The multiple forms and kinetic differences of rat colonic beta-N-acetylhexosaminidases.
Rat colonic beta-N-acetylhexosaminidase (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase, EC 126.96.36.199) has been separated into three forms by DEAE-cellulose chromatography with an increasing salt gradient. It was not possible to separate the glucosaminidase activity from the galactosaminidase activity by a variety of chromatographic procedues, but the ratio of the two specific activities varied during purification. The pH optima were however identical, for both activities and all three forms. Kinetic measurements including inhibition by substrate analogues showed differences between the two activities as well as among the three forms. A common active site model was inconsistent with the results. Data from mixed substrate experiments were consistent with a model wherein the two activities reside in seperate active sites, each able to be inhibited by the substrate for the other site. The effect of acetate and SH reagents confirmed the two-site model. Treatment with neuraminidase, thimerosal, p-hydroxymercuribenzoate, HgCl2 and AgNO3 or heating at 50 degrees C did not produce any effect on the A form that could be identified as a conversion to the B form. Measurement of the effects on both activities supported the two-site model. It is concluded that the relationship between the A and B forms in the rat colonic mucosa hexosaminidases must be different from that reported for such enzymes from other sources.


Synthesis and evaluation of the biological activities of some 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-one derivatives.
Reaction of ethyl-6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carboxylates (1a-i) with hydrazine hydrate yielded 6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carbohydrazides (2a-i). These products, on reaction with cyanogen bromide, gave 5-(5-amino-1,3,4-oxadiazol-2-yl)-6-methyl-4-aryl-3,4-dihydropyrimidin-2 (1H)-ones (3a-i). The resultant aminooxadiazolylpyrimidinones were condensed with isatin to obtain various 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-ones (4a-i). These products were characterized by IR, 1H NMR, mass spectra and elemental analysis. Products (4a-i) revealed promising antibacterial, antifungal and antioxidant activity.


Clioquinol induces autophagy by down-regulation of calreticulin in human neurotypic SH-SY5Y cells.
Clioquinol (CQ) is considered as a promising drug of neurodegenerative diseases. However, the underlying mechanism is unclear. Our previous study has proved that CQ induces S-phase cell cycle arrest through the elevation of intracellular calcium concentration ([Ca2+]i) with high levels of SERCA2. Furthermore, it could induce autophagy in an intracellular calcium independent manner in human neurotypic SH-SY5Y cells. In this study, the involvement of calreticulin (CRT) in autophagy induced by CQ was investigated. Our results illustrated the endoplasmic reticulum (ER) stress induced by CQ and DTT led to the cell death in different manners. DTT, an ER stress positive control, induced UPR accompanied with up-regulation of CRT and apoptosis, while CQ inhibited UPR accompanied with down-regulation of CRT,resulting in autophagy. Then, overexpression of CRT was shown to cause UPR and decrease [Ca2+]i, leading to cell apoptosis and inhibition of S-phase arrest induced by CQ. While the UPR was alleviated and autophagy was further enhanced in CRT deficient cells by using targeted siRNA. Meanwhile, down-regulation of CRT resulted in [Ca2+]i overload and induction of S-phase arrest. Finally, we found that the effect of CQ on the HT22 cells was similar to that on the SH-SY5Y cells. Our data showed for the first time that CQ decreased expression of CRT, leading to autophagy, an increase of [Ca2+]i, and cell S-phase arrest in the neurotypic cells. The present study describes the cellular signal pathways regulating autophagy by CQ and highlights the potential therapeutic application of CQ in neurodegenerative disorders.


Administration of rotenone enhanced voluntary alcohol drinking behavior in C57BL/6J mice.
Rotenone, a commonly used lipophic pesticide, is a high-affinity mitochondrial complex I inhibitor. The aim of this project is to study the causal relationship between changes of brain monoamine levels and drinking behavior in rotenone-treated mice. In the first experiment, we investigated the effects of acute exposure to rotenone (20 mg/kg, p.o.) on the 8-h time limited-access alcohol drinking behavior and brain monoamine levels in C57BL/6J mice at 0, 2, 8 and 24 h. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5HIAA) levels in the nucleus accumbens (ACC), caudate-putamen (C/P) and lateral hypothalamus (LH) of rotenone-treated mice were decreased at 2 and/or 8 h. Rotenone-exposed mice showed a suppression of voluntary alcohol intake at 4 and 8 h, but total daily alcohol intake did not differ significantly between the two groups. The effects of chronic exposure to rotenone (1, 5, 10 and 20 mg/kg, p.o. for 30 days) on the alcohol drinking behavior and monoamine levels of rotenone-exposed mice (10 mg/kg, p.o.) were investigated in the second experiment. The mice treated with rotenone showed increases in alcohol drinking behavior. Levels of DA and 5-HT in the ACC and C/P of chronic rotenone-treated mice were decreased, while the ratios of DOPAC to DA in the ACC and C/P and of 5HIAA to 5-HT in the ACC, C/P and DRN were increased significantly. Tyrosine hydroxylase immunoreactivity of chronic rotenone-treated mice (10 mg/kg, p.o.) slightly were decreased in both the striatum and the substantia nigra. Ethanol and acetaldehyde metabolism was not significantly different between mice treated with rotenone (10 mg/kg, p.o.) and controls. It was suggested that rotenone-treated mice had increased alcohol drinking behavior associated with increases in the DA turnover ratios of ACC and striatum to compensate for the neural degeneration.


Prognostic role of blood eosinophil and basophil levels in allergic fungal rhinosinusitis (AFRS).
Allergic fungal rhinosinusitis (AFRS) forms a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) that is mainly characterized by eosinophilic nasal polyps, allergic mucin detected in the sinuses at surgery, and specific features on computerized tomography. Which biological markers predict disease recurrence in AFRS is still not clear, and the role of blood inflammatory cells in predicting recurrent polyps after surgery has yet to be investigated. The aim of this study was to newly investigate the prognostic role (in terms of recurrence rate) of preoperative blood eosinophil and basophil levels in AFRS. A consecutive series of 17 adult patients who underwent endoscopic sinus surgery for AFRS was retrospectively assessed. Sinonasal polyps recurred in 7 of 17 patients. Considering the whole cohort, a significant positive correlation emerged between blood eosinophil and basophil counts, but not between blood and tissue eosinophil counts. Statistical analysis found significantly higher blood eosinophil and basophil levels in AFRS patients who relapsed than in those who did not. Considering the current difficulty of identifying more effective, personalized approaches to postoperative disease management in AFRS, our preliminary data support the impression that blood eosinophil and basophil levels warrant testing in further prospective and larger (preferably multi-institutional) investigations as part of the preoperative work-up for patients with AFRS in order to administer dedicated postoperative medical treatments for patients at higher risk of relapse.


The Application of Dupilumab to Pediatric Patients Aged 6-11yrs with Moderate-to-Severe Atopic Dermatitis Whose Disease is Not Adequately Controlled: The Clinical Data so Far.
While dupilumab has shown efficacy in improving atopic dermatitis, few studies have assessed the long-term clinical data of dupilumab use in pediatric patients. In the present study, we reviewed the current literature to assess reported efficacies, side effects, and risks of using dupilumab to treat atopic dermatitis in pediatric populations. Using PRISMA guidelines, the authors searched PubMed/MEDLINE and Embase for studies related to dupilumab treatment for atopic dermatitis in pediatric patients aged 6-11 years old. A total of 512 pediatric patients (ages 6-11) were included. Outcome measures assessed by EASI, SCORAD, P-NRS, IGA and C-DLQI showed significant improvements in scores from those observed at baseline to the last treatment of dupilumab. Most reported adverse effects on dupilumab were conjunctivitis and infection site reactions. All studies reported that dupilumab was well-tolerated. Limitations include the low number of studies available and observation periods of up to 16 weeks, which may be too short to evaluate the drug's effectiveness and occurrence of adverse effects. This also limits our knowledge on whether there are sustained benefits and/or diminished efficacy as well as long-term side effects. Thus far, the data demonstrates dupilumab to be safe and effective in the management of moderate-to-severe atopic dermatitis in children aged 6-11 years. Future studies should evaluate long-term dupilumab use and sustained effects.


Experience with the MLCu250 IUD.
One thousand and thirty eight patients were fitted with MLCu250 IUDs over a six year period. The women were divided into three groups: group A, 224 women in whom the IUD was inserted postpartum; group B, 352 patients who had the IUD inserted immediately after an abortion; and group C, 462 women in whom insertions were performed at the end of menstruation. All women were followed up every six months for up to 24 months. All women experienced good contraceptive effects. The mean unexpected pregnancy rate was 2.1% (group A = 2.6%, group B = 2.0% and group C = 1.7%). The mean expulsion rate was 1.8% (group A = 2.2%, group B = 2.0% and group C = 1.3%). The bleeding-pain symptom was apparent in 5.5%. The mean rate for planning pregnancy was 3.8%. Removals for medical and personal reasons were 3.6% and 1.9% respectively. The continuation rate was considered very satisfactory (mean value 78.5%, group A = 76%, group B = 77.6% and group C = 82%). In the present study no perforations or ectopic pregnancies occurred.


[Congenital or neonatal hypothyroidism with filter-paper levels of TSH less than 50 microU/ml. Conclusions on the detection strategy in France].
Between 1979 and 1983, 959 hypothyroid infants were discovered by the neonatal screening program in France. Sixteen had filter-paper TSH levels between 30 and 50 microU/ml: one was athyroid, ectopic thyroid in 5,10 had thyroids in place. These latter 16 cases argue for a second TSH control-value for filter paper TSH values between 30 and 50 microU/ml.


Receptor-operated Ca2+ influx channels in leukocytes: a therapeutic target?
Receptor-mediated activation of leukocytes by inflammatory stimuli elicits Ca2+ ion influx as a common and important activation mechanism that has been well established in the literature for over a decade. Inhibiting such receptor-operated Ca2+ influx channels is a potentially attractive strategy for developing anti-inflammatory drugs to attenuate leukocyte activation. Until very recently, the molecular identity of these channels has been unknown, which has hampered drug development in this area. However, the recent explosion of molecular information about one particular family of non-voltage-activated Ca2+ channels, the transient receptor potential (TRP) channels, together with emerging knowledge of their distribution, function and regulation, suggests that they represent a key subgroup of these channels and are therefore potentially attractive drug targets.


[Ultrasonographic evaluation of the uterine cervix length remaining after LOOP-excision].
To assess whether there is a correlation between the length of a conization specimen and the length of the cervix measured by vaginal ultrasonography after the operation Prospective observational study including patients less than 45 years with measurement of cervical length before and the day of the conization, and measuring the histological length of the specimen. Among the 40 patients enrolled, the average ultrasound measurements before conization was 26.9 mm (± 4.9 mm) against 18.1mm (± 4.4mm) after conization with a mean difference of 8.8mm (± 2.4mm) (difference statistically significant P<.0001). The extent of histological specimen was 9 mm (± 2.2mm) on average. A correlation between ultrasound and histological measurements with a correlation coefficient R=0.85 was found statistically significant (P<0.0001). Moreover, the rate of cervix length remove by loop-excision in our series is 33% (± 8.5%). A good correlation between the measurements of the specimen and the cervical ultrasound length before and after conization was found, as a significant reduction in cervical length after conization. The precise length of the specimen should be known in case of pregnancy and the prevention of prematurity due to conization rests on selected indications and efficient surgical technique.


Effects of C/N ratio variation in swine biogas slurry on soil dissolved organic matter: Content and fluorescence characteristics.
Nutrient-rich biogas slurry shows favorable prospects for application as an organic fertilizer in farmland. At the same time, due to differing sources and treatment methods, the C/N ratio of biogas slurry varies greatly. The effect of differences in C/N of biogas slurry on soil organic matter properties remains unclear. In this experiment, pig farm biogas slurry differing in C/N (3, 6, 8.84 and 12) was applied instead of fertilizer. Fluorescence spectroscopy combined with parallel factor analysis and principal component analysis were used to determine dissolved organic carbon (DOC) and fluorescent dissolved organic matter (FDOM) in soil dissolved organic matter (DOM). The experimental results showed that the DOC and FDOM contents of soil could be significantly increased at the initial stage of biogas slurry application. Compared with CK, on the 60th day, biogas slurry with a C/N of 12 exhibited the greatest improvement in DOC, FDOM as well as for Component 1, Component 2 and Component 3 contents in soil FDOM, 40.93%, 66.25%, 65.35%, 40.47%, and 78.42% respectively. However, compared with the 0th day, by the 60th day, biogas slurry with a C/N of 8.84 exhibited the greatest decrease in Component 4 content in soil FDOM, 74.68%. Biogas slurry with a C/N of 8.84 exerted the greatest promotion effect on corn growth, the utilization and transformation of Component 4 by plants and microorganisms in the soil. And it showed the strongest improvement in the degree of FDOM humification in the soil, the humification index increased from 4.16 ± 0.17 to 4.92 ± 0.58, compared with CK. This study provided new insights for the utilization of biogas slurry with respect to soil physical and chemical properties and maize plant growth.


Influence of fasting and refeeding on the elongation step of protein synthesis in rat liver of young (3M) and aging (18M) animals.
The in vitro binding capacity for AA-tRNA of ribosomes, catalysed by EF1 enzyme, was studied in livers of rats, which had been starved for 5 days and re-fed for 3, 9, and 24 hours. The experiments were carried out with 3 and 18-month-old rats. The results were compared to those obtained with normally fed rats of the same ages. For both age groups, there was a similar change in the binding capacity, including a return to normal values after 24 hours of refeeding. When ribosomes of old control animals were treated with different enzymes, we obtained lower binding activities for all the experimental groups than in homologous cell-free systems (ribosomes and EF1 isolated from the same group). The ribosomes of young animals, tested in the presence of different enzymes, display an increased binding capacity, when the enzymes used were those of old (control and re-fed) animals. The recovery of the catalytic activity of EF1 on the binding process was observed after 9 hours in old animals, whereas it was not seen for young re-fed animals at that time of refeeding. EF1 seems to play an important role in the adaptation of older animals to fasting and refeeding.


Interaction of some traditional plant extracts with uterine oestrogen or progestin receptors.
Previous work has demonstrated that stem bark extracts of Combretodendron macrocarpum (Barringtoniaceae), Cola nitida (Sterculiaceae), Afrormosia laxiflora and Pterocarpus erinaceus (Fabaceae) blocked the oestrus cycle of female rats through antigonadotropic activity. Moreover, a study of the plant substances responsible for these effects revealed the presence of phyto-anti-oestrogens in these plant extracts. In order to explain the mechanism by which these substances exert their antifertility actions, the interaction of the plant extract with oestrogen and progesterone receptors was studied. All crude extracts exerted inhibition of ((3)H)-oestradiol or ((3)H)-Organon binding to their respective receptors but their relative affinities were much lower than those of oestradiol or progesterone. Respective efficiencies of plant extracts in competing for the oestrogen receptor were as follows: A. laxiflora > P. erinaceus > C. macrocarpum > C. nitida. The efficiency order of competition for the progestin receptor was different to that of oestrogen. The most potent competitor was C. macrocarpum extract, followed by P. erinaceus, C. nitida and A. laxiflora. Moreover, the interaction between oestradiol and plant extracts with the oestrogen receptor was determined to be competitive only for C. macrocarpum and A. laxiflora, whereas all compounds produced a competitive inhibition on the progestin receptor binding. These results suggest that the plant extract binding site was the same site as for the steroid. These results suggest also that crude plant extracts may interfere with natural oestrogen and/or progestagen in vivo by binding to steroid receptors.


A comparison of the effects of acupoint injection combined with hyaluronic acid versus isolated hyaluronic acid for knee osteoarthritis: A protocol for systematic review and meta-analysis of randomized controlled trials.
Knee osteoarthritis (KOA) is a kind of degenerative osteoarthropathy, which causes joint pain and limited mobility, seriously affects the quality of life of the patient. Traditional Chinese Medicine acupuncture and moxibustion has been widely used to treat KOA, and acupoint injection is 1 of the acupuncture treatment methods. The purpose of this work is to evaluate the effectiveness of Acupoint injection combined with Hyaluronic Acid injection compared with isolated Hyaluronic Acid injection for KOA. We will search articles in 7 electronic databases including Chinese National Knowledge Infrastructure, Wanfang Data, Chinese Scientific Journals Database, Chinese databases SinoMed, PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to October 2020. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. This study will evaluate the efficacy and safety of Acupoint injection combined with Hyaluronic Acid injection compared with isolated Hyaluronic Acid injection in the treatment of KOA, to provide high-quality, evidence-based clinical recommendations. INPLASY2020100058 CONCLUSION:: This study will provide reliable evidence on whether Acupoint injection combined with Hyaluronic Acid injection compared with isolated Hyaluronic Acid injection is more effective in treating KOA.


Interferon regulatory factor-1 (IRF-1) regulates VEGF-induced angiogenesis in HUVECs.
Interferon regulatory factor-1 (IRF-1) is a tumor suppressor and transcriptional modulator that can regulate gene expression involved in cell growth control, induction of apoptosis, and post-translation modification. In this study, we found that IRF-1 inhibits endothelial cell angiogenesis using human umbilical vein endothelial cell (HUVECs) culture system. In addition, IRF-1 directly inhibited the tube formation of endothelial cells on Matrigel and reduced the expression of p-Akt, and p-eNOS, which play a significant role in angiogenesis when stimulated by VEGF. We also demonstrate that C-terminal region including transactivation domain (TA) of IRF-1 functions as a signal for its angiostatic activity, and is spliced in human tumor tissues. These findings indicate that splicing variant involving exons 7 of IRF-1 could potentially modulate anti-angiogenic effect of IRF-1. In overall, this study provides the first evidence for anti-angiogenic role of IRF-1, which may have therapeutic values for cancer and angiogenesis-associated diseases.


Improvement of Unilateral Breast Hypoplasia With Oral Spironolactone in a Patient With Becker Nevus Syndrome.
Becker nevus (BN) is a benign cutaneous smooth muscle hamartoma that presents with a hyperpigmented patch or plaque with or without hypertrichosis.1 BN may be associated with ipsilateral breast hypoplasia or other musculoskeletal abnormalities, an association which has been termed Becker nevus syndrome (BNS).


Diagnosis of thalassemia using fluorescence spectroscopy, auto-analyzer, and hemoglobin electrophoresis - A prospective study.
Hemoglobinopathies (HgP) are prevalent in certain regions of the world. The World Health Organization estimated that 5% of the world's population is a carrier of the potentially pathological hemoglobin (Hb) gene. This study aimed to compare the performance of fluorescence spectroscopy, a simple and inexpensive method, with that of conventional techniques for diagnosing thalassemia. The red blood cell (RBC) counts and levels of Hb, HbA, HbA2, and HbS were estimated via conventional methods of complete blood count and Hb electrophoresis to diagnose thalassemia. The RBCs and Hb, particularly the average values of HbA and HbA2, were lower in patients with thalassemia than in the normal controls. These hematologic parameters were also analyzed via fluorescence spectroscopybased on fluorescent biomolecules including tyrosine (275 nm), tryptophan (290 nm), nicotinamide adenine dinucleotide (NADH) (370 nm), flavin adenine dinucleotide (FAD) (450 nm), and porphyrin (585-635 nm). In thalassemia patients, all these parameters were above the normal range, primarily due to abnormal depression of NADH and elevation of FAD. Thalassemia canbe diagnosed via a fluorescent spectral method with an accuracy of 85% for blinded groups. This method may be useful for screening patients and reducing the cost of diagnosis in many rural countries.


Association of the insertion allele of the common ACE gene polymorphism with type 2 diabetes mellitus among Kuwaiti cardiovascular disease patients.
The D allele of the common angiotensin-converting enzyme (ACE) I/D gene polymorphism (rs4646994) predisposes to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). However, results on which allele predisposes to disease susceptibility remain controversial in Asian populations. This study was performed to evaluate the association of the common ACE I/D gene polymorphism with both T2DM and CVD susceptibility in an Arab population. We genotyped the ACE I/D polymorphisms by direct allele-specific PCR in 183 healthy controls and 400 CVD patients with diabetes (n=204) and without (n=196). Statistical analysis comparing between the different groups were conducted using R statistic package "SNPassoc". Two genetic models were used: the additive and co-dominant models. The I allele was found to be associated with T2DM (OR=1.84, p=0.00009) after adjusting for age, sex and body mass index. However, there was no association with CVD susceptibility (p>0.05). The ACE I allele is found to be associated with T2DM; however, no association was observed with CVD. The inconsistency between studies is suggested to be attributed to genetic diversity due to the existence of sub-populations found in Asian populations.


HCC-DETECT: a combination of nuclear, cytoplasmic, and oncofetal proteins as biomarkers for hepatocellular carcinoma.
Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.


A comparison of the anti-inflammatory effects of copper aspirinate and other copper salts in the rat and guinea pig.
A comparison of the anti-inflammatory (AI) activity of copper compounds in models of kaolin-induced paw oedema and u.v. erythema in the rat and guinea pig is described. The results demonstrated considerable species variation, the guinea pig being more sensitive to the AI and irritant effects of copper aspirinate and the other copper compounds. The route of administration of these compounds was also an important factor in interpreting AI activity obtained. Indeed, the counter-irritation effects of the copper compounds may be largely responsible for the AI activity obtained after subcutaneous administration. The comparison between copper aspirinate and aspirin, performed in order to determine whether a copper complex of an AI drug was more active than the parent AI compound, failed to produce a clear difference in activity although copper aspirinate was more effective than aspirin in certain cases. It is concluded that this study highlights the complexities of copper therapy against inflammatory processes and furthermore indicates the importance of species, the model of inflammation and route of drug administration in interpreting data obtained with copper containing compounds.


Conversion of the substrate specificity of mouse proteinase granzyme B.
Mouse granzyme B is the prototypic member of a subfamily of serine proteinases expressed in cytolytic lymphocytes. Molecular modelling of granzyme B indicated that the side chain of Arg 208 partially fills the specificity pocket, thus predicting the preference of this enzyme for substrates containing acidic side chains, a feature unique among eukaryotic serine proteinases. Replacement of Arg 208 with glycine results in an enzyme lacking this activity, but which is able to hydrolyze hydrophobic substrates. These results demonstrate unequivocally that the substrate preference of granzyme B is determined by a positive charge in the specificity pocket and also represent one of the few examples of rational and efficient alteration of serine proteinase substrate-specificity following a single amino acid substitution.


Effects of a school-based, theory-driven HIV and pregnancy prevention curriculum.
Although a number of interventions are effective at reducing risky adolescent sexual behavior, it may be possible to make them even more effective by addressing adolescents' approaches to risk-taking. Schools were assigned to teach one of three curricula in a quasi-experimental intervention study: the school's standard pregnancy and HIV prevention curriculum; the Reducing the Risk curriculum; or a modified Reducing the Risk curriculum, adapted for high sensation seekers and impulsive decision makers. A sample of 1,944 students from 17 schools was surveyed at three time points between 1995 and 1997. Mixed models regression and logistic regression were used to examine the difference in impact among curricula. Differences in the impact of the original and modified Reducing the Risk interventions were not significant for the total sample or for high sensation seekers and impulsive decision makers separately. Students from both intervention groups demonstrated short-term improvements in knowledge; students who received their schools' standard curriculum were significantly more likely than those assigned to either intervention to have initiated sexual intercourse by the third time point (odds ratio, 2.4). More work is necessary to understand the best ways to design classroom messages that will be effective in reducing the risk behaviors of high sensation seekers and impulsive decision makers.


Worse Mental Health Among More-Acculturated and Younger Immigrants Experiencing Discrimination: California Health Interview Survey, 2015-2016.
Experiences of discrimination harm mental and physical health, with the strongest penalty on mental health. Among immigrants, it remains unclear how acculturation-the process by which immigrants acquire the beliefs and practices of a host culture-influences the mental health burden of navigating discrimination. On the one hand, acculturation can be associated with upward social mobility. Conversely, the acculturative process may increase exposure to, and recognition of, discrimination. We examined the relationship between discrimination and mental illness across racial/ethnic groups, and pathways by which acculturation and age relate to the discrimination-mental health relationship. A secondary data analysis using population data from the 2015-2016 California Health Interview Survey. The Kessler 6-item Psychological Distress Scale (K6) assessed symptoms of psychological distress, with K6 score ≥ 13 associated with severe mental illness. Discrimination was measured using a self-reported measure of lifetime experience of unfair treatment in getting medical care. We used a 5-point acculturation index (constructed by measures of nativity, years living in the USA, and home language use). A weighted logistic regression model predicted mental illness as a function of discrimination. We ran mediational analysis using the Karlson-Holm-Breen method and used predictive margins to present predicted probabilities of mental illness for people reporting discrimination at different acculturation and age levels. There were independent effects on mental illness associated with increased discrimination (OR 3.85, 95% CI = 2.46, 6.03, p < 0.001) and increased acculturation (OR 1.72, 95% CI = 1.24, 2.38, p = 0.001), including when stratified across racial/ethnic groups. Higher levels of acculturation led to a significant increase in discrimination's association with mental illness. There was a higher probability of mental illness in younger age groups than in older age groups. While discrimination is associated with poor mental health, a stronger link between discrimination and mental illness exists among younger immigrants and immigrants with increased acculturation. Health practitioners should not overlook the mental health needs of younger immigrants and immigrants who may seem more integrated into US society.


Experimental stress ulcer and gastric catecholamine contents in spontaneously hypertensive rats.
To determine the role of the sympathetic nervous system in the development of stress ulcer, we carried out experiments on spontaneously hypertensive rats (SHR) exposed to restraint and water immersion stress for 7 h. Normotensive Wistar-Kyoto rats (WKY) were used as controls. Catecholamine (CA) contents in gastric tissues, divided into mucosal and muscular layers of both antrum and corpus, were quantitated by high-performance liquid chromatographic electrochemical detection (HPLC-EC). The stress ulcer formation was much less frequently induced in SHR than in WKY. The noradrenaline (NA) contents in all regions of gastric tissues were higher in SHR than in WKY. The contents of adrenaline (A) and dopamine (DA), present in small quantities in gastric tissues showed no difference between SHR and WKY. After exposure to stress, the NA contents in mucosal and muscular layers of the gastric corpus decreased significantly in both SHR and WKY, whereas the value remained higher in the former. On the contrary, a remarkable increase of A contents (probably released from the adrenal medulla by the stress) was observed in all gastric tissues, of both SHR and WKY. Increase of the A contents in the mucosal layer was remarkable in the SHR. The DA contents increased in both strains. These results suggest that the peripheral sympathetic hyperfunction in the stomach in the SHR may have an inhibitory role in stress ulcer formation.


Key genes for arsenobetaine synthesis in marine medaka (Oryzias melastigma) by transcriptomics.
Marine fish undergo detoxification to overcome As stress, forming non-toxic metabolites arsenobetaine (AsB). Genes associated with AsB synthesis remain unknown. Therefore, in this study, we explored the key genes involved in the synthesis of AsB by transcriptomic analysis in marine medaka (Oryzias melastigma), and then screened candidate genes related to AsB synthesis. In the liver, 40 genes were up-regulated and 23 genes were down-regulated, whereas in muscle, 83 genes were up-regulated and 331 genes were down-regulated. We revealed that bhmt, mat2aa, and gstt1a can play a significant role in the glutathione and methionine metabolic pathway. These three genes can affect the conversion of arsenocholine (AsC) to AsB by the vitro gene transformation experiments of E. coli BL21(DE3). E. coli BL21-bhmt overexpressing bhmt resulted in more oxidation of precursor AsC to AsB. Furthermore, the AsB concentration was decreased after E. coli BL21 overexpressing mat2aa and gstt1a, which were down-regulated in marine medaka. Therefore, we concluded that bhmt, mat2aa, and gstt1a are involved in AsB synthesis. Overall, this is the first report on transcriptome screening and identification of key genes for AsB synthesis in marine medaka. We provided important insights to reveal the mystery of AsB synthesis in marine fish.


The body buried twice.
The authors report the case of an unusual reason for an "exhumation." A young person "exhumed" a child's body involved in a road accident because he wanted to test methods for preventing or slowing down the process of postmortem decay.


Predicting the NMR spectra of nucleotides by DFT calculations: cyclic uridine monophosphate.
We present an experimental and quantum chemical NMR study of the mononucleotide cyclic uridine monophosphate in water. Spectral parameters ((1)H and (13)C chemical shifts and (1)H--(1)H, (13)C--(1)H, (31)P--(13)C and (31)P--(1)H spin-spin coupling constants) have been carefully obtained experimentally and calculated using DFT methods including the solvent effect and the conformational flexibility of the solute. This study confirms that the (1)H and (13)C spectra of polar, flexible molecules in aqueous solution can be predicted with a high level of accuracy, comparable to that obtained for less complex systems.


Nurse leaders' perceptions of competence-based management of culturally and linguistically diverse nurses: A descriptive qualitative study.
To describe nurse leaders' perceptions of culturally and linguistically diverse (CALD) nurses' competence-based management. A descriptive qualitative study of the competence-based management of CALD nurses, from the perspectives of nurse leaders in three primary and specialised medical care organisations. This study followed the COREQ guidelines. Qualitative semi-structured individual interviews were conducted with 13 nurse leaders. Eligible interviewees were required to have management experience, and experience of working with or recruiting CALD nurses. Data were collected during November 2021-March 2022. The data were analysed using inductive content analysis. Competence-based management was explored in terms of competence identification and assessment of CALD nurses, aspects which constrain and enable competence sharing with them, and aspects which support their continuous competence development. Competencies are identified during the recruitment process, and assessment is based primarily on feedback. Organisations' openness to external collaboration and work rotation supports competence sharing, as does mentoring. Nurse leaders have a key role in continuous competence development as they organise tailored induction and training, and can indirectly reinforce nurses' work commitment and wellbeing. Strategic competence-based management would enable all organisational competencies potential to be utilised more productively. Competence sharing is a key process for the successful integration of CALD nurses. The results of this study can be utilised to develop and standardise competence-based management in healthcare organisations. For nursing management, it is important to recognise and value nurses' competence. The role of CALD nurses in the healthcare workforce is growing, and there is little research into the competence-based management of such nurses. No patient or public contribution.


Sex-related differences in cadmium-induced lipid peroxidation in the rat.
Male and female rats were dosed once a day for 2 days injection with 1.5 mg of Cd/kg as CdCl2. 24 hr after administration of cadmium, lipid peroxidation determined by estimation of malondialdehyde (MDA) was greatly increased in male rat liver, but was not in female rats. Cadmium in a larger dose of 4.5 mg/kg, subcutaneous single injection, significantly increased content of MDA in female rat liver. These results suggest that sex-related differences exist in the ability of cadmium to induce MDA formation in rat liver, although administration of cadmium causes the enhancement of MDA formation in both male and female rats. The reason why sex-related differences exist in lipid peroxidation of rat liver is discussed.


Induction of apoptosis by spermine-metabolites in primary human blood cells and various tumor cell lines.
Polyamines are involved in the regulation of cellular growth and survival by interacting with processes like translation, transcription or ion transport. The aim of our study was to analyze whether polyamines induce apoptosis in hematopoetic cells and to investigate the molecular mechanisms involved. We found an induction of apoptosis by spermine in primary human cells and malignant tumor cell lines. Spermine-treatment resulted in an intracellular increase of reactive oxygen species. Apoptosis was mediated by a collapse of mitochondrial membrane potential, a decrease in Bcl-2 expression and a release of apoptosis mediating molecules from mitochondrial intermembrane space (cytochrome C, Smac/DIABLO). Spermine-mediated apoptosis was caspase-dependent. To test whether spermine mediates apoptosis through metabolites we analyzed the effects of several molecules that interfere with its catabolism. Aminoguanidine, an inhibitor of serum amine oxidase, aldehyde-dehydrogenase, which degrades aldehydes to less reactive molecules or N-acetyl-cysteine, a glutathion precursor, significantly inhibited spermine-mediated apoptosis. From these data we conclude that spermine-derived aldehydes and intracellular accumulation of reactive oxygen species result in mitochondria mediated apoptosis.


Correlation of cardiovascular magnetic resonance imaging findings and endomyocardial biopsy results in patients undergoing screening for heart transplant rejection.
Endomyocardial biopsy (EMB) is the current gold standard to screen for heart transplant rejection but has important risks and limitations. Cardiovascular magnetic resonance imaging (CMRI) is increasingly used to characterize cardiac function and myocardial tissue. We evaluated the diagnostic accuracy of CMRI compared with EMB and clinically diagnosed heart transplant rejection. Comprehensive CMRI scans were performed on adult heart transplant recipients within 24 hours of EMB (routine or clinically indicated), before initiation of any anti-rejection therapy, and blinded to EMB results. Multivariable analysis was used to create CMRI diagnostic criteria for comparison with a positive EMB (Grade ≥ 2R or antibody-mediated rejection) and clinical rejection (change in medical therapy to treat rejection). Sixty participants (75% male; mean age, 51 ± 14 years) were recruited, providing 73 comparisons between CMRI and EMB for the diagnosis of rejection. Multivariable logistic regression identified myocardial edema (T2 relaxation time) and right ventricular end-diastolic volume index as independent predictors of a positive EMB. Combining threshold right ventricular end-diastolic volume index and edema values predicted a positive EMB with very good accuracy: sensitivity, 93%; specificity, 78%; positive predictive value, 52%; and negative predictive valve, 98%. CMRI was more sensitive than EMB at predicting clinical rejection (sensitivity of 67% vs 58%). CMRI has high sensitivity and high negative predictive value in predicting biopsy-positive heart transplant rejection and may be useful as a screening test before routine EMB. CMRI also has better sensitivity for clinically diagnosed heart transplant rejection and could be helpful in cases of negative rejection on the biopsy specimen.


The reciprocal ledge closing wedge osteotomy for post traumatic coxa vara.
To report a proximal femoral osteotomy with retention of bone ledges in a reciprocal position to increase bone contact and stability. The method was applied to 5 patients over a 3-year period. All patients had coxa vara. The average length gained was 1.5 cm, and the average neck shaft angle improvement was 30°. The Harris hip score improved from an average of 63 to 82. The reciprocal ledge osteotomy is technically less demanding and also allows conversion of normal shear forces around the upper femur to stabilizing forces. This method allows easier use of the DHS implant as potential rotation about the axis of the screw is negated by the ledges and the dynamic forces.


Analysis of visual attention and team communications during neonatal endotracheal intubations using eye-tracking: An observational study.
Eye-tracking can be used to analyse visual attention (VA) of health care providers during clinical tasks. No study has examined eye-tracking during neonatal endotracheal intubation. We aimed to examine VA and team communications during endotracheal intubation using eye-tracking in the Neonatal Intensive Care Unit. Twenty-seven video-recordings were obtained using eye-tracking glasses worn by intubators during endotracheal intubation of stable neonates. Videos were analysed to obtain i) intubation duration and success, ii) areas of interest (AOIs), iii) duration spent on each AOI, iv) types and frequency of gaze-shifts between AOIs, and v) monitor looking behaviour, and vi) team communications of vital signs and verbal medication orders. Twenty-four videos were of acceptable quality and analysed. Median attempt duration was 44.7 s. Success rate was 79%. Overall, 50% of VA was directed at the infant, with 23% of VA directed at equipment. There were 415 gaze-shifts types and 0.55 gaze-shifts/sec. Intubators glanced at the monitor spontaneously and rarely reported vital signs afterwards. Language used to communicate vital signs and medication orders varied. During neonatal intubations, 50% of VA was directed away from the infant. Team communications were non-standard. Eye-tracking can be used to analyse human performance during neonatal resuscitation.


Granulocyte colony-stimulating factor and an in vitro whole blood model of melioidosis.
The study reported here was conducted in order to explore the mechanism of action of granulocyte colony-stimulating factor (G-CSF) in the treatment of Burkholderia pseudomallei infections (otherwise known as melioidosis). Use of G-CSF as an adjunct to antibiotics has been associated with decreasing mortality among patients with melioidosis in the tropical region of the Northern Territory of Australia. However, using an in vitro whole blood assay, no significant difference was detected in the bactericidal activity of samples obtained from dialysis patients, patients with type 2 diabetes mellitus and healthy controls, and there was no improvement following coincubation with G-CSF.


Endogenous information, adverse selection, and prevention: Implications for genetic testing policy.
We examine public policy toward the use of genetic information by insurers. Individuals engage in unobservable primary prevention and have access to different prevention technologies. Thus, insurance markets are affected by moral hazard and adverse selection. Individuals can choose to take a genetic test to acquire information about their prevention technology. Information has positive decision-making value, that is, individuals may adjust their behavior based on the result of the test. However, testing also exposes individuals to uncertainty over the available insurance contract, so-called classification risk, which lowers the value of information. In our analysis we distinguish between four different policy regimes, determine the value of information under each regime and associated equilibrium outcomes on the insurance market. We show that the policy regimes can be Pareto ranked, with a duty to disclose being the preferred regime and an information ban the least preferred one.


Radiographic manifestations of experimental aluminum toxicity in growing bone.
To evaluate the effect of aluminum on growing bone in the presence of normal renal function, the following experiment was performed. Eight littermate pair-fed pigs (5 weeks old) were randomly assigned to one of two study groups: control C, n = 4, or aluminum treated Al, n = 4. Daily intravenous injections of either aluminum 1.5 mg/kg/day (Al group) or vehicle only (C group) were given during the 8-week duration of the study. The radiographic findings which appeared in the aluminum-treated group and not in the controls consisted of areas of sclerosis in the submetaphyseal regions and the periphery of epiphyses. In addition there was separation of the anterior tibial tubercle. The growth plates did not increase in width despite the presence of osteomalacia and histologic evidence of extensive deposition of aluminum in bone. The area of sclerosis visualized in the radiographs correlated histologically with thickened bony trabeculae. The increased width of these trabeculae is attributable to an increase in primary spongiosum and broadened seams of osteoid.


External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia.
Imatinib is considered the standard first-line treatment in newly diagnosed patients with chronic-phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations. Therefore, this study aimed to perform an external evaluation of available imatinib popPK models developed mainly in adult patients, and to evaluate the improvement in individual model-based predictions through Bayesian forecasting computed by each model at different treatment occasions. A literature review was conducted through PubMed and Scopus to identify popPK models. Therapeutic drug monitoring data collected in adult CML patients treated with imatinib was used for external evaluation, including prediction- and simulated-based diagnostics together with Bayesian forecasting analysis. Fourteen imatinib popPK studies were included for model-performance evaluation. A total of 99 imatinib samples were collected from 48 adult CML patients undergoing imatinib treatment with a minimum of one plasma concentration measured at steady-state between January 2016 and December 2020. The model proposed by Petain et al showed the best performance concerning prediction-based diagnostics in the studied population. Bayesian forecasting demonstrated a significant improvement in predictive performance at the second visit. Inter-occasion variability contributed to reducing bias and improving individual model-based predictions. Imatinib popPK studies developed in Caucasian subjects including α1-acid glycoprotein showed the best model performance in terms of overall bias and precision. Moreover, two imatinib samples from different visits appear sufficient to reach an adequate model-based individual prediction performance trough Bayesian forecasting.


Huge left atrial thrombus with mitral stenosis in congenital factor XII deficiency.
Factor XII deficiency has been reported to be a risk factor for thromboembolism as a result of inactivation of fibrinolysis. We describe a case of a huge left atrial thrombus with mitral stenosis, which was successfully removed surgically in a Factor XII deficient patient.


An evaluation of optimal sampling strategy and adaptive study design.
We have evaluated the utility of optimal sampling strategy coupled with adaptive study design in the determination of individual patient and population pharmacokinetic parameter values. In 9 patients with cystic fibrosis receiving a short (1 minute) infusion of ceftazidime pharmacokinetic parameter values were determined with a nonlinear least-squares estimator analyzing a traditional, geometrically spaced set of 12 postinfusion serum samples drawn over 8 hours. These values were compared with values generated from four sample subsets of the 12 obtained at optimal times and analyzed by nonlinear least-squares estimator, as well as a maximum a posteriori probability Bayesian estimator with prior distributions placed on beta and clearance. The four sampling times were determined according to an adaptive design optimization technique that employs sequential updating of population prior distributions on parameter values. Compared with the 12-point determination, the four optimal points analyzed with the maximum a posteriori probability Bayesian estimator faithfully reproduced both microscopic and hybrid pharmacokinetic parameter values for individual patients and, consequently, also produced accurate measures of population central tendency and dispersion. This has important implications in being able to more efficiently derive target patient population pharmacokinetic information for new drugs. This should also allow generation of better concentration-effect relationships in populations of interest.


Collaboration accelerates safety improvements.
Participating systems take a 'non-compete' pledge to ensure transparency. Those facilities with appropriate experience, expertise are selected to lead specific initiatives. Participants meet frequently in early stages of each program, then taper off in tactical phase.


Inhibitory effect of fucoidan on the adhesion of adenocarcinoma cells to fibronectin.
Fucoidans inhibit tumour cell adhesion to various substrata, but their mechanisms of action are not fully understood. Using 3H-fucoidan, we observed that fucoidan binds to fibronectin, this binding being saturable and sensitive to ionic strength and pH. The interaction occurred on at least four different sites along the polypeptide chain, two of them being the heparin-binding sequences. Moreover, when MDA-MB-231 tumour cells were exposed to DTAF-fucoidan, internalization occurred and punctuated vesicles were observed in the perinuclear region. The treated cells also showed a different morphology with a cytoskeleton devoid of vinculin and a reorganiztion of the repartition of the integrin-alpha5 subunit on the cell surface. Based on these data, we hypothesize that fucoidan inhibits the adhesion of MDA-MB-231 cells to fibronectin i) by blocking the protein's heparin- and cell-binding domains, ii) by modulating the reorganization of the integrin alpha5 subunit and iii) by down-regulating the expression of vinculin.


A role of template cleavage in reduced excision of chain-terminating nucleotides by human immunodeficiency virus type 1 reverse transcriptase containing the M184V mutation.
Resistance to nucleoside reverse transcriptase (RT) inhibitors is conferred on human immunodeficiency virus type 1 through thymidine analogue resistance mutations (TAMs) that increase the ability of RT to excise chain-terminating nucleotides after they have been incorporated. The RT mutation M184V is a potent suppressor of TAMs. In RT containing TAMs, the addition of M184V suppressed the excision of 3'-deoxy-3'-azidothymidine monophosphate (AZTMP) to a greater extent on an RNA template than on a DNA template with the same sequence. The catalytically inactive RNase H mutation E478Q abolished this difference. The reduction in excision activity was similar with either ATP or pyrophosphate as the acceptor substrate. Decreased excision of AZTMP was associated with increased cleavage of the RNA template at position -7 relative to the primer terminus, which led to increased primer-template dissociation. Whether M184V was present or not, RT did not initially bind at the -7 cleavage site. Cleavage at the initial site was followed by RT dissociation and rebinding at the -7 cleavage site, and the dissociation and rebinding were enhanced when the M184V mutation was present. In contrast to the effect of M184V, the K65R mutation suppressed the excision activity of RT to the same extent on either an RNA or a DNA template and did not alter the RNase H cleavage pattern. Based on these results, we propose that enhanced RNase H cleavage near the primer terminus plays a role in M184V suppression of AZT resistance, while K65R suppression occurs through a different mechanism.


Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Terpenoids and Steroidal compounds as Major Constituents in Cleome viscosa Leaves.
Bioassay guided study of Cleome viscosa Linn. (Cleomaceae) leaves led to the isolation of a new cembrenoid diterpene (1: ) and three known compounds (2: - 4: ) from the hexane extract. The chemical structures of these compounds were elucidated by spectroscopic methods such as NMR (1D and 2D), HRMS and IR and identified and afforded compound 1: , malabaric acid (2: ), stigmast-4-en-3-one (3: ) and stigmast-4-ene-3,6-dione (4: ). This is the first report of compounds 1: and 2: from C. viscosa Linn. Isolates were evaluated for anti-inflammatory activity using in vitro cyclooxygenase enzyme (COX-1 and -2) inhibitory assays. The novel cembrenoid diterpene (1: ) exhibited IC50 values of 8.4 µM for COX-1 enzyme and 45.2 µM for COX-2 enzyme, respectively. Similarly, malabaric acid (2: ) exhibited IC50 values of 11.5 µM for COX-1 enzyme and 46.9 µM for COX-2 enzyme, respectively. Their inhibitory activities were in par with non-steroidal anti-inflammatory drugs aspirin, ibuprofen and naproxen. Sterols 3: and 4: gave IC50 values of 62.6 and 67.9 µM, respectively for COX-1 enzyme while indicating weak COX-2 enzyme inhibition. Lipid peroxidation inhibitory (LPO) and MTT assays were used to determine antioxidant activity of these compounds. Compounds 1: - 4: showed LPO inhibition with IC50 values between 82 and 100 µM and moderate antioxidant activity in the MTT assay. Biological activities reported for these compounds are for the first time and it support anecdotal medicinal claims of C. viscosa Linn. leaves.


Development of MAP4 Kinase Inhibitors as Motor Neuron-Protecting Agents.
Disease-causing mutations in many neurodegenerative disorders lead to proteinopathies that trigger endoplasmic reticulum (ER) stress. However, few therapeutic options exist for patients with these diseases. Using an in vitro screening platform to identify compounds that protect human motor neurons from ER stress-mediated degeneration, we discovered that compounds targeting the mitogen-activated protein kinase kinase kinase kinase (MAP4K) family are neuroprotective. The kinase inhibitor URMC-099 (compound 1) stood out as a promising lead compound for further optimization. We coupled structure-based compound design with functional activity testing in neurons subjected to ER stress to develop a series of analogs with improved MAP4K inhibition and concomitant increases in potency and efficacy. Further structural modifications were performed to enhance the pharmacokinetic profiles of the compound 1 derivatives. Prostetin/12k emerged as an exceptionally potent, metabolically stable, and blood-brain barrier-penetrant compound that is well suited for future testing in animal models of neurodegeneration.


Matrix effects during phosphorus determination with quadrupole inductively coupled plasma mass spectrometry.
A quadrupole inductively coupled plasma mass spectrometer was evaluated for use in the detection of phosphorus. The influences of nitric acid and methanol (simulating the composition of a sample solution after nitric acid digestion) on phosphorus determination were studied using two different measuring methods at different plasma conditions: detection of phosphorus ions at m/z 31 and detection of phosphorus oxide ions at m/z 47. The existence of polyatomic interferences at m/z 31 and 47 was explored. Nitric acid and methanol are shown to be the sources of polyatomic ions and therefore cause poorer detection limits. Better detection limits were achieved in such matrices when phosphorus was detected as 31P+. The presence of methanol improves the system sensitivity towards phosphorus sevenfold; however, this positive effect is hindered by the high background signal due to carbon-based polyatomic ions. For samples with an organic matrix an appropriate mineralization procedure should be applied (high excess of nitric acid and high temperature) to quantitatively oxidize organic compounds to carbon dioxide, which is easily removed from the sample, in order to achieve correct results.


A comparison of the marginal fit of three cast ceramic crown systems.
The conclusions were: 1. The Cerestore crown system produced an impressive marginal fit without technique sensitivity. However, irregularities on the crown margin due to the porosities of the fired core were noted. 2. The Dicor castable ceramic crown system in this study produced rounded marginal openings because of the shrinkage during ceramming, the treatment of the surface texture after ceramming, and damage from air abrasives. 3. The Ceplatec crown system produced a suitable marginal fit when the distortion of the foil coping during porcelain firing was controlled. The quality of the margin was ultimately determined by the skill of the technician.


Cyclic AMP stimulation of Na-K pump activity in quiescent swiss 3T3 cells.
Recently, we have found that an increase in the intracellular level of cAMP acts as a mitogenic signal for Swiss 3T3 cells (Rozengurt et al., Proc. Natl. Acad, Sci. USA, 78:4392, 1981). The results presented in this paper demonstrate that addition of cAMP-elevating agents to confluent and quiescent cultures of Swiss 3T# causes a marked increase in the rate of 86Rb+ uptake but has no effect on the rate of cation efflux. The stimulation of ion uptake is mediated by the Na-K pump as shown by the ouabain sensitivity of the 86Rb+ fluxes. The increase in Na-K pump activity occurs whether cAMP is generated endogenously by stimulation of adenylate cyclase activity by cholera toxin, adenosine agonists, or PGE1 or added exogenously as 8BrcAMP. The stimulatory effect of these compounds on 86Rb+ uptake is potentiated by inhibitors of cyclic nucleotide phosphodiesterase activity. Cholera toxin stimulates the Na-K pump in a dose-dependent manner; half-maximal effect is achieved at 0.7 ng/ml. The stimulation of ouabain-sensitive 86Rb+ uptake by cAMP-elevating agents reaches a maximum after 2-3 h of incubation. This contrasts with the rapid (within minutes) stimulation of the Na-K pump caused by serum and other mitogenic agents. Further, cAMP-elevating agents fail to increase Na+ influx into 3T3 cells whereas serum causes a marked increase in Na+ influx, under identical experimental conditions. These findings suggest that the stimulation of Na-K pump activity caused by increased cAMP levels contrasts mechanistically with the rapid control of pump activity by serum which is primarily mediated by increased Na+ entry into the cells.


Co-delivery of doxorubicin and conferone by novel pH-responsive β-cyclodextrin grafted micelles triggers apoptosis of metastatic human breast cancer cells.
Adjuvant-aided combination chemotherapy is one of the most effective ways of cancer treatment by overcoming the multidrug resistance (MDR) and reducing the side-effects of anticancer drugs. In this study, Conferone (Conf) was used as an adjuvant in combination with Doxorubicin (Dox) for inducing apoptosis to MDA-MB-231 cells. Herein, the novel biodegradable amphiphilic β-cyclodextrin grafted poly maleate-co-PLGA was synthesized by thiol-ene addition and ring-opening process. Micelles obtained from the novel copolymer showed exceptional properties such as small size of around 34.5 nm, CMC of 0.1 μg/mL, and cell internalization of around 100% at 30 min. These novel engineered micelles were used for combination delivery of doxorubicin-conferone with high encapsulation efficiency of near 100% for both drugs. Our results show that combination delivery of Dox and Conf to MDA-MB-231 cells had synergistic effects (CI < 1). According to cell cycle and Annexin-V apoptosis analysis, Dox-Conf loaded micelle significantly induce tumor cell apoptosis (more than 98% of cells population showed apoptosis at IC50 = 0.259 μg/mL). RT-PCR and western-blot tests show that Dox-Conf loaded βCD-g-PMA-co-PLGA micelle induced apoptosis via intrinsic pathway. Therefore, the unique design of multi-functional pH-sensitive micelles open a new perspective for the development of nanomedicine for combination chemo-adjuvant therapy against malignant cancer.


[Spontaneous uterine rupture after myomectomy. Case report and review of the literature].
Uterine rupture after myomectomy is rare but serious. It can occur before onset of labor and compromise vital maternofoetal outcome. We report the case of a uterine rupture at 25-week gestation in a 38-year-old primiparous woman after myomectomy and we will present a review of the literature concerning obstetric outcome after myomectomy.


Kinetics of microbial degradation of vascular plant material in two wetland ecosystems.
Vascular plant decomposition was followed during two different years in one freshwater and one marine wetland in southeastern Georgia, USA, using a modified litterbag technique. Chemical analysis of plant material revealed different rates of decomposition for different components of the plant material (soluble components, α-cellulose, hemicellulose, and lignin) and, further, that rates of decomposition of each component changed over time, such that the specific rate of decay for each fraction decreased as decomposition proceeded. Three mathematical models which differen in their treatment of the biochemical heterogeneity of vascular plant detritus were investigated with regard to their relative abilities to describe decomposition kinetics from the field incubations as well as from laboratory microcosm studies with radiolabeled plant material. A decaying coefficient model, which treats plant detritus as a single component but allows for a decreasing specific decomposition rate as material ages, was most successful in describing kinetics of decomposition. This model accomodates the changes in quality of vascular plant detritus resulting from preferential decomposition of more labile components (e.g., non-lignocellulosic material and holocellulose) and the relative accumulation of more refractory components (e.g., lignin) observed with time. The model also accomodates the potential transformation of various plant components into more refractory compounds (humification) during the decomposition process.


Phosphorylation and functional properties of the IIA domain of the lactose transport protein of Streptococcus thermophilus.
The lactose-H+ symport protein (LacS) of Streptococcus thermophilus has a carboxyl-terminal regulatory domain (IIALacS) that is homologous to a family of proteins and protein domains of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) in various organisms, of which IIAGlc of Escherichia coli is the best-characterized member. On the basis of these similarities, it was anticipated that IIALacS would be able to perform one or more functions associated with IIAGlc, i.e., carry out phosphoryl transfer and/or affect other catabolic functions. The gene fragment encoding IIALacS was overexpressed in Escherichia coli, and the protein was purified in two steps by metal affinity and anion-exchange chromatography. IIALacS was unable to restore glucose uptake in a IIAGlc-deficient strain, which is consistent with a very low rate of phosphorylation of IIALacS by phosphorylated HPr (HPr approximately P) from E. coli. With HPr approximately P from S. thermophilus, the rate was more than 10-fold higher, but the rate constants for the phosphorylation of IIALacS (k1 = 4.3 x 10(2) M-1 s-1) and dephosphorylation of IIALacS approximately P by HPr (k-1 = 1.1 x 10(3) M-1 s-1) are still at least 4 orders of magnitude lower than for the phosphoryltransfer between IIAGlc and HPr from E. coli. This finding suggests that IIALacS has evolved into a protein domain whose main function is not to transfer phosphoryl groups rapidly. On the basis of sequence alignment of IIA proteins with and without putative phosphoryl transfer functions and the known structure of IIAGlc, we constructed a double mutant [IIALacS(I548E/G556D)] that was predicted to have increased phosphoryl transfer activity. Indeed, the phosphorylation rate of IIALacS(I548E/G556D) by HPr approximately P increased (k1 = 4.0 x 10(3) M-1 s-1) and became nearly independent of the source of HPr approximately P (S. thermophilus, Bacillus subtilis, or E. coli). The increased phosphoryl transfer rate of IIALacS(I548E/G556D) was insufficient to complement IIAGlc in PTS-mediated glucose transport in E. coli. Both IIALacS and IIALacS(I548E/G556D) could replace IIAGlc, but in another function: they inhibited glycerol kinase (inducer exclusion) when present in the unphosphorylated form.


Foreign body reaction to polymethylsiloxane gel (Bioplastique) after vocal fold augmentation.
The consequences of vocal fold paralysis include voice change, airway problems and difficulty swallowing. Medialisation procedures using injected material have been used for many decades, with varying outcomes, mainly secondary to lifespan, tissue reaction or migration. Newer materials have recently become clinically available which are easier to manage and supposedly less likely to elicit foreign body reaction. Case report. We report a case of foreign body reaction and possible migration of polymethylsiloxane gel (Bioplastique), one such material, after vocal fold injection. To our knowledge, this is the second such case described. This case highlights the fact that the risk of foreign body reaction and migration is still present for this material, albeit low. We also highlight the fact that, although this material can cause foreign body reactions and may possibly migrate, it is removable by microlaryngoscopy via the microflap technique, with vocal improvement.


Cannulas for facial filler placement.
With more physicians performing injections to the face in increasingly sophisticated ways, techniques must evolve accordingly. Injectables are no longer mere wrinkle fillers but true panfacial volumizers that are placed in many different planes and tissues of the face, in contrast to fillers of the past used for the dermis. This development is providing better results previously not achievable with off-the-shelf fillers. Microcannulas represent a step forward in enhancing surgeons' ability to fill the face with less discomfort, edema, and ecchymosis, with faster recovery. Microcannulas will probably play a role in volume replacement for many years to come.


Trends in mortality from coronary heart disease and stroke among U.S. veterans; 1954-1979.
A cohort of nearly 300,000 insured veterans (Dorn Cohort), experienced a much greater percent decline in CHD death rate over the period, 1954-1979, than the population of the U.S., while for stroke, the percent decline in death rate was virtually the same as the U.S. For CHD, greater percent declines were noted over the study period for non-smokers compared to cigarette smokers, for professionals compared to non-professionals and for persons with high socioeconomic scores (SES) compared to those with low scores. In each group, younger persons experienced greater percent declines than older persons. For stroke, non-smokers experienced a somewhat greater percent decline in rate than smokers but this did not hold true for all age groups. Unlike CHD, professionals experienced a smaller percent decline in their stroke death rate than non-professionals, as did persons with high SES compared to those with low SES. The contradictory patterns observed for the two diseases with respect to occupation and SES suggest that the risk factors for stroke and coronary heart disease are not exactly the same. Throughout, the findings were much more convincing for CHD than for stroke.


The enhanced modulation of key bone matrix components by modified Titanium implant surfaces.
Modifications to Titanium (Ti) implant surfaces enhance osseointegration by promoting bone-implant contact and peri-implant bone accrual; which in vitro analyses of osteoblastic cells suggest is due to an enhancement in cellular phenotypic maturation and function. To evaluate these effects on uncommitted cells, this study examined the osteogenic mineralisation and phenotypic marker expression of human marrow derived stromal cells (hBMSCs) from three unrelated donors cultured on tissue culture plastic (TCP), polished (P), rough-hydrophobic (SLA) and rough-hydrophilic (modSLA) Ti surfaces over the course of 21 days. Transcriptional analyses indicated a significant early up-regulation of both Runx2 (p<0.05) and Osteopontin (OP) (p<0.05) but not Bone Sialoprotein 2 (BSP2) (p<0.05) by rough surfaces 1 day post seeding. The phenotypic analyses showed that whilst cellular proliferation was relatively restricted and slower on the rough substrates; osteogenic mineralisation, assessed by quantifying extracellular matrix calcium deposition, collagen formation and the ratio of collagen to mineral deposited were significantly higher (p<0.05); as was alkaline phosphatase (ALP) activity (p<0.05). The rough surfaces caused an increase of secreted osteoblastic markers Osteoprotegrin (OPG) (p<0.05), growth differentiation factor 15 (GDF-15) (p<0.05) and Osteocalcin (OC) (p<0.05). These findings suggest that modified Ti surfaces induce an enhancement in osteogenic commitment and differentiation, which likely underlie the deposition of more stable bone matrix early in the healing process in vivo.


Dermatitis herpetiformis and hemodialysis.
A case of dermatitis herpetiformis in a 60-year-old woman with polycystic kidney disease on hemodialysis is reported. Bullous dermatoses associated with hemodialysis are analyzed.


Second-order features extraction in the cat visual cortex: selective and invariant sensitivity of neurons to the shape and orientation of crosses and corners.
About 1/3 of neurons (52/174) studied in the cat striate cortex (area 17 or V1) gave a larger (by 3.2 times on average) response to a flashed cross or corner centered in the receptive field (RF) than to a single bar of optimal orientation. Most such neurons (71.4%) were found to be highly selective both to shape (angle between the lines) and to orientation of these figures. In the studied neuronal selection we also found all possible types of invariance of sensitivity to orientation and/or shape of these figures. We found neurons with selectivity to form of the figure and invariance to its orientation and vice versa. Some cells were found invariant both to form and orientation of the cross or corner but highly sensitive to flashing of any such figure in the RF. The role of RF center and surrounding area in sensitivity to cross figures was also studied in 44 additional units. Separated and combined stimulation of these zones revealed in different units summation, antagonism and absence of interaction of these zones by the selectivity index (figure/bar response ratio). Possible mechanisms of the described effects are discussed as well as their functional implication for second-order feature extraction in the visual cortex: selective or invariant sensitivity of neurons to the shape and orientation of the line-crossings.


Modulation of coffee aroma via the fermentation of green coffee beans with Rhizopus oligosporus: II. Effects of different roast levels.
This study aims to evaluate how changes of the volatile and non-volatile profiles of green coffees induced by Rhizopus oligosporus fermentation of green coffee beans (Part I) translated to changes in the volatile and aroma profiles of light, medium and dark roasted coffees and non-volatile profile of roasted coffee where fermentation effects were most distinctive (light roast). R. oligosporus fermentation resulted in 1.7-, 1.5- and 1.3-fold increases in pyrazine, 2-methylpyrazine and 2-ethylpyrazine levels in coffees of all roast degrees, respectively. This corresponded with the greater extent of amino acids degradation in light roasted fermented coffee. Ethyl palmitate was detected exclusively in medium and dark roasted fermented coffees. The sweet attribute of light and dark roasted coffees were increased following fermentation along with other aroma profile changes that were roast degree specific. This work aims to develop a direct but novel methodology for coffee aroma modulation through green coffee beans fermentation.


Splenectomy associated with increased risk of herpes zoster in a population-based cohort study.
No systematic research focuses on the association between splenectomy and herpes zoster. This study aimed to investigate the association between splenectomy and herpes zoster in Taiwan. A population-based cohort study was conducted using the database of Taiwan National Health Insurance Program. There were 640 individuals aged 20-84 years who were newly diagnosed with splenectomy in 2000-2012 as the splenectomy group and 2546 sex-matched and age-matched individuals without splenectomy as the nonsplenectomy group. The incidence of herpes zoster at the end of 2013 was estimated. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for herpes zoster associated with splenectomy. The overall incidence of herpes zoster was 1.41-fold higher in the splenectomy group than in the nonsplenectomy group (11.3 vs. 8.05 per 1000 person-years, 95% CI 1.11-1.78). After multivariable adjustments, the adjusted hazard ratio of herpes zoster was 1.57 for individuals with splenectomy (95% CI 1.08-2.29), compared with individuals without splenectomy. Individuals with splenectomy are associated with 1.57-fold increased risk for developing herpes zoster in Taiwan. Vaccination against herpes zoster may be considered among these high-risk individuals.


The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial.
Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0-0.3-1.5 g/day) in 177 healthy individuals (18-65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (-20%) and duration (-25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.


Studies on the crystallization of magnesium ammonium phosphate in urine.
The crystallization of magnesium ammonium phosphate (MAP) was studied in salt solutions and dialysed urine at similar levels of MAP supersaturation. At pH levels of 7.1 or higher crystallization occurred to the same extent in solutions with and without urinary macromolecules. Whereas crystals in the size range 3.5-5 microns were observed in the salt solution at pH 7.0, this was not so in dialysed urine. When the crystal size distribution was determined after 30 min larger crystals were observed in dialysed urine, indicating a promoting effect by urinary macromolecules on the formation of MAP crystals. A modified AP(MAP) index was formulated based on calculations with the EQUIL 2 programme in order to improve the relationship between this simplified estimate and the ion-activity product of MAP (APMAP). This index had the following form: [formula: see text] for 24-h values of magnesium (Mg), ammonium (NH4), phosphate (P), pH and urine volume (V). The APMAP required for the formation of 2,000 crystals in the size range 3.5-5 microns varied between 226 x 10(-15) and 293 x 10(-15) (mmol/l)2 in dialysed urine. An experimental system was designed based on the measurement of pH during the addition of NH4OH. At the point assumed to correspond to the start of crystallization, AP(MAP) index values between 409 and 903 were recorded. Such a test might provide useful information on the crystallization properties in urine.


Systematic review and meta-analysis of time-temperature pathogen inactivation.
Heat treatment, or thermal disinfection, is one of the simplest disinfection methods, and is widely used in the water, sanitation, and food sectors, especially in low resource settings. Pathogen reductions achieved during heat treatment are influenced by a combination of temperature and exposure time. The objective of this paper was to construct updated time-temperature pathogen inactivation curves to define "safety zones" for the reduction of four pathogen groups (bacteria, viruses, protozoan (oo)cysts, and helminth eggs) during heat treatment in a variety of matrices. A systematic review and meta-analysis were conducted to determine the times needed to achieve specified levels of pathogen reduction at different temperatures. Web of Science was searched using a Boolean string to target studies of heat treatment and pasteurization systems that exposed pathogens in water, wastewater, biosolids, soil, or food matrices to temperatures between 20 °C and 95 °C. Data were extracted from tables or figures and regression was used to assess the relationship between time and temperature. Our findings indicate that the temperatures and times needed to achieve a 1-log10 reduction of all pathogen groups are likely higher and longer, respectively, than previously reported. The type of microorganism and the matrix significantly impact T90 values reported at different temperatures. At high temperatures, the time-temperature curves are controlled by thermally stable viruses such as hepatitis A virus. Data gaps include the lack of data on protozoa, and the lack of data on all pathogen groups at low temperatures, for long exposure times, and with high log10 reductions. The findings from this study can be used by engineers, food safety specialists for the planning and design of engineered water, sanitation, and food pasteurization and treatment systems.


Titrating the Cost of Plant Toxins Against Predators: a Case Study with Common Duikers, Sylvicapra grimmia.
Foragers face many variables that influence their food intake. These may include habitat structure, time, climate, resource characteristic, food quality, and plant defenses. I conducted foraging experiments using common duikers that involved: 1) testing the effect of plant toxins on foraging, and 2) titrating toxin intake against safety. I used giving up densities (GUDs, food remaining after foraging) to test for selection among trays containing alfalfa pellets treated with water, with 10% oxalic acid, or 10% quebracho tannin. Pairs of trays were placed within islands of woody vegetation and out in open grass. I also conducted a titration experiment by offering the duikers a choice between a patch with water-treated pellets placed at a risky site, or a patch with one of three oxalic acid-treated pellets at a safe site. This made it possible to determine the concentration of oxalic acid at which the cost of toxin in the safe site equals the predation cost at the risky site. The common duikers showed no selectivity among the three treatments at 10% concentration, however, GUDs in the open grass (i.e., safe) were significantly lower than in the wooded islands (i.e., risky). As the oxalic acid concentration increased at the safe sites, the duiker's food intake from the risky sites increased significantly. The results demonstrate that foraging hazards may come in different forms such as predation and plant toxins, and their interactions may alter habitat use, foraging patterns, and perceptions of risk. These variables occur under natural situations, altering the overall habitat quality.


A new secured technique for intrahepatic cholangiojejunostomy and drainage of bile.
We designed a technique for decompression of proximal biliary tract obstruction which makes an inverted anastomosis of the intestine to the intrahepatic bile duct feasible. This approach can also be used to prepare a pancreaticointestinal anastomosis.


SERS of cylindrospermopsin cyanotoxin: Prospects for quantitative analysis in solution and in fish tissue.
Cylindrospermopsin (CYN), a cyanotoxin occurring in environmental waters as a cyanobacteria metabolite, has recently raised increased interest both in the scientific community and the environmental, food control and health care bodies due to the incidence of poisoning reports and the lack of prompt, effective detection and monitoring techniques. Here we report comprehensive Raman and SERS spectroscopy data on CYN cyanotoxin and provide a detailed characterization of the vibrational Raman signal based on DFT calculation as well as the adsorption properties with respect to the silver nanoparticles surface. Quantitative SERS analysis was achieved for concentrations range from 0.218 nM to 2.18 µM in aqueous solution. We further investigated the SERS discrimination of artificially intoxicated fish tissue from normal one, using linear discriminant analysis. Significant changes in SERS signal of toxic tissue compared to normal one allowed clear and fast differentiation of toxic tissue with 100% specificity/sensitivity. The cross-validation procedure provided 100% clear separation based on the SERS data. The results open reliable perspectives for SERS monitoring the environmental water bodies.


The Sweet Side of HIPK2.
HIPK2 is an evolutionary conserved protein kinase which modulates many molecular pathways involved in cellular functions such as apoptosis, DNA damage response, protein stability, and protein transcription. HIPK2 plays a key role in the cancer cell response to cytotoxic drugs as its deregulation impairs drug-induced cancer cell death. HIPK2 has also been involved in regulating fibrosis, angiogenesis, and neurological diseases. Recently, hyperglycemia was found to positively and/or negatively regulate HIPK2 activity, affecting not only cancer cell response to chemotherapy but also the progression of some diabetes complications. The present review will discuss how HIPK2 may be influenced by the high glucose (HG) metabolic condition and the consequences of such regulation in medical conditions.


Combustion studies of high moisture content waste in a fluidised bed.
The combustion of three high moisture content waste materials in a fluidised bed combustor has been investigated and a comparison with co-firing of these materials with coal in the same combustor has been made. Waste materials burnt were olive oil waste, municipal solid waste and potato, which is representative of vegetable waste. Mixtures of up to 20% mass concentration water in the waste were fed to the combustor. Above that value the moisture content was too high to sustain combustion without addition of coal. Measurements of CO, NOx, SO2 temperatures were made and the carbon combustion efficiency evaluated. Co-firing with coal resulted in markedly higher combustion efficiencies with an increase of approximately 10-80% when burning the simulated MSW. However, this was much lower than the value of 93% when coal was burnt on its own. It was also much lower than the value obtained, average 90%, when co-firing potato and olive oil waste with coal and there was little difference in the combustion efficiency between the two types of waste and with increasing moisture content. It was concluded that the high ash content of the simulated MSW 26%, compared with 5% in the other two waste materials resulted in slower burning and consequently the char particles were elutriated from the bed without being fully burnt. In term of gaseous emissions during co-combustion, CO emission is relatively insensitive to change in waste fraction. While emission of SO2 can be reduced as the waste fraction increases as a result of fuel-S dilution. But in terms of percent fuel-S converted, it is actually increased by increasing waste fraction. Emissions of NO and N2O increase slightly with MSW fraction.


Effective outpatient use of polyethylene glycol-electrolyte bowel preparation for radical cystectomy and ileal conduit urinary diversion.
In this prospective study we examined the oral electrolyte-overload method of bowel preparation for patients who were to undergo radical cystectomy and ileal conduit urinary diversion. We found it to be a safe and effective mechanical bowel preparation that can be used by outpatients. It was well tolerated and resulted in adequate bowel cleansing and a low incidence of postoperative wound infections and pyelonephritis. A major advantage of this method is that it reduced the period of preoperative hospitalization.


The Q10 questionnaire for detection of wearing-off phenomena in Parkinson's disease.
In Parkinson's disease (PD), wearing-off can be difficult to detect as it is very variable and may affect motor and non-motor symptoms. The Wearing-Off Questionnaire, WOQ-32 (Stacy et al., 2005), was introduced to help identify wearing-off and proved to be very efficient. Two short versions of the questionnaire (WOQ-19 or QUICK and WOQ-9) were later developed to decrease the respondent burden without loss of efficacy in terms of sensitivity. The objective of the present study was to check the ability of a new 10-item QUICK version, Q10, to identify patients with wearing-off. Q10 items were selected from the QUICK validation study data set through statistical analysis and it was then tested on a sample of 162 PD patients, 64.8% with wearing-off. Sensitivity, specificity, and accuracy were 96%, 63%, and 85% respectively with one positive response and 90%, 70%, and 83% respectively with two positive responses. The correlation with the gold standard (neurologist diagnosis of wearing-off) was substantial (kappa = 0.62-0.64). Comparison with the QUICK and WOQ-9 shows that the Q10 can be a new tool for detection of wearing-off with satisfactory properties and a good balance between brevity and performance.


Effect of partial vs complete circumferential epitendinous suture placement on the biomechanical properties and gap formation of canine cadaveric tendons.
To determine the effect of partial vs complete circumferential epitendinous suture (ES) placement in addition to a core suture on the biomechanical strength and gapping characteristics of repaired canine tendinous constructs. Ex vivo, biomechanical study. Thirty-six canine superficial digital flexor tendons. Superficial digital flexor tendons were randomly assigned to three groups (n = 12), sharply transected and repaired with a core locking-loop suture with Group 1 a partial circumferential ES, 180° on the palmar side; Group 2 a complete circumferential ES, 360° and double knotting technique; or Group 3 a complete circumferential ES, 360° and single knotting technique. After preloading, constructs were distracted to monotonic failure. Failure mode, gap formation, yield, peak, and failure forces were analyzed. Mean yield (group 1 = 68.6 N, group 2 = 106.5 N, group 3 = 114 N, P < .013), peak (group 1 = 92.8 N, group 2 = 134.6 N, group 3 = 147.3 N; P < .001), and failure (group 1 = 88.7 N, group 2 = 133.0 N, group 3 = 145.5 N, P < .001) loads differed between groups. No difference in yield (P = .874), peak (P = .434), or failure load (P = .434) was detected between complete circumferential ES groups. Force to create 1-mm (P < .001) and 3-mm (P < .038) gap formation was greater in specimens with complete vs partial circumferential ES placement. Complete circumferential ES repairs failed primarily by suture pull-through compared with suture breakage in most partial circumferential ES constructs. Addition of a complete circumferential ES with a single or double knotting technique increased the biomechanical strength of normal tendon repairs while reducing gap formation compared with partial ES placement alone. Complete circumferential ES is recommended over partial ES placement.


Restoring gingival harmony around single tooth implants.
One of the biggest challenges to restoring a single tooth implant in the esthetic zone of the mouth is the creation of harmonious gingival contour around the restoration. Soft- or hard-tissue deficiencies of the edentulous space are the most common obstacles to achieving gingival symmetry around the proposed restoration. Numerous gingival and osseous grafting and regeneration techniques are available but may complicate treatment by increasing the number of surgical procedures and sites necessary. This article describes a technique for treating mild-to-moderate ridge defects without the required additional surgical procedures or a surgical donor site. Soft-tissue overcontouring is provided around the healing abutment by modification of the surgical flap at second-stage implant surgery. Subsequent gingivoplasty allows establishment of anatomic gingival architecture that surrounds the single implant prosthesis.


Fully automatic and robust 3D registration of serial-section microscopic images.
Robust and fully automatic 3D registration of serial-section microscopic images is critical for detailed anatomical reconstruction of large biological specimens, such as reconstructions of dense neuronal tissues or 3D histology reconstruction to gain new structural insights. However, robust and fully automatic 3D image registration for biological data is difficult due to complex deformations, unbalanced staining and variations on data appearance. This study presents a fully automatic and robust 3D registration technique for microscopic image reconstruction, and we demonstrate our method on two ssTEM datasets of drosophila brain neural tissues, serial confocal laser scanning microscopic images of a drosophila brain, serial histopathological images of renal cortical tissues and a synthetic test case. The results show that the presented fully automatic method is promising to reassemble continuous volumes and minimize artificial deformations for all data and outperforms four state-of-the-art 3D registration techniques to consistently produce solid 3D reconstructed anatomies with less discontinuities and deformations.


Buprenorphine differentially alters breathing among four congenic mouse lines as a function of dose, sex, and leptin status.
The opioid buprenorphine alters breathing and the cytokine leptin stimulates breathing. Obesity increases the risk for respiratory disorders and can lead to leptin resistance. This study tested the hypothesis that buprenorphine causes dose-dependent changes in breathing that vary as a function of obesity, leptin status, and sex. Breathing measures were acquired from four congenic mouse lines: female and male wild type C57BL/6J (B6) mice, obese db/db and ob/ob mice with leptin dysfunction, and male B6 mice with diet-induced obesity. Mice were injected intraperitoneally with saline (control) and five doses of buprenorphine (0.1, 0.3, 1.0, 3.0, 10 mg/kg). Buprenorphine caused dose-dependent decreases in respiratory frequency while increasing tidal volume, minute ventilation, and respiratory duty cycle. The effects of buprenorphine varied significantly with leptin status and sex. Buprenorphine decreased minute ventilation variability in all mice. The present findings highlight leptin status as an important modulator of respiration and encourage future studies aiming to elucidate the mechanisms through which leptin status alters breathing.


More friends on SNS, more materialism? The moderating roles of self-esteem and social comparison orientation.
On social networking sites, users are continuously exposed to a variety of posts from the networked individuals. Such information may often influence recipients' perceptions of what is important and goal pursuits such as materialism. Even though several studies have examined the negative consequences of using social networking sites, less attention has been paid to the role of friends' number and its impact on people's life goal pursuits. This study aimed to investigate the dark side of online friends and explored why and when more friends in social networking sites would promote materialism. Based on a sample of 264 WeChat users, study 1 discovered that friends' number positively impacted materialism through extrinsic goal (i.e., wealth and status). Additionally, such association was moderated by social comparison orientation and self-esteem. Importantly, self-esteem buffers the detrimental effect of friends' number on materialism while social comparison orientation increases it. Study 2 further tested the causal relationship and showed that friends' number on SNS might become a signal to indicate materialism via an experiment. In conclusion, our findings add to the understanding of psychological processes regarding the dark side of online friends' number and render suggestions for developing positive personal value.


A nationwide questionnaire survey on accidental magnet ingestion in children in Japan.
The aim is to investigate the actual situation of accidental ingestion of magnets in children in Japan and the clinical features of the resulting gastrointestinal damage. We developed a questionnaire and sent it to 496 board-certified training hospitals nationwide. Information was collected on the number of children with accidental magnet intake from 2015 to 2017, witnesses of magnet intake, number and type of magnets, presence or absence of gastrointestinal injury, treatment, etc RESULTS: The number of cases of accidental ingestion of magnets within the study period was 104, with a median age of 2 years. About half of the incidents were unwitnessed. There were 33 cases of accidental ingestion of multiple magnets. Among them, oesophagogastroduodenoscopy was performed in 4 children and surgery in 10, and significantly invasive treatment was required in comparison with single-magnet ingestion. Gastrointestinal injury was observed in 11 cases, 10 of which were caused by multiple-magnet ingestion. All 10 of these patients underwent surgical treatment. There was no mortality. The incidence of accidental magnet ingestion in Japan is estimated to be 50-70 per year. Unwitnessed cases are not uncommon. Multiple magnet ingestion often causes gastrointestinal injury. Many cases of gastrointestinal injury are caused by ingestion of magnetic toys.


Assessment of the extent of oxidative stress induced by intravenous ferumoxytol, ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model.
Intravenous (i.v.) iron is associated with a risk of oxidative stress. The effects of ferumoxytol, a recently approved i.v. iron preparation, were compared with those of ferric carboxymaltose, low molecular weight iron dextran and iron sucrose in the liver, kidneys and heart of normal rats. In contrast to iron sucrose and ferric carboxymaltose, low molecular weight iron dextran and ferumoxytol caused renal and hepatic damage as demonstrated by proteinuria and increased liver enzyme levels. Higher levels of oxidative stress in these tissues were also indicated, by significantly higher levels of malondialdehyde, significantly increased antioxidant enzyme activities, and a significant reduction in the reduced to oxidized glutathione ratio. Inflammatory markers were also significantly higher with ferumoxytol and low molecular weight iron dextran rats than iron sucrose and ferric carboxymaltose. Polarographic analysis suggested that ferumoxytol contains a component with a more positive reduction potential, which may facilitate iron-catalyzed formation of reactive oxygen species and thus be responsible for the observed effects. Only low molecular weight iron dextran induced oxidative stress and inflammation in the heart.