Protein kinase C alpha and tumorigenesis of the endocrine gland.
A point mutation in the protein kinase C alpha (PKC alpha) gene has been discovered in a subpopulation of human pituitary tumors characterized by their invasive phenotype. Here we show that: (1) thyroid tumors can express the PKC alpha mutation detected in a subpopulation of follicular adenomas and carcinomas, and (2) mutated PKC alpha has modified enzymatic properties as compared to wild-type PKC alpha. It has lost its capacity to phosphorylate the S17R substrate and exhibits a higher sensitivity to degradation as compared to wild-type PKC alpha. In conclusion, the presence of the PKC alpha mutant in tumors other than pituitary tumors and the observation that the presence of the point mutation induces changes in PKC alpha properties suggest the involvement of this mutant in tumorigenesis.


Adults with acquired hearing loss: identification and referral patterns of community health workers.
Community health workers in one health region of New South Wales were surveyed about their criteria and referral patterns to identify and assist adults with acquired hearing losses. Reported or observed communication problems were the most commonly used criteria for identifying hearing loss, suggesting that a failure model was being utilised. Given that the literature has previously demonstrated reluctance on the part of individuals with acquired hearing loss to report their hearing difficulties, the implications of these results are discussed. Clients suspected of having acquired hearing losses were usually referred to their doctors for further investigation and treatment. Other hearing help services were not systematically utilised. Alternative strategies for identifying and managing acquired hearing loss at the community level are needed.


An overview of cdc2-like kinase 1 (Clk1) inhibitors and their therapeutic indications.
Over the past decade, Clk1 has been identified as a promising target for the treatment of various diseases, in which deregulated alternative splicing plays a role. First small molecules targeting Clk1 are in clinical trials for the treatment of solid cancer, where variants of oncogenic proteins derived from alternative splicing promote tumor progression. Since many infectious pathogens hi-jack the host cell's splicing machinery to ensure efficient replication, further indications in this area are under investigation, such as Influenza A, HIV-1 virus, and Trypanosoma infections, and more will likely be discovered in the future. In addition, Clk1 was found to contribute to the progression of Alzheimer's disease through causing an imbalance of tau splicing products. Interestingly, homozygous Clk1 knockout mice showed a rather mild phenotype, opposed to what might be expected in view of the profound role of Clk1 in alternative splicing. A major drawback of most Clk1 inhibitors is their insufficient selectivity; in particular, Dyrk kinases and haspin were frequently identified as off-targets, besides the other Clk isoforms. Only few inhibitors were shown to be selective over Dyrk1A and haspin, whereas no Clk1 inhibitor so far achieved selectivity over the Clk4 isoform. In this review, we carefully compiled all Clk1 inhibitors from the scientific literature and summarized their structure-activity relationships (SAR). In addition, we critically discuss the available selectivity data and describe the inhibitor's efficacy in cellular models, if reported. Thus, we provide a comprehensive overview on the current state of Clk1 drug discovery and highlight the most promising chemotypes.


The association of bone mineral density and parathyroid hormone with serum magnesium in adult patients with sickle-cell anaemia.
Bone disorders including osteopenia and osteoporosis are a frequent cause of morbidity in sickle-cell disease (SCD). Magnesium (Mg) regulates some biological processes important in bone remodelling. We aimed to investigate whether serum Mg levels (sMg) may have an impact on bone mineral density (BMD) in sickle-cell anaemia (SCA). Sixty adults with SCA in steady-state and 20 age- and race-matched healthy blood donors were included in the study. The BMD was evaluated with respect to minerals and biochemical indices of bone metabolism. Multivariate analysis was performed to determine the factors influencing BMD. The mean sMg concentration was 0.64 ±0.06 (reference range 0.7-1.2 mmol/l) for 34% of the population, and 0.86 ±0.08 mmol/l for 66%. There were significant differences between Mg groups and controls in BMD, phosphorus (PO(4)), parathyroid hormone (PTH) (p = 0.011, p = 0.011 and p = 0.0001 respectively) and osteocalcin (OC) (p = 0.030) levels. The sMg was found to be associated positively with serum calcium (Ca), PTH and OC (r = 0.585; r = 0.436; r = 0.351 respectively, all at p < 0.05), and negatively with PO(4) (r = -0.312; p < 0.05). Multivariate analysis demonstrated that only PTH (p < 0.05) was an independent factor for BMD. Moreover, it identified sMg, OC, and CTX as independent factors for PTH (all p < 0.05). These results indicate that serum Mg may be a co-contributing factor in causing low BMD. However, other possible aetiologies including decreased PTH and increased bone turnover certainly play a role. Based on the present data, it is prudent to monitor sMg routinely in this patient population and treat the condition whenever possible.


Patterns of alcohol use among adolescents living in Porto Alegre, Brazil.
A cross-sectional household survey was used to assess patterns of alcohol experimentation and consumption among Brazilian adolescents, stratified by age and sex. Trained interviewers administered a standardized questionnaire to 950 subjects, ages 10 to 18, which examined such things as age of first alcohol use, situational aspects of consumption, amounts ingested and use among peers. Lifetime prevalence of alcohol use was high (71.5%), especially in the older teens (94.4%). The mean age of first use was 10 years, and consumption of all types of alcohol, including hard liquor, was common. Alcohol use typically began in the home, at family celebrations and social occasions, and progressively evolved to street drinking with peers. This pattern was most evident in males, who reported a larger volume of alcohol consumption per episode, when compared to females. The total amount of alcohol consumption reported for all ages is very high and may be due to permissive cultural views of alcohol. Age and gender play an important role in the evolution of drinking, with male adolescents being exposed to higher concentrations of alcohol and at younger ages than females, who seem to have a more conservative attitude toward excessive drinking. Subjects considered these practices normal, with no concern about the illegality of such behaviors.


Detecting cross-linked peptides by searching against a database of cross-linked peptide pairs.
Mass spectrometric identification of cross-linked peptides can provide valuable information about the structure of protein complexes. We describe a straightforward database search scheme that identifies and assigns statistical confidence estimates to spectra from cross-linked peptides. The method is well suited to targeted analysis of a single protein complex, without requiring an isotope labeling strategy. Our approach uses a SEQUEST-style search procedure in which the database is comprised of a mixture of single peptides with and without linkers attached and cross-linked products. In contrast to several previous approaches, we generate theoretical spectra that account for all of the expected peaks from a cross-linked product, and we employ an empirical curve-fitting procedure to estimate statistical confidence measures. We show that our fully automated procedure successfully reidentifies spectra from a previous study, and we provide evidence that our statistical confidence estimates are accurate.


Enrichment of Large-Diameter Semiconducting Single-Walled Carbon Nanotubes by Conjugated Polymer-Assisted Separation.
Semiconducting single-walled carbon nanotubes (s-SWCNTs) with large diameters are highly desired in the construction of high performance optoelectronic devices. However, it is difficult to selectively prepare large-diameter s-SWCNTs since their structure and chemical stability are quite similar with their metallic counterparts. In this work, we use SWCNTs with large diameter as a raw material, conjugated polymer of regioregular poly-(3-dodecylthiophene) (rr-P3DDT) with long side chain as a wrapping agent to selectively separate large-diameter s-SWCNTs. It is found that s-SWCNTs with a diameter of ~1.9 nm are effectively enriched, which shows a clean surface. By using the sorted s-SWCNTs as a channel material, we constructed thin-film transistors showing charge-carrier mobilities higher than 10 cm2 V-1 s-1 and on/off ratios higher than 103.


Observation of Structural Wavepacket Motion: The Umbrella Mode in Rydberg-Excited N-Methyl Morpholine.
We have observed time-resolved, structural dynamics of a coherent vibrational wavepacket in Rydberg-excited N-methyl morpholine, a molecule with 48 internal degrees of freedom. The molecular structure was established by associating the time-dependent Rydberg electron binding energy, obtained from time-resolved photoionization-photoelectron spectroscopy, to the molecular structure using self-interaction corrected density functional calculations. Optical excitation at 226 nm launches an oscillatory wavepacket in the amine umbrella coordinate with a 650 fs period. Even though the Franck-Condon excitation is at an angle of 17°, the wavepacket settles into an oscillation between 4° and -10° within a fraction of a vibrational period and then dephases with a time constant of 750 fs.


Alternating phenotypic expression of two classes of Trichomonas vaginalis surface markers.
The antigenic heterogeneity of Trichomonas vaginalis is due in part to the membrane disposition of immunogens (repertoire A) among some but not all isolates and among subpopulations of trichomonads of certain isolates. Heterogeneous T. vaginalis isolates undergo phenotypic variation for the A repertoire of immunogens. The presence of immunogens on (A+ phenotype) or the absence of them from (A- phenotype) trichomonal surfaces clearly influences the virulence traits of the pathogenic human trichomonads. A- parasites, for example, possess an enhanced ability to cause cytadherence-dependent killing of HeLa cells as compared with A+ parasites. A relation between phenotype of repertoire A and adherence was further substantiated by fractionating parasites of a parent T. vaginalis isolate, yielding adherent and nonadherent subpopulations. Trichomonad proteins were identified as putative adhesin candidates (repertoire B); adhesins were synthesized only by adherent (B+ parasites). Flow cytofluorometry of B+ and B- (nonadherent) subpopulations with antibody to proteins of the A repertoire demonstrated corresponding A- B+ and A+ B- phenotypes, respectively. Data support the hypothesis that trichomonads of some isolates of T. vaginalis undergo alternating expression of at least two classes of surface markers.


Carpal Tunnel Syndrome: Open or Endoscopic Release Surgery Method?
Carpal tunnel syndrome (CTS) or median nerve neuropathy is among the causes of numbness, paresthesia, and sensory and motor dysfunction in the affected hand. The objective of this study was to compare open and endoscopic carpal tunnel release (ECTR) methods. A multicenter, historical cohort study was performed on 47 hands in 46 patients with a clinical diagnosis of CTS and a failed trial of conservative treatment. Samples were divided into two groups consisting of 23 patients receiving open carpal tunnel release (OCTR) and ECTR. Outcome measurements had been carried out six weeks after the operation and included handgrip strength, post-op pain, and missing job days. Patients in both groups were comparable regarding baseline characteristics such as age, gender, and handgrip strength. Both methods significantly improved handgrip strength. No significant difference was detected between the two groups concerning handgrip strength improvement (P=0.700) and sick leave days (P=0.564). Open carpal tunnel release resulted in more significant post-op pain (mean 5.91±1.24 compared to 2.43±0.73 after endoscopic release), which was significant (P=0.000). No complications were reported with any technique. This study revealed that apart from post-op pain, other investigated endpoints were similar in both groups. Although the small sample size has limited our ability to draw a conclusive statement, these data suggest that there is no need to utilize the endoscopic technique for the optimum result, especially when this method requires more advanced equipment and could increase surgery costs. Therefore, both approaches can result in good clinical outcomes.


Development of a 1,2-difluorofucoside activity-based probe for profiling GH29 fucosidases.
GH29 α-l-fucosidases catalyze hydrolysis of terminal α-l-fucosyl linkages with varying specificity and are expressed by prominent members of the human gut microbiota. Both homeostasis and dysbiosis at the human intestinal microbiota interface have been correlated with altered fucosidase activity. Herein we describe the development of a 2-deoxy-2-fluoro fucosyl fluoride derivative with an azide mini-tag as an activity-based probe (ABP) for selective in vitro labelling of GH29 α-l-fucosidases. Only catalytically active fucosidases are inactivated by this ABP, allowing their functionalization with a biotin reporter group via the CuAAC reaction and subsequent in-gel detection at nanogram levels. The ABP we present here is shown to be active against a GH29 α-l-fucosidase from Bacteroides fragilis and capable of labeling two other GH29 α-l-fucosidases with different linkage specificity, illustrating its broader utility. This novel ABP is a valuable addition to the toolbox of fucosidase probes by allowing identification and functional studies of the wide variety of GH29 fucosidases, including those in the gut microbiota.


Human natural killer cell microRNA: differential expression of MIR181A1B1 and MIR181A2B2 genes encoding identical mature microRNAs.
Natural killer (NK) and T lymphocytes share many properties, yet only NK cells respond rapidly to infection and cancer without pre-activation. We found that few microRNAs (miRNAs) differed significantly between human NK and T cells. Among those miRNAs, miR-181a and miR-181b levels rose during NK cell differentiation. Prior studies indicate that miR-181a and miR-181b are critical for human NK cell development and are co-transcribed from genes on chromosome 1 (MIR181A1B1) and on chromosome 9 (MIR181A2B2). We mapped human MIR181A1B1 and MIR181A2B2 transcription start sites to 78.3 kb and 34.0 kb upstream of the mature miRNAs, generating predominantly unspliced transcripts of 80-127 kb and ~60 kb, respectively. Unlike mouse thymocytes, human T cells expressed both MIR181A1B1 and MIR181A2B2. We tested the hypothesis that NK cells differentially transcribe the two genes during development and in response to immune regulatory cytokines. During NK-cell differentiation, MIR181A2B2 expression rose markedly and exceeded that of MIR181A1B1. TGF-β treatment increased NK-cell MIR181A2B2 transcription, whereas IL-2, IL-15 and IL-12/IL-18 treatments upregulated MIR181A1B1. The MIR181A2B2 promoter was strongly transactivated by SMAD3 and SMAD4 transcription factors, suggesting that TGF-β signaling upregulates MIR181A2B2 expression, at least in part, through SMAD-dependent promoter activation.


A new species of Lobesia Guenée, 1845 from Thailand (Lepidoptera: Tortricidae: Oletheutinae).
Lobesia bisacca Charoensub and Pinkaew, n.sp., is described from Thailand. Specimens were collected in light traps in Trat Province, eastern Thailand and were deposited in the Kasetsart Kamphaengsaen Insect Collection. The new species can be distinguished from all other congeners by the unusual, long, protruding process from the base of the sacculus in the male genitalia. Illustrations of the adult, male genitalia, and male secondary characters are provided.


Differences in composition of avian bone collagen following genetic selection for resistance to osteoporosis.
1. Collagen characteristics were compared in the tibiotarsus and humerus from 103 females and 38 males aged 68 to 72 weeks from the G6 generation of lines of laying hen selected for resistance or susceptibility to osteoporosis (high and low bone index (BI) lines). 2. Selection over the latest generation resulted in further divergence in the breaking strengths of humerus (from 12.3 to 21.8%) and tibia (from 22.3 to 37.3%) in hens. Males also showed line differences in bone strengths. 3. Plasma pyridinoline concentration was higher in hens in the low BI line, suggesting a greater rate of bone resorption in this line. 4. There were few differences between the lines in collagen and calcium concentrations in humerus and tibiotarsus cortical bone. 5. There were no differences between the lines in either sex in reduced immature collagen cross-link content of humerus or tibiotarsus. 6. Mature collagen cross-link content was higher in the high BI line in the male humerus but this effect was not apparent in the male tibiotarsus nor in either bone in the females. 7. Pyrrolic cross-link contents were higher in the high BI line in the female humerus and tibiotarsus and in the male tibiotarsus. 8. Over both lines combined, there were positive correlations between humeral and tibiotarsal pyrrole contents and strengths in females and between tibiotarsal pyrrole content and strength in males. 9. It is concluded that an increase in cross-linking, particularly pyrrolic cross-linking, in the collagen matrix contributes in part to the improvement in bone strength in the high BI line.


Comparison of the Computer and Hand Administered Versions of the Brown Location Test (BLT).
The Brown Location Test (BLT) was developed to remedy some of the problems in existing visual-based memory tests. The hand version has demonstrated good psychometric properties, the ability to provide lateralization information for mesial temporal lobe epilepsy patients, and has normative data. The purpose of this study was to compare the hand administered format to the more recently developed computer administered format. We used Generalizability Theory analyses to assess the degree of variability in scores across the hand and computer versions of the test, and across alternate test forms, A and B. We also compared the means and standard deviations for the different versions and forms using paired t-tests, and Pearson correlation coefficients. There was minimal variability and high levels of score similarity across the various test administration formats and forms. The high degree of comparability between versions allows one to apply the validity findings and normative data collected using the hand administered version to the computer version of the BLT.


Optimal Weights Mixed Filter for removing mixture of Gaussian and impulse noises.
In this paper we consider the problem of restoration of a image contaminated by a mixture of Gaussian and impulse noises. We propose a new statistic called ROADGI which improves the well-known Rank-Ordered Absolute Differences (ROAD) statistic for detecting points contaminated with the impulse noise in this context. Combining ROADGI statistic with the method of weights optimization we obtain a new algorithm called Optimal Weights Mixed Filter (OWMF) to deal with the mixed noise. Our simulation results show that the proposed filter is effective for mixed noises, as well as for single impulse noise and for single Gaussian noise.


Feasibility and Efficacy of a Degradable Magnesium-Alloy GBR Membrane for Bone Augmentation in a Distal Bone-Defect Model in Beagle Dogs.
We explored the feasibility and efficacy of a degradable magnesium (Mg) alloy guided bone regeneration (GBR) in the treatment of bone defects after tooth extraction. A GBR membrane (MAR-Gide (MG)) was used to treat a mandibular second molar (M2M)-distal bone defect (DBD). In eight beagle dogs, bilateral mandibular second and fourth premolars were hemi-sected. The distal roots were removed to create a two-wall bony defect of dimension 5 mm × 5 mm × 5 mm to simulate M2M-DBD. Thirty-two bone defects were assigned randomly into four groups according to GBR membranes (MG and Bio-Gide (BG)) applied and the time of killing (3 months and 6 months after surgery). The osteogenesis of bone defects and MG degradation were analyzed using micro-CT, histology (staining, tartrate-resistant acid phosphatase), and inductively coupled plasma mass spectrometry. MG did not increase the prevalence of infection, wound dehiscence, or subcutaneous emphysema compared with those using BG. Trabecular volume/total volume at 3 months (63.71 ± 10.4% vs. 59.97 ± 8.94%) was significantly higher in the group MG than that in the group BG. Implanted MG was degraded completely within 3 months, and "island-shaped" new bone was found near MG degradation products. A significant difference was not found in vertical bone height or percent of new bone formation (45.44 ± 12.28% vs. 43.49 ± 7.12%) between the groups. The concentration of rare-earth elements in mandibular lymph nodes of the group MG was significantly higher than that of the group BG (P ≤ 0.017) but did not lead to histopathological changes. In summary, MG exhibited good biocompatibility and clinical applicability compared with BG in vivo. The osteogenic effect of MG could be enhanced by regulating the degradation rate of Mg-alloy.


Effect of azelastine on the down regulation of beta-adrenoceptors in guinea pig lung.
The new antiallergic drug azelastine (E-0659, Azeptin; CAS 58581-89-8) is used in the treatment of rhinitis and bronchial asthma. In the present study, the effect of azelastine on the regulation of the beta-adrenoceptors and the down regulation of beta-adrenoceptors by terbutaline, a beta-agonist, was investigated using guinea pig lungs. Guinea pigs were divided into four groups; (1) the control (saline-treated) group, (2) the terbutaline-treated group, (3) the azelastine-treated group, (4) terbutaline plus azelastine-treated group. Guinea pigs intramuscularly injected with each agent three times a day for successive 7 days. In the terbutaline-treated group, a 26% reduction in the number of beta-adrenoceptors compared with those of the control group was observed. In the azelastine-treated group, the number of beta-adrenoceptors increased by 24% compared with those of the control group. The number of the beta-adrenoceptors in the terbutaline plus azelastine-treated group was significantly increased compared with that of the terbutaline-treated group. These results suggest that azelastine may prevent the down regulation observed during beta-agonist administration by increasing the number of beta-adrenoceptors.


Health inequalities: a global perspective.
The objective of this article is to present health inequalities as a global problem which afflicts the populations of the poorest countries, but also those of the richest countries, and whose persistence represents one of the most serious and challenging health problems worldwide. Two components of global inequalities are highlighted: inequalities between groups within the same society, and inequalities between nations. The understanding that many of these inequalities are unjust, and therefore inequities, is largely derived from the inequalities that are identified between the various social groups of a given society. Inequalities between different societies and nations, while relevant and often of greater magnitude, are not always considered to be unjust. There have been several proposed solutions, which vary according to different theoretical interpretations and explanations. At the global level, the most plausible thesis has focused on improving global governance mechanisms. While that latter are attractive and have some arguments in their favor, they are insufficient because they do not incorporate an understanding of how the historical process of the constitution of the nations occurred and the importance of the position of each country in the global productive system.


Characteristics of COVID-19 Clinical Trials in China Based on the Registration Data on ChiCTR and ClinicalTrials.gov.
This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. In total, 262 intervention clinical trials were retrieved on March 10, 2020. Overall, 181 (69.1%) trials involved two groups, 200 (76.3%) trials were randomized parallel trials, 24 (9.2%) trials were double blind, and 60.3% of trials included ≤100 participants. Sixty (22.9%) trials considered symptom improvement as the primary endpoint and 43 (16.4%) trials considered the rate or time at which the subjects became virus-free as the primary endpoint. Of 262 intervention studies, chemical drugs and biological products were studied in 105 (40.1%) intervention studies, of which antiviral drugs accounted for 15.3% and malaria drugs accounted for 8.4% of the studies. Among all trials, 27.9% of the studies used traditional Chinese medicine (TCM), 10.3% used cell therapy, and 5.0% used plasma therapy. This study is the first snapshot of the landscape of COVID-19 clinical trials registered in China and provided the basic features of clinical trial designs for the treatment and prevention of COVID-19 to offer useful information to guide future clinical trials on COVID-19 in other countries.


Epidermal nuclear IgG deposition in normal skin: characterization by anti-ribonucleoprotein IgG-Fab fragments.
Epidermal nuclear IgG deposition in clinically normal skin may occur in patients with scleroderma or scleroderma-like features. In order to evaluate the mechanisms of the fixation, Fab fragments of anti-RNP IgG antibodies, obtained after papain digestion, were incubated for increasing times with various substrates: human skin, human mononuclear cells, cultured human fibroblasts and rabbit lip. Our results showed that anit-RNP IgG-Fab fragments could penetrate most of the living cells of human skin and rabbit lip and, to a lesser degree, mononuclear cells and poorly cultured fibroblasts. No ability to fix was found either with anti-RNP IgG-Fe fragments or with anti-nDNA/DNP IgG-Fab. It was concluded that anti-RNP IgG could penetrate viable epidermal and non-epidermal cells and that surface Fe receptors must play a minor role in the cellular penetration of antibodies.


Association of prehypertension and hyperhomocysteinemia with subclinical atherosclerosis in asymptomatic Chinese: a cross-sectional study.
Comorbid hypertension and hyperhomocysteinemia is an important risk factor for carotid atherosclerotic plaque formation. We put forward the hypothesis that the subjects with comorbid prehypertension and hyperhomocysteinemia also had an increased risk of subclinical atherosclerosis, using carotid intima-media thickness (CIMT) as the marker of the atherosclerotic process. A total of 4102 asymptomatic Chinese subjects aged 18-60 years were divided into four groups according to blood pressure (BP) and homocysteine (HCY) level: the control group without prehypertension or hyperhomocysteinemia, isolated prehypertension group, simple hyperhomocysteinemia group and prehypertension with hyperhomocysteinemia group. Serum lipids, fasting blood glucose (FBG), HCY and CIMT were measured. There was significant difference in the positive rates of increased CIMT among four groups. Compared with the controls, the subjects in the other three groups had a higher risk of increased CIMT (isolated prehypertension group, OR 2.049, 95% CI 1.525 to 2.754; simple hyperhomocysteinemia group, OR 2.145, 95% CI 1.472 to 3.125; prehypertension and hyperhomocysteinemia group, OR 3.199, 95% CI 2.362 to 4.332). However, by multiple logistic regression analysis, only comorbid prehypertension and hyperhomocysteinemia was independently associated with increased CIMT (OR 1.485, 95% CI 1.047 to 2.108, P<0.05). Comorbid prehypertension and hyperhomocysteinemia was an independent risk factor of subclinical atherosclerosis in asymptomatic Chinese, but isolated prehypertension or hyperhomocysteinemia was not. Therefore, combined intervention for prehypertension and hyperhomocysteinemia may contribute to decrease the incident of cardiovascular disease.


QTL mapping for kernel-related traits in a durum wheat x T. dicoccum segregating population.
Durum wheat breeding relies on grain yield improvement to meet its upcoming demand while coping with climate change. Kernel size and shape are the determinants of thousand kernel weight (TKW), which is a key component of grain yield, and the understanding of the genetic control behind these traits supports the progress in yield potential. The present study aimed to dissect the genetic network responsible for kernel size components (length, width, perimeter, and area) and kernel shape traits (width-to-length ratio and formcoefficient) as well as their relationships with kernel weight, plant height, and heading date in durum wheat. Quantitative Trait Locus (QTL) mapping was performed on a segregating population of 110 recombinant inbred lines, derived from a cross between the domesticated emmer wheat accession MG5323 and the durum wheat cv. Latino, evaluated in four different environments. A total of 24 QTLs stable across environments were found and further grouped in nine clusters on chromosomes 2A, 2B, 3A, 3B, 4B, 6B, and 7A. Among them, a QTL cluster on chromosome 4B was associated with kernel size traits and TKW, where the parental MG5323 contributed the favorable alleles, highlighting its potential to improve durum wheat germplasm. The physical positions of the clusters, defined by the projection on the T. durum reference genome, overlapped with already known genes (i.e., BIG GRAIN PROTEIN 1 on chromosome 4B). These results might provide genome-based guidance for the efficient exploitation of emmer wheat diversity in wheat breeding, possibly through yield-related molecular markers.


Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound.
We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.


Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation.
Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.


Complete sequence of the genome-reduced Escherichia coli DGF-298.
We report the complete genome sequence and annotation of Escherichia coli DGF-298, a genome-reduced E. coli strain with interesting properties for systems and synthetic biology. DGF-298 has a single circular chromosome of 2,991,126 bp and 2,831 genes, including 2,691 coding sequences, with a mean G + C content of ~51%.


An appraisal of the ethical issues involved in high-technology cancer pain relief.
... We will turn our attention to the current state of pain relief technology and the ethical questions surrounding the use of advanced technology, otherwise referred to as "high-tech," pain relief. It is obvious that pain may decrease the quality of life for cancer patients. The availability of long-acting narcotics, such as MS Contin or methadone, affords cancer patients long-duration pain relief at minimal cost. The use of adjuvant medications may also be important. Clinical examples of the effective use of adjuvant medications include the addition of a nonsteroidal, anti-inflammatory agent to help patients cope with bone pain and the use of a serotonin blocking agent to reduce the transmission of pain impulses in the spinal cord. Only a small percentage of patients are good candidates for high-tech delivery systems for narcotic administration. In our pain management clinic, all patients are initially placed on oral medications. When the side effects of oral medications become excessive, or the patient becomes unable to take oral medications, high-tech modalities are considered for use.


Applications of CRISPR technology in cellular immunotherapy.
CRISPR technology has transformed multiple fields, including cancer and immunology. CRISPR-based gene editing and screening empowers direct genomic manipulation of immune cells, opening doors to unbiased functional genetic screens. These screens aid in the discovery of novel factors that regulate and reprogram immune responses, offering novel drug targets. The engineering of immune cells using CRISPR has sparked a transformation in the cellular immunotherapy field, resulting in a multitude of ongoing clinical trials. In this review, we discuss the development and applications of CRISPR and related gene editing technologies in immune cells, focusing on functional genomics screening, gene editing-based cell therapies, as well as future directions in this rapidly advancing field.


Comparative Analysis of P63, Maspin and Matrix Metalloproteinase 2 Expression in Mucoepidermoid Carcinoma and Adenoid Cystic Carcinoma of Salivary Glands.
The tumor suppressor role of myoepithelial cells and related mechanisms in breast tumors are well understood. However, the role of these cells in tumors of salivary glands is debatable. The present study was designed to determine the expression of p63, mammary serine protease inhibitor (maspin) and matrix metalloproteinase 2 (MMP-2) in mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ADCC) of salivary glands due to various cellular differentiation and structure. The association between the expression of these markers and clinicopathologic features and myoepithelial differentiation were also evaluated. P63, maspin, and MMP-2 expression were immunohistochemically studied in 67 cases including35 cases of MEC and 32 cases of ADCC. The smooth muscle actin (SMA) staining was also applied to confirm the presence of myoepithelial differentiation. Data was analyzed using Chi-square test, Mann-Whitney U test and t-test. The expression of p63 (p= 0.009) and maspin (p= 0.012) significantly differed between the study groups. P63 positive cells in MEC were negative for SMA staining in contrast to ADCC. Furthermore, the expression of P63 (p= 0.045) and maspin (p= 0.019) significantly and inversely correlated with histologic grade in ADCC. Likewise, positive significant correlation was detected between histologic grade and expression of P63 (p= 0.018) and MMP-2 (p= 0.003) in MEC samples. Our findings showed that MEC is devoid of myoepithelial cells. The difference in expression of P63 and maspin in ADCC and MEC highlighted the role and presence of myoepithelial cells in ADCC. Indeed, the high expression of P63 and maspin in well-differentiated ADCCs suggests the tumor suppressor effect of myoepithelial cells. Considering the association between the evaluated markers and histological grade, p63 in both tumors, maspin in ADCC and MMP-2 in MEC may be efficient predictors of clinical behavior.


Genome mining-directed activation of a silent angucycline biosynthetic gene cluster in Streptomyces chattanoogensis.
Genomic sequencing of actinomycetes has revealed the presence of numerous gene clusters seemingly capable of natural product biosynthesis, yet most clusters are cryptic under laboratory conditions. Bioinformatics analysis of the completely sequenced genome of Streptomyces chattanoogensis L10 (CGMCC 2644) revealed a silent angucycline biosynthetic gene cluster. The overexpression of a pathway-specific activator gene under the constitutive ermE* promoter successfully triggered the expression of the angucycline biosynthetic genes. Two novel members of the angucycline antibiotic family, chattamycins A and B, were further isolated and elucidated. Biological activity assays demonstrated that chattamycin B possesses good antitumor activities against human cancer cell lines and moderate antibacterial activities. The results presented here provide a feasible method to activate silent angucycline biosynthetic gene clusters to discover potential new drug leads.


Molecular weights of IgA-circulating immune complexes (CIC) in patients with IgA nephropathy: application of HPLC and solid-phase anti-C3 Facb EIA.
The detection of molecular weights of IgA-circulating immune complexes (CIC) in sera is described. Measurement of IgA-, IgG- and IgM-CIC in sera was also performed. Serum samples were obtained from nine patients with IgA nephropathy, nine patients with chronic proliferative glomerulonephritis without IgA deposits (PGN) and 19 healthy adults. Serum samples of these patients were subjected to high performance liquid chromatography (HPLC) and then divided into 50 fractions. Measurement of IgA-, IgG- and IgM-CIC in such fractions was performed using solid-phase anti-C3 Facb EIA. The levels of IgA-CIC in sera from patients with IgA nephropathy were significantly higher than those from patients with PGN or healthy adults. The peak values of molecular weights of IgA-CIC in sera from patients with IgA nephropathy ranged from 2.6 X 10(5) to 3.0 X 10(5) daltons (mean +/- SD; 2.9 +/- 2.0). It was suggested that the increase of IgA-CIC in sera from patients with IgA nephropathy may be mainly due to dimers and/or polymers.


[Growth disorders in the course of chronic juvenile arthritis].
Juvenile idiopathic arthritis (JIA) is the most common chronic arthropathy, in witch an inflammatory process may lead not only to fixed deformities but also to developmental disturbances, including growth inhibition. The study objective of the current study was to assess the relationship of the degree of physical development disturbances in children with JIA with disease duration, clinical type, the Steinbrocker class of the disease and the therapy applied. Anthropometric parameters were analysed in 97 children aged 2-18 years (45 girls and 52 boys) with JIA. Bone densitometry (DXA) was performed in 51 children to assess the mineral mass of the whole skeleton (Total BMD) and L2-L4 vertebrae. Results Growth deficiency below -2.0 SDHS--Standard Deviation Height Score (group I) was found in 25 children (25.8%), with the predominance of older children (p<0.05) suffering from a polyarticular type. Children with considerable joint destruction (class III and IV according to Steinbrocker) exhibited lower height (p<0.002) as compared to the group of children without growth disorders (group II) and with early or moderate anatomical joint damage. Significant differences in BMI were noted between group I and II (16.05 and 18.12, respectively; p<0.02). A significant reduction in total bone mineral mass were found in group I as compared to group II (total BMD 0.736 g/cm2 and 0.922 g/cm2; p<0.05). Growth deficiencies which strongly correlated with the degree of joint destruction and thus with inflammatory activity were found in 25% of the study children and adolescents with JIA. Growth retardation was accompanied by a significant bone mass reduction.


Acitretin combined with NB-UVB in the treatment of cutaneous CD30-positive anaplastic large cell lymphoma.
Cutaneous CD30+ lymphoproliferative disorders represent a spectrum of skin lymphatic reticular proliferative diseases, including lymphomatoid papulosis (LYP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL), and borderline lesions between them. Although they all express CD30 as a phenotypic marker and share overlapping immunophenotypic features, they differ in clinical manifestations, pathological features, treatment, and prognosis. LYP is a kind of benign disease characterized by recurrent papules and nodules, and may spontaneously regress. PC-ALCL presents with solitary tumor or local grouped nodules characterized by large T-cells and may completely or partially resolve in fewer than half of cases. We reported a case of patient with clinical manifestation and pathologic features consistent with LYP in its early stages, which later turned into PC-ALCL. This patient was treated with acitretin combined with NB-UVB and had an obvious response.


Abundance and subcellular distribution of GTP-binding proteins in 3T3-L1 cells before and after differentiation to the insulin-sensitive phenotype.
The abundance and the subcellular distribution of GTP-binding proteins was studied in membrane fractions (plasma membranes and low-density microsomes) from 3T3-L1 cells before and after differentiation to the insulin-sensitive phenotype. After differentiation, the abundance of alpha i (alpha subunit of GTP-binding protein Gi), alpha o (alpha subunit of GTP-binding protein G(o)), and of a 47-kDa alpha s (alpha subunit of GTP-binding protein Gs) as detected by immunoblotting with specific antisera was reduced by 10-50% when normalized per membrane protein. In contrast, a 43-kDa alpha s was increased about threefold after differentiation. Furthermore, cholera-toxin-catalyzed ADP-ribosylation of both 43-kDa and 47-kDa alpha s was disproportionately increased ninefold and threefold, respectively, possibly reflecting the increased production of an ADP-ribosylation factor in the differentiated cells. The small GTP-binding protein Ha-ras was reduced by 50%, whereas rab1 and other small GTP-binding proteins tentatively identified as rab-isoforms (ras-homologous gene products from brain) were increased by 100% and 70%, respectively. Since the total protein content of 3T3-L1 cells was increased threefold after differentiation, the observed increase of the 43-kDa alpha s, rab1 and of the other rab isoforms was eightfold, sixfold and fivefold, respectively, when normalized/cell count. With the exception of the rab isoforms, all GTP-binding proteins were predominantly, if not exclusively, located in the plasma membrane; comparable amounts of the rab isoforms were found in plasma membranes and low-density microsomes. Insulin induced the characteristic redistribution of glucose transporters GLUT4 from low-density microsomes to the plasma membranes, but failed to alter the subcellular distribution of any of the GTP-binding proteins investigated. These data suggest that the increase in the abundance of the 43-kDa alpha s subunit and of several rab isoforms might be related to specific functions of the adipocyte-like phenotype, but that none of the investigated guanine-nucleotide-binding regulatory (G)-proteins appears to be tightly associated with the GLUT4.


Granulocytic sarcomas of the head and neck.
Granulocytic sarcomas (chloromas) are rare tumors with a predilection for head and neck sites. In a review of six cases from two teaching institutions, chloromas were associated with the development of acute myelogenous leukemia or a relapse in five cases. Treatment modalities included chemotherapy and radiation therapy for problematic lesions. Our only survivor received combination therapy despite a negative bone marrow examination. Work-up should include a computed tomographic scan or magnetic resonance imaging to evaluate the extent of the tumor. Bone marrow examination and biopsy should be performed and specimens prepared for immunohistochemical studies or electron microscopy. Recommended treatment includes both aggressive chemotherapy and 2000 to 3000 cGy of external-beam radiotherapy to the tumor when possible.


Quality of the threshold algorithm in age-related macular degeneration: Stratus versus Cirrus OCT.
Automatically generated measurements of the retinal volume or the central retinal thickness are based on correctly set threshold lines on the retinal surface and the retinal pigment epithelium. The purpose of this study was to compare the accuracy of threshold algorithm lines of Stratus optical coherence tomography (OCT) with those of Cirrus OCT. A consecutive series of patients at least 50 years of age with exudative age-related macular degeneration was included. Stratus OCT (retinal thickness program) and Cirrus OCT (macular cube 512 x 128) were performed by the same examiner, the sequence of the examinations was randomized. Two independent examiners evaluated the positioning of the threshold algorithm lines and performed a grading of the failures. Logistic regression analysis was applied for evaluation of the failure rate. One hundred four patients were included. For the entire OCT examination (6 scans Stratus OCT, 128 scans Cirrus OCT) algorithm line failures were detected in 69.2% of the Stratus OCT and in 25% of the Cirrus OCT examinations, with the difference reaching statistical significance (P < 0.001). The median failure grade was 1 (0-6) for Stratus and 0 (0-5.15) for Cirrus OCT. Age, measurement sequence, and investigator did not influence the error rates. With Cirrus OCT automatically performed and therefore objective measurements of central retinal thickness and retinal volume were provided correctly in 69.2% of the scans. Furthermore, this latest software version offers the possibility of manual correction of false positioned algorithm lines (ClinicalTrials.gov number, NCT00568191).


Tissue Engineering of JAK Inhibitor-Loaded Hierarchically Biomimetic Nanostructural Scaffold Targeting Cellular Senescence for Aged Bone Defect Repair and Bone Remolding.
Cell senescence or apoptosis contributes to self-failure and functional loss in specialized cells, leading to incapacity of the body to repair specific damages. Senescent bone marrow mesenchymal stem cells (BMSCs) lose their proliferative abilities and secrete senescence-associated secretory phenotype (SASP), hindering their participation in bone defect repair. Hence, the effective suppression of cell senescence is crucial to restore the self-repair capacity of body to treat bone defects. Since the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is associated with SASP secretion, herein, a new strategy is proposed to inhibit this pathway to suppress SASP secretion and enhance osteoblast activity based on a novel hierarchically biomimetic nanostructural electrospun scaffold with JAK inhibitors (JAKi, Ruxolitinib) loaded. As validated by in vitro and in vivo experiments, the JAKi loaded scaffold reduces SASP expression effectively and alleviates senescent cell burden, creating a pro-regeneration microenvironment that enhances osteoblast function and mineralization activity as well as rejuvenating the bone repair capacity. These findings offer insights into the regulatory role of cellular senescence in bone aging and provide a new and effective strategy to treat age-related bone defects by delivery of JAKi to locally aging bone defect sites.


Imaging of carotid artery disease: from luminology to function?
There have been tremendous advances in our ability to image atheromatous disease, particularly in the carotid artery, which is accessible and large enough to image. The repertoire of methodology available is growing, giving anatomical information on luminal narrowing which is approaching the level at which conventional carotid angiography will become very uncommon as CT and contrast-enhanced MR angiographic techniques become the norm. More exciting is the tentative ability to perform functional plaque imaging addressing enhancement patterns and macrophage activity using MR or positron-emission tomography techniques. These techniques, once rigorously evaluated, may, in addition to complex mathematical modelling of plaque, eventually allow us to assess true plaque risk. Time will best judge whether we will be able to move from the use of simple luminology to assessment of plaque function.


Parent experiences and psychosocial support needs 6 months following paediatric critical injury: A qualitative study.
Parents of critically injured children can experience high levels of psychological distress post-injury, however little is known about their experiences and needs following injury. This study aimed to explore parent experiences and psychosocial support needs in the six months following child critical injury. An interpretive qualitative design was used. Semi-structured interviews were conducted with 30 parents of 23 critically injured children. Interviews explored parent experiences and psychosocial support needs. Qualitative data were managed using NVIVO 10 and analysed thematically. Four themes were identified: integrating back into home life; adjusting mentally and emotionally to injury; coping with injury as a family; and navigating resources to meet family needs. Parents and families experienced substantial ongoing emotional impacts at 6 months following child injury. Parents were unprepared for the negative changes in their child's psychological wellbeing and behaviour post injury, and parents' mental health was negatively impacted, with mothers more likely to seek emotional support than fathers. Parents reported receiving no psychosocial follow-up from the hospital and limited information about community services and accessing local community resources on returning home. There is a need to include all family members in discharge planning, and to use a family-centred continuity-of-care approach from the time of child injury through to post-discharge recovery. To strengthen parent and family wellbeing, a biopsychosocial holistic approach is recommended, including cognitive-behavioural and other psychological strategies to help reduce distress for parents and all family members and strengthen their coping capacity. A dedicated family support coordinator role to facilitate care over the child recovery trajectory, and development of accessible online and e-psychosocial support resources for parents and families are recommended.


Social exclusion decreases prosocial behavior.
In 7 experiments, the authors manipulated social exclusion by telling people that they would end up alone later in life or that other participants had rejected them. Social exclusion caused a substantial reduction in prosocial behavior. Socially excluded people donated less money to a student fund, were unwilling to volunteer for further lab experiments, were less helpful after a mishap, and cooperated less in a mixed-motive game with another student. The results did not vary by cost to the self or by recipient of the help, and results remained significant when the experimenter was unaware of condition. The effect was mediated by feelings of empathy for another person but was not mediated by mood, state self-esteem, belongingness, trust, control, or self-awareness. The implication is that rejection temporarily interferes with emotional responses, thereby impairing the capacity for empathic understanding of others, and as a result, any inclination to help or cooperate with them is undermined.


Histopathology of pseudomembranous colitis.
Pseudomembranous colitis, an uncommon affection following surgery or antibiotic therapy, is characterized by whitish plaques ( pseudomembranes ) attached to the mucosa. Serial sectioning of these pseudomembranes disclosed that each of them was related to a lymphoid aggregate in the submucosa and the lamina propria. A group of glandular crypts overlying the aggregate were dilated by mucus, fibrin, leukocytes, and cellular debris. These contents jutted out of the mucosal surface into the lumen, constituting the stem of the pseudomembrane, and could spread over the surrounding mucosa. Accordingly, a morphologic unit was recognized in pseudomembranous colitis, including the lymphoid aggregate, the dilated glandular crypts, and the pseudomembrane stem.


Disseminated Bacillus Calmette-Guerin infection after BCG vaccination.
The BCG is administered to all the newborns at birth in Iran. Systemic adverse reactions to BCG vaccine such as osteomyelitis and disseminated BCG infection are rare. This is a retrospective study of 15 cases <72 months who were admitted with systemic syndrome compatible with disseminated mycobacterial disease during 2004-07. Disseminated BCG disease occurred in eight children younger than 6-months old and 12 patient younger than 12-months old. Twelve patients were male. Nine of 15 patients had well known primary immune deficiency disorders including severe combined immunodeficiency, chronic granulomatous disease; cell mediated immune defect and HIV infection. Nine (60%) cases had good response to four anti-mycobacterial drug therapy and interferon gamma. Disseminated BCG disease is a rare but devastating complication of BCG vaccination that should be considered in the appropriate clinical setting. Severe immune-compromised infants are at greatest risk and they respond poorly to standard therapies.


[Pulsatile administration of GnRH: from the future to the present].
Since the first clinical reports of the successful induction of ovulations and pregnancies using pulsatile administration of the neuropeptide GnRH by G. Leyendecker and L. Wildt's group in 1979, the role of the hypothalamic generator, as demonstrated in primates by E. Knobil, is widely accepted in human reproduction. During this time, an increasing number of group has experienced these therapies and there continues to be some controversies about the route of administration, the indications, the need for adjuvant therapies. A correct evaluation of these therapies needs multicentric studies and more accurate criteria: the MINITEL network provides a fast, inexpensive way to collect data from different groups and to perform studies with larger sample sizes. The Life table analysis method represents the more suitable method for evaluating and for comparing various therapy regimens. LH plasma pulsatility studies have been performed in humans in order to classify various "supra-pituitary" reproductive disorders. These studies are exposed to several methodological drawbacks and must be cautiously interpreted. Modelling is one of the new methodological issues which can give access to more physiological parameters.


Federally-Assisted Healthcare Coverage among Male State Prisoners with Chronic Health Problems.
Prisoners have higher rates of chronic diseases such as substance dependence, mental health conditions and infectious disease, as compared to the general population. We projected the number of male state prisoners with a chronic health condition who at release would be eligible or ineligible for healthcare coverage under the Affordable Care Act (ACA). We used ACA income guidelines in conjunction with reported pre-arrest social security benefits and income from a nationally representative sample of prisoners to estimate the number eligible for healthcare coverage at release. There were 643,290 US male prisoners aged 18-64 with a chronic health condition. At release, 73% in Medicaid-expansion states would qualify for Medicaid or tax credits. In non-expansion states, 54% would qualify for tax credits, but 22% (n = 69,827) had incomes of ≤ 100% the federal poverty limit and thus would be ineligible for ACA-mediated healthcare coverage. These prisoners comprise 11% of all male prisoners with a chronic condition. The ACA was projected to provide coverage to most male state prisoners with a chronic health condition; however, roughly 70,000 fall in the "coverage gap" and may require non-routine care at emergency departments. Mechanisms are needed to secure coverage for this at risk group and address barriers to routine utilization of health services.


[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2004)].
From October 2004 to September 2005, we collected the specimen from 319 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 383 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 381 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78, Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S. aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin-sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and inhibited the growth of all the strains at 2 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of all the strains at 0.125 microg/mL. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P. aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP, cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the growth of all the strains at 0.063 microg/mL. Also, all the agents generally showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (57.0%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H. influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae (16.1%) also were relatively frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria relatively frequently isolated from the patients treated with macrolides were P. aeruginosa and the isolation frequency was 43.5%.


Phase II trial of irinotecan (CPT-11) in relapsed or refractory non-Hodgkin's lymphomas.
CPT11, a camptothecin analogue, is a specific DNA topoisomerase I inhibitor, with activity in tumor cell lines with MDR expression. CPT11 has a broad spectrum of activity in solid tumors (especially in colorectal, gastric and small cell lung cancers). Early reports have shown that CPT11 could be active in non-Hodgkin's lymphomas (NHL) with low-dose schedules. To further evaluate the efficacy and toxicity of CPT11 in patients with refractory or relapsed NHLs, we conducted a phase II trial with escalated doses. From 04/98 to 05/01, 28 patients with NHL were enrolled. M/F 21/7; median age: 56 years (range 28-72); Ann Arbor stage at the time of the study I/II and III/IV in 6 and 21 patients, respectively. Sixteen patients had refractory disease when they were enrolled in this phase II study and 8 patients were previously treated with high-dose therapy and stem-cell transplantation. CPT11 was administrated at the doses of 350 mg/m2 every 3 weeks. Six courses were given in patients who achieved CR, PR or stable disease. Patients were evaluated every 2 courses. If no grade II or more toxicity was observed after the first course, escalated dose (500 mg/m2) was then undertaken. 19/28 patients received more than 2 courses of CPT11 and were evaluated for response. Nine patients received one course of therapy because of either progressive disease (n = 6), toxicity (n = 2) or refusal (n = 1). Ten patients received escalated dose (500 mg/m2). Complete remission and partial was achieved in 2/19 patients, stable disease in 7/19, and progressive disease in 10/19 patients. Median duration of responses was short (3 months, range 1-8 months). Seventy-five courses were evaluated for toxicity according to the WHO criteria. Diarrhea grade 2 or 3 occurred in 9/75 courses; cholinergic syndrome grade 2 in 3/75 courses; nausea grade 3 in 7/75 courses. Hematological toxicity: leucopenia grade 3 or 4 in 21/75 courses; thrombocytopenia grade 3 in 8/75 courses; infectious episodes grade 2 or 3 in 7/75 courses. In 2/7 courses with escalated doses, grade I/IV neutropenia occurred withoutother major toxicity. CPT11 has low activity in heavily pretreated NHLs. Responses were of short duration.


Endotoxin release after antibiotic treatment and its potential pathogenetic role in coagulative disorders of patients with gram-negative sepsis.
The liberation of endotoxin by gram-negative bacteria upon antibiotic treatment might be of clinical relevance in terms of adverse effects of antibiotic therapy in patients with gram-negative infections. In this paper we have taken into consideration the endotoxic material released by Salmonella typhimurium SH9178 after treatment with either ofloxacin and norfloxacin (which act as DNA-gyrase inhibitors) or imipenem (which affects the bacterial cell wall) in its capacity to induce in-vitro production of procoagulant activity, tissue factor-like, by human mononuclear cells. Endotoxin released from Salmonella typhimurium after treatment with the above antibiotics behaves as the typical endotoxin of gram-negative bacteria in its capacity to induce procoagulant production. Indeed human mononuclear cells after prolonged incubation with supernatants of antibiotic-treated Salmonella were able to shorten the recalcification time of normal but not Factor VII deficient plasma (tissue factor-like activity). On this basis we hypothesize that this mechanism, leading to the activation of blood coagulation through the extrinsic pathway, might be closely involved in thrombohemorrhagic disorders sometimes complicating the antimicrobial therapy of gram-negative sepsis.


Evidence for declining numbers of Ebola cases--Montserrado County, Liberia, June-October 2014.
The epidemic of Ebola virus disease (Ebola) in West Africa that began in March 2014 has caused approximately 13,200 suspected, probable, and confirmed cases, including approximately 6,500 in Liberia. About 50% of Liberia's reported cases have been in Montserrado County (population 1.5 million), the most populous county, which contains the capital city, Monrovia. To examine the course of the Ebola epidemic in Montserrado County, data on Ebola treatment unit (ETU) admissions, laboratory testing of patient blood samples, and collection of dead bodies were analyzed. Each of the three data sources indicated consistent declines of 53%-73% following a peak incidence in mid-September. The declines in ETU admissions, percentage of patients with reverse transcription-polymerase chain reaction (RT-PCR) test results positive for Ebola, and dead bodies are the first evidence of reduction in disease after implementation of multiple prevention and response measures. The possible contributions of these interventions to the decline is not yet fully understood or corroborated. A reduction in cases suggests some progress; however, eliminating Ebola transmission is the critical goal and will require greatly intensified efforts for complete, high-quality surveillance to direct and drive the rapid intervention, tracking, and response efforts that remain essential.


Commotio cordis: clinical implications of blunt cardiac trauma.
Blunt cardiac trauma can result not only in major structural impairments but also in subtle derangements without an apparent organic defect. Cardiac dysrhythmias, including ventricular fibrillation and sudden cardiac arrest, can occur in both cardiac contusion and cardiac concussion (commotio cordis) and may be fatal. The true incidence of these nonstructural cardiac injuries is unknown. Continuous electrocardiographic monitoring, assessment of cardiac troponin I and transesophageal echocardiograms are important aids in the evaluation of cardiac contusion and concussion.


HLA-DR and -DQ gene polymorphism in West Africans is twice as extensive as in north European Caucasians: evolutionary implications.
The HLA genes are the most polymorphic coding loci known in humans. DRB-DQA-DQB gene polymorphism was investigated by Taq I restriction fragment length polymorphism analysis in more than 700 West Africans and found to be almost twice as extensive in West Africans as in North European Caucasians. This finding indicates that Africans comprise the oldest and genetically most diverse human population and supports the hypothesis of the occurrence of a population bottleneck in the emergence of the White race. As in Caucasians, less than one-third of possible cis-encoded DQA-DQB combinations were encountered, indicating constraints on the pairing of DQ alpha and beta polypeptides. Heterozygote advantage (i.e., positive selection) was found for DRB, DQA, and DQB alleles as well as for DQA-DQB combinations. However, in West Africans as well as in North Europeans the observed frequencies of DRB-DQA-DQB homozygotes were close to neutrality expectations. Although the hypothesis that HLA polymorphism is maintained by parasite-driven overdominant selection is attractive, there is little evidence to support that view. We propose instead that one of the forces maintaining a low frequency of HLA homozygotes might be a decreased likelihood of potentially autoreactive T-cell clones escaping thymic selection in HLA heterozygotes. This would be consistent with the central role of HLA molecules as self/non-self discriminators.


A negative feedback modulator of antigen processing evolved from a frameshift in the cowpox virus genome.
Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing.


Performance of rapid influenza testing in hospitalized children.
Influenza infection is associated with high hospitalization rates among young children. Rapid diagnosis of influenza infection is particularly useful in order to prevent nosocomial infection and allows for the timely initiation of antiviral treatment. We evaluated the performance of a rapid influenza test in hospitalized children during the influenza season. All children (aged 6 months to 14 years) hospitalized with fever and/or respiratory symptoms, admitted during the 2005 influenza season, participated in the study. A multiplex reverse transcriptase polymerase chain reaction (RT-PCR), able to identify IFV-A H1N1, H3N2, and IFV-B subtypes, was performed on nasopharyngeal aspirates. The nasal swab was tested with a lateral-flow immunoassay (QuickVue Influenza Test). The performance of the rapid test was compared with the results of PCR. Influenza infection was diagnosed by PCR in 41/217 (19%) patients. Infection with influenza A virus (H3N2) was diagnosed in all cases. The performance of the QuickVue Influenza Test was estimated as follows: sensitivity 67.5%, specificity 96%, positive predictive value 79%, and negative predictive value 93%. The sensitivity of the test was higher in infants aged 6-12 months, in those with short duration of symptoms, and in the peak phase of the epidemic. The QuickVue Influenza Test is useful and reasonably accurate to detect influenza infection in hospitalized children during the influenza season. Infection with influenza virus is unlikely if the test is negative. A positive result suggests that infection is probable if influenza virus circulates in the community.


Review: Semen sexing - current state of the art with emphasis on bovine species.
It is approaching three decades since the first public evidence of sex-sorting of semen. The technology has progressed considerably since then with a number of institutions and researchers collaborating to eventually bring this to application. The technical challenges have been quite substantial and in the early years the application was limited to only heifer inseminations. Comparable fertility of sex-sorted semen with conventional semen has been an aspirational benchmark for the industry for many years. Significant investment in research in the primary biology of sex-sorted sperm and associated sorting equipment ensured steady progress over the years and current methods particularly the new SexedULTRA-4M™ seems to have now mostly bridged this fertility gap. The dairy and beef industry have adopted this technology quite rapidly. Other animal industries are progressively testing it for application in their specific niches and environments. The current state of the art in the fundamentals of sex-sorting, the biology of the process as well as new developments in machinery are described in this review.


Selecting patients for interventional procedures to treat hypertension.
Purpose: Interventional approaches to treat hypertension are an emerging option that may be suitable for patients whose BP control cannot be achieved with lifestyle and/or pharmacotherapy and possibly for those who do not wish to take drug therapy.Materials and Methods: Interventional strategies include renal denervation with radiofrequency, ultrasound and alcohol-mediated platforms as well as baroreflex activation therapy and cardiac neuromodulation therapy. Presently renal denervation is the most advanced of the therapeutic options and is currently being commercialised in the EU.Results: It is apparent that RDN is effective in both unmedicated patients and patients with more severe hypertension including those with resistant hypertension.Conclusion: However, at present there is no evidence for the use of RDN in patients with secondary forms of hypertension and thus evaluation to rule these out is necessary before proceeding with a procedure. Furthermore, there are numerous pitfalls in the diagnosis and management of secondary hypertension which need to be taken into consideration. Finally, prior to performing an intervention it is appropriate to document presence/absence of hypertension-mediated organ damage.


Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone.
Dexamethasone (DEX) is used to prevent virilization in female fetuses at risk of congenital adrenal hyperplasia (CAH). Given that treatment has to be started before the genotype is known, 7 out of 8 fetuses will be exposed to DEX without benefit. To evaluate long-term cognitive effects of prenatal DEX therapy in healthy (non-CAH) DEX-treated children. Observational study with patient and control groups from a single research institute. Healthy (non-CAH) DEX-treated subjects (n = 34) and untreated population controls (n = 66) from Sweden, aged 7-17 years. DEX-treatment used in unborn children at risk of CAH, during first trimester of fetal life. Standardized neuropsychological tests and questionnaires were used. DEX treatment has widespread negative effects in girls. In Wechsler Intelligence Scales for Children-III scale subtests, we observed significant interactions between DEX and GENDER (coding, P = .044; block design, P = .013; vocabulary, P = .025) and a trend for the subtest digit span (P = .074). All interactions were driven by DEX effects in girls, but not boys, with DEX-treated females showing lower scores than female untreated controls (coding, P = .068, d = 0.66; block design, P = .021, d = 0.81; vocabulary, P = .014, d = 0.84; digit span, P = .001, d = 1.0). Likewise, DEX-treated girls tend to have poorer visual spatial working memory performance than controls (span board test forward: P = .065, d = .80). We observed no effects on long-term memory, handedness, speed of processing, nor self-perceived or parentally reported scholastic performance. Early prenatal DEX exposure affects cognitive functions in healthy girls, ie, children who do not benefit from the treatment. It can therefore not be considered safe to use this therapy in the context of CAH.


Effect of Morphology of Co3O4 for Oxygen Evolution Reaction in Alkaline Water Electrolysis.
In this paper, three different morphological Co3O4 electrodes for oxygen evolution reaction (OER) have been synthesized. By comparing the three morphologies of Co3O4, the electrocatalytic properties show that the urchin-like spheres of Co3O4 electrode has relative low overpotential and good electrocatalysis stability, indicating that the structure of urchin-like Co3O4 spheres exhibit an easy OER for water splitting.


Probiotics and Human Milk Oligosaccharides in Premature Infants.
Intestinal dysbiosis precedes and is a likely causative factor in necrotizing enterocolitis (NEC) and many cases of late-onset sepsis. Randomized controlled trials and observational cohort studies demonstrate decreased risk of NEC, sepsis, and death with the administration of probiotic microbes and decreased risk of NEC and sepsis with feeding of human milk. Animal studies suggest promising mechanisms by which probiotic microbes and human milk oligosaccharides alter the composition of the intestinal microbiota and may prevent disease in premature infants. Inclusion of parents in discussions of the risks and benefits of human milk and probiotics for premature infants is essential.


LagC is required for cell-cell interactions that are essential for cell-type differentiation in Dictyostelium.
Strain AK127 is a developmental mutant of Dictyostelium discoideum that was isolated by restriction enzyme-mediated integration (REMI). Mutant cells aggregate normally but are unable to proceed past the loose aggregate stage. The cloned gene, lagC (loose aggregate C), encodes a novel protein of 98 kD that contains an amino-terminal signal sequence and a putative carboxy-terminal transmembrane domain. The mutant strain AK127 shows no detectable lagC transcript upon Northern analysis, indicating that the observed phenotype is that of a null allele. Expression of the lagC cDNA in AK127 cells complements the arrest at the loose aggregate stage, indicating that the mutant phenotype results from disruption of the lagC gene. In wild-type cells, lagC mRNA is induced at the loose aggregate stage and is expressed through the remainder of development. lagC- null cells aggregate but then disaggregate and reaggregate to form small granular mounds. Mature spores are produced at an extremely low efficiency (< 0.1% of wild type), appearing only after approximately 72 hr, whereas wild-type strains produce mature spores by 26 hr. lagC- null cells accumulate reduced levels of transcripts for the prestalk-enriched genes rasD and CP2 and do not express the DIF-induced prestalk-specific gene ecmA or the cAMP-induced prespore-specific gene SP60 to significant levels. In chimeric organisms resulting from the coaggregation of lagC- null and wild-type cells, cell-type-specific gene expression is rescued in the lagC- null cells; however, lagC- prespore cells are localized to the posterior of the prespore region and do not form mature spores, suggesting that LagC protein has both no cell-autonomous and cell-autonomous functions. Overexpression of lagC from an actin promoter in both wild-type and lagC- cells causes a delay at the tight aggregate stage, the first stage requiring LagC activity. These results suggest that the LagC protein functions as a nondiffusible cell-cell signaling molecule that is required for multicellular development.


Genetic counselling in hypomelanosis of Ito: case report and review.
A 27-year-old male with hypomelanosis of Ito (HI) is reported. One of his two children had a postaxial ray defect of one leg but neither had cutaneous features of HI. Somatic mosaicism for a gene defect lethal to ectodermal derivatives offers the best explanation for HI in males, with consequent negligible recurrence risk. The limb defect is considered coincidental. The excess of girls with HI could be due to a female cohort with incontinentia pigmenti (IP) which may be indistinguishable: counselling of females must therefore take account of possible X-linked inheritance.


The elusive tripodal tris(2-pyridyl)borate ligand: a strongly coordinating tetraarylborate.
Tris(2-pyridyl)borates are introduced as a new robust and tunable "scorpionate"-type ligand family. A facile synthesis of this hitherto unknown ligand and its complexation to Fe(II) are described; the optical and electrochemical properties of the resulting iron complex are compared to complexes derived from tris(pyrazolyl)borate, tris(2-pyridyl)aluminate, and corresponding charge-neutral ligands.


Predicting growth response among Egyptian prepubertal idiopathic isolated growth hormone deficient children.
To determine the predictors of growth response to growth hormone treatment in a group of isolated idiopathic growth hormone (GH). 477 GH deficient (GHD) children with GH therapy were included in the study. Patients were followed up for a minimum of 1 year and up to 6 years. Multiple linear regressions were performed to identify predictors of growth response to rhGH in the first 4 years of treatment. In the first year, three significant predictors of growth were identified: GH peak [ln (ug/L)], age of onset of therapy and target height-height SDS. In the second and third years of therapy, growth velocity (GV) was both significantly and positively correlated to the GV (cm/year) of the previous year. Prediction models offer a valuable tool for individualization and assuring adherence to rhGH and thus a cost effective treatment, which is the ultimate goal of GH therapy.


Thrombotic thrombocytopenic purpura following cardiovascular surgery: a case report.
Thrombotic thrombocytopenic purpura, a rare clinical syndrome characterized by thrombocytopenia and microangiopathic hemolytic anemia, was almost uniformly fatal until the introduction of plasma exchange in 1970. The thrombotic thrombocytopenic purpura following cardiovascular surgeries is relatively a new entity with high mortality if untreated. Plasma exchange is the most important therapy in this disease with good clinical outcomes. With the addition of this report, there are now 13 cases of thrombotic thrombocytopenic purpura in association with coronary artery bypass graft reported in the literature.


Evaluation of acute asthma management among emergency doctors using simulation-based assessment.
Assessment of asthma management competency using conventional methods remains challenging. This study aimed to explore the baseline knowledge, diagnosis accuracy and clinical management accuracy of acute asthma among emergency doctors using simulation-based assessment. We conducted a cross-sectional study involving 65 emergency department medical officers at a tertiary center. Participants were evaluated using 2 components: knowledge assessment of acute asthma and clinical performance assessment. Knowledge was evaluated using a standardized knowledge questionnaire. Clinical performance in managing acute asthma was assessed using a simulated acute asthma scenario and a standardized asthma management checklist using real-time assessments. The mean knowledge score was 14.69 ± 2.16. No significant differences were found in diagnosis and management accuracy in relation to knowledge (H = 0.644, P = .725, df = 6; H = 1.337, P = .512, df = 2). Acute-asthma attacks of all severities were poorly assessed, with accuracies of 27.3, 41.9, and 20.1% in mild, moderate, severe, and life-threatening cases, respectively. However, all participants provided high-quality treatment (accuracy = 82.3%) regardless of severity. Knowledge score does not influence the ability to differentiate asthma severity and management accuracy according to established asthma guidelines. The overall treatment accuracy was high, regardless of the severity of asthma. However, assessment of acute asthma requires further refinement.


Crystal structures of oligonucleotides including the integrase processing site of the Moloney murine leukemia virus.
In the first step of retroviral integration, integrase cleaves the linear viral DNA within its long terminal repeat (LTR) immediately 3' to the CA dinucleotide step, resulting in a reactive 3' OH on one strand and a 5' two base overhang on the complementary strand. In order to investigate the structural properties of the 3' end processing site within the Moloney murine leukemia virus (MMLV) LTR d(TCTTTCATT), a host-guest crystallographic method was employed to determine the structures of four self-complementary 16 bp oligonucleotides including LTR sequences (underlined), d(TTTCATTGCAATGAAA), d(CTTTCATTAATGAAAG), d(TCTTTCATATGAAAGA) and d(CACAATGATCATTGTG), the guests, complexed with the N-terminal fragment of MMLV reverse transcriptase, the host. The structures of the LTR-containing oligonucleotides were compared to those of non-LTR oligonucleotides crystallized in the same lattice. Properties unique to the CA dinucleotide step within the LTR sequence, independent of its position from the end of the duplex, include a positive roll angle and negative slide value. This propensity for the CA dinucleotide step within the MMLV LTR sequence to adopt only positive roll angles is likely influenced by the more rigid, invariable 3' and 5' flanking TT dinucleotide steps and may be important for specific recognition and/or cleavage by the MMLV integrase.


Immunology of inflammatory bowel disease: summary of the proceedings of the Subcommittee on Immunosuppressive Use in IBD.
As outlined, scanty data exist with regard to immunologic therapy in children with IBD despite the fact that the pediatric population affords a unique opportunity for clinical evaluation. Children are less affected by modifying conditions such as smoking, alcohol ingestion, and the long-term use of medications, and because of their specific needs for ponderal and linear growth, children might benefit most from immunological therapy that has been proven to be steroid sparing. Therefore, clinical trials to evaluate the efficacy of 6-MP and/or azathioprine in growing children with Crohn's disease would appear to provide a fruitful avenue for collaborative research. Efforts to organize a multicenter evaluation of these agents have been initiated. The studies are crucial in evaluating the efficacy and safety of immunosuppressive therapy in the pediatric population with IBD.


Insights from Adsorption and Electron Modification Studies of Polyoxometalates on Surfaces for Molecular Memory Applications.
This Account highlights recent experimental and theoretical work focusing on the development of polyoxometalates (POMs) as possible active switching units in what may be called "molecule-based memory cells". Herein, we critically discuss how multiply charged vanadium-containing POMs, which exhibit stable metal-oxo bonds and are characterized by the excellent ability to change their redox states without significant structural distortions of the central polyoxoanion core, can be immobilized best and how they may work optimally at appropriate surfaces. Furthermore, we critically discuss important issues and challenges on the long way toward POM-based nanoelectronics. This Account is divided into four sections shedding light on POM interplay in solution and on surfaces, ion soft-landing of mass-selected POMs on surfaces, electronic modification of POMs on surfaces, and computational modeling of POMs on surfaces. The sections showcase the complex nature of far-reaching POM interactions with the chemical surroundings in solution and the properties of POMs in the macroscopic environment of electrode surfaces. Section 2 describes complex relationships of POMs with their counter-cations, solvent molecules, and water impurities, which have been shown to exhibit a direct impact on the resulting surface morphology, where a concentration-dependent formation of micellar structures can be potentially observed. Section 3 gives insights into the ion soft-landing deposition of mass-selected POMs on electrode surfaces, which emerges as an appealing method because the simultaneous deposition of agglomeration-stimulating counter-cations can be avoided. Section 4 provides details of electronic properties of POMs and their modification by external electronic stimuli toward the development of multiple-state resistive (memristive) switches. Section 5 sheds light on issues of the determination of the electronic structure properties of POMs across their interfaces, which is difficult to address by experiment. The studies summarized in these four sections have employed various X-ray-scattering, microscopy, spectroscopy, and computational techniques for imaging of POM interfaces in solution and on surfaces to determine the adsorption type, agglomeration tendency, distribution, and oxidation state of deposited molecules. The presented research findings and conceptual ideas may assist experimentalists and theoreticians to advance the exploration of POM electrical conductivity as a function of metal redox and spin states and to pave the way for a realization of ("brain-inspired") POM-based memory devices, memristive POM-surface device engineering, and energy efficient nonvolatile data storage and processing technologies.


Case report: Takayasu arteritis in a 3-month-old Chinese girl.
Takayasu arteritis is a rare large vessel systemic vasculitis that predominantly affects the aorta and its main branches in women of childbearing age. Due to nonspecific symptoms during the acute phase of disease, early diagnosis is still a challenge for pediatricians. We reported a 3-month-old girl who presented with sustained elevated levels of acutephase reactants, which could not be explained by infectious diseases and malignant diseases. The patient's angiography showed dilatation, stenosis, and inflammation of the aorta and its branches and was diagnosed as Takayasu arteritis. We prescribed glucocorticoids combined with immunosuppressive agents, which include cyclophosphamide used as an induction drug for 6 months, and mycophenolate mofetil used as a maintenance drug. Glucocorticoids gradually stopped. At present, the girl went into clinical remission with normal levels of acute-phase reactants and improvement of vascular inflammation demonstrated by angiography. This case report illustrates that Takayasu arteritis can occur in children at a very early age after birth before apparent clinical symptoms.


ITScan: a web-based analysis tool for Internal Transcribed Spacer (ITS) sequences.
Studies on fungal diversity and ecology aim to identify fungi and to investigate their interactions with each other and with the environment. DNA sequence-based tools are essential for these studies because they can speed up the identification process and access greater fungal diversity than traditional methods. The nucleotide sequence encoding for the internal transcribed spacer (ITS) of the nuclear ribosomal RNA has recently been proposed as a standard marker for molecular identification of fungi and evaluation of fungal diversity. However, the analysis of large sets of ITS sequences involves many programs and steps, which makes this task intensive and laborious. We developed the web-based pipeline ITScan, which automates the analysis of fungal ITS sequences generated either by Sanger or Next Generation Sequencing (NGS) platforms. Validation was performed using datasets containing ca. 2,000 to 40,000 sequences each. ITScan is an online and user-friendly automated pipeline for fungal diversity analysis and identification based on ITS sequences. It speeds up a process which would otherwise be repetitive and time-consuming for users. The ITScan tool and documentation are available at http://evol.rc.unesp.br:8083/itscan.


Data collection in periodontal treatment planning.
Providing successful dental care is a daily challenge. Techniques to improve our own technical skills are of obvious value, however careful consideration of all the available facts help us to maximize the benefit of our technical skills. We are frequently limited by the conditions and attitudes that are attached to our patients. I suggest we need to recognize those limitations and convey them to those that we are caring for. Our formulation of an accurate treatment plan is the result of consideration of as many of the factors influencing the disease as can be discovered.


Endothelial function in vasovagal syncope.
Vasovagal syncope (VVS) is a common form of fainting. The pathophysiology of VVS is complex and involves changes in the autonomic and vascular tone, resulting in reflex bradycardia with marked hypotension. Paradoxical peripheral vasodilation caused by endothelial dysfunction may also play a key role in inappropriate hypotension during VVS. Endothelial hyperactivity due to up regulation of nitric oxide synthase leads to profound vasodilation, much stronger than vasodilation caused by adrenergic stimulation in response to orthostatic stress alone. Studies have reported significantly higher flow-mediated dilation and higher plasma nitric oxide concentration in people with vasovagal syndrome. Patients with VVS showed decreased vasoconstrictive agent endothelin-1 levels during orthostatic stress. Coagulation and fibrinolysis activity also play important roles in endothelial function in syncopal patients. The response of the endothelium to orthostatic stress is similar to the reaction to haemorrhagic stress and is likely to be a remnant from the evolutionary adaptation of primates.


Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy.
Solute carrier family 12 member 3 (SLC12A3) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of SLC12A3 in DN. In this study, we aim to evaluate the genetic effects of the SLC12A3 gene and its Arg913Gln polymorphism with genetic and functional analyses. We genotyped SLC12A3 genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of slc12a3 in kidney development and progress of DN in zebrafish and db/db mice. We found that SLC12A3 Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of SLC12A3 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage. Slc12a3 mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. The present study provided the first biological and further genetic evidence that SLC12A3 has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease.


Abnormal branching and regression of the notochord and its relationship to foregut abnormalities.
An abnormally positioned notochord has been reported in embryos that develop foregut abnormalities, vertebral defects and other abnormalities of the VATER association. This study examines the patterns of regression of the abnormal notochord in the rat model of the VATER association and investigates the relationship between developmental abnormalities of the notochord and those of the vertebra and foregut. Timed-pregnant Sprague-Dawley rats were given daily intraperitoneal injections of 1.75 mg/kg adriamycin on gestational days 6 - 9 inclusive. Rats were sacrificed between days 14 and 20 and their embryos harvested, histologically sectioned and stained and examined serially. The location and appearance of the degenerating notochord and its relationship to regional structural defects were analysed. All 26 embryos exposed to adriamycin developed foregut abnormalities and had an abnormal notochord. The notochord disappeared by a process of apoptotic degeneration that lagged behind that of the normal embryo: the notochord persisted in the abnormal embryo beyond day 17, whereas in the normal rat it had already disappeared. Similarly, formation of the nucleus pulposus was delayed. Vertebral abnormalities occurred when the notochord was ventrally-positioned. The notochord disappears during day 16 in the normal embryo whereas abnormal branches of the notochord persist until day 19 in the adriamycin-treated embryo. Degeneration of the notochord is dominated by apoptosis. An excessively ventrally-placed notochord is closely associated with abnormalities of the vertebral column, especially hemivertebrae.


Reverse genetics approaches for the development of bunyavirus vaccines.
The Bunyavirales order is the largest group of RNA viruses, which includes important human and animal pathogens, that cause serious diseases. Licensed vaccines are often not available for many of these pathogens. The establishment of bunyavirus reverse genetics systems has facilitated the generation of recombinant infectious viruses, which have been employed as powerful tools for understanding bunyavirus biology and identifying important virulence factors. Technological advances in this area have enabled the development of novel strategies, including codon-deoptimization, viral genome rearrangement and single-cycle replicable viruses, for the generation of live-attenuated vaccine candidates. In this review, we have summarized the current knowledge of the bunyavirus reverse genetics approaches for the generation of live-attenuated vaccine candidates and their evaluation in animal models.