A branched pathway for transgene-induced RNA silencing in plants.
In plants, RNA silencing can be induced by highly transcribed sense transgenes (S-PTGS) or by transgene loci producing double-stranded RNA (dsRNA) due to the presence of inverted repeats (IR-PTGS). Both phenomena correlate with accumulation of 21-25 nt sense and anti-sense RNA homologous to the silent gene and with methylation of the coding sequence. We have challenged IR-PTGS with four viruses known to inhibit S-PTGS: CMV, TuMV, TVCV, and TCV ( this work) and in sgs2, sgs3, and ago1 mutants impaired in S-PTGS. Surprisingly, whereas the four viruses inhibit IR-PTGS, IR-PTGS and methylation of a GUS trangene and IR-PTGS of three endogeneous genes occur in the sgs2, sgs3, and ago1 mutations. Based on these results, we propose a branched pathway for RNA silencing in plants. RNA silencing would occur via the action of dsRNA produced either via the action of SGS2 (also known as SDE1), SGS3, and AGO1 on the S-PTGS branch or by transgenes arranged as inverted repeats on the IR-PTGS branch. Moreover, transgene methylation would result from production or action of dsRNA, since it does not require SGS2/SDE1, SGS3, and AGO1.


Green synthesis of ZnFe2O4@ZnO nanocomposites using Chrysanthemum spp. floral waste for photocatalytic dye degradation.
The occurrence of textile dyeing wastewater discharged into the environment has been recently increasing, resulting in harmful effects on living organisms and human health. The use of green nanoparticles for water decontamination has received much attention. Floral waste can be extracted with the release of natural compounds, which act as reducing and stabilizing agents during the biosynthesis of nanoparticles. Herein, we report the utilization of Chrysanthemum spp. floral waste extract to synthesize green ZnFe2O4@ZnO (ZFOZx) nanocomposites for the photocatalytic degradation of Congo red under solar light irradiation. The various molar ratio of ZnFe2O4 (0-50%) was incorporated into ZnO nanoparticles. The surface area of green ZFOZx nanocomposites was found to increase (7.41-42.66 m2 g-1) while their band gap energy decreased from 1.98 eV to 1.92 eV. Moreover, the results exhibited the highest Congo red dye degradation efficiency of 94.85% at a concentration of 5.0 mg L-1, and a catalyst dosage of 0.33 g L-1. The •O2- reactive species played a vital role in the photocatalytic degradation of Congo red dye. Green ZFOZ3 nanocomposites had good recyclability with at least three cycles, and an excellent stability. The germination results showed that wastewater treated by ZFOZ3 was safe enough for bean seed germination. We expect that this work contributes significantly to developing novel green bio-based nanomaterials for environmental remediation as well as reducing the harm caused by flower wastes.


The influence of pancreatic juice on 64Cu absorption in the rat.
The absorption of 64Cu from closed duodeno-jejunal loops in anaesthetized rats was significantly less in the presence of pancreatic juice compared with that in the presence of saline (9 g sodium chloride/l). The inhibition of 64Cu absorption caused by pancreatic juice was similar to that achieved with bile. Studies using solutions of electrolytes and of pancreatic extracts showed that the inhibitory effect of pancreatic secretions was due to its protein-enzyme content and not to its bicarbonate content. Pancreatic secretion and bile influence Cu absorption and thereby affect Cu homeostasis.


Complexation of vanadium(V) oxyanions with hexopyranose- and mannopyranoseuronic acid-containing polysaccharides: stereochemical considerations.
Carbohydrates containing galactopyranosyl and mannopyranosyl units with vicinal cis-diols were treated with NaVO(3) in D(2)O, and complexation was determined by (51)V NMR spectroscopy. Me alpha-Galp, Me beta-Galp (3,4-cis-diols), and Me alpha-Manp (2,3-cis-diol) complexed, but Me beta-Manp barely did so. This low degree of complexation also occurred with a beta-mannan containing alternate (1-->3)- and (1-->4)-linkages and an alginate having beta-ManpA blocks. In contrast, branched alpha-mannans complexed readily, although the (51)V resonances for one with side chains terminated with alpha-Manp-(1-->3)-alpha-Manp-(1--> differed from another with only alpha-Manp-(1-->2)-alpha-Manp-(1--> groups. The anomeric configuration of Me alpha-Galp and Me beta-Galp, each with 3,4-cis-diols remote from C-1, gave rise to three (51)V signals of complexes with similar shifts and proportions. The shifts of a galactomannan with terminal alpha-Galp-(1-->2)-alpha-Manp- were the same as those with alpha-Galp-(1-->6)-beta-Manp- groups, but fewer complexes were formed with the former structure, probably due to greater steric crowding of the vanadate esters. Most of the complexes gave rise to a signal in the delta515 region, consistent with the dimeric trigonal-bipyramidal structure.


Oxidative stress is not involved in motion sickness in mice.
Some indirect evidences indicate a possible correlation between oxidative stress and motion sickness. The aim of this research was to investigate whether oxidative stress contributing to motion sickness in mice or not. We examined the mRNA levels of peroxiredoxin 6 (PRDX6), catalase, and enzyme superoxide dismutase 1 (SOD1); reactive oxygen species (ROS); and total antioxidant capacity and SOD activity in different brain regions after rotary stimulation. Mice motion sickness index was recorded after rotation when pretreated with paraquat, vitamin C, or vitamin E. The ROS level and antioxidant capacity were both increased in cerebellum plus brainstem (CB) after rotation, a critical region determines motion sickness. However, manipulation of oxidants or antioxidants using pharmacological method in vivo had no influence on motion sickness index in mice. Oxidative stress is not involved in the development of motion sickness in mice.


Calcium antagonists for acute ischemic heart disease.
The pharmacologic and physiologic effects of the slow-channel calcium antagonists verapamil, nifedipine and diltiazem are reviewed. Relevant pathophysiologic features of various acute ischemic heart disease syndromes are also reviewed and the clinical applications of the slow-channel calcium antagonists to acute ischemic heart disease syndromes in patients are discussed.


In silico analysis of protein neoplastic biomarkers for cervix and uterine cancer.
Worldwide, cervical and uterine cancers are the most deadly cancers in women, with high prevalences, especially in developing countries. The Human Protein Atlas (HPA) portal was explored for proteins expressed in a tissue- or cervix and uterine cancer-specific manner. The group of proteins differentially expressed and with enhanced expression in the glandular and surface epithelial (squamous) cells retrieved from HPA were further explored using the Protein Information and Knowledge Extractor (PIKE) portal to compile biological information that is found in different databases, and repositories on the Internet. Thus, the lists of candidate proteins found in HPA, and PIKE portals may be used as a starting point for the discovery and validation of biomarkers for cervix and uterine cancer employing proteomics approaches as described in the present article.


[Induction of gastrointestinal tract tumors in rats with N-methyl-N-nitro-N-nitrosoguanidine (MNNG)].
Tumors of the gastrointestinal tract were induced in white non-inbred rats exposed to MNNG in various doses. Gastric tumors appeared in the dosage of 153 mg, with its 2 and 3.3 times increase no change in the frequency of gastric tumors was noted. The frequency of jejunal tumors was higher with increased MNNG dosage.


Improved Detectability of Plasmodium falciparum Clones with Repeated Sampling in Incident and Chronic Infections in Burkina Faso.
We evaluated the detectability of Plasmodium falciparum clones when assessed on 3 consecutive days in incident and chronic infections in naturally exposed children living in an area of intense malaria transmission in Burkina Faso. The median number of clones by merozoite surface protein 2 (MSP2) genotyping was 3 (interquartile range [IQR] 2-5) in incident infections compared with 6 (IQR 4-8) in chronic infections (P < 0.0001). When all clones detected on days 1-3 were considered as true complexity of infection, sampling on day 1 detected only 69.4% (109/157) or 68.3% (228/334) of all clones in incident and chronic infections, respectively. Our findings demonstrate that a large proportion of clones are missed by single time-point sampling. In addition, because of the high complexity of infection early in incident infections, our data suggest many infections may be caused by genetically complex inocula.


Endometrioid carcinoma arising from endometriosis of the sigmoid colon during estrogenic treatment.
A case of endometrioid carcinoma arising from endometriosis of the sigmoid colon is reported. The patient had been treated with unopposed continuous estrogen injection for twenty years after bilateral salpingo-oophorectomy because of severe endometriosis. The pathology, pertinent literature and implications of the present case are discussed.


Effect of vasopressin and serosal hypertonicity on toad urinary bladder.
The mucosal surface of toad urinary bladder was examined with scanning electron microscopy following its exposure to 20 mU/ml of vasopressin (VP), 10(-4) M 8-bromo-cAMP, 1 mM acetylcholine chloride, serosal hypertonicity, or a hypotonic bathing medium. After a 30-min exposure to VP, the arborizing ridge-like surface pattern typical of granular cells was transformed into microvilli, a response that was not dependent on transepithelial osmotic water movement. An identical response occurred following a 30-min exposure of the bladder to 8-bromo-cAMP, again in the absence of an osmotic gradient. Microvillus formation was not observed when cell volume was increased by incubation of tissue in half-normal amphibian Ringer's solution for 30 min, or with exposure to acetylcholine, which caused accentuation of the convexity of the apical surface of the granular cell similar to that observed with VP-induced osmotic water flow. However, 60 min of incubation in a hypertonic serosal medium (mannitol, 240 mM) caused transformation of ridges to microvilli mimicking the picture obtained with VP. These findings establish that transepithelial osmotic water flow with cell swelling is not required for microvillus formation on the apical surface of granular cells following VP stimulation, and that the surface changes are not due to cell swelling alone or to changes in the configuration of the apical plasmalemma. The results also suggest that the response to VP is mediated via the generation of cAMP. Finally, this study demonstrates that serosal hypertonicity also causes transformation of ridges to microvilli by a mechanism that is yet to be defined.


Evaluating an in-school injury prevention programme's effect on children's helmet wearing habits.
To evaluate the effectiveness of the Bikes, Blades and Boards (BB&B) programme. It was hypothesized that children who participated in the BB&B programme would demonstrate greater knowledge of how to wear their helmets safely than a control group who did not participate in the programme and retain their skills when assessed 1 year later. Single blind cluster randomized design. Twelve classes of grade 2 students (n = 162) participated; six classes were assigned to an experimental or control group. A blinded research assistant, taking 3-5 minutes per child, completed the Helmet Checklist with each group on two occasions and scores of the experimental group (post-BB&B programme) were compared to the control group. The experimental group was reassessed using the Helmet Checklist, 1 year later. The BB&B programme consisted of a presentation, bicycle helmet checklist, demonstration and individual practice and feedback. Children in the experimental group showed a better knowledge of how to wear their helmets safely compared to the control group (F = 51.84, CI = 9.11-9.71) and retained this knowledge 1 year after participating in the BB&B programme. The BB&B programme is effective in teaching grade 2 children how to wear their helmets correctly, which is knowledge they retain for at least 1 year.


Vomiting after ophthalmic surgery. Effects of intra-operative antiemetics and postoperative oral fluid restriction.
The usefulness of intra-operative antiemetics and postoperative oral fluid restriction in the prevention of vomiting following anaesthesia for ophthalmic surgery, was studied in 200 patients. They were allocated into four groups of 50 and given either saline (as control), droperidol, metoclopramide or prochlorperazine. Oral intake was restricted postoperatively in half of the patients of each group. Anaesthesia comprised morphine and atropine premedication and a halothane, nitrous oxide and oxygen spontaneous breathing technique. No significant beneficial effects resulted from intra-operative antiemetics; vomiting incidences of 26% after saline and droperidol, 28% after metoclopramide and 14% after prochlorperazine were observed. Younger patients and females vomited most frequently. Restriction of oral fluids did not decrease the incidence of vomiting but demonstrated that approximately half of those patients who vomit do so with their first postoperative oral intake. Vomiting was observed more frequently after non intra-ocular surgery than after intra-ocular surgery (37% cf. 16%, p less than 0.01) and postoperative analgesics were required by more non intra-ocular patients than by intra-ocular patients (25% cf. 5%, p less than 0.001). Squint patients vomited most frequently (48%) and most frequently required postoperative analgesia (35%).


Pain intensity trajectories among veterans seeking mental health treatment: Association with mental health symptoms and suicidal thoughts and behaviors.
The purpose of this study was to identify classes of pain intensity trajectories among veterans reporting suicidal ideation with no prior mental health treatment experience. We were interested in also assessing factors associated with the pain trajectory classes. A total 747 participants completed measures of pain, depression, suicide ideation and behaviors, insomnia, substance use, and PTSD. Follow-up assessments were completed at 1-, 3-, 6-, and 12-months post-baseline. Growth mixture modeling was conducted, and pain trajectories were modeled from baseline to month 12. Three classes were identified: mild pain intensity that increased over time to severe pain intensity (Increasing-Severe; n = 9), low pain intensity that decreased over time (Mild-Decreasing; n = 172), and moderate pain intensity that remained relatively stable over time (Moderate-Stable; n = 566). The Moderate-Stable trajectory had more severe PTSD symptoms, more frequent depression symptoms, and more severe insomnia. The odds of endorsing suicide ideation at month 12 were significantly higher in the Moderate-Stable trajectory compared to the Mild-Decreasing trajectory. This was the first study to assess classes of pain intensity trajectories among individuals who were treatment naïve for mental health issues. The findings suggest that a moderate stable trajectory of pain intensity over the course of 12 months is common and associated with a more severe clinical profile, including suicide ideation. This study underscores the importance of addressing pain intensity among individuals seeking mental health treatment, particularly for those with pain intensity that is moderate and stable over time.


Centchroman--a non-steroidal anti-cancer agent for advanced breast cancer: phase-II study.
Treatment with Centchroman (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(beta-pyrrolidinoethoxy) phenyl-7-methoxy chroman) has been evaluated in 4 male and 75 female patients with advanced breast cancer. The overall response rate, including both male and female cases, was 40.5%. Among the female patients, the overall response rate was 38.7%. The median duration of response was 6 months. One of the 4 male patients showed a complete response and 2 showed partial responses. The responses were more marked for bone, pulmonary, soft tissue, skin and lymph-node metastases than for liver metastases.


The endothelial glycocalyx in critical illness: A pediatric perspective.
The vascular endothelium is the interface between circulating blood and end organs and thus has a critical role in preserving organ function. The endothelium is lined by a glycan-rich glycocalyx that uniquely contributes to endothelial function through its regulation of leukocyte and platelet interactions with the vessel wall, vascular permeability, coagulation, and vasoreactivity. Degradation of the endothelial glycocalyx can thus promote vascular dysfunction, inflammation propagation, and organ injury. The endothelial glycocalyx and its role in vascular pathophysiology has gained increasing attention over the last decade. While studies characterizing vascular glycocalyx injury and its downstream consequences in a host of adult human diseases and in animal models has burgeoned, studies evaluating glycocalyx damage in pediatric diseases are relatively few. As children have unique physiology that differs from adults, significant knowledge gaps remain in our understanding of the causes and effects of endothelial glycocalyx disintegrity in pediatric critical illness. In this narrative literature overview, we offer a unique perspective on the role of the endothelial glycocalyx in pediatric critical illness, drawing from adult and preclinical data in addition to pediatric clinical experience to elucidate how marked derangement of the endothelial surface layer may contribute to aberrant vascular biology in children. By calling attention to this nascent field, we hope to increase research efforts to address important knowledge gaps in pediatric vascular biology that may inform the development of novel therapeutic strategies.


Overview on polycyclic aromatic hydrocarbons: occurrence, legislation and innovative determination in foods.
Polycyclic aromatic hydrocarbons are ubiquitous compounds, well-known to be carcinogenic, which can reach the food in different ways. Thus the analysis of such compounds has always been of great importance. The aim of the present review, is not only to give an overview of the most recent sample preparation and analytical approaches (such as pressurized liquid extraction, solid-phase microextraction, supercritical fluid extraction, etc.), but also to introduce such a topic to researchers who want to approach it for the first time; therefore, the most significant references related to general aspects, such as formation, toxicity, risk assessment, occurrence in food, are reported and briefly discussed.


Topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship study of dihydroxylated 2,6-diphenyl-4-aryl pyridines.
A new series of thirty-six dihydroxylated 2,6-diphenyl-4-aryl pyridines containing hydroxyl groups at the ortho, meta, or para position of 2- and 6-phenyl rings attached to the central pyridine were designed and synthesized. They were evaluated for topoisomerase I and II inhibitory activity and cytotoxicity against several human cancer cell lines for the development of novel anticancer agents. Most of the compounds with hydroxyl moiety either at the meta or para position of 2- or 6-phenyl ring in combination with thienyl or furyl group at 4-position of central pyridine displayed significant topoisomerase II inhibitory activity and cytotoxicity. Positive correlation between topoisomerase II inhibitory activity and cytotoxicity was observed for the compounds 9-11, 15-17, 19, 21-23, 28, and 41. Among all the synthesized compounds, compound 17 emerged as the most promising topoisomerase II inhibitor with significant cytotoxicity.


Gamma radiation shielding properties for polymer composites reinforced with bismuth tungstate in different proportions.
In this study, inorganic compound (Bi2(WO4)3) was added into the composite to improve the radiation shielding properties of polymer composite. A polymer matrix was prepared by combining unsaturated polyester resin with methyl ethyl ketone peroxide and cobalt octoate (6%), and Bi2(WO4)3 was added to this polymer matrix at different ratios as filling material. In order to investigate the gamma radiation attenuation properties of the obtained polymer composites, mass attenuation coefficients, radiation shielding efficiencies, radiation transmission factors, linear attenuation coefficients, half values layer, tenth values layer, mean free path values, effective atomic numbers and effective electron densities parameters were obtained. Experimental studies were carried out with the help of HPGe detector at 22 different energies emitted from 22Na, 54Mn, 57Co, 60Co, 133Ba, 137Cs, 152Eu and 241Am radioactive sources in the photon energy range of 59.5-1408.0 keV. Each obtained experimental result was compared with the theoretical results. It was observed that the sample encoded with BiWO20 is the best radiation shielding material among all studied composites (except 59.5 keV).


Rapid quality evaluation of Plantaginis Semen by near infrared spectroscopy combined with chemometrics.
To establish a rapid and comprehensive method for the quality evaluation of Plantaginis Semen (PS) by using near-infrared spectroscopy combined with chemometrics to determine the content of geniposidic acid (GEA), verbascoside (VE), isoverbascoside (IVE) and total flavonoids (TF) in PS, as well as the antioxidant activity (AOA). The content of GEA, VE and IVE in PS were determined by HPLC, the content of TF in PS was determined by UV-Vis spectrophotometry, and the AOA of PS was characterized by the DPPH, ABTS and FRAP, respectively. Then, the measured values of each item were used as reference values and were correlated with the near infrared spectra of PS. Seven quantitative models were established by the partial least squares regression. A variety of spectral preprocessing, such as standard normal variation (SNV), multiplicative scatter correction (MSC), Savitzky-Golay smoothing (SG), derivative and their combination methods, were investigated. In addition, genetic algorithm (GA), particle swarm optimization (PSO), as well as competitive adaptive reweighted sampling (CARS) were also compared. All samples were divided into a calibration set and a prediction set at the ratio of 3:1 by the descending order of reference values. The coefficients of determination (R2), root mean square error (RMSE) and residual predictive deviation (RPD) were calculated to evaluate model performance. After optimization, the performance of each model was greatly improved, where the R2 for calibration and prediction were both greater than 0.8, the RPD were both greater than 2. Such satisfactory results indicated that the present models had good prediction accuracy. Quantitative models based on near infrared spectroscopy were herein established, which proved to be able to quickly and accurately determine the content of GEA, VE and IVE and TF, as well as AOA in PS, and which might provide a new method for rapid and comprehensive quality evaluation of PS.


The perioperative effect of increased body mass index on peripheral nerve blockade: an analysis of 528 ultrasound guided interscalene blocks.
Obese patients can pose a unique perioperative anesthetic challenge, making regional anesthetic techniques an intriguing means of providing analgesia for this population. Ultrasound guidance has been touted recently as being beneficial for this population in which surface landmarks can become obscured. In this study, the effect of increased Body Mass Index (BMI) on ultrasound guided interscalene peripheral nerve blockade is investigated. This study is a retrospective review of 528 consecutive patients who received preoperative ultrasound-guided interscalene nerve blocks at the University of Wisconsin Hospital and Clinics. We examined the association between BMI and the following parameters: time required for block placement; presence of Postoperative Nausea and Vomiting (PONV); postoperative Post Anesthesia Care Unit (PACU) pain scores; volume of local anesthetic injected; acute complications; and opioid administration preoperatively, intraoperatively, and postoperatively. Univariate and multivariate least squares and logistic regression models were used. An elevated BMI was associated with an increased: time required for block placement (p-value=0.025), intraoperative fentanyl administration (p-value<0.001), peak PACU pain scores (p-value<0.001), PACU opioid administration (p-value<0.001), PACU oral opioid administration (p-value<0.001), total PACU opioid administration (p-value<0.001) and incidence of PACU nausea (p-value=0.025) Ultrasound guided interscalene nerve blocks for perioperative analgesia can be safely and effectively performed in the obese patient but they may be more difficult to perform and analgesia may not be as complete.


Within the Bounds: The Role of Relocation on Intimate Partner Violence Help-Seeking for Immigrant and Native Women With Histories of Homelessness.
Our study examines the effects of abused women's relocation and recentness to an area on informal and formal help-seeking, and how access to personal and social resources affect these relationships. Secondary data analysis was conducted using a sample of 572 women with histories of abuse and homelessness who were interviewed at shelters in the state of Florida. Findings from nested linear regressions demonstrate that relocation affects formal help-seeking while recentness to an area affects informal help-seeking. Access to personal resources also predicts women's use of both informal and formal resources. Implications for intimate partner violence help-seeking are discussed.


PD-L1: Can it be a biomarker for the prognosis or a promising therapeutic target in cervical cancer?
Cervical cancer is one of the most common in the female genital tract and remains a leading cause that threatens the health and lives of women worldwide, although preventive vaccines and early diagnosis have reduced mortality. While treatment by operation and chemoradiotherapy for early-stage patients achieve good outcomes, the great majority of cervical cancers caused by the human papilloma virus (HPV) make immunotherapy realizable for patients with advanced and recurrent cervical cancer. To date, some clinical trials of checkpoint immunotherapy in cervical cancer have indicated significant benefits of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors, providing strong evidence for PD-1/PD-L1 as a therapeutic target. In this review article, we discuss the role of PD-L1 and the application of PD-L1 inhibitors in cervical cancer, with the aim of providing direction for future research.


A possible participation of transient receptor potential vanilloid type 1 channels in the antidepressant effect of fluoxetine.
The present study investigated the influence of transient receptor vanilloid type 1 (TRPV1) channel agonist (capsaicin) and antagonist (capsazepine) either alone or in combination with traditional antidepressant drug, fluoxetine; or a serotonin hydroxylase inhibitor, para-chlorophenylalanine; or a glutamate N-methyl-D-aspartate (NMDA) receptor agonist, NMDA on the forced swim test and tail suspension test using male Swiss mice. Results revealed that intracerebroventricular injections of capsaicin (200 and 300 μg/mouse) and capsazepine (100 and 200 μg/mouse) reduced the immobility time, exhibiting antidepressant-like activity that was comparable to the effects of fluoxetine (2.5-10 μg/mouse) in both the tests. However, in the presence of inactive dose (10 μg/mouse) of capsazepine, capsaicin (300 μg/mouse) had no influence on the indices of both tests, signifying that the effects are TRPV1-mediated. Further, the antidepressant-like effects of both the TRPV1 ligands were neutralized in mice-pretreated with NMDA (0.1 μg/mouse), suggestive of the fact that decreased glutamatergic transmission might contribute to the antidepressant-like activity. In addition, co-administration of sub-threshold dose of capsazepine (10 μg/mouse) and fluoxetine (1.75 μg/mouse) produced a synergistic effect in both the tests. In contrast, inactive doses of capsaicin (10 and 100 μg/mouse) partially abolished the antidepressant effect of fluoxetine (10 μg/mouse), while its effect was potentiated by active dose of capsaicin (200 μg/mouse). Moreover, pretreatment of mice with para-chlorophenylalanine (300 mg/kg/day × 3 days, i.p.) attenuated the effects of capsaicin and capsazepine, demonstrating a probable interplay between serotonin and TRPV1, at least in parts. Thus, our data indicate a possible role of TRPV1 in depressive-like symptoms.


Synthesis of methyl glycoside derivatives of tri- and penta-saccharides related to the antithrombin III-binding sequence of heparin, employing cellobiose as a key starting-material.
Two key synthons for the title pentasaccharide derivative, methyl O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L-idopyranosyluronate)-(1----4)-6-O-acetyl- 2-azido - 3-O- benzyl-2-deoxy-beta-D-glucopyranoside and O-(methyl 2,3-di-O-benzyl-4-O- chloroacetyl-beta-D-glucopyranosyluronate)-(1----4)-3,6-di-O-acetyl-2-az ido-2- deoxy-alpha-D- glucopyranosyl bromide, were prepared from a common starting material, cellobiose. They were coupled to give a tetrasaccharide derivative that underwent O-dechloroacetylation to the corresponding glycosyl acceptor. Its condensation with the known 6-O-acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl bromide afforded a 77% yield of suitably protected pentasaccharide, methyl O-(6-O- acetyl-2-azido-3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)- O- (methyl 2,3- di-O-benzyl-beta-D-glucopyranosyluronate)-(1----4)-O-(3,6-di-O-acetyl-2- azido-2 - deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2-O-benzoyl-3-O-benzyl-alpha-L- idopyranosyluronate)- (1----4)-6-O-acetyl-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranoside. Sequential deprotection and sulfation gave the decasodium salt of methyl O-(2- deoxy-2-sulfamido-6-O-sulfo-alpha-D-glucopyranosyl)-(1----4)-O-(be ta-D- glucopyranosyl-uronic acid)-(1----4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-alpha-D-gluco pyranosyl)- (1----4)-O-(2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1----4)-2-deoxy-2- sulfamido-6-O- sulfo-beta-D-glucopyranoside (3). In a similar way, the trisaccharide derivative, the hexasodium salt of methyl O-(2-deoxy-2-sulfamido-6-O-sulfo-alpha-D- glucopyranosyl)- (1----4)-O-(beta-D-glucopyranosyluronic acid)-(1----4)-2-deoxy-2-sulfamido-3,6- di-O- sulfo-alpha-D-glucopyranoside (4) was synthesized from methyl O-(6-O-acetyl-2- azido- 3,4-di-O-benzyl-2-deoxy-alpha-D-glucopyranosyl)-(1----4)-O-(methyl 2,3-di-O- benzyl-beta- D-glucopyranosyluronate)-3,6-di-O-acetyl-2-azido-2-deoxy-alpha-D- glucopyranoside. The pentasaccharide 3 binds strongly to antithrombin III with an association constant almost equivalent to that of high-affinity heparin, but the trisaccharide 4 appears not to bind.


Catalytic Enantioselective Amination of Enol Silyl Ethers Using a Chiral Paddle-Wheel Diruthenium Complex.
A chiral paddle-wheel dinuclear ruthenium catalyst was applied to a catalytic asymmetric nitrene-transfer reaction with enol silyl ethers. The ruthenium catalyst was applicable to aliphatic enol silyl ethers as well as aryl-containing enol silyl ethers. The substrate scope of the ruthenium catalyst was superior to that of analogous chiral paddle-wheel rhodium catalysts. α-Amino ketones derived from aliphatic substrates were obtained in up to 97% ee with the ruthenium catalyst, while analogous rhodium catalysts resulted in only moderate enantioselectivity.


Evaluation of the chest radiograph in the emergency department patient.
This article discusses the differential diagnosis of abnormal radiographic patterns most commonly seen in emergency department patients with chest disease. Conditions associated with trauma are also described.


Delayed diagnosis of prostate cancer with neuroendocrine differentiation after laser TURP.
Laser transurethral resection of the prostate (TURP) is becoming widely used for surgical management of lower urinary tract symptoms from benign prostatic hyperplasia. Yet, one drawback to laser vaporization is the lack of a prostatic tissue sample for pathologic evaluation. We report the case of a 57-year-old man who presented with urinary obstruction, a normal digital rectal examination and a prostate-specific antigen level of 0.44 ng/mL. The patient then underwent transrectal ultrasonography to determine the size of his prostate (60 g). On the basis of these normal findings, laser TURP was performed. The patient's symptoms did not improve after the procedure, and cystoscopy confirmed continued prostatic obstruction. The patient subsequently underwent bipolar TURP, and the pathologic examination of the prostate chips revealed highly aggressive prostate adenocarcinoma with neuroendocrine differentiation. We discuss the potential drawbacks of laser TURP in the diagnosis of clinically undetectable prostate cancer.


Assay of acetylsalicylic acid and three of its metabolites in human plasma and urine using non-aqueous capillary electrophoresis with reversed electroosmotic flow.
The separation of acetylsalicylic acid and three of its metabolites--salicylic acid, salicyluric acid and gentisic acid--is demonstrated in a non-aqueous capillary electrophoresis system with reversed electroosmotic flow. Solvent mixtures of methanol and acetonitrile are used for the electrophoresis media and different electrolytes have been investigated. The flow is reversed by the addition of the polycation hexadimethrine bromide and thus a negative voltage is used. This system provides a fast and effective separation of the four analytes. The separation method was applied to the assay of acetylsalicylic acid and its major metabolites in plasma and urine and the limits of quantification for all of these compounds are about 5 microg ml(-1) in plasma and 25 microg ml(-1) in urine.


SARS-CoV-2 in infant urine and fecal samples after in utero COVID-19 exposure.
Coronavirus disease 2019 (COVID-19) is a pandemic that has and will continue to affect many pregnant women. Knowledge regarding the risk of vertical transmission is limited. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs typically have been used to confirm the diagnosis among infants, but whether the virus can be detected in other biological specimens, and therefore potentially transmitted in other ways, is unknown. Positive SARS-CoV-2 RT-PCR has been reported from feces and urine from adult patients. We hypothesize that the presence of SARS-CoV-2 in infant urine and fecal samples after prenatal COVID-19 exposure is low. We examined the presence of SARS-CoV-2 RNA using RT-PCR in urine and fecal samples among 42 infants born to SARS-CoV-2-infected mothers during different stages of pregnancy. A urine sample was collected from 39 of 42 infants and fecal samples from all 42 infants shortly after birth. Although the majority of the women had the symptomatic disease (85.6%), we were unable to detect the presence of SARS-CoV-2 virus from any infant urine or fecal samples. SARS-CoV-2 was not detected in infant urine or feces after maternal infection during pregnancy, providing further evidence for low rates of perinatal transmission. SARS-CoV-2 was not detected in the urine or feces of infants of mothers with COVID-19 during various time points in pregnancy. This study provides further evidence for low rates of perinatal transmission of SARS-CoV-2. Results help to provide guidance on perinatal care practices for infants exposed to COVID-19 in utero.


Statistically designed experiments in a tiered approach to screen mixtures of Fusarium mycotoxins for possible interactions.
This paper presents a test strategy to detect interactive effects between several mycotoxins using a DNA synthesis inhibition assay in L929 cells. The joint action of the Fusarium mycotoxins T-2 toxin (T2), deoxynivalenol (DON), nivalenol (NIV), zearalenone (ZEA) and fumonisin (FB1) was studied in a tiered approach. In the first stage, the mycotoxins were tested either jointly in a five-compound mixture, or individually. At the highest dose level, the mixture showed a clear less than additive action of the mycotoxins, as compared to the effects of the five individual compounds, whereas at lower dose levels the mycotoxins behaved additive. In the second stage, the non-additivity as established in the first experiment was further analyzed with a central composite design to detect interactions between specific mycotoxins in the mixture. This experiment confirmed less than additivity for five of the mixes tested. However, it also revealed four significant synergistic interactions between mycotoxins. Finally, two interactions that were established in stage 2 were further studied in full factorial designs involving two mycotoxins. One of the interactions observed in the central composite design was retrieved whereas the other two-factor interaction was not. It was concluded that several classes of mycotoxins when present simultaneously in a mixture might show interaction. The effect of the mixture cannot be predicted solely on the basis of the effect of the individual compounds.


Data Envelopment Analysis in the Presence of Measurement Error: Case Study from the National Database of Nursing Quality Indicators® (NDNQI®).
Data Envelopment Analysis (DEA) is the most commonly used approach for evaluating healthcare efficiency (Hollingsworth, 2008), but a long-standing concern is that DEA assumes that data are measured without error. This is quite unlikely, and DEA and other efficiency analysis techniques may yield biased efficiency estimates if it is not realized (Gajewski, Lee, Bott, Piamjariyakul and Taunton, 2009; Ruggiero, 2004). We propose to address measurement error systematically using a Bayesian method (Bayesian DEA). We will apply Bayesian DEA to data from the National Database of Nursing Quality Indicators® (NDNQI®) to estimate nursing units' efficiency. Several external reliability studies inform the posterior distribution of the measurement error on the DEA variables. We will discuss the case of generalizing the approach to situations where an external reliability study is not feasible.


Identification of Leishmania species by a specific DNA probe that is conserved only in the maxicircle DNA of human-infective Leishmania parasites.
An A + T-rich repeated DNA sequence cloned from maxicircle DNA of Leishmania mexicana amazonensis was found to be conserved in the maxicircles of human-infective Leishmania species but totally absent from non-human-infective ones. Differences in the pattern of distribution of this repeated sequence in the maxicircles of each human-infective Leishmania species potentially allow the development of a sensitive probe to differentiate among these species.


Progressive intracranial fusiform aneurysms and T-cell immunodeficiency.
In the pediatric population, intracranial fusiform aneurysms have been associated with human immunodeficiency virus/acquired immunodeficiency syndrome and rarely with opportunistic infections related to other immunodeficiencies. The HIV virus and other infectious organisms have been implicated in the pathophysiology of these aneurysms. We present a child with T-cell immunodeficiency but no evidence of human immunodeficiency virus or opportunistic intracranial infections that developed progressive bilateral fusiform intracranial aneurysms. Our findings suggest a role of immunodeficiency or inflammation in the formation of some intracranial aneurysms.


Increases in lung prolyl hydroxylase and superoxide dismutase activities during bleomycin-induced lung fibrosis in hamsters.
Intratracheal administration of bleomycin causes pulmonary fibrosis in hamsters. Using this model the activities of lung prolyl hydroxylase and superoxide dismutase and the accumulation of neutral salt soluble and insoluble collagens have been determined. One unit of bleomycin was injected intratracheally to hamsters, whereas control animals received an equivalent volume of sterile saline by the same route. Total lung prolyl hydroxylase activity was significantly elevated at all times following bleomycin treatment. The activity was increased as early as 2 days, peaked to a maximum value of 400% of the control at 14 days, followed by a sharp decline to 235% and 180% of the control activity at 21 and 28 days after bleomycin treatment, respectively. Except for the earliest time (2 days), lung prolyl hydroxylase specific activity was also significantly elevated at all times after bleomycin treatment. A significant increase in both total and specific activities of lung superoxide dismutase was also observed at all times after bleomycin treatment. Total activity peaked to a maximum value of 315% of the control activity at 14 days and the specific activity to a maximum value of 190% of the control at 21 days after bleomycin treatment. Thereafter, both activities declined, but were still significantly elevated over the control at 28 days after the treatment. Lung proline pool size was significantly increased at all times and attained a maximum value of 372% of the control at 14 days after bleomycin treatment. Increases in the lung prolyl hydroxylase and superoxide dismutase activities and in the proline pool size preceded the significant increases in neutral salt soluble and insoluble collagens which occurred at 7 days after bleomycin treatment and continued to be significantly elevated for the remaining period of the study.


[Hepatobiliary clearance of glycocholic acid in Gilbert's disease].
To research the behaviour of one biliary acid (glyco-cholic) i.v. injected in patients with Gilbert's disease and in healthy controls, so that contribute to the knowledge of the pathophysiological correlate between bilirubin and biliary acids. We include 15 patients with Gilbert's disease and 7 healthy voluntary ones. We injected i.v. glycocholic acid and obtained the clearance curve (CG-RIA Abbot method). We evaluated the possible biostatistically significant differences between the obtained values of both groups though the non-parametric method of Mann-Whitney. The clearance curve of both groups had a similar profile; biostatisticaly there are not significant differences between the serum values of glyco-cholic acid in both groups. The clearance of the glyco-cholic acid in patients with Gilbert's disease had a similar behaviour as in healthy controls, without biostatisticaly significant differences between both groups.


[Louis, anxiety faced with the other and language].
Faced with a child's psychosis--and its occurrences--the psychologist must remain humble. Team work will help to modify the massive transference which sometimes binds the psychologist to the psychotic subject (erotomania or persecution).


Pydna: a simulation and documentation tool for DNA assembly strategies using python.
Recent advances in synthetic biology have provided tools to efficiently construct complex DNA molecules which are an important part of many molecular biology and biotechnology projects. The planning of such constructs has traditionally been done manually using a DNA sequence editor which becomes error-prone as scale and complexity of the construction increase. A human-readable formal description of cloning and assembly strategies, which also allows for automatic computer simulation and verification, would therefore be a valuable tool. We have developed pydna, an extensible, free and open source Python library for simulating basic molecular biology DNA unit operations such as restriction digestion, ligation, PCR, primer design, Gibson assembly and homologous recombination. A cloning strategy expressed as a pydna script provides a description that is complete, unambiguous and stable. Execution of the script automatically yields the sequence of the final molecule(s) and that of any intermediate constructs. Pydna has been designed to be understandable for biologists with limited programming skills by providing interfaces that are semantically similar to the description of molecular biology unit operations found in literature. Pydna simplifies both the planning and sharing of cloning strategies and is especially useful for complex or combinatorial DNA molecule construction. An important difference compared to existing tools with similar goals is the use of Python instead of a specifically constructed language, providing a simulation environment that is more flexible and extensible by the user.


Identification and catheter ablation of a zone of slow conduction in the reentrant circuit of ventricular tachycardia in humans.
Three patients who had incessant ventricular tachycardia and in whom a zone of slow conduction was identified are presented. Each patient's tachycardia was refractory to multiple antiarrhythmic drugs and was being treated with amiodarone at the time of the electrophysiologic study. The ventricular tachycardia cycle length was 500 to 580 ms. In Patients 1 and 2, a single site at the posterolateral wall or low septum in the left ventricle was identified at which overdrive pacing during ventricular tachycardia resulted in ventricular capture with a stimulus to QRS interval of 280 to 400 ms and with little or no change in the configuration of the QRS complexes during pacing as compared with during ventricular tachycardia. In Patient 3, the same phenomenon was observed at two areas in the left ventricle: at the inferior wall, overdrive pacing during ventricular tachycardia resulted in a stimulus to QRS interval of 440 to 470 ms, whereas at the posterolateral wall, the stimulus to QRS interval was 320 to 360 ms. Transcatheter shocks of 100 to 240 J delivered at the pacing sites have been successful in preventing recurrences of ventricular tachycardia over a follow-up period of 10 to 11 months. These observations may be explained by the pacing site being located within a reentrant circuit in a zone of slow conduction bounded by inexcitable tissue between the pacing site and the exit site of the reentrant circuit. In Patient 3, the variable stimulus to QRS intervals are explained by variable proximity of the pacing sites within the slow conduction zone to the exit site of the reentrant circuit.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy assessment of local doxycycline treatment in periodontal patients using multivariate chemometric approach.
The aim of our study was application of chemometric algorithms for multivariate data analysis in efficacy assessment of the local periodontal treatment with doxycycline (DOX). Treatment efficacy was evaluated by monitoring inflammatory biomarkers in gingival crevicular fluid (GCF) samples and clinical indices before and after the local treatment as well as by determination of DOX concentration in GCF after the local treatment. The experimental values from these determinations were submitted to several chemometric algorithms: principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA). The data structure and the mutual relations of the selected variables were thoroughly investigated by PCA. The PLS-DA model identified variables responsible for discrimination of classes of data, before and after DOX treatment. The OPLS-DA model compared the efficacy of the two commonly used medications in periodontal treatment, chlorhexidine (CHX) and DOX, at the same time providing insight in their mechanism of action. The obtained results indicate that application of multivariate chemometric algorithms can be used as a valuable approach for assessment of treatment efficacy.


The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer.
The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-beta (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.


[Auscultatory detection of respiratory responses to olfactory stimuli. Approach to feigned anosmia (author's transl)].
The auscultation of breathing noise facilitates the detection of responses to smelled stimuli. In addition the noise of respiration may be recorded. The phenomenon has been used during the evaluation of nonorganic anosmia.


Demonstration of neutralizing and non-neutralizing epitopes on the trypsin-sensitive site of foot-and-mouth disease virus.
The isolation of monoclonal antibodies directed against the trypsin-sensitive site on the 140S particle of foot-and-mouth disease virus (FMDV) has enabled the demonstration of at least three distinct epitopes within this site. Reaction with two of these resulted in neutralization of virus infectivity. None of the epitopes appeared to be present on the 12S particles, and one of the neutralizing epitopes was sensitive to even milder configurational changes of the particle.


Pretransplant C-reactive protein as a prognostic marker in allogeneic stem cell transplantation: A PRISMA-compliant meta-analysis.
Numerous reports have explored the prognostic value of pretransplant serum C-reactive protein (CRP) in patients receiving allogeneic stem cell transplant (ASCT), but the results remain conflicting. Therefore, we performed a meta-analysis to comprehensively assess the prognostic value of pretransplant serum CRP in patients receiving ASCT. We systematically searched eligible studies in PubMed, Embase, and Web of Science from 1999 to September 2018. The pooled hazard ratios (HRs) and their corresponding 95% CIs were used to synthetically assess the prognostic value of pre-ASCT CRP in terms of overall survival (OS), non-relapse mortality (NRM), and acute graft versus host disease (aGVHD). A total of 14 articles with 15 studies containing 3458 patients were included in this meta-analysis. The pooled results showed that high pre-ASCT CRP level was significantly related to worse OS (HR = 1.63; 95% CI: 1.34-1.98; P < .05), to an increased risk of NRM (HR = 2.06; 95% CI: 1.62-2.62; P < .05), and aGVHD (HR = 1.35; 95% CI: 1.07-1.71; P < .05). Additionally, sensitivity and subgroup analyses demonstrated that our pooled results were stable and reliable. High pre-ASCT serum CRP was significantly associated with worse OS, as well as higher risk of NRM and aGVHD. CRP may be a candidate factor of updating the existing risk scoring systems or establishing a novel risk scoring systems, which has the potential of guiding patient selection for ASCT and proceeding with risk-adapted therapeutic strategies. However, more high-quality clinical studies and basic research are required to further validate our findings in view of several limitations in our meta-analysis.


A New Species of Typhlomys (Platacanthomyidae, Rodentia) from the Middle Pleistocene of Northern Vietnam.
A pygmy dormouse Typhlomys stegodontis sp. nov. is described on the base of the maxillary fragment and isolated teeth from the Middle Pleistocene Tham Hai cave locality in northern Vietnam (Lang Son Province). This first finding of the fossil Platacanthomyidae in Vietnam fills the Middle Pleistocene gap in the paleontological record of the family.


Clinical and radiological evaluation of surgical treatment of medial epicondyle fractures of humerus in children. A two-centre study.
The present study analyses the outcome of open reduction and internal fixation (ORIF) of humerus medial epicondyle fracture with the use of Kirschner (K) wires, and determine the effect of elbow dislocation. The study included 112 patients operated on in 2005-2016. Of these, 81presented with an isolated medial epicondyle fracture (mean age 11.6 years), and 31 with an elbow dislocation (mean age 11.9 years). Out of 112 patients tested, 98 achieved an excellent treatment result, ten good and a mean Mayo Elbow Performance Score (MEPS); no significant differences were observed between dislocated and non-dislocated elbow groups. Those with an isolated medial epicondyle fracture demonstrated a mean flexion of 140.7° and extension deficit of 3.0°, while those with an elbow dislocation displayed a mean flexion of 134.5° and extension deficit 6.1°. The dislocation group demonstrated significantly greater extension and flexion deficits (p = 0.019, p < 0.001, respectively). One patient required revision surgery due to nonunion. Ulnar nerve function was normal in 110 patients: in the other two, it resolved spontaneously in one, and the nerve was transposed in the other. Medial elbow instability was found in seven patients: two with elbow dislocation and five without. ORIF with K wires is a safe procedure for treating medial epicondyle humeral fractures that yields good or very good results. Similar outcomes are observed between patients with and without dislocation according to MEPS; however, flexion and extension are more limited in the former group.


Age-related atrophy of cortical thickness and genetic effect of ANK3 gene in first episode MDD patients.
Brain ageing is thought to be related to geriatric depression, but the relationship between ageing and depression among middle aged individuals is unknown. The present study aimed to evaluate whether the age-related reduction of brain cortical thickness (CT) can be found in adult first-episode MDD patients, as well as to identify the possible genetic effect of the ANK3 gene polymorphism age-relates CT reduction. This study recruited 153 first-episode MDD patients with a disease duration < 2 years and 276 healthy controls (HC), and the CT of 68 whole brain regions and two ANK3 SNPs (rs1994336 and rs10994359) were analyzed. The results showed that although the CT of both groups was negative correlated with age, the MDD group had significant greater age-related decrease in CT than the HC group (-9.35 × 10-3 mm/year for MDD vs. -1.23 × 10-3 mm/year for HC in the left lateral orbitofrontal lobe). The multivariate analysis of covariance (MANCOVA) results yielded significant interactions of diagnosis × age, genotype × age and diagnosis × genotype interaction for rs10994359. In HC, the C allele showed a protective effect on age-related CT reduction. The reduction in CT with age was several times as greater in non-C carriers as in C carriers (-3.54 × 10-3 vs.-0.15 × 10-3 mm/year in left supramarginal gyrus) for HC. However, this protective effect disappeared in patients with MDD. We did not find a clear effect of rs1994336 on the age-related CT reduction. The findings indicate that the widespread accelerated brain ageing occurs early in adult-onset depression and this ageing may be a pathological mechanisms of depression rather than an outcome of the disease. The ANK3 rs10994359 polymorphism may partially affect regional cortical ageing in MDD.


Novel therapeutic compound tuftsin-phosphorylcholine attenuates collagen-induced arthritis.
Treatment with helminthes and helminthes ova improved the clinical symptoms of several autoimmune diseases in patients and in animal models. Phosphorylcholine (PC) proved to be the immunomodulatory molecule. We aimed to decipher the tolerogenic potential of tuftsin-PC (TPC), a novel helminth-based compound in collagen-induced arthritis (CIA) a mouse model of rheumatoid arthritis (RA). CIA DBA/1 mice were treated with TPC subcutaneously (5 µg/0.1 ml) or orally (250 µg/0.1 ml), starting prior to disease induction. The control groups were treated with PBS. Collagen antibodies were tested by enzyme-linked immunosorbent assay (ELISA), cytokine protein levels by ELISA kits and regulatory T (Treg ) and regulatory B (Breg ) cell phenotypes by fluorescence-activated cell sorter (FACS). TPC-treated mice had a significantly lower arthritis score of 1.5 in comparison with control mice 11.8 (P < 0.0001) in both subcutaneous and orally treated groups at day 31. Moreover, histology analysis demonstrated highly inflamed joints in control mice, whereas TPC-treated mice maintained normal joint structure. Furthermore, TPC decreased the titres of circulating collagen II antibodies in mice sera (P < 0.0001), enhanced expression of IL-10 (P < 0.0001) and inhibited production of tumour necrosis factor (TNF)-α, interleukin (IL)-17 and IL-1β (P < 0.0001). TPC significantly expanded the CD4(+) CD25(+) forkhead box protein 3 (FoxP3(+) ) Treg cells and CD19(+) IL-10(+) CD5(high) CD1d(high) T cell immunoglobulin mucin-1 (TIM-1(+) ) Breg cell phenotypes (P < 0.0001) in treated mice. Our data indicate that treatment with TPC attenuates CIA in mice demonstrated by low arthritic score and normal joints histology. TPC treatment reduced proinflammatory cytokines and increased anti-inflammatory cytokine expression, as well as expansion of Treg and Breg cells. Our results may lead to a new approach for a natural therapy for early rheumatoid arthritis onset.


Intense beam of metastable Muonium.
Precision spectroscopy of the Muonium Lamb shift and fine structure requires a robust source of 2S Muonium. To date, the beam-foil technique is the only demonstrated method for creating such a beam in vacuum. Previous experiments using this technique were statistics limited, and new measurements would benefit tremendously from the efficient 2S production at a low energy muon ( < 20 keV) facility. Such a source of abundant low energy μ + has only become available in recent years, e.g. at the Low-Energy Muon beamline at the Paul Scherrer Institute. Using this source, we report on the successful creation of an intense, directed beam of metastable Muonium. We find that even though the theoretical Muonium fraction is maximal in the low energy range of 2-5 keV, scattering by the foil and transport characteristics of the beamline favor slightly higher μ + energies of 7-10 keV. We estimate that an event detection rate of a few events per second for a future Lamb shift measurement is feasible, enabling an increase in precision by two orders of magnitude over previous determinations.


Alanine transaminase and hemoglobin appear to predict the occurrence of antituberculosis medication hepatotoxicity; findings and implications in Botswana.
Tuberculosis (TB) remains a global health problem, with medications having adverse effects including drug-induced hepatotoxicity. We determined the prevalence of anti-tuberculosis drug-induced hepatotoxicity and associated risk factors. Retrospective cross-sectional study in Botswana including TB patients admitted from 1 June 2017 to 30 June 2018. Anti-TB drug-induced hepatotoxicity was categorized according to WHO criteria whereas causality assessment was made according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) scale. The association between hepatotoxicity and included variables was undertaken by binary logistic regression. Out of 112 patient files, 15 (13.4%) developed hepatotoxicity after an average of 20.4 days from the start of treatment. Grade 3 and 4 hepatotoxicity was found in 66.7% of the cases. According to the updated RUCAM tool, 86.7% of patients were categorized as having possible anti-TB-associated hepatotoxicity. Patients with elevated baseline alanine transaminase (ALT) were more likely to develop hepatotoxicity (OR = 3.484, 95% CI = 1.02-11.90). Patients with normal hemoglobin (Hb ≥ 12 g/dl) were also more likely to develop hepatotoxicity (OR = 4.413, 95% CI = 1.160-14.8). Overall, normal hemoglobin and elevated baseline ALT levels were significantly associated with anti-TB drug-induced hepatotoxicity. Additional research is needed to explore this association further.


A novel association between platelet filamin A and soluble N-ethylmaleimide sensitive factor attachment proteins regulates granule secretion.
The molecular mechanisms that underpin platelet granule secretion remain poorly defined. Filamin A (FLNA) is an actin-crosslinking and signaling scaffold protein whose role in granule exocytosis has not been explored despite evidence that FLNA gene mutations confer platelet defects in humans. Using platelets from platelet-specific conditional Flna-knockout mice, we showed that the loss of FLNA confers a severe defect in alpha (α)- and dense (δ)-granule exocytosis, as measured based on the release of platelet factor 4 (aka CXCL4) and adenosine triphosphate (ATP), respectively. This defect was observed following activation of both immunoreceptor tyrosine-based activation motif (ITAM) signaling by collagen-related peptide (CRP) and G protein-coupled receptor (GPCR) signaling by thrombin and the thromboxane mimetic U46619. CRP-induced spikes in intracellular calcium [Ca2+]i were impaired in FLNA-null platelets relative to controls, confirming that FLNA regulates ITAM-driven proximal signaling. In contrast, GPCR-mediated spikes in [Ca2+]i in response to thrombin and U46619 were unaffected by FLNA. Normal platelet secretion requires complexing of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptosomal-associated protein 23 (SNAP23) and syntaxin-11 (STX11). We determined that FLNA coimmunoprecipitates with both SNAP23 and STX11 upon platelet stimulation. FLNA regulates GPCR-driven platelet granule secretion and associates with SNAP23 and STX11 in an activation-dependent manner.


Long noncoding RNA, CCDC26, controls myeloid leukemia cell growth through regulation of KIT expression.
Accumulating evidence suggests that some long noncoding RNAs (lncRNAs) are involved in certain diseases, such as cancer. The lncRNA, CCDC26, is related to childhood acute myeloid leukemia (AML) because its copy number is altered in AML patients. We found that CCDC26 transcripts were abundant in the nuclear fraction of K562 human myeloid leukemia cells. To examine the function of CCDC26, gene knockdown (KD) was performed using short hairpin RNAs (shRNAs), and four KD clones, in which CCDC26 expression was suppressed to 1% of its normal level, were isolated. This down-regulation included suppression of CCDC26 intron-containing transcripts (the CCDC26 precursor mRNA), indicating that transcriptional gene suppression (TGS), not post-transcriptional suppression, was occurring. The shRNA targeting one of the two CCDC26 splice variants also suppressed the other splice variant, which is further evidence for TGS. Growth rates of KD clones were reduced compared with non-KD control cells in media containing normal or high serum concentrations. In contrast, enhanced growth rates in media containing much lower serum concentrations and increased survival periods after serum withdrawal were observed for KD clones. DNA microarray and quantitative polymerase chain reaction screening for differentially expressed genes between KD clones and non-KD control cells revealed significant up-regulation of the tyrosine kinase receptor, KIT, hyperactive mutations of which are often found in AML. Treatment of KD clones with ISCK03, a KIT-specific inhibitor, eliminated the increased survival of KD clones in the absence of serum. We suggest that CCDC26 controls growth of myeloid leukemia cells through regulation of KIT expression. A KIT inhibitor might be an effective treatment against the forms of AML in which CCDC26 is altered.


[Role of P38 signaling pathway in neonatal rat astrocyte swelling and aquaporin-4 expression after oxygen-glucose deprivation and recovery].
To explore the role of P38 signaling pathway in neonatal rat astrocyte swelling and the expression of aquaporin-4 (AQP4) after oxygen-glucose deprivation (OGD) and recovery (OGD/R). Primarily cultured neonatal rat astrocytes were subject to OGD for 5 h followed by oxygen-glucose recovery in the presence or absence of the P38 inhibitor SB203580 (10 µmol/L). The astrocytes were investigated at 0.5, 2, 8 and 24 h after oxygen-glucose recovery for morphological changes and cell injuries using lactate dehydrogenase (LDH) assay. The expressions of P38, P-P38, and AQP4 mRNAs and proteins in the astrocytes were detected using RT-PCR and Western blotting. OGD/R caused significantly enhanced expression of P-P38 protein, and this effect was blocked by SB203580. AQP4 mRNA and protein expression declined transiently at 0.5 h after OGD and increased gradually to reach the peak level at 8 h (P<0.05). Application of the SB203580 significantly lowered OGD-induced AQP4 mRNA and protein up-regulation (P<0.05). Astrocyte swelling occurred after OGD/R but was obviously lessened by SB203580. LDH release increased markedly after OGD/R, and was attenuated by treatment with SB203580 (P<0.01). P38 signaling pathway participates in astrocyte swelling after OGD/R, and blocking this pathway can attenuate AQP4 up-regulation and ameliorate the cell swelling.


Monocytes P2X7 purinergic receptor is modulated by glatiramer acetate in multiple sclerosis.
The aim of this study is to investigate the expression of P2X7R, IL-1beta and the ATP activity modulating ecto-apyrase CD39 on peripheral blood monocytes of MS patients and to observe the possible effects of Glatiramer Acetate (GA) on such expression. Twelve RR treatment-free MS patients were selected and peripheral blood monocytes were obtained. The expression of P2X7R, IL-1beta and CD39 on monocytes was investigated by qrt-PCR. The in vitro effects of GA on the expression of monocytes stimulated with BzATP (a potent P2X7R agonist)-were evaluated. Ten healthy donors (HDs) were similarly studied. Finally, 5 MS patients were given GA therapy and the monocytes obtained before treatment, after 3 and 12 months of GA treatment were similarly investigated. No differences were found in P2X7R, IL-1beta and CD39 expression between patients and controls. In MS Bz-ATP stimulated monocytes, GA pre-conditioning clearly downregulated P2X7R (p=0.003) but IL-1beta expression also showed a decreasing trend (p=0.07). Conversely, CD39 showed an increasing trend (p=0.07). Similar evidence was found in HDs. GA in vivo treatment induced a reduction in the expression that was clear for P2X7R and CD39 (p<0.05) but only not significant for IL-1beta after 12 months of treatment. Monocytes from both MS and control subjects express P2X7R, IL-1beta and CD39, and GA seems to interfere with such expression.


Comparison of congenital pulmonary airway malformation volume ratios calculated by ultrasound and magnetic resonance imaging.
To compare congenital pulmonary airway malformation (CPAM) volume to head circumference ratios (CVRs) determined by different imaging modalities and calculation techniques. Fetal thoracic lesion images by ultrasound (US) and magnetic resonance imaging (MRI) were retrospectively reviewed and the CVRs were calculated. The CVR(US) was determined by the standard method. The CVR(MRI) was calculated from T2-weighted sequences (HASTE/SSH-TSE) in two ways, dimensional measurements analogous to US technique (MRI-D) and by using a MRI-software calculated volume (MRI-V). CVR values between methods were compared using Wilcoxon matched-pairs signed-rank testing, Bland-Altman analyses, and Spearman correlations. Appropriate images were available to compare CVR(US) to CVR(MRI-D) for 20 patients and CVR(US) to CVR(MRI-V) for 18 patients. There were no significant differences in CVR values between modalities. By Bland-Altman analyses, the CVR measurements were largely within the limits of agreement: 18 of 20 for CVR(MRI-D) and 17 of 18 for CVR(MRI-V), with a slight bias towards larger measurements by MRI. Though values varied between modalities for individual patients, there was no systematic difference in CVRs determined by US or MRI. Fetal prognostic category for CPAMs did not change based on MRI in any patient in this series.


Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications.
Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from most adult tissues, including bone marrow, adipose, liver, amniotic fluid, lung, skeletal muscle and kidney. The term MSC is currently being used to represent both mesenchymal stem cells and multipotent mesenchymal stromal cells. Numerous reports on systemic administration of MSCs leading to functional improvements based on the paradigm of engraftment and differentiation have been published. However, it is not only difficult to demonstrate extensive engraftment of cells, but also no convincing clinical results have been generated from phase 3 trials as of yet and prolonged responses to therapy have been noted after identification of MSCs had discontinued. It is now clear that there is another mechanism by which MSCs exert their reparative benefits. Recently, MSCs have been shown to possess immunomodulatory properties. These include suppression of T cell proliferation, influencing dendritic cell maturation and function, suppression of B cell proliferation and terminal differentiation, and immune modulation of other immune cells such as NK cells and macrophages. In terms of the clinical applications of MSCs, they are being tested in four main areas: tissue regeneration for cartilage, bone, muscle, tendon and neuronal cells; as cell vehicles for gene therapy; enhancement of hematopoietic stem cell engraftment; and treatment of immune diseases such as graft-versus-host disease, rheumatoid arthritis, experimental autoimmune encephalomyelitis, sepsis, acute pancreatitis and multiple sclerosis. In this review, the mechanisms of immunomodulatory effects of MSCs and examples of animal and clinical uses of their immunomodulatory effects are described.


The role of orphan crops in the transition to nutritional quality-oriented crop improvement.
Micronutrient malnutrition is a persisting problem threatening global human health. Biofortification via metabolic engineering has been proposed as a cost-effective and short-term means to alleviate this burden. There has been a recent rise in the recognition of potential that underutilized, orphan crops can hold in decreasing malnutrition concerns. Here, we illustrate how orphan crops can serve as a medium to provide micronutrients to populations in need, whilst promoting and maintaining dietary diversity. We provide a roadmap, illustrating which aspects to be taken into consideration when evaluating orphan crops. Recent developments have shown successful biofortification via metabolic engineering in staple crops. This review provides guidance in the implementation of these successes to relevant orphan crop species, with a specific focus on the relevant micronutrients iron, zinc, provitamin A and folates.


Operation rate and cancer prevalence among thyroid nodules with FNAC report of suspicious for malignancy (TIR4) or malignant (TIR5) according to Italian classification system: a systematic review and meta-analysis.
In the Italian system for reporting thyroid cytology (ICCRTC), nodules suspicious for (TIR4) and consistent with (TIR5) malignancy are thought being 5% and 4-8% of all biopsies and having risk of malignancy of 60-80% and >95%, respectively. However, no evidence-based data exist about these figures. The present systematic review aimed at achieving solid estimates about TIR4 and TIR5 also considering potential influencing factors. The review was conducted according to MOOSE. Databases of Google Scholar and Cochrane were searched. No language restriction was used. The last search was performed on February 26th 2022. Quality assessment was performed. Proportion meta-analyses were performed using random-effect model. Statistical analyses were performed using OpenMeta [Analyst]. The online search retrieved 271 articles and 16 were finally included for quantitative analysis. The risk of bias was generally low. The pooled cancer prevalence in TIR4 was 92.5% (95%CI 89.4-95.6%) with unexplained moderate heterogeneity. The pooled cancer rate among TIR5 was 99.7% (95%CI 99.3-100%) without heterogeneity. The resection rate in TIR4 and TIR5 showed heterogeneity, being the latter explained when using their prevalence among biopsies: the higher the prevalence, the higher the operation rate. The pooled risk difference between TIR5 and TIR4 was significant (OR 11.153). These figures can form the basis for the next updated version of ICCRTC. Any institution using ICCRTC should revise its series of TIR4/TIR5 to calculate the cancer rate, and, importantly, consider the modifiers of the risk of malignancy. A cross check among institutions is advised.


Hypokalemia among patients receiving treatment for multidrug-resistant tuberculosis.
Between January 1999 and December 2000, 125 patients in Lima, Peru were enrolled in individualized treatment for multidrug-resistant tuberculosis (MDR-TB). Hypokalemia was observed to be an important adverse effect encountered in this cohort. To identify risk factors associated with the development and persistence of hypokalemia during MDR-TB therapy, and to review the incidence and management of hypokalemia in patients receiving MDR-TB therapy. A retrospective case series of 125 patients who received individualized therapy for MDR-TB between January 1, 1999, and December 31, 2000. Among 115 patients who were screened for electrolyte abnormalities, 31.3% had hypokalemia, defined as a potassium level of < 3.5 mEq/L. Mean serum potassium at time of diagnosis was 2.85 mEq/L. Diagnosis of low serum potassium occurred, on average, after 5.1 months of individualized therapy. Multivariate analysis of risk factors for this adverse reaction identified two causes: administration of capreomycin, and low initial body weight. Normalization of potassium levels was achieved in 86% of patients. Electrolyte disturbance was frequently encountered in our cohort of patients with MDR-TB. Successful screening and management of hypokalemia was facilitated by training the health-care team in the use of a standardized algorithm. Morbidity from hypokalemia can be significant; however, effective management of this side effect is possible without sacrificing MDR-TB treatment efficacy.


Reduced auditory evoked potential component N100 in schizophrenia--a critical review.
The role of a reduced N100 (or N1) component of the auditory event related potential as a potential trait marker of schizophrenia is critically discussed in this review. We suggest that the extent of the N100 amplitude reduction in schizophrenia depends on experimental and subject factors, as well as on clinical variables: N100 is more consistently reduced in studies using interstimulus intervals (ISIs) >1 s than in studies using shorter ISIs. An increase of the N100 amplitude by allocation of attention is often lacking in schizophrenia patients. A reduction of the N100 amplitude is nevertheless also observed when such an allocation is not required, proposing that both endogenous and exogenous constituents of the N100 are affected by schizophrenia. N100 is more consistently reduced in medicated than unmedicated patients, but a reduction of the N100 amplitude as a consequence of antipsychotic medication was shown in only two of seven studies. In line with that, the association between the N100 reduction and degree of psychopathology of patients appears to be weak overall. A reduced N100 amplitude is found in first degree relatives of schizophrenia patients, but the risk of developing schizophrenia is not reflected in the N100 amplitude reduction.


Acute blood pressure changes after the onset of atrioventricular nodal reentrant tachycardia: a time-course analysis.
We aimed to characterize blood pressure (BP) response at the beginning of atrioventricular nodal reentrant tachycardia (AVNRT) and its relationship to orthostatic challenge and variable atrioventricular interval. In this prospective study of 17 consecutive patients with documented AVNRT, mean BP was analyzed in the supine and upright positions during sinus rhythm, AVNRT, and pacing with atrioventricular delay of 150 msec (AV150) and 0 msec (AV0). Mean BPs were compared at 3-5 seconds, 8-10 seconds, and 28-30 seconds after the onset of AVNRT or pacing. BP decreased immediately after AVNRT initiation, with gradual recovery during the first 30 seconds from 71.9 +/- 16.5 mmHg to 86 +/- 13.8 mmHg, P < 0.01. A similar pattern was observed during AV0, but not during AV150, pacing. While supine, mean BP decrease was more pronounced during AVNRT and AV0 pacing (-26.1% and -32.1%, respectively) than during AV150 pacing (-8%, P = 0.02 and P = 0.07, respectively). This difference subsided 30 seconds after the onset of AVNRT or pacing. When upright, the mean BP time course was similar, but mean BP recovery during AVNRT was slower, and the difference between mean BP during AVNRT and AV150 persisted at 30 seconds. The initial mean BP decrease during AVNRT recovered gradually within 30 seconds. A short atrioventricular interval is associated with a greater mean BP decrease at the onset of tachycardia. These observations may explain clinical symptoms immediately after the onset of AVNRT.


Melt electrowriting of PLA, PCL, and composite PLA/PCL scaffolds for tissue engineering application.
Fabrication of well-ordered and bio-mimetic scaffolds is one of the most important research lines in tissue engineering. Different techniques have been utilized to achieve this goal, however, each method has its own disadvantages. Recently, melt electrowriting (MEW) as a technique for fabrication of well-organized scaffolds has attracted the researchers' attention due to simultaneous use of principles of additive manufacturing and electrohydrodynamic phenomena. In previous research studies, polycaprolactone (PCL) has been mostly used in MEW process. PCL is a biocompatible polymer with characteristics that make it easy to fabricate well-arranged structures using MEW device. However, the mechanical properties of PCL are not favorable for applications like bone tissue engineering. Furthermore, it is of vital importance to demonstrate the capability of MEW technique for processing a broad range of polymers. To address aforementioned problems, in this study, three ten-layered box-structured well-ordered scaffolds, including neat PLA, neat PCL, and PLA/PCL composite are fabricated using an MEW device. Printing of the composite PLA/PCL scaffold using the MEW device is conducted in this study for the first time. The MEW device used in this study is a commercial fused deposition modeling (FDM) 3D printer which with some changes in its setup and configuration becomes prepared for being used as an MEW device. Since in most of previous studies, a setup has been designed and built for MEW process, the use of the FDM device can be considered as one of the novelties of this research. The printing parameters are adjusted in a way that scaffolds with nearly equal pore sizes in the range of 140 µm to 150 µm are fabricated. However, PCL fibers are mostly narrower (diameters in the range of 5 µm to 15 µm) than PLA fibers with diameters between 15 and 25 µm. Unlike the MEW process of PCL, accurate positioning of PLA fibers is difficult which can be due to higher viscosity of PLA melt compared to PCL melt. The printed composite PLA/PCL scaffold possesses a well-ordered box structure with improved mechanical properties and cell-scaffold interactions compared to both neat PLA and PCL scaffolds. Besides, the composite scaffold exhibits a higher swelling ratio than the neat PCL scaffold which can be related to the presence of less hydrophobic PLA fibers. This scaffold demonstrates an anisotropic behavior during uniaxial tensile test in which its Young's modulus, ultimate tensile stress, and strain to failure all depend on the direction of the applied tensile force. This anisotropy makes the composite PLA/PCL scaffold an exciting candidate for applications in heart tissue engineering. The results of in-vitro cell viability test using L929 mouse murine fibroblast and human umbilical vein endothelial (HUVEC) cells demonstrate that all of the printed scaffolds are biocompatible. In particular, the composite scaffold presents the highest cell viability value among the fabricated scaffolds. All in all, the composite PLA/PCL scaffold shows that it can be a promising substitution for neat PCL scaffold used in previous MEW studies.


Reduced myelinogenesis and recovery in hyperphenylalaninemic rats. Correlation between brain phenylalanine levels, characteristic brain enzymes for myelination, and brain development.
In a previous paper (Burri et al., 1990), we have shown that experimental hyperphenylalaninemia (hyper-Phe) in 3-17 d-old rats leads to reduced myelinogenesis. Such treated rats recover during a 6 w low phenylalanine (Phe) period between days 17 and 59. In order to get more detailed information about the disturbed myelinogenesis and recovery, we measured in hyper-Phe rats the developmental pattern of two brain enzymes typical for myelination, cerebroside sulfotransferase (CST), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), and other developmental parameters. Further, we correlated brain Phe levels with the brain damage in hyper-Phe rats, and we measured brain acetylcholinesterase (AChE) as a neuronal marker. Experimental hyper-Phe rats, injected between postnatal days 3 and 17 with alpha-methylphenylalanine and phenylalanine, showed a delayed age-dependent increase of CST activity, compared to that of controls. In hyper-Phe rats, CST peak activity was reached 2-4 d later, and was lower than in controls. The age-dependent decrease of the CST activity, however, started in test and control rats at the same time, at day 21. Between days 24 and 59, hyper-Phe rats had normal CST activity. CNP activity in hyper-Phe rats was lower than in controls from day 10 to 35, and recovered to normal values between days 35 and 59. Our results indicate that recovery from reduced myelinogenesis is possible after the period of fast myelination without compensatory increased CST activity. Further, the brain damage in test rats with Phe levels higher than average is more severe than in test rats with Phe levels lower than average; and there is no effect of hyperphenylalaninemia on brain neurons containing AChE.


Combined choriocarcinoma and adenocarcinoma of the lung.
Combined choriocarcinoma and adenocarcinoma in the lung of a 71-year-old Japanese male is reported. In the upper lobe of the right lung (S1 + 2), a choriocarcinoma coexisted with an adenocarcinoma, but distinct metastatic lesions were noticed separately in the lungs, kidney, bone marrow and lymph nodes. Although immunohistochemical examination revealed intensely positive reactivity with anti-human chorionic gonadotropin (HCG) in trophoblastic cells, weak immunoreactivities were also observed in a few cells with anti-human placental lactogen (HPL), anti-pregnancy-specific beta glycoprotein (SPI), anti-epithelial membrane antigen (EMA), anti-carcinoembryonic antigen (CEA), anti-cytokeratin (keratin) and KM-93 (lung adenocarcinoma-associated antibody). In the adenocarcinoma, the tumor cells were positively stained for CEA, EMA, keratin and KM-93, but there were no positive reactivities for HCG, HPL and SPI. These findings suggest that primary choriocarcinoma of the lung may arise through dedifferentiation of adenocarcinoma.


[Comparative antirachitic activity of 1,25-dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 in the chick].
1,25-dihydroxy vitamin D3 and its synthetic analogue 1 alpha-hydroxy vitamin D3 were administered into chicken at the doses of 0.025, 0.05 and 0.1 micrograms per day within 25 days. Effect of the vitamins was estimated by a net gain of biomass, by biochemical alterations in blood, synthesis of calcium-binding protein, relative mass of parathyroid glands and by content of inorganic residue in bone tissue. Both vitamin preparations exhibited similar antirickety activity.


A prospective and randomised study comparing the incidence of infusion phlebitis during continuous and cyclic peripheral parenteral nutrition.
Phlebitis is a major obstacle to successful and prolonged peripheral parenteral nutrition (PPN). This study evaluated the effects of elective changes of the intravenous cannula and cyclic infusion of PPN on the incidence and the severity of phlebitis. 51 consecutive patients requiring PPN were randomised into three groups. Group 1 received PPN continuously through a line which was changed only on evidence of phlebitis. In Group 2 intravenous lines were changed every 24h. Group 3 patients received PPN as a 12-h infusion after which the intravenous cannula was withdrawn. All patients received 1800 non-protein calories and 9.4g nitrogen daily. Infusion sites were assessed daily for phlebitis and this was scored using a modified Maddox scale. The mean (range) duration of PPN was 7.5 (1-13), 10.0 (2-42) and 8.2 (3-14) days in the three groups respectively. Severe phlebitis occurred more frequently (p < 0.05) in Group 1 compared to Group 2 or Group 3. The overall incidence of phlebitis assessed from the mean value of the Maddox scores for each group was highest in Group 1 and was significantly greater than that observed in either Group 2 (p < 0.05) or Group 3 (p < 0.001). Group 3 patients who received cyclic PPN had the lowest incidence of phlebitis. The results of this study suggest that the incidence of infusion phlebitis is minimised during PPN by the cyclic infusion of nutrient solutions.


A concept of immune regulation of somatic cell differentiation.
On the basis of several lines of experimental evidence a hypothesis is advanced on autoimmune regulation of somatic cell differentiation in an immunologically mature organism ("self-anti-self" hypothesis of differentiation). There are supposed to be clones of lymphocytes interacting via their antigen-recognizing receptors with autologous differentiation antigens on various target cells. This interaction would modify the genetically determined rate of cell differentiation. Some implications of the hypothesis are discussed in relation to immunological memory, tolerance etc. In particular, the new concept might imply similarity (or identity) of the genes coding for autologous differentiation antigens and those responsible for the idiotypes of antigen-recognizing lymphocyte receptors.


Chemoprevention for pancreatic cancer.
For a number of solid tumors, including pancreatic cancer, efforts aimed at disease prevention may be more successful than currently available anticancer treatments. While specific interventions are emerging to prevent breast, prostate, lung, and colorectal cancer, no trials of chemoprevention are being conducted in pancreatic cancer. Importantly, there are significant obstacles to the conduct of such research. However, preclinical and epidemiologic studies suggest that several drugs may have chemopreventive potential in pancreatic cancer. These include aspirin and other non-steroidal antiinflammatory drugs (NSAIDs), selective cyclooxygenase inhibitors, somatostatin analogs, selective estrogen receptor modulators (SERMs), and anti-androgenic agents. As the oncology community evaluates some of these agents in large chemoprevention trials for breast, colon, and prostate cancer, it may be found that pancreatic cancer prevention occurs as an unintended, but desirable consequence. Moreover, other general societal trends, such as smoking cessation and the widespread use of cholesterol-lowering agents and aspirin, could have a role in reducing the risk of pancreatic cancer, and in the future, may lead to a decrease in its incidence.


Impairments in saline intake induced by deposit-free electrolytic lesions in the thalamic gustatory area.
Previous studies demonstrating impairments in sodium appetite following destruction of the thalamic gustatory relay of the rat utilized lesion procedures which depositd irritative ferric ions around the lesion site. The present study used a deposit free lesioning procedure to determine whether the disruption in sodium appetite is attributable to factors other than tissue destruction. The results showed that deposite free lesions produce deficits in sodium appetite which are similar in specificity, intensity, and uniformity to those produced by irritative lesion procedures.


EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome.
Waardenburg syndrome type I (WS1), an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1. We reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature (83.5 cm (-5.8SD)). His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 (IGF-1) was 52.7 ng/ml, lower than the normal range (55 ~ 452 ng/ml) and the peak growth hormone level was 7.57 ng/ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone (rhGH) replacement therapy, showing a 9.2 cm/year growth rate and an improvement of 1 standard deviation (SD) of height after one year treatment. CMA test of patient's DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 (hg19; chr2:221,234,146-225,697,363). PAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.


Symbion acute ventricular assist device: nursing challenge.
A cardiac patient is rapidly deteriorating and facing imminent death. The medical team decides to insert an experimental ventricular assist device (VAD) to perform the work of the dying heart. How can the critical care nurse best care for a patient with this challenging and unyielding diagnosis?


High throughput short interfering RNA (siRNA) screening of the human kinome identifies novel kinases controlling the canonical nuclear factor-κB (NF-κB) activation pathway.
Nuclear factor-κB (NF-κB) is an inducible cytoplasmic transcription factor that plays a role as a master regulator of airway mucosal inflammation. The prototypical ("canonical") NF-κB pathway controls cytoplasmic to nuclear translocation in response to stimulation by the mononuclear cytokine, TNF. Despite intensive investigation, the spectrum of kinases involved in the canonical NF-κB pathway has not yet been systematically determined. Here we have applied a high throughput siRNA-mediated loss-of-function screening assay to identify novel kinases important in TNF-induced NF-κB signaling. Type II A549 epithelial cells stably expressing an IL-8/luciferase reporter gene optimized for high throughput siRNA format (Z' score of 0.65) and siRNAs for 636 human kinases were reverse-transfected and screened in the assay. 36 candidate genes were identified that inhibited TNF signaling with a Z score deviation of <-1.3 in replicate plates. From this group, 11 kinases were selected for independent validation, of which eight were successfully silenced. Six kinases were validated, including ATM, CDK2, -5, and -7, CALM3, MAPAKP5, and MAP3K/MEKK3. The surprising function of ATM in TNF signaling was confirmed where reduced NF-κB/RelA translocation and Ser-276 phosphorylation were seen in ATM(-/-) mouse embryo fibroblasts. These data indicate that ATM is a key regulatory kinase that may control global NF-κB activation in the TNF-induced canonical pathway.


Gamma oscillations predict pro-cognitive and clinical response to auditory-based cognitive training in schizophrenia.
Cognitive impairments are pervasive and disabling features of schizophrenia. Targeted cognitive training (TCT) is a "bottom-up" cognitive remediation intervention with efficacy for neurocognitive outcomes in schizophrenia, yet individual responses are variable. Gamma oscillatory measures are leading candidate biomarkers in the development of biologically informed pro-cognitive therapeutics. Forty-two schizophrenia patients were recruited from a long-term residential treatment facility. Participants were randomized to receive either 1 h of cognitive training (TCT, n = 21) or computer games (TAU, n = 21). All participants received standard-of-care treatment; the TCT group additionally completed 30 h of cognitive training. The auditory steady-state response paradigm was used to elicit gamma oscillatory power and synchrony during electroencephalogram recordings. Detailed clinical and cognitive assessments were collected at baseline and after completion of the study. Baseline gamma power predicted cognitive gains after a full course of TCT (MCCB, R2 = 0.31). A change in gamma power after 1-h TCT exposure predicted improvement in both positive (SAPS, R2 = 0.40) and negative (SANS, R2 = 0.30) symptoms. These relationships were not observed in the TAU group (MCCB, SAPS, and SANS, all R2 < 0.06). The results indicate that the capacity to support gamma oscillations, as well as the plasticity of the underlying ASSR circuitry after acute exposure to 1 h of TCT, reflect neural mechanisms underlying the efficacy of TCT, and may be used to predict individualized treatment outcomes. These findings suggest that gamma oscillatory biomarkers applied within the context of experimental medicine designs can be used to personalize individual treatment options for pro-cognitive interventions in patients with schizophrenia.


Expression of human leukotriene A4 hydrolase cDNA in Escherichia coli.
The cDNA clone encoding human leukotriene A4 hydrolase was inserted into a vector pUC9 and expressed in Escherichia coli as a fusion protein containing the first 10 amino acid residues derived from a vector. The leukotriene A4 hydrolase activity was recovered in the soluble fraction of the transformants. The purified enzyme showed kinetic properties similar to the native enzyme, including inactivation by the substrate and sulfhydryl-modifying reagents. The results demonstrate that a protein with an Mr of 70,000 was expressed in Escherichia coli with a full enzyme activity and structural fidelity. Acquisition of the expression system makes it feasible to elucidate the reaction mechanism of the enzyme.


A survey of Canadian adult rheumatologists' knowledge, comfort level, and barriers in assessing psychosocial needs of young adults with rheumatic diseases.
To assess adult rheumatologists' comfort level, current practices, and barriers to provision of optimal care in supporting young adults with pediatric-onset rheumatic conditions in Canada. Survey questions were informed by literature review, a needs assessment, and using milestones listed by the Royal College of Physicians and Surgeons of Canada for the entrustable professional activities (EPAs) applicable to care for rheumatology patients transitioning to adult practice. The electronic survey was distributed to adult rheumatology members of the Canadian Rheumatology Association over 4 months. Four hundred and fifty-one rheumatologists received the survey, with a response rate of 15.2%. Most respondents were from Ontario and had been in practice ≥ 10 years. Three quarters reported a lack of training in transition care although the same proportion were interested in learning more about the same. Approximately 40% felt comfortable discussing psychosocial concerns such as gender identity, sexuality, contraception, drug and alcohol use, vaping, and mental health. Despite this, 45-50% reported not discussing vaping or gender identity at all. The most frequently reported barriers to providing transition care were lack of primary care providers, allied health support, and training in caring for this age group. Most adult rheumatologists lack formal training in transition care and view it as a barrier to providing care for this unique patient population. Future educational initiatives for adult rheumatology trainees should include issues pertaining to adolescents and young adults. More research is needed to assess the effectiveness of resources such as transition navigators in ensuring a successful transition process.


Low-dose bisphenol A does not affect reproductive organs in estrogen-sensitive C57BL/6N mice exposed at the sexually mature, juvenile, or embryonic stage.
Bisphenol A (BPA) is used on a large scale in the manufacture of polycarbonate plastics. BPA has been shown to bind weakly to both estrogen receptor (ER) alpha and ER beta. The objective of this study was to evaluate the effects of low-dose BPA on male sexual development after exposure at various stages of development. Mice of the estrogen-sensitive strain C57BL/6N were exposed to BPA orally at doses of 2, 20, or 200 microg/kg at various stages, i.e. adulthood, the immature stage just after weaning, or the embryonic/fetal stage, to evaluate the effects of low-dose BPA on male reproductive organs. Body weight changes, weights of reproductive organs (testes, epididymides, seminal vesicles), cauda epididymal sperm density, and histology of reproductive organs including the ventral prostate were not affected by exposure to BPA at any dose examined. The results of this study indicate that exposure of estrogen-sensitive C57BL/6N mice to low-dose BPA did not reduce sperm density or disrupt development of the male reproductive organs.