Inhibition of granulocyte function by prednisolone and non-steroid anti-inflammatory drugs. Quantitative evaluation with NBT test and its correlation with phagocytosis.
The effect of prednisolone and non-steroid anti-inflammatory drugs on PMNL (polymorphonuclear leucocytes) oxidative metabolism was quantified with a newly standardized NBT test, and it was investigated whether these effects correlate with phagocytosing capacity of PMNL. Prednisolone inhibits NBT reduction in dose dependency already at concentrations, which do not interfere with phagocytosis. Thus prednisolone dissociates phagocytosis and phagocytosis-associated oxidative metabolism. High doses of prednisolone also inhibit phagocytosis. These effects of prednisolone are still demonstrable when PMNL are washed after pre-incubation with the drug. The non-steroid anti-inflammatory drugs (indomethacin, phenylbutazone and pyrazinobutazone) inhibit phagocytosis and NBT reduction at equivalent doses. When PMNL are washed after incubation with the drugs, they regain normal capacity to phagocyse and to reduce NBT. It is suggested that these drugs inhibit phagocytosis directly, and consequently the phagocytosis-associated oxidative metabolism is suppressed.


Lapse resistance in the verbal letter reporting task.
Lapses, or misreporting errors, can affect accuracy of threshold measurements. Assumptions about lapse rate, especially in untrained observers, have consequently guided the design of at least one clinical psychophysical test. Lapse rate was assessed using a verbal letter identification paradigm like that used in visual acuity and letter contrast sensitivity testing. Subjects occasionally made slip-of-the tongue errors but spontaneously corrected them. Lapse rate (excluding such errors) was 0-3 errors per 1,536 (average rate of 0.0005). In this common clinical paradigm, in which observers set their reporting pace, and where opportunity to amend responses is available, lapse rate is negligible.


Synthesis of aryl semicarbazone of 4-aminoacetophenone and their anti-HIV activity.
The thioureido derivative of 4-aminoacetophenone aryl semicarbazone have been prepared. These derivatives have been characterised on the basis of different physicochemical evidences. The anti-HIV-1 (HTLV-IIIB) and -HIV-2 (ROD) activity and cytotoxicity of the compounds were tested. The compound VII and VIII showed maximum protection among the series.


Is It Safe to Reuse Healing Abutments? An Experimental Study on IL-1β and TNF-α Cytokine Levels in Peri-Implant Crevicular Fluid.
To compare pro-inflammatory cytokine levels in the peri-implant crevicular fluid (PICF) in unused and reused healing abutments. This study was a controlled randomized, double-blind clinical trial. Seventy-two patients who met the inclusion criteria were divided into two groups. After one-stage implant placement, in group A, an unused healing abutment, and in group B, a reused healing abutment, was connected to the implant fixture. After 2 months, clinical measurements for keratinized gingiva (KG), plaque index (PI), and bleeding index (BI) (Ainamo and Bay) were taken, and PICF sampling was performed to evaluate pro-inflammatory IL-1β and TNF-α cytokine levels using the ELISA test. Comparison of clinical measurements and cytokine levels between the two study groups was made using the Mann-Whitney test. Clinical measurements and sampling were performed on 60 patients (nA = 27, nB = 33). There was no significant difference between the two groups in clinical measurements (BI (p = 0.96) and PI (p = 0.06)) or TNF-α (p = 0.63), and IL-1β (p = 0.26) cytokine levels. Reused healing abutments that are cleaned and sterilized properly do not appear to induce further peri-implant pro-inflammatory response; therefore, they can be utilized temporarily until implant abutment insertion.


Knowledge and confidence gains after a COVID-19 vaccine continuing education program developed for nurse practitioners.
The COVID-19 pandemic has been marked by rapid innovation in vaccine development. Given that nurse practitioners (NPs) are often involved in vaccine counseling and administration, the American Association of Nurse Practitioners developed a continuing education (CE) series that covered COVID-19 vaccine development, recommendations, administration, and solutions for overcoming hesitancy. In 2020 and 2021, three separate live webinars were delivered; each webinar was updated with the latest vaccine recommendations and was then archived in an enduring format for up to 4 months. The goal of this study was to assess changes in preactivity and postactivity knowledge and confidence and to qualitatively report other learner outcomes. Across the three webinars, 3,580 unique learners who self-reported seeing patients eligible for COVID-19 vaccination completed at least one activity. Knowledge and competence improved from the preactivity to postactivity survey in all webinars, with the overall rates of correct answers increasing by 30% after webinar 1, 37% after webinar 2, and 28% after webinar 3 (all p < .001). Furthermore, mean confidence in learner's ability to address vaccine hesitancy improved across all three webinars (range, 31-32%; all p < .001). The majority of learners indicated that they planned to incorporate lessons from the activity into their clinical practice (range, 85-87%). In postactivity surveys, vaccine hesitancy was identified as an ongoing barrier by up to 33% of learners. In conclusion, this CE activity improved learner knowledge, competence, and confidence related to COVID-19 vaccination and underscores the importance of up-to-date CE targeted to NPs.


Trichomoniasis treated with a single dose of benzoylmetronidazole.
A single 2-g dose of benzoylmetronidazole (Flagyl suspension) was given to patients with vaginal trichomoniasis in the second and third trimesters of pregnancy. The preparation was well tolerated, there were very few side-effects and the overall cure rate after 7 days was 97,6%.


Clinical characteristics of nosocomial rotavirus infection in children in Taiwan.
The aim of this study was to determine the incidence and clinical characteristics of nosocomial rotavirus infection (NRI) among hospitalized children. We collected data of children in the Department of Pediatrics with positive stool rotavirus antigen tests. Cases of an admission diagnosis of acute gastroenteritis or a positive stool rotavirus antigen test within 3 days of admission, representing community-acquired infections, were excluded. Both VP4 and VP7 genotyping of the rotaviruses was done. There were 98 patients who met the inclusion criteria during the 3-year period. The incidence density was 0.58 per 1000 patient-days in our series. Among these patients, 59 (60%) had underlying diseases. The intermediate intensive care unit had the highest incidence density (2.8 per 1000 patient-days). Overcrowding of the care unit, inappropriate hand hygiene, and inadequate isolation and cohorting predisposed to the high rate. Genotypes among 79 (80%) rotaviruses tested showed that 42% belonged to the novel genotype, G9P[8]. NRI may cause significant morbidity in hospitalized children, especially young infants and those with underlying diseases. Infection control with hospital surveillance, strict isolation and cohort care should be adopted to prevent the spread of rotavirus among special care units.


Demonstration and characterization of cytosol androgen receptor in rat exorbital lacrimal gland.
The presence of a macromolecule which binds androgen with a high affinity and a low capacity was demonstrated in the cytosol of the lacrimal glands of male and female rats. Evidence was found that this macromolecule was a protein by treatment with protease, trypsin or heat. A specific 8-8.5 S peak was obtained in both sexes by glycerol gradient centrifugation in low salt condition, whereas a specific 5.2 S peak was found in high salt condition. This protein could bind to DNA-cellulose after treatment of androgen-cytosol complexes by warming (25 degrees C 15 min) or exposure under high salt (0.4 M KCl). These results suggested that this protein was an androgen receptor.


Oculomotor neuromyotonia with lid ptosis on abduction.
Ocular neuromyotonia is an episodic involuntary contraction of one or more of the extraocular muscles resulting from spontaneous neural discharges of the oculomotor nerve. It is characterized by symptomatic diplopia for the duration of the contraction and occurs either spontaneously or after a sustained eccentric gaze. Although the mechanism of ocular neuromyotonia is not fully understood, primary or secondary aberrant regeneration and consequent ephaptic transmission generally are held to be involved. We report the case of a patient with right oculomotor neuromyotonia accompanied by lid ptosis on abduction of the left eye who was successfully treated with oral carbamazepine.


A medical student-staffed outpatient oncology clinic: a 10-year Brazilian experience.
This is an update of a 10-years student-staffed oncology clinic. Students are divided into 4 teams; each sees 1 to 2 outpatients weekly. By April 2006, 95 medical students participated, 89% for 2 or more years; 70% reported activity contributed to ability to read medical papers, and 59% improved their scientific writing. Of 39 students currently involved, 33 (84%) improved clinical skills in taking history, 27 (69%) in physical examination, and 34 (87%) in physician-patient relation. A total of 21 (56%) reported increased knowledge in general internal medicine. Although only 11% of former students pursued a specialty in Medical Oncology, 77% rated this clinic as the best extracurricular activity. Attendance of outpatient clinic in medical oncology can contribute significantly to the general medical education.


The protection and therapy effects of bortezomib in murine acute graft-versus-host disease.
Acute graft-versus-host disease (aGVHD) remains a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The proteasome inhibitor bortezomib exhibits potent antitumor activity with anti-inflammatory and immunomodulatory effects. However, the effects of bortezomib on aGVHD are unclear. In this study, we assessed the effects of bortezomib on aGVHD in the C57BL/6 (H-2b+) donor to BALB/c (H-2d+) recipient major histocompatibility complex-mismatched model. Two bortezomib doses (1 mg/kg each) on days 0 and +1 after transplantation, significantly increased survival rate and attenuated clinical signs of aGVHD without altering donor reconstitution. However, GVHD-associated mortality was significantly increased when bortezomib administration was delayed to day +2 posttransplantation. Furthermore, a single dose of bortezomib on day 0 or day +1 after transplantation also decreased the GVHD protective effect. Consistent with the above data, serum cytokine levels of IL-2, IFN-γ and TNF-α were significantly decreased at day +7 posttransplantation after two doses of bortezomib compared with aGVHD control group. Moreover, two administrations of bortezomib reduced donor T-cell expansion at days +3 and +4 posttransplantation and enhanced donor CD4(+)T-cell differentiation into the T help cell 17 subset at day +7 after transplantation in spleens. These results indicated that the protective effects of bortezomib on aGVHD were dependent on the time and the frequency of bortezomib administration.


Quantification of electron-phonon scattering for determination of temperature variations at high spatial resolution in the transmission electron microscope.
This work investigates the quantification of electron-phonon thermal diffuse scattering (TDS) for detection of temperature variations with nanometer spatial resolution in transmission electron microscopy (TEM). Observations of TDS intensity for (100) single crystal Si and Ge show interdependences of temperature and sample thickness which can be understood through the angular distributions of electron-phonon scattering as a function of temperature. The temperature sensitivity of the integrated TDS intensity can be of the order of 10(-3) K(-1) for Si and Ge. This shows that measurement of the TDS intensity in the TEM is a promising means for nanoscale temperature measurement; our measurements to date have demonstrated that temperature changes as small as 5 K are detectable.


Association between short-term air pollution exposure and attention-deficit/hyperactivity disorder-related hospital admissions among adolescents: A nationwide time-series study.
Long-term air pollution exposure has been suggested to increase the risk of attention-deficit/hyperactivity disorder (ADHD). However, the association between short-term air pollution exposure and ADHD-related outcomes is still unknown. We investigated the associations between short-term exposure to particulate matter with an aerodynamic diameter ≤10 μm (PM10), nitrogen oxide (NO2), and sulfur dioxide (SO2) and hospital admissions with a principal diagnosis of ADHD among adolescents (age 10-19 years) in 16 regions of the Republic of Korea from 2013 to 2015. We estimated the region-specific relative risks (RRs) and 95% confidence intervals (CIs) from quasi-Poisson regressions adjusted for potential confounders, considering single-day and moving average lag. Consequently, we performed meta-analyses to pool the region-specific estimates. The risks of ADHD-related hospital admissions were increased in the single-day and moving average lag models for PM10 (largest association for lag 1 in the single-day lag model, RR = 1.12, 95% CI: 1.05, 1.20; lag 0-2 in the moving average lag model, RR = 1.17, 95% CI: 1.07, 1.27), NO2 (lag 3, RR = 1.47, 95% CI: 1.25, 1.73; lag 1-3, RR = 1.68, 95% CI: 1.38, 2.04), and SO2 (lag 1, RR = 1.27, 95% CI: 1.14, 1.41; lag 1-3, RR = 1.29, 95% CI: 1.12, 1.49). The associations were similar between boys and girls, but they were stronger among adolescents aged 15-19 years than those aged 10-14 years for NO2 and SO2. In conclusion, the results indicate that short-term exposure to PM10, NO2, and SO2 may be a risk factor for the exacerbation of ADHD symptoms, leading to hospitalization.


Treatment of massive tibial bone loss due to chronic draining osteomyelitis: fibula transport using the Ilizarov frame.
This article affirms the value of the application of the Ilizarov frame for gradual transport of the ipsilateral fibula to replace massive tibial bone loss following chronic refractory osteomyelitis.


HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation.
Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used the single particle cryo-electron microscopy method to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 Å resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag lattice structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 Å resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10-12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation.


Affinity requirements for control of synaptic targeting and neuronal cell survival by heterophilic IgSF cell adhesion molecules.
Neurons in the developing brain express many different cell adhesion molecules (CAMs) on their surfaces. CAM-binding affinities can vary by more than 200-fold, but the significance of these variations is unknown. Interactions between the immunoglobulin superfamily CAM DIP-α and its binding partners, Dpr10 and Dpr6, control synaptic targeting and survival of Drosophila optic lobe neurons. We design mutations that systematically change interaction affinity and analyze function in vivo. Reducing affinity causes loss-of-function phenotypes whose severity scales with the magnitude of the change. Synaptic targeting is more sensitive to affinity reduction than is cell survival. Increasing affinity rescues neurons that would normally be culled by apoptosis. By manipulating CAM expression together with affinity, we show that the key parameter controlling circuit assembly is surface avidity, which is the strength of adherence between cell surfaces. We conclude that CAM binding affinities and expression levels are finely tuned for function during development.


Polar Gini Curve: A Technique to Discover Gene Expression Spatial Patterns from Single-cell RNA-seq Data.
In this work, we describe the development of Polar Gini Curve, a method for characterizing cluster markers by analyzing single-cell RNA sequencing (scRNA-seq) data. Polar Gini Curve combines the gene expression and the 2D coordinates ("spatial") information to detect patterns of uniformity in any clustered cells from scRNA-seq data. We demonstrate that Polar Gini Curve can help users characterize the shape and density distribution of cells in a particular cluster, which can be generated during routine scRNA-seq data analysis. To quantify the extent to which a gene is uniformly distributed in a cell cluster space, we combine two polar Gini curves (PGCs)-one drawn upon the cell-points expressing the gene (the "foreground curve") and the other drawn upon all cell-points in the cluster (the "background curve"). We show that genes with highly dissimilar foreground and background curves tend not to uniformly distributed in the cell cluster-thus having spatially divergent gene expression patterns within the cluster. Genes with similar foreground and background curves tend to uniformly distributed in the cell cluster-thus having uniform gene expression patterns within the cluster. Such quantitative attributes of PGCs can be applied to sensitively discover biomarkers across clusters from scRNA-seq data. We demonstrate the performance of the Polar Gini Curve framework in several simulation case studies. Using this framework to analyze a real-world neonatal mouse heart cell dataset, the detected biomarkers may characterize novel subtypes of cardiac muscle cells. The source code and data for Polar Gini Curve could be found at http://discovery.informatics.uab.edu/PGC/ or https://figshare.com/projects/Polar_Gini_Curve/76749.


YM-24074, a new peptide antibiotic. II. Structural elucidation.
YM-24074 (formerly called YL-01869P) is a new antibiotic and type I collagenase inhibitor. The structure of this compound was elucidated by spectroscopic analysis and confirmed by acid degradation to be N-(1"-acetyl-3"-methylbutyl)-2- [2'-[(N-hydroxycarbamoyl)methyl]heptanoyl]-hexahydropyrid azine-3-carboxamide. The stereochemistry of two of three chiral centers was determined by degradation products to be 3S, 2'R.


Update on imaging techniques in oculoplastics.
Imaging is a beneficial aid to the oculoplastic surgeon especially in orbital and lacrimal disorders when the pathology is not visible from outside. It is a powerful tool that may be benefited in not only diagnosis but also management and follow-up. The most common imaging modalities required are CT and MRI, with CT being more frequently ordered by oculoplastic surgeons. Improvements in technology enabled the acquisition times to shorten incredibly. Radiologists can now obtain images with superb resolution, and isolate the site and tissue of interest from other structures with special techniques. Better contrast agents and 3D imaging capabilities make complicated cases easier to identify. Color Doppler imaging is becoming more popular both for research and clinical purposes. Magnetic resonance angiography (MRA) added so much to the vascular system imaging recently. Although angiography is still the gold standard, new software and techniques rendered MRA as valuable as angiography in most circumstances. Stereotactic navigation, although in use for a long time, recently became the focus of interest for the oculoplastic surgeon especially in orbital decompressions. Improvements in radiology and nuclear medicine techniques of lacrimal drainage system imaging provided more detailed analysis of the system.


Implementation and Evaluation of a Grip Behavior Model to Express Emotions for an Android Robot.
In this study, we implemented a model with which a robot expressed such complex emotions as heartwarming (e.g., happy and sad) or horror (fear and surprise) by its touches and experimentally investigated the effectiveness of the modeled touch behaviors. Robots that can express emotions through touching behaviors increase their interaction capabilities with humans. Although past studies achieved ways to express emotions through a robot's touch, such studies focused on expressing such basic emotions as happiness and sadness and downplayed these complex emotions. Such studies only proposed a model that expresses these emotions by touch behaviors without evaluations. Therefore, we conducted the experiment to evaluate the model with participants. In the experiment, they evaluated the perceived emotions and empathies from a robot's touch while they watched a video stimulus with the robot. Our results showed that the touch timing before the climax received higher evaluations than touch timing after for both the scary and heartwarming videos.


The role of viral co-infections in the severity of acute respiratory infections among children infected with respiratory syncytial virus (RSV): A systematic review and meta-analysis.
Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV. We conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity. Overall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR) = 7.2, 95% confidence interval (CI) = 2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI = 1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay. Our findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings. PROSPERO CRD42019154761.


Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans.
MTNR1B is a type 2 diabetes susceptibility locus associated with cross-sectional measures of insulin secretion. We hypothesised that variation in MTNR1B contributes to the absolute level of a diabetes-related trait, temporal rate of change in that trait, or both. We tested rs10830963 for association with cross-sectional diabetes-related traits in up to 1,383 individuals or with rate of change in the same phenotypes over a 3-5 year follow-up in up to 374 individuals from the family-based BetaGene study of Mexican Americans. rs10830963 was associated cross-sectionally with fasting glucose (p = 0.0069), acute insulin response (AIR; p = 0.0013), disposition index (p = 0.00078), glucose effectiveness (p = 0.018) and gestational diabetes mellitus (OR 1.48; p = 0.012), but not with OGTT 30 min Δinsulin (the difference between the 30 min and fasting plasma insulin concentration) or 30 min insulin-based disposition index. rs10830963 was also associated with rate of change in fasting glucose (p = 0.043), OGTT 30 min Δinsulin (p = 0.01) and AIR (p = 0.037). There was no evidence for an association with the rate of change in beta cell compensation for insulin resistance. We conclude that variation in MTNR1B contributes to the absolute level of insulin secretion but not to differences in the temporal rate of change in insulin secretion. The observed association with the rate of change in insulin secretion reflects the natural physiological response to changes in underlying insulin sensitivity and is not a direct effect of the variant.


MicroRNA‑144 inhibits migration and proliferation in rectal cancer by downregulating ROCK‑1.
Cancer of the colon and rectum are two distinct entities, which require different treatment strategies and separate treatment. MicroRNAs (miRNAs) act as critical regulators of genes involved in several biological processes. Aberrant alterations of miRNAs have been found in several types of cancer, including colon cancer and rectal cancer. Extensive catalogues of downregulated miRNAs have been identified for colon cancer, whereas only limited data are available for rectal cancer. An example of miRNA profiling in a previous study found that miRNA (miR)‑144 showed aberrant expression and appeared to be rectal cancer‑specific, its expression not being reported in colon cancer. In the present study, the role of miR‑144 in rectal cancer was investigated. SW837 and SW1463 cell lines were selected as rectal cell carcinoma cells. Using reverse transcription-quantitative polymerase chain reaction, western blot, BrdU, cell migration and cell viability assays, it was found that the expression levels of miR‑144 were significantly reduced in the SW837 and SW1463 cell lines, and the overexpression of miR‑144 suppressed rectal cancer cell viability, migration and proliferation. In addition, Rho‑associated coiled‑coil containing protein kinase 1 (ROCK1) was identified as a target of miR‑144 in the rectal cancer cells. The supplementation of ROCK1 markedly restored the cell migration and proliferation, which was inhibited by miR‑144. Together, the data of the present study demonstrated that miR‑144 acts as a tumor suppressor by targeting ROCK1, and indicates the potential of miR‑144 as a novel biomarker and target in the treatment of rectal cancer.


Drug-drug interaction of atazanavir on UGT1A1-mediated glucuronidation of molidustat in human.
Molidustat is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl-hydroxylase enhancing the erythropoietin (EPO) response to HIF; it is in clinical development for the treatment of anaemia related to chronic kidney disease. The predominant role of glucuronidation for molidustat clearance (formation of N-glucuronide metabolite M1) and subsequent renal excretion was confirmed in a human mass balance study, with about 85% of the drug being excreted as M1 in urine. The inhibitory effects of 176 drugs and xenobiotics from various compound classes on the UGT-mediated glucuronidation of molidustat in human liver microsomes (HLMs) were investigated. Based on preclinical findings, glucuronidation of molidustat was predominantly mediated by the 5'-diphospho-glucuronosyltransferase (UGT) isoform UGT1A1. Therefore, atazanavir, which is a potent inhibitor of UGT1A1, was chosen for the evaluation of pharmacokinetics and EPO release following a single oral dose of 25 mg molidustat. Molidustat exposure increased about twofold upon coadministration with atazanavir when considering area under plasma concentration-time curve from zero to infinity (AUC) and maximum plasma concentration (Cmax ). Baseline-corrected increase of EPO was 14% and 34% for Cmax and AUC (calculated over 24 hours), respectively. Coadministration of molidustat and atazanavir was well tolerated.


Enantiomer labelling, a method for the quantitative analysis of amino acids.
Enantiomer labelling a method for the quntitative analysis of optically active natural compounds by gas chromatography, involves the use of the unnatural enantiomer as an internal standard. With Chirasil-Val, a chiral stationary phase that is thermally stable up to up to 240 degrees, the enantiomers of amino acids and a variety of other compounds can be separated and quantitated. Incomplete recovery from the sample, incomplete derivatization, hydrolysis and thermal decomposition of the derivative and shifting response factors can be compensated for by adding the unnatural enantiomer. The accuracy of amino acid analysis by enantiomer labelling is equal or superior to that of hitherto known methods. The procedure affords a complete analysis of peptides with respect to both amino acid composition and the optical purity of each amino acid.


Prognostic significance of the new placental proteins in trophoblastic disease.
Circulating levels of four specific placental proteins, human chorionic gonadotrophin (hCG), Schwangerschafts protein 1 (SP1), placental protein 5 (PP5) and pregnancy-associated plasma protein A (PAPP-A), were measured in 31 patients with hydatidiform mole before treatment. Seven patients subsequently developed clinical choriocarcinoma and three of them had pulmonary metastases. The estimations of hCG, PP5 and PAPP-A levels were found to be of no value in the prediction of malignant sequelae. Levels of SP1 greater than or equal to 16.5 i.u./l were associated with a higher incidence of subsequent malignant disease (P less than 0.05), the risk being at least nine times greater in these patients. The predictive value of high levels of SP1 was 35%, the specificity 45.8% and sensitivity 100%.


Allelic expression at the sorbitol dehydrogenase and glucosephosphate isomerase loci in an interspecific hybrid ricefish.
1. The expression of alleles encoding the enzymes sorbitol dehydrogenase (SDH; EC 188.8.131.52) and glucosephosphate isomerase (GPI; EC 188.8.131.52) was investigated in Oryzias melastigma, O. javanicus and in O. melastigma female x O. javanicus male hybrids by acrylamide gel electrophoresis. 2. It was not possible to investigate the expression of SDH or GPI in reciprocal hybrids as these fry failed to develop past the stage of embryonic body formation. 3. The delay in appearance of isozymes of paternal SDH subunit composition, and paternal and maternal GPI-B subunit composition is in keeping with observed effects of gene regulatory divergence where alleles of maternal origin interact more effectively with maternal cytoplasmic regulatory factors than do alleles of paternal origin.


Use of a Doppler ultrasound stethoscope for intercostal nerve block.
Two cases with rib injuries are reported where intercostal nerve block without rib palpation was safely and successfully performed on six separate occasions using a Doppler blood-flow detector ultrasound stethoscope. A third case studied by a radiologist using a pulsed Doppler flowmeter, determined the source of the Doppler signals as originating from the intercostal artery. The significance of these findings is discussed.


A DFT analysis of electronic, reactivity, and NLO responses of a reactive orange dye: the role of Hartree-Fock exchange corrections.
An experimental and theoretical study based on DFT/TD-DFT approximations is presented to understand the nature of electronic excitations, reactivity, and nonlinear optical (NLO) properties of reactive orange 16 dye (RO16), an azo chromophore widely used in textile and pharmacological industries. The results show that the solvent has a considerable influence on the electronic properties of the material. According to experimental results, the absorption spectrum is formed by four intense transitions, which have been identified as [Formula: see text] states using TD-DFT calculations. However, the TD-DFT results reveal a weak [Formula: see text] in the low-lying spectral region. Continuum models of solvation indicate that these states suffer from bathochromic (ca. 15 nm) and hypsochromic shifts (ca. 4 nm), respectively. However, the expected blue shift for the absorption [Formula: see text] is only described using long-range or dispersion-corrected DFT methods. RO16 is classified as a strong electrophilic system, with electrophilicity ω > 1.5 eV. Concerning the nucleophilicity parameter (N), from vacuum to solvent, the environment is active and changes the nucleophilic status from strong to moderate nucleophile (2.0 ≤ N ≤ 3.0 eV). The results also suggest that all electrical constants are strongly dependent on long-range and Hartree-Fock exchange contributions, and the absence of these interactions gives results far from reality. In particular, the results for the NLO response show that the chromophore presents a potential application in this field with a low refractive index and first hyperpolarizability ca. 214 times bigger than the value usually reported for urea (β = 0.34 × 10- 30 esu), which is a standard NLO material. Concerning the solvent effects, the results indicate that the polarizability increases [Formula: see text] esu from gas to solvent while the first hyperpolarizability is calculated as [Formula: see text] esu, ca. 180%, regarding the vacuum. The results suggest RO16 is a potential compound in NLO applications. Graphical Abstract The frontier molecular orbitals, and the inverse relation between the energy-gap (Egap) and the first hyperpolarizability (β).


Monitoring of hydrolysis products of organophosphorus nerve agents in plant material and soil by liquid chromatography-tandem mass spectrometry.
Nerve agents are organophosphorus compounds of the highest toxicity and danger. The production, transportation and use of these substances are prohibited by the Organization for the Prohibition of Chemical Weapons. Any fact of alleged use of nerve agents is a crime against humanity and must be investigated in detail by the world community. For this purpose, such analysis objects as biological fluids (urine, blood) and environmental objects (water, soil) are well studied. The current study demonstrates the possibility of using plants as a convenient material for retrospective analysis. Methyl phosphonic acid and some of its alkyl esters (ethyl, isopropyl, isobutyl, cyclohexyl, pinacolyl) were chosen as nerve agent metabolites. Hedera Helix growing in soil was used as a carrier of the markers. The selected markers were injected once in the soil and their content in the plant and soil was monitored for 4 weeks. A fast and simple way of sample homogenization with liquid nitrogen followed by ultrasonic liquid extraction was applied. The developed HPLC-MS/MS approach with the use of deuterated internal standards for quantitative analysis was validated. The research discovered that all the studied nerve agent markers could be detected and determined both in the soil and the plant for at least one month. The results indicate the promising use of plants as additional objects of analysis in investigation of incidents involving the use of chemical warfare agents.


Synergistic effect of 4-hydroxynonenal and PPAR ligands in controlling human leukemic cell growth and differentiation.
Peroxisome proliferator-activated receptors play an important role in the differentiation of different cell lines. In this study we demonstrate that PPAR-alpha ligands (clofibrate and ciprofibrate) and PPAR-gamma ligands (troglitazone and 15d-prostaglandin J2) inhibit growth and induce monocytic differentiation in HL-60 cells, whereas only PPAR-gamma ligands inhibit growth of U937 cells. Differentiation was demonstrated by the analysis of surface antigen expression CD11b and CD14, and by the characteristic morphological changes. PPAR-gamma ligands are more effective than PPAR-alpha ligands in the inhibition of cell growth and in the induction of differentiation. The physiological product of lipid peroxidation, 4-hydroxynonenal (HNE), which alone induces granulocytic-like differentiation of HL-60 cells, potentiates the monocytic differentiation induced by ciprofibrate, troglitazone, and 15d-prostaglandin J2. The same HNE treatment significantly inhibits U937 cell growth and potentiates the inhibition of cell growth in PPAR-gamma ligand-treated cells. However, HNE does not induce a significant number of CD14-positive U937 cells. HNE causes a great increase of PPAR-gamma expression in both HL-60 and U937 cells, whereas it does not modify the PPAR-alpha expression. This observation may account for the high synergistic effect displayed by HNE and PPAR-gamma ligands in the inhibition of cell growth and differentiation induction. These results represent the first evidence of the involvement of a product of lipid peroxidation in the modulation of PPAR ligand activity and suggest a relationship between HNE and PPAR ligand pathways in leukemic cell growth and differentiation.


A Case Report of Probable Paliperidone ER-Induced Serotonin Syndrome in a 17-Year-Old Taiwanese Female With New Onset Psychosis.
A 17-year-old female with new-onset psychosis was treated with paliperidone. After increasing the paliperidone dose to 12 mg per day the patient developed a series of side effects; Tachycardia (140 bpm), severe drooling, restlessness, diaphoresis, whole-body tremor, inducible foot clonus, predominant lower limbs rigidity, bilateral pupil dilation, increased bowel sounds with watery diarrhea, and muscle hypertonicity. The symptoms subsided after stopping the paliperidone, and recurred after resuming paliperidone 9 mg per day. To our knowledge, this is the first case of a very clear and close relationship between the symptoms of serotonin syndrome and the use of paliperidone. We have to cautiously consider the diagnosis of serotonin syndrome in potential cases.


Pressor and subpressor angiotensin II administration. Two experimental models of hypertension.
Administered dose is an important determinant of the type of hypertension produced by angiotensin II. With chronic administration of pressor doses, there is salt and water retention and expansion of extracellular fluid volume, and the pressure-natriuresis curve is shifted to higher pressures. Important compensatory mechanisms, including resetting of baroreceptors, de novo synthesis of vasodilator prostaglandins, and atrial natriuretic factor release, are triggered by the acute rise of blood pressure. Histologic evidence for vascular injury confounds the interpretation of findings. When angiotensin II is administered in initially subpressor doses, the rise of blood pressure is gradual, there are no detectable changes in salt and water balance, and compensatory mechanisms do not seem to be activated. Autopotentiation of pressor and vasoconstrictor responses by angiotensin II is the characteristic feature of the early stages of hypertension induced by small doses of angiotensin II. Trophic stimulation of vascular tissue, in particular restructuring of extracellular matrix, precedes and may, therefore, be the mechanism responsible for the hemodynamic changes. The pressor and subpressor models of angiotensin II-induced hypertension draw attention to the relative importance of renal and extrarenal mechanisms in the pathogenesis of hypertension. The long-term administration of initially subpressor doses of angiotensin II mimics the development of human hypertension to a greater extent than does the administration of pressor doses.


Electrophysiological and anatomical differences of the slow pathway between the fast-slow form and slow-slow form of atrioventricular nodal reentrant tachycardia.
This study aimed to clarify whether electrophysiological and anatomical properties of the slow pathway (SP) could be different between the fast-slow form (F/S) and the slow-slow form (S/S) atrioventricular nodal reentrant tachycardia (AVNRT). Nine patients with F/S and 15 patients with S/S of atypical AVNRT were studied. The patients with S/S were divided into two groups; those with the anterograde SP being eliminated (S/S aSP-E) or preserved (S/S aSP-P) during catheter ablation. HA (CS-His) was determined as the difference of the shortest HA interval between the His bundle region and the coronary sinus (CS) region. The ratio of the amplitudes of atrial and ventricular potential (A/V ratio) of the successful ablation site of the SP was also evaluated. Effective refractory period of the retrograde SP was shorter and HA intervals during both tachycardia and ventricular pacing were longer in F/S than in S/S. HA (CS-His) did not differ between F/S and S/S (-4.3 ± 20.2 vs.-4.4 ± 18.4 ms, NS). The A/V ratio was significantly greater in the S/S aSP-P group compared with the both groups of F/S and S/S aSP-E (0.83 ± 0.29 vs. 0.38 ± 0.09 and 0.26 ± 0.15 ms, P < 0.01). Properties of the retrograde SP differ between F/S and S/S of AVNRT. Fast-slow form may utilize the same pathway for the retrograde conduction as the anterograde SP in S/S.


Health risk behavior and cultural stress among Venezuelan youth: a person centered approach.
In recent years, more than 5 million Venezuelans have left their once prosperous country, with several hundred thousand settling in the United States (US). At present, our understanding of the health risk behavior profiles of Venezuelan émigré youth, and their links with cultural stress, remains limited. Drawing from a sample of recently-immigrated Venezuelan youth in the US, we aim to identify subtypes of youth according to their involvement in health risk behaviors (i.e., substance use, sexual risk behavior, violence) and assess the associations between class membership and key constructs related to cultural stress theory (i.e., negative context of reception, family communication/support). Latent profile analysis and multinomial regression were performed using data from a community-based convenience sample of 402 recently-arrived Venezuelan immigrant youth (ages 10-17; 56% male). We identified five subtype classes: (1) "Abstainer" (36%), (2) "Alcohol Only" (24%), (3) "Alcohol/Tobacco" (24%), (4) "Aggression" (8%), and (5) "Multidimensional Risk" (8%). Compared to Class #1, youth in Classes #3 and #5 reported significantly higher levels of negative context of reception and lower levels of family functioning while controlling for demographic factors. Youth in Class #5 reported the lowest levels of family economic hardship and the longest duration in the US. It is vital that we support both Venezuelan youth who abstain from risk behavior and, at the same time, develop and implement programs that target the needs of those who are at elevated risk for serious consequences related to substance use, sexual risk behavior, and violence.


Direct sagittal computed tomography scanning of the skull and its contents.
An accessory patient table has been built for use with the wide-aperture Varian CT scanner, which makes it possible to position patients for direct (positional) sagittal CT scans of the head. No extra computer manipulation is required to produce these sagittal images. Density and spatial resolution are similar to those obtained in the axial plane. Practical applications to date include improving visualization of orbital lesions and soft tissue masses involving the face, and aiding surgical and radiotherapy treatment planning for intracranial lesions.


Is dying in hospital better than home in incurable cancer and what factors influence this? A population-based study.
Studies show that most patients with advanced cancer prefer to die at home. However, not all have equal chances and the evidence is unclear on whether dying at home is better. This study aims to determine the association between place of death, health services used, and pain, feeling at peace, and grief intensity. Mortality follow-back study of 352 cancer patients who died in hospital (n = 177) or at home (n = 175) in London, UK. Bereaved relatives identified from death registrations completed a questionnaire including validated measures of patient's pain and peace in the last week of life and their own grief intensity. We determined factors influencing death at home, and associations between place of death and pain, peace, and grief. Where people died was, for most (80%), the place where they lived during their last week of life. Four factors explained >91% of home deaths: patient's preference, relative's preference, home palliative care, or district/community nursing. The propensity of death at home also increased when the relative was aware of incurability and the patient discussed his/her preferences with family. Dying in hospital was associated with more hospital days, fewer general practitioner (GP) home visits, and fewer days taken off work by relatives. Adjusting for confounders, patients who died at home experienced similar pain levels but more peace in their last week of life (ordered log odds ratio 0.69, P = 0.007). Grief was less intense for their relatives than for those of patients who died in hospital (β, -0.15 around time of death and -0.14 at questionnaire completion, P = 0.02). The study suggests that dying at home is better than hospital for peace and grief, but requires a discussion of preferences, GP home visits, and relatives to be given time off work. National Institute of Health Research (NIHR) Clinical Research Network Portfolio. UKCRN7041.


Human rectal mucosa: proctoscopic and morphological changes caused by laxatives.
To determine whether laxatives alter the proctoscopic and morphological appearances of the human rectum, 10 normal subjects were studied prospectively, and the following manipulations were assessed in a randomized, blinded manner: no treatment; oral mannitol to induce diarrhea; isotonic saline enema; Fleet's Phospho-Soda enema; and bisacodyl (Dulcolax), 10 mg, by enema or suppository. The rectal mucosa after mannitol-induced diarrhea, or after saline enema could not be distinguished from untreated rectum by proctoscopy, light microscopy, or scanning electron microscopy. Fleet's enema, and bisacodyl invariably changed proctoscopic appearances, and frequently altered light and scanning microscopic aspects. Both Fleet's enema and bisacodyl caused sloughing of surface epithelium. In addition, bisacodyl decreased the uptake of hematoxylin and eosin by crypt epithelial cells so that the affected cells had a partially erased appearance (16 of 25 biopsies examined by light microscopy). The lamina propria of 3 of these 25 biopsies contained polymorphonuclear cells. Transmission electron microscopy revealed that the abnormal crypt epithelial cells contained fewer cytoplasmic organelles and less nuclear chromatin. All lesions resolved within 7 days. Fleet's enema and bisacodyl by rectum may mislead the proctologist and the pathologist by altering normal rectal mucosa.


Synthesis and photophysical properties of a fluorescent cyanoquinoline probe for profiling ERBB2 kinase inhibitor response.
A fluorescent probe targeting the ERBB2 receptor tyrosine was designed, synthesized and evaluated as reporter of ERBB2 dynamics in overexpressing BT474, i.e. Her2(+), cells. Two cyanoquinazoline (CQ) probes modeled after type-I (CQ1) or active state and type-II (CQ2) or inactive state inhibitors were designed and synthesized with extended π systems that impart binding-induced, turn-on fluorescence. Solution spectroscopy revealed that CQ1 exhibited attractive photophysical properties and displayed turn-on emission in the presence of purified, soluble ERBB2 kinase domain, while CQ2 was found to be non-emissive, likely due to quenching via a photoinduced electron transfer mechanism. Live cell imaging with CQ1 revealed that this probe targeted an intracellular population of ERBB2, which increased following treatment with type-I inhibitors, gefinitib and canertinib, but showed no response to type-II inhibitors. CQ1 thus provides a novel means of imaging the dynamic response of ERBB2(+) cells to kinase inhibitors.


Evaluation of a peer- and self-grading process for clinical writing assignments.
As class sizes in pharmacy education increase, faculty must develop new assessment strategies for essay writing assignments. This study evaluated accuracy and student perceptions of an innovative grading process that utilizes both peer- and self-assessment. Four SOAP note sessions were evaluated. Each session included four activities: a writing workshop, assessment workshop, and reflection session. For each assessment workshop students scored their note and a blinded peer's note using a grading form, facilitated by a faculty-led discussion. In a subsequent reflection session, students reviewed their peer- and self-assigned grades and could petition for faculty review if desired. The average self-, peer-, and final-grades were compared for each of the four SOAP note sessions using ANOVA. After the fourth session, students completed an anonymous 10-question Likert-scale survey regarding their perceptions of the process and three open-response questions. Survey results were analyzed with descriptive statistics. Approximately 140 students participated. No difference was found between the average self-, peer-, and final-grades for all four sessions (p > 0.05). The survey response rate was 65% (91/140). Survey questions were grouped into three themes. The majority of students either strongly agreed or agreed that sessions were well organized and effective (≥84%), assessment workshops enhanced learning (≥68%), and the scoring method was fair (≥72%). The lowest score (mean 2.53 on a 4-point scale) reflected satisfaction with peer-provided feedback. When asked what they liked most, respondents most commonly cited that faculty-led review and discussion enhanced clinical knowledge. The combination of a peer- and self-assessment process was accurate, well-received, and can be used to decrease faculty workload.


On the effect of prestrain and residual stress in thin biological membranes.
Understanding the difference between ex vivo and in vivo measurements is critical to interpret the load carrying mechanisms of living biological systems. For the past four decades, the ex vivo stiffness of thin biological membranes has been characterized using uniaxial and biaxial tests with remarkably consistent stiffness parameters, even across different species. Recently, the in vivo stiffness was characterized using combined imaging techniques and inverse finite element analyses. Surprisingly, ex vivo and in vivo stiffness values differed by up to three orders of magnitude. Here, for the first time, we explain this tremendous discrepancy using the concept of prestrain. We illustrate the mathematical modeling of prestrain in nonlinear continuum mechanics through the multiplicative decomposition of the total elastic deformation into prestrain-induced and load-induced parts. Using in vivo measured membrane kinematics and associated pressure recordings, we perform an inverse finite element analysis for different prestrain levels and show that the resulting membrane stiffness may indeed differ by four orders of magnitude depending on the prestrain level. Our study motivates the hypothesis that prestrain is important to position thin biological membranes in vivo into their optimal operating range, right at the transition point of the stiffening regime. Understanding the effect of prestrain has direct clinical implications in regenerative medicine, medical device design, and and tissue engineering of replacement constructs for thin biological membranes.


Acute partial paralysis alters perceptions of air hunger, work and effort at constant P(CO(2)) and V(E).
Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of central motor discharge (corollary discharge) to the forebrain. Source of motor drive (brainstem or cortex) may determine what is perceived. To test the effect of changing motor discharge at constant ventilation, we induced partial neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1); PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5 L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar between conditions (39%). Ventilation was unchanged with paralysis, indicating increased respiratory motor drive to maintain hyperpnea. Sensations were rated on a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with paralysis during both forms of hyperpnea (P<0.02, Wilcoxon signed rank). Median AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P<0.02) but not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from motor cortex activity (subjects reported engaging volitional control when paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from medullary motor activity.


In vitro activity of the flt3-inhibitor su5614 and standard cytotoxic agents in tumour cells from patients with wild type and mutated flt3 acute myeloid leukaemia.
The correlation between drug sensitivity in vitro and the mutation status of the FLT3 receptor gene was evaluated in tumour cells from 17 previously untreated AML patients. Tumour cells with internal tandem duplication (ITD) in the FLT3 receptor gene were significantly more sensitive to the FLT3 inhibitor SU5614 than tumour cells with wild type FLT3. Combinations of SU5614 with etoposide and amsacrine showed better effect (p<0.05) compared with the respective single drugs. Our results suggest that the FLT3 inhibitor SU5614 may have a therapeutic potential, especially in combination with other cytotoxic agents, in patients with FLT3-ITD positive AML.


Nanomedicine: controlling nanoparticle clearance for translational success.
Achieving complete nanoparticle (NP) clearance is a key consideration in the design of safe and translatable nanomedicines. Renal-clearable nano formulations must encompass the beneficial nanoscale functionalities whilst exhibiting clearance profiles like those of small-molecule therapeutics. Recent developments in the field have enabled the growth of novel renal-clearable NPs with transformable sizes that take advantage of alternative clearance mechanisms to achieve controlled and efficient renal excretion to improve potential clinical translation.


3-(4-Fluoro-phenyl-sulfon-yl)-5-iodo-2,7-dimethyl-1-benzofuran.
In the title compound, C(16)H(12)FIO(3)S, the 4-fluoro-phenyl ring makes a dihedral angle of 72.31 (6)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds, and by an I⋯I contact [3.7764 (3) Å]. The crystal structure also exhibits a weak C-I⋯π [3.901 (3) Å] inter-action and a slipped π-π inter-action between the furan and benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.845 (3), inter-planar distance = 3.555 (3) and slippage = 1.465 (3) Å].


Cyclosporin A in severe, therapy-resistant atopic dermatitis: report of an international workshop, April 1993.
Data on the use of oral cyclosporin A (CyA; Sandimmun) therapy for severe adult atopic dermatitis have accumulated since 1987. Details of over 200 adult patients who have received short-term CyA were presented at an international workshop in April 1993. Eighty-six of these patients had participated in three randomized, double-blind, placebo-controlled studies in which CyA was given for 6-8 weeks. The efficacy and safety of short-term CyA treatment in atopic dermatitis is established, provided that appropriate guidelines are observed. Evidence to date suggests that atopic dermatitis patients are no more prone to toxicity than patients with psoriasis, in whom more detailed and longer-term data are available. Early data also suggest that long-term CyA may be effective in atopic dermatitis, but there is concern regarding long-term safety, as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory. CyA should only be used under the direct and regular supervision of a hospital-based dermatologist who is knowledgeable in the use of cyclosporin A, and experienced in the management of severe skin disease and in the use of potentially toxic drugs.


Assays of adrenal GPCR signaling and regulation: Measuring adrenal β-arrestin activity in vivo through plasma membrane recruitment.
Production and secretion of catecholamines and aldosterone from the adrenal gland are regulated by various adrenal G protein-coupled receptors (GPCRs), including α2-adrenergic (auto)receptors (ARs) and angiotensin receptors. These hormones, in turn, regulate cardiac function and play important pathophysiological roles in heart failure (HF). Recent studies have identified the GPCR adapter proteins β-arrestins, specifically β-arrestin1, as an important mediator of the GPCR-dependent production of these hormones in the adrenal gland. Upon GPCR agonist activation, β-arrestins translocate from the cytoplasm to the plasma membrane to interact with the phosphorylated and active receptor and mediate its G protein-independent signaling. Here, we describe a simple and fast Western blotting-based technique for measuring adrenal β-arrestin plasma membrane recruitment in vivo, as an (indirect) index of its activity toward various agonist-activated adrenal GPCRs in vivo.


Multi-generation toxicity of zinc, cadmium, copper and lead to the potworm Enchytraeus albidus.
In standard chronic terrestrial toxicity tests with invertebrates, adult organisms are exposed to the contaminants and the number of offspring is quantified. These procedures do not allow the assessment of possible effects on all life stages of the organism, which may lead to an underestimation of the toxicity of the test substance. To evaluate the importance of this issue, the potworm Enchytraeus albidus was exposed to zinc, cadmium, copper and lead for two subsequent generations. Juvenile production was assessed for both generations. Considering the variability of metal toxicity data reported in the literature, it is concluded that the two generation assay did not markedly increase the sensitivity of the standard E. albidus test for the tested metals. Therefore, toxicity data obtained with the proposed test guideline with E. albidus are protective for all life stages.


Reduced zinc cytotoxicity following differentiation of neural stem/progenitor cells into neurons and glial cells is associated with upregulation of metallothioneins.
We investigated zinc cytotoxicity in mouse neural stem/progenitor cells (NSPCs) and their differentiated progeny (neuronal/glial cells) in correlation with expression of metallothionein (MT) gene. Differentiated cells were less sensitive than NSPCs to ZnCl2 (IC50: 128μM vs. 76μM). Differentiation of immature NSPCs to the differentiated cells led to an increase in expression of MT family genes (Mt1, Mt2, Mt3, and Mt4). Zinc exposure induced a dose-dependent increase in expression level of Mt1 and that of Mt2 in both NSPCs and the differentiated cells. Our results showed that the reduced cytotoxicity of zinc associated with differentiation from NSPCs into their progeny was related to the upregulation of MTs.


Three-year experience of prophylactic placement of inferior vena cava filters in women with gynecological cancer.
To evaluate the outcomes of prophylactic placement of inferior vena cava (IVC) filters to prevent pulmonary embolism (PE) in women undergoing surgery and chemotherapy for gynecological cancer. Thirty-eight IVC filters were placed in 38 women between January 2008 and January 2010; 25 of these were placed in gynecological cancer patients for prevention of PE during surgery and the postoperative period. The patients' electronic medical records, follow-up computed tomography scans, and outpatient follow-up notes were retrospectively reviewed for incidence of PE and adverse events. After 6 months of follow-up, no PE was observed and there was no mortality. Nine filters were retrieved uneventfully, and there were no clinical complications associated with any indwelling filter. IVC filters are safe and beneficial towards preventing PE in women undergoing surgery and chemotherapy for gynecological cancer.


Daily fecal pH pattern and variation in lactating dairy cows.
Evidence supports a causal link between anomalous intestinal function and impaired performance in dairy cows. Consequently, digesta pH values obtained from colon, cecum, and rectum are increasingly used to monitor intestinal function in dairy cows. We conducted a study to describe the daily dynamics of fecal pH in lactating dairy cows. The study lasted 4 d and individual records of dry matter intake, milk yield, and fecal pH were taken. Samples of feces were taken every 4 h during the 4-d study, and sampling time was adjusted ahead by 1 h daily so that a sample was obtained for each 1-h interval of the day. Data were analyzed using a mixed-effect model including time as fixed effect and cow as a random factor. We performed a cosinor analysis using pH data at different time points to determine whether fecal pH followed a biorhythmic pattern. On average, cows consumed 19.1 ± 1.55 kg/d of dry matter and produced 26.3 ± 4.16 kg/d of milk. The most relevant results confirmed a biorhythmic pattern for feces pH around feeding time: mesor (midline estimating statistic of rhythm) 6.20, amplitude 0.28, and acrophase 5.66. Additionally, we found a positive relationship between dry matter intake and amplitude, possibly because of an increase in the amount of fermentable carbohydrate reaching the hindgut in response to increasing intake. When using fecal pH as an indicator of intestinal function, it is critical to obtain samples at several time points to capture its daily rhythmicity and to report sampling time relative to feeding.


Application of Guideline-Based Echocardiographic Assessment of Left Atrial Pressure to Heart Failure with Preserved Ejection Fraction.
Early, noninvasive identification of patients with heart failure with preserved ejection fraction (HFpEF) with congestion may allow timely tailoring of decongestive therapies. The 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines provide an algorithm to assess for elevated left atrial pressure (LAP); the associations of echocardiographic LAP with clinical status and disease progression in patients with HFpEF are unclear. Participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial were categorized into one of four prespecified guideline-based echocardiographic LAP categories: (1) normal, (2) elevated, (3) atrial fibrillation (AF) at the time of echocardiography, or (4) indeterminate. Associations of echocardiographic LAP categories with baseline exercise capacity, change in exercise capacity, and change in N-terminal pro-B-type natriuretic peptide over 24 weeks were evaluated. Of 216 participants, 199 underwent mitral inflow Doppler echocardiography for LAP categorization. Participants with elevated echocardiographic LAP (n = 81) or AF (n = 57) were older and had a higher prevalence of kidney dysfunction. Compared with the normal echocardiographic LAP group (n = 28), elevated echocardiographic LAP and AF were each independently associated with a greater reduction in peak oxygen consumption over 24 weeks after adjusting for baseline values and clinical covariates (β for elevated echocardiographic LAP = -1.55 [95% CI, -2.59 to -0.51], P = .004; β for AF = -1.33 [95% CI, -2.49 to -0.17], P = .03). Indeterminate echocardiographic LAP (n = 33) was also independently associated with a reduction in exercise capacity at 24 weeks compared with normal echocardiographic LAP (β = -1.35; 95% CI, -2.51 to -0.19; P = .02). Finally, elevated echocardiographic LAP and AF were significantly associated with increases in N-terminal pro-B-type natriuretic peptide over 24 weeks compared with normal echocardiographic LAP. In patients with chronic HFpEF, elevated echocardiographic LAP and indeterminate echocardiographic LAP, as defined by contemporary guidelines, and AF were each independently associated with a reduction in exercise capacity compared with normal echocardiographic LAP. These findings suggest the potential utility of noninvasive LAP assessment in patients with HFpEF for tailoring treatments that decrease congestion.


C1632 inhibits ovarian cancer cell growth and migration by inhibiting LIN28 B/let-7/FAK signaling pathway and FAK phosphorylation.
The highly conserved RNA-binding protein LIN28B and focal adhesion kinase (FAK) are significantly upregulated in ovarian cancer (OC), serving as markers for disease progression and prognosis. Nonetheless, the correlation between LIN28B and FAK, as well as the pharmacological effects of the LIN28 inhibitor C1632, in OC cells have not been elucidated. The present study demonstrates that C1632 significantly reduced the rate of DNA replication, arrested the cell cycle at the G0/G1 phase, consequently reducing cell viability, and impeding clone formation. Moreover, treatment with C1632 decreased cell-matrix adhesion, as well as inhibited cell migration and invasion. Further mechanistic studies revealed that C1632 inhibited the OC cell proliferation and migration by concurrently inhibiting LIN28 B/let-7/FAK signaling pathway and FAK phosphorylation. Furthermore, C1632 exhibited an obvious inhibitory effect on OC cell xenograft tumors in mice. Altogether, these findings identified that LIN28 B/let-7/FAK is a valuable target in OC and C1632 is a promising onco-therapeutic agent for OC treatment.


Identification of conserved histidines and glutamic acid as key residues for isomerohydrolase activity of RPE65, an enzyme of the visual cycle in the retinal pigment epithelium.
We have recently reported that RPE65 from the retinal pigment epithelium is the isomerohydrolase, a critical enzyme in the visual cycle for regeneration of 11-cis retinal, the chromophore for visual pigments. Here, we demonstrated that mutation of any one of the absolutely conserved four histidine and one glutamic acid residues to alanine in RPE65 abolished its isomerohydrolase activity. Substitution of the conserved glutamic acid with glutamine also resulted in loss of the activity. Moreover, these mutations significantly reduced protein stability of RPE65. These results indicate that these conserved residues are essential for the isomerohydrolase activity of RPE65 and its stability.


[Interaction of s4U8 region of tRNA Phe with tRNA-(adenine-1-)-methyltransferase from Thermus thermophilus].
Photoaffinity labelling of tRNA (adenine-1-)-methyltransferase with an E. coli tRNA(Phe) derivative bearing 4-azidophenylmercuro group attached to s4U residue as well as direct photocross-linking of the native tRNA(Phe) with the enzyme via s4U residue has been studied. Both techniques labelling gave similar results, leading to covalent attachment of tRNA(Phe) to the enzyme within a specific complex. The data obtained indicate unambigously that s4U residue contacts with tRNA (adenine-1-)-methyltransferase within the corresponding specific complex.


Fibrin clot structure in patients with end-stage renal disease.
Fibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD). These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p < 0.001), less compactable (p < 0.001), and less susceptible to fibrinolysis (p < 0.001) than clots from controls. The maximum rate of turbidity increase was also higher for the patients than controls (p < 0.001), and scanning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p < 0.001). Patients had higher plasma concentrations of fibrinogen, C-reactive protein and interleukin 6 than controls. These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.


Pioglitazone on nonalcoholic steatohepatitis: A systematic review and meta-analysis of 15 RCTs.
Nonalcoholic steatohepatitis is regarded as a risk factor of many liver diseases. Relevant studies were searched from The National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science and WANFANG databases. A total of 15 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 7 English articles and 8 Chinese articles. Fifteen studies are selected for this meta-analysis, which includes totally 623 patients in the treatment group and 594 patients in the control group. As a result, 8 studies show that the total effective rate of the treatment group is higher than that of the control group [Z = 3.64, 95% confidence intervals (CI): 1.78 (1.31-2.43), P = .0003]; eleven studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group [Z = 4.38, 95% CI: -0.95 (-1.38 to -0.53), P < .0001]; ten studies show that glutamic-pyruvic transaminase levels of the experimental group are lower than that of the control group [Z = 3.69, 95% CI: -11.76 (-18.01 to -5.51), P = .0002]; 6 studies show that glutamic oxalacetic transaminase levels of the experimental group are lower than that of the control group [Z = 7.40, 95% CI: -3.01 (-3.81 to -2.22), P < .00001]; 6 studies show that gamma-glutamyl transpeptidase levels of the experimental group are lower than that of the control group [Z = 2.43, 95% CI: -23.77 (-42.98 to -4.57), P = .02]; 9 studies show that triglyceride levels of the experimental group are lower than that of the control group [Z = 3.06, 95% CI: -0.62 (-1.01 to -0.22), P = .002]; 6 studies show that the homeostasis model assessment of insulin resistance of the experimental group is lower than that of the control group [Z = 3.22, 95% CI: -2.33 (-3.75 to -0.91), P = .001]; 6 studies show that the glycated hemoglobin A1c of the experimental group is lower than that of the control group [Z = 4.50, 95% CI: -1.90 (-2.72 to -1.07), P < .00001]; five studies show that the fasting insulin of the experimental group is lower than that of the control group [Z = 3.42, 95% CI: -2.25 (-3.53 to -0.96), P = .0006]. Pioglitazone intake is effective in nonalcoholic steatohepatitis management.


Von Willebrand factor and mitral valve prolapse.
The levels of von Willebrand factor (vWF:Ag) were measured in 27 patients with mitral valve prolapse (MVP) and compared to 27 age matched controls. Decreased levels of vWF:Ag (less than 80%) were found in 59% (16/27) of those with MVP compared to only 7% (2/27) of the controls (p less than 0.001). Mean vWF: Ag levels were also significantly lower in those with MVP (68 +/- 30% versus 100 +/- 23%, p less than 0.001). In those with MVP and congestive heart failure secondary to rupture chordae tendineae, however, the mean level of vWF: Ag was not significantly different from control values (95 +/- 32). There was an increased incidence of recurrent nose bleeds in those with MVP and low levels of vWF:Ag. We conclude that there is a relationship between MVP and low levels of vWF:Ag which may explain the increased incidence of epistaxis in such patients. Increased release of vWF:Ag in those with MVP and concomitant congestive heart failure may account for the normal levels found in this subgroup.


Cataract surgery in allogeneic bone marrow transplant recipients with graft-versus-host disease(1).
To study the outcomes of cataract surgery in allogeneic bone marrow transplant recipients with documented graft-versus-host disease (GVHD) and to elucidate the concomitant ocular surface problems often encountered in these patients. W.K. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA. This retrospective study comprised 12 cataract surgeries in 7 patients with GVHD) after allogeneic bone marrow transplantation. In particular, visual acuity improvement, surgical complications, and problems associated with concomitant ocular surface disease were reviewed. The mean visual acuity improved significantly from 20/46 (logMAR 0.32) preoperatively to 20/21 (logMAR 0.02) postoperatively (P <.005). The mean postoperative follow-up was 23 months (range 3 to 48 months). All patients had dry eyes, and 3 had conjunctival cicatrization with mild keratinization. No patient had postoperative corneal breakdown. With aggressive management of dry eyes and other ocular surface problems, cataract surgery had excellent outcomes in patients with GVHD.


Patient-Reported Long-Term Outcome of Balloon Pulmonary Angioplasty for Inoperable CTEPH.
Balloon pulmonary angioplasty (BPA) is a promising interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Evidence in favor of BPA is growing, but long-term data remain scarce. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is validated for the assessment of patients with pulmonary hypertension within three domains: symptoms, activity, and quality of life (QoL). The aim of the present study was to evaluate the long-term effects of BPA on these domains in patients with inoperable CTEPH. Between March 2014 and August 2019, technically inoperable patients with target lesions for BPA were included in this prospective, observational study. CAMPHOR scores were compared between baseline (before the first BPA) and 6 months after the last intervention and also for scores assessed at annual follow-ups. A total of 152 patients had completed a full series of BPA interventions and a 28 (interquartile range [IQR]: 26-32) week follow-up. Further follow-up assessments including the CAMPHOR score were performed 96 (IQR: 70-117) weeks, 178 (IQR: 156-200) weeks, and 250 (IQR: 237-275) weeks after the last intervention. From baseline to the last follow-up, CAMPHOR scores for symptoms, activity, and QoL improved from 9 (IQR: 6-14) to 3 (IQR: 0-9) (p < 0.001), 8 (IQR: 5-12) to 4 (IQR: 2-8) (p < 0.001), and 5 (IQR: 2-9) to 1 (IQR: 0-5) (p < 0.001). BPA leads to long-lasting, significant improvement of symptoms, physical capacity, and QoL in inoperable CTEPH patients.


A Collaborative Analysis of Trends in Referrals to the Pennsylvania Student Assistance Program from 2013 to 2018.
The Student Assistance Program (SAP) is mandated kindergarten to 12th grade in Pennsylvania schools to address barriers to student academic success. Following student referral, SAP teams use a systematic process to inform recommendations for school or community-based services. To evaluate program outcomes, a review of student SAP referral trends over a 5-year period was undertaken. The Pennsylvania Network for Student Assistance Services (PNSAS), the state leadership providing oversight of SAP, partnered with Penn State College of Medicine in a retrospective analysis of student referral data from 2013 to 2018. Public school enrollment demographics were used for comparison. Frequencies and percentages were calculated. Referrals (total n = 352,640) increased by 24% over the 5 years; demographics 55% male, 69% non-Hispanic white, 16% non-Hispanic black, and 10% Hispanic. Referrals were most commonly for behavioral concerns (31%). Discontinued referrals (39%) were primarily for parent refusal/no permission. Trends included rising minority and elementary referrals over the study period. SAP referral demographics were consistent with state public school enrollment race/ethnicity breakdown suggesting lack of systematic bias. The proportion of behavioral referrals was consistent with rising youth behavioral health needs. PNSAS must consider strategies to support rising referral numbers and trends.


[Three cases of pulmonary embolism incorrectly diagnosed as lung cancer].
Pulmonary embolism is commonly misdiagnosed as lung cancer, since sputum cytological tests often show atypical or malignant cells. We report three operated cases of pulmonary embolism incorrectly diagnosed as lung cancer. The first patient is a 39-year-old male with chest pain an bloody sputum. Chest x-ray revealed abnormal shadows and subsequent sputum cytological tests identified malignant cells. The second patient is a 63-year-old male with the same diagnostic pattern as the first case. The third patient is a 72-year-old male whose routine chest x-ray showed an abnormal shadow; malignant cells were identified by cytological tests on transbronchial fiberscope brushings. These three patients were histopathologically diagnosed as suffering pulmonary embolism by wedge resection under thoracotomy. When a patient has chest pain or bloody sputum with showing temporarily malignant cells on cytology, the possibility of pulmonary embolism should be taken into consideration.


Comparative studies of pollen and fluorescent dye transport by bumble bees visiting Erythronium grandiflorum.
In the Colorado Rocky Mountains the glacier lily Erythronium grandiflorum exhibits a striking dimorphism in pollen color and is commonly pollinated by the bumble bee Bombus occidentalis. We induced bees to visit sequences of flowers in a flight cage, and compared dispersal of distinctively-colored pollen and fluorescent pigment ("dye") that the bee had picked up at a single donor flower. Nonparametric and parametric analyses showed that dispersal properties of pollen and dye differed; consistently less pollen was deposited and it was carried consistently shorter distances than dye. Dye thus does not provide an accurate means of assessing exacty where or how far pollen travels in this plant-pollinator system. On the other hand, both pollen and dye responded similarly to several experimental manipulations of donor and recipient flowers. Hence dye may well be of value for a qualitative investigation of how floral traits influence pollen dispersal.


Routine Inferior Mesenteric Artery Embolisation is Unnecessary Before Endovascular Aneurysm Repair.
A type II endoleak is the most common complication during surveillance after endovascular aneurysm repair (EVAR), and a patent inferior mesenteric artery (IMA) is a known risk factor for an endoleak. The effect of routine IMA embolisation prior to EVAR on overall outcome is unknown. The aim of the study was to compare two strategies: routine attempted IMA embolisation prior to EVAR (strategy in centre A) and leaving the IMA untouched (strategy in centre B). Patients were treated with EVAR in two centres during the period 2005 - 2015, and the data were reviewed retrospectively. The primary endpoints were re-intervention rate due to type II endoleaks and the late IMA embolisation rate. Secondary endpoints included EVAR related re-intervention, sac enlargement, aneurysm rupture, and open conversion rates. Strategy A was used to treat 395 patients. The IMA was patent in 268 (67.8%) patients, and embolisation was performed in 164 (41.5%). The corresponding figures for strategy B were 337 patients with 279 (82.8%) patent IMAs, two (0.6%) of which were embolised. The mean duration of follow up was 70 months for strategy A and 68.2 months for strategy B. The re-intervention rates due to a type II endoleak were 12.9% and 10.4%, respectively (p = .29), with no significant difference in the rate of re-interventions to occlude a patent IMA (2.0% and 4.7%, respectively; p = .039). The EVAR related re-intervention rate was similar, regardless of strategy (24.1% and 24.6%, respectively; p = .93). Significant sac enlargement was seen in 20.3% of cases treated with strategy A and in 19.6% treated with strategy B (p = .82). The rupture and conversion rates were 2.5% and 2.1% (p = .69) and 1.0% and 1.5% (p = .40), respectively. The strategy of routinely embolising the IMA does not seem to yield any significant clinical benefit and should therefore be abandoned.


A novel biosensor based on tetrahedral DNA nanostructure and terminal deoxynucleotidyl transferase-assisted amplification strategy for fluorescence analysis of uracil-DNA glycosylase activity.
Tetrahedral DNA nanostructure (TDN), as a classical bionanomaterial, which not only has excellent structural stability and rigidity, but also possesses high programmability due to strict base-pairs complementation, is widely used in various biosensing and bioanalysis fields. In this study, we first constructed a novel biosensor based on Uracil DNA glycosylase (UDG) -triggered collapse of TDN and terminal deoxynucleotidyl transferase (TDT)-induced insertion of copper nanoparticles (CuNPs) for fluorescence and visual analysis of UDG activity. In the presence of the target enzyme UDG, the uracil base modified on the TDN were specifically identified and removed to produce an abasic site (AP site). Endonuclease IV (Endo.IV) could cleave the AP site, making the TDN collapse and generating 3'-hydroxy (3'-OH), which were then elongated under the assistance of TDT to produce poly (T) sequences. Finally, Copper (II) sulfate (Cu2+) and l-Ascorbic acid (AA) were added to form CuNPs using poly (T) sequences as templates (T-CuNPs), resulting in a strong fluorescence signal. This method exhibited good selectivity and high sensitivity with a detection limit of 8.6 × 10-5 U/mL. Moreover, the strategy has been successfully applied to the screening of UDG inhibitors and the detection of UDG activity in complex cell lysates, which means that it has promising applications in clinical diagnosis and biomedical research.


[Results of corrective surgery in juvenile cyphosis (scheuermann's disease) using Harrington's compressive rods (author's transl)].
The authors present the results of 20 corrective procedures for juvenile cyphosis using Harrington compressive rods and Hibbs spondylodesis. 16 procedures date back more than one year (average 3 years, 4 months). 10 cases of pure dorsal cyphosis. The pre-operative Cobb-angles for cyphosis averaged 52 degrees, postoperatively an average of 24 degrees was measured. This reflects a 57 p.c. average immediate correction (41 p.c. for pure dorsal cyphosis, 71 p.c. for dorso-lumbar cyphosis) following surgery nearly all cases showed a significant loss of correction (average 43 p.c., dorsal 37 p.c., dorso-lumbar 49 p.c.). Three main reasons for this loss of correction are discussed and documented in detail. 1. Mal-centered and too short a length of spondylodesis; 2. insufficient corrective growth of wedge shaped vertebral bodies post surgery and 3. frequent lumbar decompensation into total round back deformity of the pure thoracic spondylodesis. The following changes in procedure to solve the problem of loss of correction are proposed. 1. Combined posterior and anterior fusions and 2. upper lumbar dorsal fusion together with extended thoracic spondylodesis. The changing indication is discussed. The main but not fatal complication was postoperative wound infection (15 p.c.).


Effect of a hepatitis B virus inhibitor, NZ-4, on capsid formation.
During the hepatitis B virus (HBV) life cycle, nucleocapsid assembly is essential for HBV replication. Both RNA reverse transcription and DNA replication occur within the HBV nucleocapsid. HBV nucleocapsid is consisted of core protein (HBcAg), whose carboxy-terminal domain (CTD) contains an Arg-rich domain (ARD). The ARD of HBcAg does contribute to the encapsidation of pregenomic RNA (pgRNA). Previously, we reported a small-molecule, NZ-4, which dramatically reduced the HBV DNA level in an in vitro cell setting. Here, we explore the possible mechanisms by which NZ-4 inhibits HBV function. As an HBV inhibitor, NZ-4 leads to the formation of genome-free capsids, including a new population of capsid that runs faster on agarose gels. NZ-4's activity was dependent on the presence of the ARD I, containing at least one positively charged amino acid. NZ-4 might provide a new option for further development of HBV therapeutics for the treatment of chronic hepatitis B.


[Central corneal thickness and retrobulbar blood flow in glaucoma patients].
A correlation between a thin cornea and the presence of vascular risk factors has recently been reported in normal-tension glaucoma patients. The present study intended to investigate the correlation between central corneal thickness and basal retrobulbar blood flow in glaucoma patients. Corneal pachymetry and colour Doppler imaging (CDI) of the retrobulbar arteries (ophthalmic, central retinal and cilliary) were performed in 63 glaucoma patients. Linear mixed effect models were used to evaluate the association of central corneal thickness and retrobulbar blood flow. There was no significant correlation between central corneal thickness and blood flow in any of the assessed arteries (p = 0.13-0.88). A statistical relationship between central corneal thickness and retrobulbar blood flow could not be found in the examined sample of glaucoma patients.


Biliary lipids in familial combined hyperlipidaemia: effects of acipimox therapy.
Biliary lipid composition and plasma lipoprotein levels were determined in nine gallstone-free male patients with familial combined hyperlipidaemia (FCHL). In the basal situation, stimulated fasting duodenal bile from the patients contained a higher relative concentration of cholesterol than bile obtained from age- and sex-matched normal controls (n = 22), 6.5 +/- 0.3 (SEM) vs. 4.7 +/- 0.2 mol % (P less than 0.01). This resulted in a higher cholesterol saturation of bile from FCHL patients, 85 +/- 6 vs. 70 +/- 2% (P less than 0.05). After 6 weeks of treatment with acipimox, 750 mg day-1, total plasma triglycerides were lowered from 7.5 +/- 1.5 to 4.6 +/- 0.7 mmol l-1 (P less than 0.05) and plasma cholesterol decreased from 8.0 +/- 0.1 to 7.1 +/- 0.3 mmol l-1 (P less than 0.05) in the FCHL patients. These changes were mainly due to a decrease in very low density lipoprotein concentrations while low density lipoprotein levels remained unaltered. The relative proportion of cholesterol in stimulated fasting duodenal bile was reduced from 6.5 +/- 0.3 to 4.3 +/- 0.5 mol % (P less than 0.01), resulting in 'normalization' of biliary cholesterol saturation, from 85 +/- 6 to 58 +/- 6% (P less than 0.005). No correlations between the changes in biliary lipid composition and those in plasma lipoprotein levels were observed. The results indicate that treatment with acipimox in patients with FCHL, a disorder commonly associated with supersaturated bile, does not increase biliary cholesterol, and presumably not the risk for gallstone formation.


ZeBRα a universal, multi-fragment DNA-assembly-system with minimal hands-on time requirement.
The recently evolved field of synthetic biology has revolutionized the way we think of biology as an "engineerable" discipline. The newly sprouted branch is constantly in need of simple, cost-effective and automatable DNA-assembly methods. We have developed a reliable DNA-assembly system, ZeBRα (Zero-Background Redα), for cloning multiple DNA-fragments seamlessly with very high efficiency. The hallmarks of ZeBRα are the greatly reduced hands-on time and costs and yet excellent efficiency and flexibility. ZeBRα combines a "zero-background vector" with a highly efficient in vitro recombination method. The suicide-gene in the vector acts as placeholder, and is replaced by the fragments-of-interest, ensuring the exclusive survival of the successful recombinants. Thereby the background from uncut or re-ligated vector is absent and screening for recombinant colonies is unnecessary. Multiple fragments-of-interest can be assembled into the empty vector by a recombinogenic E. coli-lysate (SLiCE) with a total time requirement of less than 48 h. We have significantly simplified the preparation of the high recombination-competent E. coli-lysate compared to the original protocol. ZeBRα is the least labor intensive among comparable state-of-the-art assembly/cloning methods without a trade-off in efficiency.


Self-directed learning: Alternative for traditional classroom learning in undergraduate ophthalmic education during the COVID-19 pandemic in China.
In recent years, the COVID-19 pandemic has led to a shift in medical education from traditional face-to-face to online or remote learning, which provided challenges to faculty and students that have traditionally given face-to-face instruction. Self-directed learning (SDL) has gained popularity in undergraduate education such as nursing and adult education. Although the application of SDL in many medical teachings is practical, the application of SDL in undergraduate ophthalmology education has not been well investigated. COVID-19 pandemic led to changes in the learning style of undergraduate medical students to adapt to the shift from traditional classroom learning (TCL) to online or remote learning. Self-directed learning is a process in which individuals take the initiative in diagnosing their learning needs, formulating learning goals, identifying resources for learning, choosing and implementing appropriate learning strategies and evaluating learning outcomes. This study compared students' perspectives and study outcomes of the SDL and TCL to preliminarily investigate the effect of SDL in undergraduate ophthalmology education. The students showed equal perspectives and satisfaction with both learning models. There was no difference in learning outcomes at the end of the study. The students with different interests in ophthalmology had different perspectives on SDL and TCL. Self-directed learning is an essential alternative to traditional classroom learning in undergraduate ophthalmic education during the COVID-19 pandemic in China.


Brain marker protein changes after short- and long-term ethanol intoxication and withdrawal in the rat.
The brain marker proteins, D1, D2, and D3, localised to neuronal membranes, and mitochondrial and cytoplasmic marker proteins (MM and CM), were studied during 1-6 days (short term) intragastrically-induced severe ethanol intoxication and during 1 month (long-term) ethanol intoxication established by a liquid diet regimen. The concentrations of the same brain proteins were also measured during withdrawal from the ethanol intoxication periods. Three categories of effect were encountered: decreased concentration of brain marker proteins during severe short-term intoxication the effect being most marked for D3, possibly indicating degradation of mature synapses; increased concentration of proteins D2 and MM during withdrawal, the D2 changes possibly indicating formation of new synapses; increased concentration of D1 protein and MM during long-term intoxication. We suggest that the changes in brain marker proteins reflect dynamic changes of subcellular neuronal structures which may form a part of the basis of functional tolerance to and physical dependence upon ethanol or the reversion of these states after withdrawal of ethanol.


The future of molecular imaging in the clinic needs a clear strategy and a multidisciplinary effort.
Although advances in modern medicine do already and might provide even more new tools to prevent from life-threatening cardiovascular events in the future, the virtually unchanged high numbers of cardiovascular events suggest an unmet diagnostic challenge. Prevention of cardiovascular events, which are responsible for approximately 1/3 of all deaths in the industrialised societies, therefore needs new diagnostic tools, since current morphological and functional imaging approaches seem to fail in this respect.This article outlines the principle strategy and prerequisites to come up with a clinically relevant and successful molecular imaging technology in the future.


Homogeneous synthesis of hydroxypropyl guar gum in an ionic liquid 1-butyl-3-methylimidazolium chloride.
With potassium hydroxide (KOH) as catalyst, hydroxypropyl guar gum (HPG) was successfully prepared under homogenous conditions in an ionic liquid 1-butyl-3-methylimidazolium chloride (BmimCl). The value of degree of molar substitution (MS) of HPG, which was determined by means of (1)H NMR, was easily controlled by varying the mass ratio of propylene oxide (PO) to guar gum (GG). The distribution of hydroxypropyl moieties among the seven hydroxy groups in HPGs was investigated by NMR and the results indicated that the homogeneous reaction preferentially substituted at the C3−OH of the mannosyl residues in guar gum which was quite different from the heterogeneous reaction where substitution mostly occurred at C6−OH. The average number of hydroxypropyl units per OH substitution of HPGs with MS value of 0.20, 0.37 and 0.60 was 1.82, 1.42 and 1.76, respectively.


Milia en plaque successfully treated by dermabrasion.
Milia en plaque is a rarely described benign lesion characterized by milia within an erythematous base, usually located periauricularly. No optimal treatment is known. To illustrate by a case report the clinical presentation and effect of dermabrasion on milia en plaque. A 60-year-old woman with milia en plaque at the mandibular ridge was treated with dermabrasion using a diamond fraise. Complete regression of the lesion was seen at a follow-up of 6 months. Dermabrasion seems a suitable treatment for milia en plaque.


[A case of complete circumferential aortic rupture due to blunt chest trauma].
A case of complete circumferential rupture of the thoracic aorta due to blunt chest trauma is presented. A 30-year-old man was admitted after a traffic accident. The admission chest X-ray film demonstrated mediastinal widening. About 6 hours after the traffic accident, chest CT scanning demonstrated mediastinal hematoma, left pleural effusion and partial aortic dissection. Diagnoses of aortic rupture and liver injury were made, and surgery for the thoracic aorta was performed immediately. The aorta was found to be completely disrupted for the length of 2 cm, and a vascular prosthesis was interposed between the two ends of the aorta under partial cardiopulmonary bypass. We conclude that the enhanced chest CT scanning is helpful for diagnosis, and that if other organ injuries are not severe, the emergency operation should be performed.


Variants of the hyoid-larynx complex, with implications for forensic science and consequence for the diagnosis of Eagle's syndrome.
Thorough anatomic knowledge of the hyoid-larynx complex is necessary for forensic radiologists and ear-nose-throat surgeons, given the many anatomic variations that originate in embryology. In forensics the anomalies must be distinguished from fractures because the latter are indicative of violence on the neck. In this manuscript we describe the anatomical variations that can be found in the hyoid-larynx complex and explain their etiology. 284 radiological scans of excised hyoid-larynx complexes were examined with X-ray and CT. Some rare cases from literature and historical collections were added. Two third of the examined hyoid-larynx complexes deviated from the anatomical standard and showed uni- or bilateral ankylosis in the hyoid bone and/or so-called triticeal cartilages. In one fifth of the cases we found striking anatomical variants, mostly derived from the cartilage of the second pharyngeal arch. Anatomical variations of the hyoid-larynx complex can be explained by embryological development. The aberrant hyoid apparatus and the elongated styloid processes (Eagle syndrome) should be considered as one clinical entity with two different expressions as both anomalies are derived from the cartilage of the second pharyngeal arch. Several variants can mimic fractures in this region, so our study is important for radiologists and forensic experts assessing cases of possible violence on the neck.


Multicenter study of human papillomavirus and the human papillomavirus vaccine: knowledge and attitudes among people of African descent.
To compare knowledge and attitudes of human papillomavirus (HPV) and the vaccine between different cultures of African descent. A cross-sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US and the Bahamas (BHM) was conducted. General knowledge about HPV and the HPV vaccine differed between the two countries significantly. Bahamian respondents were less likely to have higher numbers of correct knowledge answers when compared to Americans (Adjusted Odds Ratio [Adj. OR] 0.47, 95% Confidence Interval [CI] 0.30-0.75). Older age, regardless of location, was also associated with answering fewer questions correctly (Adj. OR 0.61, 95% CI 0.40-0.92). Attitudes related to HPV vaccination were similar between the US and BHM, but nearly 80% of BHM respondents felt that children should not be able to receive the vaccine without parental consent compared to 57% of American respondents. Grave lack of knowledge, safety and cost concerns, and influence of parental restrictions may negatively impact vaccine uptake among African-American and Afro-Caribbean persons. Interventions to increase the vaccine uptake in the Caribbean must include medical provider and parental involvement. Effective strategies for education and increasing vaccine uptake in BHM are crucial for decreasing cervical cancer burden in the Caribbean.