Removal of Al, Ga, As, V and Mo from alkaline wastewater using pilot-scale constructed wetlands.
The study was initiated to evaluate constructed wetland technology as a method for treating alkaline (pH 8.0-8.6) drainage high in Al, Mo, V, As and Ga originating from bauxite residue storage areas. Pilot-scale horizontal flow constructed wetlands were operated over a 40-week period using three filter materials (granitic gravel, bauxite and alum water treatment sludge), and half of the wetlands were planted with Phragmites australis and the other half left unplanted. Gravel was the least effective medium for removing the target elements, while of the two active media, water treatment sludge was more effective than bauxite. Plants removed only small amounts of elements into their above- and below-ground dry matter (0.4-4.9% of that added). Nonetheless, the presence of plants greatly increased the effectiveness of all three media since their presence decreased effluent pH values by 0.5-1.3 pH units and that of the filter media by 0.4 pH units. Removal of elements followed the order Al > Ga > V > As > Mo. For planted wetlands, total elemental removal ranged from 18 to 98% for gravel, 80 to 99% for bauxite, and 93 to 99% for water treatment sludge. The lowest removal was for Mo (ranging from 18% for gravel to 93% for water treatment sludge) and the highest for Al (ranging from 98% in gravel to 99% in water treatment sludge). A sequential fractionation scheme for As, V and Mo on filter material at the end of the experiment showed that for bauxite and water treatment sludge, V and As were concentrated in the NaOH extractable fraction while Mo was concentrated in the less strongly adsorbed NaHCO3 extractable fraction. It was concluded that a constructed wetland with water treatment sludge as an active filter material is an effective technology for removal of the target elements from the alkali drainage.


A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China.
Patients with leprosy have a very low risk of Alzheimer disease (AD) and β-amyloid (Aβ) deposition is significantly lower in the brain tissue of elderly patients with leprosy compared with age-matched controls. Apolipoprotein E (ApoE) plays a critical role in lipid metabolic pathways and in the brain, facilitating the proteolytic clearance of Aβ. We hypothesized that APOE confers risk of leprosy as lipid metabolism is involved in Mycobacterium leprae infection. To investigate the potential genetic associations between APOE and leprosy in two independent Chinese case-control cohorts from the Yuxi and Wenshan prefectures, Yunnan Province of Southwest China. Five APOE single-nucleotide polymorphisms (SNPs) were analysed in 1110 individuals (527 patients and 583 controls) from the Yuxi prefecture using a SNaPshot assay. Genetic variations in the entire APOE exons were screened in 1788 individuals (798 patients and 990 controls) from the Wenshan prefecture using next-generation sequencing technology. The AD-associated SNPs rs405509 and rs439401 increased the risk of leprosy per se and multibacillary leprosy (P < 0·005), but the APOE-ε4 allele did not. The SNPs rs405509 and rs439401 were cis expression quantitative trait loci (eQTL) for APOE expression in human skin. Differential APOE mRNA expression was observed in skin lesions of patients with type I reaction leprosy and those with multibacillary leprosy. APOE and related lipid genes are involved in an interaction network with leprosy susceptibility genes. The APOE gene is associated with leprosy, most likely by regulating lipid-metabolism-related genes.


Correction: An examination of the prospective association between physical activity and academic achievement in youth at the population level.
[This corrects the article DOI: 10.1371/journal.pone.0253142.].


[High flow nasal cannula in infants: Experience in a critical patient unit].
The high flow nasal cannula (HFNC) is a method of respiratory support that is increasingly being used in paediatrics due to its results and safety. To determine the efficacy of HFNC, as well as to evaluate the factors related to its failure and complications associated with its use in infants. An analysis was performed on the demographic, clinical, blood gas, and radiological data, as well as the complications of patients connected to a HFNC in a critical care unit between June 2012 and September 2014. A comparison was made between the patients who failed and those who responded to HFNC. A failure was considered as the need for further respiratory support during the first 48hours of connection. The Kolmogorov Smirnov, Mann-Whitney U, chi squared and the Exact Fisher test were used, as well as correlations and a binary logistic regression model for P≤.05. The study included 109 patients, with a median age and weight: 1 month (0.2-20 months) and 3.7kg (2-10kg); 95 percentile: 3.7 months and 5.7kg, respectively. The most frequent diagnosis and radiological pattern was bronchiolitis (53.2%) and interstitial infiltration (56%). Around 70.6% responded. There was a significant difference between failure and response in the diagnosis (P=.013), radiography (P=018), connection context (P<.0001), pCO2 (median 40.7mmHg [15.4-67 mmHg] versus 47.3mmHg [28.6-71.3mmHg], P=.004) and hours on HFNC (median 60.75hrs [5-621.5 hrs] versus 10.5hrs [1-29 hrs], P<.0001). The OR of the PCO2 ≥ 55mmHg for failure was 2.97 (95% CI; 1.08-8.17; P=.035). No patient died and no complications were recorded. The percentage success observed was similar to that published. In this sample, the failure of HFNC was only associated with an initial pCO2 ≥ 55mmHg. On there being no complications reported as regards it use, it is considered safe, although a randomised, controlled, multicentre study is required to compare and contrast these results.


Effectiveness of Breath-holding Pulling Exercise in Patients with Vocal Fold Atrophy.
In recent years, the incidence of vocal fold atrophy has increased among the elderly. Vocal function exercises (VFE) are performed in patients with age-related vocal fold atrophy; however, treatment could be challenging if the patient is unable to go to the hospital or in hospitals that do not have a speech pathologist. Breath-holding pulling exercises are simple and can be performed anywhere for the management of such patients. This study aimed to examine the effectiveness of breath-holding pulling exercises in patients with vocal fold atrophy. Retrospective study METHODS: With the hands folded in front of the chest, the patients were instructed to take a deep breath, pull their hands to the left and right, and then hold their breath for 5 seconds. The physician instructed the patients to do this 10 times each morning, afternoon, and evening. Speech function, acoustic analysis, pitch range, and Voice Handicap Index-10 (VHI-10) were evaluated and compared before and 4-8 weeks after treatment. Maximum phonation time (MPT), the primary endpoint, significantly improved after treatment from 14.2 ± 6.6 to 20.3 ± 9.3 seconds. Among the secondary endpoints, mean flow rate (207.5 ± 104.4 to 165.1 ± 66.5 mL/s), pitch range (22.9 ± 8.3 to 26.2 ± 8.1 semitones), VHI-10 (18.1 ± 7.2 to 12.5 ± 6.3 points) jitter (2.5±1.6 to 1.7±1.2%), and shimmer (5.9±3.5 to 4.8±3.3%) showed significant improvement. Breath-holding pulling exercises were found to be effective in patients with vocal fold atrophy. These can be performed in hospitals with no speech pathologists, in patients who are unable to go to the hospital, and in patients who are hospitalized or unable to speak loudly. Moreover, as with conventional VFE, the training method achieves a high level of patient satisfaction.


A 1H spin echo NMR study of the HeLa tumour cell.
Phosphorylcholine, phosphorylcreatine, lactate, glutathione, glycine and leucine were identified in living HeLa cells in the first study of this cell type by 1H spin echo NMR spectroscopy. The technique has the advantage that it is non-invasive, providing detailed structural information on individual species present in the cell matrix. It has been used in this case to study the rate of energy consumption following the activation of the glycolytic pathway with glucose.


Characterization and applications of lymphocytic clonal growth factor in human plasma.
Human plasma was found to contain a macromolecular protein which can grow even a single cell of human lymphocytic cell lines (B-lymphoblastoid cell line HO-323-3 and T-lymphoblastoid cell line CCRF-CEM) and human-human hybridoma clones (SH-9, SU-1 and HB4C5) in a dish, but it has no effect on the growth of epithelial cell lines (lung cancer cell lines PC-8, QG-56 and QG-90). The proliferating activity for lymphocytic cell lines was gradually decreased at 4 or -20°C and dramatically decreased by heating at more than 60°C for 15 min. From human plasma, active fractions were purified by a successive application of Ca(2+) treatment, ammonium sulfate fractionation, DEAE-5PW column chromatography (FPLC) at pH 7.6. These active fractions were divided into at least three proteins by DEAE-5PW chromatography at pH 8.5 and chromatofocusing. These purified factors, named lymphocytic clonal growth factors (LCGFs), had similar molecular weights of about 600 K and each factor consisted of a 180 K and two 210 K subunits associated with hydrogen bondings. By the addition of 5 μg/ml of each factor into culture media, incidences of human-human hybridomas and cloning efficiencies of the hybridomas increased several-fold.


Accuracy, precision, and consistency of methods for pathogen-specific cerebrospinal fluid/serum Q-value calculation.
For a CSF/serum samples pair the specific Q-value is the ratio of antibody concentrations and proportional to the pathogen-specific antibody index. It is usually extracted from optical density (OD) measurements by applying appropriate evaluation methods. Six different methods for Q-value determination, partly using parameter variation, were assessed with respect to accuracy, precision, and the methods' parameter consistency. The methods are based on the Four Parameters Logistic (4PL) equation or the α-method; one method is a polygonal line composed of calibration data. We tested on OD data of 51 CSF/serum sample pairs, measured with EUROIMMUN AG (Lübeck, Germany) ELISA tests for antibody determination in CSF, as part of INSTAND e.V. proficiency survey tests for the MRZH reaction (Measles, Rubella, Varicella zoster, Herpes simplex virus). Each method was tested with four ODs, standard curve methods additionally with only two ODs, identified by a selection rule. We found all methods to be of comparable accuracy and precision. With the standard curve methods, there were no differences between two ODs and four ODs evaluations. Consistency between method parameters and measured OD values is a key property of standard curve methods with a strong impact on accuracy and precision. We found a statistically significant difference with parameter consistency between a 4PL standard curve evaluation of this study and an α-method evaluation of data, measured with ELISAs of Siemens Healthcare GmbH (Marburg, Germany). General considerations show Q-values obtained by parameter variation to be more reliable than those resulting from selection rule application with standard curves.


The psychometric properties of the late positive potential during emotion processing and regulation.
The late positive potential (LPP) is a commonly used event-related potential (ERP) in the study of emotion and emotion regulation. The LPP has also been evaluated as a neural marker of affective psychopathology. The psychometric properties of this component have not been examined, however. The current study was conducted with the aim of addressing two questions: how internally consistent is the LPP, and how many trials are necessary to obtain a stable LPP? Fifty-eight participants completed an emotion regulation task. First, split-half reliabilities were computed for the LPP and for difference waves revealing emotion effects (negative minus neutral) and regulation effects (reappraise minus negative). Second, averages including progressively more trials were evaluated and compared to overall participant averages. These data indicated good-to-excellent reliability for neutral, negative and reappraise trials, as well as difference waves. Furthermore, the LPP varies little after 8 trials are added to the average and the difference waves vary little after 12 trials are included. Together, the findings of the current study suggest that the LPP demonstrates good internal consistency and can be adequately quantified with relatively few trials.


Undertreatment of thick head and neck melanomas: an age-based analysis.
To determine U.S. treatment patterns for pathologic staging practices in patients with thick head and neck melanomas (HNM). Patients with thick HNM without clinical evidence of in-transit, regional, or distant metastatic spread at presentation were identified from the Surveillance Epidemiology and End Results database. Treatment trends for patients were summarized, and univariate and multivariate analyses were performed to identify associations between varying practice patterns. A total of 1,230 patients with HNM meeting the inclusion criteria were identified. Surgical staging procedures were utilized in 53.5 %, including both sentinel lymph node biopsy (37 %) and elective neck dissection (16 %). Patients undergoing a surgical staging procedure were younger (64 vs. 77 years, p < 0.001) with smaller tumors (6.3 vs. 6.6 mm, p = 0.008). The rate of occult nodal disease was 22 % in patients undergoing a surgical staging procedure. The presence of a positive regional node in this subgroup of patients was associated with a significant reduction in disease-specific (44 vs. 59 months, p < 0.001) and overall survival (40 vs. 53 months, p < 0.001) on univariate analysis. On multivariate analysis, the presence of a positive node was the most significant factor for reduced overall survival (hazard ratio 2.36, 95 % confidence interval 1.71-3.23) and disease-specific survival (hazard ratio 2.84, 95 % confidence interval 1.99-4.06). Pathologic staging procedures provide independent prognostic information for patients with thick HNM. Despite this, current practice patterns demonstrate underutilization, particularly in elderly patients. Further work is needed to address the barriers to pathologic staging implementation in patients with thick HNM.


Frequency and characteristics of additionally detected ipsilateral breast lesions following recall at screening mammography.
To determine the frequency and outcome of additionally detected ipsilateral breast abnormalities following recall at screening mammography. We included a consecutive series of 130,338 screening mammograms obtained between January 1, 2014 and January 1, 2016. During 2-year follow-up, clinical data were collected of all recalls. Women with a bilateral recall (115) and women recalled for multiple lesions in one breast (165) were excluded from the analyses. Screening outcome parameters were determined for recalled women with or without evaluation of additional ipsilateral breast abnormalities following recall. A total of 3995 women were recalled (recall rate, 3.1%). In 258 (6.4%) of these women, another lesion was detected in the ipsilateral breast than the one for which she had been recalled. Biopsy was more frequently performed of additionally detected ipsilateral lesions than of recalled lesions (55.8% (144/258)) versus 39.7% (1375/3457), (p < 0.001)). The proportion of malignancy in recalled lesions and additionally detected lesions was comparable (21.5% (743/3457) versus 19.0% (49/258), p = 0.34). Of all 144 biopsies of additionally detected ipsilateral lesions, 9 revealed a synchronous tumour in addition to a malignant recalled lesion, and 33 biopsies revealed multicentric or multifocal tumours. In 5 women, the recalled lesion turned out to be benign, whereas the additional lesion in a different quadrant was malignant at biopsy. A total of 97 biopsies showed benign findings. A substantial proportion of women are analyzed for additional ipsilateral breast lesions following recall. These lesions are more frequently biopsied than recalled lesions, but have a comparable probability of being malignant. The majority of additionally detected cancerous lesions are part of multifocal or multicentric malignancies.


Does selected immunological panel possess the value of predicting the prognosis of early-stage resectable non-small cell lung cancer?
The immune status in the tumor micro-environment of lung cancer is highly informative, and expression status of some biomarkers in the tumor micro-environment may have deep connected statistical characteristics which could indicate immune status and predict related clinical outcomes. In this study, a panel of 9 immune biomarkers are selected for their possible predictive value of clinical outcomes in early-stage resectable non-small cell lung cancer (NSCLC). We introduced a new way of interpreting the expression of Immunohistochemistry-based biomarkers in predicting the prognosis of patients. Immunohistochemistry were performed on surgical samples from 139 patients with NSCLC. Cox regression and subgroup analysis were conducted for the screening of biomarkers that were significant in survival and prognosis. Afterwards, Principle Component Analysis was conducted on screened biomarkers in order to extract characteristic root, which were utilized by an Artificial Neuron Network (ANN) for the prediction of clinical outcomes. Six out of 9 biomarkers were considered significant and were selected for the data analysis. The KMO-Bartlett's Sphericity test was valid (0.658>0.5, P=0.0001). The principle component regression results indicated that the survival was associated with the principle component Z4 (Y=0.316×Z4+2.298, R=0.189, P=0.026). Also, regression-free survival was associated with the principle component Z4 and Z2 (Y=0.314×Z4+0.255×Z2+2.061, R=0.249, P=0.013). Principle components ranking (PCrank) was calculated and after the determination of a cutoff of 0.2, the intergroup comparison of subgrouphigh (PCrank value above 0.2) and subgrouplow (PCrank value below 0.2) was significant in overall survival (OS) (P=0.025). A database search validated our results. Afterwards, the ANN model successfully predicted the clinical outcome, with accuracies of 94.1% and 96.2% respectively in models 1 and 2. The selected immunological panels have promising potential for predicting the prognosis of resectable NSCLC.


[Flexion contracture of the fingers as a result of digitorum profundus tenodesis at the site of radial metaphyseal fracture].
A case of patient with flexor digitorum profundus tenodesis at the site of metaphyseal fracture of the radius is presented. The open fracture occurred when the patient was 11 years old and was treated elsewhere with plaster of paris. Progressive flexion contracture of the middle, ring and little finger was treated surgically 7 years later. Full extension and good hand function has been achieved.


Antitumor Activity and Treatment-Related Toxicity Associated With Nivolumab Plus Ipilimumab in Advanced Malignancies: A Systematic Review and Meta-Analysis.
Combining immune checkpoint inhibitors has shown its efficacy compared to monotherapy in advanced malignancies. We conducted this meta-analysis to provide latest evidence on the objective response rate (ORR) and incidence of treatment-related high-grade adverse events (AEs) during nivolumab and ipilimumab combination treatment and further explore from different drug dose level. PubMed and the 2019 American Society of Clinical Oncology (ASCO) annual meeting abstracts were searched for qualified clinical trials up to June 2019. Of the 23 clinical trials (13 from publications and 11 from ASCO abstracts) included, 2,114 and 2,674 patients were eligible for efficacy and safety analysis, respectively. Pooled analysis suggested that the overall ORR was achieved in 34.5% [95% confidence interval (CI), 29.1-40.4%] of patients. There was no significant difference between nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1-Q3W) and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3-Q3W) arms in ORR [30.8% vs 41%; odds ratio (OR), 0.72; 95% CI, 0.39-1.30; P = 0.275]. Grade 3-4 AEs related to combination therapy occurred in 39.9% (95% CI, 33.5-46.7%) of patients; the most commonly reported grade 3-4 treatment-related AEs were diarrhea (5.28%), colitis (3.96%) and increased alanine aminotransferase (3.51%). Incidence of grade 3-4 AEs were significant lower in N3I1-Q3W arm than in N1I3-Q3W arm (31.3% vs 55.9%; OR 0.52; 95% CI, 0.32-0.87; P = 0.012). Treatment-related death was rare and occurred in 2.0% (95% CI, 1.5-2.7%) of patients. Our comprehensive study provides more precise data on the incidence of treatment-related high-grade AEs and ORR among patients receiving nivolumab and ipilimumab combination regimens. Patients on the N3I1-Q3W arm had comparable ORR and significantly occurred less grade 3-4 AEs than patients on the N1I3-Q3W arm. Our finding is of great importance in assisting clinical trial design and clinical medication choice.


Association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and H-type hypertension: A systematic review and meta-analysis.
The polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T has been linked to H-type hypertension. But the conclusion remained controversial. To elucidate this issue, we performed a comprehensive meta-analysis to analyze the MTHFR C677T polymorphism and H-type hypertension. The English and Chinese databases were systematically searched to identify relevant studies until November 2020. RevMan 5.3 and Stata 12.0 software were used for meta-analysis. The odds ratio (ORs) and 95% confidence intervals (95% CIs) were used to assess the relationship between the MTHFR C677T polymorphism and H-type hypertension. A total of 14 studies involving 1769 cases and 1443 controls were included. The meta-analysis results showed the association between MTHFR C677T polymorphism and H-type hypertension with the homozygous codominant model (OR = 3.30, 95% CI = 1.94-5.60), heterozygous codominant model (OR = 2.34, 95% CI = 1.53-3.58), dominant model (OR = 1.79, 95% CI = 1.33-2.41), recessive model (OR = 2.70, 95% CI = 1.73-4.21),and the allelic model (OR = 1.82, 95% CI = 1.41-2.35). All p-values were less than 0.05. Therefore, MTHFR C677T polymorphism has a positive correlation with the risk of H-type hypertension. Among them, TT mutation has the greatest impact on the activity of this enzyme, which causes Hcy to rise and leads to H-type hypertension. In summary, our results provide sufficient data to support the hypothesis that the MTHFR C677T polymorphism is related to H-type hypertension susceptibility.


Contribution of maternal mRNA for maintenance of Ca2+-dependent reaggregating activity in dissociated cells of Xenopus laevis embryos.
Dissociated Xenopus laevis blastula cells, where reaggregation was inhibited in Ca2+-free medium, reaggregated immediately after the addition of Ca2+. This reaggregation was not inhibited by cordycepin or actinomycin D treatment during culture, although cycloheximide and puromycin were inhibitory. The reaggregation was not inhibited even when fertilized eggs were microinjected with cordycepin and their RNA synthesis was continuously inhibited through cleavage to blastula stages. In neurula cells, cordycepin treatment induced significant reduction in sizes of aggregates formed. These results suggest that the Ca2+-dependent reaggregating activity of blastula cells is maintained by the translation of maternal, rather than newly synthesized, mRNA.


An antigenic determinant which is variant in a population of Plasmodium falciparum is present in isolates of Plasmodium malariae.
A monoclonal antibody that is directed against an antigenic determinant which is variant in a population of Plasmodium falciparum also reacts with Plasmodium malariae.


Temporal variability of QT interval and changes in T wave morphology in dogs as markers of the clinical risk of drug-induced proarrhythmia.
The aim of this experiment was to establish the usefulness of assessing temporal variability of the QT interval and changes in the T wave morphology in dogs as markers of pro-arrhythmic risk in humans. For this purpose, the electrocardiographic effects of astemizole and cisapride, two well known pro-arrhythmic drugs in humans, were assessed in dogs. Astemizole was administered intravenously at single doses of 1 and 3 mg/kg whilst cisapride was administered orally at doses of 1.5 and 6 mg/kg. Electrocardiograms (ECG) were recorded before and after treatment. From each ECG tracing, QT intervals were recorded over 100 beats for calculation of the mean and standard deviation (SD) of QT and mean corrected QT (QTc). The coefficient of variation of QT (CV=SD/mean) was calculated as an indicator of QT temporal variability. The changes in T wave morphology were assessed in precordial lead CV5RL. Astemizole increased both the QTc interval and the CV of QT. Increases in these parameters also occurred after cisapride, but were less marked than after astemizole. In addition, both compounds produced a notching of the T wave, consisting of the presence of two peaks. The effects of astemizole and cisapride on the CV of QT and their propensity to induce of T wave notching are consistent with the blocking of I(Kr) channels and indicate, respectively, an increase in temporal variability of cardiac repolarization and an increased heterogeneity of the repolarization of cardiac cells across the myocardium. These changes are key triggers of arrhythmic events and are thus consistent with the pro-arrhythmic properties of these drugs. This study therefore indicates that the evaluation of CV of QT and T wave morphology in dogs may help in predicting drug-induced pro-arrhythmic risk in humans.


Focal spongy changes in the central nervous system of sheep and cattle.
A focal form of vacuolation in the white matter of the thalamus of 13 sheep and 2 cattle is described. The individual vacuoles were similar in appearance to those reported in other forms of spongy degeneration, but they were differentiated by their consistent neuroanatomical localization in the thalamic radiation of all 15 animals. Thirteen of these were sheep used in toxicity experiments and 11 had shown signs of convulsive activity.


Helicobacter pylori infection is associated with a decreased risk of developing oesophageal neoplasms.
The role of Helicobacter pylori infection in the development of oesophageal malignancies was investigated through a multivariate conditional logistic regression analysis in a nested case-control study. Blood samples and a questionnaire on smoking and alcohol habits were collected from a cohort of 32,906 city residents during a health-screening programme between 1974 and 1992. Forty-four cases of oesophageal cancer and 149 matched controls were selected. The mean interval between screening and cancer diagnosis was 11.9 years. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG. Occupation was included in the statistical analysis as an indicator of socio-economic status. Helicobacter pylori seropositivity was present in 10 of the cases (22.7%) and 67 of the controls (45.0%). In a multivariate model, with adjustment for occupation, tobacco and alcohol consumption, the odds ratio for developing an oesophageal malignancy when infected with H. pylori was 0.29 (95% confidence interval (CI): 0.12-0.67). Current smokers had an odds ratio of 17.3 (95% CI: 3.0-99.4) and the odds ratio for ex-smokers was 5.9 (95% CI: 1.15-29.9). High alcohol consumption was no longer significantly associated with oesophageal neoplasms after tobacco smoking was included into the model, odds ratio 1.22 (95% CI: 0.46-3.2). The protective effect of H. pylori was more pronounced for oesophageal adenocarcinoma (seven cases, odds ratio 0.16, 95% CI: 0.00-1.06) than for squamous-cell carcinoma (29 cases, odds ratio 0.41, 95% CI: 0.14-1.2). Helicobacter pylori infection is associated with a decreased risk of developing an oesophageal malignancy. Current smokers and ex-smokers have instead a definite increased risk of oesophageal neoplasms.


Image-guided core-needle biopsy in patients with suspected or recurrent lymphomas.
It is now commonly admitted that the diagnosis of recurrence of lymphoma can be assessed by image-guided needle biopsy (IGNB). However, the means of obtaining tissue for the original diagnosis of lymphoma is often surgery. The aim of this study was to compare the accuracy of IGNB at the time of diagnosis and at the time of recurrence or progression. The authors performed 212 IGNBs on 194 patients who eventually had a diagnosis of lymphoma. One hundred three IGNBs were obtained at original diagnosis and 109 at recurrence or progression. Large-cutting core-biopsy needles, ranging in size from 20 gauge to 14 gauge, were used. Immunohistochemistry studies were performed in all lymphoma cases. A diagnosis of lymphoma with subtyping was obtained in 88% of all cases, in 85% at initial diagnosis, and in 89% at follow-up. Therapy was initiated on the basis of IGNB in 93% of all cases, in 91% at initial diagnosis, and in 94% at follow-up. Benign complications occurred in 7.5% of cases and did not require specific treatment. IGNB was equally effective for making a specific diagnosis of lymphoma and initiating therapy at the time of original diagnosis and at follow-up. The authors recommend that IGNB be performed as the initial procedure for the diagnosis of lymphoma in the absence of peripheral lymph nodes, either at presentation or at recurrence.


Toll-like receptor 2 mediates the immune response of the bovine oviductal ampulla to sperm binding.
We previously reported that sperm binding to cultured bovine oviduct epithelial cells induces an anti-inflammatory immune response. Now we have developed a differentiated explant model to focus on the oviductal ampulla, where fertilization occurs, and to study the effect of sperm capacitation on the immune response. We used heparin to stimulate bovine sperm capacitation. Fluorescence imaging showed that 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide-labeled sperm pretreated with (Hep(+) ) or without (Hep(-) ) heparin rapidly attached to the explant ciliated epithelium in similar numbers. However, only Hep(+) sperm upregulated explant messenger RNA (mRNA) transcription of TLR2, IL8, TGFB1, and PGES, without changes in TNFA and IL-10 expression, while Hep(-) sperm only upregulated PGES. The responses were primarily anti-inflammatory, with a greater response produced by Hep(+) sperm, which also produced a substantial increase in TLR2 protein expression in the epithelium. The addition of TLR1/2 (toll-like receptor 1/2) antagonist to the Hep(+) and (Hep(-) ) sperm-explant coincubations reduced sperm attachment to the epithelium and inhibited TLR2 protein expression and some of the Hep(+) sperm-induced mRNA transcription. Our observations suggest that the ampullar epithelium immunologically reacts more strongly to sperm that have undergone heparin stimulation of capacitation. This anti-inflammatory response could serve to protect capacitated sperm as they approach the oocyte in the ampulla.


HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells.
We previously found that Homeobox containing 1 (HMBOX1) was required for bone mesenchymal stem cell (BMSC) and mouse embryonic stem cell (ESC) differentiation into vascular endothelial cells (VECs). However, the function of HMBOX1 in VECs is still unknown. In this study, we found that HMBOX1 was abundantly expressed in the cytoplasm of human umbilical vascular endothelial cells (HUVECs). Knockdown of HMBOX1 induced apoptosis and inhibited autophagy. Overexpression of HMBOX1 inhibited apoptosis induced by fibroblast growth factor 2 deprivation and promoted autophagy. Metallothionein 2A (MT2A) was identified as an interaction protein with HMBOX1 by yeast two-hybrid assay, and confirmed by co-immunoprecipitation. Overexpression of HMBOX1 elevated intracellular free zinc level. Knockdown of MT2A inhibited this phenomenon. Moreover, N,N,N = ,N = -tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, reversed the anti-apoptosis and pro-autophagy effects of HMBOX1. In conclusion, HMBOX1 regulated intracellular free zinc level by interacting with MT2A to inhibit apoptosis and promote autophagy in VECs.


Value of N-terminal pro brain natriuretic peptide levels in different types of Fontan circulation.
N-terminal pro brain natriuretic peptide (NT-proBNP) is an important biomarker in congestive heart failure. This has also been confirmed in congenital heart disease. However, its clinical value in patients with different types of Fontan circulation remains questionable. We prospectively analysed 124 patients with various types of Fontan surgery between October 2006 and February 2011. We included 49 patients with older Fontan modification [atriopulmonary connection (APC) and atrioventricular connection (AVC)] and 75 patients with total cavopulmonary connection (TCPC). The NT-proBNP levels of patients with APC/AVC were significantly higher than in patients with TCPC (P < 0.001), even after accounting for sex, age, ventricular function, atrioventricular regurgitation, ventricular morphology, and arrhythmia (P = 0.035). Levels of NT-proBNP positively correlated with atrioventricular valve regurgitation (r = 0.29, P = 0.013) and ventricular dysfunction (r = 0.23, P = 0.052) only in patients with TCPC, but not in patients with APC or AVC (r = 0.01, P = 0.509 and r = 0.10, P = 0.493, respectively). Levels of NT-pro BNP are related to the type of Fontan circulation. The older types (APC/AVC) that involve more atrial tissue in the systemic venous pathway show higher NT-proBNP levels independently of their cardiac status. Their NT-proBNP levels should be interpreted with care.


Clinical measurement of extravascular lung water.
The thermal-dye technique for the measurement of ELW is available for clinical and experimental use. This method is safe and can be performed serially in an individual patient. Although it is invasive, it requires only a central venous catheter and an arterial catheter, which are often already in place for routine hemodynamic monitoring and management. The procedure is accurate under a variety of conditions. Two obstacles argue against its routine application. First, the reliability of this approach appears to be seriously compromised when there are areas of edematous lung with poor blood perfusion. This includes aspiration and perhaps other forms of acute lung injury. Second, it remains to be demonstrated how useful routine measurements of ETVL, even if accurate, are in clinical management. However, regardless of the accuracy of the various methods for determination of ELW, the process of their development has significantly enhanced our knowledge of pulmonary edema formation and fluid distribution. We are at a transition point of soon being able to determine ELW easily. Techniques of reducing ELW can now be assessed directly in patients with pulmonary edema. As these therapies are developed and understood, the demand for the measurement of ELW will become a greater part of clinical medicine, and may stimulate further refinement of methods for quantitating lung water.


Quantitative studies of steroid bioconversions in the seminal vesicles of spawning male African catfish, Clarias gariepinus (Burchell), under natural conditions, and of non-spawning catfish under natural and fish farm conditions.
1. Steroid bioconversions in the seminal vesicles of Clarias gariepinus were studied quantitatively in vitro by tissue incubations with [3H]pregnenolone, [3H]androstenedione and [14C]11 beta-hydroxyandrostenedione, respectively. 2. Spawning and non-spawning catfish, collected in the Hula nature reserve in northern Israel during the spawning period, and non-spawning animals, collected from a fish pond in the same region during the same period, were studied. 3.Spawning animals showed a significantly higher production of 17 alpha-hydroxyprogesterone, 5 beta-pregnan-17 alpha-ol-3,20-dione and 5 beta-reduced androgens than non-spawning feral and pond catfish, as a result of a significantly increased contribution of the enzymes 5 beta-reductase and 3 alpha-hydroxysteroid dehydrogenase (HSD). 4. In spawning catfish the concentration of gonadotropin in blood plasma were also significantly higher than in the plasma of non-spawning feral and pond catfish. This increase in gonadotropin level might have induced the rise in enzyme activity of 5 beta-reductase and 3 alpha-HSD. 5. It is concluded that the absence of a shift in steroidogenesis towards the production of 5 beta-reduced steroids may be among the factors preventing spontaneous spawning in male African catfish under husbandry conditions.


Effects of rhinovirus infection on the expression and function of cystic fibrosis transmembrane conductance regulator and epithelial sodium channel in human nasal mucosa.
Changes in expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) have been found to cause airway surface liquid (ASL) derangement and to impair mucociliary clearance, both of which have been linked to the pathogenesis of rhinovirus (RV) infection. The effects of RV infection on the expression and function of CFTR and ENaC in nasal epithelial cells were investigated. Nasal epithelial cells obtained from 14 turbinoplasty patients were infected with RV serotype 16 (RV-16) for 4 hours. Expression of CFTR, α-ENaC, β-ENaC, and γ-ENaC was determined by real-time polymerase chain reaction, Western blot analysis, and confocal immunofluorescence microscopy. Functional changes in the CFTR and ENaC proteins were assessed by measuring transepithelial resistance (TER) using a voltmeter combined with ion channel modulators. Rhinovirus infection increased expression of CFTR, α-ENaC, β-ENaC, and γ-ENaC messenger RNA (mRNA) and protein compared with controls (P < .05 each) and increased the expression of all 4 proteins on confocal immunofluorescence microscopy. Treatment of cells with the ENaC blocker amiloride and the CFTR activator forskolin increased TER in RV-infected cells, whereas forskolin decreased TER in uninfected cells. The CFTR inhibitor NPPB, however, blocked CFTR more in RV-infected than in noninfected cells. Rhinovirus increased the expression of CFTR and appeared to alter its function. In contrast, ENaC expression and function were increased by RV infection. Therefore, RV infection may impair mucociliary transport of nasal epithelium by these alterations.


ACTH radioimmunocytochemistry (RICH) on rat anterior pituitary cells.
Radioimmunocytochemistry (RICH) was applied to detect corticotrophs in adult rat pituitaries and 8-day-old anterior pituitary monolayers by incubating sections and cultures with 125I-ACTH-anti ACTH immune complexes. After incubations autoradiography was made. In comparison, "conventional" immunostaining was carried out on adjacent sections and parallel cultures. It has been established that RICH is suitable for detection of corticotrophs.


Cultured C2C12 cell lines as a model for assessment of bacterial attachment to bovine primary muscle cells.
The mechanisms of bacterial attachment to meat tissues need to be understood to enhance meat safety interventions. However, little is known about attachment of foodborne pathogens to meat muscle cells. In this study, attachment of six Escherichia coli and two Salmonella strains to primary bovine muscle cells and a cultured muscle cell line, C2C12, was measured, including the effect of temperature. At 37°C, all but one strain (EC623) attached to C2C12 cells, whereas only five of eight strains (M23Sr, H10407, EC473, Sal1729a and Sal691) attached to primary cells. At 10 °C, two strains (H10407 and EC473) attached to C2C12 cells, compared to four strains (M23Sr, EC614, H10407 and Sal1729a) of primary cells. Comparing all strains at both temperatures, EC614 displayed the highest CFU per C2C12 cell (4.60±2.02CFU/muscle cell at 37 °C), whereas greater numbers of M23Sr attached per primary cell (51.88±39.43CFU/muscle cell at 37 °C). This study indicates that primary bovine muscle cells may provide a more relevant model system to study bacterial attachment to beef carcasses compared to cell lines such as C2C12.


SAG treatment ameliorates memory impairment related to sleep loss by upregulating synaptic plasticity in adolescent mice.
Adequate sleep during the developmental stage can promote learning and memory functions because synaptic protein synthesis at primed synapses during sleep profoundly affects neurological function. The Sonic hedgehog (Shh) signaling pathway affects neuroplasticity in the hippocampus during the development of the central nervous system. In this study, the changes in synaptic morphology and function induced by sleep deprivation and the potential therapeutic effect of a Shh agonist (SAG) on these changes were investigated in adolescent mice. Adolescent mice were subjected to sleep deprivation for 20 hrs (2 pm to 10 am the next day) and were free to sleep for the remaining 4 hrs per day for 10 consecutive days. Sleep-deprived mice were injected with SAG (10 mg/kg body weight, i.p.) or saline (i.p.) every day 5 min before the onset of the 20 h sleep deprivation period. Chronic sleep deprivation impaired recognition and spatial memory, decreased the number of dendritic spines and mEPSCs of hippocampal CA1 pyramidal neurons, decreased the postsynaptic density, and reduced Shh and glioma-associated oncogene homolog 1 (Gli1) expression. SAG significantly protected against sleep deprivation-induced memory dysfunction, increased the CA1 pyramidal neuronal dendritic spine number and mEPSC frequency, and increased Gli1 expression. In conclusion, sleep deprivation induces memory impairment in adolescent mice, and SAG treatment prevents this impairment, probably by enhancing synaptic function in the hippocampal CA1 region.


Cloning, characterization and expression of the extracellular lipase gene from Aureobasidium pullulans HN2-3 isolated from sea saltern.
The extracellular lipase structural gene was isolated from cDNA of Aureobasidium pullulans HN2-3 by using SMART(TM) RACE cDNA amplification kit. The gene had an open reading frame of 1245 bp long encoding a lipase. The coding region of the gene was interrupted by only one intron (55 bp). It encodes 414 amino acid residues of a protein with a putative signal peptide of 26 amino acids. The protein sequence deduced from the extracellular lipase structural gene contained the lipase consensus sequence (G-X-S-X-G) and three conserved putative N-glycosylation sites. According to the phylogenetic tree of the lipases, the lipase from A. pullulans was closely related to that from Aspergillus fumigatus (XP_750543) and Neosartorya fischeri (XP_001257768) and the identities were 50% and 52%, respectively. The mature peptide encoding cDNA was subcloned into pET-24a (+) expression vector. The recombinant plasmid was expressed in Escherichia coli BL21(DE3). The expressed fusion protein was analyzed by SDS-PAGE and western blotting and a specific band with molecular mass of about 47 kDa was found. Enzyme activity assay verified the recombinant protein as a lipase. A maximum activity of 0.96 U/mg was obtained from cellular extract of E. coli BL21(DE3) harboring pET-24a(+)LIP1. Optimal pH and temperature of the crude recombinant lipase were 8.0 and 35 degrees C, respectively and the crude recombinant lipase had the highest hydrolytic activity towards peanut oil.


Ontogenic pattern of nucleobindin-2/nesfatin-1 expression in the gastroenteropancreatic tissues and serum of Sprague Dawley rats.
Nesfatin-1 is a novel metabolic hormone that has glucose-responsive insulinotropic actions. Islet β-cells and gastrointestinal tissues have been reported as abundant sources of nesfatin-1 and its precursor hormone nucleobindin-2 (NUCB2). While nesfatin-1 is emerging as a multifunctional hormone, there are no reports on the developmental expression of NUCB2/nesfatin-1. The main objective of this study was to examine the ontogenic expression of NUCB2 mRNA, and NUCB2/nesfatin-1 immunoreactivity in the pancreas, stomach and duodenum, and the circulating levels NUCB2/nesfatin-1 in Sprague Dawley rats. In addition, we also determined the co-localization of NUCB2/nesfatin-1 and insulin immunoreactivity during development. NUCB2/nesfatin-1 immunoreactivity was found in the rat stomach from postnatal days 13-27. Furthermore, NUCB2/nesfatin-1 immunoreactivity was also detected in the enteroendocrine cells of the duodenum at postnatal days 13 and 27. Duodenal NUCB2 mRNA expression at postnatal day 27 was highest. Serum NUCB2/nesfatin-1 levels on embryonic day 21 and postnatal day 1 were lower than serum NUCB2/nesfatin-1 levels of adults and neonates at postnatal days 13, 20 and 27, gradually increasing with growth, suggesting an increase in its production and secretion from tissues including the gastrointestinal tract and pancreas. Our findings indicate that NUCB2/nesfatin-1 colocalizes with insulin in the islet β-cells at all developmental stages, but the percentage of colocalization varies in an age-dependent manner. These findings suggest that NUCB2/nesfatin-1 has potential age- and tissue-specific role in the developmental physiology of rats during growth.


Academic and personal characteristics as predictors of clinical success in medical school.
Interviewer ratings of personal characteristics such as maturity correlated with clinical success, and were more important in determining clinical success than were conventional cognitive variables of grade point average or MCAT scores for five classes of University of Missouri-Columbia medical students.


Elucidating the Nature of Interactions in Collagen Triple-Helix Wrapping.
Collagen is the most abundant protein family in the animal kingdom. Its structural motif envisages three polypeptide chains coiled in the so-called collagen triple helix. Depending on the triplet amino acid sequence of the chains, collagen has different helical arrangements. Such atomic-scale structural variations have a large impact on the large-scale structure of collagen. In this Letter, we elucidate the interactions that are responsible for a specific helical pattern of the collagen protein by means of DFT-D-based computer simulations. We demonstrate that interchain interactions and solvation effects stabilize compact helices over elongated ones. Conversely, elongated helices are stabilized by less geometrical strain and entropic factors. Our computational procedure predicts the collagen helical pattern in agreement with the experimental evidence.


Postoperative irrigation with bisphosphonates may reduce the recurrence of giant cell tumor of bone.
Giant cell tumor of bone (GCTB) is a common benign bone tumor characterized by local osteolysis and high proclivity for recurrence. Surgical excision is the preferred treatment. However, simple wide resection may cause functional and cosmetic deformities of the skeleton. Currently, intralesional curettage with adjuvant therapy is a popular treatment. Bisphosphonates are recommended as an effective adjuvant treatment, and their antitumor effects have been proved in laboratory studies. During clinical treatment, intravenous and peroral administration of bisphosphonates has been attempted and has been successful in reducing the tumor recurrence rate. However, the use of bisphosphonates in GCTB adjuvant therapy requires additional study. Irrigation is a classic method for focal clearance after surgery. Therefore, we hypothesize that postoperative irrigation with bisphosphonates may be a safe and effective treatment for GCTB. The efficacy and safety of this method are worthy of further investigation.


MiR-297 inhibits tumour progression of liver cancer by targeting PTBP3.
Whereas increasing evidences demonstrate that miR-297 contributes to the tumour development and progression, the role of miR-297 and its underlying molecular mechanisms in hepatocellular carcinoma (HCC) was still unclear. Here, we reported that the expression of miR-297 increased significantly in hepG2 cells after the treatment of the conditioned medium of human amniotic epithelial cells(hAECs) which can inhibit the proliferation and migration of hepG2. And the overexpression of miR-297 inhibits the cell proliferation, migration and invasion of HCC cell lines in vitro and suppressed the tumorigenesis of HCC in vivo. Polypyrimidine tract-binding protein 3 (PTBP3) was identified as a direct target gene of miR-297 in HCC cell lines, and mediated the function of miR-297 in HCC cells. In clinical samples, miR-297 levels have a tendency to decrease, but there are no statistically significant differences. Furthermore, in vitro cell experiments confirmed that overexpression of miR-297 could inhibit the PI3K/AKT signaling pathway by down-regulating PTBP3 expression, thereby inhibiting the proliferation, migration and invasion of HCC cells. In conclusion, our results revealed that miR-297 could down-regulate the expression of PTBP3 and inhibit the activation of PI3K/AKT signaling pathway, thereby preventing HCC growth, migration and invasion.


Sudden Death After Febrile Seizure Case Report: Cerebral Suppression Precedes Severe Bradycardia.
A 20-month-old girl with a complex chromosomal disorder had first presentation of febrile status epilepticus and was admitted to the hospital. Two days after her initial seizure, she died suddenly and unexpectedly during a video EEG monitoring study. An advanced analysis of the physiologic changes in the hours and minutes leading up to death was undertaken. The electrocardiography over the last 19 minutes of life was reviewed, and the R-R intervals were manually measured. Heart rate variability was assessed through calculation of the SD of the R-R intervals and the root mean square of successive differences over successive 100 beat periods. Instantaneous heart rate, SD of the R-R intervals, the root mean square of successive differences, and oxygen saturation were plotted against time over the last 19 minutes of life. Diffuse cerebral suppression on EEG was observed 10 minutes before death, followed minutes later by severe bradycardia and increased heart rate variability. Although the child did not meet criteria for a diagnosis of epilepsy, the sequence of physiologic changes leading up to death suggests a pathophysiology similar to sudden unexplained death in epilepsy. A comparable pattern of diffuse cerebral suppression preceding parasympathetic overactivity has been suggested in some rare cases of adults who have experienced sudden unexplained death in epilepsy during video EEG monitoring.


Valproate-Induced Lower Extremity Swelling.
New-onset severe peripheral edema warrants an extensive evaluation, including congestive heart failure, cirrhosis, nephrotic syndrome, hypoalbuminemia, or lymphatic or venous obstruction.


Regulation of mTORC1 by growth factors, energy status, amino acids and mechanical stimuli at a glance.
The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) plays a pivotal role in the regulation of skeletal muscle protein synthesis. Activation of the complex leads to phosphorylation of two important sets of substrates, namely eIF4E binding proteins and ribosomal S6 kinases. Phosphorylation of these substrates then leads to an increase in protein synthesis, mainly by enhancing translation initiation. mTORC1 activity is regulated by several inputs, such as growth factors, energy status, amino acids and mechanical stimuli. Research in this field is rapidly evolving and unraveling how these inputs regulate the complex. Therefore this review attempts to provide a brief and up-to-date narrative on the regulation of this marvelous protein complex. Additionally, some sports supplements which have been shown to regulate mTORC1 activity are discussed.


Macaca radiata (bonnet monkey): a spontaneous model of nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a well-recognized condition that includes a spectrum of clinicopathology conditions ranging from steatotosis to cirrhosis and liver failure. Available animal models are not ideal as they show only a partial resemblance to characteristic human NAFLD. This study was aimed at identifying a nonhuman primate model of NAFLD resembling features of human NAFLD, which will be useful in understanding the mechanism of the onset of this disease and for developing novel therapeutic modalities. The histological status of the liver and serum levels of triglycerides (TG), cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of aged bonnet monkeys were compared with that of the aged rhesus and adult bonnet monkeys. Histopathology and immunostaining of liver sections and oil red 'O' confirmed NAFLD in aged bonnet monkeys. Aged bonnet monkeys showed a significant (P<0.01) increase in serum TG, AST and ALT compared with aged rhesus and adult bonnet monkeys. Histopathology of the liver of aged bonnet macaques showed diffused microvesicular and macrovesicular fatty changes, perivenular and portal and perisinusoidal fibrosis with fatty degeneration of hepatocytes, and immunostaining of liver sections was suggestive of NAFLD. The spontaneous occurrence of NAFLD in normal animals is rare, but aged bonnet monkeys may serve as a unique animal model for studies related to NAFLD because they mimic pathophysiological features of human NAFLD.


The Relationship Between Autoimmune Disease and Disease-Modifying Antirheumatic Drugs on Wound Healing.
Objective: To evaluate the role of disease-modifying antirheumatic drugs (DMARDs) on wound healing outcomes of patients with autoimmune disease at our tertiary wound care center. Approach: Retrospective review of patients presenting to our wound care center between 2014 and 2018 with both chronic wounds and a history of inflammatory disease. Patient demographics, comorbid conditions, and progression to complete wound healing were compared between those taking DMARDs or not at the time of wound onset. The study adheres to the STROBE statement. Results: Fifty-eight patients with a total of 296 wounds were retrospectively reviewed. Patients were taking at least one DMARD at wound onset in 217 (73.3%) of these wounds. The average number of DMARDs at wound onset was 1.5 (standard deviation 1.2). Two hundred ten wounds progressed to heal (70.9%), with a median time to healing of 229.5 days (interquartile range 71.0-490.0). Of the 210 wounds that healed, patients taking at least one DMARD had a significantly shorter time to healing relative to patients who were not on any DMARDs (median 190.5 days vs. 340.0 days, p = 0.0156). Innovation: Characterizing wound healing outcomes at a tertiary hospital with a dedicated wound care center and analyzing the role of DMARDs in wound healing progression. Conclusions: The median time to healing in the studied cohort was 229.5 days, which is much longer than the healing time for noninfected diabetic foot ulcers at our institution. These findings highlight the wound healing challenges posed by underlying autoimmune disease.10.


Alcohol dehydrogenase polymorphism in Apis mellifera.
A polymorphic system of ADH isozymes is described in the honeybee Apis mellifera. Three and six different electrophoretic patterns were found, respectively, in drone and worker pupae analysis. The data indicate that the ADH isozymes are controlled by three alleles, Adh-1(1), Adh-1(2), and Adh-1(3). The frequency of the Adh-1 alleles is different in two analyzed subspecies, Apis mellifera adansonii (African bees) and Apis mellifera ligustica (Italian bees). In the African bees, the frequencies are 0.256 and 0.697 for Adh-1(1) and Adh-1(2), respectively. In the Italian bees, these values are shown to be 0.902 and 0.098, respectively. The allele Adh-1(3) was not detected in the Italian bee population. The effect of NAD on the resolution of this system was investigated, and only one region of ADH activity was obtained in drone pupae analysis when NAD was used in the gels. However, two different regions of activity were observed in the same samples, in the absence of the coenzyme. ADH activity was not detected in young larvae, but it increased to a maximum in prepupal and white-eyed pupal phases. It then declined progressively to total absence in the emerging bees.


Age at menarche and risk of adverse obstetric outcomes during the first childbirth in Japan: The Japan Environment and Children's Study.
Age at menarche is used as a risk indicator of gestational diabetes mellitus, preterm birth, and fetal growth. However, little is known regarding the age impact on obstetric outcomes among nulliparous women. This study investigated whether menarche age was correlated with obstetric outcomes among nulliparous women. We analyzed the data obtained for 37 645 singleton pregnancies between 2011 and 2014 in the Japan Environment and Children's Study. Age at menarche was categorized into the ≤9-, 10-, 11-, 12-, 13-, 14-, and ≥15-year-old groups (n = 363, 3155, 8390, 11 164, 6713, 5446, and 2414, respectively). We calculated the relative risk for cases of preterm birth <37 weeks, low birthweight <2500 g, small for gestational age, early and late-onset hypertension disorders of pregnancy, and early- and late-diagnosed (diagnosed < or ≧ 24 weeks) gestational diabetes mellitus using a reference of 12 years at menarche. Women with an age at menarche ≤9 years showed an increased incidence of developing early-diagnosed gestational diabetes mellitus (relative risk: 2.42; 95% confidence interval: 1.05-5.60). A high body mass index before pregnancy increased the risk of developing gestational diabetes mellitus. Age at menarche helped in assessing the risk of early-diagnosed gestational diabetes mellitus among nulliparous women. Future studies are needed to clarify the underlying mechanisms. This study is the first to use data from the largest prospective birth cohort study of Japan and to investigate the relationship between menarche age and obstetric outcomes among nulliparous women.


Normal fibronectin levels as a function of age in the pediatric population.
Fibronectin is an important non-immune opsonic protein influencing phagocytic clearance of blood-borne nonbacterial particulates which may arise in association with septic shock, tissue injury, and intravascular coagulation. In the present study, serum fibronectin was measured by both electroimmunoassay as well as rapid immunoturbidimetric assay in healthy children (n = 114) ranging in age from 1 month to 15 years in order to delineate the temporal alterations in fibronectin with age. Normal adult serum fibronectin concentrations are typically 220 micrograms/ml +/- 20 micrograms/ml. Serum concentration is 35-40% lower than normal plasma concentration due to the binding of fibronectin to fibrin during clot formation. Children between 1-12 months of age had significantly (P less than 0.05) lower serum fibronectin levels than children between the ages of 1-15 years. Progressive elevation in fibronectin levels was observed within the last 8 months of the first year of age. Fibronectin levels in children older than 1 year of age remained constant up to 15 years and were within the lower limit of the normal adult concentration. No significant (P greater than 0.05) difference in serum fibronectin was observed between male and female children at all age groups. Fibronectin levels thus, increase during the first year of age and normal levels of this blood protein in the infant are less than the normal range for adults.


NleB, a bacterial effector with glycosyltransferase activity, targets GAPDH function to inhibit NF-κB activation.
Modulation of NF-κB-dependent responses is critical to the success of attaching/effacing (A/E) human pathogenic E. coli (EPEC and EHEC) and the natural mouse pathogen Citrobacter rodentium. NleB, a highly conserved type III secretion system effector of A/E pathogens, suppresses NF-κB activation, but the underlying mechanisms are unknown. We identified the mammalian glycolysis enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as an NleB-interacting protein. Further, we discovered that GAPDH interacts with the TNF receptor-associated factor 2 (TRAF2), a protein required for TNF-α-mediated NF-κB activation, and regulates TRAF2 polyubiquitination. During infection, NleB functions as a translocated N-acetyl-D-glucosamine (O-GlcNAc) transferase that modifies GAPDH. NleB-mediated GAPDH O-GlcNAcylation disrupts the TRAF2-GAPDH interaction to suppress TRAF2 polyubiquitination and NF-κB activation. Eliminating NleB O-GlcNAcylation activity attenuates C. rodentium colonization of mice. These data identify GAPDH as a TRAF2 signaling cofactor and reveal a virulence strategy employed by A/E pathogens to inhibit NF-κB-dependent host innate immune responses.


Two new species of endemic Ecuadorean Amaryllidaceae (Asparagales, Amaryllidaceae, Amarylloideae, Eucharideae).
New species of the genera Stenomesson and Eucharis (Amaryllidaceae) are described from Ecuador. Stenomessonecuadorense is the second species of the genus reported from that country, and the only endemic one. It is related to Stenomessonminiatum and Stenomessoncampanulatum, both from Peru, with which it shares orange flower color and the fusion of the staminal corona to the perianth tube. It differs from Stenomessonminiatum by the non-urceolate perianth, from Stenomessoncampanulatum by its shorter stamens and longer perianth, and from both by its lower montane, cloud forest habitat. Eucharisruthiana, found in the vicinity of Zamora, is related to Eucharismoorei from which it differs by the narrower leaves and tepals; short, deeply cleft staminal corona; the long teeth on either side of the free filaments; the narrowly subulate, incurved free filaments; and the shorter style. The green mature fruit and campanulate floral morphology place it in Eucharissubg.Heterocharis.


Evaluation of beta-D-galactosidase from Escherichia coli and horseradish peroxidase as labels by sandwich enzyme immunoassay technique.
beta-D-galactosidase from Escherichia coli and horseradish peroxidase were evaluated as labels of Fab' in dose-response curves for human alpha-fetoprotein and human chorionic gonadotropin by sandwich enzyme immunoassay technique using fluorogenic substrates for enzyme assay. The non-specific binding of Fab'-peroxidase conjugates to IgG-coated polystyrene balls was less than that of Fab'-beta-D-galactosidase conjugates, and the affinity-purified Fab'-peroxidase conjugates gave more sensitive dose-response curves for these antigens than the corresponding beta-D-galactosidase conjugates. However, a large quantity of Fab'-peroxidase conjugates was required and a longer incubation was necessary for the peroxidase assay, since the peroxidase assay was much less sensitive than the beta-D-galactosidase assay. Other advantages and disadvantages of the two enzymes are discussed.


Food-grade delivery systems of Brazilian propolis from Apis mellifera: From chemical composition to bioactivities in vivo.
Brazilian propolis from Apis mellifera is widely studied worldwide due to its unique chemical composition and biological properties, such as antioxidant, antimicrobial, and anti-inflammatory. However, although many countries produce honey, another bee product, the consumption of propolis as a functional ingredient is linked to hydroethanolic extract. Hence, other food uses of propolis still have to be incorporated into food systems. Assuming that propolis is a rich source of flavonoids and is regarded as a food-grade ingredient for food and pharmaceutical applications, this review provides a theoretical and practical basis for optimising the bioactive properties of Brazilian propolis, encompassing the extraction processes and incorporating its bioactive compounds in the delivery systems for food applications. Overall, pharmacotechnical resources can optimise the extraction and enhance the chemical stability of phenolic compounds to ensure the bioactivity of food formulations.


Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis.
Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell-cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.


Short Review on Quantum Key Distribution Protocols.
Cryptographic protocols and mechanisms are widely investigated under the notion of quantum computing. Quantum cryptography offers particular advantages over classical ones, whereas in some cases established protocols have to be revisited in order to maintain their functionality. The purpose of this paper is to provide the basic definitions and review the most important theoretical advancements concerning the BB84 and E91 protocols. It also aims to offer a summary on some key developments on the field of quantum key distribution, closely related with the two aforementioned protocols. The main goal of this study is to provide the necessary background information along with a thorough review on the theoretical aspects of QKD, concentrating on specific protocols. The BB84 and E91 protocols have been chosen because most other protocols are similar to these, a fact that makes them important for the general understanding of how the QKD mechanism functions.


Vascular endothelial growth factor-C in activating vascular endothelial growth factor receptor-3 and chemokine receptor-4 in melanoma adhesion.
Vascular endothelial growth factor-C (VEGF-C) binds to receptor vascular endothelial growth factor receptor-3 (VEGFR-3) expressed on lymphatic endothelial and melanoma cells. Binding of VEGF-C to VEGFR-3 enhances receptor phosphorylation that activates mitogen-activated protein kinase (MAP-K) and phosphatidylinositol-3-kinase (PI3K). These signalling pathways regulate cell migration and adhesion in response to internal or external changes. In addition, the overexpression of VEGF-C upregulates chemokine receptor CXCR-4 in tumours (melanoma). CXCR-4 is expressed on cells of the immune system (natural killer cells) and facilitates the migration of leukocytes in response to the CXCL12 ligand. The latter is expressed by lymphatic endothelial cells and by stromal cells in the tumour microenvironment (TME). The gradient established between CXCR-4 expressed on tumour cells and CXCL12 produced by stromal and lymphatic endothelial cells enhances tumour cell metastasis. 3-(4-Dimethylamino-naphthalen-1-ylmethylene)-1, 3-dihydroindol-2-one, MAZ-51, is an indolinone-based synthetic molecule that inhibits the phosphorylation of the tyrosine kinase receptor VEGFR-3. CTCE-9908, a CXCR-4 antagonist derived from human CXCL12, hinders receptor phosphorylation and the subsequent signalling pathways that would be activated. VEGF-C is stimulated by transforming growth factor-beta 1 (TGF-β1), which facilitates cell-cell and cell-matrix adhesion by regulating cadherins through the activation of focal adhesion kinase (FAK) and mediates paxillin upregulation. Increased VEGF-C protein levels stimulated by TGF-β bound to VEGFR-3 impact on intracellular pathways that promote tumour cell adhesion. In addition, increased VEGF-C protein levels lead to enhanced CXCR-4 protein expression. Therefore, effective blocking of VEGR-3 and CXCR-4 may inhibit tumour cell metastasis by hampering intracellular proteins promoting adhesion.


Alcohol consumption before pregnancy causes detrimental fetal development and maternal metabolic disorders.
Alcohol consumption before or during pregnancy poses serious health risks to the fetus; however, the underlying mechanisms involved remain obscure. Here, we investigated whether ethanol consumption before pregnancy affects maternal or fetal health and whether pharmacological inhibition of CYP2E1, a major ethanol oxidation enzyme, by 4-methylpyrazole (4-MP) has therapeutic effects. We found that ethanol consumption (5%) 2 weeks before pregnancy resulted in a decrease in the number of viable fetuses and abnormal fetal development, and these effects were accompanied by impaired maternal glucose homeostasis and hepatic steatosis during pregnancy. Neonates of ethanol-fed mice had postnatal macrosomia and significantly decreased growth rates during the lactation period. However, treatment with 4-MP, a CYP2E1 inhibitor, markedly ameliorated the reduction in insulin action and glucose disposal responsiveness in the livers of ethanol-fed mice. Blockage of CYP2E1 significantly reduced the alteration in hepatic lipid deposition, fatty acid oxidation, mitochondrial energy status, and macrophage infiltration observed in ethanol-fed mice. Finally, there was a positive correlation between postnatal macrosomia or growth retardation and increased inflammatory responses. Collectively, our study suggests that even moderate ethanol intake may be detrimental to fetal development and may cause growth retardation through maternal metabolic disorders.


Endoscopic four-hands technique for pituitary tumours.
Tumours in the pituitary fossa region can be resected by endoscopic transnasal surgery using a four-hands technique. The technique, which is atraumatic, safe and minimally invasive, should be the first-line treatment for pituitary tumours and certain skull-base tumours.


A Simple Schiff Base as Fluorescent Probe for Detection of Al3+ in Aqueous Media and its Application in Cells Imaging.
A novel fluorescence probe for the detection of Al3+ was developed based on methionine protected gold nanoclusters (Met-AuNCs). A fluorescent Schiff base (an aldimine) is formed between the aldehyde group of salicylaldehyde (SA) and the amino groups of Met on the AuNCs, and developed for selective detection of Al3+ in aqueous solution. Al3+ can strongly bind with the Schiff base ligands, accompanied by the blue-shift and an obvious fluorescence emission enhancement at 455 nm. The limits of detection (LODs) of the probe are 2 pmol L-1 for Al3+. Moreover, the probe can successfully be used in fluorescence imaging of Al3+ in living cells (SHSY5Y cells), suggesting that the simple fluorescent probe has great potential use in biological imaging.


Peripheral analgesic and antiinflammatory effects of opioids.
Traditionally, opioids were considered the prototype of centrally acting analgesics. In the past decade a substantial literature has emerged demonstrating that opioids can produce potent and clinically measurable analgesia by activation of opioid receptors on peripheral terminals of primary sensory neurons. In addition, endogenous ligands of these peripheral receptors were discovered in immune cells. Major recent findings in peripheral opioid analgesia include the relative lack of tolerance under inflammatory conditions, tetrapeptides as novel peripherally restricted compounds, the potent antiinflammatory activity of mu- and kappa-agonists and the identification of selectins as important molecules governing the homing of opioid cells to injured tissue. In addition to the extensively documented efficacy of locally applied morphine in post-surgical pain, clinical studies have now moved into the field of chronic arthritic pain.


The Role of Gender, Academic Affiliation, and Subspecialty in Relation to Industry Payments to Orthopaedic Surgeons.
The Physician-Payments-Sunshine-Act (PPSA) was introduced in 2010 to provide transparency regarding physician-industry payments by making these payments publicly available. Given potential ethical implications, it is important to understand how these payments are being distributed, particularly as the women orthopaedic workforce increases. The purpose of this study was thus to determine the role of gender and academic affiliation in relation to industry payments within the orthopaedic subspecialties. The PPSA website was used to abstract industry payments to Orthopaedic surgeons. The internet was then queried to identify each surgeon's professional listing and gender. Mann-Whitney U, Chi-square tests, and multivariable regression were used to explore the relationships. Significance was set at a value of P < 0.05. In total, 22,352 orthopaedic surgeons were included in the study. Payments were compared between 21,053 men and 1299 women, 2756 academic and 19,596 community surgeons, and across orthopaedic subspecialties. Women surgeons received smaller research and non-research payments than men (both, P < 0.001). There was a larger percentage of women in academics than men (15.9% vs 12.1%, P < 0.001). Subspecialties with a higher percentage of women (Foot & Ankle, Hand, and Pediatrics) were also the subspecialties with the lowest mean industry payments (all P < 0.001). Academic surgeons on average, received larger research and non-research industry payments, than community surgeons (both, P < 0.001). Multivariable linear regression demonstrated that male gender (P = 0.006, P = 0.029), adult reconstruction (both, P < 0.001) and spine (P = 0.008, P < 0.001) subspecialties, and academic rank (both, P < 0.001) were independent predictors of larger industry research and non-research payments. A large proportion of the US orthopaedic surgeon workforce received industry payments in 2014. Academic surgeons received larger payments than community surgeons. Despite having a larger percentage of surgeons in academia, women surgeons received lower payments than their male counterparts. Women also had a larger representation in the subspecialties with the lowest payments.


Rapid and accurate 13CO2 isotopic measurement in whole blood: comparison with expired gas.
Determination of 13CO2 enrichment on the CO2 released from blood by acid has been used in situations in which breath sampling is difficult. This method can be improved by measuring this enrichment on the CO2 spontaneously released from blood. Therefore, simultaneous comparisons of 13CO2 content between breath and arterialized blood added with or without acid were performed in 51 samples from human studies, using the statistical method of Bland and Altman (J. M. Bland and D. G. Altman. Lancet 1: 307-310, 1986). Strong relationships exist between the methods (r > 0.99) expressed in atom percent excess (APE). Compared with breath, the acid method overestimates the 13CO2 enrichment (0.318 +/- 0.632 APE x 1,000, P < 0.001). The acid-free method shows similar enrichments to breath (0. 003 +/- 0.522 APE x 1,000, P = 0.97) with good precision and degree of agreement (95% confidence interval 0.15 APE x 1,000). The analysis can be performed up to 5 days after sampling with a good reproducibility. In conclusion, measuring 13CO2 enrichments on the CO2 spontaneously released from blood is feasible, gives identical results to the breath method, and lessens operator manipulations. It allows study of situations in which the breath sampling method is not feasible.


Effects of stepwise nitrogen depletion on carotenoid content, fluorescence parameters and the cellular stoichiometry of Chlorella vulgaris.
Stressful conditions can stimulate the accumulation of carotenoids in some microalgae. To obtain more knowledge of the stress response, we studied the effects of different N concentrations on unicellular content of carotenoids using Raman spectroscopic technique; cellular stoichiometric changes and the fluorescence parameters of Chlorella vulgaris were concomitantly studied. Initially, we optimized the Raman scattering conditions and demonstrated the feasibility of unicellular carotenoid analysis by Raman spectroscopic technique. The results showed that an integration time of 10 s, laser power at 0.1mW and an accumulation time of 1 were the optimum conditions, and the peak height at 1523cm-1 scaled linearly with the carotenoid content in the range of 0.625-1440mg/L with a recovery rate of 97%~103%. In the experiment, seven different nitrogen levels ranging from 0 to 2.48×105μg/L were imposed. Samples were taken at the start, exponential phase and end of the experiment. The results showed that nitrogen stress can facilitate the synthesis of carotenoids, while at the same time, excessive nitrogen stress led to lower proliferative and photosynthetic activity. Compared with carotenoids, chlorophylls were more sensitive to nitrogen stress; it declined dramatically as stress processed. There existed no significant differences for Fv/Fm among different nitrogen levels during the exponential phase, while in the end, it declined and a significant difference appeared between cells in 2.48×105μg/L N and other experimental levels. Photosynthetic efficiency, namely the C/N mole ratio in algal cells, didnot significantly change during the exponential phase; however, apparent increases ultimately occurred, except for the stable C/N in BG11 medium. This increase matched well with the carotenoid decline, indicating that an increasing cellular C/N mole ratio can be used as an indicator of excessive stress in carotenoid production. Besides, there also existed an inverse correlation with ETRmax.


Predatory journals: una amenaza emergente para autores y editores de publicaciones biomédicas.
So-called predatory publishing is a new and rising phenomenon presenting as an intellectual fraud that jeopardises the quality of scientific contribution, compromises the activity of authors, reviewers and editors of legitimate journals, damages the image of open access publications and is a very profitable business. In this paper, we review the concept and relevance of predatory journals and the characteristics that differentiate them from legitimate publications. Neurosurgical and general neuroscience journals are not immune to this problem. Academic institutions and ethics committees have a duty to raise awareness of this phenomenon and provide information and support to authors and the whole scientific community to avoid its propagation and potential control of biomedical publishing.


Omental and extraperitoneal abscesses complicating cholecystocolic fistula.
Acute cholecystitis resolves with conservative treatment in most patients, but empyema or perforation of an ischaemic area may develop, resulting in a pericholecystic abscess, bile peritonitis or a cholecysto-enteric fistula. A 63-year-old man presented with extraperitoneal and omental abscess formation complicating a cholecystocolic fistula secondary to gallbladder disease. Histological examination of the gallbladder and omentum showed xanthogranulomatous inflammation. A detailed literature review failed to demonstrate a previous report of this combination of rare complications of gallbladder disease.


Predictors of herpes zoster vaccination among Australian adults aged 65 and over.
To estimate HZ vaccine coverage in Australia among older Australians and to identify potential barriers to vaccination. Analysis of data from three cross-sectional surveys administered online between 2019 and 2020. Adults aged 65 and over residing in Australia. Self-reported herpes zoster vaccination. Among the 744 adults aged 65 and over in this sample, 32% reported being vaccinated for HZ, including 23% of participants aged 65-74, 55% of participants aged 75-84, and 0% for participants aged 85 and above. Those who are vaccinated with other immunisations are more likely to have received HZ vaccine, including seasonal influenza (OR = 4.41, 95 % CI: 2.44-7.98) and pneumococcal vaccines (OR = 4.43, 95 % CI: 2.92 - 6.75). Participants with a history of certain conditions, such as stroke (OR = 2.26, 95 % CI: 1.13-4.49), were more likely to be vaccinated against HZ. Participants that reported smoking tobacco daily were less likely to be vaccinated against HZ (OR = 0.48, 95 % CI: 0.26-0.89). Participants were less likely to be vaccinated against HZ if they preferred to develop immunity 'naturally' (OR = 0.29, 95 % CI: 0.15 - 0.57) or expressed distrust of vaccines (OR = 0.34, 95 % CI: 0.13-0.91). Further research is required to understand the barriers to HZ vaccine uptake. Increasing the funding eligibility for those who are at risk of complications from shingles, or lowering the age of eligibility, may increase vaccine coverage.


COVID-19 and delayed antenatal care impaired pregnant women's quality of life and psychological well-being: What supports should be provided? Evidence from Vietnam.
This study explored the associations between different structural and functional supports with the quality of life (QOL) and mental well-being of pregnant women whose antenatal care was delayed due to the COVID-19 pandemic in Vietnam. A multi-center cross-sectional study was performed on 868 pregnant women. The pregnant women's quality of life questionnaire (QOL-GRAV), the Edinburgh Postnatal Depression Scale (EPDS), and the Perinatal Infant Care Social Support (PICSS) instruments were employed. The satisfaction with care from different sources was measured. Multivariate Tobit Regression models were used. Seventy pregnant women (8.1%) reported that their antenatal care was influenced by the COVID-19. In this group, a higher level of satisfaction with the care of parents-in-law and a higher score of emotional support were associated with a better "Physical and Emotional changes" domain, while a higher level of appraisal support was related to poorer "Physical and Emotional changes" domain. A higher level of satisfaction with relatives' care and a higher score of emotional support were correlated with a better "Life Satisfaction" domain. EPDS score was negatively correlated with satisfaction with parents-in-law care and appraisal support. Our study highlighted that intervention programs to improve the QOL and psychological well-being of pregnant women in epidemics such as COVID-19 or other diseases in the future should involve other family members such as parents-in-law and relatives as sources of support. The cross-sectional design was unable to draw causal relationships. Recall bias might occur. The convenient sampling method might limit the generalizability of findings.


Effect of enteric micro-organisms on intestinal sugar and fatty acid absorption.
The effect of micro-organisms contaminating the upper intestinal contents of malnourished children on intestinal absorption of 3-0 methyl-alpha-D-glucopyranose (3-M.G.) and oleic acid was studied in rats in vivo. Oleci acid absorption was unaffected by non-pathogenic E. coli but decreased by E. coli 0111, Salmonella paratyphi B., Shigella sonnei and Candida sp. This effect was probably explained by intestinal secretion diluting the test solution leading to a decreased diffusion gradient for solubilised fatty acid. Inhibition of sugar absorption occurred with bacterial suspensions of Staphylococcus aureus, Streptococcus faecalis, E. coli and Candida sp. and cell-free preparations of Staphylococcus aureus, Streptococcus faecalis, a non-pathogenic E. coli, Proteus sp., Klebsiella sp., Pseudomonas sp. and Candida sp. These effects were not explained by dilution of the test solution. This indicates that numerous micro-organisms and, in some instances, their cell-free preparations can interfere with intestinal active sugar transport. These findings may be relevant to the production of malabsorption in malnourished children who have a wide variety of micro-organisms contaminating their upper intestinal contents.


Ceramides in phospholipid membranes: effects on bilayer stability and transition to nonlamellar phases.
The effects of ceramides of natural origin on the gel-fluid and lamellar-inverted hexagonal phase transitions of phospholipids (mainly dielaidoylphosphatidylethanolamine) have been studied by differential scanning calorimetry, with additional support from infrared and 31P nuclear magnetic resonance (NMR) spectroscopy. In the lamellar phase, ceramides do not mix ideally with phospholipids, giving rise to the coexistence of domains that undergo the gel-fluid transition at different temperatures. The combination of differential scanning calorimetry and infrared spectroscopy, together with the use of deuterated lipids, allows the demonstration of independent melting temperatures for phospholipid and ceramide in the mixtures. In the lamellar-hexagonal phase transitions, ceramides (up to 15 mol %) decrease the transition temperature, without significantly modifying the transition enthalpy, thus facilitating the inverted hexagonal phase formation. 31P-NMR indicates the coexistence, within a certain range of temperatures, of lamellar and hexagonal phases, or hexagonal phase precursors. Ceramides from egg or from bovine brain are very similar in their effects on the lamellar-hexagonal transition. They are also comparable to diacylglycerides in this respect, although ceramides are less potent. These results are relevant in the interpretation of certain forms of interfacial enzyme activation and in the regulation and dynamics of the bilayer structure of cell membranes.


Triglyceride to high density lipoprotein cholesterol ratio among adolescents is associated with adult hypertension: the Kangwha study.
The triglyceride to high density lipoprotein cholesterol (TG/HDL-C) ratio associated with hypertension in adults. However, whether the TG/HDL-C ratio in adolescents predicts future hypertension remains unclear. Here, we evaluated the prospective association between the TG/HDL-C ratio in adolescents and hypertension in early adulthood. The Kangwha Study is an ongoing prospective cohort study that has tracked the blood pressure of first grade elementary school students since 1986. We followed up 272 participants who completed health examinations at the age of 16 and 35 years. We excluded 27 participants with adolescent hypertension, defined as those whose blood pressures were above the age- and sex-specific 95th percentiles of the Korean population, and finally analysed 245 participants. We defined high and low TG/HDL-C ratio groups according to the age- and sex-specific 75th percentile of the TG/HDL-C ratio (1.04 for boys and 0.81 for girls) of the Korean population. Adult hypertension was defined by a systolic/diastolic blood pressure ≥ 140/90 mmHg or by taking antihypertensive medication at the age of 35 years. Logistic regression analysis was performed to evaluate the association between adolescent TG/HDL-C ratio and adult hypertension after adjusting for age at follow-up, sex, baseline systolic blood pressure, waist circumference, and total cholesterol and fasting glucose levels. During the 20-year follow-up, 11 (18.3%) individuals developed hypertension in the high TG/HDL-C ratio group and 10 (5.4%) individuals developed hypertension in the low TG/HDL-C ratio group. The adjusted odds ratio for incident hypertension in the high TG/HDL-C ratio group, compared with the low TG/HDL-C ratio group, was 3.40 (95% confidence interval 1.24-9.31). High TG/HDL-C ratio in adolescence is associated with hypertension in early adulthood.


Environmental epidemiology and risk assessment: Exploring a path to increased confidence in public health decision-making.
Throughout history, environmental epidemiology has proven crucial to identify certain threats to human health and to provide a basis for the development of life-saving public health policies. However, epidemiologists are facing challenges when studying tenuous threats such as environmental exposure to chemicals, whose association with adverse health effects may be difficult to characterize. As a result, epidemiological data can seldom be fully leveraged for quantitative risk assessment and decision-making. Despite two decades of efforts to improve a more systematic integration of human data to evaluate human health risks, assessors still heavily rely on animal data to do so, while epidemiology plays more of a secondary role. Although the need for more and better collaboration between risk assessors and epidemiologists is widely recognized, both fields tend to remain siloed. In 2017, the Health and Environmental Sciences Institute initiated a project engaging the epidemiology, exposure science, and regulatory communities with tripartite representation from regulators, industry, and academia in a dialogue on the use of environmental epidemiology for regulatory decision-making. Several focus groups attended by epidemiology, exposure science, and risk assessment experts were organized to explore incentives and barriers to collaboration, to ultimately bridge the gap between the various disciplines, and to realize the full potential of epidemiological data in risk assessment. Various ideas that have emerged from these meetings could help ensure the better integration of epidemiological data in quantitative risk assessment and contribute to building confidence in a robust and science-based regulatory decision-making process.


Gastroenterology nurse prescribing in China: A Delphi method.
This study aims to identify and reach a consensus among experts on the specific gastroenterology drugs that a gastroenterology nurse may be able to prescribe. This study employs a modified Delphi design to reach a consensus among medical and nursing experts about the gastroenterology system drugs that nurses may prescribe medication. From August 2019-November 2019, a two-round study, consisting of 26 medical and nursing experts, was conducted using the Delphi method. IBM SPSS Ver. 22 and descriptive statistical software were used to analyse the results of the consultations. A total of 37 drugs across nine categories are identified as relevant to Chinese nurses working in gastroenterology departments. Among them, four drugs are generally prescribed independently, 24 tend to be prescribed collaboratively and nine are prescribed either independently, or in collaboration with others. This list is a fundamental and dependable instrument for identifying the gastroenterology drugs that could possibly be prescribed by gastroenterology nurses in China. The research results have important guiding significance for the formulation and implementation of relevant policies for nurses to prescribe medicines. Nurse prescribing has become a global trend and is slowly gaining attention in China under the development strategy of 'Healthy China'. As such, this list will give some reference for policy formulation and implementation of future nurse prescribing in mainland China.


Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD.
We carried out morphometric measurements of steatosis to evaluate relationships between steatosis degree and other liver lesions or metabolic syndrome components in nonalcoholic fatty liver disease (NAFLD). We developed an algorithm to measure steatosis area. Two hundred and fourteen patients with NAFLD were included in derivation (10) and validation (204) groups. Controls consisted of patients who were steatosis-free (12), patients with chronic hepatitis C (188), and patients with alcoholic chronic liver disease (94). Accuracy of steatosis area was considered as good or very good in at least 72% of cases by three pathologists. Steatosis areas were as follows: NAFLD = 10.3 ± 9.7%, virus = 2.4 ± 3.1%, alcohol = 7.8 ± 8.2% (P<0.0001). Steatosis area was closely related to steatosis grades in NAFLD (P<0.0001 for linear trend). Steatosis area increased from the fibrosis stage F0 to the fibrosis state F2, then decreased in the stages F3 and F4 (cirrhosis) (P<0.0001 for quadratic trend). Fibrosis was present in an average steatosis area of approximately 4% (defining significant steatosis) and in nonalcoholic steatohepatitis by approximately 8% (defining severe steatosis). Steatosis and fibrosis area increased symmetrically until approximately 10%, then steatosis area decreased to null as average fibrosis area reached 32%. Average fasting glycemia (approximately 92 mg/dl) or triglycerides and BMI plateaued before a steatosis area of approximately 4%, then increased thereafter. Significant steatosis was present in 61.3% of NAFLD versus 20.2% of viral hepatitis (P<0.0001) and in 58.7% of alcoholic liver diseases (P=0.674). The average threshold of steatosis area is 4% for the development of fibrosis or metabolic syndrome components and 8% for nonalcoholic steatohepatitis. Steatosis area may contribute to defining the normal range and clinical course of metabolic components.


Computerized tomography appearances of pelvic haemangioma involving the large bowel in childhood.
The Computed Tomography (CT) appearance of a pelvic haemangioma involving the rectum in two children, one with the Vater association and one with Klippel-Trenaunay syndrome, is described. Both cases complained of painless rectal bleeding and the diagnosis was suggested by the presence of pelvic phleboliths on the plain abdominal radiograph. CT provides a simple, non-invasive method of diagnosing such lesions and assessing their extent.


Sonographic appearance of an advanced invasive mole and associated metastatic thrombus in the inferior vena cava.
We present a case of an advanced invasive mole with a metastatic thrombus in the inferior vena cava in which sonography clearly showed vesicles in the myometrium, ovaries, and metastatic thrombus leading to a diagnosis of invasive mole rather than choriocarcinoma.


Tumor-Targeted and Biocompatible MoSe2 Nanodots@Albumin Nanospheres as a Dual-Modality Therapy Agent for Synergistic Photothermal Radiotherapy.
Integrating multiple tumor therapy functions into one nanoplatform has been a new tumor therapy strategy in recent years. Herein, a dual-modality therapy agent consisting of molybdenum selenide nanodots (MoSe2 NDs) and bovine serum albumin (BSA) assembled nanospheres (MoSe2@BSA NSs) was successfully synthesized. After conjugation of folic acid (FA) molecules via polyethylene glycol (PEG) "bridges," the FA-MoSe2@BSA NSs were equipped with tumor-targeting function. The BSA and PEG modifications provided the unstable MoSe2 NDs with excellent physiological stability. Since the end-product FA-MoSe2@BSA NSs had strong near-infrared (NIR) and X-ray absorbance properties, they exhibited good photothermal properties with excellent photothermal stability and radio-sensitization ability, hence, were explored as photothermal radiotherapy agents. In vitro and in vivo experiments indicated that the FA-MoSe2@BSA NSs possessed highly efficient tumor-targeting effect, great biocompability, and synergistic photothermal radiotherapy effect. This work suggests that such biocompatible FA-MoSe2@BSA NSs may be a promising multifunctional dual-modality tumor therapy agent for use in combination tumor therapy.


Rat gastric relaxation induced by stimulation of endothelin-1 selective receptors.
We have investigated the smooth muscle activity of ET-1 and ET-3 on rat fundus strips in vitro as well as the effects of the peptides on gastric motility in vivo. In the isolated tissue with no precontraction ET-1 and ET-3 were potent spasmogens which produced half maximal contractions at concentrations 4.5 and 8.0 nM, respectively. In contrast, under conditions where the isolated tissue was precontracted to approx. 50% of maximum by prostaglandin E2, ET-1 dose-dependently (5 x 10(-10) - 10(-8) M) and temporarily relaxed the fundus strip, whereas ET-3 further increased the contraction. The relaxing capacity of ET-1 was absent when the tissue was precontracted by potassium yet was resistant to pretreatments with tetrodotoxin, capsaicin, propranolol, indomethacin, NG-methyl-L-arginine or glibenclamide. In addition in vivo ET-1 and ET-3 (less than 1 nmol/kg) showed opposite effects on gastric motility as the former reduced basal tonus and spontaneous activity, whereas the latter increased the motor activity of the gastric ventricle. The results support the notion that ET-1 may induce gastric relaxation by stimulation of selective receptors whereas stimulation of nonselective receptors may promote gastric smooth muscle contraction.


A simplified procedure for the quantitative extraction of lipids from brain tissue.
A method is described for the quantitative extraction of lipid from brain tissue with chloroform/methanol (C/M) that eliminates secondary purification of the lipid extract by dextran-gel chromatography or aqueous washing of the organic extract. Nonlipid substances that generally contaminate C/M lipid extracts are separated by pre-extraction of the tissue with dilute (0.25%) aqueous acetic acid. The residual tissue is extracted twice with 40 volumes of C/M (1:1, v/v). Approximately 97% of the lipid is recovered in these extractions. A third extraction which yields ca. 1% more lipid is performed if the process is discontinued at this stage in a shortened version of the method. The remainder of the lipid is recovered after treatment of the tissue with 1 N HC1 by two additional extractions, the first with 40 volumes of C/M (1:2, v/v) and the second with 40 volumes of methanol. The method, which was demonstrated with pig brain, gave a complete extraction of the lipid, including gangliosides, free of nonlipid substances.