First-principles study of ammonium ions and their hydration in montmorillonites.
Density functional theory calculations were performed to investigate the adsorption and hydration of an ammonium ion (NH4(+)) confined in the interlayer space of montmorillonites (MMT). NH4(+) is trapped in the six-oxygen-ring on the internal surface and forms a strong binding with the surface O atoms. The hydration of NH4(+) is affected significantly by the surface. Water molecules prefer the surface sites, and do not bind with the NH4(+) unless enough water molecules are supplied. Moreover, the water molecules involved in NH4(+) hydration tend to bind with the surface simultaneously. The hydration energy increases with the intercalated water molecules, in contrast to that in gas phase. In addition, the hydration leads to the extension of MMT basal spacing.


Rectification nonlinearity in cortical end-stopped perceptive fields.
End-stopped perceptive fields associated with line targets were demonstrated previously with length and width Westheimer functions. In this study we investigated rectifying non-linearity in these perceptive fields to examine whether they directly reflect the organization of cortical receptive fields. Specifically, we reversed the polarity of parts of the background field associated with a specific perceptive field sub-region and examined threshold changes in corresponding length or width Westheimer functions. Results showed full-wave rectification in end-stopping and half-wave rectification in center summation and flank-inhibition preceding linear summation in end-stopped perceptive fields. Half-wave rectification in center summation and surround-inhibition preceding linear summation was also found in circular perceptive fields associated with spot targets. These results are inconsistent with direct links between perceptive fields and cortical receptive fields. Rather they suggest that these perceptive fields are likely the second-order fields formed by pooled non-linearly rectified outputs from cortical receptive fields.


Rejection of chlorinated, brominated, and iodinated trihalomethanes by multi-stage reverse osmosis: Efficiency and mechanisms.
Reverse osmosis (RO), a promising technology for removing inorganic salts and a wide range of trace organic pollutants, is widely used in water treatment industry. In this study, the rejection of chlorinated, brominated, and iodinated trihalomethanes (THMs) by a multi-stage RO system was investigated. The results showed that the multi-stage RO system is effective in rejecting THMs, and THMs with large size, high hydrophobicity and low polarity were highly rejected. In the first stage, high percentage of THMs was adsorbed on RO membrane, and the THM rejection was dominated by both hydrophobic adsorption and size exclusion. The contribution of hydrophobic adsorption to THM rejection decreased significantly along RO stages due to decreased feed concentration, but the enhancement of size exclusion still ensured high rejection efficiencies for most THMs, indicating a compensation effect between two rejection mechanisms. Finally, to further understand the rejection in the multi-RO system from a perspective of THM property, multiple linear regression models were built. The impact of n-octanol-water partition coefficient (Log Kow) was slightly higher than that of stokes radius in the first stage, which was consistent with the rejection mechanism. But dipole moment played an increasingly important role in the second and third stage, weakening the impact of Log Kow on THM rejection.


Improving Risk Adjustment for Mortality After Pediatric Cardiac Surgery: The UK PRAiS2 Model.
Partial Risk Adjustment in Surgery (PRAiS), a risk model for 30-day mortality after children's heart surgery, has been used by the UK National Congenital Heart Disease Audit to report expected risk-adjusted survival since 2013. This study aimed to improve the model by incorporating additional comorbidity and diagnostic information. The model development dataset was all procedures performed between 2009 and 2014 in all UK and Ireland congenital cardiac centers. The outcome measure was death within each 30-day surgical episode. Model development followed an iterative process of clinical discussion and development and assessment of models using logistic regression under 25 × 5 cross-validation. Performance was measured using Akaike information criterion, the area under the receiver-operating characteristic curve (AUC), and calibration. The final model was assessed in an external 2014 to 2015 validation dataset. The development dataset comprised 21,838 30-day surgical episodes, with 539 deaths (mortality, 2.5%). The validation dataset comprised 4,207 episodes, with 97 deaths (mortality, 2.3%). The updated risk model included 15 procedural, 11 diagnostic, and 4 comorbidity groupings, and nonlinear functions of age and weight. Performance under cross-validation was: median AUC of 0.83 (range, 0.82 to 0.83), median calibration slope and intercept of 0.92 (range, 0.64 to 1.25) and -0.23 (range, -1.08 to 0.85) respectively. In the validation dataset, the AUC was 0.86 (95% confidence interval [CI], 0.82 to 0.89), and the calibration slope and intercept were 1.01 (95% CI, 0.83 to 1.18) and 0.11 (95% CI, -0.45 to 0.67), respectively, showing excellent performance. A more sophisticated PRAiS2 risk model for UK use was developed with additional comorbidity and diagnostic information, alongside age and weight as nonlinear variables.


Ecological differences among clones of Daphnia pulex Leydig.
Natural populations of Daphnia pulex that reproduce by obligate parthenogenesis include a number of clones. Studies on two common and two rare clones from southwestern Ontario revealed significant differences in their intrinsic rates of increase, competitive abilities, rates of ephippial egg production, and lifespans. Environmental factors such as temperature and food type had large inluences on the rate of increase of each clone. Differences in rates of increase among clones were most pronounced at temperatures higher than those encountered in nature. In general, the covariance of life history traits among clones was high. The outcome of competitive encounters between clones was deterministic and in most cases was unaffected by temperature. Clones with high rates of increase tended to be better competitors than those with low rates of increase.


Distribution of 35S-sulfate within the transseptal ligament of the mouse.
The distribution of 35S-sulfate-labeled macromolecules was examined within three regions of the transseptal ligament: the 1) mesial, 2) middle and 3) distal thirds. Swiss mice, 6 weeks of age, were injected with 35S-sulfate and killed after 1, 6, and 12 hours and 1, 2, 3, 4, 5, and 7 days. Silver grains and cell nuclei were counted on autoradiographs which had been counterstained by the Van Gieson method, and mean counts were analyzed statistically. Analysis of variance revealed no significant differences in mean number of cell nuclei between regions throughout the course of the experiment. 35S-sulfate was rapidly incorporated into the transseptal ligament macromolecules. Grain counts were highest 6 hours after injections: counts were highest over the middle and lowest over the mesial thirds of the ligament. The rate of grain removal was significantly higher in the middle third compared to the mesial or distal thirds (P less than 0.001) and was significantly lower in the mesial third compared to the middle or distal thirds (P less than 0.001). The half-life of labeled macromolecules was significantly greater in the mesial and distal thirds than in the middle third (P less than 0.005). The data demonstrate significantly higher rates of turnover of 35S-sulfate-labeled macromolecules in the middle region of the transseptal ligament. Since cellular density was similar throughout the transseptal ligament, higher turnover rates of 35S-sulfate-labeled macromolecules probably indicate higher rates of cellular activity in this region, possibly a result of tissue remodeling coincident to stresses generated by occlusal forces and physiologic drift of the adjacent teeth.


Lymphocyte differentiation and allograft reactivity. Experimental studies on the origin of thymic lymphocytes.
The generalization that the developing vertebrate thymus is colonized by circulating stem cells that originate in the yolk sac blood islands is questionable. The view that the yolk sac is the primary source of thymic lymphocytes is based largely on inferences drawn from experimental protocols that are highly artificial.


Plasma High-Resolution Metabolomics Differentiates Adults with Normal Weight Obesity from Lean Individuals.
This study explored underlying metabolism-related dysfunction by examining metabolomic profiles in adults categorized as lean, as having normal weight obesity (NWO), or as having overweight/obesity. Participants (N = 179) had fasting plasma analyzed by liquid chromatography and high-resolution mass spectrometry for high-resolution metabolomics. Body composition was assessed by dual-energy x-ray absorptiometry. NWO was defined as BMI < 25 and body fat > 30% for women and > 23% for men. Differentiating metabolomic features were determined by using linear regression models and likelihood ratio tests with false discovery rate correction. Mummichog was used for pathway and network analyses. A total of 222 metabolites significantly differed between the groups at a false discovery rate of q = 0.2. Linoleic acid, β-alanine, histidine, and aspartate/asparagine metabolism pathways were significantly enriched (all P < 0.01) by metabolites that were similarly upregulated in the NWO and overweight/obesity groups compared with the lean group. A module analysis linked branched-chain amino acids and amino acid metabolites as elevated in the NWO and overweight/obesity groups compared with the lean group (all P < 0.05). Metabolomic profiles of individuals with NWO reflected similar metabolic disruption as those of individuals with overweight/obesity. High-resolution metabolomics may help identify people at risk for developing obesity-related disease, despite normal BMI.


A peripherally restricted P2Y12 receptor antagonist altered rat tumor incidences with no human relevance: Mode of action consistent with dopamine agonism.
Ticagrelor is an orally available, direct acting and reversible P2Y12 receptor antagonist approved for treatment of acute coronary syndrome. The objectives of these studies were to (1) evaluate the Ticagrelor 2-year rat carcinogenicity bioassay data; (2) investigate potential mode of action (MOA) and (3) interpret human relevance. The following studies were done (1) rat two-year carcinogenicity study in male and female rats, (2) in vitro and in vivo genotoxicity assays, (3) quantitative whole body autoradiography (QWBA; male and female rats), (4) in vitro pharmacological profiling for more than 300 assays, and (5) in vivo ovariectomized rat assay. The carcinogenicity study indicated Ticagrelor increased uterine tumor incidence while decreasing mammary and pituitary tumors/hyperplasia incidences in only high dose female rats. However, this altered tumor incidences were not P2Y12 target related since marketed non-reversible P2Y12 receptor antagonists were not associated with alter tumor incidences. MOA studies determined Ticagrelor exposure in the anterior pituitary and Ticagrelor was (1) non-genotoxic, (2) peripherally-restricted, (3) a dopamine transport (DAT) inhibitor with an IC50 lower than systemic free exposure in the rat carcinogenic study and more than a log higher than the free systemic exposure seen in clinical trials and (4) an inhibitor of estradiol-induced prolactin secretion. Similar to Ticagrelor, centrally active dopamine agonists induce the same altered tumor incidence patterns that according to literature do not translate into the clinical setting, with a MOA involving decreased prolactin secretion. The Ticagrelor MOA data and literature suggest that altered dopamine levels in the hypophyseal part of the hypothalamus-hypophyseal axis (by Ticagrelor) will result in similar altered tumor incidences in rat that do not translate into the clinical setting, based on qualitative species differences. In conclusion Ticagrelor increased uterine tumors in the rat carcinogenesis study by a MOA consistent with reduced dopamine inhibition of prolactin, which is not a patient safety risk.


In vitro and in vivo delivery of intact BAC DNA -- comparison of different methods.
The ability to deliver large (>100 kb) fragments of DNA to mammalian cells in vitro and in vivo is becoming increasingly important with the availability of BAC and PAC constructs for gene expression. Here we investigate in vitro and in vivo delivery of BACs up to 157 kb. Different types of polyethylenimine (PEI) and Lipofectamine were used to deliver 150-kb BAC (bacterial artificial chromosome) DNA to mouse and human cell lines in tissue culture and the level of EGFP expression compared. To assess the intactness of the DNA delivered, a BAC carrying oriP/EBNA-1 was used to make stably transfected cell lines. Episomal DNA was then rescued into E. coli followed by analysis on a pulsed-field gel. Three different methods of in vivo delivery were also assessed for delivery of BAC DNA; intravenous injection of DNA/PEI particles, intramuscular injection with electroporation and high-volume injection into the tail vein. PEI22 (linear polymer form, 22 kDa) was found to be the most efficient method for delivery of 150-kb BAC DNA to both cell lines in tissue culture. However, Lipofectamine 2000 was found to give a higher proportion of intact DNA than PEI22 in stably transformed colonies and almost all the DNA delivered by Lipofectamine 2000 was intact. Intravenous injection of DNA/PEI particles was found to be inefficient for delivery of BAC DNA. Intramuscular injection with electroporation of pure BAC DNA was very efficient and expression was maintained for 105 days. High-volume injection of BAC DNA gave excellent expression in the liver and intact BAC DNA could be rescued 7 days after injection. These results demonstrate efficient delivery of intact, large (up to 157 kb) DNA constructs for in vitro gene expression and in vivo gene therapy applications.


Effects of nitrate addition and iron speciation on trace element transfer in coastal food webs under phosphate and iron enrichment.
Coastal organisms are often exposed to both iron enrichment and eutrophication. Trace elements transfer in coastal food webs are critical for marine life and therefore influence coastal ecosystem function and the global carbon cycle. However, how these exposures affect algal element uptake and the subsequent element transfer to marine copepods (Tigriopus japonicus) is unknown. Here we investigated the effects of nitrate addition and iron speciation (Fe (OH)3 or EDTA-Fe) on the biological uptake of Cu, Zn, and Se under phosphate and iron enrichment, using Thalassiosira weissflogii, Skeletonema costatum, and Chlorella vulgaris as model marine algae. Algal element adsorption/absorption generally increased with increasing macronutrient concentrations. Algal element assimilation efficiencies depended on iron speciation and marine algae species. Element assimilation efficiencies of copepods were significantly correlated to the intracellular element concentrations in algal cells. Element uptake and transfer were controlled by eutrophication, iron speciation, and algal species in coastal food webs.


Do orientation programs help new graduates?
There is a need for effective orientation programs that are designed to prepare new graduate nurses in providing safe, competent, and effective patient care. However, little is known regarding the overall effectiveness of these programs for nursing graduates. To determine whether the transition of the graduates into their working place included a structured orientation program, and to assess the effectiveness of the program from the graduate's perspective. Cross-sectional survey design. Data were collected from four different institutions in Israel. A questionnaire was divided among 100 graduate nurses and had a response rate of 79%. A questionnaire was designed and included closed and open questions. It was evaluated for internal consistency by standardized Cronbach's alpha coefficients (Cronbach's alpha was between 0.91 and 0.96). Only 50.6% of the nurses in the sample reported having a structured orientation program. We found positive significant correlations between having a structured orientation program to adaptation of the graduate nurses to the ward, satisfaction of the graduates on the ward. Positive correlations were also found between support that the graduates received to their satisfaction on the ward. Retention on the ward was highly correlated with having a program, satisfaction, adaptation, and support. We found differences in acclimation indices by religiosity. Different delivery approaches of orientation programs may determine satisfaction of the graduates. A transition program which overlooks individual needs or an informal individual approach may lead to dissatisfaction. A program which is "tailored" to the graduate, by an assigned one-to-one appointment of a preceptor, may lead to satisfaction, which in turn may assure an ongoing supply of competent RNs who will remain in those settings.


Oxford Hip Scores, Floor-Sitting Score Trajectories, and Postoperative Satisfaction Rates at 10 Years After Primary Total Hip Arthroplasty.
Available evidence on outcomes at 5 years and beyond for total hip arthroplasty (THA) is mainly limited to patient-reported outcome measures (PROMs). This study documented the trajectory of functional measurement using the Oxford hip score (OHS) and floor-sitting posture in Japan for up to 10 years post-THA and investigated predictors of dissatisfaction at 10 years with THA. Patients scheduled for primary THA at a university hospital in Japan between 2003 and 2006 were enrolled in this prospective study. Overall, 826 preoperative participants were eligible for follow-up, with response rates ranging from 93.6% to 69.4% at each postoperative survey point. The OHS and floor-sitting scores were calculated using a self-administered questionnaire 6 times up to 10 years postoperatively. Patient satisfaction, including general surgery, walking ability, and activities of daily living (ADL), was assessed in the 10-year survey. The linear mixed-effects model demonstrated a postoperative improvement, peaking at 7 years for OHS and 5 years earlier for the floor-sitting score. The postoperative overall surgical dissatisfaction at 10 years with THA was very low (3.2%). No predictors of surgical dissatisfaction were identified in the logistic regression analyses. Predictors of walking ability dissatisfaction were older age, men, and worse OHS at 1 year postoperatively. Predictors of ADL dissatisfaction were poorer preoperative and 1-year postoperative floor-sitting scores and 1-year postoperative OHS. The floor-sitting score is a simple PROM suitable for the Japanese population; other populations would require a scale suitable for their lifestyles.


Impact of antiplatelet agents and anticoagulants on the performance of fecal immunochemical tests: a systematic review and meta-analysis.
Antithrombotic agents may increase the bleeding tendency and affect the performance of fecal immunochemical test (FIT). We aimed to evaluate the impact of antithrombotic agents on the performance of FIT through a systematic review and meta-analysis. All relevant studies published between January 1980 and September 2020 that examined the diagnostic performance of FIT were searched through MEDLINE, EMBASE, and Cochrane Library databases. We performed a meta-analysis for the positive predictive value (PPV) of FIT for detecting advanced colorectal neoplasia (ACRN) or colorectal cancer (CRC) according to the administration of antithrombotic agents including aspirin, antiplatelet agents, and oral anticoagulants (OACs). Thirteen studies with 27,518 patients were included. Of these, 11 studies with data required for the calculation of pooled PPV were included in the meta-analysis. The pooled PPV of FIT for detecting ACRN was significantly lower in antithrombotic agent users than in non-users (odds ratio [OR] [95% confidence interval [CI]]: aspirin, 0.82 [0.68-0.99]; antiplatelet agents, 0.82 [0.69-0.96]; OACs, 0.66 [0.52-0.84]). For detecting CRC, antithrombotic agent use tended to be associated with a reduced PPV (aspirin, 0.76 [0.51-1.14]; antiplatelet agents, 0.73 [0.52-1.02]; OACs, 0.60 [0.25-1.44]). In the subgroup analysis, a FIT cutoff value of 15 μg Hb/g feces tended to be associated with lower PPVs compared to a value of 20 μg Hb/g feces in antithrombotic agent users. Aspirin, antiplatelet agents, and OACs significantly lowered the PPV of FIT for detecting ACRN. These drugs may increase the false-positive of FIT.


Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration.
Low back pain (LBP) is a very common condition and leads to serious pain, disability, and price tag all over the world. Intervertebral disk degeneration (IDD) is one of the major reasons that contributed to LBP. The levels of interleukin 1 beta (IL-1β) increase significantly in degenerative disks. IL-1β also accelerates IDD. Sinapic acid (SA) has the effect of anti-inflammatory, antioxidant and antimicrobial. However, the effect of SA on IDD has never been studied. Therefore, the aim of this study was to figure out whether SA has protective effect on nucleus pulposus (NP) cells and further explore the possible underlying mechanism. The nucleus pulposus (NP) tissues of rats were collected and cultured into NP cells. The NP cells were stimulated by IL-1β and treated with SA. In vitro treatment effects were evaluated by ELISA, Western blot assay, immunofluorescence, TUNEL method and real-time PCR. We conducted percutaneous needle puncture in the rat tail to build intervertebral disk degeneration model and treated rats with SA. In vivo treatment effects were evaluated by hematoxylin and eosin (HE) and safranin O (SO) staining and magnetic resonance imaging (MRI) method. Our results showed that SA not only inhibited apoptosis but also suppressed inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in IL-1β-stimulated NP cells. As to extracellular matrix (ECM), SA could increase collagen II and aggrecan levels and reduce the expression of MMP13 and ADAMTS5 during the stimulation of IL-1β. Furthermore, SA could activate nuclear factor-erythroid 2-related factor-2 (Nrf2) to inhibit nuclear factor κB (NF-κB) induced by IL-1β. Nrf2 knockdown partly reduced the protective effect of SA on NP cells. Correspondingly, SA ameliorated IDD by promoting Nrf2 expression. In vivo results also showed that SA could delay the progression of IDD. In conclusion, we demonstrated that SA could protect the degeneration of NP cells and revealed the underlying mechanism of SA on Nrf2 activation in NP cells.


Prognostic factors in the uveitis of juvenile rheumatoid arthritis.
Risk factors for significant visual loss were investigated in 51 patients with iridocyclitis associated with juvenile rheumatoid arthritis (JRA). Average follow-up was 12.7 years. Of 89 eyes with uveitis, 22% had visual loss to 20/200 or worse, 46% had cataracts, 30% had band keratopathy, and 27% had glaucoma. Severity of visual loss and complications correlated with the degree of inflammation found on initial ocular examination. Of 58 eyes that were initially normal or had signs of mild inflammation (cells, flare, keratitic precipitates), 3% had final vision of 20/200 or worse, 28% had cataracts, 5% had band keratopathy, and 17% had glaucoma. Of 31 eyes with posterior synechiae on initial examination, 58% had final vision of 20/200 or worse, 81% had cataracts, 77% had band keratopathy, and 45% had glaucoma. When arthritis clearly preceded uveitis, 6% of patients had a poor visual outcome compared to 67% of patients whose initial manifestation of JRA was uveitis. Systemic corticosteroid administration used primarily for arthritis correlated with cataract formation.


[The most common types of collateral circulation following occlusion of extracranial vessels--a digital subtraction angiography study].
We studied the collateral circulation of 56 patients with occlusion of the extracranial arteries. The results of this study showed that there is often a dominant collateral circulation, mainly of the anterior communications arteries, which supply the blood from one half of the brain to the other.


Many patients continue using proton pump inhibitors after negative results from tests for reflux disease.
Ambulatory reflux testing is used to evaluate symptoms of gastroesophageal reflux disease (GERD) refractory to protein pump inhibitors (PPIs). We investigated the prevalence of PPI use in patients with negative results from Bravo pH or multichannel intraluminal impedance-pH (MII-pH) tests and factors that might predict the use of PPIs. We analyzed data from patients who had undergone Bravo pH monitoring or MII-pH testing at Northwestern University, without evidence of reflux disease. Demographics, endoscopy findings, pathology results, and provider recommendations were obtained via chart review. Eligible patients (n = 90) were contacted by telephone, and a cross-sectional survey was administered with questions about symptom severity, demographics, medication use, and health behaviors. Patients were compared by current PPI use, and statistical analyses were performed by using SAS version 9.2 software. Thirty-eight patients (42.2%) reported current PPI use despite a negative result from a pH study. Only 17 patients (18.9%) recalled being instructed to stop taking PPIs; chart review showed documented instructions to stop PPI therapy for 15 patients (16.7%). There were no significant differences in demographic or clinical characteristics among patients compared by current PPI use. Patients taking a PPI were more likely than those not taking a PPI to report troublesome symptoms that affected their daily life, as measured by a questionnaire for the diagnosis of GERD (the GerdQ). More than 42% of patients with negative results from pH monitoring studies continue PPI therapy despite physiological data that they do not have GERD.


The strength with which a peptide group can form a hydrogen bond varies with the internal conformation of the polypeptide chain.
The strength of the H-bond formed between a dipeptide and a proton acceptor molecule is assessed by correlated ab initio quantum calculations for a broad range of different conformations of the dipeptide. The H-bond energy is very sensitive to the internal (phi,psi) angles, even when the geometry of the H-bond does not vary significantly from one conformation to another. This result indicates that the peptide NH is a much less potent proton donor in certain conformations than in others. In particular, extended conformations of a polypeptide are capable of only weak H-bonds. Thus, the interstrand NH...O H-bonds in parallel and antiparallel beta-sheets are expected to be significantly weaker than those found in other conformations, such as helices, ribbons, and beta-bends, even if the H-bond geometries are similar.


Selection of human embryos for transfer by Bayesian classifiers.
In this work we approach by Bayesian classifiers the selection of human embryos from images. This problem consists of choosing the embryos to be transferred in human-assisted reproduction treatments, which Bayesian classifiers address as a supervised classification problem. Different Bayesian classifiers capable of taking into account diverse dependencies between variables of this problem are tested in order to analyse their performance and validity for building a potential decision support system. The analysis by receiver operating characteristic (ROC) proves that the Bayesian classifiers presented in this paper are an appropriated and robust approach for this aim. From the Bayesian classifiers tested, the tree augmented naive Bayes, k-dependence Bayesian and naive Bayes classifiers showed to perform almost as well as the semi naive Bayes and selective naive Bayes classifiers.


Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor.
Placental growth factor (PlGF), abundantly produced from trophoblasts is involved in placental angiogenesis. The regulatory mechanism of its expression is poorly understood. Hypoxia inducible factors (HIFs) are centrally involved in the modulation of cellular function in response to low oxygen conditions. This study aimed to clarify HIF1α and HIF2α expression patterns during cytotrophoblast differentiation into syncytiotrophoblast and the impact of any changes on PlGF expression. HIF proteins were induced remarkably under low oxygen condition (2%). HIF1α expression decreased and HIF2α expression increased when syncytialization of cultured cytotrophoblasts is progressed. Those expression changes of HIF proteins in the process of in-vitro syncytialization was congruent with the immunohistochemical findings in preeclamptic placenta as well as uncomplicated placenta. Low oxygen condition was also associated with reduced PlGF production in syncytializing primary cells and BeWo choriocarcinoma cells. Small interfering RNA-mediated HIF2α knockdown in BeWo cells abrogated hypoxia-associated decreases in PlGF secretion; HIF1α silencing had no significant effect on PlGF secretion. In summary, HIF2α, rather than HIF1α, is most affected by reduced oxygen level during syncytialization and increases in HIF2α trigger a reduction of PlGF production. Our findings suggest new and important connections between HIF proteins and PlGF pathways in the regulation of placental angiogenesis.


Validation of a non-invasive prenatal test for fetal RhD, C, c, E, K and Fya antigens.
We developed and validated a next generation sequencing-(NGS) based NIPT assay using quantitative counting template (QCT) technology to detect RhD, C, c, E, K (Kell), and Fya (Duffy) fetal antigen genotypes from maternal blood samples in the ethnically diverse U.S. population. Quantitative counting template (QCT) technology is utilized to enable quantification and detection of paternally derived fetal antigen alleles in cell-free DNA with high sensitivity and specificity. In an analytical validation, fetal antigen status was determined for 1061 preclinical samples with a sensitivity of 100% (95% CI 99-100%) and specificity of 100% (95% CI 99-100%). Independent analysis of two duplicate plasma samples was conducted for 1683 clinical samples, demonstrating precision of 99.9%. Importantly, in clinical practice the no-results rate was 0% for 711 RhD-negative non-alloimmunized pregnant people and 0.1% for 769 alloimmunized pregnancies. In a clinical validation, NIPT results were 100% concordant with corresponding neonatal antigen genotype/serology for 23 RhD-negative pregnant individuals and 93 antigen evaluations in 30 alloimmunized pregnancies. Overall, this NGS-based fetal antigen NIPT assay had high performance that was comparable to invasive diagnostic assays in a validation study of a diverse U.S. population as early as 10 weeks of gestation, without the need for a sample from the biological partner. These results suggest that NGS-based fetal antigen NIPT may identify more fetuses at risk for hemolytic disease than current clinical practice, which relies on paternal genotyping and invasive diagnostics and therefore is limited by adherence rates and incorrect results due to non-paternity. Clinical adoption of NIPT for the detection of fetal antigens for both alloimmunized and RhD-negative non-alloimmunized pregnant individuals may streamline care and reduce unnecessary treatment, monitoring, and patient anxiety.


High-risk medication use for Clostridium difficile infection among hospitalized patients with cancer.
Patients with cancer are vulnerable to Clostridium difficile infection (CDI); hospitals with larger oncology populations may have worse CDI performance. Among 71 academic hospitals studied, there were significant differences in oncology patient-days per 1,000 admissions across CDI standardized infection ratio categories of better, no different, and worse; worse hospitals had the greatest number of patient-days. Oncology patients' most commonly used high-risk CDI medications were quinolones, third- and fourth-generation cephalosporins, and proton pump inhibitors.


The relationship between coping and emotion: implications for theory and research.
Historically, coping has been viewed as a response to emotion. Our purpose here is to evaluate this idea and offer a broader view based on cognitive and relational principles concerning the emotion process. We will explore the ways emotion and coping influence each other in what must ultimately be seen as a dynamic, mutually reciprocal relationship.


Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.
Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations. We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed. Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.


The production, characterisation and application of monoclonal antibodies generated by immunisation with HIV-1C clade RGP140 envelope protein.
The native HIV-1 envelope spike exists as trimers on the virion surface. Therefore antibodies elicited following immunisation with trimeric envelope vaccines may be directed against epitopes found on functional envelope spikes. Novel monoclonal antibodies were produced by priming mice with plasmid DNA expressing either HIV-1 CN54 or ZM96 gp140 sequences, and boosting with CN54 trimeric rgp140. Spleen cells were fused with NS-0 cells and hybridomas were screened for production of antibodies which bound trimeric rgp140. 18 monoclonal antibodies (MAbs) were isolated from 16 colonies, which were characterised by binding in ELISA and Western blotting, neutralisation of pseudotyped viruses and isotype. Specificity for the third variable (V3) region was detected in 5 of these antibodies, suggesting that the trimeric protein did not alter the main focus of the response compared with monomeric protein. 3 MAbs were identified as neutralising in a pseudotype assay, all of which were mapped to the V3 region. Although cross clade binding of antibodies was detected the neutralisation was C clade specific.


Acute hospital-community hospital care bundle for elderly orthopedic surgery patients: A propensity score-matched economic analysis.
While Singapore attains good health outcomes, Singapore's healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals. An Acute Hospital-Community Hospital (AH-CH) care bundle has been developed to assist patients in postoperative rehabilitation. The core concept is to transfer patients out of AHs when clinically recommended and into CHs, where they can receive more beneficial dedicated care to aid in their recovery, while freeing up bed capacities in AHs. To analyze the AH length of stay (LOS), costs, and savings associated with the AH-CH care bundle intervention initiated and implemented in elderly patients aged 75 years and above undergoing elective orthopedic surgery. A total of 862 1:1 propensity score-matched patients aged 75 years and above who underwent elective orthopedic surgery in Singapore General Hospital (SGH) before (2017-2018) and after (2019-2021) the care bundle intervention period was analyzed. Outcome measures were AH LOS, CH LOS, hospitalization metrics, postoperative 30-d mortality, and modified Barthel Index (MBI) scores. The costs of AH inpatient hospital stay in the matched cohorts were compared using cost data in Singapore dollars. Of the 862 matched elderly patients undergoing elective orthopedic surgery before and after the care bundle intervention, the age distribution, sex, American Society of Anesthesiologists classification, Charlson Comorbidity Index, and surgical approach were comparable between both groups. Patients transferred to CHs after the surgery had a shorter median AH LOS (7 d vs 9 d, P < 0.001). The mean total AH inpatient cost per patient was 14.9% less for the elderly group transferred to CHs (S$24497.3 vs S$28772.8, P < 0.001). The overall AH U-turn rates for elderly patients within the care bundle were low, with a 0% mortality rate following orthopedic surgery. When elderly patients were discharged from CHs, their MBI scores increased significantly (50.9 vs 71.9, P < 0.001). The AH-CH care bundle initiated and implemented in the Department of Orthopedic Surgery appears to be effective and cost-saving for SGH. Our results indicate that transitioning care between acute and community hospitals using this care bundle effectively reduces AH LOS in elderly patients receiving orthopedic surgery. Collaboration between acute and community care providers can assist in closing the care delivery gap and enhancing service quality.


Hemispheric processing of spatial frequencies in two commissurotomy patients.
To test the hypothesis that in humans the left brain hemisphere is specialized for processing high spatial frequencies while the right hemisphere is specialized for processing low spatial frequencies, pairs of Gaussian windowed sinusoidal gratings were presented for 167 msec within the left and right visual fields of two commissurotomy patients. The gratings employed had spatial frequencies ranging from 1 to 8 cycles per degree, and horizontal or vertical orientations. The two gratings in each pair were identical in spatial frequency but could differ in orientation. Subjects reported if their orientations were the same or different. Twelve normal controls were also run. Accuracy data provides no indication of a relative advantage for high frequencies in the RVF or low frequencies in the LVF. One commissurotomy subject showed a trend in the reverse direction; the other was better with LVF presentations for all spatial frequencies. Control subjects failed to show a spatial frequency x visual field interaction. These outcomes suggest that at the processing stages required by the task, the hemispheres are not specialized for particular ranges of spatial frequencies.


Variability and Seasonal Change of Urinary Selenium, Molybdenum, and Iodine Excretion in Healthy Young Japanese Adults.
Selenium (Se), molybdenum (Mo), and iodine (I) are essential trace elements or nutrients and their adequate intake is essential for human health. These elements in foods are easily absorbed from the digestive tract and excreted predominantly into the urine, and their nutritional status is reflected in urinary excretion; however, information on the variability of urinary excretion is limited. To characterize the urinary Se, Mo, and I concentrations and their intra- and inter-individual coefficients of variation (CV), correlation, and seasonal change, spot urine samples were collected from 24 healthy university students, 10 males and 14 females, with the mean age of 20.6 years, for 10 consecutive days in each of the four seasons according to a defined schedule of an interval of 3 months throughout 1 year. The median Se, Mo, and I concentrations for all urine samples (n = 947) were 52.8, 127.0, and 223 μg/L, respectively. The Se and Mo intakes were highest in summer and lowest in spring, while the I intake was highest in autumn and lowest in summer. In all three elements, the intra-individual CVs were smaller than their inter-individual CVs. The log-transformed intra- and inter-individual CVs were 10.5 and 14.7% for Se, 12.3 and 15.1% for Mo, and 15.5 and 18.1% for I. There was no gender difference in Se and I concentrations, while Mo and Mo/Cr values in males were higher than those in females. Our results suggest adequate nutritional status of Se, Mo, and I with a relatively smaller variability of dietary intake except for I in this population.


Rapid and simultaneous detection of blaKPC and blaNDM by use of multiplex real-time PCR.
The increasing incidence of carbapenem nonsusceptibility among clinically important species is of global concern. Identification of the molecular mechanisms underlying carbapenem nonsusceptibility is critical for epidemiological investigations. In this report, we describe a real-time PCR-based assay capable of simultaneously detecting blaKPC and blaNDM, two of the most important carbapenemases, directly from culture in less than 90 min. The assay was validated with blaKPC- and blaNDM-carrying clinical isolates and demonstrated 100% concordance with the Carba NP test.


BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL.
Vaccinations effectively prevent infections; however, patients with chronic lymphocytic leukemia (CLL) have reduced antibody responses following vaccinations. Combined humoral and cellular immune responses to novel adjuvanted vaccines are not well characterized in CLL. In an open-label, single-arm clinical trial, we measured the humoral and cellular immunogenicity of the recombinant zoster vaccine (RZV) in CLL patients who were treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitor (BTKi) therapy. The primary endpoint was antibody response to RZV (≥fourfold increase in anti-glycoprotein E [anti-gE]). Cellular response of gE-specific CD4+ T cells was assessed by flow cytometry for upregulation of ≥2 effector molecules. The antibody response rate was significantly higher in the TN cohort (76.8%; 95% confidence interval [CI], 65.7-87.8) compared with patients receiving a BTKi (40.0%; 95% CI, 26.4-53.6; P = .0002). The cellular response rate was also significantly higher in the TN cohort (70.0%; 95% CI, 57.3-82.7) compared with the BTKi group (41.3%; 95% CI, 27.1-55.5; P = .0072). A concordant positive humoral and cellular immune response was observed in 69.1% (95% CI, 56.9-81.3) of subjects with a humoral response, whereas 39.0% (95% CI, 24.1-54.0) of subjects without a humoral response attained a cellular immune response (P = .0033). Antibody titers and T-cell responses were not correlated with age, absolute B- and T-cell counts, or serum immunoglobulin levels (all P > .05). RZV induced both humoral and cellular immune responses in treated and untreated CLL patients, albeit with lower response rates in patients on BTKi therapy compared with TN patients. This trial was registered at www.clinicaltrials.gov as #NCT03702231.


Automatic landmarking of cephalograms.
This paper presents an algorithm for automatically locating certain characteristic anatomical points called landmarks on cephalograms (skull X-rays). These landmarks are used by orthodontists in diagnosis and treatment planning. The algorithm uses digital image processing and feature recognition techniques to locate the landmarks. A resolution pyramid of the digitized cephalogram is first created. The algorithm works on the smaller, lower resolution images to locate features of interest and moves to the bigger, higher resolution images if greater location accuracy is required. Prefiltering using the median filter, contrast enhancement using histogram equalization, and edge enhancement using different gradient operators are performed on the images. The algorithm uses anatomical knowledge of the human facial structure to search for features containing the landmarks. The accuracy of the algorithm in locating the landmarks is compared with values obtained from human experts. At present the algorithm attempts to locate 10 landmarks of 27 needed for a complete analysis. All 10 landmarks have been successfully located on five cephalograms of varying quality.


The mechanism of renal clearance of cisplatin (cis-dichlorodiammine platinum ii) and its modification by furosemide and probenecid.
When isolated rat kidneys are perfused with 30 microM cisplatin there is net tubular transport of platinum, resulting in excretion of platinum at a rate 125% of the rate attributable to glomerular filtration alone. Probenecid and furosemide are drugs which have been reported to protect against cisplatin nephrotoxicity, by unknown mechanisms. When probenecid 0.3 mM is included in the perfusate net transport of platinum is increased to 200% of that accounted for by glomerular filtration alone. Increasing the concentration of probenecid to 3.0 mM does not significantly further increase the rate of excretion of platinum. The inclusion of furosemide 0.3 mM in the perfusate has no effect on the net tubular transport of platinum. However, at 3.0 mM furosemide causes a decrease in the net platinum transport and only 93% of platinum filtered at the glomerulus appears in the urine. Thin-layer chromatography revealed the presence of at least three platinum compounds in the urine in addition to cisplatin. We conclude that the renal excretion of cisplatin and its transformation products, even in this model system, is a complex process involving glomerular filtration, tubular excretion and tubular reabsorption.


Infantile neurodegenerative disease with neuronal accumulation of phosphorylated neurofilaments.
A caucasian male with a history of mental retardation and intractable epilepsy since birth, developed progressive wasting and weakness of skeletal muscles, leading to death at 4 years of age. A biopsy of gastrocnemius muscle at 2 years of age revealed severe neurogenic atrophy. Sural nerve biopsies at 2 and 3 years showed progressive atrophy and loss of large myelinated nerve fibers with a paucity of neurofilaments in remaining nerve fibers. Postmortem immunohistochemical and ultrastructural examination showed that neurons were markedly distended by phosphorylated neurofilaments. Whereas large lower motor neurons were most severely involved, dorsal root ganglia and neurons in the cerebral cortex and deep gray nuclei were also affected. It is suggested that this disease is caused by a disorder of neurofilament phosphorylation and transport.


Potential use of newly isolated bacteriophage as a biocontrol against Acidovorax citrulli.
Acidovorax citrulli, the gram-negative bacteria that causes bacterial fruit blotch (BFB), has been responsible for huge worldwide economic losses in watermelon and melon production since 1980. No commercial cultivar resistant to BFB has been reported. Of the two reported genotypes of A. citrulli, genotype I is the main causal agent of BFB in melon and genotype II causes disease in watermelon. After the isolation of the first bacteriophage against A. citrulli (ACP17), efforts have been made to isolate bacteriophages with wider host ranges by collecting samples from watermelon, pumpkin, and cucumber. The newly isolated phage ACPWH, belonging to the Siphoviridae family, has a head size of 60 ± 5 nm and tail size of 180 ± 5 nm, and can infect 39 out of 42 A. citrulli strains. ACPWH has genome size of 42,499 and GC content of 64.44%. Coating watermelon seeds with bacteriophage ACPWH before soil inoculation with A. citrulli resulted in 96% germination and survival, compared to 13% germination of uncoated control seeds. These results suggest that phage ACPWH may be an effective and low-cost biocontrol agent against BFB.


Scientific resistance to research, training and utilization of eye movement desensitization and reprocessing (EMDR) therapy in treating post-war disorders.
In this study, Barber's [(1961). Resistance by scientists to scientific discovery. Science, 134, 596-602] analysis of scientists' resistance to discoveries is examined in relation to an 18-year controversy between the dominant cognitive-behavioral paradigm or zeitgeist and its chief rival - eye movement desensitization and reprocessing (EMDR) in treating trauma-related disorders. Reasons for persistent opposition to training, utilization and research into an identified 'evidence-based treatment for post-traumatic stress disorder' (EBT-PTSD) within US military and veterans' agencies closely parallels Barber's description of resistance based upon socio-cultural factors and scientific bias versus genuine scientific skepticism. The implications of sustained resistance to EMDR for combat veterans and other trauma sufferers are discussed. A unified or super-ordinate goal is offered to reverse negative trends impacting current and future mental healthcare of military personnel, veterans and other trauma survivors, and to bridge the scientific impasse.


[Evaluation of peripherally inserted central catheters in a pediatric population].
A peripherally inserted central catheter (PICC) is a central venous access mostly used in France in the adult population, whereas it is only rarely used in the pediatric population. The main objective of this study was to analyze a cohort of children treated with PICCs inserted under radiological guidance. We conducted a single-center study in the Radiology department of Nice University Hospital and the Lenval Foundation Children's Hospital. During a 43-month period between November 2008 and June 2012, a total of 67 catheter placement attempts were performed in 57 pediatric patients aged from 7 months to 18 years. We achieved 95.5% technical success with a median procedure duration of 17min. Only 6% of the PICC placements required light intravenous sedation; all the others were performed using a combination of local anesthesia, EMLA cream, and equimolar mixture of oxygen and nitrous oxide (EMONO). Subjective scale analysis of pain during catheter insertion showed a median score of 2.1. Catheter life ranged from 1 to 210 days (median, 38.3 days) with the treatment fully completed in 75% of the cases. The overall complication rate was 18.7% (4.9 per 1000 catheter-days), largely dominated by mechanical complications (9.4%) such as accidental removal (6.2%) or catheter obstruction (3.1%). Infectious complications occurred in 7.8% of the patients. The duration of catheterization and the use of tape to secure the catheter significantly affected the occurrence of complications. Peripheral insertion of central catheters was highly feasible in infants and children. It is a simple, safe, and effective alternative to intravenous central devices in the pediatric population. The occurrence of complications, typically mechanical, must be reduced and prevented by strict management of this type of central line by the nursing team.


Is sesamol present in sesame oil?
Sesame oil has been reported to contain sesamolin, sesamin and sesamol as contact allergens. A female patient had cheilitis due to sesame oil in a lipstick. She reacted to sesamolin and sesamin, but not to sesamol. We carried out analysis of the sesame oil by high performance liquid chromatography. We detected sesamolin and sesamin but not sesamol in sesame oil.


Comparison of airway assessment tests for prediction of difficult intubation in obese patients: importance of thyromental height and upper lip bite test.
Prediction of difficult intubation (DI) has remained challenging for anesthesiologists and validity of airway assessment tests has not been fully investigated. This study aims to compare predictive values of these tests for prediction of DI in obese patients. One hundred ninety-six patients with Body Mass Index (BMI) ≥30 kg/m2 were included in this prospective study. Variables including intubation Difficulty Scale (IDS), thyromental height (TMH), hyomental distance (HMD) in extent and neutral neck position, HMD ratio (HMDR), sternomental distance (SMD), thyromental distance (TMD), ratio of height to TMD (RHTMD), width of mouth opening (MO), mandibular length (ML), Cormack-lehane (C-L) grade, upper lip bite test (ULBT), history of snoring, and obstructive sleep apnea were collected. Multiple logistic regression and receiver operating characteristic (ROC) curve analysis were used to determine independent predictors of DI (defined as IDS≥5) and their cut off points. DI and difficult laryngoscopy (defined as C-L grade ≥3) were observed in 23% and 24.5% of the study population, respectively. Multiple logistic regression identified TMH (Odds ratio (OR):0.28, 95% confidence interval (CI):0.14-0.58, P=0.001), BMI (OR:1.18, 95% CI: 1.11-1.26, P<0.001), HMDR (OR:0.45, 95% CI:0.36-0.56, P<0.001) and ULBT (OR: 3.91, 95% CI: 2.14-7.14, P<0.001) as independent predictors of DI. Sensitivity of TMH<4.8 cm, BMI>34.9 kg/m2, HMDR<1.4 and ULBT class ≥2 were determined as 75.1%, 73.3%,62.3% and 93.3% respectively. TMH and ULBT had the highest sensitivity for prediction of DI in obese patients in this study and it is recommended to be considered as part of airway assessment in this patient population.


Immunohistochemical localization of 6-keto-PGF1-alpha in canine coronary vasculature.
The localization of the prostacyclin metabolite, 6-keto-PGF1-alpha, in canine coronary vasculature was accomplished using immunohistochemical techniques (avidin-biotin method of immunoperoxidase staining). Six-keto-PGF1-alpha was localized to the intimal endothelial cell layer of epicardial and intramyocardial arteries and veins. No specific staining was seen in the the media or adventitia of canine coronary vasculature, or in capillaries, or myocardial fibers. To our knowledge these studies represent the first immunohistochemical demonstration of the endothelial cell localization of the prostacyclin metabolite, 6-keto-PGF1-alpha. The described technique allows the cellular localization of prostaglandin metabolites in histologic sections.


Evaluating the effect of overharvesting on genetic diversity and genetic population structure of the coconut crab.
Birgus latro (coconut crab) is an edible crustacean that has experienced serious overharvesting throughout its whole habitat range; however, the negative effects of overharvesting on the genetic diversity within B. latro populations have not been elucidated. Here, we report sex ratio, body size, and genetic diversity in populations of B. latro in the Ryukyu Islands where large-male-biased overharvesting of B. latro has continued. In 2 of the study populations, the sex ratio was significantly skewed toward females, and in all of the study populations large males were rare, which we attributed to sex- and size-biased overharvesting. We found no differences in genetic diversity between small and large individuals, suggesting that genetic diversity, even among the large (i.e., old) individuals, may have had already been negatively affected by overharvesting. Continued monitoring of sex ratio, body size and genetic diversity are needed for effective management of the study populations.


Scintigraphic assessment of double-chambered right ventricle.
A double-chambered right ventricle is often clinically misdiagnosed and may be missed even during cardiac catheterization. We encountered a 56-year-old male who had abnormal right ventricular thallium-201 uptake and a photon deficient area in the right ventricle by radionuclide cardioangiography. These findings strongly suggested the existence of anomalous muscle band in the right ventricle. It was demonstrated by contrast angiography that the right ventricle was divided into two chambers by a hypertrophic muscular band; the pressure gradient in the right ventricle was 98 mmHg.


A BIN2-GLK1 Signaling Module Integrates Brassinosteroid and Light Signaling to Repress Chloroplast Development in the Dark.
Arabidopsis GLYCOGEN SYNTHASE KINASE 3 (GSK3)-like kinases play various roles in plant development, including chloroplast development, but the underlying molecular mechanism is not well defined. Here, we demonstrate that transcription factors GLK1 and GLK2 interact with and are phosphorylated by the BRASSINOSTEROID insensitive2 (BIN2). The loss-of-function mutant of BIN2 and its homologs, bin2-3 bil1 bil2, displays abnormal chloroplast development, whereas the gain-of-function mutant, bin2-1, exhibits insensitivity to BR-induced de-greening and reduced numbers of thylakoids per granum, suggesting that BIN2 positively regulates chloroplast development. Furthermore, BIN2 phosphorylates GLK1 at T175, T238, T248, and T256, and mutations of these phosphorylation sites alter GLK1 protein stability and DNA binding and impair plant responses to BRs/darkness. On the other hand, BRs and darkness repress the BIN2-GLK module to enhance BR/dark-mediated de-greening and impair the formation of the photosynthetic apparatus. Our results thus provide a mechanism by which BRs modulate photomorphogenesis and chloroplast development.


The effect of enzyme therapy on plasma lipid levels in the elderly.
(1) An enzyme preparation, Vasolastine, administered intramuscularly, to a group of elderly subjects (mean age 81.7) reduced fasting plasma cholesterol and triglyceride levels by amounts which were proportional to their initial concentration. (2) Triglyceride levels 3 h after a fat-rich meal were also directly dependent on the initial fasting level. This relationship is lowered significantly after 25 days of Vasolastine treatment. (3) It is suggested that these observations, taken in conjunction with the results of in vitro studies, confirm that Vasolastine acts synergistically with endogenous lipoprotein lipase.


Some efferent connections of the superficial pretectum in the goldfish.
The diencephalic nuclei known as the lateral geniculate and rotundus in goldfish appear to belong to the pretectal region. They do not project to the telencephalon. A combination of degeneration and horseradish tract-tracing experiments show that that the latter nucleus projects caudally to the so-called mammillary body and to a precerebellar cell group-nucleus lateralis valvulae.


Record ACA Enrollment; 2023 Payment Rule.
Marketplace enrollment rose significantly, and the Biden administration proposed sweeping new standards for 2023.


Long-term experience with bromocriptine in advanced parkinsonism. Results after one year's treatment.
The long-term effects of bromocriptine as an adjuvant were investigated in 32 patients (20 male, 12 female), aged 43-76 years (mean 65.4), suffering from parkinsonism for 3-20 years (mean 9.3). Patients were pretreated with levodopa/decarboxylase inhibitor for 24-116 months (mean 74.9). Bromocriptine was given because of a decline in the response to levodopa, various kinds of "on-off" phenomena, and disabling dyskinesias. Levodopa was reduced by 18%, while bromocriptine was added with a mean dose of 29 mg. The results showed a marked tremor and rigidity response, clearly greater than that of bradykinesia of the hands. The improvement after 4 weeks of bromocriptine treatment was maintained over 12 months. Only gait disturbances tended to increase. At the same time the self-ratings of the patients showed an increase in disability as far as daily activities were concerned. Likewise, the "on-off" symptoms with regard to the wearing-off effects worsened in comparison with the condition during the 4-week period. Akinesia paradoxica was never definitely influenced. An increase in dyskinesias was avoided and serious side-effects could be kept under control.


Longitudinal risk factors for obstructive sleep apnea: A systematic review.
Despite substantial disease burden, existing evidence on the risk factors for obstructive sleep apnea (OSA) have been derived primarily from cross-sectional studies without determining temporality. Therefore, we aimed to systematically synthesize the literature on longitudinal risk factors for sleep study-assessed OSA and questionnaire-assessed probable OSA from cohort studies in the general adult population settings. We systematically searched Embase and Medline (on OVID) databases. Eleven studies met the inclusion criteria. Meta-analyses were not conducted due to methodological heterogeneity of exposure and outcome measurements. There was consistent evidence that weight gain was associated with incident (n = 2) and greater severity (n = 2) of OSA. One study each observed an association of higher baseline body-mass index, male sex, asthma, a specific genetic polymorphism in rs12415421, and insulin resistance/hyperglycemia, with incident OSA. Long-term exposure to ambient air pollution (NO2, n = 1) was associated with OSA, and menopausal transitions (n = 1) with higher apnea-hypopnea index. There were no eligible studies on long-term smoking or alcohol use. In conclusion, approximately 10% increase in weight, especially in males, might alert clinicians to consider potential or worsening OSA. Large, well-designed longitudinal studies are needed to consolidate knowledge on other associations with OSA development, especially on potentially modifiable risk factors.


Prenatal androgen exposure and growth and secretion of growth hormone and prolactin in ewes postweaning.
Growth and secretion of growth hormone (GH) and prolactin (PRL) in ewe lambs exposed to androgen during fetal development were investigated. Testosterone cypionate was administered to the pregnant dams from approximately Days 28 to 84 of gestation. Ewe lambs from dams that received androgen exhibited masculinized external genitalia and some masculine behavioral characteristics. Intact androgenized ewe lambs grew faster (P less than 0.05) and were more efficient in conversion of food to body gain (P less than 0.05) than ewe lambs born to untreated dams over the period from 70 to 224 days of age. One-half of the ewe lambs in each group was ovariectomized at 58 days of age. Ovariectomy had no effect on subsequent growth or efficiency of growth in the control ewe lambs. However, ovariectomy of androgenized ewe lambs abolished the observed stimulated rate of growth and decreased the improvement in efficiency of food conversion. Blood samples were collected from the lambs at 85 and 136 days of age at 15-min intervals for 8 hr to determine parameters of GH and PRL secretion. Prenatal androgen exposure had no effect on any parameter of GH or PRL secretion. These data indicate that prenatal androgen exposure altered differentiation of growth potential in ewe lambs, but the growth response was not mediated through dramatic changes in secretion of adenohypophysial somatotropic hormones, GH and PRL.


Environmental pollutants exposure and gestational diabetes mellitus: Evidence from epidemiological and experimental studies.
Except for known sociodemographic factors, long-term exposure to environmental pollutants has been shown to contribute to the development of gestational diabetes mellitus (GDM), but the conclusions remain controversial. To provide a comprehensive overview of the association between environmental pollutants and GDM, we performed a systematic review and meta-analysis. Several electronic databases (PubMed, Embase, Web of Science, Medline and Cochrane) were searched for related epidemiological and experimental studies up to September 2022. For epidemiological studies, a meta-analysis was carried out to appraise the effect of environmental pollutants, including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), per- and polyfluoroalkyl substances (PFASs), phenols, phthalates (PAEs), polybrominated diphenyl ethers (PBDEs) and parabens exposure on GDM. Moreover, we also summarized possible biological mechanisms linking pollution exposure and GDM based on the included experimental studies. A total of 80 articles were enrolled, including 38 epidemiological studies and 42 experimental studies. Meta-analysis results showed that exposure to PAEs [OR (95%CI) = 1.07 (1.00, 1.14)], PFASs [OR (95%CI) = 1.10 (1.01, 1.19)], as well as PCBs [OR (95%CI) = 1.18 (1.02, 1.36)] and PBDEs [OR (95%CI) = 1.33 (1.17, 1.50)] significantly increased the risk of GDM, but no significant effects were found for phenols, OCPs, and parabens. In addition, experimental studies suggested that the potential biological mechanisms of environmental pollutants contributing to GDM may involve insulin resistance, β-cell dysfunction, neurohormonal dysfunction, inflammation, oxidative stress, epigenetic modification, and alterations in gut microbiome. In conclusion, long-term environmental pollutants exposure may induce the development of GDM, and there may be a synergistic effect between the homologs. However, studies conducted on the direct biological link between environmental pollutants and GDM were few. More prospective studies and high-quality in vivo and in vitro experiments were needed to investigate the specific effects and mechanisms.


'Adventure therapy' combined with cognitive-behavioral treatment for overweight adolescents.
Since peers have such an important influence on adolescents, we evaluated the efficacy of adding peer-based 'adventure therapy' to a standard cognitive-behavioral weight control program for overweight adolescents. Adolescents (N = 76) aged 13-16 years and 20 to 80% overweight (M = 60.56%, s.d.=15.17%), were randomly assigned to one of two treatment conditions: cognitive-behavioral group treatment with 'adventure therapy' similar to Outward Bound (cognitive-behavioral treatment with peer-enhanced adventure therapy (CBT + PEAT)) or cognitive-behavioral group treatment with aerobic exercise (CBT+EXER). Anthropometric and psychosocial measures were obtained at baseline, at the end of the 16-week intervention, and at 10 months following randomization. Adolescents assigned to both treatment conditions demonstrated significant weight loss over time, F = 29.06, df = 2, 53, P < 0.01. Average weight loss did not differ significantly between groups (-5.31 kg for CBT + PEAT and -3.20 kg for CBT + EXER) at the end of treatment. There was a significant difference in the percentage of participants maintaining a minimum 4.5 kg (10 pounds) weight loss (35% in the CBT + PEAT condition vs 12% in the CBT+EXER condition, P = 0.042) 10 months from randomization. We also observed a significant age by treatment group interaction, such that older adolescents randomized to CBT + PEAT demonstrated more than four times the weight loss of older adolescents assigned to CBT + EXER (M = -7.86 kg vs M = -1.72 kg) at the end of treatment. Peer-based 'adventure therapy' is a promising adjunct to standard cognitive-behavioral weight control intervention for adolescents, and may be most effective for older adolescents.


Pelvic surgery and hospitalization among Chilean women after nonsurgical sterilization with quinacrine pellets between 1977 and 1989.
Concern about quinacrine lingers because of its carcinogenic effects in rats. We describe results of long-term follow-up of women who underwent quinacrine pellet sterilization in Chile between 1977 and 1989 (N=1492). We interviewed the women or relatives in five rounds of data collection between 1991-1993 and 2006-2007, and reviewed hospital records. Median follow-up was 18.5 years; total person-time was 23,894 woman-years. This analysis focuses on pelvic and abdominal surgeries and conditions. We used survival analysis to estimate the 15-year cumulative probability of hysterectomy, other pelvic surgical procedures and relevant adverse events. Uterine fibroids were by far the most common gynecologic condition, reported by 11% of the cohort. Surgical procedures were recorded for 15% of the cohort; hysterectomy was the most frequent procedure (10%), followed by salpingectomy (2%). The 15-year probability of any pelvic or abdominal procedure was 14.7 per 100 women (95% confidence interval 12.4-16.9). The probability of hysterectomy was 9.3 per 100 women (95% confidence interval 7.4-11.1). Number of quinacrine insertions had little impact on the probabilities. During long-term follow-up of women who received quinacrine pellets for nonsurgical sterilization, the incidence of noncancer adverse outcomes was not unusually high, and no alarming patterns emerged.


Facile oxygen reduction on a three-dimensionally ordered macroporous graphitic C3N4/carbon composite electrocatalyst.
Honeycomb catalysis: a facile oxygen reduction reaction has been observed on a graphitic C(3)N(4)/carbon catalyst with three-dimensional interconnected macropores (see picture with SiO(2) template). This material not only shows catalytic activity that is comparable to that of commercial Pt/C, but also has much higher organic-fuel tolerance and long-term stability.


Anatomical distribution of residual cancer in patients with oesophageal squamous cell carcinoma who achieved clinically complete response after neoadjuvant chemoradiotherapy.
Recent advances in neoadjuvant chemoradiotherapy (nCRT) have significantly increased the rates of pathological complete response achieved by patients with oesophageal cancer. Consequently, a watchful waiting strategy based on 'active endoscopic surveillance and surgery as needed' has been proposed for cases without clinical evidence of disease after neoadjuvant chemoradiotherapy. Here, we investigated whether endoscopic surveillance is a reliable tool for the detection of the initially unidentified residual cancer in this patient group. We performed a careful pathological re-review of all cases with oesophageal squamous cell carcinoma, who attained a clinical complete response, despite showing a pathological non-complete response. The detailed anatomical locations of such unidentified malignancies were investigated in each patient to determine the prevalence of cancer involvement for each oesophageal layer. Among the 73 patients with clinical complete response, 46 (63%) patients were found to have pathological non-complete response. The majority (89.1%; n = 41) of patients had evidence of residual cancer in the oesophagus, whereas only 5 (10.9%) patients had T0N+ disease. However, a high percentage (39.1%; n = 16) of patients had no detectable cancer in the mucosa and 9 of them also had no detectable cancer in sub-mucosal layer, ultimately hampering their detection via endoscopic biopsy. Nearly 40% of patients with oesophageal squamous cell carcinoma who attained clinical complete response but showed a pathological non-complete response had residual cancer hidden underneath a cancer-free mucosa layer.


Pretreatment with pyridoxamine mitigates isolevuglandin-associated retinal effects in mice exposed to bright light.
The benefits of antioxidant therapy for treating age-related macular degeneration, a devastating retinal disease, are limited. Perhaps species other than reactive oxygen intermediates should be considered as therapeutic targets. These could be lipid peroxidation products, including isolevuglandins (isoLGs), prototypical and extraordinarily reactive γ-ketoaldehydes that avidly bind to proteins, phospholipids, and DNA and modulate the properties of these biomolecules. We found isoLG adducts in aged human retina but not in the retina of mice kept under dim lighting. Hence, to test whether scavenging of isoLGs could complement or supplant antioxidant therapy, we exposed mice to bright light and found that this insult leads to retinal isoLG-adduct formation. We then pretreated mice with pyridoxamine, a B6 vitamer and efficient scavenger of γ-ketoaldehydes, and found that the levels of retinal isoLG adducts are decreased, and morphological changes in photoreceptor mitochondria are not as pronounced as in untreated animals. Our study demonstrates that preventing the damage to biomolecules by lipid peroxidation products, a novel concept in vision research, is a viable strategy to combat oxidative stress in the retina.


When Safety Event Reporting Is Seen as Punitive: "I've Been PSN-ed!"
Reporting systems are designed to identify patient care issues so changes can be made to improve safety. However, a culture of blame discourages event reporting, and reporting seen as punitive can inhibit individual and system performance in patient safety. This study aimed to determine the frequency and factors related to punitive patient safety event report submissions, referred to as Patient Safety Net reports, or PSNs. Three subject matter experts reviewed 513 PSNs submitted between January and June 2019. If the PSN was perceived as blaming an individual, it was coded as punitive. The experts had high agreement (κ=0.84 to 0.92), and identified relationships between PSN characteristics and punitive reporting were described. A total of 25% of PSNs were punitive, 7% were unclear, and 68% were designated nonpunitive. Punitive (vs nonpunitive) PSNs more likely focused on communication (41% vs 13%), employee behavior (38% vs 2%), and patient assessment issues (17% vs 4%). Nonpunitive (vs punitive) PSNs were more likely for equipment (19% vs 4%) and patient or family behavior issues (8% vs 2%). Punitive (vs nonpunitive) PSNs were more common with adverse reactions or complications (21% vs 10%), communication failures (25% vs 16%), and noncategorized events (19% vs 8%), and nonpunitive (vs punitive) PSNs were more frequent in falls (5% vs 0%) and radiology or laboratory events (17% vs 7%). Punitive reports have important implications for reporting systems because they may reflect a culture of blame and a failure to recognize system influences on behaviors. Nonpunitive wording better identifies factors contributing to safety concerns. Reporting systems should focus on patient outcomes and learning from systems issues, not blaming individuals.


Evaluation of antimycobacterial, antiplasmodial and cytotoxic activities of preussomerins isolated from the lichenicolous fungus Microsphaeropsis sp. BCC 3050.
A new preussomerin isomer, 3'-O-demethylpreussomerin I, five known preussomerins E - I, and two known deoxypreussomerins, deoxypreussomerin A and bipendensin (palmarumycin C11), were isolated from a lichenicolous fungus Microsphaeropsis sp. BCC 3050. These structures were elucidated by spectroscopic methods, especially 1D- and 2D-NMR. The preussomerins were evaluated for their antimycobacterial and antiplasmodial activities as well as cytotoxicity against KB, BC-1 and vero cell lines.


PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients.
PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; p = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR >2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; p = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; p = 0.014). In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.


Production of human B and T cell growth factors is enhanced by thymic hormones.
The thymic preparations thymosin fraction 5 (TF5) and synthetic thymosin alpha 1 (T alpha 1) were examined for their ability to enhance growth factor production by human peripheral blood mononuclear cells (PBMC). The results showed that both TF5 and T alpha 1 were capable of enhancing the production of a B cell growth factor (BCGF-12kD) and T cell growth factor (TCGF; IL-2). Enhancement by T alpha 1 could be obtained at 100-200-fold lower concentrations than that seen with TF5. In contrast, no enhancement of growth factor production was obtained with control preparations of non-thymic tissue extracts at any concentrations used. It was observed that stimulation of BCGF-12kD and IL-2 was most significantly obtained when the PBMC were activated with lectin. Furthermore, no direct effect of thymic hormones on test B and T cells was observed. These observations provide the first direct evidence that production of B cell growth factors can be enhanced by thymic hormones. In addition, these studies suggest that thymic hormones may regulate B cell responses by acting on mature activated T lymphocytes.


Fluoride determination in plasma by ion selective electrodes: a simplified method for the clinical laboratory.
A potentiometric method for the determination of fluoride (F-) in serum and plasma is proposed; it is based on a combination of the single-known-addition method and the electrode slope-by-dilution method. This procedure provides reliable results in extremely low measuring ranges down to 2.5 mug/l, where the electrode slope deviates markedly from Nernstian behaviour. In this method no electrode calibration is required and only one standard is necessary. 1 ml of plasma is sufficient for one analysis. Apart from a 5% enrichment of all samples with a concentrated total ionic strength adjustment buffer, no further preparation of the sample is required. The simplicity of the various pipetting and analytical steps, and also of the evaluation of the readings, may render this method highly suitable for the clinical laboratory. Investigations into the accuracy and precision of the method produced satisfactory results. The recovery in plasma amounted to 99.7%, even in the low measuring ranges. The discrimination capacity of the method amounts to 0.1 mug/l. With the apparatus and experimental procedures described, 18 plasma analyses per day can be performed even at low F- concentrations with which longer electrode stabilization periods are required. Storage of the plasma samples frozen at --20 degrees C for up to 8 weeks exerts no effect on the F- concentration. Problems of sample contamination and other disturbances are discussed. Determinations of normal values in 20 test subjects resulted in a mean value of 10.4 plus or minus 4.01 mug/l (Mean plus or minus S.D.). The modal value amounted to 9.5 mug/l, and the range was between 5.9 and 18.8 mug/l. The F- content of the drinking water supplied to this group of persons amounted to 180 mug/l. The importance of the method has been illustrated using a clinico-nephrological study as an example.


Management of the first-time lateral patellar dislocation.
Little guidance exists on the management of the first-time patellar dislocation. The aim of this article was to review current guidance for management of this condition. Recent meta-analyses, systematic reviews and current consensus documents relating to first-time patellar dislocation were sourced. An instructional lecture was then created and delivered at the acute knee injuries session at the British Orthopaedic Association 2019 annual conference, which was presented on behalf of the British Association for Surgery of the Knee. This article has been written based on this lecture. There is a paucity of literature relating to management of the first-time patellar dislocation. Many studies are of poor design, with inadequate follow-up, making it difficult to draw conclusions from them. However, based upon available information and consensus from working groups it is recommended that patients presenting with first-time dislocation should be assessed to ensure they have not sustained an alternative or associated injury that may require surgical intervention, be assessed and counselled for the risk of recurrent dislocation, and be referred for initial conservative treatment. Surgical stabilisation should be reserved for patients with recurrent instability. Most patients with a first-time patellar dislocation can be managed conservatively, having excluded associated injuries. Due to the poor quality of the literature, care must be taken interpreting the results of studies. It is clear that further research is required in this field.


Effect of dietary fats on hydroperoxide-induced chemiluminescence emission and eicosanoid release in the rat heart.
The effect of diets supplemented with three different fats (olive oil, sunflower oil, pork fat) on the susceptibility of the rat heart to oxidative stress and on the rate of eicosanoid release were studied. Our results show that when fatty-acid unsaturation of heart lipids is increased or vitamin E is decreased, even to a low degree, a marked enhancement of the susceptibility to hydroperoxide-induced oxidative stress (measured by chemiluminescence emission) occurs, which is associated with an increase of eicosanoid release from the heart.


TLE1 expression in malignant mesothelioma.
Malignant mesothelioma, an aggressive and often lethal tumor commonly associated with asbestos exposure, has been morphologically classified into epithelial, biphasic, and sarcomatoid subtypes. Histological distinction between biphasic or sarcomatoid mesothelioma and synovial sarcoma may be problematic in certain circumstances of intrathoracic location because of their similar clinicopathologic features, including not only their morphology but also occasional positive immunoreaction of mesothelioma markers. TLE1, which plays an important role in Wnt pathway, has been shown to be a specific marker for synovial sarcoma and diagnostically is useful; however, TLE1 expression in malignant mesotheliomas has not been fully evaluated. We immunohistochemically examined the expression of TLE1, factors related to the Wnt pathway including β-catenin and cyclin D1, and mesothelioma markers including calretinin, HBME-1, cytokeratin 5/6, and thrombomodulin in 29 malignant mesotheliomas. TLE1 was variably expressed in 28 malignant mesotheliomas regardless of histomorphological subtype with >25% of positive cells in 20 cases (69.0%). There was no evidence of association of TLE1 expression with immunoreactivity to other markers. Our study showed no or limited value of the immunohistochemical TLE1 expression in distinguishing malignant mesothelioma and synovial sarcoma.


A widespread occurrence of extra open reading frames in plant Ty3/gypsy retrotransposons.
Long terminal repeat (LTR) retrotransposons make up substantial parts of most higher plant genomes where they accumulate due to their replicative mode of transposition. Although the transposition is facilitated by proteins encoded within the gag-pol region which is common to all autonomous elements, some LTR retrotransposons were found to potentially carry an additional protein coding capacity represented by extra open reading frames located upstream or downstream of gag-pol. In this study, we performed a comprehensive in silico survey and comparative analysis of these extra open reading frames (ORFs) in the group of Ty3/gypsy LTR retrotransposons as the first step towards our understanding of their origin and function. We found that extra ORFs occur in all three major lineages of plant Ty3/gypsy elements, being the most frequent in the Tat lineage where most (77 %) of identified elements contained extra ORFs. This lineage was also characterized by the highest diversity of extra ORF arrangement (position and orientation) within the elements. On the other hand, all of these ORFs could be classified into only two broad groups based on their mutual similarities or the presence of short conserved motifs in their inferred protein sequences. In the Athila lineage, the extra ORFs were confined to the element 3' regions but they displayed much higher sequence diversity compared to those found in Tat. In the lineage of Chromoviruses the extra ORFs were relatively rare, occurring only in 5' regions of a group of elements present in a single plant family (Poaceae). In all three lineages, most extra ORFs lacked sequence similarities to characterized gene sequences or functional protein domains, except for two Athila-like elements with similarities to LOGL4 gene and part of the Chromoviruses extra ORFs that displayed partial similarity to histone H3 gene. Thus, in these cases the extra ORFs most likely originated by transduction or recombination of cellular gene sequences. In addition, the protein domain which is otherwise associated with DNA transposons have been detected in part of the Tat-like extra ORFs, pointing to their origin from an insertion event of a mobile element.


Reproductive effort in Danish mudsnails (Hydrobiidae).
The four species of Hydrobiid mudsnails found in Danish brackish water habitats are ranked with respect to reproductive effort. The biology of the species indicate that Hydrobia neglecta and Potamopyrgus jenkinsi, showing the highest reproductive effort are also more r-selected than the other species, H. ventrosa and H. ulvae.


Medication adherence in diabetes mellitus and self management practices among type-2 diabetics in Ethiopia.
Type-2 diabetes mellitus and its complication are becoming more prevalent in Ethiopia. Evidence abound that the most important predictor of reduction of morbidity and mortality due to diabetes complication is the level of glycemic control achieved. The aim is to assess adherence to anti diabetic drug therapy and self management practice among type-2 diabetic patient in Ethiopia. The study consists of two phases. A cross-sectional review of randomly selected 384 case notes of type-2 diabetic patient that attend diabetes mellitus clinic over 3 month and cross-sectional interview, with pre tested adherence and self management and monitoring tool questioner of 347 consecutive patients that attend in Jimma university specialized hospital diabetic clinic. Oral hypoglycemic agent were prescribed for 351(91.4) of the patient while insulin and oral hypoglycemic agent was prescribed in 33(8.6%). About 312 (88.9%) patients on oral hypoglycemic agent were on mono therapy, the most frequently prescribed oral hypoglycemic agent was glibenclamide 232(74.3%) and metformine 80(25.7%). Only 41.8% of the patient had adequate glycemic control. The main external factors for non adherence were lack of finance (37.1%) followed by perceived side effect of drug 29.2%. Only 6.5% patient who missed their medications disclosed to physician during consultation. The knowledge and practice of critical component of diabetes self management behavior were generally low among the patient studied. Majority of the patient with type 2 diabetes in Ethiopia are managed by OHA monotherapy mainly glybenclamide and metformine. While the current prescribing strategy do not achieve glycemic control on majority of the patient. This is due to poor adherence with the prescribed drug regimen and poor knowledge and practice of successful self management.


Accelerating Fuzzy-C Means Using an Estimated Subsample Size.
Many algorithms designed to accelerate the Fuzzy c-Means (FCM) clustering algorithm randomly sample the data. Typically, no statistical method is used to estimate the subsample size, despite the impact subsample sizes have on speed and quality. This paper introduces two new accelerated algorithms, GOFCM and MSERFCM, that use a statistical method to estimate the subsample size. GOFCM, a variant of SPFCM, also leverages progressive sampling. MSERFCM, a variant of rseFCM, gains a speedup from improved initialization. A general, novel stopping criterion for accelerated clustering is introduced. The new algorithms are compared to FCM and four accelerated variants of FCM. GOFCM's speedup was 4-47 times that of FCM and faster than SPFCM on each of the six datasets used in experiments. For five of the datasets, partitions were within 1% of those of FCM. MSERFCM's speedup was 5-26 times that of FCM and produced partitions within 3% of those of FCM on all datasets. A unique dataset, consisting of plankton images, exposed the strengths and weaknesses of many of the algorithms tested. It is shown that the new stopping criterion is effective in speeding up algorithms such as SPFCM and the final partitions are very close to those of FCM.


Techniques and results of neuroradiologic investigations of experimentally induced brain tumors in rats.
In two comparable groups of 12 adult rats at a time, the normal anatomy of the cerebral arteries and the pathologic vascular pattern of experimentally induced brain tumors was investigated angiographically. These tumors were malignant mixed gliomas which were inoculated by percutaneous puncture through the vault with a suspension of 10,000 tumor cells. The neuroradiologic examinations consisted of selective angiographies of the internal carotid artery in vivo, postmortem radiographies of cerebrovascular casts of isolated brains as well as of microangiographic and comparative histologic investigations of the tumor. The juxtaventricular localization and the extension of the tumors in the basal ganglia could be angiographically demonstrated approximately 3 to 4 weeks after the implantation of the tumor cells. Moreover, qualitative and quantitative vascular criteria of malignancy could be shown microangiographically which correlated well with the histologic findings. The effects of several therapeutic procedures such as radiotherapy, pharmacoangiography and various techniques of embolization are being studied with this experimental tumor model in order to explore the prerequisites for appropriate treatment of cerebral lesions in man.


Elevated serum silicon levels in women with silicone gel breast implants.
The metabolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13 +/- 0.07 mg/L (range 0.06-0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/L (range 0.06-0.87 mg/L) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.


Genetic linkage: sampling issues and multipoint mapping.
Genetic linkage is an important tool in determining the genetic contribution to the etiology of behavior disorders and psychiatric disease. Successful linkage studies employ large sample sizes. It is of particular relevance in psychiatric diseases, where the clinical workup is so extensive, to evaluate sample requirements critically. Recent studies indicate that extensive sampling, out to second-degree relatives, will not assist in identifying linkages although it may inflate the sample size considerably. The impact of the assumption about the mode of inheritance of the psychiatric trait and the effect of reduced penetrance are discussed. Multipoint mapping has the added advantage of using information from many markers simultaneously. This is helpful both in identifying individuals at risk to develop disease and in locating a gene with sufficient precision to determine the gene product. There are complications in applying multipoint mapping but these are generally of a technical nature and soluble. Recent suggestions for handling complications for multipoint mapping are evaluated. The correct design of the sampling procedure for selecting families and for selecting marker loci to use will greatly reduce the volume of work required for linkage studies and enhance the chances for success.


Nitrogenase reduction of carbon-containing compounds.
Nitrogenase is an enzyme found in many bacteria and archaea that catalyzes biological dinitrogen fixation, the reduction of N2 to NH3, accounting for the major input of fixed nitrogen into the biogeochemical N cycle. In addition to reducing N2 and protons, nitrogenase can reduce a number of small, non-physiological substrates. Among these alternative substrates are included a wide array of carbon-containing compounds. These compounds have provided unique insights into aspects of the nitrogenase mechanism. Recently, it was shown that carbon monoxide (CO) and carbon dioxide (CO2) can also be reduced by nitrogenase to yield hydrocarbons, opening new insights into the mechanism of small molecule activation and reduction by this complex enzyme as well as providing clues for the design of novel molecular catalysts. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems.


Influence of incubation conditions on hydrolysis efficiency and iodine enrichment in baker's yeast.
The influence of incubation conditions, enzyme type, hydrolysis time, and potassium iodide concentration on hydrolysis and iodine enrichment were studied in supernatant and pellets of Saccharomyces cervisiae hydrolysates. The type of enzyme used and incubation time significantly influence hydrolysis efficiency and protein concentration in supernatant and pellet. The highest protein hydrolysis efficiency was obtained by 24-h incubation with papain. Significantly lower values were observed for pepsin and autolysis. The potassium iodide concentration influences the iodine content of supernatant and pellet, but not hydrolysis. Iodide enrichment of supernatant and pellet depends on the concentration of iodide using during incubation. High concentration of iodide and long incubation times were the conditions for optimal iodide enrichment and high-protein hydrolysates. The optimal hydrolysis efficiency and iodine enrichment were obtained during 24-h incubation with papain in a 4.5-mM potassium iodide medium. The efficiency reached 98.22% with iodine concentrations of 2,664.91 and 9,200.67 μg/g iodine in pellet and supernatant, respectively.


The Pediatrician's Role in Protecting Children from Environmental Hazards.
Children suffer disproportionately from disease and disability due to environmental hazards, for reasons rooted in their biology. The contribution is substantial and increasingly recognized, particularly due to ever-increasing awareness of endocrine disruption. Regulatory actions can be traced directly to reductions in toxic exposures, with tangible benefits to society. Deep flaws remain in the policy framework in industrialized countries, failing to offer sufficient protection, but are even more limited in industrializing nations where the majority of chemical production and use will occur by 2030. Evidence-based steps for reducing chemical exposures associated with adverse health outcomes exist and should be incorporated into anticipatory guidance.


Sampling and analysis of volatile organics emitted from wastewater treatment plant and drain system of an industrial science park.
Volatile organic compounds (VOCs) were monitored in the different sections of a wastewater treatment plant (WWTP), the outlet of both the WWTP and rainfall water, and the downstream of the WWTP joining the river in the area or vicinity of an industrial science park located in Hsinchu, Taiwan. Levels of VOCs were determined by collecting air samples over several sampling points and analyzed using gas chromatography. Among VOCs identified in the drainage and effluent system in each season, acetone, isopropanol (IPA) and dimethyl sulfide (DMS) were the major emission species and maximum concentrations were 400.4, 22.8 and 641.2 ppbv, respectively. The ambient air and wastewater sample analysis from neighboring wastewater streams identified pollutants being discharged from unaccounted sources other than the industrial park. According to the 24h semi-continuous monitoring data (27/7/2002-29/7/2002), the total VOC concentration was an average of 93 ppbv (acetone contributed approximately 78%) with a dramatic variation during the day and night. The emission rate of measured VOCs estimated using fixed box model projected an average of 2-4 microg m(-2) h(-1)) during the day and 9-17 microg m(-2) h(-1) during the night. In addition, the isopleth maps show that the acetone and DMS emissions influence adversely the nearby residential area located at less than 100 m downwind from the plant. Eventually, based on this study, an on-line monitoring and alerting system could be built for a long-term performance, and with regular information on the varying pollutants over time construction of a green strategy and creation of a sustainable environment can be achieved.