Delayed diagnosis of tuberculosis in patients with human immunodeficiency virus infection.
To determine the frequency with which the diagnosis of tuberculosis is delayed in patients with concomitant human immunodeficiency virus (HIV) infection, and to identify reasons for such delays. We reviewed medical records of 52 consecutive HIV-infected patients with culture-proven tuberculosis seen at a 1,900-bed general hospital serving a predominantly indigent population in Los Angeles, where the prevalences of HIV infection and tuberculosis are high. The late-treatment (LT) group consisted of 25 patients in whom tuberculosis was untreated prior to death (n = 6) or treated more than 22 days after presentation (n = 19). The early-treatment (ET) group comprised 27 patients in whom antituberculous therapy was begun less than 16 days after presentation. Symptoms, physical and laboratory findings, chest roentgenographic abnormalities suggestive of tuberculosis (hilar adenopathy, pleural effusion, miliary pattern, cavitation, predominant upper lobe infiltrate), and frequencies of concomitant nontuberculous disease were similar in LT and ET groups. Delayed diagnosis of tuberculosis was attributable to errors in management in 21 (84%) of 25 LT group patients. The most common error was failure to obtain at least three sputum samples for acid-fast smear and mycobacterial culture in patients with clinical and chest roentgenographic findings compatible with tuberculosis (15 cases). Acid-fast sputum smears were positive in 25 (61%) of 41 cases of pulmonary tuberculosis. Acid-fast smears of stool were positive in eight (42%) of 19 cases. Blood cultures yielded Mycobacterium tuberculosis in 18 (38%) of 48 cases. Delayed therapy of tuberculosis in HIV-infected patients at our medical center was common and was not due to atypical manifestations of tuberculosis. In most cases, delays could have been avoided if adequate numbers of sputum samples for acid-fast smear and mycobacterial culture had been obtained, and if empiric antituberculous therapy had been given to symptomatic patients in whom chest roentgenographic findings were suggestive of mycobacterial disease.


Expression of BAFF and BAFF-R in the synovial tissue of patients with rheumatoid arthritis.
The elevated expression of B-cell-activating factor belonging to the TNF family (BAFF) is associated with systemic autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the distribution of BAFF and its receptor BAFF-R in the cells residing in the rheumatoid synovium. The expression of BAFF and BAFF-R in synovial tissues obtained from 12 RA patients was examined by immunohistochemistry and flow cytometry. The mRNA expression of these molecules was determined by reverse transcriptase polymerase chain reaction (RT-PCR). Soluble BAFF levels were measured with an enzyme-linked immunosorbent assay (ELISA). Fibroblast-like synoviocytes (FLS) purified from the RA (RA-FLS) were co-cultured with peripheral B cells. The degree of apoptosis in the B cells was measured to assess the effects on the viability of the B cells. The RA synovium showed focal or diffuse infiltration of mononuclear cells (MNCs), and one specimen showed germinal centre (GC)-like structures. Synovial sublining cells, but not lining cells, expressed BAFF. These sublining cells were negative for BAFF-R. BAFF and BAFF-R were expressed in B and T cells extracted from the RA synovium. Notably, RA-FLS spontaneously expressed cytoplasmic BAFF after 4-6 passages; however, they did not express BAFF or BAFF-R on their cell surface. RA-FLS could support the survival of B cells by preventing their apoptosis, but its effect on B cells might not be BAFF dependent. BAFF and BAFF-R are widely expressed in the RA synovium. The cells residing in the RA synovium might affect each other through BAFF.


Bingeing rats: a model of intermittent excessive behavior?
Intermittent excessive behaviors (IEB) characterize a variety human disorders including binge eating, drug abuse, alcoholism, aberrant sexual conduct, and compulsive gambling. Clinical co-morbidity exists among IEB, and limited treatment options are available. The use of behavioral models of bingeing and other feeding protocols is beginning to clarify neural similarities and differences that exist between IEB directed toward obtaining and consuming food and IEB directed toward obtaining and consuming drugs of abuse. Research from this laboratory using a limited access binge-type eating protocol may provide new insight into IEB.


Determination of solvation descriptors for terpene hydrocarbons from chromatographic measurements.
Gas chromatographic retention data on 107 terpene hydrocarbons from the literature together with other data have been used to obtain a set of Abraham descriptors for these 107 compounds. For 88 aliphatic cyclic terpene hydrocarbons, a fragmentation scheme was constructed that allows key descriptors to be estimated just from structure. The total set of descriptors, including those estimated by the fragmentation schemes, were then used to predict water-octanol partition coefficients for the 88 compounds, there being good agreement with values calculated from a number of well-known programs. For a small number of terpene hydrocarbons, there was good agreement between predicted and experimental values of nasal pungency thresholds, and predicted and experimental gas-blood, gas-oil, and gas-water partition coefficients. It is suggested that the descriptors obtained for the 107 terpene hydrocarbons can be used to predict water-solvent partition coefficients, gas-solvent partition coefficients, and partition coefficients in a number of biological systems.


Neural connections between antrum and duodenum.
Postprandial coordination of antroduodenal motility partly takes place via intrinsic mural pathways. The nature and origin of these nerve fibers have not yet been clarified. In this investigation using fluorochromic substances injected into the antrum and duodenum it was demonstrated that common central neurons for the antroduodenal area exist in the vagal nucleus.


Immunogenicity of Torpedo acetylcholine receptor in the context of different rat MHC class II haplotypes and non-MHC genomes.
The nicotinic acetylcholine receptor (nAChR) is the autoantigen in seropositive myasthenia gravis (MG), a T-cell-dependent B-cell-mediated autoimmune disease. The nAChR is a pentameric transmembrane receptor comprising alpha alpha beta gamma delta chains. During early postnatal development the nAChR gamma chain is replaced by the nAChR epsilon chain. We tested the myasthenogenicity in experimental autoimmune myasthenia gravis (EAMG) of the native nAChR derived from the electric ray Torpedo californica (T-nAChR) in various inbred and MHC -congenic rat strains. Differences in the disease course emerged dependent on the MHC haplotype and non-MHC genes. Interestingly, no tested rat strain was completely resistant to EAMG, but there were strong differences in disease severity mainly depending on the MHC haplotype. In the LEW non-MHC genome, the B-cell response and the severity of EAMG were dependent on the expressed MHC haplotype. This study underscores the influence of genetic factors on disease severity, disease course and on the degree of the emerging antibody responses in EAMG.


A Functional Polymorphism in HIF-3α Is Related to an Increased Risk of Ischemic Stroke.
Hypoxia-inducible factor-3α (HIF-3α), a member of HIF family, can mediate adaptive responses to low oxygen and ischemia. It is believed that HIF plays crucial roles in stroke-related diseases. However, there are no reports on the association between HIF-3α genetic variants and ischemic stroke (IS) susceptibility. Therefore, we examined the association between HIF-3α gene polymorphisms (rs3826795, rs2235095, and rs3764609) and IS risk. The study population included 302 controls and 310 patients with ischemic stroke. Three polymorphisms in HIF-3α (rs3826795, rs2235095, and rs3764609) were genotyped using SNPscan technique. Our study showed a strong association of rs3826795 in HIF-3α with the risk of IS. The genotype and allele frequencies were shown to differ between the two groups. The rs3826795 in an intron of HIF-3α was related to a prominent increased IS risk (AA vs GG adjusted odd ratio [OR], 2.21; 95% confidence intervals [95% CI], 1.10-4.44; P = 0.03; AA vs AG/GG OR = 1.74, 95% CI, 1.02-2.97, P = 0.04; A vs G OR = 1.48, 95% CI, 1.05-2.07, P = 0.02). Logistic regression analysis suggested that rs3826795 posed a risk factor for IS in addition to common factors. Furthermore, when compared to controls, increased levels of homocysteic acid and level of non-esterified fatty acid were found in the cases (P < 0.01). However, no significant association was found between rs2235095 or rs3264609 and IS risk. These findings indicated that the rs3826795 polymorphism may be a potential target for predicting the risk of IS.


Referral pathways for chronic pain patients from Canadian emergency departments: emergency physicians' practices, perspectives, and recommendations.
Patients with chronic pain account for 12-20% of total emergency department (ED) and was the primary presenting concern among 37% of patients who visited the ED > 12 times per year. Despite this, emergency physicians receive little focused training managing these patients, and there is a paucity of effective referral pathways from EDs, despite strong evidence that chronic pain is best treated longitudinally in multidisciplinary clinics. This study sought to explore the practices, perspectives, and recommendations of current Canadians emergency physicians in better serving the chronic pain patient (CPP) population in the ED. An electronic cross-sectional survey was administered to members of the Canadian Association of Emergency Physicians (CAEP), consisting of 16 multiple choice and numerical response questions. Responses were summarized descriptively as percentages and as the median and inter-quartile range (IQR) for quantitative variables. The study was completed by 169/1635 respondents for a response rate of 10%. The most common presentations respondents saw were neuropathic pain and centrally mediated disorders (23% each) and low back pain (19%). 86% of respondents felt that chronic pain patients did not get appropriate referrals from the ED, and 70% of respondents were unaware of where they could even refer chronic pain patients from the ED. 96% of respondents felt that their ED did not have an effective referral pathway for chronic pain patients. Rapid access clinics for common conditions, reduced pain clinic wait times, and clear ED referral pathways were the commonest recommendations by respondents. There is a clear need to increase the accessibility to outpatient pain medicine clinics for chronic pain patients presenting to the ED. ED and pain medicine providers must collaborate to establish mutually beneficial referral pathways from EDs, and to advocate for increased funding for rapid access outpatient pain clinics.


Angular-spectrum-dependent interference.
Optical interference is not only a fundamental phenomenon that has enabled new theories of light to be derived but it has also been used in interferometry for the measurement of small displacements, refractive index changes, and surface irregularities. In a two-beam interferometer, variations in the interference fringes are used as a diagnostic for anything that causes the optical path difference (OPD) to change; therefore, for a specified OPD, greater variation in the fringes indicates better measurement sensitivity. Here, we introduce and experimentally validate an interesting optical interference phenomenon that uses photons with a structured frequency-angular spectrum, which are generated from a spontaneous parametric down-conversion process in a nonlinear crystal. This interference phenomenon is manifested as interference fringes that vary much more rapidly with increasing OPD than the corresponding fringes for equal-inclination interference; the phenomenon is parameterised using an equivalent wavelength, which under our experimental conditions is 29.38 nm or about 1/27 of the real wavelength. This phenomenon not only enriches the knowledge with regard to optical interference but also offers promise for applications in interferometry.


Assessing the performance of two dry powder inhalers in preschool children using an idealized pediatric upper airway model.
High prevalence of pulmonary diseases in childhood requires inhalable medication even for young children. Little is known about the efficiency of aerosol therapy especially in preschool children. One factor which limits the lung dose is the upper airway geometry. Based on clinical data a recently developed idealized pediatric upper airway model (children 4-5 years) was used to investigate the performance of two dry powder inhalers (Easyhaler and Novolizer). In vitro investigations were first examined using steady flow rates and an inhalation volume of 1L. Chosen flow rates were 28, 41 and 60L/min (Easyhaler) and 45, 60 and 75L/min (Novolizer). Afterwards inhalation profiles simulated by an electronic lung were included. The investigations showed high amounts of drug particles (up to 80%) which were deposited in the upper airway model. The pulmonary deposition in vitro using the Easyhaler was about 28% (28-60L/min) and 22% (inhalation profile). Using the Novolizer in vitro pulmonary doses of 8-12% (45-75L/min) and about 5% (inhalation profile) were observed. The idealized model shows good performance reproducibility of dry powder inhalers. We have shown that age-dependent models might be appropriate tools for formulation and device development in pediatric age groups.


Experimental studies of the application of the Er:YAG laser on dental hard substances: I. Measurement of the ablation rate.
Up to now lasers have not achieved any practical importance in dentistry for drilling teeth because of considerable damage to the surrounding tissue. We studied the application of pulsed 2.94 microns Er:YAG laser radiation in vitro on extracted teeth to remove enamel, dentin, and carious lesions. The depth and diameter of laser-drilled holes were measured as a function of pulse number and radiant exposure. The tissue removal is very effective both for dentin and enamel.


Evaluating anemia using contrast-enhanced spectral detector CT of the chest in a large cohort of 522 patients.
The blood of patients with anemia demonstrates distinctly lower attenuation in unenhanced CT images. However, the frequent usage of intravenous contrast hampers evaluation of anemia. Spectral detector computed tomography (SDCT) allows for reconstruction of virtual non-contrast images (VNC) from contrast-enhanced data (CE). The purpose of this study was to evaluate whether VNC allow for prediction of anemia. Five hundred twenty-two patients with CE-SDCT of the chest and accessible serum hemoglobin (HbS) were retrospectively included. Patients were assigned to three groups (severe anemia, moderate/mild anemia, and healthy) based on recent lab tests (≤ 7 days) for HbS following gender and the WHO definition of anemia. CT attenuation was determined using two ROI in the left ventricular lumen and one ROI in the descending thoracic aorta. ROI were placed on CE and copied to VNC. ANOVA, linear regression, and receiver operating characteristics were used for statistic evaluation. Average HbS was 11.6 ± 2.4 g/dl. Attenuation on VNC showed significant differences between healthy patients, patients with mild/moderate anemia, and severely anemic patients (all p ≤ 0.05). Applying cutoffs of 39.2/37.6 HU and 33.6/32.7 HU allowed to differentiate between healthy, mild/moderately, and severely anemic men/women (AUC 0.857/0.833 and 0.879/0.932). A linear relationship between HbS and attenuation on VNC was established (r2 = 0.54, HbS = - 0.875 + 0.329 × HU). An approximation of HbS and presence of anemia can be conducted based on simple attenuation measurements in contrast-enhanced SDCT examinations enabled by VNC imaging. • While the attenuation of blood is a previously described biomarker for anemia in non-contrast images, virtual non-contrast images from spectral detector CT circumvent this limitation and allow for diagnosis of anemia in contrast-enhanced scans. • Attenuation of blood in virtual non-contrast images derived from spectral detector CT shows a moderate correlation to serum hemoglobin levels. • Presence of anemia be estimated in virtual non-contrast images using proposed cutoffs of 39.2 HU and 37.6 HU for men and women, respectively, to differentiate between healthy and anemic patients.


Radiographic joint space width is correlated with 4-year clinical outcomes in patients with knee osteoarthritis: data from the osteoarthritis initiative.
To evaluate if quantitative joint space width (JSW) measurements from radiographs correlate with 4-year Knee injury and Osteoarthritis Outcome Scores (KOOS) and clinical performance measures. The study group consisted of 942 patients with symptomatic knee osteoarthritis (OA). 4-year outcomes for six measures (KOOS Pain, Symptom, Quality of Life, and Function scores, 20-m walk pace, and chair stand time) were used to create six multiple linear regression models. Primary predictors were baseline minimum JSW and 4-year change in JSW measured from fixed flexion radiographs. Age, gender, body mass index (BMI), race, knee alignment, and baseline measures of the outcomes of interest were covariates. Lower baseline minimum JSW and a greater decrease in 4-year JSW significantly correlated with worse 4-year KOOS Pain, Symptom, and Quality of Life. With all other factors constant, a 4.1, 4.8, and 5.6 mm lower baseline JSW correlated with a clinically significant eight-point drop in 4-year KOOS Pain, Symptom, and Quality of Life scores respectively. Additionally, a 3.5, 3.1, and 4.0 mm loss of JSW over 4 years correlated with a clinically significant eight-point drop in 4-year KOOS Pain, Symptom, and Quality of Life scores respectively. Our results indicate quantitative radiographic JSW measurements correlate with 4-year clinical outcomes. Since patients with narrower JSW at the onset of study had lower KOOS scores at 4 years even after controlling for 4-year change in JSW and baseline KOOS scores, clinical outcomes in knee OA may be predetermined once the disease process begins. These findings suggest early treatment with disease modifying therapies may be necessary to influence outcomes.


Effect of the acyl-CoA:cholesterol acyltransferase inhibitor, E5324, on experimental atherosclerosis in rabbits.
E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and orally absorbable acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was evaluated for its antiatherosclerotic and antihyperlipidemic effects in cholesterol-fed hypercholesterolemic rabbits. When administered concurrently with a high-cholesterol (0.5% cholesterol) diet for 12 weeks, E5324 (0.0025%, 0.005% and 0.01% in diet) lowered plasma total cholesterol levels dose-dependently (by about 55%-87% at the end of the experiment compared with the control) and also reduced atherosclerotic plaque formation (about 90% reduction at the highest dose; P < 0.01). In pre-established hypercholesterolemic rabbits, which had been pre-fed a high-cholesterol diet for 8 weeks, E5324 administered in the same diet at a dose of 0.005%, 0.01% or 0.02% for 4 weeks significantly reduced plasma cholesterol levels dose-dependently. Cholesterol content and ACAT activity in the aortic arch were also decreased (by about 72% and 58% at the highest dose, respectively) compared with the control. Another ACAT inhibitor, CI-976, had a similar action, but cholestyramine and probucol (2% and 1% in diet, respectively) lacked anti-atherosclerotic activity in this model. Furthermore, when pre-established hypercholesterolemic rabbits were fed normal rabbit chow diet with or without 0.02% E5324 for 4 weeks, changes in plasma cholesterol levels were similar in both E5324-treated and control groups. On the other hand, E5324 significantly reduced cholesterol content and ACAT activity in the aortic arch (by about 52% and 50%, respectively) compared with the control group. These results indicate that E5324 not only has hypocholesterolemic activity, but also may have a direct effect on the arterial wall in experimental atherosclerosis.


Serum proteomics in biomedical research: a systematic review.
Proteins that are important indicators of physiological or pathological states may contribute to the early diagnosis of disease, which may provide a basis for identifying the underlying mechanism of disease development. Serum, contains an abundance of proteins, offers an easy and inexpensive approach for disease detection and possesses a high potential to revolutionize the diagnostics. These differentially expressed proteins in serum have become an important role to monitoring the state for disease. Availability of emerging proteomic techniques gives optimism that serum can eventually be placed as a biomedium for clinical diagnostics. Advancements have benefited biomarker research to the point where serum is now recognized as an excellent diagnostic medium for the detection of disease. Comprehensive proteome of human serum fluid with high accuracy and availability has the potential to open new doors for disease biomarker discovery and for disease diagnostics, providing insights useful for future study. Thus, this review presents an overview of the value of serum as a credible diagnostic tool, and we aim to summarize the proteomic technologies currently used for global analysis of serum proteins and to elaborate on the application of serum proteomics to the discovery of disease biomarkers, and discuss some of the critical challenges and perspectives for this emerging field.


Bioinformatics and systems biology.
Delivering personalized therapeutic options to cancer patients based on the genetic and molecular aberrations of the tumor offers great promise to improve the outcomes of cancer therapy. Significant progress in biotechnology has allowed the measurement of tens of thousands of "omic" data points across multiple levels (DNA, RNA protein, metabolomics) from a single tumor biopsy sample in a reasonable time frame for making clinical decisions. With this data in hand, the challenge from the bioinformatics and systems biology point of view is how does one convert data into information and knowledge that can improve the delivery of personalized therapy to the patient.


Prolonged vortex formation during the ejection period in the left ventricle with low ejection fraction: a study by vector flow mapping.
Vortex formation in the left ventricle (LV) can be visualized by novel vector flow mapping (VFM) based on color Doppler and speckle tracking data. The aim of this study was to evaluate the impact of a vortex during the ejection period using VFM. Color Doppler images were obtained to produce VFM images in 80 subjects (20 normal, 29 with dilated cardiomyopathy, and 31 with old myocardial infarction). The duration of the LV vortex was measured and expressed as the ratio to the ejection time (VTRe). The VTRe showed significant correlations with EDV (ρ = 0.672, p < 0.001), ESV (ρ = 0.772, p < 0.001), EF (ρ = -0.783, p < 0.001), left atrium diameter (LAd) (ρ = 0.302, p = 0.007), stroke volume (ρ = -0.600, p < 0.001), e' (ρ = -0.389, p < 0.001), a' (ρ = -0.314, p = 0.005), s' (ρ = -0.512, p < 0.001), and E/e' (ρ = 0.330, p = 0.003). The diastolic parameters (e', a', E/e', LAd) were not correlated when they were adjusted by EF. In the normal LV, a vortex existed for only a limited time during the early ejection period. In contrast, the lower the EF was, the longer the vortex remained during systole. Evaluation of vortices by VFM may noninvasively provide novel insights into the pathophysiology of impaired cardiac function.


Multifunctional green synthetized gold nanoparticles/chitosan/ellagic acid self-assembly: Antioxidant, sun filter and tyrosinase-inhibitor properties.
This paper accounts the first example about the development of a self-assembled supramolecular system based on the use of green-synthetized gold nanoparticles (AuNPs) and chitosan (CH), for solubilizing ellagic acid (EA) in water. AuNPs were synthetized by using Punica granatum Juice (PGJ) and, after their synthesis, in order to adsorb ellagic acid on the nanoparticles surface (AuNPs/CH/EA), the chitosan wrapping was performed (AuNPs/CH). For this purpose, chitosan having high viscosity, low and medium molecular weights were used and compared to check the best condition of work. The stability of the proposed system, before and after the addition of ellagic acid, under different conditions of work, i.e. solution pH, temperature and light irradiation were investigated demonstrating the stability of the proposed functional ingredient. The supramolecular system exhibited wide ranging properties such as antioxidant, skin lightening and sunscreen. More specifically, the % of antioxidant activity occurred around 80% and 60% from the DPPH and ABTS assays respectively; the tyrosinase inhibition was around of 50% and the Sun Protection Factor was found to be 20. Thanks to the multi-properties of the proposed functional ingredient it should exhibit several advantageous in cosmetic applications. The ingredient could be a valid alternative to the traditional nanostructured TiO2 and ZnO offering the possibility to have at the same time several properties due to the use of AuNPs (having light absorption and scattering ability, are biocompatible showing low toxicity) and EA. If these positive aspects are associated with the use of an eco-friendly and low-cost protocol for AuNPs synthesis, according to the Green Chemistry principles, a great interesting space is opened towards the study of PGJ-based AuNPs, as multifunctional platform in cosmetic.


Variability in the carbon isotope composition of individual amino acids in plant proteins from different sources: 1 Leaves.
The natural carbon isotope composition of individual amino acids from plant leaf proteins has been measured to establish potential sources of variability. The plant leaves studied, taken from a range of plant groups (forbs, trees, grasses, and freshwater aquatic plants), showed no significant influence of either season or environment (water and light availability) on their Δδ(13)C values. Plant groups did, however, differ in carbon isotope composition, although no consistent differences were identified at the species level. A discriminant analysis model was constructed which allowed leaves from (1) nettles, (2) Pooideae, (3) other Poales, (4) trees and (5) freshwater higher plants to be distinguished from each other on the basis of their natural abundance (13)C/(12)C ratios of individual amino acids. Differences in carbon isotope composition are known to be retained, to some extent, in the tissues of their consumers, and hence an understanding of compound-specific variation in (13)C/(12)C fractional abundance in plants has the potential to provide dietary insights of value in archaeological and ecological studies.


Additive harmful effects of acute kidney injury and acute heart failure on mortality in hospitalized patients.
Organ crosstalk between the kidney and the heart has been suggested. Acute kidney injury (AKI) and acute heart failure (AHF) are well-known independent risk factors for mortality in hospitalized patients. This study aimed to investigate if these conditions have an additive effect on mortality in hospitalized patients, as this has not been explored in previous studies. We retrospectively reviewed the records of 101,804 hospitalized patients who visited two tertiary hospitals in the Republic of Korea over a period of 5 years. AKI was diagnosed using serum creatinine-based criteria, and AHF was classified using International Classification of Diseases codes within 2 weeks after admission. Patients were divided into four groups according to the two conditions. The primary outcome was all-cause mortality. AKI occurred in 6.8% of all patients (n = 6,920) and AHF in 1.2% (n = 1,244). Three hundred thirty-one patients (0.3%) developed both conditions while AKI alone was present in 6,589 patients (6.5%) and AHF alone in 913 patients (0.9%). Among the 5,181 patients (5.1%) who died, 20.8% died within 1 month. The hazard ratio for 1-month mortality was 29.23 in patients with both conditions, 15.00 for AKI only, and 3.39 for AHF only. The relative excess risk of interaction was 11.85 (95% confidence interval, 2.43-21.27), and was more prominent in patients aged <75 years and those without chronic heart failure. AKI and AHF have a detrimental additive effect on short-term mortality in hospitalized patients.


Discriminating pseudoprogression and true progression in diffuse infiltrating glioma using multi-parametric MRI data through deep learning.
Differentiating pseudoprogression from true tumor progression has become a significant challenge in follow-up of diffuse infiltrating gliomas, particularly high grade, which leads to a potential treatment delay for patients with early glioma recurrence. In this study, we proposed to use a multiparametric MRI data as a sequence input for the convolutional neural network with the recurrent neural network based deep learning structure to discriminate between pseudoprogression and true tumor progression. In this study, 43 biopsy-proven patient data identified as diffuse infiltrating glioma patients whose disease progressed/recurred were used. The dataset consists of five original MRI sequences; pre-contrast T1-weighted, post-contrast T1-weighted, T2-weighted, FLAIR, and ADC images as well as two engineered sequences; T1post-T1pre and T2-FLAIR. Next, we used three CNN-LSTM models with a different set of sequences as input sequences to pass through CNN-LSTM layers. We performed threefold cross-validation in the training dataset and generated the boxplot, accuracy, and ROC curve, AUC from each trained model with the test dataset to evaluate models. The mean accuracy for VGG16 models ranged from 0.44 to 0.60 and the mean AUC ranged from 0.47 to 0.59. For CNN-LSTM model, the mean accuracy ranged from 0.62 to 0.75 and the mean AUC ranged from 0.64 to 0.81. The performance of the proposed CNN-LSTM with multiparametric sequence data was found to outperform the popular convolutional CNN with a single MRI sequence. In conclusion, incorporating all available MRI sequences into a sequence input for a CNN-LSTM model improved diagnostic performance for discriminating between pseudoprogression and true tumor progression.


Searching for markers in the hereditary intestinal polyposes.
Oral abnormalities in the intestinal polyposes have been reported by numerous authors. Detection of occult osteomatous and other dental changes in the jaws before development of polyps would be of considerable importance in the early diagnosis of premalignant gastrointestinal disorders. More than 425 individuals from families in whom intestinal polyposis is segregating have received oral-facial examinations. The dental findings may permit early, noninvasive identification of individuals at risk for polyposis.


Electrochemical immunosensor with Cu(I)/Cu(II)-chitosan-graphene nanocomposite-based signal amplification for the detection of newcastle disease virus.
An electrochemical immunoassay for the ultrasensitive detection of Newcastle disease virus (NDV) was developed using graphene and chitosan-conjugated Cu(I)/Cu(II) (Cu(I)/Cu(II)-Chi-Gra) for signal amplification. Graphene (Gra) was used for both the conjugation of an anti-Newcastle disease virus monoclonal antibody (MAb/NDV) and the immobilization of anti-Newcastle disease virus polyclonal antibodies (PAb/NDV). Cu(I)/Cu(II) was selected as an electroactive probe, immobilized on a chitosan-graphene (Chi-Gra) hybrid material, and detected by differential pulse voltammetry (DPV) after a sandwich-type immune response. Because Gra had a large surface area, many antibodies were loaded onto the electrochemical immunosensor to effectively increase the electrical signal. Additionally, the introduction of Gra significantly increased the loading amount of electroactive probes (Cu(I)/Cu(II)), and the electrical signal was further amplified. Cu(I)/Cu(II) and Cu(I)/Cu(II)-Chi-Gra were compared in detail to characterize the signal amplification ability of this platform. The results showed that this immunosensor exhibited excellent analytical performance in the detection of NDV in the concentration range of 100.13 to 105.13 EID50/0.1 mL, and it had a detection limit of 100.68 EID50/0.1 mL, which was calculated based on a signal-to-noise (S/N) ratio of 3. The resulting immunosensor also exhibited high sensitivity, good reproducibility and acceptable stability.


Transforming growth factor beta decreases the immunogenicity of rat islet xenografts (rat to mouse) and prevents rejection in association with treatment of the recipient with a monoclonal antibody to interferon gamma.
Culture of rat islets of Langerhans for 1 week at 37 degrees C with recombinant transforming growth factor beta prolonged the survival of islet xenografts transplanted into diabetic mouse recipients. Treatment of diabetic recipients with a neutralizing monoclonal antibody to murine interferon gamma did not affect the survival of islet xenografts cultured 7 days in control medium. However, treatment of donor islets with transforming growth factor beta in combination with treatment of diabetic recipients with interferon gamma antibody produced a 75% survival of the islet xenografts at 100 days. Fifty percent of the recipients who had accepted their graft for more than 100 days were immune unresponsive to a transplant of freshly isolated islets from the same donor strain.


Independent endothelial functions of PIEZO1 and TRPV4 in hepatic portal vein and predominance of PIEZO1 in mechanical and osmotic stress.
PIEZO1 and TRPV4 are mechanically and osmotically regulated calcium-permeable channels. The aim of this study was to determine the relevance and relationship of these channels in the contractile tone of the hepatic portal vein, which experiences mechanical and osmotic variations as it delivers blood to the liver from the intestines, gallbladder, pancreas and spleen. Wall tension was measured in freshly dissected portal veins from adult male mice, which were genetically unmodified or modified for either a non-disruptive tag in native PIEZO1 or endothelial-specific PIEZO1 deletion. Pharmacological agents were used to activate or inhibit PIEZO1, TRPV4 and associated pathways, including Yoda1 and Yoda2 for PIEZO1 and GSK1016790A for TRPV4 agonism, respectively. PIEZO1 activation leads to nitric oxide synthase- and endothelium-dependent relaxation of the portal vein. TRPV4 activation causes contraction, which is also endothelium-dependent but independent of nitric oxide synthase. The TRPV4-mediated contraction is suppressed by inhibitors of phospholipase A2 and cyclooxygenases and mimicked by prostaglandin E2 , suggesting mediation by arachidonic acid metabolism. TRPV4 antagonism inhibits the effect of agonising TRPV4 but not PIEZO1. Increased wall stretch and hypo-osmolality inhibit TRPV4 responses while lacking effects on or amplifying PIEZO1 responses. The portal vein contains independently functioning PIEZO1 channels and TRPV4 channels in the endothelium, the pharmacological activation of which leads to opposing effects of vessel relaxation (PIEZO1) and contraction (TRPV4). In mechanical and osmotic strain, the PIEZO1 mechanism dominates. Modulators of these channels could present important new opportunities for manipulating liver perfusion and regeneration in disease and surgical procedures.


The loading problem for recursive neural networks.
The present work deals with one of the major and not yet completely understood topics of supervised connectionist models. Namely, it investigates the relationships between the difficulty of a given learning task and the chosen neural network architecture. These relationships have been investigated and nicely established for some interesting problems in the case of neural networks used for processing vectors and sequences, but only a few studies have dealt with loading problems involving graphical inputs. In this paper, we present sufficient conditions which guarantee the absence of local minima of the error function in the case of learning directed acyclic graphs with recursive neural networks. We introduce topological indices which can be directly calculated from the given training set and that allows us to design the neural architecture with local minima free error function. In particular, we conceive a reduction algorithm that involves both the information attached to the nodes and the topology, which enlarges significantly the class of the problems with unimodal error function previously proposed in the literature.


Cross-polarized photon-pair generation and bi-chromatically pumped optical parametric oscillation on a chip.
Nonlinear optical processes are one of the most important tools in modern optics with a broad spectrum of applications in, for example, frequency conversion, spectroscopy, signal processing and quantum optics. For practical and ultimately widespread implementation, on-chip devices compatible with electronic integrated circuit technology offer great advantages in terms of low cost, small footprint, high performance and low energy consumption. While many on-chip key components have been realized, to date polarization has not been fully exploited as a degree of freedom for integrated nonlinear devices. In particular, frequency conversion based on orthogonally polarized beams has not yet been demonstrated on chip. Here we show frequency mixing between orthogonal polarization modes in a compact integrated microring resonator and demonstrate a bi-chromatically pumped optical parametric oscillator. Operating the device above and below threshold, we directly generate orthogonally polarized beams, as well as photon pairs, respectively, that can find applications, for example, in optical communication and quantum optics.


Portal Closure After Segmental Posterior Labral Repair for Posterior Shoulder Instability.
Posterior instability, although an uncommon shoulder pathology, is reported most frequently in the athletic population. Arthroscopic repair has emerged as the main surgical treatment modality for posterior instability. However, when compared with arthroscopic repair for anterior instability, the results of this procedure remain suboptimal. The creation of iatrogenic defects in the capsule, due to cannula placement, is a possible culprit. Because these defects typically do not heal satisfactorily, they become stress risers within the capsule itself, which may lead to recurrent instability or an otherwise compromised repair construct. Therefore, we find that routine intraoperative repair of these defects after repair can reduce the risk of injury and possibly improve long-term outcomes. In this article, we illustrate the repair of a posterior segmental tear using all-suture knotless implants with closure of the posterior and posterior-inferior portals after stabilization.


Bilateral globus pallidus internus (GPi) deep brain stimulation for cervical dystonia: Effects on motor and non-motor symptoms within 5 years follow.
Cervical Dystonia ("CD") is a movement disorder characterised by sustained muscle contractions in the neck, causing involuntary posturing. Deep brain stimulation ("DBS") of the globus pallidal internus (GPi) is advanced treatment for pharmaco-refractory patients. As CD is a rare disease, cohort studies are often limited to patients of heterogenous disease profile, small sample size or short follow-up. This study firstly aimed to measure the efficacy of GPi-DBS on motor and non-motor symptoms of CD. A secondary aim was to evaluate if clinical factors - such as age, disease duration and baseline disease severity - influence variability of motor outcomes. 37 idiopathic CD patients were recruited from movement disorders clinics at The Walton NHS Foundation Trust, Liverpool, UK. Patients were assessed pre-operatively, and 1 year, 3 years and 5 years post-operatively with the following clinical scales: Toronto Western Spasmodic Torticollis Rating Scale ("TWSTRS"), Hospital Anxiety and Depression Scale and EuroQuol-5D. GPI-DBS significantly improved overall TWSTRS scores by 57% from baseline to 5Y FU (p < 0.001). It also significantly improved TWSTRS severity, disability, and pain sub-scores by 72%, 59% and 46% respectively. We did not find a significant improvement in mood or quality of life scores at 5 years. Similarly, clinical factors at baseline did not correlate with variability in motor outcome. We concluded that GPi-DBS is an effective treatment for motor symptoms and pain in CD. There was limited effect on mood and QoL, and no clinical predictive factors of outcome were identified.


Dioxygenases without requirement for cofactors: identification of amino acid residues involved in substrate binding and catalysis, and testing for rate-limiting steps in the reaction of 1H-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase.
1H-3-Hydroxy-4-oxoquinaldine 2,4-dioxygenase (Hod), catalyzing cleavage of its heteroaromatic substrate to form carbon monoxide and N-acetylanthranilate, belongs to the alpha/beta hydrolase fold family of enzymes. Analysis of protein variants suggested that Hod has adapted active-site residues of the alpha/beta hydrolase fold for the dioxygenolytic reaction. H251 was recently shown to act as a general base to abstract a proton from the organic substrate. Residue S101, which corresponds to the nucleophile of the catalytic triad of alpha/beta-hydrolases, presumably participates in binding the heteroaromatic substrate. H102 and residues located in the topological region of the triad's acidic residue appear to influence O2 binding and reactivity. A tyrosine residue might be involved in the turnover of the ternary complex [HodH+-3,4-dioxyquinaldine dianion-O2]. Absence of viscosity effects and kinetic solvent isotope effects suggests that turnover of the ternary complex, rather than substrate binding, product release, or proton movements, involves the rate-determining step in the reaction catalyzed by Hod.


Trends in authorship characteristics and collaboration in pharmacy practice publications: 2011-2020.
Research and scholarly publications are core expectations in academia that often require collaboration. While the number of authors per document (NAPD) has increased in every discipline, co-authorship culture and collaboration patterns vary among disciplines and countries. To determine the trends in the patterns and characteristics of authorship and collaborations in United States' pharmacy practice faculty publications from 2011 to 2020. Seven pharmacy practice journals were selected based on previous studies and data from Scimago Journal and Country Rank. Articles and reviews (document types) published during the decade were obtained from the Scopus database. Data cleaning and analysis were done using Microsoft Excel, R programming language packages, and VOSviewer. The Mann-Kendall trend test was used to determine the presence of (positive/negative) monotonic trends. Eight thousand and fifty-nine documents published in the selected journals (82.7% articles; 17.3% reviews) by 18,575 unique authors during the decade were analyzed. In most documents (69.3-78.7%), senior/corresponding authors were first authors. There were statistically significant upward trends in the mean NAPD (3.8 ± 2.2 to 4.7 ± 2.4), median NAPD, and related bibliometric indices (degree of collaboration, collaborative index, and collaborative coefficient). Conversely, productivity (document per unique author) significantly trended downward and had a strong, negative correlation with mean NAPD. The proportion of one-author publications also trended downward (12.2%-3.6%). Evidence also supports a downward trend in institutional collaboration and an upward trend in international collaboration. The assumption that last authors are senior authors does not hold in pharmacy practice publications. The increase in NAPD is not considered as authorship inflation, but rather an authorship "upcreep" that is driven by a survival strategy to publish together, predominantly within institutions rather than across institutions or countries. Therefore, faculty publication benchmarks should be crafted to mitigate the inverse relationship between collaboration and productivity, without discouraging collaboration.


School-based interventions to prevent anxiety and depression in children and young people: a systematic review and network meta-analysis.
Rates of anxiety and depression are increasing among children and young people. Recent policies have focused on primary prevention of mental disorders in children and young people, with schools at the forefront of implementation. There is limited information for the comparative effectiveness of the multiple interventions available. We did a systematic review and network meta-analysis, searching MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled trials for published and unpublished, passive and active-controlled randomised and quasi-randomised trials. We included educational setting-based, universal, or targeted interventions in which the primary aim was the prevention of anxiety and depression in children and young people aged 4-18 years. Primary outcomes were post-intervention self-report anxiety and depression, wellbeing, suicidal ideation, or self-harm. We assessed risk of bias following the Cochrane Handbook for Systematic Reviews of Interventions. We estimated standardised mean differences (SMD) using random effects network meta-analysis in a Bayesian framework. The study is registered with PROPSERO, number CRD42016048184. 1512 full-text articles were independently screened for inclusion by two reviewers, from which 137 studies of 56 620 participants were included. 20 studies were assessed as being at low risk of bias for both random sequence generation and allocation concealment. There was weak evidence to suggest that cognitive behavioural interventions might reduce anxiety in primary and secondary settings. In universal secondary settings, mindfulness and relaxation-based interventions showed a reduction in anxiety symptoms relative to usual curriculum (SMD -0·65, 95% credible interval -1·14 to -0·19). There was a lack of evidence to support any one type of intervention being effective to prevent depression in universal or targeted primary or secondary settings. Comparison-adjusted funnel plots suggest the presence of small-study effects for the universal secondary anxiety analysis. Network meta-analysis was not feasible for wellbeing or suicidal ideation or self-harm outcomes, and results are reported narratively. Considering unclear risk of bias and probable small study effects for anxiety, we conclude there is little evidence that educational setting-based interventions focused solely on the prevention of depression or anxiety are effective. Future research could consider multilevel, systems-based interventions as an alternative to the downstream interventions considered here. UK National Institute for Health Research.


Potassium secretion in rat distal colon during dietary potassium loading: role of pH regulated apical potassium channels.
Chronic dietary K+ loading increases the abundance of large conductance (210 pS) apical K+ channels in surface cells of rat distal colon, resulting in enhanced K+ secretion in this epithelium. However, the factors involved in the regulation of these K+ channels are at present unclear. To evaluate the effect of dietary K+ loading on intracellular pH and its relation to large conductance apical K+ channel activity in surface cells of rat distal colon. As assessed by fluorescent imaging, intracellular pH was higher in K+ loaded animals (7.48 (0.09)) than in controls (7.07 (0.04); p<0.01) when surface cells were bathed in NaCl solution, and a similar difference in intracellular pH was observed when cells were bathed in Na2SO4 solution (7.67 (0.09) and 6.92 (0.05) respectively; p<0.001). Ethylisopropylamiloride (EIPA; an inhibitor of Na+-H+ exchange; 1 microM) decreased intracellular pH when surface cells from K+ loaded animals were bathed in either solution, although the decrease was greater when the solution contained NaCl (DeltapH 0.50 (0.03)) rather than Na2SO4 (DeltapH 0. 18 (0.02); p<0.05). In contrast, EIPA had no effect in cells from control animals. As assessed by patch clamp recording techniques, the activity of large conductance K+ channels in excised inside-out membrane patches from distal colonic surface cells of K+ loaded animals increased twofold when the bath pH was raised from 7.40 to 7. 60. As assessed by cell attached patches in distal colonic surface cells from K+ loaded animals, the addition of 1 M EIPA decreased K+ channel activity by 50%, consistent with reversal of Na+-H+ exchange mediated intracellular alkalinisation. Intracellular alkalinisation stimulates pH sensitive large conductance apical K+ channels in rat distal colonic surface cells as part of the K+ secretory response to chronic dietary K+ loading. Intracellular alkalinisation seems to reflect an increase in EIPA sensitive Na+-H+ exchange, which may be a manifestation of the secondary hyperaldosteronism associated with this model of colonic K+ adaptation.


Guanxin V alleviates acute myocardial infarction by restraining oxidative stress damage, apoptosis, and fibrosis through the TGF-β1 signalling pathway.
Oxidative stress, apoptosis, and fibrosis have important roles in acute myocardial infarction, which is the main cause of global morbidity and mortality. Guanxin V significantly ameliorates acute myocardial infarction, the underlying mechanism, however, is still unclear. In this study, we detected the anti-oxidative, anti-apoptotic, and anti-fibrosis effects of Guanxin V on acute myocardial infarction. We used left anterior descending coronary artery ligation to construct an acute myocardial infarction model. Cardiac function, heart weight, infarction size, and histopathology were measured. Cardiomyocytes were treated with hydrogen peroxide to build an in vitro model. Cell apoptosis, fibrosis, and reactive oxygen species-related markers were tested. We observed the mitochondrial ultrastructure through transmission electron microscopy. The levels of collagens and TGF-β1 signalling were measured. The lentiviral vector containing the full-length TGF-β1 sequence was administered to investigate the rescue role of Guanxin V. Guanxin V significantly decreased apoptosis and inhibited oxidative stress damage and fibrosis in acute myocardial infarction. Hydrogen peroxide could stimulate cardiomyocytes to produce reactive oxygen species and Guanxin V could significantly reverse hydrogen peroxide-induced cell damage, inhibit oxidative stress damage, apoptosis, and fibrosis, and enhance mitochondrial dynamic balance. Mechanistically, Guanxin V attenuated oxidative stress damage, apoptosis, and fibrosis induced by the TGF-β1 signalling pathway activation. Guanxin V effectively relieved apoptosis, oxidative stress damage, and fibrosis through down-regulating the TGF-β1 signalling pathway, which enhances the knowledge of the cellular and molecular mechanism of Guanxin V in treating acute myocardial infarction.


Prenatal diagnosis and genetic counseling of a 10p11.23q11.21 duplication associated with normal phenotype.
Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Unbalanced chromosome abnormalities (UBCA) are either gains or losses or large genomic regions, but the affected person is not or only minimally clinically affected. CNVs and UBCA identified in prenatal cases need careful considerations and correct interpretation if those are harmless or harmful variants from the norm. A 24-year-old, gravida 1, para 0, woman underwent amniocentesis at 17 weeks of gestation because the noninvasive prenatal testing (NIPT) results revealed a 12.4 Mb duplication from 10p11.2 to 10q11.2. GTG-banding karyotype analysis was performed on cultured amniocytes. Chromosomal microarray analysis (CMA) on uncultured amniocytes was performed. Chromosomal GTG-banding of the cultured amniocytes revealed a karyotype of 46,XX,dup(10)(p11.2q11.2). CMA detected a 12.5-Mb chromosomal duplication in the region of 10p11.23q11.21 (arr[GRCh37] 10p11.23q11.21(30,345,109_42,826,062) × 3). The present report enlarges the known UBCA region 10p11.22-10q11.22 to 10p11.23-10q11.22. Also it highlights that an integration of prenatal ultrasound, NIPT, karyotype analysis, CMA and genetic counseling is helpful for the prenatal diagnosis of chromosomal deletions/duplications.


Highly Asymmetric Cyclopropanation With Two Sulfinyl Auxiliaries as a Way to a Useful Synthetic Intermediate.
The asymmetric cyclopropanation using double sulfinyl auxiliary gave bis-sulfoxide with full diastereoselectivity and very high enantioselectivity. One of the sulfinyl substituents can be removed by sulfinyl metal exchange. Differentiation of sulfinyl substituents made it possible to assign the place of attack of the Grignard reagent.


Interleukin-13 contributes to the occurrence of oral submucosal fibrosis.
Oral submucous fibrosis (OSF) is a chronic progressive fibrosis disease that affects in oral mucosal tissues. Interleukin (IL)-13 has been implicated in the development of fibrosis in multiple organs. Indeed, it contributes to diseases such as pulmonary fibrosis, liver cirrhosis among others. Currently, its expression in OSF and the specific mechanisms are not well understood. The aim of this study was to investigate the role of IL-13 in OSF and further explore whether IL-13 regulates-polarization of M2-macrophages in OSF. Initially, in the tissues of patients with OSF, we observed a high expression of M2-macrophages and IL-13 protein. Additionally, we found a correlation between the expression of IL-13 and the stage of OSF. Arecoline inhibited the proliferation of fibroblasts (FBs) and promoted IL-13 production in vitro. Furthermore, our observations revealed that M2-macrophages increased upon co-culturing M0-macrophages with supernatants containing the IL-13 cytokine. In conclusion, our study demonstrated that arecoline stimulates FBs leading to increased secretion of IL-13, which in turn IL-13 leads to polarization of M2-macrophages and promotes the occurrence of OSF. This suggests that IL-13 may be a potential therapeutic target of OSF.


Common processes in evidence-based adolescent HIV prevention programs.
Dissemination of evidence-based HIV prevention programs for adolescents will be increased if community interventionists are able to distinguish core, essential program elements from optional, discretionary ones. We selected five successful adolescent HIV prevention programs, used a qualitative coding method to identify common processes described in the procedural manuals, and then compared the programs. Nineteen common processes were categorized as structural features, group management strategies, competence building, and addressing developmental challenges of adolescence. All programs shared the same structural features (goal-setting and session agendas), used an active engagement style of group management, and built cognitive competence. Programs varied in attention to developmental challenges, emphasis on behavioral and emotional competence, and group management methods. This qualitative analysis demonstrated that successful HIV programs contain processes not articulated in their developers' theoretical models. By moving from the concrete specifics of branded interventions to identification of core, common processes, we are consistent with the progress of "common factors" research in psychotherapy.


An evaluation of a micropolar model for blood flow through an idealized stenosis.
In this paper, the behavior of a viscous fluid described by Newtonian constitutive theory is compared with that predicted by a model based on micropolar continuum theory. The geometry chosen for this comparative analysis is a stenosis in which gradient effects should be pronounced. A range of boundary conditions for fluid microspin are considered. Although velocities and streamlines are found to be similar for the two continuum models, striking differences in shear stresses are revealed. These differences may be as high as 50% for vanishing microspin boundary conditions. Such significant discrepancies highlight the need for further study of higher order modeling of blood flow.


FTO polymorphism, cardiorespiratory fitness, and obesity in Brazilian youth.
The aim of the present study was to evaluate the relationship between the rs9939609 fat mass and obesity-associated (FTO) polymorphism and cardiorespiratory fitness (CRF) with overweight/obesity outcomes in youth. This study included 420 youths, comprising 211 boys and 209 girls aged 7-17. Overweight/obesity were evaluated by body mass index (BMI), waist circumference (WC), and the percentage of fat (PF) according to two skinfold thickness measurements. Genotyping of the rs9939609 polymorphism was conducted using real-time Polymerase Chain Reaction (PCR) utilizing TaqMan(®) probes, and CRF was evaluated through a 9-minute run/walk test, categorized as fit or unfit. Logistic regression was utilized to evaluate a possible association between the polymorphism and CRF, with three obesity indicators evaluated. Individuals with the genotype risk (AA) of FTO polymorphism rs9939609 showed higher prevalence of overweight/obesity, as evaluated by BMI (OR: 3.21; CI: 1.71-6.05), WC (OR: 2.59; CI: 1.35-4.97), and PF (OR: 2.59; CI: 1.36-4.92). Additionally, students with the AA genotype in the unfit model had a significant odds ratio for obesity (OR: 4.40; CI: 1.83-10.61 for BMI; OR: 3.54; CI: 1.58-7.96 for WC), whereas we did not observe associations between the AA genotype with BMI and WC using the fit model. Conversely, PF was associated with the AA genotype only in the fit model (OR: 3.24; CI: 1.26-8.34). This study demonstrated that the rs9939609 (FTO) polymorphism showed a relationship with obesity in the population studied and an interaction with CRF. Students with low levels of CRF and the AA genotype have a higher risk of being overweight/obese. This association was not found in students with higher levels of CRF. Am. J. Hum. Biol. 28:381-386, 2016. © 2015 Wiley Periodicals, Inc.


Identification of key structural features of the elusive Cu-Aβ complex that generates ROS in Alzheimer's disease.
Oxidative stress is linked to the etiology of Alzheimer's disease (AD), the most common cause of dementia in the elderly. Redox active metal ions such as copper catalyze the production of Reactive Oxygen Species (ROS) when bound to the amyloid-β (Aβ) peptide encountered in AD. We propose that this reaction proceeds through a low-populated Cu-Aβ state, denoted the "catalytic in-between state" (CIBS), which is in equilibrium with the resting state (RS) of both Cu(i)-Aβ and Cu(ii)-Aβ. The nature of this CIBS is investigated in the present work. We report the use of complementary spectroscopic methods (X-ray absorption spectroscopy, EPR and NMR) to characterize the binding of Cu to a wide series of modified peptides in the RS. ROS production by the resulting Cu-peptide complexes was evaluated using fluorescence and UV-vis based methods and led to the identification of the amino acid residues involved in the Cu-Aβ CIBS species. In addition, a possible mechanism by which the ROS are produced is also proposed. These two main results are expected to affect the current vision of the ROS production mechanism by Cu-Aβ but also in other diseases involving amyloidogenic peptides with weakly structured copper binding sites.


Radiotherapy in metastatic ewing sarcoma.
To review an institutional experience with radiotherapy (RT) in patients with metastatic Ewing sarcoma. Thirty patients with metastatic Ewing sarcoma were considered. Twenty-nine received multiagent chemotherapy, whereas 22 had local therapy, which included RT in 14, surgery in 5, and surgery followed by RT in 3. The 5-year overall survival rate was 22.1%. On multivariate analysis, presence of uncommon sites of metastasis (brain, liver, spleen) (P<0.0001) and use of local therapy to the primary site (P<0.001) were adverse factors for survival. Local control was not achieved in the 8 patients receiving only chemotherapy. All long-term survivors had local therapy including RT to metastatic bony sites and whole-lung irradiation for pulmonary metastasis. The presence of uncommon sites of metastasis confers a worse prognosis. Aggressive primary treatment including RT to metastatic sites should be considered in these patients.


CD3 mAb treatment ameliorated the severity of the cGVHD-induced lupus nephritis in mice by up-regulation of Foxp3+ regulatory T cells in the target tissue: kidney.
Teff/Treg imbalance orchestrated the onset and the progression of the lupus nephritis in a DBA/2→B6D2F1 murine model with cGVHD. In this paper, we first used 145-2C11 Ab to treat these human SLE-like diseased animals. The results showed that short-term low-dose anti-CD3 antibody treatment induced a significant remission of established proteinuria, production of autoantibodies, immune complex deposition and renal parenchyma lesions in lupus nephritic mice. Of note, we found a robust up-regulation of Foxp3 mRNA expression in the target tissue: kidney from mice with anti-CD3 antibody treatment compared to those with control IgG treatment. Likewise, an increased renal mRNA abundance for IL-10 was also observed in anti-CD3 antibody treated mice. In contrast, genes associated with inflammation and fibrosis as well as cytokines related to effector T cell responses were down-regulated by anti-CD3 mAb treatment. These findings suggested that short-term low-dose anti-CD3 antibody treatment might induced an IL-10-secreting Foxp3(+) regulatory T cells in this cGVHD target tissue: kidney, that suppressed the activation of effector T cells (Th1, Th2 and Th17), thus ameliorating the severity of the lupus nephritis in mice.


Rhizoctonia solani AG 11 isolated for the first time from sugar beet in Poland.
Two isolates of Rhizoctonia solani AG11 were isolated from sugar beet seedlings from South-west Poland. Both isolates gave C2 reactions in anastomose pairings with the tester isolates of AG11. The membership of both isolates to AG11 was confirmed by analysis of pectic isozyme profiles, and by verification that the internal transcribed spacer sequences of both isolates matched the references in the GenBank database. Both AG11 isolates formed white-beige to creamy-colored mycelium with wide concentric zonation. One of them formed light-colored sclerotia. The average daily rate of hyphal growth at 21 °C was 22.8 mm and 22.6 mm on PDA. They were mildly pathogenic to sugar beet seedlings due to the mycelial and secondary metabolites' activity. The sensitivity to fungicides typically used in sugar beet protection was different for each isolate; one of them (isolate ID11) was less sensitive to thiram than the other (isolate ID3). This article discusses the worldwide occurrence of R. solani AG11, expands the currently known host range, shows its broad world distribution in regions of moderate climate, and confirms the isolates' low frequency.


PET recognition of pulmonary metastases on PET/CT imaging: impact of attenuation-corrected and non-attenuation-corrected PET images.
The aims of this study were to assess the performance of FDG PET at PET/CT imaging for the detection of pulmonary metastases and to evaluate differences in lesion detectability on attenuation-corrected (AC) and non-attenuation corrected (NAC) PET images. The institutional PET/CT database was searched for patients with pulmonary metastases of 3-60 mm in diameter. Ninety-two patients with 438 metastases to the lungs were included in the study. The primary tumours were 33 malignant melanomas, 12 carcinomas of unknown primary, 11 colorectal carcinomas, eight differentiated thyroid carcinomas, seven aggressive non-Hodgkin's lymphomas, six head and neck cancers, three breast cancers, two prostate cancers and ten others. Lesion detectability was visually compared between PET and CT and between AC and NAC PET images using a five-point scale. Of the 438 pulmonary metastases, 174 were detected with FDG PET (39.7%), six of them on NAC images only (not significant). Visual scores were higher on NAC images in 41.4% and equal in 54.6% of lesions. The sensitivity of FDG PET increased significantly from 0.405 for metastases of 5-7 mm in diameter to 0.784 for lesions of 8-10 mm and to 0.935 for lesions measuring 11-29 mm in diameter. No metastases smaller than 5 mm in diameter were seen on PET images. FDG PET/CT is useful for the assessment of pulmonary metastases. The frequency of lesion detection is similar for AC and NAC PET images. A reduced sensitivity of FDG PET has to be considered for lesions smaller than 11 mm in diameter.


A case of cortical blindness due to carbon monoxide poisoning.
We report a case of cortical blindness occurring 7 days after acute CO poisoning with no other neurological or psychic deficits apart from denial of the blindness with visual confabulation and slight loss of retentive memory. There was scant correlation between the course of the clinical pattern, which cleared completely within 6 days, and the electroencephalographic pattern with marked and diffuse slowing, which did not recede completely during 3 months observation. CT scanning of the skull, initially within normal limits, displayed 2 weeks later a faint but diffuse hypodensity of the white substance, more marked in the occipital region, which was no longer present 80 days after the first scan.


Games parents play with normal and high-risk infants.
Game playing during early infant-parent interactions provides a context for learning conversational turntaking and contingent responsivity. The types and frequency of "universally" recognized infant games were observed during face-to-face interactions of normal and high risk infant-parent dyads when the infants were four months old. Approximately six different games were played for approximately one-third of the interaction time. Except during interactions with normal male infants mothers and fathers played games equally as often. The high-risk infant-parent dyads engaged in game playing less frequently than the normal infant-parent dyads. These differences are discussed in the context of the high-risk infants being "difficult" babies and relatively less responsive.


Screening for depressive symptoms among the elderly in Israel. A reliability and validity study.
The Hadassah Elderly Depression Screening Scale (HEDSS)--a modified version of Zung's Self-Rating Depression Scale and Beck's Depression Index--was developed for use among the elderly in Israel. In a sample of 183 elderly residents of Jerusalem, the scale proved to be highly reliable and able to differentiate between persons diagnosed as depressed and those defined as healthy. Moreover, it was found to be valid among subpopulations grouped by sex, education and ethnicity. Various cutoff points were tested for targeting screening at specific populations.


Empty sella syndrome and growth deficiency in childhood.
We describe four cases of empty sella syndrome in childhood associated with growth and neuroendocrine disorders. We note that empty sella syndrome probably presents with endocrine disorders more often in childhood than in adults and that its frequency seems to be underestimated.


Relevance of electrocardiographic findings, heart failure, and infarct site in assessing risk and timing of left ventricular free wall rupture during acute myocardial infarction.
Clinical and electrocardiographic features of 227 patients who died of an acute myocardial infarction (AMI) were compared with those of 150 survivors of a first AMI. Left ventricular (LV) free wall rupture was found in 93 patients aged > 50 years, but not in 134. The incidence of healed infarct (4 [4%] vs 50 [37%], p < 0.001), heart failure (11 [12%] vs 112 [84%], p < 0.001), and bundle branch block (11 [12%] vs 54 [40%], p < 0.001) was lower in patients with than without LV rupture. In patients with anterior AMI and early rupture (1 day), admission ST elevation was higher than in those with late LV rupture (> 1 day, 6.8 +/- 4.0 vs 4.0 +/- 2.7 mm, p < 0.01). However, lateral wall AMI had minimal ST elevation and accounted for 10% of ruptures. On day 2, the decrease in ST segment in patients with late LV rupture was less than in survivors (0.5 +/- 1.6 vs 3.2 +/- 2.9 mm, p < 0.001). Admission systolic blood pressure in patients who had early rupture was higher than in survivors (155 +/- 22 vs 137 +/- 22 mm Hg, p < 0.001) and in those with late rupture (135 +/- 23 mm Hg, p < 0.001). Late rupture was associated with infarct thinning and triggered by a physical strain in 18 of 45 patients (40%); infarct thinning, however, was present only in 4 of 48 patients (8%) with early rupture (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


Generation of low-timing-jitter femtosecond pulse trains with 2 GHz repetition rate via external repetition rate multiplication.
Generation of low-timing-jitter 150 fs pulse trains at 1560 nm with 2 GHz repetition rate is demonstrated by locking a 200 MHz fundamental polarization additive-pulse mode-locked erbium fiber laser to high-finesse external Fabry-Perot cavities. The timing jitter and relative intensity noise of the repetition-rate multiplied pulse train are investigated.


Prediction of Proteases Involved in Peptide Generation.
Clinical proteomics has led to the identification of a substantial number of disease-associated peptides and protein fragments in several conditions such as cancer, kidney, or cardiovascular diseases. In silico prediction tools that can facilitate linking of identified peptide biomarkers to predicted protease activity might therefore significantly contribute to the understanding of pathophysiological mechanisms of these diseases. Proteasix is an open-source, peptide-centric tool that can be used to predict in silico the proteases involved in naturally occurring peptide generation. From an input peptide list, Proteasix allows for automatic cleavage site reconstruction and protease associations.


Mutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients.
To evaluate the contribution of eight small NSHL-AR (non-syndromic deafness, autosomal recessive) genes to hereditary hearing loss in Czech patients. Unrelated Czech patients, adults and children, diagnosed with pre-lingual hereditary hearing loss with at least one similarly affected deaf sibling and with previously excluded mutations in the GJB2 gene were investigated by Sanger sequencing of the selected eight small NSHL-AR associated genes (CABP2 - 51 patients, CIB2 - 45 patients, PJVK/DFNB59 - 53 patients, GJB3 - 46 patients, ILDR1 - 48 patients, LHFPL5 - 66 patients, LRTOMT - 60 patients, TMIE - 64 patients). Mutations were detected in the LHFPL5 (DFNB67) gene. The patient is heterozygote for two already described pathogenic variants (p.Tyr127Cys, p.Thr165Met). In five samples, five rare heterozygous variants (two novel) predicted as pathogenic were detected in genes CABP2, ILDR1, LHFPL5 and LRTOMT. Mutations in eight small NSHL-AR genes are not a frequent cause of hereditary hearing loss in the Czech Republic. This diagnostic approach permitted the clarification of HL in only one patient - two heterozygous mutations were detected in LHFPL5 gene for the first time in Central Europe. As the use of panel base MPS certainly improves the diagnostic yield, future studies should rather profit from that diagnostic strategy.


[Scales for functional assessment in multiple sclerosis].
To review the characteristics which should be met by the scales for functional assessment of patients with multiple sclerosis in relation to the degree of invalidity, incapacity and handicap. The functional scales for neurological patients which we review are Barthel's index, the PULSES Scale, Katz Index, Rankin Scale, Kenny Scale, Donaldson Scale, Garno Scale, ISS (Incapacity Status Scale) FAM Scale (Functional Assessment Measure), Hauser's Ambulant Index, Cambridge Scale (CAMBS) and London Handicap Scale (LHS). There is no single scale for the functional assessment of patients with multiple sclerosis which covers all the aspects to be assessed. Therefore it is necessary to use a combination of various scales to find exactly the degree of invalidity, incapacity and handicap. From our point of view the scales with which this assessment may be done are--apart from the usually used NRS (Neurological Scoring System) and EDSS--the Hauser Index, Cambridge Scale and London Handicap Scale.


A framework based on 2-D Taylor expansion for quantifying the impacts of sub-pixel reflectance variance and covariance on cloud optical thickness and effective radius retrievals based on the bi-spectral method.
The bi-spectral method retrieves cloud optical thickness (τ) and cloud droplet effective radius (r e ) simultaneously from a pair of cloud reflectance observations, one in a visible or near infrared (VIS/NIR) band and the other in a shortwave-infrared (SWIR) band. A cloudy pixel is usually assumed to be horizontally homogeneous in the retrieval. Ignoring sub-pixel variations of cloud reflectances can lead to a significant bias in the retrieved τ and r e . In the literature, the retrievals of τ and r e are often assumed to be independent and considered separately when investigating the impact of sub-pixel cloud reflectance variations on the bi-spectral method. As a result, the impact on τ is contributed only by the sub-pixel variation of VIS/NIR band reflectance and the impact on r e only by the sub-pixel variation of SWIR band reflectance. In our new framework, we use the Taylor expansion of a two-variable function to understand and quantify the impacts of sub-pixel variances of VIS/NIR and SWIR cloud reflectances and their covariance on the τ and r e retrievals. This framework takes into account the fact that the retrievals are determined by both VIS/NIR and SWIR band observations in a mutually dependent way. In comparison with previous studies, it provides a more comprehensive understanding of how sub-pixel cloud reflectance variations impact the τ and r e retrievals based on the bi-spectral method. In particular, our framework provides a mathematical explanation of how the sub-pixel variation in VIS/NIR band influences the r e retrieval and why it can sometimes outweigh the influence of variations in the SWIR band and dominate the error in r e retrievals, leading to a potential contribution of positive bias to the r e retrieval. We test our framework using synthetic cloud fields from a large-eddy simulation and real observations from MODIS. The predicted results based on our framework agree very well with the numerical simulations. Our framework can be used to estimate the retrieval uncertainty from sub-pixel reflectance variations in operational satellite cloud products and to help understand the differences in τ and r e retrievals between two instruments.


Patient-practitioner-remedy (PPR) entanglement. Part 3. Refining the quantum metaphor for homeopathy.
The notion of patient-practitioner-remedy (PPR) entanglement, previously proposed for homeopathy, is refined by adapting concepts derived from Greenberger, Horne, and Zeilinger's treatment of three-particle entanglement (GHZ states), and a generalised version of quantum theory, called weak quantum theory (WQT). These suggest that for maximum PPR entanglement during the therapeutic encounter, the practitioner's awareness needs to be directed inward as well as outward toward the patient, and that health and disease are mirror images of each other, similar to and represented by, the relationship of complex numbers to their complex conjugates.


The use of the Heimlich maneuver in near drowning: Institute of Medicine report.
The application of the Heimlich maneuver as the initial and perhaps only step for opening the airway in all near-drowning victims has been proposed by Henry Heimlich and Edward Patrick, contrary to current resuscitation guidelines for the treatment of near-drowning victims established by the Emergency Cardiac Care (ECC) Committee of the American Heart Association. Although the Heimlich maneuver is useful for the removal of aspirated solid foreign bodies, there is no evidence that death from drowning is frequently caused by aspiration of a solid foreign body that is not effectively treated by the current ECC recommendations. Furthermore, the evidence is insufficient to support the proposition that the Heimlich maneuver is useful for the removal of aspirated liquid. Moreover, because there is no evidence to support Heimlich's hypothesis that substantial amounts of water are aspirated by near-drowning victims or that such aspirated liquid causes brain damage and death, the available evidence does not support routine use of the Heimlich maneuver in the care of near-drowning victims. The routine use of the Heimlich maneuver for treatment of near drowning raises several concerns: (a) the amount of time it would take to repeat this maneuver and how long this would delay the initiation of artificial ventilation; (b) possible complications of the Heimlich maneuver, especially if the near drowning is associated with a cervical fracture; and (c) the prospect of teaching rescue workers a different protocol than that which is taught at present for resuscitating victims of cardiopulmonary arrest from all causes other than near drowning.(ABSTRACT TRUNCATED AT 250 WORDS)


Dissemination of blaVIM in Greece at the peak of the epidemic of 2005-2006: clonal expansion of Klebsiella pneumoniae clonal complex 147.
VIM-producing Klebsiella pneumoniae (n = 21) isolated from ten Greek hospitals during 2003-2007 were characterized with multilocus sequence typing (MLST), semi-automated repetitive sequence-based PCR (rep-PCR) (Diversilab), plasmid replicon typing, serotyping and screening for multiple resistance determinants. The isolates were selected to represent different strain clusters (defined by >80% similarity) according to pulsed-field gel electrophoresis. MLST identified three major clonal complexes (CCs); CC147 (n = 8), CC18 (n = 5) and CC14 (n = 3). Plasmid replicon typing showed that IncA/C and/or IncFIIK replicons were detected among isolates in each of the major CCs. Good concordance was observed between semi-automated-rep PCR genotyping and MLST.


Effect of ischemia--reperfusion on heat shock protein 70 and 90 gene expression in rat liver: relation to nutritional status.
Heat shock proteins are intracellular proteins associated with a generalized response of cells to stress. The purpose of this study was to assess RNA levels of heat shock protein 70 and 90 in fed or fasted rat livers during ischemia-reperfusion. Northern blot analysis of heat shock proteins was performed. Adenosine triphosphate and glutathione were assessed. In baseline conditions, livers of fasted rats showed a twofold increase in mRNA for both heat shock proteins and 38% and 43% reductions in adenosine triphosphate and glutathione, respectively, when compared with organs from fed rats. After ischemia, livers of fasted rats presented a twofold decrease in heat shock protein mRNA, while no changes were observed in livers of fed rats; reduced glutathione and adenosine triphosphate decreased 55% and 50% in fasted livers and 25% and 20% in fed organs, respectively. After 120 min of reperfusion, heat shock protein mRNA rose threefold in fasted livers, while a slight decrease was observed in the fed group; reduced glutathione and adenosine triphosphate returned to 65% and 70% of baseline values in fasted livers and 85% and 90% in fed organs, respectively. In conclusion, the nutritional status affects heat shock protein expression determined by reperfusion. The reduced antioxidant status leading to increased oxidative stress could be the mechanism underlying the phenomenon.


A prospective, randomized, double-blinded study with crossover to determine the efficacy of radio-frequency nerve ablation for the treatment of heel pain.
Previous studies have demonstrated that radio-frequency nerve ablation (RFNA) can be an effective treatment for plantar fasciosis. This study provides additional evidence in support of this treatment, with statistically significant data that demonstrate the success of this technique. In this multicenter, randomized, prospective, double-blinded study with crossover, 17 patients were divided into two groups, with eight initially receiving RFNA treatment and nine initially receiving sham treatment. If no improvement was observed after 4 weeks, a crossover was offered. Results of the treatment were evaluated by the patient and by a blinded physician using a visual analog pain scale to rate first-step pain, average pain, and peak pain in the heel region. We observed a statistically significant improvement in the symptoms of plantar fasciosis in patients actively treated with RFNA and no significant improvement in the sham-treated group. More important, those treated with sham subsequently demonstrated statistically significant improvement after subsequent RFNA treatment. Using a prospective, randomized study with sham treatment and crossover, this study demonstrates the efficacy of RFNA for the treatment of plantar fasciosis.


Antepartum severe maternal morbidity: A population-based study of risk factors and delivery outcomes.
Severe maternal morbidity (SMM) is a key indicator of maternal health. Generally explored without distinction by the timing of the event, it mainly reflects postpartum SMM. Although antepartum (pre-labour) SMM presents specific challenges in its need to optimise the risk-benefit balance for both mother and foetus, its features remain inadequately explored. We explored risk factors of antepartum SMM and described adverse delivery and neonatal outcomes associated with antepartum SMM. We designed a population-based nested case-control study based on data from the EPIMOMS study (119 maternity hospitals of 6 French regions, 2012-2013, N = 182,309 deliveries in the source cohort). This study included all women with antepartum SMM (cases, n = 601) compared to a randomly selected sample of women who gave birth without SMM in the same hospitals (controls, n = 3651). Antepartum SMM risk factors were identified with multivariable logistic regression following imputations for missing data. Antepartum SMM complicated 0.33% (95% confidence interval [CI] 0.30, 0.36) of pregnancies. Antepartum SMM risk factors were maternal age ≥35 years (adjusted odds ratio [OR] 1.55, 95% CI 1.22, 1.97), increased body mass index (OR for 5 kg/m2 increase, 1.24, 95% CI 1.14, 1.36), maternal birth in sub-Saharan Africa (OR 1.80, 95% CI 1.29, 2.53), pre-existing medical condition (OR 2.56, 95% CI 1.99, 3.30), nulliparity (OR 2.26, 95% CI 1.83, 2.80), previous pregnancy-related hypertensive disorders (OR 4.94, 95% CI 3.36, 7.26), multiple pregnancy (OR 5.79, 95% CI 3.75, 7.26), irregular prenatal care (OR 1.86, 95% CI 1.27, 2.72). For women with antepartum SMM, preterm delivery, neonatal mortality and transfer to the neonatal intensive care unit were 10 times more frequent than for controls. Emergency caesarean and general anaesthesia were more frequent in women with antepartum SMM. Antepartum SMM is rare but associated with increased rates of adverse delivery and neonatal outcomes.


Ruptured abdominal aortic aneurysms presenting as radicular compression syndromes.
Two patients are described: one with an aneurysm of the infrarenal aorta and common iliac artery that ruptured posteriorly into the iliac vein, the other with an aneurysm of the distal abdominal aorta that ruptured posteriorly into the iliopsoas muscle. Both patients had symptoms compatible with a radicular compression syndrome. Ruptured aneurysm of one of the major abdominal arteries should be considered in the differential diagnosis of affections of the lumbosacral neural outflow, because immediate operation can be life-saving.


Identifying new Risk Markers and Potential Targets: The Value of the Proteome.
Several protein biomarkers, including cardiac troponin T, cardiac troponin I, B-type natriuretic peptide, C-reactive protein and apolipoprotein A-I, are widely employed in the evaluation of cardiovascular disease. Several of such potential biomarkers, or their multiscores, have been assessed over the last years for the prediction of cardiovascular risk but only a few of them have been validated for clinical use. Substantial improvement in the cardiovascular risk prediction and reclassification relative to traditional models therefore remains a difficult task presently unresolved. Hence, a potential importance of alternative approaches which may rely on novel proteomic biomarkers among others. Plasma or serum concentrations of numerous proteins were measured using proteomic approaches to establish their relationships with cardiovascular disease; none of them was however evaluated for cardiovascular risk prediction and subject stratification in rigorous large-scale studies. Thus, further research is needed to identify novel candidates that can improve cardiovascular risk prediction, subject stratification and standard care. Proteomics will undoubtedly remain a key approach to address this major clinical and scientific challenge.


Creating highly dense and uniform protein and DNA microarrays through photolithography and plasma modification of glass substrates.
We demonstrate a method to create high density protein microarrays with excellent spot uniformity using photolithography and plasma processing on low cost commercially available microscope glass slides. Protein deposition and fluorescence signal evaluation on these substrates are performed by standard arrayers and scanners. To this end, spots of commercial photoresists (AZ5214, SU8 and Ormocomp(®)) were defined through lithography on glass substrates followed by short SF(6) plasma treatment and selective protein adsorption on these spots with respect to glass (spot to background fluorescence signal ratios 30:1 to 40:1) was demonstrated using model protein binding assays. Among the photoresists tested, Ormocomp was selected since it provided the highest protein binding capacity. No ageing of Ormocomp/glass substrates in terms of protein binding capacity was observed for at least two months. Besides to protein microarrays, DNA microarrays were also developed by spotting streptavidin-biotinylated oligonucleotide conjugates corresponding to wild- and mutant-type sequences of four deleterious BRCA1 gene mutations. For all of the examined mutations, higher specific hybridization signals (1.5-4 times) and improved discrimination ratios between wild- and mutant-type sequences as well as higher spot uniformity and repeatability were demonstrated on Ormocomp/glass substrates with intra- and inter-spot CVs of 8.0% and 4.5%, respectively, compared to commercial polystyrene (intra- and inter-spot CVs 36% and 18%) and epoxy-coated glass (intra- and inter-spot CVs 26% and 20%) slides. Thus, the proposed substrates can be readily applied to protein and DNA microarrays fabrication and, moreover, the described method for selective protein adsorption can be advantageously implemented in various analytical microdevices for multi-analyte detection.


[Posterior reversible encephalopathy syndrome].
Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely.


Transcriptional master regulator analysis in breast cancer genetic networks.
Gene regulatory networks account for the delicate mechanisms that control gene expression. Under certain circumstances, gene regulatory programs may give rise to amplification cascades. Such transcriptional cascades are events in which activation of key-responsive transcription factors called master regulators trigger a series of gene expression events. The action of transcriptional master regulators is then important for the establishment of certain programs like cell development and differentiation. However, such cascades have also been related with the onset and maintenance of cancer phenotypes. Here we present a systematic implementation of a series of algorithms aimed at the inference of a gene regulatory network and analysis of transcriptional master regulators in the context of primary breast cancer cells. Such studies were performed in a highly curated database of 880 microarray gene expression experiments on biopsy-captured tissue corresponding to primary breast cancer and healthy controls. Biological function and biochemical pathway enrichment analyses were also performed to study the role that the processes controlled - at the transcriptional level - by such master regulators may have in relation to primary breast cancer. We found that transcription factors such as AGTR2, ZNF132, TFDP3 and others are master regulators in this gene regulatory network. Sets of genes controlled by these regulators are involved in processes that are well-known hallmarks of cancer. This kind of analyses may help to understand the most upstream events in the development of phenotypes, in particular, those regarding cancer biology.


Review of the Development of First-Generation Redox Flow Batteries: Iron-Chromium System.
The iron-chromium redox flow battery (ICRFB) is considered the first true RFB and utilizes low-cost, abundant iron and chromium chlorides as redox-active materials, making it one of the most cost-effective energy storage systems. ICRFBs were pioneered and studied extensively by NASA and Mitsui in Japan in the 1970-1980s, and extensive studies on ICRFBs have been carried out over the past few decades. In addition, ICRFB is considered to be one of the most promising directions for cost-effective and large-scale energy storage applications, as its cost can theoretically be lower than that of zinc-bromine and all-vanadium RFBs, giving it the potential for large-scale promotion. With the resolution of problems such as hydrogen evolution and electrolyte intermixing, the ICRFB technology is moving out of the laboratory and striving for greater power and more stable industrialization requirements. This Review summarizes the history, development, and research status of key components (carbon-based electrode, electrolyte, and membranes) in the ICRFB system, aiming to give a brief guide to researchers who are involved in the related subject.


Functional reorganization in the developing lexicon: separable and changing influences of lexical and phonological variables on children's fast-mapping.
Neighbourhood Density (ND) and Phonotactic Probability (PP) influence word learning in children. This influence appears to change over development but the separate developmental trajectories of influence of PP and ND on word learning have not previously been mapped. This study examined the cross-sectional developmental trajectories of influence of PP and ND on fast-mapping in thirty-eight English-speaking children aged 3 ; 01-5 ; 02, in a task varying PP and ND orthogonally. PP and ND exerted separable influences on fast-mapping. Overall, low ND supported better fast-mapping. The influence of PP changed across the developmental trajectory, 'switching' from a high to a low PP advantage. A potential explanation for this 'switch' is advanced, suggesting that it represents functional reorganization in the developing lexicon, which emerges from changes in the developing lexicon, as phonological knowledge is abstracted from lexical knowledge, over development.


Medical Treatment for Rheumatic Heart Disease: A Narrative Review.
Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are rare in high-income countries; however, in Aotearoa New Zealand ARF and RHD disproportionately affect Indigenous Māori and Pacific Peoples. This narrative review explores the evidence regarding non-surgical management of patients with clinically significant valve disease or heart failure due to RHD. Medline, EMBASE and Scopus databases were searched, and additional publications were identified through cross-referencing. Included were 28 publications from 1980 onwards. Of the available interventions, improved anticoagulation management and a national RHD register could improve RHD outcomes in New Zealand. Where community pharmacy anticoagulant management services (CPAMS) are available good anticoagulation control can be achieved with a time in the therapeutic range (TTR) of more than 70%, which is above the internationally recommended level of 60%. The use of pharmacists in anticoagulation control is cost-effective, acceptable to patients, pharmacists, and primary care practitioners. There is a lack of local data available to fully assess other interventions; including optimal therapy for heart failure, equitable access to specialist RHD care, prevention, and management of endocarditis. As RHD continues to disproportionately affect Indigenous and minority groups, pro-equity tertiary prevention interventions should be fully evaluated to ensure they are reducing disease burden and improving outcomes in patients with RHD.


Ventricular buckling: a factor in the abnormal ventriculogram and peculiar hemodynamics associated with mitral valve prolapse.
Because of intractable ventricualr arrhythmias after a near-fatal episode of ventricular fibrillation, a patient with idiopathic mitral valve prolapse was subjected to mitral valve replacement. Vector analysis and intraoperative epicardial mapping localized the ectopic focus to the region of the posterior papillary muscle. The patient is alive and well two years after surgery; chronically inverted T waves have become upright. But propranolol and diphenylhydantoin are needed to prevent arrhythmias and T wave abnormalities during standing and exercise. Preoperatively, with the onset of mitral regurgitation and a second rapid phase of prolapse, the ventriculogram was deformed by abnormal midsystolic hyperkinesis at both sites of papillary muscle insertion. Postoperatively, focal hypokinesis appeared in the same areas, implying that they had been retracted by the prolapsing valve. Preoperatively, a papillary tip could be seen entering the mitral ring while coronary arteriography showed late systolic elongation of a small vessel feeding the anterior papillary muscle, suggesting that the papillary apparatus was indeed subject to damaging stress during the abnormal basal movement. Three other persons with severe mitral prolapse (but intact chordae) have had valve repacement and developed qualitatively similar changes in the ventriculogram. Papillary speciments in two showed significant fibrosis. Indication for operation in one of these was edpisodic ventricular fibrillation, which has not recurred. A spectrum of ventriculographic abnormality associated with mitral prolapse could be partly explained by hypokinesis of the papillary loops, variably disguised by retraction stress tansmitted from the billowing leaflets, translocation of blood into the expanding valve sail, and various degrees of unloading into the left atrium. Abnormal intraventicular flow may probably result from associated prolapse of the anterior leaflet and from buckling of the papillary sties toward the mitral annulus. Unusual physical findings in the operated cases and in eight other patients define a clinically recognizable syndrome in which severe prolapse abbreviates left ventricular ejection. Liability to symptoms and to progression of disease seems high in this group.


Evaluation of a follow-up protocol for patients on chloroquine and hydroxychloroquine treatment.
To review the problems found after a new follow-up protocol for patients on chloroquine and hydroxychloroquine treatment. Retrospective study was conducted between May 2012 and January 2013 on the clinical files, retinographies, fundus auto-fluorescence (FAF) images, and central-10 degree visual fields (VF) of patients who were referred to the Ophthalmology Department as they had started treatment with hydroxychloroquine. One hundred twenty-six patients were included; 94.4% were referred from the Rheumatology Department and 5.6% from Dermatology. Mean age was 59.7 years, and 73.8% were women. All of them were on hydroxychloroquine treatment, and 300mg was the most frequent daily dose. Rheumatoid arthritis was the most common diagnosis (40.5%), followed by systemic lupus erythematosus (15.9%). The mean Snellen visual acuity was 0.76, and 26 patients had lens opacities. The VF were normal in 97 patients, 8 had mild to moderate defects with no definite pattern, and in 9 the results were unreliable. Of the 51 patients older than 65years, 16 (31.4%) had altered or unreliable VF. The FAF was normal in 104 patients (82.5%), and abnormal, but consistent with ophthalmoscopic features, in 12 patients (pathological myopia, age related changes, early, middle or late age-related macular degeneration). Visual fields as a reference test for the diagnosis of AP toxicity are not quite reliable for patients over 65. Therefore, the FAF is recommended as primary test, perhaps combined with another objective test, such as SD-OCT instead of VF.