Long term efficacy of simvastatin in renal transplant recipients treated with cyclosporine or tacrolimus.
Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In this study, 14 patients who had hypercholesterolemia [total cholesterol (TC) >200 mg/dL] and hypertriglyceridemia [triglyceride (TG) >150 mg/dL] 1 month after renal transplantation (post-transplantation), seven patients each under the treatment with immunosuppressant, either cyclosporine or tacrolimus started simvastatin treatment of 5-10 mg/d and continued the treatment for 4 yr. The effect of simvastatin treatment was assessed by comparison in serum lipid levels (TC, TG, cholesterol in lipoprotein fractions, and apolipoproteins) and the lipid metabolism related enzyme activities for post-transplantation, after 6-month and 4-yr simvastatin treatment. Simvastatin treatment of 4 yr significantly decreased the elevated levels of serum TC from 234.5 +/- 30.8 to 186.3 +/- 20.5 mg/dL (p < 0.001), low density lipoprotein cholesterol (LDL-C) from 116.7 +/- 22.5 to 82.7 +/- 16.6 mg/dL (p < 0.05) and TG from 200.3 +/- 109.2 to 97.0 +/- 45.2 mg/dL (p < 0.001). In addition, there were significant decreases in elevated serum very-low-density lipoprotein cholesterol (VLDL-C) from 47.8 +/- 18.4 to 28.6 +/- 9.5 mg/dL (p < 0.001) and LDL2 cholesterol (LDL2-C) from 20.8 +/- 8.2 to 5.7 +/- 1.8 mg/dL (p < 0.001). The results indicate that 4-yr treatment of simvastatin improves profiles of the atherogenic lipids in renal transplant patients with immunosuppressant caused hypercholesterolemia and hypertriglyceridemia treated either cyclosporine or tacrolimus in similar manner.


Nanoparticles and capillary electrophoresis: A marriage with environmental impact.
The impact of nanomaterials in the environment and human health is a cause of big concern and even though intensive studies are currently being carried out, there is still a lot to elucidate. The development of validated methods for the characterization and quantification of nanomaterials and their impact on the environment should be encouraged to achieve a proper, safe, and sustainable use of nanoparticles (NPs). Recently, CE emerged as a well-adapted technique for the analysis of environmental samples. This review presents the application of NPs together with CE systems for environmental pollutants analysis, as well as the application of CE techniques for the analysis of various types of NPs.


Liposomal membrane. I. Chemical damage of liposomal membranes with functional detergent.
The interaction and reaction between liposomal membrane and a functional detergent, N-hexadecyl-N-(imidazol-4-yl)methyl-N,N-dimethylammonium chloride hydroperchlorate (Im-I), have been investigated in conjunction with the leakage of bromothymol blue encapsulated as a marker in the bilayers of liposomes. Im-I carries an imidazole moiety and was expected to behave as a simple lipase model. The reaction with Im-I significantly enhanced the leakage of bromothymol blue encapsulated in the egg lecithin and dipalmitoyl phosphatidylcholine liposomes. During the course of reaction with Im-I, the formation of acyl-imidazole intermediate was clearly identified, which was certainly connected with the bromothymol blue release. From various kinetic results on bromothymol blue release and acyl-imidazole formation, it has been suggested that the bromothymol blue release from liposomal bilayer may be caused by the local and instantaneous decomposition of lipids when Im-I penetrates into the bilayer. However, it has also been demonstrated that the immediate reconstruction of liposomes retains the barrier function to protect against the further release of bromothymol blue.


Angiotensin-converting enzyme in sarcoidosis: a British study.
Serum angiotensin-converting enzyme (ACE) activity was measured in 18 healthy controls, 26 patients with active sarcoidosis, 13 patients with inactive sarcoidosis and seven patients with extensive tuberculosis. The serum ACE activity showed no significant difference between male and female in the control or sarcoidosis groups. There was no correlation between ACE activity and age except in the female active-sarcoid group. ACE activity in the active-sarcoid group was significantly higher than in the control, inactive-sarcoid and tuberculosis groups. The ACE activities at Stages I, II and III of the disease were not significantly different.


Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.
Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia.


Host specificity of Helicobacter pylori strains and host responses in experimentally challenged nonhuman primates.
The specificity of colonization by Helicobacter pylori and complex host-bacterium interactions cannot be readily examined in humans. The aim of this study was to perform such analyses in rhesus monkeys. Four animals that had been cured of natural H. pylori colonization were challenged with a mixture of 7 strains of human origin, and bacteria recovered during periodic videogastroscopy were DNA fingerprinted. Three animals carried mixtures of several strains for 4 months, after which strain J166 predominated. In the fourth animal, only strain J238 was isolated from the earliest phase of colonization through 7 months, but strain J166 again became predominant by 10 months after the challenge. Gastritis scores and plasma gastrin and anti-H. pylori immunoglobulin G titers reached levels observed in naturally colonized animals by 4 months after the challenge; however, no plasma immunoglobulin A response was observed up to 10 months. These results show that (1) natural colonization does not elicit protective immunity against subsequent H. pylori challenge; (2) individuals differ in susceptibility to different H. pylori strains during initial stages of colonization; and (3) certain strains are better suited than others for long-term survival in different hosts. These observations show the complexity of H. pylori-host interactions.


The removal of antibiotic resistant bacteria and antibiotic resistance genes by sulfidated nanoscale zero-valent iron activating periodate: Efficacy and mechanism.
Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have drawn much more attention due to their high risk on human health and ecosystem. In this study, the performance of sulfidated nanoscale zero-valent iron (S-nZVI)/periodate (PI) system toward ARB inactivation and ARGs removal was systematically investigated. The S-nZVI/PI system could realize the complete inactivation of 1 × 108 CFU/mL kanamycin, ampicillin, and tetracycline-resistant E. coli HB101 within 40 min, meanwhile, possessed the ability to remove the intracellular ARGs (iARGs) (including aphA, tetA, and tnpA) carried by E. coli HB101. Specifically, the removal of aphA, tetA, and tnpA by S-nZVI/PI system after 40 min reaction was 0.31, 0.47, and 0.39 log10copies/mL, respectively. The reactive species attributed to the E. coli HB101 inactivation were HO• and O2•-, which could cause the destruction of E. coli HB101 morphology and enzyme system (such as superoxide dismutase and catalase), the loss of intracellular substances, and the damage of iARGs. Moreover, the influence of the dosage of PI and S-nZVI, the initial concentration of E. coli HB101, as well as the co-existing substance (such as HCO3-, NO3-, and humic acid (HA)) on the inactivation of E. coli HB101 and its corresponding iARGs removal was also conducted. It was found that the high dosage of PI and S-nZVI and the low concentration of E. coli HB101 could enhance the disinfection performance of S-nZVI/PI system. The presence of HCO3-, NO3-, and HA in S-nZVI/PI system showed inhibiting role on the inactivation of E. coli HB101 and its corresponding iARGs removal. Overall, this study demonstrates the superiority of S-nZVI/PI system toward ARB inactivation and ARGs removal.


Broad range 16S rRNA gene PCR compared to bacterial culture to confirm presumed synovial infection in horses.
The objectives of the present study were to evaluate the accuracy of broad range 16S rRNA gene PCR compared to bacterial culture for the detection of synovial infection in horses. The study included 57 synovial fluid samples from horses with presumed synovial infection and a control group consisting of 31 synovial fluid samples originating from clinically normal horses and horses with aseptic synovial inflammation. All samples were analysed by 16S PCR with reverse line blot (RLB) hybridisation. Synovial fluid samples were cultured using conventional agar plate methods (APM) and/or blood culture medium (BCM). The results of the study showed a superior detection rate (89.5%) for 16S PCR with RLB. Bacterial culture had lower sensitivity, but highly acceptable detection rates (77.6%) were observed using BCM. APM had very low sensitivity (37.8%) and infection was never detected by plate isolation without positive incubation in BCM. The highest sensitivity (91.8%) for the detection of synovial infection was achieved when the results of incubation in BCM and 16S PCR were combined. For all the tests, the specificity was higher than 90%.


Synthesis, structure and anti-acetylcholinesterase activity of 12a-O-methyl territrem B.
12a-0-methyl territrem B was synthesized from TRB by treatment with dimethyl sulfate in methanolic NaOH. The structure of 12a-0-methyl territrem B was elucidated by uv, ir nmr and mass spectra and it is 2.5 times more potent than TRB in inhibitory activity on electric eel acetylcholinesterase (E. C. 18.104.22.168.) (AChE).


Effect of N-salicyloyltryptamine (STP), a novel tryptamine analogue, on parameters of cell viability, oxidative stress, and immunomodulation in RAW 264.7 macrophages.
Immunomodulatory actions exerted by some classes of tryptamines, such as benzoyltryptamine analogues, suggest these molecules as promising candidates to develop new therapies to treat conditions associated to acute and chronic pain and inflammation. N-salicyloyltryptamine (STP) was observed to act as an anticonvulsive agent and exert antinociceptive effects in mouse. In the present work, we performed a screening of cytotoxic, cytoprotective, immunomodulatory, and redox properties of STP in RAW 264.7 macrophages challenged with hydrogen peroxide and LPS. Our results show that STP presents no cytotoxicity in the range of 0.001 to 1 μg/mL, but doses of 50 and 100 μg/mL caused loss of cell viability (IC(50) = 22.75 μg/mL). Similarly, STP at 0.001 to 1 μg/mL did not cause oxidative stress to RAW 264.7 cells, although it did not prevent cell death induced by H(2)O(2) 0.5 mM. At 1 μg/mL, STP reversed some redox and inflammatory parameters induced by LPS. These include thiol (sulfhydryl) oxidation, superoxide dismutase activation, and morphological changes associated to macrophage activation. Besides, STP significantly inhibited LPS-induced TNF-α and IL-1β release, as well as CD40 and TNF-α protein upregulation. Signaling events induced by LPS, such as phosphorylation of ERK 1/2 and IκBα and p65 nuclear translocation (NF-kB activation) were also inhibited by STP. These data indicate that STP is able to modulate inflammatory parameters at doses that do not interfere in cell viability.


Bone marrow suppression and klebsiella pneumonia septicemia due to ticlopidine and successful treatment with filgrastim; a case report.
In this report we describe an elderly lady, who after 27 days of ticlopidine treatment developed severe pancytopenia and gram (-) septicemia. No clinical response was obtained with an eight days course of empirical broad spectrum antibiotics, after which granulocyte colony stimulating factor (G-CSF, filgrastim) added to her regimen. In a period of seven days her neutrophil count was normal and she had recovered from septicemia. Twelve weeks after discharge she is fine and her blood parameters are all normal.


Post-partum thyroiditis and goitrous (Hashimoto's) thyroiditis are associated with HLA-DR4.
Using new panels of HLA-DR typing sera, we found an increase in the prevalence of HLA-DR4 in 21 patients with Hashimoto's thyroiditis (57%) and 32 patients with post-partum thyroiditis (53%) compared to controls (21%). Hashimoto's thyroiditis was previously found to be associated with HLA-DR5 and Dw5. We feel that the doubts raised by this study warrant the study of DR antigens in thyroid autoimmune disease using large panels of specific sera.


Porcelain surface characterization and staining in the office.
Chairside custom staining and characterization of porcelain can influence significantly the quality of porcelain restorations and dentist-patient relationships. Technical guidelines have been presented to assist the dentist.


A new alternative paraffinic-palmbiodiesel fuel for reducing polychlorinated dibenzo-p-dioxin/dibenzofuran emissions from heavy-duty diesel engines.
Polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F) emissions from heavy-duty diesel engines (HDDEs) fuelled with paraffinic-palmbiodiesel blends have been rarely addressed in the literature. A high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS) was used to analyze 17 PCDD/F species. Experimental results indicate that the main species of PCDD/Fs were OCDD (octachlorinated debenzo-p-dioxin) and OCDF (octachlorodibenzofuran), and they accounted for 40-50% of the total PCDD/Fs for all test fuels. Paraffinic-palmbiodiesel blends decreased PCDD/Fs by 86.1-88.9%, toxic PCDD/Fs by 91.9-93.0%, THC (total hydrocarbons) by 13.6-23.3%, CO (carbon monoxide) by 27.2-28.3%, and PM (particulate matter) by 21.3-34.2%. Using biodiesel blends, particularly BP9505 or BP8020, instead of premium diesel fuel (PDF) significantly reduced emissions of both PCDD/Fs and traditional pollutants. Using BP9505 (95vol% paraffinic fuel+5vol% palmbiodiesel) and BP8020 instead of PDF can decrease PCDD/F emissions by 5.93 and 5.99gI-TEQyear(-1) in Taiwan, respectively.


Enteral nutrition is associated with a decreased risk of surgical intervention in Crohn's disease patients with spontaneous intra-abdominal abscess.
The impact of enteral nutrition (EN) on surgical risk in Crohn's disease (CD) patients suffering from spontaneous intra-abdominal abscess (IAA) was evaluated. CD patients diagnosed with spontaneous IAA from 2008 to 2015 were included in the study. The impact of EN on surgical risk was evaluated using both univariate and multivariate analyses. A total of 87 patients were enrolled, 66 (75.9%) were male. The mean age at the development of an abscess was 30.2 ± 10.1 years and the median duration of illness from CD diagnosis until the development of an abscess was three (2-6) years. After a median follow-up of 1.9 (1.1-2.9) years, surgical intervention was performed in 42 patients (48.3%). Patients treated with EN were less likely to require surgical intervention (26.1% vs 56.3%, p = 0.01). Multivariate analysis showed that EN was an independent protective factor for the risk of surgery with a hazard ratio of 0.27 (95% confidence interval: 0.11-0.65, p = 0.004) after adjusting for abdominal pain, history of abdominal surgery, concomitant intestinal stenosis and prior use of antibiotics within three months. Surgical intervention is common for CD patients with IAA. Appropriate application of EN may help obviate the need for surgical treatment.


Origin and fate of germ cells in male and female embryos of Haplothrips verbasci (Osborn) (Insecta, Thysanoptera, Phlaeothripidae).
Comparison of germ cells in male and female embryos of the arrhenotokous thrips, Haplothrips verbasci, yields the following observations: A mean of 11 cleavage energids enter the posterior pole plasm of the egg after the sixth cleavage division and apparently become pole cells when they take up polar granules in their cytoplasm. The cells proliferate asynchronously prior to and during anatrepsis to yield a mean of 36 germ cells in male embryos and 31 in females. Visible sexual differentiation of germ cells begins during germ band elongation and is completed shortly after the appearance of appendages. Female germ cells are larger than those of the males and may contain two nucleoli. The germ cells separate into two groups just before katatrepsis and mesodermal cells collect about these to form the primary epithelial sheaths of the gonads and the primordia of the gonoducts shortly after revolution is completed. Each gonad contains a mean of 13 germ cells in male embryos and 7 in females - a number that persists until mitosis resumes after hatching. During ketatrepsis, a mean of 11 germ cells in male embryos and 2.6 in females fail to be enclosed within the gonads, become dispersed in the yolk and perhaps transform into vitellophages. Germ cell development in H. verbasci embryos resembles similar events taking place in psocid embryos, providing additional evidence for a close phylogenetic relationship between Thysanoptera and Psocoptera.


Evolution of serum progesterone levels in the very early luteal phase of stimulated IVF/ICSI cycles post hCG trigger: a proof of concept study.
Studies have suggested that controlled ovarian hyperstimulation adversely affects endometrial receptivity due to advanced endometrial maturation. This adverse effect is mainly attributed to supraphysiological levels of both estrogen and progesterone identified in stimulated cycles. There is a paucity of published data investigating the very early luteal steroid profile following hCG trigger. This prospective, observational study was undertaken to determine the increase in serum progesterone levels after human chorionic gonadotrophin (hCG) trigger in stimulated IVF/ICSI cycles. This proof-of-concept study included 11 patients requiring ovarian stimulation for IVF/ICSI and who planned to avail of pre-implantation genetic screening with embryo vitrification of their biopsied embryos at blastocyst stage. For each study participant, five additional blood samples were drawn at the following specific times in the stimulation cycle, on the morning (10.00-12.00) of the assigned day to induce final oocyte maturation with hCG trigger, immediately prior to administration of hCG for final oocyte maturation, 1 h, 2 h, and 36 h post hCG trigger. A prediction model, the Gompertz curve, was used to determine serum progesterone levels at intervals between the 2 h post hCG trigger sample and the day of oocyte retrieval. Statistically significant increases in serum progesterone levels were identified following hCG administration as early as 1 h following trigger (P4 0.57 ng/ml, p < 0.05), 2 h following trigger (P4 0.88 ng/ml, p < 0.001) and on the day of oocyte retrieval (P4 9.68 ng/ml, p < 0.001). According to our prediction model, the Gompertz curve, the projected serum progesterone level at 4 h post trigger would have achieved a level of 1.45 ng/ml, 8 h post trigger of 3.04 ng/ml, and 12 h post trigger of 4.8 ng/ml. The very early and significant increases in serum progesterone following hCG trigger are clearly demonstrated in this study. The endometrium is undoubtedly exposed to rapidly increasing serum progesterone levels post hCG trigger that would not be identified until much later in natural menstrual cycles. This study is registered with clinicaltrials.gov under the identifier NCT04417569.


Adrenal metastasis as first presentation of hepatocellular carcinoma.
Metastases from hepatocellular carcinoma (HCC) can be found in the lung and adrenal gland. We report case of a patient who presented with adrenal metastasis as the first clinical manifestation of HCC. A patient was referred for surgical treatment for a tumor in retro-peritoneal space. The computerized tomography (CT) scan revealed a mass originating from the left adrenal gland. The patient underwent left adrenalectomy and the exploration of abdominal cavity did not reveal any other palpable lesions. Histologically, the resected lesion was a poorly differentiated metastatic tumor from HCC. Seven months later patient was readmitted complaining of cachexia, icterus, and significant weight loss. CT scan revealed hyperdense lesions of the liver. HCC may have atypical presentations like in present case. Fine needle aspiration/tru-cut biopsy might be useful in the investigation of an accidentally discovered adrenal mass regardless of the size and can lead to the detection of a primary tumor.


Comparative studies of the protein binding of digoxin and its metabolites.
The protein binding of Digoxin (D), Dihydrodigoxin (DH), Digoxigenin Bisdigitoxoside (DB) and Digoxigenin Monodigitoxoside (DM) was concentration independent and unaltered by the presence of high concentrations of the analogous compounds. The respective percentage of protein binding for D, DH, DB and DM were 22%, 22%, 23% and 27%.


Integrity of the Antiviral STING-mediated DNA Sensing in Tumor Cells Is Required to Sustain the Immunotherapeutic Efficacy of Herpes Simplex Oncolytic Virus.
The dichotomic contribution of cancer cell lysis and tumor immunogenicity is considered essential for effective oncovirotherapy, suggesting that the innate antiviral immune response is a hurdle for efficacy of oncolytic viruses. However, emerging evidence is resizing this view. By sensing cytosolic DNA, the cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) axis can both counteract viral spread and contribute to the elicitation of adaptive immunity via type I interferon responses. In this paper, we analyzed the tumor-resident function of Sting-mediated DNA sensing in a combined approach of oncovirotherapy and PD-1 immune checkpoint blockade, in an immunocompetent murine model. While supporting increased lytic potential by oncolytic HER2-retargeted HSV-1 in vitro and in vivo, Sting-knockout tumors showed molecular signatures of an immunosuppressive tumor microenvironment. These signatures were correspondingly associated with ineffectiveness of the combination therapy in a model of established tumors. Results suggest that the impairment in antiviral response of Sting-knockout tumors, while favoring viral replication, is not able to elicit an adequate immunotherapeutic effect, due to lack of immunogenic cell death and the inability of Sting-knockout cancer cells to promote anti-tumor adaptive immune responses. Accordingly, we propose that antiviral, tumor-resident Sting provides fundamental contributions to immunotherapeutic efficacy of oncolytic viruses.


Mitochondrial angiopathy in cerebral blood vessels of mitochondrial encephalomyopathy.
We studied cerebral blood vessels of two autopsied patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). All the main cerebral arteries in the proximal portion at the brain base and more distal portion at the cortical surface, as well as within the brain parenchyma were examined by electron microscopy. There was a striking increase in number of mitochondria in the smooth muscle and endothelial cells, which were most prominent in the pial arterioles and small arteries up to 250 micron in diameter and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes have not hitherto been described in MELAS, or in other disorders affecting blood vessels of the brain and other organs. It is suggested that the vascular changes are caused by primary mitochondrial dysfunction in the vascular smooth muscle and endothelial cells of the brain and that they constitute the pathogenic base of the brain lesions and their unusual distribution pattern in MELAS.


Transient Visual Loss in Young Females with Crowded Optic Discs: A Proposed Aetiology.
I present four cases of transient visual loss (TVL) in young females with crowded optic discs. One patient had asymmetrical cup-to-disc ratios and only experienced TVL in the eye with the more crowded disc. I review the evidence for blood flow autoregulatory dysfunction within crowded optic discs in combination with reduced ocular perfusion pressure to propose a possible aetiology for both unilateral and bilateral TVL in young females with crowded optic discs.


PAE viewer: a webserver for the interactive visualization of the predicted aligned error for multimer structure predictions and crosslinks.
The development of AlphaFold for protein structure prediction has opened a new era in structural biology. This is even more the case for AlphaFold-Multimer for the prediction of protein complexes. The interpretation of these predictions has become more important than ever, but it is difficult for the non-specialist. While an evaluation of the prediction quality is provided for monomeric protein predictions by the AlphaFold Protein Structure Database, such a tool is missing for predicted complex structures. Here, we present the PAE Viewer webserver (http://www.subtiwiki.uni-goettingen.de/v4/paeViewerDemo), an online tool for the integrated visualization of predicted protein complexes using a 3D structure display combined with an interactive representation of the Predicted Aligned Error (PAE). This metric allows an estimation of the quality of the prediction. Importantly, our webserver also allows the integration of experimental cross-linking data which helps to interpret the reliability of the structure predictions. With the PAE Viewer, the user obtains a unique online tool which for the first time allows the intuitive evaluation of the PAE for protein complex structure predictions with integrated crosslinks.


Is the pressor response to strychnine centrally mediated?
Intravenous administration of strychnine (0.003-0.300 mg . kg-1) to curarized, chloralosed dogs induced hypertension and tachycardia. In spinal cord-transected dogs, intravenous administration of strychnine no longer elicited a rise in blood pressure and heart rate. Intracisternal injections of strychnine also produced hypertension and tachycardia but at lower doses. Similar results were obtained after intrathecal administration of strychnine in doses significantly different from those effective on intravenous and intracisternal administration. These findings suggest that the central nervous system may be involved in the haemodynamic changes induced by strychnine, but did not allow the site of action to be located.


Guidelines for immersive virtual reality in psychological research.
Virtual reality (VR) holds immense promise as a research tool to deliver results that are generalizable to the real world. However, the methodology used in different VR studies varies substantially. While many of these approaches claim to use 'immersive VR', the different hardware and software choices lead to issues regarding reliability and validity of psychological VR research. Questions arise about quantifying presence, the optimal level of graphical realism, the problem of being in dual realities and reproducibility of VR research. We discuss how VR research paradigms could be evaluated and offer a list of practical recommendations to have common guidelines for psychological VR research.


[Effect of remantadine on the immunodepressive action of influenza virus].
Inoculation of mice with strains of influenza virus toxigenic or pathogenic for these animals resulted in significant inhibition of formation of the antibody-producing cells in response to inoculation with sheep erythrocytes. Inoculation of mice with influenza virus strains having no toxicity or pathogenicity for mice did not lead to the development of immunosuppression. The treatment of mice with remantadine prevented inhibition of formation of antibody-producing cells.


Sulfonylurea receptor as a target for molecular imaging of pancreas beta cells with (99m)Tc-DTPA-glipizide.
This study was aimed to assess pancreas beta cell activity using (99m)Tc-diethyleneaminepentaacetic acid-glipizide (DTPA-GLP), a sulfonylurea receptor agent. The effect of DTPA-GLP on the blood glucose level in rats was also evaluated. DTPA dianhydride was conjugated with GLP in the presence of sodium amide, yielding 60%. Biodistribution and planar images were obtained at 30-120 min after injection of (99m)Tc-DTPA-GLP (1 mg/rat, 0.74 and 11.1 MBq per rat, respectively) in normal female Fischer 344 rats. The control group was given (99m)Tc-DTPA. To demonstrate pancreas beta cell uptake of (99m)Tc-DTPA-GLP via a receptor-mediated process, a group of rats was pretreated with streptozotocin (a beta cell toxin, 55 mg/kg, i.v.) and the images were acquired at immediately-65 min on day 5 post-treatment. The effect on the glucose levels after a single administration (ip) of DTPA-GLP was compared to glipizide (GLP) for up to 6 h. The structure of DTPA-GLP was confirmed by NMR, mass spectrometry and HPLC. Radiochemical purity assessed by ITLC was >96%. (99m)Tc-DTPA-GLP showed increased pancreas-to-muscle ratios, whereas (99m)Tc-DTPA showed decreased ratios at various time points. Pancreas could be visualized with (99m)Tc-DTPA-GLP in normal rat, however, (99m)Tc-DTPA has poor uptake suggesting the specificity of (99m)Tc-DTPA-GLP. Pancreas beta cell uptake could be blocked by pre-treatment with streptozotocin. DTPA-GLP showed an equal or better response in lowering the glucose levels compared to the existing GLP drug. It is feasible to use (99m)Tc-DTPA-GLP to assess pancreas beta cell receptor recognition. (99m)Tc-DTPA-GLP may be helpful in evaluating patients with diabetes, pancreatitis and pancreatic tumors.


Bleeding Rate for Ultrasound-Guided Paracentesis in Thrombocytopenic Patients.
The purpose of this study was to determine the rate of major bleeding complications for ultrasound-guided paracentesis performed in thrombocytopenic patients. We retrospectively reviewed the electronic medical records of patients with platelet counts of less than 50,000/μL who had ultrasound-guided paracenteses performed in the Department of Radiology without correcting preprocedural platelet transfusions between 2005 and 2011. Medical records were evaluated for evidence of major bleeding complications (grade 3 or higher as defined by the National Institutes of Health's Common Terminology Criteria for Adverse Events, version 4.03) and their clinical sequelae. Platelet count and bleeding complications were evaluated for an association, and a sensitivity analysis was performed to determine whether analysis of a control group of patients without thrombocytopenia would yield added confidence in this assessment. Among 304 procedures in 205 thrombocytopenic patients (69% male; mean age ± SD, 56.6 ± 11.9 years), the mean platelet count was 38,400 ± 9300/μL (range, 9000-49,000/μL). Three major bleeding complications requiring red blood cell transfusion were observed in patients with platelet counts of 41,000 to 46,000/μL, for a complication rate of 0.99% (95% confidence interval, 0.3%-2.9%). No patient required an additional procedure or died because of the bleeding complication. There was no association of platelet count with bleeding complications. The sensitivity analysis showed that further evaluation of patients with normal platelet counts would not add to the conclusion. The risk of major bleeding after ultrasound-guided paracentesis in thrombocytopenic patients is very low. In most patients, routine assessment of the preprocedural serum platelet concentration is not necessary, and correction of such an abnormal laboratory value is not indicated.


Eosinophilic folliculitis: a self-limiting illness in patients being treated for haematological malignancy.
Eosinophilic folliculitis is a recognized skin manifestation of human immunodeficiency virus (HIV) disease. Five cases of eosinophilic folliculitis occurring in HIV-negative patients treated for haematological malignancy are reported. In four cases this self-limiting, pruritic eruption, affecting the head and upper trunk, occurred 3 months after bone marrow transplantation, and the fifth case was a patient undergoing chemotherapy for Waldenström's macroglobulinaemia. This suggests that eosinophilic folliculitis is a consequence of disturbances of immune function, and is not specific for HIV infection.


Can multi-agent cooperation promote the ecological value realization of blue carbon in marine ranching?
Ecological value realization of blue carbon in marine ranching is essential to achieve carbon neutrality. The motivation for conducting the study is to verify whether multi-agent cooperation can promote the ecological value realization of blue carbon in marine ranching. Based on the blue carbon ecological value realization model of marine ranching enterprises, blue carbon demand enterprises, blue carbon trading platforms and government, this paper explores the cooperative governance strategy of marine ranching for each subject using cooperative game and non-cooperative game models. Further, we conduct a comparative analysis to arrive at the optimal strategy. The conclusions are as follows. Multi-agent cooperation is more conducive to the ecological value realization of blue carbon in marine ranching. Compared with non-cooperative governance, the platform's commission and blue carbon price are lower, and the blue carbon output, profit of each market subject, government utility and overall profit are higher in cooperative governance. The strengths of this paper lie in 2 aspects. First, we focuses on the ecological value of blue carbon in marine ranching instead of economic value, providing a new theoretical basis for ecological compensation in marine ranching. Second, we construct a government-led and market-oriented operation of marine ranching's blue carbon ecological value realization mechanism, incorporating blue carbon trading platform and government into the value realization model.


Disturbed circadian rhythm of the intrarenal renin-angiotensin system: relevant to nocturnal hypertension and renal damage.
The intrarenal renin-angiotensin system (RAS) plays an important role in the development of hypertension and renal damage. Disruption of diurnal blood pressure (BP) variation is an additional risk factor for renal damage. However, little is known regarding whether intrarenal RAS circadian rhythm exists or if it influences the disruption of diurnal BP and renal damage. We investigated the circadian rhythm of urinary angiotensinogen (U-AGT) that reflects intrarenal RAS activity in 14 individuals without chronic kidney disease (CKD) and 36 CKD patients classified according to circadian BP rhythms. BP values were higher during the daytime than during the nighttime in both individuals without CKD and CKD patients. U-AGT levels were not different between the daytime and nighttime in individuals without CKD, but were significantly higher in the daytime in CKD patients (log U-AGT/creatinine: daytime, 2.39 ± 0.99; nighttime, 2.24 ± 1.06; p = 0.001). Furthermore, in CKD patients showing a riser pattern of circadian BP, U-AGT levels did not decrease during the nighttime compared with those in the daytime (log U-AGT/creatinine: daytime, 2.51 ± 0.65; nighttime, 2.52 ± 0.71; p = 0.78). Circadian fluctuation of albuminuria and proteinuria occurred parallel to that of the U-AGT levels. U-AGT levels were significantly and positively correlated with the levels of BP and circadian fluctuation of U-AGT was correlated with diurnal BP changes. These data suggest that the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which are associated with diurnal BP variation.


Tongue-Strengthening Exercises in Healthy Older Adults: Does Exercise Load Matter? A Randomized Controlled Trial.
Tongue-strengthening exercises (TSE) are based on the principles of exercise and motor learning, including intensity. Intensity is manipulated by gradually adjusting the resistive load. This randomized controlled trial (RCT) investigates the effect of three different values resistive load during TSE in healthy older adults. Sixty subjects completed 8 weeks of TSE while exercising with Iowa Oral Performance Instrument (IOPI). They were randomly distributed to 4 different treatment arms: 3 exercise groups (EG1: n = 15; EG2: n = 16, EG3: n = 16) and 1 control group performing lip-strengthening exercises (CG: n = 13). Values of resistive load for EG1, EG2, and EG3 were 100, 80, and 60% 1RM, respectively. Anterior and posterior maximal isometric pressures (MIPA, MIPP) were measured at baseline, after 4 and 8 weeks of training and 4 weeks post-training. MIPA and MIPP in the EG were significantly higher than in the CG at all time points, except baseline. No significant differences between EG were found, but some trends were observable. Anteriorly, the higher the resistive load, the higher the increase in MIP. Posteriorly, 100% 1RM caused the highest values, followed by 60% and 80% 1RM. No detraining effects were measured. The degree of exercise load had a significant negative effect on the registered success rate. This RCT confirms the efficacy of TSE in healthy older adults. For MIPA and MIPP, TSE at a resistive load of 100% 1RM are the most efficient choice in this population, while lowering the resistive load will lead to an increased success rate. No detraining effects were registered.


Genome-wide identification of the traf gene family in yellow catfish (Pelteobagrus fulvidraco) and analysis of their expression in response to bacterial challenge.
Tumour necrosis factor (TNF) receptor-associated factor (TRAF) is a receptor protein that has important functions in the immune system. Nonetheless, there have been few reports of traf genes in teleost fishes. The present study aimed to identify the traf genes from the genomic information of yellow catfish (Pelteobagrus fulvidraco). Eight traf genes were identified and named, which are distributed on different chromosomes but have similar conserved protein domains. Phylogenetic and syntenic analyses demonstrated conservation of traf genes during evolution. In addition, yellow catfish has the relatively rare traf1 and traf5 genes. Gene structure and motif analysis revealed the homology and distribution diversity of the traf genes. Quantitative real-time reverse transcription PCR was used to study the expression patterns of traf genes in healthy fish tissues and after infection by Aeromonas hydrophila. The results demonstrated significant changes in traf gene expression, indicating a potential role in innate immunity.


Inhibition of EGF Uptake by Nephrotoxic Antisense Drugs In Vitro and Implications for Preclinical Safety Profiling.
Antisense oligonucleotide (AON) therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA), have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates. We identified elevation of extracellular epidermal growth factor (EGF) as a robust and sensitive in vitro biomarker of LNA-AON-induced cytotoxicity in human kidney tubule epithelial cells. We report the time-dependent negative regulation of EGF uptake and EGF receptor (EGFR) signaling by toxic but not innocuous LNA-AONs and revealed the importance of EGFR signaling in LNA-AON-mediated decrease in cellular activity. The robust EGF-based in vitro safety profiling of LNA-AON drug candidates presented here, together with a better understanding of the underlying molecular mechanisms, constitutes a significant step toward developing safer antisense therapeutics.


Failure of additional ketoanalogues of branched chain amino acids to improve the response to parenteral nutrition after experimental trauma in the rat.
The ketoanalogues of branched chain amino acids (KAA) may improve the post-traumatic protein metabolism. We studied the effects of additional KAA, supplied as a part of total parenteral nutrition (TPN), on liver protein synthesis and nitrogen balance in rats after standard surgical trauma. A TPN-regimen, containing 36 mmol/kg/day KAA and 58 mmol/kg/day amino acids was compared to an isonitrogenous (1.0 gN/kg/day) TPN-regimen containing 58 mmol/kg/day amino acids and no KAA in a 48 h experiment. The liver protein synthesis measured by perfusion with C14-leucine in vitro was similar in both groups 2 days after surgery (59.2 +/- 16.2 vs. 64.3 +/- 15.6 arbitrary units, mean +/- SD). The nitrogen balances were negative and of similar magnitude (-0.66 +/- 0.36 vs. -0.17 +/- 0.45 gN/kg/48 h, mean +/- SD). We conclude that TPN supplemented by high supply of KAA offers no systematic advantage over TPN alone after experimental surgical trauma.


pH-Triggered Size-Transformable and Bioactivity-Switchable Self-Assembling Chimeric Peptide Nanoassemblies for Combating Drug-Resistant Bacteria and Biofilms.
Drug-resistant bacteria and biofilm-associated infections are prominent problems in the field of antibacterial medicine, seriously affecting human and animal health. Despite the great potential of nanomaterials in the antibacterial field, overcoming the paradox of size and charge, efficient penetration, and retention within biofilms remain a formidable challenge. Here, self-assembling chimeric peptide nanoassemblies composed of multiple functional fragments are designed for the treatment of drug-resistant bacteria and biofilm-associated infections. Notably, the chimeric peptide self-assembles into nanofibers at pH 7.4 and is transformable into nanoparticles in the acidic biofilm-infected microenvironment at pH 5.0, and thus achieves a size reduction and charge increase, improving the penetration into the bacterial biofilms and killing drug-resistant bacteria by a mechanism dominated by membrane cleavage. In vivo mouse and piglet infection models confirm the ability of chimeric peptide nanoassemblies to reduce bacterial load within biofilms. Collectively, this research on pathological-environment-driven nanostructural transformations may provide a theoretical basis for designing high-performance antibacterial nanomaterials and advance the application of peptide-based nanomaterials in medicine and animal husbandry.


Long-term efficacy of venom immunotherapy.
The long-term efficacy of venom immunotherapy (VIT) in patients who either prematurely discontinue VIT or who experience subsequent stings after discontinuation of VIT remains uncertain. To survey sting reaction patterns in patients who had previously discontinued VIT. Patients who had received VIT between January 1, 1984, and December 31, 2004 were sent a questionnaire inquiring whether they had been stung by an insect to which the VIT had been directed. Symptoms that developed were assessed. The patients were subsequently contacted by telephone to clarify their responses. Of 227 patients who responded to the questionnaire, 181 (79.7%) received VIT for more than 3 years; 100 of these 181 patients (55.2%) were stung after discontinuing VIT. At the time of the first sting after stopping VIT, 92 patients had a local reaction and 8 had a systemic reaction. Of 40 patients who were stung more than once after ending VIT, 7 (17.5%) experienced reactions of greater severity with the subsequent stings. All the patients reported that their reactions after ending VIT were milder than before treatment. The likelihood of systemic reactions to stings was almost identical in patients treated for either longer or shorter than 3 years with VIT. In most patients, VIT provides long-term protection from severe systemic reactions. Risk of systemic reactions increases with subsequent stings after ending VIT. All the patients reported that symptoms experienced with stings after stopping VIT were milder than symptoms before VIT.


Photosynthetic recovery of resurrection spikemosses from different hydration regimes.
Patterns and mechanisms of recovery of photosynthetic activity of two resurrection spikemoss species from different hydration environments in the Chihuahuan desert of southwest Texas, USA were compared in the laboratory. Selaginella lepidophylla Hook. and Grev. is the dominant poikilohydric plant found in hot, arid low-elevation desert scrub communities and S. pilifera A. Br. is one of many poikilohydric species found in more mesic, high-elevation woodland communities in Big Bend National Park, Texas. Infrared gas analysis of CO2 exchange during hydration of desiccated plants indicated that photosynthetic competence was achieved significantly more rapidly in S. lepidophylla tha S. pilifera. Chloramphenicol, a chloroplast protein synthesis inhibitor at 100 μg·ml-1 in the hydration medium, significantly inhibited the resumption of CO2 uptake in both species, but the level of inhibition was significantly greater in S. pilifera. The level of conserved ribulose 1,5 bis phosphate carboxylase specific activity in desiccated plants was significantly greater in S. lepidophylla. These results support the hypothesis that poikilohydric plants from increasingly xeric environments are capable of more rapid photosynthetic recovery, due to increased conservation of the photosynthetic system during desiccation and a reduced requirement for photosynthetic system repair during hydration, than those from more mesic environments.


The exploitation of enzyme-based cancer immunotherapy.
Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8+ T cells, natural killer (NK) cells, tumor associated macrophages (TAMs) and stromal cells. The myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs), are also key tumor-promoting immune cells. These potent immunosuppressive networks avert tumor rejection at various stages, affecting immunotherapies' outcomes. Numerous clinical trials have elucidated that disruption of immunosuppression could be achieved via checkpoint inhibitors. Another approach utilizes enzymes that can restore the body's potential to counter cancer by triggering the immune system inhibited by the tumor microenvironment. These immunotherapeutic enzymes can catalyze an immunostimulatory signal and modulate the tumor microenvironment via effector molecules. Herein, we have discussed the immuno-metabolic roles of various enzymes like ATP-dephosphorylating ectoenzymes, inducible Nitric Oxide Synthase, phenylamine, tryptophan, and arginine catabolizing enzymes in cancer immunotherapy. Understanding the detailed molecular mechanisms of the enzymes involved in modulating the tumor microenvironment may help find new opportunities for cancer therapeutics.


Imidazoline intoxication in children.
A 15-month-old girl with rhinopharyngitis was treated with a nasal solution containing the imidazoline derivative naphazoline. She rapidly developed profound CNS depression with stupor, hypothermia, hypoventilation and bradycardia. All symptoms disappeared within 24 h. The symptomatology of 18 other paediatric cases of naphthylimidazoline exposure reported to the Belgian National Poison Centre, is also discussed. Imidazoline intoxication due to overdose or accidental ingestion but also after normal therapeutic usage is frequent in children. It can cause severe CNS depression, especially in very young children. For these reasons vasoconstrictor imidazoline containing solutions should be prescribed with caution and kept out of reach of children.


The utility and tolerability of ultrasound guided muscle biopsy in the investigation of myopathy: a follow-up study.
Open surgical muscle biopsy has traditionally been required for the histological diagnosis of myopathy but requires neurosurgical expertise with a variable diagnostic yield. Ultrasound guided percutaneous approaches are less resource intensive and invasive. This follow-up study aims to assess the diagnostic yield and tolerability of this approach to assess its utility as an adjunct to the traditional open surgical technique. Between March of 2020 and June of 2021, 24 patients underwent a muscle biopsy following discussion at our regional neuromuscular multi-disciplinary team meeting. A consultant musculoskeletal radiologist used a modified Bergstrom needle to obtain a minimum of 2 samples under 500 mmHg of suction and ultrasound guidance. These were followed up to assess the diagnostic yield. A survey was also sent to the patients to assess the tolerability of the procedure. 21 out of the 24 biopsies performed provided diagnostic information. Of these 3 non diagnostic samples were obtained, two were insufficient in size and one consisted of fatty tissue. Of the 21 patients who responded to the survey, 18 rated the procedure as good or excellent with 3 patients rated it as average or poor citing administrative or communication issues rather than procedural. All 5 patients who had previously undergone surgical biopsy expressed a preference for the ultrasound guided percutaneous approach. No patients experienced any complications. This follow-up study reinforces the conclusion of its predecessor by highlighting that ultrasound guided percutaneous muscle biopsy is a useful and tolerable adjunct to the traditional surgical technique in investigating muscle disorders.


Qualitative Interpretive Metasynthesis of Parents' Experiences of Perinatal Loss.
To identify and synthesize common, experiential themes from qualitative studies of parents who experienced perinatal loss. We searched PubMed, CINAHL, and PsycINFO for qualitative articles about parents' experiences of perinatal loss. We included research on parents' experiences of perinatal loss published in English in the last 10 years. We excluded articles on the perspectives or experiences of health care professionals or persons other than the biological parent who experienced the perinatal loss, systematic reviews, outcome studies, and gray literature. We used a priori inclusion and exclusion criteria and identified five articles in which perinatal loss was described from the parents' perspectives. We extracted thematic findings and supporting quotes from each article and documented them in a table for subsequent synthesis. We used a qualitative metasynthesis and interpretive model to synthesize findings from the included studies. Findings were synthesized into one overarching theme, The Paradox of Perinatal Loss, and four subthemes: Complex Emotional Responses, Prenatal Bonding-Acknowledging Personhood, Interactions With Health Care Professionals, and Traversing the Social Sphere. Our findings indicate that perinatal loss is often a transformative event during which parents experience multiple losses and intense, complex emotions. Interactions with health care professionals greatly affected the pregnancy experience, which places professionals in a unique position to positively influence parents' overall experiences. Therefore, it is important to develop protocols related to perinatal loss and ensure that staff are adequately trained and equipped to care for parents during this experience. Findings from this synthesis may also inform the future development of theory related to bereavement surrounding perinatal loss.


Bilateral Hyphema - An Unexpected Complication of Exercise Resistance Band Use: A Case Report.
Resistance bands commonly used for strength training exercise come with an unexpected risk for ocular trauma. In this report, we describe an unintended consequence of a 28-year-old man sustaining an unusual injury-bilateral hyphema-as a result of the use of elastic resistance bands. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Resistance bands are commonly used for strength training exercise and, in this case, a potentially severe, vision-threatening injury-traumatic hyphema-occurred. Traumatic hyphema occurs when blood pools in the anterior chamber of the eye, usually as the result of blunt force trauma or penetrating injury. Early recognition of this condition is imperative, as complications of traumatic hyphema, such as intraocular hypertension or rebleeding, can lead to permanent vision loss.


Long term potentiation of single WDR neurons in spinalized rats.
We report long-term potentiation (LTP) in single spinal wide dynamic range (WDR) neurons in urethane-anaesthetized spinalized rats with a complete neuromuscular blockade. Peripheral influences were excluded by a complete lidocaine block distal to the stimulation site on the sciatic nerve. As previously shown A-beta fibre evoked responses were not increased by the tetanic stimulation when there was a neuromuscular blockade during the experiment. Spinalization, excluding influences from supraspinal structures, increased all firing responses, and the LTP of C-fibre evoked responses when calculated in number of action potentials compared to intact animals and to previous studies. Furthermore, an LTP of the post discharge was observed after spinalization. An LTP of the post discharge has previously not been reported. Therefore, we conclude that LTP in the dorsal horn normally seems to be inhibited by descending pathways.


Effect of alanine concentration independent of changes in insulin and glucagon on alanine and glucose homeostasis in the conscious dog.
The effect of an alanine load per se on hepatic alanine balance and hepatic glucose production is unclear. To examine this question, alanine was infused into six postabsorptive dogs at a rate of 6 mumol/kg-min, while maintaining insulin and glucagon levels using the pancreatic clamp technique. The arterial alanine concentration rose from a basal level of 227 +/- 16 mumol/L to 497 +/- 40 mumol/L during alanine infusion (P less than .01). The net hepatic fractional extraction of alanine remained unchanged, while hepatic alanine uptake increased from 3.0 +/- 0.3 to 6.0 +/- 0.4 mumol/kg-min (P less than .01). Conversion of alanine into glucose increased 87% to 2.7 +/- 0.3 mumol/kg-min during alanine infusion (P less than .01) while gluconeogenic efficiency remained essentially unchanged. Despite the increased gluconeogenic rate, the total rate of glucose production was unchanged. These data suggest that an increase in the alanine load to the liver causes a proportional increase in net hepatic alanine uptake and the gluconeogenic rate, but that in an overnight fasted animal this increase is insufficient to significantly increase glucose production.


Treadmill aerobic training improve beam-walking test, up-regulate expression of main proteins of myelin and myelination in the hippocampus of cuprizone-fed mice.
Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system). The aim of this study was to investigate the effect of 6 weeks of aerobic training on the main proteins of myelin including myelin basic protein (MBP), myelin oligodendrocyte (MOG), myelin associated glycoprotein (MAG), and myelin proteolipid protein (PLP) at hippocampus of C57BL/6 mouse model of cuprizone-induced MS. Twenty-eight female C57BL/6 mice (23 ± 3 g) were randomly divided into four groups (n = 7 per group): control, exercise (Exe), cuprizone (CPZ), and cuprizone with exercise (CPZ + Exe). Exercise groups performed treadmill aerobic exercise training 5 days a week, 15-22 m/min, and 15-60 min, during 6 weeks. Cuprizone were fed to mice at CPZ and CPZ + Exe groups for 6 weeks. Animals were sacrificed after 6 weeks. Biochemical and molecular biology analyses were performed. Mice at CPZ group had decreased myelination of nerve cells in the hippocampus. In addition, the use of CPZ in the hippocampus caused a decrease in the MBP, MOG gene expression, as well as a decrease in the MAG and PLP gene and protein expression compared to the healthy control group. However, performing aerobic exercise with CPZ consumption increased MBP gene expression and increased MAG and PLP protein expression, as well as increased myelination of nerve cells in the hippocampus compared to the CPZ group (p < 0.05). It seems that regular aerobic exercise in the MS model controls the destruction of myelin in the nerve cells of hippocampus by upregulating MBP, MAG and PLP, which can have positive effects on cognitive and motor performance.


Widespread microplastic pollution across the Caribbean Sea confirmed using queen conch.
The Caribbean Sea is reported to have one of the highest levels of plastic pollution of any marine ecosystem. Much less is known about the levels of microplastics as an emerging pollutant in the marine environment, especially in the water column and benthic substrates where they can be easily ingested by marine organisms. This study was carried out to quantify marine microplastics in the Wider Caribbean using the mollusk, queen conch (Aliger gigas). We analyzed feces collected from queen conch, a non-lethal method of sampling, to investigate microplastic pollution in eleven sites across the Wider Caribbean. Microplastics were extracted by degradation of organic matter from feces with peroxide (30%) over 48 h. Microplastics were then analyzed by stereomicroscope and scanning electron microscope. Microplastics were found to be present in the feces of all 175 queen conch sampled, and in statistically different abundances among sites, but with no obvious geographical pattern. The highest and lowest levels were found in Central America; the highest being in Belize (270 ± 55 microplastics/queen conch) and Alacranes, Mexico (203 ± 29 microplastics/queen conch), whilst the lowest levels were found in Puerto Morelos, Mexico. Fibers, mostly between 1000 and 1500 μm in size, were the most frequent microplastic particle types at every site and represented between 60 and 98% of all microplastic particles found. Our results suggest that the use of queen conch feces is a suitable method for detecting benthic microplastic pollution, and have confirmed that microplastic pollution of marine benthos is widespread across the Wider Caribbean.


[Operations for glaucoma: long-term results (author's transl)].
The author compares the long-term results of operations for glaucoma with or without scleral flap and also the operation of angiodiathermocoagulation.


Differential diagnoses of gallbladder tumors using CT-based deep learning.
The differential diagnosis between gallbladder cancer (GBC) and xanthogranulomatous cholecystitis (XGC) remains quite challenging, and can possibly lead to improper surgery. This study aimed to distinguish between XGC and GBC by combining computed tomography (CT) images and deep learning (DL) to maximize the therapeutic success of surgery. We collected a dataset, including preoperative CT images, from 28 cases of GBC and 21 XGC patients undergoing surgery at our facility. It was subdivided into training and validation (n = 40), and test (n = 9) datasets. We built a CT patch-based discriminating model using a residual convolutional neural network and employed 5-fold cross-validation. The discriminating performance of the model was analyzed in the test dataset. Of the 40 patients in the training dataset, GBC and XGC were observed in 21 (52.5%), and 19 (47.5%) patients, respectively. A total of 61 126 patches were extracted from the 40 patients. In the validation dataset, the average sensitivity, specificity, and accuracy were 98.8%, 98.0%, and 98.5%, respectively. Furthermore, the area under the receiver operating characteristic curve (AUC) was 0.9985. In the test dataset, which included 11 738 patches, the discriminating accuracy for GBC patients after neoadjuvant chemotherapy (NAC) (n = 3) was insufficient (61.8%). However, the discriminating model demonstrated high accuracy (98.2%) and AUC (0.9893) for cases other than those receiving NAC. Our CT-based DL model exhibited high discriminating performance in patients with GBC and XGC. Our study proposes a novel concept for selecting the appropriate procedure and avoiding unnecessary invasive measures.


N'-(4-Hy-droxy-benzyl-idene)ferrocene-1-carbohydrazide.
In the title compound, [Fe(C(5)H(5))(2)(C(13)H(11)N(2)O(2))], the dihedral angle between the benzene ring and the cyclo-penta-diene ring bonded to the carbonyl group is 26.1 (2)°. In the crystal, bifurcated O-H⋯(O,N) and N-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network.


Cancer chemoprevention: scientific promise, clinical uncertainty.
We review fundamental processes, such as mutation, oxidative stress, and inflammation that are critical for carcinogenesis and provide specific molecular targets for new chemopreventive agents. New information from molecular biology studies has identified such targets, including regulatory molecules such as Nrf2 (nuclear factor erythroid 2-related factor 2), epidermal growth factor receptor kinases, phosphatidylinositol 3-kinase, components of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway, nuclear factor-kappaB, and cyclin D. The development of new drugs for the control of these targets that are both safe and effective will be important for the future of cancer chemoprevention.


Calreticulin inhibits repetitive intracellular Ca2+ waves.
Inositol 1,4,5-trisphosphate (IP3)-mediated calcium (Ca2+) signaling is subject to cytosolic and luminal regulatory mechanisms. In Xenopus oocytes, Ca(2+)-sensitive gating of the IP3 receptor (IP3R) produces repetitive waves of Ca2+ release. We examined the role of the luminal Ca(2+)-binding protein calreticulin (CRT) in IP3-mediated Ca2+ signaling by using Ca2+ wave activity as a sensitive Ca2+ release assay. Overexpression of CRT inhibited repetitive IP3-induced Ca2+ waves. Deletion mutagenesis demonstrated that CRT inhibition was mediated by the high affinity-low capacity Ca(2+)-binding domain, which contributes little to Ca2+ storage. This novel function of CRT in intracellular Ca2+ signaling may be regulated by Ca2+ occupancy of the high affinity binding site.


Surgical management of consecutive multisegment thoracic and lumbar tuberculosis: anterior-only approach vs. posterior-only approach.
To compare the efficacy, safety, and technical characteristics of anterior-only and posterior-only approach surgeries for the treatment of consecutive multisegment thoracic and lumbar tuberculosis. Thirty-five patients who developed consecutive multisegment thoracic and lumbar tuberculosis from September 2012 to May 2016 were retrospectively analyzed. Group A was the posterior-only surgery group, and group B was the anterior-only surgery group. The data on the surgery, deformity correction, functional scores, and complications were compared between the two groups. There was no significant difference in the operation time or blood loss between groups A and B (P > 0.05). The preoperative average Cobb angle of kyphosis in groups A and B were 36.2 ± 15.2° and 27.9 ± 7.7°, respectively, which significantly decreased to 4.9 ± 11.8° and 10.4 ± 5.6° after the operation, respectively (P < 0.05). At the final follow-up, the angles were 7.1 ± 10.5° and 14.6 ± 8.0°. The correction angle and correction rate in group A (31.3 ± 16.6°, 88.6 ± 43.6%) were greater than those in group B (17.5 ± 4.4°, 64.9 ± 14.0%) (P < 0.05). There was no significant difference in the loss angle between groups A and B (P > 0.05), but the loss rate in group B (24.0 ± 27.8%) was higher than that in group A (9.6 ± 10.2%) (P < 0.05). There was no significant difference in the incidence of complications between the two groups (P > 0.05). The posterior-only and anterior-only approaches can lead to satisfactory clinical results in the treatment of patients with consecutive multisegment thoracic and lumbar tuberculosis. With posterior-only surgery, kyphosis can be better corrected, and the correction can be better maintained than with anterior-only surgery.


Epidemiology of leukaemia.
The history of the epidemiology of leukaemia provides us with models which are very useful even today and their implications for the future are still more important. Thus, in the present study, we shall review the history and present state of the epidemiology of leukaemia, as well as its future prospects. In the fifth century B.C. Hippocrates already advocated studying the climatic, geographical and physical environment as well as the behaviour of individuals and of their eating and drinking habits in order to understand the origin of a disease. At present, the epidemiology of leukaemia is still based on these ancient precepts.


Genetic alterations of triple negative breast cancer by targeted next-generation sequencing and correlation with tumor morphology.
Triple negative breast cancer represents a heterogeneous group of breast carcinomas, both at the histologic and genetic level. Although recent molecular studies have comprehensively characterized the genetic landscape of these tumors, few have integrated a detailed histologic examination into the analysis. In this study, we defined the genetic alterations in 39 triple negative breast cancers using a high-depth targeted massively parallel sequencing assay and correlated the findings with a detailed morphologic analysis. We obtained representative frozen tissue of primary triple negative breast cancers from patients treated at our institution between 2002 and 2010. We characterized tumors according to their histologic subtype and morphologic features. DNA was extracted from paired frozen primary tumor and normal tissue samples and was subjected to a targeted massively parallel sequencing platform comprising 229 cancer-associated genes common across all experiments. The average number of non-synonymous mutations was 3 (range 0-10) per case. The most frequent somatic alterations were mutations in TP53 (74%) and PIK3CA (10%) and MYC amplifications (26%). Triple negative breast cancers with apocrine differentiation less frequently harbored TP53 mutations (25%) and MYC gains (0%), and displayed a high mutation frequency in PIK3CA and other PI3K signaling pathway-related genes (75%). Using a targeted massively parallel sequencing platform, we identified the key somatic genetic alterations previously reported in triple negative breast cancers. Furthermore, our findings show that triple negative breast cancers with apocrine differentiation constitute a distinct subset, characterized by a high frequency of PI3K pathway alterations similar to luminal subtypes of breast cancer.


Role of neurosympathetic pathways in the vascular response to sepsis.
The aim of this study was to determine the role of sympathetic neural activity in the hemodynamic adaptations to sepsis in pigs with an emphasis on circuit adaptations. A fall in resistance to venous return (RVR) was predicted in contrast to what was previously observed in sympathetically intact animals that had no change in RVR. We anesthetized and ventilated 13 pigs and gave 5 mg/kg of indomethacin. We measured cardiac output (CO) by thermodilution and measured pulmonary arterial (PAP), pulmonary capillary wedge (Pcw), right atrial pressure (Pra), and arterial pressure (MAP). Intermittent inflation of a 50-mL balloon in the right atrium was used to transiently arrest the circulation for the measurement of mean circulatory filling pressure (MCFP). RVR was calculated from (MCFP - Pra)/CO. Animals were divided into two groups; 6 received 10 mg/kg of the ganglionic blocker, hexamethonium and norepinephrine to maintain MAP; 7 had their spinal cords cut at C-2. After baseline measurements, all animals received 10 microg/kg/h of endotoxin for 2 hours, and hemodynamic measurements were repeated. Plasma samples were obtained for measurements of immunoreactive endothelin-1 (ET-1), which was assayed by a radioimmunoassay. Hexamethonium had no significant effect on hemodynamics except for an increase in heart rate. After endotoxin, MAP and SVR fell, PAP rose, and CO and RVR did not change. Spinal section resulted in an increase in heart rate and small increase in PAP and MCFR After endotoxin, there was a further increase in heart rate, PAP, and MCFP with a marked fall in MAP and CO. RVR increased from 2.1 +/- 0.46 after spinal section to 3.6 +/- 54 mm x min/L (P < .05). ET-1 in the hexamethonium group (n = 2) rose from 2.21 +/- .14 to 11.5 +/- 2.1 pg/ml at 2 hours, and in the spinal group (n = 7) from 2.04 +/- 0.77 to 6.85 +/- 3.9 pg/mL at 45 minutes. Spinal section resulted in a more profound fall in blood pressure and less increase in MCFP than in previously studied animals with sympathetic nervous system intact, but there was still an increase in RVR and PAP ET-1 is a possible mediator of the increase in RVR and PAP.


Neuroleptic antagonism of dyskinetic phenomena.
The bilateral intrastriatal administration of dopamine to guinea pigs pretreated with nialamide-induced dyskinesias characterized by gnawing, biting and licking reactions, acute twisting of the head and neck, whole body or head and neck rocking movements, and a hyperactive state. Hyperactivity was inhibited by the peripheral administration of large doses of many neuroleptic agents, e.g. haloperidol, fluphenazine, but only pimozide and oxiperomide inhibited the other forms of dyskinetic movements. This was not due to a peculiar depressant effect of these agents in the guinea pig since haloperidol was shown to be equipotent to oxiperomide and of greater potency than pimozide both in causing catalepsy and antagonising amphetamine sterotypy...


FSHB and FSHR gene variants exert mild modulatory effect on reproductive hormone levels and testis size but not on semen quality: A study of 2020 men from the general Danish population.
Spermatogenesis depends on stimulation by follicle-stimulating hormone (FSH) which binds to FSH receptors (FSHR) on testicular Sertoli cells. Three FSH-related single-nucleotide polymorphisms (SNPs), FSHB -211G>T (rs10835638), FSHR -29G>A (rs1394205) and FSHR 2039A>G (rs6166) affect FSH action, and have been suggested to affect testicular function, but the evidence is uncertain. To describe the associations between the three SNPs and testicular function in a large and well-characterised cohort of men from the general population. A cross-sectional study of 2020 Danish men unselected regarding testicular function. Outcome variables were semen parameters, reproductive hormones and testis size. Genotyping was done by competitive allele-specific quantitative PCR. Differences in genotype frequencies were tested by chi-square test and associations between genotypes and outcomes were assessed by multivariate linear regressions. The SNPs affected serum FSH; carriers of the variant affecting FSH secretion (FSHB -211G>T) had lower FSH levels while carriers of variants affecting receptor expression (FSHR -29G>A) and receptor sensitivity (FSHR 2039A>G) had higher FSH levels. Carriers of FSHB -211G>T had lower calculated free testosterone/LH ratio. Although both FSHB -211G>T and FSHR 2039A>G were associated with smaller testis size, no clear association was detected in relation to any semen parameters, except a lower total number of morphologically normal spermatozoa in the heterozygous carriers of the FSHB -211G>T DISCUSSION AND CONCLUSION: The studied polymorphisms have only minor modulating influence on testis size and function in healthy men. We detected subtle effects of the three SNPs on FSH levels, but also effects of FSHB -211G>T on calculated free testosterone/LH ratio, compatible with altered Leydig cell function. Thus, the role of these FSH-related polymorphisms is complex and modest in men with normal testicular function, but the possible importance of FSH polymorphisms in men with impaired testicular function should be evaluated in future studies in more detail.


Clinical study on treatment of primary hepatocellular carcinoma by Shenqi mixture combined with microwave coagulation.
To observe the short-term efficacy and safety of Shenqi mixture (SQM) combined with microwave coagulation in treating primary hepatocellular carcinoma (HCC). Seventy-two patients with primary HCC of stage II-III, Karnofsky scoring > or = 50 scores and predicted survival period > or = 3 months were selected and randomly assigned into two groups, the treated group and the control group, 36 in each. Microwave therapy was applied to both groups by double leads, 60 W, 800 sec once a week for two weeks. To the treated group, SQM was given additionally through oral intake of 20 ml, three times a day for 1 month. The changes in tumor size, main symptoms, serum level of alpha-fetoprotein (AFP), immune function and adverse reaction were observed after treatment and the immune parameters of the patients were compared with 30 healthy persons in the normal control group. (1) In the SQM treated group, after treatment 3 patients got completely remitted (CR), 24 partial remitted (PR), 4 unchanged (NC) and 5 progressively deteriorated (PD), the effective rate being 75.00%; while in the control group, 1 got CR, 19 PR, 9 NC and 7 PD, the effective rate being 55.56%. Comparison of the effective rate between the two groups showed significant difference (P < 0.05). (2) AFP level decreased after treatment in both groups, but the decrement in the treated group was significantly higher than that in the control group (P < 0.01). (3) After treatment, in the treated group, CD3(+), CD4(+), CD4(+)/CD8(+) and NK activity were improved, Karnofsky scores increased and liver function bettered, with these improvements significantly superior to those in the control group (P < 0.01). (4) The improvement in symptoms such as hepatic region pain, fever, weakness, poor appetite and jaundice in the treated group after treatment was also superior to that in the control group (P < 0.01). (5) The 12-month, 18-month and 24-month survival rates were higher and the recurrence rate was lower in the treated group than those in the control group, showing significant difference (P < 0.05). Combined therapy with SQM and microwave coagulation could not only kill the tumor and residue tumor cells to prevent recurrence, but also enhance the cellular immunity of organism. It is one of the effective therapies for patients with middle-advanced hepatocarcinoma, who have lost the chance of surgical operation. It could improve clinical symptoms, elevate the quality of life, prolong the survival period of patients, but shows no evident adverse reaction.


Effect of nucleotide replacements in tRNAPhe on positioning of the acceptor end in the complex with phenylalanyl-tRNA synthetase.
The effect of replacement of tRNA(Phe) recognition elements on positioning of the 3'-terminal nucleotide in the complex with phenylalanyl-tRNA synthetase (PheRS) from T. thermophilus in the absence or presence of phenylalanine and/or ATP has been studied by photoaffinity labeling with s(4)U76-substituted analogs of wild type and mutant tRNA(Phe). The double mutation G34C/A35U shows the strongest disorientation in the absence of low-molecular-weight substrates and sharply decreases the protein labeling, which suggests an initiating role of the anticodon in generation of contacts responsible for the acceptor end positioning. Efficiency of photo-crosslinking with the alpha- and beta-subunits in the presence of individual substrates is more sensitive to nucleotide replacements in the anticodon (G34 by A or A36 by C) than to changes in the general structure of tRNA(Phe) (as a result of replacement of the tertiary pair G19-C56 by U19-G56 or of U20 by A). The degree of disorders in the 3'-terminal nucleotide positioning in the presence of both substrates correlates with decrease in the turnover number of aminoacylation due to corresponding mutations. The findings suggest that specific interactions of the enzyme with the anticodon mainly promote the establishment (controlled by phenylalanine) of contacts responsible for binding of the CCA-end and terminal nucleotide in the productive complex, and the general conformation of tRNA(Phe) determines, first of all, the acceptor stem positioning (controlled by ATP). The main recognition elements of tRNA(Phe), which optimize its initial binding with PheRS, are also involved in generation of the catalytically active complex providing functional conformation of the acceptor arm.


A feasibility study of image-guided hypofractionated conformal arc therapy for inoperable patients with localized non-small cell lung cancer.
We treated 36 cases of stage I/II non-small cell lung cancer in inoperable patients. Treatments were planned to a total isocenter dose of 60Gy (8x7.5Gy) based on a dynamic field shaping arc, employing one arc to span as much area as possible and if needed additional weighted segments. The 2 year infield progression free probability is 65%. Disease-specific survival is 75% at 2 years. No patients experienced grade 3-4 toxicity.


Preparation and characterization of folic acid conjugated sulfated polysaccharides on NK cell activation and cellular uptake in HeLa cells.
In this study, the sulfated polysaccharide (SP) of Codium fragile was conjugated to folic acid (SP-FA). FT-IR and 1H NMR techniques revealed the occurrence of esterification reaction between the hydroxyl group of SP and the γ-carboxyl group of FA that confirming the SP-FA conjugation. SP and SP-FA did not show any direct toxicity on NK cells and HeLa cells. However, the treatment of SP and SP-FA enhance the NK cells cytotoxicity against HeLa cells by the upregulation of IFN-γ, TNF-α, perforin, and Granzyme-B. Moreover, NK cells activation was stimulated through NF-кB and MAPK pathways. The binding capacity studies exposed the targeting ability of HeLa cells by folate receptor (FR) which was assessed by a confocal quantitative image cytometer analysis. These results indicate that SP-FA could be used as selective drug delivery systems for targeting FR-overexpressed cancer cells with less toxicity.


Thyroxine binding and deiodination of thyroxine by human lymphocytes.
Binding and deiodination of T4 by lymphocytes from euthyroid, hypothyroid and hyperthyroid subjects were studied. Two sets of binding sites were found on normal lymphocytes. One set with equilibrium association constant of 6.9 X 10(9) l/mol and a maximal binding capacity of 3000 mol T4 per lymphocyte, and another set with equilibrium association constant of 4.1 X 10(6) l/mol and a maximal binding capacity of 7.8 X 10(6) mol T4 per lymphocyte. The major part of the binding sites were non specific and the binding reversible. Debinding assays revealed also two types of binding site and indicated that deiodination took place predominately from one type of binding site. Deiodination assay showed that the deiodination process had a maximal deiodination capacity of 6 X 10(-13) mol T4/10(6) lymphocytes. Paper chromatography revealed only I and T4 after incubation of lymphocytes with T4. In comparing the patient groups with the control group, lymphocytes from hyperthyroids and hypothyroids exerted a higher T4 turnover (deiodinated T4/bound T4) although the difference was not statistically significant. Lymphocytes exerted a high T4 turnover at low temperature (3 degrees C) and propylthiouracil inhibited deiodination of T4 but not binding.


Phenotype and functions of conventional dendritic cells are not compromised in aged mice.
Aging has profound effects on the immune system, including thymic involution, reduced diversity of the T cell receptor repertoire, reduced effector T cell and B cell function and chronic increase of proinflammatory cytokine production by innate immune cells. The precise effects of aging on conventional dendritic cells (cDC), the main antigen presenting cells of the immune system, however, are not well understood. We found that in aged mice the number of cDC in the spleen and lymph nodes remained stable, whereas the number of cDC in the lungs increased with age. Whereas cDC in mice showed similar cycling kinetics in all organs tested, cDC reconstitution by aged bone marrow precursors was relatively higher than that of their young counterparts. With the exception of CD86, young and aged cDC did not differ in their expression of co-stimulatory molecules at steady state. Most toll-like receptor (TLR) ligands induced comparable upregulation of co-stimulatory molecules CD40, CD86 and B7H1 on young and aged cDC, whereas TLR2 and TLR5 stimulation resulted in reduced upregulation of CD80 and CD86 on aged cDC in vitro. In vivo, influenza infection-induced upregulation of CD86, but not other co-stimulatory molecules, was lower in aged DC. Young and aged DC were equally capable of direct and cross presentation of antigens in vitro. Transcriptome analysis did not reveal any significant difference between young and aged cDC. These data show that unlike T and B cells, the maintenance of cDC throughout the life of a healthy animal is relatively robust during the aging process.


Caecal volvulus in an adult with an incomplete common mesentery: A case report.
A common mesentery is defined by the persistence of an embryonic anatomical arrangement secondary to an anomaly of rotation of the primary umbilical loop. Caecal volvulus is a rare cause of intestinal obstruction, which account for 1 to 1.5 % of all intestinal obstructions. A combination of both, intestinal mal rotation and caecal volvulus is rare. We report this rare entity in a 50 year old male with no history of abdominal surgery who was admitted for an acute intestinal obstruction. Clinical examination found a non-complicated right inguinal hernia. Radiological assessment showed signs of an incomplete common mesentery and an important small bowl distention with a transitional zone near the profound inguinal ring. Emergency surgery was performed. Surgical exploration didn't find signs of strangulation in the inguinal hernia which motivated midline laparotomy. We discovered a caecal volvulus with an incomplete common mesentery and ischemic lesions in the caecum. Ileocaecal resection was performed with ileocolostomy. Common mesentery can be complete or incomplete. It is often well tolerated in adulthood. This intestinal malrotation can sometimes cause serious complications such as volvulus. Their association is rare. Radiology can be very helpful in leading to the diagnosis, but the diagnostic process should not delay surgical intervention which is the basis of the treatment. Caecal volvulus is a serious complication of intestinal malrotation. This association is rare in adulthood and symptoms are not specific. Emergency surgery is necessary.


[New considerations on the role of the mouse skin surface lipids on the "in vivo" penetration of "Schistosoma mansoni" cercariae (author's transl)].
The authors have studied the effect of delipitizing and of the previously extracted skin lipids reapplication on mice experimental infected with Schistosoma mansoni cercariae. The results demonstrated that the amount of living cercariae, not penetrated, recovered after the exposition to the parasite is greater in the delipitized mice than in the other ones. The low amount of worms recovered from the treated mice might be due to the effect of the mouse skin surface lipids not only on stimulating cercarial penetration but also on allowing cercarial transformation to schistosomula during skin crossing.


Genome-wide association study of bone quality and feed efficiency-related traits in Pekin ducks.
Feeding and bone traits are vital for breeding and reproduction in the commercial duck industry. In this study, we performed a genome-wide association study for feeding and bone traits in a population of 540 lean-type Pekin ducks, followed by genotyping-by-sequencing procedures. The genetic parameters of feeding and bone traits were also estimated using genomic information. In total, seventy-eight significant SNPs were determined, and eleven of them reached the genome-wide significant level for 7 traits except for body weight at 42-day old. A peak of genome-wide significant SNPs was detected on chromosome 2 for feed conversion ratio (P-value = 7.46E-11), and the top SNP (P-value = 2.23E-08) for bone-breaking strength was also obtained in the upstream of gene RAPGEF5. This study provided a list of novel markers and candidate genes associated with feeding and bone traits in Pekin ducks, which could contribute to the genetic selection in duck breeding.


Symptomatology across the menstrual cycle in smoking and nonsmoking women.
Recent studies suggest that both smoking rates and general menstrual symptomatology increase in women premenstrually; however, no study has investigated the changes in menstrual symptomatology and smoking behavior in both smoking and nonsmoking women over an entire menstrual cycle. Thirty premenopausal women completed daily symptom checklists over an entire menstrual cycle. Smokers also recorded their smoking behavior. Results indicated that symptom severity was greatest during menses for both smoking and nonsmoking women. For cigarette consumption, analyses indicated that women smokers appear to smoke more during menses and the luteal phases than ovulation and that variability in smoking was greatest premenstrually. In summary, results indicated that general menstrual symptomatology increases during menses and the late luteal phase and that smoking-deprivation symptomatology increase in both smokers and nonsmokers. This suggests that smokers may have a difficult time quitting during menses or the luteal phase of their cycle.


Oral non-steroidal anti-inflammatory drug use in recreational runners participating in Parkrun UK: Prevalence of use and awareness of risk.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in endurance running and by elite athletes. We examined the pattern of use of NSAIDs, the purpose of use and knowledge of the adverse effects of NSAID use in a population of recreational runners at Parkrun UK. An online observational non-interventional cross-sectional survey of Parkrun UK participants being over the age of 18, on Parkrun UK's mailing list, and residing in the UK. Runners (n = 806) had a high use of NSAIDs in the past 12 months (87.8%). The average age of respondents was 48.39 years. There was a significant association between those taking an oral NSAID in the last twelve months and those with a sporting injury (χ2 = 10.89, df = 1, n = 797, P = 0.001). Ibuprofen was the most commonly used NSAID (81.1%). A third of runners had experienced an adverse drug reaction associated with NSAIDs, usually gastrointestinal. Half of runners used NSAIDs with no advice, and patient information leaflets were the most common source for those that had advice. Ninety-four per cent of runners would like more information on the harms and benefits of NSAIDs. Some recreational runners have a high use of NSAIDs, which is chronic in nature and a potential health risk. Recreational runners want more information on the harms and benefits of NSAIDs. Race event organizers should provide evidence-based advice on the use of NSAIDs.


Positron Emission Tomography (PET) radiotracers in oncology--utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC).
PET (Positron Emission Tomography) is a nuclear medicine imaging method, frequently used in oncology during the last years. It is a non-invasive technique that provides quantitative in vivo assessment of physiological and biological phenomena. PET has found its application in common practice for the management of various cancers.Lung cancer is the most common cause of death for cancer in western countries.This review focuses on radiotracers used for PET scan with particular attention to Non Small Cell Lung Cancer diagnosis, staging, response to treatment and follow-up.


Soccer-drill specificity in top-class male players with reference to peak match locomotor demands.
To compare the locomotor demands of several ball/running drills with the official match peak, locomotor demands determined across different time-windows of the same duration in top-class male soccer players (n = 40). Total distance (TD), high-speed running (HSR, 15-20 km⋅h-1), very high-speed running (VHSR, 20-24 km⋅h-1), sprint and acceleration+deceleration (Acc+Dec >±3 m⋅s-2) distances were measured during training and official matches. A total of 9372 individual observations were classified as technical-tactical drills, small-sided games (SSGs), super-SSGs (pitch-area >340 m2·player), SSGs with rules modifications (SSGmodified), individual positional drills or running drills. The relative (m·min-1) TD, HSR, VHSR, sprint and Acc+Dec were compared with the peak locomotor demands determined during official matches across different time-windows (1, 2, 3, 4 and 5-min). Individual position-specific drill, super-SSGs, SSGmodified and running drills showed similar (P > 0.05) or higher (P < 0.05; ES:1.17/4.61) than match TD, HSR and VHSR, while sprint and Acc+Dec were lower (P < 0.05). Conversely, technical-tactical drills and SSGs showed lower (P < 0.05; ES:-1.00/-3.45) TD, HSR, VHSR, sprint and Acc+Dec than official match peak demands. Locomotor loads during technical-tactical drills and SSGs were lower than peak demands, particularly for VHSR and sprint. Since training intensity is a key factor for high-performance development, these results may help to prepare top-class players for the official match peak demands.


Can the joint effect of ternary mixtures be predicted from binary mixture toxicity results?
The joint effect of the majority of chemical mixtures can be predicted using the reference model of Concentration Addition (CA). It becomes a challenge, however, when the mixtures include chemicals that synergise or antagonise the effect of each other. In this study we examine if the deviation from CA of seven ternary mixtures of interacting chemicals can be predicted from knowledge of the binary mixture responses involved. We hypothesise that the strongest interactions will take place in the binary mixtures and that the size of the ternary mixture response can be predicted from knowledge of the binary interactions. The hypotheses were tested using a stepwise modelling approach of incorporating the information held in binary mixtures into a ternary mixture model, and comparing the model predictions with observed ternary mixture toxicity data derived from studies of interacting chemical mixtures on the floating plant Lemna minor and the bacteria Vibrio fischeri. The results showed that for both the antagonistic and the synergistic ternary mixtures the ternary model predictions were superior to the conventional CA reference model and provided robust estimations of the size of the experimentally derived ternary mixture toxicity effects.


IL-10 derived from CD1dhiCD5⁺ B cells regulates experimental autoimmune myasthenia gravis.
IL-10-competent subset within CD1d(hi)CD5(+) B cells, also known as B10 cells, has been shown to regulate autoimmune diseases. In our previous study, adoptive transfer of CD1d(hi)CD5(+) B cells expanded in vivo by GM-CSF prevented and suppressed experimental autoimmune myasthenia gravis (EAMG). The goal of this study was to further examine the role and mechanism of IL-10 in the regulatory function of B10 cells in EAMG. We found that only IL-10 competent CD1d(hi)CD5(+) B cells sorted from WT mice, but not IL-10 deficient CD1d(hi)CD5(+) B cells exhibited regulatory function in vitro and in vivo. Adoptive transfer of IL-10 competent CD1d(hi)CD5(+) B cells led to higher frequency of Tregs and B10 cells, and low levels of proinflammatory cytokines and autoantibody production. We conclude that IL-10 production within CD1d(hi)CD5(+) B cells plays an important role in immune regulation of EAMG.


Design and synthesis of L- and D-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase.
Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Herein, we report the synthesis and in vitro evaluation of anti-NS5B polymerase activity of a molecular hybrid of our previously reported lead compounds 1 (IC50=7.7 μM) and 2 (IC50=10.6 μM) as represented by hybrid compound 27 (IC50=6.7 μM). We have explored the optimal substituents on the terminal phenyl ring of the 3-phenoxybenzylidene moiety in 27, by generating a set of six analogs. This resulted in the identification of compound 34 with an IC50 of 2.6 μM. To probe the role of stereochemistry towards the observed biological activity, we synthesized and evaluated the D-isomers 41 (IC50=19.3 μM) and 45 (IC50=5.4 μM) as enantiomers of the l-isomers 27 and 34, respectively. The binding site of compounds 32 and 34 was mapped to palm pocket-I (PP-I) of NS5B. The docking models of 34 and 45 within the PP-I of NS5B were investigated to envisage the molecular mechanism of inhibition.


pH-responsive polymeric micelle based on PEG-poly(β-amino ester)/(amido amine) as intelligent vehicle for magnetic resonance imaging in detection of cerebral ischemic area.
A series of pH-responsive polymeric micelles is developed to act as intelligent carriers to deliver iron oxide (Fe(3)O(4)) nanoparticles and respond rapidly to an acidic stimuli environment for magnetic resonance imaging (MRI). The polymeric micelle can be self-assembled at physiological pH by a block copolymer, consisting of a hydrophilic methoxy poly(ethylene glycol) (PEG) and a pH-responsive poly(β-amino ester)/(amido amine) block. Consequently, the Fe(3)O(4) nanoparticles can be well encapsulated into polymeric micelles due to the hydrophobic interaction, shielded by a PEG coronal shell. In an acidic environment, however, the pH-responsive component, which has ionizable tert-amino groups on its backbone, can become protonated to be soluble and release the hydrophobic Fe(3)O(4) nanoparticles. The Fe(3)O(4)-loaded polymeric micelle was measured by dynamic light scattering (DLS), superconducting quantum interference device (SQUID) and a 3.0T MRI scanner. To assess the ability of this MRI probe as a pH-triggered agent, we utilize a disease rat model of cerebral ischemia that produces acidic tissue due to its pathologic condition. We found gradual accumulation of Fe(3)O(4) nanoparticles in the brain ischemic area, indicating that the pH-triggered MRI probe may be effective for targeting the acidic environment and diagnostic imaging of pathologic tissue.


Serum factor(s) induced by restraint stress in mice and rats suppresses lymphocyte proliferation.
LACA mice were individually restrained in a specially made cylindrical cage for 10-20 h at room temperature (20 degrees C). Serum obtained from stressed mice was found to suppress normal mouse lymphocyte proliferation induced by concanavalin A, suggesting the presence of a suppressive factor(s) in the stressed serum. Adrenalectomy or injections of naltrexone (1, 10, or 20 mg/kg, ip), just prior to and in the middle of the stress period, did not affect the suppressive activity of serum from mice. However, the suppressive activity was totally abolished by general anesthesia with urethane (1.5 g/kg, ip). These results suggest that adrenal hormones and opiate receptors are not involved in the generation of the suppressive factor(s) and that the central nervous system plays a very important role in this process. SD rats were restrained in a supine position for 20 h at room temperature (20 degrees C) and serum from stressed rats was also found to be able to suppress normal mouse lymphocyte proliferation. A further analysis of "stressed serum" indicated that the suppressive factor(s) was heat stable (56 degrees C, 30 min) and acid stable (pH 3.8), but sensitive to 100 degrees C (3 min), an organic solvent (greater than 60% methanol), and proteinases (trypsin and chymotrypsin). From the measurement of gel filtration (HPLC), the molecular weights of the suppressive factor(s) were 155 and 370 kDa. Taken together, these results indicate that the suppressive factor(s) is a protein with a large molecular weight.


Performance of the wheat armyworm, Pseudaletia sequax Franclemont, on natural and artificial diets.
Armyworms in the genus Pseudaletia Franclemont are important pests of cereal crops worldwide. The development of pest management strategies is largely dependent on studies involving the relationship among the pest, its host plants and natural enemies, as well as its susceptibility to chemical and biological control strategies. Part of these studies requires rearing the species of interest under laboratory conditions, which can be greatly facilitated by the use of artificial diets. In the present study, the effects of three artificial diets on development, survival, reproduction and demographic parameters of P. sequax were compared to a natural host plant, Pennisetum clandestinum. A diet based on pinto beans, wheat germ and torula yeast provided the best results in comparison to those obtained with the host plant. The most important life history parameters used in the evaluation of the nutritional quality of the diets were fecundity, egg viability and pupae deformities. The intrinsic rate of increase and the net reproductive rate were higher when individuals were fed on the artificial diet if compared to the host plant, indicating the suitability of the tested diet for the rearing of P. sequax. This artificial diet has been used successfully for the rearing of P. sequax without any fitness effect for over 18 consecutive generations.