Composition of sand fly fauna (Diptera: Psychodidae) and detection of Leishmania DNA (Kinetoplastida: Trypanosomatidae) in different ecotopes from a rural settlement in the central Amazon, Brazil.
Phlebotomine sand flies (Diptera: Psychodidae) are vectors of Leishmania species, the etiological agents of leishmaniasis, which is one of the most important emerging infectious diseases in the Americas. In the state of Amazonas in Brazil, anthropogenic activities encourage the presence of these insects around rural homes. The present study aimed to describe the composition and distribution of sand fly species diversity among the ecotopes (intradomicile, peridomicile and forest) in an area of American cutaneous leishmaniasis transmission and detect natural infection with Leishmania DNA to evaluate which vectors are inside houses and whether the presence of possible vectors represents a hazard of transmission. Phlebotomine sand flies were collected using light traps. A total of 2469 specimens representing 54 species, predominantly females (71.2%), were collected from four sites. Polymerase chain reaction analysis was performed on 670 samples to detect Leishmania DNA. Most of the samples (79.5%) were collected in the forest, with areas closer to rural dwellings yielding a greater abundance of suspected or proven vectors and a larger number of species containing Leishmania DNA. Nyssomyia umbratilis and Bichromomyia flaviscutellata were found near rural homes, and Ny. umbratilis was also found inside homes. Leishmania DNA was detected in different species of sand flies in all ecotopes, including species with no previous record of natural infection. There is no evidence that vectors of American cutaneous leishmaniasis are becoming established inside homes, but there are sand flies, including Ny. umbratilis and other possible vectors, in environments characterized by a human presence. These species continue to be predominant in the forest but are prevalent in areas closer to ecotopes with a greater human presence. The existence of proven or suspected vectors in this ecotope is due to the structural organization of rural settlements and may represent a hazard of transmission. Although the detection of Leishmania DNA in species that were not previously considered vectors does not mean that they are transmitting the parasite, it does show that the parasite is circulating in ecotopes where these species are found.


Biosynthesis of cryptic lipopolysaccharide glycoforms in Haemophilus influenzae involves a mechanism similar to that required for O-antigen synthesis.
It is generally thought that mucosal bacterial pathogens of the genera Haemophilus, Neisseria, and Moraxella elaborate lipopolysaccharide (LPS) that is fundamentally different from that of enteric organisms that express O-specific polysaccharide side chains. Haemophilus influenzae elaborates short-chain LPS that has a role in the pathogenesis of H. influenzae infections. We show that the synthesis of LPS in this organism can no longer be as clearly distinguished from that in other gram-negative bacteria that express an O antigen. We provide evidence that a region of the H. influenzae genome, the hmg locus, is involved in the synthesis of glycoforms in which tetrasaccharide units are added en bloc, not stepwise, to the normal core glycoforms, similar to the biosynthesis of an O-antigen.


Supplementation with galacto-oligosaccharides increases the percentage of NK cells and reduces colitis severity in Smad3-deficient mice.
The gut microbiota plays an essential role in intestinal immunity. Prebiotics, including galacto-oligosaccharides (GOS), are fermentable fibers that beneficially affect the host by stimulating the growth of specific microbial populations. We investigated the effect of GOS on colitis development and on immune variables in Smad3-deficient mice treated with the pathogen Helicobacter hepaticus. Mice were supplemented daily with 5000 mg GOS/kg body weight 2 wk prior to infection and 4 wk postinfection, a time period during which colitis severity peaks in this model. Mice (n = 4-8/treatment at each time) were killed preinfection (0 d) and at 3, 7, and 28 d postinfection to evaluate immune variables in the spleen and in mesenteric lymph nodes (MsLN) by flow cytometry. Colon and cecum samples were collected for histopathologic analysis. Fecal pellets (n = 8-9/treatment) were collected prior to infection to measure relative changes in Bifidobacterium ssp. and Lactobacillum ssp. by real-time PCR. GOS significantly reduced colitis severity in response to H. hepaticus (P < 0.0001). This was associated with a significant increase in the percentage of NK cells in the spleen (P < 0.001) and in MsLN (P < 0.001) at 3 d postinfection and a 1.5-fold increase in fecal Bifidobacterium ssp. (P = 0.003). GOS stimulated NK expression of CCR9, a chemokine receptor involved in lymphocyte trafficking to the gut preinfection (0 d) in the blood (P = 0.02), spleen (P = 0.033), and MsLN (P = 0.017). In addition, GOS stimulated colonic IL-15 production 3 d postinfection (P < 0.001). These data suggest that GOS reduces colitis by modulating the function and trafficking of NK cells and may provide a novel therapeutic strategy for individuals with inflammatory bowel disease.


Oncogenic signaling is dominant to cell of origin and dictates astrocytic or oligodendroglial tumor development from oligodendrocyte precursor cells.
Stem cells, believed to be the cellular origin of glioma, are able to generate gliomas, according to experimental studies. Here we investigated the potential and circumstances of more differentiated cells to generate glioma development. We and others have shown that oligodendrocyte precursor cells (OPCs) can also be the cell of origin for experimental oligodendroglial tumors. However, the question of whether OPCs have the capacity to initiate astrocytic gliomas remains unanswered. Astrocytic and oligodendroglial tumors represent the two most common groups of glioma and have been considered as distinct disease groups with putatively different origins. Here we show that mouse OPCs can give rise to both types of glioma given the right circumstances. We analyzed tumors induced by K-RAS and AKT and compared them to oligodendroglial platelet-derived growth factor B-induced tumors in Ctv-a mice with targeted deletions of Cdkn2a (p16(Ink4a-/-), p19(Arf-/-), Cdkn2a(-/-)). Our results showed that glioma can originate from OPCs through overexpression of K-RAS and AKT when combined with p19(Arf) loss, and these tumors displayed an astrocytic histology and high expression of astrocytic markers. We argue that OPCs have the potential to develop both astrocytic and oligodendroglial tumors given loss of p19(Arf), and that oncogenic signaling is dominant to cell of origin in determining glioma phenotype. Our mouse data are supported by the fact that human astrocytoma and oligodendroglioma display a high degree of overlap in global gene expression with no clear distinctions between the two diagnoses.


Metabolic abnormalities in HIV type 1-infected children treated and not treated with protease inhibitors.
Our objective was to determine whether HIV-infected children treated with protease inhibitors (PIs) have different blood lipid, insulin, and glucose levels and body composition than HIV-infected children not treated with PIs. A cross-sectional cohort study was performed; in which 23 children were treated with combination antiretroviral therapy including a PI for at least 6 months and 12 children were treated with nucleoside reverse transcriptase inhibitors only (no-PI group). Levels of lipids, apolipoprotein B (apoB), insulin, and glucose were determined in the fasting state. Body composition and fat distribution were determined by anthropometric measurements and dual energy X-ray absorptiometry (DEXA) scan. Total cholesterol levels were higher in the PI-treated children (5.33 +/- 0.87 mM) than in the no-PI children (3.69 +/- 0.59 mM) (p < 0.0001). Similarly, low-density lipoprotein (LDL) levels were also elevated in the PI-treated children (3.27 +/- 0.76 vs. 2.14 +/- 0.51 mM) (p < 0.0001). ApoB and high-density lipoprotein (HDL), and to a lesser degree triglyceride levels, were also increased in the PI-treated children. Apart from percent arm fat as measured by DEXA, there were no differences between the two groups in measures of body composition or in their fasting glucose and insulin levels. The results from this cross-sectional cohort study suggest that the predominant lipid abnormalities associated with treatment with combination antiretroviral therapy including a PI in HIV-1-infected children are elevated total and LDL cholesterol.


Effects of coordination and pressure on sound attenuation, boson peak and elasticity in amorphous solids.
Connectedness and applied stress strongly affect elasticity in solids. In various amorphous materials, mechanical stability can be lost either by reducing connectedness or by increasing pressure. We present an effective medium theory of elasticity that extends previous approaches by incorporating the effect of compression, of amplitude e, allowing one to describe quantitative features of sound propagation, transport, the boson peak, and elastic moduli near the elastic instability occurring at a compression ec. The theory disentangles several frequencies characterizing the vibrational spectrum: the onset frequency where strongly-scattered modes appear in the vibrational spectrum, the pressure-independent frequency ω* where the density of states displays a plateau, the boson peak frequency ωBP found to scale as , and the Ioffe-Regel frequency ωIR where scattering length and wavelength become equal. We predict that sound attenuation crosses over from ω(4) to ω(2) behaviour at ω0, consistent with observations in glasses. We predict that a frequency-dependent length scale ls(ω) and speed of sound ν(ω) characterize vibrational modes, and could be extracted from scattering data. One key result is the prediction of a flat diffusivity above ω0, in agreement with previously unexplained observations. We find that the shear modulus does not vanish at the elastic instability, but drops by a factor of 2. We check our predictions in packings of soft particles and study the case of covalent networks and silica, for which we predict ωIR ≈ ωBP. Overall, our approach unifies sound attenuation, transport and length scales entering elasticity in a single framework where disorder is not the main parameter controlling the boson peak, in agreement with observations. This framework leads to a phase diagram where various glasses can be placed, connecting microscopic structure to vibrational properties.


The problems of offenders with mental disorders: a plurality of perspectives within a single mental health care organisation.
Managers, doctors, nurses, occupational therapists, social workers, psychologists, unqualified staff and service users were interviewed for a qualitative study of risk management and rehabilitation in an inner city medium secure forensic mental health care unit. Different professional orientations to service user problems were identified. Doctors focused primarily on the diagnosis of mental disorder, which they managed mainly through pharmaceutical interventions. Psychologists were principally concerned with personal factors, for example service user insight into their biographical history. Occupational therapists concentrated mainly on daily living skills, and social workers on post-discharge living arrangements. Some front line nurses, held accountable for security lapses, adopted a criminogenic approach. Service users were more likely than professionals to understand their needs in terms of their wider life circumstances. These differences are explored qualitatively in relation to four models of crossdisciplinary relationships: monoprofessional self-organisation combined with restricted communication; hermeneutic reaching out to other perspectives; the establishment of interdisciplinary sub-systems; and transdisciplinary merger. Relationships between professions working in this unit, as portrayed in qualitative interviews, corresponded mainly to the first model of monoprofessional self-organisation. Reasons for restricted crossdisciplinary understanding, particularly the wide power/status differences between the medical and other professions, and between staff and patients, are discussed.


Estimating the response and economic burden of rheumatoid arthritis patients treated with biologic disease-modifying antirheumatic drugs in Taiwan using the National Health Insurance Research Database (NHIRD).
Previous studies in Taiwan utilizing the Taiwan's National Health Insurance Database (NHIRD) have estimated the direct healthcare costs of RA patients, but they have not focused on patients on bDMARDs, or considered patients' response to therapy. The objective of this study was to estimate the rate of inadequate response for patients newly treated with biologic disease-modifying antirheumatic drugs (bDMARDs) as well as their costs and resource use. Data were from the catastrophic illness file within the NHIRD from 1/1/2009 to 12/31/2013. Patients with RA, which was categorized by the presence of a catastrophic illness card, that were previously bDMARD-naïve, were included in this study if they initiated their first bDMARD during the index period. The index period included all of 2010, a pre-index period consisting of the index date- 365 days, and a follow-up period including the index date to 365 days post-index, were also included. Previously biologically-naïve patients were indexed into the study on the date of their first claim for a bDMARD. A validated algorithm was used to examine the rate of inadequate response (IR) in the biologically-naïve cohort of patients. Inadequate responders met one or more of the following criteria during their year of follow-up: low adherence (proportion of days covered <0.80); switched to or added a second bDMARD; added a new conventional synthetic DMARD (csDMARD); received ≥1 glucocorticoid injection; or increased oral glucocorticoid dosing. All-cause mean annual direct costs and resource use were measured in the year of follow-up. Costs were converted from NT$ to USD using 1 NT$ = 0.033 USD. A total of 818 patients with RA initiated their first bDMARD (54% etanercept and 46% adalimumab) in 2010. After one year of follow-up, 32% (n = 258) were classified as stable, 66% (n = 540) had an IR, and 2% (n = 20) were lost to follow-up. During the follow-up period mean annual total direct costs were $16,136 for stable patients compared to $14,154 for patients with IR. Mean annual non-medication direct costs were $937 for stable patients and $1,574 for patients with IR. Mean annual hospitalizations were higher for patients with IR (0.46) compared to stable patients (0.10) during the one year follow-up period. The majority of patients that were previously naïve to bDMARDs had an IR to their first bDMARD during the year of follow-up. Patients with an IR had numerically increased all-cause resource utilization and non-medication costs during the follow-up period compared to patients with stable disease. This level of IR suggests an unmet need in the RA treatment paradigm.


Cortical activation during spoken-word segmentation in nonreading-impaired and dyslexic adults.
We used magnetoencephalography to elucidate the cortical activation associated with the segmentation of spoken words in nonreading-impaired and dyslexic adults. The subjects listened to binaurally presented sentences where the sentence-ending words were either semantically appropriate or inappropriate to the preceding sentence context. Half of the inappropriate final words shared two or three initial phonemes with the highly expected semantically appropriate words. Two temporally and functionally distinct response patterns were detected in the superior temporal lobe. The first response peaked at approximately 100 msec in the supratemporal plane and showed no sensitivity to the semantic appropriateness of the final word. This presemantic N100m response was abnormally strong in the left hemisphere of dyslexic individuals. After the N100m response, the semantically inappropriate sentence-ending words evoked stronger activation than the expected endings in the superior temporal cortex in the vicinity of the auditory cortex. This N400m response was delayed for words starting with the same two or three first few phonemes as the expected words but only until the first evidence of acoustic-phonetic dissimilarity emerged. This subtle delay supports the notion of initial lexical access being based on phonemes or acoustic features. In dyslexic participants, this qualitative aspect of word processing appeared to be normal. However, for all words alike, the ascending slope of the semantic activation in the left hemisphere was delayed by approximately 50 msec as compared with control subjects. The delay in the auditory N400m response in dyslexic subjects is likely to result from presemantic-phonological deficits possibly reflected in the abnormal N100m response.


Effects of a purified krill oil phospholipid rich in long-chain omega-3 fatty acids on cardiovascular disease risk factors in non-human primates with naturally occurring diabetes type-2 and dyslipidemia.
High serum levels of cholesterol, in particular low-density lipoprotein cholesterol, are considered a significant risk factor for development of cardiovascular disease. Therefore, rigorous treatment regimens with statins and other pharmaceuticals have been used extensively to reduce elevated cholesterol levels. Literature data have not clearly concluded whether long-chain omega-3 fatty acids reduce, increase or leave circulating cholesterol unaffected. In the present study a novel krill-oil derived preparation of omega-3 rich phospholipids, mainly phosphatidylcholine, was administered orally at increasing doses for 12 weeks to dyslipidemic non-human primates, and cholesterols and several other risk factors for cardiovascular disease were measured before, during and after treatment. Six dyslipidemic non-human primates suffering from naturally occurring diabetes type-2 were included, three in a vehicle control group and three being treated with the omega-3 rich phospholipid preparation. The control and test items were given daily by gavage and the doses of the test item were 50, 150 and 450 mg phospholipids/kg/day. Each dose level was given for 4 weeks. Plasma concentrations of the omega-3 fatty acids were measured in connection with change in dose and the omega-3 index in erythrocytes was determined bi-weekly. Blood lipids, apolipoproteins and diabetes, inflammatory and safety biomarkers were determined either weekly, biweekly or every 4 weeks. For the blood lipids and apolipoproteins, control-adjusted mean values are presented while absolute values are presented for the other parameters. Due to the low number of animals in each group, no statistical analyses were done. The only detectable effects measured during dosing with the lowest dose were an increase in HDL-cholesterol and apolipoprotein A1. The intermediate and high doses decreased total cholesterol, LDL-cholesterol, apolipoprotein B100 and triglycerides and increased HDL-cholesterol and apolipoprotein A1. No effects were seen on the diabetes and inflammatory markers and on safety biomarkers. The results indicate that the omega-3 rich phospholipid preparation had a positive impact on cardiovascular disease risk factors by reducing total cholesterol, LDL-cholesterol and triglycerides and increasing HDL-cholesterol. These findings justify further investigations of this preparation in animal models of dyslipidemia and, provided the current findings are confirmed, in human trials.


Frameshift Mutation Confers Function as Virulence Factor to Leucine-Rich Repeat Protein from Acidovorax avenae.
Many plant pathogens inject type III (T3SS) effectors into host cells to suppress host immunity and promote successful infection. The bacterial pathogen Acidovorax avenae causes brown stripe symptom in many species of monocotyledonous plants; however, individual strains of each pathogen infect only one host species. T3SS-deleted mutants of A. avenae K1 (virulent to rice) or N1141 (virulent to finger millet) caused no symptom in each host plant, suggesting that T3SS effectors are involved in the symptom formation. To identify T3SS effectors as virulence factors, we performed whole-genome and predictive analyses. Although the nucleotide sequence of the novel leucine-rich repeat protein (Lrp) gene of N1141 had high sequence identity with K1 Lrp, the amino acid sequences of the encoded proteins were quite different due to a 1-bp insertion within the K1 Lrp gene. An Lrp-deleted K1 strain (KΔLrp) did not cause brown stripe symptom in rice (host plant for K1); by contrast, the analogous mutation in N1141 (NΔLrp) did not interfere with infection of finger millet. In addition, NΔLrp retained the ability to induce effector-triggered immunity (ETI), including hypersensitive response cell death and expression of ETI-related genes. These data indicated that K1 Lrp functions as a virulence factor in rice, whereas N1141 Lrp does not play a similar role in finger millet. Yeast two-hybrid screening revealed that K1 Lrp interacts with oryzain α, a pathogenesis-related protein of the cysteine protease family, whereas N1141 Lrp, which contains LRR domains, does not. This specific interaction between K1 Lrp and oryzain α was confirmed by Bimolecular fluorescence complementation assay in rice cells. Thus, K1 Lrp protein may have acquired its function as virulence factor in rice due to a frameshift mutation.


Acute ingestion of sugar-free red bull energy drink has no effect on upper body strength and muscular endurance in resistance trained men.
Consumption of energy drinks by both recreational and competitive athletes has increased dramatically in recent years. The primary ingredients in many energy drinks include caffeine (CAF) in various forms and taurine. The purpose of this randomized, double-blind, crossover study was to examine the effect of sugar-free (SF) Red Bull (RB) containing CAF and taurine to a CAF only drink and a SF CAF-free placebo (PL) on 1 repetition maximum (1RM) bench press (BP) and the volume load (VL; repetitions × kg at 70% 1RM) during one BP set to failure in experienced lifters. Seventeen college-age men randomly received the following: (A) 500 mL of SF-RB containing CAF (160 mg) and taurine (2000 mg); (B) 500 mL of a SF drink containing CAF only (160 mg); or (C) a SF CAF-free 500 mL PL drink 60 minutes before testing on 3 separate occasions. After a standard warm-up, the 1RM was determined for each subject and, after 5 minutes rest, they completed repetitions to failure at 70% of their 1RM to assess VL. Differences between trials for 1RM BP and the VL were identified using repeated measures analysis of variance (p < 0.05). The results indicated that neither SF-RB nor the CAF drink had any effect on 1RM BP (115.13 ± 16.19 kg and 114.87 ± 16.16 kg, respectively) or VL (1173.08 ± 170.66 kg and 1164.14 ± 147.03 kg, respectively) compared with PL (1RM = 114.07 ± 16.09 kg; VL = 1141.46 ± 193.41 kg). Although the CAF content in the energy drinks used in the present study was low (∼2.0 mg/kg), the finding of no effect of the CAF containing energy drinks for 1RM BP are in agreement with previous studies using intakes up to 6.0 mg/kg. These findings suggest that SF-RB has no effect on upper body 1RM strength or VL in resistance trained men.


Screening for Alzheimer's disease: the memory impairment screen versus the conventional three-word memory test.
To improve screening for Alzheimer's disease (AD) with the Memory Impairment Screen (MIS), a 4-minute, four-item delayed free and cued recall memory test with controlled learning and high discriminative validity. To assess the discriminative validity of the MIS for AD and to compare it with the conventional three-word memory test, a delayed free recall task, widely recommended as a dementia-screening test in clinical practice. Cross-sectional validation study nested within a longitudinal study of aging and dementia. The MIS and the standard three-word memory task were administered as part of a comprehensive neurological and neuropsychological evaluation. Einstein Aging Study at the Albert Einstein College of Medicine, Bronx, New York. Two hundred forty community-dwelling older adults. Sensitivity, specificity, and positive predictive value (PPV) were calculated for the MIS and three-word memory test as screening tests for AD. In comparison with the three-word memory task, the MIS had higher sensitivity (.86 vs.65), higher specificity (.97 vs.85), and greater PPV (.80 vs.37) as a screen for AD. The MIS had high discriminative validity as a screening test for AD and substantially outperformed the three-word memory task. Given its validity and brevity, the MIS has important advantages as an AD screen for use in primary care.


Core verbal autopsy procedures with comparative validation results from two countries.
Cause-specific mortality statistics remain scarce for the majority of low-income countries, where the highest disease burdens are experienced. Neither facility-based information systems nor vital registration provide adequate or representative data. The expansion of sample vital registration with verbal autopsy procedures represents the most promising interim solution for this problem. The development and validation of core verbal autopsy forms and suitable coding and tabulation procedures are an essential first step to extending the benefits of this method. Core forms for peri- and neonatal, child, and adult deaths were developed and revised over 12 y through a project of the Tanzanian Ministry of Health and were applied to over 50,000 deaths. The contents of the core forms draw upon and are generally comparable with previously proposed verbal autopsy procedures. The core forms and coding procedures based on the International Statistical Classification of Diseases (ICD) were further adapted for use in China. These forms, the ICD tabulation list, the summary validation protocol, and the summary validation results from Tanzania and China are presented here. The procedures are capable of providing reasonable mortality estimates as adjudged against stated performance criteria for several common causes of death in two countries with radically different cause structures of mortality. However, the specific causes for which the procedures perform well varied between the two settings because of differences in the underlying prevalence of the main causes of death. These differences serve to emphasize the need to undertake validation studies of verbal autopsy procedures when they are applied in new epidemiological settings.


The immune responses to bacterial antigens encountered in vivo at mucosal surfaces.
Mammals have evolved a sophisticated immune system for handling antigens encountered at their mucosal surfaces. The way in which mucosally delivered antigens are handled influences our ability to design effective mucosal vaccines. Live attenuated derivatives of pathogens are one route towards the development of mucosal vaccines. However, some molecules, described as mucosal immunogens, are inherently immunogenic at mucosal surfaces. Studies on mucosal immunogens may facilitate the identification of common characteristics that contribute to mucosal immunogenicity and aid the development of novel, non-living mucosal vaccines and immunostimulators.


[Fibrous dysplasia of bone].
Fibrous dysplasia of bone is a congenital non hereditary benign bone disease, where normal bone is replaced by a fibrous-like tissue with immature osteogenesis. Prevalence is difficult to estimate, due to frequent asymptomatic lesions. Bone lesions are mono- or polyostotic and may be associated with bone pain and fragility, leading to fractures. In some patients or bone sites, they are hypertrophic, responsible for neurological complications. Imaging and, when necessary, histology are the cornerstones of the diagnosis. A common molecular defect, i.e. activating mutations of the GNAS gene, encoding the a subunit of the Gs protein in target cells, is responsible for bone cell alterations as well as for the involvement of other cells/tissues bearing the same molecular defect (melanocytes, endocrine cells). These mutations affect only somatic cells and are therefore not hereditary: antenatal diagnosis is not appropriate for this disease and genetic counselling is not very useful, except for reassuring the patients. The conventional therapeutic approach is essentially symptomatic (pain killers) and orthopaedic (prevention and treatment of bone complications). Recent publications have focused attention on pamidronate, which rapidly relieves bone pain in most patients, and progressively increases bone mineralization in osteolytic areas in about half of the patients. Tubular phosphate wasting is common and should be treated with phosphate supplement and calcitriol. The prognosis should improve with therapeutic advances, but this remains to be properly evaluated.


[Vesicorenal reflux in children under 2 years of age. Indications and results of surgical treatment].
On the basis of 133 cases, the authors analyse the clinical features and the modalities of the treatment of vesicorenal reflux in children under age 2. The number of girls is higher than that of boys. The diagnosis is most often established between 0 and 6 months of age, with a very marked peak between 0 and 1 month. The usual warning sign is a urinary infection with fever. Pyerography is normal in every second case, and retrograde cystography is the key examination, which confirms the reflux and establishes its side and degree (bilateral reflux in 53% of cases, stage II in 48% of cases). 33 children were operated at once. Another 100 first had a medical treatment, ie. urinary antibiotics, on the basis of strict criteria that are listed here. This medical treatment has been very disappointing: 20 children were lost to follow-up and 47 had secondary surgery. When surgery is necessary, advancing plasty according to Cohen's procedure yields excellent results: 98.6% of 76 operations were successful. The authors therefore think that Cohen's procedure is widely indicated, even in children under age 2.


Ethics teaching on 'Beginning of Life' issues in UK medical schools.
Medical ethics forms an essential component of an undergraduate medical programme. In the UK the Institute of Medical Ethics has released a consensus statement detailing its recommendations for a minimum curriculum for ethics. One important issue it highlights for inclusion is 'Beginning of Life', which includes a wide range of themes. This paper presents an evaluation of the current teaching and assessment of these important issues in UK medical schools, complemented by a specific analysis of students' reaction to the teaching they received at the University of Edinburgh as part of their Obstetrics and Gynaecology rotation. Schools which responded to the survey reported a wide range of teaching and assessment methods. While there was a good overall coverage of topics, only one of them was covered by every institution and the religious/cultural elements of those topics were often neglected. The medical schools viewed better clinical integration of ethics teaching as the best route to improvement, but the students reported a desire for more ethics teaching in the form of specific tutorials, lectures or discussions. It is likely that a combination of these approaches will lead to significant improvements in the delivery of ethics teaching in this area and in others.


Hispanic Use of Juramentos and Roman Catholic Priests as Auxiliaries to Abstaining from Alcohol Use/Misuse.
This self-administered mail survey study conducted along the US-Mexico border replicates and expands on research conducted in Florida regarding the prevalence of juramento use as an intervention technique for alcohol misuse. Juramentos are pledges to abstain from alcohol use for a time determined by the user. The pledge is usually to the Virgin of Guadalupe and is often done in the presence of a Roman Catholic Priest. As in Florida, the majority of Priests along the border reported they were familiar with the practice of juramentos and had already witnessed at least one. The majority of Priests who had done juramentos viewed them as effective. Since the vast majority of Priest indicated that they would begin or continue witnessing juramentos, this makes juramentos and Roman Catholic Priests a viable culturally sensitive aide for treatment among Hispanics, in particular those of Mexican descent.


Understanding those overdue for cancer screening by five years or more: A retrospective cohort study in Ontario, Canada.
Populations that are more than just slightly overdue for breast, cervical and colorectal screening should likely be targeted for policy and practice interventions. We used provincial-level administrative data to describe the Ontario population who are screen-eligible for breast, cervical and colorectal cancers but overdue by at least five years. For each cancer screening type, we created three cohorts and a binary outcome: screened at least once in the previous five years or not, using March 31, 2017 as our index date. We conducted simple descriptive analyses as well as multivariable logistic regression, where age category, immigrant status, neighbourhood income quintile, region, urban/suburban/rural status, primary care model type, and healthcare utilization were included in the models. More than 20% of Ontarians eligible for each of breast, cervical and colorectal cancer screening respectively had no history of screening in the previous five years. In multivariable analyses, people were significantly more likely to have no recent screening history if they lived in lower-income neighbourhoods (e.g. adjusted odds ratio [95% confidence interval]: 0.59 [0.58-0.59] for cervical screening), were recent immigrants, did not have a primary care provider, had a provider who practiced in a traditional fee-for-service model. Despite the presence of three provincial organized screening programs, we have found that more than one-fifth of Ontarians who are eligible for each of breast, cervical and colorectal screening respectively have not been screened for five years or more. Ensuring that all Ontarians have access to high-quality primary care, may be crucial to increasing screening uptake.


Injury risk from popular childhood physical activities: results from an Australian primary school cohort.
Children engage in various physical activities that pose different injury risks. However, the lack of adequate data on exposure has meant that these risks have not been quantified or compared in young children aged 5-12 years. To measure exposure to popular activities among Australian primary school children and to quantify the associated injury risks. The Childhood Injury Prevention Study prospectively followed up a cohort of randomly selected Australian primary and preschool children aged 5-12 years. Time (min) engaged in various physical activities was measured using a parent-completed 7-day diary. All injuries over 12 months were reported to the study. All data on exposure and injuries were coded using the International classification of external causes of injury. Injury rates per 1000 h of exposure were calculated for the most popular activities. Complete diaries and data on injuries were available for 744 children. Over 12 months, 314 injuries relating to physical activity outside of school were reported. The highest injury risks per exposure time occurred for tackle-style football (2.18/1000 h), wheeled activities (1.72/1000 h) and tennis (1.19/1000 h). Overall, boys were injured more often than girls; however, the differences were non-significant or reversed for some activities including soccer, trampolining and team ball sports. Although the overall injury rate was low in this prospective cohort, the safety of some popular childhood activities can be improved so that the benefits may be enjoyed with fewer negative consequences.


The perennial ryegrass GenomeZipper: targeted use of genome resources for comparative grass genomics.
Whole-genome sequences established for model and major crop species constitute a key resource for advanced genomic research. For outbreeding forage and turf grass species like ryegrasses (Lolium spp.), such resources have yet to be developed. Here, we present a model of the perennial ryegrass (Lolium perenne) genome on the basis of conserved synteny to barley (Hordeum vulgare) and the model grass genome Brachypodium (Brachypodium distachyon) as well as rice (Oryza sativa) and sorghum (Sorghum bicolor). A transcriptome-based genetic linkage map of perennial ryegrass served as a scaffold to establish the chromosomal arrangement of syntenic genes from model grass species. This scaffold revealed a high degree of synteny and macrocollinearity and was then utilized to anchor a collection of perennial ryegrass genes in silico to their predicted genome positions. This resulted in the unambiguous assignment of 3,315 out of 8,876 previously unmapped genes to the respective chromosomes. In total, the GenomeZipper incorporates 4,035 conserved grass gene loci, which were used for the first genome-wide sequence divergence analysis between perennial ryegrass, barley, Brachypodium, rice, and sorghum. The perennial ryegrass GenomeZipper is an ordered, information-rich genome scaffold, facilitating map-based cloning and genome assembly in perennial ryegrass and closely related Poaceae species. It also represents a milestone in describing synteny between perennial ryegrass and fully sequenced model grass genomes, thereby increasing our understanding of genome organization and evolution in the most important temperate forage and turf grass species.


Active integration: new strategies for transgenesis.
This paper presents novel methods for producing transgenic animals, with a further emphasis on how these techniques may someday be applied in gene therapy. There are several passive methods for transgenesis, such as pronuclear microinjection (PNI) and Intracytoplasmic Sperm Injection-Mediated Transgenesis (ICSI-Tr), which rely on the repair mechanisms of the host for transgene (tg) insertion. ICSI-Tr has been shown to be an effective means of creating transgenic animals with a transfection efficiency of approximately 45% of animals born. Furthermore, because this involves the injection of the transgene into the cytoplasm of oocytes during fertilization, limited mosaicism has traditionally occurred using this technique. Current active transgenesis techniques involve the use of viruses, such as disarmed retroviruses which can insert genes into the host genome. However, these methods are limited by the size of the sequence that can be inserted, high embryo mortality, and randomness of insertion. A novel active method has been developed which combines ICSI-Tr with recombinases or transposases to increase transfection efficiency. This technique has been termed "Active Transgenesis" to imply that the tg is inserted into the host genome by enzymes supplied into the oocyte during tg introduction. DNA based methods alleviate many of the costs and time associated with purifying enzyme. Further studies have shown that RNA can be used for the transposase source. Using RNA may prevent problems with continued transposase activity that can occur if a DNA transposase is integrated into the host genome. At present piggyBac is the most effective transposon for stable integration in mammalian systems and as further studies are done to elucidate modifications which improve piggyBac's specificity and efficacy, efficiency in creating transgenic animals should improve further. Subsequently, these methods may someday be used for gene therapy in humans.


Yeast increases resistance in Arabidopsis against Pseudomonas syringae and Botrytis cinerea by salicylic acid-dependent as well as -independent mechanisms.
Cell-wall and glucopeptide components of yeast have been reported to exhibit elicitor activity. The mode of action of defense activation by yeast is not known so far. In this study, we used the model plant Arabidopsis to investigate the activation of defense responses by yeast, the effect on resistance against different pathogens, and the mode of action. Treatment of Arabidopsis plants with an autoclaved yeast suspension induced the expression of systemic acquired resistance-related genes and accumulation of the phytoalexin camalexin. Symptom development and bacterial growth after infection with a virulent strain of the pathogen Pseudomonas syringae was reduced in yeast-pretreated plants. No protection was detectable in mutants affected in the salicylate pathway, while mutants in the jasmonate or camalexin pathway were protected by yeast, indicating that the salicylate pathway is necessary for the yeast-induced resistance against P. syringae. Yeast also reduced symptom development after challenge with Botrytis cinerea. This protection was detectable in all mutants tested, indicating that it is independent of the salicylate, jasmonate, and camalexin pathway.


Opto-Thermal Transient Emission Radiometry (OTTER) to image diffusion in nails in vivo.
This work describes the first application of Opto-Thermal Transient Emission Radiometry (OTTER), an infrared remote sensing technique, to probe the extent to which solvents permeate the human nail in vivo. Decanol, glycerol and butyl acetate were selected as model solvents. After application of the solvents, individually, to human volunteers, OTTER was used to depth profile the solvents. The permeation rate of the solvents was ranked as glycerol>decanol>butyl acetate. It is possible that some of the butyl acetate may have evaporated during the experiment. The ability of decanol to extract lipids from biological tissue is also considered. These preliminary results demonstrate the potential of OTTER as a tool to identify optimal excipients with which to target drugs to the nail.


Saccadic Eye Movement Abnormalities in Children with Epilepsy.
Childhood onset epilepsy is associated with disrupted developmental integration of sensorimotor and cognitive functions that contribute to persistent neurobehavioural comorbidities. The role of epilepsy and its treatment on the development of functional integration of motor and cognitive domains is unclear. Oculomotor tasks can probe neurophysiological and neurocognitive mechanisms vulnerable to developmental disruptions by epilepsy-related factors. The study involved 26 patients and 48 typically developing children aged 8-18 years old who performed a prosaccade and an antisaccade task. Analyses compared medicated chronic epilepsy patients and unmedicated controlled epilepsy patients to healthy control children on saccade latency, accuracy and dynamics, errors and correction rate, and express saccades. Patients with medicated chronic epilepsy had impaired and more variable processing speed, reduced accuracy, increased peak velocity and a greater number of inhibitory errors, younger unmedicated patients also showed deficits in error monitoring. Deficits were related to reported behavioural problems in patients. Epilepsy factors were significant predictors of oculomotor functions. An earlier age at onset predicted reduced latency of prosaccades and increased express saccades, and the typical relationship between express saccades and inhibitory errors was absent in chronic patients, indicating a persistent reduction in tonic cortical inhibition and aberrant cortical connectivity. In contrast, onset in later childhood predicted altered antisaccade dynamics indicating disrupted neurotransmission in frontoparietal and oculomotor networks with greater demand on inhibitory control. The observed saccadic abnormalities are consistent with a dysmaturation of subcortical-cortical functional connectivity and aberrant neurotransmission. Eye movements could be used to monitor the impact of epilepsy on neurocognitive development and help assess the risk for poor neurobehavioural outcomes.


What US hospitals are doing to prevent common device-associated infections during the coronavirus disease 2019 (COVID-19) pandemic: Results from a national survey in the United States.
The ways that device-associated infection prevention practices changed during the coronavirus disease 2019 (COVID-19) pandemic remain unknown. We collected data mid-pandemic to assess the use of several infection prevention practices and for comparison with historical data. Repeated cross-sectional survey. US acute-care hospitals. Infection preventionists. We surveyed infection preventionists from a national random sample of 881 US acute-care hospitals in 2021 to estimate the current use of practices to prevent catheter-associated urinary tract infection (CAUTI), central line-associated bloodstream infection (CLABSI), and ventilator-associated events (VAE). We compared the 2021 results with those from surveys occurring every 4 years since 2005. The 2021 survey response rate was 47%; previous survey response rates ranged from 59% to 72%. Regular use of most practices to prevent CLABSI (chlorhexidine gluconate for site antisepsis, 99.0%, and maximum sterile barrier precautions, 98.7%) and VAE (semirecumbent positioning, 93.4%, and sedation vacation, 85.8%) continued to increase or plateaued in 2021. Conversely, use of several CAUTI prevention practices (portable bladder ultrasound scanner, 65.6%; catheter reminders or nurse-initiated discontinuation, 66.3%; and intermittent catheterization, 37.3%) was lower in 2021, with a significant decrease for some practices compared to 2017 (P ≤ .02 for all comparisons). In 2021, 42.1% of hospitals reported regular use of the newer external urinary collection devices for women. Although regular use of CLABSI and VAE preventive practices continued to increase (or plateaued), use of several CAUTI preventive practices decreased during the COVID-19 pandemic. Structural issues relating to care during the pandemic may have contributed to a decrease in device-associated infection prevention practices.


Extraordinary optical absorption based on guided-mode resonance.
We propose a novel structure that can achieve extraordinary optical absorption over the visible spectrum, based on the guided-mode resonance effect. An optical metal grating with moderate thickness and high filling factor can lead to coupling between the quasi-guided-mode and cavity mode. The resonant interaction between the two modes can influence the field distribution, such as the magnetic field near the grating, which results in extraordinary absorption. Absorption efficiency can be optimized up to 99.16%. We also show that the absorption peak can be readily tuned just by varying the subwavelength grating period.


Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment.
Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia.


Behavior of lambda bacteriophage in a recombination deficienct strain of Escherichia coli.
The behavior of lambda phage in the Rec(-) strain JC-1569 is compared with that in the Rec(+) strain JC-1557. No difference deemed significant was noted in the adsorption rate, latent period, burst size, frequency of lysogenization, and frequency of vegetative phage recombination. The location of the prophage and its mode of insertion in the Rec(-) lysogen of wild-type lambda (lambda(+)) were inferred to be normal from the results of conjugational crosses. Spontaneous and ultraviolet (UV) irradiation induction of lambda(+) were markedly reduced in the Rec(-) lysogen. On the other hand, thermal induction of a mutant lambda (lambdacI857) lysogen of the Rec(-) strain was not reduced and was only slightly affected by UV irradiation. Phage subject to inhibition by lambda immunity failed to multiply in UV-irradiated cells of the Rec(-) lambda(+) lysogen, whereas those not inhibited by this immunity did multiply. It was concluded that the failure of UV to induce lambda(+) in the Rec(-) lysogen was not due to damage to the prophage, but rather to the inability of the irradiated cells to respond by lifting immunity. Preliminary evidence indicates that a single mutation confers recombination deficiency and the inability to lift immunity after UV irradiation. Possible relationships between recombination and the lifting of immunity are enumerated.


Molecular characterization of binding subcomponents of Clostridium botulinum type C progenitor toxin for intestinal epithelial cells and erythrocytes.
Clostridium botulinum type C 16S progenitor toxin consists of a neurotoxin (NTX), a non-toxic non-HA (NTNH), and a haemagglutinin (HA). The HA acts as an adhesin, allowing the 16S toxin to bind to intestinal epithelial cells and erythrocytes. In type C, these bindings are dependent on sialic acid. The HA consists of four distinct subcomponents designated HA1, HA2, HA3a and HA3b. To identify the binding subcomponent(s) of HA of type C 16S toxin, all of the HA-subcomponents and some of their precursor forms were produced as recombinant proteins fused to glutathione S-transferase (GST). These proteins were evaluated for their capacity to adhere to intestinal epithelial cells of guinea pig and human erythrocytes. GST-HA1, GST-HA3b and GST-HA3 (a precursor form of HA3a and HA3b) bound intestinal epithelial cells and erythrocytes, whereas GST alone, GST-HA2 and GST-HA3a did not. GST-HA3b and GST-HA3 showed neuraminidase-sensitive binding to the intestinal epithelial cells and erythrocytes, whereas GST-HA1 showed neuraminidase-insensitive binding. TLC binding assay revealed that GST-HA3b and GST-HA3 recognized sialosylparagloboside (SPG) and GM3 in the ganglioside fraction of the erythrocytes, like native type C 16S toxin [Inoue, K. et al. (1999). Microbiology 145, 2533-2542]. On the other hand, GST-HA1 recognized paragloboside (PG; an asialo- derivative of SPG) in addition to SPG and GM3. Deletion mutant analyses of GST-HA3b showed that the C-terminal region of HA3b is important for its binding activity. Based on these data, it is concluded that the HA component contains two distinct carbohydrate-binding subcomponents, HA1 and HA3b, which recognize carbohydrates in different specificities.


Depletion of CD11c+ dendritic cells in apolipoprotein E-deficient mice limits angiotensin II-induced abdominal aortic aneurysm formation and growth.
The role of chronic inflammation in abdominal aortic aneurysm (AAA) is controversial. CD11c+ antigen-presenting cells (APCs) (dendritic cells (DCs)) have been reported in human AAA samples but their role is unclear. The effect of conditional depletion of CD11c+ cells on experimental AAA was investigated in the angiotensin II (AngII)-infused apolipoprotein E-deficient (ApoE-/-) mouse model. CD11c-diphtheria toxin (DT or D.tox) receptor (DTR), ovalbumin (OVA) fragment aa 140-386, and enhanced green fluorescent protein (eGFP)-ApoE-/- (CD11c.DOG.ApoE-/-) mice were generated and CD11c+ cell depletion achieved with D.tox injections (8 ng/g body weight, i.p., every-other-day). AAA formation and growth were assessed by measurement of supra-renal aortic (SRA) diameter in vivo by serial ultrasound and by morphometry assessment of harvested aortas at the end of the study. Depletion of CD11c+ cells by administration of D.tox on alternative days was shown to reduce the maximum diameter of AAAs induced by 28 days AngII infusion compared with controls (D.tox, 1.58 ± 0.03 mm vs Vehicle control, 1.81 ± 0.06 mm, P<0.001). CD11c+ depletion commencing after AAA establishment by 14 days of AngII infusion, was also shown to lead to smaller AAAs than controls after a further 14 days (D.tox, 1.54 ± 0.04 mm vs Vehicle control, 1.80 ± 0.03 mm, P<0.001). Flow cytometry revealed significantly lower numbers of circulating CD44hi CD62Llo effector CD4 T cells, CD44hi CD62Llo effector CD8 T cells and B220+ B cells in CD11c+ cell-depleted mice versus controls. CD11c+ depletion attenuated SRA matrix degradation indicated by decreased neutrophil elastase activity (P=0.014), lower elastin degradation score (P=0.012) and higher collagen content (P=0.002). CD11c+ cell-depletion inhibited experimental AAA development and growth associated with down-regulation of circulating effector T cells and attenuated matrix degradation. The findings suggest involvement of autoreactive immune cells in AAA pathogenesis.


Online Mindfulness Training Increases Well-Being, Trait Emotional Intelligence, and Workplace Competency Ratings: A Randomized Waitlist-Controlled Trial.
A randomized waitlist-controlled trial was conducted to assess the effectiveness of an online 8-week mindfulness-based training program in a sample of adults employed fulltime at a Fortune 100 company in the United States. Baseline measures were collected in both intervention and control groups. Following training, the intervention group (N = 37) showed statistically significant increases in resilience and positive mood, and significant decreases in stress and negative mood. There were no reported improvements in the wait-list control group (N = 65). Trait mindfulness and emotional intelligence (EI) were also assessed. Following the intervention mindfulness intervention participants reported increases in trait mindfulness and increases on all trait EI facets with the exception of empathy. The control group did not report any positive changes in these variables, and reported reductions in resilience and increases in negative mood. Finally, both self and colleague ratings of workplace competencies were collected in the intervention group only and provided preliminary evidence that mindfulness training enhanced performance on key leadership competencies including competencies related to decisiveness and creativity. The present study demonstrates the effectiveness of an online-based mindfulness training program for enhancing well-being, self-perceptions of emotional intelligence, and workplace performance.


Evidence for the role of dendritic spines in the temporal filtering properties of neurons: the decoding problem and beyond.
The question of relations between structure and function acutely applies to the search for the functional role of dendritic spines. While dendritic spines are a prominent and widespread structural feature of neurons in the central nervous system, their function is poorly understood. Because the conducting core of a spine stem can be of extremely small dimensions, a large axial resistance to current flow and "low-pass" filtering of inputs have been hypothesized. Here we show that neurons in the dorsal torus semicircularis of the electric fish Eigenmannia show real-time fluctuations in their transmembrane potential that reflect modulations in the amplitude of a high-frequency sinusoidal carrier signal. In 18 neurons recorded intracellularly and labeled with Lucifer yellow, the decrease in the magnitude of these potentials with increasing rate of amplitude modulation (i.e., low-pass temporal filtering) was positively correlated (r = 0.79, P < 0.001, over a range of one to two octaves in modulation rate) with the mean dendritic spine density (range, 0-0.38 spine per micron of dendritic length) of the cell. The acquisition of synaptic input through dendritic spines may be a general mechanism for achieving the temporal filtering that underlies real-time signal processing in the central nervous system.


Impact of sludge deposition on biodiversity.
Sludge deposition in the environment is carried out in several countries. It encompasses the dispersion of treated or untreated sludge in forests, marsh lands, open waters as well as estuarine systems resulting in the gradual accumulation of toxins and persistent organic compounds in the environment. Studies on the life cycle of compounds from sludge deposition and the consequences of deposition are few. Most reports focus rather on treatment-methods and approaches, legislative aspects as well as analytical evaluations of the chemical profiles of sludge. This paper reviews recent as well as some older studies on sludge deposition in forests and other ecosystems. From the literature covered it can be concluded that sludge deposition induces two detrimental effects on the environment: (1) raising of the levels of persistent toxins in soil, vegetation and wild life and (2) slow and long-termed biodiversity-reduction through the fertilizing nutrient pollution operating on the vegetation. Since recent studies show that eutrophication of the environment is a major threat to global biodiversity supplying additional nutrients through sludge-based fertilization seems imprudent. Toxins that accumulate in the vegetation are transferred to feeding herbivores and their predators, resulting in a reduced long-term survival chance of exposed species. We briefly review current legislation for sludge deposition and suggest alternative routes to handling this difficult class of waste.


Emotional responses of mothers of late-preterm and term infants.
To compare the emotional responses of mothers of late-preterm infants (34 0/7 to 36 6/7 weeks gestation) with those of mothers of full-term infants. A mixed method comparative study. A southeastern tertiary academic medical center postpartum unit. Sixty mothers: 29 mothers of late-preterm infants and 31 mothers of full-term infants. Measures of maternal emotional distress (four standardized measures of anxiety, postpartum depression, posttraumatic stress symptoms, and worry about infant health) and open-ended semistructured maternal interviews were conducted in the hospital following birth and by phone at one month postpartum. Mothers of late-preterm infants experienced significantly greater emotional distress immediately following delivery, and their distress levels continued to be higher at one month postpartum on each of the standardized measures. Mothers of late-preterm infants also discussed the altered trajectories in their birth and postpartum experiences and feeling unprepared for these unexpected events as a source of ongoing emotional distress. Mothers of late-preterm infants have greater emotional distress than mothers of term infants for at least one month after delivery. Our findings suggest that it may not be a single event that leads to different distress levels in mothers of late-preterm and full-term infants but rather the interaction of multiple alterations in the labor and delivery process and the poorer-than-expected infant health outcomes. In the future, researchers need to examine how and when mothers' emotional responses change over time and how their responses relate to parenting and infant health and development.


Dependence of InGaP nanowire morphology and structure on molecular beam epitaxy growth conditions.
InGaP nanowires (NWs) were grown by the Au-assisted method in a gas source molecular beam epitaxy system. The dependence of InGaP composition, morphology and stacking fault density was studied with respect to group III and V impingement rate and size of the Au particle. Compositional analysis showed that the NWs had an In-rich core and a Ga-rich shell structure. The In incorporation within the NW became limited as the Au seed particle size diminished or the group III and V flux decreased. The NWs had wurtzite (WZ) crystal structure with zinc blende (ZB) segments (stacking faults). The density of the stacking faults decreased as the group III flux decreased and the group V flux increased.


Kinetic and economic analysis of reactive capture of dilute carbon dioxide with Grignard reagents.
Carbon Dioxide Utilisation (CDU) processes face significant challenges, especially in the energetic cost of carbon capture from flue gas and the uphill energy gradient for CO2 reduction. Both of these stumbling blocks can be addressed by using alkaline earth metal compounds, such as Grignard reagents, as sacrificial capture agents. We have investigated the performance of these reagents in their ability to both capture and activate CO2 directly from dried flue gas (essentially avoiding the costly capture process entirely) at room temperature and ambient pressures with high yield and selectivity. Naturally, to make the process sustainable, these reagents must then be recycled and regenerated. This would potentially be carried out using existing industrial processes and renewable electricity. This offers the possibility of creating a closed loop system whereby alcohols and certain hydrocarbons may be carboxylated with CO2 and renewable electricity to create higher-value products containing captured carbon. A preliminary Techno-Economic Analysis (TEA) of an example looped process has been carried out to identify the electrical and raw material supply demands and hence determine production costs. These have compared broadly favourably with existing market values.


Genetic Abnormalities in Oral Leukoplakia and Oral Cancer Progression.
The cancer progression of oral leukoplakia is an important watchpoint in the follow-up observation of the patients. However, potential malignancies of oral leukoplakia cannot be estimated by histopathologic assessment alone. We evaluated genetic abnormalities at the level of copy number variation (CNV) to investigate the risk for developing cancer in oral leukoplakias. The current study used 27 oral leukoplakias with histological evidence of dysplasia. The first group (progressing dysplasia) consisted of 7 oral lesions from patients with later progression to cancer at the same site. The other group (non- progressing dysplasia) consisted of 20 lesions from patients with no occurrence of oral cancer and longitudinal follow up (>7 years). We extracted DNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples and examined chromosomal loci and frequencies of CNVs using Taqman copy number assays. CNV frequently occurred at 3p, 9p, and 13q loci in progressing dysplasia. Our results also indicate that CNV at multiple loci-in contrast to single locus occurrences-is characteristic of progressing dysplasia. This study suggests that genetic abnormalities of the true precancer demonstrate the progression risk which cannot be delineated by current histopathologic diagnosis.


Control of autophagosome axonal retrograde flux by presynaptic activity unveiled using botulinum neurotoxin type a.
Botulinum neurotoxin type A (BoNT/A) is a highly potent neurotoxin that elicits flaccid paralysis by enzymatic cleavage of the exocytic machinery component SNAP25 in motor nerve terminals. However, recent evidence suggests that the neurotoxic activity of BoNT/A is not restricted to the periphery, but also reaches the CNS after retrograde axonal transport. Because BoNT/A is internalized in recycling synaptic vesicles, it is unclear which compartment facilitates this transport. Using live-cell confocal and single-molecule imaging of rat hippocampal neurons cultured in microfluidic devices, we show that the activity-dependent uptake of the binding domain of the BoNT/A heavy chain (BoNT/A-Hc) is followed by a delayed increase in retrograde axonal transport of BoNT/A-Hc carriers. Consistent with a role of presynaptic activity in initiating transport of the active toxin, activity-dependent uptake of BoNT/A in the terminal led to a significant increase in SNAP25 cleavage detected in the soma chamber compared with nonstimulated neurons. Surprisingly, most endocytosed BoNT/A-Hc was incorporated into LC3-positive autophagosomes generated in the nerve terminals, which then underwent retrograde transport to the cell soma, where they fused with lysosomes both in vitro and in vivo. Blocking autophagosome formation or acidification with wortmannin or bafilomycin A1, respectively, inhibited the activity-dependent retrograde trafficking of BoNT/A-Hc. Our data demonstrate that both the presynaptic formation of autophagosomes and the initiation of their retrograde trafficking are tightly regulated by presynaptic activity.


Pediatric papillary tumors of the pineal region: to observe or to treat following gross total resection?
Papillary tumors of the pineal region (PTPR) are rare brain tumors characterized by frequent local recurrences. Standardized treatment strategies are not yet defined. We present the case of a 3-year-old girl diagnosed with PTPR. Due to her young age, adjuvant radiotherapy was omitted after gross total tumor resection. Thirty-six months later, local tumor recurrence occurred. Considering the possible risks of secondary surgery, the recurrent tumor was irradiated with proton radiotherapy. Three months later, the tumor showed near-complete remission. Based on this experience and other pediatric case reports from the literature, local radiotherapy might be suggested also after complete tumor resection.


Super-ions of sodium cations with hydrated hydroxide anions: inorganic structure-directing agents in zeolite synthesis.
In inorganic zeolite formation, a direct correspondence between liquid state species in the synthesis and the supramolecular decoration of the pores in the as-made final zeolite has never been reported. In this paper, a direct link between the sodium speciation in the synthesis mixture and the pore structure and content of the final zeolite is demonstrated in the example of hydroxysodalite. Super-ions with 4 sodium cations bound by mono- and bihydrated hydroxide are identified as structure-directing agents for the formation of this zeolite. This documentation of inorganic solution species acting as a templating agent in zeolite formation opens new horizons for zeolite synthesis by design.


Genes mirror migrations and cultures in prehistoric Europe-a population genomic perspective.
Genomic information from ancient human remains is beginning to show its full potential for learning about human prehistory. We review the last few years' dramatic finds about European prehistory based on genomic data from humans that lived many millennia ago and relate it to modern-day patterns of genomic variation. The early times, the Upper Paleolithic, appears to contain several population turn-overs followed by more stable populations after the Last Glacial Maximum and during the Mesolithic. Some 11000 years ago the migrations driving the Neolithic transition start from around Anatolia and reach the north and the west of Europe millennia later followed by major migrations during the Bronze Age. These findings show that culture and lifestyle were major determinants of genomic differentiation and similarity in pre-historic Europe rather than geography as is the case today.


Lessons from an LPS-deficient Neisseria meningitidis mutant.
In the pathogen Neisseria meningitidis, a completely LPS-deficient but viable mutant can be obtained by insertional inactivation of the lpxA gene, encoding UDP-GlcNAc acyltransferase required for the first step of lipid A biosynthesis. The expression and assembly of integral outer membrane proteins in the absence of LPS is largely unaffected. However, the expression of iron limitation-inducible, cell surface-exposed lipoproteins is greatly reduced. Major changes were seen in the phospholipid composition, with a shift towards PE and PG species containing mostly shorter chain, saturated fatty acids. The presence of the capsular polysaccharide turned out to be essential for viability without LPS. The immunogenicity of outer membrane proteins in mice was greatly reduced for the LPS-deficient mutant, showing the importance of LPS as an internal adjuvant in such vaccines. Stimulation of MM6 cells and peripheral blood mononuclear cells showed that induction of TNF-alpha by whole meningococci was greatly reduced for the LPS-deficient mutant. However, even without LPS the mutant strain could still induce a significant inflammatory response.


A natural plant-derived dihydroisosteviol prevents cholera toxin-induced intestinal fluid secretion.
Stevioside and its major metabolite, steviol, have been reported to affect ion transport in many types of tissues, such as the kidney, pancreas, and intestine. The effect of stevioside, steviol, and its analogs on intestinal Cl(-) secretion was investigated in a human T84 epithelial cell line. Short-circuit current measurements showed that steviol and analogs isosteviol, dihydroisosteviol, and isosteviol 16-oxime inhibited in a dose-dependent manner forskolin-induced Cl(-) secretion with IC(50) values of 101, 100, 9.6, and 50 microM, respectively, whereas the parent compound stevioside had no effect. Apical Cl(-) current measurement indicated that dihydroisosteviol targeted the cystic fibrosis transmembrane regulator (CFTR). The inhibitory action of dihydroisosteviol was reversible and was not associated with changes in the intracellular cAMP level. In addition, dihydroisosteviol did not affect calcium-activated chloride secretion and T84 cell viability. In vivo studies using a mouse closed-loop model of cholera toxin-induced intestinal fluid secretion showed that intraluminal injection of 50 microM dihydroisosteviol reduced intestinal fluid secretion by 88.2% without altering fluid absorption. These results indicate that dihydroisosteviol and similar compounds could be a new class of CFTR inhibitors that may be useful for further development as antidiarrheal agents.


Meningioma transcript profiles reveal deregulated Notch signaling pathway.
Meningiomas constitute the second most common central nervous system tumor, and yet relatively little is known about the molecular events that are important for the pathogenesis and malignant progression of these tumors. We have used serial analysis of gene expression to compare the transcriptomes of nonneoplastic meninges and meningiomas of all malignancy grades. A novel finding from this screen is the induction of three components of the Notch signaling pathway: the transcription factor, hairy and enhancer of Split1 (HES1) and two members of the Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3. TLE corepressors interact and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. We have shown that the transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the Jagged1 ligand are induced in meningiomas of all grades, whereas induction of TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell lines express components of the Notch signaling pathway and an inhibitor of this pathway suppresses meningioma cell survival. These results suggest that deregulated expression of the Notch pathway is a critical event in meningioma pathogenesis and that modulation of this and potentially other signaling pathways by TLE corepressors leads to a more malignant phenotype.


Antibodies against fetal brain in sera of mothers with autistic children.
Serum antibodies in 100 mothers of children with autistic disorder (MCAD) were compared to 100 age-matched mothers with unaffected children (MUC) using as antigenic substrates human and rodent fetal and adult brain tissues, GFAP, and MBP. MCAD had significantly more individuals with Western immunoblot bands at 36 kDa in human fetal and rodent embryonic brain tissue. The density of bands was greater in fetal brain at 61 kDa. MCAD plus developmental regression had greater reactivity against human fetal brain at 36 and 39 kDa. Data support a possible complex association between genetic/metabolic/environmental factors and the placental transfer of maternal antibodies in autism.


ETView VivaSight single lumen vs. conventional intubation in simulated studies: a systematic review and meta-analysis.
The ETView VivaSight single lumen airway tube (ETView) is a tracheal tube incorporating a video camera. We carried out a meta-analysis of previous simulation studies by inexperienced personnel to determine if the ETView could improve the success rate of first-attempt intubation. We collected data from randomized controlled trials comparing the use of the ETView VivaSight single lumen versus a conventional endotracheal tube in a simulated manikin or cadaver study. Eleven studies (558 participants, 3,254 intubations, and 19 scenarios) were included. The ETView had a significantly higher success rate and shorter insertion time than conventional intubation in both normal airways (with or without chest compression) and in difficult airways. In addition, the ETView demonstrated better results in terms of a higher rate of Cormack-Lehane grade 1 and a lower incidence of dental trauma. Inexperienced personnel can insert the ETView more rapidly and with a higher intubation success rate compared with a conventional tube.


Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis.
Epithelial permeability is often increased in inflammatory bowel diseases. We hypothesized that perturbed mitochondrial function would cause barrier dysfunction and hence epithelial mitochondria could be targeted to treat intestinal inflammation. Mitochondrial dysfunction was induced in human colon-derived epithelial cell lines or colonic biopsy specimens using dinitrophenol, and barrier function was assessed by transepithelial flux of Escherichia coli with or without mitochondria-targeted antioxidant (MTA) cotreatment. The impact of mitochondria-targeted antioxidants on gut permeability and dextran sodium sulfate (DSS)-induced colitis in mice was tested. Mitochondrial superoxide evoked by dinitrophenol elicited significant internalization and translocation of E. coli across epithelia and control colonic biopsy specimens, which was more striking in Crohn's disease biopsy specimens; the mitochondria-targeted antioxidant, MitoTEMPO, inhibited these barrier defects. Increased gut permeability and reduced epithelial mitochondrial voltage-dependent anion channel expression were observed 3 days after DSS. These changes and the severity of DSS-colitis were reduced by MitoTEMPO treatment. In vitro DSS-stimulated IL-8 production by epithelia was reduced by MitoTEMPO. Metabolic stress evokes significant penetration of commensal bacteria across the epithelium, which is mediated by mitochondria-derived superoxide acting as a signaling, not a cytotoxic, molecule. MitoTEMPO inhibited this barrier dysfunction and suppressed colitis in DSS-colitis, likely via enhancing barrier function and inhibiting proinflammatory cytokine production. These novel findings support consideration of MTAs in the maintenance of epithelial barrier function and the management of inflammatory bowel diseases.


Involvement of area MT in bimanual finger movements in left-handers: an fMRI study.
The ease with which humans are able to perform symmetric movements of both hands has traditionally been attributed to the preference of the motor system to activate homologous muscles. Recently, we have shown in right-handers, however, that bimanual index finger adduction and abduction movements in incongruous hand orientations (one palm down/other up) preferentially engaged parietal perception-associated brain areas. Here, we used functional magnetic resonance imaging to investigate the influence of hand orientation in left-handers on cerebral activation during bimanual index finger movements. Performance in incongruous orientation of either hand yielded activations involving right and left motor cortex, supplementary motor area in right superior frontal gyrus (SMA and pre-SMA), bilateral premotor cortex, prefrontal cortex, bilateral somatosensory cortex and anterior parietal cortex along the intraparietal sulcus. In addition, the occipito-temporal cortex corresponding to human area MT (hMT) in either hemisphere was activated in relation to bimanual index finger movements in the incongruous hand orientation as compared with the same movements in the congruous hand orientation or with simply viewing the pacing stimuli. Comparison with the same movement condition in right-handed subjects from a former study support these hMT activations exclusively for left-handed subjects. These results suggest that left-handers use visual motion imagery in guiding incongruous bimanual finger movements.


Evaluation of the effects of an offer of a monetary incentive on the rate of questionnaire return during follow-up of a clinical trial: a randomised study within a trial.
A systematic review on the use of incentives to promote questionnaire return in clinical trials suggest they are effective, but not all studies have sufficient funds to use them. Promising an incentive once data are returned can reduce the cost-burden of this approach, with possible further cost-savings if the offer were restricted to reminder letters only. This study aimed to evaluate the effect of promising a monetary incentive at first mailout versus a promise on reminder letters only. This was a randomised Study Within A Trial (SWAT) nested within BUMPES, a multicentre randomised controlled trial of maternal position in the late stage of labour in women with an epidural. The follow-up questionnaire asked for information on the women's health, wellbeing and health service use one year following the birth of their baby. Women who consented to be contacted were randomised to a promise of a monetary incentive at first mailout or a promise on reminder letters only. Women were given an option of completing the questionnaire on paper or on online. The incentive was posted out on receipt of a completed questionnaire. The primary outcome was the overall return rate, and secondary outcomes were the return rate without any chasing from the study office, and the total cost of the vouchers. A total of 1,029 women were randomised, 508 to the first mailout group and 518 to the reminder group. There was no evidence to suggest a difference between groups in the overall return rate (adjusted RR 1.03 (95 % CI 0.96 to 1.11), however the proportion returned without chasing was higher in the first mailout group (adjusted RR 1.22, 95 % CI 1.07 to 1.39). The total cost of the vouchers per participant was higher in the first mailout group (mean difference £4.56, 95 % CI £4.02 to £5.11). Offering a monetary incentive when a reminder is required could be cost-effective depending on the sample size of the study and the resources available to administer the reminder letters. The BUMPES Trial is registered with Current Controlled Trials: ISRCTN35706297 , 26(th) August 2009.


Motor functioning differentially predicts mortality in men and women.
Research indicates gender differences in functional performance at advanced ages, but little is known about their impact on longevity for men and women. To derive a set of motor function factors from a battery of functional performance measures and examine their associations with mortality, incorporating possible gender interactions. Analyses were performed on the longitudinal Swedish Adoption/Twin Study of Aging (SATSA) including twenty-four assessments of motor function up to six times over a 19-year period. Three motor factors were derived from several factor analyses; fine motor, balance/upper strength, and flexibility. A latent growth curve model was used to capture longitudinal age changes in the motor factors and generated estimates of intercept at age 70 (I), rates of change before (S1) and after age 70 (S2) for each factor. Cox regression models were used to determine how gender in interaction with the motor factors was related to mortality. Females demonstrated lower functional performance in all motor functions relative to men. Cox regression survival analyses demonstrated that both balance/upper strength, and fine motor function were significantly related to mortality. Gender specific analyses revealed that this was true for women only. For men, none of the motor factors were related to mortality. Women demonstrated more difficulties in all functioning facets, and only among women were motor functioning (balance/upper strength and fine motor function) associated with mortality. These results provide evidence for the importance of considering motor functioning, and foremost observed gender differences when planning for individualized treatment and rehabilitation.


Visual spatial attention tracking using high-density SSVEP data for independent brain-computer communication.
The steady-state visual evoked potential (SSVEP) has been employed successfully in brain-computer interface (BCI) research, but its use in a design entirely independent of eye movement has until recently not been reported. This paper presents strong evidence suggesting that the SSVEP can be used as an electrophysiological correlate of visual spatial attention that may be harnessed on its own or in conjunction with other correlates to achieve control in an independent BCI. In this study, 64-channel electroencephalography data were recorded from subjects who covertly attended to one of two bilateral flicker stimuli with superimposed letter sequences. Offline classification of left/right spatial attention was attempted by extracting SSVEPs at optimal channels selected for each subject on the basis of the scalp distribution of SSVEP magnitudes. This yielded an average accuracy of approximately 71% across ten subjects (highest 86%) comparable across two separate cases in which flicker frequencies were set within and outside the alpha range respectively. Further, combining SSVEP features with attention-dependent parieto-occipital alpha band modulations resulted in an average accuracy of 79% (highest 87%).


Hybrid correction of highly noisy long reads using a variable-order de Bruijn graph.
The recent rise of long read sequencing technologies such as Pacific Biosciences and Oxford Nanopore allows to solve assembly problems for larger and more complex genomes than what allowed short reads technologies. However, these long reads are very noisy, reaching an error rate of around 10-15% for Pacific Biosciences, and up to 30% for Oxford Nanopore. The error correction problem has been tackled by either self-correcting the long reads, or using complementary short reads in a hybrid approach. However, even though sequencing technologies promise to lower the error rate of the long reads below 10%, it is still higher in practice, and correcting such noisy long reads remains an issue. We present HG-CoLoR, a hybrid error correction method that focuses on a seed-and-extend approach based on the alignment of the short reads to the long reads, followed by the traversal of a variable-order de Bruijn graph, built from the short reads. Our experiments show that HG-CoLoR manages to efficiently correct highly noisy long reads that display an error rate as high as 44%. When compared to other state-of-the-art long read error correction methods, our experiments also show that HG-CoLoR provides the best trade-off between runtime and quality of the results, and is the only method able to efficiently scale to eukaryotic genomes. HG-CoLoR is implemented is C++, supported on Linux platforms and freely available at https://github.com/morispi/HG-CoLoR. Supplementary data are available at Bioinformatics online.


Heterogeneity of postpartum depression: a latent class analysis.
Maternal depression in the postpartum period confers substantial morbidity and mortality, but the definition of postpartum depression remains controversial. We investigated the heterogeneity of symptoms with the aim of identifying clinical subtypes of postpartum depression. Data were aggregated from the international perinatal psychiatry consortium Postpartum Depression: Action Towards Causes and Treatment, which represents 19 institutions in seven countries. 17,912 unique subject records with phenotypic data were submitted. We applied latent class analyses in a two-tiered approach to assess the validity of empirically defined subtypes of postpartum depression. Tier one assessed heterogeneity in women with complete data on the Edinburgh postnatal depression scale (EPDS) and tier two in those with postpartum depression case status. 6556 individuals were assessed in tier one and 4245 in tier two. A final model with three latent classes was optimum for both tiers. The most striking characteristics associated with postpartum depression were severity, timing of onset, comorbid anxiety, and suicidal ideation. Women in class 1 had the least severe symptoms (mean EPDS score 10·5), followed by those in class 2 (mean EPDS score 14·8) and those in class 3 (mean EPDS score 20·1). The most severe symptoms of postpartum depression were significantly associated with poor mood (mean EPDS score 20·1), increased anxiety, onset of symptoms during pregnancy, obstetric complications, and suicidal ideation. In class 2, most women (62%) reported symptom onset within 4 weeks postpartum and had more pregnancy complications than in other two classes (69% vs 67% in class 1 and 29% in class 3). PPD seems to have several distinct phenotypes. Further assessment of PPD heterogeneity to identify more precise phenotypes will be important for future biological and genetic investigations. Sources of funding are listed at the end of the article.


Latent Classes of Nicotine Beliefs Correlate with Perceived Susceptibility and Severity of Nicotine and Tobacco Products in US young adults.
Pervasive misperceptions about nicotine may influence uptake of quit smoking aids and the impact of policies addressing nicotine as a tobacco product constituent. Latent class analyses were conducted using four items on nicotine beliefs asked of 4037 adults aged 18-40 in wave 9 (February-March 2016) of the Truth Initiative Young Adult Cohort Study. Confirmatory factor analyses identified three factors from 12 items: nicotine susceptibility (NSUS), nicotine severity (NSEV), and tobacco severity (TSEV). Analyses assessed correlations between latent classes, sociodemographics, and nicotine/tobacco factor scores. A four-class model of nicotine beliefs was the best fit, with the largest class believing that nicotine plays a major part in smoking risks (class 1, n = 2070; 52%). Class 2 shared that belief but also responded "Don't know" to addiction questions (class 2, n = 382; 11%). Fewer belonged in class 3, who reported that nicotine plays a small part in health risks (n = 1277; 30%), and class 4, who perceived nicotine as not cancer causing (n = 308; 7%). Latent class membership was correlated with sociodemographics, peer smoking, and past 30-day tobacco use. Classes 1 and 2 had similar NSUS scores and classes 3 and 4 had similar NSEV and TSEV scores. Differences in the perceptions of nicotine and tobacco-related harms can be partially explained by clustering of underlying nicotine beliefs. These classes of beliefs are correlated with sociodemographic predictors of smoking. These findings may help to identify specific beliefs or groups to be targeted by public education efforts on nicotine. The current study supports that underlying nicotine beliefs are associated with perceived harms of specific nicotine and tobacco products (relative to cigarettes), with greater false beliefs about nicotine correlated with greater perceived susceptibility to nicotine addiction. Two important inferences emerge from this study: first, that education to address nicotine beliefs may also reframe perceptions of the harms of nicotine and tobacco products; and second, that this type of education may differentially impact perceptions of the harms of nicotine products (e.g., nicotine replacement therapy and e-cigarettes) and tobacco products (e.g., cigars, smokeless, and hookah).


Ascorbic acid mitigates the myocardial injury after cardiac arrest and electrical shock.
To examine the effects of ascorbic acid (AA) administrated during cardiopulmonary resuscitation (CPR) on the myocardial injury in a rat model of ventricular fibrillation (VF) and electrical shock (ES). VF was induced in male Wistar rats and left untreated for 5 min, followed by 1 min of CPR, and then one ES of 5 J. At the start of CPR, animals received either intravenous administration of AA (100 mg/kg) or Tempol (30 mg/kg), two antioxidants, or 0.9% saline (VF + ES group). After ES, animals were immediately killed. Myocardial lipoxidation was determined by malondialdehyde (MDA) assay. The histology and ultrastructural changes of myocardium were also evaluated. The mitochondrial permeability transition pore (mPTP) opening was measured based on the mitochondrial swelling rate. The complex activities and respiration of mitochondria were assessed, too. Increased myocardial injury and mitochondrial damage in the VF + ES group were noted. AA and Tempol alleviated such damages. Both AA and Tempol improved accelerated mitochondrial swelling; decreased complex activities and respiratory dysfunction occurred in the VF + ES group. The animals receiving AA and Tempol during CPR had better successful resuscitation rates and 72-h survival than the VF + ES group. Intravenous administration of AA and Tempol at the start of CPR may reduce lipid peroxidation and myocardial necrosis, diminish mitochondrial damage, facilitate resuscitation, and improve outcomes after VF + ES.


Vibrio mimicus are the reservoirs of the heat-stable enterotoxin gene (nag-st) among species of the genus Vibrio.
Using a 0.27 kb DNA probe specific for the heat-stable enterotoxin gene (nag-st) of Vibrio cholerae non-O1, 1109 strains representing 17 species of the genus Vibrio, isolated from clinical and environmental sources were examined. The nag-st gene was preponderantly associated with strains classified as V. mimicus; 16.8% of these strains hybridized. It was more frequent in the clinical isolates (22.6%) than in the environmental isolates (13.7%). The incidence of nag-st gene-positive strains of V. mimicus isolated from different countries was uniformly high and ranged between 8.7% (Bangladesh) and 57.1% (environmental strains from USA). The incidence of the nag-st gene was much lower among strains of V. cholerae non-O1 (3.6%). Probe-positive and-negative strains of V. mimicus and V. cholerae non-O1 were used to evaluate the performance of the conventional suckling mouse assay for detection of the NAG-ST enterotoxin. Of the 31 probe-positive strains, only five (16.1%) yielded a positive fluid accumulation ratio (FA ratio) when neat heated culture supernatant was used to perform the suckling mouse assay. All the 31 probe-positive strains gave a positive FA ratio when 20-fold concentrated and heated culture supernatants of the strains were used to perform the suckling mouse assay. The need to concentrate (by at least 20-fold) the culture supernatant of strains of V. mimicus and V. Cholerae non-O1 was identified as an important step to obtain consistent results when using the suckling mouse assay for detection of NAG-ST.


Effects of retinoid X receptor-selective ligands on proliferation of prostate cancer cells.
Management of prostate cancer that either is detectable by prostate specific antigen (PSA) measurements after curative intent or has spread outside of its capsule is a serious problem. Innovative, nontoxic approaches to the disease are required. One approach might be therapy with retinoids. Retinoid activities are mediated by two distinct families of transcription factors: the retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which can induce transcriptional activation through specific DNA sites or by inhibiting the transcription factor AP-1 that usually mediates cellular proliferative signals. The RARs require heterodimerization with RXRs. RXRs can form either heterodimers or homodimers; and the latter can bind to DNA response elements that are distinct from those bound by the RAR/RXR heterodimers. A series of novel synthetic retinoids that selectively interact with RXR/RXR homodimers or RAR/RXR heterodimers, or that selectively inhibit AP-1 activity without activating transcription were evaluated for their ability to inhibit clonal growth of three human prostate cancer cell lines (PC-3, DU-145, and LNCaP). Several notable findings were: 1) RXR-selective retinoids, such as SR11246, were able to inhibit the clonal growth of prostate cancer cells. In contrast, SR11246 had little effect on clonal growth of myeloid leukemic cells. 2) RAR-selective retinoids also inhibited clonal growth of prostate cancer cells. 3) The retinoid (SR11238) with potent anti-AP-1 activity had no effect on the clonal growth of prostate cancer cells. This study shows that both RXR- and RAR-selective retinoids are worthy of further study and may be candidates for future clinical trials in prostate cancer.


Strand separation establishes a sustained lock at the Tus-Ter replication fork barrier.
The bidirectional replication of a circular chromosome by many bacteria necessitates proper termination to avoid the head-on collision of the opposing replisomes. In Escherichia coli, replisome progression beyond the termination site is prevented by Tus proteins bound to asymmetric Ter sites. Structural evidence indicates that strand separation on the blocking (nonpermissive) side of Tus-Ter triggers roadblock formation, but biochemical evidence also suggests roles for protein-protein interactions. Here DNA unzipping experiments demonstrate that nonpermissively oriented Tus-Ter forms a tight lock in the absence of replicative proteins, whereas permissively oriented Tus-Ter allows nearly unhindered strand separation. Quantifying the lock strength reveals the existence of several intermediate lock states that are impacted by mutations in the lock domain but not by mutations in the DNA-binding domain. Lock formation is highly specific and exceeds reported in vivo efficiencies. We postulate that protein-protein interactions may actually hinder, rather than promote, proper lock formation.


Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice.
The evolution of brain infarcts during permanent occlusion of the middle cerebral artery (MCA) was studied in mice using multiparametric imaging techniques. Regional protein synthesis and the regional tissue content of ATP were measured on adjacent cryostat sections at increasing intervals after vascular occlusion ranging from 1 hour to 3 days. The observed changes were correlated with the expression of the mRNA of hsp70, c-fos, c-jun, and junB, as well as the distribution of DNA double-strand breaks visualized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL). One hour after MCA occlusion, the tissue volume with suppressed protein synthesis was distinctly larger than that in which ATP was depleted. With ongoing ischemia time, the ATP-depleted area gradually expanded and, within 1 day, merged with the region of suppressed protein synthesis. Expression of hsp70 mRNA occurred mainly in the penumbra (defined as the region of suppressed protein synthesis but preserved ATP), peaking at 3 hours after vascular occlusion. Expression of the immediate-early genes c-jun, c-fos, and junB increased both in the penumbra and the periinfarct normal tissue already at 1 hour after vascular occlusion, with slightly different regional and temporal patterns for each of these genes. DNA fragmentations were clearly confined to neurons; they appeared after 1 day in the infarct core (defined as the region of suppressed ATP) and never were detected in the penumbra. The late appearance of TUNEL after infarcts had reached their final size and the absence in the penumbra points against a major pathogenetic role of apoptosis. Permanent MCA occlusion in mice thus produces a gradually expanding infarct, the final size of which is heralded by the early inhibition of protein synthesis.


Immunohistochemical determination of the P15 protein expression in cutaneous squamous cell carcinoma.
The tumor suppressor gene p15(INK4b) is a cyclin-dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor-derived cell lines. The precise role of p15(INK4b) protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15(INK4b) gene. This study is a continuation of our previous study and aims to determine the possible role of p15(INK4b) protein expression in the genesis of cutaneous SCC. P15(INK4b) protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15(INK4b) was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15(INK4b) protein expression. The absence of p15(INK4b) expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15(INK4b) could possibly be involved in the pathogenesis of cutaneous SCC.