Force dependent internalization of magnetic nanoparticles results in highly loaded endothelial cells for use as potential therapy delivery vectors.
To investigate the kinetics, mechanism and extent of MNP loading into endothelial cells and the effect of this loading on cell function. MNP uptake was examined under field on/off conditions, utilizing varying magnetite concentration MNPs. MNP-loaded cell viability and functional integrity was assessed using metabolic respiration, cell proliferation and migration assays. MNP uptake in endothelial cells significantly increased under the influence of a magnetic field versus non-magnetic conditions. Larger magnetite density of the MNPs led to a higher MNP internalization by cells under application of a magnetic field without compromising cellular respiration activity. Two-dimensional migration assays at no field showed that higher magnetite loading resulted in greater cell migration rates. In a three-dimensional migration assay under magnetic field, the migration rate of MNP-loaded cells was more than twice that of unloaded cells and was comparable to migration stimulated by a serum gradient. Our results suggest that endothelial cell uptake of MNPs is a force dependent process. The in vitro assays determined that cell health is not adversely affected by high MNP loadings, allowing these highly magnetically responsive cells to be potentially beneficial therapy (gene, drug or cell) delivery systems.


A microcomputer-based sleep system: data acquisition and system calibration programs.
A data acquisition program is described for the Apple II series of microcomputers that allows for continuous, direct monitoring of electrographic elements from cortical, hippocampal and muscle leads from rats. The program detects cortical delta waves and sigma activity, hippocampal theta activity and electromyographic activity. The detected elements are counted and stored in memory at 15 second intervals (bins). Every three hours, the data are transferred to disks for permanent storage and off-line analysis.


Dose Addition in the Induction of Craniofacial Malformations in Zebrafish Embryos Exposed to a Complex Mixture of Food-Relevant Chemicals with Dissimilar Modes of Action.
Humans are exposed to combinations of chemicals. In cumulative risk assessment (CRA), regulatory bodies such as the European Food Safety Authority consider dose addition as a default and sufficiently conservative approach. The principle of dose addition was confirmed previously for inducing craniofacial malformations in zebrafish embryos in binary mixtures of chemicals with either similar or dissimilar modes of action (MOAs). In this study, we explored a workflow to select and experimentally test multiple compounds as a complex mixture with each of the compounds at or below its no observed adverse effect level (NOAEL), in the same zebrafish embryo model. Selection of candidate compounds that potentially induce craniofacial malformations was done using in silico methods-structural similarity, molecular docking, and quantitative structure-activity relationships-applied to a database of chemicals relevant for oral exposure in humans via food (EuroMix inventory, n=1,598). A final subselection was made manually to represent different regulatory fields (e.g., food additives, industrial chemicals, plant protection products), different chemical families, and different MOAs. A final selection of eight compounds was examined in the zebrafish embryo model, and craniofacial malformations were observed in embryos exposed to each of the compounds, thus confirming the developmental toxicity as predicted by the in silico methods. When exposed to a mixture of the eight compounds, each at its NOAEL, substantial craniofacial malformations were observed; according to a dose-response analysis, even embryos exposed to a 7-fold dilution of this mixture still exhibited a slight abnormal phenotype. The cumulative effect of the compounds in the mixture was in accordance with dose addition (added doses of the individual compounds after adjustment for relative potencies), despite different MOAs of the compounds involved. This case study of a complex mixture inducing craniofacial malformations in zebrafish embryos shows that dose addition can adequately predicted the cumulative effect of a mixture of multiple substances at low doses, irrespective of the (expected) MOA. The applied workflow may be useful as an approach for CRA in general. https://doi.org/10.1289/EHP9888.


Integrative Functional Genomics for Systems Genetics in GeneWeaver.org.
The abundance of existing functional genomics studies permits an integrative approach to interpreting and resolving the results of diverse systems genetics studies. However, a major challenge lies in assembling and harmonizing heterogeneous data sets across species for facile comparison to the positional candidate genes and coexpression networks that come from systems genetic studies. GeneWeaver is an online database and suite of tools at www.geneweaver.org that allows for fast aggregation and analysis of gene set-centric data. GeneWeaver contains curated experimental data together with resource-level data such as GO annotations, MP annotations, and KEGG pathways, along with persistent stores of user entered data sets. These can be entered directly into GeneWeaver or transferred from widely used resources such as GeneNetwork.org. Data are analyzed using statistical tools and advanced graph algorithms to discover new relations, prioritize candidate genes, and generate function hypotheses. Here we use GeneWeaver to find genes common to multiple gene sets, prioritize candidate genes from a quantitative trait locus, and characterize a set of differentially expressed genes. Coupling a large multispecies repository curated and empirical functional genomics data to fast computational tools allows for the rapid integrative analysis of heterogeneous data for interpreting and extrapolating systems genetics results.


Distinct oncogenic phenotypes in hematopoietic specific deletions of Trp53.
Loss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. In order to dissect the role of P53 in the hematopoietic system, we generated and analyzed two different mouse models deficient for P53. A pan-hematopoietic P53 deletion mouse was created using Vav1-Cre based deletion; and a B-cell-specific deletion mouse was created using a CD19-Cre based deletion. The Vav1-P53CKO mice predominantly developed T-cell malignancies in younger mice, and myeloid malignancies in older mice. In T-cell malignancies, there was accelerated thymic cell maturation with overexpression of Notch1 and its downstream effectors. CD19-P53CKO mice developed marginal zone expansion in the spleen, followed by marginal zone lymphoma, some of which progressed to diffuse large B-cell lymphomas. Interestingly, marginal zone and diffuse large B-cell lymphomas had a unique gene expression signature characterized by activation of the PI3K pathway, compared with wild type marginal zone or follicular cells of the spleen. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.


Immunomodulatory and Antioxidant Potential of Biogenic Functionalized Polymeric Nutmeg Oil/Polyurethane/ZnO Bionanocomposite.
The current study is focused on the biosynthesis of nutmeg oil/ polyurethane/ZnONPs bionanocomposite film for immunomodulatory and antioxidant activities. The fabricated film was prepared by using naturally extracted nutmeg oil functionalized with ZnONPs in the presence of polyutherane (PU) medium. The bionanocomposite film was obtained by incorporating dropwise 10 % (w/v) of nutmeg oil to the PU solution/ZnONPs blend. The active constituents of nutmeg oil were determined by gas chromatography coupled with mass spectrometry (GC-MS). The morphological characteristics of the resulting bionanocomposite film were confirmed using various microscopic and spectroscopic methods. Immunomodulatory potential of bionanocomposite was evaluated for RAW 264.7 macrophages. The results exhibited an excellent reduction in inflammatory cytokines (IL-6, IL-10, and TNFα) secretions after the treatment with bionanocomposite. The bionanocomposite exerted the highest inhibitory effects on certain cell signaling constituents that influence the initiation of expression of proinflammatory cytokines. The bionanocomposite was also tested for DPPH and ABTS free radicals scavenging assays and showed excellent antioxidant potential with IC50 values (0.28 ± 0.22 and 0.49 ± 0.36), respectively. The outcomes suggested promising immunomodulatory and antioxidant potentials for the biogenic synthesized nutmeg oil/PU/ZnONPs polymeric bionanocomposite.


Thermophilin 110: a bacteriocin of Streptococcus thermophilus ST110.
A screen of thermophilic lactic acid bacteria identified Streptococcus thermophilus strain ST110 as the putative producer of a bacteriocin with high level of activity against pediococci. Thermophilin 110 was isolated from culture supernatant after 16 h of growth and partially purified by a chloroform extraction procedure. The bacteriocin inhibited the growth of several lactic acid bacteria and in the case of Pediococcus acidilactici, it induced cell lysis with the concomitant release of OD260-absorbing material and intracellular enzymes. SDS-PAGE analysis revealed two components with estimated sizes between 4.0 kDa and 4.5 kDa, respectively, with possible involvement in bacteriocin activity as indicated by agar overlay assays with P. acidilactici as the target organism. Thermophilin 110 was inactivated by several proteolytic enzymes and also by alpha-amylase, which indicated the putative requirement of a glycosidic component for activity. The bacteriocin produced by S. thermophilus may be especially useful in the food processing industries to control spoilage caused by pediococci.


Gene cloning and functional analysis of glycosaminoglycan-degrading enzyme chondroitin AC lyase from Flavobacterium columnare G4.
The chondroitin AC lyase gene, cslA, was cloned for the first time from the fish bacterial pathogen F. columnare G4. From the first transcription initiation site, the cslA extends 2620 nucleotides to the end of the 3' region. The open reading frame of cslA transcript has 2286 nucleotides encoding 762 amino acids with a 16 residues long signal peptide at the N-terminus. The gene, cslA was then successfully expressed in Escherichia coli and recombinant chondroitin AC lyase, rChonAC was purified, with its lytic activity analyzed. Zymography analysis copolymerized with chondroitin sulphate revealed the lytic activity of rChonAC and also the crude native ChonAC isolated from periplamic space of cultured F. columnare G4. The low level of lytic activity observed in crude native ChonAC may be due possibly to the low level of expression of this gene in the cultured condition. The expression and the role of this virulence factor is of interest for further research on the pathogenesis of F. columnare.


A claim for cognitive history.
History is a potential tool for cognitive scientists interested in metacognitive categories like "creativity" and "innovation." As a way of thinking, history suggests alternative accounts of the development of innovation and growth, for example. Life History Theory is one such account, but its roots in the Industrial Revolution make it a problematic tool for telling the history of that period.


Molecular properties and In silico bioactivity evaluation of (4-fluorophenyl)[5)-3-phen-(4-nitrophenyl yl-4,5-dihydro-1H-pyrazol-1-yl]methanone derivatives: DFT and molecular docking approaches.
Molecular structures, spectroscopic properties, charge distributions, frontier orbital energies, nonlinear optical (NLO) properties and molecular docking simulations were analyzed to examine the bio-usefulness of a series of (4-fluorophenyl)[5-(4-nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]methanone derivatives. The compounds were studied through computational methods. Equilibrium optimization of the compounds was performed at the B3LYP/6-31G(d,p) level of theory, and geometric parameters, frequency vibration, UV-vis spectroscopy and reactivity properties were predicted on the basis of density functional theory (DFT) calculations. The energy gap (ΔEg), electron donating/accepting power (ω-/ω+) and electron density response toward electrophiles/nucleophiles calculated for M1 and M2 revealed the importance of substituent positioning on compound chemical behavior. In addition, ω-/ω+ and ΔEn/ΔEe indicated that M6 is more electrophilic because of the presence of two NO2 groups, which enhanced its NLO properties. The hyperpolarizability (β0) of the compounds ranged from 5.21 × 10-30 to 7.26 × 10-30 esu and was greater than that of urea; thus, M1-M6 were considered possible candidates for NLO applications. Docking simulation was also performed on the studied compounds and targets (PDB ID: 5ADH and 1RO6), and the calculated binding affinity and non-bonding interactions are reported. The calculated ω- and ω+ indicated the electrophilic nature of the compounds; M6, a compound with two NO2 groups, showed enhanced effects. Molecular electrostatic potential (MEP) analysis indicated that amide and nitro groups on the compounds were centers of electrophilic attacks. The magnitude of the molecular hyperpolarizability suggested that the entire compound had good NLO properties and therefore could be explored as a candidate NLO material. The docking results indicated that these compounds have excellent antioxidant and anti-inflammatory properties.


Evaluating the accumulated dose distribution of organs at risk in combined radiotherapy for cervical carcinoma based on deformable image registration.
To evaluate the feasibility and value of deformable image registration (DIR) in calculating the cumulative doses of organs at risk (OARs) in the combined radiotherapy of cervical cancer. Thirty cervical cancer patients treated with external beam radiotherapy (EBRT) combined with intracavitary brachytherapy (ICBT) were reviewed. The simulation CT images of EBRT and ICBT were imported into Varian Velocity 4.1 for the DIR-based dose accumulation. Cumulative dose-volume parameters of D2cc for rectum and bladder were compared between the direct addition (DA) and DIR methods. The quantitative parameters were measured to evaluate the accuracy of DIR. The three-dimensional cumulative dose distribution of the tumor and OARs were graphically well illustrated by composite isodose lines. In combined EBRT and ICBT, the mean cumulative bladder D2cc calculated by DIR and DA was 86.13 Gy and 86.27 Gy, respectively. The mean cumulative rectal D2cc calculated by DIR and DA was 72.97 Gy and 73.90 Gy, respectively. No significant differences were noted between these two methods (p > 0.05). As to the parameters used to evaluate the DIR accuracy, the mean DSC, Jacobian, MDA (mm) and Hausdorff distance (mm) were 0.79, 1.0, 3.84, and 22.01 respectively for the bladder and 0.53, 1.2, 7.31, and 29.58 respectively for the rectum. In this study, the DSC seemed to be slightly lower compared with previous studies. Dose accumulation based on DIR might be an alternative method to illustrate and evaluate the cumulative doses of the OARs in combined radiotherapy for cervical cancer. However, DIR should be used with caution before overcoming the relevant limitations.


Superior Laryngeal Nerve Block in Transcutaneous Vocal Fold Injection: A Pilot Study.
Topical lidocaine remains the mainstay for anesthesia in transcutaneous vocal fold injection (VFI). While using topical lidocaine, laryngologists sometimes encounter uncontrolled reflexes or poor compliance. Superior laryngeal nerve block (SLNB) provides deep and rapid anesthesia on the larynx above the vocal folds and abolishes the glottic closure reflex. Herein, we present a pilot study to evaluate the feasibility and safety of SLNB for transcutaneous VFI and explored its usefulness. Fifty-nine patients were prospectively anesthetized with SLNB during transcutaneous VFI for unilateral vocal fold paralysis. In the SLNB group, 0.5 to 1 mL of 2% lidocaine was infiltrated on bilateral SLNs through the thyrohyoid membrane. As the control group, we included previous 47 patients who underwent VFI with topical lidocaine. In the control group, 10% lidocaine spray was applied to the laryngopharyngeal mucosa. Demographic data, laryngeal exposure, patient compliance, procedural interruption, and complications were investigated. Patient compliance was evaluated based on the frequency of cough and swallowing during VFI procedures. SLNB enabled endoscopic contact on the epiglottis and pharyngeal wall without gag reflex and provided good exposure of the procedure field on the vocal folds. In the SLNB group, the laryngeal exposure is significantly better than in the control (P = 0.005). The frequency of cough and swallowing was significantly lower in the SLNB group than in the control (P < 0.001). The number of procedural interruptions was lower in the SLNB group than in the control (P < 0.001). There was no acute or delayed complication related to SLNB such as bleeding, hematoma, delayed sensory/swallowing problems, or unscheduled hospital visits. SLNB might be safe and effective for anesthesia in transcutaneous VFI. SLNB could be a good anesthetic option for patients with poor compliance despite the sufficient application of topical lidocaine.


Lung cancer surgical treatment after solid organ transplantation: A single center 30-year experience.
Solid organ transplantation is an accepted treatment for end-stage organ failure. Long-lasting immunosuppressive therapy may increase the risk ofde novo malignancies in transplant recipients. Increased risk of bronchogenic carcinoma in this population is controversial but prolonged transplant recipients' survival (obtained in modern transplantation era) may increase the need for lung cancer surgical resection in immunosuppressed patients. Our aim was to assess morbidity, mortality and long-term survival after lung cancer surgical treatment in this population. In an observational study, the medical charts of all consecutive patients who had undergone surgical treatment for lung cancer after solid organ transplantation were reviewed. These medical records were extracted from the University of Lyon (France) Transplantation database and Thoracic Surgery database. From 1986-2016, 61 patients underwent a surgical treatment for lung cancer after solid organ transplantation. The surgical procedures consisted of 52 lobectomies, 7 pneumonectomies and 2 wedge-resections. 90-day post-operative complications, most of which were pneumonias, affected 31 patients (50.8 %). 90-day postoperative mortality was 9.8 %. Overall survival was 40.6 % at 5 years and 18 % at 10 years. Despite a higher rate of infectious complications and 90-day postoperative mortality, surgical treatment for lung cancer must be offered to these patients as it offers a chance to cure earlier- stage disease. Long-term survival rate is satisfactory and similar to that of the general population. In transplant recipients with former smoking history, close follow-up is mandatory to increase early lung cancer diagnosis.


Visualization of electrical field of electrode using voltage-controlled fluorescence release.
In this study we propose an approach to directly visualize electrical current distribution at the electrode-electrolyte interface of a biopotential electrode. High-speed fluorescent microscopic images are acquired when an electric potential is applied across the interface to trigger the release of fluorescent material from the surface of the electrode. These images are analyzed computationally to obtain the distribution of the electric field from the fluorescent intensity of each pixel. Our approach allows direct observation of microscopic electrical current distribution around the electrode. Experiments are conducted to validate the feasibility of the fluorescent imaging method.


Ultrastructure of the venous ampulla in the interradicular microvascular bed of the mandibular molars of Mus musculus.
The interradicular periodontal ligament of mandibular molars contains an apparently unique dilated vessel straddling the interradicular alveolar bone. This structure is designated a venous ampulla. The vessel possesses a luminal length and width of approximately 200 X 100 microns, respectively. Ultrastructurally, the endothelium has an average thickness of 0.35 micron, a continuous basement membrane, and an incomplete layer of pericytes. Open endothelial junctions are not present. The anatomy of the vessel wall differs markedly on the dental- and bone-related aspects. Calculated ratios for the luminal diameter to wall thickness vary from 1:80 to 1:150. Postcapillary-sized limbs from this vessel drain into the interradicular septum of bone and the ligament microvascular bed. Arterial supply to the ampulla is provided via arteriovenous anastomoses characterized by their association with myelinated and unmyelinated nerve groups. Oxytalan fibers are present throughout the wall of the venous ampulla, penetrating to the abluminal side of the endothelium where they are associated with unmyelinated axons and free nerve endings. Elsewhere, oxytalan fibers are related to the arteriovenous anastomoses and their accompanying myelinated and unmyelinated nerves located adjacent to the endothelium. Pericytes form membranous contacts with the endothelium of the arteriovenous anastomoses and have processes penetrating the endothelium basement membrane.


Aggregate analysis based on TCGA: TTN missense mutation correlates with favorable prognosis in lung squamous cell carcinoma.
Lung cancer prevalence with its high mortality rate is a trending topic globally. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The human gene TTN encoding for TITIN protein is known as major mutation gene in many types of tumor including NSCLC. However, it is still controversial that TTN is a cancer-associated candidate considering tumor heterogeneity and complex genetic structure. In-depth researches on correlation between TTN mutation and NSCLC are still limited and discussable. Related somatic mutation profiles and attached clinical data were from The Cancer Genome Atlas (TCGA) lung project. Clinical relevance analysis of TTN mutation was evaluated using univariate analysis and a binary logistic regressive model. Survival analysis and screening of independent prognostic factors in mutation types were conducted by Cox proportional hazards models and Kaplan-Meier methods. Available data covering lung adenocarcinoma (n = 517) and lung squamous cell carcinoma (n = 492) were analyzed. TTN genetic mutations exhibited significant association with lung squamous cell carcinoma. Patients with lung squamous cell carcinoma possessed favorable overall survival benefits from TTN mutant type and both favorable overall survival and disease-free survival benefits from TTN/TP53 double mutation. For patients with lung squamous cell carcinoma, about 85% of subjects with TTN mutation harbored missense variations, which was an independent indicator of good prognosis. Missense mutation of TTN may act as a beneficial role in lung squamous cell carcinoma, but not in lung adenocarcinoma.


Acid-base regulation of ion transport in rabbit ileum in vitro.
Changes in acid-base balance have a major influence on ion transport in the ileum. The goals of the present study were to delineate (a) the specific transport processes most affected by changes in acid-base metabolism, (b) the individual roles of pH, PCO2, and concentration of HCO3- in modulating ion transport, and (c) the relationship between acid-base sensitive and other ion-transport systems. Ion transport and electrical parameters were measured in rabbit ilea in vitro under short-circuit conditions with systematic variations of pH, PCO2, and concentrations of HCO3-. Increasing HCO3- concentrations, with constant PCO2 and increasing pH, caused a decrease in electroneutral Na+ and Cl- absorption. At 5 mmol/L HCO3-, net fluxes of Na+ and Cl- were 5.9 +/- 1.4 and 4.5 +/- 1.1 microEq.cm-2.h-1, while at 50 mmol/L HCO3-, net Na+ and Cl- fluxes were 0.7 +/- 0.7 and 0.2 +/- 0.6 microEq.cm-2.h-1. Transepithelial HCO3(-)-gradient experiments suggested that serosal HCO3- was the principal factor. Changes in PCO2 showed a complex biphasic response, increasing net Cl- flux as PCO2 increased from 11-30 mm Hg in 5 mmol/L HCO3-; net Na+ flux increased as PCO2 was changed from 36 to greater than 100 mm Hg in 22 mmol/L HCO3-. In contrast, increasing pH in a bicarbonate-free N-2-hydroxyethylpiperazine-N'-2 = ethane sulfonic acid buffer did not significantly alter Na+ transport. Acid-base stimulated Na+ absorption was inhibited by 10(-3) mol/L amiloride, but not by bumetanide, consistent with the involvement of Na(+)-H+ exchange rather than Na(+)-Cl- cotransport. Epinephrine did not increase Na+ absorption under acid-base stimulated conditions, but glucose did, suggesting that the rate-limiting step for electroneutral absorptive processes under these conditions occurs at the apical rather than the basolateral membrane. Combining all experiments, a significant correlation existed between net flux of Na+ and HCO3- concentration (r = -0.72, P less than 0.05) and between net flux of Na+ and pH (r = -0.68, P less than 0.01). Chloride absorption was correlated with pH (r = 0.72, P less than 0.01). These results suggest a profound regulatory role for acid-base balance in electroneutral Na(+)-Cl- transport in rabbit ileum in vitro.


Specific Anatomic Transcriptomes Drive Oncogenesis in Melanoma.
Positional identity is crucial for determining the specificity of oncogenes in melanoma subtypes.


Studies on the Ni-content of the centriole.
Nickel-containing organelles or subcellular structures have not yet been described in the literature; only some Ni-containing enzymes or "factors" acting at the cellular level have been studied. In the present study the nickel-content of centrioles and basal bodies were detected by using a new histochemical method. The centrioles and basal bodies are able to take up nickel. Evidence has also been presented that low concentrations of Ni (10(-5) M) enhance the growth rate of Tetrahymena.


The impact of generalized joint hypermobility on eating behavior of students: A case-control study.
To investigate the impact of generalized joint hypermobility (GJH) on eating behavior. Physical therapy and rehabilitation students. The Beighton evaluation (a cutoff of 5/9) for defining GJH. The Eating Attitudes Test (EAT-40) was used for eating disorders. Smoking habits and alcohol use were also questioned. Compared with 51 non-GJH students (mean age 20.5 years, 73% female), 46 students with asymptomatic GJH (20.6 years, 89% female) were more likely to have greater median EAT-40 scores (9 vs. 6, p = .002). There was no statistically significant difference between the groups in terms of the susceptibility to eating behavior disorders (6.5% vs. 2.0%), smoking habits (6.5% vs. 9.8%), and alcohol use (15.2% vs. 11.8%) (p > .05). Positive correlation (r = .221, p = .029) and positive effect (R = 0.221, R2 = 0.049; p < .05) between Beighton scores and EAT-40 scores were found. The more joint hypermobility the greater the risk for eating disorders.


Correlation of subjective pain experience with cerebral evoked responses to noxious thermal stimulations.
The relationships between different parameters of the evoked cerebral response to noxious thermal stimulation, stimulus intensity, and subjective pain were investigated in seven normal human volunteers. The evoked response was characterized by late events: a small negative peak at 164--180 ms, followed by a high amplitude positive peak at 372--391 ms. The only correlation found in this study was between the amplitude of the positive component and the qualitative and quantitative aspects of the verbal report of pain. This was manifested by a linear trend of association: an increase in the evoked response amplitude was accompanied by an increase in the magnitude of the subjective sensation. The findings suggest that the evoked response to noxious heat reflects not a mere transduction of the physical parameters of the stimulus, but rather a complex interpretative action at the cerebral level.


Use of a bupivacaine continuous wound infusion system in gynecologic oncology: a randomized trial.
The aim of the current study was to evaluate the safety and efficacy of a widely available bupivacaine continuous wound infusion system in gynecologic oncology patients undergoing laparotomy. A prospective, randomized, double-blind, placebo-controlled trial was performed. After closure of the fascia, flexible soaker catheters were placed in the deep subcutaneous space. The infusion pump was filled with 290 mL of either 0.5% bupivacaine or normal saline, to infuse over 72 hours. Daily assessments of pain scores utilized the Wisconsin Brief Pain Inventory. All patients received intravenous narcotics via patient-controlled devices. Eighty surgeries were evaluated in a total of 79 women (40 per arm). Mean age was 56 years, with 79% having invasive gynecologic pathology. The two groups were not significantly different in terms of type of surgery, length of incision, estimated blood loss, operative time, or medical history. Postoperative outcomes, including wound toxicity, time to flatus, and hospital stay, did not differ. Study patients averaged 75 mg intravenously and 107 mg total narcotic use (morphine equivalent), whereas controls averaged 60 mg intravenously and 86 mg total (P = .40 intravenously; P = .25 total). Acetaminophen and intravenous ketorolac consumption were equal between groups. The Brief Pain Inventory score for "current pain" was 2.84 for bupivacaine patients and 3.14 for controls (P = .46; least = 0, most = 10). There was no individual postoperative day when "current pain" BPI scores differed. "Worst pain" and "least pain" Brief Pain Inventory scores showed similar results. The results suggest that although the continuous infusion system seems safe, it is not efficacious in this patient population.


[Clinical treatment of small bowel diverticula: review of 32 cases].
To retrospectively summarize the pathological features and management of small bowel diverticula of in 32 cases. Complications of small bowel diverticula were effectively treated surgically with good short-term and long-term clinical outcomes. The diverticulum found during the abdominal operation should be treated in time. The complications from the small intestine diverticulum included inflammation, bleeding, stone, perforation and bowel obstruction which arised from the stagnation, impaction, and friction of the contents in the diverticulum or from adhesion zone of long diveritculum. The complications were closely related to the histology of diverticular wall, the type of heterotopic tissue of diverticular mucosa, morphology of the diverticulum and contents in the diverticulum. The complications of small bowel diverticulum are the rare cause of acute abdomen which would be surgically treated effectively.


Cytofluorescence localization of propidium iodide injected intravenously into the nervous system of the mouse.
Propidium iodide, like its analogue ethidium bromide, is a compound which can be used as a marker of nucleic acids. This substance emits a red fluorescent light after exposure to UV light and has therefore been used previously as a nuclear stain in immunofluorescence studies and in flow cytometry. The present experiments were carried out to find out if propidium iodide could be traced in sections of the nervous system after i.v. injections. Due to the general toxicity of the compound detectable amounts of propidium iodide could not be obtained by a single i.v. injection. However, multiple injections of small amounts (0.1 mg) over a period from 15 min to 8 h (total dose 0.7-1.0 mg) were tolerated without any signs of adverse effects. In such experiments propidium iodide did not extravasate into the cerebral gray or white matter, i.e., areas of the brain located within the blood-brain barrier (BBB). On the other hand, the compound spread into the choroid plexus, the circumventricular organs, the Gasserian ganglion, and sciatic nerve, i.e., regions located outside the BBB. It had a strong tendency to label the nucleus and the perikaryon of the cells in each of these territories. Perifascicular injection of propidium iodide around the sciatic nerve was followed by a marked cellular uptake not only in the epineurium but also in the endoneurium. The shape and position of the labeled nuclei strongly indicated that they were the nuclei of Schwann cells. Previous studies have shown that propidium iodide can be used as a retrograde tracer in neuroanatomic research.(ABSTRACT TRUNCATED AT 250 WORDS)


The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism.
The 1 microgram ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 microgram ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease. A prospective analysis of the performance of the 1 microgram ACTH stimulation test in a group of patients with pituitary disease. The cortisol response to 1 microgram ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11-deoxycortisol response to overnight metyrapone: normal (11-deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11-deoxycortisol < 200 nmol/l). In both controls and patients, blood was sampled for cortisol at - 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 microgram synthetic ACTH (Synacthen(R)). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11-deoxycortisol. The 65 patients with pituitary disease were categorized according to the 11-deoxycortisol response to metyrapone as follows: 53 normal (11-deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 microg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut-off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%. The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test, like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH deficiency.


Organocatalytic Enantioselective Intramolecular Michael Addition by In Situ Generated Aminoisobenzofulvenes: Construction of Spiro Quaternary Carbon Stereocenters.
An unprecedented enantioselective organocatalytic spirocyclization strategy is presented by in situ generation of aminoisobezofulvenes. The reaction sequence involves a reductive Michael/aldol-condensation/Michael addition cascade by iminium-enamine catalysis. The key success of this spirocyclization was the formation of intermediatory nucleophilic aminoisobenzofuvenes accountable for intramolecular Michael addition. Benzospirononanes featuring an all carbon qauternary spirocenter were obtained using proline-derived amino-organocatalyst in moderate to good yields and excellent diastereo- and enantioselectivities (up to >20 : 1 dr, and 99 % ee). Post-methodological manipulation of benzospirononanes was also demonstrated.


The influence of healthcare financing on cardiovascular disease prevention in people living with HIV.
People living with HIV are diagnosed with age-related chronic health conditions, including cardiovascular disease, at higher than expected rates. Medical management of these chronic health conditions frequently occur in HIV specialty clinics by providers trained in general internal medicine, family medicine, or infectious disease. In recent years, changes in the healthcare financing for people living with HIV in the U.S. has been dynamic due to changes in the Affordable Care Act. There is little evidence examining how healthcare financing characteristics shape primary and secondary cardiovascular disease prevention among people living with HIV. Our objective was to examine the perspectives of people living with HIV and their healthcare providers on how healthcare financing influences cardiovascular disease prevention. As part of the EXTRA-CVD study, we conducted in-depth, semi-structured interviews with 51 people living with HIV and 34 multidisciplinary healthcare providers and at three U.S. HIV clinics in Ohio and North Carolina from October 2018 to March 2019. Thematic analysis using Template Analysis techniques was used to examine healthcare financing barriers and enablers of cardiovascular disease prevention in people living with HIV. Three themes emerged across sites and disciplines (1): healthcare payers substantially shape preventative cardiovascular care in HIV clinics (2); physician compensation tied to relative value units disincentivizes cardiovascular disease prevention efforts by HIV providers; and (3) grant-based services enable tailored cardiovascular disease prevention, but sustainability is limited by sponsor priorities. With HIV now a chronic disease, there is a growing need for HIV-specific cardiovascular disease prevention; however, healthcare financing complicates effective delivery of this preventative care. It is important to understand the effects of evolving payer models on patient and healthcare provider behavior. Additional systematic investigation of these models will help HIV specialty clinics implement cardiovascular disease prevention within a dynamic reimbursement landscape. Clinical Trial Registration Number: NCT03643705 .


Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants.
To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of <or=1,250 g. Preterm infants were randomized to CPAP generated via high flow cannula or the Infant Flow Nasal CPAP System (VIASYS, Conshohocken, PA, USA) at extubation. Primary outcome was incidence of reintubation within 7 days. Secondary outcomes included change in oxygen use and frequency of apnea and bradycardias postextubation. Forty neonates were randomized. Twelve of 20 infants randomized to high flow cannula CPAP were reintubated compared to three of 20 using Infant Flow (P=0.003). The high flow cannula group had increased oxygen use and more apneas and bradycardias postextubation. CPAP delivered by high flow nasal cannula failed to maintain extubation status among preterm infants <or=1,250 g as effectively as Infant Flow CPAP.


The Pittsburgh Study: Learning with Communities About Child Health and Thriving.
The COVID-19 pandemic has highlighted structural inequities that are barriers to thriving for children in neighborhoods with concentrated disadvantage. Health systems are increasingly addressing health-related social needs. The "Pittsburgh Study" is a longitudinal, community-partnered study focused on child and adolescent thriving and racial equity. This initiative will elucidate critical influences on childhood health and thriving, evaluate developmentally appropriate interventions to improve outcomes from birth to high school, and establish a child health data hub. Integration of community members into scientific inquiry, rapid data-to-action cycles, and workforce development are strategies health systems may consider to enhance child health equity.


Prolonged jaundice following ketoconazole-induced hepatic injury.
Two patients developed prolonged and progressive jaundice associated with ketoconazole-induced hepatic injury although the drug was discontinued before or shortly after the onset of symptoms of hepatic toxicity. One patient, who had been jaundiced for eight weeks and was not improving, showed prompt clinical improvement and progressive resolution of jaundice following therapy with prednisolone. Liver biopsy before therapy showed marked cholestasis in all acinar zones and moderately severe fibrosis in the space of Disse. The other patient, who was less severely jaundiced, showed spontaneous resolution although he remained jaundiced for 11 weeks. Liver biopsy performed three weeks after onset of symptoms showed a moderate degree of cholestasis in acinar zone 3 and collagen deposition about the terminal hepatic venules and within the space of Disse. These cases are reported because of the unique clinical course, documentation of the morphologic features, and experience with corticosteroid therapy.


Technological infrastructure, sleep, and rest-activity patterns in a Kaqchikel Maya community.
Sleep duration, quality, and rest-activity pattern-a measure for inferring circadian rhythm-are influenced by multiple factors including access to electricity. Recent findings suggest that the safety and comfort afforded by technology may improve sleep but negatively impact rest-activity stability. According to the circadian entrainment hypothesis, increased access to electric lighting should lead to weaker and less uniform circadian rhythms, measured by stability of rest-activity patterns. Here, we investigate sleep in a Maya community in Guatemala who are in a transitional stage of industrialization. We predicted that (i) sleep will be shorter and less efficient in this population than in industrial settings, and that (ii) rest-activity patterns will be weaker and less stable than in contexts with greater exposure to the natural environment and stronger and more stable than in settings more buffered by technologic infrastructure. Our results were mixed. Compared to more industrialized settings, in our study population sleep was 4.87% less efficient (78.39% vs 83.26%). We found no significant difference in sleep duration. Rest-activity patterns were more uniform and less variable than in industrial settings (interdaily stability = 0.58 vs 0.43; intradaily variability = 0.53 vs 0.60). Our results suggest that industrialization does not inherently reduce characteristics of sleep quality; instead, the safety and comfort afforded by technological development may improve sleep, and an intermediate degree of environmental exposure and technological buffering may support circadian rhythm strength and stability.


Corneal nerves alterations in various types of systemic polyneuropathy, identified by in vivo confocal microscopy.
In vivo confocal microscopy (IVCM) is a newly developed application to assess corneal nerve morphology. The purpose of the study is to evaluate the role of IVCM in the assessment of various types of polyneuropathy, and to define alterations of corneal nerves in such conditions. Eighteen patients with various types of polyneuropathy were characterized by clinical neurological and ophthalmic examinations, as well as by electroneuromyography (ENMG). Full thickness IVCM of corneal nerves was carried out on all patients and 15 age-matched eyes using Heidelberg Retina Tomograph II (HRT II). The subbasal nerve plexus were statistically analysed regarding long nerve fiber density, nerve branch density, nerve thickness, nerve bead number and nerve tortuosity. In subbasal nerve plexus, the following three parameters were significantly reduced in patients with polyneuropathy compared to controls: long nerve fibre density (p < 0.01), nerve branch density (p < 0.001), and nerve bead number (p = 0.001). In addition, the average grade of nerve tortuosity was 2.87 +/- 0.97 in the polyneuropathic group and 1.17 +/- 0.68 in the control group (p < 0.0001). IVCM allows a non-invasive, in vivo study of corneal nerves with high resolution. It therefore appears invaluable in clinical investigations. IVCM appears to be valuable in a large variety of polyneuropathic conditions.


Geriatrics Fellows Learning Online And Together (Geri-a-FLOAT): A sustainable model of learning and support.
Geriatrics Fellows Learning Online And Together (Geri-a-FLOAT) is a virtual curriculum designed to convene fellows nationwide for learning and peer support. This paper presents the expansion and evaluation of the program from the "Wave 1" pilot to the "Wave 2" year-long curriculum. Kern's six-step approach to curriculum development was used to develop the Wave 2 curriculum. Participation was collected via Zoom. Post-session web-based surveys evaluated participant satisfaction regarding speaker, content, and overall session quality; intent-to-change; and a free-response section. A one-year follow-up survey sent to participants with valid e-mail addresses assessed sustained knowledge, skills, and behavior change. Nineteen sessions were held with mean (SD) of 23 (13) participants per session, totaling 182 unique participants. Fifteen of 19 sessions were evaluated with 96 evaluations completed (mean [SD] 6 [4] evaluations per session). Mean (SD) ratings per session that were excellent or above average was 100% (0) for content, 99% (4) for speaker, and 99% (4) overall. Mean (SD) evaluations per session noting intent to change was 90% (14). Respondents reported helpful aspects as sharing resources and examples, perspectives and experiences of others, professional connections, and collaborative discussion. Of 127 participants with valid e-mail addresses, 40 (response rate = 31%) completed the one-year follow-up survey. Mean (SD) respondents reporting some or significant sustained impact was 89% (7) across all learning outcomes. This virtual, national curriculum for geriatrics fellows was well-received and associated with high rates of self-reported, sustained impact one-year post curriculum. Geri-a-FLOAT may be a model to standardize education and build collaboration and peer support across a discipline.


New Zealand's peak year for wartime mortality burden: the important role of the Battles of Messines and Third Ypres (Passchendaele) in 1917.
At a total of 5,547 deaths among New Zealand's military personnel, the year 1917 was the worst year from a mortality perspective in the country's military history. This year had a third of the deaths in the whole of the First World War for this military population. Major drivers of this mortality burden were the Battles of Messines and Third Ypres (Passchendaele) in June and October 1917 respectively. The contribution of disease deaths to the mortality burden was relatively small at 4.5%. Disease deaths were significantly more common in the Northern Hemisphere's winter months (p=0.007), and some may have been related to crowding.


[Detection of Mycoplasma antigens (Mycoplasma arthritidis and Mycoplasma fermentans) in the tissues of experimentally infected animals by using indirect immunofluorescence and aggregate-hemagglutination reactions].
The analysis of the results obtained in the detection of mycoplasmic antigens in tissues of infected rabbits by means of the immunofluorescence test and the aggregate hemagglutination test, carried out in parallel, indicates that both these tests are highly specific, while the immunofluorescence test is more sensitive.


Divergent temporal changes of heavy metals in the soil induced by natural versus anthropogenic forces: A case study in the Yangtze River delta area, China.
The contributions of natural versus anthropogenic forces on temporal changes of metals in the soil of the Yangtze River delta region were successfully quantified by combining repeated soil sampling, geostatistics and the modified principal component scores and multiple linear regressions approach. The findings show that the mean concentrations of Cu, Cd, As, Hg, Cr and Ni generally exhibited a decrease trend from 2010 to 2020. The decline of soil Hg was most outstanding, decreased by 20 % as a whole. The result of the modified principal component scores and multiple linear regressions approach suggests that the decrease of Hg content was predominately driven by the geochemical processes, with 48 % contribution. The mean soil Pb concentration increased by 40 % from 2010 to 2020. Approximately 76 % of the Pb change was attributed to the strengthened development of Pb-containing battery industry in the south part of the Yangtze River delta region. The Pb battery industry development also contributed 48 % of the change of Cd. The anthropogenic activities involving Cu, Zn or fossil fuel consumption contributed 32-35 % of the changes of As, Cu and Zn concentrations in the soil, and the steel industries contributed 82 % of Cr and 60 % of Ni changes, respectively.


Dissection of the bacteriophage T4 late promoter complex.
Activated transcription of the bacteriophage T4 late genes is generated by a mechanism that stands apart from the common modalities of transcriptional regulation: the activator is gp45, the viral replisome's sliding clamp; two sliding-clamp-binding proteins, gp33 and gp55, replace the host RNA polymerase (RNAP) sigma subunit. We have mutagenized, reconfigured and selectively disrupted individual interactions of the sliding clamp with gp33 and gp55 and have monitored effects on transcription. The C-terminal sliding-clamp-binding epitopes of gp33 and gp55 are perfectly interchangeable, but the functions of these two RNAP-sliding clamp connections differ: only the gp33-gp45 linkage is essential for activation, while loss of the gp55-gp45 linkage impairs but does not abolish activation. Formation of transcription-ready promoter complexes by the sliding-clamp-activated wild-type T4 RNAP resists competition by high concentrations of the polyanion heparin. This avid formation of promoter complexes requires both linkages of the T4 late RNAP to the sliding clamp. Preopening the promoter compensates for loss of the gp55-gp45 but not the gp33-gp45 linkage. We interpret the relationship of these findings and our prior analysis to the common model of transcriptional initiation in bacteria in terms of two parallel pathways, with two RNAP holoenzymes and two DNA templates: (1) gp55-RNAP and the T4 late promoter execute basal transcription; (2) gp55-gp33-RNAP and the T4 late promoter with its mobile enhancer, the T4 sliding clamp, execute activated transcription. gp55 and gp33 perform sigma-like functions, gp55 in promoter recognition and gp33 (as well as gp55) in enhancer recognition. gp33 operates the switch between these two pathways by repressing basal transcription.


Comparison of a ceiling-mounted 3D flat panel detector vs. conventional intraoperative 2D fluoroscopy in plate osteosynthesis of distal radius fractures with volar locking plate systems.
To compare intraoperative 3D fluoroscopy with a ceiling-mounted flat panel detector in plate osteosynthesis of distal radius fractures (AO/OTA 2R3C1.2) with volar locking plate systems to conventional 2D fluoroscopy for detection of insufficient fracture reduction, plate misplacement and protruding screws. Using a common volar approach on 12 cadaver forearms, total intraarticular distal radius fractures were induced, manually reduced and internally fixated with a 2.4 distal radius locking compression plate. 2D (anterior-posterior and lateral) and 3D (rotational) fluoroscopic images were taken as well as computed tomographies. Fluoroscopic images, Cone Beam CT (CBCT), 360° rotating sequences (so called "Movies") and CT scans were co-evaluated by a specialist orthopedic surgeon and a specialist radiologist regarding quality of fracture reduction, position of plate, position of the three distal locking screws and position of the three diaphyseal screws. In reference to gold standard CT, sensitivity and specifity were analyzed. "Movie" showed highest sensitivity for detection of insufficient fracture reduction (88%). Sensitivity for detection of incorrect position of plate was 100% for CBCT and 90% for "Movie." For intraarticular position of screws, 2D fluoroscopy and CBCT showed highest sensitivity and specifity (100 and 91%, respectively). Regarding detection of only marginal intraarticular position of screws, sensitivity and specifity of 2D fluoroscopy reached 100% (CBCT: 100 and 83%). "Movie" showed highest sensitivity for detection of overlapping position of screws (100%). When it comes to specifity, CBCT achieved 100%. Regarding detection of only marginal overlapping position of screws, 2D fluoroscopy and "Movie" showed highest sensitivity (100%). CBCT achieved highest specifity (100%). As for assessment of quality of fracture reduction and detection of incorrect position of plate as well as overlapping position of the three diaphyseal screws CBCT and "Movie" are comparable to CT - especially when combined. Particularly sensitivity is high compared to standard 2D fluoroscopy.


Ct guided reference markers for spinal dorsal lesions: A safe and valuable tool impacting intraoperative localization time.
Intraoperative localization of the correct spine level can be challenging when dealing with the thoracic spine; especially in morbidly obese patients and in mid-thoracic spine lesions. Different radiological reference markers techniques for dorsal surgery have been reported without a clear DAP (effective dose), localization and surgical time analysis. The aim of the study is to analyze the radiological reference markers technique in terms of localization time and radiation dose during surgery for dorsal lesions. We used a radiopaque marker (fiducial) directly positioned before surgery over the lamina or the spinous process using CT scan for precise localization and vertebra count. We prospectively collected data about patients who underwent preoperative thoracic localization between April 2015 and September 2018 at Neurosurgery Department of Ferrara University Hospital. Clinical data as pathology, related surgical technique, radiological exams, localization time and radiation exposure were analyzed. 19 patients who underwent preoperative radiopaque marker (fiducial) positioning and 11 patients who underwent fluoroscopy technique were enrolled. No complications related to fiducial placement and no wrong-level occurred. The localization time with the fiducial was reduced dramatically (3 min vs 15 min of the standard technique). The average DAP (effective dose) for the fiducial group was 20 Gy-cm2 compared with 16 Gy-cm2 of the traditional group. The use of preoperative fiducial for intraoperative localization of the target level in the thoracic spine dramatically reduce the location time without a significantly higher DAP (effective dose).


The utility of collaborative biobanks for cardiovascular research.
Differences between animal and human atherosclerosis have led to the requirement for clinical data, imaging information and biological material from large numbers of patients and healthy persons. Where such "biobanks" exist, they have been fruitful sources for genomewide association, diagnostic accuracy, ethnicity, and risk stratification cohort studies. In addition once established, they attract funding for future projects. Biobanks require a network of medical contributors, secure storage facilities, bioinformatics expertise, database managers, and ethical working practices to function optimally. There is the opportunity for collaboration between individual biobanks to further amplify the advantages afforded.


Corporate social responsibility reports: A review of the evolution, approaches and prospects.
In recent years, the corporate social responsibility (CSR) report has gained strategic importance within organizations, especially after the development of strategies and different international regulations, such as the Global Compact and the United Nations' 2030 Agenda or Directive 2014/95/EU. This, together with the boom in CSR research and business management, has given rise to heterogeneity in the conceptualization and management of CSR report. Consequently, this research study proposes a bibliometric and systematic analysis of 4966 research articles, available in the Scopus repository and published during the period of 2001-2021, to improve the conceptualization and management of CSR communication. The documents analyzed were research articles that included concepts such as CSR, communication, and reporting in the title, abstract and keywords and that were published in the 21st century. The results show an exponential growth in scientific production in recent years, coinciding with the development of strategies and international regulations, and with a high percentage of authors, institutions and countries coming from the European Union. Additionally, the main characteristics of the research are obtained alongside data on the most productive authors, institutions, journals, and countries, in addition to information about their international cooperation networks. Finally, the results present the most relevant contributions in regard to the four research topics detected, namely: (a) accountability; (b) disclosure of performance; (c) management of the organization; (d) corporate strategy; and (e) corporate reputation. These results indicate a broad multidisciplinarity of this line of research. Finally, future lines of research that can contribute to improving or expanding the current findings in this research area are established.


Rhinacanthin-C, A Fat-Soluble Extract from Rhinacanthus nasutus, Modulates High-Mobility Group Box 1-Related Neuro-Inflammation and Subarachnoid Hemorrhage-Induced Brain Apoptosis in a Rat Model.
High-mobility group box 1 (HMGB1) was shown to be a major extracellular mediator involved in relayed neuro-inflammation in animals after subarachnoid hemorrhage (SAH). It is of interest to examine the effect of rhinacanthin-C (RCT-C, C25H30O5) on pro-inflammatory cytokines/HMGB1 in an SAH-related early brain injury model. A rodent double SAH model was used. RCT-C was administered orally at 100, 200, and 400 μmol/kg/day. Cerebral spinal fluid samples were obtained to assess interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α using a real-time polymerase chain reaction. Basilar arteries were harvested and cerebral cortex was examined for HMGB1 mRNA and protein expression (western blot) and caspases (real-time polymerase chain reaction). An intrathecal injection of 1 ng of HMGB-1 recombinant protein was given in the 400 μmol/kg/day RCT-C plus SAH groups. The levels of IL-1β, IL-6, and tumor necrosis factor α mRNA were significantly increased in animals subject to SAH, compared with the healthy controls, but were absent in the RCT-C groups. Cleaved caspase-9a as well as HMGB-1 mRNA and protein were significantly reduced in the 400 μmol/kg/day RCT-C treatment groups. Similarly, administration of RCT-C reduced HMGB-1 mRNA and protein expression (P <0.01). RCT-C exerts a neuroprotective effect by reducing cleaved caspase-3- and caspase-9a-related apoptosis. Decreased HMGB-1 mRNA and protein expression in the RCT-C groups corresponds to its anti-inflammatory effect. HMGB-1 recombinant protein administration impaired the neuroprotective and immunosuppressive effect of RCT-C. This finding lends credence that RCT-C modulates the HMGB-1-related pathway and attenuates brain apoptosis in the pathogenesis of SAH.


[Indicators of diabetes mellitus after liraglutide, sitagliptin/metformin, linagliptin, and sitagliptin].
The control of diabetes mellitus is multifactorial, the different therapeutic options make it necessary to compare the effectiveness with previous therapeutic schemes. Analize the indicators of control of diabetes mellitus after incorporating liraglutide, sitagliptin/metformin, linagliptin, and sitagliptin. Observational, analytical, longitudinal study. Glucose, glycosylated hemoglobin, and blood pressure were compared after the inclusion of new cues in patients with diabetes mellitus; in addition to the control indicators reported in the unit in october, november, and december 2000, with those of 2021 in the same months. A descriptive analysis was performed, T for related samples and McNemar, a value of < .05 was considered significant, a confidence level of 95%, with the IBM-SPSS 24 software. 352 files were analyzed, 59% women, aged 26 to 88 years, and the percentage of control decreased after the change of scheme (38.4% vs 35.8%) without a statistical difference (p .503). There was no statistical difference between the levels of glucose, glycated hemoglobin, weight, and blood pressure before and six months after the change. In the unit, the regimen glycemic control indicator improved in October, November, and December 2020 compared to the same months in 2021, it increased (from 17.2, 18.7, and 16.3, to 41.6, 47.2, and 46.5%). Blood pressure control went from 64.5, 66.7, and 67 to 82.4, 85.1, and 83.1%. The control indicators in the unit improved, however, the patients who used the new keys did not show any difference.


A hierarchical multinomial logit model to examine the effects of signal strategies on right-turn crash injury severity at signalised intersections.
The severity of right-turn crashes (or left-turn crashes for the roads in the US) at signalised intersections tends to be high because of the relatively high conflicting speeds and angle of impact. However, right-turn crash injury severity at signalised intersections was not sufficiently studied. In particular, the effects of signal control strategies on crash injury severity are not known. This study developed crash injury severity models for right-turn crashes at signalised intersections with a novel approach of linking crashes with signal strategies which enabled assessing the effects of signal strategies on crash injury severity. The study provided a comprehensive understanding of the impacts of signal strategies, intersection geometry and traffic factors on crash injury severity of right-turn crashes at signalised intersections. Crash injury severity models were estimated with crash data from 221 signalised intersections in Queensland from 2012 to 2018. To address the hierarchical structure of crash data, two-level hierarchical Multinomial Logit models were applied, hypothesising that the first level includes individual crash characteristics while the second level includes intersection characteristics. The applied hierarchical model accounts for the correlation among crashes within intersections. Results showed that crashes during Lagging right-turn and Diamond overlap turns are likely to be more severe than other signal strategies at intersections, with the Lagging right-turn signal being the most hazardous. The results also illustrate that the probability of severe injuries increases with the number of conflicting lanes, whereas the corresponding probability decreases with the occupancy of the conflicting lane.


After Triad, a chain is born. Former Triad leaders form Legacy Hospital Partners, aiming to make joint ventures with not-for-profits looking for capital.
Some former Triad executives have gotten together and formed a chain called Legacy Hospital Partners. Dan Moen, left, Triad's former executive vice president, is Legacy's president and chief executive officer. He and Triad's former CEO, Denny Shelton, say the company will stay out of markets where Triad operated a hospital until a noncompete clause expires in 2010.


Purification of a yeast protein that binds to origins of DNA replication and a transcriptional silencer.
Two factors that interact specifically with the chromosomal replicator, autonomously replicating sequence 1 (ARS1), were identified in whole-cell yeast extracts. One of these proteins, ARS binding factor I (ABF-I), was purified to homogeneity as a polypeptide of 135 kDa. ABF-I binds within a region previously shown to be essential for the function of ARS1 when yeast are grown under certain nutritional conditions, and deletion analysis presented here suggests that the ARS1 domain containing the ABF-I-binding site, domain B, is a complex element composed of at least two subdomains. ABF-I also binds within an ARS at the HMR silent mating locus. This ARS functions as a cis-acting transcriptional silencer, and the ABF-I-binding site within this ARS is important for both ARS and silencer function.


Evaluation of metals in several varieties of sweet potatoes (Ipomoea batatas L.): comparative study.
Sweet potatoes are a staple in the diet of some people and an excellent source of minerals. Metal monitoring in food, like sweet potatoes, provides basic information on safety aspects in regulatory processes as well as nutritional values. One hundred five samples of three varieties of sweet potatoes were randomly obtained from supermarkets, farmers markets, and farmers' plots in Tenerife (Canary Islands, Spain). The edible portion (pulp) was the only part considered for analysis. Flame atomic absorption spectrometry was used to determine the contents of sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn), while the levels of chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were determined using graphite furnace atomic absorption spectrometry. The mean concentrations were 500 Na, 4409 K, 564 Ca, 609 Mg, 1.291 Cu, 6.554 Fe, 2.324 Mn, 2.348 Zn, 0.028 Cr, 0.048 Ni, 0.001 Cd, and 0.003 Pb mg/kg, respectively. Potassium presented the highest contents in all varieties of sweet potatoes. Iron was the most abundant microelement. The orange fleshed sweet potato variety offered greater nutritional contributions to the recommended intakes than the rest of the varieties studied. The estimated mean daily intake of Ni (0.72 mg/day) detected in our samples was highly consistent with other studies. Average daily intakes of Cd (0.015 μg/day) and Pb (0.045 μg/day) were below toxicological reference values. In conclusion, the levels of Cd and Pb detected in the sweet potatoes analyzed do not represent any toxicological risk to consumers.


International survey of enteral nutrition protocols used in children with Crohn's disease.
Differing protocols have been utilized in published studies evaluating exclusive enteral nutrition (EEN) in the management of active pediatric Crohn's disease. This study aimed to ascertain the protocols currently utilized in different pediatric centers around the world and to highlight their similarities and differences. A questionnaire was circulated to individuals at pediatric centers in countries in Europe, North America and Asia-Pacific. Respondents were asked to indicate the number of children treated with EEN at their centers in the previous years and to provide details of their protocol used for administering EEN to these children. Responses were received from 35 separate centers (42% of those asked). The duration of EEN varied from <6 weeks to >12 weeks, but was most commonly 6 to 8 weeks. Although 23 different formulas were utilized across the centers, most (90%) used polymeric formulas. Flavourings were commonly added to formulas but wide variations existed between centers with the prescription of food and fluids permitted during the EEN period. The reintroduction of food after EEN also varied greatly: the most common recommendations were for an initial low-fiber diet (26%) or the gradual introduction of food quantity as the formula volume decreased (52%). This questionnaire-based study has shown the wide variations in EEN protocols used in different areas of the world. The development of consistent protocols may enhance the acceptance, efficacy and wider utilization of this therapy.


MIL-101(Fe) based biomass as permeable reactive barrier applied to EK-PRB remediation of antimony contaminated soil.
Numerous studies have demonstrated that electrokinetic-permeable reactive barrier (EK-PRB) can be used for the remediation of heavy metal contaminated soils, and their remediation efficiency is mainly determined by the filler material selected. By growing MIL-101(Fe) in situ on hollow loofah fiber (HLF), a novel material entitled HLF@MIL-101(Fe) was developed. The morphological characteristics and loading conditions were investigated, the adsorption characteristics were analyzed, and finally the synthesized composite material was applied to treat antimony-contaminated soil with EK-PRB as the reaction medium. The results show that MIL-101(Fe) is stably loaded on HLF. The adsorption capacity of Sb(III) can reach up to 82.31 mg g-1, and the adsorption is in accordance with the quasi-secondary kinetic model, which indicates that chemisorption is dominant. The isothermal adsorption model indicates that the adsorption form of HLF@MIL-101(Fe) is mainly monolayer adsorption with more uniform adsorption binding energy. In the EK-PRB experiment, when ethylenediaminetetraacetic acid (EDTA) is used as the cathodic electrolyte, it can effectively enhance the electromigration and electroosmotic effects, and the overall remediation efficiency of the soil is increased by 38.12% compared with the citric acid (CA) group. These demonstrate the feasibility of HLF@MIL-101(Fe) in collaboration with EK-PRB in the treatment of antimony-contaminated soil.


Dual parameter, quantitative cytofluorometric analysis of endogenous H-2Kk and foreign HLA class I molecules expressed at the surface of murine transformed L cells.
By using a calibrated dual laser cell sorter and monoclonal antibodies directly conjugated to fluorescein and rhodamine and specific for H-2Kk and HLA class I antigens, quantitative cytofluorometric analysis was performed on individual HLA-A3 or -CW3 transformed mouse L cells (H-2k). More than 80% of these cells expressed both HLA class I and H-2Kk molecules. Their respective levels of expression were calculated: a mean of 4 X 10(5) HLA class I and 2.3 X 10(5) H-2Kk molecules per single cell. Quantitative comparison with control untransformed L cells and double fluorescence contour maps showed a positive correlation between the levels of expression of HLA class I and H-2Kk molecules suggesting that expression of foreign class I molecules did not occur at the expense of the endogenous H-2k product.


Early anemia and neonatal morbidity in extremely low birth-weight preterm infants.
Extremely low birth-weight (ELBW) preterm infants remain at high risk for mortality and major morbidities, and nearly all need packed red blood cell transfusions within their first weeks of life. The overall objective of this study was to assess the association between anemia at admission to neonatal intensive care unit (NICU) with the neonatal morbidity and mortality in ELBW infants. This retrospective study was conducted on 106 patients with ELBW admitted at our level III NICU from January 2006 to December 2015. The subjects were divided into two groups: (1) patients with anemia at admission and (2) patients without anemia. Their characteristics and outcomes were compared. Statistical analysis was performed using the Statistical Package for the Social Sciences software, version 24.0 (IBM New York, USA), and a value of p < 0.05 was considered statistically significant. Of the 106 ELBW, 34 (32%) presented with anemia at admission and 72 (68%) without anemia. Anemia-naive presented mean hemoglobin at the admission of 12.8 ± 1.5 g/dl and nonanemic 16.8 ± 2.1 g/dl, p < .001). The anemic group presented a lower gestational age (26 ± 2 vs. 27 ± 2 SD weeks, p = .025), greater need for inotropic support (52.9 vs. 31.9%, p = .041), longer period of invasive mechanical ventilation (9 vs. 2 days, p = .012), higher FiO2 need (0.8 vs. 0.4, p < .001), more frequent hemodynamically significant patent ductus arteriosus (HS-PDA) (64.7 vs. 41.7%, p = .006) and severe intra-periventricular hemorrhage (IPVH) (41.2 vs. 16.7%, p = 0.005). The multivariate analysis confirmed an association between anemia at admission and HS-PDA (OR = 3.2; 95% CI: 1.1-9.5, p = 0.044) and severe IPVH (OR = 3.3; 95% CI: 1.0-9.9, p = .038). In anemic infants, ionotropic support and IPVH >2 were considered independent factors for mortality. In this ELBW series, the presence of anemia at admission to the NICU was associated with HS-PDA and severe IPVH. Preventive strategies for early anemia must be encouraged.


Bacterial microflora, endogenous endotoxin, and prostaglandins in small bowel obstruction.
The objective of this experimental study of small bowel obstruction was to investigate luminal bacterial colonization and assess the most likely mediator substances responsible for the pathophysiologic alterations, those being endogenous endotoxin and prostaglandins. Eighteen pigs with small bowel obstruction and 11 sham-operated control animals given constant infusion therapy were investigated over 7 days. Bacteria determinations were performed at operation and at sacrifice. Endotoxin levels were determined three times and prostaglandin levels, twice daily in portal and central venous blood. In the pigs with small bowel obstruction, greatly increased microflora with a predominance of E. coli bacteria was observed in the obstructed bowel. Endotoxin measurements proved general release into the circulation, with potentially toxic levels in the systemic circulation arising relatively late on the fourth postobstruction day. Beginning on the first postobstruction day, stimulation of the prostaglandin system occurred which was initially limited to the gastrointestinal tract but spread systemically when the obstruction persisted for more than 5 days. Vasoactive eicosanoids were predominantly involved. The control animals showed none of the alterations seen in the animals with small bowel obstruction.


Efficient Aerobic Oxidative Coupling of Methyl Heteroarenes with Indoles.
Direct oxidative coupling of inert C(sp3 )-H bond has been a great challenge. Herein, an environmentally friendly aerobic oxidative coupling of α-methyl substituted N-heteroarenes with indoles is reported. A variety of diheteroaryl ketones were prepared in good yields (up to 72 %). This protocol features simple operation and broad substrates scope (26 examples). Significantly, a plausible mechanism about catalytic cycle was proposed, and two key intermediates were confirmed by high resolution mass spectrometry.


Executive Functions and Externalizing Symptoms: Common and Unique Associations.
In discussing the four papers in this special issue, we provide our perspective on the authors' contributions and suggest directions for future research. First, we highlight the usefulness of the bi-factor model for investigating relations among specific aspects of executive functions (EFs) and externalizing symptoms. Next, we examine the role of EFs as a protective factor that can moderate the relation between risk factors - specifically, callous-unemotional behaviors - on externalizing symptoms. And finally, we address the contributions of innovative measurement approaches to understanding the relations between EFs and externalizing symptoms, using the state-space grid methodology as an example.


Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia.
The distribution of radioiodinated N-methyl-4-(4-hydroxy-3-iodobenzyl)-1,2,3,6-tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, (4-homo-MPTP), has been studied in the primate. [123I]MHTP-derived radioactivity exhibited a progressive accumulation and prolonged retention within the primate eye. Following iv injection, [123I]MHTP rapidly accumulated within the primate brain and was subsequently oxidized to a radiolabeled metabolite. The half-life of [123I]MHTP-derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter. Selective accumulation of [125I]MHTP-derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that monoamine oxidase B is involved in the bioactivation of radioiodinated MHTP.


Radiology of large transincisural masses.
A large, potentially resectable mass that crosses the tentorial incisura may present unique problems for the neurosurgeon. Fifteen patients with large transincisural extraaxial masses were reviewed. The computed tomography and angiography findings are discussed. The importance of altering the clinician to the presence of a transincisural mass and accompanying computed tomography and angiography findings are emphasized.


Effects of traditional Chinese medicine Shuxuetong injection on random skin flap survival in rats.
A Shuxuetong injection is traditionally used in Chinese medicine to treat "blood stasis and stagnation" (yu xue yu zhi). We investigated the effect of such injection on the survival of random skin flaps. McFarlane flaps were established in 60 rats divided into two groups. Postoperative celiac injections were given to both groups for 7 days. Shuxuetong was injected into the test group, and saline was injected into controls. On day 7, tissues were stained with H&E (hematoxylin-eosin) stain, immunohistochemically evaluated, and the expression levels of xanthine oxidase were determined. The mean area of flap survival in the test group was significantly higher than in controls. Expression of vascular endothelial growth factor and superoxide dismutase, and microvessel development, were markedly increased in the test group, and the malondialdehyde level was reduced. Shuxuetong promotes random skin flap survival.


Determining appropriate timing of adaptive radiation therapy for nasopharyngeal carcinoma during intensity-modulated radiation therapy.
To determine appropriate timing of an adaptive radiation therapy (ART) replan by evaluating anatomic and dosimetric changes of target volumes and organs at risk (OARs) during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC). Nineteen NPC patients were recruited. Each patient had repeat computed tomography (CT) scans after each five fractions and at treatment completion. Automatic re-contouring the targets and OARs by using deformable registration algorithm was conducted through CT-CT fusion. Anatomic changes were assessed by comparing the initial CT and repeated CT. Hybrid plans with re-contouring were generated and the dose-volume histograms (DVH) of the hybrid plan and the original plan were compared. Progressive volume reductions in gross target volume for primary disease (GTVnx), gross target volume for involved lymph nodes (GTVnd), and parotids were observed over time. Comparing with the original plan, each hybrid plan had no significant difference in homogeneity index (HI) for all the targets. Some parameters for planning target volumes for primary disease and high-risk clinical target volume (PTVnx and PTV1, respectively) improved significantly, notably starting from the 10th fraction. These parameters included mean dose (Dmean), dose to 95% of the volume (D95), percentage of the volume receiving 95% of the prescription dose (V95), and conformity index (CI) for PTVnx, and Dmean, D95, and CI for PTV1. The dosimetric parameters for PTVnd remained the same in general except for D95 and V95 which had significant improvement at specific time points; whereas for PTV2, similar trend of dosimetric changes was also observed. Dose to some OARs increased significantly at some time points. There were significant anatomic and dosimetric changes in the targets and OARs. The target dose coverage in the hybrid plans did not get worse, but overdose occurred in some critical structures. Significant dosimetric changes should be considered as a trigger point at which ART replanning is indicated. D95/V95/CI for PTV2, Dmax for the brain stem, spinal cord, right eyeball and left lens, and Dmean/V30 for the parotids and glottis were taken into account for predicting the need for ART. Two replans at the 5th and 15th fractions were suggested.


Rhythmic processing in children with developmental dyslexia: auditory and motor rhythms link to reading and spelling.
Potential links between the language and motor systems in the brain have long attracted the interest of developmental psychologists. In this paper, we investigate a link often observed (e.g., [Wolff, P.H., 2002. Timing precision and rhythm in developmental dyslexia. Reading and Writing, 15 (1), 179-206.] between motor tapping and written language skills. We measure rhythmic finger tapping (paced by a metronome beat versus unpaced) and motor dexterity, phonological and auditory processing in 10-year old children, some of whom had a diagnosis of developmental dyslexia. We report links between paced motor tapping, auditory rhythmic processing and written language development. Motor dexterity does not explain these relationships. In regression analyses, paced finger tapping explained unique variance in reading and spelling. An interpretation based on the importance of rhythmic timing for both motor skills and language development is proposed.


Kirromycin-resistant elongation factor Tu from wild-type of Lactobacillus brevis.
Properties of the elongation factor Tu from Lactobacillus brevis which is naturally insensitive to kirromycin are described. The protein is characterized by an unusual nucleotide-binding site with increased affinity for GTP and extreme heat stability. EF-Tu is sensitive to pulvomycin in the assay of polyphenylalanine synthesis. However, the failure of the protein to display pulvomycin-dependent GDP-binding and GTPase activity indicates that pulvomycin action in L. brevis differs from that in E. coli.


Identifying Patient-Centered Research Priorities in Overactive Bladder by Crowdsourcing and Targeted Recruitment.
Patient perspectives in quality-of-life improvement are critical to measuring treatment outcomes. We aimed to identify patient priorities for overactive bladder (OAB) research. Participants were recruited utilizing the Amazon Mechanical Turk database, an online marketplace where individuals receive payment for completing tasks. Those who scored 4 or higher on the OAB-V3, a simple 3-question screening survey, were requested to complete an "OAB-q and Prioritization Survey," which identified preferences for future OAB research priorities, demographic and clinical data, and symptom severity via the OAB-q. Participants must have correctly answered an attention-confirming question to have their responses included in the final analysis. Of 555 responders, 352 screened positive on the OAB-V3 and 232 completed the followup survey and met study criteria. The top 3 research preferences were: discovering the etiology of OAB (31%); individualized treatment based on age, race, gender and comorbidities (19%); and identifying the fastest OAB treatments (15%). Participants who selected etiology of OAB in the top 3 research priorities (56%) were older (38.7±2.1 vs 33.9±1.5 years, p=0.05) and had significantly lower mean health-related quality of life scores than those who did not (25.1±2.5 vs 35.5±3.9, p=0.02). Using Amazon Mechanical Turk, we present the first report of OAB research priorities identified by patients experiencing OAB symptoms. Crowdsourcing offers a timely and cost-effective manner to learn directly from people with OAB symptoms. Few participants sought treatment for OAB despite having bothersome symptoms.


A Nested Case-Control Study of Serum Fasting Lipid Profiles in Pre- Eclamptic Primigravidas in Ile-Ife, Nigeria.
Pre-eclampsia contributes significantly to both maternal and perinatal morbidities and mortalities. One of the identified pathophysiologies of pre-eclampsia is the deranged serum lipid profile of which some components have been found to be elevated early in pregnancy in women destined to develop pre-eclampsia. To compare the serum fasting lipid profiles of pre-eclamptic primigravidas with normal primigravidas at week 20, 28, and 34. We conducted a nested case-control study at Obafemi Awolowo University, Ile-Ife between November 2016 and April 2018. A cohort of 290 primigravidas was recruited at week 20 and followed up until delivery. Serum fasting lipid profiles were quantified at weeks 20, 28 and 34 for all participants. Twenty four women that developed pre-eclampsia were compared with 48 women that had a normal pregnancy. Data were analyzed with SPSS version 22. We used a linear mixed-effect regression model with random intercept and slope. Significance was established using p<0.05. Serum lipid profiles showed an average weekly increase in both groups. Primigravidas that developed pre-eclampsia had a weekly increase of 0.2(SE0.14) mmol/l in serum total cholesterol more than those with normal pregnancies. (p<0.001) Serum low-density lipoprotein also showed a differential weekly increase of 0.1(SE0.05)mmol/l in primigravidas that developed pre-eclampsia over primigravidas with normal pregnancies. (p<0.001). The average weekly increase in serum total cholesterol and low-density lipoprotein was significantly higher in primigravidas that developed pre-eclampsia when compared to the control group. These findings depicted an association between serum lipid profile and pre-eclampsia among the primigravidas.


Age- and sex-related differences in antibody responses against Schistosoma mansoni soluble egg antigen in a cohort of school children in Ethiopia.
Acquired immunity is believed to be the main factor in the age-related differences in prevalence and intensity of Schistosoma infections. We studied antibody responses against S. mansoni soluble egg antigen (SEA) by ELISA in children before treatment, 5 weeks and one year after treatment. After screening for S. mansoni infection, positive children were treated with praziquantel (40 mg per kg body weight). Infection rate was significantly higher in boys younger than 12 years than in girls in the same age group. Levels of all antibody isotypes, except IgG1 (before treatment) or IgA (one year after treatment), were higher in children older or equal to 12 years than in those younger. The difference between age groups was significant for IgE, IgM, IgG3 and IgG4 (before treatment) and IgE (one year after treatment). Similarly, all antibody isotypes, except IgE, before treatment were higher in boys than in girls. At 5 weeks after treatment, IgG, IgE and IgG1 showed an increasing tendency, whereas IgM and IgG3 tended to decrease. One year after treatment, significant decreases were observed in IgG, IgG1 and IgG4 and a significant increase in IgG2 levels. The study presents further evidence for the difference in acquired immunity between younger and older children, and between boys and girls. The study also suggests that praziquantel differentially affects antibody responses against S. mansoni SEA.


Pharmacologic Activities of 3'-Hydroxypterostilbene: Cytotoxic, Anti-Oxidant, Anti-Adipogenic, Anti-Inflammatory, Histone Deacetylase and Sirtuin 1 Inhibitory Activity.
Delineate the selected pharmacodynamics of a naturally occurring stilbene 3'-Hydroxypterostilbene. Characterize for the first time the pharmacodynamics bioactivity in several in-vitro assays with relevant roles in heart disease, inflammation, cancer, and diabetes etiology and pathophysiology. 3'-Hydroxypterostilbene was studied in in-vitro assays to identify possible bioactivity. 3'-Hydroxypterostilbene demonstrated anti-oxidant, anti-inflammatory, cytotoxic, anti-adipogenic, histone deacetylase, and sirtuin-1 inhibitory activity. The importance of understanding individual stilbene pharmacologic activities were delineated. Small changes in chemical structure of stilbene compounds result in significant pharmacodynamic differences. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.


Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18.
Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type.


Toward a consensus view of duplex RNA flexibility.
The structure and flexibility of the RNA duplex has been studied using extended molecular dynamics simulations on four diverse 18-mer oligonucleotides designed to contain many copies of the 10 unique dinucleotide steps in different sequence environments. Simulations were performed using the two most popular force fields for nucleic acids simulations (AMBER and CHARMM) in their latest versions, trying to arrive to a consensus picture of the RNA flexibility. Contrary to what was found for DNA duplex (DNA(2)), no clear convergence is found for the RNA duplex (RNA(2)), but one of the force field seems to agree better with experimental data. MD simulations performed with this force field were used to fully characterize, for the first time to our knowledge, the sequence-dependent elastic properties of RNA duplexes at different levels of resolutions. The flexibility pattern of RNA(2) shows similarities with DNA(2), but also surprising differences, which help us to understand the different biological functions of both molecules. A full mesoscopic model of RNA duplex at different resolution levels is derived to be used for genome-wide description of the flexibility of double-helical fragments of RNA.


Biochar-goethite composites inhibited/enhanced degradation of triphenyl phosphate by activating persulfate: Insights on the mechanism.
In this study, the biochar-goethite composites (MBC@FH) were synthesized through co-ball milling and the degradation of triphenyl phosphate (TPhP) was compared in persulfate (PDS) alone system and MBC@FH&PDS systems. The results showed that TPhP can be effectively degraded in PDS alone system and degradation efficiency reached up to 90 % within reaction of 8 h, at a PDS concentration of 10 mM, a reaction temperature of 30 °C and a system pH of 6.12. The obvious degradation can be ascribed to the reactive oxygen species (ROS) generated by self-decompose of PDS, among which 1O2, ∙OH and O2∙- play a major role in the degradation process. Although 350 °C biochar-goethite composites (MBC35@FH) and 800 °C biochar-goethite composites (MBC80@FH) facilitated PDS activation to produce more ROS, the catalytic degradation of TPhP was different in their systems. The degradation of TPhP was inhibited by MBC35@FH due to its stronger adsorption for TPhP, while MBC80@FH promoted TPhP degradation and degradation efficiency was up to 100 % within 6 h. 1O2 and SO4∙- played a stronger degradation role than ∙OH and O2∙- in above systems. The transformation of Fe species, functional groups (oxygen-containing functional groups, pyrrolic nitrogen) and persistent free radicals (PFRs) on the MBC@FH were involved in the PDS activation to produce ROS. Furthermore, MBC80@FH was more capable of activating PDS than MBC35@FH due to its abundant defect sites, larger specific surface area, more PFRs, higher Fe content and stronger electron transfer capability. In addition, seven possible TPhP intermediates were identified and possible degradation pathways of TPhP were proposed accordingly. This study illustrated that not all metallic carbon catalysts are necessarily beneficial for organic contaminants degradation.


Antinociceptive effects of haloperidol and its metabolites in the formalin test in mice.
Formalin-induced pain is reduced in sigma-1 (sigma1) receptor knockout mice; therefore, we hypothesized that haloperidol and its metabolites I and II, which have affinity for sigma1 receptors, may modulate formalin-induced pain. Intraplantar administration of formalin (2.5%) to CD-1 mice produced a biphasic period of pain. Haloperidol (0.03-1 mg/kg, s.c.) and reduced haloperidol (metabolite II, 0.25-8 mg/kg, s.c.) dose-dependently inhibited both phases of formalin-induced pain. Haloperidol metabolite I (4-128 mg/kg, s.c.) also produced dose-dependent antinociception in the second phase of the formalin test, but was less potent and effective against first-phase pain. Haloperidol metabolite III (16 and 128 mg/kg) and (-)sulpiride (200 mg/kg), which have no affinity for sigma1 receptors, did not produce significant antinociception in either phase of the formalin test. The order of potency of the drugs to produce their antinociceptive effect [haloperidol>metabolite II>metabolite I>>metabolite III= (-)sulpiride=inactive] correlated with their affinity for sigma1 receptors, but not with their affinity for sigma2 or dopamine D2 receptors. Naloxone (1 mg/kg, s.c.) did not antagonize the antinociception induced by haloperidol and its metabolites. None of the antinociceptive drugs in the formalin test produced any antinociception in the tail flick test. These results suggest that the antinociceptive effect of haloperidol and its metabolites in the formalin test is not due to unspecific/generalised inhibition of nociception or modulation of opioid receptors, and that it may be related, at least partially, to the ability of these drugs to interact with sigma1 receptors.


Corneal Ectasia Risk And Percentage Tissue Altered In Myopic Patients Presenting For Refractive Surgery.
A percentage tissue altered (PTA) score of ≥40% has been advocated as an independent indicator of post-operative ectasia risk following laser in-situ keratomileusis (LASIK). This study was performed to test the hypothesis that refractive procedures, such as laser-assisted sub-epithelial keratectomy (LASEK) or small incision lenticule extraction (SMILE), may alter the range of PTA, within which refractive corneal surgery can be safely performed. Refractive department, tertiary ophthalmic hospital. Retrospective observational study. Review of case notes was performed for patients who presented for refractive surgeries, other than LASIK. To determine the risk of corneal ectasia for each patient prior to refractive surgery, we estimated what each patient's PTA would have been if they had undergone LASIK. The Randleman Ectasia Risk Score System (ERSS) was also calculated. 114 eyes (66 patients) were included. 94 eyes underwent SMILE. 20 eyes underwent LASEK. A significant proportion of eyes had PTA ≥40% - SMILE eyes: up to 31.9%, LASEK eyes: up to 60.0% (at presumed LASIK flap of 120 μm). The maximum calculated PTA was up to 47.9% in the SMILE group and up to 51.5% in the LASEK group. Using ERSS, 12.8-16% of SMILE eyes and 15.0-80.0% of LASEK eyes would have been considered to have moderate-to-high ectasia risk. No post-surgical ectasia was observed at 3 years. SMILE and LASEK alter the range of PTA, within which corneal refractive surgery may be performed with a lower risk of developing post-operative corneal ectasia; a safe PTA threshold needs to be determined for these procedures before recommendations for clinical practice can be made.