Differential Activation of TRP Channels in the Adult Rat Spinal Substantia Gelatinosa by Stereoisomers of Plant-Derived Chemicals.
Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of dorsal root ganglion (DRG) neuron increases the spontaneous release of l-glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons which play a pivotal role in regulating nociceptive transmission. The TRP channels are activated by various plant-derived chemicals. Although stereoisomers activate or modulate ion channels in a distinct manner, this phenomenon is not fully addressed for TRP channels. By applying the whole-cell patch-clamp technique to SG neurons of adult rat spinal cord slices, we found out that all of plant-derived chemicals, carvacrol, thymol, carvone and cineole, increase the frequency of spontaneous excitatory postsynaptic current, a measure of the spontaneous release of l-glutamate from nerve terminals, by activating TRP channels. The presynaptic activities were different between stereoisomers (carvacrol and thymol; (-)-carvone and (+)-carvone; 1,8-cineole and 1,4-cineole) in the extent or the types of TRP channels activated, indicating that TRP channels in the SG are activated by stereoisomers in a distinct manner. This result could serve to know the properties of the central terminal TRP channels that are targets of drugs for alleviating pain.


Evaluation of Altona Diagnostics RealStar Zika Virus Reverse Transcription-PCR Test Kit for Zika Virus PCR Testing.
With the emerging Zika virus (ZIKV) epidemic, accessible real-time reverse transcription-PCR (rRT-PCR) assays are needed to streamline testing. The commercial Altona Diagnostics RealStar ZIKV rRT-PCR test kit (Altona PCR) has been approved for emergency use authorization by the U.S. FDA. Our aim was to verify the Altona PCR by comparing it to the CDC-designed dual-target ZIKV rRT-PCR reference assay (reference PCR) and describe the demographics of patients tested for ZIKV by rRT-PCR in Ontario, Canada. A large set of clinical specimens was tested for ZIKV by the Altona PCR and the reference PCR. Positive or equivocal specimens underwent PCR and Sanger sequencing targeting the ZIKV NS5 gene. A total of 671 serum specimens were tested by the reference PCR: 58 (8.6%) were positive, 193 (28.8%) were equivocal, and 420 (62.6%) were negative. Ninety percent of the reference PCR-positive patients were tested in the first 5 days after symptom onset. The Altona PCR was performed on 284/671 specimens tested by the reference PCR. The Altona PCR was positive for 53/58 (91%) reference PCR-positive specimens and 16/193 (8%) reference PCR-equivocal specimens; the ZIKV NS5 PCR was positive for all 68 Altona PCR-positive specimens and negative for all 181 Altona PCR-negative specimens that underwent the NS5 PCR. The Altona PCR has very good sensitivity (91%) and specificity (97%) compared to the reference PCR. The Altona PCR can be used for ZIKV diagnostic testing and has less extensive verification requirements than a laboratory-developed test.


[The role of the yeasts Malassezia sp. in etiopathology of atopic dermatitis].
Atopic dermatitis (AD) is one of the most common chronic, recurrent, inflammatory skin disease. Its pathogenesis is still not fully understood. The lipophilic yeasts Malassezia sp, members of the normal human cutaneous flora, can be the factors that may contribute to AD. Specific IgE antibodies to Malassezia sp., skin prick tests, atopy patch tests indicate that these yeasts may be an important allergen especially in patients with AD localized on the head and neck. During exacerbations of the AD, supplementary treatment with proper antifungal agents has been shown to be of great value.


Phosphatidylcholine and phosphatidylethanolamine plasmalogens in lipid loaded human macrophages.
Plasmalogens are either phosphatidylcholine (PC P) or phosphatidylethanolamine (PE P) glycerophospholipids containing a vinyl ether moiety in sn-1-position and an esterified fatty acid in sn-2 position. Multiple functions have been proposed, including reservoir of precursors for inflammatory mediators, modulation of membrane fluidity, and anti-oxidative properties. They could therefore play a role under conditions of metabolic stress. Especially enzymatically modified LDL (eLDL) and oxidatively modified LDL (oxLDL) represent modifications of LDL that are taken up by macrophages in atherosclerotic plaques. The aim of this study was to analyze plasmalogen related effects of eLDL and oxLDL in human monocyte derived macrophages, as well as the effects of HDL3 mediated deloading. Elutriated monocytes from nine healthy donors were differentiated in vitro for four days. Macrophages were then loaded with native LDL, eLDL and oxLDL for 24h and subsequently deloaded with HDL3 for another 24h. Lipidomic and transcriptomic profiles were obtained. Loading of macrophages with eLDL and oxLDL led to a transient but strong elevation of lysophosphatidylcholine (LPC) most likely through direct uptake. Only eLDL induced increased levels of total PC, presumably through an induction of PC synthesis. On the other hand treatment with oxLDL led to a significant increase in PC P. Analysis of individual lipid species showed lipoprotein and saturation specific effects for LPC, PC P and PE P species. Membrane fluidity was decreased by the large amount of FC contained in the lipoproteins, as indicated by a lower PC to FC ratio after lipoprotein loading. In contrast the observed changes in the saturated to mono-unsaturated fatty acid (SFA to MUFA) and saturated to poly-unsaturated fatty acid (SFA to PUFA) ratios in PE P could represent a cellular reaction to counteract this effect by producing more fluid membranes. Transcriptomic analysis showed considerable differences between eLDL and oxLDL treated macrophages. As a common feature of both lipoproteins we detected a strong downregulation of pathways for endogenous lipid synthesis as well as for exogenous lipid uptake. Deloading with HDL3 had only minor effects on total lipid class as well as on individual lipid species levels, most of the time not reaching significance. Interestingly treatment with HDL3 had no effect on membrane fluidity under these conditions, although incubation with HDL3 was partially able to counteract the oxLDL induced transcriptomic effects. To investigate the functional effect of lipoprotein treatment on macrophage polarization we performed surface marker flow cytometry. Under our experimental conditions oxLDL was able to partially shift the surface marker pattern towards a pro-inflammatory M1-like phenotype. This is consistent with the consumption of arachidonic acid containing PE P species in oxLDL treated cells, presumably for the synthesis of inflammatory mediators. Our findings provide novel data on the lipoprotein induced, lipidomic and transcriptomic changes in macrophages. This can help us better understand the development of metabolic, inflammatory diseases as well as improve our background knowledge on lipid biomarkers in serum.


Effector triggered manipulation of host immune response elicited by different pathotypes of Escherichia coli.
Effectors are virulence factors that are secreted by bacteria during an infection in order to subvert cellular processes or induce the surveillance system of the host. Pathogenic microorganisms encode effectors, toxins and components of secretion systems that inject the effectors to the host. Escherichia coli is part of the innocuous commensal microbial flora of the gastrointestinal tract. However, pathogenic E. coli can cause diarrheal and extraintestinal diseases. Pathogenic E. coli uses secretion systems to inject an array of effector proteins directly into the host cells. Herein, we discuss the effectors secreted by different pathotypes of E. coli and provide an overview of strategies employed by effectors to target the host cellular and subcellular processes as well as their role in triggering host immune response.


Apixaban Suppresses the Release of TF-Positive Microvesicles and Restrains Cancer Cell Proliferation through Directly Inhibiting TF-fVIIa Activity.
The activation of protease-activated receptor (PAR)-2 by factor Xa (fXa) promotes the release of tissue factor-positive microvesicles (TF+MV), and contributes to proliferation in cancer cells. This study examined the ability of direct oral anticoagulants (DOACs), apixaban and rivaroxaban, to inhibit the release of TF+MV from two cell lines (MDA-MB-231 and AsPC-1) as well as cell proliferation.Activation of the cells with fXa (10 nM) enhanced the release of TF+MV but was suppressed in the presence of either DOAC. These MVs were found to contain fVIIa, but not fXa. Incubation of cell lines with apixaban (1.8 µM) but not rivaroxaban (1.8 µM), in the absence of fXa decreased the release of TF+MV below that of resting cells, in a PAR2-dependent manner. Furthermore, incubation with apixaban reduced the proliferation rate in both cells lines. Incubation of purified fVIIa with apixaban but not rivaroxaban resulted in complete inhibition of fVIIa proteolytic activity as measured using two fVIIa chromogenic substrates. Pre-incubation of the cells with an inhibitory anti-fVIIa antibody, with apixaban or the blocking of PAR2 suppressed the release of TF+MV to a comparable level, and reduced cell proliferation but the effect was not cumulative.This study has established that the activation of PAR2 by TF-fVIIa complex is the principal mediator in augmenting the release of TF+MV as well as cancer cell proliferation. Importantly, for the first time we have shown that apixaban selectively inhibits the proteolytic activity of fVIIa as well as the signalling arising from the TF-fVIIa complex.


[The plague and iron - or why didn't everybody die?].
In the years of the Black Death, contemporary observers noted that wealthy men were more likely to die from plague than women and the poor. One hypothesis, seeking an explanation for this phenomenon, is that the iron stores of an individual are a significant virulence factor for Yersina pestis, since this microorganism is dependent on iron for its multiplication. Thus, iron deficiency might confer some protection, whereas sufficient or even overabundant body iron stores contribute to the mortality in plague as well as in some other infectious diseases.


Quality of life among dermatology patients: a systematic review of investigations using qualitative methods.
Quality of life may be assessed using quantitative or qualitative methods. Quantitative methods are commonly used in research settings; however, they may fail to capture the full range of patient experiences and impact on quality of life. Qualitative methods may be used to address this limitation. In this systematic review, we aim to synthesize data from articles utilizing qualitative methods to assess quality of life in dermatology patients. We performed a systematic review search using the MEDLINE, EMBASE, and SCOPUS databases. The search was conducted using the following search criteria: ("Dermatology" [MeSH]) AND ("Quality of Life" [MeSH]), AND ("Qualitative Research" [MeSH]), searching literature spanning from January 1, 1946 to October 5, 2016. The systematic review of 15 articles included 533 dermatology patients. Patients expressed frustration over the unpredictability of disease symptoms and having to compensate for the subsequent limitations by altering their daily routines. Patients also reported profound helplessness due to chronic skin disease and social isolation in an effort to hide their disease. Patients noted the patient-provider relationship as a source of support and information exchange, with the goal to form easy to use treatment plans that met both physician and patient expectations. Qualitative assessment of patient quality of life can provide new insights into the patient experience and the impact of their skin disease. Qualitative methodology may capture meaningful information that may be overlooked by quantitative methods, and it should be included in quality of life research.


Pharmacodynamics of gonadotropin-releasing hormone. 1. Effects of gonadotropin-releasing hormone pulse contour on pituitary luteinizing hormone secretion in vivo in sheep.
The gonadotropin-releasing hormone (GnRH) waveform arrives at the pituitary gonadotropes via the pituitary portal blood and provides the immediate suprapituitary stimulus to luteinizing hormone (LH) secretion. Despite their importance, nature and influence of the physiological GnRH waveform in vivo have been difficult to study. Recent pharmacological and in vitro studies have suggested the potential importance of the wave contour as a specific and independent factor in the pharmacodynamic effects of GnRH on pituitary gonadotrope LH secretion in vivo, and it has been hypothesized that the steepness of the rising edge of the GnRH wave contour is a specific determinant of pituitary LH secretion. In order to investigate the pharmacodynamic influence of GnRH pulse wave contour on pituitary LH secretion in vivo, variations in plasma LH responses to alterations in GnRH wave contour were measured in chronic ovariectomized, hypothalamopituitary-disconnected sheep undergoing physiological pulsatile GnRH maintenance regimen at a fixed dose (250 ng/pulse) and frequency (interpulse interval 120 min). Variable wave contours were then generated by administration of the same total GnRH pulse dose over various lengths of time from near-instantaneous bolus to increasing lengths of constant-rate infusion time up to 8 min. This model allowed specific examination of pulse wave contour in the absence of concurrent changes in endogenous GnRH or sex steroid secretion and holding constant GnRH pulse dose, frequency, and route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Aerosol vaccination against Newcastle disease. II. Effect of vaccine diluents.
Three diluents (deionized water, 2% dry milk, and 20% buffered glycerin) were used to suspend the Newcastle disease vaccine for aerosol-vaccination studies. Particle size and the effect on humoral antibody response in chickens was determined for each diluent. For all diluents, the greatest number of particles were found in the size range of 0.5-3 mum. Total particle counts were higher with glycerin than with either milk or water. Antibody response and resistance to challenge, however, were higher with water or milk.


Identification of chlorothiazide and hydrochlorothiazide UV-A photolytic decomposition products.
Methanol solutions of hydrochlorothiazide and chlorothiazide were irradiated with fluorescent UV-A lamps in order to simulate degradation under normal conditions. The degradation products were identified by comparison to synthetic standards featuring electrospray ionization mass spectroscopy, ultraviolet spectroscopy, and high performance liquid chromatography. The standards were characterized by high resolution fast atom bombardment MS and 1H NMR. The photolysis of chlorothiazide resulted in photodehalogenation products exclusively, while the irradiation of hydrochlorothiazide primarily yielded photodehalogenation products with significant yields of photodehydrogenation products and minor amounts of thermal hydrolysis products.


Antimony Anchored with Nitrogen-Doping Porous Carbon as a High-Performance Anode Material for Na-Ion Batteries.
Antimony represents a class of unique functional materials in sodium-ion batteries with high theoretical capacity (660 mA h g-1). The utilization of carbonaceous materials as a buffer layer has been considered an effective approach to alleviate rapid capacity fading. Herein, the antimony/nitrogen-doping porous carbon (Sb/NPC) composite with polyaniline nanosheets as a carbon source has been successfully achieved. In addition, our strategy involves three processes, a tunable organic polyreaction, a thermal annealing process, and a cost-effective reduction reaction. The as-prepared Sb/NPC electrode demonstrates a great reversible capacity of 529.6 mA h g-1 and an outstanding cycling stability with 97.2% capacity retention after 100 cycles at 100 mA g-1. Even at 1600 mA g-1, a superior rate capacity of 357 mA h g-1 can be retained. Those remarkable electrochemical performances can be ascribed to the introduction of a hierarchical porous NPC material to which tiny Sb nanoparticles of about 30 nm were well-wrapped to buffer volume expansion and improve conductivity.


Interleukin-33 and its Receptor in Pulmonary Inflammatory Diseases.
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It modulates immune responses and biological functions through binding to its membrane receptor, ST2L. ST2L is a member of the Toll-like/IL-1 (TIR)-receptor superfamily, and its isoform, soluble ST2 (sST2), functions as an inhibitor of the IL-33/ST2L pathway. Levels of IL-33 and sST2 in serum and bronchoalveolar lavage fluid (BAL) are known biomarkers for a variety of disorders such as heart failure, non-small-cell lung cancer, and pulmonary inflammatory diseases. IL-33 also exists in the nuclei, and nuclear IL-33 seems to regulate cytokine gene expression. In this review, we focus on the role of IL-33/ST2 in the pathogenesis of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung injury.


Discounting in economic evaluations: stepping forward towards optimal decision rules.
The National Institute for Clinical Excellence has recently changed its guidelines on discounting costs and effects in economic evaluations. In common with most other regulatory bodies it now requires that health effects should be discounted at the same rate as costs. We show that the guideline leads to sub-optimal decisions because it fails to account for the changing value of health. NICE (and other regulatory bodies) should either use differential discounting or stipulate how the changing value of health should otherwise be dealt with. We also show how binding health service budget constraints should be incorporated in evaluations.


A review of the structural and functional features of olmesartan medoxomil, an angiotensin receptor blocker.
The angiotensin II (A-II) type 1 (AT1) receptor-mediated effects of A-II play a key role in the pathophysiology of hypertension. Effective inhibition of A-II is provided by the latest class of antihypertensive medications, the AT1 receptor blockers (ARBs). These orally available agents were developed around a common imidazole-based structural core. The most recent member of this drug class to be approved by the Food and Drug Administration, olmesartan medoxomil, contains unique features that may explain its clinical efficacy. Key structural elements of olmesartan medoxomil include a hydroxyalkyl substituent at the imidazole 4-position and a hydrolyzable ester group at the imidazole 5-position. Inter- and intramolecular hydrogen bonding involving these groups may contribute to the potentiation of antagonist activity. After oral administration, olmesartan medoxomil is deesterified in the intestinal tract to produce the active metabolite olmesartan, which undergoes no additional metabolic change. The marked antihypertensive efficacy of olmesartan medoxomil may result from a unique pharmacological interaction of the drug with the AT1 receptor, resulting in a potent, long-lasting, dose-dependent blockade of A-II. This review article characterizes the structural features of olmesartan that may be responsible for its clinical efficacy. Inferential pharmacological studies compare and contrast the effects of olmesartan to those of other ARBs in comparable preclinical animal models.


Functional Larynx Preservation in Patients With Locally Advanced Squamous Cell Carcinoma of the Larynx and Hypopharynx Treated With Induction Chemotherapy vs. Concurrent Chemoradiation Alone.
Objectives Chemoradiation therapy (CRT) has been established as a standard treatment for locally advanced hypopharynx/larynx squamous cell carcinoma (SCC) but the role of induction chemotherapy (IC) remains unclear. The primary outcome of this study is to determine whether functional larynx-preservation survival (FLPS) is improved with the addition of IC in these patients. Secondary outcomes were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and laryngectomy rates. Methods Records for patients with AJCC 8th edition clinical stage III-IVB laryngeal and hypopharyngeal SCC treated with CRT +/- IC from 2005-2019 were reviewed. FLPS was defined as time until death, progression, laryngectomy, or non-functional larynx. Kaplan-Meier curves were generated for FLPS, OS, PFS, and DMFS. Outcomes were compared using the stratified log-rank test. Laryngectomy rates were compared using Fisher's exact test. Results We included 52 patients with laryngeal and 38 with hypopharyngeal SCC (n=90); 19 patients with laryngeal SCC and 19 with hypopharyngeal SCC received IC (median three cycles). There were no differences in the three-year FLPS (61% vs 67.8%; p=0.88), OS (73.9% vs 86.2%; p=0.42), PFS (53.6% vs 62.6%; p=0.44), or DMFS (65.2% vs 71.5%, p= 0.85) between patients who did and did not receive IC all patients. Laryngectomy rates did not differ with and without IC (18.4 % vs 7.7%; p=0.19). Conclusion In this study of advanced laryngeal and hypopharyngeal SCC, IC did not improve three-year FLPS, OS, PFS, or laryngectomy rates compared to CRT alone. A large prospective series would provide a more robust understanding of the role of IC in this group of patients.


Combination of Leflunomide and Everolimus for treatment of BK virus nephropathy.
BK nephropathy (BKN) is a common cause of graft dysfunction following kidney transplantation. Minimization of immunosuppressive therapy remains the first line of therapy, but this may lead to rejection and graft loss. In some cases, despite lowering immunosuppression, BK infection can persist, leading to chronic damage and kidney failure. Currently, there is no specific anti-BK viral therapy. Recent in vitro experiments have demonstrated a reduction in BK viral replication when infected cells are treated with the combination of Leflunomide and Everolimus. This study aims to explore the effect of this drugs combination on viral clearance and graft function in patients with persistent disease despite reduction in immunosuppression. We treated three patients with combination Leflunomide and Everolimus. Data on medical history, biochemical parameters and viral loads were collected. Significant improvement in viral loads was observed in two cases with resolution of viremia in another (Table 1). Two recipients had preserved allograft function. The remaining graft was lost because of combination of obstruction and BKN. No adverse reactions such as bone marrow toxicity were observed. Combination of Leflunomide and Everolimus is safe and should be considered as a rescue therapy in treatment of BKN, especially in those who fail to clear this infection despite reduction of immunosuppressive therapy.


Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells.
To study the structure-activity relationships of aromatic cytokinins, the cytokinin activity at both the receptor and cellular levels, as well as CDK inhibitory and anticancer properties of 38 6-benzylaminopurine (BAP) derivatives were compared in various in vitro assays. The compounds were prepared by the condensation of 6-chloropurine with corresponding substituted benzylamines. The majority of synthesised derivatives exhibited high activity in all three of the cytokinin bioassays employed (tobacco callus, wheat senescence and Amaranthus bioassay). The highest activities were obtained in the senescence bioassay. For some compounds tested, significant differences of activity were found in the bioassays used, indicating that diverse recognition systems may operate and suggesting that it may be possible to modulate particular cytokinin-dependent processes with specific compounds. Position-specific steric and hydrophobic effects of different phenyl ring substituents on the variation of biological activity were confirmed. In contrast to their high activity in bioassays, the BAP derivatives were recognised with much lower sensitivity than trans-zeatin in both Arabidopsis thaliana AHK3 and AHK4 receptor assays. The compounds were also investigated for their effects on cyclin-dependent kinase 2 (CDK2) and for antiproliferative properties on cancer and normal cell lines. Several of the tested compounds showed stronger inhibitory activity and cytotoxicity than BAP. There was also a significant positive correlation of the inhibitory effects on human and plant CDKs with cell proliferation of cancer and cytokinin-dependent tobacco cells, respectively. This suggests that at least a part of the antiproliferative effect of the new cytokinins was due to the inhibition of CDK activity.


Induction of intestinal metaplasia in the stomachs of rats by N-methyl-N'-nitro-N-nitrosoguanidine.
N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered orally to male Wistar rats at a concentration of 83 microgram/ml in the drinking water for 2, 4, 5, and 7 months; the rats were killed at about month 15. Intestinal metaplasia was found in the stomachs of 80-100% of the rats treated with MNNG for 4 or more months, of 37.5% treated with MNNG for 2 months, and of 10% of the controls. Metaplastic glands, composed of goblet cells and columnar cells with striated borders, were found in the pyloric region. Paneth's cells were found at the bottom of metaplastic glands in a rat treated with MNNG for 4 months. The incidence of well-differentiated adenocarcinomas of the stomach was 63-90% in rats treated with MNNG for 4 or more months and 25% in those treated with MNNG for 2 months.


Human melanoma inhibitory protein binds to the FN12-14 Hep II domain of fibronectin.
The heparin binding site (Hep II) of fibronectin plays a major role in tumor cell metastasis. Its interaction with heparan sulfate proteoglycans occurs in a variety of physiological processes including focal adhesion and migration. The melanoma inhibitory activity (MIA) is an important protein that is functionally involved in melanoma development, progression, and tumor cell invasion. After its secretion by malignant melanoma cells, MIA interacts with fibronectin and thereby actively facilitates focal cell detachment from surrounding structures and strongly promotes tumor cell invasion and the formation of metastases. In this report, the authors have determined the molecular basis of the interaction of MIA with the Hep II domain of fibronectin based on nuclear magnetic resonance spectroscopic binding assays. The authors have identified the type III modules 12 to 14 of fibronectin's Hep II as the major MIA binding sites. These results now provide a new target protein-protein binding interface for the discovery of novel antimetastatic agents against malignant melanoma in the future.


Multiresidue determination of fluoroquinolones in shrimp by liquid chromatography-fluorescence-mass spectrometry.
An efficient multiresidue method for analysis of fluoroquinolones in shrimp has been developed in which quantitation by fluorescence and confirmation by Multiple Stage Mass Spectrometry (MS) is achieved simultaneously. In this method, shrimp tissue is extracted with ammoniacal acetonitrile and the extract is defatted and then evaporated. After dissolution in basic phosphate buffer, fluoroquinolones in the extract are separated by liquid chromatography and quantitated, taking advantage of their intense fluorescence. Eluate from the fluorescence detector enters the MS, which allows for confirmation by monitoring ratios of 2 prominent product ions in the MS3 or MS2 spectrum. Using this method, 8 fluoroquinolones have been analyzed in shrimp samples fortified at 10, 25, 50, or 100 ppb levels. Recoveries for desethyleneciprofloxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin ranged from 75 to 92%, with relative standard deviation values of <6%. The limits of quantitation ranged from 0.1 to 1 ng/g. Enrofloxacin and ciprofloxacin were also successfully determined in enrofloxacin-incurred shrimp using this method.


Uptake and metabolism of carbamazepine (CBZ) by clam Ruditapes decussatus and its effects in biochemical responses.
1. Laboratory experiments were carried out to assess uptake and metabolism of the epilepsy drug, carbamazepine and its consequent biological responses in marine clam (Ruditapes decussatus) a model non-target organism in ecotoxicology. 2. Clams were exposed to two nominal concentrations (C1 = 30 μg/L and C2 = 50 μg/L) of CBZ for a maximum period of 14 days. Analysis of CBZ and their metabolites in clam and water after exposure to two nominal concentrations of the pharmaceutical drug were performed using UPLC-HRMS analysis. CBZ accumulation reached an average tissue concentration of 1241.59 ng/g dw and 1664.33 ng/g dw at low and high nominal concentration, respectively. 3. Furthermore, a metabolite (3-hydroxy-CBZ) was detected in tissues indicating carbamazepine translocation and metabolism inside clam, suspect screening of CBZ glucuronides was also performed by accurate mass extraction but it could not be detected. 4. Activities of antioxidant enzymes superoxide dismutase, catalase and gluthatione-S-transferase generally increased. Change in the contents of glutathione, malondialdehyde and protein carbonyl were also studied. 5. Results indicated that the bioaccumulation of CBZ resulted in the changes of the antioxidant defense system and the production of ROS with the oxidative stress, ultimately induced alteration in lipid peroxidation and protein carbonyl.


Effects of different concentrations of Platelet-rich Plasma and Platelet-Poor Plasma on vitality and differentiation of autologous Adipose tissue-derived stem cells.
Autologous fat grafts and adipose-derived stem cells (ASCs) can be used to treat soft tissue defects. However, the results are inconsistent and sometimes comprise tissue resorption and necrosis. This might be due to insufficient vascularization. Platelet-rich plasma (PRP) is a source of concentrated autologous platelets. The growth factors and cytokines released by platelets can facilitate angiogenesis. The simultaneous use of PRP might improve the regeneration potential of fat grafts. The optimal ratio has yet to be elucidated. A byproduct of PRP preparation is platelet-poor plasma (PPP). In this study we investigated the influence of different concentrations of PRP on the vitality and differentiation of ASCs. We processed whole blood with the Arthrex Angel centrifuge and isolated ASCs from the same donor. We tested the effects of different PRP and PPP concentrations on the vitality using resazurin assays and the differentiation of ASCs using oil-red staining. Both cell vitality and adipogenic differentiation increase to a concentration of 10% to 20% PRP. With a PRP concentration of 30% cell vitality and differentiation decrease. Both PRP and PPP can be used to expand ASCs without xenogeneic additives in cell culture. A PRP concentration above 20% has inhibitory effects.


Jaundice as an early diagnostic sign of urinary tract infection in infancy.
Urinary tract infections (UTIs) are a common clinical problem in febrile infants younger than 8 weeks old, with a prevalence between 5% and 11%. Previous studies have noted that jaundice may be one of the first signs of a bacterial infection in infants. Our goal was to determine the incidence of UTIs in asymptomatic, jaundiced infants younger than 8 weeks old and to determine which historical and laboratory parameters are associated with UTIs. We prospectively evaluated asymptomatic, jaundiced infants younger than 8 weeks old for evidence of a UTI (defined as >10 000 colony-forming units per milliliter of a single pathogen, obtained by bladder catheterization). A serum fractionated bilirubin level was obtained on all study patients. Detailed questionnaires were completed, which included demographic information, prenatal, intrapartum, and postnatal events. Twelve (7.5%) of 160 infants had a UTI (95% confidence interval: 3.9%-12.7%). Isolated organisms included Escherichia coli, Enterobacter cloacae, Enterococcus, Klebsiella pneumoniae, group B Streptococcus, Streptococcus viridans, and Staphylococcus aureus. Patients with the onset of jaundice after 8 days of age had a higher incidence of UTI, 6 (50%) of 12 infants in the positive culture group, versus 15 (10%) of 148 infants in the negative culture group. Abnormal urinalysis and microscopy results were noted in 5 (42%) of 12 infants with a UTI, and 6 (55%) of 11 infants had abnormal renal ultrasound results. A UTI was found in 7.5% of asymptomatic, afebrile, jaundiced infants younger than 8 weeks old. In addition, infants with the onset of jaundice after 8 days of age or patients with an elevated conjugated bilirubin fraction were more likely to have a UTI. Therefore, we recommend that testing for a UTI be included as part of the evaluation in asymptomatic, jaundiced infants presenting to the emergency department.


Burden of opioid use for pain management among adult herpes zoster patients in the US and the potential impact of vaccination.
PLAIN LANGUAGE SUMMARYWhat is the context? Herpes zoster or shingles and its complications such as postherpetic neuralgia - a painful condition that affects the nerve fibers and skin - may lead to complex pain that can be addressed using opioids in some patients.The recombinant zoster vaccine (RZV) vaccine prevents shingles and, therefore, may reduce the use of opioids and the negative health outcomes and costs associated with it.What is new? In this retrospective medical claims study, including patients between 2012 and 2017, we evaluated the receipt of pain medication including opioids in herpes zoster patients, and assessed factors associated with opioid prescription.estimated health care resource utilization and costs associated with opioid use among patients with herpes zoster.assessed the impact of vaccination on opioid prescriptions.Among subjects receiving opioids, 78.5% started with a weak opioid dose. Dose escalation was uncommon.Postherpetic neuralgia, immunocompromised status, and comorbidities are the main risk factors associated with opioid prescription.Health care costs are almost double in patients with herpes zoster receiving opioids compared with patients without an opioid prescription.In a population of 1 million adults aged 50 years or older, vaccination with the recombinant zoster vaccine could prevent over 19,000 patients from receiving opioids.What is the impact? Prevention of herpes zoster through vaccination may be a highly effective strategy to reduce opioid prescriptions and costs related to pain management in a susceptible population.Increasing RZV vaccination coverage in adults aged ≥50 years may further reduce potential opioid prescriptions through a decrease in shingles incidence.


T2*-Correction in Dynamic Contrast-Enhanced Magnetic Resonance Imaging of Glioblastoma From a Half Dose of High-Relaxivity Contrast Agent.
The aim of this study was to evaluate the arterial input function (AIF) and tissue enhancement time curve (tissue function [TF]) obtained after the administration of a half-dose gadobenate dimeglumine (0.05-mmol/kg body weight [bw]) compared with a full dose (0.1-mmol/kg bw) of a standard-relaxivity contrast agent. We enrolled 40 adult patients with glioblastoma in an interindividual comparative study. Patients were randomized to 1 of the 2 study arms: 20 patients received 0.1-mmol/kg bw of gadoterate; the other 20 patients received 0.05-mmol/kg bw of gadobenate. The patients underwent dynamic contrast-enhanced magnetic resonance imaging examinations. Arterial input function, tissue enhancement time curve (TF), tumor transfer rate (K), and tumor extracellular-extravascular volume fraction (Ve) were calculated for each patients. Averaged AIF, TF, K, and Ve of both groups were compared. A significant difference (P = 0.001) between the peak AIF values obtained with the 2 different gadolinium-based contrast agents was observed. No difference was found between TFs (P = 0.35). Comparison on kinetic parameters revealed a significant difference for K (P = 0.047) but no difference for Ve (P = 0.74). The administration of half dose of the high-relaxivity contrast agent gadobenate is effective in improving AIF by reducing T2*-shortening effects on dynamic contrast-enhanced magnetic resonance imaging and ensuring at the same time an adequate signal enhancement in tumor tissue. The use of 0.05-mmol/kg bw of gadobenate not only is feasible but also can lead to a better estimation of K based on a more accurate AIF assessment.


Large-amplitude nonlinear normal modes of the discrete sine lattices.
We present an analytical description of the large-amplitude stationary oscillations of the finite discrete system of harmonically coupled pendulums without any restrictions on their amplitudes (excluding a vicinity of π). Although this model has numerous applications in different fields of physics, it was studied earlier in the infinite limit only. The discrete chain with a finite length can be considered as a well analytical analog of the coarse-grain models of flexible polymers in the molecular dynamics simulations. The developed approach allows to find the dispersion relations for arbitrary amplitudes of the nonlinear normal modes. We emphasize that the long-wavelength approximation, which is described by well-known sine-Gordon equation, leads to an inadequate zone structure for the amplitudes of about π/2 even if the chain is long enough. An extremely complex zone structure at the large amplitudes corresponds to multiple resonances between nonlinear normal modes even with strongly different wave numbers. Due to the complexity of the dispersion relations the modes with shorter wavelengths may have smaller frequencies. The stability of the nonlinear normal modes under condition of the resonant interaction are discussed. It is shown that this interaction of the modes in the vicinity of the long wavelength edge of the spectrum leads to the localization of the oscillations. The thresholds of instability and localization are determined explicitly. The numerical simulation of the dynamics of a finite-length chain is in a good agreement with obtained analytical predictions.


Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain.
AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and are selectively recruited during activity-dependent plasticity to increase synaptic strength. A prerequisite for faithful signal transmission is the positioning and clustering of AMPARs at postsynaptic sites. The mechanisms underlying this positioning have largely been ascribed to the receptor cytoplasmic C-termini and to AMPAR-associated auxiliary subunits, both interacting with the postsynaptic scaffold. Here, using mouse organotypic hippocampal slices, we show that the extracellular AMPAR N-terminal domain (NTD), which projects midway into the synaptic cleft, plays a fundamental role in this process. This highly sequence-diverse domain mediates synaptic anchoring in a subunit-selective manner. Receptors lacking the NTD exhibit increased mobility in synapses, depress synaptic transmission and are unable to sustain long-term potentiation (LTP). Thus, synaptic transmission and the expression of LTP are dependent upon an AMPAR anchoring mechanism that is driven by the NTD.


Lycopene prevents carcinogen-induced cutaneous tumor by enhancing activation of the Nrf2 pathway through p62-triggered autophagic Keap1 degradation.
Biologically active natural products have been used for the chemoprevention of cutaneous tumors. Lycopene is the main active phytochemical in tomatoes. We herein aimed to assess the cancer preventive effects of lycopene and to find potential molecular targets. In chemically-induced cutaneous tumor mice and cell models, lycopene attenuated cutaneous tumor incidence and multiplicity as well as the tumorigenesis of normal cutaneous cells in phase-selectivity (only in the promotion phase) manners. By utilizing a comprehensive approach combining bioinformatics with network pharmacology, we predicted that intracellular autophagy and redox status were associated with lycopene's preventive effect on cutaneous tumors. Lycopene stimulated the activation of antioxidant enzymes and the translocation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) that predominantly maintained intracellular redox equilibrium. The cancer chemopreventive effects were mediated by Nrf2. Further, lycopene enhanced the expression of autophagy protein p62. Therefore this led to the degradation of Keap1(Kelch ECH associating protein 1), the main protein locking Nrf2 in cytoplasm. In conclusion, our study provides preclinical evidence of the chemopreventive effects of lycopene on cutaneous tumors and reveals the mechanistic link between lycopene's stimulation of Nrf2 signaling pathway and p62-mediated degradation of Keap1 via the autophagy-lysosomal pathway.


Distribution of cfr in Staphylococcus spp. and Escherichia coli Strains from Pig Farms in China and Characterization of a Novel cfr-Carrying F43:A-:B- Plasmid.
The multi-resistance gene cfr is widely distributed among various gram-positive and gram-negative species in livestock in China. To better understand the epidemiology of cfr among Staphylococcus spp. and E. coli isolates, 254 Staphylococcus spp. and 398 E. coli strains collected from six swine farms in China were subjected to prevalence and genetic analysis. Forty (15.7%) Staphylococcus spp. isolates, including 38 Staphylococcus sciuri strains, one Staphylococcus chromogenes strain, and one Staphylococcus lentus strain, and two (0.5%) E. coli isolates were found to contain the cfr gene. Most of the 38 S. sciuri strains were clonally unrelated; however, clonal dissemination of cfr-positive S. sciuri was detected at the same farm. In eight randomly selected cfr-positive staphylococci, a cfr-harboring module (IS21-558-cfr-ΔtnpB) was detected in six S. sciuri isolates; cfr was bracketed by two copies of ISEnfa4 or IS256 in the remaining two S. sciuri isolates. In the two E. coli isolates, EP25 and EP28, cfr was flanked by two IS26 elements in the same or opposite orientation, respectively. Complete sequence analysis of the novel F43:A-:B- plasmid pHNEP28 revealed that it contains two multi-resistance regions: cfr together with floR, qnrS1 interspersed with IS26, ΔISCR2 and ISKpn19, and blaTEM-1 together with tet(M) interspersed with IS26, ISApl1, ΔTn2, and ΔIS1B. The coexistence of cfr with other resistance genes on a conjugative plasmid may contribute to the dissemination of these genes by co-selection. Thus, rational drug use and continued surveillance of cfr in swine farms are warranted.


Kaistella flava sp. nov., isolated from Antarctic tundra soil, and emended descriptions of Kaistella yonginensis, Kaistella jeonii, Kaistella antarctica and Kaistella chaponensis.
A rod-shaped, yellow-pigmented, Gram-stain-negative, non-motile and aerobic bacterium, designated 7-3AT, was isolated from soil from King George Island, maritime Antarctica, and subjected to a polyphasic taxonomic study. Growth occurred at 4-37 °C (optimum, 20°C) and at pH 5.0-9.0 (optimum, pH 7.0-8.0). Tolerance to NaCl was up to 4 % (w/v) with optimum growth in the absence of NaCl. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 7-3AT represented a member of the family Flavobacteriaceae. Strain 7-3AT showed the highest sequence similarities with Kaistella yonginensis HMD 1043T (96.65 %), Kaistella carnis NCTC 13525T (96.53 %), Kaistella chaponensis DSM 23145T (96.27 %), Kaistella antarctica LMG 24720T (96.13 %) and Kaistella jeonii DSM 17048T (96.06 %). A whole genome-level comparison of 7-3AT with K. jeonii DSM 17048T, K. antarctica LMG 24720T, K. chaponensis DSM 23145T, and Kaistella palustris DSM 21579T revealed average nucleotide identity (ANI) values of 79.03, 82.25, 78.12, and 74.42 %, respectively. The major respiratory isoprenoid quinone was identified as MK-6 and a few ubiquinones Q-10 were identified. In addition, flexirubin-type pigments were absent. The polar lipid profile of 7-3AT was found to contain one phosphatidylethanolamine, six unidentified aminolipids (AL) and two unidentified lipids (L). The G+C content of the genomic DNA was determined to be 34.54 mol%. The main fatty acids were iso-C15 : 0, summed feature 9 (comprising iso-C17 : 1ω9c and/or C16 : 0 10-methyl), anteiso-C15 : 0, iso-C13 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). On the basis of the evidence presented in this study, a novel species of the genus Kaistella, Kaistella flava sp. nov., is proposed, with the type strain 7-3AT (=CCTCC AB 2016141T= KCTC 52492T). Emended descriptions of Kaistella yonginensis, Kaistella jeonii, Kaistella antarctica and Kaistella chaponensis are also given.


Structure of the stomach cuticle in adult and larvae of the spider crab Maja brachydactyla (Brachyura, Decapoda).
The stomach of decapods is a complex organ with specialized structures that are delimited by a cuticle. The morphology and ontogeny of the stomach are largely described, but few studies have focused on the morphology of its cuticle. This study examined the morphology of the stomach cuticle of cardiac sacs, gastric mill ossicles, cardio-pyloric valve and pyloric filters, and during various stages (zoea I and II, megalopa, first juvenile, and adult) of the common spider crab Maja brachydactyla using dissection, histology and transmission electron microscopy. The results show that cuticle morphology varies among structures (e.g., cardiac sacs, urocardiac ossicle, cardio-pyloric valve, pyloric filters), within a single structure (e.g., different sides of the urocardiac ossicle) and among different life stages. The cuticle during the larval stages is very thin and the different layers (epicuticle, exocuticle, and endocuticle) are infrequently distinguishable by histology. Major changes during larval development regarding cuticle morphology are observed after the molt to megalopa, including the increment in thickness in the gastric mill ossicles and cardio-pyloric valve, and the disappearance of the long thickened setae of the cardio-pyloric valve. The cuticle of all the stomach structures in the adults is thicker than in larval and juvenile stages. The cuticle varies in thickness, differential staining affinity and morphology of the cuticle layers. The structure-function relationship of the cuticle morphology is discussed.


What is called symptom?
There is one concept in medicine which is prominent, the symptom. The omnipresence of the symptom seems, however, not to be reflected by an equally prominent curiosity aimed at investigating this concept as a phenomenon. In classic, traditional or conventional medical diagnostics and treatment, the lack of distinction with respect to the symptom represents a minor problem. Faced with enigmatic conditions and their accompanying labels such as chronic fatigue syndrome, fibromyalgia, medically unexplained symptoms, and functional somatic syndromes, the contestation of the symptom and its origin is immediate and obvious and calls for further exploration. Based on a description of the diagnostic framework encompassing medically unexplained conditions and a brief introduction to how such symptoms are managed both within and outside of the medical clinic, we argue on one hand how unexplained conditions invite us to reconsider and re-think the concept we call a "symptom" and on the other hand how the concept "symptom" is no longer an adequate and necessary fulcrum and must be enriched by socio-cultural, phenomenological and existential dimensions. Consequently, our main aim is to expand both our interpretative horizon and the linguistic repertoire in the face of those appearances we label medically unexplained symptoms.


Expression of the insulin-like growth factor system in postpneumonectomy lung growth.
The insulin-like growth factors (IGF-I and IGF-II) may play an important role in postpneumonectomy compensatory lung growth by translating hormonal inputs and mechanical forces into cellular proliferation signals. We examined the mRNA abundance of IGF-I, IGF-II, and IGF binding proteins (IGFBPs) in lungs of rats on postoperative days 1, 2, 3, 5, and 7 following left pneumonectomy (PNX) or shamoperation (SC) and in normal animals (CON). There was no difference in the abundance of lung IGF-I mRNA (measured by Northern analysis) or serum IGF-I (measured by radioimmunoassay (RIA)) between SC and PNX animals. IGF-II mRNA abundance was initially decreased following PNX (73% decrease compared to SC animals on day 1, p < .05) and then rose to approach SC group values on subsequent days. Transcripts for IGFBP-2, -3, -4, -5, and -6 were decreased in both the SC and PNX groups compared to CON animals on the day following pneumonectomy, then rose back to baseline by postoperative day 2-3. Tissue IGFBPs, measured by ligand blot analyses, were not different in either the SC or PNX groups. In contrast, all serum IGFBP bands were increased on postoperative day 1 following either sham or PNX surgery. In addition, serum IGFBP-4 was increased in PNX animals compared to the SC group on days 1 and 2 (increase of 38% and 78%, respectively, p < .05). We conclude that the changes observed in lung IGF and IGFBP expression following pneumonectomy do not represent major.


Linguistic correlates of suicidal ideation in youth at clinical high-risk for psychosis.
Suicidal ideation (SI) is prevalent among individuals at clinical high-risk for psychosis (CHR). Natural language processing (NLP) provides an efficient method to identify linguistic markers of suicidality. Prior work has demonstrated that an increased use of "I", as well as words with semantic similarity to "anger", "sadness", "stress" and "lonely", are correlated with SI in other cohorts. The current project analyzes data collected in an SI supplement to an NIH R01 study of thought disorder and social cognition in CHR. This study is the first to use NLP analyses of spoken language to identify linguistic correlates of recent suicidal ideation among CHR individuals. The sample included 43 CHR individuals, 10 with recent suicidal ideation and 33 without, as measured by the Columbia-Suicide Severity Rating Scale, as well as 14 healthy volunteers without SI. NLP methods include part-of-speech (POS) tagging, a GoEmotions-trained BERT Model, and Zero-Shot Learning. As hypothesized, individuals at CHR for psychosis who endorsed recent SI utilized more words with semantic similarity to "anger" compared to those who did not. Words with semantic similarity to "stress", "loneliness", and "sadness" were not significantly different between the two CHR groups. Contrary to our hypotheses, CHR individuals with recent SI did not use the word "I" more than those without recent SI. As anger is not characteristic of CHR, findings have implications for the consideration of subthreshold anger-related sentiment in suicidal risk assessment. As NLP is scalable, findings suggest that language markers may improve suicide screening and prediction in this population.


Augmentation of Peri-implant Keratinized Mucosa Using a Combination of Free Gingival Graft Strip with Xenogeneic Collagen Matrix or Free Gingival Graft Alone: A Randomized Controlled Study.
Purpose: To evaluate the gain in peri-implant keratinized mucosa (KM) using a combination of a free gingival graft (FGG) strip with a xenogeneic collagen matrix (XCM) and compare it to that of an FGG alone. Materials and Methods: This randomized controlled clinical study included a total of 30 patients with a minimal amount of peri-implant KM (≤ 1 mm) in the maxillary and mandibular anterior regions (including the premolars). The study population was divided into two groups using a randomization protocol; group A (n = 15) received a combination of FGG strip and XCM, and group B (n = 15) received FGG only to augment the KM. Clinical parameters included width of KM (WKM) measured at baseline, 1 month, and 6 months; a customized pink esthetic score (PES) measured at baseline and 6 months; and patient morbidity using visual analog scale (VAS) at days 1, 7, and 14 postoperatively. Results: After 1 month, both groups showed statistically significant gain in KM that reduced slightly by the 6-month follow-up but remained statistically significant when compared to baseline. When the gain was compared between the two groups, the difference was not statistically significant. Better esthetic outcomes and lower morbidity were reported in group A compared to group B, and this difference was statistically significant. Conclusions: Within the limitations of the study, it can be concluded that the combination of FGG strip with XCM is a viable alternative to the use of FGG in augmenting peri-implant KM.


Establishment and characterization of partially differentiated chicken enterocyte cell clones.
Three enterocyte cell clones were established in vitro from the intestine of a PA12 hen embryo. These cells exhibited epithelioid morphology and grew as monolayers. The cells were continuously propagated in culture up to 250 passages. Gradual increase in growth rate with time and in anchorage-independent growth in both agar and agarose showed that the three cell clones spontaneously transformed in vitro. The clones were heteroploid with one marker chromosome. Interestingly, they had features of partly differentiated enterocytes, especially microvilli, junctions connecting adjacent cells (tight junctions, desmosomes, hemidesmosomes, gap junctions), villin and cytokeratins. In addition, cells expressed brush border enzyme activity and transepithelial resistance. The fact that the levels of dipeptidyl peptidase IV (DPP-IV) and alkaline phosphatase activities fluctuated according to culture time and that MHC class II was induced by activation of cells with interferon suggested that the state of differentiation of the 3 cell clones could be modified in vitro. These clones are the first established avian enterocyte cell clones to be described. Because each cell clone exhibited differences in the level of differentiation and sensitivity to Salmonella infection, their use will allow comparative investigations concerning markers of differentiation of avian enterocytes and infection by host-adapted bacteria and parasites.


In-depth mapping of the mouse brain N-glycoproteome reveals widespread N-glycosylation of diverse brain proteins.
N-glycosylation is one of the most prominent and abundant posttranslational modifications of proteins. It is estimated that over 50% of mammalian proteins undergo glycosylation. However, the analysis of N-glycoproteins has been limited by the available analytical technology. In this study, we comprehensively mapped the N-glycosylation sites in the mouse brain proteome by combining complementary methods, which included seven protease treatments, four enrichment techniques and two fractionation strategies. Altogether, 13492 N-glycopeptides containing 8386 N-glycosylation sites on 3982 proteins were identified. After evaluating the performance of the above methods, we proposed a simple and efficient workflow for large-scale N-glycosylation site mapping. The optimized workflow yielded 80% of the initially identified N-glycosylation sites with considerably less effort. Analysis of the identified N-glycoproteins revealed that many of the mouse brain proteins are N-glycosylated, including those proteins in critical pathways for nervous system development and neurological disease. Additionally, several important biomarkers of various diseases were found to be N-glycosylated. These data confirm that N-glycosylation is important in both physiological and pathological processes in the brain, and provide useful details about numerous N-glycosylation sites in brain proteins.


Strain heterogeneity and magnetoelastic behaviour of nanocrystalline half-doped La, Ca manganite, La0.5Ca0.5MnO3.
Elastic and anelastic properties of La0.5Ca0.5MnO3 determined by resonant ultrasound spectroscopy in the frequency range ∼100-1200 kHz have been used to evaluate the role of grain size in determining the competition between ferromagnetism and Jahn-Teller/charge order of manganites which show colossal magneto resistance. At crystallite sizes of ∼75 and ∼135 nm the dominant feature is softening of the shear modulus as the charge order transition point, Tco (∼225 K), is approached from above and below, matching the form of softening seen previously in samples with 'bulk' properties. This is consistent with a bilinear dominant strain/order parameter coupling, which occurs between the tetragonal shear strain and the Jahn-Teller (Γ3(+)) order parameter. At crystallite sizes of ∼34 and ∼42 nm the charge ordered phase is suppressed but there is still softening of the shear modulus, with a minimum near Tco. This indicates that some degree of pseudoproper ferroelastic behaviour is retained. The primary cause of the suppresion of the charge ordered structure in nanocrystalline samples is therefore considered to be due to suppression of macroscopic strain, even though MnO6 octahedra must develop some Jahn-Teller distortions on a local length scale. This mechanism for stabilizing ferromagnetism differs from imposition of either an external magnetic field or a homogeneous external strain field (from a substrate), and is likely to lead both to local strain heterogeneity within the nanocrystallites and to different tilting of octahedra within the orthorhombic structure. An additional first order transition occurs near 40 K in all samples and appears to involve some very small strain contrast between two ferromagnetic structures.


Primary structure and functional properties of cobra (Naja naja naja) venom Kunitz-type trypsin inhibitor.
A trypsin inhibitor from the venom of the cobra Naja naja naja has been isolated by a single step of reverse-phase high-performance liquid chromatography. The protein strongly inhibits trypsin (Ki = 3.5 pM). The primary structure was determined by peptide analysis of the [14C]carboxymethylated inhibitor. The 57-residue polypeptide chain belongs to the family of Kunitz-type inhibitors, and exhibits 42% residue identity with bovine pancreatic trypsin inhibitor. The structure shows only 70% identity with the corresponding peptide from the Capa cobra (Naja nevia), establishing that the inhibitor molecule exhibits extensive variations. Functionally, a basic residue at position P3' correlates with strong inhibition.


Distributed fiber surface plasmon resonance sensor based on the incident angle adjusting method.
We propose and demonstrate a distributed surface plasmon resonance (SPR) fiber sensor based on a novel, simple, and effective incident angle adjusting method. For normal fiber SPR sensors, it is hard to realize distributed sensing because it is hard to produce two dynamic ranges (resonance wavebands) with a great difference. The dynamic range depends on the incident angle, and therefore, we propose an incident angle adjusting method that is implemented by grinding an eccentric-core fiber to different angles, which helps to produce different SPR wavebands with great difference, thus realizing distributed sensing. In our two cascaded distributed configuration, with the refractive index range of 1.333-1.385, the fiber grind angles are 9° and 17°, the testing wavelength ranges are 613-760 nm and 745-944 nm, and the average testing sensitivities are 2826 nm/RIU and 4738 nm/RIU, respectively. Larger resonance wavelengths are associated with larger testing sensitivities. This distributed fiber sensor has important significance in the fields of multichannel liquid refractive indices and temperature self-reference measurements.


Phosphatidylcholine-specific phospholipase C activity is necessary for the activation of STAT6.
It is well established that Janus kinase (JAK) tyrosine kinases play a key role in the activation of STAT6 by IL-4. In this study, we investigated additional molecules involved in this process. We previously found that IL-4 and TNF-alpha cooperate in the activation of STAT6 and NF-kappaB, suggesting that these transcription factors are regulated by common intracellular signaling pathways. To test this hypothesis, we analyzed the effect of known inhibitors of NF-kappaB on the activation of STAT6. We discovered that inhibitors of phosphatidylcholine-specific phospholipase C (PC-PLC), but not other lipases, blocked the activation of STAT6 by IL-4. The activation of PC-PLC seems to be an early event in IL-4 signaling, because its inhibition abrogated JAK activation and STAT6 tyrosine phosphorylation. Interestingly, we found that the effects of pervanadate and sodium orthovanadate on STAT6 activation correspond to their effect on PC-PLC. Thus, pervanadate by itself activated PC-PLC, JAK, and STAT6, whereas sodium orthovanadate suppressed PC-PLC, JAK, and STAT6 activation by IL-4. We further found that PC-PLC activation is necessary but not sufficient to promote STAT6 activation, and therefore, additional intracellular pathways regulated by IL-4 and pervanadate may collaborate with PC-PLC to signal STAT6 activation. It has been reported that IL-4 signals PC-PLC activation; in this study, we provide evidence that this phospholipase plays a key role in IL-4 signaling.


The link between negative emotions and eating disorder behaviour in patients with anorexia nervosa.
Several theoretical models suggest that deficits in emotional regulation are central in the maintenance of anorexia nervosa (AN). Few studies have examined how patients view the relationship between negative affect and anorectic behaviour. We explored how patients with AN manage the aversive emotions sadness, anger, fear and disgust, and how they link these experiences to their eating disorder behaviours. Qualitative data were collected through semi-structured interviews with 14 women aged 19-39 years diagnosed with AN (DSM-IV). Interviews were analyzed using Grounded Theory methods. The participants tended to inhibit expression of sadness and anger in interpersonal situations and reported high levels of anger towards themselves, self-disgust and fear of becoming fat. Different emotions were managed by means of specific eating disorder behaviours. Sadness was particularly linked to body dissatisfaction and was managed through restrictive eating and purging. Anger was avoided by means of restrictive eating and purging and released through anorectic self-control, self-harm and exercising. Fear was linked to fear of fatness and was managed through restrictive eating, purging and body checking. Participants avoided the feeling of disgust by avoiding food and body focused situations. Treatment models of eating disorders highlight the significance of working with emotional acceptance and coping in this patient group. Knowledge about how patients understand the relationships between their negative emotions and their anorectic behaviour may be an important addition to treatment programmes for AN.


Evaluation of an adapted version of the International Trauma Questionnaire for use by people with intellectual disabilities.
The International Trauma Questionnaire (ITQ) is a novel assessment instrument that is aligned to the ICD-11 diagnoses of post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). The purpose of this study was to develop and evaluate an adapted version of the ITQ suitable for use by people with intellectual disabilities. The ITQ-ID follows the original ITQ, using wording developed in collaboration with a focus group of people with intellectual disabilities The ITQ-ID was administered to 40 people with intellectual disabilities recruited from learning disability forensic and community settings, alongside a Trauma Information Form and the Impact of Event Scale-Intellectual Disabilities (IES-IDs). Most participants reported multiple traumatizing events. Around half of the participants met strict criteria for a diagnosis of PTSD, and around three quarters met looser criteria. Depending on definitions, between 66% and 93% of those who met criteria for PTSD also met criteria for a diagnosis of CPTSD. The ITQ-ID showed a single-component structure, with very good-to-excellent internal consistency, excellent test-retest reliability, and evidence of concurrent, discriminant, and content validity. The results support the potential of the ITQ-ID for assessment of PTSD and CPTSD in people with intellectual disabilities in both clinical and research contexts and highlight the need for further validation work.


[Serum lipoproteins in elderly patients with cerebrovascular pathology].
Contents of 7 serum lipoprotein (LP) fractions both native and after their incubation under 37 degrees C during 24 h in the patients with atherosclerosis and hypertension discirculatory encephalopathy were investigated by a gradient gel-electrophoresis method. Two groups of patients in the age of 30-59 in the first group and 61-73 in the second one were examined. It was found that for the age interval examined in native serum of the patients with atherosclerosis and hypertension similar changes of LP contents were observed. These changes were expressed a increasing apoA- and decreasing apoB-containing LP fractions as compared with the control. After the temperature incubation of healthy persons serum the amount of LDL increases and amount of HDL3 declines. The latter is a result of LP lypolysis and etherification normal processes. On the base of the data obtained we may suppose that in the patients with hypertension these processes also have some aged peculiarities, although less intensive as compared with the healthy persons. In contrast to the latter after the temperature incubation of serum (in vitro) in the patients with atherosclerosis there were no any statistically significant changes of any LP fractions contents that may evidence about depression of LP transformation in the isolated serum in such patients.


Correlation Between Vitamin D Deficiency and Diabetic Ketoacidosis.
Both type 1 and type 2 diabetes mellitus have been associated with vitamin D deficiency. Diabetic ketoacidosis, which is a complication of type 1 and, rarely, type 2 diabetes, is also found to be associated with vitamin D levels. This review discusses studies on the correlation between diabetic ketoacidosis and vitamin D levels. Studies show that vitamin D deficiency is associated with the occurrence of diabetic ketoacidosis. Diabetic ketoacidosis is also found to affect vitamin D levels. The possible explanation of diabetic ketoacidosis affecting vitamin D levels is the inactivity of the 1-alpha-hydroxylase enzyme and an increase in the renal excretion of vitamin D binding proteins. The presence of vitamin D receptors on pancreatic beta cells explains the role of vitamin D in the causation of diabetic ketoacidosis.


Airflow obstruction and small airway dysfunction following pulmonary tuberculosis: a cross-sectional survey.
Pulmonary function impairment and chronic respiratory symptoms after tuberculosis are relatively common in low-income and middle-income countries. We aimed to estimate the impact of post-tuberculosis (post-TB) on pulmonary function. This large cross-sectional, population-based study included subjects aged 15 years or older with technically acceptable postbronchodilator spirometry measurements. Post-TB was diagnosed on the basis of radiological evidence and/or medical history. Airflow obstruction was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal of Global Lung Function Initiative (GLI) lung function equations. Small airway dysfunction was diagnosed if at least two of the following indicators were less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50% or FEF 75%. In this population sample (N=8680, mean age: 40.1 years), 610 (7.0% (95% CI 6.5 to 7.6) participants were post-TB. Post-TB subjects had more frequent respiratory symptoms (46.8% vs 28.3%). Among post-TB subjects, 130 (21.3% (95% CI 18.1 to 24.8)) had airflow obstruction; OR of airflow obstruction was significantly associated with post-TB after adjustment for other confounding factors (OR 1.31, 95% CI 1.05 to 1.62). Post-TB was also associated with small airway dysfunction (OR 1.28, 95% CI1.07 to 1.53), which was present in 297 (48.9% (95% CI 33.9 to 53.0)) post-TB subjects. Our findings support existing knowledge that post-TB is positively associated with pulmonary function impairment and make for frequent respiratory symptoms. Post-TB should be considered as a potentially important cause of airflow obstruction and respiratory symptoms in patients originating from countries with a high burden of tuberculosis.


Coronary and aortic vasoconstriction by cathinone, the active constituent of khat.
1. The psychostimulant constituent of khat leaves, S-(-)-cathinone, was examined for vascular activity on the coronary vasculature of guinea-pig-isolated perfused hearts and aortic ring preparations. 2. Cathinone caused coronary vasoconstriction, negative inotropy and negative chronotropy in isolated hearts. The major metabolite of cathinone after its ingestion, 1R.2S-(-)-norephedrine (norephedrine), also caused coronary vasoconstriction comparable with that by cathinone. Norephedrine, however, had no effect on force or rate of cardiac contractions. 3. Cocaine (10 microm) potentiated the coronary vasoconstriction and positive inotropy by noradrenaline indicating inhibition of neuronal uptake. The vasoconstriction and negative inotropy by cathinone, however, were not affected, indicating that its action was not via release of noradrenaline from sympathetic neurones. 4. The alpha(1)-adrenoceptor antagonist, prazosin, blocked the vasoconstriction by noradrenaline, but not that produced by cathinone in the presence of cocaine. This indicates that the coronary vasoconstriction by cathinone was not due to an action on alpha(1)-adrenoceptors either directly or indirectly through noradrenaline release. 5. Three repeated doses of cathinone displayed the same coronary vasoconstrictor responses, indicating a lack of tachyphylaxis and therefore confirming that the response was unlikely to be due to indirect sympathomimetic activity through release of noradrenaline. 6. In guinea-pig aortic rings, the order of vasoconstrictor activity was: noradrenaline > norephedrine > cathinone, with each causing approximately equivalent maximum responses. The time to reach plateau contractions was shortest for noradrenaline (5.1 +/- 0.5 min), then norephedrine (9.3 +/- 1.5 min) and cathinone the longest (25.4 +/- 3.2 min, 335 microm dose). 7 These results indicate that cathinone has vasoconstrictor activity which is not due to indirect or direct sympathomimetic activity. The precise mechanism for this vasoconstriction remains to be determined. The coronary vasoconstriction may explain the increased incidence of myocardial infarction in khat chewers, which may arise from coronary vasospasm.


Outcome after hepatectomy for multiple (four or more) colorectal metastases in the era of effective chemotherapy.
Hepatic resection is generally accepted as the only potential for long-term survival in patients with colorectal metastases confined to the liver. Despite an unknown benefit, hepatic resection is playing an increasing role in patients with extensive disease. A retrospective review of a prospectively maintained hepatobiliary surgical database was carried out. Outcome after hepatectomy for four or more colorectal hepatic metastases was reviewed. Between 1998 and 2002, out of a total of 584 patients, 98 (17%) with four or more colorectal hepatic metastases were resected. Actuarial 5-year survival was 33% for the entire group, with seven actual 5-year survivors. There were no perioperative deaths, and the perioperative morbidity was 28%. Positive margins and extrahepatic disease resection were independently associated with poor outcome. The median disease-free survival was 12 months, with no actuarial disease-free survivors at 5 years. Recurrence pattern, response to neoadjuvant chemotherapy, time to recurrence, and resection of recurrent disease were also associated with outcome. Long-term survival can be achieved after resection of multiple colorectal metastases; however, because most patients will experience recurrence of disease, effective adjuvant therapy and close follow-up is necessary.


Root Reinforcement Improved Performance, Productivity, and Grain Bioactive Quality of Field-Droughted Quinoa (Chenopodium quinoa).
Modern agriculture is facing multiple and complex challenges and has to produce more food and fiber to feed a growing population. Increasingly volatile weather and more extreme events such as droughts can reduce crop productivity. This implies the need for significant increases in production and the adoption of more efficient and sustainable production methods and adaptation to climate change. A new technological and environment-friendly management technique to improve the tolerance of quinoa grown to maturity is proposed using native microbial biostimulants (arbuscular mycorrhizal fungi; AMF) alone, in the consortium, or in combination with compost (Comp) as an organic matter source under two water treatments (normal irrigation and drought stress (DS)). Compared with controls, growth, grain yield, and all physiological traits under DS were significantly decreased while hydrogen peroxide, malondialdehyde, and antioxidative enzymatic functions were significantly increased. Under DS, biofertilizer application reverted physiological activities to normal levels and potentially strengthened quinoa's adaptability to water shortage as compared to untreated plants. The dual combination yielded a 97% improvement in grain dry weight. Moreover, the effectiveness of microbial and compost biostimulants as a biological tool improves grain quality and limits soil degradation under DS. Elemental concentrations, particularly macronutrients, antioxidant potential (1,1-diphenyl-2-picrylhydrazyl radical scavenging activity), and bioactive compounds (phenol and flavonoid content), were accumulated at higher levels in biofertilizer-treated quinoa grain than in untreated controls. The effects of AMF + Comp on post-harvest soil fertility traits were the most positive, with significant increases in total phosphorus (47%) and organic matter (200%) content under drought conditions. Taken together, our data demonstrate that drought stress strongly influences the physiological traits, yield, and quality of quinoa. Microbial and compost biostimulation could be an effective alternative to ensure greater recovery capability, thereby maintaining relatively high levels of grain production. Our study shows that aboveground stress responses in quinoa can be modulated by signals from the microbial/compost-treated root. Further, quinoa grains are generally of higher nutritive quality when amended and inoculated with AMF as compared to non-inoculated and compost-free plants.


Surveillance for respiratory syncytial virus in infants hospitalized for acute lower respiratory infection in Chile (1989 to 2000).
Hospitalized infants (4,618) were studied for lower respiratory infections from 1989 through 2000 by routine immunofluorescence assay and viral isolation. The hospitalization rate for respiratory syncytial virus (RSV) averaged 2% per year. The fatality rate was 0.1%. Monthly RSV detection varied from 14 to 88%, and epidemics lasted 3.5 to 6 months. From 1994 high-early versus low-late epidemic patterns alternately were observed, the first influenced by a group B strain.


CT-guided percutaneous cyanoacrylate injection targeting the spinal cerebrospinal fluid leak: a potential therapeutic option for spontaneous intracranial hypotension.
We report the first case series of spontaneous intracranial hypotension (SIH) patients who underwent CT-guided percutaneous cyanoacrylate injection targeting the cerebrospinal fluid (CSF) leak. A retrospective analysis was performed for all consecutive cases of SIH patients with CSF leak confirmed on CT myelography, treated by CT-guided percutaneous cyanoacrylate injection at our institution from 2016 to 2022. On pretreatment brain and spine MRIs, we analyzed signs of SIH according to the Bern score, and dichotomized cases into positive/negative for spinal longitudinal extradural CSF collection (SLEC-P or SLEC-N). The leaks detected on CT myelography were classified into three types according to Schievink et al. We collected the Headache Impact Test 6 (HIT-6) scores throughout a 6-month follow-up, with a brain CT scan at each visit. 11 patients were included (mean age 48.4 years, six men). Five SLEC-P type 1, three SLEC-P type 2, and three SLEC-N type 3 leaks were identified. All patients had significant signs of SIH on pretreatment brain MRI (mean Bern score 7.8±1.1). Six patients underwent a foraminal puncture, and five patients had a cervical epidural approach. Two patients experienced mild and transient locoregional pain after cervical epidural injection. Mean HIT-6 score at baseline was 66.8±3.2 and at the 6-month follow-up was 38±3.6 (P<0.001). All patients achieved improvement in their symptoms, with 82% of them (9/11) having complete resolution of headaches and SIH findings on CT scans at 6 months. No clinical worsening or recurrence was observed. CT-guided percutaneous cyanoacrylate injection may be a potential therapeutic option for the different types of CSF leak causing SIH.


Rotation in a Smoking Cessation Clinic Improves Nicotine Dependence Treatment Provided by First-Year Internal Medicine Trainees.
Over 70% of smokers visit a physician annually, and physicians are well-positioned to assist patients in smoking cessation. Residency offers the ideal setting to train physicians in best practices for treatment of nicotine dependence. We hypothesized that experiential learning during a smoking cessation medical clinic (SCMC) rotation would be associated with an improvement in smoking cessation practice of internal medicine (IM) interns in outpatient primary care and inpatient settings. This was a prospective study performed at a large university-affiliated hospital. Forty IM interns rotated through SCMC. After a lecture on nicotine addiction and treatment, interns treated SCMC patients under direct supervision of an attending pulmonologist. Interns' smoking cessation practices before and after SCMC rotation were evaluated through chart review over 1 year. Upon study completion, a survey to assess confidence was administered. Paired t tests measured changes in rates of identifying smokers, offering pharmacological treatment and counseling. A total of 5,622 outpatient and 683 inpatient charts of interns' encounters with patients were reviewed. Following SCMC rotation, there was an increase in identifying active smokers (7.1% versus 18.7%), prescribing therapy for smoking cessation (6.5% versus 18.0%), and providing counseling (30.9% versus 42.3%) to outpatients. For inpatients, there was an increase in nicotine replacement during admission (12.9% versus 37.4%) and prescription of therapy upon discharge (5.7% versus 16.1%). Interns reported confidence in providing appropriate counseling and treatment. SCMC experience positively impacted smoking cessation treatment by IM interns, causing a measurable change in their practice.


Keratoconus.
Keratoconus is a bilateral disorder of corneal shape which may be sporadic or genetically determined. Early corneal thinning suggests that a functional loss of structural elements is a primary event in the disease. Tensile strength of the cornea is reduced and is expressed by signs of rupture and scarring in Bowman's layer, scarring in the substantia propria, and rupture of Descemet's membrane. The overall stretching of the cornea results in an increase in curvature while an increased area of the corneal surfaces probably determines the onset and form of Fleischer's ring and the occurrence of endothelial polymegathism. Biochemical studies have shown an increase in collagenolysis and of reduceable collagen cross-links, but there is inconsistent evidence of altered solubility or of hydroxyproline or proteoglycan content. Of recent interest is the characterization of proteoglycan bridges along and between corneal collagen fibrils in keratoconus and the apparent loss of keratan sulphate demonstrated by electron-histochemical and x-ray diffraction techniques. The manner in which this could interfere with corneal strength is discussed.


[The usefulness of transcutaneous gas monitoring during hemorrhagic shock; discrepancy between the two transcutaneous gas tensions of anterior thorax and femur].
We measured transcutaneous gas tensions of both anterior thorax and femur. The differences between the two transcutaneous gas tensions were compared, as well as the relationship between the two transcutaneous and mixed venous blood gas tensions, in 10 dogs during hemorrhagic shock. The changes in femoral transcutaneous gas tensions correlated better with the changes in mixed venous gas tensions. The correlation between the two transcutaneous gas tensions were fairly good (oxygen tensions; r = .827, carbon dioxide tensions; r = .867). However, the discrepancy between the two gas tensions became greater in severe shock. Hence, oxygen tensions became smaller and carbon dioxide tensions became greater on femur than on anterior thorax. This indicates the possibility of "maldistribution of blood flow", which has already been detected between vital organs and skin, also exists between peripheral and central skin. Therefore, transcutaneous gas tensions should be monitored at peripheral skin, where gas tensions show greater changes and reflect systemic perfusion precisely than at central skin, during shock.


Return to Everyday Activity in the Community and Home: a feasibility study for a lifestyle intervention to sit less, move more, and be strong.
Many interventions designed to meet physical activity guideline recommendations focus on a single component (e.g., walking), to the detriment of other elements of a healthy lifestyle, such as reducing prolonged sitting and doing balance and strength exercises (i.e., bundled multiple behaviors). Adopting these multiple health behaviors within daily life routines may facilitate uptake and support longer-term behavior change. We tested feasibility for a three-part lifestyle intervention to support older women to sit less, move more, and complete balance and strength exercises. We used a convergent parallel mixed-methods, single-arm study design to test feasibility for a 6-week lifestyle intervention: Return to Everyday Activities in the Community and Home (REACH). We collected information at baseline, 3 and 6 weeks (final), and 6 months (follow-up) using questionnaires, semi-structured interviews, and performance-based measures. We describe three key elements: (1) implementation factors such as recruitment, retention, program delivery, and adherence; (2) participants' acceptability and experience with the program; and (3) health outcomes, including participants' global mobility, activity, and perceptions of their physical activity identity, and habit strength for (i) physical activity, (ii) breaking up sitting time, and (iii) balance and strength exercises. We were able to recruit enough participants in the allotted time to conduct one cycle of the REACH group-based program. There were 10 community-dwelling women, median (p25, p75) age 61 (57.5, 71) years, who completed the study. The program was feasible to deliver, with high attendance (mean 5/6 sessions) and positive overall ratings (8/10). Participants rated session content and length high, and educational materials as highly acceptable and understandable. Although participants were active walkers at baseline, few were breaking up prolonged sitting or participating in any balance and strength exercises. At final and follow-up assessments, participants reported developing habits for all three health behaviors, without diminishing physical activity. These results show acceptability of the program and its materials, and feasibility for bundling multiple health behaviors within the REACH program. It also provides confirmation to advance to testing feasibility of this three-part lifestyle intervention with older, less active, adults. ClinicalTrials.gov Identifier, NCT02786394; May 18, 2016.


Human endogenous retroviral elements as indicators of ectopic recombination events in the primate genome.
HERV elements make up a significant fraction of the human genome and, as interspersed repetitive elements, have the capacity to provide substrates for ectopic recombination and gene conversion events. To understand the extent to which these events occur and gain further insight into the complex evolutionary history of these elements in our genome, we undertook a phylogenetic study of the long terminal repeat sequences of 15 HERV-K(HML-2) elements in various primate species. This family of human endogenous retroviruses first entered the primate genome between 35 and 45 million years ago. Throughout primate evolution, these elements have undergone bursts of amplification. From this analysis, which is the largest-scale study of HERV sequence dynamics during primate evolution to date, we were able to detect intraelement gene conversion and recombination at five HERV-K loci. We also found evidence for replacement of an ancient element by another HERV-K provirus, apparently reflecting an occurrence of retroviral integration by homologous recombination. The high frequency of these events casts doubt on the accuracy of integration time estimates based only on divergence between retroelement LTRs.


On the edge: the psychoanalyst's transference.
Countertransference is a central topic in analytic work and in the literature. The concept of countertransference includes a basic question which has been understood in different ways. The author attempts to differentiate between the psychoanalyst's transference and his countertransference in the analytic process. It is hard to draw a line between them; analysts are always on the edge. The analyst's transference will be explored and described using three approaches: narcissism, regression profile and the analyst's phase of life. Regression profile is a new concept developed by the author, which may help us to understand the core of the analyst's transference in the analytic situation. She illustrates the topic by clinical vignettes.


Detection of IgG and IgA antibodies to Chlamydia trachomatis in sera of patients with chlamydial infections: use of immunoblotting and immunoperoxidase assays.
The immune response to individual structural polypeptides of Chlamydia trachomatis was studied in 75 sera from symptomatic and asymptomatic women with culture-proved genital infections and from apparently healthy women who were culture-negative for C. trachomatis. The immunoblotting technique and the single serovar (L2) inclusion immunoperoxidase assays were used for measurement of the various antibodies. Antibodies to 18 structural polypeptides, ranging in molecular weight from 29 to 204 Kdaltons, were detected by the immunoblotting technique in sera from seropositive women. The immunoperoxidase assay showed that sera with high titers of IgG and IgA antibodies to C. trachomatis reacted with more polypeptides than did sera with low titers in this test. Antibodies to the 60- and 62-Kdalton polypeptides were detected in almost all sera positive for IgG and IgA antibodies, irrespective of chlamydial shedding. About 40% of sera with high IgG and IgA titers reacted with 39-, 57-, 64-, 72-, 86-, 105-, 155-, and 204-Kdalton polypeptides. The prevalence of IgA antibodies to C. trachomatis was higher among women with culture-proved chlamydial infections than among apparently healthy controls.


Levels of lysosomal enzymes in tissues of mice infected with Mycoplasma fermentans.
The effects of a toxic dose of Mycoplasma fermentans on levels of lysosomal enzymes in mice were examined. Washed cell suspensions (approximately 10(10) colony-forming units) of a recent isolate of M. fermentans were injected intraperitoneally into 3- to 4-week-old BALB mice, and levels of acid phosphatase and beta-glucuronidase were monitored in liver, spleen, thymus, and serum. Levels of acid phosphatase remained essentially normal, but levels of beta-glucuronidase were markedly evevated in serum and to a lesser extent in liver and thymus. The peak response of serum beta-glucuronidase was noted at 8 h postinjection, with a level of 30 mug of phenolphthalein released per ml per h, representing a six-fold increase over control levels. Pretreatment with BCG did not potentiate the effect as it did with endotoxin. The implication of this increased lysosomal enzyme activity in "lethal toxicity" is that that the increase may be secondary to some other cytotoxic event, or that the affinity of mycoplasmas for biological membranes may be involved. The data suggest that the role of lysosomal enzymes in other models of mycoplasma-induced disease should be evaluated.


Insulin Detection Using a Corona Phase Molecular Recognition Site on Single-Walled Carbon Nanotubes.
Corona phase molecular recognition (CoPhMoRe) is a technique whereby an external, adsorbed phase around a colloidal nanoparticle is selected such that its molecular conformation or interaction recognizes a specific target analyte. In this work, we employ a high-throughput screening of a library of poly(ethylene glycol) (PEG)-conjugated lipids adsorbed onto near-infrared fluorescent single-walled carbon nanotubes to discover a corona phase selective for insulin. We find that a C16-PEG(2000 Da)-ceramide causes a 62% fluorescent intensity decrease of the (10,2) chirality nanotube in the presence of 20 μg/mL insulin. The insulin protein has no prior affinity toward the C16-PEG(2000 Da)-ceramide molecules in free solution, verified by isothermal titration calorimetry, and the interaction occurs only upon their adsorption onto the single-walled carbon nanotube scaffolds. Testing a panel of proteins originating from human blood as well as short 7 amino acid fragments of the insulin peptide rules out nonselective recognition mechanisms such as molecular weight, isoelectric point, and hydrophobicity-based detection. Interestingly, longer fragments of isolated α- and β-peptide chains of insulin are detected by the construct, albeit with lower affinity compared to that of the intact insulin protein, suggesting that the construct recognizes insulin in its native form and conformation. Finally, the insulin recognition and the quantification of its solution concentration were demonstrated both in buffer and in blood serum, showing that the CoPhMoRe construct works in this complex environment despite the presence of potential nonspecific adsorption. Our results further motivate the search for nonbiological synthetic recognition sites and open up a new path for continuous insulin monitoring in vivo with the hope of improving glycemic control in closed-loop artificial pancreas systems.


Level of Confidence in the 12 Roles of Medical Teacher. A Descriptive Study at Faculty of Medicine, Srinakharinwirot University, Thailand.
An appropriate faculty development program is imperative for every medical school and should be tailored to suit the needs of individuals and the institution. To measure the average level of confidence in each of the 12 roles of medical teachers and analyse if any of these factors: age, gender duration of teaching, and teaching in pre-clinical or clinical years has effect on the level of confidence in the teacher roles. The online questionnaire invitations were sent via email to all 211 faculty members at Faculty of Medicine, Srinakharinwirot University, and 118 (55.9%) responded. The questionnaire asked about demographic data, teaching experience and their specialty or disciplines. The respondents were also asked to rate their level of confidence in each of the 12 teacher roles on a 5 point Likert scale ranging from 1 (none) to 5 (great). The three most highly rated roles on the level of confidence were the clinical teacher (4.11), the on the job role model (4.11) and the lecturer (3.97). The three roles with the lowest rating were the curriculum planner (3.08), the curriculum assessor (3.23) and the mentor (3.31). Age and teaching experience were positively correlated with the level of confidence in nearly all of the 12 teacher roles. The pre-clinical year teachers had a higher mean level of confidence than clinical teachers in 6 out of the 12 roles. The future faculty development programs should aim towards supporting self-evaluation of teaching, mentoring as well as promoting facilitative roles of the teacher Retention of faculty members at the institution is also important as the teaching experience significantly correlate with confidence in the teacher roles.


Identification of differential gene expression during porcine conceptus rapid trophoblastic elongation and attachment to uterine luminal epithelium.
Early embryonic development in the pig is characterized by a rapid elongation of the conceptus trophectoderm on days 11-12 of gestation. Initially, the conceptus trophoblast is morphologically rearranged from a 10-mm sphere into a tubular shape, transitioning into a thin filamentous form >150 mm in length in 2-3 h, followed by continued expansion within the uterine lumen for several days. Conceptus elongation is critical for establishing adequate placental surface area needed for embryo and fetal survival throughout gestation. The objective of this study was to characterize conceptus gene expression during trophoblastic elongation and the early attachment to the uterine endometrium on days 11-14 of gestation with the GeneChip Porcine Genome Array. In all, 3,759 different probe sets were statistically different in at least one comparison [spherical vs. tubular, spherical vs. day 12 filamentous (D12F), spherical vs. day 14 filamentous (D14F), tubular vs. D12F, tubular vs. D14F, and D12F vs. D14F]. When restricted to the spherical vs. D12F and D12F vs. D14F comparisons, 482 and 232 genes, respectively, were statistically different with greater than twofold change in expression. Utilization of k-means clustering, in addition to the Database for Annotation, Visualization, and Integrated Discovery (DAVID), identified genes of interest. Quantitative RT-PCR expression profiles for interferon-gamma (IFNG), heat shock protein 27 kDa (HSPB1), angiomotin, B-cell linker (BLNK), chemokine ligand 14 (CXCL14), parathyroid hormone-like hormone (PTHLH), and maspin were supportive of the GeneChip Porcine Genome Array data.


[The family living with Down syndrome patients in the perspective of Humanistic Theory].
The objective of this study was to socialize the process of coexistence of the family of the bearers of syndrome of Down based in the Humanistic Theory of Paterson and Zderad. The study was realized with a research of descriptive exploratory character, with a qualitative approach and participant observation. It was accomplished in APAE/ Sobral-CE, with the use of group dynamics and a guided interview for collection of data. The results showed us that the parents don't have difference between a normal son and a special one; the treatment is the same, with a lot of love, affection, understanding and respect, however a lot of times they find some difficulties in taking care, as the communication and the feeding. We also observed that the family is very important, necessary, so that the coexistence with the bearer becomes more and more natural in spite of a society that, a lot of times, still has prejudice.


[Study on regulation of CYP450 enzyme system to reduce liver toxicity through compatibility of Aconiti Kusnezoffii Radix Cocta with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma].
Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.