[Study on the induction of skin transplantation tolerance against rejection in mice by third-party dendritic cells loaded with donor's antigens].
To investigate whether the third-party dendritic cells (DC) incubated with donor's antigens possess the similar immune functions with donor derived immature DC. Female C57 BL/6, BALB/c and Kunming mice were used as skin transplant donors, recipients and third-party, respectively. Forty BALB/c mice were randomly divided into A (normal control), B (cyclophosphamide administration), C (CTX and donor derived immature DC), D (CTX and third-party immature DC), E (CTX and third-party DC loaded with donor's antigens) groups, with 8 mice in each group. The mice in group B, C, D and E were given CTX (200 mg/Kg) 4 days before operation, while those in group A were given equivalent amount of normal saline(NS). Then in group C, D and E, DC at a dose of 1 x 10(7)/ml were intraperitoneally injected with 2 days before grafting and 12 days after operation, but the mice in group A and B were given NS in the same manner. Mean survival time (MST) of skin grafts was recorded, and biopsies of grafts on 5 and 10 post-operation days (POD) were harvested for histologic examination. Compared with group A [(16.1 +/- 3.5)d], MST of skin grafts in group C [(38.3 +/- 7.7) d] and E [(34.9 +/- 7.7) d] were significantly prolonged ( P < 0.01), while no obvious difference was observed between group C and E( P > 0.05), but there was statistically significant difference in MST between group D [(23.7 +/- 2.7) d] and E ( P < 0.05). In addition, clear epithelial structure and infiltration of inflammatory cells were observed in specimens from both groups C and E. Both donor derived immature DC and third-party DC loaded with donor's antigens can partly induce donor specific transplantation tolerance.


Private Equity: An Emerging Practice Model.
Private equity acquisitions are increasing among orthopedic practices. The concepts and vocabulary surrounding these deals may be foreign to physicians. There are both potential risks and potential benefits to physicians at the center of these complex deals, and a clear understanding of any proposed private equity acquisition is crucial. Short-term data on private equity acquisition in other procedure-based outpatient specialties have shown that private equity ownership consistently increased the number of patients seen per provider, allowed amount per claim, and utilization of advanced practice practitioners. These studies did not show consistent changes in the rates of invasive procedures or negative impacts on patient care. Each practice will need to carefully consider any potential private equity involvements.


Existence of phosphoinositide-specific phospholipase C in rat liver nuclei and its change during liver regeneration.
We found phosphoinositide-specific phospholipase C (PtdIns-PLC) activity in nuclei isolated from rat liver. The enzyme hydrolyzed phosphatidylinositol, phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol 4,5-bisphosphate in a Ca(2+)-dependent manner, and produced inositol mono-, bis-, and triphosphate, respectively. Neither phosphatidylcholine, phosphatidylethanolamine, nor phosphatidylserine was utilized as a substrate. After partial hepatectomy, the PtdIns-PLC activity in isolated nuclei increased transiently in the S phase (20-22 h post-hepatectomy), to 2.5-fold higher than in the control, when measured with PIP. This result suggests a close relationship between the nuclear PtdIns-PLC, especially its PIP-hydrolyzing activity, and cell proliferation.


Induced membrane technique: a critical literature analysis and proposal for a failure classification scheme.
The reconstruction of long-bone segmental defects remains challenging, with the three common methods of treatment being bone transport, vascularized bone transfer, and the induced membrane technique (IMT). Because of its simplicity, replicability, and reliability, usage of IMT has spread all over the world in the last decade, with more than 300 papers published in the PubMed literature database on this subject so far. Most of the clinical studies have reported high rates of bone union, yet some also include more controversial results with frequent complications and revision surgeries. At the same time, various experimental research efforts have been designed to understand and improve the biological properties of the induced membrane. This literature review aims to provide an overview of IMT clinical results in terms of bone union and complications and to compare them with those of other reconstructive procedures. In light of our findings, we then propose an original classification scheme of IMT failures distinguishing between preventable and nonpreventable failures.


Stereoselective environmental behavior and biological effects of the chiral bitertanol.
Bitertanol is a widely used chiral triazole fungicide. The stereoselective environmental behavior and biological effects of bitertanol are not clear. The present study evaluated the stereoselectivity of bitertanol, including its degradation in five typical soils (under laboratory controlled aerobic, anaerobic and sterilization conditions), metabolism in rat liver microsomes (RLM; in vitro), and the endocrine disruption effects on the estrogen receptor (ER) and thyroid hormone receptor (TR) using reporter gene assays. The results indicated that (1S,2R)-bitertanol and (1R,2S)-bitertanol had faster degradation rates in soil than the other stereoisomers. The half-lives of four bitertanol stereoisomers ranged from 9.1 d to 86.6 d in different soils under different conditions. (1S,2R)-bitertanol was preferentially metabolized in RLM. The molecular docking results confirmed the in vitro experiments that (1S,2R)-bitertanol had shortest binding distances and lowest energies with cytochrome P450 enzymes (CYPs). Four bitertanol stereoisomers showed stereoselective antagonistic effects on ER. Additionally, (1S,2R)-bitertanol and (1R,2S)-bitertanol exhibited antagonistic effects on TR. These results suggest that the use of pure (1S,2R)-bitertanol instead of the commercial stereoisomer mix, may help reduce environmental pollution and biological toxicity.


Impact of remote magnetic catheter navigation on ablation fluoroscopy and procedure time.
Remote magnetic catheter navigation (RCN) is gaining acceptance in clinical cardiac electrophysiology, but details regarding how RCN affects procedure execution are not well characterized. From January 1, 2005, to November 30, 2007, 721 cases were retrospectively analyzed and compared. Of these, 127 used RCN and 594 used manual catheter navigation (MCN). Data including procedure time, fluoroscopy time, ablation catheter, procedural success, and complications were extracted from our procedure database and compared between RCN and MCN. RCN use significantly decreased fluoroscopy time for atrial fibrillation (AF) ablation (-29 minutes, P < 0.001), atrioventricular nodal reentrant tachycardia ablation (-14 minutes, P < 0.001), and atrioventricular reentrant tachycardia ablation (-18 minutes, P = 0.045). While RCN significantly increased mean procedure time for AF (+36 minutes, P = 0.003) and atypical atrial flutter cases (+116 minutes, P = 0.016), RCN AF procedure time diminished with increasing number of cases performed. Two cases of tamponade occurred during AF ablation using MCN (2.2%, 2 of 91 cases). No tamponade occurred during all 75 AF ablations with RCN. RCN can reduce fluoroscopy time and may reduce complications during catheter ablation. While it may increase total procedure duration, procedure times decrease with increasing operator experience. (PACE 2008; 31:1399-1404).


Aperiodic switching event-triggered stabilization of continuous memristive neural networks with interval delays.
The stabilization problem is studied for memristive neural networks with interval delays under aperiodic switching event-triggered control. Note that, most of delayed memristive neural networks models studied are discontinuous, which are not the real memristive neural networks. First, a real model of memristive neural networks is proposed by continuous differential equations, furthermore, it is simplified to neural networks with interval matrix uncertainties. Secondly, an aperiodic switching event-trigger is given, and the considered system switches between aperiodic sampled-data system and continuous event-triggered system. Thirdly, by constructing a time-dependent piecewise-defined Lyapunov functional, the stability criterion and the feedback gain design are obtained by linear matrix inequalities. Compared with the existing results, the stability criterion is with lower conservatism. Finally, two neurons are taken as examples to ensure the feasibility of the results.


Relationship Between Comorbidities in Patients With Cognitive Complaint and Caregiver Burden: A Cross-Sectional Study.
Informal caregivers of patients with a cognitive impairment may face exhaustion while taking care of their relatives, and are themselves at higher risk of disease. The objective was to assess the relationship between patients' comorbidities evaluated with the Charlson index, and the caregiver burden, independently of health disorders related to cognitive impairment. Cross-sectional observational study. Memory clinic at the University Hospital of Lyon. Outpatients with cognitive complaint and consulting a Clinical and Research Memory Centre of Lyon (n = 1300). Comorbidity was measured using the Charlson Comorbidity Index related to age (CCI). The caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The relationship was assessed between the CCI and the mini-Zarit and other patients' characteristics: behavior, cognition, autonomy as assessed respectively by the Neuropsychiatric Inventory (NPI), Mini Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL), etiology, and stage of the cognitive impairment. The study included 1300 outpatients: mean age: 80.8 ± 7 years. The mean CCI was 4.8 ± 1.7. The mini-Zarit score: 3.1 ± 2.0. The caregiver burden increased by 0.22 per unit of CCI (95% confidence interval 0.15-0.28, P < .001) in unadjusted analysis. The caregiver burden remained significantly associated with CCI, after adjustment for the MMSE, IADL, and NPI. The caregiver burden is higher when patients' comorbidities increase, independently of behavioral and psychological symptoms, level of functional autonomy, and the stage of the cognitive disease. However, dementia may be the comorbidity that contributes the most to caregiver burden.


Cerebral Hyperperfusion Syndrome After Surgical Repair of Congenital Supravalvular Aortic Stenosis.
Although cerebral hyperperfusion syndrome is rarely encountered, this condition can be serious after procedures that increase cerebral blood flow; most reports are related to carotid revascularization. Sharp cerebral hemodynamic changes, along with impaired cerebrovascular autoregulation, are the main mechanisms contributing to this syndrome. We report a patient who underwent surgical correction for congenital supravalvular aortic stenosis and presented with postoperative hypertension, headache, impairment of consciousness, and cerebral edema 2 days after operation. He recovered well when the blood pressure declined and the brain edema subsided. Cerebral hyperperfusion syndrome was considered, and this uncommon neurologic complication of cardiac operations is discussed.


Antihypertensive effect of gomisin A from Schisandra chinensis on angiotensin II-induced hypertension via preservation of nitric oxide bioavailability.
Gomisin A (GA) is a small molecular weight lignan present in Schisandra chinensis, and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of GA on blood pressure (BP) in angiotensin II (Ang II)-induced hypertensive mice. C57/BL6 mice infused subcutaneously with Ang II (1 and 2 μg kg⁻¹ per min for 2 weeks) showed an increase in BP with a decrease in nitric oxide (NO) metabolites in plasma, and a negative correlation between these two parameters was demonstrated. In the thoracic aorta from Ang II-induced hypertensive mice, a decrease in vascular NO that was accompanied by a diminution of phosphorylated endothelial nitric oxide synthase (eNOS), as well as by increased reactive oxygen species (ROS) production, was demonstrated. These alterations in BP, eNOS phosphorylation and ROS production in the vasculature of Ang II-treated mice were markedly and dose-dependently reversed by simultaneous administration of GA (2 and 10 μg kg⁻¹ per min). In addition, Ang II-induced ROS production in cultured vascular cells such as endothelial cells and vascular smooth muscle cells was markedly attenuated by GA. These results suggested that GA attenuated the increase in BP via preservation of vascular NO bioavailability not only by inhibiting ROS production but also by preventing the impairment of eNOS function in the vasculature of Ang II-induced hypertensive mice.


Carbohydrate taste preferences in rats: glucose, sucrose, maltose, fructose and polycose compared.
The taste preferences of adult female rats for solutions of five different carbohydrates were evaluated using brief (3-min) two-bottle preference tests. At the lowest concentration tested (0.03 molar) the order of preference was Polycose greater than maltose greater than sucrose greater than glucose = fructose. Whereas at the highest concentrations tested (0.5 or 1.0 molar) the preference order was sucrose greater than maltose greater than or equal to Polycose greater than glucose greater than fructose. Thus, at low concentrations starch-derived polysaccharides (Polycose) are more palatable to rats than are sugars. These findings are consistent with the hypothesis that rats have separate taste receptors for sugars and for starch-derived polysaccharides. The fact that maltose is the most preferred sugar at low concentrations is attributed to its stimulation of "polysaccharide" taste receptors.


Novel gene expression domains reveal early patterning of the Xenopus endoderm.
The endoderm gives rise the respiratory and digestive tract epithelia as well as associated organs such as the liver, lungs and pancreas. Investigations examining the molecular basis of embryonic endodermal patterning and organogenesis have been hampered by the lack of regionally expressed molecular markers in the early endoderm. By differentially screening an arrayed cDNA library, combined with an in situ hybridization screen we identified 13 new genes regionally expressed in the early tailbud endoderm of the Xenopus embryo. The putative proteins encoded by these cDNAs include a cell surface transporter, secreted proteins, a protease, a protease inhibitor, an RNA-binding protein, a phosphatase inhibitor and several enzymes. We find that the expression of these genes falls into one of three re-occurring domains in the tailbud embryo; (1). a ventral midgut, (2). posterior to the midgut and (3). in the dorsal endoderm beneath the notochord. Several of these genes are also regionally expressed at gastrula and neurula stages and appear to mark territories that were previously only predicted by the endoderm fate map. This indicates that there is significant positional identity in the early endoderm long before stages 28-32 when regional specification of the endoderm is thought to occur. These new genes provide valuable tools for studying endodermal patterning and organogenesis in Xenopus.


Herlyn-Werner-Wünderlich syndrome: An unusual case with presentation of menorrhagia.
Herlyn-Werner-Wünderlich (HWW) syndrome is a rare condition in which patients present with a palpable pelvic mass and pain caused by an obstructed hemivagina. Here we present a case of HWW syndrome characterized by prolonged menstrual bleeding. A 19-year-old nonsexually active unmarried women experienced irregular menstrual cycles and menorrhagia. The duration of menstrual bleeding was 10-14 days. She also suffered from mild dysmenorrhea since menarche at the age of 13. Transabdominal sonography revealed a double uterus and a heterogeneous myoma-mimicking mass over the left cervical region. The left kidney was absent. Magnetic resonance imaging revealed a double uterus, a double vagina with an unperforated left hemivagina, and ipsilateral renal agenesis. The patient underwent cervicovaginal orifice reconstruction surgery. Left hematocolpos compression, a partially obstructed right vaginal channel, and an orifice with local venous drainage abnormalities resulted in prolonged menstrual bleeding. In HWW syndrome, the occurrence of a pelvic mass and pain is common; however, prolonged menstrual bleeding is rare.


Isolation and characterization of biochemical properties of DNA methyltransferase FauIA modifying the second cytosine in the nonpalindromic sequence 5'-CCCGC-3'.
A gene encoding DNA methyltransferase (methylase) FauIA of the restriction-modification system FauI from Flavobacterium aquatile (recognizing sequence 5'-CCCGC-3') was cloned in pJW vector. The latter was used for transformation of E. coli RRI cells followed by subsequent thermoinduction and biomass elaboration. Highly purified DNA methyltransferase FauIA preparation was obtained using chromatography on different sorbents. The molecular mass of the isolated enzyme of about 39 kD corresponds to its theoretical value. The enzyme was characterized by temperature and pH optima of 33 degrees C and pH 7.5, respectively. Methylation of a synthetic oligonucleotide by FauIA methylase followed by its cleavage with various restrictases and analysis of the resultant restriction fragments revealed that FauIA methylase modified the second cytosine residue in the sequence 5'-CCCGC-3'. Kinetic analysis revealed Km and catalytic constant values of 0.16 microM and 0.05 min(-1), respectively.


Further characterization of a herpesvirus-positive orang-utan cell line and comparative aspects of in vitro transformation with lymphotropic old world primate herpesviruses.
An orang-utan (Pongo pygmaeus) suspension line, CP81, was shown to lack myeloid markers of lysozyme activity an d phagocytosis but to be positive for lymphocytic N-alkaline phosphatase activity, and to release a B-cell-tropic herpesvirus. This herpesvirus, termed Herpesvirus pongo, had 30--40% DNA homology with EBV and was present at 2-3 genome copies per CP-81 cell. Gibbon lymphocytes transformed by H. pongo, Epstein-Barr virus (EBV), and H. papio (of baboon, Papio hamadryas, origin) were found to be virus antigen-positive B cells. Gibbon lymphocytes transformed by H. pongo and EBV and transplanted to nude mice by the intracranial (IC) route (had a 75% and a 45% success rate, respectively), while transplants of similar cells transformed by H. papio were only 10% successful. None of these lines transplanted subcutaneously (SC) nor manifested a high degree of colony formation in 0.33% agarose (less than or equal to 0.5%), Gibbon lymphocytes transformed by H. pongo were hypodiploid while those transformed by EBV or H. papio were diploid. CP-81 cells themselves could be transplanted both IC (100%) and SC (70%) and showed a relatively high degree of colony formation in agarose (6.4-7.6%). B95-8 cells (marmoset, Saguinus oedipus-EBV) could be transplanted IC (66%) but not SC and had a low but significant ability to grow in agarose (1.6%). 594S (baboon, P. hamadryas-H. papio) cells could be transplanted IC (25%) but not SC, and grew to very low levels in agarose (0.1%).


Biosynthesis of silver nanoparticles using extracts of Stevia rebaudiana and evaluation of antibacterial activity.
The present study reveals a simple, non-toxic and eco-friendly method for the "green" synthesis of Ag-NPs using hydroponic and soil medicinal plant Stevia rebaudiana extracts, the characterization of biosynthesized nanoparticles, as well as the evaluation of their antibacterial activity. Transmission electronic microscopy (TEM) and Dynamic Light Scattering (DLS) analysis confirmed that biosynthesized Ag-NPs are in the nano-size range (50-100 nm) and have irregular morphology. Biogenic NPs demonstrate antibacterial activity against Escherichia coli BW 25,113, Enterococcus hirae ATCC 9790, and Staphylococcus aureus MDC 5233. The results showed a more pronounced antibacterial effect on E. coli growth rate, in comparison with Gram-positive bacteria, which is linked to the differences in the structure of bacterial cell wall. Moreover, the Ag-NPs not only suppressed the growth of bacteria but also changed the energy-dependent H+-fluxes across the bacterial membrane. The change of H+-fluxes in presence of H+-translocating systems inhibitor, N,N'-dicyclohexylcarbodiimide (DCCD), proves the effect of Ag-NPs on the structure and permeability of the bacterial membrane. Overall, our findings indicate that the Ag-NPs synthesized by medicinal plant Stevia extracts may be an excellent candidate as an alternative to antibiotics against the tested bacteria.


Correlates of alcohol consumption: sex, age, and expectancies relate differentially to quantity and frequency.
Expectations of the effects of alcohol have been related to drinking behaviors for both problem and nonproblem drinkers. The present investigation expanded on previous research by considering age, sex, and alcohol expectancies as differential predictors of frequency and quantity of drinking. Subjects, 157 males and 168 females, completed alcohol expectancy, drinking habits, and demographic questionnaires. Results showed significant sex differences in predictors of drinking frequency. Males who reported most frequent drinking tended to have stronger expectations of increased Social and Physical Pleasure, Global Positive Changes, and Sexual Enhancement. On the other hand, frequent consumption among females was best predicted by stronger expectations that alcohol would reduce tension. The amount consumed per drinking occasion was predicted by the same two expectancy factors for males and females: Social and Physical Pleasure and Social Assertion. Age was an important contributing predictor of quantity and frequency for females only. Results indicated the importance of investigating the mediating role of expectancies (a) within sex and (b) with respect to frequency versus quantity of drinking behavior.


Protein-polysaccharide-based delivery systems for enhancing the bioavailability of curcumin: A review.
In recent years, a wide attention has been paid to curcumin in medicine due to its excellent physiological activities, including anti-inflammatory, antioxidant, antibacterial, and nerve damage repair. However, the low solubility, poor stability, and rapid metabolism of curcumin make its bioavailability low, which affects its development and application. As a unique biopolymer structure, protein-polysaccharide (PRO-POL)-based delivery system has the advantages of low toxicity, biocompatibility, biodegradability, and delayed release. Many scholars have investigated PRO-POL -based delivery systems to improve the bioavailability of curcumin. In this paper, we focus on the interactions between different proteins (e.g. casein, whey protein, soybean protein isolate, pea protein, zein, etc.) and polysaccharides (chitosan, sodium alginate, hyaluronic acid, pectin, etc.) and their effects on complexes diameter, surface charge, encapsulation drive, and release characteristics. The mechanism of the PRO-POL-based delivery system to enhance the bioavailability of curcumin is highlighted. In addition, the application of PRO-POL complexes loaded with curcumin is summarized, aiming to provide a reference for the construction and application of PRO-POL delivery systems.


Platelet antibody determination by platelet factor 3 assay (comparison with radiolabelled serotonin release and platelet aggregometry).
Platelet antibody determination by the PF3 test was carried out in 96 thrombocytopenic patients with various disorders, 31 repeatedly transfused patients with or without thrombocytopenia and 24 patients with autoimmune disease (SLE and myasthenia gravis) without thrombocytopenia. The frequency of a positive test was greatest in the patients with ITP (61%), SLE (50%) or a history of numerous blood transfusions (60%). The patients with myasthenia gravis also showed a considerable frequency (20%) of platelet antibodies detectable by the PF3 test. The PF3 test is less sensitive than the serotonin release test in detecting autoantibodies, but it is more sensitive than aggregometry in detecting isoantibodies and drug-related antibodies.


Validation of Risk Score in Predicting Early Readmissions in Decompensated Cirrhotic Patients: A Model Based on the Administrative Database.
Early readmission in patients with decompensated liver cirrhosis leads to an enormous burden on health care use. A retrospective cohort study using the 2013 and 2014 Nationwide Readmission Database (NRD) was conducted. Patients with a diagnoses of cirrhosis and at least one feature of decompensation were included. The primary outcome was to develop a validated risk model for early readmission. Secondary outcomes were to study the 30-day all-cause readmission rate and the most common reasons for readmission. A multivariable logistic regression model was fit to identify predictors of readmissions. Finally, a risk model, the Mumtaz readmission risk score, was developed for prediction of 30-day readmission based on the 2013 NRD and validated on the 2014 NRD. A total of 123,011 patients were included. The 30-day readmission rate was 27%, with 79.6% of patients readmitted with liver-related diagnoses. Age <65 years; Medicare or Medicaid insurance; nonalcoholic etiology of cirrhosis; ≥3 Elixhauser score; presence of hepatic encephalopathy, ascites, variceal bleeding, hepatocellular carcinoma, paracentesis, or hemodialysis; and discharge against medical advice were independent predictors of 30-day readmission. This validated model enabled patients with decompensated cirrhosis to be stratified into groups with low (<20%), medium, (20%-30%), and high (>30%) risk of 30-day readmissions. Conclusion: One third of patients with decompensated cirrhosis are readmitted within 30 days of discharge. The use of a simple risk scoring model with high generalizability, based on demographics, clinical features, and interventions, can bring refinement to the prediction of 30-day readmission in high-risk patients; the Mumtaz readmission risk score highlights the need for targeted interventions in order to decrease rates of readmission within this population.


Autologous NK cells propagated and activated ex vivo decrease senescence markers in human PBMCs.
Aging is a multifactorial process involving many steps including senescence. The immune system plays a critical role in aging where chronic inflammation and senescence has been shown to be detrimental. Natural killer (NK) cells are the predominant innate lymphocyte subset that mediate various responses to include surveillance and elimination of senescent cells. Here, we use autologous propagated and activated NK (aNK) cells from 5 patients to demonstrate that aNK cells decrease senescent cells in vitro and immunosenescence in humans based on markers p16 and β-galactosidase. In addition, inflammatory cytokine panel data suggest a role for removal of immunosenescence to reduce the aging-related inflammatory response.


The neural systems that mediate human perceptual decision making.
Perceptual decision making is the act of choosing one option or course of action from a set of alternatives on the basis of available sensory evidence. Thus, when we make such decisions, sensory information must be interpreted and translated into behaviour. Neurophysiological work in monkeys performing sensory discriminations, combined with computational modelling, has paved the way for neuroimaging studies that are aimed at understanding decision-related processes in the human brain. Here we review findings from human neuroimaging studies in conjunction with data analysis methods that can directly link decisions and signals in the human brain on a trial-by-trial basis. This leads to a new view about the neural basis of human perceptual decision-making processes.


Non-Debye screening of a surface charge and a bulk-ion-controlled anchoring transition in a nematic liquid crystal.
We study the anchoring mechanism due to substrate-adsorbed ions by examining a related anchoring transition. An analytical solution to the Poisson equation shows that, as their number suffices for a non-negligible anchoring contribution, the surface field is screened over some characteristic microscopic distance. It is shown both theoretically and experimentally that the critical temperature of the transition can be controlled by bulk ion density through its relation to the density of adsorbed ions.


Effects of Allium sativum on IFN-γ and IL4 concentrations in mice with cystic echinococcosis.
The aim of the current investigation was to assess the impacts of methanolic extract of Allium sativum (MEAS) on IL-4 (a cytokine derived from Th2 cells) and IFN-ɣ (a cytokine derived from Th1 cells) levels in mice infected with Echinococcus granulosus. Sixty healthy BALB/c female mice were used in this study. Each animal was intraperitoneally injected with 1500 protoscoleces. The infected animals were randomly divided into six groups: albendazole (100 mg/kg), MEAS 10 (10 mg/kg), MEAS 20 (20 mg/kg), MEAS 40 (40 mg/kg), MEAS 80 (80 mg/kg) and control group with no treatment. The studied animals received albendazole and/or MEAS through drinking water for 30 days. Serum IFN-γ concentration significantly increased in the MEAS 20 and 80 groups in comparison to the control, albendazole and MEAS 10 groups (P < 0.05). The serum IL-4 level showed no significant difference between the trial groups. The findings of this study showed that MEAS at 20 and 80 mg/kg concentrations enhanced Th1 cell response in mice with cystic echinococcosis.


Association of ICAM-1 (K469E) and MCP-1 -2518 A>G gene polymorphism with brain abscess.
Brain abscess develops in response to a parenchymal infection. Intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play vital role in central nervous system (CNS) diseases. We studied ICAM-1 (K469E) and MCP-1 (-2518 A>G) polymorphisms among brain abscess patients. The genotypic distributions of ICAM-1 (K469E) and MCP-1 (-2518 A>G) were significantly different between patients and controls. Further, patient with predisposing factors, and also with culture result, we found significant association. The study revealed that the polymorphisms of these molecules lead to increased production, which appears to be a risk for the development of brain abscess.


Application of an instructive hydrogel accelerates re-epithelialization of xenografted human skin wounds.
Poor quality (eg. excessive scarring) or delayed closure of skin wounds can have profound physical and pyschosocial effects on patients as well as pose an enormous economic burden on the healthcare system. An effective means of improving both the rate and quality of wound healing is needed for all patients suffering from skin injury. Despite wound care being a multi-billion-dollar industry, effective treatments aimed at rapidly restoring the skin barrier function or mitigating the severity of fibrotic scar remain elusive. Previously, a hydrogel conjugated angiopoietin-1 derived peptide (QHREDGS; Q-peptide) was shown to increase keratinocyte migration and improve wound healing in diabetic mice. Here, we evaluated the effect of this Q-Peptide Hydrogel on human skin wound healing using a mouse xenograft model. First, we confirmed that the Q-Peptide Hydrogel promoted the migration of adult human keratinocytes and modulated their cytokine profile in vitro. Next, utilizing our human to mouse split-thickness skin xenograft model, we found improved healing of wounded human epidermis following Q-Peptide Hydrogel treatment. Importantly, Q-Peptide Hydrogel treatment enhanced this wound re-epithelialization via increased keratinocyte migration and survival, rather than a sustained increase in proliferation. Overall, these data provide strong evidence that topical application of QHREDGS peptide-modified hydrogels results in accelerated wound closure that may lead to improved outcomes for patients.


Application of high-throughput sequencing to analyze the diet of black croaker (Atrobucca nibe) in southern coastal waters of Zhejiang.
This study investigated the feeding habits of black croaker (Atrobucca nibe) to fully understand its role in the food web in southern coastal waters of Zhejiang, China. In total, 225 black croakers were collected in a bottom trawl survey, of which 195 were used for the stomach contents analysis and 30 for high-throughput sequencing (HTS). Both approaches showed that the main prey was shrimp, with Alpheus japonicus being the most predominant. In addition, black croaker also fed on other benthic species, suggesting that it was a demersal predator. Feeding intensity also varied with black croaker body length, as did prey preference, from small-sized species to larger species with increases in fish size; in addition, prey species were more diverse in the large-bodied prey group. Canonical correspondence analysis indicated that the feeding habit of black croaker was most significantly correlated with temperature and dissolved oxygen. HTS was shown to be a feasible high precision semi-quantitative analytical approach, although it must be combined with morphological methods to obtain more complete feeding data; thus, it could provide an effective scientific basis for feeding ecology studies of marine organisms.


Synergistic effect of electrotrophic perchlorate reducing microorganisms and chemically modified electrodes for enhancing bioelectrochemical perchlorate removal.
Perchlorate has been described as an emerging pollutant that compromises water sources and human health. In this study, a new electrotrophic perchlorate reducing microorganism (EPRM) isolated from the Atacama Desert, Dechloromonas sp. CS-1, was evaluated for perchlorate removal in water in a bioelectrochemical reactor (BER) with a chemically modified electrode. BERs were operated for 17 days under batch mode conditions with an applied potential of -500 mV vs. Ag/AgCl. Surface analysis (i.e., SEM, XPS, FT-IR, RAMAN spectroscopy) on the modified electrode demonstrated heterogeneous transformation of the carbon fibers with the incorporation of nitrogen functional groups and the oxidation of the carbonaceous material. The BERs with the modified electrode and the presence of the EAM reached high cathodic efficiency (90.79 ± 9.157%) and removal rate (0.34 ± 0.007 mol m-3-day) compared with both control conditions. The observed catalytic enhancement of CS-1 was confirmed by a reduction in the charge transfer resistance obtained by electrochemical impedance spectroscopy (EIS). Finally, an electrochemical kinetic study revealed an eight-electron perchlorate bioreduction reaction at -638.33 ± 24.132 mV vs. Ag/AgCl. Therefore, our results show the synergistic effect of EPRM and chemically modified electrodes on perchlorate removal in a BER.


[Takayasu's disease (aortic arch syndrome). Usual and unusual angiographic appearances. Report of 15 cases treated by arteriography (author's transl)].
The authors report 15 cases including 9 controlled by autopsy, and discuss the usual and unusual angiographic appearances in this disease. These cases strictly fulfilled the criteria necessary for diagnosis. The two angiographic forms seemed to correspond to different therapeutic indications. Takayasu's disease remains a disease of young women and the angiographic diagnosis can only be made during the obstructive phase.


The role of methionine in carcinogenesis in vivo.
The effects of methionine on carcinogenesis and tumor development have been studied intermittently for over 35 years. These studies have generally shown that methionine confers some degree of protection against the development of liver tumors by hepatocarcinogens. Such protective effects by supplemental dietary methionine are more pronounced in animals fed methionine- and choline-deficient diets rather than methionine- and choline-adequate diets. To date few if any protective effects of methionine have been observed against tumor formation in extrahepatic tissues. The effects of methionine on hepatocarcinogenesis appear to correlate well with its effects on the liver content of S-adenosylmethionine, the chief physiologic methyl donor. Perturbation of the methyl pool is known to alter the extent of methylation of membrane phospholipids, RNA, and DNA. Thus several plausible mechanisms by which methionine may modify the carcinogenic process center upon the aberrant methylation of macromolecules.


Methylphenidate cross-sensitization with amphetamine is dose dependent but not age dependent.
Psychostimulants such as methylphenidate (MPD) and amphetamine (AMP) are often prescribed to young children and adolescents to treat behavioral disorders, or used to improve their intellectual performance in our competitive society. This is concerning as the temporal effects of how MPD exposure at a young age influences the response to MPD and AMP administration later in adulthood remains unclear. The objective of this study was to test whether MPD has the characteristics of substances that elicit behavioral symptoms of dependence and whether those effects are influenced by the initial age of MPD exposure. Three control and nine experimental groups of male rats were used. They were exposed to repetitive (chronic) 0.6, 2.5, or 10.0 mg/kg MPD in adolescence only, adulthood only, or adolescence and adulthood respectively. Then all groups were subsequently re-challenged with a single AMP dose in adulthood to test whether cross-sensitization between MPD and AMP was expressed, potentially as a result of prior MPD consumption. Exposure to 2.5 mg/kg and 10.0 mg/kg MPD in adolescence and adulthood or in adulthood alone led to cross-sensitization with AMP while exposure to 0.6 mg/kg MPD in adolescence and adulthood or in adulthood alone did not lead to cross-sensitization with AMP. Thus, these results indicate that MPD cross-sensitization with AMP is dose dependent.


Intraluminal high intensity ultrasound treatment in the esophagus under fast MR temperature mapping: in vivo studies.
New curative and palliative treatments are needed to respond to the poor prognosis of esophageal cancer. The purpose of this study was to determine whether magnetic resonance imaging (MRI) and MR thermometry can be used to monitor the thermal ablation induced by an intraluminal high-intensity ultrasound applicator positioned in the esophagus. Experiments were performed in vivo in 2 pig esophagi (25 thermal lesions per pig). Respiratory gated or cardiac gated MR thermometry was performed with segmented echo-planar imaging gradient echo sequences. All MR acquisitions were performed without susceptibility artifacts or radiofrequency interference with the ultrasound device. The experimental procedure proposed for accurate measurement of temperature in the esophagus was found to achieve an SD of +/- 1.5 degrees C for respiratory gating and +/- 3.1 degrees C for cardiac gating. Gd-enhanced T(1)-weighted images were used to depict coagulation necrosis. Autopsy was performed immediately after the treatment. Ultrasound effects were inspected visually, and the dimensions of the lesions in the liver neighboring the esophagus were compared with those determined on the MRI images. The visually assessed thermal lesions showed good correlation with the MRI data (10% mean volume difference). The feasibility of esophageal thermal ablation using intraluminal high-intensity ultrasound and of on-line MR temperature monitoring was demonstrated.


Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy.
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.


Congenital subclavian steal syndrome with multiple cerebellar infarctions caused by an atypical circumflex retroesophageal right aortic arch with atretic aberrant left subclavian artery.
A right-sided aortic arch is a rare anomaly with an incidence of 0.1% worldwide and is usually associated with a mirror image of all supra-aortic branches or an aberrant left subclavian artery. The latter is often associated with a Kommerell diverticulum, although it can rarely be hypoplastic or atretic and lead to congenital subclavian steal. In most patients, the situation is well-tolerated. In this report, we present a case of subclavian steal syndrome with multiple cerebellar infarcts in a patient with an atypical right-sided aortic arch and an atretic aberrant left subclavian artery arising from a left-sided descending thoracic aorta.


Attenuation of alcohol-induced hypothermia by cyclo (His-Pro) and its analogs.
Acute administration of cyclo (His-Pro) to rats cause a dose-dependent decrease in ethanol-induced hypothermia. Bromination of the imidazole moiety of histidine in cyclo (His-Pro) resulted in a significant increase in its potency to attenuate ethanol hypothermia. In contrast, benzylation of the imidazole moiety of histidine or the substitution of one or both of the amino acids in cyclo(His-Pro) led to a total loss of its thermomodulatory activity. In conclusion, it appears from these preliminary data that it may be possible to design analogs of CHP that may be effective antagonists for ethanol hypothermia.


Evaluation of Early Submaximal Exercise Tolerance in Adolescents with Symptomatic Sport-related Concussion.
This study aimed to compare cardiorespiratory response to a graded aerobic exercise challenge between adolescents with symptomatic sport-related concussion (SSRC) and healthy control subjects. A quasiexperimental nonrandomized study at a multidisciplinary pediatric concussion program was conducted. Thirty-four adolescents with SSRC (19 males and 15 females) and 40 healthy control subjects (13 males and 27 females) completed the Buffalo Concussion Treadmill Testing (BCTT) until either symptom exacerbation or volitional fatigue. Main outcome measures included heart rate (HR), oxygen consumption (V˙O2), carbon dioxide production (V˙CO2), and minute ventilation (V˙E) at rest and at test termination, and change from rest in variables (ΔHR, ΔV˙O2, ΔV˙CO2, and ΔV˙E) during the first five stages of the BCTT. Main outcomes were analyzed using three-way mixed-model ANOVA, with group status (control vs SSRC) and sex (male vs female) as between-subject factors, and time (BCTT stage) as the within-subject factor. No group differences in resting HR, systolic and diastolic blood pressure, ΔV˙O2, V˙CO2, and V˙E were observed. During the first five stages of the BCTT, no group differences in ΔV˙O2, V˙CO2, and V˙E were observed; however, SSRC patients demonstrated higher RPE (P < 0.0005) compared with control subjects. No sex-based differences were observed among SSRC patients on measures collected at rest and during early stages of BCTT. Although SSRC patients exhibited higher RPE during a graded aerobic exercise challenge, no differences in cardiorespiratory response were observed compared with control subjects exercising at equivalent workloads. Further work is needed to elucidate the physiological mechanisms underlying exercise intolerance after SSRC.


Metabolic quotient of the soil microflora in relation to plant succession.
In this study we propose the hypothesis that ecosystem succession is accompanied by a decrease in the metabolic quotient qCO2 (respiration-to-biomass ratio) of the soil microflora. The qCO2 is calculated from basal respiration (CO2-C·h-1) per unit microbial biomass carbon (Cmier). The hypothesis was tested by studying two primary successions on recessional moraines of the Rotmoos Ferner (Austria) and the Athabasca Glacier (Canada). For both soil seres (0->200 years) it was shown that the qCO2 decreased with time, which corroborated the hypothesis. In addition, the short term development of the qCO2 was demonstrated with a revegetation trial. We observed a rise in qCO2 for the first two years after reclamation, followed by a subsequent decrease.


NF-κB/Rel proteins and the humoral immune responses of Drosophila melanogaster.
Nuclear Factor-κB (NF-κB)/Rel transcription factors form an integral part of innate immune defenses and are conserved throughout the animal kingdom. Studying the function, mechanism of activation and regulation of these factors is crucial for understanding host responses to microbial infections. The fruit fly Drosophila melanogaster has proved to be a valuable model system to study these evolutionarily conserved NF-κB mediated immune responses. Drosophila combats pathogens through humoral and cellular immune responses. These humoral responses are well characterized and are marked by the robust production of a battery of anti-microbial peptides. Two NF-κB signaling pathways, the Toll and the IMD pathways, are responsible for the induction of these antimicrobial peptides. Signal transduction in these pathways is strikingly similar to that in mammalian TLR pathways. In this chapter, we discuss in detail the molecular mechanisms of microbial recognition, signal transduction and NF-κB regulation, in both the Toll and the IMD pathways. Similarities and differences relative to their mammalian counterparts are discussed, and recent advances in our understanding of the intricate regulatory networks in these NF-κB signaling pathways are also highlighted.


Dengue outbreak in Key West, Florida, USA, 2009.
After 3 dengue cases were acquired in Key West, Florida, we conducted a serosurvey to determine the scope of the outbreak. Thirteen residents showed recent infection (infection rate 5%; 90% CI 2%-8%), demonstrating the reemergence of dengue in Florida. Increased awareness of dengue among health care providers is needed.


Functional interactions between the nucleus tractus solitarius (NTS) and nucleus accumbens shell in modulating memory for arousing experiences.
The shell division of the nucleus accumbens receives noradrenergic input from neurons in the nucleus of the solitary tract (NTS) that transmit information regarding fluctuations in peripheral hormonal and autonomic activity. Accumbens shell neurons also receive converging inputs from limbic areas such as the hippocampus and amygdala that process newly acquired information. However, few studies have explored whether peripheral information regarding changes in emotional arousal contributes to memory processing in the accumbens. The beneficial effects on memory produced by emotional arousal and the corresponding activation of NTS neurons may be mediated through influences on neuronal activity in the accumbens shell during memory encoding. To explore this putative relationship, Experiment 1 examined interactions between the NTS and the accumbens shell in modulating memory for responses acquired after footshock training in a water-motivated inhibitory avoidance task. Memory for the noxious shock was significantly improved by posttraining excitation of noradrenergic NTS neurons. The enhanced retention produced by activating NTS neurons was attenuated by suppressing neuronal activity in the accumbens shell with bupivacaine (0.25%/0.5 microl). Experiment 2 examined the direct involvement of accumbens shell noradrenergic activation in the modulation of memory for psychologically arousing events such as a reduction in perceived reward value. Noradrenergic activation of the accumbens shell with phenylephrine (1.0 microg/0.5 microl) produced an enhancement in memory for the frustrating experience relative to control injections as evidenced by runway performance on an extended seven-day retention test. These findings demonstrate a functional relationship between NTS neurons and the accumbens shell in modulating memory following physiological arousal and identifies a role of norepinephrine in modulating synaptic activity in the accumbens shell to facilitate this process.


Advances in understanding the initiation of HIV-1 reverse transcription.
Many viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Human Immunodeficiency Virus (HIV), use RNA as their genetic material. How viruses harness RNA structure and RNA-protein interactions to control their replication remains obscure. Recent advances in the characterization of HIV-1 reverse transcriptase, the enzyme that converts its single-stranded RNA genome into a double-stranded DNA copy, reveal how the reverse transcription complex evolves during initiation. Here we highlight these advances in HIV-1 structural biology and discuss how they are furthering our understanding of HIV and related ribonucleoprotein complexes implicated in viral disease.


Sleep apps and behavioral constructs: A content analysis.
Although sleep apps are among the most popular commercially available health apps, little is known about how well these apps are grounded in behavioral theory. Three-hundred and sixty-nine apps were initially identified using the term "sleep" from the Google play store and Apple iTunes in September 2015. The final sample consisted of 35 apps that met the following inclusion criteria: 1) Stand-alone functionality; 2) Sleep tracker or monitor apps ranked by 100 + users; 3) Sleep Alarm apps ranked by 1000 + users; and 4) English language. A coding instrument was developed to assess the presence of 19 theoretical constructs. All 35 apps were downloaded and coded. The inter-rater reliability between coders was 0.996. A "1" was assigned if a construct was present in the app and "0" if it was not. Mean scores were calculated across all apps, and comparisons were made between total scores and app ratings using R. The mean behavior construct scores (BCS) across all apps was 34% (5% - 84%). Behavioral constructs for realistic goal setting (86%), time management (77%), and self-monitoring (66%) were most common. Although a positive association was observed between BCS and user ratings, this was not found to be statistically significant (p > 0.05). The mean persuasive technology score was 42% (20% to 80%), with higher scores for paid compared to free apps (p < 0.05). While the overall behavior construct scores were low, an opportunity exists to develop or modify existing apps to support sustainable sleep hygiene practices.


Behavioural tolerance to morphine analgesia is supraspinally mediated: a quantitative analysis of dose-response relationships.
Repeated exposure of a rat to a nociceptive testing environment ('habituation') enhances its sensitivity to noxious thermal stimuli20 and reduces the antinociceptive effect of a subsequent acute dose of morphine ('behavioural tolerance'). The present study quantitatively characterises the effects of habituation upon morphine antinociception using hot-plate (50 and 55 degrees C) and reflex withdrawal tests (dipping the tail and hindpaws into water at 49 degrees C). Dose-response relationships were modeled with the empirical function; E = Eo + (EMAX*DN)/(ED50N + DN) where E is the time-integrated response, EMAX is the response attributable to morphine, Eo is the baseline response, D is the dose and N is a steepness parameter. Habituation reduced EMAX in both hot-plate tests and also reduced Eo on the 50 degrees C hot-plate. In both reflex tests, habituation reduced Eo to that of spinal animals and EMAX to a value intermediate between that of intact and spinal animals. Neither the ED50 nor the value of N was altered by habituation. Acute spinal novice and habituated animals had similar dose-response curves and parameters. Sham spinalisation had no significant effect on any of the parameters. It is concluded that habituation to the nociceptive testing environment substantially reduces the bulbospinal contribution to morphine analgesia but has no effect upon the spinal component.


Role of renal expression of CD68 in the long-term prognosis of proliferative lupus nephritis.
Renal histology of proliferative lupus nephritis (LN) shows increased macrophage infiltration, but its association with renal outcome is a matter of debate. Here, we investigate the potential relationship that macrophage expression has with renal prognosis in patients with proliferative LN. Fifty patients newly diagnosed with proliferative LN were followed for a median of 8 years. Laboratory testing was conducted at diagnosis, after induction therapy and at the final follow-up evaluation. Renal biopsies were obtained at diagnosis and underwent immunohistochemical analysis with anti-CD68 and monocyte chemoattractant protein 1 monoclonal antibodies. Patients were stratified at final follow-up evaluation into glomerular filtration rate (GFR) >60 ml/min/1.73 m2 (non-progressor group; n = 24) and GFR ≤60 ml/min/1.73 m2 (progressor group; n = 26). All patients were treated with prednisone and six pulses of cyclophosphamide on induction therapy. Conventional maintenance therapy was administered in both groups. Compared to progressors, the non-progressor group showed a lower chronicity index (p = 0.01) and fewer CD68-positive cells in the renal tubules (p = 0.01) and particularly in the renal interstitium (p = 0.0003). Baseline and final serum creatinine correlated positively with the chronicity index (r = 0.3, p = 0.01 and r = 0.3, p = 0.04, respectively), and final serum creatinine correlated positively with interstitial expression of CD68 (r = 0.4, p = 0.0006). Renal expression of CD68 and the chronicity index are associated with progression to chronic kidney disease in patients with proliferative LN.


Management of croup.
Croup, or laryngotracheobronchitis, is a common childhood illness most often caused by viral infections. It is usually a benign, self-limiting disease, but can result in life-threatening upper airway obstruction. Until recently, it was not uncommon for children with severe croup to be admitted to intensive care for intubation. Management used to be limited to supportive measures, including mist therapy. The use of corticosteroids in patients with croup was controversial for many years but has, in the last decade, transformed the management of this disorder. Although corticosteroids do not alter the history of the viral infection, an adequate dose of oral or parenteral dexamethasone or nebulized budesonide has been shown to have a beneficial effect on the symptoms of croup.


Pharmacological chaperones improve intra-domain stability and inter-domain assembly via distinct binding sites to rescue misfolded CFTR.
Protein misfolding is involved in a large number of diseases, among which cystic fibrosis. Complex intra- and inter-domain folding defects associated with mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, among which p.Phe508del (F508del), have recently become a therapeutical target. Clinically approved correctors such as VX-809, VX-661, and VX-445, rescue mutant protein. However, their binding sites and mechanisms of action are still incompletely understood. Blind docking onto the 3D structures of both the first membrane-spanning domain (MSD1) and the first nucleotide-binding domain (NBD1), followed by molecular dynamics simulations, revealed the presence of two potential VX-809 corrector binding sites which, when mutated, abrogated rescue. Network of amino acids in the lasso helix 2 and the intracellular loops ICL1 and ICL4 allosterically coupled MSD1 and NBD1. Corrector VX-445 also occupied two potential binding sites on MSD1 and NBD1, the latter being shared with VX-809. Binding of both correctors on MSD1 enhanced the allostery between MSD1 and NBD1, hence the increased efficacy of the corrector combination. These correctors improve both intra-domain folding by stabilizing fragile protein-lipid interfaces and inter-domain assembly via distant allosteric couplings. These results provide novel mechanistic insights into the rescue of misfolded proteins by small molecules.


A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense.
Infectivity of Trypanosoma brucei rhodesiense to humans is due to its resistance to a lytic factor present in human serum. In the ETat 1 strain this character was associated with antigenic variation, since expression of the ETat 1.10 variant surface glycoprotein was required to generate resistant (R) clones. In addition, in this strain transcription of a gene termed SRA was detected in R clones only. We show that the ETat 1.10 expression site is the one selectively transcribed in R variants. This expression site contains SRA as an expression site-associated gene (ESAG) and is characterized by the deletion of several ESAGs. Transfection of SRA into T.b. brucei was sufficient to confer resistance to human serum, identifying this gene as one of those responsible for T.b. rhodesiense adaptation to humans.


Suppression of RPL34 Inhibits Tumor Cell Proliferation and Promotes Apoptosis in Glioblastoma.
Accumulating evidence indicates Ribosomal protein 34 (RPL34) promotes tumor malignance and its expression is associated with poor prognosis in multiple cancer cells. However, the physiological role and biological mechanism of RPL34 in glioblastoma (GBM) remain unclear. Hence, this study aimed to investigate the expression and the role of RPL34 in GBM. A total of 59 glioma samples and 12 normal brains for epilepsy surgery were used to determine the underlying mechanisms and the biological behaviors of RPL34 in GBM. In this study, we identified that RPL34 expression was significantly (p < 0.05) enriched in GBM tumors compared with low-grade glioma and normal brain, and its expression was associated with poor survival. Additionally, RPL34 was functionally required for tumor proliferation in vitro. Mechanically, inhibition of RPL34 induced glioma cell apoptosis by activation of Bad/Caspase7/PARP signaling pathway. The RPL34 promotes cell survival in GBM and could be a potential therapeutic target for GBM.


Children and Adolescents' Anthropometrics Body Composition from 3-D Optical Surface Scans.
This study aimed to explore the accuracy and precision of three-dimensional optical (3DO) whole-body scanning for automated anthropometry and estimating total and regional body composition. Healthy children and adolescents (n = 181, ages 5-17 years) were recruited for the Shape Up! Kids study. Each participant underwent whole-body dual-energy x-ray absorptiometry and 3DO scans; multisite conventional tape measurements served as the anthropometric criterion measure. 3DO body shape was described using automated body circumference, length, and volume measures. 3DO estimates were compared with criterion measures using simple linear regression by the stepwise selection method. Of the 181 participants, 112 were used for the training set, 49 were used for the test set, and 20 were excluded for technical reasons. 3DO body composition estimates were strongly associated with dual-energy x-ray absorptiometry measures for percent body fat, fat mass, and fat-free mass (R2 : 0.83, 0.96, and 0.98, respectively). 3DO provided reliable measurements of fat mass (coefficient of variation, 3.30; root mean square error [RMSE], 0.53), fat-free mass (coefficient of variation, 1.34; RMSE, 0.53 kg), and percent body fat (RMSE = 1.2%). 3DO surface scanning provides accurate and precise anthropometric and body composition estimates in children and adolescents with high precision. 3DO is a safe, accessible, and practical method for evaluating body shape and composition in research and clinical settings.


Unprecedented side reactions in Stille coupling: desired ones for Stille polycondensation.
Two types of unprecedented side reactions were identified in the Stille coupling reaction, including the direct C-H stannylation of the α-hydrogen of thiophene and the stannylation of arylbromides with trialkylstannane bromide. These results reveal the major source of enhancements for Stille polycondensation efficiency.


Study of the role of breast self-examination in the reduction of mortality from breast cancer. The Russian Federation/World Health Organization Study.
The protocol of a study, sponsored by the World Health Organization, of the role of breast self-examination (BSE) in reduction of mortality from breast cancer is presented. The major objective of the study is to determine the effect of a BSE programme on mortality from breast cancer. A population of of over 193,000 women aged 40 to 64 has been defined in Moscow and St Petersburg and randomised to study and control groups. In Moscow the education programme is based on a two-way communication principle allowing efficient person-to-person education in groups of up to 20 individuals and feedback information through specially designed personal calendars. In St Petersburg, class and individual instruction is carried out. After a 1-year feasibility study the project is planned to last for 15 years. It consists of an aggressive education programme, during and following which, all newly diagnosed breast cancers will be registered and treated, and followed up for 3 to 15 years. A key issue of the study is compliance of the population with BSE. The frequency and competence of BSE practice has been defined in subsamples of 400 randomly selected women by means of surveys at 6 months, 1, 2 and 3 years after the start of the project. The study is expected to result in the accrual of more than 1470 new breast cancer cases and 778 deaths from breast cancer. The power of the study is expected to permit detection of a 30% reduction in cumulative breast cancer mortality, assuming that 50-70% of the women in the study group practise BSE.


Detecting the corneal neovascularisation area using artificial intelligence.
To create and assess the performance of an artificial intelligence-based image analysis tool for the measurement and quantification of the corneal neovascularisation (CoNV) area. Slit lamp images of patients with CoNV were exported from the electronic medical records and included in the study. An experienced ophthalmologist made manual annotations of the CoNV areas, which were then used to create, train and evaluate an automated image analysis tool that uses deep learning to segment and detect CoNV areas. A pretrained neural network (U-Net) was used and fine-tuned on the annotated images. Sixfold cross-validation was used to evaluate the performance of the algorithm on each subset of 20 images. The main metric for our evaluation was intersection over union (IoU). The slit lamp images of 120 eyes of 120 patients with CoNV were included in the analysis. Detections of the total corneal area achieved IoU between 90.0% and 95.5% in each fold and those of the non-vascularised area achieved IoU between 76.6% and 82.2%. The specificity for the detection was between 96.4% and 98.6% for the total corneal area and 96.6% and 98.0% for the non-vascularised area. The proposed algorithm showed a high accuracy compared with the measurement made by an ophthalmologist. The study suggests that an automated tool using artificial intelligence may be used for the calculation of the CoNV area from the slit-lamp images of patients with CoNV.


Physical activity in adults with epilepsy: clinical aspects and relationship with cognition and quality of life.
There are several factors associated with lower participation in regular physical activity (PA) in adult patients with epilepsy (PWEs). To assess the relationship between the regular practice of PA with clinical and cognitive variables and quality of life (QoL) in PWEs. Habitual Physical Activity Questionnaire (HPAQ) was related to clinical variables, scores on the Mini-Mental State Examination (MMSE), on the Brief Cognitive Battery-Edu (BCB-Edu), on the Satisfaction Scale for Physical Activity (SSPA), and on the Quality of Life in Epilepsy Inventory (QOLIE)-31 in 60 PWEs, with a significance level of p<0.05. The PWEs had a mean age of 42.4±13.6 years, 50% of whom were female. Longer length of epilepsy correlated with lower PA in leisure time (Pearson correlation [r]= -0.276; p-value [p]=0.036). The occupational physical activity scores of the HPAQ correlated positively with perception (r=0.300; p=0.021), memory (r=0.381; p=0.003), semantic verbal fluency test (SVF) (r=0.427; p=0.001), and with the total score in the MMSE (r=0.327; p=0.012). The total HPAQ score correlated with the SVF (r=0.336; p=0.009) and with the MMSE (r=0.254; p=0.049). There was no correlation among the QOLIE-31, the HPAQ, and the SSPA. Longer duration of epilepsy was associated with the lower practice of PA. Physical activity was associated with better performance in aspects of cognition. There was no relationship between QoL and practice and satisfaction with PA, suggesting different psychosocial aspects involved.


Minimally Invasive Anterior Semitendinosus Harvest: A Technique to Decrease Saphenous Nerve Injury.
Hamstring tendon harvest, especially semitendinosus harvest, has been widely used in anterior cruciate ligament reconstruction for many years. However, donor site morbidity has been described regarding the infrapatellar branch of the saphenous nerve. Minimally invasive anterior semitendinosus harvest is a simple, safe, reproducible, and elegant technique. A 2-cm vertical incision above the pes anserinus is performed 2 cm medial to the tibial anterior tubercle. The fascia superficialis is opened with a horizontal incision, and the gracilis is isolated using a retractor. The semitendinosus is grabbed with a probe, and the vincula are hooked one by one. The tendon is harvested with a closed stripper. The expansions are cut, and the tendon is detached from the bone with part of the periosteum.


A general method for precalculation of parameters for sustained off resonance irradiation/collision-induced dissociation.
Sustained off resonance irradiation (SORI) collision-induced dissociation (CID) is a commonly used method of collisionally activating ions for fragmentation in Fourier transform mass spectrometric experiments. To achieve the degree of fragmentation desired, both the irradiation frequency and amplitude must be optimized. This is a time-consuming procedure, particularly when the m/z values of the precursor ions vary over a broad range. We present an approach that simplifies this optimization by precalculating the irradiation frequency of the ions to be fragmented as a constant percentage of the reduced cyclotron frequency. Using this approach, the optimal amplitude was found to be significantly less dependent on the m/z value of the precursor ion, and therefore required little or no adjustment. This method considerably simplified optimization of SORI-CID for analysis of carbohydrates, glycoconjugates, and peptides over the mass range m/z 300-3500, requiring optimization of only a single experimental parameter, the irradiation amplitude, and only for the first MS/MS stage.


Outcomes after peritoneal dialysis catheter placement.
The purpose of this study was to review surgical outcomes after elective placement of peritoneal dialysis (PD) catheters in children with end-stage renal disease. Children with PD catheters placed between February 2002 and July 2014 were retrospectively reviewed. Outcomes were catheter life, late (>30days post-op) complications (catheter malfunction, catheter malposition, infection), and re-operation rates. Comparison groups included laparoscopic versus open placement, age<2, and weight<10kg. Univariate and multivariate analysis were performed. One hundred sixteen patients had 173 catheters placed (122 open, 51 laparoscopic) with an average patient age of 9.7±6.3years. Mean catheter life was similar in the laparoscopic and open groups (581±539days versus 574±487days, p=0.938). The late complication rate was higher for open procedures (57% versus 37%, p=0.013). Children age<2 or weight<10kg had higher re-operation rates (64% versus 42%, p=0.014 and 73% versus 40%, p=0.001, respectively). Adjusted for age and weight, open technique remained a risk factor for late complications (OR 2.44, 95% CI 1.20-4.95) but not re-operation. Laparoscopic placement appears to reduce the rate of late complications in children who require PD dialysis catheters. Children <2years age or <10kg remain at risk for complications regardless of technique.


Molecular fingerprints of conazoles via functional genomic profiling of Saccharomyces cerevisiae.
Conazoles were designed to inhibit ergosterol biosynthesis. Conazoles have been widely used as agricultural fungicides and are frequently detected in the environment. Although conazoles have been reported to have adverse effects, such as potential carcinogenic effects, the underlying molecular mechanisms of toxicity remain unclear. Here, the molecular fingerprints of five conazoles (propiconazole (Pro), penconazole (Pen), tebuconazole (Teb), flusilazole (Flu) and epoxiconazole (Epo)) were assessed in Saccharomyces cerevisiae (yeast) via functional genome-wide knockout mutant profiling. A total of 169 (4.49%), 176 (4.67%), 198 (5.26%), 218 (5.79%) and 173 (4.59%) responsive genes were identified at three concentrations (IC50, IC20 and IC10) of Pro, Pen, Teb, Flu and Epo, respectively. The five conazoles tended to have similar gene mutant fingerprints and toxicity mechanisms. "Ribosome" (sce03010) and "cytoplasmic translation" (GO: 0002181) were the common KEGG pathway and GO biological process term by gene set enrichment analysis of the responsive genes, which suggested that conazoles influenced protein synthesis. Conazoles also affected fatty acids synthesis because "biosynthesis of unsaturated fatty acids" pathway was among the top-ranked KEGG pathways. Moreover, two genes, YGR037C (acyl-CoA-binding protein) and YCR034W (fatty acid elongase), were key fingerprints of conazoles because they played vital roles in conazole-induced toxicity. Overall, the fingerprints derived from the yeast functional genomic screening provide an alternative approach to elucidate the molecular mechanisms of environmental pollutant conazoles.


Digging for Significant Genes in Microarray Expression Data Based on Systematic Sampling and Hierarchal Clustering Algorithm.
Obesity is a worldwide health problem. Eating habits have changed during this decade and an increase in high-fat foods as well as sugar intake has been observed, which is associated with obesity and weight gaining. Therefore, in this chapter, we have analysed microarray expression data for obese and lean individuals. The microarray technology simultaneously records the expression levels of thousands of genes across related samples and during biological process. The microarray data sets are enriched with crucial information which have to be examined. In the study discussed in this chapter, the microarray data sets are pre-processed prior to analysis, in which upregulated and downregulated gene groups have been identified. Clustering is one of the learning techniques and it is applied in different fields of study. Clustering with microarray data can be accomplished based on genes or samples and depending on the type of datasets. Hierarchal clustering algorithm was used to detect gene patterns in our candidate datasets, since microarray data are considered big and complex. Systematic sampling technique was used to reduce the complexity of microarray datasets and to enhance the clustering quality. This technique is a simple and conductive sampling technique. The proposed algorithm, that is, Systematic Sampling with Hierarchal Clustering (SSHC), could detect significant gene patterns in the datasets, and the proposed system (SSHC) shows a better performance. The validity index utilized to evaluate the SSHC algorithm is adjusted Rand index (ARI).


Generation and characterization of a knock-in mouse model for spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM).
Solute carrier family 1 member 4 (SLC1A4), also referred to as Alanine/Serine/Cysteine/Threonine-preferring Transporter 1 (ASCT1), is a sodium-dependent neutral amino acid transporter. It is expressed in many tissues, including the brain, where it is expressed primarily on astrocytes and plays key roles in neuronal differentiation and development, maintaining neurotransmitter homeostasis, and N-methyl-D-aspartate neurotransmission, through regulation of L- and D-serine. Mutations in SLC1A4 are associated with the rare autosomal recessive neurodevelopmental disorder spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM, OMIM 616657). Psychomotor development and speech are significantly impaired in these patients, and many develop seizures. We generated and characterized a knock-in mouse model for the most common mutant allele, which results in a single amino acid change (p.Glu256Lys, or E256K). Homozygous mutants had increased D-serine uptake in the brain, microcephaly, and thin corpus callosum and cortex layer 1. While p.E256K homozygotes showed some significant differences in exploratory behavior relative to wildtype mice, their performance in assays for motor coordination, endurance, learning, and memory was normal, and they showed no significant differences in long-term potentiation. Taken together, these results indicate that the impact of the p.E256K mutation on cognition and motor function is minimal in mice, but other aspects of SLC1A4 function in the brain are conserved. Mice homozygous for p.E256K may be a good model for understanding the developmental basis of the corpus callosum and microcephaly phenotypes observed in SPATCCM patients and assessing whether they are rescued by serine supplementation.


[Desquamative interstitial pneumonia. Clinical, optic, ultrastructural, histo-immunoligical and enzymatic study of a case].
The desquamative intersitial pneumonia is a rare, sometimes curable from of diffuse interstitial fibrosis. A clinical, optical and ultrastructural, immunochemical and histo-enzymologic study of one case proved the macrophage nature of the intra-alveolar cells and suggested in the histo-genesis an immunological mechanism depending on lymphocytes.


Simplified anesthesia technique for scleral tunnel phacoemulsification.
A simplified anesthesia technique for sutureless scleral tunnel, small incision, one-port phacoemulsification is described. Step 1: Mild intravenous sedation is achieved with 1 mg of midazolam and 10 mg of propofol. Step 2: A tetracaine- or preservative-free-lidocaine-soaked Weck cell sponge is applied to the superior bulbar conjunctiva and the superior episcleral tissue for localized anesthesia. Step 3: Preservative-free lidocaine 1%, 0.75 cc, is injected into the anterior chamber for intraocular anesthesia. This technique can be used in the presence of all types of cataracts, requires about 10 seconds to complete, and can be used with all phacoemulsification techniques. Results of the technique in a study population are reported.


E-Health Interventions for Eating Disorders: Emerging Findings, Issues, and Opportunities.
This study aimed to review the emerging findings regarding E-health interventions for eating disorders and to critically discuss emerging issues as well as challenges for future research. Internet-based cognitive behavioral therapy and guided self-help have demonstrated promising results in terms of reducing eating disorder psychopathology. Emerging findings also suggest that E-health interventions reach an underserved population and improve access to care. The use of smartphone applications is becoming increasingly popular and has much potential although their clinical utility and effectiveness is presently unknown and requires investigation. Important challenges include the diagnostic process in E-health interventions, the optimization of E-health within existing health care models, and the investigation and implementation of blended care. More high-quality research is needed to bring the field forward and to determine the place for E-health in our health care service delivery systems.


Fractures of the odontoid: a laboratory and clinical study of mechanisms.
Previous reports and a study of the mechanism of injury in 25 cases of fracture of the odontoid suggest that the fracture usually results from a high velocity force directed to the head, producing flexion, extension, or rotation of the upper cervical spine. In a laboratory biomechanical study using cadaver preparations, fractures of the odontoid were produced in 20 specimens from the upper cervical spine, which were loaded in failure in forward and lateral modes.


The predictive value of the epicardial adipose thickness in the rate of expansion of the aortic root.
Epicardial adipose tissue (ECAT) is metabolically active and is involved in the development of atherosclerosis. The thickness of ECAT has been positively correlated with the dimensions of the ascending aorta. We aimed to examine whether ECAT thickness predicted the expansion of the aortic dimensions. The imaging results of patients who had undergone transthoracic echocardiographic (TTE) examinations more than twice during the period 2005-2015 were surveyed. We included adult patients who had undergone TTE examinations at least 1 year apart. The ECAT was measured in the parasternal long-axis view from the index TTE study. End-diastolic dimensions in three consecutive beats were averaged for all measurements. The annulus, root, and sinotubular junction (STJ) were also measured. The amount of increase (if any) in aortic dimensions per year was calculated and the correlation of this increase with the initial thickness of the ECAT was analyzed. In total, 429 examinations were performed with 197 patients (17 females), from which 394 examinations were analyzed. The ECAT thickness was 8.6 ± 3.6 mm. In the initial examinations, the annulus, STJ, and root measured 23 ± 4, 28 ± 4, and 34 ± 4 mm, respectively. In univariate analysis, for every 1 mm of ECAT thickness, the STJ expanded 0.056 (95% CI: 0.001-0.112 mm/year; p = 0.030) and the aortic root expanded 0.088 mm/year (p < 0.001). In multivariate analysis, ECAT thickness remained an independent predictor of the aortic root expansion. For every 1‑mm increase in ECAT thickness, the aortic root expanded by 0.036 mm (95% CI: 0.010-0.062) per year (p = 0.007). The thickness of the ECAT is a predictor of more rapid increases in the dimensions of the aortic root. Further studies of patients with established aortic aneurysm are warranted.


Immunohistochemical distributions of cathepsin B and basement membrane antigens in human lung adenocarcinoma: association with invasion and metastasis.
The distributions of cathepsin B (CB) a lysosomal cysteine proteinase, type IV collagen (CIV) and laminin (LM), which are main components of basement membranes (BMs) were studied in a series of 64 human lung adenocarcinomas using an immunohistochemical technique. Over-expression of CB (> 80% positive cells) was significantly associated with the grade of tumour differentiation (p < 0.01), with lymph node metastasis (p < 0.01) and with BM degradation (p < 0.01) detected by the staining pattern of CIV and LM. It was significantly associated with a prognostic disadvantage (p < 0.01). The immunohistochemical staining pattern of CB has a close relationship with degradation of BM, and may be used as a marker for tumour metastasis and prognosis in lung adenocarcinoma.


Assessment of in vitro antimicrobial efficacy of biologically synthesized metal nanoparticles against pathogenic bacteria.
The microbial infections due to biofilm forming bacterial pathogens are very common in human subjects. The intensive application of antibiotics in integrated disease management strategy has led to increased multidrug resistance incommon pathogens. Thus, indicating need of developing an alternative method for the control of these multidrug resistant pathogens. Present study involves the Moringa oleifera aqueous extract mediated biological synthesis of silver (Ag nanoparticles (NPs)- Avg. size 82.5 nm; zeta potential = -27.9 mV), copper oxide (CuONPs- Avg. size 61 nm; zeta potential = -19.3 mV), iron oxide (FeONPs- Avg. size 83.3 nm; zeta potential = -9.37 mV) and alumina (AlONPs- Avg. size 87.3 nm; zeta potential = -10.9 mV) nanoparticles. Biological nanoparticles were detected by visual observation, spectrophotometric detection followed by zeta potential analysis, nanoparticle tracking analysis, Fourier transform infrared spectrometry and X-ray diffraction analysis. Nanoparticles were further evaluated for their in vitro antimicrobial potential, membrane damage effectiveness, biofilm inhibition activity by MTT assay. Nanoparticles were assessed against human pathogens viz. two Gram-positive (Bacillus subtilis MTCC 441 and Staphylococcus haemolyticus MTCC 3383) and two Gram-negative bacteria (Enterobacter aerogenes MTCC 111 and Salmonella enterica ser. Typhi MTCC 8767). The nanoparticles exhibited akin activity pattern against all pathogens studied i.e. AgNPs > CuONPs > AlONPs > FeONPs. Tested nanoparticles registered lower MIC values and more intensified growth inhibition against Gram-negative bacteria compared to their Gram-positive counterparts. These results pointed out that the M. oleifera mediated nanoparticles can be prospectivelyutilized in the development of alternative antimicrobials against diverse bacterial infections.


Pathological complete response after neoadjuvant chemotherapy with FOLFOX for locally advanced sigmoid colon cancer with diverticulitis: A case report.
The standard treatment for locally advanced colon cancer (LACC) without distant metastasis is curative surgery followed by adjuvant chemotherapy, but the long-term outcomes of this strategy are not satisfactory. Neoadjuvant chemotherapy (NAC) is a promising novel option to overcome this issue. Tumor regression is an expected effect of NAC for LACC, but pathological complete response (pCR) is rare. In this report, we present a rare case of pCR after NAC with FOLFOX for LACC in the sigmoid colon. A 66-year-old woman presented to our hospital with fever and abdominal pain. The diagnosis was LACC in the sigmoid colon with possible invasion of the uterus and pelvic wall, stage IIIC (T4bN1bM0). Furthermore, the tumor was complicated by diverticulitis. A colostomy was performed, followed by NAC with FOLFOX. Six cycles were completed without significant adverse events, and the lesion shrunk remarkably. We performed a curative sigmoidectomy without any postoperative complications. Pathological examination revealed no viable cancer cells, indicating pCR. To the best of our knowledge, this is the first report of pCR after NAC for LACC complicated by diverticulitis. Colostomy before NAC, regimen, and cycle of NAC may be the key to this favorable course. We present a rare case of pathological complete after neoadjuvant chemotherapy with FOLFOX for locally advanced colon cancer in the sigmoid colon complicated by diverticulitis. Our experience may be valuable in determining the optimal treatment strategy for LACC complicated by diverticulitis.


Pyloric motor response to intraduodenal dextrose involves muscarinic mechanisms.
The delivery of dextrose solutions to the duodenum is associated with the stimulation of phasic and tonic pyloric contraction. In this study, the effects of intravenous atropine on the antropyloroduodenal motor responses to intraduodenal infusions of 25% dextrose were assessed in 10 normal volunteers. Antropyloroduodenal pressures were recorded with a manometric assembly incorporating a sleeve sensor spanning the pylorus, and sideholes in the antrum and duodenum. In each experiment, three intraduodenal infusions of 25% dextrose were given at a rate of 4 ml/min, for a median duration of 19 min (range 17-20). During the second dextrose infusion, intravenous atropine was given as a bolus (15 micrograms/kg) followed by an infusion (4 micrograms/kg.min), which was continued until the end of each experiment. Before atropine was given, the pyloric motor response to the second dextrose infusion was not significantly different from the response to the first infusion, but after administration of atropine there was a rapid decrease in the rate of isolated pyloric pressure waves, from 0.8 to 0.1 per minute (p less than 0.05). The isolated pyloric pressure wave response to the third dextrose infusion was completely blocked, and there was a much smaller maximum increase in basal pyloric pressure compared with the first infusion (p less than 0.01). This study indicates that intraduodenal dextrose reproducibly stimulates isolated pyloric pressure waves and increases basal pyloric pressure by mechanisms that involve muscarinic receptors.


Formal ontology for natural language processing and the integration of biomedical databases.
The central hypothesis underlying this communication is that the methodology and conceptual rigor of a philosophically inspired formal ontology can bring significant benefits in the development and maintenance of application ontologies [A. Flett, M. Dos Santos, W. Ceusters, Some Ontology Engineering Procedures and their Supporting Technologies, EKAW2002, 2003]. This hypothesis has been tested in the collaboration between Language and Computing (L&C), a company specializing in software for supporting natural language processing especially in the medical field, and the Institute for Formal Ontology and Medical Information Science (IFOMIS), an academic research institution concerned with the theoretical foundations of ontology. In the course of this collaboration L&C's ontology, LinKBase, which is designed to integrate and support reasoning across a plurality of external databases, has been subjected to a thorough auditing on the basis of the principles underlying IFOMIS's Basic Formal Ontology (BFO) [B. Smith, Basic Formal Ontology, 2002. http://ontology.buffalo.edu/bfo]. The goal is to transform a large terminology-based ontology into one with the ability to support reasoning applications. Our general procedure has been the implementation of a meta-ontological definition space in which the definitions of all the concepts and relations in LinKBase are standardized in the framework of first-order logic. In this paper we describe how this principles-based standardization has led to a greater degree of internal coherence of the LinKBase structure, and how it has facilitated the construction of mappings between external databases using LinKBase as translation hub. We argue that the collaboration here described represents a new phase in the quest to solve the so-called "Tower of Babel" problem of ontology integration [F. Montayne, J. Flanagan, Formal Ontology: The Foundation for Natural Language Processing, 2003. http://www.landcglobal.com/].


Observation of aerosol size distribution and new particle formation at a coastal city in the Yangtze River Delta, China.
Aerosol number size distribution in the range of 10nm-10μm, trace gases (O3, CO, SO2 and NO2), particular matter (PM: PM2.5 and PM10) and meteorological elements were measured from the 1st to the 31st of May, 2015, in the coastal city of Jiaxing in the Yangtze River Delta (YRD). The average number concentration and surface area concentration were 19,639cm(-3) and 427μm(2)cm(-3) during the observation period. The different mode particle concentrations ranked in the order of Aitken mode (12,361cm(-3))>nucleation (4926.7cm(-3))>accumulation (2349.3cm(-3))>coarse mode (1.7cm(-3)). The average concentrations of CO, SO2, NO2, O3, PM2.5 and PM10 were 0.545mgm(-3), 14.7, 35.1, 89.8, 43.5 and 64.6μgm(-3), respectively. Eight precipitation processes and 15 new particle formation (NPF) events (3 NPF events occurred on a rainy day) were observed. Results show that the precipitation process had greater scavenging effects on particles smaller than 120nm and larger than 2μm. The spectral distributions of number concentrations were unimodal at different weather conditions, with peaks at 20nm, 40-60nm, 50-80nm on NPF days, rainy days and normal days. During the NPF events, the formation rate (FR), growth rate (GR), condensational sink (CS), vapor source rate (Q) and condensing vapor concentration (C) were in the range of 4.0-17.0cm(-3)s(-1), 2.2-15.7nmh(-1), 1.5-5.8×10(-2)s(-1), 0.5-7.7×10(6)cm(-3)s(-1) and 3.0-21.5×10(7)cm(-3), with mean values of 9.6cm(-3)s(-1), 6.8nmh(-1), 3.4×10(-2)s(-1), 3.3×10(6)cm(-3)s(-1) and 9.4×10(7)cm(-3), respectively. NPF events normally occurred under clean atmospheric conditions with low PM concentrations but high levels of trace gases. It was also found that SO2 plays an important role in NPF and growth in Jiaxing.


Clinico-pathological correlation of glucagon-positive pancreatic endocrine tumours: a presentation of five cases.
The clinicopathologic correlation of five cases of glucagon-positive pancreatic tumours is reviewed. Two cases with the typical glucagonoma syndrome but with atypical manifestations in the central nervous system are presented. These neurological manifestations might constitute a new paraneoplastic syndrome. The last three cases illustrate how glucagon positivity can be present in pancreatic endocrine tumours other than in the classical glucagonoma.


Erythropoietin enhancer stimulates production of a recombinant protein by Chinese hamster ovary (CHO) cells under hypoxic condition.
Oxygen is a limiting nutrient in animal cell culture and its supply is still worthy of improvement for production of useful proteins with a high efficiency. From a different point of view, development of the system by which a high productivity can be maintained even under hypoxic condition as well as under normoxic condition may be important. A number of hypoxia-inducible genes have been found in eucaryotic cells and the induction in most cases, if not all, is due to hypoxic activation of the gene transcription. Transcription of erythropoietin gene is highly hypoxia-inducible and the induction is achieved by binding of a protein, which is widely distributed in animal cells, to a short DNA stretch (erythropoietin enhancer) in the 3' flanking region of erythropoietin gene. Using a hepatoma cell line (Hep3B) that produces the endogenous erythropoietin in an oxygen-dependent manner and Chinese hamster ovary cells that have been widely used for production of recombinant proteins, we show that, under hypoxic condition, the erythropoietin enhancer can activate not only the promoter of erythropoietin gene but also promoters of cytomegalovirus early genes and eucaryotic polypeptide chain elongation factor gene, both of which are very active in animal cells under normoxic condition.


Stress incontinence: classification and surgical approach.
We present a modified classification for stress urinary incontinence based on the nature of vesical neck descent and the integrity of the intrinsic sphinteric mechanism. Surgical treatment was undertaken in 72 patients with this classification. With a minimum followup of 18 months there was a 94 per cent cure rate with respect to stress incontinence. However, in 14 patients significant frequency and urgency developed, which persisted for at least 6 months postoperatively. Of these patients 13 had undergone a pubovaginal sling procedure, 3 of whom had refractory symptoms, including urge incontinence, which resulted in augmentation cystoplasty in 2 and supravesical urinary diversion in 1.


Fcγ Receptor-Dependent Internalization and Off-Target Cytotoxicity of Antibody-Drug Conjugate Aggregates.
Antibody-drug conjugates (ADCs), which are monoclonal antibodies (mAbs) conjugated with highly toxic payloads, achieve high tumor killing efficacy due to the specific delivery of payloads in accordance with mAbs' function. On the other hand, the conjugation of payloads often increases the hydrophobicity of mAbs, resulting in reduced stability and increased aggregation. It is considered that mAb aggregates have potential risk for activating Fcγ receptors (FcγRs) on immune cells, and are internalized into cells via FcγRs. Based on the mechanism of action of ADCs, the internalization of ADCs into target-negative cells may cause the off-target toxicity. However, the impacts of aggregation on the safety of ADCs including off-target cytotoxicity have been unclear. In this study, we investigated the cytotoxicity of ADC aggregates in target-negative cells. The ADC aggregates were generated by stirring stress or thermal stress. The off-target cytotoxicity of ADC aggregates was evaluated in several target-negative cell lines, and FcγR-activation properties of ADC aggregates were characterized using a reporter cell assay. Aggregation of ADCs enhanced the off-target cytotoxicity in several target-negative cell lines compared with non-stressed ADCs. Notably, ADC aggregates with FcγR-activation properties showed dramatically enhanced cytotoxicity in FcγR-expressing cells. The FcγR-mediated off-target cytotoxicity of ADC aggregates was reduced by using a FcγR-blocking antibody or Fc-engineering for silencing Fc-mediated effector functions. These results indicated that FcγRs play an important role for internalization of ADC aggregates into non-target cells, and the aggregation of ADCs increases the potential risk for off-target toxicity.


Do postonset segments define a lexical neighborhood?
Previous research has demonstrated that the number and frequency of lexical neighbors affects the perception of individual sounds within a nonword in a phoneme identification task. In the present research, the issue of what items should be considered part of a word's neighborhood was explored. These experiments, in which both lexical decision and phoneme identification tasks were used, demonstrate that lexical neighborhood effects are not limited to words that match the target item syllable initially (the cohort). Words that differ from a target only in their first phoneme influence the process of lexical access. This argues against the notion that word onsets serve a unique or special purpose in word recognition.


Stimulating Duddingtonia flagrans chlamydospore production through dehydration.
Duddingtonia flagrans is a nematode-trapping fungus that has shown promising results as a tool to combat parasitic nematode infections in livestock. The fungus interrupts the parasitic lifecycle by trapping and killing larval stages on pasture to prevent re-infection of animals. One barrier to the fungus' commercial use is scaling up production of the fungus, and specifically of chlamydospores, which survive the digestive tract to grow in fecal pats on pasture, thus have potential as a feed through anthelmintic. The purpose of this study was to evaluate the effect of dehydration on sporulation of the fungus. Disks of Duddingtonia flagrans type strain (ATCC® 13423™) were grown on 17% cornmeal agar for 26 days at 30 °C, then split into three groups; dried quickly at 38 °C and 37% humidity over 48 h ("incubated"), dried more slowly at 24 °C and 55% humidity over 10 days ("air-dried"), or kept at 30 °C and sealed with parafilm to prevent loss of moisture as a control ("wet"). Half of each dried culture was resuspended in water, then heated to liquify and homogenized through vortexing. Spores were then counted in a Neubauer hematocytometer. Both the "air-dried" and "incubated" drying techniques yielded significantly more spores than the "wet" control (Welch's two sample t test p values of .0359 and .0411, respectively). The difference in average chlamydospores per milliliter was insignificant between the two drying techniques, although a visual representation of the data shows less spore count variability in the "air-dried" technique.


Opportunities for Participation in Randomized Controlled Trials for Patients with Multiple Myeloma: Trial Access Depends on Restrictive Eligibility Criteria and Patient Expectations.
Randomized controlled trials (RCT) are the driver of therapeutic innovations. However, it has been frequently shown that less than 5% of adult cancer patients enroll in clinical trials, although 70% of patients are considered as being willing to participate. Barriers to trial participation have been extensively studied. Although there is evidence that trial participation correlates with improved survival and reduced mortality, the rate of participation has not changed substantially. We provide retrospective data from a single-center analysis of 411 patients with multiple myeloma (MM) who were treated at the University Hospital Duesseldorf in Germany between January 2014 and December 2016. Each patient was analyzed for the real-world possibility of participating in a clinical study, based on the inclusion and exclusion (I/E) criteria and the recruiting period of open studies. The overall rate of study participation was 19%. A total of 53% of NDMM patients were eligible for first-line studies (GMMG-HD6, LenaMain). Of these, 80% consented to enrolment (42% of all). In contrast, only 38% of the RRMM population was eligible (GMMG-Relapse, Castor, Tourmaline, Admyre). Of these, only 22% (7% of all) consented. This was confirmed by virtual analysis, showing that only 29% of all RRMM patients would have been eligible for six internationally recruiting trials leading to later drug approval. The majority of cases were rendered ineligible by only one I/E criterion. The most common criteria were study-specific (prior therapies or refractory disease to a specific drug), kidney disease, and previous malignancy, followed by internal, neurologic, and infectious disease. In summary, this single-center analysis showed that I/E criteria permit study participation for most NNDM patients, with a dramatic decrease in the RRMM population. This is aggravated by the fact that the willingness for study participation also significantly declines in RRMM. Thus, addressing patient expectations and priorities seems to be the most promising approach to increasing patient enrollment in clinical trials.