The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.
Myopia is a common ocular disorder, and progression of myopia in children is of increasing concern. Modern overnight orthokeratology (ortho-k) is effective for myopic reduction and has been claimed to be effective in slowing the progression of myopia (myopic control) in children, although scientific evidence for this has been lacking. This 2 year pilot study was conducted to determine whether ortho-k can effectively reduce and control myopia in children. We monitored the growth of axial length (AL) and vitreous chamber depth (VCD) in 35 children (7-12 years of age), undergoing ortho-k treatment and compared the rates of change with 35 children wearing single-vision spectacles from an earlier study (control). For the ortho-k subjects, we also determined the changes in corneal curvature and the relationships with changes of refractive errors, AL and VCD. The baseline spherical equivalent refractive errors (SER), the AL, and VCD of the ortho-k and control subjects were not statistically different. All the ortho-k subjects found post-ortho-k unaided vision acceptable in the daytime. The residual SER at the end of the study was -0.18 +/- 0.69 D (dioptre) and the reduction (less myopic) in SER was 2.09 +/- 1.34 D (all values are mean +/- SD). At the end of 24 months, the increases in AL were 0.29 +/- 0.27 mm and 0.54 +/- 0.27 mm for the ortho-k and control groups, respectively (unpaired t test; p = 0.012); the increases in VCD were 0.23 +/- 0.25 mm and 0.48 +/- 0.26 mm for the ortho-k and control groups, respectively (p = 0.005). There was significant initial corneal flattening in the ortho-k group but no significant relationships were found between changes in corneal power and changes in AL and VCD. Ortho-k can have both a corrective and preventive/control effect in childhood myopia. However, there are substantial variations in changes in eye length among children and there is no way to predict the effect for individual subjects.


The impact of antihypertensive drug therapy on endotoxemia in elderly patients with chronic kidney disease.
Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT). We recruited 40 hypertensive nondiabetic patients (≥70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay. Mean age was 76 ± 5 years, estimated GFR (eGFR) (CKD group) was 40 ± 14 ml/min per 1.73 m(2), and achieved BP was 128/69 mmHg. Washout ET was 0.042 ± 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 ± 0.028 EU/ml; P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein. Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.


Employers' implicit attitudes about the competence of people who are blind.
The purpose of this study was to develop and validate an implicit measure of attitudes about the competence of people who are blind, to be used with employers, and to report on these implicit attitudes with a national sample of employers. A sample of 343 employers (i.e., business professionals responsible for making hiring decisions) participated in an online survey that involved answering questions and completing formal instruments, including explicit and implicit attitude measures about blind employees and a knowledge measure about how blind people can perform typical work tasks. The implicit measure was an Implicit Association Test-Blind/Visually Impaired (the IAT-BVI) that was developed for this study. Employers have strong negative implicit attitudes about the competence of people who are blind, with results indicating a very large IAT effect. These implicit attitudes were not associated with personal characteristics, exposure to people who are blind, or explicit attitudes. Implicit attitudes were significantly associated with knowledge about how blind people perform work tasks and, for employers who had hired a blind person, performance ratings of those employees. Employers' implicit attitudes about the competence of blind people were mostly unrelated to other measures, as expected, with the exception of knowledge and performance ratings of blind employees. These findings provide support for the validity of the IAT-BVI, and indicate the importance of rehabilitation professionals working with employers to provide education about how blind people perform work tasks as a potential avenue to improve employment opportunities for people who are blind. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


A comparison of the frequency of major affective disorder in Huntington's disease and Alzheimer's disease.
Matched groups of patients suffering from Huntington's disease and Alzheimer's disease were compared for psychiatric morbidity prior to the onset of dementia. The Huntington's disease group showed twice the incidence of major affective disorder. This finding suggests a specific relationship between Huntington's disease and major affective disorder rather than the latter being a non-specific prodromal feature of dementia.


Bright, coherent, ultrafast soft X-ray harmonics spanning the water window from a tabletop light source.
We demonstrate fully phase-matched high harmonic emission spanning the water window spectral region important for nano- and bioimaging and a breadth of materials and molecular dynamics studies. We also generate the broadest bright coherent bandwidth (≈300 eV) to date from any light source, small or large, that is consistent with a single subfemtosecond burst. The harmonic photon flux at 0.5 keV is 10³ higher than demonstrated previously. This work extends bright, spatially coherent, attosecond pulses into the soft x-ray region for the first time.


[In vitro RNA-synthesis on immobilized DNA-templates].
The possibility of RNA-synthesis by E. coli RNA-polymerase using denatured DNA-templates from mouse liver, immobilized on nitrocellulose filters was shown. The size of RNA molecules, synthesized on immobilized templates was estimated by electrophoresis in polyacrylamide gel. The length of the RNA molecules was found to be about 30 nucleotides. Data from alkaline hydrolisys and sedimentation in sucrose density gradient suggest that there is no connection between the DNA-primer and the RNA-product, therefore the DNA-primer is not necessary for the initiation of RNA-synthesis.


Are DXA/aBMD and QCT/FEA Stiffness and Strength Estimates Sensitive to Sex and Age?
Dual X-ray absorptiometry (DXA) measures areal bone mineral density (aBMD) by simplifying a complex 3D bone structure to a 2D projection and is not equally effective for explaining fracture strength in women and men. Unlike DXA, subject-specific quantitative computed tomography-based finite element analysis (QCT/FEA) estimates fracture strength using 3D bone mineral distribution and geometry. By using experimentally-measured femoral stiffness and strength from a one hundred sample cadaveric cohort that included variations in sex and age, we wanted to determine if QCT/FEA estimates were able to better predict the experimental variations than DXA/aBMD. For each femur, DXA/aBMD was assessed and a QCT/FEA model was developed to estimate femoral stiffness and strength. Then, the femur was mechanically tested to fracture in a sideways fall on the hip position to measure stiffness and strength. DXA/aBMD and QCT/FEA estimates were compared for their sensitivity to sex and age with multivariate statistical analyses. When comparing the measured data with DXA/aBMD predictions, both age and sex were significant (p ≤ 0.0398) for both femoral stiffness and strength. However, QCT/FEA predictions of stiffness and strength showed sex was insignificant (p ≥ 0.23). Age was still significant (p ≤ 0.0072). These results indicate that QCT/FEA, unlike DXA/aBMD, accounted for bone differences due to sex.


Enhanced in vivo antiviral activity against pseudorabies virus through transforming gallic acid into graphene quantum dots with stimulation of interferon-related immune responses.
With the urgent need for antiviral agents, antiviral materials with high biocompatibility and antiviral effects have attracted a lot of attention. In this study, gallic acid, a natural polyphenolic compound, was transformed into biocompatible graphene quantum dots (GAGQDs) which exhibit enhanced antiviral activity against pseudorabies virus (PRV). The as-prepared GAGQDs inhibit PRV proliferation with a 104-fold reduction in viral titers. Investigation of the antiviral mechanism revealed that GAGQDs inhibit the adsorption, invasion and replication of PRV infection. Treatment with GAGQDs regulates the expression levels of interferon-related antiviral proteins, including mitochondrial antiviral-signaling protein (MAVS), signal transducer and activator of transcription 1 (STAT1) and 2',5'-oligoadenylate synthetase 1 (OAS1), suggesting that GAGQDs can stimulate innate antiviral immune responses, resulting in enhanced antiviral effects. More importantly, GAGQD treatments alleviate clinical symptoms and reduce mortality in PRV-infected mice. Our results reveal the enhanced therapeutic effects of GAGQDs against PRV infection in vitro and in vivo, suggesting the potential of GAGQDs as a promising novel antiviral agent.


Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2 French Canadian families with high risk of breast cancer.
The Nijmegen Breakage Syndrome is a chromosomal instability disorder characterized by microcephaly, growth retardation, immunodeficiency, and increased frequency of cancers. Familial studies on relatives of these patients indicated that they also appear to be at increased risk of cancer. In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the NBN gene in our cohort of 97 high-risk non-BRCA1 and -BRCA2 breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. In silico programs (ESEfinder, NNSplice, Splice Site Finder and MatInspector) were used to assess the putative impact of the variants identified. The effect of the promoter variant was further studied by luciferase gene reporter assay in MCF-7, HEK293, HeLa and LNCaP cell lines. Twenty-four variants were identified in our case series and their frequency was further evaluated in healthy controls. The potentially deleterious p.Ile171Val variant was observed in one case only. The p.Arg215Trp variant, suggested to impair NBN binding to histone gamma-H2AX, was observed in one breast cancer case and one healthy control. A promoter variant c.-242-110delAGTA displayed a significant variation in frequency between both sample sets. Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines. Our analysis of NBN sequence variations indicated that potential NBN alterations are present, albeit at a low frequency, in our cohort of high-risk breast cancer cases. Further analyses will be needed to fully ascertain the exact impact of those variants on breast cancer susceptibility, in particular for variants located in NBN promoter region.


Five common cancers in Iran.
Iran as a developing nation is in epidemiological transition from communicable to non-communicable diseases. Although, cancer is the third cause of death in Iran, it;s mortality are on the rise during recent decades. This mini-review was carried out to provide a general viewpoint on common cancers incidence in Iran and to explain incidental differences that may help us to establish early detection programs and investigate population risk factors. A detailed PubMed, Scopus and Google scholar search were made from 2000 to 2009. The basic inclusion criteria were all relevant studies focused on cancer epidemiological data from Iran. Overall age-standard incidence rate per 100 000 population according to primary site is 110.43 in males and 98.23 in females. The five most common cancers (except skin cancer) are stomach, esophagus, colon-rectum, bladder and leukemia in males, and in females are breast, esophagus, stomach, colon-rectum and cervix uteri. The incidence rates of gastrointestinal cancers are high in Iran (it is one of the known areas with a high incidence of GI cancers). Breast cancer mainly affects Iranian women about a decade earlier than Western countries and younger cases are affected by an increasing rate of colorectal cancer in Iran, near the Western rates.


Quantitation of myosin light chain phosphorylation in small tissue samples.
A method to quantitate the extent of phosphorylation of the 20,000-dalton phosphorylatable myosin light chain (P-light chain) in cardiac, smooth, or skeletal muscle samples which have limited amounts of tissue and myosin is presented. Native myosin is isolated from other cellular proteins in crude homogenates prepared from a few milligrams of muscle by pyrophosphate-polyacrylamide gel electrophoresis. The extent of P-light chain phosphorylation is maintained throughout this procedure by the inclusion of myosin light chain kinase and phosphatase inhibitors. Myosin obtained by pyrophosphate-gel electrophoresis is subjected to isoelectric focusing on polyacrylamide gels to separate the phosphorylated from the nonphosphorylated forms of the P-light chain. Following staining with ammonial-silver phosphorylation is quantitated on a mole of phosphate incorporated per mol of P-light chain basis by densitometric scanning of the isoelectric focusing gels. Direct comparison of this methodology with another method used for quantitating phosphorylation revealed no difference between the techniques in measuring the extent of P-light chain phosphorylation in muscle biopsy samples. This methodology provides the means for examination of the possible regulatory roles of P-light chain phosphorylation in contraction of cardiac, smooth, skeletal muscle.


Preparation and characterization of silybin-loaded nanostructured lipid carriers.
Nanostructured lipid carriers (NLC) are a new generation of lipid nanoparticles, which are produced by controlled mixing of solid lipids with spatially incompatible liquid lipids leading to special nanostructures with improved drug incorporation and release properties. In this study, silybin-loaded nanostructured lipid carriers with various liquid lipid content were successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature. The size and morphology of nanoparticles were significantly influenced by the liquid lipid content. As the liquid lipid content increased to 20 wt%, the obtained particles showed distinguished smaller size. Compared with solid lipid nanoparticles (SLN), NLC presented improved drug loading capacity which increased with increasing the liquid lipid content. The differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis indicated that the incorporation of liquid lipids could interfere with the crystallization of solid lipids. The drug in vitro release behavior from NLC displayed a biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards, and the successful controlled release rate can be achieved by controlling the liquid lipid content.


Isolation and characterization of human amniotic fluid and SH-SY5Y/ BE(2)-M17 cell derived exosomes.
The application of stem cells as a therapy for degenerative disease holds great promise. Substantial evidence suggests that stem cell derived exosomes are a novel cell-free therapy for the corresponding cells. Exosomes are less complex as compared to their parental cells, due to the fewer number of membrane proteins. In addition, the smaller size and lower risk of immunogenicity makes exosomes potentially safe therapeutic nano-carriers. A large number of ongoing research studies are focused on characterizing exosomes that were derived from different sources, for their potential use in various therapeutic applications. In the present study, we focused on characterizing human amniotic fluid stem cell derived exosomes for future therapeutic applications, such as paracrine therapy/nano carrier. In addition, we characterized exosomes derived from SH-SY5Y and BE(2)-M17 cells, which are a known neuronal model, for further characteristic analyses of neuronal differentiation and neurobiology. Finally, we compared various exosome isolation techniques and procedures and evaluated exosome yield.


[Treatment of idiopathic and uremic restless legs syndrome with L-dopa--a double-blind cross-over study].
In a randomized, controlled and double-blind cross-over trial with L-Dopa and placebo we evaluated the effects of a single bedtime dose of L-Dopa 100 to 200 mg on sleep quality and frequency of periodic leg movements (PLM) in 17 patients with idiopathic and in 11 patients with uremic restless legs syndrome (RLS) by polysomnography, actigraphy, and subjective ratings. Treatment with L-Dopa showed significant reduction of the number of periodic leg movements and the PLM-index most pronounced during the first 4 hours of bedtime. Subjective evaluation confirmed improvement of sleep quality. L-Dopa proved to be effective in idiopathic and uremic RLS without any severe side effects.


Endothelium-derived stromal cells contribute to hematopoietic bone marrow niche formation.
Bone marrow stromal cells (BMSCs) play pivotal roles in tissue maintenance and regeneration. Their origins, however, remain incompletely understood. Here we identify rare LNGFR+ cells in human fetal and regenerative bone marrow that co-express endothelial and stromal markers. This endothelial subpopulation displays transcriptional reprogramming consistent with endothelial-to-mesenchymal transition (EndoMT) and can generate multipotent stromal cells that reconstitute the bone marrow (BM) niche upon transplantation. Single-cell transcriptomics and lineage tracing in mice confirm robust and sustained contributions of EndoMT to bone precursor and hematopoietic niche pools. Interleukin-33 (IL-33) is overexpressed in subsets of EndoMT cells and drives this conversion process through ST2 receptor signaling. These data reveal generation of tissue-forming BMSCs from mouse and human endothelial cells and may be instructive for approaches to human tissue regeneration.


[Effect of the drug stibyl on the enzymatic activity of the antioxidant defense system in chickens].
We have investigated the change of peroxidase, catalase, glutathione reductase and glutathione peroxidase activity in the organs and tissues of chickens when introducing the products of albumens interaction with carbohydrates into the ration under the conditions of Maiyer's reaction (stibel preparation). It was found that the effect of stibel on the activity of antioxidant enzymes of chickens has age peculiarities. When introducing the addition to the chickens ration in the starting period (1-30 days) it causes the decrease of superoxide dismutase and catalase activity, and increase of peroxidase and glutathione peroxidase activity. In the finishing period (30-59 days) the drug stimulates the activity of superoxide dismutase and inhibits other enzymes of the chicken antioxidant system. The degree of expression of the mentioned effects depends on the organ specificity and on the nature of albumen and carbohydrate components of food addition and also on the ration saturation with metabolic energy and protein.


Detection of low levels of HCG by simple immunoassays, and clinical implications.
Traditional, less sensitive simple immunoassays ('Placentex' and 'Pregnosis') were performed concurrently with newer, more sensitive, but simple immunoassays ('Sensitex' and a capillary tube pregnancy test) and radioimmunoassays for beta-HCG from two commercial sources (Roche Diagnostics and Monitor Science Corporation). Generally these various assays agreed, but of particular importance for the early screening of urinary HCG (prior to the first missed but expected period) was that the commercial half-unit tube test ('Sensi-tex') gave early positive results comparable to the half-unit research capillary tube test previously reported. These sensitive simple immunoassays (SSIA) may improve the management of patients very early in pregnancy and following termination of pregnancy.


Increased immune gene expression and immune cell infiltration in high-grade astrocytoma distinguish long-term from short-term survivors.
Survival in the majority of high-grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors. A better understanding of the biological factors associated with long-term survival in HGA would aid development of more effective therapy and survival prediction. Factors associated with long-term survival have not been extensively studied using unbiased genome-wide expression analyses. In the current study, gene expression microarray profiles of HGA from long-term survivors were interrogated for discovery of survival-associated biological factors. Ontology analyses revealed that increased expression of immune function-related genes was the predominant biological factor that positively correlated with longer survival. A notable T cell signature was present within this prognostic immune gene set. Using immune cell-specific gene classifiers, both T cell-associated and myeloid linage-associated genes were shown to be enriched in HGA from long-term versus short-term survivors. Association of immune function and cell-specific genes with survival was confirmed independently in a larger publicly available glioblastoma gene expression microarray data set. Histology was used to validate the results of microarray analyses in a larger cohort of long-term survivors of HGA. Multivariate analyses demonstrated that increased immune cell infiltration was a significant independent variable contributing to longer survival, as was Karnofsky/Lansky performance score. These data provide evidence of a prognostic anti-tumor adaptive immune response and rationale for future development of immunotherapy in HGA.


Permanent lunar surface magnetism and its deflection of the solar wind.
Magnetic compressions intermittently observed outside the lunar wake in the solar wind may be limb shocks caused by the presence of local regions of permanent magnetism on the lunar limb. Observable compression would be due to regions of length scale (radius) at least as great as several tens of kilometers and field strength greater, similar 10 gammas. Thousands of such regions might exist on the lunar surface. The steady magnetic field measured at the Apollo 12 site probably has length scale less, similar 10 kilometers and probably does not produce an observable limb shock.


Circulating 27-hydroxycholesterol and Risk of Colorectal Adenomas and Serrated Polyps.
The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (<138 ng/mL), those with circulating 27-OHC at or above the fourth quartile (≥201 ng/mL) had 24% higher risk of adenomas (RR, 1.24; 95% CI, 1.05-1.47) and 89% higher risk of advanced adenomas (RR, 1.89; 95% CI, 1.17-3.06). Stronger associations were observed among participants with advanced adenomas at baseline. Circulating 27-OHC was not associated with risk of hyperplastic polyps (RR, 0.90; 95% CI, 0.66-1.22) or sessile serrated adenomas/polyps (RR, 1.02; 95% CI, 0.50-2.07). Circulating 27-OHC may be a risk factor for colorectal adenomas but not serrated polyps. PREVENTION RELEVANCE: This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.


A health intervention or a kitchen appliance? Household costs and benefits of a cleaner burning biomass-fuelled cookstove in Malawi.
Pneumonia is the leading cause of mortality for children under five years in sub-Saharan Africa. Household air pollution has been found to increase risk of pneumonia, especially due to exposure from dirty burning biomass fuels. It has been suggested that advanced stoves, which burn fuel more efficiently and reduce smoke emissions, may help to reduce household air pollution in poor, rural settings. This qualitative study aims to provide an insight into the household costs and perceived benefits from use of the stove in Malawi. It was conducted alongside The Cooking and Pneumonia Study (CAPS), the largest village cluster-level randomised controlled trial of an advanced combustion cookstove intervention to prevent pneumonia in children under five to date. In 2015, using 100 semi-structured interviews this study assessed household time use and perceptions of the stove from both control and intervention participants taking part in the CAPS trial in Chilumba. Household direct and indirect costs associated with the intervention were calculated. Users overwhelming liked using the stove. The main reported benefits were reduced cooking times and reduced fuel consumption. In most interviews, the health benefits were not initially identified as advantages of the stove, although when prompted, respondents stated that reduced smoke emissions contributed to a reduction in respiratory symptoms. The cost of the stove was much higher than most respondents said they would be willing to pay. The stoves were not primarily seen as health products. Perceptions of limited impact on health was subsequently supported by the CAPS trial data which showed no significant effect on pneumonia. While the findings are encouraging from the perspective of acceptability, without innovative financing mechanisms, general uptake and sustained use of the stove may not be possible in this setting. The findings also raise the question of whether the stoves should be marketed and championed as 'health interventions'.


Gamma interferon responses to Plasmodium falciparum liver-stage antigen 1 and thrombospondin-related adhesive protein and their relationship to age, transmission intensity, and protection against malaria.
Gamma interferon (IFN-gamma) responses to the Plasmodium falciparum antigens liver-stage antigen 1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) are thought to be important in protection against malaria. Optimal methods of testing and the effects of age and transmission intensity on these responses are unknown. IFN-gamma responses to LSA-1 and TRAP peptides were assessed by the enzyme-linked immunospot assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA) in children and adults from areas of stable and unstable malaria transmission in Kenya. Adults in the areas of stable and unstable transmission had similar frequencies and levels of IFN-gamma responses to LSA-1 and TRAP as determined by ELISPOT and ELISA. In contrast, IFN-gamma responses to the LSA-1 T3 peptide (assessed by ELISPOT) and to any LSA-1 peptide (assessed by ELISA) were less frequent in children in the area of unstable transmission than in children in the area of stable transmission. IFN-gamma responses to LSA-1 were more frequently detected by ELISA than by ELISPOT in the stable-transmission area. IFN-gamma responses detected by ELISA and ELISPOT did not correlate with each other. In children in the stable-transmission area, IFN-gamma responses to LSA-1 peptides assessed by ELISA, but not by ELISPOT, were associated with protection against clinical malaria and anemia. IFN-gamma responses to LSA-1 appear to require repeated P. falciparum exposure and/or increased age and, as measured by ELISA, are associated with protection against clinical malaria and anemia.


Spermine biphasically affects N-type calcium channel currents in adult dorsal root ganglion neurons of the rat.
Spermine (Spe) is a polyamine co-secreted with neurotransmitters. In this work its effects on N-type Ca2+ channel (CaV2.2) have been studied on adult sensory neurons of the rat by means of whole-cell patch-clamp. Spe exerted biphasic effects when added to the external solution: at 500 microM decreased N-type Ca2+ channel currents, reducing the maximum whole-cell conductance, shifting the activation curve to the right on the voltage axes and decreasing its slope; conversely, at lower concentration (500 nM) Spe induced completely opposite effects. In 62% of the neurons the inhibitory effects were accompanied by a slowing down of the activation kinetics relieved by a conditioning pre-pulse to +50 mV. The biphasic effects and their rapid onset and offset time course may be explained if multiple sites of action with a different affinity for Spe are present directly on the channel. The effects of Spe on HVA Ca2+ currents were strongly dependent on [Ca2+]ext, high [Ca2+] powerfully reducing Spe effects. This may be explained if we take into account that as Spe has four positive charges at physiological pH; it may compete with divalent cations for some negatively charged regulatory sites. In these experiments, Spe was effective at concentrations possibly reached in physiological conditions.


Polyhydroxy Fullerenes Enhance Antibacterial and Electrocatalytic Activity of Silver Nanoparticles.
Silver nanoparticles (AgNPs) are known and widely used for their antibacterial properties. However, the ever-increasing resistance of microorganisms compels the design of novel nanomaterials which are able to surpass their capabilities. Herein, we synthesized silver nanoparticles using, for the first time, polyhydroxy fullerene (PHF) as a reducing and capping agent, through a one-pot synthesis method. The resulting nanoparticles (PHF-AgNPs) were compared to AgNPs that were synthesized using sodium citrate (citrate-AgNPs). They were characterized using high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering, and UV-visible spectroscopy. Our results showed that PHF-AgNPs have a smaller size and a narrower size distribution than citrate-AgNPs, which suggests that PHF may be a better capping agent than citrate. Antibacterial assays using E. coli showed enhanced antimicrobial activity for PHF-AgNPs compared to citrate-AgNPs. The electrocatalytic activity of nanoparticles towards oxygen evolution and reduction reaction (OER and ORR, respectively) was tested through cyclic voltammetry. Both nanoparticles are found to promote OER and ORR, but PHF-AgNPs showed a significant increase in activity with respect to citrate-AgNPs. Thus, our results demonstrate that the properties of forming nanoparticles can be tuned by choosing the appropriate reducing/capping agent. Specifically, this suggests that PHF-AgNPs can find potential applications for both catalytic and biomedical applications.


GC4S: A bioinformatics-oriented Java software library of reusable graphical user interface components.
Modern bioinformatics and computational biology are fields of study driven by the availability of effective software required for conducting appropriate research tasks. Apart from providing reliable and fast implementations of different data analysis algorithms, these software applications should also be clear and easy to use through proper user interfaces, providing appropriate data management and visualization capabilities. In this regard, the user experience obtained by interacting with these applications via their Graphical User Interfaces (GUI) is a key factor for their final success and real utility for researchers. Despite the existence of different packages and applications focused on advanced data visualization, there is a lack of specific libraries providing pertinent GUI components able to help scientific bioinformatics software developers. To that end, this paper introduces GC4S, a bioinformatics-oriented collection of high-level, extensible, and reusable Java GUI elements specifically designed to speed up bioinformatics software development. Within GC4S, developers of new applications can focus on the specific GUI requirements of their projects, relying on GC4S for generalities and abstractions. GC4S is free software distributed under the terms of GNU Lesser General Public License and both source code and documentation are publicly available at http://www.sing-group.org/gc4s.


Outcomes with Orbital and Rotational Atherectomy for Inpatient Percutaneous Coronary Intervention.
Our objective was to describe the contemporary outcomes of orbital atherectomy (OA) vs. rotational atherectomy (RA) use for inpatient percutaneous coronary intervention (PCI) in the United States. Data on the use of OA vs. RA in contemporary inpatient PCI are limited. We queried the Nationwide Readmission Database (NRD) from January to November for the years 2016-2017 to identify hospitalizations of patients who underwent PCI with atherectomy. We conducted a multivariate regression analysis to identify variables associated with in-hospital mortality. We included 77,040 records of patients who underwent inpatient PCI with atherectomy. Of those, 71,610 (93%) had RA, and 5430 (7%) had OA. There was no significant change in the trend of using OA or RA over 2016 and 2017. OA was less utilized in patients presenting with ST-segment elevation myocardial infarction (STEMI) (4.3% vs. 46.8%, p < 0.001). In our cohort, OA was associated with lower in-hospital mortality (3.1% vs. 5%, p < 0.001) and 30-day urgent readmission (< 0.01% vs. 0.2%, p = 0.009), but a higher risk of coronary perforation (1.7% vs. 0.6%, p < 0.001) and cardiac tamponade (1% vs. 0.3%, p < 0.001) and a higher cost of index hospitalization ($28,199 vs. $23,188, p < 0.001) compared with RA. RA remains the predominant atherectomy modality for inpatient PCI in the United States (93%). There was no change in the trend of use for either modality over the years 2016 and 2017. OA was noted to have a lower incidence of in-hospital death, but a higher risk of coronary perforation and a higher cost of index hospitalization for the overall unmatched cohorts.


The Role of Tissue Macrophage-Mediated Inflammation on NAFLD Pathogenesis and Its Clinical Implications.
The obese phenotype is characterized by a state of chronic low-grade systemic inflammation that contributes to the development of comorbidities, including nonalcoholic fatty liver disease (NAFLD). In fact, NAFLD is often associated with adipocyte enlargement and consequent macrophage recruitment and inflammation. Macrophage polarization is often associated with the proinflammatory state in adipose tissue. In particular, an increase of M1 macrophages number or of M1/M2 ratio triggers the production and secretion of various proinflammatory signals (i.e., adipocytokines). Next, these inflammatory factors may reach the liver leading to local M1/M2 macrophage polarization and consequent onset of the histological damage characteristic of NAFLD. Thus, the role of macrophage polarization and inflammatory signals appears to be central for pathogenesis and progression of NAFLD, even if the heterogeneity of macrophages and molecular mechanisms that govern their phenotype switch remain incompletely understood. In this review, we discuss the role of adipose and liver tissue macrophage-mediated inflammation in experimental and human NAFLD. This focus is relevant because it may help researchers that approach clinical and experimental studies on this disease advancing the knowledge of mechanisms that could be targeted in order to revert NAFLD-related fibrosis.


Transcriptional and Small RNA Responses of the White Mold Fungus Sclerotinia sclerotiorum to Infection by a Virulence-Attenuating Hypovirus.
Mycoviruses belonging to the family Hypoviridae cause persistent infection of many different host fungi. We previously determined that the white mold fungus, Sclerotiniasclerotiorum, infected with Sclerotinia sclerotiorum hypovirus 2-L (SsHV2-L) exhibits reduced virulence, delayed/reduced sclerotial formation, and enhanced production of aerial mycelia. To gain better insight into the cellular basis for these changes, we characterized changes in mRNA and small RNA (sRNA) accumulation in S.sclerotiorum to infection by SsHV2-L. A total of 958 mRNAs and 835 sRNA-producing loci were altered after infection by SsHV2-L, among which >100 mRNAs were predicted to encode proteins involved in the metabolism and trafficking of carbohydrates and lipids. Both S. sclerotiorum endogenous and virus-derived sRNAs were predominantly 22 nt in length suggesting one dicer-like enzyme cleaves both. Novel classes of endogenous small RNAs were predicted, including phasiRNAs and tRNA-derived small RNAs. Moreover, S. sclerotiorum phasiRNAs, which were derived from noncoding RNAs and have the potential to regulate mRNA abundance in trans, showed differential accumulation due to virus infection. tRNA fragments did not accumulate differentially after hypovirus infection. Hence, in-depth analysis showed that infection of S. sclerotiorum by a hypovirulence-inducing hypovirus produced selective, large-scale reprogramming of mRNA and sRNA production.


Sensory handedness is not reflected in cortical responses after basic nerve stimulation: a MEG study.
Motor dominance is well established, but sensory dominance is much less clear. We therefore studied the cortical evoked magnetic fields using magnetoencephalography (MEG) in a group of 20 healthy right handed subjects in order to examine whether standard electrical stimulation of the median and ulnar nerve demonstrated sensory lateralization. The global field power (GFP) curves, as an indication of cortical activation, did not depict sensory lateralization to the dominant left hemisphere. Comparison of the M20, M30, and M70 peak latencies and GFP values exhibited no statistical differences between the hemispheres, indicating no sensory hemispherical dominance at these latencies for each nerve. Field maps at these latencies presented a first and second polarity reversal for both median and ulnar stimulation. Spatial dipole position parameters did not reveal statistical left-right differences at the M20, M30 and M70 peaks for both nerves. Neither did the dipolar strengths at M20, M30 and M70 show a statistical left-right difference for both nerves. Finally, the Laterality Indices of the M20, M30 and M70 strengths did not indicate complete lateralization to one of the hemispheres. After electrical median and ulnar nerve stimulation no evidence was found for sensory hand dominance in brain responses of either hand, as measured by MEG. The results can provide a new assessment of patients with sensory dysfunctions or perceptual distortion when sensory dominance occurs way beyond the estimated norm.


Sex chromosome meiotic drive systems in Drosophila melanogaster I. Abnormal spermatid development in males with a heterochromatin-deficient X chromosome (sc-4sc-8).
The meiotic drive chracteristics of the In(1)sc-4Lsc-8R/Y system have been examined by genetic analysis and by light and electron microscopy. sc-4sc8-/Y males show a direct correlation between nondisjunction frequency and meiotic drive. Temperature-shift experiments reveal that the temperature-sensitive period for nondisjunction is at meiosis, whereas that for meiotic drive has both meiotic and post-meiotic components. Cytological analyses in the light and electron microscopes reveal failures in spermiogenesis in the tests of sc-4sc-8 males. The extent of abnormal spermatid development increases as nondisjunction becomes more extreme.


Selective use of corifollitropin for controlled ovarian stimulation for IVF in patients with low anti-Müllerian hormone.
Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian hyperstimulation syndrome (OHSS) when used in standard patients. We administered corifollitropin selectively to patients with anticipated low to moderate ovarian response based on antimüllerian hormone levels in the lower quartile. The end points were oocyte distribution and occurrence of OHSS in women with AMH ≤15 pmol/L. The study included a cohort of 368 patients treated in 599 cycles. Post hoc the cohort was subdivided according to AMH. With increasing baseline AMH, the number of oocytes increased from a mean of 2.7 (range 0-8 with AMH <3 pmol/L) to 6.3 (range 0-15 with AMH 10-15 pmol/L) oocytes. Cancellations of retrievals and transfers decreased significantly with increasing AMH. Overall, the ongoing live pregnancy rate per started cycle was 15.2%. None developed OHSS. No cycles were cancelled or needed triggering of ovulation using a GnRH agonist due to risk of OHSS. Selective use of corifollitropin in patients with AMH in the lower quartile is a safe and appropriate way of optimising stimulation.


Comparison of metabolic, oxidative and inflammatory status of Simmental × Holstein crossbred with parental breeds during the peripartal and early lactation periods.
The aim of the research reported in this paper was to evaluate plasma concentrations of energy, oxidative and inflammatory biomarkers of Simmental (sire) × Holstein (dam) crossbred cows, in comparison with the two parental breeds during the peripartal and early lactation periods and to estimate the effects of heterosis for these traits. Thirty-three animals, managed under the same conditions, 8 Simmental (SI), 9 Holstein (HO) and 16 crossbred (CR) cows were enrolled in this study. Glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), total protein, albumin, creatinine and urea were determined in blood sampled at six different time points (30 ± 3 and 15 ± 3 d before the expected calving date, at calving and 15, 30 and 60 d after calving). Furthermore, derived reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), interleukin-6 (IL-6), haptoglobin (Hp) and serum amyloid A protein (SAA) were determined to evaluate inflammatory and oxidative status. Results showed that the CR group had significantly lower average values of glucose and NEFA when compared to HO group; signifcantly lower values of urea than SI group and significantly higher values of creatinine than HO. Furthermore, CR cows showed the lowest average value of d-ROMs with respect to SI and HO parental breeds. Finally, the average value of haptoglobin was significantly lower in CR and HO groups, when compared to SI group. As for the heterosis we found the highest (positive) percentage for CK (98%) and BAP (47%) and the lowest (negative) percentage for OSi (-75%) and d-ROMs (-39%). A negative percentage was also found for the glucose (-11%) and NEFA (-20%) toward the Simmental parental breed. Our results suggest a different response among the three genetic groups during the peripartal and early lactation periods. In particular, CR and SI cows seem more adaptable regarding energy metabolism and oxidative status. Heterosis led to a positive effect on those parameters in Simmental (sire) × Holstein (dam) crossbred cows F1 population (50% Simmental and 50% Holstein).


Impact of model assumptions on the inference of the evolution of ectomycorrhizal symbiosis in fungi.
Ectomycorrhiza (ECM) is a symbiotic relation between plant and fungi that is essential for nutrient uptake of many stand forming trees. There are two conflicting views about the evolution of ECM in fungi suggesting (1) relatively few transitions to ECM followed by reversals to non-ECM, or (2) many independent origins of ECM and no reversals. In this study, we compare these, and other, hypotheses and test the impact of different models on inference. We assembled a dataset of five marker gene sequences (nuc58, nucLSU, nucSSU, rpb1, and rpb2) and 2,174 fungal taxa covering the three subphyla: Agaricomycotina, Mucoromycotina and Pezizomycotina. The fit of different models, including models with variable rates in clades or through time, to the pattern of ECM fungal taxa was tested in a Bayesian framework, and using AIC and simulations. We find that models implementing variable rates are a better fit than models without rate shift, and that the conclusion about the relative rate between ECM and non-ECM depend largely on whether rate shifts are allowed or not. We conclude that standard constant-rate ancestral state reconstruction models are not adequate for the analysis of the evolution of ECM fungi, and may give contradictory results to more extensive analyses.


FERROCHELATASE: THE CONVERGENCE OF THE PORPHYRIN BIOSYNTHESIS AND IRON TRANSPORT PATHWAYS.
Ferrochelatase (also known as PPIX ferrochelatase; Enzyme Commission number 126.96.36.199.1) catalyzes the insertion of ferrous iron into PPIX to form heme. This reaction unites the biochemically synchronized pathways of porphyrin synthesis and iron transport in nearly all living organisms. The ferrochelatases are an evolutionarily diverse family of enzymes with no more than six active site residues known to be perfectly conserved. The availability of over thirty different crystal structures, including many with bound metal ions or porphyrins, has added tremendously to our understanding of ferrochelatase structure and function. It is generally believed that ferrous iron is directly channeled to ferrochelatase in vivo, but the identity of the suspected chaperone remains uncertain despite much recent progress in this area. Identification of a conserved metal ion binding site at the base of the active site cleft may be an important clue as to how ferrochelatases acquire iron, and catalyze desolvation during transport to the catalytic site to complete heme synthesis.


Understanding health and illness: research at the interface between science and indigenous knowledge.
Indigenous knowledge cannot be verified by scientific criteria nor can science be adequately assessed according to the tenets of indigenous knowledge. Each is built on distinctive philosophies, methodologies, and criteria. While there is considerable debate around their relative merits, contests about the validities of the two systems tend to serve as distractions from explorations of the interface, and the subsequent opportunities for creating new knowledge that reflects the dual persuasions. Maori researchers in Aotearoa/New Zealand have been able to apply the methods and values of both systems in order to reach more comprehensive understandings of health and illness. Two case studies are used to demonstrate how the incorporation of indigenous beliefs into research protocols and measurements can enhance health research and understandings of health and illness.


Counseling Veterans Applying for Service Connection Status for Mental Health Conditions.
Veterans with mental health conditions that were either caused or aggravated by their military service are eligible to receive service-connected disability benefits from the Department of Veterans Affairs. The process of applying for service connection status is complex, and it is not surprising that veterans frequently develop beliefs about service connection that may not be accurate and that could interfere with treatment. The authors describe some of these beliefs and offer suggestions to clinicians for addressing them. Veterans may believe that their clinician is directly involved in service connection determination or that therapy notes will determine the outcome of the claim. Veterans may not understand the basis for award of service connection and may interpret rejection of their claim as reflecting disrespect for their service or degree of distress. The authors argue that discussing these beliefs with veterans might enhance therapy by demonstrating familiarity with an important aspect of veterans' experience and by helping veterans address a significant and distressing issue.


Peripheral arterial disease in community-based patients with diabetes in Singapore: Results from a Primary Healthcare Study.
Peripheral arterial disease (PAD) is an important complication of diabetes mellitus (DM), significantly associated with increased morbidity and mortality secondary to amputations, strokes and coronary artery disease. Information on DM patients with PAD is limited in our ethnically diverse population in Singapore. We aimed to determine the prevalence, risk factors and co-morbidities of PAD in patients managed for DM in the primary care setting. A cross-sectional study was conducted among 521 diabetics in 9 of the 18 government-aided clinics in the community. Data including demographics, presence of co-morbidities and vascular risk factors were collected using an interviewer-administered questionnaire, and Ankle-Brachial Index (ABI) was calculated from systolic ankle and brachial pressure measurements. The prevalence of PAD, defi ned as resting ABI of <0.9 on either leg and/or a history of gangrene or non-traumatic amputation was 15.2% [95% confidence interval (CI), 12.3-18.5]. This prevalence of PAD was higher in patients with pre-existing microvascular and other macrovascular complications. In multivariate analysis, prevalence of PAD was positively associated with increasing age (OR, 1.08; 95% CI, 1.05-1.12), Malay versus Chinese ethnicity (OR, 2.27; 95% CI, 1.09-4.70), low HDL-cholesterol (OR, 1.87; 95% CI, 1.04- 3.37), and insulin treatment (OR, 2.98; 95%CI, 1.39-6.36). PAD is an important cause of concern among patients with diabetes, with a high prevalence which further increases with increasing age and duration of DM, and exhibits ethnic variation. Risk factors identified in this study may improve early identification of PAD, allowing for prompt interventions, with a potential to reduce long-term morbidity and mortality.


The short-term impact of generic versus individualized environmental supports on functional outcomes and target behaviors in schizophrenia.
We examined the short-term efficacy of two treatments using environmental supports (e.g. signs, alarms, pill containers, and checklists) to improve target behaviors in individuals with schizophrenia. 120 participants were randomized into one of the following three treatment groups: 1) Cognitive Adaptation Training (CAT; a manual-driven set of environmental supports customized to individual cognitive impairments and behaviors, and established and maintained in participants' homes on weekly visits; 2) Generic Environmental Supports (GES; a generic set of supports given to patients at a routine clinic visit and replaced on a monthly basis); and 3) treatment as usual (TAU; standard follow-up provided by a community mental health center). Global level of functional outcome and target behaviors, including orientation, grooming and hygiene, and medication adherence, were assessed at baseline and 3 months. Results of an analysis of covariance indicated that patients in both CAT and GES had better scores on global functional outcome at 3 months than those in TAU. Results of Chi Square analyses indicated that patients in CAT were more likely to improve on target behaviors, including orientation, hygiene, and medication adherence, than those in GES. Irrespective of treatment group, individuals who were high utilizers of environmental supports were more likely to improve on target behaviors than individuals who were low utilizers of supports.


Proton Pump Inhibitors and the Risk for Fracture at Specific Sites: Data Mining of the FDA Adverse Event Reporting System.
Proton pump inhibitors (PPIs) are widely used to treat gastric acid-related disorders. Concerns have been raised about potential fracture risk, especially at the hip, spine and wrist. However, fracture risk at other bone sites has not been as well studied. We investigated the association between PPIs and specific fracture sites using an aggregated knowledge-enhanced database, the Food and Drug Administration Adverse Event Reporting System Data Mining Set (AERS-DM). Proportional reporting ratio (PRR) was used to detect statistically significant associations (signals) between PPIs and fractures. We analyzed both high level terms (HLT) and preferred terms (PT) for fracture sites, defined by MedDRA (Medical Dictionary for Regulatory Activities). Of PPI users reporting fractures, the mean age was 65.3 years and the female to male ratio was 3.4:1. Results revealed signals at multiple HLT and PT fracture sites, consistent for both sexes. These included fracture sites with predominant trabecular bone, not previously reported as being associated with PPIs, such as 'rib fractures', where signals were detected for overall PPIs as well as for each of 5 generic ingredients (insufficient data for dexlansoprazole). Based on data mining from AERS-DM, PPI use appears to be associated with an increased risk for fractures at multiple sites.


Controversy: Does repetitive transcranial magnetic stimulation/ transcranial direct current stimulation show efficacy in treating tinnitus patients?
Tinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Functional imaging has demonstrated a relationship between the intensity of tinnitus and the degree of reorganization in the auditory cortex. Experimental studies have further shown that tinnitus is associated with synchronized hyperactivity in the auditory cortex. Therefore, targeted modulation of auditory cortex has been proposed as a new therapeutic approach for chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive methods that can modulate cortical activity. These techniques have been applied in different ways in patients with chronic tinnitus. Single sessions of high-frequency rTMS over the temporal cortex have been successful in reducing the intensity of tinnitus during the time of stimulation and could be predictive for treatment outcome of chronic epidural stimulation using implanted electrodes. Another approach that uses rTMS as a treatment for tinnitus is application of low-frequency rTMS in repeated sessions, to induce a lasting change of neuronal activity in the auditory cortex beyond the duration of stimulation. Beneficial effects of this treatment have been consistently demonstrated in several small controlled studies. However, results are characterized by high interindividual variability and only a moderate decrease of the tinnitus. The role of patient-related (for example, hearing loss, tinnitus duration, age) and stimulation-related (for example, stimulation site, stimulation protocols) factors still remains to be elucidated. Even in this early stage of investigation, there is a convincing body of evidence that rTMS represents a promising tool for pathophysiological assessment and therapeutic management of tinnitus. Further development of this technique will depend on a more detailed understanding of the neurobiological effects mediating the benefit of TMS on tinnitus perception. Moreover clinical studies with larger sample sizes and longer follow-up periods are needed.


Behavioural adaptations to flight into thin air.
Soaring raptors can fly at high altitudes of up to 9000 m. The behavioural adjustments to high-altitude flights are largely unknown. We studied thermalling flights of Himalayan vultures (Gyps himalayensis) from 50 to 6500 m above sea level, a twofold range of air densities. To create the necessary lift to support the same weight and maintain soaring flight in thin air birds might modify lift coefficient by biophysical changes, such as wing posture and increasing the power expenditure. Alternatively, they can change their flight characteristics. We show that vultures use the latter and increase circle radius by 35% and airspeed by 21% over their flight altitude range. These simple behavioural adjustments enable vultures to move seamlessly during their annual migrations over the Himalaya without increasing energy output for flight at high elevations.


Circumventing immune tolerance through epigenetic modification.
In recent decades our understanding of immune cell activation and homeostasis has significantly expanded. Such progress helped to better define the cellular, molecular, and epigenetic networks involved in the immune response in the tumor microenvironment and renewed the enthusiasm towards the potential power of cancer immunotherapy. However, successful translation of novel mechanistic discoveries into effective immunotherapy was hindered by a number of obstacles, among them the ability of tumors to tolerize host lymphocytes rendering them functionally incompetent and the tumor's ability to evade antigen-specific immune recognition through a variety of genetic, epigenetic, and stromal factors. These immunosuppressive strategies have, thus far, blunted our efforts to effectively unleash anti-cancer immunity. Fortunately, the wealth of new information regarding the interactions between tumors and the immune system and the regulation of certain highly antigenic tumor proteins has led to novel approaches with the potential to render cancer cells helpless towards immune attack. Here we summarize recent findings on cancer-induced T-lymphocyte tolerance and discuss a novel "vaccinate-induce" strategy conceived to counteract these effects at an epigenetic level.


Prediction Interval: What to Expect When You're Expecting … A Replication.
A challenge when interpreting replications is determining whether the results of a replication "successfully" replicate the original study. Looking for consistency between two studies is challenging because individual studies are susceptible to many sources of error that can cause study results to deviate from each other and the population effect in unpredictable directions and magnitudes. In the current paper, we derive methods to compute a prediction interval, a range of results that can be expected in a replication due to chance (i.e., sampling error), for means and commonly used indexes of effect size: correlations and d-values. The prediction interval is calculable based on objective study characteristics (i.e., effect size of the original study and sample sizes of the original study and planned replication) even when sample sizes across studies are unequal. The prediction interval provides an a priori method for assessing if the difference between an original and replication result is consistent with what can be expected due to sample error alone. We provide open-source software tools that allow researchers, reviewers, replicators, and editors to easily calculate prediction intervals.


IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells.
IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.


Carcinoembryonic antigen gene family: molecular biology and clinical perspectives.
The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin super-gene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed.


Herpes simplex virus type 1 infection of activated cytotoxic T cells: Induction of fratricide as a mechanism of viral immune evasion.
Herpes simplex virus type 1 (HSV1), a large DNA-containing virus, is endemic in all human populations investigated. After infection of mucocutaneous surfaces, HSV1 establishes a latent infection in nerve cells. Recently, it was demonstrated that HSV1 can also infect activated T lymphocytes. However, the consequences of T cell infection for viral pathogenesis and immunity are unknown. We have observed that in contrast to the situation in human fibroblasts, in human T cell lines antigen presentation by major histocompatibility complex class I molecules is not blocked after HSV1 infection. Moreover, HSV1 infection of T cells results in rapid elimination of antiviral T cells by fratricide. To dissect the underlying molecular events, we used a transgenic mouse model of HSV1 infection to demonstrate that CD95 (Apo-1, Fas)-triggered apoptosis is essential for HSV1-induced fratricide, whereas tumor necrosis factor (TNF) also contributes to this phenomenon but to a lesser extent. By contrast, neither TRAIL (TNF-related apoptosis-inducing ligand) nor perforin were involved. Finally, we defined two mechanisms associated with HSV1-associated fratricide of antiviral T cells: (a) T cell receptor-mediated upregulation of CD95 ligand and (b) a viral "competence-to-die" signal that renders activated T lymphocytes susceptible to CD95 signaling. We propose that induction of fratricide is an important immune evasion mechanism of HSV1, helping the virus to persist in the host organism throughout its lifetime.


[A typology of homicides committed by youth groups].
Based on a complete survey of homicides committed by young people between the age of 14 and 21 (juvenile and adolescent offenders) in the German state of Brandenburg during a period of 10 years, two typologies are presented to describe homicidal acts. The first typology is based on motivation and identifies the basic social attitude of the offender manifested in the concrete offence, whereas the typology based on group context deals with the social conditions influencing the offender in his actions in the youth group. Both are supported by comprehensive data regarding the personal and social circumstances of the offenders and offences. In the typology based on motivation, our study distinguishes between homicide committed out of conviction, homicide due to the social background and homicide for egoistic reasons in order to satisfy a sudden urge in an overpowering situation. In the typology based on group context, a distinction is made between solo and group offences with the latter being subdivided into emotional/non-emotional and planned/ unplanned acts. By typologizing offences according to motivation, perpetrators can be categorized according to their affiliation with a certain milieu and their emotional and ideological disposition. Contrary to conventional criminological studies, the typology according to group context suggests a high percentage of group-based violent crime, which has so far been described on the margin only.


Mechanism of Ca++ antagonist-induced vasodilation. Intracellular actions.
We studied the effects of Ca++ antagonists on intact and skinned muscles of rabbit mesenteric artery. Intact muscle contractions were inhibited by 10(-6) M diltiazem, whereas greater levels were required to abolish contractions in skinned muscle fibers. In contrast, nisoldipine had no effect on skinned muscle contractions, although it inhibited, almost completely, the contraction of intact muscle at concentrations below 10(-6) M. In the presence of EGTA, norepinephrine-induced contractions result from a release of Ca++ from an intracellular store. Diltiazem inhibited these contractions at concentrations between 10(-6) and 10(-4) M. Higher doses were required in studies with skinned muscle preparations. Unlike diltiazem, nisoldipine only partially inhibited the Ca++-free norepinephrine-induced contractions in the range of 10(-7) to 10(-5) M. From these results, we assumed that at low concentrations (below 10(-6) M), diltiazem induced relaxation by blocking Ca++ influx, whereas at relatively high concentrations (above 10(-6) M), an inhibition of Ca++ release from an intracellular store also occurred. A similar conclusion was reached regarding the mechanism whereby nisoldipine inhibits force developments.


The efficacy of pelvic arterial embolisation for the treatment in massive vaginal haemorrhage in obstetric and gynaecological emergencies: a single-centre experience.
This study aimed to identify the role, efficacy and safety of pelvic arterial embolisation (PAE) in the management of massive vaginal haemorrhage occurring in 25 patients with obstetric and gynaecological emergencies where bleeding could not be controlled by conservative treatment methods. Nine of the cases had disseminated intravascular coagulation (DIC) and eight were haemodynamically unstable. PAE was successful in 23 of 25 patients without any major complication. Vascular blush was the most common (100%) angiographic finding. Active extravasation was observed in 9 of 25 of the cases. Permanent embolic agents including polyvinyl alcohol (PVA) particles or N-butyl-2-cyanoacrylate (NBCA) were used in all cases. Technical success in patients with disseminated intravascular coagulation (DIC), and in patients who were haemodynamically unstable were 9 of 11 and 6 of 8 cases, respectively. PAE was successful in all seven patients who had hysterectomy before PAE. PAE is a safe and effective alternative to surgical hysterectomy in obstetric and gynaecological emergencies when conservative management failed to control haemorrhage. It is an effective treatment option in cases of coagulation impairment and when bleeding cannot be controlled despite hysterectomy. Impact statement What is already known on this subject: Postpartum haemorrhage (PPH) is one of the most common causes of maternal morbidity and mortality worldwide. Most patients with PPH are treated conservatively but where this approach fails, hysterectomy is the standard option with loss of reproductive ability. During the past 20 years, pelvic arterial embolisation (PAE) has emerged as a safe, effective and preferred minimally invasive technique in most tertiary centres as an alternative to surgical treatments including hypogastric artery ligation and hysterectomy. The reported success rate of PAE using temporary and permanent embolic agents is 75-90% in cases of massive vaginal bleeding due to obstetric and gynaecological reasons. What the results of this study add? PAE showed high success rate in patients with coagulation disorders and in haemodynamically unstable patients. Permanent embolic agents such as polyvinyl alcohol particles (PVAs) or, N-butyl-2-cyanoacrylate (NBCA) should be used for embolisation in coagulation disorders or haemodynamic instability. The most important advantage of NBCA is that the embolisation effect occurs independently of the inherent coagulation cascade. What are the implications of these findings for clinical practice and/or further research? PAE is an effective and minimally invasive treatment option in cases of coagulopathy and in patients with bleeding that cannot be controlled despite hysterectomy. Our results suggest that haemodynamic instability and DIC should not be considered a contraindication for PAE. Embolic agent selection and the long-term effects of permanent embolic agents on fertilisation is an important issue requiring further investigation.


Strategic plans provide lasting solutions to rural crisis.
Strapped for money and time, many rural hospitals could be tempted by temporary fixes to their financial struggles. Strategic planning helps develop a broader, long-range blueprint for survival. Its steps include making financial evaluations of services; undertaking market and patient origin studies; assessing competitors; involving community leaders; and defining possibilities for joint projects and facility mergers.


Annihilation dynamics of topological defects induced by microparticles in nematic liquid crystals.
The annihilation dynamics of s = ±1 topological defects with and without microparticles in a nematic liquid crystal were investigated and compared. The microparticle with a homeotropic surface anchoring can act as a s = +1 defect and produce a corresponding s = -1 defect nearby. Both of them attract and move towards each other. The speed of the positive defect induced by the microparticle is much slower than that of the negative defect, contrary to the situation without particles. The effects of electric field strength and frequency, particle size, the confining cell gap, and temperature were systematically investigated. The study shows that the dynamics of the annihilation process is related to a complex interplay between elastic attractions, viscous drag forces, backflow effects, director configurations and cell confinement.


A PET study of visuomotor learning under optical rotation.
We measured the regional cerebral blood flow (rCBF) in six healthy volunteers with PET (positron emission tomography) and H(15)(2)O to identify the areas of the human brain involved in sensorimotor learning. The learning task was visually guided reaching with sensorimotor discrepancy caused by optical rotation. PET measurements were performed in the early and late stages of the adaptation to the sensorimotor perturbation. Control measurements were obtained during an eye movement task and a reaching task without optical rotation. The rCBF data of each learning stage were compared to those of both control conditions. During the early stage, rCBF increases were detected in the rostral premotor cortex bilaterally, the posterior part of the left superior parietal lobule (SPL), and the right SPL including the intraparietal sulcus (IPS). During the late stage, rCBF increases were detected in the left caudal premotor area, the left supplementary motor area proper, the left SPL, the right SPL including the IPS, and the right postcentral sulcus extending to the inferior parietal lobule. These results reveal that sensorimotor learning accompanies changes in the recruited cortical areas during different stages of the adaptation, reflecting the different functional roles of each area for different components of adaptation, from learning of new sensorimotor coordination to retention or retrieval of acquired coordination.


Culture, rehabilitation, and facial birth defects: international case studies.
Responses to birth defects are influenced by their cultural and social context. Two multicultural societies, Israel and Nigeria, are reviewed for attitudes toward birth defects. Israel is a developed society where cultural and national origin affect utilization of health services. Differences between Western Jews, Oriental Jews, and Arabs exist in their explanations of etiology and their attitudes toward rehabilitation and community participation. Nigeria is a developing nation with limited health resources. Facial birth defects are stigmatized, infanticide remains a practice, and attitudinal barriers to the development of rehabilitation resources exist. The economic, demographic, and spiritual causes of infanticide are reviewed historically. The persistence of infanticide, though illegal, is discussed relative to issues facing the response of Western medicine to seriously afflicted newborns as well as prenatal genetic diagnosis. The importance of culture as a variable in cleft lip and palate research is stressed.


Graphene oxide flakes as a cellular adhesive: prevention of reactive oxygen species mediated death of implanted cells for cardiac repair.
Mesenchymal stem cell (MSC) implantation has emerged as a potential therapy for myocardial infarction (MI). However, the poor survival of MSCs implanted to treat MI has significantly limited the therapeutic efficacy of this approach. This poor survival is primarily due to reactive oxygen species (ROS) generated in the ischemic myocardium after the restoration of blood flow. ROS primarily causes the death of implanted MSCs by inhibiting the adhesion of the MSCs to extracellular matrices at the lesion site (i.e., anoikis). In this study, we proposed the use of graphene oxide (GO) flakes to protect the implanted MSCs from ROS-mediated death and thereby improve the therapeutic efficacy of the MSCs. GO can adsorb extracellular matrix (ECM) proteins. The survival of MSCs, which had adhered to ECM protein-adsorbed GO flakes and were subsequently exposed to ROS in vitro or implanted into the ischemia-damaged and reperfused myocardium, significantly exceeded that of unmodified MSCs. Furthermore, the MSC engraftment improved by the adhesion of MSCs to GO flakes prior to implantation enhanced the paracrine secretion from the MSCs following MSC implantation, which in turn promoted cardiac tissue repair and cardiac function restoration. This study demonstrates that GO can effectively improve the engraftment and therapeutic efficacy of MSCs used to repair the injury of ROS-abundant ischemia and reperfusion by protecting implanted cells from anoikis.


Childhood trauma, temperament, and character in subjects with major depressive disorder and bipolar disorder.
In nonclinical samples, childhood trauma (CT) has been found to negatively affect temperament/character traits. In major depressive disorder (MDD) and bipolar disorder (BD), abnormal personality traits have been found to impair clinical course/treatment outcome. Although a link between CT and MDD/BD is firmly established, no previous studies explored the relationship between CT and temperament/character in these populations. We investigated this issue in a preliminary sample of inpatients with MDD (n = 29) or BD (n = 50). We assessed CT (sexual/physical/emotional abuse, physical/emotional neglect) (Childhood Trauma Questionnaire), personality traits (Temperament and Character Inventory-Revised version), and illness severity (Brief Psychiatric Rating Scale). We found significant (p < 0.01) associations between emotional neglect, emotional abuse, physical neglect, and low self-directedness (SD). Potential underlying mechanisms are discussed. Because low SD has been previously associated with illness severity and poor outcome, the relationship between CT and low SD might partly explain the well-known negative impact of CT on course and outcome of MDD/BD.


Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies.
To evaluate the toxicity, pharmacokinetics, immunogenicity, and antitumor activity of anti-Tac(Fv)-PE38 (LMB-2), an anti-CD25 recombinant immunotoxin that contains an antibody Fv fragment fused to truncated Pseudomonas exotoxin. Patients with CD25(+) hematologic malignancies for whom standard and salvage therapies failed were treated with LMB-2 at dose levels that ranged from 2 to 63 microg/kg administered intravenously over 30 minutes on alternate days for three doses (QOD x 3). LMB-2 was administered to 35 patients for a total of 59 cycles. Dose-limiting toxicity at the 63 microg/kg level was reversible and included transaminase elevations in one patient and diarrhea and cardiomyopathy in another. LMB-2 was well tolerated in nine patients at the maximum-tolerated dose (40 microg/kg QOD x 3); toxicity was transient and most commonly included transaminase elevations (eight patients) and fever (seven patients). Only six of 35 patients developed significant neutralizing antibodies after the first cycle. The median half-life was 4 hours. One hairy cell leukemia (HCL) patient achieved a complete remission, which is ongoing at 20 months. Seven partial responses were observed in cutaneous T-cell lymphoma (one patient), HCL (three patients), chronic lymphocytic leukemia (one patient), Hodgkin's disease (one patient), and adult T-cell leukemia (one patient). Responding patients had 2 to 5 log reductions of circulating malignant cells, improvement in skin lesions, and regression of lymphomatous masses and splenomegaly. All four patients with HCL responded to treatment. LMB-2 has clinical activity in CD25(+) hematologic malignancies and is relatively nonimmunogenic. It is the first recombinant immunotoxin to induce major responses in cancer. LMB-2 and similar agents that target other cancer antigens merit further clinical development.


Calcium currents and peptide release from neurohypophysial terminals are inhibited by ethanol.
The effects of EtOH on peptide release and on high-threshold, voltage-activated calcium (Ca++) channels were examined in acutely dissociated rat neurohypophysial terminals. These terminals release the peptide hormones, arginine vasopressin (AVP) and oxytocin. Release of AVP from isolated intact neurohypophyses, induced by either electrical stimulation or elevated potassium, was inhibited by clinically relevant concentrations of EtOH. "Whole-cell" patch-clamp recording methods were used to study the effects of EtOH on voltage-activated Ca++ currents (ICa) in the peptidergic nerve terminals. Amplitudes of both fast-inactivating ICa and long-lasting ICa were reduced in EtOH, and the reduction in ICa did not result from a shift in its current-voltage or steady-state inactivation relationships. Only the fast-inactivating component recovered after removal of EtOH. The effects of EtOH on ICa could not be attributed to changes in osmolarity. In contrast to ICa, the fast, transient K+ current was insensitive to EtOH. These results suggest that EtOH-induced reduction of ICa in the peptidergic nerve terminals produces a decrease in AVP release, resulting in lowered plasma AVP levels.


[Care in situation of severe renal insufficiency: social representations elaborated by adolescents].
The objective of the study was to apprehend the social representations of teenagers in relation to care in situation of Severe Renal Insufficiency. It was applied the test of free association of words to 70 teenagers and interview semi-structured with eight teenagers. It was evoked 1630 words from the stimulus disease, health, dialysis, care of oneself, professional care and familiar care. From the interviews it was constructed two thematic cores that bring meanings about the familiar care and professional care that influence in ways of notice and act in relation to care to health. It concluded that social representation of teenager focuses the meanings of sickening and care, marked by linking among the practices of care and psycho-affective and social relations impregnated in their living.


Pien Tze Huang inhibits liver metastasis by targeting TGF-β signaling in an orthotopic model of colorectal cancer.
Metastasis is the leading cause of cancer-related mortality in almost all types of cancers, including colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a critical process during the metastatic cascade. This process may be a potential target for the diagnosis and treatment of CRC. Pien Tze Huang (PZH), a well-known traditional Chinese formula, has been demonstrated to be clinically effective in treating various types of human malignancies, including CRC. Our published data suggest that PZH can induce apoptosis, as well as inhibit cell proliferation and tumor angiogenesis, thus suppressing CRC growth in vitro and in vivo. We evaluated the therapeutic efficacy of PZH against CRC metastasis using a CRC liver metastasis mouse model to further explore the mechanisms underlying the antitumor action of PZH. MTT, migration, and Matrigel invasion assays were used to assess the effect of PZH on cell viability, migration and invasion. We then established an orthotopic liver metastasis model of colon cancer using microsurgical techniques. Mice were intragastrically administered 234 mg/kg/day dose of either PZH or saline for 14 days. The body and tumor weights of the mice were measured after they were sacrificed. Moreover, we examined the effect of PZH inhibition on liver metastasis. Finally, EMT-related proteins and the TGF-β signaling pathway were assessed using immunohistochemical staining (IHS). The present data revealed that PZH significantly inhibited the migration and invasion of CT-26 cells in a dose-dependent manner, which affirmed the inhibitory effect of PZH on CRC cell metastasis. No significant change was observed between the in vivo primary tumor growth and body weight. However, the control group had five cases of liver metastasis (5/6), whereas one case was found in the PZH group (1/6). Thus, PZH exhibited therapeutic efficacy against CRC metastasis without apparent toxicity. The inhibitory effect of PZH on EMT resulted in an increase in E-cadherin expression, as well as a decrease in N-cadherin expression. In addition, PZH significantly inhibited TGF-β, as well as the phosphorylation of Smad2/3 and Smad4 in the tumor tissues, indicating its suppressive action on TGF-β signaling. These molecular effects ultimately resulted in the inhibition of cancer cell EMT and tumor metastasis.


Validity and reliability of an Italian version of the revised Leeds disability questionnaire for patients with ankylosing spondylitis.
The purpose of the present study was to produce an Italian version of the Revised Leeds Disability Questionnaire (LDQ) in a group of patients with ankylosing spondylitis, and to examine the psychometric properties of this version, evaluating its internal consistency, external validity and reliability. The LDQ was administered to 60 Caucasian patients affected by ankylosing spondylitis (50 males, 10 females, mean age 46.1 +/- 14.2 yr, range 22-74, median disease duration 4.5 yr, range 1-24) together with the Italian version of the Stanford Health Assessment Questionnaire (HAQ), and anthropometric measurements. Thirty patients completed the questionnaire after a 10-day interval. Internal consistency was evaluated with Cronbach's alpha coefficient of reliability. Construct validity of the LDQ was evaluated using the correlation between the HAQ and anthropometric measurements. Test-retest reliability was assessed with the intraclass correlation coefficient. All patients completed the validation study. The questionnaire was internally consistent (alpha=0.90). A significant correlation was recorded between the LDQ and the HAQ score (rho=0.841, P<0.01) and the anthropometric measurements. Test-retest reliability showed a good correlation coefficient (intraclass correlation=0.97). The Italian LDQ is a valid and reliable instrument for detecting and measuring functional disability in patients with ankylosing spondylitis. Our results confirm the utility of this questionnaire as a valid and feasible functional measure for patients with ankylosing spondylitis.


Drosophila as a Model for Tumor-Induced Organ Wasting.
In humans, cancer-associated cachexia is a complex syndrome that reduces the overall quality of life and survival of cancer patients, particularly for those undergoing chemotherapy. The most easily observable sign of cachexia is organ wasting, the dramatic loss of skeletal muscle and adipose tissue mass. Estimates suggest that 80% of patients in advanced stages of cancer show signs of the syndrome and about 20% of cancer patients die directly of cachexia. Because there is no treatment or drug available to ameliorate organ wasting induced by cancer, cachexia is a relevant clinical problem. However, it is unclear how cachexia is mediated, what factors drive interactions between tumors and host tissues, and which markers of cachexia might be used to allow early detection before the observable signs of organ wasting. In this chapter, we review the current mammalian models of cachexia and the need to use new models of study. We also explain recent developments in Drosophila as a model for studying organ wasting induced by tumors and how fly studies can help unravel important mechanisms that drive cachexia. In particular, we discuss what lessons have been learned from tumor models recently reported to induce systemic organ wasting in Drosophila.


Statistical Analyses for Key Risk Factor Identification and Prediction of Chronic Kidney Disease.
Chronic renal disease, also known as chronic kidney disease (CKD) is a common disease and is a concern of public health management. Effective techniques for early CKD prediction are desirable. Given a set of biomarkers, Machine learning techniques are known for predicting CKD. This work aims of predicting CKD given clinical data. The proposed work suggests a methodology that includes data prepossessing (i.e. data cleaning, addressing null values and normalizing), applying statistical methodologies for finding key risk factors. Finally, using the most significant risk factors, machine learning techniques is applied to prognosticate the onset of CKD. The proposed approach has been tested with two data sets and proves to be fast, cost-effective and accurate compared to the existing state of the art techniques.Clinical relevance- Prognosticating CKD with a higher accuracy using a minimum number of risk factors is a significant aspects of healthcare informatics, where the treatment cost and predictive results both are optimized towards the betterment of patients.


Infliximab has no apparent effect in the inner ear hearing function of patients with rheumatoid arthritis and ankylosing spondylitis.
Animal studies suggest that tumor necrosis factor (TNF) alpha blockers may pass to the inner ear in adequate concentration. In this prospective study, we aimed to evaluate the effect of infliximab on the inner ear hearing function in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). The patients with high disease activity, who were planned to begin infliximab for therapy by physical medicine and rehabilitation department, were referred to ear-nose-throat clinic for consultation. After physical and otoscopic examination, audiological tests were performed. Air conduction thresholds between 250 and 8,000 Hz, bone conduction thresholds between 500 and 4,000 Hz, pure tone average, speech discrimination scores, distortion product otoacoustic emission (DPOAE) were used to evaluate the hearing function. The tests were repeated 2 and 6 months after the initiation of the drug "infliximab." A total of 44 ears of 22 patients (17 males and 5 females) were evaluated. Fifteen patients had a diagnosis of AS, and seven patients had RA. After initiation of infliximab therapy, statistically significant improvement was observed in disease activity scores [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, Disease Activity Score 28 (DAS-28) for RA] after 2 and 6 months (p < 0.05). We did not find any statistically significant difference between the air conduction thresholds, bone conduction thresholds, pure tone average, speech discrimination scores, and measurements of DPOAE before the initiation of treatment and after 2 and 6 months (p > 0.05). Any problem about the balance, vertigo, or dizziness was not reported from the patients during the treatment period. As a result, our study showed that there was no notable change or deterioration in the hearing function of the patients with AS and RA who were treated with infliximab. Further studies with higher number of patients with AS and RA and also with different TNF alpha inhibitors are needed to make more valid conclusion.


Intestinal parasite infections in a rural community of Rio de Janeiro (Brazil): Prevalence and genetic diversity of Blastocystis subtypes.
Intestinal parasitic infections are considered a serious public health problem and widely distributed worldwide, mainly in urban and rural environments of tropical and subtropical countries. Globally, soil-transmitted helminths and protozoa are the most common intestinal parasites. Blastocystis sp. is a highly prevalent suspected pathogenic protozoan, and considered an unusual protist due to its significant genetic diversity and host plasticity. A total of 294 stool samples were collected from inhabitants of three rural valleys in Rio de Janeiro, Brazil. The stool samples were evaluated by parasitological methods, fecal culture, nested PCR and PCR/Sequencing. Overall prevalence by parasitological analyses was 64.3% (189 out of 294 cases). Blastocystis sp. (55.8%) was the most prevalent, followed by Endolimax nana (18.7%), Entamoeba histolytica complex (7.1%), hookworm infection (7.1%), Entomoeba coli (5.8%), Giardia intestinalis (4.1%), Iodamoeba butchilii (1.0%), Trichuris trichiura (1.0%), Pentatrichomonas hominis (0.7%), Enterobius vermicularis (0.7%), Ascaris lumbricoides (0.7%) and Strongyloides stercoralis (0.7%). Prevalence of IPIs was significantly different by gender. Phylogenetic analysis of Blastocystis sp. and BLAST search revealed five different subtypes: ST3 (34.0%), ST1 (27.0%), ST2 (27.0%), ST4 (3.5%), ST8 (7.0%) and a non-identified subtype. Our findings demonstrate that intestinal parasite infection rates in rural areas of the Sumidouro municipality of Rio de Janeiro, Brazil are still high and remain a challenge to public health. Moreover, our data reveals significant genetic heterogeneity of Blastocystis sp. subtypes and a possible novel subtype, whose confirmation will require additional data. Our study contributes to the understanding of potential routes of transmission, epidemiology, and genetic diversity of Blastocystis sp. in rural areas both at a regional and global scale.


Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.
Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3delta/als3delta mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin-cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins.


A framework for image-based classification of mitotic cells in asynchronous populations.
High content screening (HCS) has emerged an important tool for drug discovery because it combines rich readouts of cellular responses in a single experiment. Inclusion of cell cycle analysis into HCS is essential to identify clinically suitable anticancer drugs that disrupt the aberrant mitotic activity of cells. One challenge for integration of cell cycle analysis into HCS is that cells must be chemically synchronized to specific phases, adding experimental complexity to high content screens. To address this issue, we have developed a rules-based method that utilizes mitotic phosphoprotein monoclonal 2 (MPM-2) marker and works consistently in different experimental conditions and in asynchronous populations. Further, the performance of the rules-based method is comparable to established machine learning approaches for classifying cell cycle data, indicating the robustness of the features we use in the framework. As such, we suggest the use of MPM-2 analysis and its associated expressive features for integration into HCS approaches.


Maternal emotional distress and infant sleep: A longitudinal study from pregnancy through 18 months.
This longitudinal study examined whether changes in maternal emotional distress (depressive, anxiety, and parenting-stress symptoms) predict changes over time in subjective and objective infant sleep. We recruited 226 Israeli expectant mothers (M age 28.8 ± 3.3), most representing the middle-upper socioeconomic class. Maternal depressive and anxiety symptoms were assessed in the third trimester of pregnancy. After delivery (3, 6, 12, and 18 months), infant sleep quality and duration were assessed for 5 nights using actigraphy and the Brief Infant Sleep Questionnaire. Maternal depressive and anxiety symptoms were reassessed, and maternal parenting-stress was measured at all postpartum assessments. The findings demonstrated significant correlations between maternal emotional distress and mothers' subjective ratings of infant sleep problems (rs >.16 and < .46). Latent trajectory analyses indicated no significant effects of changes in maternal emotional distress variables on changes in infant subjective or objective sleep. Post hoc power analyses demonstrated that we had enough statistical power to reject the null hypothesis. The results suggest that mothers with higher emotional distress symptoms-and especially those with parenting-stress symptoms-are more likely to experience their infant's sleep as problematic. However, our results challenge the assumption that maternal emotional distress symptoms contribute to infant sleep disturbances over time. The findings are relevant to mothers with mild to moderate emotional distress symptoms and must not be generalized to mothers who experience major clinical depression. Future studies should evaluate whether maternal emotional distress interacts with other risk factors, such as infant temperament, to predict infant sleep disturbances. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Design and application of electron-transporting organic materials.
Operating lifetime is the main problem that complicates the use of polymeric light-emitting diodes (LEDs). A class of electron transport (ET) polymers [poly(aryl acrylate) and poly(aryl ether)s] is reported in which moieties with high electron affinities are covalently attached to stable polymer backbones. Devices based on poly(p-phenylenevinylene) (PPV) prepared with these materials exhibited a 30-fold improvement in stability and, in one case, dramatically lower (10 volts versus about 30 volts) operating voltage relative to those having conventional ET layers. The current-carrying capacity of indium tin oxide-PPV-polymeric ET layer-aluminum LEDs was also increased by a factor of 30. These improvements lead to an enhancement in power efficiency of nearly an order of magnitude. Choosing polymers with high glass transition temperatures increases device lifetime.