To act or not to act, that is the question? Barriers and facilitators of bystander intervention.
A promising line of inquiry in sexual violence prevention involves training potential bystanders to intervene in situations where there is risk for violence. Theories of bystander intervention often discuss barriers to helping behavior, but there has been little empirical inquiry into this question. We will present findings of a study of both barriers and facilitators of helping behavior in the context of sexual violence among first-semester college students. Two hundred and forty-two first year college students completed surveys during their first year of college. Measures included assessment of bystander behavior, perceived barriers to helping, as well as a variety of other variables identified in the literature as key correlates of helping. Quantitative and qualitative analyses were used to (a) describe barriers and facilitators of helping, (b) examine the relationship between barriers and self-reports of helping, and (c) model individual differences in helping behavior. In quantitative analyses, barriers, as assessed in this study, were better predictors of helping behavior directed at strangers than helping of friends. Results suggested that open-ended responses about the facilitators and barriers to helping for sexual violence map well onto social-psychological models of bystander behavior, and that greater prosocial tendencies, an intrapersonal variable, increase actual helping behavior. A more specific understanding of what promotes and hinders helping can be used to enhance prevention education efforts focused on increasing helpful bystander actions.


WebOnCOLL: medical collaboration in regional healthcare networks.
This paper presents WebOnCOLL, a web-based medical collaboration environment, which has been designed in the context of the regional healthcare network of Crete. WebOnCOLL employs the infrastructure of regional healthcare networks to provide integrated services for virtual workspaces, annotations, e-mail, and on-line collaboration. Virtual workspaces support collaborative concepts like personal web pages, bulletin boards, discussion lists, shared workspaces, and medical case folders. Annotations provide a natural way for people to interact with multimedia content, while e-mail is one of the most popular forms of communication today. On-line collaboration satisfies the need for a more direct form of communication.


Thyroid hormones and coronary artery calcification in euthyroid men and women.
Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone. In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification.


Sensitivity to the parvovirus minute virus of mice as a probe for azatyrosine-mediated phenotypic reversion of spontaneously transformed cells.
It has been shown that cells transformed by known oncogenes could be reverted to an untransformed phenotype by the antibiotic Azatyrosine (AzTyr). In order to evaluate the reverting effect of AzTyr on five spontaneously transformed FR3T3C cell clones, we performed three assays: soft agar clonability, tumorigenicity in nude mice and susceptibility to killing by the parvovirus minute virus of mice (MVMp). In contrast to untransformed cells, transformed or tumorigenic cells are permissive for the lytic replication of MVMp and are killed. Our results demonstrate that although the cell populations that emerged after AzTyr treatment of FR3T3C clones had different phenotypes (two were untransformed and two had an altered transformed phenotype), they all behaved like untransformed cells, as judged from their resistance to MVMp infection. Our results demonstrate that susceptibility to MVMp is a valuable way to monitor the reversion.


Serum endotrophin, a type VI collagen cleavage product, is associated with increased mortality in chronic kidney disease.
Patients with chronic kidney disease (CKD) are at increased risk of end-stage renal disease (ESRD) and early mortality. The underlying pathophysiological processes are not entirely understood but may include dysregulation of extracellular matrix formation with accelerated systemic and renal fibrosis. We assessed the relationship between endotrophin (ETP), a marker of collagen type VI formation, and adverse outcomes in a cohort of patients with CKD. We measured serum ETP levels in 500 patients from the Renal Impairment in Secondary Care (RIISC) study, a prospective observational study of patients with high-risk CKD. Patients were followed up until death or progression to ESRD. Cox regression analysis was used to assess the relationship between ETP and risk of adverse outcomes. During a median follow-up time of 37 months, 104 participants progressed to ESRD and 66 died. ETP level was significantly associated with progression to ESRD (HR 1.79 [95% CI 1.59-2.02] per 10 ng/mL increase; HR 11.05 [4.98-24.52] for highest vs lowest quartile; both P<0.0001). ETP level was also significantly associated with mortality (HR 1.60 [1.35-1.89] per 10 ng/mL increase; HR 12.14 [4.26-34.54] for highest vs lowest quartile; both P<0.0001). After adjustment for confounding variables, ETP was no longer significantly associated with progression to ESRD but remained independently associated with mortality (HR 1.51 [1.07-2.12] per 10 ng/mL increase, P = 0.019). Serum ETP level is independently associated with mortality in CKD. This study provides the basis for further exploratory work to establish whether collagen type VI formation is mechanistically involved in the increased mortality risk associated with CKD.


The metabolism of four sulphonamides in cows.
1. The metabolism of sulphanilamide, sulphadimidine (4,6-dimethyl-2-sulphanilamidopyrimidine), sulphamethoxazole (5-methyl-3-sulphanilamidoisoxazole) and sulphadoxine (5,6-dimethoxy-4-sulphanilamidopyrimidine) given by intravenous injection has been examined in cows. 2. The sulphonamides were present mainly as unchanged drugs in blood samples collected 2h after administration. 3. The sulphonamides were excreted in the milk partly as unchanged drugs and partly as conjugated metabolites whereas only small amounts were excreted as the N(4)-acetyl derivatives. 4. The unchanged drug and the N(4)-acetyl derivative were the major constituents in urine samples after administration of sulphanilamide, sulphamethoxazole and sulphadoxine. 5. Besides the unchanged drug, the N(4)-acetyl derivative and the conjugated metabolites, three further metabolites of sulphadimidine were isolated from urine samples and identified. They were 5-hydroxy-4,6-dimethyl-2-sulphanilamidopyrimidine, 4-hydroxymethyl-6-methyl-2-sulphanilamidopyrimidine and sulphaguanidine.


Decreased expression of protooncogenes c-fos, c-myc, and c-jun following polyamine depletion in IEC-6 cells.
Direct exposure of small intestinal mucosal cells to luminal polyamines stimulates proliferation. This study tests the hypothesis that the protooncogenes c-fos, c-myc, c-jun, and junB are involved in the mechanism by which polyamines modulate mucosal growth. Studies were conducted in the IEC-6 cell line, derived from rat small intestinal crypt cells. Cells were grown in Dulbecco's minimal essential medium containing 5% dialyzed fetal bovine serum (dFBS) in the presence of absence of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, which is the rate-limiting enzyme for polyamine synthesis. Cellular polyamine levels, cell growth, and relative abundance of c-fos, c-myc, c-jun, and junB mRNAs, were measured at 1, 2, 4, 6, 8, and 12 days after initial plating. The intracellular polyamines, spermidine and spermine, and their precursor, putrescine, in DFMO-treated cells decreased significantly at 2 days and remained depleted thereafter. Although DFMO profoundly decreased growth and final cell number, both control and DFMO-treated cells entered a plateau phase by 6 days. In control cells, c-myc and c-jun mRNA levels significantly increased on days 4-6 and then returned to a basal level of expression, which was maintained thereafter. c-fos mRNA in quiescent cells after 24 h serum deprivation was significantly stimulated by 5% dFBS, although a steady-state level of c-fos mRNA was undetectable in control cells. Treatment with DFMO not only prevented increased expression of c-myc and c-jun protooncogenes at 4 days, but also significantly reduced steady-state levels of c-myc and c-jun mRNA between 6 and 12 days.(ABSTRACT TRUNCATED AT 250 WORDS)


Sf29 gene of Spodoptera frugiperda multiple nucleopolyhedrovirus is a viral factor that determines the number of virions in occlusion bodies.
The genome of Spodoptera frugiperda multiple nucleopolyhedrovirus (NPV) was inserted into a bacmid (Sfbac) and used to produce a mutant lacking open reading frame 29 (Sf29null). Sf29null bacmid DNA was able to generate an infection in S. frugiperda. Approximately six times less DNA was present in occlusion bodies (OBs) produced by the Sf29null bacmid in comparison to viruses containing this gene. This reduction in DNA content was consistent with fewer virus particles being packaged within Sf29null bacmid OBs, as determined by fractionation of dissolved polyhedra and comparison of occlusion-derived virus (ODV) infectivity in cell culture. DNA from Sfbac, Sf29null, or Sf29null-repair, in which the gene deletion had been repaired, were equally infectious when used to transfect S. frugiperda. All three viruses produced similar numbers of OBs, although those from Sf29null were 10-fold less infectious than viruses with the gene. Insects infected with Sf29null bacmid died approximately 24 h later than positive controls, consistent with the reduced virus particle content of Sf29null OBs. Transcripts from Sf29 were detected in infected insects 12 h prior to those from the polyhedrin gene. Homologs to Sf29 were present in other group II NPVs, and similar sequences were present in entomopoxviruses. Analysis of the Sf29 predicted protein sequence revealed signal peptide and transmembrane domains, but the presence of 12 potential N-glycosylation sites suggest that it is not an ODV envelope protein. Other motifs, including zinc-binding and threonine-rich regions, suggest degradation and adhesion functions. We conclude that Sf29 is a viral factor that determines the number of ODVs occluded in each OB.


Paratuberculosis infection of nonruminant wildlife in Scotland.
Recent reports of natural paratuberculosis (or Johne's disease) in rabbits, foxes, and stoats has focused debate on the presence and importance of wildlife reservoirs in the epidemiology of this disease. This paper describes an extensive study investigating 18 nonruminant wildlife species for evidence of paratuberculosis. Using both culture and histopathological analysis, fox, stoat, weasel, crow, rook, jackdaw, rat, wood mouse, hare, and badger were found to harbor Mycobacterium avium subsp. paratuberculosis, the causative organism of paratuberculosis, suggesting that the epidemiology of this disease is more complex than previously realized.


Angioedema and Fatty Acids.
Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently has specific therapeutic options, angioedema is sometimes intractable with current treatments, especially histamine-mediated angioedema, suggesting that some other mediators might contribute to the development of angioedema. Fatty acids are an essential fuel and cell component, and act as a mediator in physiological and pathological human diseases. Recent updates of studies revealed that these fatty acids are involved in vascular permeability and vasodilation, in addition to bradykinin and histamine-mediated reactions. This review summarizes each fatty acid's function and the specific receptor signaling responses in blood vessels, and focuses on the possible pathogenetic role of fatty acids in angioedema.


RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation.
In Drosophila melanogaster, the male-specific lethal (MSL) complex plays a key role in dosage compensation by stimulating expression of male X-chromosome genes. It consists of MSL proteins and two long noncoding RNAs, roX1 and roX2, that are required for spreading of the complex on the chromosome and are redundant in the sense that loss of either does not affect male viability. However, despite rapid evolution, both roX species are present in diverse Drosophilidae species, raising doubts about their full functional redundancy. Thus, we have investigated consequences of deleting roX1 and/or roX2 to probe their specific roles and redundancies in D. melanogaster. We have created a new mutant allele of roX2 and show that roX1 and roX2 have partly separable functions in dosage compensation. In larvae, roX1 is the most abundant variant and the only variant present in the MSL complex when the complex is transmitted (physically associated with the X-chromosome) in mitosis. Loss of roX1 results in reduced expression of the genes on the X-chromosome, while loss of roX2 leads to MSL-independent upregulation of genes with male-biased testis-specific transcription. In roX1 roX2 mutant, gene expression is strongly reduced in a manner that is not related to proximity to high-affinity sites. Our results suggest that high tolerance of mis-expression of the X-chromosome has evolved. We propose that this may be a common property of sex-chromosomes, that dosage compensation is a stochastic process and its precision for each individual gene is regulated by the density of high-affinity sites in the locus.


Prevalence and prognosis of chronic obstructive pulmonary disease among 8167 Middle Eastern patients with acute coronary syndrome.
The purpose of this study was to report the prevalence and the significance of clinically recognized chronic obstructive pulmonary disease (COPD) during acute coronary syndrome (ACS). COPD in patients with ACS is associated with worse outcome. Data were derived from a prospective, multicenter, multinational study of 8167 consecutive patients hospitalized with ACS from February to June 2007 in 6 Middle Eastern countries. Data were analyzed according to the presence or absence of COPD. Demographic, management, and in-hospital outcomes were compared. The prevalence of COPD was 5.3%. When compared with non-COPD patients, COPD patients were older and more likely to have diabetes, hypertension, and dyslipidemia. Atypical presentations were more common in COPD patients (P = 0.001). COPD patients were less likely to be treated with thrombolytic therapy (P = 0.001), beta-blockers (P = 0.001), and glycoprotein IIb/IIIa inhibitors, and more likely to receive angiotensin-converting enzyme (ACE) inhibitors. Although there was no difference in in-hospital mortality between the 2 groups, patients with COPD were more likely to have heart failure (P = 0.001). Despite the fact that COPD patients with ST-segment elevation myocardial infarction were less likely to receive thrombolytic therapy, they suffered more bleeding complications (2.8% vs 1%, P = 0.04), resulting in prolonged hospitalization. COPD was not an independent predictor of increased in-hospital mortality. In this large cohort of patients with ACS, the prevalence of COPD was 5.3%. Atypical presentation is common among COPD patients, and this may result in delayed therapy. ACS in COPD patients was associated with higher risk of heart failure and major bleeding complications without increased risk of in-hospital mortality.


Ribavirin inhibits mast cell mediator release.
Ribavirin (1-beta-D-ribofuranosyl-1,2-4-triazole-3-carboxamide) is a promising antiviral agent as well as a structural analog of guanosine. Although at different concentrations it has been reported to induce either immunosuppression or immune stimulation, its effects upon immediate hypersensitivity reactions are largely unknown. Because purine metabolism appears to be important in mast cell secretion, the effects of ribavirin on mouse bone marrow-derived mast cell functions were investigated. When ribavirin was added to mast cells at the time of stimulation with A23187 or specific antigen, no effect on the release of beta-hexosaminidase, a preformed mediator, was evident. However, mast cells cultured in 1 to 20 microM ribavirin for 1 to 7 days exhibited dose- and time-dependent inhibitions of stimulated beta-hexosaminidase and leukotriene C4 releases without altering mast cell mediator content. This inhibition occurred even when ribavirin had no effect on cell growth. A concomitant decrease in antigen-challenged mast cell intracellular Ca concentration was also observed after ribavirin treatment. Chronic ribavirin exposure in vitro inhibits mast cell secretory processes stimulated by both immunoglobulin E- and nonimmunoglobulin E-related signals. Its precise mechanism of action and any potential efficacy as an antiallergic agent remain to be elucidated.


Glutamine modulates sepsis-induced changes to intestinal intraepithelial γδT lymphocyte expression in mice.
This study investigated the effect of glutamine (GLN) on intestinal intraepithelial lymphocyte (IEL) γδT-cell cytokines and immune regulatory factor gene expressions in a mouse model of polymicrobial sepsis. Mice were randomly assigned to a normal group, a sepsis with saline (SS) group, or a sepsis with GLN (SG) group. All mice were fed a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The SS group was injected with saline, and the SG group was given 0.75 g GLN/kg body weight once via a tail vein 1 h after CLP. Septic mice were killed 12 h after CLP, and IEL γδT cells of the animals were isolated for further analysis. Results showed that compared with normal mice, sepsis resulted in lower IEL γδT-cell percentage and higher messenger RNA expressions of interferon γ, tumor necrosis factor α, interleukin 4 (IL-4), IL-13, IL-17, retinoid acid receptor-related orphan receptor γt, and complement 5a receptor by IEL γδT cells. These immunomodulatory mediator genes exhibited decreases, whereas IL-7 receptor expression increased in IEL γδT cells in septic mice with GLN administration. Annexin V/7-amino-actinomycin D stain revealed significantly lower rates of apoptosis, and IEL γδT-cell percentage was higher in the SG group. The histological findings also showed that damage to intestinal epithelial cells was less severe in the SG group. These results indicated that a single dose of GLN administered as treatment after the initiation of sepsis prevented apoptosis of IEL γδT cells and downregulated γδT cell-expressed inflammatory mediators that may consequently ameliorate the severity of sepsis-induced intestinal epithelial injury.


Ten cases with 46,XX testicular disorder of sex development: single center experience.
To present clinical, chromosomal and hormonal features of ten cases with SRY-positive 46,XX testicular disorder of sex development who were admitted to our infertility clinic. Records of the cases who were admitted to our infertility clinic between 2004 and 2015 were investigated. Ten 46,XX testicular disorder of sex development cases were detected. Clinical, hormonal and chromosomal assessments were analized. Mean age at diagnosis was 30.4, mean body height was 166.9cm. Hormonal data indicated that the patients had a higher FSH, LH levels, lower TT level and normal E2, PRL levels. Karyotype analysis of all patients confirmed 46,XX karyotype, and FISH analysis showed that SRY gene was positive and translocated to Xp. The AZFa, AZFb and AZFc regions were absent in 8 cases. In one case AZFb and AZFc incomplete deletion and normal AZFa region was present. In the other one all AZF regions were present. Gonadal development disorders such as SRY-positive 46,XX testicular disorder of sex development can be diagnosed in infertility clinics during infertility workup. Although these cases had no chance of bearing a child, they should be protected from negative effects of testosterone deficiency by replacement therapies.


[Extracorporeal shockwave lithotripsy on the Sonolith-3000 apparatus].
The authors observed 812 patients with nephrolithiasis who underwent 876 sessions of shock-wave lithotripsy on Sonolith-3000 lithotriptor supplied with an ultrasonic system of the stone localization. The size of nephroliths ranged from 0.7 to 4.2 cm. Large-size nephroliths required repeated sessions and pretreatment establishment of the stent. The procedure proceeded without anesthesia. Subsequent renal colic was reported in 126 (15.5%), an exacerbation of pyelonephritis in 45 (5.5%), subcapsular hematoma in 4 (0.5%) of the patients. 790 patients showed clinical response (97.3%), with a complete destruction of the stone in 446 (54.9%) and partial one in 344 (42.4%) cases. 27 subjects were treated in outpatient setting. According to the authors, lithotripsy is contraindicated in urinary tract obstruction below the stone, renal failure, chronic pyelonephritis in the active phase of inflammation, marked impairment of cardiac rhythm.


The construction and use of nomograms for cerebral blood flow calculation using a 133Xe inhalation technique.
Measurement of cerebral blood flow (CBF) using a 133Xe inhalation technique requires monitoring the clearance rate of the radioisotope from the head using externally situated detectors and also from arterial blood using a detector to monitor the expired air activity. The end-tidal concentration function is assumed to be proportional to the arterial concentration function and this has to be deconvoluted from the clearance functions obtained from the head to enable CBF to be calculated. A digital computer is generally considered to be essential for this. In this paper a procedure using three-dimensional nomograms is derived and tested. It is shown that results obtained using the nomograms do not differ significantly from results obtained using a full deconvolution procedure, and so it is not essential to use a computer to calculate CBF by the inhalation technique.


Circadian rhythm of peripheral perfusion during 10-day hypoxic confinement and bed rest.
Future planetary habitats will be hypobaric and hypoxic to reduce the risk of decompression sickness during preparation for extra-vehicular activities. This study was part of a research programme investigating the combined effects of hypoxia and microgravity on physiological systems. We tested the hypothesis that hypoxia-induced peripheral vasoconstriction persists at night and is aggravated by bed rest. Since sleep onset has been causally linked to nocturnal vasodilatation, we reasoned that hypoxia-induced vasoconstriction at night may explain sleep disturbances at altitude. Peripheral perfusion alterations as a consequence of bed rest may explain poor sleep quality reported during sojourns on the International Space Station. Eleven males underwent three 10-day interventions in a randomised order: (1) hypoxic ambulatory confinement; (2) hypoxic bed rest; (3) normoxic bed rest. During each intervention we conducted 22-h monitoring of peripheral perfusion, as reflected by the skin temperature gradient. Measurements were conducted on the first (D 1) and last day (D 10) of each intervention. All interventions resulted in a decrease in daytime toe perfusion from D 1 to D 10. There was no difference in the magnitude of the daytime reduction in toe perfusion between the three interventions. There was a significant vasodilatation of the toes in all interventions by 11 pm. The fingertips remained well perfused throughout. Daytime vasoconstriction induced by hypoxia and/or bed rest is abolished at night, lending further support to the theory that changes in peripheral skin temperature may be functionally linked to sleep onset.


Simulations of the role of water in the protein-folding mechanism.
There are many unresolved questions regarding the role of water in protein folding. Does water merely induce hydrophobic forces, or does the discrete nature of water play a structural role in folding? Are the nonadditive aspects of water important in determining the folding mechanism? To help to address these questions, we have performed simulations of the folding of a model protein (BBA5) in explicit solvent. Starting 10,000 independent trajectories from a fully unfolded conformation, we have observed numerous folding events, making this work a comprehensive study of the kinetics of protein folding starting from the unfolded state and reaching the folded state and with an explicit solvation model and experimentally validated rates. Indeed, both the raw TIP3P folding rate (4.5 +/- 2.5 micros) and the diffusion-constant corrected rate (7.5 +/- 4.2 micros) are in strong agreement with the experimentally observed rate of 7.5 +/- 3.5 micros. To address the role of water in folding, the mechanism is compared with that predicted from implicit solvation simulations. An examination of solvent density near hydrophobic groups during folding suggests that in the case of BBA5, there are water-induced effects not captured by implicit solvation models, including signs of a "concurrent mechanism" of core collapse and desolvation.


The memory T cell response to West Nile virus in symptomatic humans following natural infection is not influenced by age and is dominated by a restricted set of CD8+ T cell epitopes.
We examined the West Nile virus (WNV)-specific T cell response in a cohort of 52 patients with symptomatic WNV infections, including neuroinvasive and non-invasive disease. Although all virus proteins were shown to contain T cell epitopes, certain proteins, such as E, were more commonly targeted by the T cell response. Most patients exhibited reactivity toward 3-4 individual WNV peptides; however, several patients exhibited reactivity toward >10 individual peptides. The relative hierarchy of T cell reactivities in all patients showed a fixed pattern that was sustained throughout the 12-mo period of the current study. Surprisingly, we did not observe any relationship between age and either the breadth or magnitude of the T cell response following infection. We also did not observe a relationship between disease severity and either the breadth or magnitude of the T cell response. The T cell epitopes were distributed in a non-random fashion across the viral polyprotein and a limited number of epitopes appeared to dominate the CD8(+) T cell response within our cohort. These data provide important new insight into the T cell response against WNV in humans.


Estimation of the Uncertainties Related to the Measurement of the Size and Quantities of Individual Silver Nanoparticles in Confectionery.
E174 (silver) is a food additive that may contain silver nanoparticles (AgNP). Validated methods are needed to size and quantify these particles in a regulatory context. However, no validations have yet been performed with food additives or real samples containing food additives requiring a sample preparation step prior to analysis. A single-particle inductively coupled plasma mass spectrometry (spICP-MS) method was developed and validated for sizing and quantifying the fraction of AgNP in E174 and in products containing E174, and associated uncertainties related to sample preparation, analysis and data interpretation were unraveled. The expanded measurement uncertainty for AgNP sizing was calculated to be 16% in E174-containing food products and increased up to 23% in E174 itself. The E174 food additives showed a large silver background concentration combined with a relatively low number of nanoparticles, making data interpretation more challenging than in the products. The standard uncertainties related to sample preparation, analysis, and challenging data interpretation were respectively 4.7%, 6.5%, and 6.0% for triplicate performances. For a single replicate sample, the uncertainty related to sample preparation increased to 6.8%. The expanded measurement uncertainty related to the concentration determination was 25-45% in these complex samples, without a clear distinction between additives and products. Overall, the validation parameters obtained for spICP-MS seem to be fit for the purpose of characterizing AgNP in E174 or E174-containing products.


Leukoencephalopathy with calcifications and cysts (LCC): 5 cases and literature review.
Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive cerebral angiomatous-like microangiopathy characterized by diffuse and asymmetric white-matter lesions associated with multiple calcifications and cysts. The disease is caused by SNORD118 mutations. The entire clinical spectrum of LCC is not yet fully determined. To define the clinical spectrum of LCC, we analyzed data from recently diagnosed cases and from the litterature. Both clinical and imaging features from our five LCC cases harboring compound heterozygous SNORD118 mutations were presented and all cases reported in the litterature reviewed. Ninety-two LCC cases including our five patients were identified. Consanguinity was rare (4%), and 97% of cases were symptomatic. Mean age of first clinical manifestations was 16.1±16.1 years (range 1 month-71 years) and was earlier in men (10.3±14.3 years) than in women (20.2±22.8 years) (P=0.02). The main inaugural symptoms were seizures (36%; mean age at onset: 5.2±9.5 years) and progressive neurological symptoms including ataxia, dystonia and spasticity (26%; 27.8±23.6 years). Intracranial hypertension was less frequently observed (14%), mostly in adults (mean age 31.5±13.2 years). Ischemic or hemorrhagic strokes were inaugural symptoms in two adults (2%). During follow-up, most patients developed progressive extrapyramidal, cerebellar and pyramidal signs (83%), cognitive decline (56%), seizures (37%), intracranial hypertension (30%) or stroke (2%). In LCC, the clinical spectrum is largely heterogeneous and the course of the disease appears highly variable in contrast to other hereditary cerebral small vessel diseases.


Envoplakin, a novel precursor of the cornified envelope that has homology to desmoplakin.
The cornified envelope is a layer of transglutaminase cross-linked protein that is deposited under the plasma membrane of keratinocytes in the outermost layers of the epidermis. We present the sequence of one of the cornified envelope precursors, a protein with an apparent molecular mass of 210 kD. The 210-kD protein is translated from a 6.5-kb mRNA that is transcribed from a single copy gene. The mRNA was upregulated during suspension-induced terminal differentiation of cultured human keratinocytes. Like other envelope precursors, the 210-kD protein became insoluble in SDS and beta-mercaptoethanol on activation of transglutaminases in cultured keratinocytes. The protein was expressed in keratinizing and nonkeratinizing stratified squamous epithelia, but not in simple epithelia or nonepithelial cells. Immunofluorescence staining showed that in epidermal keratinocytes, both in vivo and in culture, the protein was upregulated during terminal differentiation and partially colocalized with desmosomal proteins. Immunogold EM confirmed the colocalization of the 210-kD protein and desmoplakin at desmosomes and on keratin filaments throughout the differentiated layers of the epidermis. Sequence analysis showed that the 210-kD protein is homologous to the keratin-binding proteins desmoplakin, bullous pemphigoid antigen 1, and plectin. These data suggest that the 210-kD protein may link the cornified envelope to desmosomes and keratin filaments. We propose that the 210-kD protein be named "envoplakin."


N-acetylcysteine in the treatment of steroid-resistant acute graft-versus-host-disease: preliminary results. Gruppo Italiano Trapianto di Midollo Osseo (GITMO).
Acute graft-versus-host disease (GVHD) results from reactivity of donor immunocompetent cells versus host tissues. Its pathogenesis involves co-stimulatory molecules, cytokines, free radicals, and oxidative stress products. N-Acetylcysteine (NAC) is an antioxidant that inhibits the B7-1/CD28 expression in vitro, and it may contrabalance the effects of free radicals and oxidative stress; it has been tested in eight patients with steroid-resistant acute GVHD. NAC was given at the dose of 150 mg/kg bolus intravenously, followed by 50 mg/kg intravenous continuous infusion over 3 weeks or less up, to clinical GVHD resolution. In four patients, flow cytometric analysis of co-stimulatory molecules was performed on peripheral mononuclear cells before and after NAC therapy. We achieved prompt response in six patients: four had complete response, two partial response. Two patients died of acute GVHD, and four of intercurrent disease. We noticed significant decrease in CD80, CD25, and CD8+ cells after NAC therapy. NAC therapy is feasible; it may give response in steroid-resistant acute GVHD. More extensive studies are needed to confirm these data.


Negative self-efficacy and goal effects revisited.
The authors address the verification of the functional properties of self-efficacy beliefs and document how self-efficacy beliefs operate in concert with goal systems within a sociocognitive theory of self-regulation in contrast to the focus of control theory on discrepancy reduction. Social cognitive theory posits proactive discrepancy production by adoption of goal challenges working in concert with reactive discrepancy reduction in realizing them. Converging evidence from diverse methodological and analytic strategies verifies that perceived self-efficacy and personal goals enhance motivation and performance attainments. The large body of evidence, as evaluated by 9 meta-analyses for the effect sizes of self-efficacy beliefs and by the vast body of research on goal setting, contradicts findings (J. B. Vancouver, C. M. Thompson, & A. A. Williams, 2001; J. B. Vancouver, C. M. Thompson, E. C. Tischner, & D. J. Putka 2002) that belief in one's capabilities and personal goals is self-debilitating.


Overdiagnosis and overtreatment of breast cancer.
Breast cancer is the most common cancer in women. Through greater awareness, mammographic screening, and aggressive biopsy of calcifications, the proportion of low-grade, early stage cancers and in situ lesions among all breast cancers has risen substantially. The introduction of molecular testing has increased the recognition of lower risk subtypes, and less aggressive treatments are more commonly recommended for these subtypes. Mammographically detected breast cancers are much more likely to have low-risk biology than symptomatic tumors found between screenings (interval cancers) or that present as clinical masses. Recognizing the lower risk associated with these lesions and the ability to confirm the risk with molecular tests should safely enable the use of less aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or what have been called stage I cancers, in and of themselves are not life-threatening. In situ lesions have been treated in a manner similar to that of invasive cancer, but there is little evidence to support that this practice has improved mortality. It is also being recognized that DCIS lesions are heterogeneous, and a substantial proportion of them may in fact be precursors of more indolent invasive cancers. Increasing evidence suggests that these lesions are being overtreated. The introduction of molecular tests should be able to help usher in a change in approach to these lesions. Reclassifying these lesions as part of the spectrum of high-risk lesions enables the use of a prevention approach. Learning from the experience with active surveillance in prostate cancer should empower the introduction of new approaches, with a focus on preventing invasive cancer, especially given that there are effective, United States Food and Drug Administration (FDA)-approved breast cancer preventive interventions.


Nonactin biosynthesis: unexpected patterns of label incorporation from 4,6-dioxoheptanoate show evidence of a degradation pathway for levulinate through propionate in Streptomyces griseus.
The polyketide nonactin, a polyketide possessing antitumor and antibacterial activity, is produced by an unusual biosynthesis pathway in Streptomyces griseus that uses both enantiomers of the nonactin precursor, nonactic acid. Despite many studies with labeled precursors, much of the biosynthesis pathway remains unconfirmed, particularly the identity of the last achiral intermediate in the pathway, which is believed to be 4,6-diketoheptanoyl-CoA. We set out to confirm the latter hypothesis with feeding studies employing [4,5-(13)C(2)]-, [5,6-(13)C(2)]-, and [6,7-(13)C(2)]-4,6-diketoheptanoate thioester derivatives. In each case the isotopic label was incorporated efficiently into nonactin; however, at positions inconsistent with the currently accepted biosynthesis pathway. To resolve the discrepancy, we conducted additional feeding studies with a [3,4-(13)C(2)]levulinate thioester derivative and again observed efficient label incorporation. The latter result was intriguing, as levulinate is not an obvious precursor to nonactin. Levulinate, however, is known to be efficiently degraded into propionate even though the pathway for the conversion is not known. On the basis of both our levulinate and diketoheptanoate isotope incorporation data we can now postulate a pathway from levulinate to propionate that can also account for the conversion of 4,6-diketoheptanoate into levulinate in S. griseus.


[A new blackfly species Cnetha itelmenica sp. n. (Diptera: Simuliidae) from Kamchatka].
The description of a new species Cnetha itehnenica Chubareva et Yankovsky, sp. n. is given. Only 6 species of the genus Cnetha have the simple lobes of rectal organ (C. fontia, C. garniensis, C. gejgelensis, C. costata, C. subcostata and C. karzhantavica). These species distribute only in Southern Europe, Northern Africa and Transcaucasia, excluding C. subcostata distributed in NE China, Korea and Japan. C. itelmenica differs from C. fontia and C. garniensis in having a deep inlet of the head capsula, from C. costata, C. subco- stata and C. karzhantavica in the different number of hook rows in the posterior circlet (86-90 versus 96-100 in C. gejgelensis and C. costata, 68 in C. karzhantavica). The new species differs from other Siberian and Far Eastern species of the genus (C. cornifera, C. paracornifera, C. patrushevae, C. pugetensis, C. shutovae) in having simple lobes of the rectal organ, from C. gejgelensis in having another pattern of setae arrangement on the submentum (by 1 line, versus 2 lines in C. gejgelensis), from C. shutovae, C. pugetensis and C. patrushevae in the different number of hook rows in the posterior circlet (86-90 versus 60-62 in C. shutovae and 62-66 in remains), and from C. pugetense and C. patrushevae in the number of primary fans (36-40 versus 41-52). C. itelmenica differs from C. vernum (as base standard), as well as from other studied species of the genus, in having a species-specific disk pattern, three wide homozygous inversions in IS, IL, IIIL, and a little homozygous inversion in IIS. It differs from C. fontia, C. garniensis, C. costata and C. zakhariensis in the absence of chromocenter and presence of additional heterochromatic B-chromosomes.


Eosinophilic cystitis.
Authors report on two rare cases of eosinophilic cystitis, giving a review of the etiologic assumptions and pathogenetic, pathologic aspects of the disease, based on the available literary data. The course of the disease can be either acute or subacute, and is most often chronic. Relapse and progression can interchange in irregular manner, attention is therefore called to the importance of follow-ups. Resection deep into the intact--also containing muscle fibre--as well as histologic examination are considered essential as the only method of differentiation, giving precise diagnosis in the present two cases, too.


Nuclear and structural dynamics during the establishment of a specialized effector-secreting cell by Magnaporthe oryzae in living rice cells.
To cause an economically important blast disease on rice, the filamentous fungus Magnaporthe oryzae forms a specialized infection structure, called an appressorium, to penetrate host cells. Once inside host cells, the fungus produces a filamentous primary hypha that differentiates into multicellular bulbous invasive hyphae (IH), which are surrounded by a host-derived membrane. These hyphae secrete cytoplasmic effectors that enter host cells presumably via the biotrophic interfacial complex (BIC). The first IH cell, also known as the side BIC-associated cell, is a specialized effector-secreting cell essential for a successful infection. This study aims to determine cellular processes that lead to the development of this effector-secreting first IH cell inside susceptible rice cells. Using live-cell confocal imaging, we determined a series of cellular events by which the appressorium gives rise to the first IH cell in live rice cells. The filamentous primary hypha extended from the appressorium and underwent asymmetric swelling at its apex. The single nucleus in the appressorium divided, and then one nucleus migrated into the swollen apex. Septation occurred in the filamentous region of the primary hypha, establishing the first IH cell. The tip BIC that was initially associated with the primary hypha became the side BIC on the swollen apex prior to nuclear division in the appressorium. The average distance between the early side BIC and the nearest nucleus in the appressorium was estimated to be more than 32 μm. These results suggest an unknown mechanism by which effectors that are expressed in the appressorium are transported through the primary hypha for their secretion into the distantly located BIC. When M. oryzae was inoculated on heat-killed rice cells, penetration proceeded as normal, but there was no differentiation of a bulbous IH cell, suggesting its specialization for establishment of biotrophic infection. Our studies reveal cellular dynamics associated with the development of the effector-secreting first IH cell. Our data raise new mechanistic questions concerning hyphal differentiation in response to host environmental cues and effector trafficking from the appressorium to the BIC.


Soft-tissue tumor with abnormal amianthoid collagen fibers.
Electron microscopic examination of a solitary soft-tissue tumor from the face demonstrated large areas with abnormal amianthoid collagen fibers in the neoplasm. The lesion was classified as a benign neoplasm of myofibroblasts and tentatively named a myofibroblastoma. The significance of the amianthoid collagen fibers is unknown. Normal native collagen fibers were found in some parts of the neoplasm.


Lennart Heimer: concepts of the ventral striatum and extended amygdala.
Dr. Lennart Heimer, the famous neuroanatomist of Swedish descent, died last year but left a legacy that will impact the neurosciences and potentially psychosurgery for years to come. He developed an anatomical technique for demonstrating the terminal boutons that helped to delineate basal forebrain anatomy. During these studies, he realized the relationship of basal forebrain structures to the limbic system, thus initiating the concept of the ventral striatum and parallel basal ganglia circuitry. Heimer excelled as a teacher as well and honed his brain dissection technique to one of the most effective tools for understanding neuroanatomy. His legendary sessions with neurosurgical residents resulted in his recognition as one of the world's leading fiber tract dissectors. His gentle, engaging manner has been documented in several media formats.


Multiplanar breast kinematics during different exercise modalities.
Multiplanar breast movement reduction is crucial to increasing physical activity participation amongst women. To date, research has focused on breast movement during running, but until breast movement is understood during different exercise modalities, the breast support requirements for specific activities are unknown. To understand breast support requirements during different exercise modalities, this study aimed to determine multiplanar breast kinematics during running, jumping and agility tasks. Sixteen 32D participants had markers attached to their right nipple and torso. Relative multiplanar breast displacement was calculated during bare-breasted treadmill running (10 kph), maximum countermovement jumping and an agility t-test. Exercise modality influenced the magnitude and direction of breast displacement, velocity and acceleration (p < .05). Jumping produced greater vertical breast displacement (.09 m) but less mediolateral breast displacement (.05 m) than running or the agility task, but agility tasks produced the highest multiplanar breast velocities and acceleration. Breast movement during jumping was predominantly in the vertical direction, whereas the agility task produced a greater percentage of mediolateral breast acceleration than running or jumping. Exercise modality impacted upon the magnitude and distribution of bare-breasted multiplanar breast kinematics in this homogenous 32D cohort. Therefore, to reduce breast movement in women of a 32D bra size, manufacturers may wish to design sport-specific products, with greater vertical support for exercise modalities incorporating jumping and greater mediolateral support for agility tasks.


Urinary bisphenol A levels in young men: association with reproductive hormones and semen quality.
Few human studies have examined bisphenol A (BPA) exposure in relation to semen quality and reproductive hormones in men, and results are divergent. We examined associations between urinary BPA concentration and reproductive hormones, as well as semen quality, in young men from the general population. Our study population consisted of 308 young men from the general population. Urinary BPA concentration was measured by isotope dilution TurboFlow-liquid chromatography-tandem mass spectrometry. We used multiple linear regression analysis to estimate associations between BPA concentration and reproductive hormones and semen quality, adjusting for confounding factors. We found that 98% of the men had detectable urinary levels of BPA. Median (5th-95th percentiles) BPA concentration was 3.25 ng/mL (0.59-14.89 ng/mL). Men with BPA concentrations above the lowest quartile had higher concentrations of serum testosterone, luteinizing hormone (LH), estradiol, and free testosterone compared with the lowest quartile (p trend ≤ 0.02). Men in the highest quartile of BPA excretion had on average 18% higher total testosterone (95% CI: 8, 28%), 22% higher LH (95% CI: 6, 39%), and 13% higher estradiol (95% CI: 4, 24%) compared with lowest quartile. Men in the highest quartile of BPA also had significantly lower percentage progressive motile spermatozoa compared with men in the lowest quartile (-6.7 percentage points, 95% CI: -11.76, -1.63). BPA was not associated with other semen parameters. Adjusting for dietary patterns did not influence the results. The pattern of associations between BPA and reproductive hormones could indicate an antiandrogenic or antiestrogenic effect, or both, of BPA on the hypothalamic-pituitary-gonadal hormone feedback system, possibly through a competitive inhibition at the receptor level. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.


Disclosure of HIV Status to Infected Children in South India: Perspectives of Caregivers.
This study was designed to examine the rates of HIV serostatus disclosure in a sample of HIV-infected children in the state of Karnataka in South India, their reactions to learning their HIV-positive status and the reasons for and barriers to disclosure from the point of view of their caregivers. We enrolled 233 HIV-infected children, aged 5-18 years and their caregivers between July 2011 and February 2013 at HIV clinics in three tertiary care centers. Caregiver interviews included information about demographic characteristics, medical history, type of disclosure to the child and other related factors, including disclosure barriers. Three quarters (n = 185) of the caregivers reported that there had been no disclosure to the child, 15.4% (n = 38) reported partial disclosure (e.g. telling the child he or she had a 'chronic illness') and only 9.7% (n = 24) reported full disclosure, at a mean age of 10.9 (SD: 2.5) years. Caregivers, who planned to disclose in the future, stated on average that 16 years would be the right age. Those who favored a later disclosure reported that they feared strong negative emotional reactions from the child (p = 0.03) and social isolation (p < 0.001) following disclosure. These results show that that the level of full disclosure is low among South Indian youth living with HIV, and that when disclosure occurs, it is most likely to be partial. The majority of children who learned their status had been informed by a health-care provider, possibly reflecting the difficulty for a caregiver of having this conversation. The caregivers reported multiple disadvantages of disclosure, mostly because of fears of stigma and discrimination. Despite some evidence from the literature that disclosure can have positive effects on a child's health, it is thus clear that we need to develop, implement and evaluate community-based stigma reduction programs to reduce the social barriers to disclosure.


Glyceride-cysteine lipoproteins and secretion by Gram-positive bacteria.
The membrane penicillinases of Bacillus licheniformis and Bacillus cereus are lipoproteins with N-terminal glyceride thioether modification identical to that of the Escherichia coli outer membrane lipoprotein. They are readily labeled with [3H]palmitate present during exponential growth. At the same time, a few other proteins in each organism become labeled and can be detected by fluorography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total membrane proteins. We distinguish these proteins from the O-acyl proteolipids by demonstrating the formation of glyceryl cysteine sulfone after performic acid oxidation and hydrolysis of the protein. By this criterion, B. licheniformis and B. cereus contain sets of lipoproteins larger in average molecular weight than that of E. coli. Members of the sets probably are under a variety of physiological controls, as indicated by widely differing relative labeling intensity in different media. The set in B. licheniformis shares with membrane penicillinase a sensitivity to release from protoplasts by mild trypsin treatment, which suggests similar orientation on the outside of the membrane. At least one protein is the membrane-bound partner of an extracellular hydrophilic protein, the pair being related as membrane and exopenicillinases are. We propose that the lipoproteins of gram-positive organisms are the functional equivalent of periplasmic proteins in E. coli and other gram-negative bacteria, prevented from release by anchorage to the membrane rather than by a selectively impermeable outer membrane.


Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis.
Mitochondria are dynamic organelles that play a key role in energy conversion. Optimal mitochondrial function is ensured by a quality-control system tightly coupled to fusion and fission. In this connection, mitofusin 2 (Mfn2) participates in mitochondrial fusion and undergoes repression in muscle from obese or type 2 diabetic patients. Here, we provide in vivo evidence that Mfn2 plays an essential role in metabolic homeostasis. Liver-specific ablation of Mfn2 in mice led to numerous metabolic abnormalities, characterized by glucose intolerance and enhanced hepatic gluconeogenesis. Mfn2 deficiency impaired insulin signaling in liver and muscle. Furthermore, Mfn2 deficiency was associated with endoplasmic reticulum stress, enhanced hydrogen peroxide concentration, altered reactive oxygen species handling, and active JNK. Chemical chaperones or the antioxidant N-acetylcysteine ameliorated glucose tolerance and insulin signaling in liver-specific Mfn2 KO mice. This study provides an important description of a unique unexpected role of Mfn2 coordinating mitochondria and endoplasmic reticulum function, leading to modulation of insulin signaling and glucose homeostasis in vivo.


The walking school bus and children's physical activity: a pilot cluster randomized controlled trial.
To evaluate the impact of a "walking school bus" program on children's rates of active commuting to school and physical activity. We conducted a pilot cluster randomized controlled trial among 4th-graders from 8 schools in Houston, Texas (N = 149). Random allocation to treatment or control conditions was at the school level. Study staff walked with children to and from school up to 5 days/week. Outcomes were measured the week before (time 1) and during weeks 4 and 5 of the intervention (time 2). The main outcome was the weekly rate of active commuting, and a secondary outcome was moderate-to-vigorous physical activity. Covariates included sociodemographics, distance from home to school, neighborhood safety, child BMI z score, parent self-efficacy/outcome expectations, and child self-efficacy for active commuting. A mixed-model repeated measures regression accounted for clustering by school, and stepwise procedures with backward elimination of nonsignificant covariates were used to identify significant predictors. Intervention children increased active commuting (mean ± SD) from 23.8% ± 9.2% (time 1) to 54% ± 9.2% (time 2), whereas control subjects decreased from 40.2% ± 8.9% (time 1) to 32.6% ± 8.9% (time 2) (P < .0001). Intervention children increased their minutes of daily moderate-to-vigorous physical activity from 46.6 ± 4.5 (time 1) to 48.8 ± 4.5 (time 2), whereas control children decreased from 46.1 ± 4.3 (time 1) to 41.3 ± 4.3 (time 2) (P = .029). The program improved children's active commuting to school and daily moderate-to-vigorous physical activity.


Beauty Beware: Associations between Perceptions of Harm and Safer Hair-Product-Purchasing Behaviors in a Cross-Sectional Study of Adults Affiliated with a University in the Northeast.
(1) Background: Widespread personal care product (PCP) use can expose individuals to endocrine-disrupting chemicals (EDCs) associated with adverse health outcomes. This study investigated the association between harm perceptions and hair-product-purchasing behaviors in adults enrolled in a cross-sectional study. (2) Methods: Respondents rated their agreement with five PCP-related harm statements using a five-point Likert scale. Multivariable-adjusted logistic regression models were used to examine the associations between harm perceptions with hair-product-purchasing behaviors and hair product use (i.e., number of products used). (3) Results: Among 567 respondents (non-Hispanic White, 54.9%; non-Hispanic Black, 9.5%; Hispanic/Latinx, 10.1%; Asian American/Pacific Islander, 20.1%; and multiracial/other, 5.5%), stronger harm perceptions around PCP use were associated with potentially "safer" hair-product-purchasing behaviors. Respondents who strongly agreed that consumers should be concerned about the health effects of PCPs had more than fourfold increased odds of always/usually using healthy product apps (OR 4.10, 95% CI: 2.04-8.26); reading ingredient labels (OR 4.53, 95% CI: 2.99-6.87); and looking for natural, non-toxic, or eco-friendly product labels (OR 4.53, 95% CI: 2.99-6.88) when buying hair products. (4) Conclusions: Promoting environmental health literacy and raising awareness of potential PCP use-related harms might encourage healthier hair product use behaviors.


Adaptation of Saccharomyces cerevisiae to saline stress through laboratory evolution.
Most laboratory evolution studies that characterize evolutionary adaptation genomically focus on genetically simple traits that can be altered by one or few mutations. Such traits are important, but they are few compared with complex, polygenic traits influenced by many genes. We know much less about complex traits, and about the changes that occur in the genome and in gene expression during their evolutionary adaptation. Salt stress tolerance is such a trait. It is especially attractive for evolutionary studies, because the physiological response to salt stress is well-characterized on the molecular and transcriptome level. This provides a unique opportunity to compare evolutionary adaptation and physiological adaptation to salt stress. The yeast Saccharomyces cerevisiae is a good model system to study salt stress tolerance, because it contains several highly conserved pathways that mediate the salt stress response. We evolved three replicate lines of yeast under continuous salt (NaCl) stress for 300 generations. All three lines evolved faster growth rate in high salt conditions than their ancestor. In these lines, we studied gene expression changes through microarray analysis and genetic changes through next generation population sequencing. We found two principal kinds of gene expression changes, changes in basal expression (82 genes) and changes in regulation (62 genes). The genes that change their expression involve several well-known physiological stress-response genes, including CTT1, MSN4 and HLR1. Next generation sequencing revealed only one high-frequency single-nucleotide change, in the gene MOT2, that caused increased fitness when introduced into the ancestral strain. Analysis of DNA content per cell revealed ploidy increases in all the three lines. Our observations suggest that evolutionary adaptation of yeast to salt stress is associated with genome size increase and modest expression changes in several genes.


An intervention to improve the inhalatory technique of children and adolescents with asthma.
most patients use their inhalers incorrectly and recent asthma management clinical guidelines recommend demonstrating skills and correcting performance at each asthma follow-up visit. However, this statement is poorly evidence-based and few intervention studies have assessed quantitatively the effectiveness of this recommendation. from a total of 3,076 children and adolescents with asthma attending an outpatient clinic, a random, representative sample of 255 was obtained and assessed at baseline with a standardised questionnaire regarding their skills when using one of three inhaler devices: pressurised direct aerosol (PDA), dry powder (DP) and aerosol pressurised in expanded camera (APEC). Structured sessions of correct use and handling of inhalers were offered and a new assessment was undertaken after an average of 10.5 months (SD 4.5). only 142 asthmatics maintained the same inhaler device during the study period. An increase of correct manoeuvres was observed for all three devices, and the relative risk and 95% confidence interval (RR and 95% CI) of incorrect post-intervention use was 0.23 (95% CI 0.10-0.56) for PDA, 0.59 (95% CI 0.38-0.92) for DP, and 0.54 (95% CI 0.32-0.90) for APEC. A multivariate analysis indicates that this improvement was observed irrespective of gender and age interval, and that it was even better when parents cooperated with medical and nursing staff. a dramatic improvement in correct manoeuvres with any of three inhaler devices after active performance training was observed. This easy, highly effective, low cost (in terms of time and personnel) intervention should be routinely implemented in any control visit of asthmatics, leading to a better management of asthma.


Biochemical profiles of rat primary cultured hepatocytes following treatment with rotenone, FCCP, or (+)-usnic acid.
The metabolomic profiles of rat primary hepatocytes following treatment with rotenone, FCCP, or (+)-usnic acid were determined using liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-mass spectrometry. Significant and similar changes in the levels of 283 biochemical metabolites were associated with the three treatments compared with solvent control samples. Overall, the three treatments generated similar global biochemical profiles, with some minor differences associated with rotenone treatment. All three treatments resulted in a shift in energy metabolism as demonstrated by decreased glycogen stores and glycolysis. A reduced antioxidant response was detected in cells following all treatments. In addition, bile acid biosynthesis decreased as a potential consequence of increased oxidative stress by all three treatments. Conversely, rotenone treatment induced a number of changes after 1 hr, which were not detected in FCCP- or (+)-usnic acid-treated samples; these changes were not sustained over time and included increased NAD+ salvage and lysine degradation. In conclusion, these biochemical profiles could provide new insights into the mechanism(s) of mitochondrial toxicity.


Conophylline and betacellulin-delta4: an effective combination of differentiation factors for pancreatic beta cells.
Conophylline and betacellulin-delta4 reproduce differentiation-inducing activity of activin A and betacellulin, respectively. We examined the effect of conophylline and betacellulin-delta4 on beta cell differentiation. In AR42J cells, conophylline and betacellulin-delta4 converted them into insulin-producing cells. Cells treated with conophylline and betacellulin-delta4 continued to grow after differentiation. Thus, cell number and insulin content were much greater compared to cells treated with activin A and betacellulin. Furthermore, cells treated with conophylline and betacellulin-delta4 secreted insulin in response to glucose. Likewise, conophylline and betacellulin-delta4 converted pancreatic ductal cells into insulin-producing cells. Insulin content, cell number and glucose-evoked insulin secretion were significantly greater than those in cells treated with activin A and betacellulin. Transplantation of pseudoislets prepared using ductal cells treated with conophylline and betacellulin-delta4 was able to reduce effectively the plasma glucose concentration in streptozotocin-treated nude mice. Conophylline and betacellulin-delta4 are effective in inducing differentiation of beta cells from progenitors.


Social style and resilience of macaques' networks, a theoretical investigation.
Group-living animals rely on efficient transmission of information for optimal exploitation of their habitat. How efficient and resilient a network is depend on its structure, which is a consequence of the social interactions of the individuals that comprise the network. In macaques, network structure differs according to dominance style. Networks of intolerant species are more modular, more centralized, and less connected than those of tolerant ones. Given these structural differences, networks of intolerant species are potentially more vulnerable to fragmentation and decreased information transmission when central individuals disappear. Here we studied network resilience and efficiency in artificial societies of macaques. The networks were produced with an individual-based model that has been shown to reproduce the structural features of networks of tolerant and intolerant macaques. To study network resilience, we deleted either central individuals or individuals at random and studied the effects of these deletions on network cohesiveness and efficiency. The deletion of central individuals had more negative effects than random deletions from the networks of both tolerant and intolerant artificial societies. Central individuals thus appeared to aid in the maintenance of network cohesiveness and efficiency. Further, the networks of both intolerant and tolerant societies appeared to be robust to the loss of individuals, as network fragmentation was never observed. Our results suggest that despite differences in network structure, networks of tolerant and intolerant macaques may be equally resilient.


Thrombin clotting activity measurement and standardization with lyophilized plasma.
Thrombin-induced clotting times were inversely proportional to fibrinogen concentrations within the range of 98 to 2900 nmol/L; these reciprocal velocity measurements had units of seconds per clot. By analogy with classical enzyme kinetics, we defined rectangular hyperbolic parameters where Km(clot) ranged from 0.14 to 0.56 mumol/L and kclot from 0.020 to 0.075 clot per second. Specificity ratios (kclot/Km(clot)) showed that reconstituted lyophilized human plasma is as good, if not better, a source of clottable fibrinogen as the purified protein itself. These ratios also showed that the presence of greater than 98% of the autoproteolytic forms (beta- and gamma-thrombins) of the human enzyme did not interfere with clotting activity attributable to alpha-thrombin. Contrary to simple enzyme kinetics, velocities (reciprocal clotting times) were rectangular hyperbolically related to clotting activities. Clotting times between 5 and 90 s/clot correlated (r greater than 0.999) with reciprocal alpha-thrombin concentrations, permitting standardization with lyophilized plasma (1000 U.S. "NIH" thrombin-clotting units/L corresponded to approximately 21 s/clot with these plasma). Lyophilized plasma re-examined after 15 months displayed no change in clottability.


Childhood intussusception: a literature review.
Postlicensure data has identified a causal link between rotavirus vaccines and intussusception in some settings. As rotavirus vaccines are introduced globally, monitoring intussusception will be crucial for ensuring safety of the vaccine programs. To obtain updated information on background rates and clinical management of intussusception, we reviewed studies of intussusception in children <18 years of age published since 2002. We assessed the incidence of intussusception by month of life among children <1 year of age, seasonality, method of diagnosis, treatment, and case-fatality. We identified 82 studies from North America, Asia, Europe, Oceania, Africa, Eastern Mediterranean, and Central & South America that reported a total of 44,454 intussusception events. The mean incidence of intussusception was 74 per 100,000 (range: 9-328) among children <1 year of age, with peak incidence among infants 5-7 months of age. No seasonal patterns were observed. A radiographic modality was used to diagnose intussusception in over 95% of the cases in all regions except Africa where clinical findings or surgery were used in 65% of the cases. Surgical rates were substantially higher in Africa (77%) and Central and South America (86%) compared to other regions (13-29%). Case-fatality also was higher in Africa (9%) compared to other regions (<1%). The primary limitation of this review relates to the heterogeneity in intussusception surveillance across different regions. This review of the intussusception literature from the past decade provides pertinent information that should facilitate implementation of intussusception surveillance for monitoring the postlicensure safety of rotavirus vaccines.


Ziprasidone and the corrected QT interval: a comprehensive summary of clinical data.
Prolongation of the corrected QT interval (QTc) is understood to be a predictor of risk for ventricular arrhythmia; consequently, data on QTc effects of drugs are used by regulatory bodies to evaluate potential safety risks. Clinical pharmacology studies in adults receiving oral ziprasidone demonstrated a dose-dependent mean increase (4.5-19.5 milliseconds [ms]) in QTc over the range of 40-160 mg/d with a small incremental increase (22.5 ms) at 320 mg/d. In a comparative study of ziprasidone versus five antipsychotics, the mean QTc increase at steady state maximum concentration (C(max)) for ziprasidone was 15.9 ms. Accordingly, the effects of ziprasidone on QTc were studied in phase II-IV randomized controlled trials (RCTs). The objective of this study was to provide clinicians and clinical researchers with a comprehensive analysis of QTc changes associated with ziprasidone based on data from Pfizer-sponsored phase II-IV RCTs in schizophrenia or bipolar disorder patients, safety reports and post-marketing surveillance. The following analyses of data were conducted to obtain a comprehensive summary of QTc data on ziprasidone: (i) post hoc analyses (using primarily descriptive statistics) of pooled QTc data (Fridericia correction) from more than 40 phase II-IV adult ziprasidone RCTs organized according to the following subgroups: all monotherapy studies in schizophrenia and bipolar disorder, all intramuscular (IM) studies, adjunctive studies in bipolar disorder and fixed-dose oral studies; (ii) post hoc analyses from 36 phase II-IV adult ziprasidone RCTs exploring the relationship between QTc change from baseline and baseline QTc in adults; (iii) post hoc analyses from phase II-IV adult ziprasidone RCTs modelling QTc change as a function of ziprasidone concentration in both adult (17 studies) and paediatric (5 studies) subjects; (iv) cardiac adverse event (AE) reports from all phase II-IV adult ziprasidone RCTs in schizophrenia; (v) a large simple trial entitled Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) in 18 154 subjects with schizophrenia (the only previously reported results included here); and (vi) cardiac-related AEs presented in a ziprasidone post-marketing surveillance report created in 2007. A total of 4306 adults received ziprasidone in placebo- and active-comparator phase II-IV RCTs and had evaluable QTc data. One subject reached a QTc ≥480 ms; 33 (0.8%) had a QTc ≥450 ms. QTc prolongation ≥30 ms was observed in 389 subjects (9.0%); ≥60 ms in 30 (0.7%); and ≥75 ms in 12 (0.3%). In the placebo-controlled studies, mean change in QTc from baseline to end of study was 3.6 (± 20.8) ms in the ziprasidone group; the corresponding QTc change in the pooled placebo group was -0.3 (± 20.6) ms. Data from IM studies, and bipolar studies in which ziprasidone was used adjunctively with lithium, valproate or lamotrigine, demonstrated similar QTc effects. A scatter-plot of QTc prolongation against baseline QTc showed QTc prolongation ≥60 ms exclusively in adult subjects with a baseline QTc ≤400 ms. The final concentration-response analysis model, comprising 2966 data points from 1040 subjects, estimates an increase in QTc of 6 ms for each 100 ng/mL increase in ziprasidone concentration. The large simple trial (ZODIAC) failed to show that ziprasidone is associated with an elevated risk of non-suicidal mortality relative to olanzapine in real-world use. Post-marketing data over a 5-year period did not show a signal of increased cardiac AEs. These analyses provide the first comprehensive summary of QTc changes associated with ziprasidone based on Pfizer-sponsored phase II-IV RCTs, safety reports and post-marketing surveillance. The results of the analyses of pooled data from phase II-IV RCTs in adults demonstrate a modest mean increase in QTc, infrequent QTc prolongation ≥60 ms (<1.0%) and rare observation of QTc ≥480 ms. These data are consistent with results from ziprasidone clinical pharmacology studies, safety reports and post-marketing surveillance. Taken together, they provide the most comprehensive evidence published to date that ziprasidone appears to be safe when used as indicated in patients with schizophrenia or bipolar disorder.


Exposure to positive peer sentiment about nicotine replacement therapy in an online smoking cessation community is associated with NRT use.
Little is known about the influence of online peer interactions on health behavior change. This study examined the relationship between exposure to peer sentiment about nicotine replacement therapy (NRT) in an online social network for smoking cessation and NRT use. Participants were 3297 current smokers who enrolled in an Internet smoking cessation program, participated in a randomized trial, and completed a 3-month follow-up. Half received free NRT as part of the trial. Automated text classification identified 27,038 posts about NRT that one or more participants were exposed to in the social network. Sentiment towards NRT was rated on Amazon Mechanical Turk. Participants' exposure to peer sentiment about NRT was determined by analysis of clickstream data. Modified Poisson regression examined self-reported use of NRT at 3-months as a function of exposure to NRT sentiment, controlling for study arm and post exposure. One in five participants (19.3%, n = 639) were exposed to any NRT-related posts (mean exposure = 6.5 ± 14.7, mean sentiment = 5.4 ± 0.8). The association between sentiment exposure and NRT use varied by receipt of free NRT. Greater exposure to positive NRT sentiment was associated with an increased likelihood of NRT use among participants who did not receive free NRT (adjusted rate ratio 1.22, 95% CI 1.01, 1.47; p = .043), whereas no such relationship was observed among participants who did receive free NRT (p = .48). Exposure to positive sentiment about NRT was associated with increased NRT use when smokers obtained it on their own. Highlighting user-generated content containing positive NRT sentiment may increase NRT use among treatment-seeking smokers.


Extracellular Electron Transfer via Outer Membrane Cytochromes in a Methanotrophic Bacterium Methylococcus capsulatus (Bath).
Electron exchange reactions between microbial cells and solid materials, referred to as extracellular electron transfer (EET), have attracted attention in the fields of microbial physiology, microbial ecology, and biotechnology. Studies of model species of iron-reducing, or equivalently, current-generating bacteria such as Geobacter spp. and Shewanella spp. have revealed that redox-active proteins, especially outer membrane c-type cytochromes (OMCs), play a pivotal role in the EET process. Recent (meta)genomic analyses have revealed that diverse microorganisms that have not been demonstrated to have EET ability also harbor OMC-like proteins, indicating that EET via OMCs could be more widely preserved in microorganisms than originally thought. A methanotrophic bacterium Methylococcus capsulatus (Bath) was reported to harbor multiple OMC genes whose expression is elevated by Cu starvation. However, the physiological role of these genes is unknown. Therefore, in this study, we explored whether M. capsulatus (Bath) displays EET abilities via OMCs. In electrochemical analysis, M. capsulatus (Bath) generated anodic current only when electron donors such as formate were available, and could reduce insoluble iron oxides in the presence of electron donor compounds. Furthermore, the current-generating and iron-reducing activities of M. capsulatus (Bath) cells that were cultured in a Cu-deficient medium, which promotes high levels of OMC expression, were higher than those cultured in a Cu-supplemented medium. Anodic current production by the Cu-deficient cells was significantly suppressed by disruption of MCA0421, a highly expressed OMC gene, and by treatment with carbon monoxide (CO) gas (an inhibitor of c-type cytochromes). Our results provide evidence of EET in M. capsulatus (Bath) and demonstrate the pivotal role of OMCs in this process. This study raises the possibility that EET to solid compounds is a novel survival strategy of methanotrophic bacteria.


Effects of altering organ of Corti on cochlear distortion products f2 - f1 and 2f1 - f2.
1. Single cochlear nerve fiber recordings from unexposed chinchillas show spatial distributions of amplitude and phase of the distortion products f2 - f1 and 2f1 - f2 similar to those previously reported for the cat (35, 37, 42). 2. Damaging the organ of Corti in the region corresponding to the frequencies of a two-tone stimulus substantially reduces the amplitude of these distortion products at their characteristic places. 3. The distortion products 2f - f1 and 2f1 - f2 thus appear to be generated in the organ of Corti in the region of the primary-frequency places. 4. The neural responses suggest that the distortion products are propagated in the motion of the cochlear partition like externally applied stimulus tones at the distortion frequencies wih a similar spatial distribution of distortion product amplitude and phase. Models of the cochlea that assume nonlinear cochlear-partition dynamics can account for the similarity by demonstrating that distortion products generated by cochlear-partition nonlinearity can propagate apicalward in the motion of the cochlear partition. 5. Models of the cochlea using a linear-system model for cochlear partition motion, in cascade with a nonlinear transduction stage and a subsequent sharp filter, are inadequate to account for present observations, unless two currently implausible assumptions are made: a) stimulus tones near 4 kHz must propagate in normal cochleas at least as far apically as the 300-Hz place with sufficient amplitude to generate f2 - f1 there, and b) damage to the organ of Corti must interfere with this propagation of 4-kHz stimulus tones to the 300-Hz place. 6. Distortion generation in the cochlea is sensitive to delicate alterations of the organ of Corti. Short moderate-intensity exposures to sound can reversibly reduce the amplitudes of the distortion products f2 - f1 and 2f1 - f2 seen in responses from cochlear nerve fibers with characteristic frequencies (CF) near the distortion frequencies. Since such exposures do ot produce permanent structural changes visible under light microscopy, it seems most reasonable to believe that subtle changes in the organ of Corti (most likely in the hair cells themselves) in the region most responsive to f1 and f2 reduce the generation of mechanically present distortion products.


Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome.
Fetal alcohol syndrome (FAS) can result in cognitive dysfunction. Cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting-state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. Previous reports varied substantially regarding the exact nature of findings. The purpose of this study was to assess FC of cognition-related networks in young adults with FAS. Cross-sectional rs-fMRI study in participants with FAS (n = 39, age: 20.9 ± 3.4 years) and healthy participants without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on linear models comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks based on the Higher Criticism (HC) approach for detecting rare and weak effects in high-dimensional data. Finally, group differences in single connections were assessed using conventional multiple-comparison correction. In an additional exploratory analysis, dynamic FC states were assessed. Comparing FAS participants with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in attention-related network components. Findings also spanned across subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the conventional high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences of dynamic FC states. FC in cognition-related networks was altered in adults with FAS. Effects were widely distributed across networks, potentially reflecting the diversity of cognitive deficits in FAS. However, no altered single connections could be determined in the most detailed analysis level. Findings were pronounced in networks in line with attentional deficits previously reported.


Variability between nursing homes in prevalence of antipsychotic use in patients with dementia.
Antipsychotic drugs (APD) are widely prescribed for people with dementia residing in long term care facilities (LTCFs). Concern has been expressed that such prescribing is largely inappropriate. The objective of this study is to examine if differences in facility-level prevalence of APD use in a sample of LTCFs for patients with dementia can be explained by patient and facility-related characteristics. A point prevalence study was conducted using data from the VU University Resident Assessment Instrument (VURAI) database from nursing homes and residential care facilities in the Netherlands. Patients were selected who had a diagnosis of dementia. LTCF and patient characteristics were extracted from the VURAI; facility-level resident satisfaction surveys were provided by the National Institute for Public Health. In total, 20 LTCFs providing care for 1,090 patients with dementia were investigated. Overall, 31% of patients used an APD. In facilities with a high prevalence of APD use behavioral symptoms were present in 62% of their patients. In facilities with medium APD use behavioral problems remained frequent (57%), and in facilities with low prevalence of APD use 54% of the patients had behavioral symptoms. Facilities with a high prevalence of APD use were often large, situated in urban communities, and scored below average on staffing, personal care, and recreational activities. There was considerable variation between the participating LTCFs in the prevalence of APD use. Variability was related to LTCF characteristics and patient satisfaction. This indicates potential inappropriate prescribing because of differences in institutional prescribing culture.


Crop-to-wild gene flow and its fitness consequences for a wild fruit tree: Towards a comprehensive conservation strategy of the wild apple in Europe.
Crop-to-wild gene flow can reduce the fitness and genetic integrity of wild species. Malus sylvestris, the European crab-apple fruit tree in particular, is threatened by the disappearance of its habitat and by gene flow from its domesticated relative, Malus domestica. With the aims of evaluating threats for M. sylvestris and of formulating recommendations for its conservation, we studied here, using microsatellite markers and growth experiments: (i) hybridization rates in seeds and trees from a French forest and in seeds used for replanting crab apples in agrosystems and in forests, (ii) the impact of the level of M. domestica ancestry on individual tree fitness and (iii) pollen dispersal abilities in relation to crop-to-wild gene flow. We found substantial contemporary crop-to-wild gene flow in crab-apple tree populations and superior fitness of hybrids compared to wild seeds and seedlings. Using paternity analyses, we showed that pollen dispersal could occur up to 4 km and decreased with tree density. The seed network furnishing the wild apple reintroduction agroforestry programmes was found to suffer from poor genetic diversity, introgressions and species misidentification. Overall, our findings indicate supported threats for the European wild apple steering us to provide precise recommendations for its conservation.


Diagnostic Accuracy of Office Blood Pressure Measurement and Home Blood Pressure Monitoring for Hypertension Screening Among Adults: Results From the IDH Study.
Using high awake blood pressure (BP; ≥130/80 mm Hg) on ambulatory BP monitoring (ABPM) as a reference, the purpose of this study was to determine the accuracy of high office BP (≥130/80 mm Hg) at an initial visit and high confirmatory office BP (≥130/80 mm Hg), and separately, high home BP (≥130/80 mm Hg) among participants with high office BP (≥130/80 mm Hg) at an initial office visit. The accuracy of office BP measurements using the oscillometric method for detecting high BP on ABPM was determined among 379 participants with complete office BP and ABPM data in the IDH (Improving the Detection of Hypertension) study. For detecting high BP on ABPM, the accuracy of high confirmatory office BP using the oscillometric method and, separately, high home BP was also determined among the subgroup of 122 participants with high office BP at an initial visit and complete home BP monitoring data. High office BP had moderate sensitivity (0.61 [95% CI, 0.53-0.68]) and high specificity (0.85 [95% CI, 0.80-0.90]) for high awake BP. High confirmatory office BP and high home BP had moderate sensitivity (0.69 [95% CI, 0.59-0.79] and 0.79 [95% CI, 0.71-0.87], respectively) and low and moderate specificity (0.44 [95% CI, 0.27-0.61] and 0.72 [95% CI, 0.56-0.88], respectively). Many individuals with high BP on ABPM do not have high office BP. Confirmatory office BP and home blood pressure monitoring also had limited ability to identify individuals with high BP on ABPM.


Resonances in the cardiovascular system caused by rhythmical muscle tension.
Paced 0.1 Hz breathing causes high-amplitude HR oscillation, triggering resonance in the cardiovascular system (CVS). This oscillation is considered to be a primary therapeutic factor in HRV biofeedback treatments. This study examined whether rhythmical skeletal muscle tension (RSMT) can also cause 0.1 Hz resonance in the CVS, and compared oscillatory reactivity in CVS functions caused by RSMT and paced breathing (PB). Sixteen young healthy participants completed five tasks: baseline, three RSMT tasks at frequencies of 0.05, 0.1, and 0.2 Hz, and a 0.1 Hz PB task. ECG, respiration, finger pulse, and skin conductance data were collected. Results showed that 0.1 Hz RSMT as well as 0.1 Hz PB triggered resonance in the CVS and caused equivalent oscillations in all measured CVS functions, although in women, RSMT compared to PB caused lower HR oscillation. Clinical application of 0.1 Hz RSMT is discussed.


Response-repetition costs in choice-RT tasks: biased expectancies or response inhibition?
Repetition effects are often viewed as informative regarding the cognitive mechanisms of action control. One particular finding, namely costs for repeating the same response in subsequent trials, especially challenges theorizing. Costs for response repetitions have recently been reported in task-switch studies on task-switch trials (whereas benefits usually arise in task-repetition trials), but also in some choice-RT task studies. In three experiments, two of the most successful accounts for the response-repetition costs in choice-RT task studies and task switching were tested: an expectancy-based explanation, and an inhibition-based account. Using a choice-RT task introduced by Smith (1968) and manipulating the response-stimulus interval (RSI) and the categorizability of the stimuli, some specific predictions of the two accounts were tested. The results clearly revealed that expectancy-based explanations fail to account for the observed patterns of effects, whereas they are well in line with the predictions from the inhibition-based account. Finally, the results are further discussed with respect to alternative accounts from the field of task switching.


A monomorphic haplotype of chromosome Ia is associated with widespread success in clonal and nonclonal populations of Toxoplasma gondii.
Toxoplasma gondii is a common parasite of animals that also causes a zoonotic infection in humans. Previous studies have revealed a strongly clonal population structure that is shared between North America and Europe, while South American strains show greater genetic diversity and evidence of sexual recombination. The common inheritance of a monomorphic version of chromosome Ia (referred to as ChrIa*) among three clonal lineages from North America and Europe suggests that inheritance of this chromosome might underlie their recent clonal expansion. To further examine the diversity and distribution of ChrIa, we have analyzed additional strains with greater geographic diversity. Our findings reveal that the same haplotype of ChrIa* is found in the clonal lineages from North America and Europe and in older lineages in South America, where sexual recombination is more common. Although lineages from all three continents harbor the same conserved ChrIa* haplotype, strains from North America and Europe are genetically separate from those in South America, and these respective geographic regions show limited evidence of recent mixing. Genome-wide, array-based profiling of polymorphisms provided evidence for an ancestral flow from particular older southern lineages that gave rise to the clonal lineages now dominant in the north. Collectively, these data indicate that ChrIa* is widespread among nonclonal strains in South America and has more recently been associated with clonal expansion of specific lineages in North America and Europe. These findings have significant implications for the spread of genetic loci influencing transmission and virulence in pathogen populations. Understanding parasite population structure is important for evaluating the potential spread of pathogenicity determinants between different geographic regions. Examining the genetic makeup of different isolates of Toxoplasma gondii from around the world revealed that chromosome Ia is highly homogeneous among lineages that predominate on different continents and within genomes that were otherwise quite divergent. This pattern of recent shared ancestry is highly unusual and suggests that some gene(s) found on this chromosome imparts an unusual fitness advantage that has resulted in its recent spread. Although the basis for the conservation of this particularly homogeneous chromosome is unknown, it may have implications for the transmission of infection and spread of human disease.


[The profile of memory disturbance in early Lewy body dementia differs from that in Alzheimer's disease].
It may be difficult to distinguish Lewy body dementia (LBD) from Alzheimer's disease (AD) especially at an early stage. Clinical diagnostic criteria for LBD still lack sensitivity. We compared memory performance in early AD and LBD to identify features that may help to distinguish these two conditions. Patients with Mini Mental State scores equal or above 18 were consecutively selected retrospectively from the University Out-patient Memory Clinic database. Probable LBD and AD were respectively diagnosed according to the international consensus criteria and the NINCDS-ADRDA criteria. Short-term memory was assessed with the digit span subtest of the Wechsler Memory Scale and the Corsi block-tapping test. Long term verbal memory was assessed with a French version of the Grober and Buschke test. Long-term visual memory was tested with the recall of four geometric figures of the CERAD battery. There was no difference between the two groups in short-term or long-term visual memory. Except for the immediate and first free recalls, DCL patients performed significantly better than AD patients in all subtests of the Grober and Buschke test. The more striking differences were seen with the third total and delayed total recall. These results highlight the differences of memory impairment pattern in early LBD and AD. Episodic verbal memory is better in LBD patients who benefit more from cues, reflecting the subcortical component of the disease. Such neuropsychological data should be validated prospectively and further be part of the diagnostic criteria.


Synergic effect of salivary pH baselines and low pH intakes on the force relaxation of orthodontic latex elastics.
Latex elastics are still in common use due to their low cost and high flexibility to improve sagittal discrepancies or interdigitation of teeth. Mechanical properties of elastics are influenced by several environmental factors such as pH changes. This study evaluated similar latex elastics to define the influence of synergic effect of intermittent low pH and various baselines pH of saliva. Four groups of latex elastics (3-M Unitek, 3/16 inch) were tested (n = 15 in each group). Two groups of elastics were immersed in two tanks of artificial saliva with different pH levels of 7 and 5, and two groups were immersed in two tanks of artificial saliva with intermittent drop of pH to 4. The force was measured when the elastics were stretched to 25 mm. These measurements were taken in 0, 4, 8, 12, 24, 36, and 48 h for each group. Repeated measures analysis of variance (RMANOVA) and post-hoc Tukey's test were used to assess the findings. The level of significance was 0.05%. The interaction between pH and time analyzed with RMANOVA showed no significant differences (P > 0.05) except in 36 h (P = 0.014). The Tukey's analysis showed that each comparison between any two groups did not indicate significant differences (P > 0.05) except between Groups 1 and 3 and between Groups 2 and 3 (P < 0.05). No significant correlation was seen between fluctuation of pH and force degradation in latex elastic band except in 36 h.


Hybrid learning as alternative approach to improve Indonesian medical students' attitude towards clinical skills during COVID-19 pandemic.
Hybrid learning has been chosen as an alternative method in the conduction of clinical skill lectures during coronavirus disease 2019 (COVID-19) pandemic since students need to learn skills applied in emergency situations. This study aims to analyze students' attitudes between hybrid and online learning methods. A non-randomized study was conducted between hybrid group (HG) and online group (OG) on three courses (intravenous [IV]-line insertion, nasogastric tube [NGT] insertion, and neonatal resuscitation). We developed a preformed validated questionnaire to assess students' attitudes in five domains (willingness, understanding, capacity, self-efficacy, and intended behavior). The questionnaire was applied at the pre- and post-intervention. A total of 100 participants were included (n=49 in HG, n=51 in OG). Post-course attitudes were significantly higher in online (IV-line, p=0.000; NGT, p=0.000; resuscitation, p=0.000) and hybrid (IV-line, p=0.000; NGT, p=0.000; resuscitation, p=0.000) groups compared to their pre-course. There were no significant differences in post-course attitude between groups (IV-line, p=0.072; NGT, p=0.163; resuscitation, p=0.146). Normalized-gain scores of all subjects were higher in HG (IV-line, p=0.012; NGT, p=0.085; resuscitation, p=0.033). In conclusion, hybrid learning could be considered as a better alternative in clinical skill lectures to maximize students' attitudes, especially during COVID-19 pandemic.


[Perception of emotional intonation of noisy speech signal with different acoustic parameters by adults of different age and gender].
The listener-distinctive features of recognition of different emotional intonations (positive, negative and neutral) of male and female speakers in the presence or absence of background noise were studied in 49 adults aged 20-79 years. In all the listeners noise produced the most pronounced decrease in recognition accuracy for positive emotional intonation ("joy") as compared to other intonations, whereas it did not influence the recognition accuracy of "anger" in 65-79-year-old listeners. The higher emotion recognition rates of a noisy signal were observed for speech emotional intonations expressed by female speakers. Acoustic characteristics of noisy and clear speech signals underlying perception of speech emotional prosody were found for adult listeners of different age and gender.


Contextualizing Colossus: Codebreaking Technology and Institutional Capabilities.
The Bletchley Park codebreaking center sits close to the heart of Britain's collective sense of historical greatness. Historians view it as a highly successful but largely ad-hoc institutional response to novel cryptographic challenges, depicting both its reliance on elite mathematicians and a large labor force as ruptures with peacetime practice. In contrast, this article suggests that Bletchley Park's success relied on institutional capabilities established in the prewar British state. It focuses on the celebrated "Colossus" electronic codebreaking devices as one element of a highly successful institutional collaboration between Bletchley Park, where they were used, and the Post Office research station at Dollis Hill, where they were designed and built. Correcting previous accounts, this article shows that this partnership was sponsored at the highest levels of government and supported by managers on both sides.


[Ussuriĭsk military hospital celebrates 130th anniversary].
On the authority of the order issued by Military Department d.d. 13 September 1882 No 278 since 1 January 1883 in village Nikolskoe of Primorsk territory was established the local hospital with bed capacity--115 beds. In the following years this capacity was being increased. In 1914 hospital was renamed into Nikols-Ussuriysk military hospital. This hospital took part in treatment-and-evacuation supply of wounded and ill soldiers during wars and armed conflicts. In 1982 Nikols-Ussuriysk military hospital awarded the Red Star. Employees of this hospital prepared and defended 25 doctoral and candidate's dissertations. In 2010 hospital was joined 301st District military clinical hospital and became it's branch.