Zinc oxide nanoparticles: A comprehensive review on its synthesis, anticancer and drug delivery applications as well as health risks.
In recent years, zinc oxide nanoparticles (ZnONPs) emerged as an excellent candidate in the field of optical, electrical, food packaging and particularly in biomedical research. ZnONPs show cancer cell specific toxicity via the pH-dependent (low pH) dissolution into Zn2+ ions, which generate reactive oxygen species and induce cytotoxicity in cancer cells. Further, ZnONPs have also been used as an effective carrier for the targeted delivery of several anticancer drugs into tumor cells. The increasing focus on ZnONPs resulted in the development of various synthesis approaches including chemical, pHysical, and green or biological for the manufacturing of ZnONPs. In this article, at first we have discussed the various synthesis methods of ZnONPs and secondly its biomedical applications. We have extensively reviewed the anticancer mechanism of ZnONPs on different types of cancers considering its size, shape and surface charge dependent cytotoxicity. Photoirradiation with UV light or NIR laser further increase its anticancer activity via synergistic chemo-photodynamic effect. The drug delivery applications of ZnONPs with special emphasis on drug loading mechanism, stimuli-responsive controlled release and therapeutic effects have also been discussed in this review. Finally, its side effects to vital body organs with mechanism via different exposure routes, the future direction of the ZnONPs research and application are also discussed.


Noninvasive tests for eosinophilic esophagitis: Ready for use?
To summarize the existing literature for several promising minimally invasive tests to measure disease activity in eosinophilic esophagitis (EoE). Literature searches were performed using PubMed. Keyword combinations included eosinophilic esophagitis and minimally invasive techniques, including the esophageal string test, Cytosponge, transnasal endoscopy, technetium-labeled heparin, and noninvasive biomarkers. Retrospective and prospective observational studies, peer-reviewed reviews, and systematic reviews were selected. Data were reviewed and summarized. Various techniques have been developed in recent years to measure disease activity in EoE without the need for conventional endoscopy. Our review summarizes the data on these techniques, the benefits and limitations, and future directions for implementation in both research and clinical care. Tremendous progress has been made toward developing minimally invasive techniques to measure disease activity in EoE. Each of the techniques mentioned in this review has advantages and disadvantages, and some are closer to widespread use than others.


The reliability of transthoracic and transesophageal echocardiography in predicting the size of atrial septal defect.
To determine the reliability of transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) in predicting the size of an atrial septal defect (ASD). The study included 16 patients who underwent the catheter-based procedures to close an atrial septal defect between February 2008 and December 2011 at the Paediatrics Clinic, CCU Sarajevo, after clinical and TTE and TEE evaluation. In order to determine the assumed diameter of the balloon (A-SBD), we used the formula of quantification A-SBD=TTE defect diameter×1:09 + 3.9 mm and A-SBD=1.1× transesophageal diameter of ASD+2.0 mm. The ASD was examined using the long-axis view, the basal short-axis view, the apical four-chamber view and the subcostal view to observe its position, diameter and relation to neighbouring structures. The largest diameter was selected as the reference diameter. Of the total number of treated patients, 11 were female. Treatment was conducted by a foreign and local team of invasive cardiologists. The average age of the patients was 8.43 years (2 -17 years). Apart from a transient disturbance of rhythm in the youngest patients, there were no other intra and postprocedural complications. The obtained formulas represent "our" default size of the SBD, based on measurements of TTE and TEE: A-SBD (TTE)=6.02+0.86×TTE and A-SBD (TEE)=3.93+0.86×TEE. ASD diameter determined by TTE and TEE can reliably determine the appropriate size needed Amplatzer Septal Occluder device.


Plasma and muscle free amino acids in maintenance hemodialysis patients without protein malnutrition.
To investigate how uremia modified by maintenance hemodialysis treatment influences the extra- and intracellular amino acid pattern, we collected muscle samples by percutaneous muscle biopsy and plasma samples for determination of free amino acids in 11 functionally anephric patients (creatinine clearance less than 1 ml/min), who had been treated with hemodialysis for greater than 6 months and had no clinical or laboratory signs of protein malnutrition. Five patients had mild acidosis (standard bicarbonate pre-dialysis 18 to 21 mmol/liter). The amino acid results were compared with data from age- and sex-matched healthy controls and with data obtained earlier from non-dialyzed patients with chronic uremia. In the hemodialysis patients threonine, serine and valine were significantly reduced in plasma compared to the controls, whereas the plasma concentrations of aspartate, glycine, citrulline, cysteine and arginine were elevated. In aspartate, glycine, citrulline, cysteine and arginine were elevated. In muscle, valine, serine and the tyrosine to phenylalanine ratio were low. Compared with the untreated uremic patients the hemodialysis patients exhibited fewer significant abnormalities, but the general pattern was similar, demonstrating that hemodialysis is unable to fully correct the amino acid abnormalities of chronic uremia. There was a significant positive correlation between both pre-dialysis and post-dialysis plasma bicarbonate and the muscle valine concentration, suggesting that mild acidosis may be causally related to the inbalance of the branched-chain amino acids in uremia. Extra- and intracellular serine depletion in the presence of high plasma glycine may reflect a defect in the metabolism of glycine to serine in hemodialysis patients, related to a lack of metabolizing renal tissue.


Localization of chick retinal 24,000 dalton protein (visinin)-like immunoreactivity in the rat lower brain stem.
The distribution of visinin, a 24,000 dalton peptide, in the lower brain stem of the rat was examined by means of an indirect immunofluorescent method. Visinin-immunoreactive structures were found to be unevenly distributed only in the neuronal elements. The following neuronal systems were strongly labeled by the antiserum; the Purkinje cell system, mammillotegmental system, habenulointerpeduncular system, the second layer of the superior colliculus, ventral tegmental area, substantia nigra pars lateralis, area medial to the medial geniculate body, parabrachial area, dorsal and ventral nuclei of the lateral lemniscus, pontine reticular formation just medial to the trigeminal principal nucleus, superior olivary nucleus, solitarii nucleus, external layer of the inferior colliculus and spinal trigeminal nucleus. The densities of the labeled fibers in these areas paralleled those of the labeled cells. In addition, highly dense visinin-immunoreactive fiber plexuses were seen in the zona compacta of the substantia nigra, lateral portion of the interpeduncular nucleus, ventral tegmental nucleus of Gudden and vestibular nucleus.


Functional kinesiology in haemophilia, an area yet to be explored.
In haemophilic arthropathy there is a progressive limitation of the range of motion (ROM) which may lead to disabilities in the activities of daily living (ADL). In the literature the pathology of haemophilic arthropathy is described extensively, but only one paper describing functional limitations caused by limited range of motion (LOM) in haemophilia was found. The aim of the pilot study was to estimate on theoretical grounds, how many patients with haemophilia might suffer from functional disabilities. ROM of elbows, knees and ankles of 155 Haemophilia A and B patients. Flexion and extension were measured with an ordinary goniometer. The ROM of joints of patients with haemophilia was compared with normal values. 39 of 155 patients had a normal ROM in both elbows; 22 in one elbow; 34 patients had disabilities in ADL with both arms; 14 with one arm; 18 were able to compensate; 89 had no problems; 79 of 155 patients had a near normal ROM of both knees; 38 patients could not ride an ordinary bicycle. Only limited data are available concerning the normal ROM needed for individual ADL. Until additional data are available, it is not possible to predict which patients will be disabled in their activities of daily living and individual counselling should be done during the yearly outpatient comprehensive care clinics. Conservative and surgical measures should be taken to ensure elbow flexion of at least 120 degrees and knee flexion of 100 degrees for Western societies. In Asian countries patients with haemophilia need maximum knee flexion and ankle dorsi flexion.


Amphetamine and 2-phenylethylamine in post-mortem Parkinsonian brain after (-)deprenyl administration.
Deprenyl is an inhibitor of monoamine oxidase type B, the enzyme responsible for 2-phenylethylamine oxidation, and is used in conjunction with L-Dopa therapy in Parkinson's disease. Post-mortem studies in human brain tissue have shown that after (-)deprenyl administration to parkinsonian patients amphetamine is present in concentrations up to 56 ng/g. It also could be shown that phenylethylamine concentrations are substantially increased in such patients. Phenylethylamine and amphetamine have been investigated using a gas chromatographic technique.


[Chemical contrast research on Buyang Huanwu complex ultramicro powder soak and traditional decoction].
To study the chemical composition of Buyang Huanwu complex ultramicro powder soak and traditional decoction. Extractive determination, heavy metal and arsenic determination, TLC and HPLC were used to analysis the chemical composition. The extract of Buyang Huanwu complex ultramicro powder soak was higher than that of traditional decoction. The lamellar spot of Buyang Huanwu complex ultramicro powder soak was clearer than that of traditional decoction. Astragalin in Buyang Huanwu complex ultramicro powder soak was correspond with the traditional decoction. The way of soaking ultramicro powder not only can avoid losing active component, but also can release it quickly.


CFTR processing, trafficking and interactions.
Mutations associated with cystic fibrosis (CF) have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common CF mutation, F508del, disrupts the processing to and stability at the plasma membrane and function as a Cl- channel. CFTR is surrounded by a dynamic network of interacting components, referred to as the CFTR Functional Landscape, that impact its synthesis, folding, stability, trafficking and function. CFTR interacting proteins can be manipulated by functional genomic approaches to rescue the trafficking and functional defects characteristic of CF. Here we review recent efforts to elucidate the impact of genetic variation on the ability of the nascent CFTR polypeptide to interact with the proteostatic environment. We also provide an overview of how specific components of this protein network can be modulated to rescue the trafficking and functional defects associated with the F508del variant of CFTR. The identification of novel proteins playing key roles in the processing of CFTR could pave the way for their use as novel therapeutic targets to provide synergistic correction of mutant CFTR for the greater benefit of individuals with CF.


Subacute arsenic exposure through drinking water reduces the pharmacodynamic effects of ketoprofen in male rats.
We evaluated the modulatory role of the groundwater contaminant arsenic on the pharmacodynamic responses of the nonsteroidal analgesic-antipyretic drug ketoprofen and the major pro-inflammatory mediators linked to the mechanism of ketoprofen's therapeutic effects. Rats were pre-exposed to sodium arsenite (0.4, 4 and 40 ppm) through drinking water for 28 days. The pharmacological effects of orally administered ketoprofen (5 mg/kg) were evaluated the following day. Pain, inflammation and pyretic responses were, respectively, assessed through formalin-induced nociception, carrageenan-induced inflammation and lipopolysaccharide-induced pyrexia. Arsenic inhibited ketoprofen's analgesic, anti-inflammatory and antipyretic effects. Further, arsenic enhanced cyclooxygenase-1 and cyclooxygenase-2 activities and tumor necrosis factor-α, interleukin-1β and prostaglandin-E(2) production in hind paw muscle. These results suggest a functional antagonism of ketoprofen by arsenic. This may relate to arsenic-mediated local release of tumor necrosis factor-α and interleukin-1β, which causes cyclooxygenase induction and consequent prostaglandin-E(2) release. In conclusion, subacute exposure to environmentally relevant concentrations of arsenic through drinking water may aggravate pain, inflammation and pyrexia and thereby, may reduce the therapeutic efficacy of ketoprofen.


Polysialylation controls immune function of myeloid cells in murine model of pneumococcal pneumonia.
Polysialic acid (polySia) is a post-translational modification of a select group of cell-surface proteins that guides cellular interactions. As the overall impact of changes in expression of this glycan on leukocytes during infection is not known, we evaluate the immune response of polySia-deficient ST8SiaIV-/- mice infected with Streptococcus pneumoniae (Spn). Compared with wild-type (WT) mice, ST8SiaIV-/- mice are less susceptible to infection and clear Spn from airways faster, with alveolar macrophages demonstrating greater viability and phagocytic activity. Leukocyte pulmonary recruitment, paradoxically, is diminished in infected ST8SiaIV-/- mice, corroborated by adoptive cell transfer, microfluidic migration experiments, and intravital microscopy, and possibly explained by dysregulated ERK1/2 signaling. PolySia is progressively lost from neutrophils and monocytes migrating from bone marrow to alveoli in Spn-infected WT mice, consistent with changing cellular functions. These data highlight multidimensional effects of polySia on leukocytes during an immune response and suggest therapeutic interventions for optimizing immunity.


Cerebrocortical modulation of S2-receptors and turnover rate of 5-hydroxytryptamine in ischemia.
A possible relationship between the changes in the properties of S2-receptor binding sites and the turnover rate of 5-hydroxytryptamine (5-HT) has been investigated in cerebral ischemia associated with either little or marked edema. Bilateral common carotid artery occlusion for 5 or 15 min with 1 hour of reestablished blood flow in gerbils served as a model for the respective studies. An alteration in kinetic characteristics of S2-receptor binding sites labeled with [3H]ketanserin (the potent 5-HT antagonist for postsynaptic receptors) was detected in the synaptosomes separated from brains of gerbils subjected to 1 hour release after 15 but not following 5 min of bilateral ischemia. At the same time, an increased turnover rate of 5-HT was found in the cerebro-cortical homogenate. The duration of ischemic insult which leads to the changes in the properties of S2-binding sites and the increase in turnover rate of 5-HT has been identical with that needed for the marked accumulation of water in the gerbil brain reported previously. Thus, these findings are consistent with the implicated involvement of 5-HT in the formation of ischemic cerebral edema.


Kopsiyunnanines J1 and J2, new strychnos-type homo-monoterpenoid indole alkaloids from Kopsia arborea.
Two new indole alkaloids, kopsiyunnanines J1 and J2, were isolated from Yunnan Kopsia arborea, and their structures were determined by spectroscopic analyses. Kopsiyunnanines J1 and J2 are unprecedented Strychnos-type indole alkaloids having an additional C1 unit in the secologanin moiety of the molecule.


Exploring the gelation of aqueous cellulose nanocrystals (CNCs)-hydroxyethyl cellulose (HEC) mixtures.
We investigated the gelation and microstructure of cellulose nanocrystals (CNCs) in nonionic hydroxyethyl cellulose (HEC) solutions. Cellulose nanocrystals (CNCs) with a particle length of 90 nm and width of 8 nm currently produced by acid hydrolysis of wood pulp were used in this study. The microstructures of CNCs/polymer suspensions were investigated by performing linear small amplitude oscillatory shear (SAOS) and nonlinear large amplitude oscillatory shear (LAOS), in addition to constructing CNCs phase diagrams and measuring steady-state shear viscosities. Significant viscosity increases at low shear rates coupled with high shear thinning behaviors were observed in CNCs in HEC solutions above the overlapping concentration of HEC. The physical strength of CNCs/HEC solution gels increased with the increase in CNCs concentration and resembled the weakly crosslinked gels according to the scaling of linear dynamic mechanical experiments. According to LAOS analysis, CNCs/HEC mixtures showed type III behavior with intercycle stress softening, while the samples showed stress stiffening in single cycles.


Naloxone-induced changes in tachykinin NK3 receptor modulation of experimental anxiety in mice.
This study investigates the influence of naloxone, an opioid antagonist, upon the effects of drugs acting on tachykinin NK3 receptor in the elevated plus-maze test. Mice were intracerebroventricularly (i.c.v.) injected either with vehicle, 10 pmol of senktide, an NK3 agonist, or 100 pmol of [Trp7beta-Ala8]NKA(4-10) or SR142801, NK3 antagonists. Senktide alone significantly increased the frequency of entries and the time spent in open arms, an anxiolytic-like effect, whereas the NK3 antagonists alone showed no effect at the dose used. Naloxone alone did not alter the behavior of the animals on the plus-maze apparatus. Nevertheless, animals pretreated with naloxone (2 mg/kg, i.p.) showed an increase in senktide's anxiolytic-like effect and a similar profile of action for [Trp7beta-Ala8]NKA(4-10), but not for SR142801, which presented an anxiogenic-like effect. Altogether, these findings indicate a putative neurokinin-opioid relationship in the modulation of experimental anxiety in mice.


NIMRA-survey: NSAIDs impact on mortality. Results of an Austrian Survey in 2006.
This survey is based on a sample of over two thousand patients who were in the first eight months of the year 2006 hospitalised due to a diagnosis of coronary heart disease (CHD) or rheumatic diseases (RD). Their demographic, anamnestic data were assessed according to a prospectively defined analysis plan together with the associated mortality. The main survey questions--whether the data suggest an association between rheumatism as compared to CHD and mortality and which conclusions with respect to NSAID (non-steroidal anti-inflammatory drug) consumption can be drawn in this pilot project--can be answered with some degree of statistical robustness bearing in mind the sampling uncertainties and the omnipresent fuzziness of medical data including mortality. Rheumatism is generally associated with a lower risk of death (1%) as compared to CHD patients with a death risk of 3% (p < 0.01). As there are many confounding risk factors which show statistically highly significant effects and might be associated with substantial interactions on the mortality outcome it seems advisable to interpret the available data with caution and take this as the main results of a survey which is characterised mainly by its pilot nature. Additional research in this area with more sophisticated tools and based on much larger samples is judged to provide final and conclusive epidemiologic evidence. For the time being NSAIDs did not imply any relevant increases in mortality in RD or CHD patients as compared to patients who were not prescribed NSAIDs. Coronary heart diseases constitute a relevant and significant prognostic factor for an increased mortality as compared to rheumatic diseases.


The COX-2-derived PGE2 autocrine contributes to bradykinin-induced matrix metalloproteinase-9 expression and astrocytic migration via STAT3 signaling.
The matrix metalloproteinase-9 (MMP-9) is up-regulated by several proinflammatory mediators in the central nervous system (CNS) diseases. Increasing reports show that MMP-9 expression is an inflammatory biomarker of several CNS disorders, including the CNS inflammation and neurodegeneration. Bradykinin (BK) is a common proinflammatory mediator and elevated in several brain injury and inflammatory disorders. The raised BK may be detrimental effects on the CNS that may aggravate brain inflammation through MMP-9 up-regulation or cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production in brain astrocytes. However, the relationship between BK-induced MMP-9 expression and COX-2-derived PGE2 release in brain astrocytes remains unclear. Herein we used rat brain astrocytes (RBA) to investigate the role of the COX-2/PGE2 system in BK-induced MMP-9 expression. We used zymographic, RT-PCR, EIA, and Western blotting analyses to confirm that BK induces MMP-9 expression via a COX-2/PGE2-dependent pathway. Our results show activation of native COX-2 by BK led to PGE2 production and release. Subsequently, PGE2 induced MMP-9 expression via PGE2 receptor (EP)-mediated c-Src, Jak2, ERK1/2, and then activated signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, up-regulation of MMP-9 by BK via the pathway may promote astrocytic migration. These results demonstrated that a novel autocrine pathway for BK-induced MMP-9 protein expression is mediated through activation of STAT3 by native COX-2/PGE2-mediated c-Src/Jak2/ERK cascades in brain astrocytes. Video Abstract.


[Ultrasonography of the pancreas. Diagnostic problems and findings in cases of solid pancreatic masses (author's transl)].
By using rigourous examination techniques and interpretive criteria, ultrasonography of the pancreas can, in many cases, confirm the etiological diagnosis of solid pancreatic masses. Factors influencing diagnosis are the volume and shape of the pancreas, the ultrasound structure, the attenuation of ultrasounds, the outline of the pancreas, and the effect on neighbouring structures. The association of signs is often characteristic and can differentiate benign from malignant masses.


[External adrenal pheochromocytoma].
To improve the diagnosis of external adrenal pheochromocytoma. From 1958 to 1998, 66 cases of external adrenal pheochromocytoma, 23.3% of pheochromocytomas, at the same period in the Department of Urology, RuiJin Hospital were reviewed. In the 66 cases, the malignant rate was high (33%). (131)I-MIBG is important in the diagnosis and treatment of external adrenal pheochromocytoma. Long-term follow up after operation is imperative to the cases of external adrenal pheochromocytoma.


The effect of mono(2-ethylhexyl) phthalate on Sertoli cell transferrin secretion in vitro.
We have examined the effect of mono(2-ethylhexyl) phthalate (MEHP) on the secretion of rat transferrin (rTf) by Sertoli cells (SC) in the presence and absence of FSH. Significant decreases in rTf secretion were observed in SC cultures exposed to 50 and 75 microM MEHP, in the absence of FSH. Treatment of SC with FSH (300 ng/ml) obviated this suppression of rTf secretion by MEHP. These findings indicate an effect of MEHP on rTf secretion by SC in vitro which could account for the testicular toxicity of MEHP in vivo.


Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance.
In adult male primates, estrogens play a role in both gonadotropin feedback and sexual behavior. Inhibition of aromatization in intact male monkeys acutely elevates serum levels of luteinizing hormone, an effect mediated, at least partially, within the brain. High levels of aromatase (CYP19) are present in the monkey brain and regulated by androgens in regions thought to be involved in the central regulation of reproduction. Androgens regulate aromatase pretranslationally and androgen receptor activation is correlated with the induction of aromatase activity. Aromatase and androgen receptor mRNAs display both unique and overlapping distributions within the hypothalamus and limbic system suggesting that androgens and androgen-derived estrogens regulate complimentary and interacting genes within many neural networks. Long-term castrated monkeys, like men, exhibit an estrogen-dependent neural deficit that could be an underlying cause of the insensitivity to testosterone that develops in states of chronic androgen deficiency. Future studies of in situ estrogen formation in brain in the primate model are important for understanding the importance of aromatase not only for reproduction, but also for neural functions such as memory and cognition that appear to be modulated by estrogens.


Neurosonographic and biochemical correlates of periventricular leukomalacia in low-birth-weight infants.
The incidence of periventricular leukomalacia (PVL) was investigated by ultrasound in a group of 119 consecutively scanned low-birth-weight infants during a period of 3 years. The overall incidence of PVL was 6.7% while the incidence of peri-intraventricular hemorrhage was 44.5%. Ultrasound evidence of posthemorrhagic lesions was seen early and related strongly to follow-up findings. Evidence of cystic degeneration appeared later. The presence of PVL was confirmed by computed tomography at 5 months of age and anticipated by serial measurements of creatine kinase brain isoenzyme performed in the first 60 h of life. A significant correlation was observed between neurosonographic findings of PVL and high cord blood values of enzymatic pattern (p less than 0.02). Both were correlated with poor neurodevelopmental outcome at 12 months corrected age.


Transcriptional activity of quinone methides derived from the tumor promoter butylated hydroxytoluene in HepG2 cells.
Butylated hydroxytoluene (BHT) is a pulmonary toxin and tumor promoter in mice presumably due to the formation of two quinone methides (QMs) that alkylate cellular nucleophiles. The activation of stress genes by these electrophilic metabolites was investigated with an assay system consisting of 14 recombinant cell lines derived from the human hepatoma line HepG2, each carrying a unique promoter or response element construct fused to the reporter gene for chloramphenicol acetyl transferase (CAT). The largest responses to QMs occurred in cells containing either the metallothionein IIA, glutathione S-transferase Ya, or 70 kDa heat shock protein promoter, or the xenobiotic response element. The other cell lines exhibited only small or no effects. These results are consistent with transcriptional activities reported for several other electrophiles known to undergo covalent interactions with proteins.


Asymptotic velocity of one dimensional diffusions with periodic drift.
We consider the asymptotic behavior of the solution of one dimensional stochastic differential equations and Langevin equations in periodic backgrounds with zero average. We prove that in several such models, there is generically a non-vanishing asymptotic velocity, despite of the fact that the average of the background is zero.


Light and electron microscopic immunocytochemical localization of parvalbumin in the dorsal lateral geniculate nucleus of the cat: evidence for coexistence with GABA.
The coexistence in individual neurons of parvalbumin and gamma-aminobutyric acid (GABA) was studied in the dorsal lateral geniculate nucleus (dLGN) of the cat using pre- and postembedding immunocytochemical methods. PV(+) cell bodies and processes were found in the perigeniculate nucleus (PGN) and throughout all laminae of the dLGN. PV(+) neurons were relatively small and had circular to fusiform shapes. Electron microscopy revealed PV(+) reaction product within the perikarya, axons, and dendrites of labeled cells. It was associated preferentially with microtubules, postsynaptic densities, and intracellular membranes. PV(+) presynaptic boutons were identified on the basis of their synaptic relations and ultrastructure as retinal terminals (RLP) and as profiles originating from inhibitory interneurons (F1 and F2). Immunopositive somata and dendrites received asymmetric synaptic contacts from labeled RLP and non-identified, non-immunoreactive synaptic boutons. Moreover, PV(+) dendrites were postsynaptic to labeled F profiles. In the PGN all neurons were both PV(+) and GABA-immunoreactive and in the dLGN the vast majority of PV(+) neurons showed GABA-immunoreactivity. It is suggested that the high incidence of PV in GABAergic neurons is related to the particular activation patterns of these neurons and the resulting demand for calcium buffer systems.


Contribution of nitrogen fixation to nitrogen nutrition in an alpine sedge community (Caricetum curvulae).
In situ acetylene reduction assays (ARA) were carried out over two growing seasons at 2550 m in the upper alpine zone of the Tyrolean Central Alps of Austria. For comparative purposes, some Fabaceae species introduced into the upper alpine zone from lower elevation (2000 m) were subjected to ARA. At the end of the growing season the potted plants were transferred to the laboratory where their acetylene reducing activities were measured again. In situ nitrogenase activity is very low. The highest values were found in association with Leucanthemopsis alpina and Veronica bellidioides (150 and 217 nmol ethylene 24 h-1 per pot respectively). Higher levels of activity were detected in pots transferred to the laboratory (maximum value 750 nmol ethylene 24 h-1 per pot; assay temperature about 12°C higher than in the field) and in the Fabaceae transferred to the upper alpine zone (14×103 nmol ethylene 24 h-1 per pot of Trifolium badium and T. pallescens). Maximum nitrogen input in the field is in the range of 8 mg m-2 a-1. Therefore, under natural circumstances biological nitrogen fixation contributes only very small amounts of nitrogen to this alpine vegetation system, the process being inhibited by low soil temperatures. Possible alternative sources and patterns of N acquisition are discussed in relation to the overall nitrogen economics of plants of the upper alpine zone.


Meaning in life among adolescents: Factorial invariance of the purpose in life test and buffering effect on the relationship between emotional dysregulation and hopelessness.
The purpose of the present study was threefold: first, to analyse the psychometric properties of a 10-item Spanish version of the Purpose in Life Test, which assesses meaning in life (MiL), in a sample of community adolescents; second, to analyse the differences between the age and gender groups; and third, to analyse whether MiL buffers the relationship between emotional dysregulation and hopelessness. Participants were 1,599 adolescents from 12 to 19 years old, M = 15.69, SD = 2.14. The Purpose in Life Test-10 Items, the Beck Hopelessness Scale, and the Difficulties in Emotional Regulation Scale were used. A nine-item version showed good fit, psychometric properties (internal consistency, construct, and concurrent validity), and factorial invariance across gender and age (12-15 years/16-19 years). Difference in MiL between boys and girls was not significant, whereas between age groups was significant. MiL had a strong buffering effect on the relationship between emotional dysregulation and hopelessness. It is desirable to promote the sense of MiL in adolescents. MiL plays a significant and strong mediator role in the relationship between emotional dysregulation and hopelessness, reinforcing the positive role of MiL in mental health and as a resource for facing adversity.


Chronic musculoskeletal pain and function improve with a plant-based diet.
Chronic musculoskeletal pain, often debilitating, affects all genders, ethnicities, and age groups. Research suggests consumption of a plant-based diet may improve the status of persons with chronic pain. A diet rich in fruits, vegetables and whole grains has been shown to reduce chronic pain and disability associated with musculoskeletal conditions. The purpose of this study was to examine the value of a plant-based diet in the management of chronic musculoskeletal pain and functional limitations. Fourteen subjects participated in the eight-week study. Baseline evaluation included anthropometric measurements and completion of two self-reported outcome measures: Numeric Pain Rating Scale (NPRS) and the Short Form Health Survey (SF-36). A registered dietitian nutritionist provided a sample menu cycle and education on a plant-based diet. Subjects utilized a phone app to log food intake and receive support from the dietitian. Post data collection included a repeat of the baseline measures and the Patient Global Impression of Change Scale. The sample was small. Twenty subjects began, 14 completed. No comparison group was used. Results should be considered with caution. The diet intervention resulted in decreased pain and improvement in quality of life. Diet adherence by ten of fourteen subjects was 89% based on completion of food intake records and adherence to allowed foods. Consumption of a plant-based diet produced positive improvements in chronic pain and function. Interprofessional collaboration between physical therapists and registered dietitian nutritionists, along with other healthcare practitioners, can encourage and promote diet interventions that positively affect chronic pain.


Best Practices for the Catheter Ablation of Ventricular Arrhythmias.
Techniques for catheter ablation have evolved to effectively treat a range of ventricular arrhythmias. Pre-operative electrocardiographic and cardiac imaging data are very useful in understanding the arrhythmogenic substrate and can guide mapping and ablation. In this review, we focus on best practices for catheter ablation, with emphasis on tailoring ablation strategies, based on the presence or absence of structural heart disease, underlying clinical status, and hemodynamic stability of the ventricular arrhythmia. We discuss steps to make ablation safe and prevent complications, and techniques to improve the efficacy of ablation, including optimal use of electroanatomical mapping algorithms, energy delivery, intracardiac echocardiography, and selective use of mechanical circulatory support.


Lack of influence of DAT1 and DRD2 gene variants on antidepressant response in generalized anxiety disorder.
Although antidepressant drugs are used as first-line intervention to treat patients with generalized anxiety disorder (GAD), only one-third of patients respond positively to treatment. In our study, we investigated whether functional genetic polymorphisms in the dopamine active transporter 1 (DAT1) and dopamine receptor D2 (DRD2) may play a role in antidepressant treatment response in GAD. We examined 156 patients diagnosed with GAD who received venlafaxine Extended-Release (XR) treatment as part of an 18-month relapse-prevention study to determine whether variation in these genes had an effect on treatment response after 6 months of open-label treatment. Genotypes were obtained for rs1076560 (DRD2), rs1800497 (DRD2), rs2550948 (DAT1), and a variable number tandem repeat in the 3' untranslated region of the DAT1 gene using standard methods. Results show that none of the tested variants were associated with treatment response to venlafaxine XR in GAD. Genotype and allele frequencies did not differ statistically significantly between responders and non-responders using either the Hamilton Anxiety or Clinical Global Impressions of Improvement Scale at 6 months. Although we detected no association in our sample, future studies using larger samples and more comprehensive gene coverage are needed to evaluate potential effects of dopaminergic variants on antidepressant treatment response in anxiety disorders.


The Value and Relevance of the T Cell Lymphoma Registries and International Collaborations: the Case of COMPLETE and the T-Cell Project.
Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of lymphoid malignancies that portend a poor prognosis and have an undefined optimal therapeutic strategy. Data on best practices stem from prior studies that have generally included B cell lymphomas. However, the enhanced ability to diagnose PTCLs, the development of newer agents specific for PTCLs, and its increased incidence have called the scientific community to develop better strategies to combat these neoplasms. To that end, T cell lymphoma registries were developed in an attempt to answer relevant questions on the prognosis and management of PTCLs. The largest registries currently enrolling patients are the Comprehesive Oncology Measures for PeripheraL T-cEll Lymphoma TrEatment (COMPLETE) and the T-Cell Project. Despite the inherent limitations of these studies, valuable information are being collected to refine our management approaches and to aid in designing future clinical trials. This review illustrates the value of these registries and describes the critical questions that need to be answered.


Artificially raised roost temperatures lead to larger body sizes in wild bats.
Climate warming has major consequences for animal populations, as ambient temperature profoundly influences all organisms' physiology, behavior, or both.1 Body size in many organisms has been found to change with increased ambient temperatures due to influences on metabolism and/or access to resources.2,3,4,5,6 Changes in body size, in turn, can affect the dynamics and persistence of populations.7 Notably, in some species, body size has increased over the last decades in response to warmer temperatures.3,8 This has primarily been attributed to higher food availability,3 but might also result from metabolic savings in warmer environments.9,10 Bechstein's bats (Myotis bechsteinii) grow to larger body sizes in warmer summers,11 which affects their demography as larger females reproduce earlier at the expense of a shorter life expectancy.12,13 However, it remains unclear whether larger body sizes in warmer summers were due to thermoregulatory benefits or due to increased food availability. To disentangle these effects, we artificially heated communal day roosts of wild maternity colonies over four reproductive seasons. We used generalized mixed models to analyze these experimental results along with 25 years of long-term data comprising a total of 741 juveniles. We found that individuals raised in heated roosts grew significantly larger than those raised in unheated conditions. This suggests that metabolic savings in warmer conditions lead to increased body size, potentially resulting in the decoupling of body growth from prey availability. Our study highlights a direct mechanism by which climate change may alter fitness-relevant traits, with potentially dire consequences for population persistence.


The effects of mesenchymal stromal cells and platelet-rich plasma treatments on cutaneous wound healing.
Cellular therapy and platelet-rich plasma (PRP) have been used as a treatment for skin wounds. Previous evidence has shown that mesenchymal stromal cells (MSC) may improve skin wound healing. In contrast, contradictory effects have been reported by using PRP treatment on skin wound healing. However, there is evidence that PRP constitutes an excellent scaffold for tissue engineering. In this work, we aim to study the effect of MSC on skin wound healing. We used an experimental murine model of full-thickness wounds. Wounds were treated with human bone marrow-MSC contained in a PRP clot. Untreated or PRP-treated wounds were used as controls. Wound healing was evaluated by macroscopic observation and histological analysis at day 7 post-wounding. Immunohistochemical studies were performed to detect the presence of epithelial progenitor cells (EPC) and the expression of basic fibroblast growth factor (bFGF). MSC/PRP implantation induced a significant wound closure and re-epithelialization as compared with the controls. Increase of CD34+ cells and bFGF was observed in the wounds treated with MSC/PRP. Our results show that MSC included in PRP clot induce cutaneous wound repair by promoting re-epithelialization, migration of EPC and expression of bFGF. PRP alone does not exert a significant effect on wound healing. Our results support the possible clinical use of MSC in PRP scaffold as potential treatment of skin wounds.


The value of perfusion CT in predicting the short-term response to synchronous radiochemotherapy for cervical squamous cancer.
To determine the value of the perfusion parameters in predicting short-term tumour response to synchronous radiochemotherapy for cervical squamous carcinoma. Ninety-three patients with cervical squamous carcinoma later than stage IIB were included in this study. Perfusion CT was performed for all these patients who subsequently received the same synchronous radiochemotherapy. The patients were divided into responders and non-responders according to short-term response to treatment. Baseline perfusion parameters of the two groups were compared. The perfusion parameters that might affect treatment effect were analysed by using a multivariate multi-regression analysis. The responders group had higher baseline permeability-surface area product (PS) and blood volume (BV) values than the non-responders group (P < 0.05). There was no statistical difference in baseline mean transit time (MTT) and blood flow (BF) value between the two groups (P >0.05). At multivariate multi-regression analysis, BV, PS and tumour size were significant factors in the prediction of treatment effect. Small tumours usually had high PS and BV values, and thus had a good treatment response. Perfusion CT can provide some helpful information for the prediction of the short-term effect. Synchronous radiochemotherapy may be more effective in cervical squamous carcinoma with higher baseline PS and BV. • Perfusion CT can reflect tumour vascular physiology in cervical squamous carcinoma. • Perfusion CT helps predict the short-term effect before treatment • Synchronous radiochemotherapy may be more effective in patients with higher baseline BV and PS.


Evolutionary Insight into the Clock-Associated PRR5 Transcriptional Network of Flowering Plants.
Circadian clocks regulate the daily timing of metabolic, physiological, and behavioral activities to adapt organisms to day-night cycles. In the model plant Arabidopsis thaliana, transcript-translational feedback loops (TTFL) constitute the circadian clock, which is conserved among flowering plants. Arabidopsis TTFL directly regulates key genes in the clock-output pathways, whereas the pathways for clock-output control in other plants is largely unknown. Here, we propose that the transcriptional networks of clock-associated pseudo-response regulators (PRRs) are conserved among flowering plants. Most PRR genes from Arabidopsis, poplar, and rice encode potential transcriptional repressors. The PRR5-target-like gene group includes genes that encode key transcription factors for flowering time regulation, cell elongation, and chloroplast gene expression. The 5'-upstream regions of PRR5-target-like genes from poplar and rice tend to contain G-box-like elements that are potentially recognized by PRRs in vivo as has been shown in Arabidopsis. Expression of PRR5-target-like genes from poplar and rice tends to decrease when PRRs are expressed, possibly suggesting that the transcriptional network of PRRs is evolutionarily conserved in these plants.


NADES assisted integrated biorefinery concept for pectin recovery from kinnow (Citrus reticulate) peel and strategic conversion of residual biomass to L(+) lactic acid.
The present study aims to establish an integrated strategy for valorization of kinnow peel waste. A total of ten natural deep eutectic solvents (NADESs) were exploited for extraction of pectin. The highest yield of pectin enriched material was reported 35.66 % w/dw using choline chloride-Maltose based NADES. The extraction process parameters and chemical composition of NADES influenced the yield and different associated physico-chemical attributes of the pectin enriched material. All the recovered pectin enriched materials found to be composed of low methoxy pectin (degree of methylation: 18.41-40.26 %) and galacturonic acid (GalA) content was in range of 67.56-78.22 %. The Principal Component Analysis (PCA) was used to categorise isolated pectin enriched materials based on similarities and differences. The liquid fraction upon pectin extraction presented a considerable amount of fermentable sugar which was further utilized for lactic acid production by microbial intervention. The microbial strain Lactobacillus amylophilus GV6 was exploited for lactic acid fermentation where the highest yield reached 55.59 g/L. A sustainable and straight-forward biorefinery concept was developed for extraction of pectin enriched material and lactic acid production from kinnow peel waste with potential application in food and biotechnological sectors.


Determination of 210Po in various foodstuffs and its annual effective dose to inhabitants of Qena City, Egypt.
The concentration of 210Po was determined in different foodstuffs of plant origin purchased from markets in Qena City, Upper Egypt. Measurement of 210Po has been carried out using alpha spectrometry technique in different food categories such as vegetables, fruits, cereals beverages and herbs. The general range of 210Po activity levels ranged widely from <0.010-18.6±0.910 mBq g(-1), with minimum being in cereal samples and maximum being in beverage samples. Tea samples recorded highest activity concentrations of 210Po with lowest value of 10±0.54 mBq g(-1) for Crown tea and highest value of 18.6±0.910 mBq g(-1) for El maabad tea. The daily intake of 210Po from food consumption reveals that vegetables are the biggest contributors, while beverages are the lowest. The effective ingestion dose has been estimated for Qena City residents and it was found in the range 0.008-38.3 μSv y(-1).


Vesicular stomatitis virus infection reduces the number of active DNA-dependent RNA polymerases in myeloma cells.
Infection of mouse myeloma (MPC-11) cells with vesicular stomatitis virus resulted in rapid loss in activity of cellular RNA polymerases associated with nuclear chromatin. No RNA polymerase inhibitor could be detected in extracts of infected cell nuclei. Reconstitution experiments with solubilized RNA polymerases dissociated from chromatin of infected and uninfected cells demonstrated that vesicular stomatitis viral infection did not affect the ability of the polymerases to function on endogenous or exogenous templates; nor did infection alter the template capability of the chromatin. Measurement of the number of actively growing RNA chains revealed that infected cell nuclei contained fewer active polymerase units; however, the rates of RNA chain elongation were the same in nuclei from infected and uninfected cells. Quantitation of the number of polymerase units active in nuclear chromatin revealed that the alpha-amantin-sensitive polymerase II was more severely reduced by viral infection than were polymerases I and III.


Ephedra in perspective--a current review.
Although the traditional use of Ephedra 'ma huang' has been established for thousands of years, its resurgence in the US as a herbal dietary supplement is currently a matter of national controversy. At the heart of the debate are three important questions: (1) the identity and composition of Ephedra products with regard to ephedrine and related alkaloids; (2) the potential therapeutic utility of Ephedra supplements for weight loss or performance enhancement; and (3) potential health risks associated with such uses of Ephedra, particularly in sensitive individuals or in cases of intentional abuse for its stimulant properties. This review surveys the literature on Ephedra with regard to traditional uses, botany, chemistry, analytics, pharmacological effects and health risks. A brief discussion of the central issues in the current debate on the regulation of Ephedra in the United States is included as this is where most of the problems have occurred to date.


Residential area greenness and hypertension: a national assessment on urban adults in Bangladesh.
This study investigated the associations between greenness and blood pressure (BP) metrics (systolic BP [SBP], diastolic BP [DBP], hypertension) among urban adults in Bangladesh and the potential mediation effects of body mass index (BMI) using 2011 Bangladesh Demographic and Health Survey data for 2360 urban adults (aged ≥35 years). The Enhanced Vegetation Index was used as a measure of residential area greenness. Associations between greenness and BP metrics were estimated using linear and binary logistic regression models. We also conducted mediation analyses. Greater area-level greenness was inversely associated with SBP (β -1.33, 95%CI: -2.46, -.20), DBP (β -.83, 95%CI: -1.64, -.02), and hypertension (adjusted odds ratio .87, 95%CI: .77, .98). BMI substantially mediated associations between greenness and BP metrics. Adopting urban greening policies could reduce the risk of hypertension, thus can contribute to reduction of non-communicable disease burden in Bangladesh. Longitudinal studies are required to further investigate the causal pathways.


Polymorphisms in the interleukin-4 receptor alpha chain gene influence susceptibility to HIV-1 infection and its progression to AIDS.
Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor alpha chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV+ long-term nonprogressors (LTNP), 36 HIV+ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus+), and 97 healthy controls (HC), all Caucasians and lacking CCR5Delta32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p = 0.005; relative risk ratio = 3.4, 95% confidence interval (CI) = 1.12-10.6, p = 0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV+ individuals (n = 64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p = 0.01; odds ratio (OR) = 2.14, 95% CI = 1.25-3.67, p = 0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR = 2.10, 95% CI = 1.03-4.21, p = 0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p = 0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.


Farnesyl anthranilate suppresses the growth, in vitro and in vivo, of murine B16 melanomas.
The numbers of isoprene residues and unsaturated bonds, cis/trans configuration, and head group polarity influence the tumor-suppressive potency of acyclic isoprenoid hydrocarbons and alcohols; within the series tested, trans, trans farnesol had the greatest potency. Geraniol esters had increased potency relative to that of the free alcohol. Farnesyl anthranilate induced a concentration-dependent decrease in the B16 melanoma cell population, in part due to an increased proportion of cells in the G1 phase of the cell cycle and in part by the increased the proportion of apoptotic cells. Farnesyl anthranilate (1.5 mmol/kg diet) significantly suppressed the growth of implanted B16 melanomas and lowered the plasma cholesterol levels of tumor-free mice.


Newcastle survey of deaths in early childhood 1974/76, with special reference to sudden unexpected deaths. Working party for early childhood deaths in Newcastle.
All early childhood deaths within a total population of 297 000 were studied by prospective methods. 70 deaths of children aged 1 week to 5 years occurred during a 27-month period; 36 died at home, 29 suddenly and unexpectedly. An extensive standardized necropsy showed a disease process clearly or probably related to death in half the sudden unexpected deaths; in the remainder no recognized disease process was identified. The events preceding sudden unexpected death, and the child's environment, were investigated by a controlled parental interview. Symptoms of serious illness within 24 hours of death were identified in 9 of the 29 children, but in the majority symptoms were thought to have been absent or no more severe than those of the control children. Most children with major symptoms had been seen by a doctor within a few days of death. The two most striking social findings were that 16 of the 29 sudden unexpected deaths occurred at a weekend or bank holiday, and that 45% occurred in three adjacent city wards which contain only 13% of the under-five study population. The additional support and explanation provided during the home visits was greatly appreciated by the bereaved families.


QSAR model and mechanism research on color removal efficiency of dying wastewater by FeCl3 coagulation.
Coagulation is the most widely used method in the treatment of printing and dying wastewater. To better understand the relationship between the coagulation effect and dye molecular structures, quantitative structure activity relationship (QSAR) analyses were performed to elucidate the factors affecting the coagulation in ferric chloride (FeCl3) coagulation process. First, the coagulation experiments on 38 dye molecules were conducted to determine their color removal rates (Rexp) by FeCl3 under different pH conditions (i.e., pH = 4 and 10). The results showed that the average Rexp of dyes were 41.36% ± 2.40% at pH value of 4 and 55.70% ± 2.83% at pH value of 10. Subsequently, a multiple linear regression (MLR) method was used to construct QSAR models based on Rexp and 42 molecular parameters calculated by Gaussian 09, Materials Studio 7.0 and Multiwfn. The developed QSAR models exhibited excellent stability, reliability, and robustness with values of R2 = 0.7950, 0.8170, Q2INT = 0.6401, 0.7382, Q2EXT = 0.5168, 0.5441, at pH values of 4 and 10, respectively. Through analysis of quantum parameter values, electrostatic adsorption and hydrogen bonding adsorption were primarily responsible for the coagulation process. Therefore, this study could be useful in providing critical information for evaluating the removal efficiency and a feasible way to predict the removal rate of dyes by FeCl3 when no coagulation experiments were conducted.


Sarcoma of the abdominal aorta involving marginal arteries of the small intestine: a case report.
Primary sarcoma of the aorta is extremely rare. In the past, the disease was commonly diagnosed on autopsy. However, now it is possible to make a diagnosis preoperatively using various imaging studies such as computed tomographic scanning and magnetic resonance imaging. The authors have experienced one case of abdominal aortic sarcoma in a patient who complained of the symptoms of typical intestinal angina. We diagnosed an aortic sarcoma preoperatively but failed to resect the tumor on thoracolaparotomy because of the tumor extension to marginal arteries of the whole small intestine. We recommend preoperative laparoscopy for evaluation of tumor extension to marginal arteries of the small intestine in a patient having aortic sarcoma and intestinal angina if the patient is considered to be a surgical candidate.


IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate.
Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.


The geometries of interacting arginine-carboxyls in proteins.
The geometries are reported for interacting arginine-carboxyl pairs obtained from 37 high resolution protein structures solved to a resolution of 2.0 A or better. The closest interatomic distance between the guanidinium and carboxyl is less than 4.2 A for 74 arginine and carboxyl groups, with the majority of these lying within hydrogen-bonding distance (2.6-3.0 A). Interacting pairs have been transformed into a common orientation, and arginine-carboxyl, and carboxyl-arginine geometries have been calculated. This has been defined in terms of the spherical polar angles T theta, T phi, and the angle P, between the guanidinium and carboxyl planes. Results show a clear preference for the guanidinium and carboxyl groups to be approximately coplanar, and for the carboxyl oxygens to hydrogen bond with the guanidinium nitrogens. Single nitrogen-single oxygen is the most common type of interaction, however twin nitrogen-twin oxygen interactions also occur frequently. The majority of these occur between the carboxyl oxygens and the NH1 and NE atoms of the arginine, and are only rarely observed for NH1 and NH2. The information presented may be of use in the modelling of arginine-carboxyl interactions within proteins.


Modified GLIM Status as a Predictor of Morbidity and Mortality After Radical Cystectomy: A Propensity Matched Analysis.
To assess the modified Global Leadership Initiative on Malnutrition (mGLIM) status as a predictor of postoperative mortality and morbidity in patients undergoing Radical Cystectomy (RC). The American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) dataset was used to select patients who underwent RC between the years 2011 to 2020. A positive mGLIM status includes patients with preoperative albumin levels < 3.5 g/L or patients with ≥ 10% weight loss over 6 months or BMI ≤ 21 kg/m2. We compared prolonged length of stay, mortality, major morbidity and Clavien-Dindo complications between mGLIM positive and negative patients. A multivariable logistic regression model was also performed to control for possible confounders. Furthermore, a sensitivity analysis was performed by propensity score matching. Our cohort consisted of 12,760 patients who underwent RC. The matched cohort yielded 4864 matched patients. After propensity score matching, patients with a positive mGLIM status had higher odds of prolonged length of stay (OR = 1.99, 95%CI [1.75, 2.27]), mortality (OR 1.56, 95%CI [1.08, 2.26]), major morbidity (OR = 1.69, 95%CI [1.51, 1.90]), Clavien-Dindo class I and II (OR = 1.77, 95%CI [1.58, 1.99]), and lower odds of Clavien-Dindo class III (OR = 0.72, 95%CI [0.57, 0.92]) as compared to those with a negative mGLIM status (P < .018). A positive mGLIM status is associated with prolonged hospital stay, morbidity, and mortality following RC. This indicates that the mGLIM criteria could serve as an independent predictor of morbidity and mortality in an attempt to optimize patient counseling and preoperative care.


Low-frequency otoacoustic emissions in schoolchildren measured by two commercial devices.
Click evoked otoacoustic emissions in children are known to be good indicators of hearing function when used in the frequency range 1.5-4 kHz. Using two commercial devices, the present study investigates the usefulness of responses in the lower frequency range of 0.5-1 kHz evoked by 0.5 kHz tone bursts. Otoacoustic emissions (OAEs) were recorded from the ears of 37 schoolchildren (age 12-13 years). OAE measurements were then made using two devices: the ILO 292 (Otodynamics) and the HearId (Mimosa Acoustics). Each device was used for two measurements: first with a standard click stimulus at 80 dB pSPL (CEOAEs) and a second using a 0.5 kHz tone burst at 80 dB pSPL (TBOAEs). Pure tone audiometry and tympanometry were also conducted. Half-octave-band values of OAE signal to noise ratios (SNRs) and response levels were used to assess statistical differences. Both devices provided similar SNR results for click and tone burst stimuli, although the ILO device generated slightly higher response levels for clicks. For the 0.5 kHz tone bursts, both devices evoked very weak responses at 0.5 kHz and the peak response occurred at 0.7-1 kHz. Generally, CEOAE SNRs were about 10 dB in the 1-4 kHz range, while SNRs for 0.5 kHz TBOAEs were about 10 dB at 0.7-1 kHz. 0.5 kHz TBOAEs could be measured in children as effectively as CEOAEs. They can provide additional information about the 0.7-1 kHz frequency range, a range over which CEOAEs do not usually contain responses above the noise floor. The main difficulty was that the maxima of the 0.5 kHz TBOAEs occurred at frequencies of 0.7-1 kHz, probably because of spectral splatter from the short tone burst stimulus and from rapidly falling responses of the cochlea and the recording system at low frequencies.


Identification of an Archaeal type II isopentenyl diphosphate isomerase in methanothermobacter thermautotrophicus.
Isopentenyl diphosphate (IPP):dimethylallyl diphosphate isomerase catalyzes the interconversion of the fundamental five-carbon homoallylic and allylic diphosphate building blocks required for biosynthesis of isoprenoid compounds. Two different isomerases have been reported. The type I enzyme, first characterized in the late 1950s, is widely distributed in eukaryota and eubacteria. The type II enzyme was recently discovered in Streptomyces sp. strain CL190. Open reading frame 48 (ORF48) in the archaeon Methanothermobacter thermautotrophicus encodes a putative type II IPP isomerase. A plasmid-encoded copy of the ORF complemented IPP isomerase activity in vivo in Salmonella enterica serovar Typhimurium strain RMC29, which contains chromosomal knockouts in the genes for type I IPP isomerase (idi) and 1-deoxy-D-xylulose 5-phosphate (dxs). The dxs gene was interrupted with a synthetic operon containing the Saccharomyces cerevisiae genes erg8, erg12, and erg19 allowing for the conversion of mevalonic acid to IPP by the mevalonate pathway. His6-tagged M. thermautotrophicus type II IPP isomerase was produced in Escherichia coli and purified by Ni2+ chromatography. The purified protein was characterized by matrix-assisted laser desorption ionization mass spectrometry. The enzyme has optimal activity at 70 degrees C and pH 6.5. NADPH, flavin mononucleotide, and Mg2+ are required cofactors. The steady-state kinetic constants for the archaeal type II IPP isomerase from M. thermautotrophicus are as follows: K(m), 64 microM; specific activity, 0.476 micromol mg(-1) min(-1); and k(cat), 1.6 s(-1).


Lung injury following thoracic aortic occlusion: comparison of sevoflurane and propofol anaesthesia.
Halogenated anaesthetics have been shown to reduce ischaemia-reperfusion injuries in various organs due to pre- and post-conditioning mechanisms. We compared volatile and total intravenous anaesthesia with regard to their effect on remote pulmonary injury after thoracic aortic occlusion and reperfusion. Eighteen pigs were randomized after sternotomy and laparotomy (fentanyl-midazolam anaesthesia) to receive either sevoflurane or propofol in an investigator-blinded fashion. Ninety minutes of thoracic aortic occlusion was induced by a balloon catheter. During reperfusion, a goal-directed resuscitation protocol was performed. After 120 min of reperfusion, the anaesthetic regimen was changed to fentanyl-midazolam again for another 180 min. The oxygenation index and intra-pulmonary shunt fractions were calculated. After 5 h of reperfusion, a bronchoalveolar lavage was performed. The total protein content and lactate dehydrogenase activity were measured in epithelial lining fluid (ELF). Alveolar macrophage oxidative burst was analysed. The wet to dry ratio was calculated and tissue injury was graded using a semi-quantitative score. Ten animals (n=5 for each anaesthetic) without aortic occlusion served as time controls. The oxygenation index decreased and the intra-pulmonary shunt fraction increased significantly in both occlusion groups. There were no significant differences between sevoflurane and propofol with respect to the oxygenation index, ELF composition, morphologic lung damage, wet to dry ratio and alveolar macrophage burst activity. Differences were, however, seen in terms of systemic haemodynamic stability, where catecholamine requirements were less pronounced with sevoflurane. We conclude that the severity of remote lung injury was not different between sevoflurane and propofol anaesthesia in this porcine model of severe lower-body ischaemia and reperfusion injury.


Leadership training in UAFs supported by the Division of Maternal and Child Health.
University Affiliated Facilities (UAFs) were established to promote improved care for mentally retarded and handicapped children and their families. Specifically, they are charged with the interdisciplinary training of professionals who provide leadership within their respective disciplines and, thus, impact a greater service delivery system. A definition of leadership training and two potential models for implementation within the UAF system are developed. Data available for FY 1983-1984 indicate the UAFs funded by the Division of Maternal and Child Health (DMCH) trained 3,450 graduate or post-graduate students. Preliminary estimates indicate that approximately 25% of long-term UAF trainees eventually fill positions of leadership within the service delivery system. More systematic assessment of the impact of UAF training is suggested.


Purification and separation of two soluble fucosyltransferase activities of small intestinal mucosa.
1. Rat small intestinal soluble fucosyltransferase is purified more than 2000-fold using chromatographic procedures with DEAE-cellulose, CM-cellulose, GDP-Sepharose and Concanavalin A-Sepharose. 2. Chromatography on Sephadex G15 of the final enzymatic fraction clearly separates two activities: a first peak incorporates fucose on asialoserotransferrin and a second peak on asialofetuin. 3. The use of small saccharidic acceptors (phenylgalactose, lactose, lacto-N-fucopentaose I) and the analysis of fucosylated asialoglycoproteins indicate that the first activity corresponds to an alpha-(3/4)-fucosyltransferase and the second one to an alpha-(1-2)-fucosyltransferase. 4. Protein analysis by polyacrylamide gel electrophoresis in the presence of SDS for each enzyme shows two bands corresponding to a mol. wt of about 65,000 and 70,000. The two enzymes have the same sensitivity to the action of N-ethylmaleimide.


Characterization of IgA response among women with incident HPV 16 infection.
Previous studies have characterized the prevalence and duration of serum IgG antibodies to human papillomavirus type 16 (HPV 16) in a well-studied cohort of college women, using viruslike particle- (VLP) based ELISAs. In this study IgA antibodies in cervical secretions and sera were examined using a newly developed capsomer-based ELISA and the patterns observed for serum IgG, serum IgA, and cervical IgA antibodies were compared. The median time to antibody detection from the first detection of HPV 16 DNA was 10.5 months for IgA in cervical secretions and 19.1 months for serum IgA. Serum IgA antibody conversion was observed less frequently and occurred later than IgA conversion in cervical secretions (P = 0.011) or serum IgG conversion (P = 0.051). The median time to antibody reversion, following seroconversion, was 12.0 months for IgA in cervical secretions and 13.6 months for serum IgA, whereas approximately 20% of women with serum IgG antibodies reverted within 36 months. Thus, the duration of IgA in cervical secretions and sera was shorter than the duration of serum IgG (P = 0.007 and 0.001).


Energy expenditure in anorexia nervosa: can fat-free mass as measured by bioelectrical impedance predict energy expenditure in hospitalized patients?
Anorexia nervosa (AN) is associated with a reduced metabolically active fat-free mass (FFM) and basal metabolic rate (BMR). Excessive refeeding results in major fat deposition which is not well tolerated by patients. Prediction of BMR is, therefore, a clinical issue during refeeding, but measurement by indirect calorimetry is time-consuming and not widely available. The study aim was to determine if and when BMR could be estimated from prediction formulas based on FFM derived from bioelectrical impedance analysis (BIA) in AN patients during refeeding. Indirect calorimetry and BIA were prospectively measured bi-weekly in 9 AN patients (body mass index 13.7 +/- 0.5 kg/m2) for 10 weeks of refeeding. Initial BMR was 969 +/- 46.7 kcal/d and 27.7 +/- 1.4 kcal/kg FFM, and at week 10 increased to 1360 +/- 44.6 kcal/d and 35.8 +/- 0.8 kcal/kg FFM. While correlations improved with increasing weight, FFM and body mass index, prediction formulas are insufficient to permit prediction of BMR based on weight or FFM, even after 10 weeks of refeeding. To allow for optimal nutritional support, indirect calorimetry measurements may be useful in the early weeks of refeeding because of a large variability of basal metabolic rate between patients.


Certification of methylmercury in cod fish tissue certified reference material by species-specific isotope dilution mass spectrometric analysis.
A new cod fish tissue certified reference material, NMIJ CRM 7402-a, for methylmercury analysis was certified by the National Metrological Institute of Japan in the National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). Cod fish was collected from the sea close to Japan. The cod muscle was powdered by freeze-pulverization and was placed into 600 glass bottles (10 g each), which were sterilized with gamma-ray irradiation. The certification was carried out using species-specific isotope dilution gas chromatography inductively coupled plasma mass spectrometry (SSID-GC-ICPMS), where (202)Hg-enriched methylmercury (MeHg) was used as the spike compound. In order to avoid any possible analytical biases caused by nonquantitative extraction, degradation and/or formation of MeHg in sample preparations, two different extraction methods (KOH/methanol and HCl/methanol extractions) were performed, and one of these extraction methods utilized two different derivatization methods (ethylation and phenylation). A double ID method was adopted to minimize the uncertainty arising from the analyses. In order to ensure not only the reliability of the analytical results but also traceability to SI units, the standard solution of MeHg used for the reverse-ID was prepared from high-purity MeHg chloride and was carefully assayed as follows: the total mercury was determined by ID-ICPMS following aqua regia digestion, and the ratio of Hg as MeHg to the total Hg content was estimated by GC-ICPMS. The certified value given for MeHg is 0.58 +/- 0.02 mg kg(-1) as Hg.


[Comparison of the effectiveness of bupivacaine with xylocaine and xylocaine alone used for akinesia and retrobulbar anesthesia in cataract surgery].
The paper presents a comparison of the efficacy of Bupivacaine with Xylocaine and Xylocaine alone used for retrobulbar injection and akinesia in cataract surgery. Two groups comprising 50 patients each were subjected to evaluation. The results obtained encourage to put into practice the mixture of Bupivacaine with Xylocaine for local anaesthesia in cataract operations.


Planning of suicide attempts among depressed inpatients ages 50 and over.
Suicidal behavior is heterogeneous; suicide attempts can be impulsive (lower planned) or reflect forethought and preparation (higher planned). Lower planned and higher planned attempts may have different correlates that require different prevention strategies. Based on a model of suicide planning relevant to middle-aged and older adults, we tested the following hypotheses: physical illness burden, decreased functional capacity, hopelessness, and living alone are associated with suicide attempts that are more extensively planned; lower cognitive functioning is associated with suicide attempts that are more impulsive. Subjects were 117 inpatients ages 50 and over diagnosed with major depression based on semi-structured clinical research interviews, the medical record, plus other records when available. All subjects had attempted suicide within 1 month of admission. The degree of planning prior to the suicide attempt was quantified using Beck's Suicide Intent Scale. Multivariate linear regression analysis identified correlates of planning. As hypothesized, lower cognitive functioning was associated with lower levels of planning. Contrary to the hypothesis, impaired physical self-care was associated with lower (not higher) planning. Results pertaining to living alone were equivocal. The study was limited by the cross-sectional research design and unclear generalizability to completed suicide or to racial/ethnic minorities. Depressed patients with lower cognitive functioning and impairments in physical self-care may be especially vulnerable to impulsive suicidal behavior. The potential role of living alone in higher planned suicidal acts requires further investigation.


The Role of β-Carboline Alkaloids in the Pathogenesis of Essential Tremor.
Essential tremor (ET) is one of the most prevalent neurological disorders in the world. Environmental factors have been implicated in the pathogenesis of ET. In particular, epidemiological studies have suggested that neurotoxic agents, especially β-carboline alkaloids (βCAs), might be generated through Maillard-type reaction. βCAs are molecules which are members of a large group of heterocyclic amines (HCAs, the so-called products of cooking meat). βCAs are highly tremorogenic in animals, producing a marked generalized action tremor soon after systemic administration in a wide range of laboratory animals such as mice, rats and monkeys. Administration of βCAs remains currently the main experimental model of ET. We review the pathogenesis of ET, with a focus on the biochemistry of βCAs, their occurrence and biological activity, their endogenous biosynthesis, their formation in food, their toxicokinetics and their neurotoxicity. We highlight open questions regarding the effects of βCAs in humans.


Schwann cell derived-peroxiredoxin protects motor neurons against hydrogen peroxide-induced cell death in mouse motor neuron cell line NSC-34.
Schwann cells and oligodendrocytes secrete proteins that promote neuron survival, but their role in amyotrophic lateral sclerosis (ALS) is unclear. To address this question, we evaluated the effect of molecules secreted by Schwann cells on reactive oxygen species (ROS)-induced motor neuronal cell death. We observed that in motor neuron cell line NSC-34 cultures, the conditioned medium (CM) from Schwann cell line YST-1 (YST-1 CM) cultures had a protective effect against hydrogen peroxide-induced cell death. However, this protective effect of YST-1 CM was abolished by removing peroxiredoxin 1-4 (PRDX1-4) from the CM. We found that the expression of PRDX1 mRNA was markedly downregulated in the lumbar spinal cord of the superoxide dismutase 1 (SOD1)G93A mouse model of ALS. We also found that transient transfection of YST-1 cells with G93A SOD1 resulted in reduced PRDX1 mRNA expression. Additionally, in the mutant transfected cells, YST-1 CM showed decreased neuroprotective effect against hydrogen peroxide-induced NSC-34 cell death compared to those transfected with WT SOD1. Our results suggest that Schwann cells protect motor neurons from oxidative stress by secreting PRDX1 and that the reduction of PRDX secreted from Schwann cells contributes to increased ROS and associated motor neuronal death in ALS.


IRF-3 releases its inhibitions.
Interferon regulatory factor (IRF) 3 plays a critical role in triggering the activation of interferon antiviral genes. The structure of IRF-3 in association with the CBP/p300 coactivator by in this issue of Structure illuminates the mechanism of IRF activation and the structural flexibilities inherent in CBP/p300.


Assessment of Interobserver Reliability of Nephrologist Examination of Urine Sediment.
Urine sediment microscopy is commonly performed during the evaluation of kidney disease. Interobserver reliability of nephrologists' urine sediment examination has not been well studied. Assess interobserver reliability of the urine sediment examination. In this diagnostic test study, urine samples were prospectively collected from a convenience sample of adult patients from an academic hospital in the United States undergoing kidney biopsy from July 11, 2018, to March 20, 2019. Digital images and videos of urine sediment findings were captured using a bright-field microscope. These images and videos along with urine dipstick results were incorporated in online surveys and sent to expert nephrologists at 15 US teaching hospitals. They were asked to identify individual sediment findings and the most likely underlying disease process. Urine dipstick results and urine sediment images from patients undergoing native kidney biopsy. Interobserver reliability of urine sediment microscopy findings estimated by overall percent agreement and Fleiss κ coefficients. Secondary outcomes included concordance of diagnoses suspected by nephrologists with corresponding kidney biopsy results. In total, 10 surveys from 10 patients containing 76 study questions on individual features were sent to 21 nephrologists, 14 (67%) of whom completed them all. Their combined 1064 responses were analyzed. Overall percent agreement for casts was an estimated 59% (95% CI, 50%-69%), κ = 0.52 (95% CI, 0.42-0.62). For other sediment findings, overall percent agreement was an estimated 69% (95% CI, 61%-77%), κ = 0.65 (95% CI, 0.56-0.73). The κ estimates ranged from 0.13 (95% CI, 0.10-0.17) for mixed cellular casts to 0.90 (95% CI, 0.87-0.94) for squamous epithelial cells. In this study, substantial variability occurred in the interpretation of urine sediment findings, even among expert nephrologists. Educational or technological innovations may help improve the urine sediment as a diagnostic tool.


Tissue adhesives and applications in plastic and reconstructive surgery.
The search for the perfect surgical "glue" is ongoing. Throughout the centuries, surgeons and scientists have sought an ideal sealant and adhesive: one that is safe, biologically compatible, effective, and affordable. A tissue sealant with these attributes would have unlimited applications in the field of plastic and reconstructive surgery. Simple wound closure, sealing of cavities, attachment of graft and flaps, and decreasing of bleeding, bruising, and edema are problems that all aesthetic and reconstructive surgeons face every day in their practice.


Association of STAT4 and PTPN22 polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children.
To investigate the impact of signal transducer and activator of transcription 4 (STAT4) and the protein tyrosine phosphatase N22 (PTPN22) gene single nucleotide polymorphisms (SNPs), gene-gene interactions and haplotype on type-1 Autoimmune Hepatitis (AIH) risk. Logistic regression analysis showed that type 1 AIH was significantly higher in carriers of T allele of rs7574865 than those with GG genotype (P- value less than 0.001), higher in carriers of C allele of rs7582694 than those with GG genotype (P- value < 0.001), and lower in carriers of T allele of rs2476601 than those with CC genotype (P- value < 0.001). GMDR model indicated a significant two-locus model (p = 0.0100) involving rs7582694 and rs2476601. Participants with GC or CC of rs7582694 and CC of rs2476601 genotype have the highest type 1 AIH risk (P- value < 0.001), after covariates adjustment. Haplotype containing the rs7582694-C and rs7574865-T alleles were associated with a statistically increased type 1 AIH risk (P < 0.001). Logistic regression was performed to investigate association between SNPs within STAT4 and PTPN22 gene and susceptibility to type 1 AIH. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combinations among the 4 SNPs. We conclude that rs7574865 and rs7582694 in STAT4 gene minor alleles, interaction between rs7582694 and rs2476601, and haplotype containing the rs7582694-C and rs7574865-T alleles are associated with increased type 1 AIH risk, but rs2476601 in PTPN22 gene minor allele is associated with decreased type 1 AIH risk.


Antipyretic effect of central arginine8-vasopressin treatment: V1 receptors specifically involved?
Intracerebroventricular (i.c.v.) administration of the neurohypophyseal neuropeptide arginine8-vasopressin (AVP) results in a dose-dependent attenuation of endotoxin-induced fever (EIF) in rats. Specific antagonists of the neuropeptided(CH2)5[Tyr(Me)2]AVP for V1 receptors, d(CH2)5[dlle2lle4]AVP for the V2 receptors and Des-Gly,NH2d(CH2)5[Tyr)Me2)Thr4Orn8]vasotocin, an antagonist of the oxytocin receptors (AOXT), failed to modify EIF when administered i.c.v. Relatively high doses (100 ng) of all three peptide antagonists effectively blocked the antipyretic effect of AVP. Administered in smaller doses (10 or 30 ng), however, a more specific interaction was observed, i.e. the V1 antagonist being the only effective compound in preventing the effect of AVP. Although the data indicate that peptide-antagonist interactions should be interpreted carefully, the present experiments confirm previous observations on the involvement of V1-type receptors in the antipyretic action of AVP and suggest additional interactions with V2 vasopressinergic and oxytocinergic receptors.


A comparison of the surfactant associated lipids derived from reptilian and mammalian lungs.
The lungs of the central netted dragon Ctenophorus nuchalis are bag-like, with most of the gas exchange region located in the anterior third. Although the faveoli are much larger than the mammalian alveoli, the lizard at 37 degrees C has approximately 70 times more surfactant phospholipid per unit area of respiratory surface than does a similar sized mammal. However, when expressed as per wet lung weight, lizards and rats possessed similar amounts of phospholipids. Dipalmitoylphosphatidylcholine was the principal phospholipid in both species. However, major differences existed in the phospholipid, neutral lipid and fatty acid profiles. Whereas the lizard contained neither phosphatidylglycerol nor phosphatidylethanolamine it had more cholesterol, esterified cholesterol, acylglycerides and unsaturated fatty acids. Although the ratio of saturated:unsaturated fatty acids was similar in rats and lizards, palmitic acid predominated in the former. The composition of lizard surfactant suggests that it would adsorb rapidly at reduced body temperature.


Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.
A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.


Bio-Ethics and One Health: A Case Study Approach to Building Reflexive Governance.
Surveillance programs supporting the management of One Health issues such as antibiotic resistance are complex systems in themselves. Designing ethical surveillance systems is thus a complex task (retroactive and iterative), yet one that is also complicated to implement and evaluate (e.g., sharing, collaboration, and governance). The governance of health surveillance requires attention to ethical concerns about data and knowledge (e.g., performance, trust, accountability, and transparency) and empowerment ethics, also referred to as a form of responsible self-governance. Ethics in reflexive governance operates as a systematic critical-thinking procedure that aims to define its value: What are the "right" criteria to justify how to govern "good" actions for a "better" future? The objective is to lay the foundations for a methodological framework in empirical bioethics, the rudiments of which have been applied to a case study to building reflexive governance in One Health. This ongoing critical thinking process involves "mapping, framing, and shaping" the dynamics of interests and perspectives that could jeopardize a "better" future. This paper proposes to hybridize methods to combine insights from collective deliberation and expert evaluation through a reflexive governance functioning as a community-based action-ethics methodology. The intention is to empower individuals and associations in a dialogue with society, which operation is carried out using a case study approach on data sharing systems. We based our reasoning on a feasibility study conducted in Québec, Canada (2018-2021), envisioning an antibiotic use surveillance program in animal health for 2023. Using the adaptive cycle and governance techniques and perspectives, we synthesize an alternative governance model rooted in the value of empowerment. The framework, depicted as a new "research and design (R&D)" practice, is linking operation and innovation by bridging the gap between Reflexive, Evaluative, and Deliberative reasonings and by intellectualizing the management of democratizing critical thinking locally (collective ethics) by recognizing its context (social ethics). Drawing on the literature in One Health and sustainable development studies, this article describes how a communitarian and pragmatic approach can broaden the vision of feasibility studies to ease collaboration through public-private-academic partnerships. The result is a process that "reassembles" the One Health paradigm under the perspective of global bioethics to create bridges between the person and the ecosystem through pragmatic ethics.


The influence of minimally invasive esophagectomy versus open esophagectomy on postoperative pulmonary function in esophageal cancer patients: a meta-analysis.
To compare the influence of minimally invasive esophagectomy (MIE) and open esophagectomy (OE) on postoperative pulmonary function in patients with esophageal cancer. Studies about the influence of MIE and OE on postoperative pulmonary function in esophageal cancer patients were searched from PubMed, EMBASE, the Cochrane Library, CNKI, Chinese Science and Technology Journal Database, CBM, and Wanfang Data from inception to March 18, 2021. Meta-analysis was performed using the RevMan 5.3. This analysis included eight studies, enrolling 264 patients who underwent MIE and 257 patients who underwent OE. The meta-analysis results showed that the MIE group had a higher outcome regarding the percent predicted vital capacity (%VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum voluntary ventilation (MVV) 1 month after surgery than the OE group. In addition, those who underwent MIE had lower ΔVC%, ΔFVC, and ΔFEV1 between pre-operation and 1 month after surgery than those who underwent OE. There is no statistical difference between the two groups in ΔMVV. Compared with OE, MIE has a more protective effect on postoperative pulmonary function. However, due to the small number of included literature and all cohort studies, this finding needs to be validated with larger samples and higher quality RCT studies.


Solution structure of tertiapin determined using nuclear magnetic resonance and distance geometry.
The solution structure of tertiapin, a 21-residue bee venom peptide, has been characterized by circular dichroism (CD), two-dimensional nuclear magnetic resonance (NMR) spectroscopy, and distance geometry. A total of 21 lowest error structures were obtained from distance geometry calculations. Superimposition of these structures shows that the backbone of tertiapin is very well defined. One type-I reverse turn from residue 4 to 7 and an alpha-helix from residue 12 to 19 exist in the structure of tertiapin. The alpha-helical region is best defined from both conformational analysis and structural superimposition. The overall three-dimensional structure of tertiapin is highly compact resulting from side chain interactions. The structural information obtained from CD and NMR are compared for both tertiapin and apamin (ref. 3), another bee venom peptide. Tertiapin and apamin have some similar secondary structure, but display different tertiary structures.


Inhibition of muscular glucose uptake by lipid infusion in man.
During a high-dose intravenous infusion of a mixed MCT/LCT-lipid emulsion and a conventional LCT-emulsion respectively, muscle substrate metabolism was investigated using the human forearm technique. With both lipid emulsions, a decrease in fractional muscular glucose extraction was seen, leading to significantly reduced muscular glucose uptake rates. An inverse linear relation between arterial tree fatty acids supply and fractional glucose extraction was seen suggesting that a mechanism according to Randle's glucose fatty acid concept is operating in skeletal muscle in man.


Familial lecithin:cholesterol acyltransferase deficiency. Further studies on plasma lipoproteins and plasma postheparin lipase activity of a patient with normal renal function.
Plasma lipoproteins and postheparin plasma were investigated in a patient with familial LCAT deficiency with normal renal function and without proteinuria. As revealed by gelfiltration the large molecular weight LDL2 was not present, and myelin structures were not found in LDL1 or LDL2 when she was on her ordinary diet. After 60--65% fat diet for one week the large molecular LDL2 was found, but only in low concentration. We have no explanation for the difference in the lipoprotein abnormalities of this patient and others with this disease. There is no major difference in the fat content in the ordinary diet of the Norwegian patients with familial LCAT deficiency, nor has our patient any clinical signs of malabsorption. Furthermore, there was no difference in lipoprotein lipase or hepatic lipase activity in postheparin plasma between our patient and others with the same disease. However, whereas hepatic lipase activity was within the reference values, lipoprotein lipase activity was rather low in all patients investigated. We suggest that impaired VLDL catabolism in plasma, because of LCAT deficiency and low lipoprotein lipase activity, may partly explain the low HDL concentration consistently found in patients with familial LCAT deficiency.


Diagnosis and treatment of kidney disease.
Lupus nephritis remains a strong predictor for death and the development of end-stage renal disease (ESRD) in patients with SLE. Definition of renal involvement varies but overt renal disease is found in at least one-third of SLE patients, with up to 60% of adults and 80% of children developing lupus nephritis. Clinical presentation has been found to bear little relationship to renal biopsy findings. Renal biopsy is therefore informative for all patients with SLE with abnormal urinalysis or reduced renal function, even with serum creatinine in the normal range, to guide treatment decisions. Current treatment regimens combine corticosteroids with cyclophosphamide, azathioprine or ciclosporin, although mycophenolate mofetil has received much recent attention as a potentially superior immune suppressive. The toxicity of current drug regimens contributes significantly to existing morbidity and mortality. A new era of biological therapies holds the potential for safer, more effective therapies in the future.


Serum Calcium Predicts Cognitive Decline and Clinical Progression of Alzheimer's Disease.
Relationship between serum calcium and Alzheimer's disease (AD) remains unclear. The aim of this study is to test whether serum calcium is associated with other AD-associated biomarkers and could predict clinical progression in nondemented elders. This was a longitudinal population-based study. The sample was derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, which included 1224 nondemented elders: 413 cognitively normal (CN) and 811 mild cognition impairment (MCI). Associations were investigated between serum calcium and longitudinal changes in Aβ/tau pathologic features, brain structure, cognitive function, and disease progression. Serum calcium concentrations increased with disease severity. Serum calcium predicted longitudinal cognitive decline and conversion from nondemented status to AD dementia (adjusted HR = 1.41, 95% CI 1.13-1.76). Furthermore, serum calcium levels were negatively correlated with CSF-Aβ42 (β = - 0.558, P = 0.008), FDG-PET (β = - 0.292, P < 0.001), whole brain volume (β = - 0.148, P = 0.001), and middle temporal volume (β = - 0.216, P = 0.042). Similar results were obtained in CN and MCI groups. Higher serum calcium status (even if not hypercalcemia) may increase the risk of AD in elders. Serum calcium is a useful biomarker in predicting clinical progression in nondemented elders. More researches are needed in the future to explore the underlying mechanism.


Glucocorticoid induction of pulmonary maturation in the rabbit fetus. The effect of maternal injection of betamethasone on the activity of enzymes in fetal lung.
1. Maternal administration of betamethasone (0.2 mg/kg) on day 25 or 26 of gestation produced a significant decrease in the lung/body weight ratio of the rabbit fetuses within 24 h. 2. The incorporation of [14C]choline but not [14C]ethanolamine into the lipids of fetal lung slices was significantly increased, indicating that there was a specific effect on phosphatidylcholine synthesis. 3. The activities of a number of marker enzymes for subcellular organelles were elevated, especially in the lungs of fetuses delivered on day 26. The increases in monoamine oxidase (mitochondrial outer membrane), beta-glycerophosphatase and aqueously dispersed phosphatidic acid-dependent phosphatidic acid phosphohydrolase (lysosomal) activities were significant. 4. Although the activity of cholinephosphotransferase was not affected by glucocorticoid treatment, the activities of glycerol-3-phosphate phosphatidyltransferase and the activities of two enzymes in the auxiliary pathways for the production of disaturated phosphatidylcholine (lysophosphatidylcholine:lysophosphatidylcholine transacylase and lysophosphatidylcholine:acyl-CoA acyl-transferase) were significantly increased. 5. Membrane-bound phosphatidic acid-dependent phosphatidic acid phosphohydrolase activity was elevated to a lesser extent than the aqueously dispersed phosphatidate-dependent activity and this increase was not significant. 6. The incorporation of E135S]methionine into protein by slices of fetal lung was significantly reduced after maternal treatment with betamethosone. 7. These results are consistent with the general view that glucocorticoids can induce pulmonary maturation and surfactant production in the rabbit fetus but indicate that some of the former hypotheses regarding the mechanism by which lipid synthesis is accelerated must be reevaluated.


Classification of white matter lesions on magnetic resonance imaging in elderly persons.
White matter lesions, commonly seen on MRIs of elderly people, are related to various geriatric disorders, including cerebrovascular diseases, cardiovascular diseases, dementia, and psychiatric disorders. Currently, white matter lesions are divided into periventricular white matter lesions and deep white matter lesions. Although the meaning of these terms varies by study and this dichotomization itself is still in debate, a possible dissimilarity in pathogenic mechanisms between periventricular white matter lesions and deep white matter lesions are providing some clues for understanding pathophysiology of many geriatric syndromes associated with white matter lesions. We have reviewed the distinctions between periventricular white matter lesions and deep white matter lesions in terms of etiology, histopathology, functional correlates, and imaging methodologies. We suggest a new subclassification of white matter lesions that might have better etiological and functional relevance than the current simple dichotomization. The new categories are juxtaventricular, periventricular, deep white, and juxtacortical. This new classification scheme might contribute to reducing the heterogeneity of white matter lesion findings in future research.