Long-term results of early gastric cancer accomplished in a European institution by Japanese-type radical resection.
BACKGROUND: Long-term survival following Japanese-type radical surgery for 130 consecutively performed early gastric cancers (EGC) in a single Austrian institution between January 1, 1984 and May 31, 1998 was analyzed in terms of long-term survival, postoperative morbidity, and mortality.METHODS: Extended D2 lymphadenectomy as defined by the JRSGC was performed in 129 patients with EGC. The surgical process was consistent as nearly all patients were operated on by only two surgeons. Overall survival and factors influencing survival were analyzed with particular regard to the depth of tumor infiltration, histological type, tumor grading, Lauren classification, tumor diameter, macroscopic appearance, localization, and lymph node involvement.RESULTS: Of 678 gastric cancer patients surgically treated in the mentioned period, 130 patients (19.2%) were qualified as EGC. In 70 patients the tumor was limited to the mucosa and in 60 patients the tumor had not yet invaded the submucosa. The percentage of patients with positive lymph nodes increased from 2.9% with mucosal invasion to 21.7% with submucosal tumor involvement. The overall 5- and 10-year observed survival rate, postoperative mortality not excluded, was 74.6% and 62.1%, respectively, and 91.1% and 91.1%, respectively, when calculated as tumor specific. The 5- and 10-year observed survival rate of tumors limited to the mucosa was 77.2% and 72.1%, respectively, and 98.1% and 98.1%, respectively, when calculated as tumor specific. The respective values for submucosal invasion were 71.6% and 51.7%, and 82.7% and 82.7%. Postoperative complications occurred in 17 patients (13.1%) and postoperative hospital mortality totaled 1.5% (2/130). In multivariate analysis, only lymph node metastases were found to have independent prognostic influence on survival ( P < 0.001; hazard ratio, 8.25).CONCLUSION: Japanese-type radical lymph node dissection for EGC in a European surgical institution yielded long-term survival nearly identical to that reported repeatedly by Japanese authors. Postoperative morbidity and mortality was not sacrificed by our comparatively radical surgical approach.


Modeling the effect of VOCs from biomass burning emissions on ozone pollution in upper Southeast Asia.
We used a Weather Research and Forecasting Model with Chemistry (WRF-CHEM) model that includes anthropogenic emissions from EDGAR-HTAP, biomass burning from FINN, and biogenic emissions from MEGAN to investigate the main volatile organic compound (VOC) ozone precursors during high levels of biomass burning emissions in March 2014 over upper Southeast Asia. A comparison between the model and ground-based measurement data shows that the WRF-CHEM model simulates the precipitation and 2 m temperature reasonably well, with index of agreement (IOA) values ranging from 0.76 to 0.78. Further, the model predicts O3, NO2, and CO fairly well, with IOA values ranging from 0.50 to 0.57. However, the magnitude of the simulated NO2 concentration was generally underestimated compared to OMI satellite observations. The model result shows that CO and VOCs such as BIGENE play an important role in atmospheric oxidation to surface O3. In addition, biomass burning emissions are responsible for increasing surface O3 by ∼1 ppmv and increasing the reaction rate of CO and BIGENE by approximately 0.5 × 106 and 1 × 106 molecules/cm3/s, respectively, in upper Southeast Asia.


Separation of the inspiratory and expiratory reflex effects of alternate-breath oscillation of PACO2 during hypoxia.
Four healthy young men and women, selected for the responsiveness and steadiness of their breathing, were studied in rest and mild exercise (58 runs) while receiving alternate inspirates of low and high PCO2 (0 and 8.6 kPa). PACO2 oscillated between ca. 6 and 7.5 kPa (45-55 torr); PACO2 was held steady at more than one level between 6 and 9.6 kPa (45-72 torr). Using cross-correlation analysis, the phase relations were determined between the alternating PACO2 and the following reflex outputs: mean inspiratory and expiratory flows (VI and VE) and the reciprocal of the duration of expiration (1/TE), the two expiratory variables being lumped together for purposes of expression, but not of calculation. T1, being relatively unaffected alternating PACO2, was not re-studied (see companion paper). The common patterns of significant reflex alternation were: VI alone, usually in phase (with PACO2), 24%; VE alone, usually in phase, 17%; both inspiratory and expiratory variables, in phase with CO2 and each other, 15%; both inspiratory and expiratory variables, the expiratory being out of phase with both CO2 and with the inspiratory, 23%. Some runs showed a mixture of phase relations. In 71%, end-expiratory lung volume (VL,E' formerly called FRC) alternated significantly. It is concluded that expiratory events can be influenced by peripheral chemoreceptors independently of inspiration.


Handwriting legibility and fluency and their patterns of concurrent relations with spelling, graphomotor, and selective attention skills.
Recent research suggests that handwriting comprises two separate subskills: legibility and fluency. It remains unclear, however, how these subskills differ in their relationship to other abilities associated with handwriting, including spelling, graphomotor, and selective attention skills. In this study, we sought to examine the extent and nature of concurrent relationships that may exist among these skills. Children in Year 3 (n = 293), Year 4 (n = 291), and Year 5 (n = 283) completed a large, group-administered battery to assess each of the above skills. Using multigroup structural equation modeling, we found that spelling, graphomotor, and selective attention skills together explained a moderate amount of variance in handwriting legibility (R2 = .37-.42) and fluency (R2 = .41-.58) and that these subskills differed in their concurrent relations. Graphomotor skills accounted for a relatively greater proportion of variance in legibility than did spelling. Conversely, there were relatively stronger contributions from variations in spelling ability to variations in fluency than from graphomotor skills. Furthermore, selective attention predicted handwriting fluency only, and it partially mediated the influence of graphomotor skills. This study further demonstrates that handwriting legibility and fluency are separable and complex skills, each differentially related to spelling, graphomotor, and attentional abilities even during later primary school years.


Reducing Opioid Prescriptions Lowers Consumption Without Detriment to Patient-Reported Pain Interference Scores After Total Hip and Knee Arthroplasties.
Opioid addiction is endemic in the United States. We developed a standardized opioid-prescribing schedule (SOPS) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) and evaluated opioid usage alongside Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference scores. We hypothesized that opioid usage would be less than prescribed and reducing prescription would decrease consumption without negatively impacting the PROMIS scores. A prospective observational study was performed on all patients undergoing primary THA and TKA from April 7, 2018, to August 10, 2019. Opioid consumption and pain interference were determined 2 weeks after discharge via telephone and email surveys. SOPSs were implemented during the study. Outcomes were compared in patients before and after the SOPS. A total of 715 patients met inclusion criteria; 201 patients completed surveys. Before the SOPS, the mean opioid prescription was 81.2 ± 15.3 tablets for THA and 82.9 ± 10.6 for TKA. The mean usage was 35.1 ± 29.4 tablets and 35.4 ± 33.4, respectively. After the SOPS, the mean usage decreased to 19.4 ± 16.8 (P = .04) and 31.6 ± 20.9 (P = .52), respectively. After implementation of a second SOPS for THA, the mean number of tablets consumed was 21.5 ± 18.6 (P = .05 compared with pre-SOPS). The PROMIS 6B responses in patients who underwent THA demonstrated no significant changes. PROMIS 6B responses for TKA showed an increase in interference with recreational activities (P = .04) and tasks away from home (P = .04), but otherwise had no significant impact on reported scores. Implementation of the SOPS reduced postoperative opioid prescription and consumption without significantly impacting the reported pain interference, supporting the need to decrease opioid prescription after THA and TKA.


Promoting colonoscopy screening among low-income Latinos at average risk of colorectal cancer: A randomized clinical trial.
Screening colonoscopy (SC) for colorectal cancer (CRC) is underused by Latino individuals. The current randomized clinical trial examined the impact of 3 interventions: 1) patient navigation; 2) patient navigation plus standard Centers for Disease Control and Prevention print materials; and 3) patient navigation plus culturally targeted print materials for Latinos referred for SC. Demographic, personal and health history, and psychometric factors associated with SC also were examined. A total of 344 urban Latino individuals aged 50 to 85 years with no personal and/or immediate family history of CRC diagnosed before age 60 years, no personal history of a gastrointestinal disorder, no colonoscopy within the past 5 years, with insurance coverage, and with a referral for SC were consented. Participants were randomized to patient navigation (20%), patient navigation plus standard Centers for Disease Control and Prevention print materials (40%), and patient navigation plus culturally targeted print materials (40%). The completion of SC was assessed at 12 months. The interventions had an overall SC rate of 82%. Counterintuitively, patients with an average income of <$10,000 were found to have higher SC rates (87%) than those with a greater income (75%). The addition of standard or culturally targeted print materials did not appear to increase SC rates above those for patient navigation. Indeed, after controlling for other variables, culturally targeted print materials were found to be associated with lower SC rates among Puerto Rican individuals.


Inferring bladder cancer research prioritization from patient-generated online content.
Patients and their families utilize online resources when dealing with a diagnosis of bladder cancer. Many patients have questions regarding clinical management options. Online research forums may help researchers and providers identify research areas of interest. Our objective was to review online forums and identify research questions that are important to patients and families impacted by bladder cancer diagnosis. We reviewed 1 month of online content from the Bladder Cancer Advocacy Network Inspire online community ( https://www.inspire.com/groups/bladder-cancer-advocacy-network ). Using affinity diagramming, we categorized the submitted content from patient users into themes stratified by the cancer severity of the patient user (non-muscle-invasive bladder cancer, muscle-invasive bladder cancer, metastatic bladder cancer). We categorized the content by the audience of forum posts (i.e., inwardly directed, those seeking support, vs. outwardly directed, those sharing personal experiences) and constructed comparative effectiveness research questions from the submitted content. From 14 July 2014 to 14 August 2014, a total of 394 forum posts were collected, of which 3 were excluded from analysis due to non-relevant content, leaving 391 comments for final analysis. Almost 38% of posts involved muscle-invasive bladder cancer and 25% of posts were from people other than the patient. Inwardly and outwardly directed posts were commonly related to clinical treatment concerns. Review of online patient-generated content may offer insight into comparative effectiveness research topics of importance to bladder cancer patients. A more formalized process may better represent research priorities among bladder cancer patients.


Human fetal organ alkaline phosphatases.
The properties of human fetal alkaline phosphatase (ALP) have been compared with those of purified human adult hepatic and intestinal ALPs. The ALPs from different human fetal organs were divided into two groups. One terminated universal type was presented in fetal liver, spleen, adrenal, kidney, lung, heart, pancreas, thymus and bone, and was similar to adult hepatic-type ALP. The other terminated intestinal type was presented in fetal intestine and meconium and was similar to adult intestinal ALP. The activity of human fetal intestinal ALP increased markedly with the advance of intra-uterine life during fetal development, and that of human fetal thymus ALP increased slightly.


Abnormal vasoconstrictor responses to angiotensin II and noradrenaline in isolated small arteries from patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by ultrastructural abnormalities in small cerebral and systemic vessels. We assessed vasomotor function in systemic small arteries in CADASIL. We studied 10 CADASIL patients and 10 control subjects. Resistance arteries isolated from gluteal biopsies were mounted on small-vessel myographs, and concentration responses were determined for vasoconstrictors (noradrenaline, angiotensin II, and endothelin-I) and vasodilators (acetylcholine, bradykinin, spermine-NONOate, and nifedipine). Maximum data are shown as percent potassium contraction. There was reduced potency for noradrenaline in CADASIL (CADASIL [38 arteries]: EC50, 240 nmol/L; control subjects [27 arteries]: EC50, 100 nmol/L; 2-way analysis of variance, F=9.76, P=0.002). Maximum response to angiotensin II was greater in CADASIL (120+/-8% versus 97+/-5% in control subjects; F=4.28, P=0.043). Tachyphylaxis to angiotensin II occurred in all control subjects studied but in only 3 of 9 CADASIL subjects (P=0.011, Fisher's exact test). Vasodilation was similar in CADASIL patients compared with control subjects for endothelium-dependent dilators (acetylcholine and bradykinin) and endothelium-independent dilators (spermine-NONOate and nifedipine). These results suggest a selective systemic microvascular vasoconstrictor abnormality in CADASIL in noradrenaline and angiotensin II pathways that is not explained by vasodilator impairment in endothelium or vascular smooth muscle. This could have important implications for prophylaxis and treatment of CADASIL.


The effect of propylbenzilylcholine mustard on contraction and radioligand binding parameters of muscarinic receptors in guinea pig ileum.
The receptor occupancy-biological effect relationship for muscarinic receptors in guinea pig ileal smooth muscle has been studied by comparison of radioligand binding and contractile response. Muscarinic receptors in homogenates of ileal smooth muscle were labeled with [3H]-1-Quinuclidinyl benzilate. Treatment with propylbenzilylcholine mustard (PrBCM), to inactivate irreversibly muscarinic receptors, caused a large dose dependent rightward shift of the dose-response curve to three agonistic furtrethonium derivatives with a concomitant decrease in maximal response. Using those data, the fraction of receptors remaining unoccupied (q-values) and "true affinity constants" (-log KA-values) were calculated. Exposure to 20 or 60 nM PrBCM for 15 minutes resulted in a 39% and a 61% reduction in specific [3H]-1-Quinuclidinyl benzilate binding sites respectively to be compared with a 62% and a 85% decrease expected from calculated q-values. KA-values for the methyl and ethyl derivative agreed well with the dissociation constants for the high affinity agonist sites determined from displacement of [3H-]-1-Quinuclidinyl benzilate. The KA-value for the propylfurtrethonium corresponds to the low affinity agonist dissociation constant. The fraction of receptors in the high affinity agonist state differs considerably for the three furtrethonium derivatives investigated. Neither the fraction of receptors in the high affinity agonist state, nor the ratio of dissociation constants for these states is affected by the alkylation of 85% of the functional muscarinic receptors. The inactivation of components of the effector system by PrBCM seems unlikely.


Motion in depth induced by brightness changes in the background.
A disc of unvarying brightness and position is presented against a background whose brightness is continuously changing up and down. This change is perceived as a pendular movement to and from the subject and, in its turn, clearly induces an analogous but contrary movement in the disc.


P450 reductase and cytochrome b5 interactions with cytochrome P450: effects on house fly CYP6A1 catalysis.
The interactions of protein components of the xenobiotic-metabolizing cytochrome P450 system, CYP6A1, P450 reductase, and cytochrome b5 from the house fly (Musca domestica) have been characterized. CYP6A1 activity is determined by the concentration of the CYP6A1-P450 reductase complex, regardless of which protein is present in excess. Both holo- and apo-b5 stimulated CYP6A1 heptachlor epoxidase and steroid hydroxylase activities and influenced the regioselectivity of testosterone hydroxylation. The conversion of CYP6A1 to its P420 form was decreased by the addition of apo-b5. The effects of cytochrome b5 may involve allosteric modification of the P450 enzyme that modify the conformation of the active site. The overall stoichiometry of the P450 reaction was substrate-dependent. High uncoupling of CYP6A1 was observed with generation of hydrogen peroxide, in excess over the concomitant testosterone hydroxylation or heptachlor epoxidation. Inclusion of cytochrome b5 in the reconstituted system improved efficiency of oxygen consumption and electron utilization from NADPH, or coupling of the P450 reaction. Depending on the reconstitution conditions, coupling efficiency varied from 8 to 25% for heptachlor epoxidation, and from 11 to 70% for testosterone hydroxylation. Because CYP6A1 is a P450 involved in insecticide resistance, this suggests that xenobiotic metabolism by constitutively overexpressed P450s may be linked to significant oxidative stress in the cell that may carry a fitness cost.


Early carotid endarterectomy in symptomatic patients is associated with poorer perioperative outcomes.
The optimal timing of carotid endarterectomy (CEA) after ipsilateral hemispheric stroke is controversial. Although early studies suggested that an interval of about 6 weeks after a completed stroke was preferred, more recent data have suggested that delaying CEA for this period of time is not necessary. With these issues in mind, we reviewed our experience to examine perioperative outcome with respect to the timing of CEA in previously symptomatic patients. A retrospective review of a prospectively maintained database of all CEAs performed at our institution from 1992 to 2003 showed that 2537 CEA were performed, of which 1,158 (45.6%) were in symptomatic patients. Patients who were operated on emergently <or=48 hours of symptoms for crescendo transient ischemic attacks (TIAs) or stroke-in-evolution were excluded from analysis (n = 25). CEA was considered "early" if performed <or=4 weeks of symptoms, and "delayed" if performed after a minimum of a 4-week interval following the most recent symptom. Of nonurgent CEAs in symptomatic patients, in 87 instances the exact time interval from symptoms to surgery could not be precisely determined secondary to the remoteness of the symptoms (>18 months), and these were excluded from further analysis. Of the remaining 1,046 cases, 62.7% had TIAs and 37.3% had completed strokes as their indication for surgery. Among the entire cohort, patients who underwent early CEA were significantly more likely to experience a perioperative stroke than patients who underwent delayed CEA (5.1% vs 1.6%, P = .002). Patients with TIAs alone were more likely to be operated on early rather than in a delayed fashion (64.3% vs 46.7%, P < .0001), likely reflecting institutional bias in selecting delayed CEA for stroke patients. However, even when examined as two separate groups, both TIA patients (n = 656) and CVA patients (n = 390) were significantly more likely to experience a perioperative stroke when operated upon early rather than in a delayed fashion (TIA patients, 3.3% vs 0.9%, P = .05; CVA patients, 9.4% vs 2.4%, P = .003). There were no significant differences in demographics or other meaningful variables between patients who underwent early CEA and those who underwent delayed CEA. In a large institutional experience, patients who underwent CEA <or=4 weeks of ipsilateral TIA or stroke experienced a significantly increased rate of perioperative stroke compared with patients who underwent CEA in a more delayed fashion. This was true for both TIA and stroke patients, although the results were more impressive among stroke patients. On the basis of these results, we continue to recommend that waiting period of 4 weeks be considered in stroke patients who are candidates for CEA.


[Causes of the formation of hernias after laparoscopic cholecystectomy].
The authors made an analysis of postoperative hernias in 32 patients. General and local causes are considered. The proposed technical methods used for exclusion of local causes allowed the frequency of postoperative hernias to be reduced from 1.9% to 0.5%.


[Müllerian papillary adeno-fibromata and müllerian adenosarcomata. Mülleromas and mixed malignant müllerian growths contingent with benign epithelium (author's transl)].
The authors present 6 cases of müllerian papillary adeno-fibromata (or mixed mesodermal müllerian benign tumours) of which 4 are anatomo-clinical presentations and 2 are histological presentations, as well as 3 cases of müllerian adenosarcoma (mixed müllerian mesodermal tumour with stroma only sarcomatous). The study of these cases added on to those found in the literature leads to the following conclusions: The first group can be accepted. The second group will be of mild malignancy. All the same, 4 of which the sarcomatous nature is not in doubt at all (malignant from the start) recurred rapidly. Those in which the sarcomatous nature was attenuated or doubtful (15 cases) seemed to have a much longer evolution with some local recurrences. Only 3 patients have been followed up for more than 5 years. It is absolutely essential to carry out further observations before confirming for certain the prognosis of this new type of tumour.


Protein dynamics by neutron scattering.
Neutron scattering techniques represent a powerful tool for characterizing both the structure and dynamical properties of bio-systems, for example, proteins and membranes interacting with their solvents. In this paper, Elastic Neutron Scattering (ENS) data collected at the Institut Laue-Langevin (Grenoble, France) on dry and D2O hydrated lysozyme by varying hydration level are presented, and compared with previously published data on the same protein system, also with the addition of bio-protectants. The data have been collected with three different spectrometers, i.e. IN13, IN10 and IN4. This set of ENS data gives direct access to the temperature behavior of both (i) the Mean Square Displacement (MSD) and (ii) the characteristic system relaxation time. As a result, an explicative hypothesis on the relationship between the so-called "protein dynamical transition" (PDT) and the "fragile-to-strong dynamical crossover" (FSC) is formulated. Furthermore, by taking into proper account the effect of the finite instrumental energy resolution of the used spectrometers, the vibrational MSD of dry and hydrated lysozyme is calculated. The vibrational MSD of the lysozyme in the dry state resulted to be higher than the one in the hydrated state; the latter reaches the former at a temperature value of T=220K that corresponds to the temperature at which the FSC occurs. As a result, a cage effect resulting from the hydration water on the protein surface is hypothesized and subsequently linked to the FSC.


Gold-Plated Electrode with High Scratch Strength for Electrophysiological Recordings.
Multi electrode arrays (MEA) have been exploited in different electrophysiological applications. In neurological applications, MEAs are the vital interfaces between neurons and the electronic circuits with dual role; transmitting electric signal to the neurons and converting neural activity to the electric signal. Since the performance of the electrodes has a direct effect on the quality of the recorded neuronal signal, as well as the stimulation, the true choice of electrode material for MEA is crucial. Gold is one of the best candidates for fabrication of MEAs due to its high electrical conductivity, biocompatibility and good chemical stability. However, noble metals such as gold do not adhere well to the glass substrate. Consequently while exposing to the water, gold films are damaged, which impose limitations in the exploiting of gold thin films as the electrode. In this paper, a simple and cost effective method for the fabrication of gold electrode arrays is proposed. Using various mechanical (adhesion test and scratch strength), morphological (AFM and SEM) and electrochemical methods, the fabricated electrodes are characterized. The results show that the fabricated electrode arrays have significantly high scratch strength and stability within the aqueous medium. In addition, the electrical properties of the electrodes have been improved. The proposed electrodes have the potential to be exploited in other applications including electronics, electrochemistry, and biosensors.


The enigma of olfactory learning.
It has been suggested, on the basis of neuroanatomical and behavioural data, that olfactory discrimination in the rat provides privileged access to higher cognitive processes, involves the acquisition of a learning-set and, importantly, can be used to model human hippocampal function and dysfunction. In this article, Ian C. Reid and Richard G. M. Morris question the assumptions upon which these claims have been based and criticize the application of odour discrimination learning in the rat to the study of human memory.


A novel inflammatory endotype diagnostic model based on cytokines in chronic rhinosinusitis with nasal polyps.
Type 2 CRSwNP is characterized by severe symptoms, multiple comorbidities, longer recovery course and high recurrence rate. A simple and cost-effective diagnostic model for CRSwNP endotype integrating clinical characteristics and histopathological features is urgently needed. To establish a clinical diagnostic model of inflammatory endotype in CRSwNP based on the clinical characteristics, pathological characteristics, and cytokines profile in the polyp tissue of patients. A total of 244 participants with CRSwNP were enrolled at 2 different centers in China and Belgium from 2018 to 2020. IL-5 level of nasal polyp tissue was used as gold standard. Clinical characteristics were used to establish diagnostic models. The area under the receiver operating curve (AUC) was used to evaluate the diagnostic performance. The study was approved by the ethics board of the First Affiliated Hospital of Sun Yat-sen University ([2020] 302), and written informed consent was obtained from all subjects before inclusion. In total, 134 patients from China (training set) and 110 patients from Belgium (validation set) were included. The logistic regression (LR) model in predicting inflammatory endotype of CRSwNP showed the AUC of 83%, which was better than the diagnostic performance of machine learning models (AUC of 61.14%-82.42%), and single clinical variables. We developed a simplified scoring system based on LR model which shows similar diagnostic performance to the LR model (P = 0.6633). The LR model in this diagnostic study provided greater accuracy in prediction of inflammatory endotype of CRSwNP than those obtained from the machine learning model and single clinical variable. This indicates great potential for the use of diagnostic model to facilitate inflammatory endotype evaluation when tissue cytokines are unable to be measured.


Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure.
To assess the potential utility of piroximone (MDL-19,205), an investigational inotrope-vasodilator agent, in severe heart failure, 15 patients with severe left ventricular failure refractory to conventional agents were enrolled in an acute hemodynamic study. After incremental intravenous dosing (mean total dose 1.8 +/- 0.4 mg/kg body weight), cardiac index increased (1.7 +/- 0.3 to 2.6 +/- 0.6 liters/min per m2; p less than 0.001) and left ventricular filling pressure decreased (25 +/- 7 to 19 +/- 7 mm Hg; p less than 0.001). Also decreasing significantly were right atrial pressure (13 +/- 6 to 7 +/- 5 mm Hg; p less than 0.005) and systemic vascular resistance (1,633 +/- 394 to 1,183 +/- 278 dynes.s.cm-5; p less than 0.001). Heart rate and mean arterial pressure did not change, whereas stroke work index increased significantly (13.3 +/- 4.3 to 21.6 +/- 7.3 g.m/m2; p less than 0.005). The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone. Similar responses were obtained after incremental doses of piroximone in oral solution. After oral doses of piroximone tablets, cardiac index also increased significantly (2.1 +/- 0.6 to 2.4 +/- 0.5 liters/min per m2; p less than 0.05), although this magnitude of increase was comparatively low. In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01).


The influence of cystathionine on neurochemical quantification in brain tumor in vivo MR spectroscopy.
To evaluate the ability of the PRESS sequence (TE = 97 ms, optimized for 2-hydroxyglutarate detection) to detect cystathionine in gliomas and the effect of the omission of cystathionine on the quantification of the full neurochemical profile. Twenty-three subjects with a glioma were retrospectively included based on the availability of both MEGA-PRESS and PRESS acquisitions at 3T, and the presence of the cystathionine signal in the edited MR spectrum. In eight subjects, the PRESS acquisition was performed also in normal tissue. Metabolite quantification was performed using LCModel and simulated basis sets. The LCModel analysis for the PRESS data was performed with and without cystathionine. All subjects with glioma had detectable cystathionine levels >1 mM with Cramér-Rao lower bounds (CRLB) <15%. The mean cystathionine concentrations were 3.49 ± 1.17 mM for MEGA-PRESS and 2.20 ± 0.80 mM for PRESS data. Cystathionine concentrations showed a significant correlation between the two MRS methods (r = 0.58, p = .004), and it was not detectable in normal tissue. Using PRESS, 19 metabolites were quantified with CRLB <50% for more than half of the subjects. The metabolites that were significantly (p < .0028) and mostly affected by the omission of cystathionine were aspartate, betaine, citrate, γ-aminobutyric acid (GABA), and serine. Cystathionine was detectable by PRESS in all the selected gliomas, while it was not detectable in normal tissue. The omission from the spectral analysis of cystathionine led to severe biases in the quantification of other neurochemicals that may play key roles in cancer metabolism.


Targeting Hypoxia-Inducible Factor-1α for the Management of Hepatocellular Carcinoma.
Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.


High-performance liquid chromatography-mass spectrometric analysis of ramipril and its active metabolite ramiprilat in human serum: application to a pharmacokinetic study in the Chinese volunteers.
This study presents a rapid, specific and sensitive LC-MS/MS assay for the determination of ramipril and ramiprilat in human serum using enalapril as an internal standard (IS). A Waters Atlantis C18 column (2.1 mm x 100 mm, 3 microm) and a mobile phase consisting of 0.1% formic acid-methanol (25:75, v/v) were used for separation. The analysis was performed by the selected reaction monitoring (SRM) method, and the peak areas of the m/z 417.3-->234.3 and m/z 389.3-->206.2 transition for ramipril and ramiprilat, respectively, were measured versus that of the m/z 377.3-->234.2 for IS to generate the standard curves. The assay linearities of ramipril and ramiprilat were confirmed over the range 0.10-100 ngml(-1) and 0.25-100 ngml(-1), respectively, and limits of quantitation for them were 0.10 and 0.25 ngml(-1), respectively. The linear ranges correspond well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations of ramipril and ramiprilat were 2.8-6.4% and 4.3-4.6%, 4.4-6.7% and 3.5-4.7%, respectively. The recoveries of ramipril and ramiprilat from serum were in the range of 81.0-98.2%. The developed LC-MS procedures were applied for the determination of the pharmacokinetic parameters of ramipril and ramiprilat following a single oral administration of 10mg ramipril tablets in 18 Chinese healthy male volunteers.


Long-Term Outcomes and Clinical Predictors of Mortality Following Occurrence of Stent Thrombosis.
Background Stent thrombosis (ST) remains a significant medical issue. In particular, longer-term mortality and clinical predictors after ST occurrence have yet to be elucidated. Methods and Results This was a multicenter, retrospective, observational study. A total of 187 definite ST cases from January 2008 to December 2017 were enrolled, and the long-term clinical outcomes were investigated. The primary outcome measure was the cumulative mortality after ST occurrence. In addition, independent predictors of mortality were assessed. Among the stent types causing ST, bare-metal stent, first-generation drug-eluting stent, second-generation drug-eluting stent, and third-generation drug-eluting stent comprised 31.0%, 19.3%, 36.9%, and 6.4% of cases, respectively. Median duration from stent implantation to ST was 680.5 (interquartile range, 33.8-2450.5) days. Cumulative mortality was 14.6%, 17.4%, 21.2%, 24.4%, and 33.8% at 1, 2, 3, 5 and 10 years, respectively. The cumulative mortality did not significantly differ by type of stent, and mortality of late ST was higher than that of early ST and very late ST; however, it did not reach statistical significance after the multivariate analysis. Independent predictors of mortality were hemodialysis (hazard ratio [HR], 7.80; 95% CI, 3.07-19.81; P<0.001), culprit lesions in the left main trunk (HR, 8.14; 95% CI, 1.71-38.75; P=0.008), culprit lesions in the left coronary artery (HR, 2.77; 95% CI, 1.10-6.96; P=0.030), and peak creatine kinase (HR, 1.017; 95% CI, 1.011-1.022; P<0.001). Conclusions The 10-year cumulative mortality after ST reached 33.8%. Close follow-up is thus mandatory for patients with ST, especially with hemodialysis, culprit lesions in the left main trunk and left coronary artery, and high peak creatine kinase.


AXS Vecta 0.071-0.074 Inch Aspiration Catheters for Mechanical Thrombectomy: Case Series and Literature Review.
Aspiration catheters are widely used for thrombectomy either alone or in combination with a stent-retriever, with a distal inner diameter and trackability keys to their success. In an illustrative case series, we report our clinical experience with AXS Vecta (Stryker Neurovascular, Fremont, CA, USA), available in both 0.071-inch and 0.074-inch distal inner diameters, including the first 2 Vecta 74 cases reported. A literature review on AXS Vecta is also provided. In our series, 9 thrombectomies were performed (Vecta 71: 2 M1, 5 M2 occlusions; Vecta 74: 1 M1 and 1 ICA-terminus occlusion). The AXS Vecta was successfully delivered to the target site in all cases. In 7 of 9 cases, the catheter was delivered over a Tenzing 7 delivery catheter (Route 92 Medical, San Mateo, CA, USA). For 2 of 9 combination approach cases, Vecta was delivered using the stent-retriever wire as a rail. The median improvement in NIHSS score during hospitalization was 9 (IQR 5-12). Successful mTICI 2C or 3 recanalization was achieved in 8 of 9 (89%) patients after a median 2 (IQR 1-2) passes. Our median groin-to-reperfusion time was 23 (IQR 12.5-32) minutes, with no procedural complications. Two previous clinical studies of a total of 29 patients treated with Vecta 71 reported successful mTICI 2b-3 recanalization in 89-90% of cases. The Median groin-to-reperfusion time was 30 minutes. Complications were seen in 2 of 29 (6.9%) cases (vessel perforation and/or intracerebral hemorrhage). These data support the efficacy, deliverability, and safety of AXS Vecta for mechanical thrombectomy.


Contribution of the musculature to rotatory laxity and torsional stiffness at the knee.
The relationships between the mean rectified EMG from two muscle groups crossing the knee joint and the rotational stiffness and laxity about the longitudinal axis of the lower leg were investigated. The EMG signals from three of the quadricep muscle group and two of the hamstring muscle group were monitored using surface electrodes. Each subject sustained self-induced muscle activity from specific muscle combinations while the foot was twisted internally and externally by the researcher. Joint rotation was measured using an electrogoniometer. Analyses of the data showed increased joint stiffness with increased numbers of active muscles. The stiffness measurements ranged from 0.16 to 2.54 Nm degree-1 depending upon the combination of active muscles. The stiffness measured in different tests were very repeatable with standard deviations ranging from 0.02 to 0.25 Nm degree-1. Increases in joint stiffness of over 400% by activation of these muscles were measured.


Cholinergic inhibition of meal stimulated plasma neurotensin like immunoreactivity in man.
Meal stimulated plasma neurotensin like immunoreactivity (NTLI) was compared during saline or atropine infusion in six volunteers over six hours. Plasma gastrin and pancreatic polypeptide were also measured to compare the timing of their release to that of NTLI. Like plasma gastrin and PP, plasma NTLI rose rapidly following the meal, rising from 27 +/- 7 pmol/l to a peak of 45 +/- 8 pmol/l at 20 minutes (p less than 0.05). Also, like that of pancreatic polypeptide, the release of NTLI was biphasic. Sixty minutes after the meal, plasma NTLI had returned to basal values, followed by a rise to a prolonged peak of 64 +/- 10 pmol/l between 90-180 minutes (p less than 0.05) returning once more to basal values by 240 minutes. Following atropine, basal plasma NTLI fell from 22 +/- 4 pmol/l to 11 +/- 2 pmol/l (p less than 0.05), but rose to basal levels 30-60 minutes after the meal, where it remained unaltered for the remainder of the study. We conclude that both basal and meal stimulated plasma NTLI are inhibited by cholinergic blockade. Further, the similar temporal relationship between plasma NTLI and pancreatic polypeptide in the late phase of the meal response, suggests that a component of NTLI may mediate part of the intestinal phase of pancreatic polypeptide release.


Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.
The function of the central cannabinoid receptor (CB1) was investigated by invalidating its gene. Mutant mice did not respond to cannabinoid drugs, demonstrating the exclusive role of the CB1 receptor in mediating analgesia, reinforcement, hypothermia, hypolocomotion, and hypotension. The acute effects of opiates were unaffected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome were strongly reduced. These observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.


Examining potential risk factors for anxiety in early childhood.
Anxiety disorders are amongst the most prevalent psychiatric disorders in children and adolescents, with occurrence emerging early in the developmental trajectory. This study was one of the first to investigate potential risk factors for anxiety (i.e., behavioural inhibition, parental negative affect, parenting stress) in early childhood. Examination of risk factors was achieved through structural equation modelling and based on mothers' and fathers' report of 236 preschool aged children (4-6 years) in Brisbane, Australia. The structural model was found to fit the data well. All direct predictors of early childhood anxiety were significant and behavioural inhibition partially mediated parents' negative affectivity and mother's parenting stress. Results highlight the unique contribution of both parents in the aetiology of early childhood anxiety and assist in informing the development of intervention and prevention programs for young children.


Childhood membranous nephropathy, circulating antibodies to the 58-kD TIN antigen, and anti-tubular basement membrane nephritis: an 11-year follow-up.
Childhood membranous nephropathy (MNP) with anti-tubular basement membrane (anti-TBM) nephritis is a rare disorder that may have extrarenal manifestations. This article describes a new case to be added to the 10 previously reported. A renal biopsy specimen from a 1-year-old white boy with nephrotic syndrome, microhematuria, and hypertension showed MNP (granular global IgG, IgA and C3, and segmental IgM and C1q) associated with hypercellularity and granular deposits of IgM and C1q in the mesangium, arteriolar IgA, and linear TBM IgG, IgA, and C3. A biopsy at age 4 years showed MNP (IgG and C3) and linear IgG and C3 along the TBM. Six months later, temporary glucosuria suggested a mild tubular dysfunction. Biopsy at age 8 years showed sclerosing MNP (IgG and C3), linear TBM IgG and C3, and chronic active tubulointerstitial nephritis (TIN). Indirect immunofluorescence showed circulating anti-TBM antibodies, and the enzyme-linked immunosorbent assay (ELISA) approach verified strong reactivity with the 58-kd TIN antigen. Despite trials with steroids, chlorambucil, azathioprine, and cyclosporine, end-stage renal disease developed by the age of 9 years. At age 10 years, the patient received a cadaveric kidney transplant. With the patient now aged 12 years, the graft is still functioning well, without any clinical evidence of disease recurrence. Neurological, ocular, and abdominal symptoms, including nonbacterial diarrhea, were observed during the follow-up period. The pathophysiology of these extrarenal symptoms remains unclear. Serotyping and genotyping of HLA antigens (A2, A10, B12, B41, DR5 [1101, 1103-4, 1106 or 1108-1113], DR6 [1303, 1312, or 1413], DRB3 [*0101 and 0201-2 or 0301], DQA1 [*0501 homozygous], and DQB1 [*0301 homozygous]) did not indicate any HLA association similar to those described previously in childhood MNP with anti-TBM nephritis (HLA-B7 in four patients, HLA-DR8 in two patients). The presented case is the fifth in the literature that displays reactivity with the 58-kd TIN antigen, and for which data on HLA antigens are reported.


High-performance liquid chromatographic determination of nafimidone and its major metabolite nafimidone alcohol in human plasma and urine.
A rapid, sensitive and selective method for the determination in plasma and urine of nafimidone, a new antiepileptic drug, and its major metabolite, nafimidone alcohol, has been developed which uses a high-performance liquid chromatographic system and a fluorescence detector for nafimidone or ultraviolet detector for nafimidone alcohol. The detection limits for nafimidone and nafimidone alcohol are 5.0 and 12.5 ng/ml, respectively.


A nomogram to predict cadmium-induced renal tubular dysfunction.
Cadmium-induced renal dysfunction varies between individuals. It would be valuable to figure out those susceptible individuals or predict the risk of cadmium induced renal dysfunction. In the present study, we used a nomogram model to identify high-risk of cadmium-induced renal tubular dysfunction. 342 subjects living in low and moderately cadmium polluted areas were included in this study. The daily cadmium intake from food (FCd) was estimated using food survey. The cadmium in blood (BCd) and urine (UCd) were detected by using flame atomic absorption spectrometry. Urinary β2Microglobulin (UBMG) was chosen as indicator of renal dysfunction. Logistic regression was used to select the independent risk factors for renal dysfunction. Bootstrap self-sampling and calibration curves were performed to quantify our modeling strategy. Age, sex, BCd and TCd were used to construct the nomogam in total population; age, BCd and TCd were adopted in women; age and BCd were used in men. The internal validation showed the C-index was 0.76 (95% 47 confidence interval (CI): 0.71-0.82) in total population, 0.74 (95% CI: 0.69-0.79) in men and 0.78 (95% CI: 0.72-0.84) in women. The area under the curve of the nomogram was 0.77 (95% CI: 0.71-0.83) in total population, 0.82(95% CI: 0.74-0.90) in women and 0.74(95% CI: 0.66-0.82) in men. Nomogram may be a rapid and simple risk assessment tool for predicting high-risk of renal tubular dysfunction in subjects exposed cadmium.


The Effect of Missing Data on the Measurement of Cardiac Arrest Outcomes According to Race.
High-quality data are important to understanding racial differences in outcome following out of hospital cardiac arrest (OHCA). Previous studies have shown differences in OHCA outcomes according to both race and socioeconomic status. EMS reporting of data on race is often incomplete. We aim to determine the effect of missing data on the determination of racial differences in outcomes for OHCA patients. We performed a secondary analysis of a data set developed by probabilistically linking the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) and the Michigan Inpatient Database (MIDB). Adult OHCA patients (age >18) who survived to hospital admission between 2014 and 2017 were included. Both datasets recorded patient race and ethnicity with CARES using a single race/ethnicity variable. Patients were categorized as White, Black, other, or missing and only a single choice was allowed. Due to the small number of Hispanic patients and the combined race/ethnicity variable, these patients were excluded. The outcomes of interest were survival to hospital discharge and survival to discharge with Cerebral Performance Category 1 or 2 (good outcome). Outcomes were stratified according to EMS- or hospital-documented race. We included 3,756 matched patients, after excluding 34 Hispanic patients from analysis. Documentation of patient race was missing in 892 (22.1%) of CARES and 212 (5.6%) of MIDB patients. When both datasets documented Black or White race, agreement in race documentation was excellent (κ=0.83). White patients were more likely to have good outcomes than Black in both the CARES (27.3% vs 14.8%) and MIDB (26.9% vs 16.1%) databases (both p < 0.001), but were not more likely to survive (30.8% vs 27.3% p = 0.22; 30.3% vs 28.1%, p = 0.07). Moreover, we found no significant difference in outcome measures based on race documentation for White vs Black patients (good outcome [27.3 vs 26.9% (MIDB)] and [16.1% vs 14.8% (CARES)] respectively and survival [30.8% vs 30.3% (MIDB)] and [27.3 vs 28.1% (CARES)] respectively). Despite higher rates of missing EMS documentation, we identified statistically similar rates in OHCA outcome measures between databases. Further work is needed to determine the true effect of missing documentation of race on OHCA outcome measures.


Measurement of biceps tendon retraction after arthroscopic tenotomy.
One of the treatment options for long head of the biceps tendon (LHBT) pathology is tenotomy. To our knowledge, no study in the literature has evaluated the degree of retraction after tenotomy. The goals of this study were to determine the distance of this retraction and to identify its relationship with patient characteristics. We conducted an observational prospective survey over a 3-month period among 30 patients operated on arthroscopically by the same surgeon between August 2018 and April 2019. A radiopaque device was introduced inside the LHBT before tenotomy. Radiographs were obtained to evaluate the distance of retraction on day 1, day 30, and day 90. Thirty patients were included, of whom 63.3% (19) were women. Surgery was performed for a rotator cuff tear in 10 patients (33.3%) and for subacromial impingement in the remainder of patients (66.7%) after failure of conservative management. The mean retraction of the LHBT (distance between the glenoid and clip) increased from 1.9 cm (day 1) to 3.5 cm (day 90). Three radiographic measurements were performed, and all 3 showed significant increases from day 1 to day 90. According to the Student t test, the mean retraction in the subacromial impingement group was significantly higher than that in the rotator cuff tear group on day 1, day 30, and day 90. Body mass index, younger age, sex, and dominant hand did not show any relation with LHBT retraction (P > .05). The mean LHBT retraction was significantly higher on day 90 in patients presenting with a positive Popeye sign (P < .05). At 3 months of follow-up, the mean LHBT retraction was 3.5 cm from the glenoid and 2.5 cm from the greater tuberosity. It dynamically increased from day 1 to day 90. The LHBT will retract and sit beyond the transverse humeral ligament in the bicipital groove. The LHBT retracts significantly more when early mobilization of the shoulder is allowed.


Current status of quality of life assessment in schizophrenic patients.
Though the need to evaluate the quality of life of schizophrenic patients is well recognized, there are significant issues that remain unsolved. Are these patients capable of judging their own quality of life or does their illness invalidate their responses? Are there any psychometrically valid instruments that enable us to assess quality of life in these patients? When should quality of life be assessed in schizophrenics? While the ERIQA European Group completes their work and provide us with some common guidelines concerning quality of life assessment in medicine, this article provides some simple action guidelines regarding these questions. These guidelines are the result of analyzing the most up-to-date literature in the field. It also takes a brief look at the most universally used tools.


Arthroscopic rotator cuff repair performed with intra-articular tranexamic acid: could it provide improved visual clarity and less postoperative pain? A prospective, double-blind, randomized study of 63 patients.
Tranexamic acid (TXA) has been widely used in orthopedic surgery with the aim of reducing intraoperative and postoperative bleeding, as well as bleeding-related complications. The purpose of this study was to assess whether intra-articular use of TXA during arthroscopic rotator cuff tear (RCT) repair could improve visual clarity, shorten the duration of the operation, and provide superior pain management as compared with placebo. We conducted a prospective, randomized, double-blind, placebo-controlled study. Patients aged ≥18 years with a magnetic resonance imaging-confirmed RCT and a history of failed conservative treatment for ≥6 months were included. Patients with a history of coagulopathy; a history of cardiac, renal, or hepatic disease; a history of conservative treatment for <6 months; and/or acute RCTs were excluded. Visual clarity as the primary outcome was assessed using an arthroscopic visual scale comprising 5 grades-ranging from grade 1, best visual clarity, to grade 5, worst visual clarity (requiring conversion to open surgery)-after the procedure by the operating surgeon every 10 minutes throughout the video of the operation. Secondary outcomes were operative duration and postoperative pain scores. A total of 63 patients with similar demographic data (age and sex) and intraoperative mean arterial pressure were enrolled and randomized into 2 groups: The TXA group comprised 32 patients with a mean age of 56.46 years, and the placebo group comprised 31 patients with a mean age of 57.83 years. The TXA group was reported to have significantly superior visual clarity (mean arthroscopic visual scale score, 1.5 ± 0.5 vs. 2.86 ± 1.7; P < .001), with a significantly higher percentage of grade 1 visual clarity (78.1% vs. 32.2%, P < .001) and a significantly lower percentage of grade 4 visual clarity (0% vs. 3.2%, P = .003). Grade 5 visual clarity was not recorded in any patient in either group. The TXA group showed a significantly shorter operative duration (55.73 minutes vs. 67.26 minutes, P = .001) and superior pain scores at 8 hours (2.3 vs. 3.6, P = .002) and 24 hours (1.6 vs. 2.4, P < .001) postoperatively. No complications were recorded in either group. This study showed that during arthroscopic rotator cuff repair procedures, intra-articular use of TXA was able to provide superior arthroscopic visual clarity while shortening the total operative duration significantly and providing significantly superior pain management in the first 8 and 24 hours postoperatively as compared with placebo. This study underlines the safety and efficacy of intra-articular TXA use in arthroscopic rotator cuff repair.


[Neuroimaging of the endolymphatic hydrops of the labyrinth in severe and moderately severe Meniere's disease].
The results of magnetic resonance imaging (MRI) of the inner ear 24 hours after intratympanic administration of 1 ml of diluted (1:7) contrast substance for gadolinium-based MRI in 43 patients with moderate and severe Meniere's disease course are presented. It has been revealed that in case of severe and moderate course of Meniere's disease endolymphatic hydrops is presented in all departments of labyrinth: cochlea, vestibule, semicircular canals, but is most pronounced in vestibular department of labyrinth: horizontal semicircular canal and vestibule. The neuroimaging method according to the presented protocol is safe and can be applied in a wide practice both to assess the presence and localization, and the degree of expression of the endolymphatic hydrops.


CD44 adhesion molecule and neuro-glial proteoglycan NG2 as invasive markers of glioma.
Glioma invasion into the CNS involves the interaction of tumor cells with the host's cells and extracellular matrix (ECM) molecules. In this study, the expression of ECM-associated and cell-associated proteins such as the transmembrane CD44 adhesion molecule and neuro-glial proteoglycan 2 (NG2), a member of the chondroitin sulfate proteoglycan family, were evaluated during glioma progression, in vitro and in vivo, using a model of a highly invasive and aggressive intracerebral mouse G-26 glioma. We found a marked increase in CD44 and NG2 expression in brain tissue containing glioma. The glioma levels of these proteins gradually increased over time to reach 3-15 times the levels in the contralateral control. NG2 and CD44 expression paralleled progression of the glioma, being higher on days 14 and 21 than on day 2 post-glioma implant. In addition, when invading glioma crossed the midline in the advanced tumor stage, levels of each of these proteins in the contralateral tissue were elevated, but were still significantly lower than in the ipsilateral, tumor-bearing hemisphere. Immunohistochemistry of advanced stage G-26 glioma (day 21) showed CD44 expression to be most prominent at the front of the glioma invasion line, sharply separated from normal brain parenchyma which expressed glial fibrillary acidic protein (GFAP). However, single CD44 positive cells that escaped the tumor mass penetrated between the astrocytes that encased the tumor at its periphery. In contrast, NG2 was expressed on nearly all glioma cells within the tumor mass but less so at the leading edge of the tumor. The NG2 positive cells were clearly demarcated and morphologically distinguishable from GFAP positive cells and only sporadic, small groups of NG2 positive cells were seen in the GFAP positive zone of the neuropil. Taken together, these data show that during glioma progression in the brain, the level and pattern of glioma-associated molecules such as CD44 and NG2 may aid in tracing and targeting the invading glioma cells.


Regulation of zymogen granule exocytosis by Ca2+, cAMP, and PKC in pancreatic acinar cells.
The effect of cAMP and PKC on zymogen granule exocytosis was investigated by simultaneously measuring cytosolic Ca2+ concentration ([Ca2+]c) and individual zymogen granule exocytosis in isolated mouse pancreatic acini. When acinar cells were stimulated with acetylcholine (ACh, 10 microM), exocytic events were detected through granule-attached apical membranes with [Ca2+]c rise. Application of secretin, forskolin (an adenylate cyclase activator), or PMA (a PKC activator) alone did not elicit any [Ca2+]c rise or zymogen granule exocytosis, but co-stimulation with ACh led to exocytosis in that the total number of secreted granules increased markedly without a significant difference in [Ca2+]c rises. When we evoked exocytosis by [Ca2+]c ramps, pretreatment with forskolin or PMA elicited exocytosis at lower [Ca2+]c levels. These results indicate that PKC or cAMP alone could not directly elicit zymogen granule exocytosis, but that they increase the total releasable pool by rendering zymogen granules more sensitive to Ca2+.


Spatially distributed responses induced by contrast reversal in cat visual cortex.
Field potentials were recorded from cat striate cortex, either between an epidural screw electrode and a cannula-electrode inserted deep in the gray matter (transcortical recording) or with a pair of metal microelectrodes. Electrodes were placed bilaterally near the cortical projection of the area centralis. The horizontal separation of the recording tips was approximately 2 mm and approximately 300 microns, respectively. The area of the visual field providing input to the recording site (receptive field) was determined by measuring the field potentials generated by contrast reversal of high-contrast, achromatic bar gratings. Five-degree-diameter grating patches were presented individually over a large area of the visual field. The gratings were contrast-reversed at 4, 6 or 10 Hz, while also being swept in spatial frequency between 0.56 and 5.24 c/deg. The receptive fields were approximately 20 deg across or more, substantially larger than expected on the basis of cortical retinotopy. Responses were also elicited by stimulation of the hemi-field contralateral to that contributing to the classical receptive field, implicating the presence of a callosal projection. The large, spatially distributed receptive fields consisted of patches of high and low sensitivity. Continuous cortical infusion of either 100 microM tetrodotoxin or 10 mM muscimol at the recording site totally suppressed the transcortically recorded field potentials, proving that the local field potentials were generated postsynaptically. The present findings suggest that a cluster of cortical cells near the projection site of the area centralis receives input from remote cortical regions to an extent that is comparable with that of anatomically demonstrated long-range lateral connections.


De novo 11q13.3q13.4 deletion in a patient with Fanconi renotubular syndrome and intellectual disability: Case report and review of literature.
To explore the genetic etiology of a child with facial dysmorphia, developmental delay, intellectual disability, Fanconi renotubular syndrome, and Chiari malformations. Whole exome sequencing (WES), Copy number variation sequencing (CNV-seq), and mitochondrial gene detection (Long-PCR + NGS) were applied to detect possible pathogenic mutations and chromosomal copy number variations (CNVs), together with databases and literature reviews to clarify the pathological significance of the candidate mutations. The WES revealed a 2.10 Mb interstitial deletion from 11q13.3 to 11q13.4, which was later confirmed by CNV-seq involving 11 OMIM genes, among which SHANK2, DHCR7, NADSYN1, FADD, NUMA1, IL18BP, ANO1, and FGF3 are disease-causing. The mitochondrial gene shows no variations. The child has carried a de novo 11q13.3q13.4 microdeletion, in which SHANK2 genes may be the key gene responsible for the phenotype of intellectual disability. The renal manifestation of the child, which can be diagnosed as Fanconi renotubular syndrome, has an unknown cause but may result from the effect of the ANO1 gene. This case adds a new phenotype to the deletion of this region.


Treatment of fish parasites. 10. Effects of a new triazine derivative, HOE 092 V, on Monogenea: a light and transmission electron microscopy study.
For chemotherapy of fish parasitized by monogeneans, a novel triazine derivative, 2-[3,5-alpha-dichloro-4-(4-methyl-sulfonylphenoxy)-phenyl]-1-methy l- hexahydro-1,2,4-triazine-3,5-dion (HOE 092 V), was tested in vivo against the gill- and skin-parasitizing species Dactylogyrus extensus, D. vastator, and Gyrodactylus arcuatus. Naturally infected fish were incubated in aerated, separate tanks at 22 degrees C for 1, 2, 3, and 4 h in water containing 0, 1, 5, 10, or 15 micrograms HOE 092 V/ml, whereas Pseudodactylogyrus bini was tested in vitro at 10 micrograms HOE 092 V/ml for 2.25 h. As seen by means of transmission electron microscopy, in vivo treatment against D. extensus caused vacuolization and lysis of the parasite's tegument at a dose as low as 1 micrograms/ml over a 3-h exposure period. Higher doses, such as 5 and 10 micrograms/ml over the same exposure period, produced lesions in the circular and longitudinal musculature of D. extensus and differing degrees of damage to the ciliary cells of protonephridia and immature vitelline cells. There was 100% mortality in D. vastator when incubation was done with 10 micrograms HOE 092 V/ml for 4 h (G. arcuatus; 5 micrograms/ml for 4 h; 10 micrograms/ml for 1 h) and in P. bini after 2.25 h in vitro exposure. In all species tested, the anterior portion and the opisthaptor region were most sensitive to the drug action.(ABSTRACT TRUNCATED AT 250 WORDS)


Small bowel obstruction caused by a fast-growing desmoid tumor.
Desmoid tumors are rare tumors which can cause intestinal obstructions. Surgical wide excision is currently the treatment of choice, with the goal of achieving free resection margins.


Informant-Administered Cognitive Screening as a Component of Memory Clinic Assessment: Overcoming Ethical and Practical Challenges.
Possin and Rosen provide a robust commentary exploring the challenges of using caregivers as cognitive testers. Informants have an important and often overlooked role in diagnosing cognitive impairment. O'Caoimh et al. show they can support cognitive screening in advance of clinic, suggesting new research avenues including the potential for home-monitoring. Although concerns testing may engender bias, introduce practice effects, and impact patient autonomy are valid and require examination, these should be viewed in light of patient preference, clinical need, and the broader ethics of assessing dementia. The importance of distinguishing concerns over accuracy and ethical appropriateness is also discussed.


Development and global validation of a 1-week-old piglet head finite element model for impact simulations.
Child head injury under impact scenarios (e.g. falls, vehicle crashes, etc.) is an important topic in the field of injury biomechanics. The head of piglet was commonly used as the surrogate to investigate the biomechanical response and mechanisms of pediatric head injuries because of the similar cellular structures and material properties. However, up to date, piglet head models with accurate geometry and material properties, which have been validated by impact experiments, are seldom. We aim to develop such a model for future research. In this study, first, the detailed anatomical structures of the piglet head, including the skull, suture, brain, pia mater, dura mater, cerebrospinal fluid, scalp and soft tissue, were constructed based on CT scans. Then, a structured butterfly method was adopted to mesh the complex geometries of the piglet head to generate high-quality elements and each component was assigned corresponding constitutive material models. Finally, the guided drop tower tests were conducted and the force-time histories were ectracted to validate the piglet head finite element model. Simulations were conducted on the developed finite element model under impact conditions and the simulation results were compared with the experimental data from the guided drop tower tests and the published literature. The average peak force and duration of the guide drop tower test were similar to that of the simulation, with an error below 10%. The inaccuracy was below 20%. The average peak force and duration reported in the literature were comparable to those of the simulation, with the exception of the duration for an impact energy of 11 J. The results showed that the model was capable to capture the response of the pig head. This study can provide an effective tool for investigating child head injury mechanisms and protection strategies under impact loading conditions.


Flow-cytometric analysis of mixed cell populations using intermediate filament antibodies.
Using two human tumour cell lines, T24 bladder carcinoma and Molt-4 leukemia, flow-cytometric DNA analysis of pure and mixed cell populations was performed using cellular cytokeratin content to distinguish cytokeratin-containing carcinoma cells from leukemia cells which do not contain cytokeratin. Using cytokeratin content to gate DNA analysis, the same specificity and sensitivity of cellular DNA content and distribution measurement could be achieved by single-pass FCM analysis of a mixture of the two cell types as was seen when analysing pure populations of the two cell lines. This technique has broad applicability to FCM analysis of mixed populations composed of cells from different tissues of origin.


Which tonometry in eyes with keratoconus?
To compare intraocular pressure (IOP) measurements obtained with Goldmann applanation tonometery (GAT), dynamic contour tonometry (DCT), tonopen (TP), and ocular response analyzer (ORA), and to determine the influence of Amsler grade and central corneal thickness (CCT) on the IOP readings in eyes with keratoconus that are classified into four groups according to the Amsler-Krumeich classification. All eyes with keratoconus were separated into four groups using Amsler-Krumeich classification for keratoconus. IOP was measured in 202 eyes of 202 patients with keratoconus using GAT, DCT, TP, and ORA. The IOP differences revealed no significant difference among the Amsler degree in the DCT and corneal-compensated IOP (IOPcc) measurements (P>0.05 for all). There was no statistically significant difference in terms of IOP differences between GAT and IOPcc (P>0.05), TP and Goldmann-correlated measure of IOP (IOPg; P>0.05) in the Amsler I, while the IOP measurements revealed significant difference among the measurements of the four different tonometers in the Amsler II, Amsler III, and Amsler IV (P<0.05 for all). There was no significant association between DCT IOP or IOPcc and CCT in eyes with keratoconus; no statistically significant difference was found between keratoconus stages and the control group in terms of the IOP analyzed with these two techniques. These two techniques may be the most stable in the measurement of IOP in different keratoconus stages. However, no IOP technique can be used interchangeably with other techniques in the follow-up of keratoconus patients.


Characterization and influence of ipsilateral scapula fractures among patients who undergo surgical stabilization of sub-scapular rib fractures.
Current decision algorithms involving surgical stabilization of rib fractures (SSRF) do not consider either specific fracture locations or other chest wall bony injuries. Our objective was to characterize the impact of scapula fractures on morbidity among patients who underwent fixation of sub-scapular rib fractures. We hypothesized that an ipsilateral scapula fracture was associated with poor acute and long-term outcomes. Retrospective review of two institutions' prospectively maintained SSRF databases (October 2010 to January 2019). Patients who underwent repair of ≥ 1 sub-scapular rib fracture were included. Patients were grouped by the presence of an ipsilateral scapula fracture. Outcomes were acute SSRF complications, long-term rib implant removal, and quality of life via phone survey. A total of 144 patients were analyzed; 53 (36.8%) had an ipsilateral scapula fracture. Patients with a scapula fracture had a higher injury severity score (p = 0.02), degree of pulmonary contusion (p < 0.01), and RibScore (p < 0.01). The overall incidence of both acute re-operation (n = 4, 2.8%) and long-term implant removal (n = 5, 3.8%) following SSRF was low and did not vary by the presence of a scapula fracture. Only twenty-one patients completed phone questionnaires a median of 38 months after SSRF; both shoulder and rib outcomes were excellent and did not vary by the presence of a scapula fracture. Ipsilateral scapula fractures are common in patients who undergo surgical stabilization of sub-scapular rib fractures. Despite higher injury severity, patients with an ipsilateral scapula fracture did not incur worse outcomes.


Cost-effectiveness of hepatic venous pressure gradient measurements for prophylaxis of variceal re-bleeding.
Measurement of the hepatic venous pressure gradient may identify a sub-optimal response to drug prophylaxis in patients with a history of variceal bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide secondary prophylaxis has not been examined. A Markov model was constructed using specialized software (DATA 3.5, Williamstown, MA, USA). Three strategies involved secondary prophylaxis without haemodynamic monitoring using beta-blockers alone, beta-blockers plus isosorbide mononitrate or endoscopic variceal ligation alone. Four strategies involved secondary prophylaxis with beta-blockers plus isosorbide mononitrate or beta-blockers alone, accompanied by one or two hepatic venous pressure gradient measurements to identify haemodynamic non-responders, who underwent endoscopic variceal ligation as an alternative. The total expected costs, variceal bleeding episodes and total deaths were calculated for each strategy over 3 years. The two most effective strategies were combination therapy alone and combination therapy with two hepatic venous pressure gradient measurements. The incremental cost-effectiveness ratio of the latter strategy was 136,700 dollars per year of life saved compared with combination therapy alone. The ratio improved as the time horizon was extended or the rates of variceal re-bleeding were increased. The cost-effectiveness of haemodynamic monitoring to guide secondary prophylaxis of recurrent variceal bleeding is highly dependent on local hepatic venous pressure gradient measurement costs, life expectancy and re-bleeding rates.


[Identification of diagnostic tumour markers and therapeutic targets in testicular tumours].
Today, tumour classification has been expanded due to immunohistochemical and molecular-pathological analyses due to corresponding patterns/profiles of protein and gene expression. The latter analyses often include growth factors and their ligands, intracellular signalling pathways, DNA-binding proteins, and oncogenes and suppressor genes, thus functionally including primarily the regulation of growth including angiogenesis and apoptosis as well as the induction of metastases to adhesion and migration disorders. Based on observations that testicular tumours often show microcalcifications, possibly due to impaired calcium metabolism, we focused on calcium-dependent transmembrane proteins, particularly cadherins, in the search for new tumour markers and therapeutic targets. N‑cadherin is expressed differently in the various subtypes of germ cell tumours and is useful in N‑cadherin-positive germ cell tumours as a novel therapeutic targeting structure, particularly in cisplatin resistance, due to functional analysis. In the tumours of the sex cord stroma beta-catenin and the transcription factor SOX-9 give a clear classification of these tumours. Thus, morphological investigations prove to be pilot experiments to purposefully narrow the spectrum of functionally important proteins and thus to establish promising new differential diagnostic markers or target structures.


A new osteonecrosis animal model of the femoral head induced by microwave heating and repaired with tissue engineered bone.
The objective of this research was to induce a new animal model of osteonecrosis of the femoral head (ONFH) by microwave heating and then repair with tissue engineered bone. The bilateral femoral heads of 84 rabbits were heated by microwave at various temperatures. Tissue engineered bone was used to repair the osteonecrosis of femoral heads induced by microwave heating. The roentgenographic and histological examinations were used to evaluate the results. The femoral heads heated at 55 degrees C for ten minutes showed low density and cystic changes in X-ray photographs, osteonecrosis and repair occurred simultaneously in histology at four and eight weeks, and 69% femoral heads collapsed at 12 weeks. The ability of tissue engineered bone to repair the osteonecrosis was close to that of cancellous bone autograft. The new animal model of ONFH could be induced by microwave heating, and the tissue engineering technique will provide an effective treatment.


Which is the eligible patient to be treated with pioglitazone? The expert view.
Pioglitazone has an important role in the treatment of patients with Type 2 diabetes. The drug can help patients to achieve sustained glycemic control and may delay the requirement for insulin. Pioglitazone may provide benefits beyond its effects on glycemia, with data suggesting it may confer anti-atherosclerotic and cardioprotective properties. Attention should be given to possible side effects relating to class effects of TZD, and selection of appropriate patients to be prescribed pioglitazone will enable optimum benefits to be derived from pioglitazone treatment.


Acanthopanax senticosus suppresses reactive oxygen species production by mouse peritoneal macrophages in vitro and in vivo.
Excess production of reactive oxygen species by macrophages has been implicated in many inflammatory diseases. The present study investigated the inhibitory effect of the stem bark extract of Acanthopanax senticosus on the production of superoxide anion and hydrogen peroxide in mouse peritoneal macrophages in vitro and in vivo. Exposure of mouse peritoneal macrophages to A. senticosus extract significantly suppressed superoxide anion production induced by zymosan in a dose-dependent manner. Similarly, exposure of mouse peritoneal macrophages to A. senticosus extract significantly inhibited hydrogen peroxide production induced by phorbol 12-myristate 13-acetate (PMA) in a dose-dependent manner. Intraperitoneal administration of A. senticosus extract to KM mice reduced the ex vivo production of zymosan induced-superoxide anion and PMA-induced hydrogen peroxide by their peritoneal macrophages. Exposure to A. senticosus extract did not affect the cell viability or systemic toxicity. A. senticosus inhibited reactive oxygen species production by mouse peritoneal macrophages in vitro and in vivo and may be partly responsible for the antiinflammatory function.


Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study.
Oxidative stress (OS) and reduced nitric oxide (NO) bioavailability contribute to the pathogenesis of pulmonary hypertension (PH). Whether there are associations between OS and NO signaling biomarkers and whether these biomarkers are associated with the severity of PH remain unclear. Blood samples were collected from 35 healthy controls and 35 patients with pulmonary arterial hypertension (PAH, n = 12) or chronic thromboembolic pulmonary hypertension (CTEPH, n = 23). The mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were measured by right heart catheterization. We measured the derivative of reactive oxygen molecules (d-ROMs), biological antioxidant potential (BAP) and superoxide dismutase (SOD) by automatic biochemical analyzer, malondialdehyde (MDA) and asymmetric dimethylarginine (ADMA) by enzyme-linked immunosorbent assay. The relationship between oxidative-antioxidative biomarkers and ADMA, as well as their association with pulmonary hemodynamics, were analyzed. Compared with age- and gender-matched controls, there was no significant difference of d-ROMs in PAH and CTEPH patients; MDA was increased in CTEPH patients (P = 0.034); BAP and SOD were decreased in PAH (P = 0.014, P < 0.001) and CTEPH patients (P = 0.015, P < 0.001); ADMA level was significantly higher in PAH (P = 0.007) and CTEPH patients (P < 0.001). No association between oxidative-antioxidative biomarkers and ADMA was found. Serum ADMA concentration was correlated with mPAP (r = 0.762, P = 0.006) and PVRI (r = 0.603, P = 0.038) in PAH patients. The antioxidative potential and NO signaling are impaired in PAH and CTEPH. Increased serum ADMA level is associated with unfavorable pulmonary hemodynamics in PAH patients. Thus, ADMA may be useful in the severity evaluation and risk stratification of PAH.


Micellization and catalytic activity of the cetyltrimethylammonium bromide-Brij 97-water mixed micellar system.
Surface tension measurements and the kinetic study of the basic hydrolysis of ethyl p-nitrophenyl chloromethyl phosphonate were used to examine the structural behavior and catalytic activity of the cethyltrimethylammonium bromide (CTAB)-polyoxyethylene (10) oleyl ether, C(18)H(35)(OCH(2)CH(2))(10)OH (Brij 97)-water mixed micellar system. Application of the regular solution model to the experimental data yields the value of the interaction parameter beta as -4.6, which indicates an attractive interaction of the surfactants in the mixed micelle and reflects synergistic solution behavior of the mixture. The mixed micellar composition is found to be enriched in the surfactant with the lower critical micelle concentration (cmc). In the kinetic study a nonmonotonic change in the pseudo-first-order rate constant of basic hydrolysis of the substrate is observed with increasing mole fraction of nonionic surfactant. The pseudophase micellar model reveals that the concentration factor mainly contributes to the catalytic effect, while the microenvironmental factor plays a negative role.


Characterization of an Aeromonas hydrophila strain isolated on a septicemic out-break in a fish-farm of Spain.
An Aeromonas hydrophila strain (AH-3) was isolated from a septicemic out-break on a gold-fish farm near Barcelona (Spain). On the bases of their virulence and surface characteristics was classified as moderate to weakly virulent.


An immunocytochemical study on the localization of S-100 protein in the retina of rats.
The localization of S-100 protein in the retina was studied by immuno-electron microscopy. The immunoreaction for S-100 is specifically confined to Müller cells and astrocytes. Long slender cytoplasmic processes of Müller cells and their participation in the formation of the inner and outer limiting membrane were clearly demonstrated with this immunoreaction. The cytoplasmic processes were also revealed to form continuous sheets surrounding blood vessels. Some somata of Müller cells were found in the outer nuclear layer. The results show that immunostaining for S-100 is useful for selective visualization of Müller cells in the mature retina.


Prognostics of Systemic Malignancy ICD-O Topography and Morphology Types on Brain Metastases: An NCDB Time-to-event Cohort.
The primary site and histology of systemic malignancy are known predictors of progression to brain metastases (BM). We investigated the combinational interactions of International Classification of Diseases for Oncology (ICD-O) primary topography and morphology types on the survival of BM after adjusting for relevant clinical and demographic prognostic factors. The cohort included all adult patients with BM at diagnosis of an invasive malignancy in the National Cancer Database (2010 to 2018). The sample consisted of 180,150 entries out of 14,279,749 cancer patients screened. A survival analysis of the topography-specific and histology-specific time to death was performed. Multivariate Cox regression revealed violations of the proportional hazard assumption for multiple covariates. Parametric models using a log-logistic distribution best described the population survival pattern. The primary topography "prostate" and morphology "choriocarcinoma" provided the strongest survival benefit among ICD-O types, whereas BM from prostate demonstrated a 14-month median overall increase in survival probability. Favorable prognostics were BM from breast, bone/joints, and testis; also, the morphologies of carcinoid tumor, mature B-cell lymphoma, and papillary adenocarcinoma. Poor prognostics were BM from gastrointestinal (liver, biliary tree, pancreas, and gallbladder) and gynecologic malignancies. All morphologies of spindle cell carcinoma, hemangiosarcoma, undifferentiated carcinoma, Ewing sarcoma, pseudosarcomatous carcinoma, renal cell carcinoma/sarcomatoid, signet ring cell carcinoma, spindle cell sarcoma, and squamous cell carcinoma/spindle cell were associated with poor survival. This is the largest cohort providing an unbiased estimate of the adjusted ICD-O topography and morphology effect sizes. The results can be summarized as a booklet for prognostic classification of disease in patients with BM secondary to systemic malignancy.


Predicting the requiring intubation and invasive mechanical ventilation among asthmatic exacerbation-related hospitalizations.
To identify the predictors of requiring intubation and invasive mechanical ventilation (IMV) in asthmatic exacerbation (AE)-related hospitalizations. This study was conducted in southern Thailand between October 2016 and September 2018. The characteristics and clinical findings of patients admitted for AE requiring intubation and IMV were analyzed. The variables were evaluated by univariate and multivariate analysis to identify the independent predictors. A total of 509 patients with a median age of 53 years were included in the study. Being female (60.2%), having no previous use of a controller (64.5%), having a history of smoking, and having a high level of white blood cell count (14,820 cells/mm3) were the significantly more common characteristics of the patients requiring mechanical ventilation. Univariate analysis showed that being male (OR = 1.96 95% CI, 1.22-3.13), having a history of 1-2 AEs in the past 12 months (OR = 3.27 95% CI, 1.75-6.12), and having an absolute eosinophil count ≥300 cells/mm3 (OR = 1.68 95% CI, 1.05-2.69) were associated with patients requiring IMV, whereas the patients who were taking a reliever (OR = 0.36 95% CI, 0.23-0.57) and controller (OR = 0.42 95% CI, 0.27-0.68) were associated with a decreased risk of requiring intubation and IMV. In multivariate analysis, only 1-2 AEs within the past 12 months (OR = 3.12, 95% CI, 1.19-8.21) was an independent predictor of requiring intubation and IMV in patients with AE-related hospitalization (p = 0.021). This study found that a history of 1-2 AEs in the past 12 months was a strong independent predictor for the requirement of intubation and IMV in patients hospitalized for AE-related conditions.


Delayed activation of human microglial cells by high dose ionizing radiation.
Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia.


SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis.
Methylation of proteins is emerging to be an important regulator of protein function. SET7/9, a protein lysine methyltransferase, catalyses methylation of several proteins involved in diverse biological processes. SET7/9-mediated methylation often regulates the stability, sub-cellular localization and protein-protein interactions of its substrate proteins. Here, we aimed to identify novel biological processes regulated by SET7/9 by identifying new interaction partners. For this we used yeast two-hybrid screening and identified the large subunit ribosomal protein, eL42 as a potential interactor of SET7/9. We confirmed the SET7/9-eL42 interaction by co-immunoprecipitation and GST pulldown studies. The N-terminal MORN domain of SET7/9 is essential for its interaction with eL42. Importantly, we identified that SET7/9 methylates eL42 at three different lysines - Lys53, Lys80 and Lys100 through site-directed mutagenesis. By puromycin incorporation assay, we find that SET7/9-mediated methylation of eL42 affects global translation. This study identifies a new role of the functionally versatile SET7/9 lysine methyltransferase in the regulation of global protein synthesis.


Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors.
Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3-20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3-9%) and G2 high (Ki67 10-20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.


Endocrine disrupting chemical exposure and maladaptive behavior during adolescence.
Studies suggest that exposure to endocrine disrupting chemicals (EDCs), including phthalates, phenols, and parabens may influence childhood behavior, but the relationship during adolescence has not been assessed. We investigated the association between urinary biomarker concentrations of potential EDCs, including some phthalate and bisphenol A replacement chemicals, and behavior in adolescents. Participants were from the New Bedford Cohort (NBC), a prospective birth cohort of residents near the New Bedford Harbor Superfund site in Massachusetts. We measured urinary concentrations of 16 phthalate metabolites or replacements, 8 phenols, and 4 parabens in 205 NBC adolescents and estimated associations between select EDCs and adolescent behavior assessed with the Behavior Assessment System for Children, Second Edition -Teacher Rating Scale (BASC-2). Of note, up to 32 of the 205 in our assessment had missing outcome information imputed. Increased urinary concentrations of the sum of 11 antiandrogenic phthalate metabolites were associated with an increase in maladaptive behaviors (Externalizing Behavior, Behavioral Symptoms Index, and Developmental Social Disorders or DSD), and a decrease in Adaptive Skills. For example, a doubling of urinary concentrations of antiandrogenic phthalate metabolites was associated with an increased risk of Externalizing Behavior (RR=1.04; 95% CI: 1.01-1.08). While associations were generally stronger in males, sex differences were not statistically significant. Urine concentrations of phenols and parabens were not associated with adverse behavior. Our findings support the importance of exposure to antiandrogenic phthalates during adolescence as a potential correlate of maladaptive behaviors including Externalizing Behavior, DSD behaviors, and decrements in Adaptive Skills.


Subglottic laryngitis--Changes in therapy approach over the past 20 years.
To show changes in the management of subglottic laryngitis over the last twenty years in Croatia. We sent questionnaires to paediatricians and otolaryngologists (ENT) in 9 Croatian hospitals in 1993, 2003 and 2013. In the questionnaire we presented a case of a child with moderately difficult subglottic laryngitis, after which they had to answer questions about the management of this kind of a patient and common therapy practice in their hospitals. All data were categorical, described in absolute frequencies and with relative percentages. The Cochran-Armitage test for trend was used in the analysis of different treatments over the years among ENT and paediatricians. Associations were statistically significant if p<0.05. During a twenty-year period main novelties included the introduction of racemic epinephrine use (ENT from 3.3% in 1993 to 92.3% in 2013; paediatricians from 17.2% in 1993 to 100.0% in 2013) and downfall of humidification (ENT from 60.0% to 23.3%; paediatricians from 60.0% to 12.0%), antibiotic (ENT from 53.0% to 2.3%; paediatricians from 21.0% to 0.0%) and antihistaminic use (ENT from 67.7% to 0%; paediatricians from 43.2% to 2%), while corticosteroids (both parenteral and nebulized form) remained the cornerstone in treatment of moderately severe subglottic laryngitis. Main novelties included the use of racemic epinephrine and downfall of antibiotic, antihistaminic and humidification therapy use, while corticosteroids remained the cornerstone in the treatment of moderately severe subglottic laryngitis. Differences between approaches among specialities are minimized during 20-year period.


Dimeric benzylisoquinoline alkaloids from Thalictrum delavayi and their biological activities.
A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A-E (1-5), together with six known congeners (6-11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A-E (1-5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC50 value of 2.1 μM, compared with the positive CPT-11 (IC50 = 3.0 μM). In addition, 5-7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents.


Enhanced Thermal-to-Flexible Phase Change Materials Based on Cellulose/Modified Graphene Composites for Thermal Management of Solar Energy.
The applications of phase change materials (PCMs) in some practical circumstances are currently limited due to the constant strong rigidity, poor thermal conductivity, and low photoabsorption property. Therefore, the design of flexibility-enhanced, highly efficient PCMs is greatly desirable and challenging. In this work, novel PCM composites (CPmG-x) with stable forms and thermally induced flexibility were successfully prepared by grafting the comblike poly(hexadecyl acrylate) polymer (PA16, phase change working substance) onto a cellulose support by atom transfer radical polymerization (ATRP). Modified graphene (GN16) was incorporated into the synthesized material to enhance its enthalpy, thermal conductivity, and physical strength. The prepared CPmG-x composites exhibit excellent softness and flexibility after phase transition of PA16. The addition of GN16 increases the thermal conductivity and enthalpy of CPmG-x materials to 1.32 W m-1 K-1 (9 wt % GN16) and 103 J g-1 (5 wt % GN16), respectively. Assessments of the solar-to-thermal energy conversion and storage efficiencies indicate that CPmG-x composites possess great potential for use in thermal energy management applications and solar energy collection systems.


The human 5-HT2 receptor is encoded by a multiple intron-exon gene.
Serotonin (5-hydroxytryptamine; 5-HT) mediates many central and peripheral nervous system functions by its interaction with specific neuronal receptors. Here we report the genomic structure of the human 5-HT2 receptor. The SacI-EcoRI restriction fragment of rat 5-HT2 receptor cDNA was used as a probe to identify and isolate two positive clones of 8.5 and 7.0 kb from an EcoRI restriction digest of a chromosome 13 specific EcoRI fragment lambda-phage human genomic library. Subcloning and sequencing of these fragments showed the 8.5 kb fragment (designated lambda SE-5) contained the first two exons of the 5-HT2 receptor gene. The 7.0 kb insert (lambda SE-2) contained an incomplete third exon. A HindIII-EcoRI fragment of this insert was used as a probe to isolate a 9.0 kb clone (lambda SH-2), which contained the entire third exon, from a chromosome 13 specific HindIII-fragment lambda-phage human genomic library. The isolation of these three clones (lambda SE-5, lambda SE-2 and lambda SH-2) shows that the human 5-HT2 receptor gene consists of three exons separated by two introns and spans over 20 kb. The deduced amino acid sequence of the human, mouse and rat 5-HT2 receptors are highly conserved and all three share a 90% sequence similarity.


Probabilistic linguistic fuzzy cognitive maps: applications to the critical factors affecting the health of rural older adults.
Achieving healthy ageing has become the only way for China to alleviate the pressure of ageing, especially in rural areas. However, the factors affecting the health of rural older adults are numerous and complex. It is important to identify the critical factors that affecting the health of older adults in rural areas and provide decision-making support for targeted health interventions. To overcome some limitations of existing works, an extended probabilistic linguistic fuzzy cognitive map model is proposed in this paper as a useful tool for modeling the cause-effect relationship between factors. The proposed model integrates the advantages of probabilistic linguistic term sets and fuzzy cognitive maps. In the end, to rank and identify the critical factors affecting the health, a novel similarity measure based on Euclidean distance and Z-mapping function is proposed. The proposed model can effectively deal with the uncertainty of experts and reflect different opinions of groups well. In terms of representing uncertainty and ambiguity, the proposed method outperforms other models in modeling complex systems. In the real-world case analysis, we find that education is the most important factor affecting the health of rural older adults, followed by previous occupational experiences, psychology, and physical exercise, among other things. Intergenerational relationship has become another important factor affecting the health of rural older adults in China as the development of Chinese society. From a macro perspective, social economic status, living environment, lifestyle, and health management, are the variables that have the greatest impact on the health of rural older adults. As a result, providing more precise health interventions with the characteristics of factors influencing health is a crucial guarantee for preserving and improving the health of rural older adults in China.