter 1 (Hxt1-EGFP) was influenced by the absence of C4-OH and/or C2-OH. Notably, the fluorescence recovery of Hxt1-EGFP was dramatically decreased in the sur2Δ mutant (absence of C4-OH) under the csg1Δcsh1Δ background, in which mannosylation of IPC is blocked leading to IPC accumulation, while the recovery in the scs7Δ mutant (absence of C2-OH) under the same background was modestly decreased. In addition, the amount of low affinity tryptophan transporter 1 (Tat1)-EGFP was markedly decreased in the sur2Δcsg1Δcsh1Δ mutant and accumulated in intracellular membranes in the scs7Δcsg1Δcsh1Δ mutant without altering its protein expression. These results suggest that C4-OH and C2-OH are most probably critical factors for maintaining membrane fluidity and proper turnover of membrane molecules in yeast containing complex sphingolipids with only one hydrophilic head group.


[Pott puffy tumor: case report].
We present the case of a child with frontal sinusitis, who also suffers from a severe intracranial disease. Although sinusitis intracranial issues are rare nowadays, they include a wide range of serious entities such as meningitis, brain abscesses and thrombosis of the cavernous sinus. We emphasize the importance of early diagnosis and an adequate initial empirical treatment to prevent possible complications. Once they are presented, an aggressive surgical medical treatment is required for its resolution.


The regulation of ATP-dependent nucleosome remodelling factors.
The plasticity of chromatin is governed by multi-subunit protein complexes that enzymatically regulate chromosomal structure and activity. Such complexes include ATP-dependent chromatin remodelling factors that are involved in many fundamental processes such as transcription, DNA repair, replication and chromosome structure maintenance. Because ATP-dependent chromatin remodelling factors play important roles, it is not surprising to find that their functions are regulated in a plethora of ways, including post-translational modifications of their subunits and subunit composition changes. The activity of these enzymes is modulated by many factors, including linker histones, histone variants, histone chaperones, non-histone chromatin constituents such as HMG-proteins and secondary messengers, such as inositolpolyphosphates. Additionally, specific histone modifications and interaction with site-specific transcriptional regulators direct the targeting of these activities. Understanding the network of mechanisms that control ATP-dependent chromatin remodelling will constitute an important challenge towards our understanding of chromatin dynamics.


Legal implications of fetal heart assessment.
The standard of care requires perinatal nurses to perform fetal heart (FH) assessment competently and safely. Failure to adhere to established guidelines and standards for FH assessment may result in negative outcomes for the fetus or newborn and contributes to claims of nursing negligence. The perinatal nurse must be fully cognizant of professional guidelines and standards for FH assessment and comply with agency policies and procedures when conducting assessment of the fetal heart. Guidelines for FH assessment during the antepartum and intrapartum period are discussed within the context of restructured health care settings and today's medicolegal climate.


The stimulation by the tumour promoters 12-O-tetradecanoylphorbol-13-acetate and phenobarbital of the growth of primary neonatal rat hepatocytes.
A single exposure to a wide range of concentrations (10(-15)-10(-4) mol/l) of the tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phenobarbital (PB) significantly stimulated the flow into DNA synthesis and mitosis of neonatal rat hepatocytes in 4-day-old primary cultures kept in high-calcium (1.8 mmol/l) Eagle's FBS-MEM. Maximal effects were observed in the dose range 10(-12)-10(-6) mol/l. Moreover, both xenobiotics retained their full mitogenic effectiveness when given to hepatocytes incubated in calcium-deficient (0.01 mmol/l) FBS-MEM, thereby evoking a neoplastic phenotype in otherwise normal (i.e., non-initiated) cells. Proliferation kinetic studies showed that TPA and PB acted according to the actual cell cycle setting of the cells: they committed a fraction of the quiescent (GO) hepatocytes to grow, and enabled hepatocytes previously poised at the G1/S and G2/M boundaries to start cycling again, but exerted no influence on liver cells already engaged by themselves in active cycling. These diverse activities of TPA and PB were independent of serum (growth) factors; they were also fully elicited in hepatocytes grown in synthetic media (Eagle's MEM or HiWoBa2000), and were not changed by the addition of a mitogenically effective dose (10(-10) mol/l) of epidermal growth factor/urogastrone (EGF) with or without FBS. Conversely, the addition of the specific plasmalemmal calcium chelator, EGTA, or displacer, La3+, or of the anticalmodulin drugs, W-13 and calmidazolium (or R24571: an agent hardly entering cells) fully inhibited the mitogenic activities of tumour promoters in quiescent and intra-cycle-blocked hepatocytes, while having no effect on untreated or xenobiotic-treated liver cells already cycling by themselves. Such inhibitory effects were in all instances independent of the actual extracellular calcium concentration and took place according to time-related double kinetics. Hence, xenobiotic-activated processes taking place at the plasmalemmal level and involving the activation of calcicalmodulin-dependent enzymes were of critical importance for both the G0/G1 and G1/S transitions in primary hepatocytes.


The impact of Resolvin E1 on bone regeneration in critical-sized calvarial defects of rat model-A gene expression and micro-CT analysis.
To investigate, in vivo, the effect of local application of Resolvin E1 (RvE1) on the bone regeneration of critical-size defects (CSDs) in Wistar rats utilizing gene expression and micro-computed tomographic (micro-CT) analysis. The inflammation-resolving actions of RvE1 are well established. The molecular mechanism of its bone-regenerative actions has been of significant interest in recent years; however, there is limited information regarding the same. Thirty Wistar rats with a 5 mm induced critical-size calvarial defect were randomly allocated into four groups: no treatment/negative control (n = 5), treatment using bovine bone grafts/positive control (n = 5), treatment using local delivery of RvE1 (n = 11) and treatment using RvE1 mixed with bovine bone graft (n = 9). After 4 weeks, RNA isolation, complementary DNA synthesis and real-time polymerase chain reaction were used for genetic expression of alkaline phosphatase (ALP), osteocalcin (OCN) and osteopontin (OPN). The rats were sacrificed after 12 weeks and micro-CT imaging was performed to analyse the characteristics of the newly formed bone (NFB). The data were analysed using ANOVA and the least significant difference tests (α ≤ .05). The RvE1 + bovine graft group had statistically highest mean NFB (20.75 ± 2.67 mm3 ) compared to other groups (p < .001). Similarly, RvE1 + bovine graft group also demonstrated statistically highest mean genetic expression of ALP (31.71 ± 2.97; p = .008) and OPN (34.78 ± 3.62; p < .001) compared to negative control and RvE1 groups. Resolvin E1 with adjunct bovine bone graft demonstrated an enhanced bone regeneration compared to RvE1 or bovine graft alone in the calvarial defect of Wistar rats.


The osteoprotective effect of Herba epimedii (HEP) extract in vivo and in vitro.
Herba epimedii (HEP) is one of the most frequently used herbs prescribed for treatment of osteoporosis in China. In the present study, the in vivo effects of HEP extract on bone metabolism were evaluated using 4-month-old ovariectomized (OVX) or sham-operated (Sham) female Sprague-Dawley rats orally administered with HEP extract (110 mg kgd), 17ss-estrogen (2 mg kgd) or its vehicle for 3 months. HEP extract significantly decreased urinary calcium excretion, suppressed serum alkaline phosphatase (ALP) activity and urinary deoxypyridinoline levels in OVX rats (P < 0.05 versus vehicle-treated OVX rats). Histomorphometric analysis indicated that HEP extract could prevent OVX-induced bone loss by increasing tibial trabecular bone area and decreasing trabecular separation in OVX rats (P < 0.05 versus vehicle-treated OVX group). The in vitro effects of HEP extract were also studied using rat osteoblast-like UMR 106 cells. HEP extract significantly stimulated cell proliferation in a dose-dependent manner (P < 0.01 versus vehicle-treated) and increased ALP activity at 200 microgml (P < 0.01 versus vehicle-treated) in UMR 106 cells. It modulated osteoclastogenesis by increasing osteoprotegrin (OPG) mRNA and decreasing receptor activator of NF-kappaB ligand (RANKL) mRNA expression, resulting in a dose-dependent increase in OPG/RANKL mRNA ratio (P < 0.01 versus vehicle-treated). Taken together, HEP treatment can effectively suppress the OVX-induced increase in bone turnover possibly by both an increase in osteoblastic activities and a decrease in osteoclastogenesis. The present study provides the evidence that HEP can be considered as a complementary and alternative medicine for treatment of post-menopausal osteoporosis.


Changes in Smoking Behavior, Stress, and Sleep Duration Among Israeli Hospital Workers During the COVID-19 Pandemic: A Cross-sectional Study.
Being on the COVID-19 frontline could negatively impact healthcare workers mental health. We examined smoking behavior changes and the association with changes in stress levels and sleeping patterns among hospital workers during the pandemic. An online survey was conducted among employees of a large tertiary medical center in Israel. Data collected included sociodemographic characteristics, smoking status, changes in smoking behavior (for smokers only), stress levels, and sleeping duration during the pandemic, perceptions of risk for COVID-19 infection and disease severity, presence of a chronic illness, COVID-19 exposure and infection status, and involvement in treating COVID-19 patients. Multinominal logistic regression modeling assessed the effects of covariates on smoking behavior change. Overall, 920 healthcare workers participated. More than half (59%) reported an increase in stress and 28% reported changes in sleep duration. Thirty-five percent of current smokers (n = 132), reported smoking more. Increased stress was associated with an increase in smoking (odds ratio [OR] = 3.45, 95% confidence interval [CI] 1.2-9.4, p = .016), and an increase in sleeping hours was significantly associated with a decrease in smoking (OR = 6.42, 95% CI 1.2-32, p = .02). Among smokers who reported perceived levels of stress to be the same or slightly higher than prepandemic, a strong inverse association was observed between sleep and smoking. The mental health consequences of the pandemic, specifically for health workers, could lead to negative changes in smoking behaviors. Together with offering stress-management skills and coping strategies, mental health support should target smoking behaviors and sleep disturbances. A high proportion of healthcare employees working in a large tertiary medical center in Israel reported increased stress levels during the COVID-19 pandemic. Among smokers, increased stress levels were associated with increased smoking, suggesting that smoking may be a coping mechanism for COVID-19-related stress. Offering stress-management skills and coping strategies can mitigate the negative impact on health workers' smoking behavior, and reduce stress-related increases in smoking behavior.


Lessons from medical students' perceptions of learning reflective skills: a multi-institutional study.
A core competency during undergraduate medical training is the development of reflective learning. The current literature is limited to demonstrating how reflective learning has been implemented or the approaches to its development. There is a lack of insight into students' perceptions of reflection and the factors that support development of reflective practice. Bridging this gap may provide insight into how reflective learning within the curriculum can be better developed to increase engagement from learners. Eight focus group interviews with second year students from four UK medical schools were held. Results were thematically analysed. Students have a high level of understanding of the purpose of reflection in practice but they perceive that there is a tension between public and private reflections. Assessment of the reflective process was perceived to be useful for developing reflective skills but grading of their reflective writing was not considered to be useful. Staff who champion the development of reflective skills and mentor students were perceived to play key roles in aiding the development of reflective skills. Appropriate experiences were seen to be a key part of developing reflective skills. These findings highlight potential ways to revise and improve engagement with the reflective learning components of undergraduate courses.


MnemoCity Task: Assessment of Childrens Spatial Memory Using Stereoscopy and Virtual Environments.
This paper presents the MnemoCity task, which is a 3D application that introduces the user into a totally 3D virtual environment to evaluate spatial short-term memory. A study has been carried out to validate the MnemoCity task for the assessment of spatial short-term memory in children, by comparing the children's performance in the developed task with current approaches. A total of 160 children participated in the study. The task incorporates two types of interaction: one based on standard interaction and another one based on natural interaction involving physical movement by the user. There were no statistically significant differences in the results of the task using the two types of interaction. Furthermore, statistically significant differences were not found in relation to gender. The correlations between scores were obtained using the MnemoCity task and a traditional procedure for assessing spatial short-term memory. Those results revealed that the type of interaction used did not affect the performance of children in the MnemoCity task.


Wearer-Prosthesis Interaction for Symmetrical Gait: A Study Enabled by Reinforcement Learning Prosthesis Control.
With advances in robotic prostheses, rese-archers attempt to improve amputee's gait performance (e.g., gait symmetry) beyond restoring normative knee kinematics/kinetics. Yet, little is known about how the prosthesis mechanics/control influence wearer-prosthesis' gait performance, such as gait symmetry, stability, etc. This study aimed to investigate the influence of robotic transfemoral prosthesis mechanics on human wearers' gait symmetry. The investigation was enabled by our previously designed reinforcement learning (RL) supplementary control, which simultaneously tuned 12 control parameters that determined the prosthesis mechanics throughout a gait cycle. The RL control design facilitated safe explorations of prosthesis mechanics with the human in the loop. Subjects were recruited and walked with a robotic transfemoral prosthesis on a treadmill while the RL controller tuned the control parameters. Stance time symmetry, step length symmetry, and bilateral anteroposterior (AP) impulses were measured. The data analysis showed that changes in robotic knee mechanics led to movement variations in both lower limbs and therefore gait temporal-spatial symmetry measures. Consistent across all the subjects, inter-limb AP impulse measurements explained gait symmetry: the stance time symmetry was significantly correlated with the net inter-limb AP impulse, and the step length symmetry was significantly correlated with braking and propulsive impulse symmetry. The results suggest that it is possible to personalize transfemoral prosthesis control for improved temporal-spatial gait symmetry. However, adjusting prosthesis mechanics alone was insufficient to maximize the gait symmetry. Rather, achieving gait symmetry may require coordination between the wearer's motor control of the intact limb and adaptive control of the prosthetic joints. The results also indicated that the RL-based prosthesis tuning system was a potential tool for studying wearer-prosthesis interactions.


The role of attentional focus on walking efficiency among older fallers and non-fallers.
This study evaluated the effect of attentional focus instructions on movement efficiency during a level-ground walking task in older adults with and without a history of falls. One hundred and thirty-four community-dwelling older adults were categorised into older fallers (OF) (n = 37) and older non-fallers (ONF) (n = 97). Each participant was instructed to walk at a self-selected pace along a 6 m walkway under three attentional focus conditions (i.e. internal, goal-directed and control) for a total of nine trials. Average muscle activity indices of lower limb co-contractions were measured using surface electromyography. Both shank and thigh muscle co-contractions were higher in OF than in ONF in all three conditions. OF also demonstrated higher shank muscle co-contraction under the internal relative to the goal-directed condition, with no such change observed in ONF. Despite no significant between-group differences in functional balance and balance confidence, relative walking inefficiencies were observed in OF compared with ONF. This finding demonstrates the debilitating consequences of falling that can occur with relative independence from various physiological or psychological factors that are commonly associated with falling and used to rationalise behavioural change. We also provide evidence that OF are more susceptible to conditions that provoke them to allocate attention internally. Therefore, in clinical contexts (e.g. gait rehabilitation), verbal instructions that refer to body movements (internal focus) might serve to compromise movement efficiency in older adults with a history of falls. Such changes will, theoretically, lessen the ability to react efficiently to changing environments experienced in daily life.


Human cerebrospinal fluid somatostatin in neurologic disease.
Concentrations of somatostatin-like immunoreactivity (SLI) were examined in human cerebrospinal fluid (CSF). To validate the assay it was shown that CSF which had been run over a somatostatin immunoaffinity column showed no interference with binding of synthetic standards. Reversed phase HPLC showed that the immunoreactive material coeluted with SS14 and SS28 as well as a higher molecular weight precursor. Concentrations of human CSF SLI were stable at both room temperature and 4 degrees C for up to 72 h while repeated freezing and thawing resulted in a significant loss of immunoreactive material after the 3rd repetition. In normal control patients less than 55 years of age, CSF SLI was 54.7 +/- 1.9 pg/ml, while in those older than 55 CSF SLI was 56.2 +/- 2.2 pg/ml. Febrile infants had significantly higher levels (75.4 +/- 7.3) pg/ml. CSF SLI was normal in patients with aseptic meningitis (54.4 +/- 3.4 pg/ml), suggesting that increased CSF protein and white cell counts do not affect concentrations. Concentrations of CSF SLI were significantly increased in intervertebral disc disease (65.1 +/- 5.6 pg/ml), intrinsic spinal cord pathology (101.0 +/- 23.9 pg/ml), central nervous system tumors (78.0 +/- 7.8 pg/ml) and acute cortical damage of varied etiology (277.8 +/- 81.6 pg/ml). Patients with pseudotumor cerebri had concentrations of 43.2 +/- 2.5 pg/ml. Concentrations of CSF SLI were significantly reduced (P less than 0.01) in multiple sclerosis (38.8 +/- 5.5 pg/ml) and old cortical pathology (23.2 +/- 3.9 pg/ml). Serial CSF analysis in patients with acute CNS lesions, suggest that CSF SLI may be a neurochemical marker of acute pathology, as the initially elevated levels fell to or below normal with resolution of the pathologic process.


Elastography using harmonic ultrasonic imaging: a feasibility study.
Tissue Harmonic Imaging (THI) is a relatively new modality that has had a significant impact in the ultrasound field. In the recent past, imaging the mechanical properties of tissues using elastography has also gained great interest. In this paper, we investigate the feasibility of combining these two state-of-the-art ultrasound-imaging modalities. The performance of elastograms obtained using harmonic ultrasonic signals is studied with simulations and compared to the performance of conventional elastograms using standard statistical methods. Experiments are used as a proof of the technical feasibility of generating tissue-harmonic elastograms using experimental harmonic signals. The results of our simulation study indicate that all image quality factors considered in this study (elastographic signal-to-noise ratio, elastographic contrast-to-noise ratio and spatial resolution) may be improved when using harmonic ultrasonic signals, provided that the ultrasound system is characterized by high bandwidth, high sampling frequency and large lateral sampling. Preliminary experimental results suggest that it is technically feasible to generate experimental elastograms using harmonic signals, provided that the sonographic signal-to-noise ratio of the pre- and postcompression harmonic frames is sufficiently high to guarantee reliable values of correlation.


Fairy tales: a compass for children's healthy development--a qualitative study in a Greek island.
Fairy tales have always been an integrated part of children's everyday life. In our days, they still represent important ways of helping the children share their desires and express their agonies and inner conflicts. The present descriptive qualitative study aims to describe parents' opinions and children's preferences regarding storytelling. Four hundred and seventy parents took part in the study and were interviewed following a semi-structured guide with open-ended trigger questions. Data were processed via content analysis methods. Three main themes were constructed. The vast majority of interviewees acknowledged their strong belief in the power of fairy tales and stated that their children listen to stories at least once a week. Most of them use storytelling as an instructive tool, in order to soothe their children's anxieties or set examples for them. Concerning children's preferences, the majority of them choose classic fairy tales over modern ones with Little Red Riding Hood taking precedence over other famous stories. All participants acknowledged the fact that their children are amused and positively affected by storytelling, while young readers share their enthusiasm for fairy tales in many ways, mostly by talking about their favourite character. Finally, in relation to the villains, children seem to be satisfied or relieved when they are punished and only a small number of participants stated that the cruel punishment of bad characters creates feelings of fear to their kids. The findings of this study emphasize the crucial role that storytelling plays in children's life and normal development.


Absolute blood volume in hemodialysis patients: why is it relevant, and how to measure it?.
Intradialytic hypotension (IDH) is the most common complication during hemodialysis and is associated with significant morbidity. It occurs as a consequence of a reduction in blood volume during ultrafiltration. Today, devices for monitoring relative blood volume (i.e. the intradialytic blood volume as a fraction of the blood volume at the start of the dialysis treatment) are routinely available and have been used to analyze the relationship between changes in relative blood volume and the occurrence of IDH in an attempt to derive critical thresholds that, when observed, would help avoid hypotensive episodes during the treatment. However, the results have been unsatisfactory in many patients. Here we illustrate the importance of absolute blood volume in hemodialysis patients, summarize the acute physiologic mechanisms involved in the preservation of adequate circulation during ultrafiltration, and outline why hemodialysis patients are often particularly vulnerable to reductions in blood volume. We then discuss the shortcomings of relative blood volume measurements, make a case for the superiority of absolute blood volume measurements, and introduce the reader to a mathematical concept that allows relative blood volume devices to be used for the estimation of absolute blood volume. Finally, we discuss the implications of absolute blood volume beyond IDH and propose a paradigm shift in the approach to dry weight attainment.


In vitro activity of daptomycin alone and in combination with various antimicrobials against Gram-positive cocci.
The increasing prevalence of resistant Gram-positive cocci requires the need to search for more effective agents and synergistic combinations. Forty-two vancomycin-resistant Enterococcus faecium (VREF), 30 methicillin-resistant Staphylococcus aureus (MRSA) and 36 Staphylococcus epidermidis (MRSE) strains were studied. Minimum inhibitory concentrations (MICs) were determined and synergy testing was performed by using E test for daptomycin, ampicillin-sulbactam, piperacillin-tazobactam and ticarcillin-clavulanate against staphylococci; for daptomycin, ampicillin, rifampin, and gentamicin against enterococci. Daptomycin in combination with ampicillin, rifampin, and gentamicin was tested against enterococci; daptomycin in combination with ampicillin-sulbactam, piperacillin-tazobactam, and ticarcillin-clavulanate was tested against staphylococci. Interaction categories were defined by the fractional inhibitory concentration (FIC) index. All strains of staphylococci and enterococci were susceptible to daptomycin. All three combinations showed synergy against more than 70% of the MRSA strains. Daptomycin in combination with ampicillin, rifampin, and gentamicin against enterococci showed synergies of 64.2%, 57.1% and 21.4%, respectively. This study indicates that daptomycin alone and combined with beta-lactams seems to be effective against MRSA, but further in vitro and in vivo studies on the subject are required before clinical use can be recommended.


Genomic regions involved in yield potential detected by genome-wide association analysis in Japanese high-yielding rice cultivars.
High-yielding cultivars of rice (Oryza sativa L.) have been developed in Japan from crosses between overseas indica and domestic japonica cultivars. Recently, next-generation sequencing technology and high-throughput genotyping systems have shown many single-nucleotide polymorphisms (SNPs) that are proving useful for detailed analysis of genome composition. These SNPs can be used in genome-wide association studies to detect candidate genome regions associated with economically important traits. In this study, we used a custom SNP set to identify introgressed chromosomal regions in a set of high-yielding Japanese rice cultivars, and we performed an association study to identify genome regions associated with yield. An informative set of 1152 SNPs was established by screening 14 high-yielding or primary ancestral cultivars for 5760 validated SNPs. Analysis of the population structure of high-yielding cultivars showed three genome types: japonica-type, indica-type and a mixture of the two. SNP allele frequencies showed several regions derived predominantly from one of the two parental genome types. Distinct regions skewed for the presence of parental alleles were observed on chromosomes 1, 2, 7, 8, 11 and 12 (indica) and on chromosomes 1, 2 and 6 (japonica). A possible relationship between these introgressed regions and six yield traits (blast susceptibility, heading date, length of unhusked seeds, number of panicles, surface area of unhusked seeds and 1000-grain weight) was detected in eight genome regions dominated by alleles of one parental origin. Two of these regions were near Ghd7, a heading date locus, and Pi-ta, a blast resistance locus. The allele types (i.e., japonica or indica) of significant SNPs coincided with those previously reported for candidate genes Ghd7 and Pi-ta. Introgression breeding is an established strategy for the accumulation of QTLs and genes controlling high yield. Our custom SNP set is an effective tool for the identification of introgressed genome regions from a particular genetic background. This study demonstrates that changes in genome structure occurred during artificial selection for high yield, and provides information on several genomic regions associated with yield performance.


Risk for incident arterial or venous vascular events varies over the course of systemic lupus erythematosus.
We describe the pattern of incidence of thrombovascular events after diagnosis of systemic lupus erythematosus (SLE) in a cohort of lupus patients. Descriptive study of prospectively collected data using incidence rates of thrombovascular events and 95% confidence intervals (CI) calculated for predetermined periods of observation. Kaplan-Meier survival curves were plotted to estimate thrombovascular event-free survival. Among 426 individuals, person-years contributed were as follows: 399 persons and 4356.0 person-years for all events; 417 persons and 4691.9 person-years for arterial events; and 408 persons and 4846.6 person-years for venous events. The incidence of thrombovascular events was highest during the first year after SLE diagnosis (4.00, 95% CI 2.24-6.59) and after 20 years (ranging from 3.32, 95% CI 1.52-6.30, to 4.99, 95% CI 0.60-18.01), and was lowest between 1 and 5 years after SLE diagnosis (1.00, 95% CI 0.53-1.72). A similar pattern was observed for arterial events, while venous events showed a higher incidence rate only in the first 30 days after SLE diagnosis (12.06, 95% CI 3.29-30.87) and remained low afterwards. The probabilities of remaining event-free at 5, 10, and 15 years were as follows: 0.92, 0.85, and 0.78, respectively, for all thrombovascular events; 0.95, 0.88, and 0.82, respectively, for arterial events; and 0.98, 0.95, and 0.94, respectively, for venous events. Thrombovascular events occur throughout the course of lupus, with the highest risk of arterial or venous events in the first year after diagnosis, and the pattern of occurrence varying thereafter.


Development of a novel patient focussed symptom severity index for use in assessing and treating inflammatory conditions of the lactating breast: a Delphi study.
To investigate the content and face validity of a patient-reported outcome measure used by Australian physiotherapists in the assessment of inflammatory conditions of the lactating breast. Sixty one experts representing 'women who previously had inflammatory conditions of the lactating breast' (48%), 'clinicians' (38%) and 'academics' (8%) interested in women's health and 7% unidentified participants were invited to complete a three round Delphi study. Ninety five percent of participants agreed that overall, the patient-reported outcome measure was appropriate for use in assessing and treating inflammatory conditions of the lactating breast. The item 'impact' was added to ensure the appropriate assessment of functional aspects of daily life. The item terminology used in the patient-reported outcome measure was simplified to 'pain', 'redness', 'hardness/tightness', 'temperature of affected area', 'sickness/wellness' and 'affected area. A clinician script was developed to ensure the patient-reported outcome measure has utility and consistency regardless of the experience of the women presenting with inflammatory conditions of the lactating breast or the clinician. The resultant Breast Inflammatory Symptom Severity Index (BISSI) is a patient-reported outcome measure for use in the diagnosis and monitoring of clinical changes of symptoms associated with inflammatory conditions of the lactating breast including engorgement, blocked ducts and mastitis. It utilizes person-centred language and assesses symptoms considered important to both patient and clinician. The development of the clinician script facilitates utility regardless of the experience of either the woman with the inflammatory condition or the treating clinician.


Are the Neural Correlates of Consciousness in the Front or in the Back of the Cerebral Cortex? Clinical and Neuroimaging Evidence.
The role of the frontal cortex in consciousness remains a matter of debate. In this Perspective, we will critically review the clinical and neuroimaging evidence for the involvement of the front versus the back of the cortex in specifying conscious contents and discuss promising research avenues.Dual Perspectives Companion Paper: Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?, by Brian Odegaard, Robert T. Knight, and Hakwan Lau.


Microglia Negatively Regulate the Proliferation and Neuronal Differentiation of Neural Stem/Progenitor Cells Isolated from Poststroke Mouse Brains.
We previously demonstrated that neural stem/progenitor cells (NSPCs) were induced within and around the ischemic areas in a mouse model of ischemic stroke. These injury/ischemia-induced NSPCs (iNSPCs) differentiated to electrophysiologically functional neurons in vitro, indicating the presence of a self-repair system following injury. However, during the healing process after stroke, ischemic areas were gradually occupied by inflammatory cells, mainly microglial cells/macrophages (MGs/MΦs), and neurogenesis rarely occurred within and around the ischemic areas. Therefore, to achieve neural regeneration by utilizing endogenous iNSPCs, regulation of MGs/MΦs after an ischemic stroke might be necessary. To test this hypothesis, we used iNSPCs isolated from the ischemic areas after a stroke in our mouse model to investigate the role of MGs/MΦs in iNSPC regulation. In coculture experiments, we show that the presence of MGs/MΦs significantly reduces not only the proliferation but also the differentiation of iNSPCs toward neuronal cells, thereby preventing neurogenesis. These effects, however, are mitigated by MG/MΦ depletion using clodronate encapsulated in liposomes. Additionally, gene ontology analysis reveals that proliferation and neuronal differentiation are negatively regulated in iNSPCs cocultured with MGs/MΦs. These results indicate that MGs/MΦs negatively impact neurogenesis via iNSPCs, suggesting that the regulation of MGs/MΦs is essential to achieve iNSPC-based neural regeneration following an ischemic stroke.


Glucose transporter expression in eutopic endometrial tissue and ectopic endometriotic lesions.
Endometriosis is an extremely prevalent disorder characterized by the growth of endometrial tissue at ectopic locations. Glycolysis is an energy-producing mechanism that occurs in almost all cells and requires an adequate uptake of glucose mediated by glucose transporter (GLUT) proteins. At present, however, very little is known about their expression in either the endometrium or the endometriotic lesions. The objective of this study was to examine the expression of SLC2A genes in the endometrium of women with and without endometriosis and in the matching ectopic tissue, and to confirm the presence of the GLUT proteins in ectopic lesions. There was a significantly higher expression of SLC2A3 and a significantly lower expression of SLC2A4 in women with endometriosis compared with those without. In women with endometriosis, the ectopic expression of SLC2A3, SLC2A4 and SLC2A5 was significantly higher than that observed in the matching eutopic tissue. GLUT1 protein expression was present in both epithelial and stromal cells and GLUT3 was confined to CD45-positive leukocytes. GLUT4 expression was strong in both ectopic epithelial and stromal cells and localized to the cellular membrane in epithelial cells. These results show that GLUT expression is altered between eutopic and ectopic tissue and between women with and without endometriosis, and that GLUT4 may represent a significant entry route for glucose into the endometriotic epithelial cells. The inducible nature of GLUT4 and its limited cellular expression may make GLUT4 an attractive target for non-hormone-based treatments of endometriosis.


Prevention of urinary and fecal incontinence in adults.
To assess the prevalence of and risk factors for urinary (UI) and fecal (FI) incontinence in adults in long-term care (LTC) settings and in the community, the effectiveness of diagnostic methods to identify adults at risk and patients with incontinence, and to review the effectiveness of clinical interventions to reduce the risk of incontinence. MEDLINE (PubMed), CINAHL, and Cochrane Databases. Observational studies were reviewed to examine the prevalence and incidence of UI and FI and the association with risk factors. The effects of treatments on patient outcomes were analyzed from randomized controlled and multicenter clinical trials. The diagnostic values of the tests were compared from the original epidemiologic studies of different designs. Of the 6,097 articles identified, 1,077 articles were eligible for analysis. The prevalence of UI, FI, and combined incontinence increased with age and functional dependency. Cognitive impairment, limitations in daily activities, and prolonged institutionalization in nursing homes were associated with a higher risk of incontinence. Stroke, diabetes, obesity, poor general health, and comorbidities were associated with UI and FI in community dwelling adults. Parity, anal trauma, and vaginal prolapse in women and urological surgery and radiation for prostate cancer in men are risk factors for UI and FI. Intensive individualized management and rehabilitation programs improved continence status in nursing home residents and adults after stroke. Self-administered behavioral interventions including pelvic floor muscle training with biofeedback and bladder training resolved UI in incontinent women. Electrical stimulation and sacral neuromodulation improved urge UI, but improvement for FI was inconsistent. Tension-free vaginal tape procedures and modified surgical techniques for prolapse to support the bladder neck resolved stress UI in the majority of treated women. Behavioral treatments of FI resulted in small improvements in severity and quality of life related to incontinence. The effects on FI of surgical techniques for hemorrhoids, rectal prolapse, rectal cancer, and anal fissures are not consistent across studies. Surgical interventions in patients with ulcerative colitis resulted in the same rates of fecal continence when compared to each other. The few clinical interventions to treat FI that were tested in well-designed trials had no clear evidence of better effects of the compared treatments. Instrumental outcomes to evaluate the effectiveness of treatments did not correlate with patient outcomes. Epidemiologic surveys to detect persons at risk and patients with undiagnosed UI have the same diagnostic value and less cost compared to professional examinations and diagnostic tests. Self-reported questionnaires and scales have unsatisfactory validity to diagnose FI. Epidemiologic surveys are cost-effective ways to estimate the prevalence of UI in large nationally representative population groups. Routine clinical evaluation should include an assessment of the risk factors, symptoms, and signs of incontinence. Pregnant or menopausal women, women with vaginal prolapse, males treated for prostate disease, patients with rectal prolapse, and frail elderly and nursing home residents are high risk groups. Individualized management programs can improve continence in LTC facilities but are hard to sustain. Regular monitoring and documentation of the continence status in relation to implemented continence services should be quality of care indicators for nursing homes. Pelvic floor muscle trainings with biofeedback can resolve incontinence and improve quality of life. Surgery is effective in curing stress UI in females. Clinical interventions for UI in males and for FI in adults need future investigation. A list of research recommendations is offered.


[MYCOBACTERIOSIS ASSOCIATED WITH ADMINISTRATION OF BIOLOGICS].
In recent years, administration- of biologics for immunologic inflammatory diseases, particularly rheumatoid arthritis, has increased obviously. These substances have dramatic effects, but complications of various infections such as tuberculosis are increasing. Biologics is an antonym for synthetic products (compounds), which are the most common type of pharmaceuticals, made by bioengineering materials derived from living organisms including humans. As concerns preparations which inhibit TNF-α that constitutes the basis of human immunity to tuberculosis, there was a fear that there might be an increase in tuberculosis in Japan, where many people have a history of tuberculosis infection due to past epidemics. However, it was confirmed in post-marketing all- case surveillance in Japan that tuberculosis dan be prevented by screening for latent tuberculosis infection (LTBI) in the target patient population, and administering an anti-tubercu- losis drug to patients with the finding of infection before administering a TNF-α inhibitor. The efficacy of prophylaxis is not 100%, however, so there were some patients who not only had complications of tuberculosis, but in whom symp- toms rapidly exacerbated and resulted in death. Since there is a high possibility that death was due to an immune reconstitu- tion inflammatory syndrome, it is necessary to consider re-administering biologics, or administer them continuously without'interruption. As concerns non-tuberculous mycobac- teriosis (NTM) which is rapidly increasing in Japan, on the other hand; its clinical manifestation is non-uniform and lacks effective therapeutic drugs, so administration of biologics had been considered to be contraindicated, but from a close analysis of clinical cases, there is a growing recognition that biologics can be administered under certain conditions.


The postulated mechanism of the protective effect of ginger on the aspirin induced gastric ulcer: Histological and immunohistochemical studies.
There are many available drugs for treating gastric ulcer, but they have various side effects. Ginger is a folk, herbal medicine, which is used for treatment of various diseases including gastric ulcer. This study investigates the possible mechanism of the protective effect of ginger on aspirin induced gastric ulcer. Forty adult male albino rats were randomized into four groups (10 animal per each group) and orally received the followings once daily for 5 days: Group I: 3 ml of 1% carboxymethyl cellulose; Group II: ginger powder (200 mg/kg body weight) suspended in 3 mL of 1% carboxymethylcellulose; Group III: aspirin (400 mg/kg body weight) suspended in 3 ml of 1% carboxymethylcellulose in water. Group IV: ginger and 30 minutes later, received aspirin suspended in 1% carboxymethylcellulose, in similar doses as received in groups II and III. On day 6, rats were sacrificed. The animals were anesthetized and the stomach was removed for the macroscopic, histological (Haematoxylin & Eosin and Periodic Acid Shiff) and immunohistochemical investigations (Bax, inducible nitric oxide synthase and heat shock protein 70). Aspirin induced a significant increase of the macroscopic ulcer score, shed and disrupted epithelium, mucosal hemorrhage, submucosal edema and leukocyte infiltration, loss of the mucus of the mucosal surface significantly increased expression of apoptosis regulator Bax, inducible nitric oxide synthase (iNOS) and heat shock protein 70 (HSP70). Ginger ameliorated the histological changes by reducing Bax and iNOS and increasing HSP70 expressions.


Puzzling associations between childhood infections and the later occurrence of asthma and atopy.
The current unfavourable trends in asthma and atopy prevalences have raised great concern and have challenged investigators to accelerate search for new risk factors for atopic diseases. The lack or scarcity of intense, systemic infections in early life has been postulated to increase susceptibility of becoming sensitized to otherwise harmless allergens in later life. This hygiene hypothesis is considered one of the most plausible explanations for the current trends in atopic diseases to date. There are data to suggest that measles, hepatitis A, and Mycobacterium tuberculosis infection in early life may prevent the subsequent development of atopic diseases. The hypothesis is based on the concept that certain viral and bacterial infections, which induce a strongly polarized T helper (Th)-1 type response and a long-lasting memory immunity, are in early life able to reverse or prevent the biased Th1/Th2 balance in individuals prone to atopy and asthma. Evidence for the ability of mycobacterial infections to alter the Th1/Th2 balance has also been obtained from murine models. In humans, the critical time period during which immunomodulation with long-lasting effects is considered most successful is within the first two years of life. Possibly also nonpathogenic residents of the intestinal mucosa are involved in the proper maturation of the immune system. The use of antibiotics has been shown to be positively associated with the development of asthma and atopy. The mechanisms underlying these associations remain largely unknown.


Characterization of the angular memory effect of scattered light in biological tissues.
High resolution optical microscopy is essential in neuroscience but suffers from scattering in biological tissues and therefore grants access to superficial brain layers only. Recently developed techniques use scattered photons for imaging by exploiting angular correlations in transmitted light and could potentially increase imaging depths. But those correlations ('angular memory effect') are of a very short range and should theoretically be only present behind and not inside scattering media. From measurements on neural tissues and complementary simulations, we find that strong forward scattering in biological tissues can enhance the memory effect range and thus the possible field-of-view by more than an order of magnitude compared to isotropic scattering for ∼1 mm thick tissue layers.


Robust hierarchical 3D carbon foam electrode for efficient water electrolysis.
Herein we report a 3D heterostructure comprising a hierarchical macroporous carbon foam that incorporates mesoporous carbon nanotubes decorated with cobalt oxide nanoparticles as an unique and highly efficient electrode material for the oxygen evolution reaction (OER) in electrocatalytic water splitting. The best performing electrode material showed high stability after 10 h, at constant potential of 1.7 V vs. RHE (reversible hydrogen electrode) in a 0.1 M KOH solution and high electrocatalytic activity in OER with low overpotential (0.38 V vs RHE at 10 mA cm-2). The excellent electrocatalytic performance of the electrode is rationalized by the overall 3D macroporous structure and with the firmly integrated CNTs directly grown on the foam, resulting in a large specific surface area, good electrical conductivity, as well as an efficient electrolyte transport into the whole electrode matrix concurrent with an ability to quickly dispose oxygen bubbles into the electrolyte. The eminent properties of the three-dimensional structured carbon matrix, which can be synthesized through a simple, scalable and cost effective pyrolysis process show that it has potential to be implemented in large-scale water electrolysis systems.


Responses in refractory hairy cell leukemia to a recombinant immunotoxin.
We report major responses in 4 of 4 patients with hairy cell leukemia (HCL) who have recently been treated on a phase I trial with the recombinant immunotoxin LMB-2. The immunotoxin, designed to target CD25(+) malignancies, is composed of the Fv portion of the anti-Tac (anti-CD25) antibody, fused to a 38-kD truncated form of Pseudomonas exotoxin A, and has previously been called anti-Tac(Fv)-PE38. All 4 HCL patients were resistant to standard and salvage therapies for HCL, including 2-chlorodeoxyadenosine (CdA) and interferon alpha, and all patients responded to LMB-2 after a single cycle. One patient treated with 2 cycles had a complete remission (CR), with regression of HCL cells from the blood and marrow and resolution of splenomegaly and pancytopenia. As is typical for patients in CR after treatment with CdA, minimal residual disease was detectable by flow cytometry of the bone marrow aspirate. This patient has not relapsed after 11 months. Three other patients had 98% to 99.8% reductions in malignant circulating cells. These results represent a proof of principal that targeted therapy with recombinant Fv-containing proteins can be clinically useful. LMB-2 may be an effective new therapy for patients with chemotherapy-resistant CD25(+) HCL.


Prevalence of homelessness and co-occurring problems: A comparison of young adults in Victoria, Australia and Washington State, United States.
Homelessness is associated with various co-occurring health and social problems yet; few contemporary international studies have examined these problems in young adulthood. This descriptive study presents cross-state comparison of the prevalence of young adult homelessness in Washington State, USA and Victoria, Australia using state representative samples from the International Youth Development Study (IYDS; n = 1,945, 53% female). Associations between young adult homelessness and a range of co-occurring problems were examined using a modified version of the Communities That Care youth survey. Results showed significantly higher rates of past year homelessness were reported by young adults in Washington State (5.24% vs. 3.25% in Victoria). Cross-state differences were evident in levels of friends' drug use, antisocial behavior, weekly income and support from peers. Unemployment (Adjusted Odds Ratio [AOR] = 2.67), antisocial behavior (AOR = 3.54) and victimization (AOR = 3.37) were more likely among young adults reporting homelessness in both states. Young adults with higher weekly income were less likely to report homelessness (AOR = .69) in both states. No significant association between mental health problem symptoms, substance use, family conflict or interaction with antisocial peers and homelessness were found in either state. Rates of violent behavior were more strongly related to young adult homelessness in Washington State than Victoria. The current findings suggest that programs that enable young adults to pursue income and employment, reduce antisocial behavior and include services for those who have been victimized, may help to mitigate harm among young adults experiencing homelessness.


Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells.
Tension of the actomyosin cell cortex plays a key role in determining cell-cell contact growth and size. The level of cortical tension outside of the cell-cell contact, when pulling at the contact edge, scales with the total size to which a cell-cell contact can grow [J.-L. Maître et al., Science 338, 253-256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell-cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell-cell contact size is limited by tension-stabilizing E-cadherin-actin complexes at the contact.


Spectrum of Delta(7)-dehydrocholesterol reductase mutations in patients with the Smith-Lemli-Opitz (RSH) syndrome.
The Smith-Lemli-Opitz syndrome (SLOS; also known as the RSH syndrome) is an autosomal recessive genetic disorder, leading to characteristic multi-organ developmental abnormalities, dysmorphic facies, limb malformations and mental retardation. Mutations in the gene for Delta(7)-dehydrocholesterol reductase (Delta(7)-reductase), which catalyzes the last step in cholesterol biosynthesis, cause the disease. We screened 32 patients with SLOS, 28 from the USA and four from Sweden. Twenty-two different nucleotide changes, predicted to be disease-causing mutations, were identified; 20 missense mutations, one nonsense mutation and one splice-site mutation involving the exon 9 acceptor site (IVS8 -1G-->C) were detected. All probands were heterozygous for mutations. Twelve of these mutations have not been reported previously, including missense mutations L148R, F168I, D175H, P179L, P243R, F284L, N287K, F302L, R404S, Y462H, R469P and one nonsense mutation W37X [corrected]. Coupled with previously reported mutations, these findings bring the total of different Delta(7)-reductase mutations to 36. These are distributed throughout the coding sequence of the Delta(7)-reductase gene except exons 3 and 5, with a clustering in exon 9. Three mutations account for 54% of those observed in our cohort, the splice acceptor site mutation IVS8 -1G-->C (22/64 alleles, 34%), T93M (8/64, 12.5%) and V326L (5/64, 7.8%). Severity of SLOS was negatively correlated with both plasma cholesterol and relative plasma cholesterol, but not with 7-dehydrocholesterol, the immediate precursor, confirming previous observations. However, no correlation was observed between mutations and phenotype, suggesting that the degree of severity may be affected by other factors. We estimate that between 33 and 42% of the variation in the SLOS severity score is accounted for by variation in plasma cholesterol. Thus, factors other than plasma cholesterol are additionally involved in determining severity.


Social networks as predictors of colorectal cancer screening in African Americans.
Early detection can reduce colorectal cancer (CRC) mortality by 15%-33%, and screening is widely recommended for average-risk adults beginning at age 50 years. Colorectal cancer mortality rates are higher in African Americans than in whites, while screening rates are somewhat lower. Individual social networks can reduce emotional and/or logistical barriers to health-promoting but distasteful procedures such as CRC screening. The aim of this study was to examine social network interactions, and their impact on CRC screening among African Americans. We hypothesized a positive association between social network index (SNI) scores and CRC screening. In a community intervention trial with four arms, we previously demonstrated the efficacy of a small group educational intervention to promote CRC screening among African Americans. This intervention outperformed a one-on-one educational intervention, a reduced out-of-pocket expense intervention, and a control condition. In the present analysis, we compared the SNI scores for participants in the small group intervention cohort with a comparison group comprised of the other three cohorts. Social networks were assessed using the Social Network Index developed by Cohen. Small group participants had a significantly higher network diversity score (Mean difference 0.71; 95% CI, 0.12-1.31; p=0.0017) than the comparison group. In the second component of the SNI score - the number of people talked to over a two week period - the small group intervention cohort also scored significantly higher than the comparison group. (Mean difference, 9.29; 95% CI, 3.963-14.6266; p=0.0004). The findings suggest that social interaction and support was at least partially responsible for the relatively high post-intervention screening rate in the small group intervention participants. Education in small groups could foster strong social networks. Strong and positive network diversity and a large number of people in social networks may enhance CRC screening rates among African Americans.


Identification of major factors in Australian primary care pharmacists' practice environment that have a bearing on the implementation of professional models of practice.
Objective The aim of the present study was to describe an environmental framework for pharmacists in primary care in Australia and determine the major factors within that environment that have the greatest bearing on their capacity to implement patient-focused models of professional practice. Methods A draft framework for pharmacists' practice was developed by allocating structures, systems and related factors known to the researchers or identified from the literature as existing within pharmacists' internal, operational and external environments to one of five domains: Social, Technological, Economic, Environmental or Political [STEEP]. Focus groups of pharmacists used an adapted nominal group technique to assess the draft and add factors where necessary. Where applicable, factors were consolidated into groups to establish a revised framework. The three major factors or groups in each domain were identified. The results were compared with the enabling factors described in the profession's vision statement. Results Seventy-eight individual factors were ultimately identified, with 86% able to be grouped. The three dominant groups in each of the five domains that had a bearing on the implementation of professional models of practice were as follows: (1) Social: the education of pharmacists, their beliefs and the capacity of the pharmacist workforce; (2) Technological: current and future practice models, technology and workplace structures; (3) Economic: funding of services, the viability of practice and operation of the Pharmaceutical Benefits Scheme; (4) Environmental: attitudes and expectations of stakeholders, including consumers, health system reform and external competition; and (5) Political: regulation of practice, representation of the profession and policies affecting practice. Conclusions The three dominant groups of factors in each of the five STEEP environmental domains, which have a bearing on pharmacists' capacity to implement patient-focused models of practice, correlate well with the enabling factors identified in the profession's vision statement, with the addition of three factors in the Environmental domain of stakeholder attitudes, health system reform and external competition. What is known about the topic? The extensive range of patient-focused professional programs developed for application by pharmacists in primary care in Australia has yet to be widely implemented. What does this paper add? Factors both within and beyond the pharmacists' immediate practice environment that have a bearing on the uptake of professional programs have been identified and prioritised using a structured thematic approach. What are the implications for practitioners? The results demonstrate the need for a multifactorial approach to the implementation of professional models of practice in this setting.