Candesartan cilexetil ameliorates NOSTRIN-NO dependent portal hypertension in cirrhosis and ACLF.
In decompensated cirrhosis, the severity of portal hypertension (PHT) is associated with increased hepatic endothelial nitric oxide synthase (eNOS) trafficking inducer (Nostrin), but the mechanism remains unclear. AIM: To investigate: (1) Whether in cirrhosis-PHT models, ± superimposed inflammation to mimic acute-on-chronic liver failure (ACLF) modulates hepatic nitric oxide synthase trafficking inducer (NOSTRIN) expression, nitric oxide (NO) synthesis, and/or endothelial dysfunction (ED); and (2) Whether the "angiotensin II type 1 receptor blocker" candesartan cilexetil (CC) affects this pathway. CD-1 mice received intraperitoneal carbon tetrachloride injections (CCl4 15% v/v in corn oil, 0.5 mL/kg) twice weekly for 12 wk to induce cirrhosis. After 12 wk, mice were randomized to receive 2-wk oral administration of CC (8 mg/kg) ± LPS. At sacrifice, plasma (biochemical indicators, cytokines, and angiotensin II) and liver tissues (histopathology, Sirius-red stains, and molecular studies) were analysed. Moreover, Nostrin gene knockdown was tested in human umbilical vein endothelial cells (HUVECs). When compared to naïve animals, CCl4-treated animals showed markedly elevated hepatic Nostrin expression (P < 0.0001), while hepatic peNOS expression (measure of eNOS activity) was significantly reduced (P < 0.05). LPS challenge further increased Nostrin and reduced peNOS expression (P < 0.05 for both) in cirrhotic animals. Portal pressure and subsequent hepatic vascular resistance were also increased in all cirrhotic animals following LPS challenge. In CCl4 ± LPS-treated animals, CC treatment significantly reduced Nostrin (P < 0.05) and increased hepatic cGMP (P < 0.01). NOSIP, caveolin-1, NFκB, and iNOS protein expression were significantly increased in CCl4-treated animals (P < 0.05 for all). CC treatment non-significantly lowered NOSIP and caveolin-1 expression while iNOS and NFκB expression was significantly reduced in CCl4 + LPS-treated animals (P < 0.05 for both). Furthermore, Nostrin knockdown significantly improved peNOS expression and associated NO synthesis and reduced inflammation in HUVECs. This study is the first to indicate a potential mechanistic role for the Nostrin-eNOS-NO pathway in cirrhosis and ACLF development. Moreover, this pathway provides a potential therapeutic target given the ameliorative response to Candesartan treatment.


Analysis of charge transport in gels containing polyoxometallates using methods of different sensitivity to migration.
Two methods have been used for examination of transport of charge in gels soaked with DMF and containing dissolved polyoxometallates. The first method is based on the analysis of both Cottrellian and steady-state currents and therefore is capable of giving the concentration of the electroactive redox centres and their transport (diffusion-type) coefficient. The second method provides the real diffusion coefficients, i.e. transport coefficients free of migrational influence, for both the substrate and the product of the electrode reaction. Several gels based on poly(methyl methacrylate), with charged (addition of 1-acrylamido-2-methyl-2-propanesulphonic acid to the polymerization mixture) and uncharged chains, have been used in the investigation. The ratio obtained for the diffusion coefficient (second method) and transport coefficient (first method) was smaller for the gels containing charged polymer chains than for the gels with uncharged chains. In part these changes could be explained by the contribution of migration to the transport of polyoxomatallates in the gels. However, the impact of the changes in the polymer-channel capacity at the electrode surface while the electrode process proceeds was also considered. These structural changes should affect differently the methods based on different time domains.


MK-801-induced symptoms of sensitization. The lack of correlation with the extracellular concentration of dopamine in the rat prefrontal cortex.
It was found that MK-801 evoked signs of behavioral sensitization to its own behavioral effects. A second injection of MK-801 (0.4 mg/kg) given 24 h after the first one (also 0.4 mg/kg) evoked stronger behavioral effects than the first dose. MK-801 (0.4 mg/kg) enhanced the extracellular concentration of dopamine (DA) in the prefrontal cortex (PFC). A second dose of MK-801 (0.4 mg/kg) given 24 h after the first one, evoked a quantitatively similar effect on the extracellular concentration of DA. The above results indicate that, at least in the PFC, the enhanced behavioral responsiveness to subsequent doses of MK-801 is not correlated with alterations in the extracellular concentration of DA.


Effect of the Time Delay between Spin State Preparation and Measurement on Electron Spin Teleportation in a Covalent Donor-Acceptor-Radical System.
We recently demonstrated photodriven quantum teleportation of an electron spin state in a covalent donor-acceptor-radical (D-A-R•) system. Following specific spin state preparation on R• with a microwave pulse, photoexcitation of A results in two-step electron transfer producing D•+-A-R-, where the spin state on R• is teleported to D•+. This study examines the effects of varying the time (τD) between spin state preparation and photoinitiated teleportation. Using pulse electron paramagnetic resonance spectroscopy, the spin echo of D•+ resulting from teleportation shows a damped oscillation as a function of τD that is simulated using a density matrix model, which provides a fundamental understanding of the echo behavior. Teleportation fidelity calculations also show oscillatory behavior as a function of τD due to the accumulation of a phase factor between ⟨Sx⟩ and ⟨Sy⟩. Understanding experimental parameters intrinsic to quantum teleportation in molecular systems is crucial to leveraging this phenomenon for quantum information applications.


Assessment of grain yield indices in response to drought stress in wheat (Triticum aestivum L.).
Drought stress constricts crop production in the world. Increasing human population and predicted temperature increase owing to global warming will lead ruthless problems for agricultural production in near future. Hence, use of high yielding genotypes having drought tolerance and scrutinize of drought sensitive local cultivars for making them tolerant may be the proficient approaches to cope its detrimental outcomes. The current study was executed during 20015-2016 and 2016-2017 in field using randomized complete block design under factorial arrangements on 50 wheat genotypes for exploring their sensitivity and tolerance against drought. Some of the attributes of grain yield and drought tolerance indices were recorded. Grain yield showed negative correlations with tolerance index (TOL), drought index (DI) and stress susceptibility index (SSI) while positive correlation with mean productivity (MP) and geometric mean productivity (GMP) under drought condition. These findings depicted that tolerant genotypes could be chosen by high MP and GMP values and low SSI and TOL values. Based on the results, genotypes GA-02, Faisalabad-83, 9444, Sehar-06, Pirsabak-04 and Kohistan-97 were more tolerant and recognized as suitable for both normal and drought conditions. Genotypes of Chenab-00, Kohsar-95, Parwaz-94 and Kohenoor-83 confirmed more sensitive due to high grain yield loss under drought stress.


Schisandrin B down-regulated lncRNA BCYRN1 expression of airway smooth muscle cells by improving miR-150 expression to inhibit the proliferation and migration of ASMC in asthmatic rats.
The mechanism of Schisandrin B on the proliferation and migration of airway smooth muscle cells (ASMCs) in asthmatic rats was explored. SD rats were divided into three groups: control (group 1), model (group 2) and model + Schisandrin B (group 3). miR-150 and lncRNA BCYRN1 levels were measured by qRT-PCR. The combination of BCYRN1 and miR-150 was detected by RNA pull down. ASMCs' viability/proliferation/migration were examined by WST-1 assay and 24-well Transwell system. Schisandrin B up-regulated miR-150 expression and down-regulated BCYRN1 expression in sensitized rats. Schisandrin B reversed the expression of miR-150 and BCYRN1 in MV-treated ASMCs. In addition, Schisandrin B inhibited the viability, proliferation and migration of MV-induced ASMCs. We also found miR-150 inhibited BCYRN1 expression which was proved by experiments using ASMCs transfected with miR-150 inhibitor. Schisandrin B increased miR-150 expression and decreased BCYRN1, and BCYRN1 expression was inhibited by miR-150, which indicated that Schisandrin B could regulate BCYRN1 through miR-150.


Ultra-fast and accurate electron ionization mass spectrum matching for compound identification with million-scale in-silico library.
Spectrum matching is the most common method for compound identification in mass spectrometry (MS). However, some challenges limit its efficiency, including the coverage of spectral libraries, the accuracy, and the speed of matching. In this study, a million-scale in-silico EI-MS library is established. Furthermore, an ultra-fast and accurate spectrum matching (FastEI) method is proposed to substantially improve accuracy using Word2vec spectral embedding and boost the speed using the hierarchical navigable small-world graph (HNSW). It achieves 80.4% recall@10 accuracy (88.3% with 5 Da mass filter) with a speedup of two orders of magnitude compared with the weighted cosine similarity method (WCS). When FastEI is applied to identify the molecules beyond NIST 2017 library, it achieves 50% recall@1 accuracy. FastEI is packaged as a standalone and user-friendly software for common users with limited computational backgrounds. Overall, FastEI combined with a million-scale in-silico library facilitates compound identification as an accurate and ultra-fast tool.


Effect of carbon nanofiber functionalization on the adsorption properties of volatile organic compounds.
The effect of the chemical activation, using HNO3, of a commercial carbon nanofiber (CNF) on its surface chemistry and adsorption properties is studied in this work. The adsorption of different alkanes (linear and cyclic), aromatic compounds and chlorohydrocarbons on both the parent and the oxidized CNF were compared. Temperature-programmed desorption results, in agreement with X-ray photoelectron spectroscopy experiments, reveal the existence of oxygen groups on the surface of the treated CNF. Capacity of adsorption was derived from the adsorption isotherms, whereas thermodynamic properties (enthalpy of adsorption, surface free energy characteristics) have been determined from chromatographic retention data. Both the capacity and the strength of adsorption decrease after the oxidant treatment of the carbon nanofibers, although in the case of chlorinated compounds the specific component of the surface energy shows an important increase. For n-alkanes and cyclic compounds, it was demonstrated that the presence of oxygen surface groups does not affect their interaction, the morphology of the surface being the key parameter. The oxidation of the nanofiber leads to steric limitations of the adsorption. In the adsorption of aromatic compounds, these limitations are compensated by the nucleophilic interactions between the aromatic ring and surface oxygenated groups, leading to similar performances of both materials. The absence of nucleophilic groups in the chlorinated compounds hinders their adsorption on the activated nanofibers.


TMJ disorders and pain: assessment by contrast-enhanced MRI.
Though magnetic resonance (MRI) is a widely accepted standard for the assessment of patients with temporomandibular joint (TMJ) disorders, efforts to correlate symptoms to MRI findings have often given controversial results. Aim of this study was to investigate the correlation between TMJ pain and findings of contrast-enhanced MRI. Thirty-eight consecutive patients with TMJ dysfunction syndrome (study group) were examined with MRI. Protocol included T2 turbo spin-echo sequence, T1 spin-echo sequence, and T2 gradient-echo (acquired with closed jaw, at intermediate and maximal opening). Post-contrast phase was obtained through a fat sat 3D T1 gradient-echo sequence (VIBE). Post-contrast findings in the study group were matched with those obtained in a control group of 33 patients submitted to MRI of the paranasal sinuses. Statistically significant difference was found between condylar medullary bone enhancement in painful TMJ, in painless TMJ and control group. In addition the average thickness of joint soft tissue enhancement in painful TMJ was superior to painless TMJ (p<0.0001) and to control group. On multivariate logistic regression analysis, the odds ratio that a painful TMJ showed disk displacement, osteoarthrosis, effusion and JST enhancement were 3.05, 3.18, 1.2 and 11.36, respectively. Though not histologically proven, TMJ enhancement could reflect the presence of inflammation in painful joints. Furthermore, the administration of contrast could be of help for the assessment of patients with orofacial pain, particularly when clinical exploration is insufficient to ascribe the pain to TMJ.


Detection of Campylobacter species in different types of samples from dairy farms.
Livestock, domestic pets and wildlife can be intestinal carriers of thermotolerant Campylobacter species. These reservoirs can in turn contaminate the environment and food products, thus creating pathways to campylobacteriosis in human beings. The purposes of this study were to investigate sampling strategies applied for surveillance of Campylobacter on dairy cattle farms and to identify the presence and species of Campylobacter in different age groups. Boot sock and faecal samples were collected from five dairy herds from three age groups-cows, heifers and calves younger than 12 months-and from milk filters. Campylobacter species were isolated in 152 of 250 samples, of which 93 isolates were identified as C jejuni, 51 as C hyointestinalis, two as C lari and one as C coli, whereas five isolates could not be identified to species level. Campylobacter species were isolated from 86 of 110 faecal samples, 60 of 97 sock samples and six of 43 milk filter samples. Faecal samples were the optimal sample type for detection of Campylobacter on dairy farms. However, taking multiple types of samples could be recommended in order to optimise the recovery rate and variety of Campylobacter species detected when investigating the presence of Campylobacter on dairy farms.


Constructing a Computer-Aided Differential Diagnosis Engine from Open-Source APIs.
This paper describes the design and implementation of an application that parses and analyzes radiology report text to provide a radiologic differential diagnosis. The system was constructed using a combination of freely available web-based APIs and originally developed during the Society for Imaging Informatics in Medicine (SIIM) 2014 Hackathon. Continued development has refined and increased the accuracy of the algorithm. This project demonstrates the power and possibilities of combining existing technologies to solve unique problems as well as the stimulus of the hackathon setting to spur innovation.


Upregulation of estrogen receptor alpha (ERα) expression in transgenic mice expressing human CYP4Z1.
CYP4Z1 is a human cytochrome P450 enzyme involved in breast cancer progression and prognosis, but its functional role in these processes is not understood. In order to gain more insight into CYP4Z1's properties it was recombinantly expressed in a host animal that does not have an endogenous homologue. We generated a transgenic mouse model that specifically expresses human CYP4Z1 in breast tissue under the control of the whey acidic protein promoter. Complementary experiments were done using cell lines derived from human breast cell. Induction of CYP4Z1 expression led to reduction of body weight, activity, and birth rates. Histological analysis revealed no evidence for tumor formation. However, a strong increase in estrogen receptor alpha was observed by immunohistochemistry; weaker but significantly increased immunoreactivity was also detected for collagen I and fibronectin. Overexpression of CYP4Z1 in the human breast cancer cell line MCF7 also led to increased ERα expression. Moreover, increased expression of both CYP4Z1 and ERα was observed in MCF-10A normal breast cells upon cocultivation with MCF-7 cells (with or without overexpression of CYP4Z1). These data suggest that CYP4Z1 facilitates breast cancer development by induction of ERα expression via an as yet undefined mechanism.


Genome-wide gene-environment interactions on quantitative traits using family data.
Gene-environment interactions may provide a mechanism for targeting interventions to those individuals who would gain the most benefit from them. Searching for interactions agnostically on a genome-wide scale requires large sample sizes, often achieved through collaboration among multiple studies in a consortium. Family studies can contribute to consortia, but to do so they must account for correlation within families by using specialized analytic methods. In this paper, we investigate the performance of methods that account for within-family correlation, in the context of gene-environment interactions with binary exposures and quantitative outcomes. We simulate both cross-sectional and longitudinal measurements, and analyze the simulated data taking family structure into account, via generalized estimating equations (GEE) and linear mixed-effects models. With sufficient exposure prevalence and correct model specification, all methods perform well. However, when models are misspecified, mixed modeling approaches have seriously inflated type I error rates. GEE methods with robust variance estimates are less sensitive to model misspecification; however, when exposures are infrequent, GEE methods require modifications to preserve type I error rate. We illustrate the practical use of these methods by evaluating gene-drug interactions on fasting glucose levels in data from the Framingham Heart Study, a cohort that includes related individuals.


Sequence variation of Vanabin2-like vanadium-binding proteins in blood cells of the vanadium-accumulating ascidian Ascidia sydneiensis samea.
The blood cells of ascidians accumulate extremely high levels of the transition metal vanadium. We previously isolated four vanadium-binding proteins (Vanabins 1-4) and a homologous protein (VanabinP) from the vanadium-rich ascidian Ascidia sydneiensis samea. In the present study, we identified cDNAs encoding five different Vanabin2-related proteins in A. sydneiensis samea blood cells. It was notable that the sequences of the encoded proteins vary from that of Vanabin2 at up to 14 specific positions, while both the polypeptide length and the 18 cysteine residues were completely conserved. The most divergent protein, named 14MT, differed from Vanabin2 at all 14 positions. Using immobilized metal-ion affinity chromatography, we found that Vanabin2 and 14MT have the same metal-ion selectivity, but the overall affinity of 14MT for VO(2+) is higher than that of Vanabin2. Binding number for VO(2+) ions was the same between Vanabin2 and 14MT as assessed by gel filtration. These results suggested that sequence variations were under strict evolutionary constraints and high-affinity binding sites for VO(2+) are conserved among Vanabin2 variants.


The Effect of Early Rounds of ex vivo Expansion and Cryopreservation on the Adipogenic Differentiation Capacity of Adipose-Derived Stromal/Stem Cells.
Multipotent adipose-derived stromal/stem cells (ASCs) are candidates for use in cellular therapies for the treatment of a variety of conditions/diseases. Ex vivo expansion of freshly isolated ASCs may be necessary prior to clinical application to ensure that clinically relevant cell numbers are administered during treatment. In addition, cryopreserving cells at early passages allows for storage of freshly isolated cells for extended periods of time before expanding these cells for clinical usage. There are however several concerns that these laboratory-based procedures may alter the characteristics of the cells and in so doing decrease their regenerative potential. In this study we report on the impact of early rounds of cryopreservation (P0) and ex vivo expansion (P0 to P5) on the phenotypic characteristics and adipogenic differentiation potential of ASCs. Our results show that ASCs that upregulate CD36 expression during adipogenic differentiation gradually decrease with increasing expansion rounds. The consequent decrease in adipogenic differentiation capacity was evident in both gene expression and flow cytometry-based phenotypic studies. Successive rounds of expansion did not however alter cell surface marker expression of the cells. We also show that early cryopreservation of ASCs (at P0) does not affect the adipogenic differentiation potential of the cells.


Seasonal variation in the photoperiodic responses of a pea aphid population: evidence for long-distance movements between populations.
The purpose of the study was to quantify long distance movements in populations of pea aphid, Acyrthosiphon pisum (Harris), by estimating origins and distances travelled by immigrants into a southern Manitoba population. A strong relationship was demonstrated between latitude of origin and photoperiods at which pea aphid populations are stimulated to produce the diapause stage (Smith 1987). Therefore, the approach was to use photoperiodic response as a physiological marker to identify the source of immigrant aphids. The responses of 89 clones from Glenlea, Manitoba (49°38'N), sampled 5 times over 2 seasons, were measured. One sample of clones collected the first season had photoperiodic responses similar to those of a population about 300 km to the south, and significantly different from clones collected in spring of the same year at the same site. Weather analysis corroberates that the migrants were probably carried into Manitoba on a southerly flow of air during the previous 24 to 36 h.


The Z-band lattice in a slow skeletal muscle.
Structural features of the Z-lattice were examined in cross-sections of rat soleus muscle. Optical diffraction analysis of individual myofilament bundles revealed highly ordered, tightly packed tetragonal lattice regions with abrupt shifts in orientation. Optical reconstructions of cross-sections of the Z-lattice in regions having the same axial filament spacing showed both the basket weave and the small square lattice forms, as well as intermediate structures. Analysis of these regions in three dimensions and in two-dimensional projections suggests that a change in diameter together with a change in curvature of the cross-connecting filaments can explain the different appearances of the Z-lattice at a given sarcomere length.


Stability of Mueller-Hinton agar supplemented with glucose and methylene blue for disk diffusion testing of fluconazole and voriconazole.
The shelf life of Mueller-Hinton agar supplemented with 2% glucose and methylene blue (0.5 micro g/ml) (MH-GMB) prepared in the laboratory to test disk diffusion of voriconazole and fluconazole was assessed using quality control (QC) strains of Candida albicans ATCC 90028, Candida krusei ATCC 6258, and Candida parapsilosis ATCC 22019. MH-GMB agar plates were prepared as described in National Committee for Clinical Laboratory Standards document M44-P, and isolates were tested using 25- micro g fluconazole disks and 1- micro g voriconazole disks over a 36-day period. Zone diameters for fluconazole and voriconazole varied by no more than 4 mm over the study period, and 95 to 100% of results were within the established QC limits for the strains tested. Prepared MH-GMB agar plates provide acceptable performance for disk diffusion testing for at least 30 days when stored at 5 degrees C.


Dissociation by cooling of hormone and cholera toxin activation of adenylate cyclase in intact cells.
Cholera toxin, through adenylate cyclase activation reproduced cyclic AMP-mediated effects of thyroid-stimulating hormone (TSH) in dog thyroid slices, i.e. protein iodination, [1-14C]glucose-oxidation and hormone secretion. Iodide and carbamylcholine decreased the cyclic AMP accumulation induced by cholera toxin as well as by TSH, which supports the hypothesis of an action of these agents beyond the steps of hormone-receptor and receptor-adenylate cyclase interaction. Cooling to 20 degrees C did not impair the TSH induced cyclic AMP accumulation in thyroid slices, but completely suppressed the cholera toxin effect. This observation has been extended to other hormones and target tissues, such as the parathyroid hormone (PTH) (kidney cortex), adrenocorticotropic hormone (ACTH) (adrenal cortex) and luteinizing hormone (LH) (ovary systems). As in thyroid, cooling dissociated the cholera toxin and hormonal effects on cyclic AMP accumulation. In homogenate, cooling decreased cyclic AMP generation in the presence of cholera toxin but at 20 degrees C and 16 degrees C a cholera toxin stimulation was still observed. These results bear strongly against the hypothesis that the glycoprotein hormones TSH and LH acetivate adenylate cyclase by a mechanism identical to cholera toxin.


Abnormalities of myocardial perfusion and glucose metabolism in patients with isolated left ventricular non-compaction.
The prevalence of myocardial perfusion and glucose metabolic abnormalities and their significance in patients with isolated left ventricular non-compaction (ILVNC) have not been well investigated. Seventeen ILVNC patients who underwent cardiac magnetic resonance (CMR) and (99m)Tc-sestamibi SPECT/fluorine-18 deoxyglucose ((18)F-FDG) PET imaging were included. Left ventricular non-compaction, regional wall motion abnormalities, left ventricular ejection fraction (LVEF), and delayed enhancement (DE) were estimated using CMR. Myocardial perfusion and metabolism were evaluated with SPECT/PET. Ninety-five (32.9%) segments were considered non-compacted. DE was present in 52 (18.0%) segments and 10 (58.8%) patients. The rate of occurrence of DE was significantly higher in compacted segments than in non-compacted segments (22.7% vs 8.4%, P = .003). Myocardial perfusion abnormalities were present in 92 (31.8%) segments, of which 66 were perfusion/metabolism match and 26 were perfusion/metabolism mismatch. The rate of occurrence of perfusion abnormality was similar between compacted and non-compacted segments (32.0% vs 31.6%, P = .948), but it was significantly higher in segments with DE than in those without DE (51.9% vs 27.4%, P = .001). None of the imaging features alone (non-compaction, DE, perfusion abnormalities, match or mismatch) showed significant correlations with LVEF (all P > .05). In the current study, myocardial perfusion/metabolism mismatch and match were observed in both non-compacted and compacted myocardium in ILVNC patients. Further research is warranted to determine their pathologic and clinical significance.


Theoretical investigation of uranyl dihydroxide: oxo ligand exchange, water catalysis, and vibrational spectra.
Density functional theory is employed to investigate uranyl dihydroxide, UO2(OH)2, isomerization reaction energy barriers, including those occurring via proton shuttles. The ground-state structure of a uranyl dihydroxide complex containing a uranyl moiety with a near 90 degrees O=U=O bond angle is reported for the first time. Furthermore, we predict the vibrational spectra of these compounds. Scalar-relativistic effects for uranium are treated by employing a relativistic effective core potential.


Wnt signaling preserves progenitor cell multipotency during adipose tissue development.
Mesenchymal stem/progenitor cells are essential for tissue development and repair throughout life, but how they are maintained under chronic differentiation pressure is not known. Using single-cell transcriptomics of human progenitor cells we find that adipose differentiation stimuli elicit two cellular trajectories: one toward mature adipocytes and another toward a pool of non-differentiated cells that maintain progenitor characteristics. These cells are induced by transient Wnt pathway activation and express numerous extracellular matrix genes and are therefore named structural Wnt-regulated adipose tissue cells. We find that the genetic signature of structural Wnt-regulated adipose tissue cells is present in adult human adipose tissue and adipose tissue developed from human progenitor cells in mice. Our results suggest a mechanism whereby adipose differentiation occurs concurrently with the maintenance of a mesenchymal progenitor cell pool, ensuring tissue development, repair and appropriate metabolic control over the lifetime.


Measuring gesture: its cultural and clinical correlates.
An ultrasonic system for measuring psychomotor behaviour is described, and then applied to compare the extent to which English and French students gesticulate. The findings supported the hypotheses that: (1) French students gesticulate more than the English both when using descriptive speech and when discussing their feelings; (2) descriptive speech elicits more gesture then affectively-toned speech; (3) when verbal expression is more difficult the use of gesture increases; (4) individuals tend to maintain a characteristic level of gesturing. We concluded the ultrasonic system provides a reliable and sensitive method for measuring gesture activity and can be applied clinically to the study of psychomotor behaviour.


Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.
The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype.


Allo-exposure status and leucocyte antibody positivity of blood donors show a similar relation with TRALI.
The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8.3% (95% confidence interval (CI): 5.1-11.5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: -5.0 to 36%). These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.


Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610.
Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer. The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from the RTOG tissue repository. Hematoxylin and eosin slides were reviewed, and paraffin blocks were immunohistochemically stained for VEGF expression and graded by Intensity score (0-3). Cox or Fine and Gray's proportional hazards models were used. Sufficient pathologic material was available from 103 (23%) of the 456 analyzable patients enrolled in the RTOG 8610 study. There were no statistically significant differences in the pre-treatment characteristics between the patient groups with and without VEGF intensity data. Median follow-up for all surviving patients with VEGF intensity data is 12.2 years. Univariate and multivariate analyses demonstrated no statistically significant correlation between the intensity of VEGF expression and overall survival, distant metastasis, local progression, disease-free survival, or biochemical failure. VEGF expression was also not statistically significantly associated with any of the endpoints when analyzed by treatment arm. This study revealed no statistically significant prognostic or predictive value of VEGF expression for locally advanced prostate cancer. This analysis is among one of the largest sample bases with long-term follow-up in a well-characterized patient population. There is an urgent need to establish multidisciplinary initiatives for coordinating further research in the area of human prostate cancer biomarkers.


Cohort profile: maternal and child health and parenting practices during the COVID-19 pandemic in Ceará, Brazil: birth cohort study (Iracema-COVID).
Maternal and child health and parenting practices during the COVID-19 pandemic in Ceará (Iracema-COVID) is a longitudinal, prospective population-based birth cohort designed to understand the effects of the pandemic and social withdrawal in maternal mental health, child development and parenting practices of mothers and families. A sample of mothers who gave birth in July and August 2020 (n=351) was enrolled in the study in January 2021. Interviews were conducted by telephone. Data were collected through standardised questionnaires that, in addition to sociodemographic and economic data, collected information on breast feeding, mental health status and COVID-19. Results from the first wave show that the majority of participants have 9-11 years of schooling (54.4%; 95% CI 61.0 to 70.9) and are of mixed race (71.5%; 95% CI 66.5 to 76.0). At the time of the survey, 27.9% of the participants were out of the labor force (95% CI 23.5 to 32.9) and 78.6% reported a decrease in family income after restrictions imposed due to the pandemic (95% CI 74.0 to 82.6). The prevalence of maternal common mental disorder symptoms was 32.5% (95% CI 27.8 to 37.6). Follow-up visits are planned to occur every 6 months for the next five years (2021-2025). Additional topics will be included in future waves (eg, food insecurity and parenting practices). Communication strategies for bonding, such as picture cards, pictures of mothers with their children and phone calls to the participants, will be used to minimise attrition. Results of this prospective cohort will generate novel knowledge on the impact of the COVID-19 pandemic on maternal and child health and parenting practices in a population of women and children living in fifth largest city of Brazil.


Brief report: risk-taking behaviors in a non-western urban adolescent sample.
This study analyzes the age and gender related risk-taking behaviors of Turkish adolescents in an urban sample. A self-report risk taking scale was administered to 280 adolescents between the ages of 12-21. Results revealed that both the type and the frequency of risk-taking behaviors were changed according to age and gender. All risky behaviors except hitchhiking increased until the college level and than decreased. Boys outperformed the girls in most of the risk-taking behaviors.


Enclosing chromatin: reassembly of the nucleus after open mitosis.
During mitosis in vertebrate cells, the nuclear envelope undergoes extensive structural reorganization, starting with the retraction of nuclear membranes into the ER at mitotic onset and ending with the re-enclosure of chromatin by ER-derived membranes during mitotic exit. Here, we review our current understanding of postmitotic nuclear assembly.


Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy.
Adenosine monophosphate-activated protein kinase (AMPK) acts as a major sensor of cellular energy status in cancers and is critically involved in cell sensitivity to anticancer agents. Here, we showed that AMPK was inactivated in lymphoma and related to the upregulation of the mammalian target of rapamycin (mTOR) pathway. AMPK activator metformin potentially inhibited the growth of B- and T-lymphoma cells. Strong antitumor effect was also observed on primary lymphoma cells while sparing normal hematopoiesis ex vivo. Metformin-induced AMPK activation was associated with the inhibition of the mTOR signaling without involving AKT. Moreover, lymphoma cell response to the chemotherapeutic agent doxorubicin and mTOR inhibitor temsirolimus was significantly enhanced when co-treated with metformin. Pharmacologic and molecular knock-down of AMPK attenuated metformin-mediated lymphoma cell growth inhibition and drug sensitization. In vivo, metformin induced AMPK activation, mTOR inhibition and remarkably blocked tumor growth in murine lymphoma xenografts. Of note, metformin was equally effective when given orally. Combined treatment of oral metformin with doxorubicin or temsirolimus triggered lymphoma cell autophagy and functioned more efficiently than either agent alone. Taken together, these data provided first evidence for the growth-inhibitory and drug-sensitizing effect of metformin on lymphoma. Selectively targeting mTOR pathway through AMPK activation may thus represent a promising new strategy to improve treatment of lymphoma patients.


Using patient-reported outcome measures to assess psychological well-being in a non-representative US general population during the COVID-19 pandemic.
The impact of the COVID-19 pandemic on psychological well-being will likely be long-lasting. Efforts directed towards monitoring the onset and progression of distress and mental health disorders are needed to identify and prioritize at-risk populations. This study assesses the psychological well-being of the United States (US) general population during the early phase of the COVID-19 COVID-19 pandemic using validated patient-reported outcome measures (PROMs). A cross-sectional study design was used. Adults (18 years or older) who could read and write in English were recruited through Prolific in May 2020. Participants completed a REDCap survey including demographic and health-related questions and three PROMs measuring global health (PROMIS-10 Global Health), anxiety [Generalized Anxiety Disorder Scale-7 (GAD-7)], and depression [Patient Health Questionnaire-9 (PHQ-9)]. A multivariable linear regression was used to identify key factors associated with worse psychological well-being. Mean age of the 2023 participants was 31.92 ± 11.57 years (range, 18-82). Participants were mainly White (64.7%, n = 1309), female (52.2%, n = 1057), working full-time before the pandemic (43.5%, n = 879), and completed a college, trade, or university degree (40.7%, n = 823). Most participants reported mild to severe anxiety (57.3%, n = 1158) and depression (60%, n = 1276) on the GAD-7 and PHQ-9, respectively. Patient characteristics associated with worse psychological well-being included: age ≤ 39 years, non-White, female or gender diverse, BMI ≥ 30, uninsured, annual income ≤ $49,999 (USD), lower educational attainment, and belief that COVID-19 is deadlier than flu. PROMs can be used to assess and monitor psychological well-being during the COVID-19 pandemic and to inform the planning and delivery of targeted public health interventions to support at-risk populations.


A fraction of barrier-to-autointegration factor (BAF) associates with centromeres and controls mitosis progression.
Barrier-to-Autointegration Factor (BAF) is a conserved nuclear envelope (NE) component that binds chromatin and helps its anchoring to the NE. Cycles of phosphorylation and dephosphorylation control BAF function. Entering mitosis, phosphorylation releases BAF from chromatin and facilitates NE-disassembly. At mitotic exit, PP2A-mediated dephosphorylation restores chromatin binding and nucleates NE-reassembly. Here, we show that in Drosophila a small fraction of BAF (cenBAF) associates with centromeres. We also find that PP4 phosphatase, which is recruited to centromeres by CENP-C, prevents phosphorylation and release of cenBAF during mitosis. cenBAF is necessary for proper centromere assembly and accurate chromosome segregation, being critical for mitosis progression. Disrupting cenBAF localization prevents PP2A inactivation in mitosis compromising global BAF phosphorylation, which in turn leads to its persistent association with chromatin, delays anaphase onset and causes NE defects. These results suggest that, together with PP4 and CENP-C, cenBAF forms a centromere-based mechanism that controls chromosome segregation and mitosis progression.


Mechanisms of anterograde and retrograde memory impairment following experimental traumatic brain injury.
Memory impairment is common following traumatic brain injury. However, the specific processes underlying the impairments remain unknown. Traumatic brain injury may interfere with several of the stages of the learning and memory process. In two separate experiments, we examined the specific nature of both anterograde and retrograde memory dysfunction following fluid percussion brain injury in rats. In Experiment 1, we examined the retention of spatial memory in the MWM after equating initial learning between sham and injured animals. Animals were trained to criterion and then tested for retention 4, 8, or 24 h post-training. Although injured animals displayed deficits in task acquisition, retention performance was not significantly different between groups. In Experiment 2, we examined the effects of injury on the retention of retrograde spatial memories in the MWM. Animals were injured either 1 or 14 days post-training and then received retention probe trials followed by a reminding procedure and second probe trial 14 days post-injury. All injured animals displayed retention deficits in the probe trials 14 days post-injury. However, after the reminding procedure, injured animals displayed sham-level performance during the second probe trial. The results of these experiments suggest that with anterograde memory impairment induced by traumatic brain injury, the primary deficit lies in task acquisition, not the retention of information within long-term memory. Retrograde memory impairment following injury appears to be mediated primarily by deficits in memory retrieval.


Long-Term Results of Stent Placement in Patients with Outflow Block After Living-Donor-Liver Transplantation.
To evaluate long-term results of stent placement retrospectively in patients with outflow block after living-donor-liver transplantation (LDLT). For this institutional review board approved retrospective study conducted during 2002-2012, stents were placed in outflow veins in 15 patients (11.3%, 15/133) (12 men; 3 female) in whom outflow block developed after LDLT. Their mean age was 52.3 years ± 15.3 (SD) (range, 4-69 years). Venous stenosis with a pressure gradient ≥5 mmHg (outflow block) was observed in the inferior vena cava in seven patients, hepatic vein in seven patients, and both in one patient. Technical success, change in a pressure gradient and clinical manifestations, and complications were evaluated. Overall survival of 15 patients undergoing outflow block stenting was compared with that of 116 patients without outflow block after LDLT. Stents were placed across the outflow block veins without complications, lowering the pressure gradient ≤ 3 mmHg in all patients (100%, 15/15). Clinical manifestations improved in 11 patients (73.3%, 11/15), and all were discharged from the hospital. However, they did not improve in the other 4 patients (26.7%, 4/15) who died in the hospital 1.0-3.7 months after stenting (mean, 2.0 ± 1.2 months). No significant difference in 5-year survival rates was found between patients with and without outflow block after LDLT (61.1 vs. 72.2%, p = .405). Stenting is a feasible, safe, and useful therapeutic option to resolve outflow block following LDLT, providing equal survival to that of patients without outflow block.


Is the area under blood pressure curve the best parameter to evaluate 24-h ambulatory blood pressure monitoring data?
Ambulatory blood pressure monitoring (ABPM) provides relevant data about blood pressure over a 24-h period. The analysis of parameters to determine the blood pressure profile from these data is of great importance. To calculate areas under systolic and diastolic blood pressure curves (SBP-AUC/DBP-AUC) and compare with systolic and diastolic blood pressure load (SBPL/DBPL) and 24-h systolic and diastolic blood pressure (24-h SBP/24-h DBP) in order to determine which provides the best correlation with left ventricular mass index (LVMI). ABPM measurements (1143 individuals) were analyzed to obtain 24-h SBP/24-h DBP, SBPL/DBPL, and SBP-AUC/ DBP-AUC, using Spacelabs (90207) and CardioSistemas devices. Left ventricular mass was determined using an echocardiograph HP Sonos 5500 and LVMI was calculated. The correlations between all possible pairs within the group 24-h SBP/SBPL/SBP-AUC and 24-h DBP/DBPL/DBP-AUC were high and statistically significant. The correlations between 24-h SBP/24-h DBP and SBP-AUC/DBP-AUC with SBPL/DBPL close to 100%, were lower than those mentioned above. The correlations of the parameters obtained by ABPM with LVMI were also high and statistically significant, except for blood pressure load between 90 and 100%, and for 24-h SBP of 135 mmHg or less and SBPL higher than 50%. SBPL/DBPL and SBP-AUC/DBP-AUC can be used for the evaluation of ABPM data owing to the strong correlation with 24-h SBP/24-h DBP and with LVMI, except when SBPL is close to 100% or 24-h SBP is below 135 mmHg but SBPL is above 50%. SBP-AUC/DBP-AUC, however, are a better alternative because they do not have the limitations of blood pressure load or even of 24-h blood pressure present.


Simultaneous or staged resection of synchronous colorectal cancer liver metastases: a 13-year institutional follow-up.
This study compared postoperative outcomes and survival rates of patients who underwent simultaneous or staged resection for synchronous colorectal cancer liver metastases. Between 2005 and 2018, 126 patients were registered prospectively at a university hospital in Sweden, 63 patients who underwent simultaneous resection were matched against 63 patients who underwent staged resection. The length of hospital stay was shorter for the simultaneous resection group, at 11 vs 16 days, p = <0.001. Fewer patients experienced recurrence in the simultaneous resection group 39 vs 50 patients, p = 0.012. There were no significant differences in disease-free survival and overall survival between the groups. Age (hazard ratio [HR] 1.72; 95% CI 1.01-2.94; p = 0.049) and Clavien-Dindo score (HR 2.22; 95% CI 1.06-4.67; p = 0.035) had impact on survival. Colorectal cancer with synchronous liver metastases can be resected simultaneously, and enables a shorter treatment time without jeopardizing oncological outcomes.


Pharmacokinetic comparison of the one-point method with other methods in predicting steady state drug concentrations in multiple dosing.
Using blood level-time profiles of five different drugs, the maximum and minimum drug concentrations,c'max and c'min, were determined according to four different methods. It was demonstrated that the one-point method results in an acceptable estimate allowing prediction of steady state concentrations and adjustment of dose regimen based on one single blood level concentration determined during the later part of the first dosing interval, and utilizing literature on the biological half-life and the time to reach the peak. In case of renal impairment a correction can be made after determination of serum creatinine in the one blood sample taken.


Pretranslational control of tyrosine aminotransferase synthesis by 8-bromo-cyclic AMP in H-4 rat hepatoma cells.
The H-4 rat hepatoma cell line grown in tissue culture was used as a model system to investigate the action of cAMP in tyrosine aminotransferase induction. An immunoprecipitation technique was used to quantitate the amount and the rate of synthesis of tyrosine aminotransferase; the level of mRNA coding for tyrosine aminotransferase was determined by in vitro translation of poly(A)+ RNA isolated from hepatoma cells. Our results demonstrated that 8-bromo-cAMP gave time-dependent and proportionate increases in the tyrosine aminotransferase activity, the amount of immunoprecipitable tyrosine aminotransferase, the rate of synthesis of tyrosine aminotransferase, and the level of mRNATAT in H-4 hepatoma cells. The time course of increase in mRNATAT preceded the increase in synthesis of tyrosine aminotransferase and was dependent on the continuous production of poly(A)+ RNA. Pretreatment of the cells with cordycepin completely abolished the 8-bromo-cAMP-evoked increase in mRNATAT activity. These results provided evidence that the primary action of cAMP in tyrosine aminotransferase induction is the increase of functional mRNATAT and that this increase can completely account for the increase in tyrosine aminotransferase activity.


Effects of Telephone-Based Brief Motivational Interviewing on Self-Management, Medication Adherence, and Glycemic Control in Patients with Uncontrolled Type 2 Diabetes Mellitus in a Rural Community in Thailand.
Owing to the increased prevalence of type 2 diabetes mellitus (T2DM) and the high proportion of patients with uncontrolled T2DM, effective interventions for disease management are needed. The study aim was to test the effects of brief motivational interviewing (MI) on patients' self-management, medication adherence, and glycemic control. A single-group repeated measures trial was used to examine the effects of usual care only and usual care plus telephone-based brief MI. Participants were 29 patients with uncontrolled T2DM recruited from a rural primary care setting in Nakhon Sawan, Thailand. Participants received usual care during the first 4 weeks, followed by usual care plus brief MI during weeks 4-8. Outcomes of self-management, medication adherence, fasting blood sugar (FBS) levels, and hemoglobin A1c (HbA1c) levels were assessed at baseline, 4 weeks, and 8 weeks. Data were analyzed using descriptive statistics, one-way repeated measures analysis of variance, and Friedman test. Significant changes in self-management (p < 0.001), medication adherence (p < 0.001), and FBS (p < 0.05) were observed over the 8-week study. In multiple comparisons, self-management was the only parameter significantly different across baseline, 4, and 8 weeks (p <0.05, <0.001, and <0.001, respectively); medication adherence was significantly different between 4 and 8 weeks (p < 0.05), and between baseline and 8 weeks (p < 0.001); and FBS was significantly different between 4 and 8 weeks (p < 0.05). HbA1c declined over the 8-week study, but not significantly. An intervention combining telephone-based brief MI with usual care significantly increased self-management, medication adherence, and glycemic control (ie, FBS) after 4 weeks, whereas usual care only significantly increased self-management. Phone-based brief MI may be an effective way for healthcare providers to remotely enhance patients' self-management and glycemic control, thus reducing barriers related to time and geographic location.


Postoperative testicular abscess with bacteremia due to Actinomyces neuii.
Bacteremia due to Actinomyces neuii has been reported in the literature 14 times. A. neuii is an endogenous organism that has been cultured in clinical specimens of the genitourinary tract; we are reporting a unique case of A. neuii postoperative testicular abscess with bacteremia which was successfully treated with surgery and a short course of parenteral antimicrobials.


Moderate mental retardation and nonspecific dysmorphic syndrome associated with ring chromosome 9.
A ring chromosome 9 is reported in a 12-year-old, moderately mentally retarded boy. As in other ring chromosome 9 patients, the clinical stigmata are nonspecific and their expressivity is mild. The finding of two normal cells of a total of 121 cells examined favors the hypothesis of a postzygotic, mitotic origin of the ring chromosome formation.


[Clinical manifestations of cluster headache accompanied by chronic nasosinusitis].
To master the clinical manifestations of rhinogenic headache and improve the diagnostic ability of chronic rhinosinusitis accompanied by primary headache. The clinical manifestations, the diagnostic process, and the treatment of 1 patient with headache were analyzed, and also the related articles were studied. Rhinogenic headache and primary headache had different clinical features and different treatment. In clinical work misdiagnosis were easily made if not being carefully analyzed. Diagnosis of rhinogenic headache do need strong clinical evidence, but the differential diagnosis of other headache should be made.


Influence of spontaneous activity on peak-ratio analysis.
To prove or disprove this assumption that in neuropathy patients with abundant spontaneous activity, peak-ratio interference pattern analysis may lead to false negative results. Spontaneous activity >100 microV, automatically analysed by turn/amplitude analysis and expressed as (turns/second)/2 ((T/S)/2), and interference patterns, analysed by the peak-ratio technique, were recorded, one after the other, from the right anterior tibial muscle of 21 patients with neuropathy, aged 36-87 years. The mean number of spontaneous discharges ((T/S)/2) was 12.3 (range 5.5-26) and its mean amplitude 261 microV (range 146-478 microV). Despite this abundant spontaneous activity, peak-ratio analysis was neurogenic in 81% of the patients. All peak-ratio parameters were independent on the amount and amplitude of spontaneous discharges. Spontaneous discharges >100 microV could be adequately assessed by means of the turn/amplitude analysis and did not influence peak-ratio analysis in neuropathies.


Influence of oral polyunsaturated and saturated phospholipid treatment on the lipid composition and fatty acid profile of chimpanzee lipoproteins.
The influence of treatment with polyunsaturated lecithin (EPL) and with saturated lecithin on the lipoprotein composition and fatty acid profile was investigated in 4 male chimpanzees. The animals were successively given 3 isocaloric diets containing the same amount of fat with a degree of saturation varying from 1 in the control diet to 0.2 in the diet enriched with polyunsaturated lecithin, to 4 in the diet enrich with saturated lecithin. The VLDL, LDL and HDL3 fractions were isolated by ultracentrifugal flotation; changes in their lipid and fatty acid composition were followed and their microviscosity was measured. The treatment with polyunsaturated lecithin increases the cholesterol esters and lysolecithin content in HDL3, presumably via activation of the enzyme LCAT. These modified HDL particles have a more fluid surface and a denser core and are susceptible to act as better cholesterol carriers. A complementary effect of this treatment is a decrease of the plasma triglycerides and VLDL concentration, an increase in the unsaturation ratio of the triglycerides which might take place via activation of triglyceride lipase. The saturated lecithin treatment increases the plasma VLDL and LDL concentrations and the triglyceride levels and increases mostly the saturation ratio of the cholesterol esters. These effects are likely to enhance the progression of atherosclerosis.


Curcuma as an anti-inflammatory component in treating osteoarthritis.
Osteoarthritis (OA) is nowadays the most common musculoskeletal progressive condition. In recent decades, incidence and prevalence of OA have increased significantly. It is estimated that the prevalence of OA among adults older than 60 is 12%, affecting about 240 million people globally. The cause has not been fully elucidated, and therefore, there is no cure at the moment. It is a multifactorial degenerative disease with an inflammatory component mediated by numerous proinflammatory and anti-inflammatory cytokines, chemokines, and growth factors. OA is not yet fully understood; therefore, therapeutic interventions are aimed primarily at reducing symptoms and slowing the progression of joint destruction. Of the therapeutic options available, the most often prescribed are nonsteroidal antirheumatic drugs, which have numerous side effects. Therefore, a need for a safe, effective substance is differentiated, which will be used in adjuvant treatment, but also in disease prevention, and which will comparatively have no or fewer side effects. One such substance is curcumin, a hydrophobic polyphenol that forms the active component of the rhizome of the Curcuma longa plant. Several studies have shown its potent antioxidant and anti-inflammatory effect, non-toxicity, and safety at high daily doses. In addition to blocking chondrocyte apoptosis, curcumin also blocks the expression of cyclooxygenase, prostaglandin E-2 and proinflammatory cytokines in chondrocytes, potentially alleviating symptomatic diseases. Although there are significant variations in quality, methodology, and research results conducted on curcumin efficiency in OA treatment, curcumin is primarily recommended as systematic short-term and medium-term adjuvant therapy that reduces inflammatory biochemical factors. Reducing inflammation leads to better pain regulation and improved joint function, significantly reducing standard prescribed doses of drugs. The most researched daily doses of curcumin intake are 1000-2000 mg/day, which would also be the doses that most of the authors recommend. Further research is needed to determine the preventive role of curcumin in the pathogenesis of OA, the effects of long-term usage of curcumin in preventive purposes and treatment of osteoarthritis, as well as to determine optimal therapeutic dosages.


Phenotypes of the fourth complement component (C4) in black Americans from the southeastern United States.
C4 is composed of two tightly linked genes (C4A and C4B) lying within the major histocompatibility complex of chromosome 6 that can be demonstrated by agarose gel electrophoresis. Seven alleles and five alleles at the C4A and C4B loci, respectively, were detected in 169 black individuals from the southeastern United States. Furthermore, the phenotypic frequencies of C4A6, C4A5, C4A4, C4B4, C4B3 and C4BQ0 were significantly different between black and white Americans.


The CHARGE syndrome ortholog CHD-7 regulates TGF-β pathways in Caenorhabditis elegans.
CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein-7 (CHD7) and characterized by retarded growth and malformations in the heart and nervous system. Despite the public health relevance of this disorder, relevant cellular pathways and targets of CHD7 that relate to disease pathology are still poorly understood. Here we report that chd-7, the nematode ortholog of Chd7, is required for dauer morphogenesis, lifespan determination, stress response, and body size determination. Consistent with our discoveries, we found chd-7 to be allelic to scd-3, a previously identified dauer suppressor from the DAF-7/ tumor growth factor-β (TGF-β) pathway. Epistatic analysis places CHD-7 at the level of the DAF-3/DAF-5 complex, but we found that CHD-7 also directly impacts the expression of multiple components of this pathway. Transcriptomic analysis revealed that chd-7 mutants fail to repress daf-9 for execution of the dauer program. In addition, CHD-7 regulates the DBL-1/BMP pathway components and shares roles in male tail development and cuticle synthesis. To explore a potential conserved function for chd-7 in vertebrates, we used Xenopus laevis embryos, an established model to study craniofacial development. Morpholino-mediated knockdown of Chd7 led to a reduction in col2a1 messenger RNA (mRNA) levels, a collagen whose expression depends on TGF-β signaling. Both embryonic lethality and craniofacial defects in Chd7-depleted tadpoles were partially rescued by overexpression of col2a1 mRNA. We suggest that Chd7 has conserved roles in regulation of the TGF-β signaling pathway and pathogenic Chd7 could lead to a defective extracellular matrix deposition.


Investigations of the relationship betw een disease and airborne (1-->3)-beta-D-glucan in buildings.
Studies on the relationship between symptoms in indoor air and the amount of airborne (1-->3)-beta-D-glucan were reviewed. Relationships were found for symptoms and objective tests of airways inflammation. The data suggest that (1-->3)-beta-D-glucan could be a causative agent.


[Alcoholic hepatopathy].
To extensively discuss clinical features, laboratory data and pathology findings associated with alcoholic hepatitis as well as the new insights into pathogenesis and the appropriate therapy. Review of current literature. Acetaldehyde gives rise to neoantigens by complexing with various proteins, which, in turn, favors the appearance of autoantibodies. Antibodies against the hepatic lipoprotein and a number of hepatocyte surface glycoproteins have been detected in alcoholic hepatitis. Experimental studies have shown that acetaldehyde and malonyldialdehyde form highly immunogenic aggregates (MAA adducts). Antibody titers are usually higher in patients with more advanced disease, which argues for a major etiologic role. HLA antigens such as B8, DR3, DR4, which are usually associated with autoimmune diseases, are more frequently observed in alcoholic hepatitis patients. Despite the above, it is still questionable whether alcoholic hepatitis pathogenesis is autoimmune in origin. Why do only 15-20% of subjects who have long been abused alcohol develop hepatitis? What are the predisposing factors? What events trigger the immunologic reactivity? If MAA adducts play a role, why are not all the alcohol abusers affected by hepatitis? Transplantation outcome in well selected patients with alcoholic hepatitis is as good as--or even better than--the one reported for patients with different types of hepatitis.


Inhibition of TAK1/TAB2 complex formation by costunolide attenuates obesity cardiomyopathy via the NF-κB signaling pathway.
Chronic and persistent obesity can lead to various complications, including obesity cardiomyopathy. Inhibition of the inflammatory response is an effective measure for the intervention of obesity cardiomyopathy. Numerous studies indicate that costunolide (Cos) can reduce inflammation. However, the role of Cos in obesity cardiomyopathy and its molecular targets remains unknown. We aimed to clarify potential cardioprotective effects and mechanism of Cos against obesity cardiomyopathy. The model of obesity cardiomyopathy was established by feeding mice with a high-fat diet for 24 weeks. Cos at 10 and 20 mg/kg or vehicle (1% CMCNa solution) was administered once every two days via oral gavage from the 17th to 24th week. Body weight, heart weight/tibia length, cardiac function, myocardial injury markers, pathological morphology of the heart, hypertrophic and fibrotic markers, inflammatory factors were assessed. The targets of Cos were predicted through molecular docking. Pull-down assay and biolayer interferometry were used to confirm the target of Cos. Cos effectively reduces obesity-induced cardiomyocyte inflammation, cardiac hypertrophy and fibrosis, thereby improving cardiac function. We confirmed that Cos can interact with TAK1 and inhibit downstream NF-κB pathway activation by blocking the formation of the TAK1/TAB2 complex, thus inhibiting inflammatory cytokine release in cardiomyocytes. Our results demonstrated that Cos significantly improved myocardial remodeling and cardiac dysfunction against obesity cardiomyopathy by reducing myocardial inflammation. Therefore, Cos may serve as a promising therapeutic agent in obesity cardiomyopathy.


Spontaneous regeneration of the parotid salivary gland following juvenile recurrent parotitis.
Sialograms of an 18-year-old female patient known to suffer from juvenile recurrent parotitis (JRP) disclosed the destructive glandular changes typical of the disease. During the 10 years subsequent to the sialographic examination, the patient did not experience any further attacks of JRP. Sialograms carried out when the patient was 28 years of age demonstrated a normal gland. This case illustrates that a damaged parotid gland is capable of regeneration following JRP.


Calcium-induced activation of a mutant G-protein-coupled receptor causes in vitro transformation of NIH/3T3 cells.
The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that is widely expressed, has tissue-specific functions, and regulates cell growth. Activating mutations of this receptor cause autosomal dominant hypocalcemia, a syndrome characterized by hypocalcemia and hypercalciuria. The identification of a family with an activating mutation of the CaR (Thr151Met) in which hypocalcemia cosegregates with several unusual neoplasms led us to examine the transforming effects of this mutant receptor. Transfection of NIH/3T3 cells with the mutant but not the normal receptor supported colony formation in soft agar at subphysiologic calcium concentrations. The mutant CaR causes a calcium-dependent activation of the extracellular signal-regulated protein kinase (ERK) 1/2 and Jun-N-terminal kinase/stress-activated (JNK/ SAPK) pathways, but not P38 MAP kinase. These findings contribute to a growing body of information suggesting that this receptor plays a role in the regulation of cellular proliferation, and that aberrant activation of the mutant receptor in this family may play a role in the unusual neoplastic manifestations.


Evaluation of Flow Rate, pH, Buffering Capacity, Calcium, Total Proteins and Total Antioxidant Capacity Levels of Saliva in Caries Free and Caries Active Children: An In Vivo Study.
The purpose of this study was to evaluate the relationship between the physicochemical properties of saliva such as flow rate, pH, buffering capacity, calcium level, total protein and total antioxidant levels in caries free and caries active children. The present study included one hundred and twenty healthy children who were divided into two groups; group I and group II comprising of age groups 7-10 and 11-14 years, respectively. Both the groups were then sub-divided equally according to gender. They were further divided into caries free and caries active with 15 children in each group. Unstimulated saliva was collected by suction method and flow rates were determined. The samples were then analyzed for pH, buffering capacity, total protein, calcium and total antioxidant capacity. The data was statistically analyzed using student t test (unpaired). The results revealed that when all these parameters were compared among the caries free and caries active children, flow rate, pH, buffering capacity were slightly reduced in caries active children, but total protein and total antioxidant capacity of saliva increased significantly in caries active children and the total calcium decreased significantly in caries active children. Within the limitation of this study, we conclude that, the physicochemical properties of saliva play a major role in the development of caries.


The Impact of Skip vs. Non-Skip N2 Lymph Node Metastasis on the Prognosis of Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.
Objective: The skip N2 metastases were frequent in non-small-cell lung cancer (NSCLC) and the better prognosis of NSCLC with a skip over non-skip N2 lymph node metastases is controversial. The primary aim of this study is to investigate the prognosis effect of skip N2 lymph node metastases on the survival of NSCLC. Setting: A literature search was conducted in PubMed, EMBASE, and Cochrane Library with the term of "N2" or "mediastinal lymph node" or "mediastinal nodal metastases", and "lung cancer" and "skip" or "skipping" in the title/abstract field. The primary outcomes of interests are 3- and 5-year survival in NSCLC. Participants: Patients who underwent complete resection by lobectomy, bilobectomy, or pneumonectomy with systemic ipsilateral lymphadenectomy and were staged as pathologically N2 were included. Primary and Secondary Outcome Measures: The 3- and 5-year survival of NSCLC was analyzed. The impact of publication year, number of patients, baseline mean age, gender, histology, adjuvant therapy, number of skip N2 stations, and survival analysis methods on the primary outcome were also analyzed. Results: A total of 21 of 409 studies with 6,806 patients met the inclusion criteria and were finally included for the analysis. The skip N2 lymph node metastases NSCLC had a significantly better overall survival (OS) than the non-skip N2 NSCLC [hazard ratio (HR), 0.71; 95% CI, 0.62-0.82; P < 0.001; I 2 = 40.4%]. The skip N2 lymph node metastases NSCLC had significantly higher 3- and 5-year survival rates than the non-skip N2 lymph node metastases NSCLC (OR, 0.75; 95% CI, 0.66-0.84; P < 0.001; I 2 = 60%; and OR, 0.78; 95% CI, 0.71-0.86; P < 0.001; I 2 = 67.1%, respectively). Conclusion: This meta-analysis suggests that the prognosis of skip N2 lymph node metastases NSCLC is better than that of a non-skip N2 lymph node.


Low-density lipoprotein profile changes during the neonatal period.
To investigate natural change of low-density lipoprotein (LDL) profile during the neonatal period and the impact of gestational age and birth weight on those changes. We measured lipid composition in LDL fraction, LDL particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age. Low-density lipoprotein cholesterol and apoB concentrations increased from birth to 5 days of age, and the concentration persisted at 1 month in breast-fed and mixed-fed infants. However, in formula-fed infants, the concentration decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were smaller and more cholesterol rich than at 5 days of age. Single regression analyses showed that gestational age had influenced the LDL profile at birth and 5 days of age, while at 1 month milk determined the profile. The number of LDL particles increased rapidly during the first 5 days of life, and the composition of LDL particles is modulated by TG content throughout the neonatal period. Gestational age and milk, rather than birth weight, determine postnatal changes in LDL profile.


Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis.
Pendrin (SLC26A4) is a Cl(-)/anion exchanger expressed in the epithelium of inflamed airways where it is thought to facilitate Cl(-) absorption and HCO3 (-) secretion. Studies using pendrin knockout mice and airway epithelial cells from hearing-impaired subjects with pendrin loss of function suggest involvement of pendrin in inflammatory lung diseases, including cystic fibrosis (CF), perhaps by regulation of airway surface liquid (ASL) volume. Here we identified small-molecule pendrin inhibitors and demonstrated their efficacy in increasing ASL volume. A cell-based, functional high-throughput screen of ∼36,000 synthetic small molecules produced 3 chemical classes of inhibitors of human pendrin. After structure-activity studies, tetrahydropyrazolopyridine and pyrazolothiophenesulfonamide compounds reversibly inhibited pendrin-facilitated Cl(-) exchange with SCN(-), I(-), NO3 (-), and HCO3 (-) with drug concentration causing 50% inhibition down to ∼2.5 μM. In well-differentiated primary cultures of human airway epithelial cells from non-CF and CF subjects, treatment with IL-13, which causes inflammation with strong pendrin up-regulation, strongly increased Cl(-)/HCO3 (-) exchange and the increase was blocked by pendrin inhibition. Pendrin inhibition significantly increased ASL depth (by ∼8 μm) in IL-13-treated non-CF and CF cells but not in untreated cells. These studies implicate the involvement of pendrin-facilitated Cl(-)/HCO3 (-) in the regulation of ASL volume and suggest the utility of pendrin inhibitors in inflammatory lung diseases, including CF.-Haggie, P. M., Phuan, P.-W., Tan, J.-A., Zlock, L., Finkbeiner, W. E., Verkman, A. S. Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis.


Quorum sensing responses of activated sludge to free nitrous acid: Zoogloea deformation, AHL redistribution, and microbiota acclimatization.
Free nitrous acid (FNA) has been widely employed for improvement of wastewater management by altering sludge characteristic and function based on its polymer lysing and biocidal capacity. Sludge characteristic and function are commonly considered as the joint consequence of microbial individual behaviors and quorum sensing (QS) involved collective behaviours, but the role of the latter in FNA treatment was still as-yet-unidentified and addressed in this research. The results of sludge morphology and component characterized FNA-induced zoogloea deformation, including inner cell exposure, half of extracellular polymeric substances (EPS) reduction and adsorption site depletion. During zoogloea deformation, four acyl-homoserine lactones (AHLs), including C4-HSL, C8-HSL, C10-HSL and C12-HSL, transferred inward of microbiota, and their total contents reduced by 66% because of depressed signal production, augmented decomposer and recognition. Transcriptome analysis revealed that differentially expressed QS driven by AHL redistribution facilitated microbiota acclimatization including cellular motility and hydrolase synthesis for EPS consumption. Boosted motility may favor escaping from stress spot and moderating intercellular acidity based on cell motility test. Feasible EPS consumption provided nutrition for heterotrophic metabolisms testified by pure culture with EPS as sole nutrition. Our work thus comprehensively revealed QS behaviours responding to FNA and deepened the understanding to FNA treatment performance in wastewater management.


Surgical outcomes of ERCP-guided transpapillary gallbladder drainage versus percutaneous cholecystostomy as bridging therapies for acute cholecystitis followed by interval cholecystectomy.
Select patients with acute cholecystitis (AC) are not candidates for index cholecystectomy. We compared the influence of ERCP-guided transpapillary gallbladder drainage (ERGD) versus percutaneous cholecystostomy (PC) on delayed cholecystectomy outcomes. Consecutive patients undergoing ERGD or PC for AC from January 2007 to October 2018 were included. Primary outcome was the rate of conversion to open cholecystectomy and perioperative complications in groups. The study included 52 patients with ERGD and 140 with PC prior to cholecystectomy (median 68 days [IQR: 47-105.5]). Technical success was higher in the PC group (100% vs 91%; P = 0.0004). There was a nonsignificant trend to lower postoperative complications with ERGD (30.7% vs 43.5%; P = 0.07). No difference in conversion to open cholecystectomy OR: 1.5 (95% CI: 0.68-3.65; P = 0.28) or severity of complications (Clavien-Dindo grade >2) OR: 0.60, (95% CI: 0.19-1.87; P = 0.38) was noted between the ERGD and PC groups. PC was associated with higher rates of unplanned repeat intervention (16.4% vs 7.7%; P = 0.02). ERGD is suitable for patients with AC who is candidates for delayed cholecystectomy and should be considered for gallbladder drainage in patients with concomitant choledocholithiasis or cholangitis who require ERCP.


Therapeutic communication improves patient comfort during venipuncture in children: a single-blinded intervention study.
The aim of this study was to examine whether therapeutic communication improves children's comfort during venipuncture compared to standard communication. This study was registered in the Dutch trial register (NL8221), December 10, 2019. This single-blinded interventional study was carried out in an outpatient clinic of a tertiary hospital. Inclusion criteria were age between 5 and 18 years, use of topical anesthesia (EMLA) and sufficient understanding of the Dutch language. 105 children were included, 51 assigned to the standard communication group (SC group) and 54 patients to the therapeutic communication group (TC group). The primary outcome measure was self-reported pain based on the Faces Pain Scale Revised (FPS-R). Secondary outcome measures were observed pain (numeric rating scale (NRS)), self-reported/observed anxiety in child and parent (NRS), self-reported satisfaction in child, parent and medical personnel (NRS), and procedural time. No difference was found for self-reported pain. Self-reported and observed anxiety (by parents and medical personnel) was lower in the TC group (p-values ranged from p = 0.005 to p = 0.048). Procedural time was lower in the TC group (p = 0.011). Satisfaction level of medical personnel was higher in the TC group (p = 0.014). Conclusion: TC during venipuncture did not result in lower self-reported pain. However, secondary outcomes (observed pain, anxiety and procedural time) were significantly improved in the TC group. What is Known: • Medical procedures, especially needle related procedures, cause anxiety and fear in children and adults. • In adults communication techniques based on hypnosis are effective in reducing pain and anxiety during medical procedures. What is New: • Our study found that with a small change in communication technique (called therapeutic communication or TC), the comfort of children during venipuncture improves. • This improved comfort was mainly reflected by reduced anxiety scores and shorter procedural time. This makes TC suitable for the outpatient setting.


Actinomycosis caecum. A case report.
A case of caecal actinomycosis presenting as a lump in the right iliac fossa is discussed. A right hemicolectomy was performed with complete cure. Clinical awareness of this condition is necessary for proper management and to differentiate it from tumour.


Role of central NMDA versus non-NMDA receptor in spinal withdrawal reflex in spinal anesthetized rats under normal and hyperexcitable conditions.
The present study aimed to investigate the role of central N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the spinal withdrawal reflex assessed by recording single motor unit (SMU) electromyogram (EMG) response to peripheral mechanical (pressure, pinch) stimuli and repeated electrical stimuli at 3 and 20 Hz. During normal conditions, intrathecal administration of MK-801 and CNQX apparently depressed mechanically and electrically (3 Hz) evoked EMG responses in a dose-dependent manner (10, 20 and 40 nmol in 10 microl). In contrast, the after-discharges to 20 Hz electrical stimuli were suppressed only by CNQX treatment, not by MK-801 treatment. This indicates that the central mechanisms underlying the different frequencies of electrically evoked withdrawal reflex may be different. During peripheral bee venom (BV, 0.2 mg/50 microl) induced inflammation and central sensitization, the enhanced SMU EMG responses including after-discharges to pinch stimuli and 3 Hz electrical stimuli were depressed significantly by treatments with both MK-801 and CNQX. However, the enhanced SMU activities to innocuous pressure stimuli were depressed only by treatment with CNQX. Likewise, enhanced long lasting after-discharges elicited by 20 Hz electrical stimuli were also only depressed by CNQX, indicating that different central mechanisms are involved in the persistent hyperexcitability during BV-induced inflammation. The data suggest that both central NMDA and non-NMDA receptors play important roles in the transmission of nociceptive information under normal conditions. In BV-induced inflammation, however, central non-NMDA receptors, but not NMDA receptors, play a pivotal role in the generation of persistent hyperexcitability to mechanical and electrical stimuli at different frequencies (3 Hz, 20 Hz).


The change of pain classes over time: a latent transition analysis.
Pain is common in older adults, and associated with increased morbidity and reduced quality of life. Recent research has highlighted different classes of older adults with pain, each with differing impacts on their life. It has not yet been investigated if, and how, such classes change over time and what influences individuals to prospectively transition to a profile of either improved or worsened pain impact. Latent transition analysis (LTA) is a longitudinal model-based approach to identifying underlying subgroups in a population. LTA was used to model the change in pain of people aged 50 and above, from The Irish Longitudinal Study on Ageing, across three waves (n = 5,925). The LTA model was extended to include biopsychosocial covariates to predict transition probabilities between classes over time. Three latent classes were identified based on three pain indicators (pain presence; pain affects daily life; pain requires medication) and were characterized as "No Pain", "Low-Moderate Impact Pain" and "High Impact Pain". Results indicate that the pain class of many changes over time. However, poor physical or mental health increased the risk of transitioning to a more severe pain class, from Wave 1 to Wave 2 and Wave 2 to Wave 3. These findings show the change in pain of older adults over time, with both marked improvement and deterioration being observed. Critically, the predictors of individuals transitioning between classes reflect the breadth of biopsychosocial factors involved in pain. This article identified differing classes of pain in older adults, using latent transition analysis. The analysis demonstrated how the pain classes of older adults are broadly consistent over time, however both improvement and deterioration in pain impact were observed. Transitions between classes were associated with several biopsychosocial factors. These results have important implications for the health and quality of life of older adults. Consideration of health, lifestyle and socio-demographic factors may enhance assessment and management of pain in older adults.


Communication Through Coherence by Means of Cross-frequency Coupling.
The theory of communication through coherence (CTC) posits the synchronization of brain oscillations as a key mechanism for information sharing and perceptual binding. In a parallel literature, hippocampal theta activity (4-10 Hz) has been shown to modulate the appearance of neocortical fast gamma oscillations (100-150 Hz), a phenomenon known as cross-frequency coupling (CFC). Even though CFC has also been previously associated with information routing, it remains to be determined whether it directly relates to CTC. In particular, for the theta-fast gamma example at hand, a critical question is to know if the phase of the theta cycle influences gamma synchronization across the neocortex. To answer this question, we combined CFC (modulation index) and CTC (phase-locking value) metrics in order to detect the modulation of the cross-regional high-frequency synchronization by the phase of slower oscillations. Upon applying this method, we found that the inter-hemispheric synchronization of neocortical fast gamma during REM sleep depends on the instantaneous phase of the theta rhythm. These results show that CFC is likely to aid long-range information transfer by facilitating the synchronization of faster rhythms, thus consistent with classical CTC views.


Lymph Node Examination and Patterns of Nodal Metastasis Among Patients with Left- Versus Right-Sided Intrahepatic Cholangiocarcinoma After Major Curative-Intent Resection.
We sought to investigate whether the unique lateral patterns of lymphatic drainage impacted lymphadenectomy (LND), lymph node metastasis (LNM), and long-term survival of patients after curative hemi-hepatectomy for left- versus right-sided intrahepatic cholangiocarcinoma (ICC). Data on patients who underwent curative hemi-hepatectomy for left- or right-sided ICC were collected from 15 high-volume centers worldwide, as well as from the Surveillance, Epidemiology, and End Results (SEER) registry. Primary outcomes included overall survival (OS) and disease-free survival (DFS). Among 697 patients identified from the multi-institutional database, patients who underwent hemi-hepatectomy for left-sided ICC (n = 363, 52.1%) were more likely to have an increased number of LND versus patients with right-sided ICC (n = 334, 47.9%) (median, left 5 versus right 3, p = 0.012), although the frequency (left 66.4% versus right 63.8%, p = 0.469) and station (beyond station no. 12, left 25.3% versus right 21.1%, p = 0.293) were similar. Consequently, left-sided ICC was associated with higher incidence of LNM (left 33.3% versus right 25.7%, p = 0.036), whereas the station and number of LNM were not different (both p > 0.1). There was no difference in OS (median, left 34.9 versus right 29.6 months, p = 0.130) or DFS (median, left 14.5 versus right 15.2 months, p = 0.771) among patients who underwent hemi-hepatectomy for left- versus right-sided ICC, which were also verified in the SEER dataset. LNM beyond station no. 12 was associated with even worse long-term survival versus LNM within station no. 12 among patients with either left- or right-sided ICC after curative-intent resection (all p < 0.05). The unique lateral patterns of lymphatic drainage were closely related to utilization of LND, as well as LNM of left- versus right-sided ICC.


Synthesis and spectral properties of a highly soluble push-pull type of quinoidal thiophenes.
[structures: see text] A series of push-pull quinoidal thiophenes 5a,b and 6a-c substituted with an electron-donating 1,3-dithiol-2-ylidene unit and an electron-withdrawing dicyanomethylene unit at the terminals is developed. They are highly soluble in common solvents and deeply colored with extension of the thienoquinoid skeleton.


Not just semantics: strong frequency and weak cognate effects on semantic association in bilinguals.
To investigate the possibility that knowledge of two languages influences the nature of semantic representations, bilinguals and monolinguals were compared in a word association task. In Experiment 1, bilinguals produced less typical responses relative to monolinguals when given cues with a very common associate (e.g., given bride, bilinguals said "dress" instead of "groom"). In Experiment 2, bilinguals produced responses as typical as those of monolinguals when given cues with high-frequency associates, but not when given cues with low-frequency associates. Bilinguals' responses were also affected, to a certain extent, by the cognate status of the stimulus word pairs: They were more similar to monolinguals' responses when the cue and its strongest associate were both cognates (e.g., minute-second is minuto-segundo in Spanish), as opposed to both being noncognates. Experiment 3 confirmed the presence of a robust frequency effect on bilingual but not on monolingual association responses. These findings imply a lexical locus for the bilingual effect on association responses and reveal the association task to be not quite as purely semantic as was previously assumed.


Cholesterol crystals in synovial and bursal fluid.
Cholesterol crystals were found in two patients with classic rheumatoid arthritis (RA). In one patient, cholesterol crystals were found in synovial fluid from both shoulder joints, and in the second they were in an olecranon bursa. To examine the possible systemic etiology of cholesterol crystals in synovial and bursal fluid, lipid concentrations and the presence of serum antilipoprotein antibodies were measured. Antilipoprotein antibodies were not found. The concentration of lipid and lipoproteins, as well as the normal pattern of lipoprotein on agarose gel, eliminates the possibility of hyperlipoproteinemia. Results seemed to exclude a systemic etiology for the formation of cholesterol crystals in synovial and bursal fluid in the RA patients. It appears that several local factors such as defective drainage, local destruction, increased permeability of synovial membrane, and intraarticular (bursal) bleeding are possible etiologies.


Multiplex bead binding assays using off-the-shelf components and common flow cytometers.
The ability to quantify protein-ligand interactions in an accurate and high-throughput manner is important in diverse areas of biology and medicine. Multiplex bead binding assays (MBBAs) are powerful methods that allow for simultaneous analysis of many protein-ligand interactions. Although there are a number of well-established MBBA platforms, there are few platforms suitable for research and development that offer rapid experimentation at low costs and without the need for specialized reagents or instruments dedicated for MBBA. Here, we describe a MBBA method that uses low-cost reagents and standard cytometers. The key innovation is the use of the essentially irreversible biotin-streptavidin interaction. We prepared a biotin-conjugated fluorescent dye and used it to produce streptavidin-coated magnetic beads that are labeled at distinct levels of fluorescence. We show the utility of our method in characterization of phage-displayed antibodies against multiple antigens of SARS-CoV-2, which substantially improves the throughput and dramatically reduces antigen consumption compared with conventional phage ELISA methods. This approach will make MBBAs more broadly accessible.


Expert clinical decision support systems to enhance antimicrobial stewardship programs: insights from the society of infectious diseases pharmacists.
Health care-associated infections (HAIs) are a leading cause of in-hospital mortality and adverse events such as antimicrobial resistance. These infections place tremendous burdens on the health care system and create situations for misuse of antimicrobial drugs. Recognition of these factors has led professional societies, clinicians, and hospitals to develop programs to improve the management of HAIs and the use of antimicrobial drugs. The clinical literature is replete with examples of these programs, often referred to as antimicrobial stewardship. Traditionally, antimicrobial stewardship programs have relied on manual methods combined with clinical oversight and intervention. The advent of modern health care information technology offers the opportunity to expand the breadth and depth of these programs. Expert clinical decision support systems are the most promising of these information technology advances.


[Clinical and epidemiological characteristics of human immunodeficiency virus infection in foreigners residing in Elche, Spain (1998-2003)].
To determine the characteristics of HIV-infection in foreign patients residing in Elche, Spain. A retrospective comparative analysis of clinical and epidemiological characteristics was performed to study HIV-infection in foreign immigrants, foreigners who were not immigrants and the native Spanish population between January 1998 and December 2003. Among the 659 patients attended, 30 (4.6%) were foreign immigrants and 11 (1.7%) foreign non-immigrants. The percentage of affected immigrants increased during the study period from 1.6% to 9.8% (p < 0.001). There was a higher percentage of women in the immigrant group (36.7%) than in the foreign non-immigrant (27.3%) and native (18.4%) groups (p = 0.04). Mean age of the immigrants was lower than that of the foreign non-immigrants and native population (p = 0.02). Sexual transmission as a risk factor for acquiring HIV infection was higher in the immigrant (80%) group than in the foreign non-immigrant (27.3%) and native populations (14.7%), (p = 0.005). Antiretroviral treatment and mortality were similar in immigrant and non-immigrant patients. The epidemiology of HIV infection in foreign patients was different from that observed in the native population, but access to antiretroviral treatment and mortality were similar.


5'-triphosphate recycles independently of acetylcholine in cholinergic synaptic vesicles.
The effect of hemicholinium-3 (HC-3) on vesicular contents in acetylcholine (ACh) and 5-triphosphate (ATP) and the vesicular incorporation of 14C-label derived from [14C]choline ,nd 3H-label derived from [3H]adenosine was investigated after low frequency stimulation (with a subsequent rest period) of the Torpedo electric organ. HC-3 (100 microM) caused an increased depletion of vesicular ACh and blocked the incorporation of 14C-label whereas contents in vesicular ATP and 3H-incorporation were identical with and without HC-3. HC-3 also blocked the recovery of electrical response of the tissue after stimulation but did not cause a change in vesicle numbers. The result suggest that synaptic vesicles continue to recycle ATP in the absence of recycling of ACh and that vesicular uptake and storage of the two components are not coupled to each other.


Strategies for preventing distractions and interruptions in the OR.
Stakeholders in the automotive industry, airline industry, and anesthesia profession have identified critical periods of time in which distractions and interruptions of normal processes can have devastating effects. Just as reducing distractions improves safety in an automobile or airplane cockpit, limiting distractions and interruptions during critical times in the perioperative setting can increase patient safety. We assessed perioperative nurses and identified what they perceived as critical phases of nursing care. We also worked with our anesthesia partners to address their concerns about interruptions during the administration of nerve blocks. The perioperative nurses at our hospital initiated strategies to reduce distractions or interruptions to their practice at critical points, and, in collaboration with surgical committee members, we developed strategies to reduce or eliminate distractions for anesthesia professionals during the preoperative administration of nerve blocks and to eliminate distractions for the RN circulator and scrub person during the final counts.


Expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in pituitary adenomas.
Hypoxia-inducible factor (HIF)-1alpha is a transcription factor in hypoxia adaptation mechanisms. In malignant tumors, HIF-1alpha upregulates vascular endothelial growth factor (VEGF) expression to induce tumor angiogenesis. Although VEGF and HIF-1alpha are expressed in pituitary adenomas, the relationships of these factors remain unclear. Therefore, we examined the expression of HIF-1alpha and VEGF using real-time RT-PCR and immunohistochemistry to clarify the relationship of these factors in pituitary adenomas. HIF-1alpha mRNA and VEGF mRNA levels in pituitary adenoma tissues from 25 operated patients were quantified using real-time RT-PCR. Some tissues were also studied by double fluorescent immunohistochemical methods. HIF-1alpha mRNA and protein were expressed in all pituitary adenomas examined. Their expression tended to be higher in GH-producing and lower in ACTH-producing tumors. VEGF mRNA and protein were also expressed in all pituitary adenomas. There was no significant correlation in the expression levels of HIF-1alpha and VEGF mRNA. The mutual expression of HIF-1alpha and VEGF was of no significance; in only a few cells were HIF-1alpha and VEGF co-localized. Our results suggest that in pituitary adenomas VEGF expression may not depend strongly on HIF-1alpha expression.


Deferred treatment for clinically localized prostate cancer.
With the available data, deferred treatment is definitely an option for patients with low grade clinically localized prostate cancer if their life expectancy is 10 years or less and avoids the side-effects of treatment. Many patients will avoid the need for therapy of their prostate cancer during their remaining lifetime.


A bacterial lipooligosaccharide that naturally mimics the epitope of the HIV-neutralizing antibody 2G12 as a template for vaccine design.
The broadly neutralizing antibody 2G12 binds a fairly conserved cluster of oligomannose sugars on the HIV surface glycoprotein gp120, which has led to the hypothesis that these sugars pose potential vaccine targets. Here, we present the chemical analysis, antigenicity, and immunogenicity of a bacterial lipooligosaccharide (LOS) comprised of a manno-oligosaccharide sequence analogous to the 2G12 epitope. Antigenic similarity of the LOS to oligomannose was evidenced by 2G12 binding to the LOS and the inability of sera elicited against synthetic oligomannosides, but incapable of binding natural oligomannose, to bind the LOS. Immunization with heat-killed bacteria yielded epitope-specific serum antibodies with the capacity to bind soluble gp120. Although these sera did not exhibit specific anti-HIV activity, our data suggest that this LOS may find utility as a template for the design of glycoconjugates to target HIV.