A single coadministration of subeffective doses of ascorbic acid and ketamine reverses the depressive-like behavior induced by chronic unpredictable stress in mice.
In this study, we investigated the ability of a single coadministration of subeffective doses of ascorbic acid and ketamine to reverse the depressive-like behavior induced by chronic unpredictable stress (CUS) in mice. Moreover, we examined the effect of combined administration of ascorbic acid and ketamine on hippocampal phosphorylation of p70S6K and immunocontents of GLUA1 and PSD-95 in mice submitted to the CUS procedure. CUS procedure was applied for 21 days. Animals received a single coadministration of subeffective doses of ascorbic acid (0.1 mg/kg) and ketamine (0.1 mg/kg) and were subjected to behavioral evaluation 24 h after the treatments. Immediately after the behavioral observations the hippocampi were dissected for Western blotting analyses. Our results revealed that a single administration of subeffective doses of ascorbic acid and ketamine completely reversed the depressive-like behavior induced by CUS, however, this effect was not accompanied by changes in the phosphorylation of p70S6K and immunocontent of GLUA1 or PSD95 in the hippocampus. These findings point to a synergistic antidepressant-like effect of ascorbic acid and ketamine, paving the way for additional studies on the combined use of these compounds for the management of major depressive disorder (MDD).


Transformation of rodent fibroblasts by herpes simplex virus: presence of morphological transforming region 1 (MTR 1) is not required for the maintenance of the transformed state.
Studies on the mechanisms of transformation of mammalian cells by herpes simplex virus (HSV) in vitro have been prevented so far by the extremely low transformation frequencies obtained in monolayer culture. Here we present a transformation system that relies on the direct seeding in soft agar of infected single cells, thus avoiding negative interactions between normal and transformed cells. We took advantage of HSV-I temperature-sensitive mutants at the UL9 locus, which codes for a DNA-binding protein necessary for viral DNA replication. At the non-permissive temperature, viral DNA synthesis and late gene expression are prevented. Viral gene expression is restricted to immediate early and early genes. Induction of transformation was highly efficient in our one-step transformation system. It depended on intact viral particles and viral DNA. Immediate early and/or early viral gene expression was sufficient to induce transformation. Colonies were stably transformed and did not show any rescue of viable virus after temperature downshift and co-cultivation with susceptible cells. Transformed cells maintained the transformed state in the absence of viral DNA. Our data therefore support the "hit-and-run" hypothesis for the transforming effect of HSV.


Exploration of computational methods for classification of movement intention during human voluntary movement from single trial EEG.
To explore effective combinations of computational methods for the prediction of movement intention preceding the production of self-paced right and left hand movements from single trial scalp electroencephalogram (EEG). Twelve naïve subjects performed self-paced movements consisting of three key strokes with either hand. EEG was recorded from 128 channels. The exploration was performed offline on single trial EEG data. We proposed that a successful computational procedure for classification would consist of spatial filtering, temporal filtering, feature selection, and pattern classification. A systematic investigation was performed with combinations of spatial filtering using principal component analysis (PCA), independent component analysis (ICA), common spatial patterns analysis (CSP), and surface Laplacian derivation (SLD); temporal filtering using power spectral density estimation (PSD) and discrete wavelet transform (DWT); pattern classification using linear Mahalanobis distance classifier (LMD), quadratic Mahalanobis distance classifier (QMD), Bayesian classifier (BSC), multi-layer perceptron neural network (MLP), probabilistic neural network (PNN), and support vector machine (SVM). A robust multivariate feature selection strategy using a genetic algorithm was employed. The combinations of spatial filtering using ICA and SLD, temporal filtering using PSD and DWT, and classification methods using LMD, QMD, BSC and SVM provided higher performance than those of other combinations. Utilizing one of the better combinations of ICA, PSD and SVM, the discrimination accuracy was as high as 75%. Further feature analysis showed that beta band EEG activity of the channels over right sensorimotor cortex was most appropriate for discrimination of right and left hand movement intention. Effective combinations of computational methods provide possible classification of human movement intention from single trial EEG. Such a method could be the basis for a potential brain-computer interface based on human natural movement, which might reduce the requirement of long-term training. Effective combinations of computational methods can classify human movement intention from single trial EEG with reasonable accuracy.


Microwave assisted aqua regia extraction of thallium from sediment and coal fly ash samples and interference free determination by continuum source ETAAS after cloud point extraction.
A simple cloud point extraction method is described for the separation and pre-concentration of thallium from the microwave assisted aqua regia extracts of sediment and coal fly ash samples. The method is based on the formation of extractable species of thallium and its interaction with hydrophobic solubilizing sites of Triton X-114 micelles in the presence of aqua regia and electrolyte NaCl. These interactions of micelles are used for extraction of thallium from a bulk aqueous phase into a small micelles-rich phase. The potential chloride interferences are eliminated effectively, which enabled interference free determination of thallium from aqua regia extracts using continuum source ETAAS. The parameters affecting the extraction process are optimized. Under the optimized conditions, pre-concentration factor and limit of detection are 40 and 0.2 ng g(-1), respectively. The recoveries are in the range of 95-102%. A characteristic mass, 13 pg was obtained. The accuracy of the method is verified by analyzing certified reference materials such as NIST 1633b coal fly ash, NIST 1944 marine sediment and GBW 07312 stream sediments. The results obtained are in good agreement with the certified values and method is also applied to real samples.


Automated processing of first-pass radionuclide angiocardiography by factor analysis of dynamic structures.
A method for automatic processing of cardiac first-pass radionuclide study is presented. This technique, factor analysis of dynamic structures (FADS) provides an automatic separation of anatomical structures according to their different temporal behaviour, even if they are superimposed. FADS has been applied to 76 studies. A description of factor patterns obtained in various pathological categories is presented. FADS provides easy diagnosis of shunts and tricuspid insufficiency. Quantitative information derived from the factors (cardiac output and mean transit time) were compared to those obtained by the region of interest method. Using FADS, a higher correlation with cardiac catheterization was found for cardiac output calculation. Thus compared to the ROI method, FADS presents obvious advantages: a good separation of overlapping cardiac chambers is obtained; this operator independant method provides more objective and reproducible results. A number of parameters of the cardio-pulmonary function can be assessed by first-pass radionuclide angiocardiography (RNA) [1,2]. Usually, they are calculated using time-activity curves (TAC) from regions of interest (ROI) drawn on the cardiac chambers and the lungs. This method has two main drawbacks: (1) the lack of inter and intra-observers reproducibility; (2) the problem of crosstalk which affects the evaluation of the cardio-pulmonary performance. The crosstalk on planar imaging is due to anatomical superimposition of the cardiac chambers and lungs. The activity measured in any ROI is the sum of the activity in several organs and 'decontamination' of the TAC cannot easily be performed using the ROI method [3]. Factor analysis of dynamic structures (FADS) [4,5] can solve the two problems mentioned above. It provides an automatic separation of anatomical structures according to their different temporal behaviour, even if they are superimposed. The resulting factors are estimates of the time evolution of the activity in each structure (underlying physiological components), and the associated factor images are estimates of the spatial distribution of each factor. The aim of this study was to assess the reliability of FADS in first pass RNA and compare the results to those obtained by the ROI method which is generally considered as the routine procedure.


Conditional learning and memory impairments following neurotoxic lesion of the CA1 field of the hippocampus.
Monkeys with bilateral lesions of the CA1 field of the hippocampus produced by the injection of neurotoxin diagonally along the length of the hippocampus were found to have a severe impairment on the retention of a conditional task learnt prior to surgery and on the new acquisition of several types of this task. They were equally impaired on conditional tasks that required a spatial response or an object choice in response to either visual or spatial cues. They were not impaired on simple visual discrimination tasks, simple spatial discrimination tasks or reversal learning of these tasks. This patterns of impairment resembles that seen in the same species with neurotoxic lesions within the vertical limb of the diagonal band of Broca or transection of the fornix. Monkeys with subtotal lesions of the adjacent medial temporal area were not consistently impaired on any of these tasks. The results suggest that hippocampal lesions produce anterograde and retrograde amnesia for information other than reward association.


Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases.
Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases.


[An isolated fetal kidney cyst as a sign of congenital neuroblastoma. A case report and overview of the literature].
As a normal scan at 20 weeks of gestation a pregnant woman was referred at 36 weeks because of a cystic tumour in the fetal kidney. The cyst, 27 mm in diameter, was localised at the cranial pole of the right kidney. A fetal neuroblastoma was suspected. At the fourth day after birth adrenalectomy was performed and the histological finding confirmed the prenatal diagnosis. Two years later the child is healthy. In review of the literature we found that sonographic pattern and localisation of fetal neuroblastoma are different, but in all cases the detection was performed in the third trimester of gestation.


A conceptual model to inform the design of healthcare simulations that promote errors as a catalyst for learning: A discussion paper.
Previous studies have demonstrated that students who are engaged in learning tasks and make errors before receiving instruction on how to complete them, achieve better learning outcomes than students who first receive instruction and then complete the learning activities with the aim of avoiding errors. Although simulation literature often refers to errors as learning opportunities, to date, there is limited understanding of how pedagogical approaches that promote learning from errors can guide the design of simulation-based learning in healthcare education. To (a) present the Learning from Errors conceptual model; and (b) provide an example of how educators can use this model. The Learning from Errors model is drawn from critical elements of two pedagogical approaches, productive failure and error management training and pedagogical features of high-quality healthcare simulations. We describe the Learning from Errors model, which emphasises the need for adopting pedagogical methods that explicitly use errors as learning opportunities and ultimately inform simulation design. We then illustrate the application of this model to a simulation example. The model includes the following elements: i) normalisation of errors, ii) challenging simulation scenarios, iii) self-directed learning, iv) collaborative teamwork and v) comparison with best practice. This discussion paper presents the Learning from Errors conceptual model, an evidence-based approach that can assist educators in the design of simulations that embrace errors as a catalyst for learning.


Molecular interactions of cord factor with dipalmitoylphosphatidylcholine monolayers: implications for lung surfactant dysfunction in pulmonary tuberculosis.
Molecular interactions between mycobacterial cell wall lipid, cord factor (CF) and the abundant surfactant lipid, dipalmitoylphosphatidylcholine (DPPC) were investigated using Langmuir monolayers at physiological temperatures (37 degrees C). Surface topography of the films was visualized by atomic force microscopy (AFM). Thermodynamic behavior of the mixed monolayers was evaluated by investigating the molecular area excess, excess Gibbs free energy of mixing and maximum compressibility modulus (SCM(max)). Cord factor formed immiscible and thermodynamically unstable monolayers with DPPC. Monolayer presence of cord factor altered the physical state of DPPC monolayers from liquid condensed to liquid expanded with the lowering of SCM(max) from 160 to 40 mN/m, respectively. AFM imaging exhibited smooth homogenous surface topography of DPPC films which in the presence of cord factor was markedly altered with the appearance of aggregates and increased surface roughness. The results highlight the capacity of cord factor to disturb DPPC monolayer organization and structure. Interfacial presence of cord factor results in DPPC monolayer fluidization. Lung surfactant function is attributed to its ability to form well packed low compressibility films. Such molecular interactions suggest a dysfunction of lung surfactant in pulmonary tuberculosis due to surfactant monolayer fluidization.


Govanosides C-F, unprecedented steroidal saponins with rare sugars from rhizomes of Trillium govanianum and their antagonistic effects on acetylcholinesterase.
Four previously undescribed steroidal saponins named govanosides C-F (1-4) and nine known compounds (5-13) were isolated from the rhizomes of Trillium govanianum Wall. ex D.Don. Govanosides C-E contained a rare sugar moiety i.e., 6-deoxy allose, while govanoside F has acetylated rhamnose moiety in its glycan part. Also, this is the first report on the isolation of feruloyl sucrose derivatives (11-12) and (E)-4-hydroxy-dodec-2-enedioic acid (13) from the Trillium genus. The structure of isolated compounds was deduced using 1D and 2D NMR, HRESIMS, LC-MS/MS, GC-MS, and saccharide linkage analysis. Steroidal scaffold isolates (1-10) were evaluated for their antagonistic effects on acetylcholinesterase inhibitory activity. Govanoside C (1) significantly inhibited acetylcholinesterase (IC50: 2.38 μM). Molecular docking experiments have also been performed to depict the molecule's interaction and binding free energy with acetylcholinesterase.


The superior colliculus simultaneously modifies the responses of the lateral geniculate cells and of the oculomotor nuclei.
Descending and ascending influences of the superior colliculus (CS) were studied in the following way. In anesthetized and paralyzed rabbits two tungsten micro-electrodes were lowered in the (CS) and the Lateral Geniculate Nucleus (LGN) for single unit recordings. A third semi-micro-electrode (dia. 100 microns) was positioned in the vicinity of the oculomotor nuclei. The final position of this electrode was determined at a location which yielded an eye movement with the lowest intensity of the electrical pulse. The typical experimental procedures required that a spontaneous collicular spike triggered the flash presentation and data acquisition. Results indicated that collicular endogeneous activity may be capable of modifying simultaneously the evoked neuronal responses of the LGN and in the vicinity of the oculomotor nuclei.


Cone beam computed tomography number errors and consequences for radiotherapy planning: an investigation of correction methods.
The potential of keV cone beam computed tomography (CBCT) for guiding adaptive replanning is well-known. There are impediments to this, one being CBCT number accuracy. The purpose of this study was to investigate CBCT number correction methods and the affect of residual inaccuracies on dose deposition. Four different correction strategies were applied to the same patient data to compare performance and the sophistication of correction-method needed for acceptable dose errors. Planning CT and CBCT reconstructions were used for 12 patients (6 brain, 3 prostate, and 3 bladder cancer patients). All patients were treated using Elekta linear accelerators and XVI imaging systems. Two of the CBCT number correction methods investigated were based on an algorithm previously proposed by the authors but only previously applied to phantoms. Two further methods, based on an approach previously suggested in the research literature, were also examined. Dose calculations were performed using scans of a "worst" subset of patients using the Pinnacle³ version 9.0 treatment planning system and the patients' clinical plans. All mean errors in CBCT number were <50 HU, and all correction methods performed well or adequately in dose calculations. The worst single dose discrepancy identified for any of the examined methods or patients was 3.0%. Mean errors in the doses to treatment volumes or organs at risk were negatively correlated with the mean error in CT number. That is, a mean CT number that was too large, averaged over the entire CBCT volume, implied an underdosing in a volume-of-interest and vice versa. Results suggest that (1) the correction of CBCT numbers to within a mean error of 50 HU in the scan volume provides acceptable discrepancies in dose (<3%) and (2) this is achievable with even quite unsophisticated correction methods.


Angiotensin-converting enzyme inhibitors after renal transplantation.
The blockade of the renin-angiotensin-aldosterone system may limit the progression of graft dysfunction in patients receiving kidney transplantations. We retrospectively evaluated the safety and efficacy of angiotensin-converting enzyme inhibitors (ACEI) in renal allograft recipients. Fifty-seven cadaveric kidney recipients (58% of recipients), were prescribed an ACEI (lisinopril). The indications for ACEI were isolated proteinuria (1 patient), erythrocytosis (6 patients), and arterial hypertension (50 patients). The choice of an ACEI for blood pressure control was due to presence of left ventricular hypertrophy (2 patients), mild proteinuria (4 patients), and high hemoglobin (4 patients). There was a significant reduction in the mean arterial pressure after 1 month (P = .0004) and 1 year (P = .0002) of therapy. Overall, the estimated glomerular filtrate rate (eGFR), calculated using the Cockcroft-Gault equation, remained unchanged. Among patients who had serum creatinine values above 2.0 mg/dL at the beginning of ACEI therapy, there was a significant rise in eGFR from 39.3 +/- 13.2 to 44.1 +/- 16.8 mL/min after 6 months (P = .01), and 43.3 +/- 17.3 mL/min after 1 year (P = .04). In patients with erythrocytosis, the hemoglobin showed a significant and sustained reduction after 1 month (P = .004) and 1 year (P = .001). Six patients suspended ACEI owing to adverse events: cough (n = 4), worsening of graft function (n = 1), and hypotension (n = 1). Six patients required erythropoiesis-stimulating agents. No patient suspended treatment owing to hyperkalemia. In conclusion, ACEI were well tolerated, safe, and effective antihypertensive agents in kidney graft recipients. They seemed to have some beneficial effect in preserving GFR in patients with worse graft function.


Hepatic microsomal activities of cholesterol 7 alpha-hydroxylase and 3-hydroxy-3-methylglutaryl-CoA reductase in the prairie dog. An animal model for cholesterol gallstone disease.
The prairie dog is a useful experimental animal model for studies of cholesterol gallstone pathogenesis. The unique susceptibility to rapid induction of gallstones solely by feeding of a 1.2% cholesterol diet in this species could result from low levels of hepatic cholesterol 7 alpha-hydroxylase. With optimal assay conditions in hepatic microsomes, a basal specific activity of about 25 pmol/min per g protein was found. Administration of diets containing 1.2% cholesterol or 5% cholestyramine caused hydroxylase levels to increase 60 and 250%, respectively. This response pattern is similar to that observed in other species under the same conditions, indicating that abnormally low basal or inappropriately unresponsive hydroxylase levels are not susceptibility factors unique to this model. With optimal assay conditions for hydroxymethylglutaryl-CoA reductase, a Km of 32.5 microM (S-HMG-CoA) and basal specific activities of between 60 and 175 pmol/min per mg protein were found. Following feeding of either sodium chenodeoxycholate or sodium cholate, in reasonable pharmacologic doses, no suppression of hydroxylase and reductase levels was found. These findings undermine the widely held view that the therapeutic effect of oral chenodeoxycholate in man for cholesterol gallstone dissolution is directly mediated by suppression of the activities of these enzymes.


Impact of the COVID-19 pandemic on severe non-SARS-CoV-2 community-acquired pneumonia in Reunion Island: a multicenter retrospective observational study, 2016-2021.
The Coronavirus 2019 (COVID-19) pandemic has had a considerable impact on the incidence of severe community-acquired pneumonia (CAP) worldwide. The aim of this study was to assess the early impact of the COVID-19 pandemic in the Reunion Island. This multicenter retrospective observational study was conducted from 2016 to 2021 in the hospitals of Reunion Island. The incidence of severe non-SARS-CoV-2 CAP, microorganisms, characteristics and outcomes of patients hospitalized in intensive care unit were compared between the pre-COVID-19 period (January 1, 2016 to February 29, 2020) and the early COVID-19 period (March 1, 2020 to October 31, 2021). Over the study period, 389 patients developed severe non-SARS-CoV-2 CAP. The incidence of severe non-SARS-CoV-2 CAP significantly decreased between the two periods (9.16 vs. 4.13 cases per 100,000 person-years). The influenza virus was isolated in 43.5% patients with severe non-SARS-CoV-2 CAP in the pre-COVID-19 period and in none of the 60 patients in the early COVID-19 period (P < 0.0001). The only virus that did not decrease was rhinovirus. Streptococcus pneumoniae was the most frequently isolated bacterial microorganism, with no significant difference between the two periods. In Reunion Island, the COVID-19 pandemic led to a significant decrease in the incidence of influenza, which likely explains the observed decrease in the incidence of severe non-SARS-CoV-2 CAP. The pandemic had no impact on the incidence of other viral and bacterial severe non-SARS-CoV-2 CAP. Monitoring influenza incidence is crucial now that COVID-19 control measures have been removed.


How do plants reprogramme the fate of differentiated cells?
Being able to change cell fate after differentiation highlights the remarkable developmental plasticity of plant cells. Recent studies show that phytohormones, such as auxin and cytokinin, promote cell cycle reactivation, a critical first step to reprogramme mitotically inactive, differentiated cells into organogenic stem cells. Accumulating evidence suggests that wounding provides an additional cue to convert the identity of differentiated cells by promoting the loss of existing cell fate and/or acquisition of new cell fate. Differentiated cells can also alter cell fate without undergoing cell division and in this case, wounding and phytohormones induce master regulators that can directly assign new cell fate.


Utilization of the halophytic shrubs Atriplex nummularia Lindl and Rhagodia preissii Moq as crops in salt-affected semi-arid regions: How temperature, salinity, seed weight and size affect seed germination.
The perennial halophytic shrubs Atriplex nummularia and Rhagodia preissii are native to Australia and can be planted on saline land to produce sheep and cattle feed during the autumn. However, an impediment to the adoption of the species on saline land has been the challenges in achieving successful establishment by direct seeding due to a lack of knowledge of the optimal conditions for germination. Therefore, the optimal germination requirements in relation to temperature, salinity level and seed size was assessed for each species to ascertain the optimal conditions for successful establishment by direct seeding on saline land. Seeds of both species showed optimal germination temperature at 10°C. Atriplex nummularia seeds were more tolerant to temperatures above or below 10°C than R. preissii. The germination percentage of A. nummularia was unchanged at 0-200 mM NaCl2. The germination percentage of Rhagodia preissii declined when the NaCl2 content exceeded 50 mM. There was no correlation between seed size, germination and emergence for any of the species. Based on the study, we suggest that sowing operations are performed during the cold winter months in subtropical areas or autumn and spring in temperate areas, to improve the successful establishment of these shrubs by direct seeding.


Thermodynamics of binding of cadmium to bovine serum albumin.
The binding isotherm of Cd2+ ion to bovine serum albumin (BSA) has been investigated by microcalorimetry at 310.15 K and pH 7.0. The thermodynamic parameters of the binding reaction have been determined, and the stoichiometry of the complex is 2:1, indicating that there exist two identical binding sites of BSA with Cd2+ ion. The value of deltarHthetam is -28.4+/-1.7 kJ mol(-1), the free energy of binding deltarGthetam is -25.2 kJ mol(-1), and the entropy of binding deltarSthetam is -10.3 J mol(-1) K(-1). The negative deltarHthetam and deltarSthetam values are observed for the binding reaction of Cd2+ ion and BSA, suggesting that the binding reaction is mainly enthalpy-driven and the entropy is unfavorable for it.


Coagulation defects in thalassemic patients.
Regular blood transfusion and compliance with iron chelation therapy has markedly improved life expectancy in thalassemia; however, this improvement is accompanied by several complications of this chronic disease including thromboembolic disorders. The objective of this work is to study natural coagulation inhibition as well as the fibrinolysis processes in thalassemic children who are otherwise in a steady state with no overt clinical manifestations of thromboembolism. In a case-control study design conducted at Sohag University Hospital, Sohag, Egypt, 50 thalassemic children and 20 age- and sex-matched healthy controls were compared as regards prothrombin concentration, international normalized ratio, partial thromboplastin time, protein C, protein S, antithrombin III, D-dimers, and thrombin activatable fibrinolysis inhibitor (TAFI). When compared to healthy controls, natural coagulation inhibitors (protein C, protein S, and antithrombin-III) were significantly lower in thalassemic children (p < 0.0001). While D-dimers showed a significant increase in thalassemic children, TAFI was significantly lower (p < 0.0001). Splenectomized thalassemic children showed significantly lower levels of protein C, protein S and TAFI (p < 0.001, p < 0.0001, p < 0.0001, respectively) when compared to nonsplenectomized thalassemic children. Significant changes in natural coagulation inhibition and fibrinolysis processes favoring thromboembolism can be detected in otherwise healthy thalassemic children. Because these changes are more pronounced in splenectomized patients, study of primary prophylactic strategies in this subgroup is warranted.


Copolymerization of Natural Camphor-Derived Rigid Diol with Various Dicarboxylic Acids: Access to Biobased Polyesters with Various Properties.
In this work, alicyclic (1R,3S)-1,2,2-trimethylcyclopentane-1,3-dimethanol (TCDM), derived from natural camphor, was copolymerized with linear α,ω-diacids, terephthalic acid (TPA), and 2,5-furandicarboxylic acid (FDCA), affording a series of polyesters with functional properties. 2D NMR spectroscopy revealed that the stereoconfiguration of TCDM was preserved after polymerization. The TCDM polyester based on TPA showed high thermostability, high Tg value (115 °C), high modulus (1.3 GPa), and high ultimate strength (29.8 MPa). The TCDM polyester based on 1,4-succinic acid exhibited excellent ductility and resilience. Lastly, the rigidity analysis based on van Krevelen's group contribution method, coupled with the comparisons between TCDM- and sugar-based polyesters, confirmed that TCDM is a highly reactive and rigid diol. Results indicate that TCDM polyesters are suitable for a wide range of applications, including hot-filled containers and transparent packaging materials. This work addresses some critical needs for high performance biopolymers such as achieving high Tg values, high thermostability, and high transparency.


Optical-Field-Driven Electron Tunneling in Metal-Insulator-Metal Nanojunction.
Optical-field driven electron tunneling in nanojunctions has made demonstrable progress toward the development of ultrafast charge transport devices at subfemtosecond time scales, and have evidenced great potential as a springboard technology for the next generation of on-chip "lightwave electronics." Here, the empirical findings on photocurrent the high nonlinearity in metal-insulator-metal (MIM) nanojunctions driven by ultrafast optical pulses in the strong optical-field regime are reported. In the present MIM device, a 14th power-law scaling is identified, never achieved before in any known solid-state device. This work lays important technological foundations for the development of a new generation of ultracompact and ultrafast electronics devices that operate with suboptical-cycle response times.


PROUD: effects of preoperative long-term immunonutrition in patients listed for liver transplantation.
Patients with end stage liver disease are characteristically malnourished which is associated with poor outcome. Formulas enriched with arginine, omega-3 fatty acids, and nucleotides, "immunonutrients", potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term "immunonutrition" of patients with end-stage liver disease while on the waiting list for liver transplantation. A randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long-term administration of ORAL IMPACT, an "immunonutrient" formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include improved patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intraabdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection), acute and chronic rejection, and mortality. Formulas enriched with arginine, omega-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect. ClinicalTrials.gov NCT00495859.


Early Assessment of Circumferential Anterior Segment Structures Following Implantable Collamer Lens V4c Implantation Via SS-OCT.
To explore early changes in circumferential anterior segment structures following Implantable Collamer Lens (ICL) V4c implantation via swept-source optical coherence tomography (SS-OCT). In 103 eyes of 56 myopic patients undergoing ICL V4c surgery, anterior segments were measured via SS-OCT to compute local anterior chamber angle (ACA) parameters on the nasal-temporal (0°-180°), superior-inferior (90°-270°), and superior nasal-inferior temporal (80°-260°) meridians, including angle-opening distance at 500 µm (AOD500), trabecular-iris space area at 500 µm (TISA500), trabecular-iris angle at 500 µm (TIA500), and circumferential ACA parameters, including AOD area at 500 µm (AODA500), trabecular-iris circumference volume at 500 µm (TICV500), and the index and area of iris-trabecular contact (ITC). ACA parameters were compared preoperatively and at 1 week, 1 month, and 3 months postoperatively and compared among quadrants. Mixed-effects model was used to evaluate the parameters correlated with the post-ITC parameters. The mean AOD500, TISA500, TIA500, AODA500, and TICV500 were decreased by 65.4% to 71%, 64.1% to 69.3%, 53.8% to 61.5%, 69.9%, and 69.2%, respectively, at 1 week postoperatively. The ITC index and area values rose from 1.436% ± 4.427% and 0.070 ± 0.254 mm2 to 12.343% ± 13.216% and 0.903 ± 1.304 mm2 (all P < 0.05). No further decreases in ACA parameters were observed beyond 1 week postoperatively (all P > 0.05). Significant differences were observed among quadrants, with the narrowest in the superior-nasal quadrant, followed by the superior quadrant. The 3-month vault was significantly correlated with the ITC index and area at 3 months postoperatively. Anterior segment structures were significantly shallow at 1 week with no further decreases thereafter. In light of anatomical variability, we recommend circumferential meridian scan to assess angle status, with special attention to the superior-nasal and superior quadrants. We investigated the early changes in circumferential anterior segment structures following ICL V4c implantation, thus providing a better perspective for understanding anterior segment structural characteristics after ICL V4c surgery.


Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3β pathway.
Approaches for controlling inflammatory responses and reducing the mortality rate of septic patients remain clinically ineffective; new drugs need to be identified that can induce anti-inflammatory responses. Ephedrine hydrochloride (EH) is a compound that is widely used in cardiovascular diseases, especially to treat hypotension caused by either anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of the inflammatory response. EH increased IL-10 and decreased proinflammatory cytokine (IL-6, tumor-necrosis factor (TNF)-α, IL-12 and IL-1β) expression in primary peritoneal macrophages and Raw264.7 cells treated with peptidoglycan (PGN), a Gram-positive cell wall component. The anti-inflammatory role of EH was also demonstrated in an experimental mouse model of peritonitis induced by intraperitoneal PGN injection. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway was found to be responsible for the EH-mediated increase in IL-10 production and decrease in IL-6 expression. Therefore, our results illustrated that EH can help maintain immune equilibrium and diminish host damage by balancing the production of pro- and anti-inflammatory cytokines after PGN challenge. EH may be a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection.


A new conditioning paradigm: conditioned limb movements in locomoting decerebrate ferrets.
These experiments address the hypothesis that the trajectory of a forelimb in decerebrate ambulating ferrets can be conditioned to avoid an obstacle encountered during the locomotor cycle. The perturbation was produced by interjecting a bar into the trajectory of the forelimb during swing phase. Over 5-15 steps the flexion of the elbow progressively increased until the forelimb was elevated over the bar. Avoiding the bar often required that the maximum height of the paw during swing phase was doubled. When the bar was no longer thrust into the trajectory of the forelimb, the conditioned behavior persisted for several step cycles. The results indicate that decerebrate ferrets are capable of acquiring a conditioned limb movement that is not a typical conditioned reflex but rather an accentuation of a component of the step cycle performed to avoid an interruption of swing phase.


9-phenyl acridine exhibits antitumour activity by inducing apoptosis in A375 cells.
Several acridine derivatives have been screened for their therapeutic potential and some are already established as antiprotozoan, antibacterial or anticancer agents. However, phenyl derivative at C-9 position of acridine had remained unexplored for their biological activity so far. In this report, we present our findings with 9-phenyl acridine (ACPH) as an anticancer agent. Both A375 and HeLa, two human cancer cell lines, were more sensitive to ACPH than normal cells namely human lymphocytes and also Chinese hamster V79 cells. ACPH also led to regression of tumour volume in mice. In A375 cells, we have shown that it caused DNA damage and blocked cell cycle progression at G(2)-M phase. Treatment with ACPH led to lowering of mitochondrial potential, upregulation of bax, release of cytochrome C and activation of caspase 3. As a new agent showing lower toxicity to normal cells and greater sensitivity towards cancerous cell line, ACPH shows promise as an effective cancer chemotherapeutic agent. ACPH treatment resulted in apoptotic death of cells through mitochondria-mediated caspase-dependent pathway.


A continuous information theoretic approach to the analysis of cutaneous receptor neurons.
Information theoretic and statistical techniques for determining the number of discernible levels in cutaneous receptor neurons are reviewed. Reasons for the large variance in these results are discussed. A new continuous information theoretic analysis technique is presented that overcomes many of the problems in the other methods of analysis discussed. Comparison of this new method of analysis with a statistical technique developed by Schreiner et al. (1978) clearly shows some of the misconceptions that are associated with statistical analysis techniques, and why these problems cannot arise in the new information theoretic technique discussed here.


Aspects of psychodynamic neuropsychiatry III: magic spells, the placebo effect, and neurobiology.
Through a case study, the importance of supporting the positive transference is stressed-from both a psychological and neurobiological perspective. The article argues that the neurobiology of expectation underlies transference. This neurobiology has been investigated particularly over the past several decades in work concerning the placebo effect. By understanding the neurobiology of expectation, one gains a better understanding of the neurobiology of the transference. This enables clinical predictions-and decisions-that are informed not just by the teachings of psychology but also by the science of biology.


5'isomiR-183-5p|+2 elicits tumor suppressor activity in a negative feedback loop with E2F1.
MicroRNAs (miRNAs) and isomiRs play important roles in tumorigenesis as essential regulators of gene expression. 5'isomiRs exhibit a shifted seed sequence compared to the canonical miRNA, resulting in different target spectra and thereby extending the phenotypic impact of the respective common pre-miRNA. However, for most miRNAs, expression and function of 5'isomiRs have not been studied in detail yet. Therefore, this study aims to investigate the functions of miRNAs and their 5'isomiRs. The expression of 5'isomiRs was assessed in The Cancer Genome Atlas (TCGA) breast cancer patient dataset. Phenotypic effects of miR-183 overexpression in triple-negative breast cancer (TNBC) cell lines were investigated in vitro and in vivo by quantifying migration, proliferation, tumor growth and metastasis. Direct targeting of E2F1 by miR-183-5p|+2 was validated with a 3'UTR luciferase assay and linked to the phenotypes of isomiR overexpression. TCGA breast cancer patient data indicated that three variants of miR-183-5p are highly expressed and upregulated, namely miR-183-5p|0, miR-183-5p|+1 and miR-183-5p|+2. However, TNBC cell lines displayed reduced proliferation and invasion upon overexpression of pre-miR-183. While invasion was reduced individually by all three isomiRs, proliferation and cell cycle progression were specifically inhibited by overexpression of miR-183-5p|+2. Proteomic analysis revealed reduced expression of E2F target genes upon overexpression of this isomiR, which could be attributed to direct targeting of E2F1, specifically by miR-183-5p|+2. Knockdown of E2F1 partially phenocopied the effect of miR-183-5p|+2 overexpression on cell proliferation and cell cycle. Gene set enrichment analysis of TCGA and METABRIC patient data indicated that the activity of E2F strongly correlated with the expression of miR-183-5p, suggesting transcriptional regulation of the miRNA by a factor of the E2F family. Indeed, in vitro, expression of miR-183-5p was regulated by E2F1. Hence, miR-183-5p|+2 directly targeting E2F1 appears to be part of a negative feedback loop potentially fine-tuning its activity. This study demonstrates that 5'isomiRs originating from the same arm of the same pre-miRNA (i.e. pre-miR-183-5p) may exhibit different functions and thereby collectively contribute to the same phenotype. Here, one of three isomiRs was shown to counteract expression of the pre-miRNA by negatively regulating a transcriptional activator (i.e. E2F1). We speculate that this might be part of a regulatory mechanism to prevent uncontrolled cell proliferation, which is disabled during cancer progression.


Enantioselective addition of arylboronic acids to methyl 2-formylbenzoates by using a ruthenium/Me-BIPAM catalyst for synthesis of chiral 3-aryl-isobenzofuranones.
Ruthenium/Me-BIPAM-catalyzed asymmetric addition of arylboronic acids to methyl 2-formylbenzoates afforded chiral 3-aryl-isobenzofuranones. [RuCl2(p-cymene)]2/Me-BIPAM and RuCl2(PPh3)3/Me-BIPAM catalyst systems tolerate a variety of functional groups and give high yields with high enantioselectivities.


Molecular basis of neurophysiological and antioxidant roles of Szechuan pepper.
The balance between anti- and pro-oxidant activities is of great important to maintain the biochemical and physiological homeostasis in the human body. Developing new therapeutic strategies to reduce health risks caused by free radicals has always been research focus over the past decades. Szechuan pepper, a characteristic pungent-flavored spice in Sichuanese cuisine, recently attracts the attention of researchers for its widespread therapeutic effects on acute and chronic diseases. The plant produces the innocuous 'tingling and numbing' sensations across the oral cavity by stirring specific neuron types, which are mechanically distinct from those excited by capsaicin. Furthermore, the extracts or the compounds of Szechuan pepper are biochemically proven to possess strong antioxidant activities that could scavenge free radicals and inhibit overactive peroxidase system in pathological models. Herein, the review emphasizes the molecular basis underlying the neurophysiological and antioxidant activities of the plant by a comprehensive analysis of various signaling pathways in disease models treated by Szechuan pepper. Further, we performed a broadening analysis to unearth potential signaling pathways associated with the antioxidant roles of the plant.


Carotid endarterectomy.
Although controversies still exist, recently reported trials have confirmed the efficacy of carotid endarterectomy and more clearly elucidated the appropriate indications for surgical therapy. The efforts to optimize outcomes for patients with carotid artery disease have expanded to the asymptomatic patient, the patient suffering from stroke, and the patient with coexistent cardiac symptoms.


Extensive small bowel necrosis due to congenital para duodenal hernia: A diagnostic and therapeutic challenge: Case Report.
A paraduodenal hernia is a rare variety of hernia, however it is the most usual type of internal hernias. Clinical presentation is nonspecific. The clinical presentation is variable: indeed, the patient can be completely asymptomatic or present with symptoms which severity is variable according to the mechanism. The most common cause is an acute intestinal occlusion that could progress even to ischemia and intestinal necrosis. Depending on the clinical presentation and the suspected diagnosis, computed tomography can be of considerable help in demonstrating a para duodenal hernia. We describe the case of a young man aged 18 years, who presented to the emergency unit with severe abdominal pain associated with incoercible vomiting. The surgical exploration had confirmed a para duodenal hernia responsible for an extensive necrosis of the small intestine allowing viable 90 cm only. Paraduodenal hernias are rare and their diagnosis is not always easy. Therefore, they should be considered especially in the case of an occlusive syndrome occurring in a young patient who has never been operated on. If no treatment is undertaken, the evolution is drastic and the mortality rate is significant. Successful surgical management requires knowledge of the intra-abdominal peritoneal spaces and management of suggestive clinical situations in order to reduce postoperative morbidity and mortality resulting from delayed diagnosis and treatment.


Glucose-1-phosphatase (AgpE) from Enterobacter cloacae displays enhanced phytase activity.
Using a screening procedure developed for detection of phytate hydrolysing enzymes, the gene agpE encoding glucose-1-phosphatase was cloned from an Enterobacter cloacae VKPM B2254 plasmid library. Sequence analysis revealed 78% identity on nucleotide and 79% identity on peptide level to Escherichia coli glucose-1-phosphatase characterising the respective gene product as a representative of acid histidine phosphatases harbouring the RH(G/N)RXRP motif. The purified recombinant protein displayed maximum specific activity of 196 U mg(-1) protein against glucose-1-phosphate but was also active against other sugar phosphates and p-nitrophenyl phosphate. High-performance ion chromatography of hydrolysis products revealed that AgpE can act as a 3-phytase but is only able to cleave off the third phosphate group from the myo-inositol sugar ring. Based on sequence comparison and catalytic behaviour against phytate, we propose to classify bacterial acid histidine phosphatases/phytases in the three following subclasses: (1) AppA-related phytases, (2) PhyK-related phytases and (3) Agp-related phytases. A distinguished activity of 32 U mg(-1) of protein towards myo-inositol-hexa-phosphate, which is two times higher than that of E. coli Agp, suggests that possibly functional differences in terms of phytase activity between Agp- and AppA-like acid histidine phosphatases are fluent.


Ovarian toxicity induced by dietary cadmium in hen.
To investigate the toxicity of cadmium (Cd) on female reproduction in birds, this study was conducted to determine the changes in biochemical parameters of serum and ovary tissue caused by dietary cadmium in hens. Ninety 50-day-old hyline white hens were randomly divided into three groups (30 hens per group): a control group was fed with basal diet, a low dose group was fed with basal diet containing 140 mg/kg CdCl(2) and a high dose group was fed with basal diet containing 210 mg/kg CdCl2. After being treated with Cd for 20, 40 and 60 days, ovary and serum samples were collected and examined for Cd content, histological evaluations, malondialdehyde (MDA) content, glutathione peroxidase (GPx) content, activities of superoxide dismutase (SOD), nitric oxide (NO) content, nitric oxide synthase (NOS) activity, and serum estradiol and progestogen levels. The results showed that the content of Cd, MDA, NO and the activity of NOS in ovary and serum were increased (P < 0.05), while the level of GPx and the activity of SOD were decreased (P < 0.05) in low dose and high dose groups. A time- and dose-dependent correlation was observed between serum and ovary tissue cadmium levels. The number of apoptotic cells in the ovary was increased in the Cd treatment group (P < 0.05). Extensive damage was observed in the ovary. The level of estradiol and progestogen in the serum of low dose and high dose groups was decreased significantly (P < 0.05). It indicated that Cd exposure resulted in oxidative damage of hens' ovary tissue by altering antioxidant defense enzyme systems, lipid peroxidation, apoptosis and endocrine disturbance which may be possible underlying reproductive toxicity mechanisms induced by Cd.


Risk factors for Alzheimer's disease during aging. Impacts of glucose/energy metabolism.
The majority of Alzheimer patients is of late onset and with unknown etiology. However, several risk factors have been discussed among which age is a most important one with respect to sporadic Alzheimer type dementia (SDAT). Age includes changes in brain glucose/energy metabolism, in both insulin and acetylcholine signal transduction and in membrane function to name the functionally most important ones. Variations in these parameters can form the basis for ongoing changes in terms of the principle of self-organized critically inducing catastrophic i.e. disease processes. Subsequent abnormalities at the cellular and molecular levels may develop including the formation of both amyloid plaques and neurofibrillary tangles.


Seasonal Patterns of Phytoplankton Taxon Richness in Lakes: Effects of Temperature, Turnover and Abundance.
Species richness is a key ecological characteristic that influences numerous ecosystem functions. Here we analyse the patterns and possible causes of phytoplankton taxon richness in seasonal datasets from twenty contrasting lakes in the English Lake District over six years and near-weekly datasets over 33 years from Windermere. Taxon richness was lowest in winter and highest in summer or autumn in all of the lakes. Observed richness was very similar to richness estimated from coverage and sampling effort, implying that it closely reflected true seasonal patterns. Summer populations were dominated by Chlorophyta and functional groups X1, F, N and P (sensu Reynolds). In Windermere, weekly taxon richness was strongly positively correlated with surface water temperature, as was the number of functional groups and the number of taxa per functional group. Turnover in richness of taxa and functional groups were positively correlated and both were related to surface temperature. This suggests that high taxon richness in summer is linked to higher water temperature, promoting a turnover in richness of taxa and functional groups in these lakes. However, since the number of taxa per unit concentration of chlorophyll a decreased with increasing concentration of chlorophyll a, competition might occur when abundance is high.


Revelation of ancestral roles of KNOX genes by a functional analysis of Physcomitrella homologues.
KNOX genes are indispensable elements of indeterminate apical growth programmes of vascular plant sporophytes. Since little is known about the roles of such genes in non-vascular plants, functional analysis of moss KNOX homologues (MKN genes) was undertaken using the genetically amenable model plant, Physcomitrella patens. Three MKN genes were inactivated by targeted gene knockout to produce single, double and triple mutants. MKN2 (a class 1 KNOX gene) mutants were characterised by premature sporogenesis, abnormal sporophyte ontogeny and irregular spore development. MKN4 (a second class 1 gene) mutants were phenotypically normal. MKN1-3 (a class 2 KNOX gene) mutants exhibited defects in spore coat morphology. Analysis of double and triple mutants revealed that the abnormal sporophytic phenotype of MKN2 mutants was accentuated by mutating MKN4 and to a lesser degree by mutating MKN1-3. The aberrant spore phenotype of MKN1-3 and MKN2 mutants was exacerbated by mutating MKN4. This study provides the first instance in which an abnormal phenotype has been associated with the disruption of a class 2 KNOX gene as well as the first demonstrated case of functional redundancy between a class 1 and a class 2 KNOX gene. We conclude that KNOX genes play significant roles in programming sporophytic development in moss and we provide evidence that ancestral function(s) of this gene family were instrumental in the successful transition of plants to a terrestrial environment.


High Spatial Resolution Imaging of Endogenous Hydrogen Peroxide in Living Cells by Solid-State Fluorescence.
Herein, we describe selective imaging of hydrogen peroxide using a precipitating dye conjugated to a boronic acid-based immolative linker. We achieved visualization of endogenous hydrogen peroxide in phagosomes by solid-state two-photon fluorescence imaging in living cells with exceptionally high spatial resolution.


Challenges in the diagnosis and management of acromegaly: a focus on comorbidities.
Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.


Initial Experience with Transradial Intraoperative Angiography in Aneurysm Clipping: Technique, Feasibility, and Case Series.
The transradial approach has slowly been gaining momentum in neuroendovascular procedures. We sought to assess its feasibility and safety and present a case series of transradial intraoperative angiography (IOA) during microsurgical clip ligation of intracranial aneurysms. The setup and technique for transradial intraoperative angiography are described. Data on 10 consecutive patients undergoing IOA through the radial artery are presented. All target vessels were successfully catheterized transradially, and conversion to the transfemoral access was not required in any of the cases. There was no access-site complication, such as hand ischemia, hematoma, or radial artery spasm. There were also no thromboembolic events causing a stroke. The average time for the IOA was 9.3 minutes. Our initial experience shows the transradial approach for IOA in clip ligation of aneurysms to be feasible and safe, with potential advantages over transfemoral IOA.


Association of Family History of Cancer with Clinical and Pathological Outcomes for Prostate Cancer Patients on Active Surveillance.
The impact of germline mutations associated with hereditary cancer syndromes in patients on active surveillance (AS) for prostate cancer is poorly defined. We examined the association between family history of prostate cancer (FHP) or family history of cancer (FHC) and risk of progression or adverse pathology at radical prostatectomy (RP) in patients on AS. Patients on AS at a single tertiary-care center between 2000-2019 were categorized by family history. Disease progression was defined as an increase in Gleason grade on biopsy. Adverse pathology was defined as upgrading/upstaging at RP. Multivariable Cox and logistic regression models were used to assess association between family history and time to progression or adverse pathology, respectively. Among 3,211 evaluable patients, 669 (21%) had FHP, 34 (1%) had FHC and 95 (3%) had both; 753 progressed on AS and 481 underwent RP. FHP was associated with increased risk of progression (HR 1.31; 95% CI, 1.11-1.55; p=0.002) but FHC (HR 0.67; 95% CI, 0.30-1.50; p=0.3) or family history of both (HR 1.22; 95% CI, 0.81-1.85; p=0.3) were not. FHP, FHC or both were not associated with adverse pathology at RP (p >0.4). While FHP was associated with an increased risk of progression on AS, wide confidence intervals render this outcome of unclear clinical significance. FHC was not associated with risk of progression on AS. In the absence of known genetically defined hereditary cancer syndrome, we suggest FHP and/or FHC should not be used as a sole trigger to preclude patients from enrolling on AS.


Resuscitative endovascular balloon occlusion of the aorta (REBOA) for temporization of hemorrhage in adolescent trauma patients.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged as an alternative technique for traumatic hemorrhage control in the adult population. The purpose of this study is to describe the details of REBOA placement in adolescent trauma patients. Patients 18 years of age or less who received REBOA for aortic occlusion (AO) from August 2013 to February 2017 at 2 urban tertiary care centers were included. 7 adolescent trauma patients received REBOA by trauma surgeons for both blunt (n = 4) and penetrating mechanisms (n = 3); mean age was 17 + 1.5 years, mean admission lactate 13.0 + 4.85 mmol/L, and mean Hgb 10.7 + 2.7 g/dL. 3 patients received REBOA through a 12Fr sheath and 4 through a 7Fr sheath. AO occurred mostly at the distal thoracic aorta (Zone I) (85.7%) and also in the distal abdominal aorta (Zone III) (14.3%). 57% of patients were in arrest with ongoing CPR at the time of REBOA. In-hospital mortality was 57%; all of these patients were in arrest at the time of REBOA, had return of spontaneous circulation (ROSC), and survived to the operating room. No complications from REBOA were identified. REBOA appears to be feasible for use in adolescents despite their smaller caliber vessels, even with use of a 12Fr sheath. REBOA results in improved physiology and can bridge adolescent trauma patients presenting in extremis to the operating room. Treatment/therapeutic study LEVEL OF EVIDENCE: Level IV.


Plasma membrane phosphoproteins in normal and Rous sarcoma virus transformed chick embryo fibroblasts: characterization by in vitro phosphorylation.
Plasma membranes isolated from normal and RSV transformed chick embryo fibroblasts were phosphorylated in vitro using endogenous protein kinase and ATP (gamma32P) and the labeled phosphoproteins were analyzed by SDS-PAGE. A number of protein phosphorylation changes were observed following transformation, however in most cases they were relatively small quantitative differences. The four major changes were in proteins of 47,000, 58,000, 75,000 and 135,000 daltons. Decreased phosphorylation of the 47,000 dalton polypeptide was found in transformed cell membranes but this alteration was shown to be due to differences in cell growth rather than transformation. Increase phosphorylation of the 75,000 dalton protein was at least partially related to virus infection. However, increased phosphorylation of the 58,000 and 135,000 dalton polypeptides were entirely transformation specific.


Characteristic fragmentations of nitroaromatic compounds (NACs) in Orbitrap HCD and integrated strategy for recognition of NACs in environmental samples.
Nitroaromatic compounds (NACs) are high of concern due to their mutagenicity, and carcinogenicity to organisms. Here, we attempted to establish a novel searching-validation-evaluation workflow that is tailored to recognize unknown NACs in environmental samples using liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (LC-Orbitrap-HRMS). We studied the fragmentation process of NAC standards in Orbitrap higher-energy collision dissociation (HCD) cells and observed that the mass loss of NO was the most prevalent among all NAC standards at both low and medium levels of collision energy. Thus, neutral loss of NO was considered as a diagnostic fragment of nitro groups and was used to screen out NACs in environmental samples. This technique is mass-loss-dependent, which enhances the recognition efficiency of NACs. Candidates exported from the PubChem compound database were further evaluated to obtain possible structures. This strategy was applied for the analysis of 24 surface soil, and we tentatively discovered two novel NACs in the analyzed samples. The semi-quantification results demonstrated that the concentrations of novel NACs were comparable to those of the ten targeted NACs in soil samples. This study provides an integrated strategy for the recognition of known and unknown NACs, which could be extended to other environmental matrices.


Histologic and ultrastructural study on statin graft in rabbit skulls.
To study the early healing pattern of statin-induced osteogenesis, we examined the early histologic and ultrastructural pictures of bone defect healing with and without statin. Twenty-eight bone defects were created in the parietal bone of 14 New Zealand White rabbits. In the Statin Group of 7 rabbits, the defects were grafted with collagen matrix carriers mixed with statin solution. In the Collagen Matrix Group of 7 rabbits, the defects were grafted with collagen matrix carriers mixed with water for injection. The Statin Group and the Collagen Matrix Group were killed on day 1, 2, 3, 4, 5, 6, or 14 after surgery. Bone defects with surrounding tissues were prepared for histologic assessment. Bone defects of day 14 were also prepared for ultrastructural assessment. New bone was formed on day 5 in the defects grafted with statin. No cartilage intermediate stage was detected. This occurred 1 day earlier than for those grafted with the carrier alone. The bone defects of day 14 showed that an abundance of bone was formed in the Statin Group and osteocytes were identified ultrastructurally. This study supported statin-induced and accelerated bone formation locally.


Reliability and validity of general health questionnaire (GHQ-12) for male tannery workers: a study carried out in Kanpur, India.
The purpose of this study was to test the reliability, validity and factor structure of GHQ-12 questionnaire on male tannery workers of India. We have tested three different factor models of the GHQ-12. This paper used primary data obtained from a cross-sectional household study of tannery workers from Jajmau area of the city of Kanpur in northern India, which was conducted during January-June, 2015, as part of a doctoral program. The study covered 286 tannery workers from the study area. An interview schedule containing GHQ-12 was used for tannery workers who had completed at least 1 year at their present occupation preceding the survey. To test reliability, Cronbach's alpha test was used. The convergent test was used for validity. Confirmatory factor analysis was used to compare three factor structures for the GHQ-12. A total of 286 samples were analyzed in this study. The mean age of the tannery workers in this study was 38 years (SD = 1.42). We found the alpha coefficient to be 0.93 for the complete sample. The value of alpha represents the acceptable internal consistency for all the groups. Each item of scale showed almost the same internal consistency of 0.93 for the male tannery workers. The correlation between factor 1 (Anxiety and Depression) and factor 2 (Social Dysfunction) was 0.92. The correlation between factor 1 (Anxiety and Depression) and factor 3 (Loss of confidence) was the highest 0.98. Comparative fit index (CFI) estimate best-fitted for model-III that gave the CFI value 0.97. The SRMR indicator gave the lowest value 0.031 for the model-III. The findings suggest that the Hindi version of GHQ-12 is a reliable and valid tool for measuring psychological distress in male tannery workers of Kanpur city, India. Study found that the model proposed by the Graetz was the best fitted model for the data.


[Complete popliteal artery rupture one month after arthroscopic partial meniscectomy].
A patient suffered a complete popliteal artery injury one month after a partial arthroscopic meniscectomy. The patient complained of progressive and severe distal pain. A complete lesion of the popliteal artery was found. Distal vascular flow was barely supported by two geniculate arteries. Vascular repair was performed using open vascular surgery. Although the popliteal neurovascular bundle is close to the posterior capsule of the knee and is obviously potentially vulnerable, injuries in arthroscopy of the knee are very rare. To avoid catastrophic consequences, the possibility of vascular injuries following arthroscopy of the knee, even several weeks after the surgery must not be ruled out.


Preparation and characterization of SNARE-containing nanodiscs and direct study of cargo release through fusion pores.
This protocol describes an assay that uses suspended nanomembranes called nanodiscs to analyze fusion events. A nanodisc is a lipid bilayer wrapped by membrane scaffold proteins. Fluorescent lipids and a protein that is part of a fusion machinery, VAMP2 in the example detailed herein, are included in the nanodiscs. Upon fusion of a nanodisc with a nonfluorescent liposome containing cognate proteins (for instance, the VAMP2 cognate syntaxin1/SNAP-25 complex), the fluorescent lipids are dispersed in the liposome and the increase in fluorescence, initially quenched in the nanodisc, is monitored on a plate reader. Because the scaffold proteins restrain pore expansion, the fusion pore eventually reseals. A reducing agent, such as dithionite, which can quench the fluorescence of accessible lipids, can then be used to determine the number of fusion events. A fluorescence-based approach can also be used to monitor the release of encapsulated cargo. From data on the total cargo release and the number of the much faster lipid-mixing events, the researcher may determine the amount of cargo released per fusion event. This assay requires 3 d for preparation and 4 h for data acquisition and analysis.


The nature of the neutral Na+-Cl(-)-coupled entry at the apical membrane of rabbit gallbladder epithelium: II. Na+-Cl- symport is independent of K+.
In the epithelium of rabbit gallbladder, in the nominal absence of bicarbonate, intracellular Cl- activity is about 25 mM, about 4 times higher than intracellular Cl- activity at the electrochemical equilibrium. It is essentially not affected by 10(-4) M acetazolamide and 10(-4) M 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS) even during prolonged exposures: it falls to the equilibrium value by removal of Na+ from the lumen without significant changes of the apical membrane potential difference. Both intracellular Cl- and Na+ activities are decreased by luminal treatment with 25 mM SCN-; the initial rates of change are not significantly different. In addition, the initial rates of change of intracellular Cl- activity are not significantly different upon Na+ or Cl- entry block by the appropriate reduction of the concentration of either ion in the luminal solution. Luminal K+ removal or 10(-5) M bumetanide do not affect intracellular Cl- and Na+ activities or Cl- influx through the apical membrane. It is concluded that in the absence of bicarbonate NaCl entry is entirely due to a Na+-Cl- symport on a single carrier which, at least under the conditions tested, does not cotransport K+.


Mutational analysis of the WASP gene in 2 Korean families with Wiskott-Aldrich syndrome.
Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by thrombocytopenia with undersized platelets, eczema, and immune deficiency, is caused by mutations in the WASP gene. In this study, we investigated WASP gene mutations and WASP protein expression in 2 unrelated Korean WAS patients. Flow cytometry was used to evaluate WASP expression in lymphocytes. Two previously reported nonsense mutations (Arg211stop and Arg13stop) were identified in this study, a finding that suggested these codons are mutational hotspots. Both mothers showed normal WASP expression in flow cytometric analysis, even though they had heterozygotic patterning, which is indicative of carrier status. Furthermore, an X-chromosome inactivation assay revealed that these carrier mothers had skewed X inactivation. To our knowledge, this is the first report on molecular diagnosis of WAS in Korea. In addition, we detected normal WASP expression in lymphocytes from carrier mothers, a finding consistent with the data on skewed X inactivation.


Laparoscopic resection of solitary adrenal metastasis from lung carcinoma: a case report.
Patients with adrenal metastases from bronchogenic carcinoma are considered incurable and any surgical treatment is usually excluded. A review of the few cases of adrenalectomy for metastases from lung cancer that have been reported in the literature shows that good results can be achieved in selected patients. We propose a laparoscopic approach to perform the adrenalectomy in these patients. A right laparoscopic adrenalectomy for metastasis from lung adenocarcinoma was performed. The right adrenal was resected using the anterior transperitoneal laparoscopic approach. The tumor was resected in total. The operating time was two hours. One year after surgery the patient remains well. The current indications for laparoscopic adrenalectomy can include the removal of small metastatic adrenal lesions in selected cases.


Biofeedback treatment of atopic dermatitis: controlled case studies of eight cases.
To investigate the feasibility of a behaviorally oriented intervention program with atopic dermatitis, 12 patients were exposed to a fixed sequence of treatment phases including a no-treatment baseline phase, a phase incorporating nonspecific treatment factors, and a phase involving frontal electromyographic (EMG) feedback and relaxation instructions. Photographic analyses of involved skin areas revealed significant remission of dermatological problems across the entire program, although significant changes could not be attributable to any specific phase. Ratings of itching level decreased within but not across treatment sessions, and variable correlations across subjects were found between frontal EMG and itching level. MMPI results from the dermatitis subjects were within normal limits. Overall, the results provided mixed support for the hypothesis that atopic dermatitis may be amenable to intervention through behaviorally oriented treatment procedures.


P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells.
Our previous study demonstrated that extracellular adenosine 5'-triphosphate (ATP) stimulated prostate cancer cell invasion via P2Y receptors. However, the purinergic receptor subtype(s) involved in this process remains unclear. Here we aimed to determine whether P2Y2, one subtype of P2Y receptors, was involved in the invasion and metastasis of prostate cancer cells, and elucidated the underlying mechanism. RNAi was introduced to silence the expression of P2Y2. In vitro invasion and migration assays and in vivo experiments were carried out to examine the role of P2Y2 receptor in cell invasion and metastasis. cDNA microarray was performed to identify the differentially expressed genes downstream of ATP treatment. P2Y2 was significantly expressed in the prostate cancer cells. Knockdown of P2Y2 receptor suppressed cell invasion and metastasis in vitro and in vivo. Further experiments identified that ATP could promote IL-8 and Snail expression and inhibit E-cadherin and Claudin-1 expression. Knockdown of P2Y2 receptor affected the expression of these EMT/invasion-related genes in vitro and in vivo. P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells via some EMT/invasion-related genes. Thereby, P2Y2 receptor could be a potential therapeutic target for the treatment of prostate cancer.


Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients.
Elevated plasma vasopressin concentrations have been documented in antipsychotic drug-treated patients as well as a drug-free acutely psychotic patients. To evaluate the effects of antipsychotic drugs on plasma vasopressin, we measured vasopressin response to a single dose of intramuscular chlorpromazine or intravenous haloperidol in normal individuals and to 2 weeks of oral antipsychotics in patients with acute schizophrenia. Neither intramuscular chlorpromazine nor intravenous haloperidol affected plasma vasopressin in normals, except in one subject who developed high plasma vasopressin concentrations coincident with marked hypotension following chlorpromazine. Prior to antipsychotics, two acute schizophrenia patients had elevated plasma vasopressin concentrations, which normalized during antipsychotic drug treatment. We conclude that antipsychotics do not directly stimulate vasopressin release, but may indirectly stimulate vasopressin release by well-described baroreceptor reflex mechanisms if hypotension occurs. Also, acute schizophrenia may be associated with increased plasma vasopressin levels in some patients.


Mechanobiological simulations of peri-acetabular bone ingrowth: a comparative analysis of cell-phenotype specific and phenomenological algorithms.
Several mechanobiology algorithms have been employed to simulate bone ingrowth around porous coated implants. However, there is a scarcity of quantitative comparison between the efficacies of commonly used mechanoregulatory algorithms. The objectives of this study are: (1) to predict peri-acetabular bone ingrowth using cell-phenotype specific algorithm and to compare these predictions with those obtained using phenomenological algorithm and (2) to investigate the influences of cellular parameters on bone ingrowth. The variation in host bone material property and interfacial micromotion of the implanted pelvis were mapped onto the microscale model of implant-bone interface. An overall variation of 17-88 % in peri-acetabular bone ingrowth was observed. Despite differences in predicted tissue differentiation patterns during the initial period, both the algorithms predicted similar spatial distribution of neo-tissue layer, after attainment of equilibrium. Results indicated that phenomenological algorithm, being computationally faster than the cell-phenotype specific algorithm, might be used to predict peri-prosthetic bone ingrowth. The cell-phenotype specific algorithm, however, was found to be useful in numerically investigating the influence of alterations in cellular activities on bone ingrowth, owing to biologically related factors. Amongst the host of cellular activities, matrix production rate of bone tissue was found to have predominant influence on peri-acetabular bone ingrowth.


[Changes in the size of the nuclei of adrenal cortex cells of rats after repeated physical stress].
Nuclear volumes of cells in rat adrenal cortex were measured. The rats were forced to swim during one month for 3 hours a day. During the experiment, the extension of nuclear hypetrophy in the external zona fasciculata underwent some phasic changes, phases being as follows: 1) increase in hypertrophy up to the maximum (2nd and 5th days of experiment); 2) the stability of hypertrophy close to the maximum (12th, 18th and 24th days), and the decrease in hypertrophy (30th day). The phases are assumed to correspond, respectively, to stages of alarm reaction, resistance and exhaustion caused by chronic stress. The increased nuclear volume of cells was also observed in the internal zona fasciculata. The discrepancy between nuclear volumes of zona reficularis in the experiment and in the control was statistically insignificant.


The interactions in the carboxyl terminus of human 4-hydroxyphenylpyruvate dioxygenase are critical to mediate the conformation of the final helix and the tail to shield the active site for catalysis.
4-Hydroxylphenylpyruvate dioxygenase (4-HPPD) is an important enzyme for tyrosine catabolism, which catalyzes the conversion of 4-hydroxylphenylpyruvate (4-HPP) to homogentisate. In the present study, human 4-HPPD was cloned and expressed in E. coli. The kinetic parameters for 4-HPP conversion were: k cat=2.2 ± 0.1 s(-1); and K m=0.08 ± 0.02 mM. Sequence alignments show that human 4-HPPD possesses an extended C-terminus compared to other 4-HPPD enzymes. Successive truncation of the disordered tail which follows the final α-helix resulted in no changes in the K m value for 4-HPP substrate but the k cat values were significantly reduced. The results suggest that this disordered C-terminal tail plays an important role in catalysis. For inspection the effect of terminal truncation on protein structure, mutant models were built. These models suggest that the different conformation of E254, R378 and Q375 in the final helix might be the cause of the activity loss. In the structure E254 interacts with R378, the end residue in the final helix; mutation of either one of these residues causes a ca. 95% reductions in k cat values. Q375 provides bifurcate interactions to fix the tail and the final helix in position. The model of the Q375N mutant shows that a solvent accessible channel opens to the putative substrate binding site, suggesting this is responsible for the complete loss of activity. These results highlight the critical role of Q375 in orientating the tail and ensuring the conformation of the terminal α-helix to maintain the integrity of the active site for catalysis.


Comparative evaluation of magnetic hyperthermia performance and biocompatibility of magnetite and novel Fe-doped hardystonite nanoparticles for potential bone cancer therapy.
Hyperthermia-increasing temperature of cancerous tissue for a short period of time-is considered as an effective treatment for various cancer types such as malignant bone tumors. Superparamagnetic and ferromagnetic particles have been studied for their hyperthermic properties in treating various types of cancers. The activation of magnetic nanoparticles by an alternating magnetic field is currently being explored as a technique for targeted therapeutic heating of different tumors and is being studied as an adjuvant to conventional chemotherapy and radiation therapy. In the case of bone cancers, to increase the efficiency of treatment in the hyperthermia therapy, employed materials should support bone regeneration as well. Magnetite is one of the most attractive magnetic nanoceramics used in hyperthermia application. However, biocompatibility and bioactivity of this material have raised questions. There is a high demand for extremely efficient hyperthermia materials which are equally biocompatible to non-tumor cells and tissues. We report the development of a biocompatible and bioactive material with desirable magnetic properties that show excellent hyperthermia properties and can be used for destruction of the cancerous tissue in addition to supporting tissue regeneration for treatment of bone tumors. In the current study, iron (Fe3+)-containing HT nanostructured material was prepared, and its biocompatibility, bioactivity, and hyperthermia abilities were studied. The developed materials showed effective hyperthermic properties with increased biocompatibility as compared to magnetite.


Location of Usual Source of Care among Children and Adolescents in the United States, 1997-2013.
To examine national trends in the percentage of children whose usual source of care is at a clinic, health center, or hospital outpatient department (hereafter "clinics") and whether trends differ by sociodemographic subpopulations. Analysis of serial, cross-sectional, nationally representative in-person household surveys, the 1997-2013 National Health Interview Surveys, was conducted to identify children with a usual source of care (n = 190,571), and the percentage receiving that care in a clinic. We used joinpoint regression to identify changes in linear trends, and logistic regression with predictive margins to obtain per-year changes in percentages, both unadjusted and adjusted for sociodemographic factors. Interaction terms in logistic regressions were used to assess whether trends varied by sociodemographic subgroups. Of all children with a usual source of care, the percentage receiving that care in a clinic declined 0.44 percentage points per year (P < .001) from 22.97% in 1997 to 19.31% in 2002. Thereafter, it increased approximately 0.57 percentage points per year (P < .001), reaching 26.1% in 2013. Trends for some sociodemographic subgroups varied from these overall trends. No changes were observed between 2003 and 2013 for non-Hispanic black and Medicaid/State Children's Health Insurance Program insured children. This study shows that, although the percentage of children with a usual source of care in a clinic declined between 1997 and 2002, it has steadily increased since that time.


Mutually Reinforced Polymer-Graphene Bilayer Membranes for Energy-Efficient Acoustic Transduction.
Graphene holds promise for thin, ultralightweight, and high-performance nanoelectromechanical transducers. However, graphene-only devices are limited in size due to fatigue and fracture of suspended graphene membranes. Here, a lightweight, flexible, transparent, and conductive bilayer composite of polyetherimide and single-layer graphene is prepared and suspended on the centimeter scale with an unprecedentedly high aspect ratio of 105 . The coupling of the two components leads to mutual reinforcement and creates an ultrastrong membrane that supports 30 000 times its own weight. Upon electromechanical actuation, the membrane pushes a massive amount of air and generates high-quality acoustic sound. The energy efficiency is ≈10-100 times better than state-of-the-art electrodynamic speakers. The bilayer membrane's combined properties of electrical conductivity, mechanical strength, optical transparency, thermal stability, and chemical resistance will promote applications in electronics, mechanics, and optics.


Skin cancer knowledge and prevention practices among Turkish bus drivers.
To determine skin cancer knowledge levels and prevention practices among bus drivers. The cross sectional study was conducted in Aydin province, western Turkey, from April to June 2018, and comprised bus drivers who came to the primary health centre. Data was collected using a predesigned questionnaire based on sociodemographic characteristics and the Skin Cancer and Sun Knowledge Scale. Data was analysed using SPSS 16. There were 125 male bus drivers with a mean age of 42.0±9.1 years. There was a significant relationship between history of skin cancer in the family and the presence of freckles (p<0.05). Those who were exposed to the sun for one or two hours a day scored higher on the knowledge scale than those with a sun exposure of >2 hours a day (p<0.05). The bus drivers did not have enough knowledge about the critical significance of skin cancer.


Purification of hepoxilin epoxide hydrolase from rat liver.
Hepoxilin epoxide hydrolase activity was demonstrated in rat liver cytosol using as substrate [1-14C] hepoxilin A3, a recently described hydroxy epoxide derivative of arachidonic acid. The enzyme was isolated and purified to apparent homogeneity using conventional chromatographic procedures resulting in 41-fold purification. The protein eluted during isoelectric focusing at a pI in the 5.3-5.4 range. The specific activity of the purified protein was 1.2 ng/microgram protein/20 min at 37 degrees C. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under denaturing conditions, a molecular mass value of 53 kDa was observed. Using native polyacrylamide gel electrophoresis, enzyme activity corresponded to the main protein band. The purified protein used hepoxilin A3 as preferred substrate converting it to trioxilin A3. The enzyme was marginally active toward other epoxides such as leukotriene A4 and styrene oxide. The Mr, pI, and substrate specificity of the hepoxilin epoxide hydrolase indicate that this enzyme is different from the recently reported leukotriene A4 hydrolase from human erythrocytes and rat and human neutrophils and constitutes a hitherto undescribed form of epoxide hydrolase with specificity toward hepoxilin A3. Tissue screening for enzyme activity revealed that this enzyme is ubiquitous in the rat.


Overexpressed MALAT1 promotes invasion and metastasis of gastric cancer cells via increasing EGFL7 expression.
Long non-coding RNAs (lncRNAs) have been demonstrated to participate in various cancers. Here, the role and its potential mechanism of MALAT1 in invasion and migration of gastric cancer (GC) were investigated. Gastric adenocarcinoma tissues and matched normal adjacent tissues were isolated from 25 patients with GC. The expression of epidermal growth factor-like domain-containing protein 7 (EGFL7) was detected in the normal gastric mucosa epithelial GES-1 cell line and three different differentiation GC cell lines, including MKN28 (well-differentiated adenocarcinoma), SGC7901 (moderately differentiated adenocarcinoma) and BGC823 (poorly differentiated adenocarcinoma). Tumor xenotransplant mouse model was established with the injection of cell line pretreated with lentiviral vectors for si-MALAT1 or si-control. The expression of MALAT1 was up-regulated in GC tissues and three cell lines. Si-MALAT1/pcDNA-MALAT1 induced the decrease of cell invasion and migration, while the effects were reversed by the transfection of pcDNA-EGFL7/si-EGFL7. ChIP assay showed that MALAT1 regulated EGFL7 expression by altering the level of H3 histone acetylation in EGFL7 promoter. In tumor xenotransplant mice, down-regulated MALAT1 contributed to the inhibition of tumor metastasis. Up-regulated MALAT1 promoted the invasion and metastasis of GC, and the increase of EGFL7 expression was a potential mechanism via altering its H3 histone acetylation level.


Active right atrial emptying fraction predicts reduced survival and increased adverse events in childhood pulmonary arterial hypertension.
Right atrial (RA) function has been studied rarely in childhood pulmonary arterial hypertension (PAH). We sought to determine if RA and right ventricular (RV) area changes measured by echocardiography predicted outcomes. We reviewed data from children with PAH undergoing cardiac catheterization and echocardiography. RA and RV areas were obtained from the apical 4-chamber view. Clinical worsening indicated initiation of parenteral prostanoid therapy, heart and/or lung transplantation, Potts shunt surgery or death. We studied 57 children (27 females), median age 3 years (range 0.30-17 years), body surface area 0.56 m2 (0.2-1.8), follow up 3 years (0.21-8.35), time to clinical worsening was 1.14 years (0.03-6.14) and mortality was 1.55 years (range 0.88-4.95). We determined from receiver operator curves that RA active emptying fraction (RA EaF) ≥60% predicted clinical worsening (sensitivity 78%, specificity 69%, AUC 0.7) and mortality (sensitivity 100%, specificity 65%, AUC 0.82). RV fractional area change (RVFAC) <25% predicted clinical worsening (sensitivity 72%, specificity 79%, AUC 0.85) and death (sensitivity 67%, specificity 69%, AUC 0.77). The combination of RA EaF ≥60% and RVFAC <33% were best predictors of clinical worsening (sensitivity 72%, specificity 82%, partial AUC 0.65) and mortality (sensitivity 100%, specificity 77%, partial AUC 0.75). In childhood PAH, RA EaF ≥ 60% and RVFAC <25% were associated with poor outcomes. RA EaF ≥60% and RVFAC <33% were best predictors of clinical worsening and may be useful markers in children with PAH who require closer observation and more intensive therapy.


Presence of aflatoxins in hazelnut paste in Turkey and a risk assessment study.
Two hundred and two hazelnut paste samples from various hazelnut processing plants in the Black Sea Region of Turkey were analysed for the incidence of aflatoxins (AFs) by liquid chromatography coupled with fluorescence detection (LC-FLD). All 202 (100%) hazelnut paste samples were contaminated with various AFs ranged from 0.17 to 12.96 µg kg-1. AF contamination level of four (1.98%) samples exceeded legal limits. Risk assessment for hazelnut paste was determined by using AF incidence results, and the margin of exposure (MOE) and hepatocellular carcinoma (HCC) risk approach were applied. For the adult Turkish population (15+ years age group), the average lower bound (LB) and upper bound (UB) exposure levels for aflatoxin B1 (AFB1) and total aflatoxins (AFT) were 0.0106-0.0107 ng kg-1 body weight (bw) per day and 0.0250 ng kg-1 bw per day, respectively. MOE estimates for mean and 95th percentile exposures to AFB1 for hazelnut paste were higher than 10,000, which indicates no potential health concern for Turkish adults. HCC for the Turkish population was 0.00023 cases per 100,000 people per year. The study indicates that Turkish population is not under this toxicological risk when consuming hazelnut paste containing food products.


Has the incidence of primary gastric lymphoma increased?
Various reports from the surgical and gastroenterologic literature have stated that the incidence of primary gastric lymphoma has increased. Other reports have claimed that this is a relative increase or represents referral center bias. The current study was designed to determine if the incidence of primary gastric lymphoma has increased in the community hospital setting. A total of 147 cases of gastric neoplasms were reviewed over a 10-year study period. The cases were divided into two 5-year periods, i.e., 1978-82 and 1983-87. There were two new cases (2.8%) of primary gastric lymphoma in the period 1978-82 and 11 new cases (19%) in the period 1983-87. The difference in proportion of primary gastric lymphoma between these two time periods was statistically significant (P = 0.01 by chi-square analysis). This increased incidence of primary gastric lymphoma is difficult to explain, but it must be recognized by surgeons and endoscopists.


Relationship and distribution of Salmonella enterica serovar I 4,[5],12:i:- strain sequences in the NCBI Pathogen Detection database.
Of the > 2600 Salmonella serovars, Salmonella enterica serovar I 4,[5],12:i:- (serovar I 4,[5],12:i:-) has emerged as one of the most common causes of human salmonellosis and the most frequent multidrug-resistant (MDR; resistance to ≥3 antimicrobial classes) nontyphoidal Salmonella serovar in the U.S. Serovar I 4,[5],12:i:- isolates have been described globally with resistance to ampicillin, streptomycin, sulfisoxazole, and tetracycline (R-type ASSuT) and an integrative and conjugative element with multi-metal tolerance named Salmonella Genomic Island 4 (SGI-4). We analyzed 13,612 serovar I 4,[5],12:i:- strain sequences available in the NCBI Pathogen Detection database to determine global distribution, animal sources, presence of SGI-4, occurrence of R-type ASSuT, frequency of antimicrobial resistance (AMR), and potential transmission clusters. Genome sequences for serovar I 4,[5],12:i:- strains represented 30 countries from 5 continents (North America, Europe, Asia, Oceania, and South America), but sequences from the United States (59%) and the United Kingdom (28%) were dominant. The metal tolerance island SGI-4 and the R-type ASSuT were present in 71 and 55% of serovar I 4,[5],12:i:- strain sequences, respectively. Sixty-five percent of strain sequences were MDR which correlates to serovar I 4,[5],12:i:- being the most frequent MDR serovar. The distribution of serovar I 4,[5],12:i:- strain sequences in the NCBI Pathogen Detection database suggests that swine-associated strain sequences were the most frequent food-animal source and were significantly more likely to contain the metal tolerance island SGI-4 and genes for MDR compared to all other animal-associated isolate sequences. Our study illustrates how analysis of genomic sequences from the NCBI Pathogen Detection database can be utilized to identify the prevalence of genetic features such as antimicrobial resistance, metal tolerance, and virulence genes that may be responsible for the successful emergence of bacterial foodborne pathogens.


Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.
Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.


Caruifolin D from artemisia absinthium L. inhibits neuroinflammation via reactive oxygen species-dependent c-jun N-terminal kinase and protein kinase c/NF-κB signaling pathways.
This work aims to evaluate the anti-neuroinflammatory effects of natural sesquiterpene dimer caruifolin D from Artemisia absinthium L., which is an edible vegetable or traditional medicinal food in East Asia due to its sedation, anti-asthma and antipruritic effects. In this study, we reported that caruifolin D significantly inhibited the productions of various neuroinflammatory mediators from microglia in response to bacterial lipopolysaccharide stimulation. Moreover, anti-inflammatory mechanism study showed that caruifolin D markedly suppressed the production of intracellular reactive oxygen species, which was an important player involved in neuroinflammation, leading to inhibitory effects on the activations of protein kinase C (PKC) and c-Jun N-terminal kinase (JNK), which were two major neuroinflammatory signaling pathways in the brains. Furthermore, caruifolin D protected neurons against microglia-mediated neuronal inflammatory damages by up-regulating neuronal viability and maintaining healthy neuronal morphology. Taken together, these results expanded our knowledge about the anti-neuroinflammatory and neuroprotective mechanism of Artemisia absinthium L., and also suggested that caruifolin D was a major anti-inflammatory component from Artemisia absinthium L., which might be developed as a drug candidate for neuroinflammation-related diseases.


Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor.
The primary structures of two types of bovine brain substance P precursors have been determined. One precursor contains a sequence homologous to that of the amphibian peptide kassinin. This new tachykinin sequence is bounded by paired basic amino acids Lys-Arg, which suggests that, like substance P, it can be liberated from the precursor and may serve as an endogenous hormone or neuromediator in mammalian organisms.