Tp53 and its potential therapeutic role as a target in bladder cancer.
Despite more than 30 years of research on p53 resulting in >50,000 publications, we are now beginning to figure out the complexity of the p53 pathway, gene ontology and conformational structure of the molecule. Recent years brought great advances in p53 related drugs and the potencial ways in which p53 is inactivated in cancer. Areas covered: We searched for related publications on Pubmed and ClinicalTrial.gov using the following keywords 'p53, Tp53, p53 and bladder cancer, p53 and therapeutic target'. Relevant articles improved the understanding on p53 pathways and their potential as candidate to targeted therapy in bladder cancer. Expert opinion: Novel strategies developed to restore the function of mutants with chemical chaperones or by using compounds to improved pharmacokinetic properties are in development with potential to be applied in the oncology clinic. Other strategies targeting aberrantly overexpressed p53 regulators with wild-type p53 are also an active area of research. In particular, studies inhibiting the interaction of p53 with its negative regulators MDMX and MDM2 are an important field in drug discovery. Small molecules for inhibition of MDM2 are now in clinical trials process. However, personalized anticancer therapy might eventually advance through analyses of p53 status in cancer patients.


Distribution of trace elements in sediment and soil from river Vardar Basin, Macedonia/Greece.
A systematic study was carried out to investigate the distribution of 59 elements in the sediment and soil samples collected from the river Vardar (Republic of Macedonia and Greece) and its major tributaries. The samples were collected from 28 sampling sites. Analyses were performed by inductively coupled plasma-mass spectrometry. R-mode factor analysis (FA) was used to identify and characterise element associations. Seven associations of elements were determined by the method of multivariate statistics. Every factor (Factors 1-3 and 6 and 7 as geogenic and Factors 4 and 5 as anthropogenic associations of elements) are examined and explained separately. The distribution of various elements showed that there is a presence of anthropogenic elements (Ag, Cd, Cu, Ge, Pb, Sn and Zn) introduced in the river sediments and soils from the mining, metallurgical, industrial and agricultural activities in Vardar River Basin, which covers most of the Republic of Macedonia and Central-northern part of Greece.


Epigenetic Control of Apolipoprotein E Expression Mediates Gender-Specific Hematopoietic Regulation.
Epigenetic alterations play a central role in the control of normal and malignant blood cell development. We demonstrate here that expression of a truncated DNA methyltransferase 3B isoform DNMT3B7, which has been shown to alter cellular epigenetic patterns, decreases the overall number of hematopoietic stem and progenitor cells (HSPCs), and markedly diminishes blood cell reconstitution within the female hormonal microenvironment. Gene expression profiling of HSPCs isolated from DNMT3B7 transgenic embryos identified Apolipoprotein E (Apoe) as overexpressed. The CpG island controlling Apoe expression had lower levels of modified cytosines in DNMT3B7 transgenic HSPCs, corresponding with the observed increase in gene expression. Furthermore, we observed that spleens and bone marrows of female mice transplanted with DNMT3B7 transgenic HSPCs express very high levels of Apoe. Finally, the introduction of Apoe-overexpressing HSPCs into male recipients decreased bone marrow engraftment, recapitulating our original observations in female recipients. Our work reveals a dynamic interplay between the intrinsic epigenetic changes in HSPCs and extrinsic endocrine factors acting on these cells to regulate the efficiency of HSPC engraftment and reconstitution. We have identified a novel mechanism by which gender-specific hormones modulate HSPC function, which could serve as a target for augmenting hematopoiesis in cases with limited HSC functionality.


Neutron RBEs for mouse skin at low doses per fraction.
The effect of low doses of 240 kVp X rays or of 3 MeV neutrons has been investigated using skin reactions on mouse feet as the biological system. Eight or nine repeated small doses of radiation were used, followed by graded "top-up" doses to bring the reactions into a detectable range. By comparing dose-response curves, the RBE has been determined for neutron doses per fraction ranging from 0.25-1.0 Gy. The data are consistent with a limiting RBE of between 7 and 10 at very low doses. A review of other published RBE values for low doses per fraction shows a wide range of RBEs . Very few studies show a plateau value for the RBE. These findings are more consistent with dose-response data that fit a linear-quadratic model than with a multitarget single-hit model.


Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity?
Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.


Regulation of cancer-related pathways by protein NEDDylation and strategies for the use of NEDD8 inhibitors in the clinic.
Post-translational modification of proteins with ubiquitin and ubiquitin-like molecules (UBLs) controls a vast if not every biological process in the cell. It is not surprising that deregulation in ubiquitin and UBL signalling has been implicated in the pathogenesis of many diseases and that these pathways are considered as major targets for therapeutic intervention. In this review, we summarise recent advances in our understanding of the role of the UBL neural precursor cell expressed developmentally downregulated-8 (NEDD8) in cancer-related processes and potential strategies for the use of NEDD8 inhibitors as chemotherapeutics.


Semisupervised Seizure Prediction in Scalp EEG Using Consistency Regularization.
Early prediction of epilepsy seizures can warn the patients to take precautions and improve their lives significantly. In recent years, deep learning has become increasingly predominant in seizure prediction. However, existing deep learning-based approaches in this field require a great deal of labeled data to guarantee performance. At the same time, labeling EEG signals does require the expertise of an experienced pathologist and is incredibly time-consuming. To address this issue, we propose a novel Consistency-based Semisupervised Seizure Prediction Model (CSSPM), where only a fraction of training data is labeled. Our method is based on the principle of consistency regularization, which underlines that a robust model should maintain consistent results for the same input under extra perturbations. Specifically, by using stochastic augmentation and dropout, we consider the entire neural network as a stochastic model and apply a consistency constraint to penalize the difference between the current prediction and previous predictions. In this way, unlabeled data could be fully utilized to improve the decision boundary and enhance prediction performance. Compared with existing studies requiring all training data to be labeled, the proposed method only needs a small portion of data to be labeled while still achieving satisfactory results. Our method provides a promising solution to alleviate the labeling cost for real-world applications.


Prescription Stimulant Use and Hospitalization for Psychosis or Mania: A Population-Based Study.
Small studies suggest that prescription stimulants can precipitate psychosis and mania. We conducted a population-based case-crossover study to examine whether hospitalization for psychosis or mania was associated with initiation of stimulant therapy. Between October 1, 1999 and March 31, 2013, we studied 12,856 young people who received a stimulant prescription and were subsequently hospitalized for psychosis or mania. Of these, 183 commenced treatment during 1 of 2 prespecified 60-day intervals (defined as the "risk interval" and "control interval," respectively) prior to admission. We found that stimulant initiation was associated with an increased risk of hospitalization for psychosis or mania in the subsequent 60 days (odds ratio, 1.86; 95% confidence interval, 1.39-2.56). The risk was marginally higher in patients treated with antipsychotic drugs (odds ratio, 2.06; 95% confidence interval, 1.38-3.28), but remained in patients with no such history (odds ratio, 1.66; 95% confidence interval, 1.09-2.66). One third of subjects received another stimulant prescription after hospital discharge. Of these, 45% were readmitted with psychosis or mania shortly thereafter. We conclude that initiation of prescription stimulants is associated with an increased risk of hospitalization for psychosis or mania. Resumption of therapy is common, which may reflect a lack of awareness of the potential causative role of these drugs.


Two roles for Rad50 in telomere maintenance.
We describe two roles for the Rad50 protein in telomere maintenance and the protection of chromosome ends. Using fluorescence in situ hybridisation (FISH) and fibre-FISH analyses, we show that absence of AtRad50 protein leads to rapid shortening of a subpopulation of chromosome ends and subsequently chromosome-end fusions lacking telomeric repeats. In the absence of telomerase, mutation of atrad50 has a synergistic effect on the number of chromosome end fusions. Surprisingly, this 'deprotection' of the shortened telomeres does not result in increased exonucleolytic degradation, but in a higher proportion of anaphase bridges containing telomeric repeats in atrad50/tert plants, compared to tert mutant plants. Absence of AtRad50 thus facilitates the action of recombination on these shortened telomeres. We propose that this protective role of Rad50 protein on shortened telomeres results from its action in constraining recombination to sister chromatids and thus avoiding end-to-end interactions.


Red blood cell alloimmunisation in multi-transfused patients from an haemodialysis service in Burkina Faso.
In Burkina Faso, red blood cell (RBC) transfusion remains the crucial anaemia treatment following chronic renal failure (CRF) as erythropoietin and its analogues are unavailable. However, blood group matching beyond the ABO and Rhesus is not common in Burkina Faso. Thus, alloimmunisation is a potential issue for transfused patients. Our study aimed to identify anti-erythrocyte antibodies in multi-transfused CRF patients at the Yalgado Ouedraogo Teaching Hospital, Ouagadougou, Burkina Faso. This cross-sectional study, conducted from October 2018 to November 2019, included CRF patients who had received at least two RBC units. We screened patients for the presence of RBC antibodies using three commercial Cells panels and identified antibody specificities for positive screenings using 11 Cells panels for an indirect antiglobulin test (IAT) in a low ionic strength microcolumn gel-card system. Two hundred and thirty-five patients (45.1% female; average age: 41.5 years) were included. The median number of blood units received per patient was 10 (interquartile range: 5-20). The overall alloimmunisation rate was 5.9% (14/235). Antibodies identified included: anti-D (1 case), anti-C (1 case), anti-D+C (4 cases), anti-CW (1 case), anti-E (1 case), anti-S (1 case) and anti-Lea (1 case). In four positive patients, the specificity of the antibodies was indeterminate. No risk factors were associated with alloimmunisation. In Burkina Faso, screening for RBC alloantibodies should be mandated for patients at risk. The high rate of indeterminate antibodies suggests the need to develop a local RBC antibody panel adapted to the local population.


Severe child form of primary hyperoxaluria type 2 - a case report revealing consequence of GRHPR deficiency on metabolism.
Primary hyperoxaluria type 2 is a rare monogenic disorder inherited in an autosomal recessive pattern. It results from the absence of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR). As a consequence of deficient enzyme activity, excessive amounts of oxalate and L-glycerate are excreted in the urine, and are a source for the formation of calcium oxalate stones that result in recurrent nephrolithiasis and less frequently nephrocalcinosis. We report a case of a 10-month-old patient diagnosed with urolithiasis. Screening of inborn errors of metabolism, including the performance of GC/MS urine organic acid profiling and HPLC amino acid profiling, showed abnormalities, which suggested deficiency of GRHPR enzyme. Additional metabolic disturbances observed in the patient led us to seek other genetic determinants and the elucidation of these findings. Besides the elevated excretion of 3-OH-butyrate, adipic acid, which are typical marks of ketosis, other metabolites such as 3-aminoisobutyric acid, 3-hydroxyisobutyric acid, 3-hydroxypropionic acid and 2-ethyl-3-hydroxypropionic acids were observed in increased amounts in the urine. Direct sequencing of the GRHPR gene revealed novel mutation, described for the first time in this article c.454dup (p.Thr152Asnfs*39) in homozygous form. The frequent nucleotide variants were found in AGXT2 gene. The study presents metabolomic and molecular-genetic findings in a patient with PH2. Mutation analysis broadens the allelic spectrum of the GRHPR gene to include a novel c.454dup mutation that causes the truncation of the GRHPR protein and loss of its two functional domains. We also evaluated whether nucleotide variants in the AGXT2 gene could influence the biochemical profile in PH2 and the overproduction of metabolites, especially in ketosis. We suppose that some metabolomic changes might be explained by the inhibition of the MMSADH enzyme by metabolites that increase as a consequence of GRHPR and AGXT2 enzyme deficiency. Several facts support an assumption that catabolic conditions in our patient could worsen the degree of hyperoxaluria and glyceric aciduria as a consequence of the elevated production of free amino acids and their intermediary products.


The production of placental protein 14 and interleukin 6 by human endometrial cells in culture.
Epithelial and stromal cells prepared from endometrium taken at different times in the menstrual cycle were grown in primary culture and the production of placental protein 14 (PP14) and interleukin-6 (IL6) measured. Only the epithelial cells produced PP14. Epithelial cells from endometrium in the late secretory phase produced significantly greater amounts of PP14 (42 +/- 5.8 ng/24 h) compared with that produced by cells from early secretory and proliferative endometrium (16 +/- 1.7 and 11 +/- 1.9 ng/24 h respectively). PP14 production by cells from endometrium at all stages in the cycle was increased by progesterone, or progesterone and oestradiol together, while oestradiol alone had no effect on PP14 production. The greatest stimulation was seen during the early secretory phase when stimulated levels of PP14 reached those obtained during the late secretory phase. IL6 production by epithelial cells also varied depending on the phase of the menstrual cycle. More IL6 was produced by the cells prepared from the endometrium in the proliferative phase (10.9 +/- 0.56 ng/24 h) compared with that produced by cells from early and late secretory endometrium (2.5 +/- 0.19 and 1.45 +/- 0.09 ng/24 h respectively). Addition of steroids to the media stimulated the production of IL6 by cells from proliferative and early secretory endometrium but decreased IL6 production from cells in the late secretory phase. IL6 was also produced by stromal cells but could only be detected in supernatants of cells prepared from late secretory endometrium, and the amounts produced (0.8 +/- 0.09 ng/24 h) were less than that produced by epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Comprehensive Analysis of the Fungal Microbiota of the Human External Auditory Canal Using Pyrosequencing.
We previously reported that the Malassezia microbiota of the external auditory canal were composed principally of Malassezia slooffiae and Malassezia restricta. In the present study, the fungal microbiota of the external auditory canal were comprehensively analyzed by pyrosequencing on an FLX-454 platform. Of 17 samples tested, the fungal microbiota of 14 samples were composed of > 90% Malassezia species; either M. slooffiae or M. restricta was abundant in individual samples. The external auditory canal exhibits a lower fungal diversity than do other bodily sites.


Diagnostic value of Elisa serological tests in childhood tuberculosis.
Two separate studies (study I and study II) were conducted to evaluate the efficacy of ELISA serological test for the detection of IgG antibodies against specific glycolipid antigen (PGLTb1) and ESAT 6 antigen of Mycobacterium tuberculosis, respectively. These results were compared with bacteriological tests [Ziehl Neelson (ZN) staining for acid-fast bacilli and culture on Lowenstein Jensen (LJ) medium] and polymerase chain reaction (PCR) targeting IS6110 sequence. Both studies were carried out on children with pulmonary, central nervous system, lymph node, and gastrointestinal tuberculosis along with matching controls (65 cases and 27 controls for study I and 83 cases and 22 controls for study II). Informed consents of their parents or guardians were taken. They were subjected to clinical examination, relevant laboratory investigations, tuberculin test and chest radiograph. Relevant body fluids were subjected to bacteriological tests and PCR. Sera samples were analyzed for antibodies against PGLTbl and ESAT 6 antigen in study I and study II, respectively. ELISA tests showed a significantly higher sensitivity (49% study I; 53%, study II) as compared with LJ medium culture method (15.4%, study I; 28.9% study II) and ZN staining (27.7%, study I; 20.5%, study II) in all patients (p < 0.05). The results were comparable with PCR (40%, study I; 42.2% study II). Specificity of ELISA test was 100% in all the patients except in those with pulmonary disease (92.8%, study I; 84.8%, study II). In view of the convenience, low cost and comparable sensitivity with PCR, these ELISA tests have a promising future in the diagnosis of childhood tuberculosis.


Functional recovery results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE).
ConstaTRE is an open-label, randomised, controlled, relapse prevention trial in patients with stable schizophrenia or schizoaffective disorder switched to risperidone long-acting injectable (RLAI) or oral quetiapine, and was designed to test the hypothesis that injectable antipsychotic treatment with risperidone would be more effective than oral therapy with quetiapine. Here we report the functional recovery results from the ConstaTRE trial. Clinically stable adults previously treated with oral risperidone, olanzapine, or oral first-generation antipsychotics were randomised to RLAI or quetiapine for 24 months. Functional recovery was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS) and two quality-of-life (QoL) measures [Medical Outcomes Survey Short Form-12 (SF-12) and Schizophrenia Quality-of-Life Scale Revision 4 (SQLS-R4)]. A total of 666 patients were randomised and treated with RLAI (n = 329) or quetiapine (n = 337). Relapse occurred in 16.5% RLAI and 31.3% quetiapine patients. Significant improvements in SOFAS, SF-12, and SQLS-R4 scores were observed from baseline to month 24 with both RLAI and quetiapine. At months 6, and 12, and endpoint, improvement in SOFAS score was significantly greater for RLAI than quetiapine (p < 0.05). Among patients with stable schizophrenia or schizoaffective disorder, the likelihood of functional recovery appears to be higher in those switching to RLAI than to quetiapine, although improvements in functional status and QoL were observed with both treatments.


[Behavior of fetal hemoglobin during isoelectric focusing].
The results of isoelectrofusing applied to haemolysates of newborns, a case of beta thalassaemia and a case of hereditary persistence of fetal haemoglobin show that fetal haemoglobin F(alpha 2 gamma 2) can be oxidized into two products. The first corresponds to fetal ferrihaemoglobin (alpha +2 gamma +2), the oxidation product of the four Fe atoms of the molecule. The second, which is called fetal intermedial methaemoglobin, and has the same pH as adult ferrihaemoglobin A1, represents probably a product of partial oxydation of fetal haemoglobin.


Malignant ameloblastoma with pulmonary metastasis and hypercalcemia. Report of an autopsy case and review of the literature.
A case of malignant ameloblastoma with hypercalcemia in a 67-year-old Japanese woman is presented. The tumor of the maxilla was removed and diagnosed as a follicular ameloblastoma. The tumor recurred in the lower orbita-zygoma region, and multiple tumors of the lungs and hypercalcemia were detected eight months after the second operation. The recurrent tumor resembled the primary tumor but was less well differentiated. Autopsy revealed widespread lung metastasis of the malignant ameloblastoma, nephrocalcinosis, and sigmoid colon cancer. Histologic examination showed the metastatic ameloblastoma to be composed of nests and strands of basaloid and spindle-shaped cells surrounded by columnar cells arranged in palisade formation, with focal areas of squamous differentiation and occasional cystic degeneration. Only two cases of malignant ameloblastoma with hypercalcemia have previously been reported. This is the first case of malignant ameloblastoma with hypercalcemia and sigmoid colon cancer. In addition, prostaglandin E2 assay revealed that ameloblastoma produces prostaglandin E2, which results in hypercalcemia.


Avoiding false discovery in biomarker research.
Human tyrosine-protein phosphatase non-receptor type substrate 1α (SIRPA) is a surface marker identified in cardiomyocytes differentiated from human embryonic stem cells. Our objective was to determine if circulating SIRPA levels can serve as a biomarker of cardiac injury in children undergoing open heart surgery. Paired pre- and post-operative serum samples from 48 pediatric patients undergoing open heart surgery and from 6 pediatric patients undergoing non-cardiac surgery (controls) were tested for SIRPA protein levels using commercially available SIRPA ELISA kits from two manufacturers. Post-operative SIRPA concentrations were significantly higher in patients after cardiac surgery compared to non-cardiac surgery when tested using SIRPA ELISA kits from both manufacturers. To verify the identity of the protein detected, recombinant human SIRPA protein (rhSIRPA) was tested on both ELISA kits. The calibrator from both ELISA kits was analyzed by Western blot as well as by Mass Spectrometry (MS). Western blot analysis of calibrators from both kits did not identity SIRPA. MS analysis of calibrators from both ELISA kits identified several inflammatory markers and albumin but no SIRPA was detected. We conclude that commercially available ELISA kits for SIRPA give false-positive results. Verifying protein identity using robust protein characterization is critical to avoid false biomarker discovery when using commercial ELISA kits.


[Effect of acute phosgene inhalation on antioxidant enzymes, nitric oxide and nitric-oxide synthase in rats].
To study the effect of acute phosgene inhalation on the antioxidant enzymes, nitric oxide (NO) and nitric oxide synthase (NOS) in rats. Phosgene was produced by decomposing bis (trichdomethyl) carbonate in the presence of N,N-dimethyl formamide. SD rats were randomly divided into two groups: control and phosgene exposure groups. In a special experimental device with equipment modulating the gas flow, phosgene exposed rats inhaled phosgene quantitatively for five minutes. Two hours later, all the rats were sacrificed and the ratio of wet weight to dried weight of lung (WW/DW) was calculated. Peripheral blood, serum and liver were collected to examine the activities of antioxidant enzymes including glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), NOS, and NO level. The total content of proteins were also determined. The WW/DW ratio of lung in phosgene exposure group was much higher than that in control group (P < 0.01). The activities of GST in serum and liver of phosgene exposure group increased significantly (P < 0.05). The activities of SOD, CAT, GSHPx and NOS in serum or blood and liver of phosgene exposure group were also increased significantly (P < 0.05). But the content of NO was significantly decreased (P < 0.01). Acute phosgene inhalation may cause a dramatically changes of several antioxidant enzyme activities, and acute injury of liver to some extent in rats. The latter is related to reactive oxygen species. But the elevation of antioxidant enzyme activities suggests that antioxidative treatment for acute phosgene poisoning should not be considered first.


Timing of beta oscillatory synchronization and temporal prediction of upcoming stimuli.
Modulations of beta oscillatory power serve a predictive role, in preparation of future actions. It is well known that beta amplitude decreases prior to voluntary movements and expected tactile stimuli. Paradoxically, recent studies have reported a beta amplitude increase prior to expected visual and auditory stimuli. Moreover, it has been suggested that, in isochronic stimulus series, the rising beta slope is adjusted to the duration of the interstimulus interval. We investigated the characteristics of such timing related pre-stimulus beta power increases using visual stimulus sequences that were presented at three regular rates (0.61, 0.74 and 0.95Hz). EEG was recorded from twenty participants while they attended the sequences by performing a clock reading task. Time-frequency analyses showed a consistent pattern of beta modulation: the post-stimulus beta power decrease was followed by a steep increase. Contrary to recent views, we found that the peaks of beta power, for the three presentation rates, were reached at a similar latency post-stimulus, instead of a fixed interval preceding the next stimulus. This demonstrates that, at interstimulus intervals between 1-2s, beta synchronization slopes are not modulated by timing mechanisms related to prediction of upcoming stimuli. We reconcile the discrepant results by proposing that when shorter interval durations are used, as in previous studies, beta resynchronization is interrupted by the presentation of a new stimulus, making it seem as if beta power peaks prior to upcoming stimuli. We emphasize caution with respect to the notion that the timing of beta synchronization is an expression of predictive timing.


The incorporation of acetate and palmitate into lipids by human platelets.
The optimal conditions for the incorporation of acetate-1-(14)C and palmitic acid-1-(14)C into platelet lipids have been described. In buffer incubations with acetate there was a sharp pH optimum at 6.8; in plasma incubations, there was a broad pH optimum between 6.8-7.4. Maximal incorporation of acetate occurred at a final concentration of 1.5 mmoles/liter. In buffer, no labeled lipids were released from platelets into the medium. In plasma, 40% of newly formed lipids was recovered in the plasma. 75% of the incorporated acetate could be recovered in ceramide, lecithin, and free fatty acids. Platelet fatty acids were formed both by de novo synthesis and chain elongation. The fatty acids formed by de novo synthesis exchanged with plasma free fatty acids. In buffer incubations no turnover of newly labeled lipids occurred, but in the plasma incubations exchange of newly labeled lecithin with plasma lipids was demonstrable. Palmitic acid-1-(14)C added to plasma was incorporated into platelet lipids. The distribution among the lipid classes of palmitate taken up from plasma was the same as that of palmitate formed intracellularly by de novo synthesis.


Arterial oxygen tension of patients with abnormal lungs treated with hyperbaric oxygen is greater than predicted.
The arterial oxygen (O2) tension (PaO2) of patients with normal gas exchange treated with hyperbaric oxygen (HBO2) can be predicted from their pre-HBO2 arterial to alveolar O2 tension ratio (a/A) which remains constant up to a PaO2 of 2,000 mm Hg. We observed that the a/A could not be used to predict the PaO2 of patients with impaired gas exchange (reduced pre-HBO2 a/As) treated with HBO2. Our study provides information about the PaO2 of patients with abnormal lungs treated with HBO2. For clinical reasons, we measured the PaO2 of 24 patients treated with HBO2. We obtained arterial blood gas values from patients with lung dysfunction (a/A < 0.75) prior to, during, and after HBO2. The pre-HBO2 a/A = 0.45 +/- 0.17 (mean +/- 1 SD). During HBO2 the a/A ranged from 0.7 to 0.8 depending on chamber pressure and returned to the pre-HBO2 baseline after HBO2. We conclude the following: (1) The hyperbaric PaO2s of patients with a/A < 0.75 is greater than expected. (2) However, the PaO2 is lower than in patients with normal lung function (a/A > 0.75). Possible explanations include improvement in ventilation/perfusion matching, reduction of venous admixture, and/or extra-alveolar uptake of O2. (3) Exposures to HBO2 treatment pressures greater than recommended by existing protocols may be required in patients with impaired transfer of O2 across the lung to achieve PaO2s similar to patients with normal lung function treated with HBO2.


Prevalence of hypertension among type 2 diabetes mellitus patients in China: a systematic review and meta-analysis.
This study aimed to estimate the prevalence of hypertension in Chinese patients with type 2 diabetes mellitus (T2DM) using the results of a regional study. The studies were reviewed using PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine, Wan Fang Data and Chinese Science Citation Database. After screening articles and data extraction, Stata V.16 was used for statistical analysis. This study was registered in the Prospective Register Systematic Reviews (CRD42020170649). A total of 2126 articles were identified, and nine papers were finally included. Random-effects modelling showed that the pooled prevalence of hypertension among Chinese patients with T2DM was 54% (95% CI 47 to 61%). Subgroup analysis showed that the prevalence in men (59.8%; 95% CI 49.0 to 70.7%) was higher than that in women (40.2%; 95% CI 29.3 to 59.2%). The prevalence in North China was higher than that in East China. The prevalence in institution-based settings (56%; 95% CI 48 to 64%) was higher than that in community-based settings (51%; 95% CI 34 to 69%). Appropriate preventive measures should be undertaken, such as health education, to control and reduce the risk of hypertension in diabetic patients and reduce the burden of cardiovascular disease.


Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer.
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression. Serum kynurenine levels as well as tumoral IDO1 expression were lower in patients with ER-positive than ER-negative tumors and an inverse relationship between IDO1 and estrogen receptor mRNA was observed across 14 breast cancer data sets. Analysis of whole genome bisulfite sequencing, 450k, MassARRAY and pyrosequencing data revealed that the IDO1 promoter is hypermethylated in ER-positive compared with ER-negative breast cancer. Reduced induction of IDO1 was also observed in human ER-positive breast cancer cell lines. IDO1 induction was enhanced upon DNA demethylation in ER-positive but not in ER-negative cells and methylation of an IDO1 promoter construct reduced IDO1 expression, suggesting that enhanced methylation of the IDO1 promoter suppresses IDO1 in ER-positive breast cancer. The association of ER overexpression with epigenetic downregulation of IDO1 appears to be a particular feature of breast cancer as IDO1 was not suppressed by IDO1 promoter hypermethylation in the presence of high ER expression in cervical or endometrial cancer.


The Severity of Acute Illness and Functional Trajectories in Hospitalized Older Medical Patients.
Acute diseases and hospitalization are associated with functional deterioration in older persons. Although most of the functional decline occurs before hospitalization in response to the acute diseases, the role played by comorbidity in the functional trajectories around hospitalization is unclear. Observational prospective study of 696 elderly individuals hospitalized in two Italian general medicine wards. Functional status of the elderly patients at 2 weeks before hospitalization (baseline), at hospital admission, and at discharge was measured by the Barthel Index. Comorbidity was measured at admission by the Geriatric Index of Comorbidity (GIC), a tool mostly based on illness severity. The association of GIC with changes in functional status before hospitalization (between baseline and admission), during hospitalization (between admission and discharge), and in the overall period between baseline and discharge was assessed by logistic regression analyses. Hospitalization-associated disability (HAD) was defined as a functional decline between baseline and discharge. Illness severity (GIC 3-4 vs 1-2: odds ratio [OR] 2.2, 95% CI [confidence interval] 1.5-3.3, p < .0001) and older age significantly predicted prehospital functional decline (between baseline and admission). Illness severity (OR 1.9, 95% CI 1.2-3, p = .004) and older age were also predictive of HAD, even after adjustment for each coded primary discharge diagnosis. After adjustment for the occurrence of prehospital functional decline, however, illness severity and older age were not predictive of HAD anymore. The severity of illnesses was strongly associated with adverse functional outcomes around hospitalization, but frailty, intended as functional vulnerability to the acute disease before hospitalization, was a stronger predictor of HAD than illness severity and age.


Contribution of visuospatial attention, short-term memory and executive functions to performance in number interval bisection.
Number interval bisection consists of estimating the mid-number within a pair (1-9=>5). Healthy adults and right-brain damage patients can show biased performance in this task, underestimating and overestimating the mid-number, respectively. The role of visuospatial attention during this task, and its interplay with other cognitive abilities (e.g., working memory) is still object of debate. In this study we explored the relation between visuospatial attention and individual differences in working memory and executive functions during number interval bisection. To manipulate the deployment of visuospatial attention, healthy participants tracked a dot moving to the left or moving to the right while bisecting numerical intervals. We also collected information concerning verbal and visuospatial short-term memory span, and concerning verbal and visuospatial fluency scores. Beside replicating what is typically observed in this task (e.g., underestimation bias), a correlation was observed between verbal short-term memory and bisection bias, and an interesting relation between performance in the number interval bisection, verbal short-term memory, and visuospatial attention. Specifically, performance of those participants with low verbal span was affected by the direction of the moving dot, underestimating at a larger extent when the dot moved leftward than rightward. Finally, it was also observed that participants' verbal fluency ability contributed in the generation of biases in the numerical task. The finding of the involvement of abilities belonging to the verbal domain contributes to unveil the multi-componential nature of number interval bisection. Considering the debate on the nature of number interval bisection and its use in the clinical assessment of deficits following brain damage, this finding may be interesting also from a clinical perspective.


Sodium Correction Practice and Clinical Outcomes in Profound Hyponatremia.
To assess the epidemiology of nonoptimal hyponatremia correction and to identify associated morbidity and in-hospital mortality. An electronic medical record search identified all patients admitted with profound hyponatremia (sodium <120 mmol/L) from January 1, 2008, through December 31, 2012. Patients were classified as having optimally or nonoptimally corrected hyponatremia at 24 hours after admission. Optimal correction was defined as sodium correction in 24 hours of 6 through 10 mmol/L. We investigated the association between sodium correction and demographic and outcome variables, including occurrence of osmotic demyelination syndrome (ODS). Baseline characteristics by correction outcome categories were compared using the Kruskal-Wallis test for continuous variables and the χ(2) test for categorical variables. Odds ratios for in-hospital mortality between groups were assessed using logistic regression. Adjusted differences in hospital length of stay (LOS) and intensive care unit (ICU) LOS were assessed using the Dunnett 2-tailed t test. A total of 412 patients satisfied inclusion criteria of whom 174 (42.2%) were admitted to the ICU. A total of 211 (51.2%) had optimal correction of their hyponatremia at 24 hours, 87 (21.1%) had undercorrected hyponatremia, and 114 (27.9%) had overcorrected hyponatremia. Both patient factors and treatment factors were associated with nonoptimal correction. There was a single case of ODS. Overcorrection was not associated with in-hospital mortality or ICU LOS. When adjusted for patient factors, undercorrection of profound hyponatremia was associated with an increase in hospital LOS (9.3 days; 95% CI, 1.9-16.7 days). Nonoptimal correction of profound hyponatremia is common. Fortunately, nonoptimal correction is associated with serious morbidity only infrequently.


Nonresective treatments for uterine fibroids: a systematic review of uterine and fibroid volume reductions.
Patients are increasingly seeking uterus-preserving, minimally invasive treatments for symptomatic uterine fibroids. This has led to a greater use of nonresective treatments such as uterine artery embolization (UAE), focused ultrasound (FUS) and more recently, radiofrequency ablation (RFA) of fibroids. This systematic review, following PRISMA guidelines, examines the change in uterine and fibroid volumes associated with UAE, FUS, and RFA. Pubmed and MedlinePlus databases were searched from 1956 to 2016. The keywords used were 'radiofrequency ablation,' 'magnetic resonance guided focused ultrasound,' 'ultrasound guided focused ultrasound', 'uterine artery embolization,' 'uterine fibroid embolization,' and 'leiomyoma' or 'fibroid'. Publications with at least 20 patients were included. Data were collected and analyzed using Microsoft Excel® (Microsoft Corporation, Redmond, WA) software. Eighty-one relevant papers were identified: 52 related to UAE, 11 to RFA, 17 to FUS, 1 compared UAE and FUS. We report the published uterine volume and fibroid volume changes seen in these studies at 1 to 36 months. The pooled fibroid volume reductions at six months seen with RFA were 70%, UAE 54% and FUS 32%. All three types of nonresective treatment result in fibroid volume reduction. However, fibroid volume reduction is most marked with RFA, with UAE resulting in the next most volume reduction. Additional larger cohort studies, including those that are randomized and/or comparative, would enable definitive conclusions. This is the first systematic review comparing uterine and fibroid volume reduction after RFA, UAE and MRgFUS.


Effects of acute and chronic L-arginine treatment in experimental hyperuricemia.
Experimental hyperuricemia (HU) results in preglomerular arteriolopathy, cortical vasoconstriction, and glomerular hypertension. Recently, uric acid has been shown to induce endothelial dysfunction. We therefore studied the effect of acute and chronic administration of l-arginine (a substrate for endothelial nitric oxide synthase) on the renal hemodynamic and vascular structural alterations induced by HU. To induce HU, oxonic acid (OA; 750 mg.kg(-1).day(-1)) was administered in male Sprague-Dawley rats. To study the acute effect of arginine, nine rats received l-arginine (l-Arg; 15 mg.kg(-1).min(-1)) during micropuncture. To elucidate the chronic effect of l-Arg, OA + 1% l-Arg (n = 8) and OA + 2.5% l-Arg (n = 6; drinking water) were evaluated throughout the 5-wk period. Eight normal control (N), and eight OA, rats were also studied. Kidneys were fixed by perfusion and afferent arteriole morphology was evaluated. HU rats developed the renal functional and structural alterations described and had suppressed urinary excretion of NO(2)(-)/NO(3)(-). Acute stimulation of nitric oxide (NO) synthesis markedly increased urinary NO(2)(-)/NO(3)(-), lowered systemic blood pressure, and relieved cortical vasoconstriction despite a significant increment of glomerular hypertension and afferent arteriole damage. Increasing doses of chronic l-Arg were associated with increasing excretion of urinary NO(2)(-)/NO(3)(-), reduction of systemic hypertension, and prevention of cortical vasoconstriction (2.5% l-Arg). In addition, both doses prevented glomerular hypertension and preglomerular arteriolopathy. Thus an acute relief of renal vasoconstriction in the setting of afferent arteriole damage cannot reverse glomerular hypertension, likely due to impairment in preglomerular autoregulation. On the other hand, chronic l-Arg preserved arteriolar structures probably mediated by the antiproliferative effect of NO on vascular smooth muscle cells.


Chemical and electronic structure imaging of graphene on Cu: a NanoARPES study.
Electronic structure, which describes the distribution of electronic states in reciprocal space, is one of the most fundamental concepts in condensed matter physics, since it determines the electrical, optical and magnetic behaviours of materials. Graphene has great promise for both fundamental physics and future applications. Chemical vapour deposition (CVD) is currently the dominant technology for its scaled growth on metal foils. The polycrystalline nature of metal foil makes NanoARPES, one energy-momentum dispersion probe with spatial resolution down to a few tens of nanometers, a unique tool to study the intrinsic electronic structure of polycrystalline graphene films. In this topical review, we present the latest NanoARPES studies on graphene grains and films grown on copper foil by CVD. The comprehensive chemical and electronic images probed by NanoARPES provide deep insight about graphene and point out potential ways to functionalize graphene properties. This knowledge may stimulate us to look into the future of this field from both the material synthesis and the instrumental characterisation.


Parathyroid apoplexy manifesting as fever of unknown origin.
To describe a rare clinical presentation of necrosis of a parathyroid adenoma, manifesting as fever of unknown origin. We present a case report, including detailed clinical and laboratory data, of a patient with previously undiagnosed primary hyperparathyroidism in whom necrosis of a parathyroid adenoma developed during a psychiatric admission for depression. A 40-year-old woman was admitted with severe depression. During her hospitalization, she was found to have osteitis fibrosa cystica, pathologic fractures of her left femur, and primary hyperparathyroidism. Shortly after her admission, spontaneous necrosis of her parathyroid adenoma developed, in association with high-grade fever, acute hypercalcemic crisis, neck pain, hypophonia, and shortness of breath. Findings on extensive evaluation of the fever remained unremarkable, with persistent high-grade temperatures that resolved postoperatively. Spontaneous necrosis of a parathyroid adenoma is a rare but well-documented complication of primary hyperparathyroidism. Fever, a previously undocumented associated finding, might be a part of the clinical syndrome of this complication.


Adsorption-induced changes in ribonuclease A structure and enzymatic activity on solid surfaces.
Ribonuclease A (RNase A) is a small globular enzyme that lyses RNA. The remarkable solution stability of its structure and enzymatic activity has led to its investigation to develop a new class of drugs for cancer chemotherapeutics. However, the successful clinical application of RNase A has been reported to be limited by insufficient stability and loss of enzymatic activity when it was coupled with a biomaterial carrier for drug delivery. The objective of this study was to characterize the structural stability and enzymatic activity of RNase A when it was adsorbed on different surface chemistries (represented by fused silica glass, high-density polyethylene, and poly(methyl-methacrylate)). Changes in protein structure were measured by circular dichroism, amino acid labeling with mass spectrometry, and in vitro assays of its enzymatic activity. Our results indicated that the process of adsorption caused RNase A to undergo a substantial degree of unfolding with significant differences in its adsorbed structure on each material surface. Adsorption caused RNase A to lose about 60% of its native-state enzymatic activity independent of the material on which it was adsorbed. These results indicate that the native-state structure of RNase A is greatly altered when it is adsorbed on a wide range of surface chemistries, especially at the catalytic site. Therefore, drug delivery systems must focus on retaining the native structure of RNase A in order to maintain a high level of enzymatic activity for applications such as antitumor chemotherapy.


Pharmacological manipulation of anterior pituitary dopamine content in the male rat: relationship to serum prolactin concentration and lysosomal enzyme activity.
The content of dopamine (DA) and the activity of beta-glucuronidase (a marker for lysosomal enzymes) in the anterior pituitary and the concentration of PRL in serum were determined in male rats that were treated with a variety of drugs that influence the release, storage, or actions of DA. Drugs that increase DA in hypophysial portal blood (amphetamine, methylphenidate and L-dopa) increased DA content, decreased PRL secretion, and had no effect on lysosomal enzyme activity. Drugs that activate DA receptors in the anterior pituitary (apomorphine and bromocriptine) decreased serum PRL but had no effect on DA content or lysosomal enzyme activity. Drugs that decrease DA in the hypophysial portal blood (alpha-methyltyrosine, gamma-butyrolactone, and reserpine) or block DA receptors (haloperidol) increased PRL secretion and decreased DA content and lysosomal enzyme activity. These results suggest that there is no obvious relationship between anterior pituitary DA content and PRL secretion. In addition, lysosomal enzyme activity is not stimulated by increasing the concentration of DA or activating DA receptors in the anterior pituitary, but lysosomal enzyme activity does appear to be tonically stimulated by DA in the control animals since decreasing DA concentrations or receptor activation in the anterior pituitary decreases beta-glucuronidase activity. This latter proposal was confirmed by the demonstration that apomorphine reduced the alpha-methyltyrosine-induced increase in serum PRL and prevented the decrease in anterior pituitary DA content and beta-glucuronidase activity. Furthermore, pretreatment with bromocriptine and L-dopa blocked both the increase in serum PRL concentration and the decrease in anterior pituitary DA content induced by alpha-methyltyrosine and gamma-butyrolactone. On the other hand, bromocriptine and L-dopa blocked the increase in serum PRL concentration but not the reduction in anterior pituitary DA content caused by reserpine, indicating that reserpine has a direct action on DA storage mechanisms in the anterior pituitary. These data suggest that the ability of DA to inhibit PRL secretion and the incorporation of DA into the anterior pituitary are not causally related.


Alcohol consumption, strength of religious beliefs, and risky sexual behavior in college students.
Relationships among alcohol use, strength of religious convictions, and unsafe sexual practices of 210 students at a large public university in the "bible belt" were examined. The women with strong religious beliefs consumed less alcohol and were less likely to engage in risky sexual behavior than were female participants with weaker religious convictions. Among the men, religious conviction was not significantly correlated with alcohol consumption or risky sexual behavior, but alcohol consumption and inconsistent use of condoms and multiple sexual partners were significantly correlated. Men had higher rates of alcohol consumption and unprotected sexual activity than women did, yet the two groups did not differ in overall frequency of sexual activity. Future research is needed to (a) provide greater understanding of gender differences in alcohol use, risky sexual behavior, and religious beliefs of college students in the region and (b) determine whether similar correlations exist in other areas of the country.


Bioorganic mechanisms of the formation of free radicals catalyzed by glucose oxidase.
In this communication, we have described the activation of several xenobiotics by glucose oxidase from Aspergillus niger. The following compounds are readily reduced by d-glucose, in the presence of glucose oxidase: p-nitroso-N,N-dimethylaniline, methyl-1,4-benzoquinone, and 7,7,8,8-tetracyano-quinodimethane. In each case, the products of enzymatic reduction undergo a dismutation reaction with the parent compound and thus afford the formation of free radicals. In some cases, and at an appropriate pH value, the transformation of a parent compound into free radicals is almost quantitative. Under optimal conditions, free radicals are stable for several minutes in aqueous solutions under physiological conditions.


High Areal Capacity Si/LiCoO2 Batteries from Electrospun Composite Fiber Mats.
Freestanding nanofiber mat Li-ion battery anodes containing Si nanoparticles, carbon black, and poly(acrylic acid) (Si/C/PAA) are prepared using electrospinning. The mats are compacted to a high fiber volume fraction (≈0.85), and interfiber contacts are welded by exposing the mat to methanol vapor. A compacted+welded fiber mat anode containing 40 wt % Si exhibits high capacities of 1484 mA h g-1 (3500 mA h g-1Si ) at 0.1 C and 489 mA h g-1 at 1 C and good cycling stability (e.g., 73 % capacity retention over 50 cycles). Post-mortem analysis of the fiber mats shows that the overall electrode structure is preserved during cycling. Whereas many nanostructured Si anodes are hindered by their low active material loadings and densities, thick, densely packed Si/C/PAA fiber mat anodes reported here have high areal and volumetric capacities (e.g., 4.5 mA h cm-2 and 750 mA h cm-3 , respectively). A full cell containing an electrospun Si/C/PAA anode and electrospun LiCoO2 -based cathode has a high specific energy density of 270 Wh kg-1 . The excellent performance of the electrospun Si/C/PAA fiber mat anodes is attributed to the: i) PAA binder, which interacts with the SiOx surface of Si nanoparticles and ii) high material loading, high fiber volume fraction, and welded interfiber contacts of the electrospun mats.


Construction of Bacillus thuringiensis Simulant Strains Suitable for Environmental Release.
For a surrogate bacterium to be used in outdoor studies, it is important to consider environmental and human safety and ease of detection. Recently, Bacillus thuringiensis, a popular bioinsecticide bacterium, has been gaining attention as a surrogate bacterium for use in biodefense. In this study, we constructed simulant strains of B. thuringiensis with enhanced characteristics for environmental studies. Through transposon mutagenesis, pigment genes were inserted into the chromosome, producing yellow-colored colonies for easy detection. To prevent persistence of spores in the environment, a genetic circuit was designed to produce a spore without sporulation capability. Two loxP sites were inserted, one on each side of the spo0A gene, which encodes a sporulation master regulator, and a sporulation-dependent Cre expression cassette was inserted into the chromosome. This genetic circuit successfully deleted spo0A during sporulation, producing spores that lacked the spo0A gene. In addition, two major α/β-type small acid-soluble spore protein (SASP) genes, predicted by synteny analysis, were deleted. The spores of the mutant strain showed increased UV-C sensitivity and quickly lost viability when tested in a solar simulator. When the spores of the mutant strain were administered to the lungs of BALB/c mice, cells were quickly removed from the body, suggesting enhanced in vivo safety. All strains constructed in this study contain no antibiotic resistance markers and all heterologous genes were inserted into the chromosome, which are useful features for simulants to be released into the environment.IMPORTANCEB. thuringiensis has recently been receiving increasing attention as a good spore simulant in biodefense research. However, few studies were done to properly address many important features of B. thuringiensis as a simulant in environmental studies. Since spores can persist in the environment for years after release, environmental contamination is a big problem, especially when genetically engineered strains are used. To solve these problems, we report here the development of B. thuringiensis simulant strains that are capable of forming yellow colonies for easy detection, incapable of forming spores more than once due to a genetic circuit, and lacking in two major SASP genes. The genetic circuit to produce a spore without sporulation capability, together with the deletion of SASP genes, ensures the environmental and human safety of the simulant strains developed in this study. All of these features will allow wider use of B. thuringiensis as a simulant for Bacillus anthracis in environmental release studies.


From skeleton to cytoskeleton: osteocalcin transforms vascular fibroblasts to myofibroblasts via angiotensin II and Toll-like receptor 4.
The expression of osteocalcin is augmented in human atherosclerotic lesions. How osteocalcin triggers vascular pathogenesis and remodeling is unclear. To investigate whether osteocalcin promotes transformation of adventitial fibroblast to myofibroblasts and the molecular mechanism involved. Immunohistochemistry indicated that osteocalcin was expressed in the neointima of renal arteries from diabetic patients. Western blotting and wound-healing assay showed that osteocalcin induced fibroblast transformation and migration, which were attenuated by blockers of the renin-angiotensin system and protein kinase Cδ (PKCδ), toll-like receptor 4 (TLR4) neutralizing antibody, and antagonist and inhibitors of free radical production and cyclooxygenase-2. Small interfering RNA silencing of TLR4 and PKCδ abolished fibroblast transformation. Angiotensin II level in the conditioned medium from the osteocalcin-treated fibroblasts was found elevated using enzyme immunoassay. Culturing of fibroblasts in conditioned medium collected from differentiated osteoblasts promoted fibroblast transformation. The expression of fibronectin, TLR4, and cyclooxygenase-2 is augmented in human mesenteric arteries after 5-day in vitro exposure to osteocalcin. Osteocalcin transforms adventitial fibroblasts to myofibroblasts through stimulating angiotensin II release and subsequent activation of PKCδ/TLR4/reactive oxygen species/cyclooxygenase-2 signaling cascade. This study reveals that the skeletal hormone osteocalcin cross-talks with vascular system and contributes to vascular remodeling.


Gas chromatographic analysis of acetophenone oxime and its metabolites.
A gas-liquid chromatographic (GLC) method has been developed for monitoring the metabolic reduction of acetophenone oxime or oxidative metabolism of the corresponding amine, alpha-methylbenzylamine in liver homogenates. The oxime, amine, n-hydroxy-alpha-methylbenzylamine and acetophenone are quantitatively determined after GLC separation of components with temperature programming on an SP-2401-DB-coated column. The first three compounds were silylated with N,O-bis(trimethylsilyl)-acetamide prior to chromatographic analysis to enhance the stability and improve the chromatographic properties of these components. The effluent gas was monitored with flame ionization detection, and permitted quantitation of components at sub-microgram/ml levels with reproducibility between injections of +/-2%. The optimal composition of enantiomeric mixtures of (R,S)-alpha-methylbenzylamines formed during metabolic reduction of acetophenone oximes were determined by conversion to diastereomeric amides and subsequent GLC analysis.


Building a Nurse-Led Collaborative Care Delivery Model for Behavioral Health Patients Boarding on a Pediatric Medical Unit.
With the current global mental health crisis, hospitals have experienced an exponential increase in behavioral health patients boarding on medical and surgical units. Nursing leaders are challenged with adapting existing infrastructure to deliver safe high-quality care to this patient population. This article describes 1 medical center's nurse-led effort to improve safety and quality care experiences for pediatric behavioral health patients boarding on a medical unit and for the staff providing care.


Treatment of occlusal plane canting using miniscrew anchorage.
Two patient therapies introduce the use of miniscrew anchorage in adult patients for the correction of mild to moderate occlusal plane canting without severe facial asymmetries. A miniscrew implanted in the infrazygomatic buttress was used as anchorage for intruding the overerupted maxillary quadrant. As unilateral intrusion of maxillary posterior teeth will develop a posterior unilateral open bite, box elastics were subsequently used to extrude the opposing teeth in the mandibular arch. These treatments show that miniscrew anchorage offers a simple, efficient method of correcting occlusal plane canting and mild facial asymmetries.


BCL2-Family Dysregulation in B-Cell Malignancies: From Gene Expression Regulation to a Targeted Therapy Biomarker.
BCL2-family proteins have a central role in the mitochondrial apoptosis machinery and their expression is known to be deregulated in many cancer types. Effort in the development of small molecules that selectively target anti-apoptotic members of this family i.e., Bcl-2, Bcl-xL, Mcl-1 recently opened novel therapeutic opportunities. Among these apoptosis-inducing agents, BH3-mimetics (i.e., venetoclax) led to promising preclinical and clinical activity in B cell malignancies. However, several mechanisms of intrinsic or acquired resistance have been described ex vivo therefore predictive markers of response as well as mechanism-based combinations have to be designed. In the present study, we analyzed the expression of the BCL2-family genes across 10 mature B cell malignancies through computational normalization of 21 publicly available Affimetrix datasets gathering 1,219 patient samples. To better understand the deregulation of anti- and pro-apoptotic members of the BCL2-family in hematological disorders, we first compared gene expression profiles of malignant B cells to their relative normal control (naïve B cell to plasma cells, n = 37). We further assessed BCL2-family expression according to tissue localization i.e., peripheral blood, bone marrow, and lymph node, molecular subgroups or disease status i.e., indolent to aggressive. Across all cancer types, we showed that anti-apoptotic genes are upregulated while pro-apoptotic genes are downregulated when compared to normal counterpart cells. Of interest, our analysis highlighted that, independently of the nature of malignant B cells, the pro-apoptotic BH3-only BCL2L11 and PMAIP1 are deeply repressed in tumor niches, suggesting a central role of the microenvironment in their regulation. In addition, we showed selective modulations across molecular subgroups and showed that the BCL2-family expression profile was related to tumor aggressiveness. Finally, by integrating recent data on venetoclax-monotherapy clinical activity with the expression of BCL2-family members involved in the venetoclax response, we determined that the ratio (BCL2+BCL2L11+BAX)/BCL2L1 was the strongest predictor of venetoclax response for mature B cell malignancies in vivo.


Genetic differences between benign phyllodes tumors and fibroadenomas revealed through targeted next generation sequencing.
Breast fibroepithelial lesions are biphasic tumors which comprise the common benign fibroadenomas (FAs) and the rarer phyllodes tumors (PTs). This study analyzed 262 (42%) conventional FAs, 45 (7%) cellular FAs, and 321 (51%) benign PTs contributed by the International Fibroepithelial Consortium, using a previously curated 16 gene panel. Benign PTs were found to possess a higher number of mutations, and higher rates of cancer driver gene alterations than both groups of FAs, in particular MED12, TERT promoter, RARA, FLNA, SETD2, RB1, and EGFR. Cases with MED12 mutations were also more likely to have TERT promoter, RARA, SETD2, and EGFR. There were no significant differences detected between conventional FAs and cellular FAs, except for PIK3CA and MAP3K1. TERT promoter alterations were most optimal in discriminating between FAs and benign PTs. Our study affirms the role of sequencing and key mutations that may assist in refining diagnoses of these lesions.


Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat.
Inorganic phosphate (Pi) reabsorption was studied during Pi infusion, after acute or chronic thyroparathyroidectomy (TPTX), in rats stabilized on a high-phosphorus (1% P) or a low-phosphorus (0.02% P) diet. After acute TPTX, there were no consistent differences in Pi reabsorption between the high- and low-phosphorus dietary groups. After chronic TPTX, the rats stabilized on the low-phosphorus diet exhibited nearly complete Pi reabsorption at every plasma Pi level, while the animals receiving the high-phosphorus diet manifested a marked phosphaturic response to Pi infusion. In addition, Pi reabsorption was significantly increased in the chronic TPTX low-phosphorus rats which achieved the highest filtered Pi loads, while their urine remained essentially phosphate-free. Dietary phosphorus-dependent alterations in Pi reabsorption may play a significant role in establishing the rate of Pi excretion per nephron under certain circumstances and should be considered in the interpretation of studies investigating renal Pi handling. The ability of phosphorus-depleted animals to maintain a phosphate-free urine during Pi loading would favor the rapid repletion of body phosphorus stores.


Tailoring the Surface and Interface Structures of Copper-Based Catalysts for Electrochemical Reduction of CO2 to Ethylene and Ethanol.
Electrochemical CO2 reduction to valuable ethylene and ethanol offers a promising strategy to lower CO2 emissions while storing renewable electricity. Cu-based catalysts have shown the potential for CO2 -to-ethylene/ethanol conversion, but still suffer from low activity and selectivity. Herein, the effects of surface and interface structures in Cu-based catalysts for CO2 -to-ethylene/ethanol production are systematically discussed. Both reactions involve three crucial steps: formation of CO intermediate, CC coupling, and hydrodeoxygenation of C2 intermediates. For ethylene, the key step is CC coupling, which can be enhanced by tailoring the surface structures of catalyst such as step sites on facets, Cu0 /Cuδ+ species and nanopores, as well as the optimized molecule-catalyst and electrolyte-catalyst interfaces further promoting the higher ethylene production. While the controllable hydrodeoxygenation of C2 intermediate is important for ethanol, which can be achieved by tuning the stability of oxygenate intermediates through the metallic cluster induced special atomic configuration and bimetallic synergy induced the double active sites on catalyst surface. Additionally, constraining CO coverage by the complex-catalyst interface and stabilizing CO bond by N-doped carbon/Cu interface can also enhance the ethanol selectivity. The structure-performance relationships will provide the guidance for the design of Cu-based catalysts for highly efficient reduction of CO2 .


A modification to the isotope-dilution technique for estimating milk intake of pigs using pig serum.
The aim of this study was to compare the measurement of deuterium oxide (D2O) directly in pig serum with that in sublimed whole blood. This was to assess whether excluding vacuum sublimation before analysis would cause any significant loss of accuracy in estimates of pig milk intake. Water and serum standards were made in deionized water and serum, respectively, and were assayed with samples under the same conditions on a fixed-filter, infrared spectrophotometer. The mean concentration of D2O in sublimed samples was 2,244 microg/mL of body water, and the mean concentration of D2O in serum samples was 2,184 microg/mL of body water. The mean ratio of D2O concentration in deionized water to the D2O concentration in serum was 1.0275, which was used as a correction factor to convert serum D2O concentration to D2O concentrations in body water. Using this method, the mean concentration of D2O in all serum samples was identical to that in sublimed samples (i.e., 2,244 microg/mL of body water). Mean milk intake of pigs based on sublimed samples was 1,006 g/d and that based on serum samples was 1,012 g/d. This confirms that milk intake determined from measurement of D2O directly in pig serum is sufficiently precise.


Effect of Multidisciplinary Assessment on Paediatric Patients with Monosymptomatic Nocturnal Enuresis.
This study aimed to investigate the effect of multidisciplinary assessment in paediatric patients with monosymptomatic nocturnal enuresis (MNE). From July 2018 to June 2021, 242 patients with enuresis who received diagnosis and treatment in our hospital were retrospectively enrolled. They were divided into the multidisciplinary assessment group (n = 130) and routine assessment group (n = 112). Multidisciplinary assessments were completed by a multidisciplinary team, and the data included structured medical history, physical and neurological examinations, bladder and bowel diaries, sleep diaries, questionnaires, psychological assessments, urinary ultrasonography, blood and urine laboratory tests, polysomnography and balance assessments. A higher proportion of patients with enuresis associated with other conditions was identified in the multidisciplinary assessment group than in the routine assessment group (27.7% vs 15.2%, p = 0.019). With regard to treatment response to the enuresis alarm, the treatment response rate was 52.9% (17/33) in the conventional assessment group, whereas such a response was significantly higher in the multidisciplinary assessment group (82.1%, 32/39; p = 0.028). Compared with the routine assessment group, the multidisciplinary assessment group had a significantly higher treatment response rate for desmopressin (83.3% vs 52.0%; p = 0.022) and alarms combined with desmopressin (74.2% vs 44.4%; p = 0.045). After treatment, the Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) score in the multidisciplinary assessment group was significantly higher than that in the routine assessment group (91.9 ± 6.3 vs 87.1 ± 7.3; p < 0.001). Multidisciplinary evaluation can identify more children with enuresis caused by other diseases, which promotes the differential diagnosis of MNE. In addition, multidisciplinary assessment can determine the appropriate treatment response in children with MNE.


[A study of evoked potentials in the brains of very low birth weight infants].
This work studies the behaviour of the N200 and P300 waves of the brain evoked potentials (BEP) in a group of very low birth weight infants and results are compared with a second group of children whose weight was normal at birth. The objective of this study was to determine whether the N200 and, more especially, the P300 waves in children under the age of 3 could be used to assess the development and prognosis of their disorders. BEP were performed in very low birth weight infants (taken as the test group) and in others whose weight at birth was normal (control group); the difference in ages when the potentials were recorded was not statistically significant. The EEG index was evaluated for both the test and the control group, and a difference was found with a significance of p < 0.001. Latency, in milliseconds, of the N200 wave and the P300 wave was recorded at the same sites for the test and control groups and showed differences with a significance of p < 0.001. The findings from the EEG and the latencies of the N200 and P300 waves in the BEP of very low birth weight infants are pathological and are linked to immaturity of the brain, which is characteristic of this population. This tool could help to detect developmental disorders and to facilitate a better approach to attending these children.


Building market share in the Latino Community.
Within the next few years, the Latino community will become the largest cultural segment in the United States. Hospitals face many barriers in addressing the needs of the Latino community, including language, cultural influences, and perception of health care. Economics, demographics, and regulations dictate the need to take action, but concerns over costs, lack of skills, and negative attitudes create barriers to success. A unique partnership in Washington, D.C., between La Clinica de Pueblo, a grassroots clinic serving the Latino community, and Howard University Hospital offers insight into an effective strategy that hospitals can adopt to meet the needs of this community appropriately.


The effect of genetic increases in egg production and age and sex on breast muscle development of turkeys.
Pectoralis major muscle morphology was studied in both sexes of a turkey line (E) selected long-term for increased egg production and its randombred control (RBC1) from 25 d of incubation through 20 wk posthatch. Pectoralis major muscle samples from 10 individuals from each line-sex-age subgroup were obtained in a manner to prevent contraction. The muscle samples were dehydrated, cleared, embedded in paraffin, sectioned, incubated, and rehydrated before staining with hematoxylin and eosin. Representative sections were given a score by 4 individuals based on breast muscle morphology. The scores ranged from 1 (little extracellular matrix and indistinct muscle fibers) to 5 (large extracellular space and distinct muscle fibers). Scores from 2 to 4 were intermediate to these extremes. The pectoralis major muscle morphology scores were highest at 25 d of incubation and declined greatly at 1 wk of age. The scores increased from 1 to 4 wk of age and remained constant through 20 wk of age. Males had higher scores than females. In the current study, there was no significant difference between the E and RBC1 lines. Based on the results of 3 experiments (2 published and the present one) using the E and RBC1 lines, it appears that genetic increases in egg production may be associated with a slight reduction in pectoralis major muscle morphology scores at 16 wk of age.


A Supramolecular Platform Technology for Bacterial Cell Surface Modification.
In an era of antimicrobial resistance, a better understanding of the interaction between bacteria and the sentinel immune system is needed to discover new therapeutic targets for combating bacterial infectious disease. Sentinel immune cells such as macrophages phagocytose intact bacteria and thereby initiate ensuing immune responses. The bacterial surface composition is a key element that determines the macrophage signaling. To study the role of the bacterial cell surface composition in immune recognition, we developed a platform technology for altering bacterial surfaces in a controlled manner with versatile chemical scaffolds. We show that these scaffolds are efficiently loaded onto both Gram-positive and -negative bacteria and that their presence does not impair the capacity of monocyte-derived macrophages to phagocytose bacteria and subsequently signal to other components of the immune system. We believe this technology thus presents a useful tool to study the role of bacterial cell surface composition in disease etiology and potentially in novel interventions utilizing intact bacteria for vaccination.


"Shape activity": a continuous-state HMM for moving/deforming shapes with application to abnormal activity detection.
The aim is to model "activity" performed by a group of moving and interacting objects (which can be people, cars, or different rigid components of the human body) and use the models for abnormal activity detection. Previous approaches to modeling group activity include co-occurrence statistics (individual and joint histograms) and dynamic Bayesian networks, neither of which is applicable when the number of interacting objects is large. We treat the objects as point objects (referred to as "landmarks") and propose to model their changing configuration as a moving and deforming "shape" (using Kendall's shape theory for discrete landmarks). A continuous-state hidden Markov model is defined for landmark shape dynamics in an activity. The configuration of landmarks at a given time forms the observation vector, and the corresponding shape and the scaled Euclidean motion parameters form the hidden-state vector. An abnormal activity is then defined as a change in the shape activity model, which could be slow or drastic and whose parameters are unknown. Results are shown on a real abnormal activity-detection problem involving multiple moving objects.


A case report and literature review: Identification of a novel AIRE gene mutation associated with Autoimmune Polyendocrine Syndrome Type 1 in East Asians.
Autoimmune polyendocrine syndrome type 1 (APS-1), also referred as the autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy (APECED), is a rare autosomal inherited disease predominantly among Caucasians from Northern Europe. This syndrome is very rare in East Asian population. Here, we describe a case of a 15-year-old Chinese boy admitted due to a 1-month history of intermittent fatigue, nausea, vomiting, and diarrhea. His symptom became worse accompanied with chest tightness 4 days before admission. On physical examination, his temperature was 38.5°C, blood pressure was 75/38 mm Hg, and pulse was 98/min. He was a thin boy with mild hyperpigmentation and xanthochromia. After abdominal computed technology and laboratory tests, his diagnosis was APS-1 accompanied with adrenal crisis. Further investigation on whole-exome sequencing revealed a novel homozygous mutation c.47C>G (p.T16R) in exon 1 in the autoimmune regulator (AIRE) gene. This patient underwent replacement therapy of glucocorticoids, corticosteroid, and levothyroxine, as well as calcium and calcitriol supplementation. He continues to do well 4 years after his hospitalization. During his last follow-up, he had serum thyroid-stimulating hormone level of 3.07 μIU/mL, free triiodothyronine level of 1.92 pg/mL, and free thyroxine level of 13.95 pg/mL. His serum cortisol and ACTH (8 a.m.) levels were 28.53 μg/dL and 69.48 pg/mL, respectively. APS-1 is very rare in East Asians and the variable clinical presentations of the disease make the initial diagnosis especially difficult. Autoimmune thyroiditis, type 1 diabetes mellitus, and hepatitis were the three most frequent minor components of APS-1 in East Asian patients with age of onset in late teens and 20s. Sequence analysis of AIRE gene is necessary to verify its diagnostic efficacy in association with clinical findings.


A column chromatographic method for the combined analysis of creatine kinase-MB (CPK-MB) and lactate dehydrogenase 1,2 (LDH 1,2) isoenzymes.
A column chromatographic method for the simultaneous single-eluate isolation of CPK-MB and LDH 1,2 has been evaluated. The method is rapid in that the entire isolation is completed in less than an hour and subsequent analysis can be performed using presently available spectrophotometric methods and reagents without the need for electrophoresis equipment. In addition, since the isoenzymes are directly isolated, quantitation of enzymatic activity can be performed with precision. This technic permits detection of CPK-MB and LDH 1,2 in samples with normal values of total CPK and LDH utilizing a routine laboratory spectrophotometer. The sensitivities for diagnosis of acute myocardial infarction are 95% for LDH 1,2 and 100% for CPK-MB. The specificities for diagnosis of acute myocardial infarction are 86% for LDH 1,2 and 96% for CPK-MB.


The association between dietary tryptophan intake and migraine.
Migraineurs have been identified to have chronically decreased serotonin levels while its concentrations markedly increase during ictal periods. Regarding the importance of adequate tryptophan intake in regulating serotonin homeostasis and subsequent effect on migraine attacks, we designed the current study. The migraine group (n = 514, diagnosed according to the ICHDIII criteria) was recruited from a tertiary headache clinic. The controls consisted of 582 sex-matched healthy volunteers who were randomly selected from general population. After collecting demographic and anthropometric data, a validated 168-item semi-quantitative food frequency questionnaire (FFQ) was used for dietary intake assessments. Multiple regression models were applied to explore the relationship between migraine and tryptophan intake. The mean (SD) of the age of participants in the controls and migraine group was 44.85 (13.84) and 36.20 (9.78) years, respectively. The multiple regression models were adjusted for age (year), sex, body mass index (BMI) (kg/m2), total daily energy intake (kcal/day), dietary intakes of total carbohydrates (g/day), animal-based protein (g/day), plant-based protein (g/day), total fat (g/day), saturated fat (g/day), and cholesterol (mg/day). It was shown that there is a negative association between tryptophan intake and migraine risk ((OR in the 3rd quartile = 0.46; 95% CI = 0.25-0.85) (OR in the 4th quartile = 0.40; 95% CI = 0.16-0.98) compared with the first quartile; P for trend = 0.045). Therefore, our results showed that subjects who had a median intake of 0.84-1.06 g of tryptophan per day had reduced odds of developing migraine by approximately 54-60%, relative to those consumed ≤ 0.56 g/day.


Long-Term Electroclinical and Employment Follow up in Temporal Lobe Epilepsy Surgery. A Cuban Comprehensive Epilepsy Surgery Program.
The purpose of this paper is to present a long- term electroclinical and employment follow up in temporal lobe epilepsy (TLE) patients in a comprehensive epilepsy surgery program. Forty adult patients with pharmacoresistant TLE underwent detailed presurgical evaluation. Electroencephalogram (EEG) and clinical follow up assessment for each patient were carried out. The occurrence of interictal epileptiform activity (IEA) and absolute spike frequency (ASF) were tabulated before and after 1, 6, 12, 24 and 72 months surgical treatment. Employment status pre- to post-surgery at the last evaluated period was also examined. Engel scores follow-up was described as follows: at 12 months 70% (28) class I, 10% (4) class II and 19% (8) class III-IV; at 24 months after surgery 55.2% (21) of the patients were class I, 28.9% (11) class II and 15.1% (6) class III-IV. After one- year follow up 23 (57.7%) patients were seizure and aura-free (Engel class IA). These figures changed to 47.3%, and 48.6% respectively two and five years following surgery whereas 50% maintained this condition in the last follow up period. A decline in the ASF was observed from the first year until the sixth year after surgery in relation to the preoperative EEG. The ASF one year after surgery allowed to distinguish "satisfactory" from "unsatisfactory" seizure relief outcome at the last follow up. An adequate social functioning in terms of education and employment in more than 50% of the patients was also found. Results revealed the feasibility of conducting a successful epilepsy surgery program with favorable long term electroclinical and psychosocial functioning outcomes in a developing country as well.


Prognostic significance of nucleolar organizer regions in ovarian epithelial tumors.
Recent studies have shown that the silver-stained nucleolar organizer region (AgNOR) score is related to the cell growth rate in several neoplasms. In the work presented here, we tested the AgNOR technique in 79 ovarian epithelial tumors (13 benign, 10 borderline, 56 malignant) to evaluate the diagnostic potential of AgNOR count in distinguishing between ovarian borderline tumors and carcinomas and to assess its prognostic value in carcinomas. Ovarian carcinomas exhibited higher mean AgNOR values than borderline and benign tumors, but statistically significant differences were found only in the serous type. Statistical analysis showed a positive correlation of higher AgNOR score, advanced tumor stage, and adverse prognosis. On the contrary, low AgNOR counts identified stages I and II carcinomas with disease-free follow-up. These results suggest that the AgNOR count may improve the prognostic evaluation of ovarian epithelial tumors by representing a reliable indicator of survival.


Epiphyas postvittana (Lepidoptera: Tortricidae)-Botrytis cinerea (Helotiales: Sclerotiniaceae)-Vitis vinifera (Vitales: Vitaceae) Interaction: The Role of B. cinerea on the Development of E. postvittana in Synthetic Nutritional Media.
Epiphyas postvittana (Walker) (light-brown apple moth) is a polyphagous herbivore of economic significance, which also feeds on Vitis vinifera L. The E. postvittana-V. vinifera interacting system also involves the participation of the fungus Botrytis cinerea Persoon ex Fries. We have been exploring the relationship among E. postvittana-V. vinifera-B. cinerea over the past two years. In this article, we report the preference and performance of the larvae of E. postvittana raised solely on a synthetic diet incorporated with the mycelial material of B. cinerea (Diet B). To characterize the effect of fungus on the development of E. postvittana, another synthetic diet was prepared that included the lyophilized leaf material of V. vinifera (Diet C). When raised on Diets B and C, a decrease in the duration of larval development and an increase in the survival and fecundity rate of E. postvittana occurred. Diet B influenced the pupal mass, but a significant increase occurred when the larvae were fed on Diet C. The larval emergence rate was the greatest in E. postvittana raised on Diet B, followed by those on Diet C. The F(2) generation of the larvae reared on Diet B showed similar effects as F(1) on the life-history performance of the larvae. Diet B enhanced the life-history performance of E. postvittana, although the larvae of E. postvittana showed little preference to Diet B. The greater fertility rate of E. postvittana reared on Diet B suggests the importance of sterols as shown in Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae) and in a few Myrmicinae (Hymenoptera: Formicidae), which serve as precursors to different ecdysteroids that regulate many critical processes through embryonic development.


Verbal fluency in bilingual Lebanese adults: Is the prominent language advantage due to executive processes, language processes, or both?
Although bilingualism is widespread, little data on verbal fluency tasks (VFTs) within bilingualism subtypes and the underlying mechanisms exist. The study's objective was to explore executive and language processes in 10 semantic and letter VFTs and a set of language and executive tests among 100 elderly Arabic-French bilinguals from three bilingualism subgroups: Arabic-dominant, French-dominant, and balanced. We observed a prominent-language advantage for semantic and letter VFTs in French but not for letter VFTs in Arabic. This advantage in the VFT was associated with a sustained rate of late production, a higher percentage of specific words, a higher number of clusters, and a larger cluster size, and was related mainly to language processes. Our results suggest that the strategic search processes underlying VFTs operate on the two phonological output lexicons of bilinguals with similar characteristics in different languages and thus support the hypothesis of a single, centralized, strategic search process.


Consumer preference for chicken breast may be more affected by information on organic production than by product sensory properties.
Conventional chicken from a fast-growing strain (CC), organic chicken from a slow-growing strain (OSG), and organic chicken from a fast-growing strain (OFG) were used to assess descriptive sensory differences between organic and conventional breasts, to verify whether differences were perceived by consumers and to evaluate the effect of information about organic production on liking. A conventional quantitative-descriptive analysis was performed by a trained panel of 10 members on breast slices (1 cm thick) grilled at 300°C. A 150-member consumer panel (from southern, central, and northern Italy) rated CC, OSG, and OFG breasts according to 3 types of evaluation: tasting without information (perceived liking), information without tasting (expected liking), and tasting with information (actual liking). Breasts from different sources were clearly discriminated by the trained panel as meat from CC was perceived more tender than OFG (P < 0.05) and OSG (P < 0.001), more fibrous than OFG (P < 0.05) and OSG (P < 0.001), and leaving more residue than OFG (P < 0.05) and OSG (P < 0.001), whereas OSG was assessed as less juicy before swallowing than OFG and CC (P < 0.05) and less fibrous than OFG (P < 0.05). No significant differences were observed by consumers for perceived liking. However, consumer expected liking scores were higher for organic than for conventional products (P < 0.001) and actual liking of organic breasts moved toward the expectancy. In particular, actual liking scores were higher than perceived liking in blind conditions (P < 0.001 and P < 0.01 for OFG and OSG, respectively). We conclude that trained panelists were able to discriminate chicken breasts from different sources, whereas untrained consumers were not. However, consumer liking was markedly affected by the information given on the organic production system, thus providing a tool to differentiate the product in an increasingly competitive market.


Comparing Techniques for Mesenteric Defects Closure in Laparoscopic Gastric Bypass Surgery-a Register-Based Cohort Study.
Routine closure of mesenteric defects is generally considered standard part of laparoscopic gastric bypass surgery today. Controversy still exists regarding the optimal method for mesenteric defects closure. The objective was to compare different methods for mesenteric defects handling in laparoscopic gastric bypass surgery. Primary laparoscopic gastric bypass procedures from 2010 until 2015 reported to the Scandinavian Obesity Surgery Registry (SOReg), where the mesenteric defects closure method was identifiable, were included. Main outcome measures were serious postoperative complication within 30 days after surgery, and reoperation for small bowel obstruction within 5 years after surgery. Quality-of-life before and after surgery, duration of surgery, and risk factors for complication were also analyzed. Information on operation for small bowel obstruction was based on data from the SOReg, the Swedish National Patient Register and reviews of hospital charts. In all, 34,707 patients were included. Serious postoperative complication occurred in 174 (2.9%) patients with sutures, in 592 (3.1%, adjusted p = 0.079) with clips, and 278 (3.1%; adjusted p = 0.658) in the non-closure group. Reoperation for small bowel obstruction within 5 years after surgery was lower with sutures (cumulative incidence 6.9%) and clips (cumulative incidence 7.3%; adjusted HR 1.16, 95% CI 1.02-1.32, p = 0.026), compared to non-closure (cumulative incidence 11.2%; adjusted HR 1.63, 95% CI 1.44-1.84, p < 0.0001). Closure of the mesenteric defects using either non-absorbable metal clips or non-absorbable running sutures is a safe and effective measure to reduce the risk for small bowel obstruction after laparoscopic gastric bypass surgery. Sutures appear slightly more effective and should remain gold standard for mesenteric defects closure.


Noninvasive intracranial pressure estimation by orbital subarachnoid space measurement: the Beijing Intracranial and Intraocular Pressure (iCOP) study.
The orbital subarachnoid space surrounding the optic nerve is continuous with the circulation system for cerebrospinal fluid (CSF) and can be visualized by using magnetic resonance imaging (MRI). We hypothesized that the orbital subarachnoid space width (OSASW) is correlated with and can serve as a surrogate for intracranial pressure (ICP). Our aim was to develop a method for a noninvasive measurement of the intracranial CSF-pressure (CSF-P) based on MRI-assisted OSASW. The prospective observational comparative study included neurology patients who underwent lumbar CSF-P measurement and 3.0-Tesla orbital magnetic resonance imaging (MRI) for other clinical reasons. The width of the orbital subarachnoid space (OSASW) around the optic nerve was measured with MRI at 3, 9, and 15 mm behind the globe. The study population was randomly divided into a training group and a test group. After adjusting for body mass index (BMI) and mean arterial blood pressure (MABP), algorithms for the associations between CSF-P and OSASW were calculated in the training group. The algorithms were subsequently verified in the test group. Main outcome measures were the width of the orbital subarachnoid space (OSASW) and the lumbar cerebrospinal fluid pressure (CSF-P). Seventy-two patients were included in the study. In the training group, the algorithms for the associations between CSF-P and OSASW were as follows: (a) CSF-P = 9.31 × OSASW (at 3 mm) + 0.48 × BMI + 0.14 × MABP-19.94; (b) CSF-P = 16.95 × OSASW (at 9 mm) + 0.39 × BMI + 0.14 × MABP-20.90; and (c) CSF-P = 17.54 × OSASW (at 15 mm) + 0.47 × BMI + 0.13 × MABP-21.52. Applying these algorithms in the independent test group, the measured lumbar CSF-P (13.6 ± 5.1 mm Hg) did not differ significantly from the calculated MRI-derived CSF-P (OSASW at 3 mm: 12.7 ± 4.2 mm Hg (P = 0.07); at 9 mm: 13.4 ± 5.1 mm Hg (P = 0.35); and at 15 mm: 14.0 ± 4.9 mm Hg (P = 0.87)). Intraclass correlation coefficients (ICCs) were higher for the CSF-P assessment based on OSASW at 9 mm and at 15 mm behind the globe (all ICCs, 0.87) than for OSASW measurements at 3 mm (ICC, 0.80). In patients with normal, moderately decreased or elevated ICP, MRI-assisted measurement of the OSASW appears to be useful for the noninvasive quantitative estimation of ICP, if BMI and MABP as contributing parameters are taken into account. Clinical trial registered with the Chinese Clinical Trial Registry: ChiCTR-OCC-11001271.


Susceptibility of captive adult winter-run Chinook salmon Oncorhynchus tshawytscha to waterborne exposures with infectious hematopoietic necrosis virus (IHNV).
Sexually mature female Chinook salmon Oncorhynchus tshawytscha with no prior history of exposure to infectious hematopoietic necrosis virus (IHNV) were susceptible to experimental infection induced by additions of virus to the water. The resulting infections resembled those observed among naturally infected hatchery and wild populations of Chinook salmon. Virus was detected as early as 4 d post-exposure (p.e.) and subsequently in all virus-exposed fish that died or that were examined at 14 d p.e. when the study was terminated. The greatest concentrations of virus, up to 10(8) plaque-forming units (pfu) ml(-1), were found in the ovarian fluid at 13 to 14 d p.e., but the virus was also found in high concentrations in the gill, kidney/spleen and plasma. In contrast, the virus was not recovered from unexposed control adult salmon that died or were sampled at the end of the study. Despite detecting concentrations of IHNV in excess of 10(7) pfu g(-1) of tissue, no specific microscopic lesions were found in IHNV-exposed compared to unexposed control salmon. The results of this initial study suggest that virus in the spawning environment, either from adult salmon or other sources, may contribute to its rapid spread among adult Chinook salmon, thereby considerably increasing the prevalence of IHNV infection in both wild and hatchery populations of adult Chinook salmon.


Distribution of the insertion element IS240 among Bacillus thuringiensis strains.
The presence of IS240 was investigated in 69 Bacillus thuringiensis (Bt) strains including strains from serotype H1 to H45 and additional strains with known Dipteran larvae toxicity. Restriction digests of total DNA and PCR products obtained with a single 16-bases primer corresponding to the IS240 inverted repeated sequence were hybridized with the IS240A element. The results indicate that 67% of the Bt strains tested, including all known mosquitocidal strains, possess at least one IS240-related element. PCR experiments indicate that IS240 represents a family of insertion sequences with several variants.


Perceptual consequences of feature-based attention.
Attention modulates visual processing along at least two dimensions: a spatial dimension, which enhances the representation of stimuli within the focus of attention, and a feature dimension, which is thought to enhance attended visual features (e.g., upward motion) throughout the visual field. We investigate the consequences of feature-based attention onto visual perception, using dual-task human psychophysics and two distant drifting Gabor stimuli to systematically explore 64 combinations of visual features (orientations and drift speeds) and tasks (discriminating orientation or drift speed). The resulting single, consistent data set suggests a functional model, which predicts a maximum rule by which only the dominant product of feature enhancement and feature benefit by feature relevance may benefit perception.


Localized prostate cancer and robot-assisted laparoscopic radical prostatectomy: a retrospective, comparative study between pre- and post-operative Gleason scores.
To compare the pre- and post-operative Gleason scores (GS) in patients with localized prostate cancer treated with robot-assisted laparoscopic radical prostatectomy. A single center, retrospective comparison between pre- and post-operative GS. Age, prostate volume, PSA, number of biopsies, number of positive cores, biopsy GS, cTNM, final pathology GS and pTNM of 286 patients were retrieved. They were divided into risk groups. A total of 286 patients with a mean age at surgery of 64.64 ± 7.81 y and mean PSA-value of 9.35 ± 8.38 ng/mL. Mean prostate volume was 55.09 ± 24.93 mL, mean number of biopsies was 11.90 ± 4.63. Mean percentage of positive cores was 36.90 ± 22.42%. A GS of <7 was seen in 23.4%, 66.8% had a GS of 7 and 9.7% of >7 in final pathology. Of the total, 38.1% were pre-operative low risk, 58.7% of them had an upgrade in GS on final pathology, 45.1% were in the intermediate risk group, 5.4% showed a downgrade, 64.3% remained stable and 30.2% had an upgrade in GS. Also, 16.8% were high risk patients of which 35.4% had a downgrade, 39.6% remained stable and 25% showed an upgrade of the GS. We found a substantial underestimation of the GS in the pre-operative setting when compared to the GS in final pathology.


Characterization of Shigella dysenteriae serotypes 11, 12, and 13.
We conducted serologic and biochemical studies on strains of three provisional Shigella serotypes. Included were 19 strains of serotype 3873-50 from three countries (1 from Mexico, 1 from Netherlands Antilles, and 17 from the United States), 13 strains of serotype 3341-55 from three countries (1 from Canada, 1 from Bulgaria, and 11 from the United States), and 19 strains of serotype 19809-73 from two countries (16 from Israel and 3 from the United States). Reactions of these strains with homologous and heterologous Shigella antisera showed that serotypes 3873-50 and 19809-73 were unique. Strains of serotype 3341-55 shared an identical antigen with Shigella boydii 18; however, they were distinguished from S. boydii 18 biochemically and with absorbed sera. Strains of the three serotypes were biochemically most similar to Shigella dysenteriae. Like other shigellae, strains from each serotype were invasive in the Serény assay. Although biochemically similar to S. dysenteriae, none of the provisional serotypes produced Shiga toxin or the biologically related toxin, Shiga-like toxin II, produced by some strains of Escherichia coli. On the basis of these results and other published findings, we support earlier proposals to add the three provisional serotypes 3873-50, 3341-55, and 19809-73 to the Shigella schema and will include them as S. dysenteriae 11, 12, and 13, respectively.