Development of an inventory to assess perceived barriers related to PKU treatment.
According to studies of phenylketonuria (PKU), the Brazilian population's metabolic control shows unsatisfactory indexes from childhood. Research on patients' perceived difficulties or barriers to adherence to treatment can help us to comprehend how these outcomes are associated. The present study aimed to: (1) describe the development of an inventory for identifying the most frequent and relevant perceived barriers to PKU treatment from the perspective of patients, caregivers, and healthcare professionals; (2) evaluate certain psychometric characteristics of the new measure; and, (3) explore potential predictors (sociodemographic and medical characteristics) that may contribute to increasing the number of perceived barriers and examine whether the number of barriers is associated with the degree of adherence shown by the patient. Participants in the study were 23 patients with PKU (M age = 18.0 years; SD = 7.3; range 6 to 34 years; 69% early-treated) in classical (n = 11) and mild (n = 12) form, and 11 caregivers. The inventory, developed to ascertain perceived barriers to treatment, was completed by patients (≥ 13 years) and caregivers of patients aged 6 to 17 years. Analyses were conducted to investigate whether barrier inventory scores were associated with adherence to treatment as measured by phenylalanine levels in patients' medical records. Scores on the inventory differed across the patient age groups: adolescents had lower scores (i.e. reported fewer barriers) compared with those of adults (U = 8.000, p = 0.008); patients with better recent metabolic control also reported fewer perceived barriers than did patients with poor adherence (U = 20.000, p = 0.009); and the number of perceived barriers was positively associated with recent blood phenylalanine concentration (Kendall's taub = 0.41; p = 0.001). These results suggest that the inventory has merit in assessing perceived barriers and support the need for further research on barriers perceived by PKU patients.


Analysis of the time dependency of ammonia-oxidizing bacterial community dynamics in an activated sludge bioreactor.
An autoregressive error term model was applied to examine the dynamic oscillation of ammonia-oxidizing bacterial (AOB) lineages found in an activated sludge bioreactor. The current abundance of AOB lineages was affected by the past abundance of AOB lineages and past environmental and operational factors as well as current influencing factors.


An improved method for large-scale purification of recombinant human glucagon.
Glucagon was expressed in Escherichia coli as a fusion protein including the glucagon sequence [Ishizaki et al. (1992), Appl. Microbiol. Biotechnol. 36, 483-486]. The high-level expression of a protein in E. coli often results in an insoluble aggregate called an inclusion body containing a fusion protein. In our previous report [Yoshikawa et al. (1992), J. Protein Chem. 11, 517-525], we solubilized this inclusion body by using guanidinium chloride. However, the existence of denaturant caused problems such as a low proteolytic activity for transforming the fusion protein into glucagon and complicated purification methods. We tried to improve the method to enable large-scale purification. At alkaline pH, the inclusion body could be solubilized to a high concentration and cleaved by amino acid-specific endopeptidases. By utilizing isoelectric precipitations as a new economical purification method for glucagon from intermediates, the glucagon obtained was shown to be over 99.5% pure by analytical RP-HPLC. The yield was almost equal that of our previous method, and the glucagon produced was chemically and biochemically equivalent to natural glucagon.


Prevalence of and factors associated with difficult peripheral venipuncture in adult surgical patients.
To determine the prevalence of difficult venous access in adult patients admitted to a surgical unit. This observational prospective cohort study included 235 patients from a Brazilian hospital. Clinical data were collected by direct observation and analyzed by descriptive, inferential statistics, and multiple binomial logistic regressions. Odds ratios were also calculated. Most of the patients (66.4%) were men and self-reported as white (59.2%). The prevalence of difficult intravenous access was 32.8%. Predictors of peripheral intravenous cannula insertion failure were history of difficult intravenous access and nonvisibility of the vein. History of difficult intravenous access and a nonvisible venous network were significant predictors of peripheral cannula insertion failure in adults undergoing clinical surgery. The prevalence of difficult intravenous access was 32.8%.


Nongenomic actions of aldosterone: physiological or pathophysiological role?
The actions of aldosterone are usually divided into persistent genomic mediated by the classical mineralocorticoid receptor versus acute nongenomic actions. Rapid, nongenomic effects of aldosterone have been shown in a variety of tissues, although the physiological relevance of these nongenomic actions remains to be established. There is now growing evidence that both the nongenomic and genomic actions of aldosterone, are mediated via the same classical mineralocorticoid receptor, and there is cross talk between the nongenomic and classical actions of steroid hormones. Activation of tissue-specific, second messenger pathways may contribute to integration of nongenomic and classical actions of aldosterone. Further studies are required to determine the physiological or pathophysiological role of these nongenomic actions of aldosterone and whether they might amplify pathophysiological effects of aldosterone.


Serum vaspin levels in women with and without gestational diabetes mellitus during pregnancy and postpartum.
Although vaspin is regarded an insulin-sensitizing adipokine, its role in gestational diabetes mellitus (GDM) is currently unknown. We aimed to evaluate serum vaspin levels and their correlation with insulin resistance in women with and without GDM. Forty-four women with GDM [GDM Group - 20 managed with diet only (GDM-diet) and 24 with diet plus insulin (GDM-insulin)] and 44 age-matched pregnant women with normal glucose tolerance (Control Group) were studied. Serum glucose, lipids, uric acid, insulin and vaspin were measured at the 2nd and 3rd trimester of pregnancy and postpartum. The quantitative insulin sensitivity check index (QUICKI) and homeostasis model of assessment-insulin resistance (HOMA-IR) were calculated. Circulating vaspin levels decreased significantly postpartum in all groups (p<0.001), but did not differ between GDM or GDM Subgroups and Control Group in any time point. At the 3rd trimester of pregnancy vaspin was positively correlated to insulin (p=0.022), HOMA-IR (p=0.016) and triglycerides (p=0.033) and negatively correlated to QUICKI (p=0.016) in the GDM women, but not in the Controls. These correlations were not observed at the 2nd trimester or postpartum. Vaspin, in contrast to HOMA-IR, could not independently predict GDM in binary logistic regression. In patients with GDM, insulin treatment did not affect vaspin levels. In conclusion, our data suggest that vaspin levels gradually decrease from the 2nd trimester to postpartum; however, decreases are similar between women with or without GDM. Serum vaspin cannot independently predict GDM and it is not affected by the degree of glucose metabolism deregulation or the exogenous administration of insulin.


Kallikrein-like enzymes from Crotalus atrox venom.
The symptoms which immediately follow envenomation by many crotalid snakes include hypotension, hypovolemia, hemoconcentration, and shock. We have isolated and characterized two proteases (EI and EII) from the venom of Crotalus atrox which may be involved in the onset of these symptoms. EI and EII have molecular weights of 27,500 and 29,200 and isoelectric points of 4.7 and 4.3, respectively. Specific esterolytic activities of EI and EII on N alpha-p-tosyl-L-arginine methyl ester are 51.5 mumol min-1mg-1 and 48.1 mumol min-1 mg-1, respectively. Both enzymes are rather specific in their substrate requirements in that neither was demonstrated to have any proteolytic activity against either of the oxidized chains of insulin, or glucagon. Neither enzyme was shown to have plasmin or fibrinolytic activity. Both enzymes are able to cleave a kininogen analog to release bradykinin. This proteolytic activity is inhibited by aprotinin and phenylmethanesulfonyl fluoride but not by ethylenediaminetetraacetate. The enzymes are active upon the kallikrein substrates S2666 and S2302. The Km values of the enzymes with these substrates are similar to those reported for kallikrein. Structural similarity between the two enzymes was demonstrated by ultraviolet and circular dichroic spectroscopy, and amino acid analysis. Tryptic peptide mapping of the two native enzymes also suggested a large degree of structural similarity. Furthermore, sequence studies on the NH2-terminal regions of the enzymes indicate that they share a significant degree of sequence homology with porcine kallikrein and crotalase, a kallikrein-like enzyme from Crotalus adamanteus. The main physical difference between the two kallikreins reported here appears to be due to the carbohydrate moieties on the enzymes. At present the in vivo role of venom kallikreins in envenomation pathology is uncertain; however, it is possible that they play an important part in giving rise to the initial symptoms of hypotension and shock.


Bacteriocin-Like Inhibitory Substance (BLIS) Activity of Enterococcus faecium DB1 Against Biofilm Formation by Clostridium perfringens.
The antibiofilm effect of bacteriocin-like inhibitory substance (BLIS) from Enterococcus faecium DB1 against Clostridium perfringens was investigated in the present study. BLIS of E. faecium DB1 significantly reduced biofilm formation by C. perfringens in a dose-dependent manner for 24 and 48 h. In particular, treatment with BLIS of E. faecium DB1 significantly inhibited biofilm formation by C. perfringens on chicken meat and stainless steel coupon surfaces. Moreover, BLIS of E. faecium DB1 decreased the viability of C. perfringens biofilm and planktonic cells, indicating that the reduction of biofilm formation by C. perfringens might be achieved by killing the bacterial cells. Taken together, the present results suggest that BLIS of E. faecium DB1 can be a promising antibiofilm agent to eradicate C. perfringens.


Acute isovolemic hemodilution and blood transfusion. Effects on regional function and metabolism in myocardium with compromised coronary blood flow.
The use of isovolemic hemodilution to prevent adverse side effects of homologous blood transfusions has increased. The lowest level of hemoglobin that can be tolerated without regional myocardial dysfunction, however, had not been precisely defined for left ventricular myocardium with compromised coronary blood flow. This level was determined in our study in 19 dogs with critical stenosis of the left anterior descending coronary artery during graded isovolemic hemodilution. Regional function was assessed by sonomicrometry in the territory supplied by the left anterior descending coronary artery, as well as in two noncompromised left ventricular areas; oxygen extraction and consumption in the left anterior descending coronary artery region were assessed by analysis of anterior descending coronary venous oxygen saturation. The median lowest level of hemoglobin tolerated without contractile dysfunction of the territory supplied by the left anterior descending artery was 7.5 gm/dl, with lower and upper quartiles of 6 and 9 gm/dl. In addition to a marked increase in cardiac output and transstenotic left anterior descending flow, global cardiac and regional myocardial functions were unchanged at a hemoglobin level of 7.5 gm/dl, as compared with a control level of hemoglobin of 12.0 +/- 0.4 gm/dl. At a mean level of hemoglobin of 6.0 +/- 0.4 gm/dl, marked contractile dysfunction developed in the left anterior descending region: Systolic shortening decreased from 24.2% +/- 2.1% to 17.9% +/- 1.9% (p < 0.01); postsystolic shortening increased from 4.0% +/- 3.0% to 12.2% +/- 3.8% (p < 0.01); and in the left anterior descending region, oxygen consumption decreased. The increase of arterial level of hemoglobin by only 1.9 +/- 0.2 gm/dl restored contractile function in the left anterior descending region, regional oxygen consumption, and oxygen extraction across the left anterior descending region. Moderate isovolemic hemodilution is relatively well tolerated in left ventricular myocardium with compromised coronary blood flow, and hemodilution regional contractile dysfunction induced by hemodilution is reversible by minimal blood transfusion.


Synthesis of bimetallic core-shelled nanoparticles modified by 2-mercaptoethanol as SERS substrates for detecting ferbam and thiabendazole in apple puree.
Modification of surface-enhanced Raman spectroscopy (SERS) substrates with thiol ligands is an emerging approach in enhancing the stability and sensitivity of metal substrates due to their good affinity with metals such as Au, Ag, and Cu. Thus, in the current study, 2-mercaptoethanol was used to modify the surface of silver-coated gold nanoparticles to develop a novel SERS substrate for the rapid assessment of fungicide residues in fruit samples. Results showed that the substrate could achieve the detection of ferbam and thiabendazole residues in apple puree with limits of detection of approximately 0.0042 and 0.0064 ppm, high coefficients of determination of 0.9946 and 0.9968, good recoveries ranging from 80 to 105 and 81 to 107% and relative standard deviations of 3.5-7.5 and 3.8-7.9 %, respectively. Therefore, the substrate developed could potentially be utilised to assess other toxic agrochemicals in future.


Endosomal trafficking protein TBC-2 modulates stress resistance and lifespan through DAF-16-dependent and independent mechanisms.
The FOXO transcription factor, DAF-16, plays an integral role in insulin/IGF-1 signaling (IIS) and stress response. In conditions of stress or decreased IIS, DAF-16 moves to the nucleus where it activates genes that promote survival. To gain insight into the role of endosomal trafficking in resistance to stress, we disrupted tbc-2, which encodes a GTPase activating protein that inhibits RAB-5 and RAB-7. We found that tbc-2 mutants have decreased nuclear localization of DAF-16 in response to heat stress, anoxia, and bacterial pathogen stress, but increased nuclear localization of DAF-16 in response to chronic oxidative stress and osmotic stress. tbc-2 mutants also exhibit decreased upregulation of DAF-16 target genes in response to stress. To determine whether the rate of nuclear localization of DAF-16 affected stress resistance in these animals, we examined survival after exposure to multiple exogenous stressors. Disruption of tbc-2 decreased resistance to heat stress, anoxia, and bacterial pathogen stress in both wild-type worms and stress-resistant daf-2 insulin/IGF-1 receptor mutants. Similarly, deletion of tbc-2 decreases lifespan in both wild-type worms and daf-2 mutants. When DAF-16 is absent, the loss of tbc-2 is still able to decrease lifespan but has little or no impact on resistance to most stresses. Combined, this suggests that disruption of tbc-2 affects lifespan through both DAF-16-dependent and DAF-16-independent pathways, while the effect of tbc-2 deletion on resistance to stress is primarily DAF-16-dependent. Overall, this work demonstrates the importance of endosomal trafficking for the proper nuclear localization of DAF-16 during stress and that perturbation of normal endosomal trafficking is sufficient to decrease both stress resistance and lifespan.


Corrigendum: Together Apart: The Mitigating Role of Digital Communication Technologies on Negative Affect During the COVID-19 Outbreak in Italy.
[This corrects the article DOI: 10.3389/fpsyg.2020.554678.].


Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications.
The discovery of underlying molecular genetic abnormalities in gastrointestinal stromal tumors (GISTs) such as activating mutations in the tyrosine kinase genes, KIT and platelet derived growth factor receptor-alpha (PDGFRA), has led to remarkable clinical advances in treatment. Small molecule inhibitors such as imatinib and sunitinib are known to inhibit the aberrantly activated KIT and PDGFRA receptor signaling and can lead to excellent clinical outcomes for patients with GIST. Though the majority of GISTs appear to arise sporadically, a number of families with high frequencies of GISTs have been reported and germline mutations have been identified. This review will highlight the various inherited mutations associated with familial GIST syndromes and describe how an improved understanding of these genetic syndromes has important clinical implications for future understanding of this heterogeneous disease.


The Tousled gene in A. thaliana encodes a protein kinase homolog that is required for leaf and flower development.
Mutation at the TOUSLED locus of A. thaliana results in a complex phenotype, the most dramatic aspect of which being the abnormal flowers produced in mutant plants. tsl flowers show a random loss of floral organs, and organ development is impaired. The TSL gene appears to be required in the floral meristem for correct initiation of floral organ primordia and for proper development of organ primordia. Loss of TSL function also affects flowering time and leaf morphology. Using a mutation derived by T-DNA insertion mutagenesis, we have cloned the TSL gene and found that it encodes a protein kinase homolog with a novel N-terminal domain. This protein kinase gene identifies a novel signaling/regulatory pathway used during development in Arabidopsis.


Hurricane flooding and acute gastrointestinal illness in North Carolina.
Hurricanes often flood homes and industries, spreading pathogens. Contact with pathogen-contaminated water can result in diarrhea, vomiting, and/or nausea, known collectively as acute gastrointestinal illness (AGI). Hurricanes Matthew and Florence caused record-breaking flooding in North Carolina (NC) in October 2016 and September 2018, respectively. To examine the relationship between hurricane flooding and AGI in NC, we first calculated the percent of each ZIP code flooded after Hurricanes Matthew and Florence. Rates of all-cause AGI emergency department (ED) visits were calculated from NC's ED surveillance system data. Using controlled interrupted time series, we compared AGI ED visit rates during the three weeks after each hurricane in ZIP codes with a third or more of their area flooded to the predicted rates had these hurricanes not occurred, based on AGI 2016-2019 ED trends, and controlling for AGI ED visit rates in unflooded areas. We examined alternative case definitions (bacterial AGI) and effect measure modification by race and age. We observed an 11% increase (rate ratio (RR): 1.11, 95% CI: 1.00, 1.23) in AGI ED visit rates after Hurricanes Matthew and Florence. This effect was particularly strong among American Indian patients and patients aged 65 years and older after Florence and elevated among Black patients for both hurricanes. Florence's effect was more consistent than Matthew's effect, possibly because little rain preceded Florence and heavy rain preceded Matthew. When restricted to bacterial AGI, we found an 85% (RR: 1.85, 95% CI: 1.37, 2.34) increase in AGI ED visit rate after Florence, but no increase after Matthew. Hurricane flooding is associated with an increase in AGI ED visit rate, although the strength of effect may depend on total storm rainfall or antecedent rainfall. American Indians and Black people-historically pushed to less desirable, flood-prone land-may be at higher risk for AGI after storms.


Prediction of dMRI signals with neural architecture search.
There is growing interest in the neuroscience community in estimating and mapping microscopic properties of brain tissue non-invasively using magnetic resonance measurements. Machine learning methods are actively investigated to predict the signals measured in diffusion magnetic resonance imaging (dMRI). We applied the neural architecture search (NAS) to train a recurrent neural network to generate a multilayer perceptron to predict the dMRI data of unknown signals based on the different acquisition parameters and training data. The search space of NAS is the number of neurons in each layer of the multilayer perceptron network. To our best knowledge, this is the first time to apply NAS to solve the dMRI signal prediction problem. The experimental results demonstrate that the proposed NAS method can achieve fast training and predict dMRI signals accurately. For dMRI signals with four acquisition strategies of double diffusion encoding (DDE), double oscillating diffusion encoding (DODE), multi-shell and DSI-like pulsed gradient spin-echo (PGSE), the mean squared errors of the multilayer perceptron network designed by NAS are 0.0043, 0.0034, 0.0147 and 0.0199, respectively. We also compared NAS with other machine learning prediction methods, such as support vector regression (SVR), decision tree (DT) and random forest (RF), k-nearest neighbors (KNN), adaboost regressor (AR), gradient boosting regressor (GBR) and extra-trees regressor (ET). NAS achieved the better prediction performance in most cases. In this study, NAS was developed for the prediction of dMRI signals and could become an effective prediction tool.


Covert orientation of visual attention in Parkinson's disease: an impairment in the maintenance of attention.
Covert orientation of attention was studied in a group of patients with idiopathic Parkinson's disease and compared to a matched control group using a cued reaction time task which measured disengagement, covert movement and engagement of attention. Parkinson patients had an increased response latency and disengaged from attended locations more readily than controls. This impairment in the maintenance of attention in Parkinson's disease was comparable to that produced in a previous study by pharmacological blockade of brain catecholamines in normal subjects. It is suggested that an impairment in the maintenance of oriented attention may underlie some of the cognitive deficits reported in Parkinson's disease.


Characteristics and outcomes of fetuses with pericardial effusions.
Little is known about the characteristics and outcomes of fetuses with pericardial effusions (PEs); therefore, this study sought to identify factors associated with fetal PEs and the natural histories and outcomes of fetuses with PEs. Large PEs are associated with a greater likelihood of structural heart disease, impaired cardiac function, and chromosomal abnormalities, and PEs with hydrops or extracardiac malformations are associated with death. Most fetal PEs resolve, and fetuses with isolated PEs have a very good prognosis.


Purification and partial amino acid sequence of a mu opioid receptor from rat brain.
A rat brain opioid receptor protein was isolated by binding [epsilon-biotinyl-Lys32] beta-endorphin to membranes, solubilizing the receptor-ligand (R.L) complex with deoxycholate-lysophosphatidylcholine and purifying on immobilized streptavidin and wheat germ agglutinin. The purified glycoprotein had a molecular mass of 60-70 kDa. Recovery of this protein was blocked by the nonselective opioid antagonist naloxone and the highly mu-selective agonist [D-Ala2,N-methyl-Phe4,Glyol5]-enkephalin but not by the highly delta-selective agonist [D-Pen2,4'-Cl-Phe4,D-Pen5]enkephalin when these compounds were added as competitors at the binding step. The 60-70-kDa receptor protein co-purified through the streptavidin column with 40-kDa protein recognized by anti-Gi alpha antibodies. GTP and Na+ influenced dissociation of the solubilized R.125I-L complex and elution of the receptor and G protein from streptavidin in fashions consistent with the pharmacology of mu-opioid receptors. A 23-amino acid residue sequence from the purified receptor differs at 4 positions from a similar sequence in the murine delta-opioid receptor and is encoded within a novel rat brain cDNA isolated by polymerase chain reaction with oligonucleotide primers related to the murine delta-opioid receptor gene.


Increased cell proliferation activity and decreased cell death are associated with the emergence of hormone-refractory recurrent prostate cancer.
The tumour growth kinetics (cell proliferation and apoptosis) of ten hormone-refractory locally recurrent prostate cancers were compared with their matched untreated primary tumour specimens. All recurrent tumours had a higher cell proliferation activity, as defined by Ki-67 immunohistochemistry, than corresponding primary tumours from the same patients. The mean cell proliferation activity in recurrences (13.5 +/- 3.8 per cent) was over two times higher (P < 0.0001) than that in primary tumours (5.5 +/- 2.4 per cent), suggesting that cell clones which progress during androgen withdrawal are actively stimulated to proliferate. The mean percentage of apoptotic cells, as estimated by the in situ end-labelling technique, was 5.4 +/- 4.7 per cent in untreated primary tumours, whereas it was 2.3 +/- 1.5 per cent in locally recurrent tumours (P = 0.05). In all but two cases, the apoptotic index was lower in recurrent than in corresponding primary tumours, suggesting that recurrent prostate carcinomas are able to avoid apoptosis in the androgen-deprived environment. In conclusion, the clinical progression of prostate cancer during androgen withdrawal is associated with increased cell proliferation and decreased apoptosis.


CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production.
Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163+ cells were detected diffusely all over the tumor and connective tissue area, while CD204+ and CD206+ cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206+ TAMs strongly produced EGF compared with CD163+ and CD204+ TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206+ TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206+ TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206+ TAMs might play a critical role in the proliferation of OSCC via EGF production.


Measurement of association between malocclusion, nutritional status, and dental trauma in adolescents: A cross-sectional study.
With the decrease in the incidence of dental caries globally, traumatic dental injury (TDI) has emerged as a major cause of morbidity and distress among adolescents. The aim of this study was to assess the prevalence of TDI and explore its association with malocclusion and nutritional status among adolescent population of Udupi taluk, Karnataka state, India. The sample consisted of 770 children, from randomly selected schools in Udupi taluk. An anthropometric measurement was done to record the "body mass index", an oral examination was done to record the "Dental Aesthetic Index" for malocclusion and "Andreasen classification" for TDI. Statistical analysis included chi-square test and bivariate and multivariate binary logistic regression. A p value of ≤0.05 was considered statistically significant. The prevalence of TDI was 11.8%. The prevalence of overweight and obesity was 20.3%. The prevalence of malocclusion recorded in the study population was 49.8%. When prevalence of TDI was compared against gender, the type of school attended, and presence/absence of malocclusion, it was found that there was a statistically significant difference in prevalence of trauma between the aforementioned parameters (p ≤ 0.05). Results of the multivariate analysis through logistic regression indicated that being a male [3.87 (3.21-4.72)], attending a public school [1.41 (1.19-1.63)], and having malocclusion [1.55 (1.32-1.71)] significantly increased the odds of sustaining TDI. The results indicated a strong association between TDI, gender, the type of school attended, and malocclusion, and they have important implications toward the health and well-being of the individual communities.


Physical parameters effect on ozone-initiated formation of indoor secondary organic aerosols with emissions from cleaning products.
The effect of air exchange rate (ACH), temperature (T), and relative humidity (RH) on the formation of indoor secondary organic aerosols (SOAs) through ozonolysis of biogenic organic compounds (BVOCs) emitted from floor cleaner was investigated in this study. The total particle count (with D(p) of 6-225 nm) was up to 1.2 × 10(3)#cm(-3) with ACH of 1.08 h(-1), and it became much more significant with ACH of 0.36 h(-1) (1.1 × 10(4)#cm(-3)). This suggests that a higher ventilation rate can effectively dilute indoor BVOCs, resulting in a less ultrafine particle formation. The total particle count increased when temperature changed from 15 to 23 °C but it decreased when the temperature further increased to 30 °C. It could be explained that high temperature restrained the condensation of formed semi-volatile compounds resulting in low yields of SOAs. When the RH was at 50% and 80%, SOA formation (1.1-1.2 × 10(4)#cm(-3)) was the more efficient compared with that at RH of 30% (5.9 × 10(3)#cm(-3)), suggesting higher RH facilitating the initial nucleation processes. Oxidation generated secondary carbonyl compounds were also quantified. Acetone was the most abundant carbonyl compound. The formation mechanisms of formaldehyde and acetone were proposed.


Lymphocyte cytotoxicity assay for predicting preterm delivery of small for date babies.
Cytotoxic activity of lymphocytes, obtained from 84 pregnant women was tested, using human embryonic fibroblast cells as target cells. Lymphocytes of 8 women who delivered small for date babies before term and those of 3 women who had spontaneous abortions were significantly more cytotoxic (p less than 0.001) than lymphocytes of women who delivered small for date babies at term, appropriately grown babies before term, or appropriately grown babies at term. Data suggest that a higher level of in vitro lymphocyte cytotoxic activity of pregnant women forecasts either the preterm delivery of small for date babies or the occurrence of spontaneous abortions.


Azathioprine in paediatric inflammatory bowel disease: an Italian multicentre survey.
To assess the efficacy and safety of azathioprine in a paediatric population with inflammatory bowel disease. One hundred and twenty-three Italian children treated with azathioprine were studied retrospectively. The treatment duration and causes of its discontinuation, side-effects and variation in corticosteroid dose were assessed. The mean age at inflammatory bowel disease diagnosis was 9.8 +/- 3.6 years, and at the start of azathioprine therapy 11.8 +/- 4.3 years. The mean duration of treatment was 19 +/- 16 months. Fifty patients (41%) stopped treatment due to surgery (12%), prolonged remission (11%), non-response (7%), severe side-effects (7%) and poor compliance (3%). Of the 73 patients (59%) remaining on azathioprine, 11 had never been treated with corticosteroids, 27 were able to stop them and 35 were still on a very low daily dose (91% < 0.3 mg/kg). The difference in the daily corticosteroid dose between the beginning of azathioprine treatment (1 +/- 0.6 mg/kg) and the conclusion of the study (0.18 +/- 0.16 mg/kg) was statistically significant. Side-effects were recorded in 48 of the 123 patients (39%), but only eight required discontinuation of azathioprine. Azathioprine was efficacious in 70% of patients, but ineffective in 20% and induced severe toxicity in 7%. Corticosteroids were stopped or markedly reduced in 62% of patients, but they were never given in 9%.


The effect of cleaning and repainting on the ship drag penalty.
Although the hull of a recently dry-docked large ship is expected to be relatively smooth, surface scanning and experimentation reveal that it can exhibit an "orange-peel" roughness pattern with an equivalent sand-grain roughness height ks = 0. 101 mm. Using the known ks value and integral boundary layer evolution, a recently cleaned and coated full-scale ship was predicted to experience a significant increase in the average coefficient of friction %ΔC¯f and total hydrodynamic resistance %ΔR¯T during operation. Here the report also discusses two recently reported empirical estimations that can estimate ks directly from measured surface topographical parameters, by-passing the need for experiments on replicated surfaces. The empirical estimations are found to have an accuracy of 4.5 - 5 percentage points in %ΔC¯f.


Radial head replacement with unipolar and bipolar SBi system: a clinical and radiographic analysis after a 2-year mean follow-up.
Radial head prosthetic replacement is indicated in case of comminuted fracture not amenable to internal fixation, especially when the radial head fracture is part of a pattern of lesions configuring a complex instability of the elbow. Thirty-one SBi radial head prostheses were implanted in 30 patients (one bilateral simultaneous fracture) over a 2 years period. In 10 patients, the mean time from trauma to surgical treatment was 2.4 days, while the remaining 20 patients were treated as "second opinion" cases presenting with elbow stiffness or instability after an average of 19 days from trauma. The implants were monopolar in 12 cases and bipolar in 19. The clinical results were evaluated through the Mayo Elbow performance scoring system. At an average follow-up of 2 years (range 13-36 months), the mean MEPS was 90 points (range 65-100). At late radiographic analysis, radiolucent lines around the stem were found in 11 of the 31 cases. Heterotopic ossifications were found in 14 cases. Bone resorption was observed in 9 cases. Two of the 31 prostheses were removed after 16 and 20 months, in one case to correct stiffness in pronation/supination, in the other one for asymptomatic aseptic mobilization. These short-term results are satisfactory, especially when considering that they were obtained in complex elbow lesions treated in many cases at a delayed stage. Our preference over time went more and more to bipolar implants, but from a comparison of the results we could find no evidence of a superiority of bipolar or monopolar implants. The evolution of these prostheses needs to be evaluated with further studies to assess mid-term and long-term follow-up results.


A thiol-specific fluorescent probe and its application for bioimaging.
A fluorescent probe based on fluorescein displays an excellent selectivity and sensitivity for thiols and its application for bioimaging is described.


A survey of the smokefree status of pedestrian-only spaces in 10 New Zealand local government areas.
To describe the smokefree status and signage of outdoor pedestrian-only plazas/malls/boulevards in 10 New Zealand local government (council) areas. The 10 council areas were a convenience sample. Council websites were examined for smokefree policies, and a systematic attempt was made to identify the five largest pedestrian-only sites with permanent seating in each council area (10 sites each for two larger cities). Field visits were conducted to all selected sites during January-May 2021. Smokefree policies with components covering smokefree outdoor plazas/malls/boulevards were common (80%; 8/10 councils), albeit with some gaps (eg, around signage and vaping policy). A total of 60 relevant pedestrianised sites with permanent seating were identified and surveyed. Of these, 63% were officially designated smokefree. Smokefree signage was only present in 15% (9/60) of all the sites and in 24% (9/38) of the designated smokefree sites. In these designated sites, the average number of smokefree signs was only 1.4 (range: 0 to 14). Issues identified with the signs included small size, being only a small part of a larger other sign, limited use of te reo Māori wording and not covering vaping. At sites where tables were present, 12% had ash trays on the tables (none at smokefree sites). Smokefree plazas/malls/boulevards in this survey had multiple policy and signage deficiencies that are inconsistent with achieving the national Smokefree 2025 goal. There is scope to address these issues with an upgrade to the national smokefree law.


Can component-based microarray replace fluorescent enzimoimmunoassay in the diagnosis of grass and cypress pollen allergy?
Few data on the diagnostic accuracy in pollinosis of the microarray ISAC of allergens are available. We aim to comparatively analyse ISAC CRD103 with the whole-extract ImmunoCAP in grass and cypress pollen allergy, evaluating the suitability of the manufacturer's recommended cut-off points for both techniques. We studied 120 atopic patients grouped into grass and cypress pollen-allergic patients and controls based on clinical history and skin prick tests. Specific IgE against Phleum pratense and Cupressus arizonica by ImmunoCAP and ISAC CRD103 were performed on all subjects. In the grass pollen group (43 allergic/26 controls), both microarray and CAP showed high sensitivity (Se) and specificity (Sp) values (ISAC: Se 97.7, Sp 92.3; CAP: Se 95.3, Sp 96.1) for recommended cut-off points. Comparing the optimal (ISAC: 0.4 ISU; CAP: 0.33 kU/L) with the recommended cut-off points within the same technique, diagnostic agreement was observed in both techniques. Thus, CAP and ISAC showed similar diagnostic performance in grass pollen allergy when using recommended cut-off points. In cypress pollen group (12 allergic/92 controls), the microarray (Se: 91.7, Sp 91.3) showed similar Se but significantly higher Sp (P=0.034) than CAP (Se: 91.7, Sp: 80.4) using recommended cut-off points. However, although diagnostic performance of the microarray did not change when comparing the optimal (0.82 ISU) with the recommended cut-off point, CAP improved diagnosis of cypress pollen allergy, when applying the optimal (0.66 kU/L)(CAP Se: 91.7, Sp: 89.1) instead of the manufacturer's recommended cut-off point. Thus, when the most suitable cut-off point for both techniques (ISAC: 0.3 ISU; CAP: 0.66 kU/L) is selected, microarray and CAP provide equivalent diagnoses. Component-based microarray ISAC CRD103 and whole-allergen CAP showed high Se and Sp diagnosing equally grass and cypress pollen allergy. The cut-off point for each allergen should be properly applied for both techniques.


Reducing variations in clinical nurse educator roles: a service improvement project standardising roles and career pathways.
There is limited research evaluating the implementation and effectiveness of clinical nurse educator (CNE) roles in clinical practice. UK employers tend to use generic nursing job profiles, although the definition, expectations and implementation of nurse educator roles are interpreted differently between employers. This project intended to reduce variation and standardise job titles, job descriptions and job plans for CNEs ranging from band 5 to band 7 and identify the academic requirements and professional experience required of each band. An evaluative service review of existing CNE roles was conducted across a large division of a major NHS hospital trust. Focus group interviews were conducted to identify CNEs' and matrons' perceptions of the role. Themes identified from the coding of narrative data included: the importance of the role; variations in expectations of the role, job titles, job descriptions and plans; and a lack of career progression pathways. This service improvement project demonstrates that a standardised approach to the implementation of CNE roles can be achieved with the support of a unified senior nursing team. Clearer role definition and career progression pathways would improve job satisfaction and may help retain CNEs in post.


Immobilized lysozyme onto 1,2,3,4-butanetetracarboxylic (BTCA)-modified magnetic cellulose microsphere for improving bio-catalytic stability and activities.
Novel carboxyl-functionalized core-shell magnetic cellulose microspheres (MCMS) were prepared by surface modification with 1,2,3,4-butanetetracarboxylic acid (BTCA) and then applied in the immobilization of lysozyme via covalent bonding. The successful preparation of particles has been verified by transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and Fourier-transform infrared spectroscopy (FTIR) techniques. The optimal temperature and pH of the immobilized lysozyme were shown to be respectively 40 °C and 7. The immobilized lysozyme exhibited excellent performances within wide pH and temperature ranges as well as the high storage and thermal stabilities compared to free lysozyme. The apparent kinetic characterization of immobilized lysozyme revealed that its Km value was 1.37 times higher than that of free lysozyme and that its Vmax was slightly lower. The immobilized lysozyme demonstrated an acceptable reusability and showed 51.9±2.2% of activity after six cycles. This study demonstrated the application potential of BTCA-modified MCMS as an immobilized carrier for lysozyme.


M-FISH in gastric lymphoma.
The majority of gastric B-cell lymphomas histologically are classified as low grade mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphomas (DLBCL). There is evidence that the different histologic types are genetically heterogeneous, evolving through different pathogenetic pathways. Recurrent cytogenetic aberrations have been found in MALT lymphoma, whereas in DLBCL, limited cytogenetic data are available. We report here a DLBCL and a Burkitt-like gastric lymphoma case, cytogenetically studied by G-banding and M-FISH technique. In the first case, gains of chromosome 3, 7, 13, and 18 were found. An additional ring chromosome 1 identified as a clonal abnormality suggested clonal evolution. In the second case, trisomy 8, del(6)(q13), as well as t(8;14), t(1;5), and t(1;7), were observed. To our knowledge, cytogenetic data for gastric Burkitt-like lymphoma have not been reported, and M-FISH has not previously been used in the study of gastric lymphomas.


Left ventricular function many years after recovery from pre-eclampsia.
Epidemiological observations have shown that women with pre-eclampsia are at increased risk for subsequent development of cardiovascular disease. We evaluated maternal haemodynamics in asymptomatic women many years after pre-eclampsia and HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome. Case-control study. University-based department of obstetrics. Forty-eight women, 13-18 years after the affected pregnancy: 17 women with a history of HELLP syndrome, 14 women with a history of pre-eclampsia and 17 women following normal pregnancy (control group). Echocardiographic examination was performed in all groups, recording the isovolumetric contraction time and isovolumetric relaxation time (ICT + IVRT), ejection time (ET), myocardial performance index (MPI), transmitral early to atrial filling velocity ratio (MV-E/MV-A), stroke volume (SV) and cardiac output (CO). Cardiac function. Women with previous HELLP syndrome showed a significantly increased MPI (0.34 versus 0.26; P = 0.008) and ICT + IVRT (442.16 versus 415.03; P = 0.01); MV-E/A, SV, ET and CO were not significantly different. Women with a history of pre-eclampsia showed a significantly increased MPI (0.36 versus 0.26; P = 0.006) and decreased ET (317.3 versus 328.93; P = 0.04); ICT + IVRT, MV-E/A, SV and CO were not significantly different. This study confirms epidemiological observations that women with pre-eclampsia are at increased risk for subsequent development of cardiovascular disease. Many years after HELLP syndrome or pre-eclampsia, asymptomatic women have an increased risk for impaired cardiac function as shown by an increased MPI.


Proposal of New Radiological Classification and Treatment Strategy for Transverse Fractures of the C2 Axis Body.
To investigate the characteristics of transverse fractures of the C2 axis body diagnosed on sagittal computed tomography (CT) and to propose new classification and appropriate treatment strategies. A retrospective study was performed by enrolling 49 patients (26 men and 23 women) with transverse fractures of the C2 axis body who were treated at four national trauma centers of tertiary university hospitals from January 2000 to December 2017. The mean age of the patients was 60.8 years (ranging from 21 to 90 years). We classified 49 transverse fractures of the C2 body into three types based on fracture trajectories involving superior articular facet (SAF) and lateral cortex (LC) of the C2 body on coronal CT as follows: Type 1, involvement of C2 SAF on both sides; Type 2, unilateral involvement of C2 SAF on one side and LC on the other side; Type 3, involvement of LC on both sides. The characteristics, treatment methods, and results of 49 transverse fractures of the C2 body were analyzed. Mean follow-up was 12.6 months (ranging from 12 to 26 months). Twenty-six (53.1%) patients were Type 1, 21 (42.9%) were Type 2, and 2 (4.0%) were Type 3. Correlation coefficients for intra-observer and inter-observer reliabilities of classification were 0.723 and 0.598 (both, P < 0.001), respectively. About 40.8% (7 Type 1 and 13 Type 2) of the patients had fracture displacement >3 mm; Incidence of fracture displacement >3 mm was higher in Type 2 than Type 1 (61.9% vs 26.9%, P < 0.05). About 79.6% (20 Type 1, 17 Type 2 and 2 Type 3) of the patients were treated conservatively, and 20.4% (6 Type 1 and 4 Type 2) underwent surgery. At last follow-up, 47 out of 49 patients achieved fusion; overall fusion rate was 95.9%. All conservatively treated Type 1 and Type 3 patients achieved fusion. Out of 17 conservatively treated Type 2 patients, 15 achieved fusion but two developed nonunion; however, two nonunion patients opted not to undergo surgery. Subgroup analysis showed that Philadelphia brace caused nonunion significantly in fracture displacement >3 mm compared to Minerva brace/Halovest (100% vs 0%, P < 0.05). All surgically treated Type 1 and 2 patients achieved fusion. In terms of clinical outcomes, neck pain visual analog scale and neck disability index were significantly improved (both, P < 0.01). According to Odom's criteria, 93.9% (46/49) of the patients achieved satisfactory outcomes. No major complications occurred. The majority of transverse fractures of C2 body can be treated conservatively. However, surgery or rigid Minerva brace/Halovest should be considered for Type 2 transverse fractures of the C2 body with fracture displacement >3 mm.


Enterococcal resistance to vancomycin and related cyclic glycopeptide antibiotics.
Enterococci belonging to various species resistant to vancomycin and related cyclic glycopeptide antibiotics have been isolated from hospitalized patients in France, the UK and the USA. All such strains examined display inducible synthesis of a membrane protein associated with resistance. The mechanism by which the membrane protein acts has not been definitively established, but it may block the access of the antibiotic to its peptidoglycan target. That the protein could be a bypass enzyme has not been ruled out. Transfer of glycopeptide resistance by conjugation to either Enterococcus faecium or Enterococcus faecalis and by transformation of Streptococcus sanguis Challis has been reported. The structural and regulatory genes encoding this resistance can be localized on plasmid and, apparently, chromosomal DNA. The plasmids encoding this resistance appear to differ from each other and have variable host ranges, but share at least some DNA sequence homology.


High and intermediate risk pulmonary embolism in the ICU.
Pulmonary embolism (PE) is a common and important medical emergency, encountered by clinicians across all acute care specialties. PE is a relatively uncommon cause of direct admission to the intensive care unit (ICU), but these patients are at high risk of death. More commonly, patients admitted to ICU develop PE as a complication of an unrelated acute illness. This paper reviews the epidemiology, diagnosis, risk stratification, and particularly the management of PE from a critical care perspective. Issues around prevention, anticoagulation, fibrinolysis, catheter-based techniques, surgical embolectomy, and extracorporeal support are discussed.


Pneumorrhachis in emphysematous pyelonephritis: A rare finding in an uncontrolled diabetic patient.
Emphysematous pyelonephritis (EPN) is a life-threatening infection of kidney with the presence of gas in the renal parenchyma, collecting system, and the surrounding retroperitoneum. We present a case of EPN in a diabetic patient with extension of gas into the spinal epidural space of the lumbar vertebral canal. He was managed conservatively with minimally invasive intervention along with supportive medical management and recovered well.


Involvement of pore-forming molecules in immune defense and development of the Mediterranean mussel (Mytilus galloprovincialis).
The membrane attack complex and perforin (MACPF) superfamily is one of the largest families of pore-forming molecules. Although MACPF proteins are able to destruct invading microbes, several MACPF proteins play roles in embryonic development, neural migration or tumor suppression. We describe two apextrin-like proteins (ApelB and ApelP) and one MACPF-domain-containing protein (Macp) in Mytilus galloprovincialis. The two apextrin-like proteins did not present any conserved domain. The Macp protein contained the membrane/attack complex domain and its signature motif. Gene expression during larval development was analyzed by RT-PCR. There was a stage-specific up-regulation of the three proteins, suggesting that they play a role in development. Apextrin-like proteins were highly expressed at blastula and trochophore stage, whereas Macp was expressed at veliger stage. RT-PCR revealed up-regulation of the three genes in tissues and hemocytes from adults treated with bacteria and pathogen-associated molecular patterns, suggesting that they may be involved in the immune response.


NCoR1: Putting the Brakes on the Dendritic Cell Immune Tolerance.
Understanding the mechanisms fine-tuning immunogenic versus tolerogenic balance in dendritic cells (DCs) is of high importance for therapeutic approaches. We found that NCoR1-mediated direct repression of the tolerogenic program in conventional DCs is essential for induction of an optimal immunogenic response. NCoR1 depletion upregulated a wide variety of tolerogenic genes in activated DCs, which consequently resulted in increased frequency of FoxP3+ regulatory T cells. Mechanistically, NCoR1 masks the PU.1-bound super-enhancers on major tolerogenic genes after DC activation that are subsequently bound by nuclear factor-κB. NCoR1 knockdown (KD) reduced RelA nuclear translocation and activity, whereas RelB was unaffected, providing activated DCs a tolerogenic advantage. Moreover, NCoR1DC-/- mice depicted enhanced Tregs in draining lymph nodes with increased disease burden upon bacterial and parasitic infections. Besides, adoptive transfer of activated NCoR1 KD DCs in infected animals showed a similar phenotype. Collectively, our results demonstrated NCoR1 as a promising target to control DC-mediated immune tolerance.


On demand triggering of edge localized instabilities using external nonaxisymmetric magnetic perturbations in toroidal plasmas.
The application of nonaxisymmetric magnetic fields is shown to destabilize edge-localized modes (ELMs) during otherwise ELM-free periods of discharges in the National Spherical Torus Experiment (NSTX). Profile analysis shows the applied fields increased the temperature and pressure gradients, decreasing edge stability. This robust effect was exploited for a new form of ELM control: the triggering of ELMs at will in high performance H mode plasmas enabled by lithium conditioning, yielding high time-averaged energy confinement with reduced core impurity density and radiated power.


Natural history of cystoid macular edema in pseudophakic bullous keratopathy.
A retrospective review of 25 consecutive patients having penetrating keratoplasty (PKP) with the preoperative diagnoses of pseudophakic bullous keratopathy (PBK) and cystoid macular edema (CME) was undertaken to analyze the natural history of preoperative CME following keratoplasty. Follow-up ranged from 13 to 54 months with a mean of 27 months. All patients had intraocular lens exchanges with 24 receiving posterior chamber lenses; 23 had lenses sutured to the posterior iris. Sixteen patients (64%) recovered a visual acuity of 20/40 or better. The average time for visual recovery to 20/40 was nine months with a range of two to 45 months. Eighteen (72%) had resolution of angiographic CME. Three patients previously diagnosed as having chronic CME recovered visual acuity of 20/40 or better. Cases of PBK with CME may have an excellent visual prognosis if the IOL is managed properly at the time of PKP.


Mice immunized to insulin develop antibody to the insulin receptor.
We immunized mice with insulin and found that those strains that develop insulin antibodies subsequently produce insulin-like activity in amount equivalent to 300-400 ng insulin per ml serum. The activity was due exclusively to IgG2 antibodies. Bioactivity could be blocked efficiently by insulin antibodies from guinea pigs and from mice. The active IgG2 also displaced labeled insulin from fat cells. Preliminary in vivo studies have indicated that the appearance of insulin-like antibodies in the mouse resulted in abnormal glucose homeostasis and "down regulation" of insulin receptors. These results indicate that immunization to insulin can initiate an idiotype-anti-idiotype network resulting in antibodies to the hormone receptor.


Accurate mass measurements and ultrahigh-resolution: evaluation of different mass spectrometers for daily routine analysis of small molecules in negative electrospray ionization mode.
Six mass spectrometers based on different mass analyzer technologies, such as time-of-flight (TOF), hybrid quadrupole-TOF (Q-TOF), orbitrap, Fourier transform ion cyclotron resonance (FT-ICR), and triple quadrupole (QqQ), installed at independent laboratories have been tested during a single day of work for the analysis of small molecules in negative electrospray ionization (ESI) mode. The uncertainty in the mass measurements obtained from each mass spectrometer has been determined by taking the precision and accuracy of replicate measurements into account. The present study is focused on calibration processes (before, after, and during the mass measurement), the resolving power of the mass spectrometers, and the data processing for obtaining elemental formulae. The mass range between m/z 100 and 600 has been evaluated with a mix of four standards. This mass range includes small molecules usually detected in food and environmental samples. Negative ESI has been tested as there is almost no data on accurate mass (AM) measurements in this mode. Moreover, it has been used because it is the ESI mode for analysis of many compounds, such as pharmaceutical, herbicides, and fluorinated compounds. Natural organic matter has been used to demonstrate the significance of ultrahigh-resolution in complex mixtures. Sub-millidalton accuracy and precision have been obtained with Q-TOF, FT-ICR, and orbitrap achieving equivalent results. Poorer accuracy and precision have been obtained with the QqQ used: 11 mDa root-mean-square error and 6-11 mDa standard deviation. Some advice and requirements for daily AM routine analysis are also discussed here.


Advances in Glycation: from food to human health and disease.
This Special Issue on "Advances in Glycation: from food to human health and disease" was planned after the XXV International Symposium on Glycoconjugates (Glyco25) in Milan in order to ask special attention of importance of glycation to glycoscience community. In addition, we also celebrate the 30th anniversary of JMARS (Japan Maillard Reaction Society), and dedicated to one of the pioneers of this field, Professor Vincent Monnier, MD. He contributed enormously to studies on glycation related to aging and diseases to date and also he contributed to establish IMARS (International Maillard Reaction Society) as well as JMARS.


Mitogenic inhibition and effect on survival of mice bearing L1210 leukemia using a combination of dehydroascorbic acid and hydroxycobalamin.
The present study was designed to test the effect of a combination of dehydroascorbic acid (DHA) and hydroxycobalamin (vitamin B12) on the survival of mice bearing L1210 leukemia. Results showed a significant increase in survival of treated mice compared with controls (p less than or equal to 0.0001) (Student's t-test). This positive effect was significantly lost when DHA was substituted by ascorbic acid (AA) in the same experimental conditions. In vitro findings also revealed that the DHA-B12 combination specifically inhibited mitoses of L1210 cells while non-neoplastic L929 cells were not affected.


Infantile hemangiopericytoma of nasal cavity.
Hemangiopericytoma is an uncommon vascular tumour. Of the 26 intranasal hemangiopericytomas reported in the English literature only two paediatric cases have been noted. A benign course is more common in the nose and paranasal sinuses. A pre-operative diagnosis being not possible, definitive treatment cannot be preplanned. Wide surgical excision by a lateral rhinotomy approach is still the treatment of choice. The appropriate investigations and treatment line followed are described. A lifelong followup is mandatory.


Cerato-platanins: elicitors and effectors.
Cerato-platanins are an interesting group of small, secreted, cysteine-rich proteins that have been implicated in virulence of certain plant pathogenic fungi. The relatively recent discovery of these proteins in plant beneficial fungi like Trichoderma spp., and their positive role in induction of defense in plants against invading pathogens has raised the question as to whether these proteins are effectors or elicitor molecules. Here we present a comprehensive review on the occurrence of these conserved proteins across the fungal kingdom, their structure-function relationships, and their physiological roles in plant pathogenic and symbiotic fungi. We also discuss the usefulness of these proteins in evolving strategies for crop protection through a transgenic approach or direct application as elicitors.


Trends in the utilization of, spending on, and prices for outpatient antifungal agents in US Medicaid programs: 1991-2009.
The incidence of invasive fungal infections (IFIs) has increased substantially in the recent past. Advances in medical technology, including broad-spectrum antibiotics, may increase the risk for fungal infections. Moreover, immunocompromised patients with cancer, HIV/AIDS, and/or transplants are susceptible to IFIs. Meanwhile, superficial fungal infections (SFIs) are common and can be difficult to cure. To provide a historical perspective on a dynamic market with expensive medications, this study describes trends in the utilization of, spending on, and average per-prescription spending on outpatient antifungal medications individually, in classes (for IFIs or SFIs), and overall, by the US Medicaid programs from 1991 to 2009. The publicly available Medicaid State Drug Utilization Data, maintained by the Centers for Medicare & Medicaid Services, were used. Annual prescription counts and reimbursement amounts were calculated for each of the antifungals reimbursed by Medicaid. Average per-prescription spending as a proxy for drug price was calculated by dividing reimbursement by the number of prescriptions. Overall utilization for Medicaid beneficiaries remained steady, with 4.56 million prescriptions in 1991 and 4.51 million in 2009. Expenditures rose from $93.87 million to $143.76 million (in current-year US$) over the same time period. The drop in the utilization of first-generation azoles over the last 5 years of the study period can be explained in part by the movement of dual-eligibles from Medicaid to Medicare Part D and in part to a rise in fungal infections better treated with second-generation azoles or echinocandins. Whereas the average per-prescription price for generic (oral) fluconazole was $8 in 2009, the price per prescription of branded (intravenous) voriconazole was $2178. Overall spending by Medicaid on outpatient antifungal medications increased more slowly than did the growth of the Medicaid programs from 1991 to 2009. However, the utilization of antifungal agents for IFIs increased almost 10-fold over this period, far outpacing the rise in the number of Medicaid beneficiaries.


Simple flow injection for determination of sulfite by amperometric detection using glassy carbon electrode modified with carbon nanotubes-PDDA-gold nanoparticles.
A new approach is presented for sensitive and selective measurement of sulfite (SO3(2-)) in beverages based on a simple flow injection system with amperometric detection. In this work, the sulfite sensor was a glassy carbon electrode modified with multiwall carbon nanotubes-poly(diallyldimethylammonium chloride)-gold nanoparticles composites (CNTs-PDDA-AuNPs/GC). Electrochemical oxidation of sulfite with this electrode was first studied in 0.1M phosphate buffer (pH 7.0) using cyclic voltammetry. The results indicated that the CNTs-PDDA-AuNPs/GC electrode possesses electrocatalytic activity for the oxidation of sulfite with high sensitivity and selectivity. Sulfite was quantified using amperometric measurement with the new sensor at +0.4V vs Ag/AgCl in conjunction with flow injection. The linear working range for the quantitation of sulfite was 2-200 mg L(-1) (r(2)=0.998) with a detection limit of 0.03 mg L(-1) (3σ of blank) and an estimated precision of 1.5%.The proposed method was successfully applied to the determination of sulfite in fruit juices and wines with a sample throughput of 23 samples per hour.


Abnormal innervation of lower limb epineurial arterioles in human diabetes.
A quantitative ultrastructural analysis was made of the terminal innervation of epineurial arterioles in the sural nerve of 6 diabetic and 6 non-diabetic patients of comparable age (mean +/- SD: 68 +/- 9 non-diabetic, 65 +/- 16 diabetic) with end stage peripheral vascular disease. The results demonstrated specific differences, identifiable morphometrically, in the pattern of innervation of epineurial vessels of diabetics compared with non-diabetics. The differences were: 1) in the diabetic group the proportion of perivascular axons found less than 7 microns from the nearest smooth muscle cell was significantly less than in the non-diabetic group (p less than 0.001); 2) the mean distance of the axons from their effector sites, the vascular smooth muscle cells, was nearly twice as far in the diabetic group compared with the non-diabetic group (p less than 0.05); and 3) the mean absolute number of axons less than 7 microns from the arteriole in the diabetic group was significantly less than in the non-diabetic group (p less than 0.01). These results demonstrate that the neuropathy associated with diabetes mellitus also involves the autonomic terminal innervation of some blood vessels. In addition, this neuropathy selectively affects the vasomotor nerves closer than 7 microns to the media.


The therapeutic effects of Periploca forrestii Schltr. Stem extracts on collagen-induced arthritis by inhibiting the activation of Src/NF-κB signaling pathway in rats.
Periploca forrestii Schltr. is a classical traditional Chinese medicine (TCM) called Heilonggu (HLG) in China. According to the theory of TCM, it possesses the efficacy of eliminating wind and removing dampness. In clinical practice, it is commonly used for the treatment of rheumatoid arthritis. The present work aimed to evaluate the anti-rheumatism activity of HLG ethanol extract and reveal the underlying molecular mechanism by employing an animal model of collagen-induced rheumatoid arthritis (CIA) in rats. The CIA was induced in male Sprague-Dawley rats by intradermal injection of bovine collagen-II in complete Freund's adjuvant (CFA) at the base of tail. The rats received oral administration of HLG (200 and 400mg/kg) from day 1, with the treatment lasting for 28 days. A variety of indicators were measured for evaluation of anti-rheumatism effect, including paw swelling, arthritis scores, and histopathological changes. Furthermore, the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2), as well as cyclooxygenase-2 (COX-2), nuclear factor NF-κB p65 and Src kinase in joint synovial tissues were detected to explore the possible mechanisms. The administration of HLG significantly restored type II collagen-induced arthritis in rats as evidenced by decrease in paw swelling and inflammatory factors in serum. Meanwhile, this treatment also notably reduced NF-κB p65 and COX-2 expression. Surprisingly, the activity of Src kinase was also inhibited demonstrated by downregulation of phosphorylated Src. Our results revealed that HLG possessed observable therapeutic action on collagen-induced arthritis by inhibiting the activation of Src and nuclear translocation of NF-κB in rats. HLG may serve as a potential candidate for the management of patients with RA.


Transcriptional and physiological data revealed cold tolerance in a photo-thermo sensitive genic male sterile line Yu17S.
Rice is highly sensitive to chilling stress during the seedling stage. However, the adaptable photo-thermo sensitive genic male sterile (PTGMS) rice line, Yu17S, exhibits tolerance to low temperatures. Currently, the molecular characteristics of Yu17S are unclear. To evaluate the molecular mechanisms behind cold responses in rice seedlings, a comparative transcriptome analysis was performed in Yu17S during seedling development under normal temperature and low temperature conditions. In total, 9317 differentially expressed genes were detected. Gene ontology and pathway analyses revealed that these genes were involved mostly in photosynthesis, carotenoid biosynthesis, carbohydrate metabolism and plant hormone signal transduction. An integrated analysis of specific pathways combined with physiological data indicated that rice seedlings improved the performance of photosystem II when exposed to cold conditions. Genes involved in starch degradation and sucrose metabolism were activated in rice plants exposed to cold stress treatments, which was accompanied by the accumulation of soluble sugar, trehalose, raffinose and galactinol. Furthermore, chilling stress induced the expression of phytoene desaturase, 15-cis-ζ-carotene isomerase, ζ-carotene desaturase, carotenoid isomerase and β-carotene hydroxylase; this was coupled with the activation of carotenoid synthase activity and increases in abscisic acid (ABA) levels in rice seedlings. Our results suggest that Yu17S exhibited better tolerance to cold stress with the activation of carotenoid synthase activity and increasing of ABA levels, and as well as the expression of photosynthesis-related genes under cold condition in rice seedlings.


Dual surgeon operating lists for complex revision arthroplasty surgery: changing orthopaedic surgical practice.
There is an increasing trend towards dual surgeon operating in complex surgeries in various specialties. This is driven by regionalisation of services, increasing complexity of surgical procedures, the ageing population and challenges imposed by changes in surgical training. Dual surgeon cases have lower complication rates and better quality of patient care. This practice not only facilitates professional and personal development, but also provides valuable support to surgeons in the early part of their career. There is a paucity of literature to support this practice, however, and prospective studies are required to demonstrate the benefit of this approach.


Fertility onset, spermatogenesis, and pubertal development in male rats: effect of graded underfeeding.
Undernutrition has proven to be a useful model for exploring the relationship between growth and pubertal development in female rats, such as the "critical body weight" hypothesis of pubertal timing, but corresponding studies in the male have been hampered by lack of specific discrete markers of puberty similar to vaginal opening or first estrus in females. In the current study, we explored the effect of five different levels of food intake (as low as one-third of normal) beginning at weaning on pubertal development and timing in male rats, using the date of the initial successful conception with normal females as a discrete marker for puberty in males. In underfed males, there was a weak inverse correlation (r = -0.31, p less than 0.05) between the age at puberty and the growth rate, the latter being used as an index of the degree of underfeeding. In contrast, there was a strong direct correlation (r=0.78, p less than 0.001) between body weight at puberty and growth rate. In the most severely underfed groups, the Lee index of body fat remained subnormal before and after puberty. Initial litter size also tended to be reduced when the males were underfed. At age 51 days (prior to puberty), graded underfeeding led to progressive reductions in serum luteinizing hormone and follicle-stimulating hormone levels as well as in parameters of androgen status (serum and testicular testosterone, prostate, and seminal vesicle weights). Testicular size was also reduced, but daily sperm production rate was not greatly affected by underfeeding.(ABSTRACT TRUNCATED AT 250 WORDS)


Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends.
Contemporary preclinical in vitro and in vivo methods have been imperfect in predicting drug-induced Torsades de Pointes (TdP) in humans. A better understanding of additional relevant factors in the genesis of drug-induced TdP is necessary. New sophisticated in vitro techniques, such as arterially perfused ventricular wedge preparations or isolated perfused hearts, potentially offer a better understanding of torsadogenic mechanisms and a refinement of drug testing. Of particular interest are the dispersion of repolarization and the refractoriness of different cell types across the ventricular wall, triangulation of the action potential, reverse use dependence and instability of the action potential duration. In vivo models are currently refined by establishing parameters such as beat-to-beat variability and T-wave morphology as derived from the in vitro proarrhythmia indices. Animal models of proarrhythmia are to date not recommended for routine evaluation. A pharmacodynamic interaction with combinations of torsadogenic compounds is another area to be considered. Little is known about channel/receptor cross talk, although considerable evidence exists that cardiac G protein-coupled receptors can modulate hERG channel function. More investigations are necessary to further evaluate the role of altered gene expression, mutations, and polymorphisms in drug-induced TdP. A novel mechanism of drug-induced torsadogenesis is the reduced expression of hERG channel protein on the plasma membrane due to a trafficking defect. Pharmacokinetic and metabolism data are crucial for calculating the risk of a torsadogenic potential in man. Consideration of intracardiac accumulation can help in delineating pharmacokinetic-pharmacodyamic relationships. In silico virtual screening procedures with new chemical entities to predict hERG block may develop as a promising tool. The role of in silico modeling of TdP arrhythmia is likely to become increasingly important for organizing and integrating the vast amount of generated data. At present, however, in silico methods cannot replace existing preclinical in vitro and in vivo models.


State legislation on abortion after Roe v. Wade: selected constitutional issues.
Over the past three years, a great volume of legislation on abortion has been produced by state legislatures in an attempt to fill the vacuum created by the United States Supreme Court's 1973 decision in Roe v. Wade. This Article examines several of the most common types of statutory provisions and assesses their constitutionality in light of Roe v. Wade and other applicable federal and state legal standards.


Treatment with monoclonal antibodies to ICAM-1 and LFA-1 in rat heart allograft rejection.
During allograft rejection, leukocyte infiltration in the graft is regulated by various adhesion molecules. Treatment with monoclonal antibodies to ICAM-1 and LFA-1 (CD11 a) induces specific tolerance after murine heart transplantation. In this study, we investigated the possibility of tolerance induction using these antibodies in a fully incompatible rat heart transplant model. Heterotopic, intra-abdominal heart transplantation was performed using Dark Agouti (DA) rats as donors and Lewis (LEW) rats as recipients. Group A (n = 6) received no immunosuppression and served as controls. In group B (n = 6) 500 micrograms/kg per day 1A29 (anti-ICAM-1) was administered intravenously (i.v.) for 5 days; group C rats received the same dosage of WT.1 (anti-CD11 a) i.v. for 5 days. In group D (n = 6), rats received combined i.v. administration of anti-CD11 a and anti-ICAM-1 (500 micrograms/kg per day of each, for 5 days. The antibodies used were monoclonal mouse anti-rat antibodies produced from hybridomas. Allograft survival was monitored by daily palpation of the graft. There was no statistically significant difference in allograft survival between the groups (A: 5.7 +/- 0.5 days; B: 5.7 +/- 0.5 days; C: 5.7 +/- 0.5 days; D: 6.2 +/- 0.4 days). Treatment with monoclonal antibodies to ICAM-1 and LFA-1 alone or in combination had no effect on allograft survival after heart transplantation between fully incompatible rat strains. We conclude that induction of tolerance using these antibodies seems inconceivable in human heart transplantation.


Developing oligodendroglia express mRNA for insulin-like growth factor-I, a regulator of oligodendrocyte development.
Insulin-like growth factors IGF-I and IGF-II are potent inducers of oligodendrocyte development. Because IGF-I is produced, in some cases, by the same cells that respond to it (autocrine/paracrine action), we examined the possibility that IGF-I is expressed by developing oligodendroglial cells. We employed a sensitive method, reverse transcriptase-polymerase chain reaction (RT-PCR), to detect IGF-I mRNA in purified populations of oligodendroglial cells isolated from rat brain during the period of oligodendrocyte development. Cells were purified by fluorescence activated cell sorting (FACS), using antibodies to the cell surface antigenic markers O4 and galactocerebroside (GC). RNA was isolated from the sorted cells, reverse-transcribed, and PCR-amplified, using a strategy that recognizes IGF-I mRNA but not DNA. The amplified band was identified as IGF-I by size, hybridization to an IGF-I-specific antisense probe, and restriction analysis. IGF-I mRNA was detected in O4-positive/GC-negative oligodendrocyte precursors and, more weakly, in GC-positive oligodendrocytes. IGF-I mRNA could be detected reproducibly in RNA extracted from 100-cell samples of O4-positive cells, making it unlikely that the mRNA was derived from contaminants in the FACS-sorted cell populations. We conclude that IGF-I is expressed by developing oligodendroglia. Autocrine expression of IGF-I by developing oligodendroglial cells suggests that oligodendrocyte development is, in part, autoregulatory.


Liver tolerance of raltegravir-containing antiretroviral therapy in HIV-infected patients with chronic hepatitis C.
To evaluate the liver safety of raltegravir-including combinations in HIV/hepatitis C virus (HCV) co-infected patients. Grade 3-4 transaminase elevations (TEs) and grade 4 total bilirubin elevations (TBEs) were assessed during 12 months in 108 HIV/HCV co-infected patients starting antiretroviral therapy including raltegravir in a retrospective cohort study. Furthermore, the relationship between baseline fibrosis and hepatotoxic events was determined. Eight patients (7.4%) developed grade 3 TEs and two (1.9%) patients showed grade 4 TEs. TBE grade 4 was detected in two (1.9%) patients. No patient permanently discontinued raltegravir because of hepatotoxic events. Of the patients with and without significant fibrosis, six (9.4%) and two (11.8%), respectively, showed grade 3-4 TEs (P = 0.769). Grade 3-4 TEs was observed in four (9.8%) patients in whom cirrhosis was ruled out, while none of the patients diagnosed with cirrhosis developed grade 3-4 TEs (P = 0.303). During the follow-up, the median (Q1-Q3) CD4 cell count increased from 257 (145-421) cells/mm(3) to 407 (213-587) cells/mm(3) (P < 0.0001) and the number of patients with an undetectable HIV viral load augmented from 33 (30.6%) to 73 (81.1%) (P = 0.002). Raltegravir-containing regimens are safe in HIV/HCV co-infected patients. The incidence of severe liver toxicity of raltegravir in these individuals is in the range of boosted protease inhibitors in clinical trials. The frequencies of grade 3-4 TEs and grade 4 TBEs were similar in patients receiving raltegravir with or without significant fibrosis or cirrhosis.


Theoretical prediction of emulsion color.
The perceived quality of many commercial products that are based on emulsions is determined by their color. In this article, a theory is presented to relate the color of emulsions to their composition and microstructure. First, the scattering characteristics (Qs and g) of individual droplets are calculated using Mie Theory. Second, the scattering (S) and absorption (K) coefficients of a concentrated emulsion are calculated using radiative transfer theory. Third, the reflectance spectrum (R) of the emulsion is calculated using Kubelka-Munk Theory. Finally, the tristimulus coordinates (XYZ, or L*a*b*) of the emulsion are calculated using color theory. There is excellent agreement between theoretical predictions and experimental measurements of the influence of droplet and chromophore characteristics on the tristimulus coordinates of concentrated oil-in-water emulsions.


Reticular fiber deficiency in the intracranial arteries of patients with dissecting aneurysm and review of the possible pathogenesis of previously reported cases.
The pattern of reticular fibers in the tunica media of the major intracranial arteries was investigated in two patients with dissecting aneurysm. In numerous circumscribed areas, the reticular fibers were absent close to the internal elastic lamina in all major arteries of each patient. It is suggested that the subintimal deficiency in reticular fibers results in insufficient fixing of the tunica intima to the media contributing to their separation when the internal elastic lamina becomes defective. The presumed etiologies of the previously reported cases are reviewed and the possible origin of the deficiency in reticular fibers is discussed.


The influence of breast density and key demographics of radiographers on mammography reporting performance - a pilot study.
A high demand has been placed on radiologists to perform screen reads due to higher number of women undergoing mammography. This study aims to examine radiographer performance in reporting low compared with high-mammographic density (MD) images; and to assess the influence of key demographics of Jordanian radiographers on their performance. Thirty mammograms with varied MD were reported by 12 radiographers using the Breast Imaging-Reporting and Data System (BI-RADS). Radiographer performance was measured using sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and area under the receiver operating characteristic curve (ROC AUC). Performance measures were compared between cases with low- and high-MD and between subgroups of radiographers according to key demographics. All performance measures were significantly higher in low- compared to high-MD cases (P value < 0.0). The mean sensitivity, specificity, PPV, NPV and ROC AUC were 0.58, 0.68, 0.67, 0.63 and 0.69 respectively. PPV was significantly different for readers who had different years of experience in mammography, hours and cases per week P value = 0.023, 0.01, 0.017 respectively. ROC AUC was significantly different for radiographers with different number of hours and cases performed per week (P value = 0.001 and 0.004 respectively). The results of this pilot study are encouraging however a more extensive study is required to determine if Jordanian radiographers are capable of successfully taking part in breast screen reading. The lack of skills and knowledge required for correct and consistent reporting of high-MD images highlights the need for any formal training in mammographic interpretation to focus on the dense breast.


Withdrawal symptoms in neonates from intrauterine exposure to diazepam.
Three infants are presented who had withdrawal symptoms after prolonged, intrauterine exposure to diazepam. Symptoms, clinical course, management, and laboratory findings are described. Some physiologic aspects of diazepam in the fetus and neonate are discussed. One infant died at six weeks of age; death was attributed to the sudden infant death syndrome.


A self-administered questionnaire for basal osteoarthritis of the thumb.
Basal osteoarthritis of the thumb is a common condition for which numerous operations have been proposed without any particular one having been shown to be superior. One of the problems in evaluating the results of surgery is that there is no validated outcome score specifically for the condition. The purpose of this study was to construct a self-administered questionnaire (the Nelson score) to assess the outcome following surgery for this condition and to test its properties. Correlating the questionnaire score with physical findings on clinical examination showed external validity and test-retest reliability was high. Simultaneous administration of the score with the DASH score, both before and after surgery, showed it to be more sensitive to change (P=0.056). In addition, it is shorter than the DASH score, which may make it more acceptable to patients.


Model of calf muscle tear during a simulated eccentric contraction, comparison between ex-vivo experiments and discrete element model.
The tearing of the muscle-tendon complex (MTC) is one of the common sports-related injuries. A better understanding of the mechanisms of rupture and its location could help clinicians improve the way they manage the rehabilitation period of patients. A new numerical approach using the discrete element method (DEM) may be an appropriate approach, as it considers the architecture and the complex behavior of the MTC. The aims of this study were therefore: first, to model and investigate the mechanical elongation response of the MTC until rupture with muscular activation. Secondly, to compare results with experimental data, ex vivo tensile tests until rupture were done on human cadavers {triceps surae muscle + Achilles tendon}. Force/displacement curves and patterns of rupture were analyzed. A numerical model of the MTC was completed in DEM. In both numerical and experimental data, rupture appeared at the myotendinous junction (MTJ). Moreover, force/displacement curves and global rupture strain were in agreement between both studies. The order of magnitude of rupture force was close between numerical (858 N for passive rupture and 996 N-1032 N for rupture with muscular activation) and experimental tests (622 N ± 273 N) as for the displacement of the beginning of rupture (numerical: 28-29 mm, experimental: 31.9 mm ± 3.6 mm). These differences could be explained by choices of DEM model and mechanical properties of MTC's components or their rupture strain values. Here we show that he MTC was broken by fibers' delamination at the distal MTJ and by tendon disinsertion at the proximal MTJ in agreement with experimental data and literature.


A streamlined technique for on-grid electron immunocytochemistry.
The unlabelled antibody enzyme technique for on-grid immunostaining demands exacting conditions of cleanliness. These can be met with minimal trouble by two technical modifications. Large supplies of all the solutions are millipore-filtered in advance and are then stored frozen in sealed plastic bags and allowed to thaw when required. A disposable, contamination-free surface with depressions to hold drops of staining solution is prepared from a strip of parafilm.


Aluminum hydroxide exposure induces neurodevelopmental impairment in hESC-derived cerebral organoids.
Aluminum (Al) has been classified as a cumulative environmental pollutant that endangers human health. There is increasing evidence to suggest the toxic effects of Al, but the specific action on human brain development remains unclear. Al hydroxide (Al(OH)3), the most common vaccine adjuvant, is the major source of Al and poses risks to the environment and early childhood neurodevelopment. In this study, we explored the neurotoxic effect of 5 μg/ml or 25 μg/ml Al(OH)3 for six days on neurogenesis by utilizing human cerebral organoids from human embryonic stem cells (hESCs). We found that early Al(OH)3 exposure in organoids caused a reduction in the size, deficits in basal neural progenitor cell (NPC) proliferation, and premature neuron differentiation in a time and dose-dependent manner. Transcriptomes analysis revealed a markedly altered Hippo-YAP1 signaling pathway in Al(OH)3 exposed cerebral organoid, uncovering a novel mechanism for Al(OH)3-induced detrimental to neurogenesis during human cortical development. We further identified that Al(OH)3 exposure at day 90 mainly decreased the production of outer radial glia-like cells(oRGs) but promoted NPC toward astrocyte differentiation. Taken together, we established a tractable experimental model to facilitate a better understanding of the impact and mechanism of Al(OH)3 exposure on human brain development.


Extended-release niacin/laropiprant lipid-altering consistency across patient subgroups.
In patients with primary hypercholesterolemia or mixed dyslipidemia, extended-release niacin/laropiprant (ERN/LRPT) improves key lipid parameters associated with increased atherosclerotic coronary heart disease (CHD) risk. This analysis examined data from four Phase III, randomised, double-blind trials to determine the consistency of ERN/LRPT's lipid-altering efficacy among subgroups of patients. Data from four Phase III, randomised, double-blind trials of ERN/LRPT were analysed to determine the consistency of ERN/LRPT's lipid-altering efficacy among subgroups of gender, race (white, non-white), region (US, ex-US), baseline age (<65, ≥65 years), use of statin therapy, CHD risk status (low, multiple, high) and type of hyperlipidemia (primary hypercholesterolemia, mixed dyslipidemia), as well as across baseline low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. End-points included the per cent change from baseline in LDL-C, HDL-C and TG levels. Consistency of the treatment effects on LDL-C, HDL-C and TG across subgroups was evaluated by examining treatment difference estimates with 95% confidence intervals. Treatment with ERN/LRPT significantly improved LDL-C, HDL-C and TG levels compared with placebo/active comparator in each study cohort. These effects were generally consistent across all examined subgroups. Extended-release niacin/laropiprant represents an effective therapeutic option for the treatment of dyslipidemia across a range of patient types.


Glucose transport activity in isolated plasma membrane vesicles from Saccharomyces cerevisiae.
Purified plasma membranes prepared from yeast cells by mechanical agitation with glass beads exhibit no detectable sugar transport activity. However, the addition of phospholipid (asolectin) liposomes to the purified plasma membranes followed by freezing, thawing, and brief sonication produces membrane vesicles which exhibit D-glucose-specific transport activity. The characteristics of zero trans, equilibrium exchange, and influx counterflow exhibited by the membrane vesicles are similar to those of intact cells.


Skin necrosis secondary to low-molecular weight heparin in a patient with antiphospholipid antibody syndrome.
Skin necrosis is a rare complication of subcutaneous heparin therapy that usually occurs at injection sites. It occasionally accompanies the heparin-associated thrombocytopenia and thrombosis syndrome. We describe a patient with the antiphospholipid syndrome who had skin necrosis develop from low-molecular weight heparin therapy at sites distant from injection sites.


Diagnostic performance of the Gynecology Imaging Reporting and Data System for malignant adnexal masses.
To evaluate the Gynecology Imaging Reporting and Data System (GI-RADS) for diagnosis of malignant adnexal masses in a Chinese population. A retrospective study was conducted of patients who underwent evaluation of suspected adnexal masses at a hospital in Tianjin, China, between January 1, 2015, and January 31, 2016. Ultrasonographic diagnosis was based on the GI-RADS classification-a standardized summary of imaging data that estimates the risk of malignancy-and compared with the final pathological diagnosis. Among 242 patients, thick wall, solid papillary projection, solid area, central blood flow, ascites, and GI-RADS classification were associated with malignancy (P<0.05 for all variables). The 263 masses evaluated were classified as GI-RADS 2 (functional cyst; n=65), GI-RADS 3 (benign neoplasm; n=68), GI-RADS 4 (one or two morphological findings suggestive of malignancy; n=101), and GI-RADS 5 (≥3 morphological findings suggestive of malignancy; n=28). Four malignant cases with false-negative findings were misclassified as GI-RADS 3, whereas 24 benign cases with false-positive findings were misclassified as GI-RADS 4. The sensitivity, specificity, false-positive rate, false-negative rate, accuracy, and Youden index of the GI-RADS classification were 96.4%, 84.3%, 18.5%, 3.0%, 89.3%, and 80.7%, respectively. The GI-RADS classification performed well in the diagnosis of malignant adnexal masses.


Bis(2-amino-5-chloro-pyridinium) tetra-chloridozincate.
The asymmetric unit of the title compound, (C(5)H(6)ClN(2))(2)[ZnCl(4)], contains two 2-amino-5-chloro-pyridinium cations and one [ZnCl(4)](2-) dianion which are held together by N-H⋯Cl and C-H⋯Cl hydrogen bonds. The [ZnCl(4)](2-) anions have a distorted tetra-hedral geometry. Weak inter-molecular π-π stacking inter-actions exist between neighbouring aromatic rings of the cations with a centroid-centroid distance of 3.712 (7) Å.


Mucocele of the appendix causing tubal factor infertility.
To report on the safety of conservative management of a young woman with pseudomyxoma peritonei of appendiceal origin desiring fertility preservation. Case report. IVF Center at Tertiary Hospital. A 32-year-old woman with primary infertility. Appendectomy, conservative second-look laparoscopy, and IVF. Persistence of active mucinous lesions in the peritoneal cavity, presence of abnormalities at colonoscopy, and maternal/fetal complications from IVF. Normal second-look laparoscopy, no evidence of persistent disease, and successful intrauterine twin pregnancy following IVF. Pseudomyxoma peritonei of appendiceal origin is rare in young female patients. Although traditional therapy in older patients often involves aggressive surgical therapy, this case report demonstrates that patients desiring fertility can be managed conservatively and safely and still maintain successful pregnancy.


Considerations and Challenges in the Remdesivir COVID-19 Pediatric Development Program.
The US Food and Drug Administration is committed to the development of effective antiviral regimens for pediatric patients with coronavirus disease 2019 (COVID-19), including infants and neonates. On April 25, 2022, the approved indication of remdesivir (RDV) was expanded to include pediatric patients 28 days and older and weighing at least 3 kg with positive results of direct severe acute respiratory syndrome coronavirus 2 viral testing, who are: Hospitalized, or Not hospitalized and have mild to moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death. Given the similar course of COVID-19 in adults and pediatric patients, the approval of RDV for use in pediatric patients is supported by the safety and efficacy data from adequate and well-controlled phase 3 trials in adults and adolescents; and by the safety and pharmacokinetic data from a single-arm, open-label, phase 2/3 pediatric clinical trial of 53 pediatric patients at least 28 days of age and weighing at least 3 kg with confirmed severe acute respiratory syndrome coronavirus 2 infection and mild, moderate, or severe COVID-19. At the time of the April 25, 2022, approval action, the US Food and Drug Administration also revoked the emergency use authorization for RDV that previously covered this pediatric population. This article summarizes key issues and regulatory considerations involved in the RDV COVID-19 pediatric development program, including the evolution of the emergency use authorization issued for RDV as results from registrational studies became available, and discusses lessons learned.


An altered response of virally transformed 3T3 cells to ouabain.
The effect of ouabain on K+ transport was examined in 3T3 and virally transformed 3T3 cells. A 10 min exposure to ouabain (10(-3) M) produced approximately 40% inhibition of the unidirectional K+ influx in all cell lines. In 3T3 cells the response was not significantly altered by up to 70 min exposure to the drug. In contrast, the continued exposure of transformed cells to ouabain produced a time-dependent increase in the K+ influx. This increased influx was shown to be accompanied by an increase in the K+ efflux. The results suggest that, in transformed cells, ouabain produces both an inhibition of Na+-K+ exchange and a stimulation of K+-K+ exchange. The latter was shown to be more readily reversible than the former.


Impact of Rotavirus Vaccine Introduction and Postintroduction Etiology of Diarrhea Requiring Hospital Admission in Haydom, Tanzania, a Rural African Setting.
No data are available on the etiology of diarrhea requiring hospitalization after rotavirus vaccine introduction in Africa. The monovalent rotavirus vaccine was introduced in Tanzania on 1 January 2013. We performed a vaccine impact and effectiveness study as well as a quantitative polymerase chain reaction (qPCR)-based etiology study at a rural Tanzanian hospital. We obtained data on admissions among children <5 years to Haydom Lutheran Hospital between 1 January 2010 and 31 December 2015 and estimated the impact of vaccine introduction on all-cause diarrhea admissions. We then performed a vaccine effectiveness study using the test-negative design. Finally, we tested diarrheal specimens during 2015 by qPCR for a broad range of enteropathogens and calculated pathogen-specific attributable fractions (AFs). Vaccine introduction was associated with a 44.9% (95% confidence interval [CI], 17.6%-97.4%) reduction in diarrhea admissions in 2015, as well as delay of the rotavirus season. The effectiveness of 2 doses of vaccine was 74.8% (95% CI, -8.2% to 94.1%) using an enzyme immunoassay-based case definition and 85.1% (95% CI, 26.5%-97.0%) using a qPCR-based case definition. Among 146 children enrolled in 2015, rotavirus remained the leading etiology of diarrhea requiring hospitalization (AF, 25.8% [95% CI, 24.4%-26.7%]), followed by heat-stable enterotoxin-producing Escherichia coli (AF, 18.4% [95% CI, 12.9%-21.9%]), Shigella/enteroinvasive E. coli (AF, 14.5% [95% CI, 10.2%-22.8%]), and Cryptosporidium (AF, 7.9% [95% CI, 6.2%-9.3%]). Despite the clear impact of vaccine introduction in this setting, rotavirus remained the leading etiology of diarrhea requiring hospitalization. Further efforts to maximize vaccine coverage and improve vaccine performance in these settings are warranted.


Prediction of 5-Year Mortality in Patients with Chronic Coronary Syndrome Treated with Elective Percutaneous Coronary Intervention: Role of the ACEF Score.
We evaluated the predictive power of age, creatinine, and ejection fraction (ACEF) score on mortality at 5-year follow-up in a population of 471 patients with chronic coronary syndrome (CCS) treated with percutaneous coronary intervention (PCI). Patients in the ACEF-High tertile showed the highest incidence of death at 5 years (15.7% vs. 2.6% in ACEF-Low and 4.3% in ACEF-Mid; log rank p<0.001). The ACEF score could significantly discriminate between patients who died and those who were still alive at 5 years (AUC 0.741, 95% CI 0.654-0.828), and an ACEF score >1.32 was identified as the optimal cutoff point to predict 5-year mortality (sensitivity 74%, specificity 68%). An ACEF score >1.32 was an independent predictor of 5-year mortality (HR 5.77, 95% CI 2.70-12.31; p<0.001). Our study shows that the ACEF score can predict mortality at 5-year follow-up in patients with CCS treated with PCI.