Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-α.
In this review article, we aimed to discuss intricate roles of SD in modulating depression in preclinical and clinical studies. Decades of research have shown the inconsistent effects of SD on depression, focusing on SD duration. However, inconsistent role of SD seems to be more complicated, and SD duration cannot be the only one factor. Regarding this issue, we chose some important factors involved in the effects of SD on cognitive functions and mood including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), serotonin, cortisol, and tumor necrosis factor-alpha (TNF-α). It was concluded that SD has a wide-range of inconsistent effects on BDNF, VEGF, serotonin, and cortisol levels. It was noted that BDNF diurnal rhythm is significantly involved in the modulatory role of SD in depression. Furthermore, the important role of VEGF in blood-brain barrier permeability which is involved in modulating depression was discussed. It was also noted that there is a negative correlation between cortisol and BDNF that modulates depression. Eventually, it was concluded that TNF-α regulates sleep/wake cycle and is involved in the vulnerability to cognitive and behavioral impairments following SD. TNF-α also increases the permeability of the blood-brain barrier which is accompanied by depressive behavior. In sum, it was suggested that future studies should focus on these mechanisms/factors to better investigate the reasons behind intricate roles of SD in modulating depression.


Aqueous Extract of Brazilian Berry (Myrciaria jaboticaba) Peel Improves Inflammatory Parameters and Modulates Lactobacillus and Bifidobacterium in Rats with Induced-Colitis.
Natural compounds could be a complementary alternative to inflammatory bowel disease (IBD) management. This study determined the effects of an aqueous extract of Myrciaria jaboticaba peel (EJP) (50 g L-1) on 2,4,6-trinitrobenzenesulfonic acid-induced colitis. Wistar rats were randomized into five groups: HC-healthy control, CC-colitis control, DC-drug control, SJ-short-term treatment with EJP, and LJ-long-term treatment with EJP. The EJP treatments reduced body weight loss, stool consistency score, and spleen enlargement. Gut microbiota was modulated through increased Lactobacillus and Bifidobacterium counts after EJP treatment. Short-chain fatty acids were also higher in the EJP treatment groups. The antioxidant enzyme activities were greater than CC or DC controls. Myeloperoxidase activity (LJ), inducible nitric oxide synthase (LJ/SJ), and intercellular adhesion molecule (SJ) levels were lower than in the CC group. EJP decreased histological scoring, mucosal thickness, and preserved the crypts and histological structure. Therefore, EJP showed beneficial effects and could be potentially used as an adjuvant in IBD treatment.


Jacobsen protocols for large-scale epoxidation of cyclic dienyl sulfones: application to the (+)-pretazettine core.
A Jacobsen epoxidation protocol using H2O2 as oxidant was designed for the large-scale preparation of various epoxy vinyl sulfones. A number of cocatalysts were screened, and pH control led to increased reaction rate, higher turnover number, and improved reliability.


Gas-liquid chromatographic determination of ibuprofen in human plasma.
A gas-liquid chromatographic method for the estimation of Ibuprofen in human plasma is described. The procedure is rapid with the free drug being analysed thus eliminating the need for any derivatisation steps. The method allows the drug concentrations to be analysed down to a level of 2 mg/l using 2 ml plasma.


Correlation of the Health Sciences Reasoning Test with student admission variables.
To assess the association between scores on the Health Sciences Reasoning Test (HSRT) and pharmacy student admission variables. During the student admissions process, cognitive data, including undergraduate grade point average and Pharmacy College Admission Test (PCAT) scores, were collected from matriculating doctor of pharmacy (PharmD) students. Between 2007 and 2009, the HSRT was administered to 329 first-year PharmD students. Correlations between HSRT scores and cognitive data, previous degree, and gender were examined. After controlling for other predictors, 3 variables were significantly associated with HSRT scores: percentile rank on the reading comprehension (p<0.001), verbal (p<0.001), and quantitative (p<0.001) subsections of the PCAT. Scores on the reading comprehension, verbal, and quantitative sections of the PCAT were significantly associated with HSRT scores. Some elements of critical thinking may be measured by these PCAT subsections. However, the HSRT offers information absent in standard cognitive admission criteria.


Diuretic activity of Artemisia thuscula, an endemic Canary species.
A pharmacological evaluation for diuretic activity of infusions at 5, 10 and 15% of Artemisia thuscula Cav. was carried out. Urinary excretion of water, pH, density, conductivity and Na(+), K(+) and Cl(-) content were investigated in saline-loaded rats. The infusions showed a dose-dependent decrease diuretic effect, but augmented significantly with respect to the control group for the urinary excretion of water and sodium. Furthermore, a potassium-sparing effect at 5 and 10% was showed. The diuretic effect does not seem to be related to the potassium content of the starting material. The results justify the use of Artemisia thuscula as diuretic agent by the canary traditional medicine.


Inhibition of native TRPC6 channel activity by phosphatidylinositol 4,5-bisphosphate in mesenteric artery myocytes.
The present work investigates the effect of phosphatidylinositol-4,5-bisphosphate (PIP(2)) on native TRPC6 channel activity in freshly dispersed rabbit mesenteric artery myocytes using patch clamp recording and co-immunoprecipitation methods. Inclusion of 100 microM diC8-PIP(2) in the patch pipette and bathing solutions, respectively, inhibited angiotensin II (Ang II)-evoked whole-cell cation currents and TRPC6 channel activity by over 90%. In inside-out patches diC8-PIP(2) also inhibited TRPC6 activity induced by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) with an IC(50) of 7.6 microM. Anti-PIP(2) antibodies potentiated Ang II- and OAG-evoked TRPC6 activity by about 2-fold. Depleters of tissue PIP(2) wortmannin and LY294002 stimulated TRPC6 activity, as did the polycation PIP(2) scavenger poly-L-lysine. Wortmannin reduced Ang II-evoked TRPC6 activity by over 75% but increased OAG-induced TRPC6 activity by over 50-fold. Co-immunoprecipitation studies demonstrated association between PIP(2) and TRPC6 proteins in tissue lysates. Pre-treatment with Ang II, OAG and wortmannin reduced TRPC6 association with PIP(2). These results provide for the first time compelling evidence that constitutively produced PIP(2) exerts a powerful inhibitory action on native TRPC6 channels.


Reliable phase quantification in focused probe electron ptychography of thin materials.
Electron ptychography provides highly sensitive, dose efficient phase images which can be corrected for aberrations after the data has been acquired. This is crucial when very precise quantification is required, such as with sensitivity to charge transfer due to bonding. Drift can now be essentially eliminated as a major impediment to focused probe ptychography, which benefits from the availability of easily interpretable simultaneous Z-contrast imaging. However challenges have remained when quantifying the ptychographic phases of atomic sites. The phase response of a single atom has a negative halo which can cause atoms to reduce in phase when brought closer together. When unaccounted for, as in integrating methods of quantification, this effect can completely obscure the effects of charge transfer. Here we provide a new method of quantification that overcomes this challenge, at least for 2D materials, and is robust to experimental parameters such as noise, sample tilt.


A new sensitive and selective detection of Ga3+ by thiophene-based 'turn-on' fluorescent chemosensor.
We designed a thiophene-based fluorescent chemosensor DHTC ((E)-2-([3,5-dichloro-2-hydroxybenzylidene]amino)thiophene-3-carboxamide) for detecting gallium (Ga3+ ). DHTC could probe Ga3+ using fluorescence enhancement. The limit of detection for Ga3+ by DHTC was 0.39 μM. The binding mode of DHTC to Ga3+ was determined as a 1:1 ratio from analysis by Job's plot and electrospray ionization-mass spectrometry (ESI-MS). In addition, DHTC could selectively detect Ga3+ using test kits. The sensing process of Ga3+ by DHTC was presented using ultraviolet-visible light titration, Job's plot, ESI-MS, 1 H nuclear magnetic resonance titration, and density functional theory calculation.


Prolonged infusion of cycloheximide does not block mossy fiber sprouting in a model of temporal lobe epilepsy.
The role of protein synthesis in mossy fiber sprouting is unclear. Conflicting reports exist on whether a single dose of the protein synthesis-blocker cycloheximide administered around the time of an epileptogenic injury can block the eventual development of mossy fiber sprouting. In rats, osmotic minipumps and cannulae were implanted to deliver 8 mg/ml cycloheximide to one dentate gyrus and vehicle to the other. This method has been used to block protein synthesis in the infused region for up to 5 days with minimal neurotoxic effects (Taha and Stryker, Neuron 2002;34:425-36). After 2 days of infusion, rats were treated with pilocarpine to induce status epilepticus. Pumps were removed 3 days later. Thirty days after pilocarpine treatment, rats were perfused, and hippocampal sections were processed for Timm staining. Timm staining revealed aberrant mossy fiber sprouting in the inner molecular layer regardless of whether hippocampi were treated with cycloheximide or vehicle. Cycloheximide-treated hippocampi displayed more aberrant Timm staining and more tissue damage around the infusion site than did vehicle-treated hippocampi. Prolonged infusion of cycloheximide, spanning the period of pilocarpine treatment, did not block mossy fiber sprouting. This finding suggests that protein-dependent mechanisms around the time of an epileptogenic injury are not necessary for the eventual development of synaptic reorganization.


Propionate inhibits fat deposition via affecting feed intake and modulating gut microbiota in broilers.
As one of the 3 main short-chain fatty acids, the role of propionate in chicken fat metabolism is largely unknown. In this study, we demonstrated that dietary supplementation of coated sodium propionate (SP) moderately inhibits fat deposition in broiler chickens, as evidenced by the decreased adipocyte mean area (P < 0.01), the lowered triglyceride content in abdominal fat tissue (P < 0.01), and the reduced transcription of several lipogenic genes in liver and abdominal fat tissues (P < 0.05). Surprisingly, the propionate content was not significantly elevated either in serum or in the cecal chyme by SP administration (P > 0.05). However, SP application significantly decreased the average daily feed intake of broilers (P < 0.05). In addition, the composition of the cecal microbial communities was altered, with the ratio of Firmicutes to Bacteroidetes decreasing in particular (P < 0.05). At the genus level, SP application increased the richness of Alistipes, Lactobacillus, and Bifidobacterium, while reduced the abundance of Lachnospiraceae and Helicobacter significantly (P < 0.05). Moreover, in vitro experiments indicated that, although physiological concentrations of propionate (0.01 to 0.1 mmol) upregulated or downregulated the transcription of some fat synthesis-associated genes (P < 0.05), they did not significantly affect the triglyceride accumulation in hepatocytes and adipocytes (P > 0.05). These results suggest that feed supplementation with SP inhibits fat deposition in broilers by reducing feed and caloric intake, but not via direct regulation on hepatic fat synthesis or adipocytic fat deposition. Alteration in the relative populations of the gut microflora suggests that SP may have gut health implications.


Toxic air pollutants--assessing their importance.
Toxic air pollutants (TAP) are a major concern for air pollution scientists, yet our state of knowledge concerning these contaminants is not comprehensive. The paper that follows contains a critical analysis of various aspects of TAP such as regulatory controls, sources, atmospheric concentrations and health impacts. Throughout the discussion specific examples are used to illustrate particular points, and while a large body of information is referenced, the literature review is not meant to be exhaustive. Toxic air pollutants present a challenge to the air pollution scientist; the true significance of these environmental contaminants on human health has not yet been quantified, although certain studies appear to indicate that they may have important impacts on respiratory health.


Stomach carcinogenicity of caffeic acid, sesamol and catechol in rats and mice.
The carcinogenic potential of caffeic acid, sesamol and catechol was examined in male and female F344 rats and B6C3F1 mice, groups of 30 animals being treated with diets containing 2% caffeic acid, 2% sesamol or 0.8% catechol for 104 weeks (rats) or 96 weeks (mice). Histological examination revealed that caffeic acid induced forestomach squamous cell carcinoma in 57% (P less than 0.001 vs. controls) and 50% (P less than 0.001) of male and female rats, respectively, whereas sesamol was associated with squamous cell carcinoma at incidences of 31% (P less than 0.001) in male rats, and 38% (P less than 0.001) and 17% (P less than 0.05) in male and female mice, respectively. Catechol induced glandular stomach adenocarcinomas in 54% (P less than 0.001) and 43% (P less than 0.001) of male and female rats, respectively. The results thus clearly demonstrated that all three antioxidants are carcinogenic in rodent stomach epithelia.


Drinking saccharin increases food intake and preference--I. Comparison with other drinks.
To examine the orosensory and postingestive effects of saccharin solution on food intake and food preference, freely feeding rats were given flavored food to eat and a solution to drink for 2 h on eight to ten occasions. Relative to trials with a different flavored food and only water to drink, food intake was increased by drinking 0.2% saccharin or 0.45% NaCl, unaffected by drinking 1% almond extract, and decreased by drinking 10% glucose. Food preference, which was assessed in a choice test with simultaneous access to the two flavored foods, was increased by drinking 0.2% saccharin or 10% glucose and unaffected by drinking 1% almond extract or 0.45% NaCl. These results are consistent with the possibility that a combination of the oral and hydrational properties of saccharin solution increase food intake. Saccharin's sweet taste may be responsible for its effects on food preference.


Differential bystander signaling between radioresistant chondrosarcoma cells and fibroblasts after x-ray, proton, iron ion and carbon ion exposures.
Chondrosarcoma is well known as a radioresistant tumor, but the mechanisms underlying that resistance are still unclear. The bystander effect is well documented in the field of radiation biology. We investigated the bystander response induced by X-rays, protons, carbon ions, and iron ions in chondrosarcoma cells using a transwell insert co-culture system that precludes physical contact between targeted and bystander cells. Human chondrosarcoma cells were irradiated with 0.1-, 0.5-, 1-, and 2-Gy X-rays, protons, carbon ions or iron ions using a transwell insert co-culture system. Formation of micronuclei and p53 binding protein 1 staining in bystander and irradiated cells were analyzed and bystander signaling between mixed cultures of chondrosarcoma cells, and normal human skin fibroblasts was investigated. In this study, we show that the fraction of cells with DNA damages in irradiated chondrosarcoma cells showed dose-dependent increases with all beams. However, the fraction of cells with DNA damages in all bystander chondrosarcoma cells did not show any change from the levels in control cells. In the bystander signaling between mixed cultures of chondrosarcoma cells and fibroblasts, the amount of micronucleus formation in all bystander chondrosarcoma cells co-cultured with irradiated fibroblasts were the same as the levels for control cells. However, all bystander fibroblasts co-cultured with irradiated chondrosarcoma cells showed significant increases in the fraction of micronucleated cells compared to the rate of control cells. We conclude that chondrosarcoma cells in the transwell insert co-culture system could release bystander stimulations but could not develop bystander responses.


Comparative pharmacokinetic profiles of metoprolol and chlorthalidone administered alone or in combination to healthy volunteers.
A potential pharmacokinetic interaction between the beta-blocking drug, metoprolol, and the diuretic, chlorthalidone, has been investigated in three single or multiple dose studies in healthy volunteers. The pharmacokinetic profile of metoprolol 100 mg was not affected by pretreatment with or co-administration of chlorthalidone 25 mg twice daily. Similarly, the pre-dosing steady-state level of chlorthalidone during chronic treatment and its blood level profile after a single 25 mg dose were not affected by metoprolol. The bioavailabilities of the 2 drugs administered in combination were identical to those observed when each drug was administered alone. These studies demonstrate that there is no pharmacokinetic interaction between metoprolol and chlorthalidone when doses of 100 and 25 mg, respectively, are co-administered twice daily.


Tailored Chemodynamic Nanomedicine Improves Pancreatic Cancer Treatment via Controllable Damaging Neoplastic Cells and Reprogramming Tumor Microenvironment.
Pancreatic ductal adenocarcinoma (PDAC) strongly resists standard therapies since KRAS-mutated cancer cells harbor endogenous resistance toward chemotherapy-induced apoptosis and tumor-associated macrophages (TAMs) activate stroma cells to create the nearly impenetrable matrix. Herein, we developed a tailored nanocomplex through the self-assembly of synthetic 4-(phosphonooxy)phenyl-2,4-dinitrobenzenesulfonate and Fe3+ followed by hyaluronic acid decoration, realizing chemodynamic therapy (CDT) to combat PDAC. By controllably releasing its components in a GSH-sensitive manner under the distinctive redox homeostasis in cancer cells and TAMs, the nanocomplex selectively triggered a Fenton reaction to induce oxidative damage in cancer cells and simultaneously repolarized TAMs to deactivate stromal cells and thus attenuate stroma. Compared to gemcitabine, CDT remarkably inhibited tumor growth and prolonged animal survival in orthotopic PDAC models without noticeable side effects. This study provides a promising strategy to improve the treatment of PDAC through CDT-mediated controlled cancer cells damage and reprogramming of the stromal microenvironment.


Bis(3,5-di-nitro-benzoato-κO)bis-(ethane-1,2-di-amine-κ2 N,N')cadmium(II).
During systematic investigations of bioavailability and biological action enhancement of well known compounds with low bioactivity, a new mixed-ligand metal complex, [Cd(DNBA)2(en)2)] (DNBA = 3,5-di-nitro-benzoate, C7H3N2O6; en = ethyl-endi-amine, C2H8N2), has been synthesized. The complex mol-ecules are located on inversion centers. Two DNBA anions monodentately coordinate the CdII atom through an oxygen atom of the carboxyl-ate group while two en mol-ecules coordinate in a chelate fashion, resulting in a distorted O2N4 coordination set. There is a weak intra-molecular hydrogen bond of 3.099 (4) Å between the non-coordinating oxygen atom of the carboxyl-ate group and one of the en amine groups. Three relatively weak inter-molecular N-H⋯O hydrogen bonds associate complex mol-ecules into sheets extending parallel to (01), which are further stabilized by π-π inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯O/O⋯H (50.2%) and H⋯H (21.1%) inter-actions.


An outbreak of tuberculosis in an Oxfordshire school.
A primary school teacher was found to have pulmonary tuberculosis. Subsequent investigations showed that nine of her 32 pupils had been infected. The problem is discussed in the light of current recommendations designed to protect schoolchildren.


Measurement of atherosclerotic carotid plaque size in vivo using high resolution magnetic resonance imaging.
Current imaging modalities, such as contrast angiography, accurately determine the degree of luminal narrowing but provide no direct information on plaque size. Magnetic resonance imaging (MRI), however, has potential for noninvasively determining arterial wall area (WA). This study was conducted to determine the accuracy of in vivo MRI for measuring the cross-sectional maximum wall area (MaxWA) of atherosclerotic carotid arteries in a group of patients undergoing carotid endarterectomy. Fourteen patients scheduled for carotid endarterectomy underwent preoperative carotid MRI using a custom-made phased-array coil. The plaques were excised en bloc and scanned using similar imaging parameters. MaxWA measurements from the ex vivo MRI were used as the reference standard and compared with MaxWA measurements from the corresponding in vivo MR study. Agreement between the in vivo and ex vivo measurement was analyzed using the Bland-Altman method. The paired in vivo and ex vivo MaxWA measurements strongly agreed: the mean difference (in vivo minus ex vivo) in MaxWA was 13.1+/-6.5 mm2 for T1-weighted (T1W) imaging (mean MaxWA in vivo=94.7 mm2, ex vivo=81.6 mm2) and 14.1+/-11.7 mm2 for proton density-weighted (PDW) imaging (mean MaxWA in vivo=93.4 mm2, ex vivo=79.3 mm2). Intraobserver and interobserver variability was small, with intraclass correlation coefficients ranging from 0.90 to 0.98. MRI is highly accurate for in vivo measurement of artery WA in atherosclerotic carotid lesions. This imaging technique has potential application monitoring lesion size in studies examining plaque progression and/or regression.


Isolation and identification of pollen allergens of Artemisia scoparia.
The allergenic proteins of Artemisia scoparia pollen were separated and identified with ammonium sulfate precipitation, ion-exchange chromatography, gel filtration, and RAST-inhibition techniques. The important allergenic component Artemisia VI b that constitutes 29% of total protein in the extract was purified to homogeneity. It was found to be an acidic protein with isoelectric point 3.8 and molecular weight of 14,300. It was rich in carbohydrate, but the carbohydrate portion did not appear to be important for allergenicity. In the crossed immunoelectrophoresis reference pattern of the whole pollen extract, 37 precipitin lines could be identified on the anodic side, whereas Artemisia VI b could be observed as a single precipitin line. Immunologically, the whole pollen extract of A. scoparia demonstrated shared antigenic and allergenic determinants with Ageratum conyzoides-pollen extract. The use of fast protein liquid chromatography in partial purification of allergenic components is also discussed.


Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels.
Recombinant gamma interferon (rIFN-gamma) inhibits IgE synthesis in vitro by human peripheral blood mononuclear cells (PBMC). These data suggest a role for rIFN-gamma in the treatment of patients with severe atopic dermatitis (AD) and elevated IgE levels. The purpose of this study was to determine the effect of rIFN-gamma treatment on IgE production in patients with AD. Twenty-two patients with chronic severe AD were treated with rIFN-gamma. In part I of the study, 14 patients were treated with daily subcutaneous injections at three successive dose levels (0.01 mg/m2, 0.05 mg/m2, and 0.1 mg/m2) for 5 days with 2 days off between each dose level. In part II, eight patients received rIFN-gamma at 0.05 mg/m2, daily for 6 weeks. One patient from part I and eight patients from part II of the study received three times per week maintenance thereby for up to 14 months. Prior to and at selected times during and after treatment, the clinical and immunologic status of the patients was assessed. In part I, spontaneous de novo IgE synthesis by PBMC was inhibited in 10 patients receiving rIFN-gamma at 0.01 mg/m2 (p = 0.038) and in nine at 0.1 mg/m2 (p = 0.066). There was no reduction of serum IgE levels at any of the three dose levels. Total clinical severity showed improvement at each dose level (p less than 0.04) with worsening 3 days after discontinuation of treatment. In part II, there was no significant inhibition of spontaneous IgE synthesis by PBMC nor was there any reduction of serum IgE. Nevertheless, there was a progressive and significant reduction (p less than 0.01) in total clinical severity over the 6 weeks of daily rIFN-gamma with a sustained improvement during maintenance therapy. The results of this pilot study suggest that rIFN-gamma may be efficacious in the treatment of AD and that further clinical trials are warranted.


Isolation and characterization of two genes encoding polygalacturonase-inhibiting protein from Populus deltoides.
Polygalacturonase-inhibiting proteins (PGIPs) are extracellular proteins that belong to the leucine-rich repeat (LRR) protein superfamily. PGIPs inhibit fungal polygalacturonases (PGs) and promote accumulation of oligogalacturonides, which activate plant defense responses. PGIPs play important roles in resistance to infection of pathogens. In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) were used to isolate the full-length PGIP cDNA from Populus deltoides (GenBank accession no. of PdPGIP2 and PdPGIP4: EF684913 and EF684912). Domain analysis revealed that the deduced amino acid sequences of PdPGIP2 and PdPGIP4 had a typical PGIP topology. Phylogenetic analysis of known PGIPs indicated that the two PdPGIPs were clustered to the defense-related PGIP clade. Using real-time RT-PCR, the expression patterns of the two PdPGIPs following treatment with a fungal pathogen and defense-related signaling molecules were studied. The expression levels of PdPGIP2 and PdPGIP4 were both up-regulated when inoculated with the phytopathogenic fungus Marssonina brunnea. Therefore, it was proposed that the two PGIPs might be involved in the resistance to Marssonina brunnea in P. deltoides.


Interactions of Extracellular Vesicles from Pathogenic Fungi with Innate Leukocytes.
Several studies have shown the immunomodulatory effects of extracellular vesicles (EVs) released by pathogenic fungi. Herein, we discuss the data regarding the immunomodulatory properties of fungal EVs, but also of EVs produced by infected leukocytes. This characterizes a two-way path, in which both host and fungal EVs could coexist and play crucial roles in disease progression or protection in fungal infections. We suggest that EVs can dictate the progress of fungal diseases, and their potential as therapeutic targets.


Long-Term Outcomes and Return to Work After Isolated Coronal Shear Fractures of the Capitellum.
The purpose of this study was to analyze the ability of patients to return to work after ORIF of isolated capitellar shear fractures and assess long-term functional outcomes. We retrospectively reviewed the cases of 18 patients with isolated capitellar shear fractures with or without lateral trochlear extension and investigated demographic data, occupation, worker's compensation status, injury characteristics, surgical details, motion, radiographic appearance at final in-person follow-up, complications, and return to work status via in-person and long-term telemedicine follow-ups. Final follow-up was at an average of 76.6 (7-222.6) months or 6.4 (0.58-18.6) years. Of the 14 patients working at the time of injury, 13 patients had returned to work at final clinical follow-up. The work status of the remaining patient was not documented. Mean elbow motion at final follow-up was 4° (range, 0-30) to 138° (range, 130-145) of flexion, 83° of supination, 83° of pronation. Two patients had complications that required reoperation but had no further complications. For the 13 of 18 patients with long-term telemedicine follow-up, the average Quick Disabilities of the Arm, Shoulder, and Hand score was 6.8 (0-25). In our series, rates of return to work were high after ORIF of coronal shear fractures of the capitellum with or without lateral trochlear extension. This was true across all occupational classes including manual labor, clerical, and professional. With anatomic restoration of articular congruity, stable internal fixation, and postoperative rehabilitation, these patients had excellent ROM and functional scores at an average of 7.9 years of follow-up. After ORIF of isolated capitellar shear fractures with or without lateral trochlear extension, patients can expect a high rate of return to work with excellent ROM and functionality and low long-term disability.


Plant Proteomic Research 4.0: Frontiers in Stress Resilience.
Large-scale high-throughput multi-omics technologies are indispensable components of systems biology in terms of discovering and defining parts of the system [...].


Optic edge design as long-term factor for posterior capsular opacification rates.
To compare the difference in posterior capsular opacification (PCO) between highly refractive silicone and hydrophobic acrylic foldable intraocular lenses (IOLs) with sharp and round edge designs 3 years after in-the-bag IOL implantation in subjects undergoing bilateral cataract surgery. Open-label, prospective, randomized, multicenter clinical trial. Two hundred and eighty-eight patients with bilateral surgery for senile cataract operated in German university clinics, eye hospitals, and private ophthalmic surgical centers (Aachen, Ahaus, Bad Hersfeld, Frankfurt/Main, Jena, Rosenheim, and Sulzbach/Saar). At each center, a highly refractive index silicone IOL with a sharp optic edge (CeeOn) was intraindividually compared either with a high-refractive index silicone IOL with a round optic edge (PhacoFlex) in 108 patients or with an acrylic IOL with a sharp optic edge (AcrySof) in 139 patients. All patients received standard phacoemulsification with IOL implantation in the bag in both eyes from the same surgeon. A morphological evaluation of PCO was performed by the Evaluation of the Posterior Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 and 35 to 37 months after surgery. The blinded digital pictures were evaluated by an independent investigator. Posterior capsular opacification was statistically evaluated by paired comparisons of 3-year cumulative incidences of neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment and EPCO scores. Posterior capsular opacification. The 3-year cumulative incidences of Nd:YAG laser capsulotomy were 2.1% (CeeOn), compared with 2.1% (AcrySof) (risk difference, 0%; 90% confidence interval, -3.4% to 3.4%), and 5.7% (CeeOn), compared with 17.0% (PhacoFlex) (risk difference, -11.4%; 90% confidence interval, -18.1% to -4.7%). In patients without Nd:YAG laser treatment, medians of the total area EPCO score were 0.0005 (CeeOn) versus 0.0440 (AcrySof) and 0 (CeeOn) versus 0.0700 (PhacoFlex) at 3 years. Functional results, safety, and handling did not significantly differ for the 3 lenses. Our results suggest that modern foldable IOLs have a low incidence of PCO after 3 years. There is less PCO for sharp optic edge designs independent of IOL material.


Petrous Bone Cholesteatoma: Radical Excision with an Endeavour for Hearing Preservation.
To describe surgical outcomes following resection of giant petrous bone cholesteatoma. Retrospective cohort study was undertaken at a tertiary care centre on patients who had undergone surgery for petrous bone cholesteatoma (PBC) from August 2014 to September 2017. For patients with serviceable hearing preoperatively, labyrinth preserving techniques, namely, modified transmastoid translabyrinthine approach (massive PBC-1) and supralabyrinthine approach (supralabyrinthine PBC-1) were considered. In the former, bony labyrinth which had been destroyed due to the disease process, membranous labyrinth remained anatomically and functionally intact following meticulous dissection to remove cholesteatoma matrix. In the latter, supralabyrinthine cell tracts were exenterated without disturbing the cochlea and labyrinth with a canal wall down mastoidectomy. For the remaining patients, labyrinth ablative approach was undertaken (translabyrinthine/transotic). Facial nerve function was evaluated using House-Brackman grading system. Hearing was evaluated using pure tone audiometry. 7 patients were identified (massive-2, supralabyrinthine-3, supralabyrinthine apical-1, infralabyrinthine apical 1). None of the patients experienced deterioration of postoperative bone conduction or facial nerve function (preop-grade 5-4, grade 6-3; postop-grade 2-1, grade 3-2, grade 4-4). Facial nerve was decompressed and anatomically intact in 3 cases. In the remaining, facial hypoglossal anastomosis was done in 3 and facial masseteric anastomosis was done in 1 patient. With a median follow-up of 26 months, recurrence in the form of keratin pearl was seen in 1 patient. Modified translabyrinthine approach preserving membranous labyrinth is a promising hearing preservation strategy.


The synthesis and turnover of spermidine and spermine in mouse brain.
Following the administration to mice of radiolabeled putrescine by intraventricular injection, changes in the specific radioactivity of putrescine, spermidine, and spermine have been measured. Putrescine decline was biphasic, being more rapid over the first 12 hr(t 1/2 = 5 hr) than over the remainder of the 48-hr period (t 1/2 = 11 hr) that significant labeling was detected. Spermidine was rapidly labeled during the decline in putrescine radioactivity and maximum incorporation of label occurred at 18 hr. Subsequently, spermidine specific activity declined with a half-life of 22 days. Spermine synthesis was slower, with maximum labeling occurring after 4 days. Spermine turnover, measured at a time when spermidine radioactivity had substantially declined, was extremely slow (t 1/2 = 92 days). The data supports the view that putrescine is a precursor of spermidine which in turn is required for spermine synthesis.


Discriminative stimulus properties of clozapine and chlorpromazine.
Rats were trained to discriminate pairs of drug states in a two-lever operant paradigm for food reinforcement. One group learned to discriminate clozapine from vehicle, a second group learned to discriminate chlorpromazine from vehicle, and a third group learned to discriminate clozapine from chlorpromazine. The result that the clozapine versus chlorpromazine discrimination was acquired, as well as the results of substitution tests with non-training drugs, suggest that the stimulus properties of the classical neuroleptics and other psychotherapeutic agents indicate that the stimulus properties of antipsychotics are distinct from other classes of psychotropic agents, and support the hypothesis that clozapine may be a unique antipsychotic. It is suggested that the unique discrimination stimulus produced by clozapine may be related to the differential effect of the drug on the extrapyramidal versus accumbens dopamine system.


The day-of-invitation effect on participation in web-based studies.
Several methods have been proposed to promote participation in web-based research. Here, we examine a technique that is available at no cost: Inviting respondents per e-mail on a particular day of the week. We base our reasoning on such a day-of-invitation effect upon theories on variations in mood and work performance over the week. We conducted five experiments with large and heterogeneous samples to find out whether such effects apply for response rate (i.e., visiting the first page of a study) and retention rate (i.e., completing the study) in web-based studies. We found evidence of a small but significant day-of-invitation effect. Response rate is high at the beginning of the workweek and falls to a low on Friday. Exploratory analyses showed that this decline is higher for employed (vs. nonemployed) persons. Effects on retention rate appear to follow a less straightforward pattern. We discuss possible mechanisms that might account for the day-of-invitation effect and recommend inviting participants on Monday or Tuesday.


Formation and three-dimensional architecture of Leishmania adhesion in the sand fly vector.
Attachment to a substrate to maintain position in a specific ecological niche is a common strategy across biology, especially for eukaryotic parasites. During development in the sand fly vector, the eukaryotic parasite Leishmania adheres to the stomodeal valve, as the specialised haptomonad form. Dissection of haptomonad adhesion is a critical step for understanding the complete life cycle of Leishmania. Nevertheless, haptomonad studies are limited, as this is a technically challenging life cycle form to investigate. Here, we have combined three-dimensional electron microscopy approaches, including serial block face scanning electron microscopy (SBFSEM) and serial tomography to dissect the organisation and architecture of haptomonads in the sand fly. We showed that the attachment plaque contains distinct structural elements. Using time-lapse light microscopy of in vitro haptomonad-like cells, we identified five stages of haptomonad-like cell differentiation, and showed that calcium is necessary for Leishmania adhesion to the surface in vitro. This study provides the structural and regulatory foundations of Leishmania adhesion, which are critical for a holistic understanding of the Leishmania life cycle.


Voltage-clamp analysis of the potassium current that produces a negative-going action potential in Ascaris muscle.
1. A voltage clamp has been developed for the pharyngeal muscle of the nematode Ascaris lumbricoides and has been used to analyse the potassium current that produces a negative-going, regenerative action potential in this muscle. 2. Depolarizing voltage steps elicit a sustained inward current; returning the membrane voltage to the resting level evokes a strong, transient, outward current. This outward current reverses direction at the same voltage as that reached by the negative-going spike and is identified as the negative spike current. 3. The negative spike current decays with a time constant of 30 msec at voltages more negative than -30mV. This inactivation of the negative spike conductance is removed by holding the membrane at potentials more positive than -15mV. The time constant for removal of inactivation decreases from more than 300 msec at -15 mV to about 30 msec at +10 mV. 4. When inactivation has been removed, the negative spike conductance is turned on by stepping to potentials more negative than -15 mV. 5. Although the reversal potential for this current depends strongly on [K+]o (42 mV/decade), the potential at which the conductance is turned on is independent of [K+]o. 6. External Na+ seems to facilitate the negative spike current. Reduction of [Na+]o reduces its conductance and shifts the reversal potential to more positive values. 7. External Rb+ and Cs+ show voltage-dependent blocking of this current. 8. This K current is different from all the K currents which have been studied previously; however, it is analogous to the classical Na current of nerve and muscle, except for an inversion of the voltage dependencies.


Exploring the gating mechanism in the ClC chloride channel via metadynamics.
Computer simulations have been used to probe the gating mechanism in the Salmonella serovar typhimurium chloride channel (st-ClC). Specifically, the recently developed metadynamics methodology has been exploited to construct free energy surfaces as a function of the positions of either one or two chloride ions inside the pore, the position and protonation state of the key E148 residue, and the number of water molecules coordinating the translocating ions. The present calculations confirm the multi-ion mechanism in which an ion-push-ion effect lowers the main barriers to chloride ion translocation. When a second anion is taken into account, the barrier for chloride passage through the E148 narrow region is computed to be 6 kcal/mol in the wild-type channel, irrespective of the protonation state of the E148 residue, which is shown to only affect the entrance barrier. In the E148A mutant, this barrier is much lower, amounting to 3 kcal/mol. The metadynamics calculations reported herein also demonstrate that before reaching the periplasmic solution, chloride ions have to overcome an additional barrier arising from two different effects, namely the rearrangement of their solvation shell and a flip in the backbone angles of the residues E148 and G149, which reside at the end of the alphaF helix.


Evaluation and treatment of leg ulcers associated with chronic venous insufficiency.
The successful management of patients who have leg ulcers related to chronic venous disease requires optimal management of the wound bed, elimination of edema with compression, and correction of venous hypertension whenever possible. Healing of the wound itself requires compression, debridement, bacterial control, and stimulation of the wound bed. Prevention of ulcer recurrence is most effective if the patient is amenable to correction of the venous insufficiency. This is most successful when the superficial or perforator veins are the primary source. Quality diagnostic studies are critical in determining the anatomy and hemodynamic importance of various venous abnormalities and can guide appropriate interventional treatment. Venous corrective procedures usually can be performed using minimally invasive endovenous methods, which are associated with fewer complications and more rapid recovery than are major surgical techniques.


Neuropathology of the Common Forms of Dementia.
Dementias encompass a range of debilitating neurologic conditions. Here, we summarize the neuropathology of common forms of dementia, focusing on Alzheimer disease (AD) and related dementias. AD is part of a spectrum of neurodegenerative diseases that consists of various protein inclusions (ie, proteinopathies) but other brain abnormalities are also related to dementia. Beta-amyloid and tau aggregates are hallmarks of AD. Other tissue substrates include Lewy bodies, TDP-43 inclusions, vascular brain lesions, and mixed pathologies. This review highlights the complexity of neurodegenerative and other disease substrates and summarizes topography of these lesions and concepts of mixed brain pathologies, resistance, and resilience.


Laminin alpha-3 and thrombospondin-1 differently regulate the survival and differentiation of hepatocytes and hepatic stem cells from neonatal mice.
The aim of this study was to search and identify the extracellular matrix/adhesion molecules potentially regulating liver regeneration. By using pathway-focused PCR array, we investigated the dynamic changes in the expression of extracellular matrix and adhesion molecules in normal livers or cholestatic livers following partial hepatectomy in adult mice. To confirm the data from PCR array, we further evaluated how laminin alpha-3 and thrombospondin-1 mediate the survival and differentiation of matured hepatocytes and immature hepatic stem cells by using primarily isolated liver cells from neonatal mice. According to the different changes in the expression of extracellular matrix and adhesion molecules between normal livers and cholestatic livers, we could find a number of potential molecules involved in liver regeneration. Our in vitro evaluations indicated that laminin alpha-3 significantly increased the number of liver cells (P<0.01 vs. Control) but decreased the proportion of claudin-3-positive hepatic stem cells (P<0.05 vs. Control). In contrast, thrombospondin-1 significantly reduced cell apoptosis (P<0.05 vs. Control) and maintained the proportion of claudin-3-positive hepatic stem cells. Otherwise, the combination of laminin alpha-3 and thrombospondin-1 increased the proliferation of liver cells. Based on our data, laminin alpha-3 and trombospondin-1 differently regulate the survival and differentiation of hepatocytes and hepatic stem cells, but relevant mechanisms are required to be elucidated by further study.


How users adopt healthcare information: An empirical study of an online Q&A community.
The emergence of social media technology has led to the creation of many online healthcare communities, where patients can easily share and look for healthcare-related information from peers who have experienced a similar problem. However, with increased user-generated content, there is a need to constantly analyse which content should be trusted as one sifts through enormous amounts of healthcare information. This study aims to explore patients' healthcare information seeking behavior in online communities. Based on dual-process theory and the knowledge adoption model, we proposed a healthcare information adoption model for online communities. This model highlights that information quality, emotional support, and source credibility are antecedent variables of adoption likelihood of healthcare information, and competition among repliers and involvement of recipients moderate the relationship between the antecedent variables and adoption likelihood. Empirical data were collected from the healthcare module of China's biggest Q&A community-Baidu Knows. Text mining techniques were adopted to calculate the information quality and emotional support contained in each reply text. A binary logistics regression model and hierarchical regression approach were employed to test the proposed conceptual model. Information quality, emotional support, and source credibility have significant and positive impact on healthcare information adoption likelihood, and among these factors, information quality has the biggest impact on a patient's adoption decision. In addition, competition among repliers and involvement of recipients were tested as moderating effects between these antecedent factors and the adoption likelihood. Results indicate competition among repliers positively moderates the relationship between source credibility and adoption likelihood, and recipients' involvement positively moderates the relationship between information quality, source credibility, and adoption decision. In addition to information quality and source credibility, emotional support has significant positive impact on individuals' healthcare information adoption decisions. Moreover, the relationships between information quality, source credibility, emotional support, and adoption decision are moderated by competition among repliers and involvement of recipients.


Enzymic and chemical O-methylation of a 4-hydroxyestrone N-acetylcysteine conjugate.
4-Hydroxyestrone N-acetylcysteine conjugate (4-OHE1-2SR) is considered to be an important compound for monitoring the in vivo formation of catechol estrogen quinones, an intermediary in estrogen carcinogenicity. This article describes the selective synthesis of isomeric monomethyl ethers of 4-OHE1-2SR utilizing the formation of a seven-membered ring lactone by dehydration with acetic anhydride. Using these authentic specimens, enzymic and chemical O-methylation were examined. Enzymic O-methylation, using a rat liver cytosolic fraction, of 4-OHE1-2SR gave its 3-methyl ether as the sole product, while preferential O-methylation of 4-hydroxyestrone (4-OHE1) at the C-4 position was confirmed under the same conditions. Methylation of 4-OHE1-2SR with diazomethane gave initially carboxylate methylation, then the corresponding 3-methyl ether almost exclusively, while methylation of 4-OHE1 also gave its 3-methyl ether preferentially. However, much more rapid formation of the 3-methyl ether was observed with 4-OHE1-2SR than with 4-OHE1 itself. These results show that the hydroxy group at the C-3 position of 4-OHE1-2SR is more reactive than that at the C-4 position, both chemically and enzymatically.


Spinal anesthesia in ambulatory surgery.
Spinal anesthesia is a safe alternative to general anesthesia but remains underrepresented in the ambulatory setting. Most concerns relate to low flexibility of spinal anesthesia duration and the management of urinary retention in the outpatient setting. This review focuses on the characterization and safety of the local anesthetics that are available to adapt spinal anesthesia very flexibly to the needs of ambulatory surgery. Furthermore, recent studies on the management of postoperative urinary retention provide evidence for safe, but report wider discharge criteria and much lower hospital admission rates. With the local anesthetics that have current approval for usage in spinal anesthesia, most requirements for ambulatory surgeries can be met. The reported evidence on local anesthetics without approval supports clinically established off-label use and can improve the results even further.


Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.
T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions.


Effect of two hemicholiniums on the disposition and distribution of endogenous free choline in anaesthetized rabbits.
1 The effects of hemicholinium no. 3 (HC-3) and its p-terphenyl analogue (TPHC-3) on the disposition and distribution of free choline were studied in rabbits under pentobarbitone anaesthesia. Free choline was determined by bioassay. 2 The respiration of animals given 0.35 mumol/kg of HC-3 was hardly affected; however, 4 out of 6 rabbits given the same dose of TPHC-3 exhibited varying degrees of respiratory impairment. All animals that received 2 injections (1 h apart) of either HC-3 (1.4 mumol/kg) or TPHC-3 (0.7 mumol/kg) developed respiratory difficulty about 1 h after the second injection. 3 The respiratory distress was accompanied by a 2 to 15-fold rise in plasma choline concentration. This rise has been attributed to hypoxia. 4 In experiments in which choline has been infused it was observed that HC-3 could impair the animal's ability to dispose of exogenous choline. In control rabbits neither HC-3 nor TPHC-3 produced changes in plasma choline concentrations unless the respiration was depressed. 5 Either HC-3 or TPHC-3 (both at 0.35 mumol/kg) significantly (P less than 0.05) reduced the kidney choline concentration by 40% and 30% respectively; both hemicholiniums raised the lung choline concentration by about 35%. Only TPHC-3 caused a significant rise (40%) in liver choline. The choline concentrations in other tissues were unaffected by the hemicholiniums.


Assessment of Perioperative Atelectasis Using Lung Ultrasonography in Patients Undergoing Pneumoperitoneum Surgery in the Trendelenburg Position: Aspects of Differences according to Ventilatory Mode.
During robotic gynecologic pneumoperitoneum surgery in the Trendelenburg position, aeration loss leads to perioperative atelectasis. Recently developed ventilator mode pressure-controlled ventilation volume-guaranteed (PCV-VG) mode could provide adequate ventilation with lower inspiratory pressure compared to volume-controlled ventilation (VCV); we hypothesized that PCV-VG mode may be beneficial in reducing perioperative atelectasis via low tidal volume (VT) of 6 mL/kg ventilation during robotic gynecologic pneumoperitoneum surgery in the Trendelenburg position. We applied lung ultrasound score (LUS) for detecting perioperative atelectasis. We aimed to compare perioperative atelectasis between VCV and PCV-VG with a low VT of 6 mL/kg during pneumoperitoneum surgery in the Trendelenburg position using LUS. Patients scheduled for robotic gynecologic surgery were randomly allocated to the VCV (n = 41) or PCV-VG group (n = 41). LUS, ventilatory, and hemodynamic parameters were evaluated at T1 (before induction), T2 (10 minutes after induction in the supine position), T3 (10 minutes after desufflation of CO2 in the supine position), and T4 (30 minutes after emergence from anesthesia in the recovery room). Eighty patients (40 with PCV-VG and 40 with VCV) were included. Demographic data showed no significant differences between the groups. The total LUS has changed from baseline to T4, 0.63 (95% confidence interval [CI], 0.32, 0.94) to 1.77 (95% CI, 1.42, 2.21) in the VCV group and 0.86 (95% CI, 0.56, 1.16) to 1.43 (95% CI, 1.08, 1.78) in the PCV-VG group (P = 0.170). In both groups, total LUS increased significantly compared to the baseline values. Using a low VT of 6 mL/kg during pneumoperitoneum surgery in the Trendelenburg position, our study showed no evidence that PCV-VG ventilation was superior to VCV in terms of perioperative atelectasis. Clinical Research Information Service Identifier: KCT0006404.


High density lipoprotein cholesterole levels in peripheral vascular disease and in women on oral contraception.
Male patients with peripheral vascular disease (PVD) had significantly lower high density lipoprotein cholesterol (HDL-Ch) levels than their corresponding controls, while no significant difference could be demonstrated for female patients with PVD. No significant difference of HDL-Ch was found between women who used oral contraception and those who did not.


Organization of ribosomal RNA genes in Mycoplasma capricolum.
DNA segments carrying rRNA genes of Mycoplasma capricolum have been cloned and characterized by restriction endonuclease mapping, DNA-RNA hybridization and nucleotide sequencing. The M. capricolum genome has two sets of rRNA gene clusters, where the arrangement is in the order of (5')16S-23S-5S(3'). The spacer region between 16S and 23S rDNA is extremely rich in AT and does not carry any tRNA genes.


Neurocognitive and behavioral markers in DUI recidivists.
Objective: Driving under the influence (DUI) of alcohol recidivism may be a risk-taking behavior motivated by a change in decision-making capacity. Decision-making capacity has been investigated by event-related potentials (ERPs) acquisition and specifically by analyzing feedback-related negativity (FRN) reflecting the activity of medial prefrontal cortex. Thus, the aim of our study was to test the role of FRN as a possible neurophysiological marker of underestimation of risk associated with DUI recidivism to provide novel insights into the influence of neurocognitive aspects of driving ability.Methods: The research was structured as a case-control study. The total cohort (30 Italian male subjects) was divided into 2 groups, according to positive or negative history of DUI recidivism. The protocol included informed consent collection, medical history and clinical examination, ERP registration, and sensation-seeking scale administration. ERPs were acquired during a gambling task. The data were analyzed with 2 analysis of variance (ANOVA) repeated measures. Statistical analyses were conducted using R to test the participants' risk behaviors. A multivariate ANOVA was run to compare the personality traits of the groups. ANOVAs and planned comparisons were performed with StatSoft software.Results: FRN amplitude analyses showed that the interaction Reward Magnitude × Valence (large vs. small × gains vs. losses) was significant for recidivists (F(1,13) = 11.75, P < .01) but not for controls (F(1,14) = 0.04, P = .84). The results of the logistic generalized linear models analysis showed that the 2 groups differed in risk-taking behavior (z = -3.65; P < .001) with an average of 70 risky choices for recidivists and 63 for controls. Both groups were homogeneous for personality traits.Conclusions: The FRN and gambling task results suggest that DUI recidivists seemed attracted by the prospect of a large reward and appeared unable to recognize small losses read as wins These results, if confirmed in a larger sample, could indicate the usefulness of ERP analysis in clinical and forensic evaluation of DUI subjects.


Alterations in myocardial hydrogen ion concentration after temporary coronary occlusion: a sign of irreversible cell damage.
Alterations of hydrogen ion (H+) concentration in the myocardium of 60 cats were determined before release of coronary ligation of 30, 45, 60, 90 or 180 minutes' duration, or 5, 30 and 90 minutes after release of the occlusion, by pressing pH indicator paper on unfixed frozen heart sections. The H+ concentration had clearly increased (pH less than 6.0) in a transmural extension in the left ventricle before release of the coronary ligature. This elevated H+ concentration persisted some time in the subendocardial region despite release of the coronary occlusion, thus proving that the so-called no reflow phenomenon exists in involved myocardium after temporary coronary occlusion. A diminished H+ concentration (pH 7.4) was found in the border zone between the acid-reacting area and the normal muscle when the coronary occlusion lasted 180 minutes before release of the ligature or 30 minutes after release of the occlusion when the previous period of temporary occlusion had been longer than 30 minutes. Although areas manifesting an acid reaction vanished or diminished in size after release of coronary occlusion, the extent of alkaline-reacting zones showed no reduction in size, and muscle cell necrosis developed in these alkaline-reacting areas. It is assumed therefore that an alkaline reaction of the myocardium is an early sign of irreversible muscle cell damage.


Experimental seizure-induced brain damage: electrophysiological, metabolic and pathological correlation.
Limbic seizures elicited by an intra-amygdaloid KA injection is the only and unique model which can produce unilateral hippocampal degenerative lesions and atrophy. This model is important not only to investigate neurophysiological epileptogenesis but also to study the causative process of human mesial temporal sclerosis observed in patients with intractable complex partial seizure.


[Actinomyces meyeri actinomycosis: a case with thoracic and tibial localization].
Apart from the rarity of the causal agent, this case is of interest because of the absence of cervico-facial involvement and the presence of multiple cutaneous nodules at a distance from the visceral localisation.


Surgical Management of Neuroendocrine Tumor Liver Metastases.
Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue. For patients with large hepatic tumor burdens, high-grade disease, or comorbidities precluding surgery, liver-directed and systemic therapies can be used to palliate symptoms and improve progression-free survival.


TLR2-activated B cells are phenotypically similar to the abnormal circulating B cells seen preceding the diagnosis of AIDS-related NHL diagnosis.
AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype. Stored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry. An elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV- controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis. These results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection-associated B-cell activation, potentially contributing to the genesis of AIDS-NHL.


Comparison of transcriptome responses of the liver, tail fin, and olfactory epithelium of Rana [Lithobates] catesbeiana tadpoles disrupted by thyroid hormones and estrogen.
Thyroid hormones (THs) are important developmental regulators in vertebrates, including during the metamorphosis of a tadpole into a frog. Metamorphosis is a post-embryonic developmental period initiated by TH production in the tadpole thyroid gland. The two main bioactive forms of TH are L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3); these hormones have overlapping but distinct mechanisms of action. Premetamorphic tadpoles are highly responsive to TH and can be induced to metamorphose through exogenous TH exposure, making them an important model for both the study of vertebrate TH signaling and endocrine disrupting chemicals (EDCs). It is important to differentiate TH-mediated responses from estrogenic responses in premetamorphic tadpoles when assessing dysregulation by EDCs as crosstalk between the two endocrine systems is well-documented. Herein, we compare the RNA-sequencing-derived transcriptomic profiles of three TH-responsive tissues (liver, olfactory epithelium, and tail fin) in premetamorphic bullfrog (Rana [Lithobates] catesbeiana) tadpoles exposed to T3, T4, and estradiol (E2). These profiles were generated using the latest available genome assembly for the species. The data indicate that there is a clear distinction, and little overlap, between the transcriptomic responses elicited by E2 and the THs. In contrast, within the THs, the T3- and T4-induced transcriptomic profiles generally show considerable overlap; however, the degree of overlap is highly tissue-dependent, illustrating the importance of distinguishing the two THs and the affected signaling pathways within the target tissue type when evaluating hormone active agents. The data herein also show that E2 and TH treatment can uniquely induce significant changes in expression of their respective "classic" bioindicator transcripts vtg (E2) and thra, thrb, and thibz (THs). However, care must be taken in the interpretation of increased vep or esr1 transcripts as a change in transcript levels can be induced by THs rather than solely E2.


Homeostatic PD-1 signaling restrains EOMES-dependent oligoclonal expansion of liver-resident CD8 T cells.
The co-inhibitory programmed death (PD)-1 signaling pathway plays a major role in the context of tumor-specific T cell responses. Conversely, it also contributes to the maintenance of peripheral tolerance, as patients receiving anti-PD-1 treatment are prone to developing immune-related adverse events. Yet, the physiological role of the PD-1/PDL-1 axis in T cell homeostasis is still poorly understood. Herein, we show that under steady-state conditions, the absence of PD-1 signaling led to a preferential expansion of CD8+ T cells in the liver. These cells exhibit an oligoclonal T cell receptor (TCR) repertoire and a terminally differentiated exhaustion profile. The transcription factor EOMES is required for the clonal expansion and acquisition of this differentiation program. Finally, single-cell transcriptomics coupled with TCR repertoire analysis support the notion that these cells arise locally from liver-resident memory CD8+ T cells. Overall, we show a role for PD-1 signaling in liver memory T cell homeostasis.


How Can High-Frequency Sensors Capture Collaboration? A Review of the Empirical Links between Multimodal Metrics and Collaborative Constructs.
This paper reviews 74 empirical publications that used high-frequency data collection tools to capture facets of small collaborative groups-i.e., papers that conduct Multimodal Collaboration Analytics (MMCA) research. We selected papers published from 2010 to 2020 and extracted their key contributions. For the scope of this paper, we focus on: (1) the sensor-based metrics computed from multimodal data sources (e.g., speech, gaze, face, body, physiological, log data); (2) outcome measures, or operationalizations of collaborative constructs (e.g., group performance, conditions for effective collaboration); (3) the connections found by researchers between sensor-based metrics and outcomes; and (4) how theory was used to inform these connections. An added contribution is an interactive online visualization where researchers can explore collaborative sensor-based metrics, collaborative constructs, and how the two are connected. Based on our review, we highlight gaps in the literature and discuss opportunities for the field of MMCA, concluding with future work for this project.


Buthionine sulfoximine has anti-Trypanosoma cruzi activity in a murine model of acute Chagas' disease and enhances the efficacy of nifurtimox.
L-buthionine (S,R)-sulfoximine (BSO) at a dose of 220 mg/kg of body weight/day showed an anti-Trypanosoma cruzi effect in infected mice, increasing their survival rate and decreasing the parasitemias and parasite burden in the hearts. Treatment with BSO plus nifurtimox caused an increase in the survival rate in comparison to the rates with treatment with each drug alone.


A hybrid approach of handling missing data under different missing data mechanisms: VISIBLE 1 and VARSITY trials for ulcerative colitis.
Missing data is common in clinical trials. Depending on the volume and nature of missing data, it may reduce statistical power for detecting treatment difference, introduce potential bias and invalidate conclusions. Non-responder imputation (NRI), where patients with missing information to determine endpoint status are considered as treatment failures, is widely used to handle missing data for dichotomous efficacy endpoints in inflammatory bowel disease (IBD) trials. However, it does not consider the mechanisms leading to missing data and can potentially underestimate the treatment effect. We proposed a hybrid imputation approach combining NRI and multiple imputation (MI) as an alternative to NRI to assess the impact of dropouts for different missing data mechanisms (categorized as "missing not at random [MNAR]" and "missing at random [MAR]"). Two phase 3 vedolizumab clinical trials under different study designs in patients with moderate-to-severe ulcerative colitis (UC), VISIBLE 1 and VARSITY, are presented to illustrate how the proposed hybrid approach can be implemented as a pre-specified sensitivity analysis in practice. The proposed hybrid imputation provided consistent efficacy results with those using NRI, and can serve as a useful pre-specified sensitivity analysis to assess the impact of dropouts under different missing data mechanisms and evaluate the robustness of efficacy conclusions.


The time-varying association between previous antibiotic use and antibiotic resistance.
The objective of the study was to estimate how the time elapsed from previous antibiotic use is associated with antibiotic resistance. Data comprised electronic medical records of all patients in an Israeli hospital who had a positive bacterial culture from 2016 to 2019. These included susceptibility testing results and clinical and demographic data. Mixed-effects time-varying logistic models were fitted to estimate the association between the time elapsed since the last use of aminoglycosides and gentamicin resistance (n = 13 095), cephalosporins and ceftazidime resistance (n = 13 051), and fluoroquinolones and ciprofloxacin resistance (n = 15 364) while adjusting for multiple covariates. For all examined antibiotics, previous antibiotic use had a statistically significant association with resistance (p < 0.001). These associations exhibited a clear decreasing pattern over time, which we present as a flexible function of time. Nonetheless, previous antibiotic use remained a significant risk factor for resistance for at least 180 days when the adjusted ORs were 1.94 (95% CI, 1.40-2.69), 1.33 (95% CI, 1.10-1.61), and 2.25 (95% CI, 1.49-3.41) for gentamicin, ceftazidime, and ciprofloxacin, respectively. The association between prior antibiotic use and resistance decreases over time. Commonly used cut-offs for prior antibiotic use can either misclassify patients still at higher risk when too recent or provide a diluted estimate of the effects of antibiotic use on future resistance when too distant. Hence, prior antibiotic use should be considered a time-dependent risk factor for resistance in both epidemiological research and clinical practice.


Relative influences of perceived parental monitoring and perceived peer involvement on adolescent risk behaviors: an analysis of six cross-sectional data sets.
To assess: (a) the relative impact of monitoring and peer involvement among six cohorts of African-American youth in their mid-adolescent years, over a decade of research in one urban area, and (b) the consistency of the impact of the two influences over time. Baseline data were collected from six cohorts involving 1279 low income African-American youth aged 13 to 16 years involved in community based studies conducted over a decade in an urban area. Self-reported behaviors, and perceptions of parental monitoring and peer risk-involvement were assessed through structured questions. Data were analyzed by frequency distribution, one-way ANOVA, and multiple logistic regression. There was a rapid increase in sexual activity and substance use behaviors during mid-adolescence. Monitoring had a protective influence on substance use behaviors and sexual activity, but had no impact on condom use or drug trafficking. Peer involvement influenced all evaluated risk behaviors. The influences overall did not statistically change over time. Despite the marked increase in risk behaviors during mid-adolescence, monitoring and peer involvement both influenced adolescent behaviors across each cohort.


Predicting the Recurrence of Common Bile Duct Stones After ERCP Treatment with Automated Machine Learning Algorithms.
Recurrence of common bile duct stones (CBDs) commonly happens after endoscopic retrograde cholangiopancreatography (ERCP). The clinical prediction models for the recurrence of CBDs after ERCP are lacking. We aim to develop high-performance prediction models for the recurrence of CBDS after ERCP treatment using automated machine learning (AutoML) and to assess the AutoML models versus the traditional regression models. 473 patients with CBDs undergoing ERCP were recruited in the single-center retrospective cohort study. Samples were divided into Training Set (65%) and Validation Set (35%) randomly. Three modeling approaches, including fully automated machine learning (Fully automated), semi-automated machine learning (Semi-automated), and traditional regression were applied to fit prediction models. Models' discrimination, calibration, and clinical benefits were examined. The Shapley additive explanations (SHAP), partial dependence plot (PDP), and SHAP local explanation (SHAPLE) were proposed for the interpretation of the best model. The area under roc curve (AUROC) of semi-automated gradient boost machine (GBM) model was 0.749 in Validation Set, better than the other fully/semi-automated models and the traditional regression models (highest AUROC = 0.736). The calibration and clinical application of AutoML models were adequate. Through the SHAP-PDP-SHAPLE pipeline, the roles of key variables of the semi-automated GBM model were visualized. Lastly, the best model was deployed online for clinical practitioners. The GBM model based on semi-AutoML is an optimal model to predict the recurrence of CBDs after ERCP treatment. In comparison with traditional regressions, AutoML algorithms present significant strengths in modeling, which show promise in future clinical practices.


n-Propyldiazonium ion alkylates O6 of guanine with rearrangement, but alkylates N-7 without rearrangement.
Treatment of guanosine with n-propylnitrosourea yields 7-n-propylguanine (after acid hydrolysis) but O6-isopropylguanosine. Similarly, injection of [3H]di-n-propylnitrosamine into Sprague--Dawley rats resulted in isolation of 7-n-propylguanine from RNA, but O6-isopropylguanosine. The amounts of the different adducts indicate that attack at both N-7 and O6 of guanine proceed by bimolecular substitution (otherwise significant levels of 7-isopropylguanine should have been seen), but the observed rearrangement indicates that the transition state for reaction at O6 may be much looser than that for reaction at N-7.


Attenuation of morphine-induced analgesia in mice by exposure to magnetic resonance imaging: separate effects of the static, radiofrequency and time-varying magnetic fields.
Exposure of adult male mice to a magnetic resonance imaging (MRI) procedure has been shown to abolish the nocturnal analgesic responses observed following treatment with morphine. The field component(s) responsible for this inhibitory effect were examined by exposing mice to either the static, time-varying or rf magnetic field components associated with an MRI procedure. In the middle of the night portion of their day-night cycle, mice were exposed for 23.2 min to one of the above field components, intraperitoneally injected with morphine sulphate (10 mg/kg) and then exposed to the field conditions for another 23.2 min, after which analgesic responses were determined. Analgesia was quantitated by determining the length of time mice were content to be on a hot surface (50 degrees C) before they showed discomfort by licking their paws. It was observed that the time-varying magnetic field completely abolished, the rf field significantly reduced, while the static field component (0.15 T) had no evident effect on morphine-induced analgesia. These results indicate that the time-varying, and to a lesser extent the rf, fields associated with the MRI procedure inhibit morphine-induced analgesia in mice. These data also raise the possibility that exposure in humans to some of the magnetic field components associated with MRI may have clinically relevant effects on the actions of narcotic drugs such as morphine.


Sequence characterization and expression patterns of defensin and lysozyme encoding genes from the gut of the reduviid bug Triatoma brasiliensis.
The cDNAs encoding an intestinal defensin (def1) and lysozyme (lys1) of the reduviid bug Triatoma brasiliensis have been amplified by PCR using specific oligonucleotide primers and 5'- and 3'-RACE, cloned and sequenced. The 576 bp clone has an open reading frame of 282 bp and encodes a pre-prodefensin with 94 amino acid residues, containing a putative signal and activation peptide cleavage site at Ser19 and Arg51, respectively. The genomic DNA contains a second defensin gene with similar characteristics, 88.3% identity and also one intron of 107 nucleotides. The 538 bp clone has an open reading frame of 417 bp, encoding a pre-lysozyme with 139 amino acid residues. The putative signal peptide is cleaved at alanine 18. Using whole mount in situ hybridization, high expression of both genes has been found, distributed uniformly throughout the entire cardia and the blood-storing stomach and to a much lower extent in the digesting small intestine. Using quantitative real-time PCR, the expression level of def1 was also shown to be very low in small intestine, rectum and salivary glands; in the stomach, expression was 500-2500 times higher than in the cardia and fat body. No expression of lys1 could be detected in the salivary glands and rarely a very low expression in the small intestine, rectum and fat body. Lys1 expression in the stomach was 60-300 times higher than in the cardia. Comparing the levels in unfed fifth instars and up to 15 days after feeding, a strong def1 induction was evident in the fat body at 15 days after feeding and in the stomach a maximum level of def1 and lys1 at 5 days after feeding.


Use of long-lasting insecticide-treated bed nets in a population with universal coverage following a mass distribution campaign in Uganda.
Uganda conducted an LLIN mass distribution campaign in 2013 with the goal of achieving universal coverage. Using data from the 2014 malaria indicator survey, this analysis estimated the proportion of the population with access to an LLIN that slept under one the night before the survey and factors associated with not using an LLIN in households that had achieved universal coverage. This was a secondary data analysis using the 2014 malaria indicator survey dataset. The outcome was use of an LLIN among households that achieved universal coverage, while independent variables include age, gender, number of household members, residence, number of sleeping rooms, spraying of rooms with insecticide, number of children under 5 years of age, number of women of child-bearing age, relationship structure and community distribution of ant-malarial medicine. Overall, 3361 (62 %) households of the 5345 achieved universal coverage and were included in the analysis giving a total population of 14,450 individuals. Of these, 11,884 (80.10 %) reported to have slept under an LLIN the night before the survey. Children between 6 and 14 years were significantly less likely to use an LLIN when compared to those under 5 years (75.26 vs 83.12 %), [adjusted OR, 1.29 (1.11-1.49), p = 0.001]. The odds of not using an LLIN, significantly increased from households with five members when compared to those that had one member (79.53 vs 84.88 %), [adjusted OR, 2.16 (1.38-3.38), p = 0.001] and rising even further in households with six or more members (78.04 vs 84.88 %), [OR, 2.27 (1.36-3.71), p = 0.003]. This analysis has showed that 80 % of the population used an LLIN among households that achieved universal coverage following the 2013 mass distribution campaign, especially among children under 5 years, an operational success in this category. However, children between 6 and 14 years and individuals from households with five or more numbers are less likely to use the LLINs. In order to improve usage in these categories, it may require re-focusing the behaviour change communication message to be all-inclusive, especially in era of universal coverage, and to increase the number of LLINs distributed in households with more than four members during future mass distribution campaigns, respectively.


Interstitial Collagen Loss, Myocardial Remodeling, and Function in Primary Mitral Regurgitation.
Interstitial collagen loss and cardiomyocyte ultrastructural damage accounts for left ventricular (LV) sphericity and decrease in LV twist and circumferential strain. Normal LV diastolic function belies significantly abnormal left atrial (LA) function and early LV diastolic untwist rate. This underscores the complex interplay of LV and LA myocardial remodeling and function in the pathophysiology of primary mitral regurgitation. In this study, we connect LA function with LV systolic and diastolic myocardial remodeling and function using cardiac magnetic resonance tissue tagging in primary mitral regurgitation.


The relationship between Type D personality with atherosclerotic plaque and cardiovascular events: The mediation effect of inflammation and kynurenine/tryptophan metabolism.
Cardiovascular events and coronary plaque vulnerability are linked to Type D personality. However, the fundamental mechanism has not been clarified. Our study determined to illustrate whether inflammatory status in plasma, in combination with kynurenine pathway activity in Type D individuals, is associated with plaque vulnerability and cardiovascular events in patients with coronary artery disease (CAD). The Type D personality of 177 CAD patients were evaluated. Plasma biomarkers of inflammation (TNF-α, IL-6, and hs-CRP) were measured and pooled into standardized sumscores. Tryptophan and kynurenine metabolites were measured, and the kynurenine/tryptophan ratio (KTR) was calculated. Plaque vulnerability was measured in vivo by optical coherence tomography. All patients had a follow up of 2 years in which cardiovascular adverse events were recorded. Type D individuals exhibited elevated TNF-α (p = 0.007), IL-6 (p = 0.049), inflammation sumscores (p = 0.002), kynurenine (p = 0.008), and KTR (p = 0.005) than non-Type D group. The serial-multiple mediation showed that the Type D personality with a direct, favorable impact on plaque vulnerability, including thin cap fibroatheroma (TCFA) (point estimate = 0.81; 95% CI = 0.09-1.53), macrophages (point estimate = 0.79; 95% CI = 0.05-1.51), and major adverse cardiac events (MACE) (point estimate = 0.88, 95% CI = 0.08-1.70). In addition, the standardized inflammation sumscores and KTR were mediators of the Type D personality associations with TCFA, macrophages and MACE. These results demonstrated that the connection between Type D personality and poor cardiovascular outcomes in CAD patients can be mediated by pro-inflammatory biomarkers and KTR.


Mitral valve replacement and subsequent composite graft replacement of the aortic root for infantile Marfan syndrome.
The cardiovascular lesions commonly seen in Marfan syndrome can frequently be the primary cause of premature death. Cardiac lesions involving both the mitral valve and the aortic root are commonly observed among patients diagnosed during early infancy, as so-called infantile Marfan syndrome. Since the lesions tend to progress rapidly with the end results of high morbidity and mortality, the majority of patients require surgical intervention at a young age. However, patients who undergo surgical intervention for both lesions during the first decade of life have been rarely reported in literature. In this report, we present a case of a 9-year-old boy who underwent aortic root replacement with a composite graft at 3.5 years after a prior prosthetic valve replacement of the mitral valve. Although the immediate result was satisfactory, the long-term result remains to be seen.


A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy.
Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) and a hypoxia-responsive prodrug for multifunctional image-guided combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence and photoacoustic (PA) brightness for the strong light absorption ability, as well as amplified type I and type II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating the high-performance AIEgen with a hypoxia-responsive paclitaxel (PTX) prodrug into nanoparticles, and further camouflaging with macrophage cell membrane, a tumor-targeting theranostic agent is built. The integration of fluorescence and PA imaging helps to delineate tumor site sensitively, providing accurate guidance for tumor treatment. The light-induced PDT effect could consume the local oxygen and lead to severer hypoxia, accelerating the release of PTX drug. As a result, the combination of PDT and PTX chemotherapy induces immunogenic cancer cell death, which could not only elicit strong antitumor immunity to suppress the primary tumor, but also inhibit the growth of distant tumor in 4T1 tumor-bearing female mice. Here, we report a strategy to develop theranostic agents via rational molecular design for boosting antitumor immunotherapy.


[Congestive myocardiopathy and early dyastolic closure of the tricuspid valve. Report of a case with acute tricuspidization].
A case with congestive cardiomiopathy and early diastolic closure of the tricuspid valve is presented. This abnormal echocardiographic finding was probably the result of severe tricuspid regurgitation occurring in a restricted right ventricle. The absence of paradoxical septum was determinedly the left ventricular pathology. In this case, echocardiography was more sensitive for the detection of the left sided abnormalities, than the heart cath data.


The value of radionuclide myelography in the evaluation of spinal arachnoiditis.
On the basis of myelographic findings, spinal adhesive arachnoiditis was classified into three types: type I (peripheral or marginal), type II (central), and type III (advanced). Depending on its location and extent, it may be divided into group A (lumbar), group B (thoracic), and group C (cervical). In view of the fact that intrathecal injection both of oily and of water-soluble contrast media tends to produce spinal arachnoiditis, we have been using radionuclides for pre- and postoperative myelography to evaluate arachnoiditis. Radionuclide myelography with 131I-HSA or 111In-DTPA is a safe modality which provides useful information regarding spinal arachnoiditis.


Transfer of mink genes into mouse cells by means of isolated lipid-encapsulated nuclei.
A method for gene transfer by means of interphase nuclei encapsulated within lipid membranes was developed. The method was based on passage of interphase nuclei through a layer of organic solvents containing phospholipids. Evidence was obtained indicating that the nuclei become surrounded by a protective phospholipid membrane: measurements of bound labelled or non-labelled phospholipids; decrease in the permeability of lipid-encapsulated nuclei for high molecular compounds; visualization by direct electron microscopy. Lipid-encapsulated nuclei of mink fibroblasts were used for transformation of mutant mouse LMTK- cells (deficient for thymidine kinase). The frequency of occurrence of HAT-resistant colonies/recipient cell was 1.9 X 10(-5). Biochemical analysis of 14 independent clones demonstrated that they all contained TK1 of mink origin. Analysis of 15 other biochemical markers located on 12 of the mink chromosomes revealed the activities of mink galactokinase (a syntenic marker) in 5 transformed clones, and that of mink aconitase-1 (the marker of mink chromosome 12) in 1 clone. No cytogenetically visible donor chromosomes were identified in the transformed clones. Nine transformed clones were tested for the stability of the TK+ phenotype; of these, the phenotype was expressed stably in 3 and unstably in 6. The method suggested is similar to the gene transfer procedure using total DNA. Its advantage is in ensuring efficient gene transfer and donor DNA integrity.


Cholesterol ester exchange between human plasma high and low density lipoproteins mediated by a plasma protein factor.
Although unesterified cholesterol and phospholipids exchange freely, a protein factor from the d greater than 1.25 g/ml plasma fraction was found to be necessary for cholesterol esters to transfer from HDL to LDL. This transfer was reversible, time-dependent and a function of the concentration of the d greater than 1.25 fraction, but independent of lecithin : cholesterol acyltransferase reaction. The transfer represented an equilibration of molecules, but no net mass transfer of cholesterol esters could be demonstrated from HDL to LDL.


An x-ray backlit Talbot-Lau deflectometer for high-energy-density electron density diagnostics.
X-ray phase-contrast techniques can measure electron density gradients in high-energy-density plasmas through refraction induced phase shifts. An 8 keV Talbot-Lau interferometer consisting of free standing ultrathin gratings was deployed at an ultra-short, high-intensity laser system using K-shell emission from a 1-30 J, 8 ps laser pulse focused on thin Cu foil targets. Grating survival was demonstrated for 30 J, 8 ps laser pulses. The first x-ray deflectometry images obtained under laser backlighting showed up to 25% image contrast and thus enabled detection of electron areal density gradients with a maximum value of 8.1 ± 0.5 × 10(23) cm(-3) in a low-Z millimeter sized sample. An electron density profile was obtained from refraction measurements with an error of <8%. The 50 ± 15 μm spatial resolution achieved across the full field of view was found to be limited by the x-ray source-size, similar to conventional radiography.


Local neurotoxicity of epidural clofelin.
Morphological and quantitative histoenzymological changes in neurons of dog spinal cord and spinal ganglion were studied in acute and chronic experiments with epidural administration of 0.01% clofelin. No morphofunctional changes were revealed after bolus injection of clofelin in a single dose of 6.5 mg/kg. After administration of clofelin in a daily dose of 15 microg/kg for 14 days permeability of capillaries in the nervous tissue decreased at the site of injection, but increased in intact areas. Compensatory changes in energy supply to neurons manifested in activation of aerobic and anaerobic oxidation. Sufficient level of nucleic acids synthesis confirms qualitative validity of nervous cells. Epidural clofelin did not cause dystrophy and necrosis in neurons of the spinal and spinal ganglion.


Salvage pathways as targets of chemotherapy.
This paper discussed the significance of the activities of purine and pyrimidine salvage enzymes in cancer cells and the targeting against them of chemotherapy. 1. The activities of salvage enzymes in the rat liver were orders of magnitude higher than those of the rate-limiting enzymes of de novo biosynthesis. A similar relationship was observed in rat hepatomas of different growth rates and in primary colon carcinoma in human. 2. The concentrations of nucleosides and nucleobases were measured in plasma, liver and hepatoma 3924A in the rat. The freeze-clamp method was required to determine the concentrations of these precursors in rat liver and hepatoma in a reliable and precise fashion because ischemia markedly altered the concentrations of nucleosides, nucleobases and, as shown earlier, nucleotides in these tissues. The results indicated that the liver markedly concentrated the purine precursors, hypoxanthine, guanine and adenine, but not thymidine, which was one-third that of the plasma. Uridine and deoxycytidine occurred in the same concentration as in plasma, but cytidine was 3-fold higher in liver. In the hepatoma in comparison to the liver the concentrations of the nucleosides and bases were altered and for some of the changes the enzymic differences between liver and hepatoma appeared to be accountable. 3. Kinetic parameters for purine and pyrimidine synthetic enzymes and for the substrates and co-factors were determined in liver and hepatoma 3924A. When enzymic activities were calculated at the tissue steady-state concentrations of the various ligands, the activities of the salvage enzymes were markedly higher than those of the rate-limiting enzymes. 4. Hepatoma cells were highly sensitive to the action of the transport inhibitor, dipyridamole, in lag and log phases. However, plateau phase cells lost their sensitivity to dipyridamole. 5. Amphotericin B rendered plateau phase cells sensitive to the inhibitory action of dipyridamole for the incorporation of thymidine. 6. Amphotericin B enhanced cytotoxicity of dipyridamole in hepatoma and human colon cancer HT-29 cells. 7. In these studies we discovered the decreased responsiveness to dipyridamole of plateau phase cells and the ability of amphotericin B to restore the sensitivity. Moreover, dipyridamole and amphotericin B were synergistic in their cytotoxic action in rat hepatoma cells and human colon cancer cells.(ABSTRACT TRUNCATED AT 400 WORDS)


[Changes in the functional activity of the sympathetico-adrenal system after correction of electrolyte metabolism in patients with hypertension].
Parameters of the sympathoadrenal system were studied in 81 patients with I-II stages essential hypertension. Their changes were analysed depending on the disease stage; study also included the interrelation between electrolyte metabolism, and sympathoadrenal and renin-aldosterone systems. Moderate consumption of common salt in "salt-sensitive" patients caused a significant decrease in the activity of the sympathoadrenal system, while in "salt nonsensitive", patients with paradoxical reaction this correction of salt regimen of nutrition activated the sympathoadrenal system. Thus, use of this non-pharmacological method of treatment with limitation of common salt in essential hypertension patients requires a differential approach, depending on "salt sensitivity".


Erratum: Joint Correction Regarding Declarations of Interest.
[This corrects the article DOI: 10.1016/j.ympdx.2020.100035.][This corrects the article DOI: 10.1016/j.ympdx.2019.100010.][This corrects the article DOI: 10.1016/j.ympdx.2020.100025.][This corrects the article DOI: 10.1016/j.ympdx.2019.100002.].


Synthesis, hydrolytic activation and cytotoxicity of etoposide prodrugs.
Two 4'-propylcarbonoxy derivatives (2,3) of etoposide (1), a topoisomerase II inhibitor, were synthesized and evaluated as potential prodrugs for anticancer therapy. Their activation via hydrolysis mechanisms was determined as a function of pH in buffer solutions, in human serum and in the presence of carboxyl ester hydrolase. Cytotoxicity was determined on various tumor cell lines and compared to the parent compound. On cell lines exhibiting resistance to etoposide we observed an enhanced cytotoxicity of the prodrugs of up to three orders of magnitude.


Plica mediopatellaris--arthroscopic resection under local anesthesia.
A consecutive series of 28 patients (31 knees) with a symptomatic mediopatellar plica without concomitant lesions excised arthroscopically under local anaesthesia in the outpatient department is described. The results were classified as excellent or good in 26/31 cases after a median follow-up period of 15 months. It is concluded that excising a fibrosed mediopatellar plica large enough to cover the medial femoral condyle during flexion is followed by good results; local anaesthesia is sufficient and economical, and arthroscopic excision under local anaesthesia carries a low morbidity.


Application of a newly recorded diazotrophic cyanobacterium in acidified and Cd contaminated paddy soil: Promotes rice yield and decreases Cd accumulation.
Acidification caused by excessive fertilization and heavy metals contamination are two prominent problems of agricultural soils. Diazotrophic cyanobacteria play important role in nitrogen (N) input in agricultural ecosystem. However, the effects of diazotrophic cyanobacteria on the growth of rice and heavy metal uptake by rice grain in acidified and heavy metal contaminated paddy soil remain unknown. In this study, a newly recorded diazotrophic cyanobacterium Aliinostoc sp. YYLX235 was isolated from acidified paddy soil. The results of pot experiment and in situ field plot experiment demonstrated that Aliinostoc sp. YYLX235 could promote rice grain yield and decrease cadmium (Cd) accumulation in rice grain. Nitrogen input by N2-fixation and increase of bio-available phosphorus (P) by promotion of activity of soil phosphatase may be the main mechanisms for growth-promoting effects of Aliinostoc sp. YYLX235 on rice. Binding and immobilization of Cd through hydroxyl, carboxyl, and amino groups may be the reason for decrease of Cd accumulation in rice grain by Aliinostoc sp. YYLX235 inoculation. The results presented in this study suggest that diazotrophic cyanobacteria have great potential in safe cropping in acidified and Cd contaminated paddy soils.